| Product Description: | Propofol Injectable Emulsion, 1%, 200 mg/20 mL (10 mg/mL), 20 mL Single patient infusion vials, packaged in 5 Units per carton, Rx only, Hospira, Inc., Lake Forest, IL 60045, NDC 0409-4699-30. |
|---|---|
| Status: | Ongoing |
| City: | Lake Forest |
| State: | IL |
| Country: | US |
| Voluntary/Mandated: | Voluntary: Firm Initiated |
| Initial Firm Notification: | Telephone |
| Distribution Pattern: | Distribution limited to one shipment to The Harvard Drug Group, Livonia, MI for the lots of Vancomycin 500 mg, Ketorolac tromethamine 60 mg/2 mL (30 mg/mL), and Propofol 1% 200 mg/20 mL (10 mg/mL), these lots remained within the control of the distributor and were not further distributed. Distribution was Nationwide for the Vancomycin 1 g product. |
| Classification: | Class I |
| Product Quantity: | 2,500 vials |
| Reason For Recall: | Temperature Abuse: Products experienced uncontrolled temperature excursions during transit. |
| Recall Initiation Date: | 20141006 |
| Report Date: | 20150225 |
| Product Description: | Propofol Injectable Emulsion, 1%, 200 mg/20 mL (10 mg/mL), 20 mL Single patient infusion vials, packaged in 5 Units per carton, Rx only, Hospira, Inc., Lake Forest, IL 60045, NDC 0409-4699-30. |
|---|---|
| Status: | Ongoing |
| City: | Lake Forest |
| State: | IL |
| Country: | US |
| Voluntary/Mandated: | Voluntary: Firm Initiated |
| Initial Firm Notification: | Telephone |
| Distribution Pattern: | Distribution limited to one shipment to The Harvard Drug Group, Livonia, MI for the lots of Vancomycin 500 mg, Ketorolac tromethamine 60 mg/2 mL (30 mg/mL), and Propofol 1% 200 mg/20 mL (10 mg/mL), these lots remained within the control of the distributor and were not further distributed. Distribution was Nationwide for the Vancomycin 1 g product. |
| Classification: | Class I |
| Product Quantity: | 2,500 vials |
| Reason For Recall: | Temperature Abuse: Products experienced uncontrolled temperature excursions during transit. |
| Recall Initiation Date: | 20141006 |
| Report Date: | 20150225 |
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Questions & Answers
Side Effects & Adverse Reactions
Use of Propofol Injectable Emulsion has been associated with both fatal and life-threatening anaphylactic and anaphylactoid reactions.
For general anesthesia or monitored anesthesia care (MAC) sedation, Propofol Injectable Emulsion should be administered only by persons trained in the administration of general anesthesia and not involved in the conduct of the surgical/diagnostic procedure. Sedated patients should be continuously monitored, and facilities for maintenance of a patent airway, providing artificial ventilation, administering supplemental oxygen, and instituting cardiovascular resuscitation must be immediately available. Patients should be continuously monitored for early signs of hypotension, apnea, airway obstruction, and/or oxygen desaturation. These cardiorespiratory effects are more likely to occur following rapid bolus administration, especially in the elderly, debilitated, or ASA-PS III or IV patients.
For sedation of intubated, mechanically ventilated patients in the Intensive Care Unit (ICU), Propofol Injectable Emulsion should be administered only by persons skilled in the management of critically ill patients and trained in cardiovascular resuscitation and airway management.
Use of Propofol Injectable Emulsion infusions for both adult and pediatric ICU sedation has been associated with a constellation of metabolic derangements and organ system failures, referred to as Propofol Infusion Syndrome, that have resulted in death. The syndrome is characterized by severe metabolic acidosis, hyperkalemia, lipemia, rhabdomyolysis, hepatomegaly, cardiac and renal failure. The following appear to be major risk factors for the development of these events: decreased oxygen delivery to tissues; serious neurological injury and/or sepsis; high dosages of one or more of the following pharmacological agents: vasoconstrictors, steroids, inotropes and/or prolonged, high-dose infusions of propofol (> 5 mg/kg/h for > 48h). The syndrome has also been reported following large-dose, short-term infusions during surgical anesthesia. In the setting of prolonged need for sedation, increasing propofol dose requirements to maintain a constant level of sedation, or onset of metabolic acidosis during administration of a propofol infusion, consideration should be given to using alternative means of sedation.
Abrupt discontinuation of Propofol Injectable Emulsion prior to weaning or for daily evaluation of sedation levels should be avoided. This may result in rapid awakening with associated anxiety, agitation, and resistance to mechanical ventilation. Infusions of Propofol Injectable Emulsion should be adjusted to maintain a light level of sedation through the weaning process or evaluation of sedation level (see PRECAUTIONS).
Propofol Injectable Emulsion should not be coadministered through the same IV catheter with blood or plasma because compatibility has not been established. In vitro tests have shown that aggregates of the globular component of the emulsion vehicle have occurred with blood/plasma/serum from humans and animals. The clinical significance of these findings is not known.
There have been reports in which failure to use aseptic technique when handling Propofol Injectable Emulsion was associated with microbial contamination of the product and with fever, infection, sepsis, other life-threatening illness, and death. Do not use if contamination is suspected. Discard unused portions as directed within the required time limits (see DOSAGE AND ADMINISTRATION, Handling Procedures ).
Legal Issues
There is currently no legal information available for this drug.
FDA Safety Alerts
There are currently no FDA safety alerts available for this drug.
Manufacturer Warnings
There is currently no manufacturer warning information available for this drug.
FDA Labeling Changes
There are currently no FDA labeling changes available for this drug.
Uses
Propofol Injectable Emulsion is an IV sedative-hypnotic agent that can be used as described in the table below.
Table 3. Indications for Propofol Injectable Emulsion
| Indication |
Approved Patient Population |
| Initiation and maintenance of Monitored Anesthesia Care (MAC) sedation |
Adults only |
| Combined sedation and regional anesthesia |
Adults only (see PRECAUTIONS) |
| Induction of General Anesthesia |
Patients ≥ 3 years of age |
| Maintenance of General Anesthesia |
Patients ≥ 2 months of age |
| Intensive Care Unit (ICU) sedation of intubated, mechanically ventilated patients |
Adults only |
Safety, effectiveness and dosing guidelines for Propofol Injectable Emulsion have not been established for MAC Sedation in the pediatric population; therefore, it is not recommended for this use (see PRECAUTIONS, Pediatric Use).
Propofol Injectable Emulsion is not recommended for induction of anesthesia below the age of 3 years or for maintenance of anesthesia below the age of 2 months because its safety and effectiveness have not been established in those populations.
In the Intensive Care Unit (ICU), Propofol Injectable Emulsion can be administered to intubated, mechanically ventilated adult patients to provide continuous sedation and control of stress responses only by persons skilled in the medical management of critically ill patients and trained in cardiovascular resuscitation and airway management.
Propofol Injectable Emulsion is not indicated for use in Pediatric ICU sedation since the safety of this regimen has not been established (see PRECAUTIONS, Pediatric Use).
Propofol Injectable Emulsion is not recommended for obstetrics, including Cesarean section deliveries. Propofol Injectable Emulsion crosses the placenta, and as with other general anesthetic agents, the administration of Propofol Injectable Emulsion may be associated with neonatal depression (see PRECAUTIONS).
Propofol Injectable Emulsion is not recommended for use in nursing mothers because Propofol Injectable Emulsion has been reported to be excreted in human milk, and the effects of oral absorption of small amounts of propofol are not known (see PRECAUTIONS).
History
There is currently no drug history available for this drug.
Other Information
Propofol Injectable Emulsion, USP is a sterile, nonpyrogenic emulsion containing 10 mg/mL of propofol suitable for intravenous administration. Propofol is chemically described as 2,6-diisopropylphenol. The structural formula is:
C12H18O M.W. 178.27
Propofol is slightly soluble in water and, thus, is formulated in a white, oil-in-water emulsion. The pKa is 11. The octanol/water partition coefficient for propofol is 6761:1 at a pH of 6 to 8.5. In addition to the active component, propofol, the formulation also contains soybean oil (100 mg/mL), glycerol (22.5 mg/mL), egg lecithin (12 mg/mL); and disodium edetate (0.005%); with sodium hydroxide to adjust pH. The Propofol Injectable Emulsion, USP is isotonic and has a pH of 7 to 8.5.
Sources
Propofol Manufacturers
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App Pharmaceuticals, Llc
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Propofol | App Pharmaceuticals, Llc
Propofol blood concentrations at steady state are generally proportional to infusion rates, especially in individual patients. Undesirable effects such as cardiorespiratory depression are likely to occur at higher blood concentrations which result from bolus dosing or rapid increases in the infusion rate. An adequate interval (3 to 5 minutes) must be allowed between dose adjustments to allow for and assess the clinical effects.
Shake well before use. Do not use if there is evidence of excessive creaming or aggregation, if large droplets are visible, or if there are other forms of phase separation indicating that the stability of the product has been compromised. Slight creaming, which should disappear after shaking, may be visible upon prolonged standing.
When administering Propofol Injectable Emulsion by infusion, syringe or volumetric pumps are recommended to provide controlled infusion rates. When infusing Propofol Injectable Emulsion to patients undergoing magnetic resonance imaging, metered control devices may be utilized if mechanical pumps are impractical.
Changes in vital signs indicating a stress response to surgical stimulation or the emergence from anesthesia may be controlled by the administration of 25 mg (2.5 mL) to 50 mg (5 mL) incremental boluses and/or by increasing the infusion rate of Propofol Injectable Emulsion.
For minor surgical procedures (e.g., body surface) nitrous oxide (60% to 70%) can be combined with a variable rate Propofol Injectable Emulsion infusion to provide satisfactory anesthesia. With more stimulating surgical procedures (e.g., intra-abdominal), or if supplementation with nitrous oxide is not provided, administration rate(s) of Propofol Injectable Emulsion and/or opioids should be increased in order to provide adequate anesthesia.
Infusion rates should always be titrated downward in the absence of clinical signs of light anesthesia until a mild response to surgical stimulation is obtained in order to avoid administration of Propofol Injectable Emulsion at rates higher than are clinically necessary. Generally, rates of 50 to 100 mcg/kg/min in adults should be achieved during maintenance in order to optimize recovery times.
Other drugs that cause CNS depression (hypnotics/sedatives, inhalational anesthetics, and opioids) can increase CNS depression induced by propofol. Morphine premedication (0.15 mg/kg) with nitrous oxide 67% in oxygen has been shown to decrease the necessary propofol injection maintenance infusion rate and therapeutic blood concentrations when compared to non-narcotic (lorazepam) premedication.
Induction of General Anesthesia
Adult Patients
Most adult patients under 55 years of age and classified as ASA-PS I or II require 2 to 2.5 mg/kg of Propofol Injectable Emulsion for induction when unpremedicated or when premedicated with oral benzodiazepines or intramuscular opioids. For induction, Propofol Injectable Emulsion should be titrated (approximately 40 mg every 10 seconds) against the response of the patient until the clinical signs show the onset of anesthesia. As with other sedative-hypnotic agents, the amount of intravenous opioid and/or benzodiazepine premedication will influence the response of the patient to an induction dose of Propofol Injectable Emulsion.
Elderly, Debilitated, or ASA-PS III or IV Patients
It is important to be familiar and experienced with the intravenous use of Propofol Injectable Emulsion before treating elderly, debilitated, or ASA-PS III or IV patients. Due to the reduced clearance and higher blood concentrations, most of these patients require approximately 1 to 1.5 mg/kg (approximately 20 mg every 10 seconds) of Propofol Injectable Emulsion for induction of anesthesia according to their condition and responses. A rapid bolus should not be used, as this will increase the likelihood of undesirable cardiorespiratory depression including hypotension, apnea, airway obstruction, and/or oxygen desaturation (see DOSAGE AND ADMINISTRATION).
Pediatric Patients
Most patients aged 3 years through 16 years and classified ASA-PS I or II require 2.5 to 3.5 mg/kg of Propofol Injectable Emulsion for induction when unpremedicated or when lightly premedicated with oral benzodiazepines or intramuscular opioids. Within this dosage range, younger pediatric patients may require higher induction doses than older pediatric patients. As with other sedative‑hypnotic agents, the amount of intravenous opioid and/or benzodiazepine premedication will influence the response of the patient to an induction dose of Propofol Injectable Emulsion. A lower dosage is recommended for pediatric patients classified as ASA-PS III or IV. Attention should be paid to minimize pain on injection when administering Propofol Injectable Emulsion to pediatric patients. Boluses of Propofol Injectable Emulsion may be administered via small veins if pretreated with lidocaine or via antecubital or larger veins (see PRECAUTIONS, General).
Neurosurgical Patients
Slower induction is recommended using boluses of 20 mg every 10 seconds. Slower boluses or infusions of Propofol Injectable Emulsion for induction of anesthesia, titrated to clinical responses, will generally result in reduced induction dosage requirements (1 to 2 mg/kg) (see PRECAUTIONS and DOSAGE AND ADMINISTRATION).
Cardiac Anesthesia
Propofol Injectable Emulsion has been well-studied in patients with coronary artery disease, but experience in patients with hemodynamically significant valvular or congenital heart disease is limited. As with other anesthetic and sedative-hypnotic agents, Propofol Injectable Emulsion in healthy patients causes a decrease in blood pressure that is secondary to decreases in preload (ventricular filling volume at the end of the diastole) and afterload (arterial resistance at the beginning of the systole). The magnitude of these changes is proportional to the blood and effect site concentrations achieved. These concentrations depend upon the dose and speed of the induction and maintenance infusion rates.
In addition, lower heart rates are observed during maintenance with Propofol Injectable Emulsion, possibly due to reduction of the sympathetic activity and/or resetting of the baroreceptor reflexes. Therefore, anticholinergic agents should be administered when increases in vagal tone are anticipated.
As with other anesthetic agents, Propofol Injectable Emulsion reduces myocardial oxygen consumption. Further studies are needed to confirm and delineate the extent of these effects on the myocardium and the coronary vascular system.
Morphine premedication (0.15 mg/kg) with nitrous oxide 67% in oxygen has been shown to decrease the necessary Propofol Injectable Emulsion maintenance infusion rates and therapeutic blood concentrations when compared to non‑narcotic (lorazepam) premedication. The rate of Propofol Injectable Emulsion administration should be determined based on the patient's premedication and adjusted according to clinical responses.
A rapid bolus induction should be avoided. A slow rate of approximately 20 mg every 10 seconds until induction onset (0.5 to 1.5 mg/kg) should be used. In order to assure adequate anesthesia, when Propofol Injectable Emulsion is used as the primary agent, maintenance infusion rates should not be less than 100 mcg/kg/min and should be supplemented with analgesic levels of continuous opioid administration. When an opioid is used as the primary agent, Propofol Injectable Emulsion maintenance rates should not be less than 50 mcg/kg/min, and care should be taken to ensure amnesia. Higher doses of Propofol Injectable Emulsion will reduce the opioid requirements (see Table 4). When Propofol Injectable Emulsion is used as the primary anesthetic, it should not be administered with the high-dose opioid technique as this may increase the likelihood of hypotension (see PRECAUTIONS, Cardiac Anesthesia).
Table 4. Cardiac Anesthesia Techniques
Primary Agent
Rate
Secondary Agent/Rate
(Following Induction with Primary Agent)
Propofol Injectable Emulsion
OPIOIDa/0.05 to 0.075 mcg/kg/min (no bolus)
Preinduction
Anxiolysis
25 mcg/kg/min
Induction
0.5 to 1.5 mg/kg
over 60 sec
Maintenance
(Titrated to Clinical
Response)
100 to 150 mcg/kg/min
OPIOIDb
Propofol Injectable Emulsion/50 to 100 mcg/kg/min
(no bolus)
Induction
25 to 50 mcg/kg
Maintenance
0.2 to 0.3 mcg/kg/min
aOPIOID is defined in terms of fentanyl equivalents, i.e.,
1 mcg of fentanyl = 5 mcg of alfentanil (for bolus)
= 10 mcg of alfentanil (for maintenance)
or
= 0.1 mcg of sufentanil
bCare should be taken to ensure amnesia.
Maintenance of General Anesthesia
Adult Patients
In adults, anesthesia can be maintained by administering Propofol Injectable Emulsion by infusion or intermittent IV bolus injection. The patient's clinical response will determine the infusion rate or the amount and frequency of incremental injections.
Continuous Infusion
Propofol Injectable Emulsion 100 to 200 mcg/kg/min administered in a variable rate infusion with 60% to 70% nitrous oxide and oxygen provides anesthesia for patients undergoing general surgery. Maintenance by infusion of Propofol Injectable Emulsion should immediately follow the induction dose in order to provide satisfactory or continuous anesthesia during the induction phase. During this initial period following the induction dose, higher rates of infusion are generally required (150 to 200 mcg/kg/min) for the first 10 to 15 minutes. Infusion rates should subsequently be decreased 30% to 50% during the first half-hour of maintenance. Generally, rates of 50 to 100 mcg/kg/min in adults should be achieved during maintenance in order to optimize recovery times.
Other drugs that cause CNS depression (hypnotics/sedatives, inhalational anesthetics, and opioids) can increase the CNS depression induced by propofol.
Intermittent Bolus
Increments of Propofol Injectable Emulsion 25 mg (2.5 mL) to 50 mg (5 mL) may be administered with nitrous oxide in adult patients undergoing general surgery. The incremental boluses should be administered when changes in vital signs indicate a response to surgical stimulation or light anesthesia.
Pediatric Patients
Propofol Injectable Emulsion administered as a variable rate infusion supplemented with nitrous oxide 60% to 70% provides satisfactory anesthesia for most children 2 months of age or older, ASA-PS I or II, undergoing general anesthesia.
In general, for the pediatric population, maintenance by infusion of Propofol Injectable Emulsion at a rate of 200 to 300 mcg/kg/min should immediately follow the induction dose. Following the first half-hour of maintenance, infusion rates of 125 to 150 mcg/kg/min are typically needed. Propofol Injectable Emulsion should be titrated to achieve the desired clinical effect. Younger pediatric patients may require higher maintenance infusion rates than older pediatric patients. (See Table 2 Clinical Trials.)
Propofol Injectable Emulsion has been used with a variety of agents commonly used in anesthesia such as atropine, scopolamine, glycopyrrolate, diazepam, depolarizing and nondepolarizing muscle relaxants, and opioid analgesics, as well as with inhalational and regional anesthetic agents.
In the elderly, debilitated, or ASA-PS III or IV patients, rapid bolus doses should not be used, as this will increase cardiorespiratory effects including hypotension, apnea, airway obstruction, and oxygen desaturation.
Monitored Anesthesia Care (MAC) Sedation
Adult Patients
When Propofol Injectable Emulsion is administered for MAC sedation, rates of administration should be individualized and titrated to clinical response. In most patients, the rates of Propofol Injectable Emulsion administration will be in the range of 25 to 75 mcg/kg/min.
During initiation of MAC sedation, slow infusion or slow injection techniques are preferable over rapid bolus administration. During maintenance of MAC sedation, a variable rate infusion is preferable over intermittent bolus dose administration. In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation (see WARNINGS). A rapid bolus injection can result in undesirable cardiorespiratory depression including hypotension, apnea, airway obstruction, and oxygen desaturation.
Initiation of MAC Sedation
For initiation of MAC sedation, either an infusion or a slow injection method may be utilized while closely monitoring cardiorespiratory function. With the infusion method, sedation may be initiated by infusing Propofol Injectable Emulsion at 100 to 150 mcg/kg/min (6 to 9 mg/kg/h) for a period of 3 to 5 minutes and titrating to the desired clinical effect while closely monitoring respiratory function. With the slow injection method for initiation, patients will require approximately 0.5 mg/kg administered over 3 to 5 minutes and titrated to clinical responses. When Propofol Injectable Emulsion is administered slowly over 3 to 5 minutes, most patients will be adequately sedated, and the peak drug effect can be achieved while minimizing undesirable cardiorespiratory effects occurring at high plasma levels.
In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation (see WARNINGS). The rate of administration should be over 3 to 5 minutes and the dosage of Propofol Injectable Emulsion should be reduced to approximately 80% of the usual adult dosage in these patients according to their condition, responses, and changes in vital signs (see DOSAGE AND ADMINISTRATION).
Maintenance of MAC Sedation
For maintenance of sedation, a variable rate infusion method is preferable over an intermittent bolus dose method. With the variable rate infusion method, patients will generally require maintenance rates of 25 to 75 mcg/kg/min (1.5 to 4.5 mg/kg/h) during the first 10 to 15 minutes of sedation maintenance. Infusion rates should subsequently be decreased over time to 25 to 50 mcg/kg/min and adjusted to clinical responses. In titrating to clinical effect, allow approximately 2 minutes for onset of peak drug effect.
Infusion rates should always be titrated downward in the absence of clinical signs of light sedation until mild responses to stimulation are obtained in order to avoid sedative administration of Propofol Injectable Emulsion at rates higher than are clinically necessary.
If the intermittent bolus dose method is used, increments of Propofol Injectable Emulsion 10 mg (1 mL) or 20 mg (2 mL) can be administered and titrated to desired clinical effect. With the intermittent bolus method of sedation maintenance, there is increased potential for respiratory depression, transient increases in sedation depth, and prolongation of recovery.
In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation (see WARNINGS). The rate of administration and the dosage of Propofol Injectable Emulsion should be reduced to approximately 80% of the usual adult dosage in these patients according to their condition, responses, and changes in vital signs (see DOSAGE AND ADMINISTRATION).
Propofol Injectable Emulsion can be administered as the sole agent for maintenance of MAC sedation during surgical/diagnostic procedures. When Propofol Injectable Emulsion sedation is supplemented with opioid and/or benzodiazepine medications, these agents increase the sedative and respiratory effects of Propofol Injectable Emulsion and may also result in a slower recovery profile (see PRECAUTIONS, Drug Interactions).
ICU Sedation
(See WARNINGS and DOSAGE AND ADMINISTRATION, Handling Procedures.)
Abrupt discontinuation of Propofol Injectable Emulsion prior to weaning or for daily evaluation of sedation levels should be avoided. This may result in rapid awakening with associated anxiety, agitation, and resistance to mechanical ventilation. Infusions of Propofol Injectable Emulsion should be adjusted to assure a minimal level of sedation is maintained throughout the weaning process and when assessing the level of sedation (see PRECAUTIONS).
Adult Patients
For intubated, mechanically ventilated adult patients, Intensive Care Unit (ICU) sedation should be initiated slowly with a continuous infusion in order to titrate to desired clinical effect and minimize hypotension (see DOSAGE AND ADMINISTRATION).
Most adult ICU patients recovering from the effects of general anesthesia or deep sedation will require maintenance rates of 5 to 50 mcg/kg/min (0.3 to 3 mg/kg/h) individualized and titrated to clinical response (see DOSAGE AND ADMINISTRATION). With medical ICU patients or patients who have recovered from the effects of general anesthesia or deep sedation, the rate of administration of 50 mcg/kg/min or higher may be required to achieve adequate sedation. These higher rates of administration may increase the likelihood of patients developing hypotension. Administration should not exceed 4 mg/kg/hour unless the benefits outweigh the risks (see WARNINGS).
Dosage and rate of administration should be individualized and titrated to the desired effect, according to clinically relevant factors including the patient’s underlying medical problems, preinduction and concomitant medications, age, ASA-PS classification, and level of debilitation of the patient. The elderly, debilitated, and ASA-PS III or IV patients may have exaggerated hemodynamic and respiratory responses to rapid bolus doses (see WARNINGS).
Propofol Injectable Emulsion should be individualized according to the patient's condition and response, blood lipid profile, and vital signs (see PRECAUTIONS, Intensive Care Unit Sedation). For intubated, mechanically ventilated adult patients, Intensive Care Unit (ICU) sedation should be initiated slowly with a continuous infusion in order to titrate to desired clinical effect and minimize hypotension. When indicated, initiation of sedation should begin at 5 mcg/kg/min (0.3 mg/kg/h). The infusion rate should be increased by increments of 5 to 10 mcg/kg/min (0.3 to 0.6 mg/kg/h) until the desired level of sedation is achieved. A minimum period of 5 minutes between adjustments should be allowed for onset of peak drug effect. Most adult patients require maintenance rates of 5 to 50 mcg/kg/min (0.3 to 3 mg/kg/h) or higher. Administration should not exceed 4 mg/kg/hour unless the benefits outweigh the risks (see WARNINGS). Dosages of Propofol Injectable Emulsion should be reduced in patients who have received large dosages of narcotics. Conversely, the Propofol Injectable Emulsion dosage requirement may be reduced by adequate management of pain with analgesic agents. As with other sedative medications, there is interpatient variability in dosage requirements, and these requirements may change with time (see SUMMARY OF DOSAGE GUIDELINES). Evaluation of level of sedation and assessment of cns function should be carried out daily throughout maintenance to determine the minimum dose of PROPOFOL required for sedation (see Clinical Trials , Intensive Care Unit (ICU) Sedation). Bolus administration of 10 or 20 mg should only be used to rapidly increase depth of sedation in patients where hypotension is not likely to occur. Patients with compromised myocardial function, intravascular volume depletion, or abnormally low vascular tone (e.g., sepsis) may be more susceptible to hypotension (see PRECAUTIONS).
SUMMARY OF DOSAGE GUIDELINES :
Dosages and rates of administration in the following table should be individualized and titrated to clinical response. Safety and dosing requirements for induction of anesthesia in pediatric patients have only been established for children 3 years of age or older. Safety and dosing requirements for the maintenance of anesthesia have only been established for children 2 months of age and older.
For complete dosage information, see DOSAGE AND ADMINISTRATION.
INDICATION
DOSAGE AND ADMINISTRATION
Induction of General Anesthesia:
Healthy Adults Less Than 55 Years of Age:
40 mg every 10 seconds until induction onset (2 to 2.5 mg/kg).
Elderly, Debilitated, or ASA-PS III or IV Patients:
20 mg every 10 seconds until induction onset (1 to 1.5 mg/kg).
Cardiac Anesthesia:
20 mg every 10 seconds until induction onset (0.5 to 1.5 mg/kg).
Neurosurgical Patients:
20 mg every 10 seconds until induction onset (1 to 2 mg/kg)
Pediatric Patients – healthy, from 3 years to 16 years of age:
2.5 to 3.5 mg/kg administered over 20 to 30 seconds.
(see PRECAUTIONS, Pediatric Use and CLINICAL PHARMACOLOGY, Pediatrics)
Maintenance of General Anesthesia:
Infusion
Healthy Adults Less Than 55 Years of Age:
100 to 200 mcg/kg/min (6 to 12 mg/kg/h).
Elderly, Debilitated, ASA-PS III or IV Patients:
50 to 100 mcg/kg/min (3 to 6 mg/kg/h).
Cardiac Anesthesia: Most patients require:
Primary Propofol Injectable Emulsion with Secondary Opioid –
100 to 150 mcg/kg/min
Low-Dose Propofol Injectable Emulsion with Primary Opioid –
50 to 100 mcg/kg/min
(see DOSAGE AND ADMINISTRATION, Table 4)
Neurosurgical Patients:
100 to 200 mcg/kg/min (6 to 12 mg/kg/h).
Pediatric Patients - healthy, from 2 months of age to 16 years of age:
125 to 300 mcg/kg/min (7.5 to 18 mg/kg/h)
Following the first half hour of maintenance, if clinical signs of light
anesthesia are not present, the infusion rate should be decreased.
(see PRECAUTIONS, Pediatric Use and CLINICAL PHARMACOLOGY, Pediatrics)
Maintenance of General Anesthesia:
Intermittent Bolus
Healthy Adults Less Than 55 Years of Age:
Increments of 20 to 50 mg as needed.
Initiation of MAC Sedation:
Healthy Adults Less Than 55 Years of Age:
Slow infusion or slow injection techniques are recommended to avoid apnea
or hypotension. Most patients require an infusion of 100 to 150 mcg/kg/min
(6 to 9 mg/kg/h) for 3 to 5 minutes or a slow injection of 0.5 mg/kg over 3
to 5 minutes followed immediately by a maintenance infusion.
Elderly, Debilitated, Neurosurgical, or ASA-PS III or IV Patients:
Most patients require dosages similar to healthy adults.
Rapid boluses are to be avoided (see WARNINGS).
Maintenance of MAC Sedation:
Healthy Adults Less Than 55 Years of Age:
A variable rate infusion technique is preferable over an intermittent bolus
technique. Most patients require an infusion of 25 to 75 mcg/kg/min
(1.5 to 4.5 mg/kg/h) or incremental bolus doses of 10 mg or 20 mg.
In Elderly, Debilitated, Neurosurgical, or ASA-PS III or IV Patients:
Most patients require 80% of the usual adult dose. A rapid (single or
repeated) bolus dose should not be used (see WARNINGS).
Initiation and Maintenance of ICU Sedation in Intubated, Mechanically Ventilated
Adult Patients - Because of the residual effects of previous anesthetic or
sedative agents, in most patients the initial infusion should be 5 mcg/kg/min
(0.3 mg/kg/h) for at least 5 minutes. Subsequent increments of 5 to 10
mcg/kg/min (0.3 to 0.6 mg/kg/h) over 5 to 10 minutes may be used until
desired clinical effect is achieved. Maintenance rates of 5 to 50 mcg/kg/min
(0.3 to 3 mg/kg/h) or higher may be required. Administration should not
exceed 4 mg/kg/hour unless the benefits outweigh the risks (see WARNINGS).
Evaluation of clinical effect and assessment of CNS function should be
carried out daily throughout maintenance to determine the minimum
dose of Propofol Injectable Emulsion required for sedation.
The tubing and any unused portions of Propofol Injectable Emulsion
should be discarded after 12 hours because Propofol Injectable
Emulsion contains no preservatives and is capable of supporting growth
of microorganisms (see WARNINGS and DOSAGE AND ADMINISTRATION ).
Administration with Lidocaine
If lidocaine is to be administered to minimize pain on injection of Propofol, it is recommended that it be administered prior to Propofol administration or that it be added to Propofol immediately before administration and in quantities not exceeding 20 mg lidocaine/200 mg Propofol.
Compatibility and Stability
Propofol Injectable Emulsion should not be mixed with other therapeutic agents prior to administration.
Dilution Prior to Administration
Propofol Injectable Emulsion is provided as a ready-to-use formulation. However, should dilution be necessary, it should only be diluted with 5% Dextrose Injection, USP, and it should not be diluted to a concentration less than 2 mg/mL because it is an emulsion. In diluted form it has been shown to be more stable when in contact with glass than with plastic (95% potency after 2 hours of running infusion in plastic).
Administration with Other Fluids
Compatibility of Propofol Injectable Emulsion with the coadministration of blood/serum/plasma has not been established (see WARNINGS). When administered using a y-type infusion set, Propofol Injectable Emulsion has been shown to be compatible with the following intravenous fluids.
- 5% Dextrose Injection, USP
- Lactated Ringers Injection, USP
- Lactated Ringers and 5% Dextrose Injection
- 5% Dextrose and 0.45% Sodium Chloride Injection, USP
- 5% Dextrose and 0.2% Sodium Chloride Injection, USP
Handling Procedures
General
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
Clinical experience with the use of in-line filters and Propofol Injectable Emulsion during anesthesia or ICU/MAC sedation is limited. Propofol Injectable Emulsion should only be administered through a filter with a pore size of 5 micron or greater unless it has been demonstrated that the filter does not restrict the flow of Propofol Injectable Emulsion and/or cause the breakdown of the emulsion. Filters should be used with caution and where clinically appropriate. Continuous monitoring is necessary due to the potential for restricted flow and/or breakdown of the emulsion.
Do not use if there is evidence of separation of the phases of the emulsion.
Rare cases of self-administration of Propofol Injectable Emulsion by health care professionals have been reported, including some fatalities (see DRUG ABUSE AND DEPENDENCE).
Strict aseptic technique must always be maintained during handling. Propofol Injectable Emulsion is a single-use parenteral product which contains 0.005% disodium edetate to inhibit the rate of growth of microorganisms, up to 12 hours, in the event of accidental extrinsic contamination. However, Propofol Injectable Emulsion can still support the growth of microorganisms as it is not an antimicrobially preserved product under USP standards. Accordingly, strict aseptic technique must still be adhered to. Do not use if contamination is suspected. Discard unused portions as directed within the required time limits (see DOSAGE AND ADMINISTRATION, Handling Procedures). There have been reports in which failure to use aseptic technique when handling Propofol Injectable Emulsion was associated with microbial contamination of the product and with fever, infection/sepsis, other life-threatening illness, and/or death.
Propofol, with EDTA inhibits microbial growth for up to 12 hours, as demonstrated by test data for representative USP microorganisms.
Guidelines for Aseptic Technique for General Anesthesia/MAC Sedation
Propofol Injectable Emulsion should be prepared for use just prior to initiation of each individual anesthetic/sedative procedure. The vial syringe rubber stopper should be disinfected using 70% isopropyl alcohol. Propofol Injectable Emulsion should be drawn into sterile syringes immediately after vials are opened. When withdrawing Propofol Injectable Emulsion from vials, a sterile vent spike should be used. The syringe(s) should be labeled with appropriate information including the date and time the vial was opened. Administration should commence promptly and be completed within 12 hours after the vials have been opened.
Propofol Injectable Emulsion should be prepared for single-patient use only. Any unused portions of Propofol Injectable Emulsion, reservoirs, dedicated administration tubing and/or solutions containing Propofol Injectable Emulsion must be discarded at the end of the anesthetic procedure or at 12 hours, whichever occurs sooner. The IV line should be flushed every 12 hours and at the end of the anesthetic procedure to remove residual Propofol Injectable Emulsion.
Guidelines for Aseptic Technique for ICU Sedation
Propofol Injectable Emulsion should be prepared for single-patient use only. When Propofol Injectable Emulsion is administered directly from the vial, strict aseptic techniques must be followed. The vial rubber stopper should be disinfected using 70% isopropyl alcohol. A sterile vent spike and sterile tubing must be used for administration of Propofol Injectable Emulsion. As with other lipid emulsions, the number of IV line manipulations should be minimized. Administration should commence promptly and must be completed within 12 hours after the vial has been spiked. The tubing and any unused portions of Propofol Injectable Emulsion must be discarded after 12 hours.
If Propofol Injectable Emulsion is transferred to a syringe or other container prior to administration, the handling procedures for General anesthesia/MAC sedation should be followed, and the product should be discarded and administration lines changed after 12 hours.
Induction of General Anesthesia
Adult Patients
Most adult patients under 55 years of age and classified as ASA-PS I or II require 2 to 2.5 mg/kg of Propofol Injectable Emulsion for induction when unpremedicated or when premedicated with oral benzodiazepines or intramuscular opioids. For induction, Propofol Injectable Emulsion should be titrated (approximately 40 mg every 10 seconds) against the response of the patient until the clinical signs show the onset of anesthesia. As with other sedative-hypnotic agents, the amount of intravenous opioid and/or benzodiazepine premedication will influence the response of the patient to an induction dose of Propofol Injectable Emulsion.
Elderly, Debilitated, or ASA-PS III or IV Patients
It is important to be familiar and experienced with the intravenous use of Propofol Injectable Emulsion before treating elderly, debilitated, or ASA-PS III or IV patients. Due to the reduced clearance and higher blood concentrations, most of these patients require approximately 1 to 1.5 mg/kg (approximately 20 mg every 10 seconds) of Propofol Injectable Emulsion for induction of anesthesia according to their condition and responses. A rapid bolus should not be used, as this will increase the likelihood of undesirable cardiorespiratory depression including hypotension, apnea, airway obstruction, and/or oxygen desaturation (see DOSAGE AND ADMINISTRATION).
Pediatric Patients
Most patients aged 3 years through 16 years and classified ASA-PS I or II require 2.5 to 3.5 mg/kg of Propofol Injectable Emulsion for induction when unpremedicated or when lightly premedicated with oral benzodiazepines or intramuscular opioids. Within this dosage range, younger pediatric patients may require higher induction doses than older pediatric patients. As with other sedative‑hypnotic agents, the amount of intravenous opioid and/or benzodiazepine premedication will influence the response of the patient to an induction dose of Propofol Injectable Emulsion. A lower dosage is recommended for pediatric patients classified as ASA-PS III or IV. Attention should be paid to minimize pain on injection when administering Propofol Injectable Emulsion to pediatric patients. Boluses of Propofol Injectable Emulsion may be administered via small veins if pretreated with lidocaine or via antecubital or larger veins (see PRECAUTIONS, General).
Neurosurgical Patients
Slower induction is recommended using boluses of 20 mg every 10 seconds. Slower boluses or infusions of Propofol Injectable Emulsion for induction of anesthesia, titrated to clinical responses, will generally result in reduced induction dosage requirements (1 to 2 mg/kg) (see PRECAUTIONS and DOSAGE AND ADMINISTRATION).
Cardiac Anesthesia
Propofol Injectable Emulsion has been well-studied in patients with coronary artery disease, but experience in patients with hemodynamically significant valvular or congenital heart disease is limited. As with other anesthetic and sedative-hypnotic agents, Propofol Injectable Emulsion in healthy patients causes a decrease in blood pressure that is secondary to decreases in preload (ventricular filling volume at the end of the diastole) and afterload (arterial resistance at the beginning of the systole). The magnitude of these changes is proportional to the blood and effect site concentrations achieved. These concentrations depend upon the dose and speed of the induction and maintenance infusion rates.
In addition, lower heart rates are observed during maintenance with Propofol Injectable Emulsion, possibly due to reduction of the sympathetic activity and/or resetting of the baroreceptor reflexes. Therefore, anticholinergic agents should be administered when increases in vagal tone are anticipated.
As with other anesthetic agents, Propofol Injectable Emulsion reduces myocardial oxygen consumption. Further studies are needed to confirm and delineate the extent of these effects on the myocardium and the coronary vascular system.
Morphine premedication (0.15 mg/kg) with nitrous oxide 67% in oxygen has been shown to decrease the necessary Propofol Injectable Emulsion maintenance infusion rates and therapeutic blood concentrations when compared to non‑narcotic (lorazepam) premedication. The rate of Propofol Injectable Emulsion administration should be determined based on the patient's premedication and adjusted according to clinical responses.
A rapid bolus induction should be avoided. A slow rate of approximately 20 mg every 10 seconds until induction onset (0.5 to 1.5 mg/kg) should be used. In order to assure adequate anesthesia, when Propofol Injectable Emulsion is used as the primary agent, maintenance infusion rates should not be less than 100 mcg/kg/min and should be supplemented with analgesic levels of continuous opioid administration. When an opioid is used as the primary agent, Propofol Injectable Emulsion maintenance rates should not be less than 50 mcg/kg/min, and care should be taken to ensure amnesia. Higher doses of Propofol Injectable Emulsion will reduce the opioid requirements (see Table 4). When Propofol Injectable Emulsion is used as the primary anesthetic, it should not be administered with the high-dose opioid technique as this may increase the likelihood of hypotension (see PRECAUTIONS, Cardiac Anesthesia).
Table 4. Cardiac Anesthesia Techniques
Primary Agent
Rate
Secondary Agent/Rate
(Following Induction with Primary Agent)
Propofol Injectable Emulsion
OPIOIDa/0.05 to 0.075 mcg/kg/min (no bolus)
Preinduction
Anxiolysis
25 mcg/kg/min
Induction
0.5 to 1.5 mg/kg
over 60 sec
Maintenance
(Titrated to Clinical
Response)
100 to 150 mcg/kg/min
OPIOIDb
Propofol Injectable Emulsion/50 to 100 mcg/kg/min
(no bolus)
Induction
25 to 50 mcg/kg
Maintenance
0.2 to 0.3 mcg/kg/min
aOPIOID is defined in terms of fentanyl equivalents, i.e.,
1 mcg of fentanyl = 5 mcg of alfentanil (for bolus)
= 10 mcg of alfentanil (for maintenance)
or
= 0.1 mcg of sufentanil
bCare should be taken to ensure amnesia.
Maintenance of General Anesthesia
Adult Patients
In adults, anesthesia can be maintained by administering Propofol Injectable Emulsion by infusion or intermittent IV bolus injection. The patient's clinical response will determine the infusion rate or the amount and frequency of incremental injections.
Continuous Infusion
Propofol Injectable Emulsion 100 to 200 mcg/kg/min administered in a variable rate infusion with 60% to 70% nitrous oxide and oxygen provides anesthesia for patients undergoing general surgery. Maintenance by infusion of Propofol Injectable Emulsion should immediately follow the induction dose in order to provide satisfactory or continuous anesthesia during the induction phase. During this initial period following the induction dose, higher rates of infusion are generally required (150 to 200 mcg/kg/min) for the first 10 to 15 minutes. Infusion rates should subsequently be decreased 30% to 50% during the first half-hour of maintenance. Generally, rates of 50 to 100 mcg/kg/min in adults should be achieved during maintenance in order to optimize recovery times.
Other drugs that cause CNS depression (hypnotics/sedatives, inhalational anesthetics, and opioids) can increase the CNS depression induced by propofol.
Intermittent Bolus
Increments of Propofol Injectable Emulsion 25 mg (2.5 mL) to 50 mg (5 mL) may be administered with nitrous oxide in adult patients undergoing general surgery. The incremental boluses should be administered when changes in vital signs indicate a response to surgical stimulation or light anesthesia.
Pediatric Patients
Propofol Injectable Emulsion administered as a variable rate infusion supplemented with nitrous oxide 60% to 70% provides satisfactory anesthesia for most children 2 months of age or older, ASA-PS I or II, undergoing general anesthesia.
In general, for the pediatric population, maintenance by infusion of Propofol Injectable Emulsion at a rate of 200 to 300 mcg/kg/min should immediately follow the induction dose. Following the first half-hour of maintenance, infusion rates of 125 to 150 mcg/kg/min are typically needed. Propofol Injectable Emulsion should be titrated to achieve the desired clinical effect. Younger pediatric patients may require higher maintenance infusion rates than older pediatric patients. (See Table 2 Clinical Trials.)
Propofol Injectable Emulsion has been used with a variety of agents commonly used in anesthesia such as atropine, scopolamine, glycopyrrolate, diazepam, depolarizing and nondepolarizing muscle relaxants, and opioid analgesics, as well as with inhalational and regional anesthetic agents.
In the elderly, debilitated, or ASA-PS III or IV patients, rapid bolus doses should not be used, as this will increase cardiorespiratory effects including hypotension, apnea, airway obstruction, and oxygen desaturation.
Monitored Anesthesia Care (MAC) Sedation
Adult Patients
When Propofol Injectable Emulsion is administered for MAC sedation, rates of administration should be individualized and titrated to clinical response. In most patients, the rates of Propofol Injectable Emulsion administration will be in the range of 25 to 75 mcg/kg/min.
During initiation of MAC sedation, slow infusion or slow injection techniques are preferable over rapid bolus administration. During maintenance of MAC sedation, a variable rate infusion is preferable over intermittent bolus dose administration. In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation (see WARNINGS). A rapid bolus injection can result in undesirable cardiorespiratory depression including hypotension, apnea, airway obstruction, and oxygen desaturation.
Initiation of MAC Sedation
For initiation of MAC sedation, either an infusion or a slow injection method may be utilized while closely monitoring cardiorespiratory function. With the infusion method, sedation may be initiated by infusing Propofol Injectable Emulsion at 100 to 150 mcg/kg/min (6 to 9 mg/kg/h) for a period of 3 to 5 minutes and titrating to the desired clinical effect while closely monitoring respiratory function. With the slow injection method for initiation, patients will require approximately 0.5 mg/kg administered over 3 to 5 minutes and titrated to clinical responses. When Propofol Injectable Emulsion is administered slowly over 3 to 5 minutes, most patients will be adequately sedated, and the peak drug effect can be achieved while minimizing undesirable cardiorespiratory effects occurring at high plasma levels.
In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation (see WARNINGS). The rate of administration should be over 3 to 5 minutes and the dosage of Propofol Injectable Emulsion should be reduced to approximately 80% of the usual adult dosage in these patients according to their condition, responses, and changes in vital signs (see DOSAGE AND ADMINISTRATION).
Maintenance of MAC Sedation
For maintenance of sedation, a variable rate infusion method is preferable over an intermittent bolus dose method. With the variable rate infusion method, patients will generally require maintenance rates of 25 to 75 mcg/kg/min (1.5 to 4.5 mg/kg/h) during the first 10 to 15 minutes of sedation maintenance. Infusion rates should subsequently be decreased over time to 25 to 50 mcg/kg/min and adjusted to clinical responses. In titrating to clinical effect, allow approximately 2 minutes for onset of peak drug effect.
Infusion rates should always be titrated downward in the absence of clinical signs of light sedation until mild responses to stimulation are obtained in order to avoid sedative administration of Propofol Injectable Emulsion at rates higher than are clinically necessary.
If the intermittent bolus dose method is used, increments of Propofol Injectable Emulsion 10 mg (1 mL) or 20 mg (2 mL) can be administered and titrated to desired clinical effect. With the intermittent bolus method of sedation maintenance, there is increased potential for respiratory depression, transient increases in sedation depth, and prolongation of recovery.
In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation (see WARNINGS). The rate of administration and the dosage of Propofol Injectable Emulsion should be reduced to approximately 80% of the usual adult dosage in these patients according to their condition, responses, and changes in vital signs (see DOSAGE AND ADMINISTRATION).
Propofol Injectable Emulsion can be administered as the sole agent for maintenance of MAC sedation during surgical/diagnostic procedures. When Propofol Injectable Emulsion sedation is supplemented with opioid and/or benzodiazepine medications, these agents increase the sedative and respiratory effects of Propofol Injectable Emulsion and may also result in a slower recovery profile (see PRECAUTIONS, Drug Interactions).
ICU Sedation
(See WARNINGS and DOSAGE AND ADMINISTRATION, Handling Procedures.)
Abrupt discontinuation of Propofol Injectable Emulsion prior to weaning or for daily evaluation of sedation levels should be avoided. This may result in rapid awakening with associated anxiety, agitation, and resistance to mechanical ventilation. Infusions of Propofol Injectable Emulsion should be adjusted to assure a minimal level of sedation is maintained throughout the weaning process and when assessing the level of sedation (see PRECAUTIONS).
Adult Patients
For intubated, mechanically ventilated adult patients, Intensive Care Unit (ICU) sedation should be initiated slowly with a continuous infusion in order to titrate to desired clinical effect and minimize hypotension (see DOSAGE AND ADMINISTRATION).
Most adult ICU patients recovering from the effects of general anesthesia or deep sedation will require maintenance rates of 5 to 50 mcg/kg/min (0.3 to 3 mg/kg/h) individualized and titrated to clinical response (see DOSAGE AND ADMINISTRATION). With medical ICU patients or patients who have recovered from the effects of general anesthesia or deep sedation, the rate of administration of 50 mcg/kg/min or higher may be required to achieve adequate sedation. These higher rates of administration may increase the likelihood of patients developing hypotension. Administration should not exceed 4 mg/kg/hour unless the benefits outweigh the risks (see WARNINGS).
Dosage and rate of administration should be individualized and titrated to the desired effect, according to clinically relevant factors including the patient’s underlying medical problems, preinduction and concomitant medications, age, ASA-PS classification, and level of debilitation of the patient. The elderly, debilitated, and ASA-PS III or IV patients may have exaggerated hemodynamic and respiratory responses to rapid bolus doses (see WARNINGS).
Propofol Injectable Emulsion should be individualized according to the patient's condition and response, blood lipid profile, and vital signs (see PRECAUTIONS, Intensive Care Unit Sedation). For intubated, mechanically ventilated adult patients, Intensive Care Unit (ICU) sedation should be initiated slowly with a continuous infusion in order to titrate to desired clinical effect and minimize hypotension. When indicated, initiation of sedation should begin at 5 mcg/kg/min (0.3 mg/kg/h). The infusion rate should be increased by increments of 5 to 10 mcg/kg/min (0.3 to 0.6 mg/kg/h) until the desired level of sedation is achieved. A minimum period of 5 minutes between adjustments should be allowed for onset of peak drug effect. Most adult patients require maintenance rates of 5 to 50 mcg/kg/min (0.3 to 3 mg/kg/h) or higher. Administration should not exceed 4 mg/kg/hour unless the benefits outweigh the risks (see WARNINGS). Dosages of Propofol Injectable Emulsion should be reduced in patients who have received large dosages of narcotics. Conversely, the Propofol Injectable Emulsion dosage requirement may be reduced by adequate management of pain with analgesic agents. As with other sedative medications, there is interpatient variability in dosage requirements, and these requirements may change with time (see SUMMARY OF DOSAGE GUIDELINES). Evaluation of level of sedation and assessment of cns function should be carried out daily throughout maintenance to determine the minimum dose of PROPOFOL required for sedation (see Clinical Trials , Intensive Care Unit (ICU) Sedation). Bolus administration of 10 or 20 mg should only be used to rapidly increase depth of sedation in patients where hypotension is not likely to occur. Patients with compromised myocardial function, intravascular volume depletion, or abnormally low vascular tone (e.g., sepsis) may be more susceptible to hypotension (see PRECAUTIONS).
SUMMARY OF DOSAGE GUIDELINES :
Dosages and rates of administration in the following table should be individualized and titrated to clinical response. Safety and dosing requirements for induction of anesthesia in pediatric patients have only been established for children 3 years of age or older. Safety and dosing requirements for the maintenance of anesthesia have only been established for children 2 months of age and older.
For complete dosage information, see DOSAGE AND ADMINISTRATION.
INDICATION
DOSAGE AND ADMINISTRATION
Induction of General Anesthesia:
Healthy Adults Less Than 55 Years of Age:
40 mg every 10 seconds until induction onset (2 to 2.5 mg/kg).
Elderly, Debilitated, or ASA-PS III or IV Patients:
20 mg every 10 seconds until induction onset (1 to 1.5 mg/kg).
Cardiac Anesthesia:
20 mg every 10 seconds until induction onset (0.5 to 1.5 mg/kg).
Neurosurgical Patients:
20 mg every 10 seconds until induction onset (1 to 2 mg/kg)
Pediatric Patients – healthy, from 3 years to 16 years of age:
2.5 to 3.5 mg/kg administered over 20 to 30 seconds.
(see PRECAUTIONS, Pediatric Use and CLINICAL PHARMACOLOGY, Pediatrics)
Maintenance of General Anesthesia:
Infusion
Healthy Adults Less Than 55 Years of Age:
100 to 200 mcg/kg/min (6 to 12 mg/kg/h).
Elderly, Debilitated, ASA-PS III or IV Patients:
50 to 100 mcg/kg/min (3 to 6 mg/kg/h).
Cardiac Anesthesia: Most patients require:
Primary Propofol Injectable Emulsion with Secondary Opioid –
100 to 150 mcg/kg/min
Low-Dose Propofol Injectable Emulsion with Primary Opioid –
50 to 100 mcg/kg/min
(see DOSAGE AND ADMINISTRATION, Table 4)
Neurosurgical Patients:
100 to 200 mcg/kg/min (6 to 12 mg/kg/h).
Pediatric Patients - healthy, from 2 months of age to 16 years of age:
125 to 300 mcg/kg/min (7.5 to 18 mg/kg/h)
Following the first half hour of maintenance, if clinical signs of light
anesthesia are not present, the infusion rate should be decreased.
(see PRECAUTIONS, Pediatric Use and CLINICAL PHARMACOLOGY, Pediatrics)
Maintenance of General Anesthesia:
Intermittent Bolus
Healthy Adults Less Than 55 Years of Age:
Increments of 20 to 50 mg as needed.
Initiation of MAC Sedation:
Healthy Adults Less Than 55 Years of Age:
Slow infusion or slow injection techniques are recommended to avoid apnea
or hypotension. Most patients require an infusion of 100 to 150 mcg/kg/min
(6 to 9 mg/kg/h) for 3 to 5 minutes or a slow injection of 0.5 mg/kg over 3
to 5 minutes followed immediately by a maintenance infusion.
Elderly, Debilitated, Neurosurgical, or ASA-PS III or IV Patients:
Most patients require dosages similar to healthy adults.
Rapid boluses are to be avoided (see WARNINGS).
Maintenance of MAC Sedation:
Healthy Adults Less Than 55 Years of Age:
A variable rate infusion technique is preferable over an intermittent bolus
technique. Most patients require an infusion of 25 to 75 mcg/kg/min
(1.5 to 4.5 mg/kg/h) or incremental bolus doses of 10 mg or 20 mg.
In Elderly, Debilitated, Neurosurgical, or ASA-PS III or IV Patients:
Most patients require 80% of the usual adult dose. A rapid (single or
repeated) bolus dose should not be used (see WARNINGS).
Initiation and Maintenance of ICU Sedation in Intubated, Mechanically Ventilated
Adult Patients - Because of the residual effects of previous anesthetic or
sedative agents, in most patients the initial infusion should be 5 mcg/kg/min
(0.3 mg/kg/h) for at least 5 minutes. Subsequent increments of 5 to 10
mcg/kg/min (0.3 to 0.6 mg/kg/h) over 5 to 10 minutes may be used until
desired clinical effect is achieved. Maintenance rates of 5 to 50 mcg/kg/min
(0.3 to 3 mg/kg/h) or higher may be required. Administration should not
exceed 4 mg/kg/hour unless the benefits outweigh the risks (see WARNINGS).
Evaluation of clinical effect and assessment of CNS function should be
carried out daily throughout maintenance to determine the minimum
dose of Propofol Injectable Emulsion required for sedation.
The tubing and any unused portions of Propofol Injectable Emulsion
should be discarded after 12 hours because Propofol Injectable
Emulsion contains no preservatives and is capable of supporting growth
of microorganisms (see WARNINGS and DOSAGE AND ADMINISTRATION ).
Administration with Lidocaine
If lidocaine is to be administered to minimize pain on injection of Propofol, it is recommended that it be administered prior to Propofol administration or that it be added to Propofol immediately before administration and in quantities not exceeding 20 mg lidocaine/200 mg Propofol.
Compatibility and Stability
Propofol Injectable Emulsion should not be mixed with other therapeutic agents prior to administration.
Dilution Prior to Administration
Propofol Injectable Emulsion is provided as a ready-to-use formulation. However, should dilution be necessary, it should only be diluted with 5% Dextrose Injection, USP, and it should not be diluted to a concentration less than 2 mg/mL because it is an emulsion. In diluted form it has been shown to be more stable when in contact with glass than with plastic (95% potency after 2 hours of running infusion in plastic).
Administration with Other Fluids
Compatibility of Propofol Injectable Emulsion with the coadministration of blood/serum/plasma has not been established (see WARNINGS). When administered using a y-type infusion set, Propofol Injectable Emulsion has been shown to be compatible with the following intravenous fluids.
- 5% Dextrose Injection, USP
- Lactated Ringers Injection, USP
- Lactated Ringers and 5% Dextrose Injection
- 5% Dextrose and 0.45% Sodium Chloride Injection, USP
- 5% Dextrose and 0.2% Sodium Chloride Injection, USP
Handling Procedures
General
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
Clinical experience with the use of in-line filters and Propofol Injectable Emulsion during anesthesia or ICU/MAC sedation is limited. Propofol Injectable Emulsion should only be administered through a filter with a pore size of 5 micron or greater unless it has been demonstrated that the filter does not restrict the flow of Propofol Injectable Emulsion and/or cause the breakdown of the emulsion. Filters should be used with caution and where clinically appropriate. Continuous monitoring is necessary due to the potential for restricted flow and/or breakdown of the emulsion.
Do not use if there is evidence of separation of the phases of the emulsion.
Rare cases of self-administration of Propofol Injectable Emulsion by health care professionals have been reported, including some fatalities (see DRUG ABUSE AND DEPENDENCE).
Strict aseptic technique must always be maintained during handling. Propofol Injectable Emulsion is a single-use parenteral product which contains 0.005% disodium edetate to inhibit the rate of growth of microorganisms, up to 12 hours, in the event of accidental extrinsic contamination. However, Propofol Injectable Emulsion can still support the growth of microorganisms as it is not an antimicrobially preserved product under USP standards. Accordingly, strict aseptic technique must still be adhered to. Do not use if contamination is suspected. Discard unused portions as directed within the required time limits (see DOSAGE AND ADMINISTRATION, Handling Procedures). There have been reports in which failure to use aseptic technique when handling Propofol Injectable Emulsion was associated with microbial contamination of the product and with fever, infection/sepsis, other life-threatening illness, and/or death.
Propofol, with EDTA inhibits microbial growth for up to 12 hours, as demonstrated by test data for representative USP microorganisms.
Guidelines for Aseptic Technique for General Anesthesia/MAC Sedation
Propofol Injectable Emulsion should be prepared for use just prior to initiation of each individual anesthetic/sedative procedure. The vial syringe rubber stopper should be disinfected using 70% isopropyl alcohol. Propofol Injectable Emulsion should be drawn into sterile syringes immediately after vials are opened. When withdrawing Propofol Injectable Emulsion from vials, a sterile vent spike should be used. The syringe(s) should be labeled with appropriate information including the date and time the vial was opened. Administration should commence promptly and be completed within 12 hours after the vials have been opened.
Propofol Injectable Emulsion should be prepared for single-patient use only. Any unused portions of Propofol Injectable Emulsion, reservoirs, dedicated administration tubing and/or solutions containing Propofol Injectable Emulsion must be discarded at the end of the anesthetic procedure or at 12 hours, whichever occurs sooner. The IV line should be flushed every 12 hours and at the end of the anesthetic procedure to remove residual Propofol Injectable Emulsion.
Guidelines for Aseptic Technique for ICU Sedation
Propofol Injectable Emulsion should be prepared for single-patient use only. When Propofol Injectable Emulsion is administered directly from the vial, strict aseptic techniques must be followed. The vial rubber stopper should be disinfected using 70% isopropyl alcohol. A sterile vent spike and sterile tubing must be used for administration of Propofol Injectable Emulsion. As with other lipid emulsions, the number of IV line manipulations should be minimized. Administration should commence promptly and must be completed within 12 hours after the vial has been spiked. The tubing and any unused portions of Propofol Injectable Emulsion must be discarded after 12 hours.
If Propofol Injectable Emulsion is transferred to a syringe or other container prior to administration, the handling procedures for General anesthesia/MAC sedation should be followed, and the product should be discarded and administration lines changed after 12 hours.
-
App Pharmaceuticals, Llc
Propofol | App Pharmaceuticals, Llc
Propofol blood concentrations at steady state are generally proportional to infusion rates, especially in individual patients. Undesirable effects such as cardiorespiratory depression are likely to occur at higher blood concentrations which result from bolus dosing or rapid increases in the infusion rate. An adequate interval (3 to 5 minutes) must be allowed between dose adjustments to allow for and assess the clinical effects.
Shake well before use. Do not use if there is evidence of excessive creaming or aggregation, if large droplets are visible, or if there are other forms of phase separation indicating that the stability of the product has been compromised. Slight creaming, which should disappear after shaking, may be visible upon prolonged standing.
When administering Propofol Injectable Emulsion by infusion, syringe or volumetric pumps are recommended to provide controlled infusion rates. When infusing Propofol Injectable Emulsion to patients undergoing magnetic resonance imaging, metered control devices may be utilized if mechanical pumps are impractical.
Changes in vital signs indicating a stress response to surgical stimulation or the emergence from anesthesia may be controlled by the administration of 25 mg (2.5 mL) to 50 mg (5 mL) incremental boluses and/or by increasing the infusion rate of Propofol Injectable Emulsion.
For minor surgical procedures (e.g., body surface) nitrous oxide (60% to 70%) can be combined with a variable rate Propofol Injectable Emulsion infusion to provide satisfactory anesthesia. With more stimulating surgical procedures (e.g., intra-abdominal), or if supplementation with nitrous oxide is not provided, administration rate(s) of Propofol Injectable Emulsion and/or opioids should be increased in order to provide adequate anesthesia.
Infusion rates should always be titrated downward in the absence of clinical signs of light anesthesia until a mild response to surgical stimulation is obtained in order to avoid administration of Propofol Injectable Emulsion at rates higher than are clinically necessary. Generally, rates of 50 to 100 mcg/kg/min in adults should be achieved during maintenance in order to optimize recovery times.
Other drugs that cause CNS depression (hypnotics/sedatives, inhalational anesthetics, and opioids) can increase CNS depression induced by propofol. Morphine premedication (0.15 mg/kg) with nitrous oxide 67% in oxygen has been shown to decrease the necessary propofol injection maintenance infusion rate and therapeutic blood concentrations when compared to non-narcotic (lorazepam) premedication.
Induction of General Anesthesia
Adult Patients
Most adult patients under 55 years of age and classified as ASA-PS I or II require 2 to 2.5 mg/kg of Propofol Injectable Emulsion for induction when unpremedicated or when premedicated with oral benzodiazepines or intramuscular opioids. For induction, Propofol Injectable Emulsion should be titrated (approximately 40 mg every 10 seconds) against the response of the patient until the clinical signs show the onset of anesthesia. As with other sedative-hypnotic agents, the amount of intravenous opioid and/or benzodiazepine premedication will influence the response of the patient to an induction dose of Propofol Injectable Emulsion.
Elderly, Debilitated, or ASA-PS III or IV Patients
It is important to be familiar and experienced with the intravenous use of Propofol Injectable Emulsion before treating elderly, debilitated, or ASA-PS III or IV patients. Due to the reduced clearance and higher blood concentrations, most of these patients require approximately 1 to 1.5 mg/kg (approximately 20 mg every 10 seconds) of Propofol Injectable Emulsion for induction of anesthesia according to their condition and responses. A rapid bolus should not be used, as this will increase the likelihood of undesirable cardiorespiratory depression including hypotension, apnea, airway obstruction, and/or oxygen desaturation (see DOSAGE AND ADMINISTRATION).
Pediatric Patients
Most patients aged 3 years through 16 years and classified ASA-PS I or II require 2.5 to 3.5 mg/kg of Propofol Injectable Emulsion for induction when unpremedicated or when lightly premedicated with oral benzodiazepines or intramuscular opioids. Within this dosage range, younger pediatric patients may require higher induction doses than older pediatric patients. As with other sedative‑hypnotic agents, the amount of intravenous opioid and/or benzodiazepine premedication will influence the response of the patient to an induction dose of Propofol Injectable Emulsion. A lower dosage is recommended for pediatric patients classified as ASA-PS III or IV. Attention should be paid to minimize pain on injection when administering Propofol Injectable Emulsion to pediatric patients. Boluses of Propofol Injectable Emulsion may be administered via small veins if pretreated with lidocaine or via antecubital or larger veins (see PRECAUTIONS, General).
Neurosurgical Patients
Slower induction is recommended using boluses of 20 mg every 10 seconds. Slower boluses or infusions of Propofol Injectable Emulsion for induction of anesthesia, titrated to clinical responses, will generally result in reduced induction dosage requirements (1 to 2 mg/kg) (see PRECAUTIONS and DOSAGE AND ADMINISTRATION).
Cardiac Anesthesia
Propofol Injectable Emulsion has been well-studied in patients with coronary artery disease, but experience in patients with hemodynamically significant valvular or congenital heart disease is limited. As with other anesthetic and sedative-hypnotic agents, Propofol Injectable Emulsion in healthy patients causes a decrease in blood pressure that is secondary to decreases in preload (ventricular filling volume at the end of the diastole) and afterload (arterial resistance at the beginning of the systole). The magnitude of these changes is proportional to the blood and effect site concentrations achieved. These concentrations depend upon the dose and speed of the induction and maintenance infusion rates.
In addition, lower heart rates are observed during maintenance with Propofol Injectable Emulsion, possibly due to reduction of the sympathetic activity and/or resetting of the baroreceptor reflexes. Therefore, anticholinergic agents should be administered when increases in vagal tone are anticipated.
As with other anesthetic agents, Propofol Injectable Emulsion reduces myocardial oxygen consumption. Further studies are needed to confirm and delineate the extent of these effects on the myocardium and the coronary vascular system.
Morphine premedication (0.15 mg/kg) with nitrous oxide 67% in oxygen has been shown to decrease the necessary Propofol Injectable Emulsion maintenance infusion rates and therapeutic blood concentrations when compared to non‑narcotic (lorazepam) premedication. The rate of Propofol Injectable Emulsion administration should be determined based on the patient's premedication and adjusted according to clinical responses.
A rapid bolus induction should be avoided. A slow rate of approximately 20 mg every 10 seconds until induction onset (0.5 to 1.5 mg/kg) should be used. In order to assure adequate anesthesia, when Propofol Injectable Emulsion is used as the primary agent, maintenance infusion rates should not be less than 100 mcg/kg/min and should be supplemented with analgesic levels of continuous opioid administration. When an opioid is used as the primary agent, Propofol Injectable Emulsion maintenance rates should not be less than 50 mcg/kg/min, and care should be taken to ensure amnesia. Higher doses of Propofol Injectable Emulsion will reduce the opioid requirements (see Table 4). When Propofol Injectable Emulsion is used as the primary anesthetic, it should not be administered with the high-dose opioid technique as this may increase the likelihood of hypotension (see PRECAUTIONS, Cardiac Anesthesia).
Table 4. Cardiac Anesthesia Techniques
Primary Agent
Rate
Secondary Agent/Rate
(Following Induction with Primary Agent)
Propofol Injectable Emulsion
OPIOIDa/0.05 to 0.075 mcg/kg/min (no bolus)
Preinduction
Anxiolysis
25 mcg/kg/min
Induction
0.5 to 1.5 mg/kg
over 60 sec
Maintenance
(Titrated to Clinical
Response)
100 to 150 mcg/kg/min
OPIOIDb
Propofol Injectable Emulsion/50 to 100 mcg/kg/min
(no bolus)
Induction
25 to 50 mcg/kg
Maintenance
0.2 to 0.3 mcg/kg/min
aOPIOID is defined in terms of fentanyl equivalents, i.e.,
1 mcg of fentanyl = 5 mcg of alfentanil (for bolus)
= 10 mcg of alfentanil (for maintenance)
or
= 0.1 mcg of sufentanil
bCare should be taken to ensure amnesia.
Maintenance of General Anesthesia
Adult Patients
In adults, anesthesia can be maintained by administering Propofol Injectable Emulsion by infusion or intermittent IV bolus injection. The patient's clinical response will determine the infusion rate or the amount and frequency of incremental injections.
Continuous Infusion
Propofol Injectable Emulsion 100 to 200 mcg/kg/min administered in a variable rate infusion with 60% to 70% nitrous oxide and oxygen provides anesthesia for patients undergoing general surgery. Maintenance by infusion of Propofol Injectable Emulsion should immediately follow the induction dose in order to provide satisfactory or continuous anesthesia during the induction phase. During this initial period following the induction dose, higher rates of infusion are generally required (150 to 200 mcg/kg/min) for the first 10 to 15 minutes. Infusion rates should subsequently be decreased 30% to 50% during the first half-hour of maintenance. Generally, rates of 50 to 100 mcg/kg/min in adults should be achieved during maintenance in order to optimize recovery times.
Other drugs that cause CNS depression (hypnotics/sedatives, inhalational anesthetics, and opioids) can increase the CNS depression induced by propofol.
Intermittent Bolus
Increments of Propofol Injectable Emulsion 25 mg (2.5 mL) to 50 mg (5 mL) may be administered with nitrous oxide in adult patients undergoing general surgery. The incremental boluses should be administered when changes in vital signs indicate a response to surgical stimulation or light anesthesia.
Pediatric Patients
Propofol Injectable Emulsion administered as a variable rate infusion supplemented with nitrous oxide 60% to 70% provides satisfactory anesthesia for most children 2 months of age or older, ASA-PS I or II, undergoing general anesthesia.
In general, for the pediatric population, maintenance by infusion of Propofol Injectable Emulsion at a rate of 200 to 300 mcg/kg/min should immediately follow the induction dose. Following the first half-hour of maintenance, infusion rates of 125 to 150 mcg/kg/min are typically needed. Propofol Injectable Emulsion should be titrated to achieve the desired clinical effect. Younger pediatric patients may require higher maintenance infusion rates than older pediatric patients. (See Table 2 Clinical Trials.)
Propofol Injectable Emulsion has been used with a variety of agents commonly used in anesthesia such as atropine, scopolamine, glycopyrrolate, diazepam, depolarizing and nondepolarizing muscle relaxants, and opioid analgesics, as well as with inhalational and regional anesthetic agents.
In the elderly, debilitated, or ASA-PS III or IV patients, rapid bolus doses should not be used, as this will increase cardiorespiratory effects including hypotension, apnea, airway obstruction, and oxygen desaturation.
Monitored Anesthesia Care (MAC) Sedation
Adult Patients
When Propofol Injectable Emulsion is administered for MAC sedation, rates of administration should be individualized and titrated to clinical response. In most patients, the rates of Propofol Injectable Emulsion administration will be in the range of 25 to 75 mcg/kg/min.
During initiation of MAC sedation, slow infusion or slow injection techniques are preferable over rapid bolus administration. During maintenance of MAC sedation, a variable rate infusion is preferable over intermittent bolus dose administration. In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation (see WARNINGS). A rapid bolus injection can result in undesirable cardiorespiratory depression including hypotension, apnea, airway obstruction, and oxygen desaturation.
Initiation of MAC Sedation
For initiation of MAC sedation, either an infusion or a slow injection method may be utilized while closely monitoring cardiorespiratory function. With the infusion method, sedation may be initiated by infusing Propofol Injectable Emulsion at 100 to 150 mcg/kg/min (6 to 9 mg/kg/h) for a period of 3 to 5 minutes and titrating to the desired clinical effect while closely monitoring respiratory function. With the slow injection method for initiation, patients will require approximately 0.5 mg/kg administered over 3 to 5 minutes and titrated to clinical responses. When Propofol Injectable Emulsion is administered slowly over 3 to 5 minutes, most patients will be adequately sedated, and the peak drug effect can be achieved while minimizing undesirable cardiorespiratory effects occurring at high plasma levels.
In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation (see WARNINGS). The rate of administration should be over 3 to 5 minutes and the dosage of Propofol Injectable Emulsion should be reduced to approximately 80% of the usual adult dosage in these patients according to their condition, responses, and changes in vital signs (see DOSAGE AND ADMINISTRATION).
Maintenance of MAC Sedation
For maintenance of sedation, a variable rate infusion method is preferable over an intermittent bolus dose method. With the variable rate infusion method, patients will generally require maintenance rates of 25 to 75 mcg/kg/min (1.5 to 4.5 mg/kg/h) during the first 10 to 15 minutes of sedation maintenance. Infusion rates should subsequently be decreased over time to 25 to 50 mcg/kg/min and adjusted to clinical responses. In titrating to clinical effect, allow approximately 2 minutes for onset of peak drug effect.
Infusion rates should always be titrated downward in the absence of clinical signs of light sedation until mild responses to stimulation are obtained in order to avoid sedative administration of Propofol Injectable Emulsion at rates higher than are clinically necessary.
If the intermittent bolus dose method is used, increments of Propofol Injectable Emulsion 10 mg (1 mL) or 20 mg (2 mL) can be administered and titrated to desired clinical effect. With the intermittent bolus method of sedation maintenance, there is increased potential for respiratory depression, transient increases in sedation depth, and prolongation of recovery.
In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation (see WARNINGS). The rate of administration and the dosage of Propofol Injectable Emulsion should be reduced to approximately 80% of the usual adult dosage in these patients according to their condition, responses, and changes in vital signs (see DOSAGE AND ADMINISTRATION).
Propofol Injectable Emulsion can be administered as the sole agent for maintenance of MAC sedation during surgical/diagnostic procedures. When Propofol Injectable Emulsion sedation is supplemented with opioid and/or benzodiazepine medications, these agents increase the sedative and respiratory effects of Propofol Injectable Emulsion and may also result in a slower recovery profile (see PRECAUTIONS, Drug Interactions).
ICU Sedation
(See WARNINGS and DOSAGE AND ADMINISTRATION, Handling Procedures.)
Abrupt discontinuation of Propofol Injectable Emulsion prior to weaning or for daily evaluation of sedation levels should be avoided. This may result in rapid awakening with associated anxiety, agitation, and resistance to mechanical ventilation. Infusions of Propofol Injectable Emulsion should be adjusted to assure a minimal level of sedation is maintained throughout the weaning process and when assessing the level of sedation (see PRECAUTIONS).
Adult Patients
For intubated, mechanically ventilated adult patients, Intensive Care Unit (ICU) sedation should be initiated slowly with a continuous infusion in order to titrate to desired clinical effect and minimize hypotension (see DOSAGE AND ADMINISTRATION).
Most adult ICU patients recovering from the effects of general anesthesia or deep sedation will require maintenance rates of 5 to 50 mcg/kg/min (0.3 to 3 mg/kg/h) individualized and titrated to clinical response (see DOSAGE AND ADMINISTRATION). With medical ICU patients or patients who have recovered from the effects of general anesthesia or deep sedation, the rate of administration of 50 mcg/kg/min or higher may be required to achieve adequate sedation. These higher rates of administration may increase the likelihood of patients developing hypotension. Administration should not exceed 4 mg/kg/hour unless the benefits outweigh the risks (see WARNINGS).
Dosage and rate of administration should be individualized and titrated to the desired effect, according to clinically relevant factors including the patient’s underlying medical problems, preinduction and concomitant medications, age, ASA-PS classification, and level of debilitation of the patient. The elderly, debilitated, and ASA-PS III or IV patients may have exaggerated hemodynamic and respiratory responses to rapid bolus doses (see WARNINGS).
Propofol Injectable Emulsion should be individualized according to the patient's condition and response, blood lipid profile, and vital signs (see PRECAUTIONS, Intensive Care Unit Sedation). For intubated, mechanically ventilated adult patients, Intensive Care Unit (ICU) sedation should be initiated slowly with a continuous infusion in order to titrate to desired clinical effect and minimize hypotension. When indicated, initiation of sedation should begin at 5 mcg/kg/min (0.3 mg/kg/h). The infusion rate should be increased by increments of 5 to 10 mcg/kg/min (0.3 to 0.6 mg/kg/h) until the desired level of sedation is achieved. A minimum period of 5 minutes between adjustments should be allowed for onset of peak drug effect. Most adult patients require maintenance rates of 5 to 50 mcg/kg/min (0.3 to 3 mg/kg/h) or higher. Administration should not exceed 4 mg/kg/hour unless the benefits outweigh the risks (see WARNINGS). Dosages of Propofol Injectable Emulsion should be reduced in patients who have received large dosages of narcotics. Conversely, the Propofol Injectable Emulsion dosage requirement may be reduced by adequate management of pain with analgesic agents. As with other sedative medications, there is interpatient variability in dosage requirements, and these requirements may change with time (see SUMMARY OF DOSAGE GUIDELINES). Evaluation of level of sedation and assessment of cns function should be carried out daily throughout maintenance to determine the minimum dose of PROPOFOL required for sedation (see Clinical Trials , Intensive Care Unit (ICU) Sedation). Bolus administration of 10 or 20 mg should only be used to rapidly increase depth of sedation in patients where hypotension is not likely to occur. Patients with compromised myocardial function, intravascular volume depletion, or abnormally low vascular tone (e.g., sepsis) may be more susceptible to hypotension (see PRECAUTIONS).
SUMMARY OF DOSAGE GUIDELINES :
Dosages and rates of administration in the following table should be individualized and titrated to clinical response. Safety and dosing requirements for induction of anesthesia in pediatric patients have only been established for children 3 years of age or older. Safety and dosing requirements for the maintenance of anesthesia have only been established for children 2 months of age and older.
For complete dosage information, see DOSAGE AND ADMINISTRATION.
INDICATION
DOSAGE AND ADMINISTRATION
Induction of General Anesthesia:
Healthy Adults Less Than 55 Years of Age:
40 mg every 10 seconds until induction onset (2 to 2.5 mg/kg).
Elderly, Debilitated, or ASA-PS III or IV Patients:
20 mg every 10 seconds until induction onset (1 to 1.5 mg/kg).
Cardiac Anesthesia:
20 mg every 10 seconds until induction onset (0.5 to 1.5 mg/kg).
Neurosurgical Patients:
20 mg every 10 seconds until induction onset (1 to 2 mg/kg)
Pediatric Patients – healthy, from 3 years to 16 years of age:
2.5 to 3.5 mg/kg administered over 20 to 30 seconds.
(see PRECAUTIONS, Pediatric Use and CLINICAL PHARMACOLOGY, Pediatrics)
Maintenance of General Anesthesia:
Infusion
Healthy Adults Less Than 55 Years of Age:
100 to 200 mcg/kg/min (6 to 12 mg/kg/h).
Elderly, Debilitated, ASA-PS III or IV Patients:
50 to 100 mcg/kg/min (3 to 6 mg/kg/h).
Cardiac Anesthesia: Most patients require:
Primary Propofol Injectable Emulsion with Secondary Opioid –
100 to 150 mcg/kg/min
Low-Dose Propofol Injectable Emulsion with Primary Opioid –
50 to 100 mcg/kg/min
(see DOSAGE AND ADMINISTRATION, Table 4)
Neurosurgical Patients:
100 to 200 mcg/kg/min (6 to 12 mg/kg/h).
Pediatric Patients - healthy, from 2 months of age to 16 years of age:
125 to 300 mcg/kg/min (7.5 to 18 mg/kg/h)
Following the first half hour of maintenance, if clinical signs of light
anesthesia are not present, the infusion rate should be decreased.
(see PRECAUTIONS, Pediatric Use and CLINICAL PHARMACOLOGY, Pediatrics)
Maintenance of General Anesthesia:
Intermittent Bolus
Healthy Adults Less Than 55 Years of Age:
Increments of 20 to 50 mg as needed.
Initiation of MAC Sedation:
Healthy Adults Less Than 55 Years of Age:
Slow infusion or slow injection techniques are recommended to avoid apnea
or hypotension. Most patients require an infusion of 100 to 150 mcg/kg/min
(6 to 9 mg/kg/h) for 3 to 5 minutes or a slow injection of 0.5 mg/kg over 3
to 5 minutes followed immediately by a maintenance infusion.
Elderly, Debilitated, Neurosurgical, or ASA-PS III or IV Patients:
Most patients require dosages similar to healthy adults.
Rapid boluses are to be avoided (see WARNINGS).
Maintenance of MAC Sedation:
Healthy Adults Less Than 55 Years of Age:
A variable rate infusion technique is preferable over an intermittent bolus
technique. Most patients require an infusion of 25 to 75 mcg/kg/min
(1.5 to 4.5 mg/kg/h) or incremental bolus doses of 10 mg or 20 mg.
In Elderly, Debilitated, Neurosurgical, or ASA-PS III or IV Patients:
Most patients require 80% of the usual adult dose. A rapid (single or
repeated) bolus dose should not be used (see WARNINGS).
Initiation and Maintenance of ICU Sedation in Intubated, Mechanically Ventilated
Adult Patients - Because of the residual effects of previous anesthetic or
sedative agents, in most patients the initial infusion should be 5 mcg/kg/min
(0.3 mg/kg/h) for at least 5 minutes. Subsequent increments of 5 to 10
mcg/kg/min (0.3 to 0.6 mg/kg/h) over 5 to 10 minutes may be used until
desired clinical effect is achieved. Maintenance rates of 5 to 50 mcg/kg/min
(0.3 to 3 mg/kg/h) or higher may be required. Administration should not
exceed 4 mg/kg/hour unless the benefits outweigh the risks (see WARNINGS).
Evaluation of clinical effect and assessment of CNS function should be
carried out daily throughout maintenance to determine the minimum
dose of Propofol Injectable Emulsion required for sedation.
The tubing and any unused portions of Propofol Injectable Emulsion
should be discarded after 12 hours because Propofol Injectable
Emulsion contains no preservatives and is capable of supporting growth
of microorganisms (see WARNINGS and DOSAGE AND ADMINISTRATION ).
Administration with Lidocaine
If lidocaine is to be administered to minimize pain on injection of Propofol, it is recommended that it be administered prior to Propofol administration or that it be added to Propofol immediately before administration and in quantities not exceeding 20 mg lidocaine/200 mg Propofol.
Compatibility and Stability
Propofol Injectable Emulsion should not be mixed with other therapeutic agents prior to administration.
Dilution Prior to Administration
Propofol Injectable Emulsion is provided as a ready-to-use formulation. However, should dilution be necessary, it should only be diluted with 5% Dextrose Injection, USP, and it should not be diluted to a concentration less than 2 mg/mL because it is an emulsion. In diluted form it has been shown to be more stable when in contact with glass than with plastic (95% potency after 2 hours of running infusion in plastic).
Administration with Other Fluids
Compatibility of Propofol Injectable Emulsion with the coadministration of blood/serum/plasma has not been established (see WARNINGS). When administered using a y-type infusion set, Propofol Injectable Emulsion has been shown to be compatible with the following intravenous fluids.
- 5% Dextrose Injection, USP
- Lactated Ringers Injection, USP
- Lactated Ringers and 5% Dextrose Injection
- 5% Dextrose and 0.45% Sodium Chloride Injection, USP
- 5% Dextrose and 0.2% Sodium Chloride Injection, USP
Handling Procedures
General
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
Clinical experience with the use of in-line filters and Propofol Injectable Emulsion during anesthesia or ICU/MAC sedation is limited. Propofol Injectable Emulsion should only be administered through a filter with a pore size of 5 micron or greater unless it has been demonstrated that the filter does not restrict the flow of Propofol Injectable Emulsion and/or cause the breakdown of the emulsion. Filters should be used with caution and where clinically appropriate. Continuous monitoring is necessary due to the potential for restricted flow and/or breakdown of the emulsion.
Do not use if there is evidence of separation of the phases of the emulsion.
Rare cases of self-administration of Propofol Injectable Emulsion by health care professionals have been reported, including some fatalities (see DRUG ABUSE AND DEPENDENCE).
Strict aseptic technique must always be maintained during handling. Propofol Injectable Emulsion is a single-use parenteral product which contains 0.005% disodium edetate to inhibit the rate of growth of microorganisms, up to 12 hours, in the event of accidental extrinsic contamination. However, Propofol Injectable Emulsion can still support the growth of microorganisms as it is not an antimicrobially preserved product under USP standards. Accordingly, strict aseptic technique must still be adhered to. Do not use if contamination is suspected. Discard unused portions as directed within the required time limits (see DOSAGE AND ADMINISTRATION, Handling Procedures). There have been reports in which failure to use aseptic technique when handling Propofol Injectable Emulsion was associated with microbial contamination of the product and with fever, infection/sepsis, other life-threatening illness, and/or death.
Propofol, with EDTA inhibits microbial growth for up to 12 hours, as demonstrated by test data for representative USP microorganisms.
Guidelines for Aseptic Technique for General Anesthesia/MAC Sedation
Propofol Injectable Emulsion should be prepared for use just prior to initiation of each individual anesthetic/sedative procedure. The vial syringe rubber stopper should be disinfected using 70% isopropyl alcohol. Propofol Injectable Emulsion should be drawn into sterile syringes immediately after vials are opened. When withdrawing Propofol Injectable Emulsion from vials, a sterile vent spike should be used. The syringe(s) should be labeled with appropriate information including the date and time the vial was opened. Administration should commence promptly and be completed within 12 hours after the vials have been opened.
Propofol Injectable Emulsion should be prepared for single-patient use only. Any unused portions of Propofol Injectable Emulsion, reservoirs, dedicated administration tubing and/or solutions containing Propofol Injectable Emulsion must be discarded at the end of the anesthetic procedure or at 12 hours, whichever occurs sooner. The IV line should be flushed every 12 hours and at the end of the anesthetic procedure to remove residual Propofol Injectable Emulsion.
Guidelines for Aseptic Technique for ICU Sedation
Propofol Injectable Emulsion should be prepared for single-patient use only. When Propofol Injectable Emulsion is administered directly from the vial, strict aseptic techniques must be followed. The vial rubber stopper should be disinfected using 70% isopropyl alcohol. A sterile vent spike and sterile tubing must be used for administration of Propofol Injectable Emulsion. As with other lipid emulsions, the number of IV line manipulations should be minimized. Administration should commence promptly and must be completed within 12 hours after the vial has been spiked. The tubing and any unused portions of Propofol Injectable Emulsion must be discarded after 12 hours.
If Propofol Injectable Emulsion is transferred to a syringe or other container prior to administration, the handling procedures for General anesthesia/MAC sedation should be followed, and the product should be discarded and administration lines changed after 12 hours.
Induction of General Anesthesia
Adult Patients
Most adult patients under 55 years of age and classified as ASA-PS I or II require 2 to 2.5 mg/kg of Propofol Injectable Emulsion for induction when unpremedicated or when premedicated with oral benzodiazepines or intramuscular opioids. For induction, Propofol Injectable Emulsion should be titrated (approximately 40 mg every 10 seconds) against the response of the patient until the clinical signs show the onset of anesthesia. As with other sedative-hypnotic agents, the amount of intravenous opioid and/or benzodiazepine premedication will influence the response of the patient to an induction dose of Propofol Injectable Emulsion.
Elderly, Debilitated, or ASA-PS III or IV Patients
It is important to be familiar and experienced with the intravenous use of Propofol Injectable Emulsion before treating elderly, debilitated, or ASA-PS III or IV patients. Due to the reduced clearance and higher blood concentrations, most of these patients require approximately 1 to 1.5 mg/kg (approximately 20 mg every 10 seconds) of Propofol Injectable Emulsion for induction of anesthesia according to their condition and responses. A rapid bolus should not be used, as this will increase the likelihood of undesirable cardiorespiratory depression including hypotension, apnea, airway obstruction, and/or oxygen desaturation (see DOSAGE AND ADMINISTRATION).
Pediatric Patients
Most patients aged 3 years through 16 years and classified ASA-PS I or II require 2.5 to 3.5 mg/kg of Propofol Injectable Emulsion for induction when unpremedicated or when lightly premedicated with oral benzodiazepines or intramuscular opioids. Within this dosage range, younger pediatric patients may require higher induction doses than older pediatric patients. As with other sedative‑hypnotic agents, the amount of intravenous opioid and/or benzodiazepine premedication will influence the response of the patient to an induction dose of Propofol Injectable Emulsion. A lower dosage is recommended for pediatric patients classified as ASA-PS III or IV. Attention should be paid to minimize pain on injection when administering Propofol Injectable Emulsion to pediatric patients. Boluses of Propofol Injectable Emulsion may be administered via small veins if pretreated with lidocaine or via antecubital or larger veins (see PRECAUTIONS, General).
Neurosurgical Patients
Slower induction is recommended using boluses of 20 mg every 10 seconds. Slower boluses or infusions of Propofol Injectable Emulsion for induction of anesthesia, titrated to clinical responses, will generally result in reduced induction dosage requirements (1 to 2 mg/kg) (see PRECAUTIONS and DOSAGE AND ADMINISTRATION).
Cardiac Anesthesia
Propofol Injectable Emulsion has been well-studied in patients with coronary artery disease, but experience in patients with hemodynamically significant valvular or congenital heart disease is limited. As with other anesthetic and sedative-hypnotic agents, Propofol Injectable Emulsion in healthy patients causes a decrease in blood pressure that is secondary to decreases in preload (ventricular filling volume at the end of the diastole) and afterload (arterial resistance at the beginning of the systole). The magnitude of these changes is proportional to the blood and effect site concentrations achieved. These concentrations depend upon the dose and speed of the induction and maintenance infusion rates.
In addition, lower heart rates are observed during maintenance with Propofol Injectable Emulsion, possibly due to reduction of the sympathetic activity and/or resetting of the baroreceptor reflexes. Therefore, anticholinergic agents should be administered when increases in vagal tone are anticipated.
As with other anesthetic agents, Propofol Injectable Emulsion reduces myocardial oxygen consumption. Further studies are needed to confirm and delineate the extent of these effects on the myocardium and the coronary vascular system.
Morphine premedication (0.15 mg/kg) with nitrous oxide 67% in oxygen has been shown to decrease the necessary Propofol Injectable Emulsion maintenance infusion rates and therapeutic blood concentrations when compared to non‑narcotic (lorazepam) premedication. The rate of Propofol Injectable Emulsion administration should be determined based on the patient's premedication and adjusted according to clinical responses.
A rapid bolus induction should be avoided. A slow rate of approximately 20 mg every 10 seconds until induction onset (0.5 to 1.5 mg/kg) should be used. In order to assure adequate anesthesia, when Propofol Injectable Emulsion is used as the primary agent, maintenance infusion rates should not be less than 100 mcg/kg/min and should be supplemented with analgesic levels of continuous opioid administration. When an opioid is used as the primary agent, Propofol Injectable Emulsion maintenance rates should not be less than 50 mcg/kg/min, and care should be taken to ensure amnesia. Higher doses of Propofol Injectable Emulsion will reduce the opioid requirements (see Table 4). When Propofol Injectable Emulsion is used as the primary anesthetic, it should not be administered with the high-dose opioid technique as this may increase the likelihood of hypotension (see PRECAUTIONS, Cardiac Anesthesia).
Table 4. Cardiac Anesthesia Techniques
Primary Agent
Rate
Secondary Agent/Rate
(Following Induction with Primary Agent)
Propofol Injectable Emulsion
OPIOIDa/0.05 to 0.075 mcg/kg/min (no bolus)
Preinduction
Anxiolysis
25 mcg/kg/min
Induction
0.5 to 1.5 mg/kg
over 60 sec
Maintenance
(Titrated to Clinical
Response)
100 to 150 mcg/kg/min
OPIOIDb
Propofol Injectable Emulsion/50 to 100 mcg/kg/min
(no bolus)
Induction
25 to 50 mcg/kg
Maintenance
0.2 to 0.3 mcg/kg/min
aOPIOID is defined in terms of fentanyl equivalents, i.e.,
1 mcg of fentanyl = 5 mcg of alfentanil (for bolus)
= 10 mcg of alfentanil (for maintenance)
or
= 0.1 mcg of sufentanil
bCare should be taken to ensure amnesia.
Maintenance of General Anesthesia
Adult Patients
In adults, anesthesia can be maintained by administering Propofol Injectable Emulsion by infusion or intermittent IV bolus injection. The patient's clinical response will determine the infusion rate or the amount and frequency of incremental injections.
Continuous Infusion
Propofol Injectable Emulsion 100 to 200 mcg/kg/min administered in a variable rate infusion with 60% to 70% nitrous oxide and oxygen provides anesthesia for patients undergoing general surgery. Maintenance by infusion of Propofol Injectable Emulsion should immediately follow the induction dose in order to provide satisfactory or continuous anesthesia during the induction phase. During this initial period following the induction dose, higher rates of infusion are generally required (150 to 200 mcg/kg/min) for the first 10 to 15 minutes. Infusion rates should subsequently be decreased 30% to 50% during the first half-hour of maintenance. Generally, rates of 50 to 100 mcg/kg/min in adults should be achieved during maintenance in order to optimize recovery times.
Other drugs that cause CNS depression (hypnotics/sedatives, inhalational anesthetics, and opioids) can increase the CNS depression induced by propofol.
Intermittent Bolus
Increments of Propofol Injectable Emulsion 25 mg (2.5 mL) to 50 mg (5 mL) may be administered with nitrous oxide in adult patients undergoing general surgery. The incremental boluses should be administered when changes in vital signs indicate a response to surgical stimulation or light anesthesia.
Pediatric Patients
Propofol Injectable Emulsion administered as a variable rate infusion supplemented with nitrous oxide 60% to 70% provides satisfactory anesthesia for most children 2 months of age or older, ASA-PS I or II, undergoing general anesthesia.
In general, for the pediatric population, maintenance by infusion of Propofol Injectable Emulsion at a rate of 200 to 300 mcg/kg/min should immediately follow the induction dose. Following the first half-hour of maintenance, infusion rates of 125 to 150 mcg/kg/min are typically needed. Propofol Injectable Emulsion should be titrated to achieve the desired clinical effect. Younger pediatric patients may require higher maintenance infusion rates than older pediatric patients. (See Table 2 Clinical Trials.)
Propofol Injectable Emulsion has been used with a variety of agents commonly used in anesthesia such as atropine, scopolamine, glycopyrrolate, diazepam, depolarizing and nondepolarizing muscle relaxants, and opioid analgesics, as well as with inhalational and regional anesthetic agents.
In the elderly, debilitated, or ASA-PS III or IV patients, rapid bolus doses should not be used, as this will increase cardiorespiratory effects including hypotension, apnea, airway obstruction, and oxygen desaturation.
Monitored Anesthesia Care (MAC) Sedation
Adult Patients
When Propofol Injectable Emulsion is administered for MAC sedation, rates of administration should be individualized and titrated to clinical response. In most patients, the rates of Propofol Injectable Emulsion administration will be in the range of 25 to 75 mcg/kg/min.
During initiation of MAC sedation, slow infusion or slow injection techniques are preferable over rapid bolus administration. During maintenance of MAC sedation, a variable rate infusion is preferable over intermittent bolus dose administration. In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation (see WARNINGS). A rapid bolus injection can result in undesirable cardiorespiratory depression including hypotension, apnea, airway obstruction, and oxygen desaturation.
Initiation of MAC Sedation
For initiation of MAC sedation, either an infusion or a slow injection method may be utilized while closely monitoring cardiorespiratory function. With the infusion method, sedation may be initiated by infusing Propofol Injectable Emulsion at 100 to 150 mcg/kg/min (6 to 9 mg/kg/h) for a period of 3 to 5 minutes and titrating to the desired clinical effect while closely monitoring respiratory function. With the slow injection method for initiation, patients will require approximately 0.5 mg/kg administered over 3 to 5 minutes and titrated to clinical responses. When Propofol Injectable Emulsion is administered slowly over 3 to 5 minutes, most patients will be adequately sedated, and the peak drug effect can be achieved while minimizing undesirable cardiorespiratory effects occurring at high plasma levels.
In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation (see WARNINGS). The rate of administration should be over 3 to 5 minutes and the dosage of Propofol Injectable Emulsion should be reduced to approximately 80% of the usual adult dosage in these patients according to their condition, responses, and changes in vital signs (see DOSAGE AND ADMINISTRATION).
Maintenance of MAC Sedation
For maintenance of sedation, a variable rate infusion method is preferable over an intermittent bolus dose method. With the variable rate infusion method, patients will generally require maintenance rates of 25 to 75 mcg/kg/min (1.5 to 4.5 mg/kg/h) during the first 10 to 15 minutes of sedation maintenance. Infusion rates should subsequently be decreased over time to 25 to 50 mcg/kg/min and adjusted to clinical responses. In titrating to clinical effect, allow approximately 2 minutes for onset of peak drug effect.
Infusion rates should always be titrated downward in the absence of clinical signs of light sedation until mild responses to stimulation are obtained in order to avoid sedative administration of Propofol Injectable Emulsion at rates higher than are clinically necessary.
If the intermittent bolus dose method is used, increments of Propofol Injectable Emulsion 10 mg (1 mL) or 20 mg (2 mL) can be administered and titrated to desired clinical effect. With the intermittent bolus method of sedation maintenance, there is increased potential for respiratory depression, transient increases in sedation depth, and prolongation of recovery.
In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation (see WARNINGS). The rate of administration and the dosage of Propofol Injectable Emulsion should be reduced to approximately 80% of the usual adult dosage in these patients according to their condition, responses, and changes in vital signs (see DOSAGE AND ADMINISTRATION).
Propofol Injectable Emulsion can be administered as the sole agent for maintenance of MAC sedation during surgical/diagnostic procedures. When Propofol Injectable Emulsion sedation is supplemented with opioid and/or benzodiazepine medications, these agents increase the sedative and respiratory effects of Propofol Injectable Emulsion and may also result in a slower recovery profile (see PRECAUTIONS, Drug Interactions).
ICU Sedation
(See WARNINGS and DOSAGE AND ADMINISTRATION, Handling Procedures.)
Abrupt discontinuation of Propofol Injectable Emulsion prior to weaning or for daily evaluation of sedation levels should be avoided. This may result in rapid awakening with associated anxiety, agitation, and resistance to mechanical ventilation. Infusions of Propofol Injectable Emulsion should be adjusted to assure a minimal level of sedation is maintained throughout the weaning process and when assessing the level of sedation (see PRECAUTIONS).
Adult Patients
For intubated, mechanically ventilated adult patients, Intensive Care Unit (ICU) sedation should be initiated slowly with a continuous infusion in order to titrate to desired clinical effect and minimize hypotension (see DOSAGE AND ADMINISTRATION).
Most adult ICU patients recovering from the effects of general anesthesia or deep sedation will require maintenance rates of 5 to 50 mcg/kg/min (0.3 to 3 mg/kg/h) individualized and titrated to clinical response (see DOSAGE AND ADMINISTRATION). With medical ICU patients or patients who have recovered from the effects of general anesthesia or deep sedation, the rate of administration of 50 mcg/kg/min or higher may be required to achieve adequate sedation. These higher rates of administration may increase the likelihood of patients developing hypotension. Administration should not exceed 4 mg/kg/hour unless the benefits outweigh the risks (see WARNINGS).
Dosage and rate of administration should be individualized and titrated to the desired effect, according to clinically relevant factors including the patient’s underlying medical problems, preinduction and concomitant medications, age, ASA-PS classification, and level of debilitation of the patient. The elderly, debilitated, and ASA-PS III or IV patients may have exaggerated hemodynamic and respiratory responses to rapid bolus doses (see WARNINGS).
Propofol Injectable Emulsion should be individualized according to the patient's condition and response, blood lipid profile, and vital signs (see PRECAUTIONS, Intensive Care Unit Sedation). For intubated, mechanically ventilated adult patients, Intensive Care Unit (ICU) sedation should be initiated slowly with a continuous infusion in order to titrate to desired clinical effect and minimize hypotension. When indicated, initiation of sedation should begin at 5 mcg/kg/min (0.3 mg/kg/h). The infusion rate should be increased by increments of 5 to 10 mcg/kg/min (0.3 to 0.6 mg/kg/h) until the desired level of sedation is achieved. A minimum period of 5 minutes between adjustments should be allowed for onset of peak drug effect. Most adult patients require maintenance rates of 5 to 50 mcg/kg/min (0.3 to 3 mg/kg/h) or higher. Administration should not exceed 4 mg/kg/hour unless the benefits outweigh the risks (see WARNINGS). Dosages of Propofol Injectable Emulsion should be reduced in patients who have received large dosages of narcotics. Conversely, the Propofol Injectable Emulsion dosage requirement may be reduced by adequate management of pain with analgesic agents. As with other sedative medications, there is interpatient variability in dosage requirements, and these requirements may change with time (see SUMMARY OF DOSAGE GUIDELINES). Evaluation of level of sedation and assessment of cns function should be carried out daily throughout maintenance to determine the minimum dose of PROPOFOL required for sedation (see Clinical Trials , Intensive Care Unit (ICU) Sedation). Bolus administration of 10 or 20 mg should only be used to rapidly increase depth of sedation in patients where hypotension is not likely to occur. Patients with compromised myocardial function, intravascular volume depletion, or abnormally low vascular tone (e.g., sepsis) may be more susceptible to hypotension (see PRECAUTIONS).
SUMMARY OF DOSAGE GUIDELINES :
Dosages and rates of administration in the following table should be individualized and titrated to clinical response. Safety and dosing requirements for induction of anesthesia in pediatric patients have only been established for children 3 years of age or older. Safety and dosing requirements for the maintenance of anesthesia have only been established for children 2 months of age and older.
For complete dosage information, see DOSAGE AND ADMINISTRATION.
INDICATION
DOSAGE AND ADMINISTRATION
Induction of General Anesthesia:
Healthy Adults Less Than 55 Years of Age:
40 mg every 10 seconds until induction onset (2 to 2.5 mg/kg).
Elderly, Debilitated, or ASA-PS III or IV Patients:
20 mg every 10 seconds until induction onset (1 to 1.5 mg/kg).
Cardiac Anesthesia:
20 mg every 10 seconds until induction onset (0.5 to 1.5 mg/kg).
Neurosurgical Patients:
20 mg every 10 seconds until induction onset (1 to 2 mg/kg)
Pediatric Patients – healthy, from 3 years to 16 years of age:
2.5 to 3.5 mg/kg administered over 20 to 30 seconds.
(see PRECAUTIONS, Pediatric Use and CLINICAL PHARMACOLOGY, Pediatrics)
Maintenance of General Anesthesia:
Infusion
Healthy Adults Less Than 55 Years of Age:
100 to 200 mcg/kg/min (6 to 12 mg/kg/h).
Elderly, Debilitated, ASA-PS III or IV Patients:
50 to 100 mcg/kg/min (3 to 6 mg/kg/h).
Cardiac Anesthesia: Most patients require:
Primary Propofol Injectable Emulsion with Secondary Opioid –
100 to 150 mcg/kg/min
Low-Dose Propofol Injectable Emulsion with Primary Opioid –
50 to 100 mcg/kg/min
(see DOSAGE AND ADMINISTRATION, Table 4)
Neurosurgical Patients:
100 to 200 mcg/kg/min (6 to 12 mg/kg/h).
Pediatric Patients - healthy, from 2 months of age to 16 years of age:
125 to 300 mcg/kg/min (7.5 to 18 mg/kg/h)
Following the first half hour of maintenance, if clinical signs of light
anesthesia are not present, the infusion rate should be decreased.
(see PRECAUTIONS, Pediatric Use and CLINICAL PHARMACOLOGY, Pediatrics)
Maintenance of General Anesthesia:
Intermittent Bolus
Healthy Adults Less Than 55 Years of Age:
Increments of 20 to 50 mg as needed.
Initiation of MAC Sedation:
Healthy Adults Less Than 55 Years of Age:
Slow infusion or slow injection techniques are recommended to avoid apnea
or hypotension. Most patients require an infusion of 100 to 150 mcg/kg/min
(6 to 9 mg/kg/h) for 3 to 5 minutes or a slow injection of 0.5 mg/kg over 3
to 5 minutes followed immediately by a maintenance infusion.
Elderly, Debilitated, Neurosurgical, or ASA-PS III or IV Patients:
Most patients require dosages similar to healthy adults.
Rapid boluses are to be avoided (see WARNINGS).
Maintenance of MAC Sedation:
Healthy Adults Less Than 55 Years of Age:
A variable rate infusion technique is preferable over an intermittent bolus
technique. Most patients require an infusion of 25 to 75 mcg/kg/min
(1.5 to 4.5 mg/kg/h) or incremental bolus doses of 10 mg or 20 mg.
In Elderly, Debilitated, Neurosurgical, or ASA-PS III or IV Patients:
Most patients require 80% of the usual adult dose. A rapid (single or
repeated) bolus dose should not be used (see WARNINGS).
Initiation and Maintenance of ICU Sedation in Intubated, Mechanically Ventilated
Adult Patients - Because of the residual effects of previous anesthetic or
sedative agents, in most patients the initial infusion should be 5 mcg/kg/min
(0.3 mg/kg/h) for at least 5 minutes. Subsequent increments of 5 to 10
mcg/kg/min (0.3 to 0.6 mg/kg/h) over 5 to 10 minutes may be used until
desired clinical effect is achieved. Maintenance rates of 5 to 50 mcg/kg/min
(0.3 to 3 mg/kg/h) or higher may be required. Administration should not
exceed 4 mg/kg/hour unless the benefits outweigh the risks (see WARNINGS).
Evaluation of clinical effect and assessment of CNS function should be
carried out daily throughout maintenance to determine the minimum
dose of Propofol Injectable Emulsion required for sedation.
The tubing and any unused portions of Propofol Injectable Emulsion
should be discarded after 12 hours because Propofol Injectable
Emulsion contains no preservatives and is capable of supporting growth
of microorganisms (see WARNINGS and DOSAGE AND ADMINISTRATION ).
Administration with Lidocaine
If lidocaine is to be administered to minimize pain on injection of Propofol, it is recommended that it be administered prior to Propofol administration or that it be added to Propofol immediately before administration and in quantities not exceeding 20 mg lidocaine/200 mg Propofol.
Compatibility and Stability
Propofol Injectable Emulsion should not be mixed with other therapeutic agents prior to administration.
Dilution Prior to Administration
Propofol Injectable Emulsion is provided as a ready-to-use formulation. However, should dilution be necessary, it should only be diluted with 5% Dextrose Injection, USP, and it should not be diluted to a concentration less than 2 mg/mL because it is an emulsion. In diluted form it has been shown to be more stable when in contact with glass than with plastic (95% potency after 2 hours of running infusion in plastic).
Administration with Other Fluids
Compatibility of Propofol Injectable Emulsion with the coadministration of blood/serum/plasma has not been established (see WARNINGS). When administered using a y-type infusion set, Propofol Injectable Emulsion has been shown to be compatible with the following intravenous fluids.
- 5% Dextrose Injection, USP
- Lactated Ringers Injection, USP
- Lactated Ringers and 5% Dextrose Injection
- 5% Dextrose and 0.45% Sodium Chloride Injection, USP
- 5% Dextrose and 0.2% Sodium Chloride Injection, USP
Handling Procedures
General
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
Clinical experience with the use of in-line filters and Propofol Injectable Emulsion during anesthesia or ICU/MAC sedation is limited. Propofol Injectable Emulsion should only be administered through a filter with a pore size of 5 micron or greater unless it has been demonstrated that the filter does not restrict the flow of Propofol Injectable Emulsion and/or cause the breakdown of the emulsion. Filters should be used with caution and where clinically appropriate. Continuous monitoring is necessary due to the potential for restricted flow and/or breakdown of the emulsion.
Do not use if there is evidence of separation of the phases of the emulsion.
Rare cases of self-administration of Propofol Injectable Emulsion by health care professionals have been reported, including some fatalities (see DRUG ABUSE AND DEPENDENCE).
Strict aseptic technique must always be maintained during handling. Propofol Injectable Emulsion is a single-use parenteral product which contains 0.005% disodium edetate to inhibit the rate of growth of microorganisms, up to 12 hours, in the event of accidental extrinsic contamination. However, Propofol Injectable Emulsion can still support the growth of microorganisms as it is not an antimicrobially preserved product under USP standards. Accordingly, strict aseptic technique must still be adhered to. Do not use if contamination is suspected. Discard unused portions as directed within the required time limits (see DOSAGE AND ADMINISTRATION, Handling Procedures). There have been reports in which failure to use aseptic technique when handling Propofol Injectable Emulsion was associated with microbial contamination of the product and with fever, infection/sepsis, other life-threatening illness, and/or death.
Propofol, with EDTA inhibits microbial growth for up to 12 hours, as demonstrated by test data for representative USP microorganisms.
Guidelines for Aseptic Technique for General Anesthesia/MAC Sedation
Propofol Injectable Emulsion should be prepared for use just prior to initiation of each individual anesthetic/sedative procedure. The vial syringe rubber stopper should be disinfected using 70% isopropyl alcohol. Propofol Injectable Emulsion should be drawn into sterile syringes immediately after vials are opened. When withdrawing Propofol Injectable Emulsion from vials, a sterile vent spike should be used. The syringe(s) should be labeled with appropriate information including the date and time the vial was opened. Administration should commence promptly and be completed within 12 hours after the vials have been opened.
Propofol Injectable Emulsion should be prepared for single-patient use only. Any unused portions of Propofol Injectable Emulsion, reservoirs, dedicated administration tubing and/or solutions containing Propofol Injectable Emulsion must be discarded at the end of the anesthetic procedure or at 12 hours, whichever occurs sooner. The IV line should be flushed every 12 hours and at the end of the anesthetic procedure to remove residual Propofol Injectable Emulsion.
Guidelines for Aseptic Technique for ICU Sedation
Propofol Injectable Emulsion should be prepared for single-patient use only. When Propofol Injectable Emulsion is administered directly from the vial, strict aseptic techniques must be followed. The vial rubber stopper should be disinfected using 70% isopropyl alcohol. A sterile vent spike and sterile tubing must be used for administration of Propofol Injectable Emulsion. As with other lipid emulsions, the number of IV line manipulations should be minimized. Administration should commence promptly and must be completed within 12 hours after the vial has been spiked. The tubing and any unused portions of Propofol Injectable Emulsion must be discarded after 12 hours.
If Propofol Injectable Emulsion is transferred to a syringe or other container prior to administration, the handling procedures for General anesthesia/MAC sedation should be followed, and the product should be discarded and administration lines changed after 12 hours.
-
App Pharmaceuticals, Llc
Propofol | App Pharmaceuticals, Llc
Propofol blood concentrations at steady state are generally proportional to infusion rates, especially in individual patients. Undesirable effects such as cardiorespiratory depression are likely to occur at higher blood concentrations which result from bolus dosing or rapid increases in the infusion rate. An adequate interval (3 to 5 minutes) must be allowed between dose adjustments to allow for and assess the clinical effects.
Shake well before use. Do not use if there is evidence of excessive creaming or aggregation, if large droplets are visible, or if there are other forms of phase separation indicating that the stability of the product has been compromised. Slight creaming, which should disappear after shaking, may be visible upon prolonged standing.
When administering Propofol Injectable Emulsion by infusion, syringe or volumetric pumps are recommended to provide controlled infusion rates. When infusing Propofol Injectable Emulsion to patients undergoing magnetic resonance imaging, metered control devices may be utilized if mechanical pumps are impractical.
Changes in vital signs indicating a stress response to surgical stimulation or the emergence from anesthesia may be controlled by the administration of 25 mg (2.5 mL) to 50 mg (5 mL) incremental boluses and/or by increasing the infusion rate of Propofol Injectable Emulsion.
For minor surgical procedures (e.g., body surface) nitrous oxide (60% to 70%) can be combined with a variable rate Propofol Injectable Emulsion infusion to provide satisfactory anesthesia. With more stimulating surgical procedures (e.g., intra-abdominal), or if supplementation with nitrous oxide is not provided, administration rate(s) of Propofol Injectable Emulsion and/or opioids should be increased in order to provide adequate anesthesia.
Infusion rates should always be titrated downward in the absence of clinical signs of light anesthesia until a mild response to surgical stimulation is obtained in order to avoid administration of Propofol Injectable Emulsion at rates higher than are clinically necessary. Generally, rates of 50 to 100 mcg/kg/min in adults should be achieved during maintenance in order to optimize recovery times.
Other drugs that cause CNS depression (hypnotics/sedatives, inhalational anesthetics, and opioids) can increase CNS depression induced by propofol. Morphine premedication (0.15 mg/kg) with nitrous oxide 67% in oxygen has been shown to decrease the necessary propofol injection maintenance infusion rate and therapeutic blood concentrations when compared to non-narcotic (lorazepam) premedication.
Induction of General Anesthesia
Adult Patients
Most adult patients under 55 years of age and classified as ASA-PS I or II require 2 to 2.5 mg/kg of Propofol Injectable Emulsion for induction when unpremedicated or when premedicated with oral benzodiazepines or intramuscular opioids. For induction, Propofol Injectable Emulsion should be titrated (approximately 40 mg every 10 seconds) against the response of the patient until the clinical signs show the onset of anesthesia. As with other sedative-hypnotic agents, the amount of intravenous opioid and/or benzodiazepine premedication will influence the response of the patient to an induction dose of Propofol Injectable Emulsion.
Elderly, Debilitated, or ASA-PS III or IV Patients
It is important to be familiar and experienced with the intravenous use of Propofol Injectable Emulsion before treating elderly, debilitated, or ASA-PS III or IV patients. Due to the reduced clearance and higher blood concentrations, most of these patients require approximately 1 to 1.5 mg/kg (approximately 20 mg every 10 seconds) of Propofol Injectable Emulsion for induction of anesthesia according to their condition and responses. A rapid bolus should not be used, as this will increase the likelihood of undesirable cardiorespiratory depression including hypotension, apnea, airway obstruction, and/or oxygen desaturation (see DOSAGE AND ADMINISTRATION).
Pediatric Patients
Most patients aged 3 years through 16 years and classified ASA-PS I or II require 2.5 to 3.5 mg/kg of Propofol Injectable Emulsion for induction when unpremedicated or when lightly premedicated with oral benzodiazepines or intramuscular opioids. Within this dosage range, younger pediatric patients may require higher induction doses than older pediatric patients. As with other sedative‑hypnotic agents, the amount of intravenous opioid and/or benzodiazepine premedication will influence the response of the patient to an induction dose of Propofol Injectable Emulsion. A lower dosage is recommended for pediatric patients classified as ASA-PS III or IV. Attention should be paid to minimize pain on injection when administering Propofol Injectable Emulsion to pediatric patients. Boluses of Propofol Injectable Emulsion may be administered via small veins if pretreated with lidocaine or via antecubital or larger veins (see PRECAUTIONS, General).
Neurosurgical Patients
Slower induction is recommended using boluses of 20 mg every 10 seconds. Slower boluses or infusions of Propofol Injectable Emulsion for induction of anesthesia, titrated to clinical responses, will generally result in reduced induction dosage requirements (1 to 2 mg/kg) (see PRECAUTIONS and DOSAGE AND ADMINISTRATION).
Cardiac Anesthesia
Propofol Injectable Emulsion has been well-studied in patients with coronary artery disease, but experience in patients with hemodynamically significant valvular or congenital heart disease is limited. As with other anesthetic and sedative-hypnotic agents, Propofol Injectable Emulsion in healthy patients causes a decrease in blood pressure that is secondary to decreases in preload (ventricular filling volume at the end of the diastole) and afterload (arterial resistance at the beginning of the systole). The magnitude of these changes is proportional to the blood and effect site concentrations achieved. These concentrations depend upon the dose and speed of the induction and maintenance infusion rates.
In addition, lower heart rates are observed during maintenance with Propofol Injectable Emulsion, possibly due to reduction of the sympathetic activity and/or resetting of the baroreceptor reflexes. Therefore, anticholinergic agents should be administered when increases in vagal tone are anticipated.
As with other anesthetic agents, Propofol Injectable Emulsion reduces myocardial oxygen consumption. Further studies are needed to confirm and delineate the extent of these effects on the myocardium and the coronary vascular system.
Morphine premedication (0.15 mg/kg) with nitrous oxide 67% in oxygen has been shown to decrease the necessary Propofol Injectable Emulsion maintenance infusion rates and therapeutic blood concentrations when compared to non‑narcotic (lorazepam) premedication. The rate of Propofol Injectable Emulsion administration should be determined based on the patient's premedication and adjusted according to clinical responses.
A rapid bolus induction should be avoided. A slow rate of approximately 20 mg every 10 seconds until induction onset (0.5 to 1.5 mg/kg) should be used. In order to assure adequate anesthesia, when Propofol Injectable Emulsion is used as the primary agent, maintenance infusion rates should not be less than 100 mcg/kg/min and should be supplemented with analgesic levels of continuous opioid administration. When an opioid is used as the primary agent, Propofol Injectable Emulsion maintenance rates should not be less than 50 mcg/kg/min, and care should be taken to ensure amnesia. Higher doses of Propofol Injectable Emulsion will reduce the opioid requirements (see Table 4). When Propofol Injectable Emulsion is used as the primary anesthetic, it should not be administered with the high-dose opioid technique as this may increase the likelihood of hypotension (see PRECAUTIONS, Cardiac Anesthesia).
Table 4. Cardiac Anesthesia Techniques
Primary Agent
Rate
Secondary Agent/Rate
(Following Induction with Primary Agent)
Propofol Injectable Emulsion
OPIOIDa/0.05 to 0.075 mcg/kg/min (no bolus)
Preinduction
Anxiolysis
25 mcg/kg/min
Induction
0.5 to 1.5 mg/kg
over 60 sec
Maintenance
(Titrated to Clinical
Response)
100 to 150 mcg/kg/min
OPIOIDb
Propofol Injectable Emulsion/50 to 100 mcg/kg/min
(no bolus)
Induction
25 to 50 mcg/kg
Maintenance
0.2 to 0.3 mcg/kg/min
aOPIOID is defined in terms of fentanyl equivalents, i.e.,
1 mcg of fentanyl = 5 mcg of alfentanil (for bolus)
= 10 mcg of alfentanil (for maintenance)
or
= 0.1 mcg of sufentanil
bCare should be taken to ensure amnesia.
Maintenance of General Anesthesia
Adult Patients
In adults, anesthesia can be maintained by administering Propofol Injectable Emulsion by infusion or intermittent IV bolus injection. The patient's clinical response will determine the infusion rate or the amount and frequency of incremental injections.
Continuous Infusion
Propofol Injectable Emulsion 100 to 200 mcg/kg/min administered in a variable rate infusion with 60% to 70% nitrous oxide and oxygen provides anesthesia for patients undergoing general surgery. Maintenance by infusion of Propofol Injectable Emulsion should immediately follow the induction dose in order to provide satisfactory or continuous anesthesia during the induction phase. During this initial period following the induction dose, higher rates of infusion are generally required (150 to 200 mcg/kg/min) for the first 10 to 15 minutes. Infusion rates should subsequently be decreased 30% to 50% during the first half-hour of maintenance. Generally, rates of 50 to 100 mcg/kg/min in adults should be achieved during maintenance in order to optimize recovery times.
Other drugs that cause CNS depression (hypnotics/sedatives, inhalational anesthetics, and opioids) can increase the CNS depression induced by propofol.
Intermittent Bolus
Increments of Propofol Injectable Emulsion 25 mg (2.5 mL) to 50 mg (5 mL) may be administered with nitrous oxide in adult patients undergoing general surgery. The incremental boluses should be administered when changes in vital signs indicate a response to surgical stimulation or light anesthesia.
Pediatric Patients
Propofol Injectable Emulsion administered as a variable rate infusion supplemented with nitrous oxide 60% to 70% provides satisfactory anesthesia for most children 2 months of age or older, ASA-PS I or II, undergoing general anesthesia.
In general, for the pediatric population, maintenance by infusion of Propofol Injectable Emulsion at a rate of 200 to 300 mcg/kg/min should immediately follow the induction dose. Following the first half-hour of maintenance, infusion rates of 125 to 150 mcg/kg/min are typically needed. Propofol Injectable Emulsion should be titrated to achieve the desired clinical effect. Younger pediatric patients may require higher maintenance infusion rates than older pediatric patients. (See Table 2 Clinical Trials.)
Propofol Injectable Emulsion has been used with a variety of agents commonly used in anesthesia such as atropine, scopolamine, glycopyrrolate, diazepam, depolarizing and nondepolarizing muscle relaxants, and opioid analgesics, as well as with inhalational and regional anesthetic agents.
In the elderly, debilitated, or ASA-PS III or IV patients, rapid bolus doses should not be used, as this will increase cardiorespiratory effects including hypotension, apnea, airway obstruction, and oxygen desaturation.
Monitored Anesthesia Care (MAC) Sedation
Adult Patients
When Propofol Injectable Emulsion is administered for MAC sedation, rates of administration should be individualized and titrated to clinical response. In most patients, the rates of Propofol Injectable Emulsion administration will be in the range of 25 to 75 mcg/kg/min.
During initiation of MAC sedation, slow infusion or slow injection techniques are preferable over rapid bolus administration. During maintenance of MAC sedation, a variable rate infusion is preferable over intermittent bolus dose administration. In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation (see WARNINGS). A rapid bolus injection can result in undesirable cardiorespiratory depression including hypotension, apnea, airway obstruction, and oxygen desaturation.
Initiation of MAC Sedation
For initiation of MAC sedation, either an infusion or a slow injection method may be utilized while closely monitoring cardiorespiratory function. With the infusion method, sedation may be initiated by infusing Propofol Injectable Emulsion at 100 to 150 mcg/kg/min (6 to 9 mg/kg/h) for a period of 3 to 5 minutes and titrating to the desired clinical effect while closely monitoring respiratory function. With the slow injection method for initiation, patients will require approximately 0.5 mg/kg administered over 3 to 5 minutes and titrated to clinical responses. When Propofol Injectable Emulsion is administered slowly over 3 to 5 minutes, most patients will be adequately sedated, and the peak drug effect can be achieved while minimizing undesirable cardiorespiratory effects occurring at high plasma levels.
In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation (see WARNINGS). The rate of administration should be over 3 to 5 minutes and the dosage of Propofol Injectable Emulsion should be reduced to approximately 80% of the usual adult dosage in these patients according to their condition, responses, and changes in vital signs (see DOSAGE AND ADMINISTRATION).
Maintenance of MAC Sedation
For maintenance of sedation, a variable rate infusion method is preferable over an intermittent bolus dose method. With the variable rate infusion method, patients will generally require maintenance rates of 25 to 75 mcg/kg/min (1.5 to 4.5 mg/kg/h) during the first 10 to 15 minutes of sedation maintenance. Infusion rates should subsequently be decreased over time to 25 to 50 mcg/kg/min and adjusted to clinical responses. In titrating to clinical effect, allow approximately 2 minutes for onset of peak drug effect.
Infusion rates should always be titrated downward in the absence of clinical signs of light sedation until mild responses to stimulation are obtained in order to avoid sedative administration of Propofol Injectable Emulsion at rates higher than are clinically necessary.
If the intermittent bolus dose method is used, increments of Propofol Injectable Emulsion 10 mg (1 mL) or 20 mg (2 mL) can be administered and titrated to desired clinical effect. With the intermittent bolus method of sedation maintenance, there is increased potential for respiratory depression, transient increases in sedation depth, and prolongation of recovery.
In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation (see WARNINGS). The rate of administration and the dosage of Propofol Injectable Emulsion should be reduced to approximately 80% of the usual adult dosage in these patients according to their condition, responses, and changes in vital signs (see DOSAGE AND ADMINISTRATION).
Propofol Injectable Emulsion can be administered as the sole agent for maintenance of MAC sedation during surgical/diagnostic procedures. When Propofol Injectable Emulsion sedation is supplemented with opioid and/or benzodiazepine medications, these agents increase the sedative and respiratory effects of Propofol Injectable Emulsion and may also result in a slower recovery profile (see PRECAUTIONS, Drug Interactions).
ICU Sedation
(See WARNINGS and DOSAGE AND ADMINISTRATION, Handling Procedures.)
Abrupt discontinuation of Propofol Injectable Emulsion prior to weaning or for daily evaluation of sedation levels should be avoided. This may result in rapid awakening with associated anxiety, agitation, and resistance to mechanical ventilation. Infusions of Propofol Injectable Emulsion should be adjusted to assure a minimal level of sedation is maintained throughout the weaning process and when assessing the level of sedation (see PRECAUTIONS).
Adult Patients
For intubated, mechanically ventilated adult patients, Intensive Care Unit (ICU) sedation should be initiated slowly with a continuous infusion in order to titrate to desired clinical effect and minimize hypotension (see DOSAGE AND ADMINISTRATION).
Most adult ICU patients recovering from the effects of general anesthesia or deep sedation will require maintenance rates of 5 to 50 mcg/kg/min (0.3 to 3 mg/kg/h) individualized and titrated to clinical response (see DOSAGE AND ADMINISTRATION). With medical ICU patients or patients who have recovered from the effects of general anesthesia or deep sedation, the rate of administration of 50 mcg/kg/min or higher may be required to achieve adequate sedation. These higher rates of administration may increase the likelihood of patients developing hypotension. Administration should not exceed 4 mg/kg/hour unless the benefits outweigh the risks (see WARNINGS).
Dosage and rate of administration should be individualized and titrated to the desired effect, according to clinically relevant factors including the patient’s underlying medical problems, preinduction and concomitant medications, age, ASA-PS classification, and level of debilitation of the patient. The elderly, debilitated, and ASA-PS III or IV patients may have exaggerated hemodynamic and respiratory responses to rapid bolus doses (see WARNINGS).
Propofol Injectable Emulsion should be individualized according to the patient's condition and response, blood lipid profile, and vital signs (see PRECAUTIONS, Intensive Care Unit Sedation). For intubated, mechanically ventilated adult patients, Intensive Care Unit (ICU) sedation should be initiated slowly with a continuous infusion in order to titrate to desired clinical effect and minimize hypotension. When indicated, initiation of sedation should begin at 5 mcg/kg/min (0.3 mg/kg/h). The infusion rate should be increased by increments of 5 to 10 mcg/kg/min (0.3 to 0.6 mg/kg/h) until the desired level of sedation is achieved. A minimum period of 5 minutes between adjustments should be allowed for onset of peak drug effect. Most adult patients require maintenance rates of 5 to 50 mcg/kg/min (0.3 to 3 mg/kg/h) or higher. Administration should not exceed 4 mg/kg/hour unless the benefits outweigh the risks (see WARNINGS). Dosages of Propofol Injectable Emulsion should be reduced in patients who have received large dosages of narcotics. Conversely, the Propofol Injectable Emulsion dosage requirement may be reduced by adequate management of pain with analgesic agents. As with other sedative medications, there is interpatient variability in dosage requirements, and these requirements may change with time (see SUMMARY OF DOSAGE GUIDELINES). Evaluation of level of sedation and assessment of cns function should be carried out daily throughout maintenance to determine the minimum dose of PROPOFOL required for sedation (see Clinical Trials , Intensive Care Unit (ICU) Sedation). Bolus administration of 10 or 20 mg should only be used to rapidly increase depth of sedation in patients where hypotension is not likely to occur. Patients with compromised myocardial function, intravascular volume depletion, or abnormally low vascular tone (e.g., sepsis) may be more susceptible to hypotension (see PRECAUTIONS).
SUMMARY OF DOSAGE GUIDELINES :
Dosages and rates of administration in the following table should be individualized and titrated to clinical response. Safety and dosing requirements for induction of anesthesia in pediatric patients have only been established for children 3 years of age or older. Safety and dosing requirements for the maintenance of anesthesia have only been established for children 2 months of age and older.
For complete dosage information, see DOSAGE AND ADMINISTRATION.
INDICATION
DOSAGE AND ADMINISTRATION
Induction of General Anesthesia:
Healthy Adults Less Than 55 Years of Age:
40 mg every 10 seconds until induction onset (2 to 2.5 mg/kg).
Elderly, Debilitated, or ASA-PS III or IV Patients:
20 mg every 10 seconds until induction onset (1 to 1.5 mg/kg).
Cardiac Anesthesia:
20 mg every 10 seconds until induction onset (0.5 to 1.5 mg/kg).
Neurosurgical Patients:
20 mg every 10 seconds until induction onset (1 to 2 mg/kg)
Pediatric Patients – healthy, from 3 years to 16 years of age:
2.5 to 3.5 mg/kg administered over 20 to 30 seconds.
(see PRECAUTIONS, Pediatric Use and CLINICAL PHARMACOLOGY, Pediatrics)
Maintenance of General Anesthesia:
Infusion
Healthy Adults Less Than 55 Years of Age:
100 to 200 mcg/kg/min (6 to 12 mg/kg/h).
Elderly, Debilitated, ASA-PS III or IV Patients:
50 to 100 mcg/kg/min (3 to 6 mg/kg/h).
Cardiac Anesthesia: Most patients require:
Primary Propofol Injectable Emulsion with Secondary Opioid –
100 to 150 mcg/kg/min
Low-Dose Propofol Injectable Emulsion with Primary Opioid –
50 to 100 mcg/kg/min
(see DOSAGE AND ADMINISTRATION, Table 4)
Neurosurgical Patients:
100 to 200 mcg/kg/min (6 to 12 mg/kg/h).
Pediatric Patients - healthy, from 2 months of age to 16 years of age:
125 to 300 mcg/kg/min (7.5 to 18 mg/kg/h)
Following the first half hour of maintenance, if clinical signs of light
anesthesia are not present, the infusion rate should be decreased.
(see PRECAUTIONS, Pediatric Use and CLINICAL PHARMACOLOGY, Pediatrics)
Maintenance of General Anesthesia:
Intermittent Bolus
Healthy Adults Less Than 55 Years of Age:
Increments of 20 to 50 mg as needed.
Initiation of MAC Sedation:
Healthy Adults Less Than 55 Years of Age:
Slow infusion or slow injection techniques are recommended to avoid apnea
or hypotension. Most patients require an infusion of 100 to 150 mcg/kg/min
(6 to 9 mg/kg/h) for 3 to 5 minutes or a slow injection of 0.5 mg/kg over 3
to 5 minutes followed immediately by a maintenance infusion.
Elderly, Debilitated, Neurosurgical, or ASA-PS III or IV Patients:
Most patients require dosages similar to healthy adults.
Rapid boluses are to be avoided (see WARNINGS).
Maintenance of MAC Sedation:
Healthy Adults Less Than 55 Years of Age:
A variable rate infusion technique is preferable over an intermittent bolus
technique. Most patients require an infusion of 25 to 75 mcg/kg/min
(1.5 to 4.5 mg/kg/h) or incremental bolus doses of 10 mg or 20 mg.
In Elderly, Debilitated, Neurosurgical, or ASA-PS III or IV Patients:
Most patients require 80% of the usual adult dose. A rapid (single or
repeated) bolus dose should not be used (see WARNINGS).
Initiation and Maintenance of ICU Sedation in Intubated, Mechanically Ventilated
Adult Patients - Because of the residual effects of previous anesthetic or
sedative agents, in most patients the initial infusion should be 5 mcg/kg/min
(0.3 mg/kg/h) for at least 5 minutes. Subsequent increments of 5 to 10
mcg/kg/min (0.3 to 0.6 mg/kg/h) over 5 to 10 minutes may be used until
desired clinical effect is achieved. Maintenance rates of 5 to 50 mcg/kg/min
(0.3 to 3 mg/kg/h) or higher may be required. Administration should not
exceed 4 mg/kg/hour unless the benefits outweigh the risks (see WARNINGS).
Evaluation of clinical effect and assessment of CNS function should be
carried out daily throughout maintenance to determine the minimum
dose of Propofol Injectable Emulsion required for sedation.
The tubing and any unused portions of Propofol Injectable Emulsion
should be discarded after 12 hours because Propofol Injectable
Emulsion contains no preservatives and is capable of supporting growth
of microorganisms (see WARNINGS and DOSAGE AND ADMINISTRATION ).
Administration with Lidocaine
If lidocaine is to be administered to minimize pain on injection of Propofol, it is recommended that it be administered prior to Propofol administration or that it be added to Propofol immediately before administration and in quantities not exceeding 20 mg lidocaine/200 mg Propofol.
Compatibility and Stability
Propofol Injectable Emulsion should not be mixed with other therapeutic agents prior to administration.
Dilution Prior to Administration
Propofol Injectable Emulsion is provided as a ready-to-use formulation. However, should dilution be necessary, it should only be diluted with 5% Dextrose Injection, USP, and it should not be diluted to a concentration less than 2 mg/mL because it is an emulsion. In diluted form it has been shown to be more stable when in contact with glass than with plastic (95% potency after 2 hours of running infusion in plastic).
Administration with Other Fluids
Compatibility of Propofol Injectable Emulsion with the coadministration of blood/serum/plasma has not been established (see WARNINGS). When administered using a y-type infusion set, Propofol Injectable Emulsion has been shown to be compatible with the following intravenous fluids.
- 5% Dextrose Injection, USP
- Lactated Ringers Injection, USP
- Lactated Ringers and 5% Dextrose Injection
- 5% Dextrose and 0.45% Sodium Chloride Injection, USP
- 5% Dextrose and 0.2% Sodium Chloride Injection, USP
Handling Procedures
General
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
Clinical experience with the use of in-line filters and Propofol Injectable Emulsion during anesthesia or ICU/MAC sedation is limited. Propofol Injectable Emulsion should only be administered through a filter with a pore size of 5 micron or greater unless it has been demonstrated that the filter does not restrict the flow of Propofol Injectable Emulsion and/or cause the breakdown of the emulsion. Filters should be used with caution and where clinically appropriate. Continuous monitoring is necessary due to the potential for restricted flow and/or breakdown of the emulsion.
Do not use if there is evidence of separation of the phases of the emulsion.
Rare cases of self-administration of Propofol Injectable Emulsion by health care professionals have been reported, including some fatalities (see DRUG ABUSE AND DEPENDENCE).
Strict aseptic technique must always be maintained during handling. Propofol Injectable Emulsion is a single-use parenteral product which contains 0.005% disodium edetate to inhibit the rate of growth of microorganisms, up to 12 hours, in the event of accidental extrinsic contamination. However, Propofol Injectable Emulsion can still support the growth of microorganisms as it is not an antimicrobially preserved product under USP standards. Accordingly, strict aseptic technique must still be adhered to. Do not use if contamination is suspected. Discard unused portions as directed within the required time limits (see DOSAGE AND ADMINISTRATION, Handling Procedures). There have been reports in which failure to use aseptic technique when handling Propofol Injectable Emulsion was associated with microbial contamination of the product and with fever, infection/sepsis, other life-threatening illness, and/or death.
Propofol, with EDTA inhibits microbial growth for up to 12 hours, as demonstrated by test data for representative USP microorganisms.
Guidelines for Aseptic Technique for General Anesthesia/MAC Sedation
Propofol Injectable Emulsion should be prepared for use just prior to initiation of each individual anesthetic/sedative procedure. The vial syringe rubber stopper should be disinfected using 70% isopropyl alcohol. Propofol Injectable Emulsion should be drawn into sterile syringes immediately after vials are opened. When withdrawing Propofol Injectable Emulsion from vials, a sterile vent spike should be used. The syringe(s) should be labeled with appropriate information including the date and time the vial was opened. Administration should commence promptly and be completed within 12 hours after the vials have been opened.
Propofol Injectable Emulsion should be prepared for single-patient use only. Any unused portions of Propofol Injectable Emulsion, reservoirs, dedicated administration tubing and/or solutions containing Propofol Injectable Emulsion must be discarded at the end of the anesthetic procedure or at 12 hours, whichever occurs sooner. The IV line should be flushed every 12 hours and at the end of the anesthetic procedure to remove residual Propofol Injectable Emulsion.
Guidelines for Aseptic Technique for ICU Sedation
Propofol Injectable Emulsion should be prepared for single-patient use only. When Propofol Injectable Emulsion is administered directly from the vial, strict aseptic techniques must be followed. The vial rubber stopper should be disinfected using 70% isopropyl alcohol. A sterile vent spike and sterile tubing must be used for administration of Propofol Injectable Emulsion. As with other lipid emulsions, the number of IV line manipulations should be minimized. Administration should commence promptly and must be completed within 12 hours after the vial has been spiked. The tubing and any unused portions of Propofol Injectable Emulsion must be discarded after 12 hours.
If Propofol Injectable Emulsion is transferred to a syringe or other container prior to administration, the handling procedures for General anesthesia/MAC sedation should be followed, and the product should be discarded and administration lines changed after 12 hours.
Induction of General Anesthesia
Adult Patients
Most adult patients under 55 years of age and classified as ASA-PS I or II require 2 to 2.5 mg/kg of Propofol Injectable Emulsion for induction when unpremedicated or when premedicated with oral benzodiazepines or intramuscular opioids. For induction, Propofol Injectable Emulsion should be titrated (approximately 40 mg every 10 seconds) against the response of the patient until the clinical signs show the onset of anesthesia. As with other sedative-hypnotic agents, the amount of intravenous opioid and/or benzodiazepine premedication will influence the response of the patient to an induction dose of Propofol Injectable Emulsion.
Elderly, Debilitated, or ASA-PS III or IV Patients
It is important to be familiar and experienced with the intravenous use of Propofol Injectable Emulsion before treating elderly, debilitated, or ASA-PS III or IV patients. Due to the reduced clearance and higher blood concentrations, most of these patients require approximately 1 to 1.5 mg/kg (approximately 20 mg every 10 seconds) of Propofol Injectable Emulsion for induction of anesthesia according to their condition and responses. A rapid bolus should not be used, as this will increase the likelihood of undesirable cardiorespiratory depression including hypotension, apnea, airway obstruction, and/or oxygen desaturation (see DOSAGE AND ADMINISTRATION).
Pediatric Patients
Most patients aged 3 years through 16 years and classified ASA-PS I or II require 2.5 to 3.5 mg/kg of Propofol Injectable Emulsion for induction when unpremedicated or when lightly premedicated with oral benzodiazepines or intramuscular opioids. Within this dosage range, younger pediatric patients may require higher induction doses than older pediatric patients. As with other sedative‑hypnotic agents, the amount of intravenous opioid and/or benzodiazepine premedication will influence the response of the patient to an induction dose of Propofol Injectable Emulsion. A lower dosage is recommended for pediatric patients classified as ASA-PS III or IV. Attention should be paid to minimize pain on injection when administering Propofol Injectable Emulsion to pediatric patients. Boluses of Propofol Injectable Emulsion may be administered via small veins if pretreated with lidocaine or via antecubital or larger veins (see PRECAUTIONS, General).
Neurosurgical Patients
Slower induction is recommended using boluses of 20 mg every 10 seconds. Slower boluses or infusions of Propofol Injectable Emulsion for induction of anesthesia, titrated to clinical responses, will generally result in reduced induction dosage requirements (1 to 2 mg/kg) (see PRECAUTIONS and DOSAGE AND ADMINISTRATION).
Cardiac Anesthesia
Propofol Injectable Emulsion has been well-studied in patients with coronary artery disease, but experience in patients with hemodynamically significant valvular or congenital heart disease is limited. As with other anesthetic and sedative-hypnotic agents, Propofol Injectable Emulsion in healthy patients causes a decrease in blood pressure that is secondary to decreases in preload (ventricular filling volume at the end of the diastole) and afterload (arterial resistance at the beginning of the systole). The magnitude of these changes is proportional to the blood and effect site concentrations achieved. These concentrations depend upon the dose and speed of the induction and maintenance infusion rates.
In addition, lower heart rates are observed during maintenance with Propofol Injectable Emulsion, possibly due to reduction of the sympathetic activity and/or resetting of the baroreceptor reflexes. Therefore, anticholinergic agents should be administered when increases in vagal tone are anticipated.
As with other anesthetic agents, Propofol Injectable Emulsion reduces myocardial oxygen consumption. Further studies are needed to confirm and delineate the extent of these effects on the myocardium and the coronary vascular system.
Morphine premedication (0.15 mg/kg) with nitrous oxide 67% in oxygen has been shown to decrease the necessary Propofol Injectable Emulsion maintenance infusion rates and therapeutic blood concentrations when compared to non‑narcotic (lorazepam) premedication. The rate of Propofol Injectable Emulsion administration should be determined based on the patient's premedication and adjusted according to clinical responses.
A rapid bolus induction should be avoided. A slow rate of approximately 20 mg every 10 seconds until induction onset (0.5 to 1.5 mg/kg) should be used. In order to assure adequate anesthesia, when Propofol Injectable Emulsion is used as the primary agent, maintenance infusion rates should not be less than 100 mcg/kg/min and should be supplemented with analgesic levels of continuous opioid administration. When an opioid is used as the primary agent, Propofol Injectable Emulsion maintenance rates should not be less than 50 mcg/kg/min, and care should be taken to ensure amnesia. Higher doses of Propofol Injectable Emulsion will reduce the opioid requirements (see Table 4). When Propofol Injectable Emulsion is used as the primary anesthetic, it should not be administered with the high-dose opioid technique as this may increase the likelihood of hypotension (see PRECAUTIONS, Cardiac Anesthesia).
Table 4. Cardiac Anesthesia Techniques
Primary Agent
Rate
Secondary Agent/Rate
(Following Induction with Primary Agent)
Propofol Injectable Emulsion
OPIOIDa/0.05 to 0.075 mcg/kg/min (no bolus)
Preinduction
Anxiolysis
25 mcg/kg/min
Induction
0.5 to 1.5 mg/kg
over 60 sec
Maintenance
(Titrated to Clinical
Response)
100 to 150 mcg/kg/min
OPIOIDb
Propofol Injectable Emulsion/50 to 100 mcg/kg/min
(no bolus)
Induction
25 to 50 mcg/kg
Maintenance
0.2 to 0.3 mcg/kg/min
aOPIOID is defined in terms of fentanyl equivalents, i.e.,
1 mcg of fentanyl = 5 mcg of alfentanil (for bolus)
= 10 mcg of alfentanil (for maintenance)
or
= 0.1 mcg of sufentanil
bCare should be taken to ensure amnesia.
Maintenance of General Anesthesia
Adult Patients
In adults, anesthesia can be maintained by administering Propofol Injectable Emulsion by infusion or intermittent IV bolus injection. The patient's clinical response will determine the infusion rate or the amount and frequency of incremental injections.
Continuous Infusion
Propofol Injectable Emulsion 100 to 200 mcg/kg/min administered in a variable rate infusion with 60% to 70% nitrous oxide and oxygen provides anesthesia for patients undergoing general surgery. Maintenance by infusion of Propofol Injectable Emulsion should immediately follow the induction dose in order to provide satisfactory or continuous anesthesia during the induction phase. During this initial period following the induction dose, higher rates of infusion are generally required (150 to 200 mcg/kg/min) for the first 10 to 15 minutes. Infusion rates should subsequently be decreased 30% to 50% during the first half-hour of maintenance. Generally, rates of 50 to 100 mcg/kg/min in adults should be achieved during maintenance in order to optimize recovery times.
Other drugs that cause CNS depression (hypnotics/sedatives, inhalational anesthetics, and opioids) can increase the CNS depression induced by propofol.
Intermittent Bolus
Increments of Propofol Injectable Emulsion 25 mg (2.5 mL) to 50 mg (5 mL) may be administered with nitrous oxide in adult patients undergoing general surgery. The incremental boluses should be administered when changes in vital signs indicate a response to surgical stimulation or light anesthesia.
Pediatric Patients
Propofol Injectable Emulsion administered as a variable rate infusion supplemented with nitrous oxide 60% to 70% provides satisfactory anesthesia for most children 2 months of age or older, ASA-PS I or II, undergoing general anesthesia.
In general, for the pediatric population, maintenance by infusion of Propofol Injectable Emulsion at a rate of 200 to 300 mcg/kg/min should immediately follow the induction dose. Following the first half-hour of maintenance, infusion rates of 125 to 150 mcg/kg/min are typically needed. Propofol Injectable Emulsion should be titrated to achieve the desired clinical effect. Younger pediatric patients may require higher maintenance infusion rates than older pediatric patients. (See Table 2 Clinical Trials.)
Propofol Injectable Emulsion has been used with a variety of agents commonly used in anesthesia such as atropine, scopolamine, glycopyrrolate, diazepam, depolarizing and nondepolarizing muscle relaxants, and opioid analgesics, as well as with inhalational and regional anesthetic agents.
In the elderly, debilitated, or ASA-PS III or IV patients, rapid bolus doses should not be used, as this will increase cardiorespiratory effects including hypotension, apnea, airway obstruction, and oxygen desaturation.
Monitored Anesthesia Care (MAC) Sedation
Adult Patients
When Propofol Injectable Emulsion is administered for MAC sedation, rates of administration should be individualized and titrated to clinical response. In most patients, the rates of Propofol Injectable Emulsion administration will be in the range of 25 to 75 mcg/kg/min.
During initiation of MAC sedation, slow infusion or slow injection techniques are preferable over rapid bolus administration. During maintenance of MAC sedation, a variable rate infusion is preferable over intermittent bolus dose administration. In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation (see WARNINGS). A rapid bolus injection can result in undesirable cardiorespiratory depression including hypotension, apnea, airway obstruction, and oxygen desaturation.
Initiation of MAC Sedation
For initiation of MAC sedation, either an infusion or a slow injection method may be utilized while closely monitoring cardiorespiratory function. With the infusion method, sedation may be initiated by infusing Propofol Injectable Emulsion at 100 to 150 mcg/kg/min (6 to 9 mg/kg/h) for a period of 3 to 5 minutes and titrating to the desired clinical effect while closely monitoring respiratory function. With the slow injection method for initiation, patients will require approximately 0.5 mg/kg administered over 3 to 5 minutes and titrated to clinical responses. When Propofol Injectable Emulsion is administered slowly over 3 to 5 minutes, most patients will be adequately sedated, and the peak drug effect can be achieved while minimizing undesirable cardiorespiratory effects occurring at high plasma levels.
In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation (see WARNINGS). The rate of administration should be over 3 to 5 minutes and the dosage of Propofol Injectable Emulsion should be reduced to approximately 80% of the usual adult dosage in these patients according to their condition, responses, and changes in vital signs (see DOSAGE AND ADMINISTRATION).
Maintenance of MAC Sedation
For maintenance of sedation, a variable rate infusion method is preferable over an intermittent bolus dose method. With the variable rate infusion method, patients will generally require maintenance rates of 25 to 75 mcg/kg/min (1.5 to 4.5 mg/kg/h) during the first 10 to 15 minutes of sedation maintenance. Infusion rates should subsequently be decreased over time to 25 to 50 mcg/kg/min and adjusted to clinical responses. In titrating to clinical effect, allow approximately 2 minutes for onset of peak drug effect.
Infusion rates should always be titrated downward in the absence of clinical signs of light sedation until mild responses to stimulation are obtained in order to avoid sedative administration of Propofol Injectable Emulsion at rates higher than are clinically necessary.
If the intermittent bolus dose method is used, increments of Propofol Injectable Emulsion 10 mg (1 mL) or 20 mg (2 mL) can be administered and titrated to desired clinical effect. With the intermittent bolus method of sedation maintenance, there is increased potential for respiratory depression, transient increases in sedation depth, and prolongation of recovery.
In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation (see WARNINGS). The rate of administration and the dosage of Propofol Injectable Emulsion should be reduced to approximately 80% of the usual adult dosage in these patients according to their condition, responses, and changes in vital signs (see DOSAGE AND ADMINISTRATION).
Propofol Injectable Emulsion can be administered as the sole agent for maintenance of MAC sedation during surgical/diagnostic procedures. When Propofol Injectable Emulsion sedation is supplemented with opioid and/or benzodiazepine medications, these agents increase the sedative and respiratory effects of Propofol Injectable Emulsion and may also result in a slower recovery profile (see PRECAUTIONS, Drug Interactions).
ICU Sedation
(See WARNINGS and DOSAGE AND ADMINISTRATION, Handling Procedures.)
Abrupt discontinuation of Propofol Injectable Emulsion prior to weaning or for daily evaluation of sedation levels should be avoided. This may result in rapid awakening with associated anxiety, agitation, and resistance to mechanical ventilation. Infusions of Propofol Injectable Emulsion should be adjusted to assure a minimal level of sedation is maintained throughout the weaning process and when assessing the level of sedation (see PRECAUTIONS).
Adult Patients
For intubated, mechanically ventilated adult patients, Intensive Care Unit (ICU) sedation should be initiated slowly with a continuous infusion in order to titrate to desired clinical effect and minimize hypotension (see DOSAGE AND ADMINISTRATION).
Most adult ICU patients recovering from the effects of general anesthesia or deep sedation will require maintenance rates of 5 to 50 mcg/kg/min (0.3 to 3 mg/kg/h) individualized and titrated to clinical response (see DOSAGE AND ADMINISTRATION). With medical ICU patients or patients who have recovered from the effects of general anesthesia or deep sedation, the rate of administration of 50 mcg/kg/min or higher may be required to achieve adequate sedation. These higher rates of administration may increase the likelihood of patients developing hypotension. Administration should not exceed 4 mg/kg/hour unless the benefits outweigh the risks (see WARNINGS).
Dosage and rate of administration should be individualized and titrated to the desired effect, according to clinically relevant factors including the patient’s underlying medical problems, preinduction and concomitant medications, age, ASA-PS classification, and level of debilitation of the patient. The elderly, debilitated, and ASA-PS III or IV patients may have exaggerated hemodynamic and respiratory responses to rapid bolus doses (see WARNINGS).
Propofol Injectable Emulsion should be individualized according to the patient's condition and response, blood lipid profile, and vital signs (see PRECAUTIONS, Intensive Care Unit Sedation). For intubated, mechanically ventilated adult patients, Intensive Care Unit (ICU) sedation should be initiated slowly with a continuous infusion in order to titrate to desired clinical effect and minimize hypotension. When indicated, initiation of sedation should begin at 5 mcg/kg/min (0.3 mg/kg/h). The infusion rate should be increased by increments of 5 to 10 mcg/kg/min (0.3 to 0.6 mg/kg/h) until the desired level of sedation is achieved. A minimum period of 5 minutes between adjustments should be allowed for onset of peak drug effect. Most adult patients require maintenance rates of 5 to 50 mcg/kg/min (0.3 to 3 mg/kg/h) or higher. Administration should not exceed 4 mg/kg/hour unless the benefits outweigh the risks (see WARNINGS). Dosages of Propofol Injectable Emulsion should be reduced in patients who have received large dosages of narcotics. Conversely, the Propofol Injectable Emulsion dosage requirement may be reduced by adequate management of pain with analgesic agents. As with other sedative medications, there is interpatient variability in dosage requirements, and these requirements may change with time (see SUMMARY OF DOSAGE GUIDELINES). Evaluation of level of sedation and assessment of cns function should be carried out daily throughout maintenance to determine the minimum dose of PROPOFOL required for sedation (see Clinical Trials , Intensive Care Unit (ICU) Sedation). Bolus administration of 10 or 20 mg should only be used to rapidly increase depth of sedation in patients where hypotension is not likely to occur. Patients with compromised myocardial function, intravascular volume depletion, or abnormally low vascular tone (e.g., sepsis) may be more susceptible to hypotension (see PRECAUTIONS).
SUMMARY OF DOSAGE GUIDELINES :
Dosages and rates of administration in the following table should be individualized and titrated to clinical response. Safety and dosing requirements for induction of anesthesia in pediatric patients have only been established for children 3 years of age or older. Safety and dosing requirements for the maintenance of anesthesia have only been established for children 2 months of age and older.
For complete dosage information, see DOSAGE AND ADMINISTRATION.
INDICATION
DOSAGE AND ADMINISTRATION
Induction of General Anesthesia:
Healthy Adults Less Than 55 Years of Age:
40 mg every 10 seconds until induction onset (2 to 2.5 mg/kg).
Elderly, Debilitated, or ASA-PS III or IV Patients:
20 mg every 10 seconds until induction onset (1 to 1.5 mg/kg).
Cardiac Anesthesia:
20 mg every 10 seconds until induction onset (0.5 to 1.5 mg/kg).
Neurosurgical Patients:
20 mg every 10 seconds until induction onset (1 to 2 mg/kg)
Pediatric Patients – healthy, from 3 years to 16 years of age:
2.5 to 3.5 mg/kg administered over 20 to 30 seconds.
(see PRECAUTIONS, Pediatric Use and CLINICAL PHARMACOLOGY, Pediatrics)
Maintenance of General Anesthesia:
Infusion
Healthy Adults Less Than 55 Years of Age:
100 to 200 mcg/kg/min (6 to 12 mg/kg/h).
Elderly, Debilitated, ASA-PS III or IV Patients:
50 to 100 mcg/kg/min (3 to 6 mg/kg/h).
Cardiac Anesthesia: Most patients require:
Primary Propofol Injectable Emulsion with Secondary Opioid –
100 to 150 mcg/kg/min
Low-Dose Propofol Injectable Emulsion with Primary Opioid –
50 to 100 mcg/kg/min
(see DOSAGE AND ADMINISTRATION, Table 4)
Neurosurgical Patients:
100 to 200 mcg/kg/min (6 to 12 mg/kg/h).
Pediatric Patients - healthy, from 2 months of age to 16 years of age:
125 to 300 mcg/kg/min (7.5 to 18 mg/kg/h)
Following the first half hour of maintenance, if clinical signs of light
anesthesia are not present, the infusion rate should be decreased.
(see PRECAUTIONS, Pediatric Use and CLINICAL PHARMACOLOGY, Pediatrics)
Maintenance of General Anesthesia:
Intermittent Bolus
Healthy Adults Less Than 55 Years of Age:
Increments of 20 to 50 mg as needed.
Initiation of MAC Sedation:
Healthy Adults Less Than 55 Years of Age:
Slow infusion or slow injection techniques are recommended to avoid apnea
or hypotension. Most patients require an infusion of 100 to 150 mcg/kg/min
(6 to 9 mg/kg/h) for 3 to 5 minutes or a slow injection of 0.5 mg/kg over 3
to 5 minutes followed immediately by a maintenance infusion.
Elderly, Debilitated, Neurosurgical, or ASA-PS III or IV Patients:
Most patients require dosages similar to healthy adults.
Rapid boluses are to be avoided (see WARNINGS).
Maintenance of MAC Sedation:
Healthy Adults Less Than 55 Years of Age:
A variable rate infusion technique is preferable over an intermittent bolus
technique. Most patients require an infusion of 25 to 75 mcg/kg/min
(1.5 to 4.5 mg/kg/h) or incremental bolus doses of 10 mg or 20 mg.
In Elderly, Debilitated, Neurosurgical, or ASA-PS III or IV Patients:
Most patients require 80% of the usual adult dose. A rapid (single or
repeated) bolus dose should not be used (see WARNINGS).
Initiation and Maintenance of ICU Sedation in Intubated, Mechanically Ventilated
Adult Patients - Because of the residual effects of previous anesthetic or
sedative agents, in most patients the initial infusion should be 5 mcg/kg/min
(0.3 mg/kg/h) for at least 5 minutes. Subsequent increments of 5 to 10
mcg/kg/min (0.3 to 0.6 mg/kg/h) over 5 to 10 minutes may be used until
desired clinical effect is achieved. Maintenance rates of 5 to 50 mcg/kg/min
(0.3 to 3 mg/kg/h) or higher may be required. Administration should not
exceed 4 mg/kg/hour unless the benefits outweigh the risks (see WARNINGS).
Evaluation of clinical effect and assessment of CNS function should be
carried out daily throughout maintenance to determine the minimum
dose of Propofol Injectable Emulsion required for sedation.
The tubing and any unused portions of Propofol Injectable Emulsion
should be discarded after 12 hours because Propofol Injectable
Emulsion contains no preservatives and is capable of supporting growth
of microorganisms (see WARNINGS and DOSAGE AND ADMINISTRATION ).
Administration with Lidocaine
If lidocaine is to be administered to minimize pain on injection of Propofol, it is recommended that it be administered prior to Propofol administration or that it be added to Propofol immediately before administration and in quantities not exceeding 20 mg lidocaine/200 mg Propofol.
Compatibility and Stability
Propofol Injectable Emulsion should not be mixed with other therapeutic agents prior to administration.
Dilution Prior to Administration
Propofol Injectable Emulsion is provided as a ready-to-use formulation. However, should dilution be necessary, it should only be diluted with 5% Dextrose Injection, USP, and it should not be diluted to a concentration less than 2 mg/mL because it is an emulsion. In diluted form it has been shown to be more stable when in contact with glass than with plastic (95% potency after 2 hours of running infusion in plastic).
Administration with Other Fluids
Compatibility of Propofol Injectable Emulsion with the coadministration of blood/serum/plasma has not been established (see WARNINGS). When administered using a y-type infusion set, Propofol Injectable Emulsion has been shown to be compatible with the following intravenous fluids.
- 5% Dextrose Injection, USP
- Lactated Ringers Injection, USP
- Lactated Ringers and 5% Dextrose Injection
- 5% Dextrose and 0.45% Sodium Chloride Injection, USP
- 5% Dextrose and 0.2% Sodium Chloride Injection, USP
Handling Procedures
General
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
Clinical experience with the use of in-line filters and Propofol Injectable Emulsion during anesthesia or ICU/MAC sedation is limited. Propofol Injectable Emulsion should only be administered through a filter with a pore size of 5 micron or greater unless it has been demonstrated that the filter does not restrict the flow of Propofol Injectable Emulsion and/or cause the breakdown of the emulsion. Filters should be used with caution and where clinically appropriate. Continuous monitoring is necessary due to the potential for restricted flow and/or breakdown of the emulsion.
Do not use if there is evidence of separation of the phases of the emulsion.
Rare cases of self-administration of Propofol Injectable Emulsion by health care professionals have been reported, including some fatalities (see DRUG ABUSE AND DEPENDENCE).
Strict aseptic technique must always be maintained during handling. Propofol Injectable Emulsion is a single-use parenteral product which contains 0.005% disodium edetate to inhibit the rate of growth of microorganisms, up to 12 hours, in the event of accidental extrinsic contamination. However, Propofol Injectable Emulsion can still support the growth of microorganisms as it is not an antimicrobially preserved product under USP standards. Accordingly, strict aseptic technique must still be adhered to. Do not use if contamination is suspected. Discard unused portions as directed within the required time limits (see DOSAGE AND ADMINISTRATION, Handling Procedures). There have been reports in which failure to use aseptic technique when handling Propofol Injectable Emulsion was associated with microbial contamination of the product and with fever, infection/sepsis, other life-threatening illness, and/or death.
Propofol, with EDTA inhibits microbial growth for up to 12 hours, as demonstrated by test data for representative USP microorganisms.
Guidelines for Aseptic Technique for General Anesthesia/MAC Sedation
Propofol Injectable Emulsion should be prepared for use just prior to initiation of each individual anesthetic/sedative procedure. The vial syringe rubber stopper should be disinfected using 70% isopropyl alcohol. Propofol Injectable Emulsion should be drawn into sterile syringes immediately after vials are opened. When withdrawing Propofol Injectable Emulsion from vials, a sterile vent spike should be used. The syringe(s) should be labeled with appropriate information including the date and time the vial was opened. Administration should commence promptly and be completed within 12 hours after the vials have been opened.
Propofol Injectable Emulsion should be prepared for single-patient use only. Any unused portions of Propofol Injectable Emulsion, reservoirs, dedicated administration tubing and/or solutions containing Propofol Injectable Emulsion must be discarded at the end of the anesthetic procedure or at 12 hours, whichever occurs sooner. The IV line should be flushed every 12 hours and at the end of the anesthetic procedure to remove residual Propofol Injectable Emulsion.
Guidelines for Aseptic Technique for ICU Sedation
Propofol Injectable Emulsion should be prepared for single-patient use only. When Propofol Injectable Emulsion is administered directly from the vial, strict aseptic techniques must be followed. The vial rubber stopper should be disinfected using 70% isopropyl alcohol. A sterile vent spike and sterile tubing must be used for administration of Propofol Injectable Emulsion. As with other lipid emulsions, the number of IV line manipulations should be minimized. Administration should commence promptly and must be completed within 12 hours after the vial has been spiked. The tubing and any unused portions of Propofol Injectable Emulsion must be discarded after 12 hours.
If Propofol Injectable Emulsion is transferred to a syringe or other container prior to administration, the handling procedures for General anesthesia/MAC sedation should be followed, and the product should be discarded and administration lines changed after 12 hours.
-
Fresenius Kabi Usa, Llc
Propofol | Fresenius Kabi Usa, Llc
Propofol blood concentrations at steady state are generally proportional to infusion rates, especially in individual patients. Undesirable effects such as cardiorespiratory depression are likely to occur at higher blood concentrations which result from bolus dosing or rapid increases in the infusion rate. An adequate interval (3 to 5 minutes) must be allowed between dose adjustments to allow for and assess the clinical effects.
Shake well before use. Do not use if there is evidence of excessive creaming or aggregation, if large droplets are visible, or if there are other forms of phase separation indicating that the stability of the product has been compromised. Slight creaming, which should disappear after shaking, may be visible upon prolonged standing.
When administering Propofol Injectable Emulsion by infusion, syringe or volumetric pumps are recommended to provide controlled infusion rates. When infusing Propofol Injectable Emulsion to patients undergoing magnetic resonance imaging, metered control devices may be utilized if mechanical pumps are impractical.
Changes in vital signs indicating a stress response to surgical stimulation or the emergence from anesthesia may be controlled by the administration of 25 mg (2.5 mL) to 50 mg (5 mL) incremental boluses and/or by increasing the infusion rate of Propofol Injectable Emulsion.
For minor surgical procedures (e.g., body surface) nitrous oxide (60% to 70%) can be combined with a variable rate Propofol Injectable Emulsion infusion to provide satisfactory anesthesia. With more stimulating surgical procedures (e.g., intra-abdominal), or if supplementation with nitrous oxide is not provided, administration rate(s) of Propofol Injectable Emulsion and/or opioids should be increased in order to provide adequate anesthesia.
Infusion rates should always be titrated downward in the absence of clinical signs of light anesthesia until a mild response to surgical stimulation is obtained in order to avoid administration of Propofol Injectable Emulsion at rates higher than are clinically necessary. Generally, rates of 50 to 100 mcg/kg/min in adults should be achieved during maintenance in order to optimize recovery times.
Other drugs that cause CNS depression (hypnotics/sedatives, inhalational anesthetics, and opioids) can increase CNS depression induced by propofol. Morphine premedication (0.15 mg/kg) with nitrous oxide 67% in oxygen has been shown to decrease the necessary propofol injection maintenance infusion rate and therapeutic blood concentrations when compared to non-narcotic (lorazepam) premedication.
Induction of General Anesthesia
Adult Patients
Most adult patients under 55 years of age and classified as ASA-PS I or II require 2 to 2.5 mg/kg of Propofol Injectable Emulsion for induction when unpremedicated or when premedicated with oral benzodiazepines or intramuscular opioids. For induction, Propofol Injectable Emulsion should be titrated (approximately 40 mg every 10 seconds) against the response of the patient until the clinical signs show the onset of anesthesia. As with other sedative-hypnotic agents, the amount of intravenous opioid and/or benzodiazepine premedication will influence the response of the patient to an induction dose of Propofol Injectable Emulsion.
Elderly, Debilitated, or ASA-PS III or IV Patients
It is important to be familiar and experienced with the intravenous use of Propofol Injectable Emulsion before treating elderly, debilitated, or ASA-PS III or IV patients. Due to the reduced clearance and higher blood concentrations, most of these patients require approximately 1 to 1.5 mg/kg (approximately 20 mg every 10 seconds) of Propofol Injectable Emulsion for induction of anesthesia according to their condition and responses. A rapid bolus should not be used, as this will increase the likelihood of undesirable cardiorespiratory depression including hypotension, apnea, airway obstruction, and/or oxygen desaturation (see DOSAGE AND ADMINISTRATION).
Pediatric Patients
Most patients aged 3 years through 16 years and classified ASA-PS I or II require 2.5 to 3.5 mg/kg of Propofol Injectable Emulsion for induction when unpremedicated or when lightly premedicated with oral benzodiazepines or intramuscular opioids. Within this dosage range, younger pediatric patients may require higher induction doses than older pediatric patients. As with other sedative‑hypnotic agents, the amount of intravenous opioid and/or benzodiazepine premedication will influence the response of the patient to an induction dose of Propofol Injectable Emulsion. A lower dosage is recommended for pediatric patients classified as ASA-PS III or IV. Attention should be paid to minimize pain on injection when administering Propofol Injectable Emulsion to pediatric patients. Boluses of Propofol Injectable Emulsion may be administered via small veins if pretreated with lidocaine or via antecubital or larger veins (see PRECAUTIONS, General).
Neurosurgical Patients
Slower induction is recommended using boluses of 20 mg every 10 seconds. Slower boluses or infusions of Propofol Injectable Emulsion for induction of anesthesia, titrated to clinical responses, will generally result in reduced induction dosage requirements (1 to 2 mg/kg) (see PRECAUTIONS and DOSAGE AND ADMINISTRATION).
Cardiac Anesthesia
Propofol Injectable Emulsion has been well-studied in patients with coronary artery disease, but experience in patients with hemodynamically significant valvular or congenital heart disease is limited. As with other anesthetic and sedative-hypnotic agents, Propofol Injectable Emulsion in healthy patients causes a decrease in blood pressure that is secondary to decreases in preload (ventricular filling volume at the end of the diastole) and afterload (arterial resistance at the beginning of the systole). The magnitude of these changes is proportional to the blood and effect site concentrations achieved. These concentrations depend upon the dose and speed of the induction and maintenance infusion rates.
In addition, lower heart rates are observed during maintenance with Propofol Injectable Emulsion, possibly due to reduction of the sympathetic activity and/or resetting of the baroreceptor reflexes. Therefore, anticholinergic agents should be administered when increases in vagal tone are anticipated.
As with other anesthetic agents, Propofol Injectable Emulsion reduces myocardial oxygen consumption. Further studies are needed to confirm and delineate the extent of these effects on the myocardium and the coronary vascular system.
Morphine premedication (0.15 mg/kg) with nitrous oxide 67% in oxygen has been shown to decrease the necessary Propofol Injectable Emulsion maintenance infusion rates and therapeutic blood concentrations when compared to non‑narcotic (lorazepam) premedication. The rate of Propofol Injectable Emulsion administration should be determined based on the patient's premedication and adjusted according to clinical responses.
A rapid bolus induction should be avoided. A slow rate of approximately 20 mg every 10 seconds until induction onset (0.5 to 1.5 mg/kg) should be used. In order to assure adequate anesthesia, when Propofol Injectable Emulsion is used as the primary agent, maintenance infusion rates should not be less than 100 mcg/kg/min and should be supplemented with analgesic levels of continuous opioid administration. When an opioid is used as the primary agent, Propofol Injectable Emulsion maintenance rates should not be less than 50 mcg/kg/min, and care should be taken to ensure amnesia. Higher doses of Propofol Injectable Emulsion will reduce the opioid requirements (see Table 4). When Propofol Injectable Emulsion is used as the primary anesthetic, it should not be administered with the high-dose opioid technique as this may increase the likelihood of hypotension (see PRECAUTIONS, Cardiac Anesthesia).
Table 4. Cardiac Anesthesia Techniques
Primary Agent
Rate
Secondary Agent/Rate
(Following Induction with Primary Agent)
Propofol Injectable Emulsion
OPIOIDa/0.05 to 0.075 mcg/kg/min (no bolus)
Preinduction
Anxiolysis
25 mcg/kg/min
Induction
0.5 to 1.5 mg/kg
over 60 sec
Maintenance
(Titrated to Clinical
Response)
100 to 150 mcg/kg/min
OPIOIDb
Propofol Injectable Emulsion/50 to 100 mcg/kg/min
(no bolus)
Induction
25 to 50 mcg/kg
Maintenance
0.2 to 0.3 mcg/kg/min
aOPIOID is defined in terms of fentanyl equivalents, i.e.,
1 mcg of fentanyl = 5 mcg of alfentanil (for bolus)
= 10 mcg of alfentanil (for maintenance)
or
= 0.1 mcg of sufentanil
bCare should be taken to ensure amnesia.
Maintenance of General Anesthesia
Adult Patients
In adults, anesthesia can be maintained by administering Propofol Injectable Emulsion by infusion or intermittent IV bolus injection. The patient's clinical response will determine the infusion rate or the amount and frequency of incremental injections.
Continuous Infusion
Propofol Injectable Emulsion 100 to 200 mcg/kg/min administered in a variable rate infusion with 60% to 70% nitrous oxide and oxygen provides anesthesia for patients undergoing general surgery. Maintenance by infusion of Propofol Injectable Emulsion should immediately follow the induction dose in order to provide satisfactory or continuous anesthesia during the induction phase. During this initial period following the induction dose, higher rates of infusion are generally required (150 to 200 mcg/kg/min) for the first 10 to 15 minutes. Infusion rates should subsequently be decreased 30% to 50% during the first half-hour of maintenance. Generally, rates of 50 to 100 mcg/kg/min in adults should be achieved during maintenance in order to optimize recovery times.
Other drugs that cause CNS depression (hypnotics/sedatives, inhalational anesthetics, and opioids) can increase the CNS depression induced by propofol.
Intermittent Bolus
Increments of Propofol Injectable Emulsion 25 mg (2.5 mL) to 50 mg (5 mL) may be administered with nitrous oxide in adult patients undergoing general surgery. The incremental boluses should be administered when changes in vital signs indicate a response to surgical stimulation or light anesthesia.
Pediatric Patients
Propofol Injectable Emulsion administered as a variable rate infusion supplemented with nitrous oxide 60% to 70% provides satisfactory anesthesia for most children 2 months of age or older, ASA-PS I or II, undergoing general anesthesia.
In general, for the pediatric population, maintenance by infusion of Propofol Injectable Emulsion at a rate of 200 to 300 mcg/kg/min should immediately follow the induction dose. Following the first half-hour of maintenance, infusion rates of 125 to 150 mcg/kg/min are typically needed. Propofol Injectable Emulsion should be titrated to achieve the desired clinical effect. Younger pediatric patients may require higher maintenance infusion rates than older pediatric patients. (See Table 2 Clinical Trials.)
Propofol Injectable Emulsion has been used with a variety of agents commonly used in anesthesia such as atropine, scopolamine, glycopyrrolate, diazepam, depolarizing and nondepolarizing muscle relaxants, and opioid analgesics, as well as with inhalational and regional anesthetic agents.
In the elderly, debilitated, or ASA-PS III or IV patients, rapid bolus doses should not be used, as this will increase cardiorespiratory effects including hypotension, apnea, airway obstruction, and oxygen desaturation.
Monitored Anesthesia Care (MAC) Sedation
Adult Patients
When Propofol Injectable Emulsion is administered for MAC sedation, rates of administration should be individualized and titrated to clinical response. In most patients, the rates of Propofol Injectable Emulsion administration will be in the range of 25 to 75 mcg/kg/min.
During initiation of MAC sedation, slow infusion or slow injection techniques are preferable over rapid bolus administration. During maintenance of MAC sedation, a variable rate infusion is preferable over intermittent bolus dose administration. In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation (see WARNINGS). A rapid bolus injection can result in undesirable cardiorespiratory depression including hypotension, apnea, airway obstruction, and oxygen desaturation.
Initiation of MAC Sedation
For initiation of MAC sedation, either an infusion or a slow injection method may be utilized while closely monitoring cardiorespiratory function. With the infusion method, sedation may be initiated by infusing Propofol Injectable Emulsion at 100 to 150 mcg/kg/min (6 to 9 mg/kg/h) for a period of 3 to 5 minutes and titrating to the desired clinical effect while closely monitoring respiratory function. With the slow injection method for initiation, patients will require approximately 0.5 mg/kg administered over 3 to 5 minutes and titrated to clinical responses. When Propofol Injectable Emulsion is administered slowly over 3 to 5 minutes, most patients will be adequately sedated, and the peak drug effect can be achieved while minimizing undesirable cardiorespiratory effects occurring at high plasma levels.
In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation (see WARNINGS). The rate of administration should be over 3 to 5 minutes and the dosage of Propofol Injectable Emulsion should be reduced to approximately 80% of the usual adult dosage in these patients according to their condition, responses, and changes in vital signs (see DOSAGE AND ADMINISTRATION).
Maintenance of MAC Sedation
For maintenance of sedation, a variable rate infusion method is preferable over an intermittent bolus dose method. With the variable rate infusion method, patients will generally require maintenance rates of 25 to 75 mcg/kg/min (1.5 to 4.5 mg/kg/h) during the first 10 to 15 minutes of sedation maintenance. Infusion rates should subsequently be decreased over time to 25 to 50 mcg/kg/min and adjusted to clinical responses. In titrating to clinical effect, allow approximately 2 minutes for onset of peak drug effect.
Infusion rates should always be titrated downward in the absence of clinical signs of light sedation until mild responses to stimulation are obtained in order to avoid sedative administration of Propofol Injectable Emulsion at rates higher than are clinically necessary.
If the intermittent bolus dose method is used, increments of Propofol Injectable Emulsion 10 mg (1 mL) or 20 mg (2 mL) can be administered and titrated to desired clinical effect. With the intermittent bolus method of sedation maintenance, there is increased potential for respiratory depression, transient increases in sedation depth, and prolongation of recovery.
In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation (see WARNINGS). The rate of administration and the dosage of Propofol Injectable Emulsion should be reduced to approximately 80% of the usual adult dosage in these patients according to their condition, responses, and changes in vital signs (see DOSAGE AND ADMINISTRATION).
Propofol Injectable Emulsion can be administered as the sole agent for maintenance of MAC sedation during surgical/diagnostic procedures. When Propofol Injectable Emulsion sedation is supplemented with opioid and/or benzodiazepine medications, these agents increase the sedative and respiratory effects of Propofol Injectable Emulsion and may also result in a slower recovery profile (see PRECAUTIONS, Drug Interactions).
ICU Sedation
(See WARNINGS and DOSAGE AND ADMINISTRATION, Handling Procedures.)
Abrupt discontinuation of Propofol Injectable Emulsion prior to weaning or for daily evaluation of sedation levels should be avoided. This may result in rapid awakening with associated anxiety, agitation, and resistance to mechanical ventilation. Infusions of Propofol Injectable Emulsion should be adjusted to assure a minimal level of sedation is maintained throughout the weaning process and when assessing the level of sedation (see PRECAUTIONS).
Adult Patients
For intubated, mechanically ventilated adult patients, Intensive Care Unit (ICU) sedation should be initiated slowly with a continuous infusion in order to titrate to desired clinical effect and minimize hypotension (see DOSAGE AND ADMINISTRATION).
Most adult ICU patients recovering from the effects of general anesthesia or deep sedation will require maintenance rates of 5 to 50 mcg/kg/min (0.3 to 3 mg/kg/h) individualized and titrated to clinical response (see DOSAGE AND ADMINISTRATION). With medical ICU patients or patients who have recovered from the effects of general anesthesia or deep sedation, the rate of administration of 50 mcg/kg/min or higher may be required to achieve adequate sedation. These higher rates of administration may increase the likelihood of patients developing hypotension. Administration should not exceed 4 mg/kg/hour unless the benefits outweigh the risks (see WARNINGS).
Dosage and rate of administration should be individualized and titrated to the desired effect, according to clinically relevant factors including the patient’s underlying medical problems, preinduction and concomitant medications, age, ASA-PS classification, and level of debilitation of the patient. The elderly, debilitated, and ASA-PS III or IV patients may have exaggerated hemodynamic and respiratory responses to rapid bolus doses (see WARNINGS).
Propofol Injectable Emulsion should be individualized according to the patient's condition and response, blood lipid profile, and vital signs (see PRECAUTIONS, Intensive Care Unit Sedation). For intubated, mechanically ventilated adult patients, Intensive Care Unit (ICU) sedation should be initiated slowly with a continuous infusion in order to titrate to desired clinical effect and minimize hypotension. When indicated, initiation of sedation should begin at 5 mcg/kg/min (0.3 mg/kg/h). The infusion rate should be increased by increments of 5 to 10 mcg/kg/min (0.3 to 0.6 mg/kg/h) until the desired level of sedation is achieved. A minimum period of 5 minutes between adjustments should be allowed for onset of peak drug effect. Most adult patients require maintenance rates of 5 to 50 mcg/kg/min (0.3 to 3 mg/kg/h) or higher. Administration should not exceed 4 mg/kg/hour unless the benefits outweigh the risks (see WARNINGS). Dosages of Propofol Injectable Emulsion should be reduced in patients who have received large dosages of narcotics. Conversely, the Propofol Injectable Emulsion dosage requirement may be reduced by adequate management of pain with analgesic agents. As with other sedative medications, there is interpatient variability in dosage requirements, and these requirements may change with time (see SUMMARY OF DOSAGE GUIDELINES). Evaluation of level of sedation and assessment of cns function should be carried out daily throughout maintenance to determine the minimum dose of PROPOFOL required for sedation (see Clinical Trials, Intensive Care Unit (ICU) Sedation). Bolus administration of 10 or 20 mg should only be used to rapidly increase depth of sedation in patients where hypotension is not likely to occur. Patients with compromised myocardial function, intravascular volume depletion, or abnormally low vascular tone (e.g., sepsis) may be more susceptible to hypotension (see PRECAUTIONS).
SUMMARY OF DOSAGE GUIDELINES:
Dosages and rates of administration in the following table should be individualized and titrated to clinical response. Safety and dosing requirements for induction of anesthesia in pediatric patients have only been established for children 3 years of age or older. Safety and dosing requirements for the maintenance of anesthesia have only been established for children 2 months of age and older.
For complete dosage information, see DOSAGE AND ADMINISTRATION.
INDICATION
DOSAGE AND ADMINISTRATION
Induction of General Anesthesia:
Healthy Adults Less Than 55 Years of Age:
40 mg every 10 seconds until induction onset (2 to 2.5 mg/kg).
Elderly, Debilitated, or ASA-PS III or IV Patients:
20 mg every 10 seconds until induction onset (1 to 1.5 mg/kg).
Cardiac Anesthesia:
20 mg every 10 seconds until induction onset (0.5 to 1.5 mg/kg).
Neurosurgical Patients:
20 mg every 10 seconds until induction onset (1 to 2 mg/kg)
Pediatric Patients – healthy, from 3 years to 16 years of age:
2.5 to 3.5 mg/kg administered over 20 to 30 seconds.
(see PRECAUTIONS, Pediatric Use and CLINICAL PHARMACOLOGY, Pediatrics)
Maintenance of General Anesthesia:
Infusion
Healthy Adults Less Than 55 Years of Age:
100 to 200 mcg/kg/min (6 to 12 mg/kg/h).
Elderly, Debilitated, ASA-PS III or IV Patients:
50 to 100 mcg/kg/min (3 to 6 mg/kg/h).
Cardiac Anesthesia: Most patients require:
Primary Propofol Injectable Emulsion with Secondary Opioid –
100 to 150 mcg/kg/min
Low-Dose Propofol Injectable Emulsion with Primary Opioid –
50 to 100 mcg/kg/min
(see DOSAGE AND ADMINISTRATION, Table 4)
Neurosurgical Patients:
100 to 200 mcg/kg/min (6 to 12 mg/kg/h).
Pediatric Patients - healthy, from 2 months of age to 16 years of age:
125 to 300 mcg/kg/min (7.5 to 18 mg/kg/h)
Following the first half hour of maintenance, if clinical signs of light
anesthesia are not present, the infusion rate should be decreased.
(see PRECAUTIONS, Pediatric Use and CLINICAL PHARMACOLOGY, Pediatrics)
Maintenance of General Anesthesia:
Intermittent Bolus
Healthy Adults Less Than 55 Years of Age:
Increments of 20 to 50 mg as needed.
Initiation of MAC Sedation:
Healthy Adults Less Than 55 Years of Age:
Slow infusion or slow injection techniques are recommended to avoid apnea
or hypotension. Most patients require an infusion of 100 to 150 mcg/kg/min
(6 to 9 mg/kg/h) for 3 to 5 minutes or a slow injection of 0.5 mg/kg over 3
to 5 minutes followed immediately by a maintenance infusion.
Elderly, Debilitated, Neurosurgical, or ASA-PS III or IV Patients:
Most patients require dosages similar to healthy adults.
Rapid boluses are to be avoided (see WARNINGS).
Maintenance of MAC Sedation:
Healthy Adults Less Than 55 Years of Age:
A variable rate infusion technique is preferable over an intermittent bolus
technique. Most patients require an infusion of 25 to 75 mcg/kg/min
(1.5 to 4.5 mg/kg/h) or incremental bolus doses of 10 mg or 20 mg.
In Elderly, Debilitated, Neurosurgical, or ASA-PS III or IV Patients:
Most patients require 80% of the usual adult dose. A rapid (single or
repeated) bolus dose should not be used (see WARNINGS).
Initiation and Maintenance of ICU Sedation in Intubated, Mechanically Ventilated
Adult Patients - Because of the residual effects of previous anesthetic or
sedative agents, in most patients the initial infusion should be 5 mcg/kg/min
(0.3 mg/kg/h) for at least 5 minutes. Subsequent increments of 5 to 10
mcg/kg/min (0.3 to 0.6 mg/kg/h) over 5 to 10 minutes may be used until
desired clinical effect is achieved. Maintenance rates of 5 to 50 mcg/kg/min
(0.3 to 3 mg/kg/h) or higher may be required. Administration should not
exceed 4 mg/kg/hour unless the benefits outweigh the risks (see WARNINGS).
Evaluation of clinical effect and assessment of CNS function should be
carried out daily throughout maintenance to determine the minimum
dose of Propofol Injectable Emulsion required for sedation.
The tubing and any unused portions of Propofol Injectable Emulsion
should be discarded after 12 hours because Propofol Injectable
Emulsion contains no preservatives and is capable of supporting growth
of microorganisms (see WARNINGS and DOSAGE AND ADMINISTRATION).
Administration with Lidocaine
If lidocaine is to be administered to minimize pain on injection of Propofol, it is recommended that it be administered prior to Propofol administration or that it be added to Propofol immediately before administration and in quantities not exceeding 20 mg lidocaine/200 mg Propofol.
Compatibility and Stability
Propofol Injectable Emulsion should not be mixed with other therapeutic agents prior to administration.
Dilution Prior to Administration
Propofol Injectable Emulsion is provided as a ready-to-use formulation. However, should dilution be necessary, it should only be diluted with 5% Dextrose Injection, USP, and it should not be diluted to a concentration less than 2 mg/mL because it is an emulsion. In diluted form it has been shown to be more stable when in contact with glass than with plastic (95% potency after 2 hours of running infusion in plastic).
Administration with Other Fluids
Compatibility of Propofol Injectable Emulsion with the coadministration of blood/serum/plasma has not been established (see WARNINGS). When administered using a y-type infusion set, Propofol Injectable Emulsion has been shown to be compatible with the following intravenous fluids.
- 5% Dextrose Injection, USP
- Lactated Ringers Injection, USP
- Lactated Ringers and 5% Dextrose Injection
- 5% Dextrose and 0.45% Sodium Chloride Injection, USP
- 5% Dextrose and 0.2% Sodium Chloride Injection, USP
Handling Procedures
General
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
Clinical experience with the use of in-line filters and Propofol Injectable Emulsion during anesthesia or ICU/MAC sedation is limited. Propofol Injectable Emulsion should only be administered through a filter with a pore size of 5 micron or greater unless it has been demonstrated that the filter does not restrict the flow of Propofol Injectable Emulsion and/or cause the breakdown of the emulsion. Filters should be used with caution and where clinically appropriate. Continuous monitoring is necessary due to the potential for restricted flow and/or breakdown of the emulsion.
Do not use if there is evidence of separation of the phases of the emulsion.
Rare cases of self-administration of Propofol Injectable Emulsion by health care professionals have been reported, including some fatalities (see DRUG ABUSE AND DEPENDENCE).
Strict aseptic technique must always be maintained during handling. Propofol Injectable Emulsion is a single-use parenteral product which contains 0.005% disodium edetate to inhibit the rate of growth of microorganisms, up to 12 hours, in the event of accidental extrinsic contamination. However, Propofol Injectable Emulsion can still support the growth of microorganisms as it is not an antimicrobially preserved product under USP standards. Accordingly, strict aseptic technique must still be adhered to. Do not use if contamination is suspected. Discard unused portions as directed within the required time limits (see DOSAGE AND ADMINISTRATION, Handling Procedures). There have been reports in which failure to use aseptic technique when handling Propofol Injectable Emulsion was associated with microbial contamination of the product and with fever, infection/sepsis, other life-threatening illness, and/or death.
Propofol, with EDTA inhibits microbial growth for up to 12 hours, as demonstrated by test data for representative USP microorganisms.
Guidelines for Aseptic Technique for General Anesthesia/MAC Sedation
Propofol Injectable Emulsion should be prepared for use just prior to initiation of each individual anesthetic/sedative procedure. The vial syringe rubber stopper should be disinfected using 70% isopropyl alcohol. Propofol Injectable Emulsion should be drawn into sterile syringes immediately after vials are opened. When withdrawing Propofol Injectable Emulsion from vials, a sterile vent spike should be used. The syringe(s) should be labeled with appropriate information including the date and time the vial was opened. Administration should commence promptly and be completed within 12 hours after the vials have been opened.
Propofol Injectable Emulsion should be prepared for single-patient use only. Any unused portions of Propofol Injectable Emulsion, reservoirs, dedicated administration tubing and/or solutions containing Propofol Injectable Emulsion must be discarded at the end of the anesthetic procedure or at 12 hours, whichever occurs sooner. The IV line should be flushed every 12 hours and at the end of the anesthetic procedure to remove residual Propofol Injectable Emulsion.
Guidelines for Aseptic Technique for ICU SedationPropofol Injectable Emulsion should be prepared for single-patient use only. When Propofol Injectable Emulsion is administered directly from the vial, strict aseptic techniques must be followed. The vial rubber stopper should be disinfected using 70% isopropyl alcohol. A sterile vent spike and sterile tubing must be used for administration of Propofol Injectable Emulsion. As with other lipid emulsions, the number of IV line manipulations should be minimized. Administration should commence promptly and must be completed within 12 hours after the vial has been spiked. The tubing and any unused portions of Propofol Injectable Emulsion must be discarded after 12 hours.
If Propofol Injectable Emulsion is transferred to a syringe or other container prior to administration, the handling procedures for General anesthesia/MAC sedation should be followed, and the product should be discarded and administration lines changed after 12 hours.
Induction of General Anesthesia
Adult Patients
Most adult patients under 55 years of age and classified as ASA-PS I or II require 2 to 2.5 mg/kg of Propofol Injectable Emulsion for induction when unpremedicated or when premedicated with oral benzodiazepines or intramuscular opioids. For induction, Propofol Injectable Emulsion should be titrated (approximately 40 mg every 10 seconds) against the response of the patient until the clinical signs show the onset of anesthesia. As with other sedative-hypnotic agents, the amount of intravenous opioid and/or benzodiazepine premedication will influence the response of the patient to an induction dose of Propofol Injectable Emulsion.
Elderly, Debilitated, or ASA-PS III or IV Patients
It is important to be familiar and experienced with the intravenous use of Propofol Injectable Emulsion before treating elderly, debilitated, or ASA-PS III or IV patients. Due to the reduced clearance and higher blood concentrations, most of these patients require approximately 1 to 1.5 mg/kg (approximately 20 mg every 10 seconds) of Propofol Injectable Emulsion for induction of anesthesia according to their condition and responses. A rapid bolus should not be used, as this will increase the likelihood of undesirable cardiorespiratory depression including hypotension, apnea, airway obstruction, and/or oxygen desaturation (see DOSAGE AND ADMINISTRATION).
Pediatric Patients
Most patients aged 3 years through 16 years and classified ASA-PS I or II require 2.5 to 3.5 mg/kg of Propofol Injectable Emulsion for induction when unpremedicated or when lightly premedicated with oral benzodiazepines or intramuscular opioids. Within this dosage range, younger pediatric patients may require higher induction doses than older pediatric patients. As with other sedative‑hypnotic agents, the amount of intravenous opioid and/or benzodiazepine premedication will influence the response of the patient to an induction dose of Propofol Injectable Emulsion. A lower dosage is recommended for pediatric patients classified as ASA-PS III or IV. Attention should be paid to minimize pain on injection when administering Propofol Injectable Emulsion to pediatric patients. Boluses of Propofol Injectable Emulsion may be administered via small veins if pretreated with lidocaine or via antecubital or larger veins (see PRECAUTIONS, General).
Neurosurgical Patients
Slower induction is recommended using boluses of 20 mg every 10 seconds. Slower boluses or infusions of Propofol Injectable Emulsion for induction of anesthesia, titrated to clinical responses, will generally result in reduced induction dosage requirements (1 to 2 mg/kg) (see PRECAUTIONS and DOSAGE AND ADMINISTRATION).
Cardiac Anesthesia
Propofol Injectable Emulsion has been well-studied in patients with coronary artery disease, but experience in patients with hemodynamically significant valvular or congenital heart disease is limited. As with other anesthetic and sedative-hypnotic agents, Propofol Injectable Emulsion in healthy patients causes a decrease in blood pressure that is secondary to decreases in preload (ventricular filling volume at the end of the diastole) and afterload (arterial resistance at the beginning of the systole). The magnitude of these changes is proportional to the blood and effect site concentrations achieved. These concentrations depend upon the dose and speed of the induction and maintenance infusion rates.
In addition, lower heart rates are observed during maintenance with Propofol Injectable Emulsion, possibly due to reduction of the sympathetic activity and/or resetting of the baroreceptor reflexes. Therefore, anticholinergic agents should be administered when increases in vagal tone are anticipated.
As with other anesthetic agents, Propofol Injectable Emulsion reduces myocardial oxygen consumption. Further studies are needed to confirm and delineate the extent of these effects on the myocardium and the coronary vascular system.
Morphine premedication (0.15 mg/kg) with nitrous oxide 67% in oxygen has been shown to decrease the necessary Propofol Injectable Emulsion maintenance infusion rates and therapeutic blood concentrations when compared to non‑narcotic (lorazepam) premedication. The rate of Propofol Injectable Emulsion administration should be determined based on the patient's premedication and adjusted according to clinical responses.
A rapid bolus induction should be avoided. A slow rate of approximately 20 mg every 10 seconds until induction onset (0.5 to 1.5 mg/kg) should be used. In order to assure adequate anesthesia, when Propofol Injectable Emulsion is used as the primary agent, maintenance infusion rates should not be less than 100 mcg/kg/min and should be supplemented with analgesic levels of continuous opioid administration. When an opioid is used as the primary agent, Propofol Injectable Emulsion maintenance rates should not be less than 50 mcg/kg/min, and care should be taken to ensure amnesia. Higher doses of Propofol Injectable Emulsion will reduce the opioid requirements (see Table 4). When Propofol Injectable Emulsion is used as the primary anesthetic, it should not be administered with the high-dose opioid technique as this may increase the likelihood of hypotension (see PRECAUTIONS, Cardiac Anesthesia).
Table 4. Cardiac Anesthesia Techniques
Primary Agent
Rate
Secondary Agent/Rate
(Following Induction with Primary Agent)
Propofol Injectable Emulsion
OPIOIDa/0.05 to 0.075 mcg/kg/min (no bolus)
Preinduction
Anxiolysis
25 mcg/kg/min
Induction
0.5 to 1.5 mg/kg
over 60 sec
Maintenance
(Titrated to Clinical
Response)
100 to 150 mcg/kg/min
OPIOIDb
Propofol Injectable Emulsion/50 to 100 mcg/kg/min
(no bolus)
Induction
25 to 50 mcg/kg
Maintenance
0.2 to 0.3 mcg/kg/min
aOPIOID is defined in terms of fentanyl equivalents, i.e.,
1 mcg of fentanyl = 5 mcg of alfentanil (for bolus)
= 10 mcg of alfentanil (for maintenance)
or
= 0.1 mcg of sufentanil
bCare should be taken to ensure amnesia.
Maintenance of General Anesthesia
Adult Patients
In adults, anesthesia can be maintained by administering Propofol Injectable Emulsion by infusion or intermittent IV bolus injection. The patient's clinical response will determine the infusion rate or the amount and frequency of incremental injections.
Continuous Infusion
Propofol Injectable Emulsion 100 to 200 mcg/kg/min administered in a variable rate infusion with 60% to 70% nitrous oxide and oxygen provides anesthesia for patients undergoing general surgery. Maintenance by infusion of Propofol Injectable Emulsion should immediately follow the induction dose in order to provide satisfactory or continuous anesthesia during the induction phase. During this initial period following the induction dose, higher rates of infusion are generally required (150 to 200 mcg/kg/min) for the first 10 to 15 minutes. Infusion rates should subsequently be decreased 30% to 50% during the first half-hour of maintenance. Generally, rates of 50 to 100 mcg/kg/min in adults should be achieved during maintenance in order to optimize recovery times.
Other drugs that cause CNS depression (hypnotics/sedatives, inhalational anesthetics, and opioids) can increase the CNS depression induced by propofol.
Intermittent Bolus
Increments of Propofol Injectable Emulsion 25 mg (2.5 mL) to 50 mg (5 mL) may be administered with nitrous oxide in adult patients undergoing general surgery. The incremental boluses should be administered when changes in vital signs indicate a response to surgical stimulation or light anesthesia.
Pediatric Patients
Propofol Injectable Emulsion administered as a variable rate infusion supplemented with nitrous oxide 60% to 70% provides satisfactory anesthesia for most children 2 months of age or older, ASA-PS I or II, undergoing general anesthesia.
In general, for the pediatric population, maintenance by infusion of Propofol Injectable Emulsion at a rate of 200 to 300 mcg/kg/min should immediately follow the induction dose. Following the first half-hour of maintenance, infusion rates of 125 to 150 mcg/kg/min are typically needed. Propofol Injectable Emulsion should be titrated to achieve the desired clinical effect. Younger pediatric patients may require higher maintenance infusion rates than older pediatric patients. (See Table 2 Clinical Trials.)
Propofol Injectable Emulsion has been used with a variety of agents commonly used in anesthesia such as atropine, scopolamine, glycopyrrolate, diazepam, depolarizing and nondepolarizing muscle relaxants, and opioid analgesics, as well as with inhalational and regional anesthetic agents.
In the elderly, debilitated, or ASA-PS III or IV patients, rapid bolus doses should not be used, as this will increase cardiorespiratory effects including hypotension, apnea, airway obstruction, and oxygen desaturation.
Monitored Anesthesia Care (MAC) Sedation
Adult Patients
When Propofol Injectable Emulsion is administered for MAC sedation, rates of administration should be individualized and titrated to clinical response. In most patients, the rates of Propofol Injectable Emulsion administration will be in the range of 25 to 75 mcg/kg/min.
During initiation of MAC sedation, slow infusion or slow injection techniques are preferable over rapid bolus administration. During maintenance of MAC sedation, a variable rate infusion is preferable over intermittent bolus dose administration. In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation (see WARNINGS). A rapid bolus injection can result in undesirable cardiorespiratory depression including hypotension, apnea, airway obstruction, and oxygen desaturation.
Initiation of MAC Sedation
For initiation of MAC sedation, either an infusion or a slow injection method may be utilized while closely monitoring cardiorespiratory function. With the infusion method, sedation may be initiated by infusing Propofol Injectable Emulsion at 100 to 150 mcg/kg/min (6 to 9 mg/kg/h) for a period of 3 to 5 minutes and titrating to the desired clinical effect while closely monitoring respiratory function. With the slow injection method for initiation, patients will require approximately 0.5 mg/kg administered over 3 to 5 minutes and titrated to clinical responses. When Propofol Injectable Emulsion is administered slowly over 3 to 5 minutes, most patients will be adequately sedated, and the peak drug effect can be achieved while minimizing undesirable cardiorespiratory effects occurring at high plasma levels.
In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation (see WARNINGS). The rate of administration should be over 3 to 5 minutes and the dosage of Propofol Injectable Emulsion should be reduced to approximately 80% of the usual adult dosage in these patients according to their condition, responses, and changes in vital signs (see DOSAGE AND ADMINISTRATION).
Maintenance of MAC Sedation
For maintenance of sedation, a variable rate infusion method is preferable over an intermittent bolus dose method. With the variable rate infusion method, patients will generally require maintenance rates of 25 to 75 mcg/kg/min (1.5 to 4.5 mg/kg/h) during the first 10 to 15 minutes of sedation maintenance. Infusion rates should subsequently be decreased over time to 25 to 50 mcg/kg/min and adjusted to clinical responses. In titrating to clinical effect, allow approximately 2 minutes for onset of peak drug effect.
Infusion rates should always be titrated downward in the absence of clinical signs of light sedation until mild responses to stimulation are obtained in order to avoid sedative administration of Propofol Injectable Emulsion at rates higher than are clinically necessary.
If the intermittent bolus dose method is used, increments of Propofol Injectable Emulsion 10 mg (1 mL) or 20 mg (2 mL) can be administered and titrated to desired clinical effect. With the intermittent bolus method of sedation maintenance, there is increased potential for respiratory depression, transient increases in sedation depth, and prolongation of recovery.
In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation (see WARNINGS). The rate of administration and the dosage of Propofol Injectable Emulsion should be reduced to approximately 80% of the usual adult dosage in these patients according to their condition, responses, and changes in vital signs (see DOSAGE AND ADMINISTRATION).
Propofol Injectable Emulsion can be administered as the sole agent for maintenance of MAC sedation during surgical/diagnostic procedures. When Propofol Injectable Emulsion sedation is supplemented with opioid and/or benzodiazepine medications, these agents increase the sedative and respiratory effects of Propofol Injectable Emulsion and may also result in a slower recovery profile (see PRECAUTIONS, Drug Interactions).
ICU Sedation
(See WARNINGS and DOSAGE AND ADMINISTRATION, Handling Procedures.)
Abrupt discontinuation of Propofol Injectable Emulsion prior to weaning or for daily evaluation of sedation levels should be avoided. This may result in rapid awakening with associated anxiety, agitation, and resistance to mechanical ventilation. Infusions of Propofol Injectable Emulsion should be adjusted to assure a minimal level of sedation is maintained throughout the weaning process and when assessing the level of sedation (see PRECAUTIONS).
Adult Patients
For intubated, mechanically ventilated adult patients, Intensive Care Unit (ICU) sedation should be initiated slowly with a continuous infusion in order to titrate to desired clinical effect and minimize hypotension (see DOSAGE AND ADMINISTRATION).
Most adult ICU patients recovering from the effects of general anesthesia or deep sedation will require maintenance rates of 5 to 50 mcg/kg/min (0.3 to 3 mg/kg/h) individualized and titrated to clinical response (see DOSAGE AND ADMINISTRATION). With medical ICU patients or patients who have recovered from the effects of general anesthesia or deep sedation, the rate of administration of 50 mcg/kg/min or higher may be required to achieve adequate sedation. These higher rates of administration may increase the likelihood of patients developing hypotension. Administration should not exceed 4 mg/kg/hour unless the benefits outweigh the risks (see WARNINGS).
Dosage and rate of administration should be individualized and titrated to the desired effect, according to clinically relevant factors including the patient’s underlying medical problems, preinduction and concomitant medications, age, ASA-PS classification, and level of debilitation of the patient. The elderly, debilitated, and ASA-PS III or IV patients may have exaggerated hemodynamic and respiratory responses to rapid bolus doses (see WARNINGS).
Propofol Injectable Emulsion should be individualized according to the patient's condition and response, blood lipid profile, and vital signs (see PRECAUTIONS, Intensive Care Unit Sedation). For intubated, mechanically ventilated adult patients, Intensive Care Unit (ICU) sedation should be initiated slowly with a continuous infusion in order to titrate to desired clinical effect and minimize hypotension. When indicated, initiation of sedation should begin at 5 mcg/kg/min (0.3 mg/kg/h). The infusion rate should be increased by increments of 5 to 10 mcg/kg/min (0.3 to 0.6 mg/kg/h) until the desired level of sedation is achieved. A minimum period of 5 minutes between adjustments should be allowed for onset of peak drug effect. Most adult patients require maintenance rates of 5 to 50 mcg/kg/min (0.3 to 3 mg/kg/h) or higher. Administration should not exceed 4 mg/kg/hour unless the benefits outweigh the risks (see WARNINGS). Dosages of Propofol Injectable Emulsion should be reduced in patients who have received large dosages of narcotics. Conversely, the Propofol Injectable Emulsion dosage requirement may be reduced by adequate management of pain with analgesic agents. As with other sedative medications, there is interpatient variability in dosage requirements, and these requirements may change with time (see SUMMARY OF DOSAGE GUIDELINES). Evaluation of level of sedation and assessment of cns function should be carried out daily throughout maintenance to determine the minimum dose of PROPOFOL required for sedation (see Clinical Trials, Intensive Care Unit (ICU) Sedation). Bolus administration of 10 or 20 mg should only be used to rapidly increase depth of sedation in patients where hypotension is not likely to occur. Patients with compromised myocardial function, intravascular volume depletion, or abnormally low vascular tone (e.g., sepsis) may be more susceptible to hypotension (see PRECAUTIONS).
SUMMARY OF DOSAGE GUIDELINES:
Dosages and rates of administration in the following table should be individualized and titrated to clinical response. Safety and dosing requirements for induction of anesthesia in pediatric patients have only been established for children 3 years of age or older. Safety and dosing requirements for the maintenance of anesthesia have only been established for children 2 months of age and older.
For complete dosage information, see DOSAGE AND ADMINISTRATION.
INDICATION
DOSAGE AND ADMINISTRATION
Induction of General Anesthesia:
Healthy Adults Less Than 55 Years of Age:
40 mg every 10 seconds until induction onset (2 to 2.5 mg/kg).
Elderly, Debilitated, or ASA-PS III or IV Patients:
20 mg every 10 seconds until induction onset (1 to 1.5 mg/kg).
Cardiac Anesthesia:
20 mg every 10 seconds until induction onset (0.5 to 1.5 mg/kg).
Neurosurgical Patients:
20 mg every 10 seconds until induction onset (1 to 2 mg/kg)
Pediatric Patients – healthy, from 3 years to 16 years of age:
2.5 to 3.5 mg/kg administered over 20 to 30 seconds.
(see PRECAUTIONS, Pediatric Use and CLINICAL PHARMACOLOGY, Pediatrics)
Maintenance of General Anesthesia:
Infusion
Healthy Adults Less Than 55 Years of Age:
100 to 200 mcg/kg/min (6 to 12 mg/kg/h).
Elderly, Debilitated, ASA-PS III or IV Patients:
50 to 100 mcg/kg/min (3 to 6 mg/kg/h).
Cardiac Anesthesia: Most patients require:
Primary Propofol Injectable Emulsion with Secondary Opioid –
100 to 150 mcg/kg/min
Low-Dose Propofol Injectable Emulsion with Primary Opioid –
50 to 100 mcg/kg/min
(see DOSAGE AND ADMINISTRATION, Table 4)
Neurosurgical Patients:
100 to 200 mcg/kg/min (6 to 12 mg/kg/h).
Pediatric Patients - healthy, from 2 months of age to 16 years of age:
125 to 300 mcg/kg/min (7.5 to 18 mg/kg/h)
Following the first half hour of maintenance, if clinical signs of light
anesthesia are not present, the infusion rate should be decreased.
(see PRECAUTIONS, Pediatric Use and CLINICAL PHARMACOLOGY, Pediatrics)
Maintenance of General Anesthesia:
Intermittent Bolus
Healthy Adults Less Than 55 Years of Age:
Increments of 20 to 50 mg as needed.
Initiation of MAC Sedation:
Healthy Adults Less Than 55 Years of Age:
Slow infusion or slow injection techniques are recommended to avoid apnea
or hypotension. Most patients require an infusion of 100 to 150 mcg/kg/min
(6 to 9 mg/kg/h) for 3 to 5 minutes or a slow injection of 0.5 mg/kg over 3
to 5 minutes followed immediately by a maintenance infusion.
Elderly, Debilitated, Neurosurgical, or ASA-PS III or IV Patients:
Most patients require dosages similar to healthy adults.
Rapid boluses are to be avoided (see WARNINGS).
Maintenance of MAC Sedation:
Healthy Adults Less Than 55 Years of Age:
A variable rate infusion technique is preferable over an intermittent bolus
technique. Most patients require an infusion of 25 to 75 mcg/kg/min
(1.5 to 4.5 mg/kg/h) or incremental bolus doses of 10 mg or 20 mg.
In Elderly, Debilitated, Neurosurgical, or ASA-PS III or IV Patients:
Most patients require 80% of the usual adult dose. A rapid (single or
repeated) bolus dose should not be used (see WARNINGS).
Initiation and Maintenance of ICU Sedation in Intubated, Mechanically Ventilated
Adult Patients - Because of the residual effects of previous anesthetic or
sedative agents, in most patients the initial infusion should be 5 mcg/kg/min
(0.3 mg/kg/h) for at least 5 minutes. Subsequent increments of 5 to 10
mcg/kg/min (0.3 to 0.6 mg/kg/h) over 5 to 10 minutes may be used until
desired clinical effect is achieved. Maintenance rates of 5 to 50 mcg/kg/min
(0.3 to 3 mg/kg/h) or higher may be required. Administration should not
exceed 4 mg/kg/hour unless the benefits outweigh the risks (see WARNINGS).
Evaluation of clinical effect and assessment of CNS function should be
carried out daily throughout maintenance to determine the minimum
dose of Propofol Injectable Emulsion required for sedation.
The tubing and any unused portions of Propofol Injectable Emulsion
should be discarded after 12 hours because Propofol Injectable
Emulsion contains no preservatives and is capable of supporting growth
of microorganisms (see WARNINGS and DOSAGE AND ADMINISTRATION).
Administration with Lidocaine
If lidocaine is to be administered to minimize pain on injection of Propofol, it is recommended that it be administered prior to Propofol administration or that it be added to Propofol immediately before administration and in quantities not exceeding 20 mg lidocaine/200 mg Propofol.
Compatibility and Stability
Propofol Injectable Emulsion should not be mixed with other therapeutic agents prior to administration.
Dilution Prior to Administration
Propofol Injectable Emulsion is provided as a ready-to-use formulation. However, should dilution be necessary, it should only be diluted with 5% Dextrose Injection, USP, and it should not be diluted to a concentration less than 2 mg/mL because it is an emulsion. In diluted form it has been shown to be more stable when in contact with glass than with plastic (95% potency after 2 hours of running infusion in plastic).
Administration with Other Fluids
Compatibility of Propofol Injectable Emulsion with the coadministration of blood/serum/plasma has not been established (see WARNINGS). When administered using a y-type infusion set, Propofol Injectable Emulsion has been shown to be compatible with the following intravenous fluids.
- 5% Dextrose Injection, USP
- Lactated Ringers Injection, USP
- Lactated Ringers and 5% Dextrose Injection
- 5% Dextrose and 0.45% Sodium Chloride Injection, USP
- 5% Dextrose and 0.2% Sodium Chloride Injection, USP
Handling Procedures
General
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
Clinical experience with the use of in-line filters and Propofol Injectable Emulsion during anesthesia or ICU/MAC sedation is limited. Propofol Injectable Emulsion should only be administered through a filter with a pore size of 5 micron or greater unless it has been demonstrated that the filter does not restrict the flow of Propofol Injectable Emulsion and/or cause the breakdown of the emulsion. Filters should be used with caution and where clinically appropriate. Continuous monitoring is necessary due to the potential for restricted flow and/or breakdown of the emulsion.
Do not use if there is evidence of separation of the phases of the emulsion.
Rare cases of self-administration of Propofol Injectable Emulsion by health care professionals have been reported, including some fatalities (see DRUG ABUSE AND DEPENDENCE).
Strict aseptic technique must always be maintained during handling. Propofol Injectable Emulsion is a single-use parenteral product which contains 0.005% disodium edetate to inhibit the rate of growth of microorganisms, up to 12 hours, in the event of accidental extrinsic contamination. However, Propofol Injectable Emulsion can still support the growth of microorganisms as it is not an antimicrobially preserved product under USP standards. Accordingly, strict aseptic technique must still be adhered to. Do not use if contamination is suspected. Discard unused portions as directed within the required time limits (see DOSAGE AND ADMINISTRATION, Handling Procedures). There have been reports in which failure to use aseptic technique when handling Propofol Injectable Emulsion was associated with microbial contamination of the product and with fever, infection/sepsis, other life-threatening illness, and/or death.
Propofol, with EDTA inhibits microbial growth for up to 12 hours, as demonstrated by test data for representative USP microorganisms.
Guidelines for Aseptic Technique for General Anesthesia/MAC Sedation
Propofol Injectable Emulsion should be prepared for use just prior to initiation of each individual anesthetic/sedative procedure. The vial syringe rubber stopper should be disinfected using 70% isopropyl alcohol. Propofol Injectable Emulsion should be drawn into sterile syringes immediately after vials are opened. When withdrawing Propofol Injectable Emulsion from vials, a sterile vent spike should be used. The syringe(s) should be labeled with appropriate information including the date and time the vial was opened. Administration should commence promptly and be completed within 12 hours after the vials have been opened.
Propofol Injectable Emulsion should be prepared for single-patient use only. Any unused portions of Propofol Injectable Emulsion, reservoirs, dedicated administration tubing and/or solutions containing Propofol Injectable Emulsion must be discarded at the end of the anesthetic procedure or at 12 hours, whichever occurs sooner. The IV line should be flushed every 12 hours and at the end of the anesthetic procedure to remove residual Propofol Injectable Emulsion.
Guidelines for Aseptic Technique for ICU SedationPropofol Injectable Emulsion should be prepared for single-patient use only. When Propofol Injectable Emulsion is administered directly from the vial, strict aseptic techniques must be followed. The vial rubber stopper should be disinfected using 70% isopropyl alcohol. A sterile vent spike and sterile tubing must be used for administration of Propofol Injectable Emulsion. As with other lipid emulsions, the number of IV line manipulations should be minimized. Administration should commence promptly and must be completed within 12 hours after the vial has been spiked. The tubing and any unused portions of Propofol Injectable Emulsion must be discarded after 12 hours.
If Propofol Injectable Emulsion is transferred to a syringe or other container prior to administration, the handling procedures for General anesthesia/MAC sedation should be followed, and the product should be discarded and administration lines changed after 12 hours.
-
Teva Parenteral Medicines, Inc.
Propofol | Teva Parenteral Medicines, Inc.
Propofol blood concentrations at steady-state are generally proportional to infusion rates, especially in individual patients. Undesirable effects such as cardiorespiratory depression are likely to occur at higher blood concentrations which result from bolus dosing or rapid increases in the infusion rate. An adequate interval (3 to 5 minutes) must be allowed between dose adjustments to allow for and assess the clinical effects.
Shake well before use. Do not use if there is evidence of excessive creaming or aggregation, if large droplets are visible, or if there are other forms of phase separation indicating that the stability of the product has been compromised. Slight creaming, which should disappear after shaking, may be visible upon prolonged standing.
When administering propofol injectable emulsion by infusion, syringe or volumetric pumps are recommended to provide controlled infusion rates. When infusing propofol injectable emulsion to patients undergoing magnetic resonance imaging, metered control devices may be utilized if mechanical pumps are impractical.
Contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.
Changes in vital signs indicating a stress response to surgical stimulation or the emergence from anesthesia may be controlled by the administration of 25 mg (2.5 mL) to 50 mg (5 mL) incremental boluses and/or by increasing the infusion rate of propofol injectable emulsion.
For minor surgical procedures (e.g., body surface) nitrous oxide (60% to 70%) can be combined with a variable rate propofol injectable emulsion infusion to provide satisfactory anesthesia. With more stimulating surgical procedures (e.g., intra-abdominal), or if supplementation with nitrous oxide is not provided, administration rate(s) of propofol injectable emulsion and/or opioids should be increased in order to provide adequate anesthesia.
Infusion rates should always be titrated downward in the absence of clinical signs of light anesthesia until a mild response to surgical stimulation is obtained in order to avoid administration of propofol injectable emulsion at rates higher than are clinically necessary. Generally, rates of 50 to 100 mcg/kg/min in adults should be achieved during maintenance in order to optimize recovery times.
Other drugs that cause CNS depression (hypnotics/sedatives, inhalational anesthetics, and opioids) can increase CNS depression induced by propofol. Morphine premedication (0.15 mg/kg) with nitrous oxide 67% in oxygen has been shown to decrease the necessary propofol injection maintenance infusion rate and therapeutic blood concentrations when compared to non-narcotic (lorazepam) premedication.
Induction of General Anesthesia Adult PatientsMost adult patients under 55 years of age and classified as ASA-PS I or II require 2 to 2.5 mg/kg of propofol injectable emulsion for induction when unpremedicated or when premedicated with oral benzodiazepines or intramuscular opioids. For induction, propofol injectable emulsion should be titrated (approximately 40 mg every 10 seconds) against the response of the patient until the clinical signs show the onset of anesthesia. As with other sedative-hypnotic agents, the amount of intravenous opioid and/or benzodiazepine premedication will influence the response of the patient to an induction dose of propofol injectable emulsion.
Elderly, Debilitated, or ASA-PS III or IV PatientsIt is important to be familiar and experienced with the intravenous use of propofol injectable emulsion before treating elderly, debilitated, or ASA-PS III or IV patients. Due to the reduced clearance and higher blood concentrations, most of these patients require approximately 1 to 1.5 mg/kg (approximately 20 mg every 10 seconds) of propofol injectable emulsion for induction of anesthesia according to their condition and responses. A rapid bolus should not be used, as this will increase the likelihood of undesirable cardiorespiratory depression including hypotension, apnea, airway obstruction, and/or oxygen desaturation (see DOSAGE AND ADMINISTRATION).
Pediatric PatientsMost patients aged 3 years through 16 years and classified ASA-PS I or II require 2.5 to 3.5 mg/kg of propofol injectable emulsion for induction when unpremedicated or when lightly premedicated with oral benzodiazepines or intramuscular opioids. Within this dosage range, younger pediatric patients may require higher induction doses than older pediatric patients. As with other sedative-hypnotic agents, the amount of intravenous opioid and/or benzodiazepine premedication will influence the response of the patient to an induction dose of propofol injectable emulsion. A lower dosage is recommended for pediatric patients classified as ASA-PS III or IV. Attention should be paid to minimize pain on injection when administering propofol injectable emulsion to pediatric patients. Boluses of propofol injectable emulsion may be administered via small veins if pretreated with lidocaine or via antecubital or larger veins (see PRECAUTIONS, General).
Neurosurgical PatientsSlower induction is recommended using boluses of 20 mg every 10 seconds. Slower boluses or infusions of propofol injectable emulsion for induction of anesthesia, titrated to clinical responses, will generally result in reduced induction dosage requirements (1 to 2 mg/kg) (see PRECAUTIONS and DOSAGE AND ADMINISTRATION).
Cardiac AnesthesiaPropofol injectable emulsion has been well-studied in patients with coronary artery disease, but experience in patients with hemodynamically significant valvular or congenital heart disease is limited. As with other anesthetic and sedative-hypnotic agents, propofol injectable emulsion in healthy patients causes a decrease in blood pressure that is secondary to decreases in preload (ventricular filling volume at the end of the diastole) and afterload (arterial resistance at the beginning of the systole). The magnitude of these changes is proportional to the blood and effect site concentrations achieved. These concentrations depend upon the dose and speed of the induction and maintenance infusion rates.
In addition, lower heart rates are observed during maintenance with propofol injectable emulsion, possibly due to reduction of the sympathetic activity and/or resetting of the baroreceptor reflexes. Therefore, anticholinergic agents should be administered when increases in vagal tone are anticipated.
As with other anesthetic agents, propofol injectable emulsion reduces myocardial oxygen consumption. Further studies are needed to confirm and delineate the extent of these effects on the myocardium and the coronary vascular system.
Morphine premedication (0.15 mg/kg) with nitrous oxide 67% in oxygen has been shown to decrease the necessary propofol injectable emulsion maintenance infusion rates and therapeutic blood concentrations when compared to non-narcotic (lorazepam) premedication. The rate of propofol injectable emulsion administration should be determined based on the patient's premedication and adjusted according to clinical responses.
A rapid bolus induction should be avoided. A slow rate of approximately 20 mg every 10 seconds until induction onset (0.5 to 1.5 mg/kg) should be used. In order to assure adequate anesthesia, when propofol injectable emulsion is used as the primary agent, maintenance infusion rates should not be less than 100 mcg/kg/min and should be supplemented with analgesic levels of continuous opioid administration. When an opioid is used as the primary agent, propofol injectable emulsion maintenance rates should not be less than 50 mcg/kg/min, and care should be taken to ensure amnesia. Higher doses of propofol injectable emulsion will reduce the opioid requirements (see Table 4). When propofol injectable emulsion is used as the primary anesthetic, it should not be administered with the high-dose opioid technique as this may increase the likelihood of hypotension (see PRECAUTIONS, Cardiac Anesthesia).
Table 4. Cardiac Anesthesia Techniques Primary Agent Rate Secondary Agent/Rate
(Following Induction with Primary Agent)Propofol Injectable Emulsion
OPIOIDa/0.05 to 0.075 mcg/kg/min
(no bolus)Preinduction
Anxiolysis
25 mcg/kg/min
Induction
0.5 to 1.5 mg/kg
over 60 secMaintenance (Titrated to Clinical Response)
100 to 150 mcg/kg/min
OPIOIDb
Propofol Injectable
Emulsion/50 to 100 mcg/kg/min (no bolus)Induction
25 to 50 mcg/kg
Maintenance
0.2 to 0.3 mcg/kg/min
aOPIOID is defined in terms of fentanyl equivalents, i.e.,
1 mcg of fentanyl = 5 mcg of alfentanil (for bolus)
= 10 mcg of alfentanil (for maintenance)
or
= 0.1 mcg of sufentanilbCare should be taken to ensure amnesia.
Maintenance of General AnesthesiaPropofol injectable emulsion has been used with a variety of agents commonly used in anesthesia such as atropine, scopolamine, glycopyrrolate, diazepam, depolarizing and nondepolarizing muscle relaxants, and opioid analgesics, as well as with inhalational and regional anesthetic agents.
In the elderly, debilitated, or ASA-PS III or IV patients, rapid bolus doses should not be used, as this will increase cardiorespiratory effects including hypotension, apnea, airway obstruction, and oxygen desaturation.
Adult PatientsIn adults, anesthesia can be maintained by administering propofol injectable emulsion by infusion or intermittent IV bolus injection. The patient's clinical response will determine the infusion rate or the amount and frequency of incremental injections.
Continuous InfusionPropofol injectable emulsion 100 to 200 mcg/kg/min administered in a variable rate infusion with 60% to 70% nitrous oxide and oxygen provides anesthesia for patients undergoing general surgery. Maintenance by infusion of propofol injectable emulsion should immediately follow the induction dose in order to provide satisfactory or continuous anesthesia during the induction phase. During this initial period following the induction dose, higher rates of infusion are generally required (150 to 200 mcg/kg/min) for the first 10 to 15 minutes. Infusion rates should subsequently be decreased 30% to 50% during the first half-hour of maintenance. Generally, rates of 50 to 100 mcg/kg/min in adults should be achieved during maintenance in order to optimize recovery times.
Other drugs that cause CNS depression (hypnotics/sedatives, inhalational anesthetics, and opioids) can increase the CNS depression induced by propofol.
Intermittent BolusIncrements of propofol injectable emulsion 25 mg (2.5 mL) to 50 mg (5 mL) may be administered with nitrous oxide in adult patients undergoing general surgery. The incremental boluses should be administered when changes in vital signs indicate a response to surgical stimulation or light anesthesia.
Pediatric PatientsPropofol injectable emulsion administered as a variable rate infusion supplemented with nitrous oxide 60% to 70% provides satisfactory anesthesia for most children 2 months of age or older, ASA-PS I or II, undergoing general anesthesia.
In general, for the pediatric population, maintenance by infusion of propofol injectable emulsion at a rate of 200 to 300 mcg/kg/min should immediately follow the induction dose. Following the first half-hour of maintenance, infusion rates of 125 to 150 mcg/kg/min are typically needed. Propofol injectable emulsion should be titrated to achieve the desired clinical effect. Younger pediatric patients may require higher maintenance infusion rates than older pediatric patients (see Table 2 Clinical Trials).
Monitored Anesthesia Care (MAC) Sedation Adult PatientsWhen propofol injectable emulsion is administered for MAC sedation, rates of administration should be individualized and titrated to clinical response. In most patients, the rates of propofol injectable emulsion administration will be in the range of 25 to 75 mcg/kg/min.
During initiation of MAC sedation, slow infusion or slow injection techniques are preferable over rapid bolus administration. During maintenance of MAC sedation, a variable rate infusion is preferable over intermittent bolus dose administration. In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation (see WARNINGS). A rapid bolus injection can result in undesirable cardiorespiratory depression including hypotension, apnea, airway obstruction, and oxygen desaturation.
Initiation of MAC SedationFor initiation of MAC sedation, either an infusion or a slow injection method may be utilized while closely monitoring cardiorespiratory function. With the infusion method, sedation may be initiated by infusing propofol injectable emulsion at 100 to 150 mcg/kg/min (6 to 9 mg/kg/h) for a period of 3 to 5 minutes and titrating to the desired clinical effect while closely monitoring respiratory function. With the slow injection method for initiation, patients will require approximately 0.5 mg/kg administered over 3 to 5 minutes and titrated to clinical responses. When propofol injectable emulsion is administered slowly over 3 to 5 minutes, most patients will be adequately sedated, and the peak drug effect can be achieved while minimizing undesirable cardiorespiratory effects occurring at high plasma levels.
In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation (see WARNINGS). The rate of administration should be over 3 to 5 minutes and the dosage of propofol injectable emulsion should be reduced to approximately 80% of the usual adult dosage in these patients according to their condition, responses, and changes in vital signs (see DOSAGE AND ADMINISTRATION).
Maintenance of MAC SedationFor maintenance of sedation, a variable rate infusion method is preferable over an intermittent bolus dose method. With the variable rate infusion method, patients will generally require maintenance rates of 25 to 75 mcg/kg/min (1.5 to 4.5 mg/kg/h) during the first 10 to 15 minutes of sedation maintenance. Infusion rates should subsequently be decreased over time to 25 to 50 mcg/kg/min and adjusted to clinical responses. In titrating to clinical effect, allow approximately 2 minutes for onset of peak drug effect.
Infusion rates should always be titrated downward in the absence of clinical signs of light sedation until mild responses to stimulation are obtained in order to avoid sedative administration of propofol injectable emulsion at rates higher than are clinically necessary.
If the intermittent bolus dose method is used, increments of propofol injectable emulsion 10 mg (1 mL) or 20 mg (2 mL) can be administered and titrated to desired clinical effect. With the intermittent bolus method of sedation maintenance, there is increased potential for respiratory depression, transient increases in sedation depth, and prolongation of recovery.
In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation (see WARNINGS). The rate of administration and the dosage of propofol injectable emulsion should be reduced to approximately 80% of the usual adult dosage in these patients according to their condition, responses, and changes in vital signs (see DOSAGE AND ADMINISTRATION).
Propofol injectable emulsion can be administered as the sole agent for maintenance of MAC sedation during surgical/diagnostic procedures. When propofol injectable emulsion sedation is supplemented with opioid and/or benzodiazepine medications, these agents increase the sedative and respiratory effects of propofol injectable emulsion and may also result in a slower recovery profile (see PRECAUTIONS, Drug Interactions).
ICU Sedation(See WARNINGS and DOSAGE AND ADMINISTRATION, Handling Procedures.)
Abrupt discontinuation of propofol injectable emulsion prior to weaning or for daily evaluation of sedation levels should be avoided. This may result in rapid awakening with associated anxiety, agitation, and resistance to mechanical ventilation. Infusions of propofol injectable emulsion should be adjusted to assure a minimal level of sedation is maintained throughout the weaning process and when assessing the level of sedation (see PRECAUTIONS).
Adult PatientsFor intubated, mechanically ventilated adult patients, Intensive Care Unit (ICU) sedation should be initiated slowly with a continuous infusion in order to titrate to desired clinical effect and minimize hypotension (see DOSAGE AND ADMINISTRATION).
Most adult ICU patients recovering from the effects of general anesthesia or deep sedation will require maintenance rates of 5 to 50 mcg/kg/min (0.3 to 3 mg/kg/h) individualized and titrated to clinical response (see DOSAGE AND ADMINISTRATION). With medical ICU patients or patients who have recovered from the effects of general anesthesia or deep sedation, the rate of administration of 50 mcg/kg/min or higher may be required to achieve adequate sedation. These higher rates of administration may increase the likelihood of patients developing hypotension. Administration should not exceed 4 mg/kg/hour unless the benefits outweigh the risks (see WARNINGS).
Dosage and rate of administration should be individualized and titrated to the desired effect, according to clinically relevant factors including the patient's underlying medical problems, preinduction and concomitant medications, age, ASA-PS classification, and level of debilitation of the patient. The elderly, debilitated, and ASA-PS III or IV patients may have exaggerated hemodynamic and respiratory responses to rapid bolus doses (see WARNINGS).
Propofol injectable emulsion should be individualized according to the patient's condition and response, blood lipid profile, and vital signs (see PRECAUTIONS, Intensive Care Unit Sedation). For intubated, mechanically ventilated adult patients, Intensive Care Unit (ICU) sedation should be initiated slowly with a continuous infusion in order to titrate to desired clinical effect and minimize hypotension. When indicated, initiation of sedation should begin at 5 mcg/kg/min (0.3 mg/kg/h). The infusion rate should be increased by increments of 5 to 10 mcg/kg/min (0.3 to 0.6 mg/kg/h) until the desired level of sedation is achieved. A minimum period of 5 minutes between adjustments should be allowed for onset of peak drug effect. Most adult patients require maintenance rates of 5 to 50 mcg/kg/min (0.3 to 3 mg/kg/h) or higher. Administration should not exceed 4 mg/kg/hour unless the benefits outweigh the risks (see WARNINGS). Dosages of propofol injectable emulsion should be reduced in patients who have received large dosages of narcotics. The propofol injectable emulsion dosage requirement may also be reduced by adequate management of pain with analgesic agents. As with other sedative medications, there is interpatient variability in dosage requirements, and these requirements may change with time (see SUMMARY OF DOSAGE GUIDELINES). Evaluation of level of sedation and assessment of CNS function should be carried out daily throughout maintenance to determine the minimum dose of propofol injectable emulsion required for sedation (see Clinical Trials, Intensive Care Unit (ICU) Sedation). Bolus administration of 10 or 20 mg should only be used to rapidly increase depth of sedation in patients where hypotension is not likely to occur. Patients with compromised myocardial function, intravascular volume depletion, or abnormally low vascular tone (e.g., sepsis) may be more susceptible to hypotension (see PRECAUTIONS).
SUMMARY OF DOSAGE GUIDELINESDosages and rates of administration in the following table should be individualized and titrated to clinical response. Safety and dosing requirements for induction of anesthesia in pediatric patients have only been established for children 3 years of age or older. Safety and dosing requirements for the maintenance of anesthesia have only been established for children 2 months of age and older.
For complete dosage information, see DOSAGE AND ADMINISTRATION.
INDICATION DOSAGE AND ADMINISTRATIONInduction of General Anesthesia:
Healthy Adults Less Than 55 Years of Age:
40 mg every 10 seconds until induction onset (2 to 2.5 mg/kg).Elderly, Debilitated, or ASA-PS III or IV Patients:
20 mg every 10 seconds until induction onset (1 to 1.5 mg/kg).Cardiac Anesthesia:
20 mg every 10 seconds until induction onset (0.5 to 1.5 mg/kg).Neurosurgical Patients:
20 mg every 10 seconds until induction onset (1 to 2 mg/kg).Pediatric Patients - healthy, from 3 years to 16 years of age:
2.5 to 3.5 mg/kg administered over 20 to 30 seconds (see PRECAUTIONS, Pediatric Use and CLINICAL PHARMACOLOGY, Pediatrics).Maintenance of General Anesthesia:
Infusion
Healthy Adults Less Than 55 Years of Age:
100 to 200 mcg/kg/min (6 to 12 mg/kg/h).Elderly, Debilitated, ASA-PS III or IV Patients:
50 to 100 mcg/kg/min (3 to 6 mg/kg/h).Cardiac Anesthesia: Most patients require:
Primary propofol injectable emulsion with Secondary Opioid – 100 to 150 mcg/kg/min.
Low-Dose propofol injectable emulsion with Primary Opioid – 50 to 100 mcg/kg/min (see DOSAGE AND ADMINISTRATION, Table 4).Neurosurgical Patients:
100 to 200 mcg/kg/min (6 to 12 mg/kg/h).Pediatric Patients - healthy, from 2 months of age to 16 years of age:
125 to 300 mcg/kg/min (7.5 to 18 mg/kg/h) Following the first half hour of maintenance, if clinical signs of light anesthesia are not present, the infusion rate should be decreased (see PRECAUTIONS, Pediatric Use and CLINICAL PHARMACOLOGY, Pediatrics).Maintenance of General Anesthesia:
Intermittent Bolus
Healthy Adults Less Than 55 Years of Age:
Increments of 20 to 50 mg as needed.Initiation of MAC Sedation:
Healthy Adults Less Than 55 Years of Age:
Slow infusion or slow injection techniques are recommended to avoid apnea or hypotension. Most patients require an infusion of 100 to 150 mcg/kg/min (6 to 9 mg/kg/h) for 3 to 5 minutes or a slow injection of 0.5 mg/kg over 3 to 5 minutes followed immediately by a maintenance infusion.Elderly, Debilitated, Neurosurgical, or ASA-PS III or IV Patients:
Most patients require dosages similar to healthy adults. Rapid boluses are to be avoided (see WARNINGS).Maintenance of MAC Sedation:
Healthy Adults Less Than 55 Years of Age:
A variable rate infusion technique is preferable over an intermittent bolus technique. Most patients require an infusion of 25 to 75 mcg/kg/min (1.5 to 4.5 mg/kg/h) or incremental bolus doses of 10 mg or 20 mg.In Elderly, Debilitated, Neurosurgical, or ASA-PS III or IV Patients:
Most patients require 80% of the usual adult dose. A rapid (single or repeated) bolus dose should not be used (see WARNINGS).Initiation and Maintenance of ICU Sedation in Intubated, Mechanically Ventilated
Adult Patients - Because of the residual effects of previous anesthetic or sedative agents, in most patients the initial infusion should be 5 mcg/kg/min (0.3 mg/kg/h) for at least 5 minutes. Subsequent increments of 5 to 10 mcg/kg/min (0.3 to 0.6 mg/kg/h) over 5 to 10 minutes may be used until desired clinical effect is achieved. Maintenance rates of 5 to 50 mcg/kg/min (0.3 to 3 mg/kg/h) or higher may be required. Administration should not exceed 4 mg/kg/hour unless the benefits outweigh the risks (see WARNINGS).
Evaluation of clinical effect and assessment of CNS function should be carried out daily throughout maintenance to determine the minimum dose of propofol injectable emulsion required for sedation.
The tubing and any unused propofol injectable emulsion drug product should be discarded after 12 hours because propofol injectable emulsion contains no preservatives and is capable of supporting growth of microorganisms (see WARNINGS and DOSAGE AND ADMINISTRATION).
Administration with LidocaineIf lidocaine is to be administered to minimize pain on injection of propofol injectable emulsion, it is recommended that it be administered prior to propofol injectable emulsion administration or that it be added to propofol injectable emulsion immediately before administration and in quantities not exceeding 20 mg lidocaine/200 mg propofol injectable emulsion.
Compatibility and StabilityPropofol injectable emulsion should not be mixed with other therapeutic agents prior to administration.
Dilution Prior to AdministrationPropofol injectable emulsion is provided as a ready-to-use formulation. However, should dilution be necessary, it should only be diluted with 5% Dextrose Injection, USP, and it should not be diluted to a concentration less than 2 mg/mL because it is an emulsion. In diluted form it has been shown to be more stable when in contact with glass than with plastic (95% potency after 2 hours of running infusion in plastic).
Administration with Other FluidsCompatibility of propofol injectable emulsion with the coadministration of blood/serum/plasma has not been established (see WARNINGS). When administered using a y-type infusion set, propofol injectable emulsion has been shown to be compatible with the following intravenous fluids.
- 5% Dextrose Injection, USP - Lactated Ringers Injection, USP - Lactated Ringers and 5% Dextrose Injection - 5% Dextrose and 0.45% Sodium Chloride Injection, USP - 5% Dextrose and 0.2% Sodium Chloride Injection, USP Handling Procedures GeneralParenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
Clinical experience with the use of in-line filters and propofol injectable emulsion during anesthesia or ICU/MAC sedation is limited. Propofol injectable emulsion should only be administered through a filter with a pore size of 5 micron or greater unless it has been demonstrated that the filter does not restrict the flow of propofol injectable emulsion and/or cause the breakdown of the emulsion. Filters should be used with caution and where clinically appropriate. Continuous monitoring is necessary due to the potential for restricted flow and/or breakdown of the emulsion.
Do not use if there is evidence of separation of the phases of the emulsion.
Rare cases of self-administration of propofol injectable emulsion by health care professionals have been reported, including some fatalities (see DRUG ABUSE AND DEPENDENCE).
Strict aseptic technique must always be maintained during handling. Propofol injectable emulsion is a single access parenteral product (single patient infusion vial) which contains sodium metabisulfite (0.25 mg/mL) to retard the rate of growth of microorganisms in the event of accidental extrinsic contamination. However, propofol injectable emulsion can still support the growth of microorganisms as it is not an antimicrobially preserved product under USP standards. Do not use if contamination is suspected. Discard unused drug product as directed within the required time limits. There have been reports in which failure to use aseptic technique when handling propofol injectable emulsion was associated with microbial contamination of the product and with fever, infection/sepsis, other life-threatening illness, and/or death.
There have been reports, in the literature and other public sources, of the transmission of bloodborne pathogens (such as Hepatitis B, Hepatitis C, and HIV) from unsafe injection practices, and use of propofol vials intended for single use on multiple persons. Propofol injectable emulsion vials are never to be accessed more than once or used on more than one person.
Propofol injectable emulsion, with sodium metabisulfite, inhibits microbial growth for up to 12 hours, as demonstrated by test data for representative USP microorganisms.
Guidelines for Aseptic Technique for General Anesthesia/MAC SedationPropofol injectable emulsion must be prepared for use just prior to initiation of each individual anesthetic/sedative procedure. The vial rubber stopper should be disinfected using 70% isopropyl alcohol. Propofol injectable emulsion should be drawn into a sterile syringe immediately after a vial is opened. When withdrawing propofol injectable emulsion from vials, a sterile vent spike should be used. The syringe should be labeled with appropriate information including the date and time the vial was opened. Administration should commence promptly and be completed within 12 hours after the vial has been opened.
Propofol injectable emulsion must be prepared for single-patient use only. Any unused propofol injectable emulsion drug product, reservoirs, dedicated administration tubing and/or solutions containing propofol injectable emulsion must be discarded at the end of the anesthetic procedure or at 12 hours, whichever occurs sooner. The IV line should be flushed every 12 hours and at the end of the anesthetic procedure to remove residual propofol injectable emulsion.
Guidelines for Aseptic Technique for ICU SedationPropofol injectable emulsion must be prepared for single-patient use only. Strict aseptic techniques must be followed. The vial rubber stopper should be disinfected using 70% isopropyl alcohol. A sterile vent spike and sterile tubing must be used for administration of propofol injectable emulsion. As with other lipid emulsions, the number of IV line manipulations should be minimized. Administration should commence promptly and must be completed within 12 hours after the vial has been spiked. The tubing and any unused propofol injectable emulsion drug product must be discarded after 12 hours.
If propofol injectable emulsion is transferred to a syringe prior to administration, it should be drawn into a sterile syringe immediately after a vial is opened. When withdrawing propofol injectable emulsion from a vial, a sterile vent spike should be used. The syringe should be labeled with appropriate information including the date and time the vial was opened. Administration should commence promptly and be completed within 12 hours after the vial has been opened. Propofol injectable emulsion should be discarded and administration lines changed after 12 hours.
-
Sagent Pharmaceuticals
Propofol | Sagent Pharmaceuticals
Propofol blood concentrations at steady-state are generally proportional to infusion rates, especially in individual patients. Undesirable effects such as cardiorespiratory depression are likely to occur at higher blood concentrations which result from bolus dosing or rapid increases in the infusion rate. An adequate interval (3 to 5 minutes) must be allowed between dose adjustments to allow for and assess the clinical effects.
Shake well before use. Do not use if there is evidence of excessive creaming or aggregation, if large droplets are visible, or if there are other forms of phase separation indicating that the stability of the product has been compromised. Slight creaming, which should disappear after shaking, may be visible upon prolonged standing.
When administering propofol injectable emulsion by infusion, syringe or volumetric pumps are recommended to provide controlled infusion rates. When infusing propofol injectable emulsion to patients undergoing magnetic resonance imaging, metered control devices may be utilized if mechanical pumps are impractical.
Contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.
Changes in vital signs indicating a stress response to surgical stimulation or the emergence from anesthesia may be controlled by the administration of 25 mg (2.5 mL) to 50 mg (5 mL) incremental boluses and/or by increasing the infusion rate of propofol injectable emulsion.
For minor surgical procedures (e.g., body surface) nitrous oxide (60% to 70%) can be combined with a variable rate propofol injectable emulsion infusion to provide satisfactory anesthesia. With more stimulating surgical procedures (e.g., intra-abdominal), or if supplementation with nitrous oxide is not provided, administration rate(s) of propofol injectable emulsion and/or opioids should be increased in order to provide adequate anesthesia.
Infusion rates should always be titrated downward in the absence of clinical signs of light anesthesia until a mild response to surgical stimulation is obtained in order to avoid administration of propofol injectable emulsion at rates higher than are clinically necessary. Generally, rates of 50 to 100 mcg/kg/min in adults should be achieved during maintenance in order to optimize recovery times.
Other drugs that cause CNS depression (hypnotics/sedatives, inhalational anesthetics, and opioids) can increase CNS depression induced by propofol. Morphine premedication (0.15 mg/kg) with nitrous oxide 67% in oxygen has been shown to decrease the necessary propofol injection maintenance infusion rate and therapeutic blood concentrations when compared to non-narcotic (lorazepam) premedication.
Induction of General Anesthesia Adult PatientsMost adult patients under 55 years of age and classified as ASA-PS I or II require 2 to 2.5 mg/kg of propofol injectable emulsion for induction when unpremedicated or when premedicated with oral benzodiazepines or intramuscular opioids. For induction, propofol injectable emulsion should be titrated (approximately 40 mg every 10 seconds) against the response of the patient until the clinical signs show the onset of anesthesia. As with other sedative-hypnotic agents, the amount of intravenous opioid and/or benzodiazepine premedication will influence the response of the patient to an induction dose of propofol injectable emulsion.
Elderly, Debilitated, or ASA-PS III or IV PatientsIt is important to be familiar and experienced with the intravenous use of propofol injectable emulsion before treating elderly, debilitated, or ASA-PS III or IV patients. Due to the reduced clearance and higher blood concentrations, most of these patients require approximately 1 to 1.5 mg/kg (approximately 20 mg every 10 seconds) of propofol injectable emulsion for induction of anesthesia according to their condition and responses. A rapid bolus should not be used, as this will increase the likelihood of undesirable cardiorespiratory depression including hypotension, apnea, airway obstruction, and/or oxygen desaturation (see DOSAGE AND ADMINISTRATION).
Pediatric PatientsMost patients aged 3 years through 16 years and classified ASA-PS I or II require 2.5 to 3.5 mg/kg of propofol injectable emulsion for induction when unpremedicated or when lightly premedicated with oral benzodiazepines or intramuscular opioids. Within this dosage range, younger pediatric patients may require higher induction doses than older pediatric patients. As with other sedative-hypnotic agents, the amount of intravenous opioid and/or benzodiazepine premedication will influence the response of the patient to an induction dose of propofol injectable emulsion. A lower dosage is recommended for pediatric patients classified as ASA-PS III or IV. Attention should be paid to minimize pain on injection when administering propofol injectable emulsion to pediatric patients. Boluses of propofol injectable emulsion may be administered via small veins if pretreated with lidocaine or via antecubital or larger veins (see PRECAUTIONS, General).
Neurosurgical PatientsSlower induction is recommended using boluses of 20 mg every 10 seconds. Slower boluses or infusions of propofol injectable emulsion for induction of anesthesia, titrated to clinical responses, will generally result in reduced induction dosage requirements (1 to 2 mg/kg) (see PRECAUTIONS and DOSAGE AND ADMINISTRATION).
Cardiac AnesthesiaPropofol injectable emulsion has been well-studied in patients with coronary artery disease, but experience in patients with hemodynamically significant valvular or congenital heart disease is limited. As with other anesthetic and sedative-hypnotic agents, propofol injectable emulsion in healthy patients causes a decrease in blood pressure that is secondary to decreases in preload (ventricular filling volume at the end of the diastole) and afterload (arterial resistance at the beginning of the systole). The magnitude of these changes is proportional to the blood and effect site concentrations achieved. These concentrations depend upon the dose and speed of the induction and maintenance infusion rates.
In addition, lower heart rates are observed during maintenance with propofol injectable emulsion, possibly due to reduction of the sympathetic activity and/or resetting of the baroreceptor reflexes. Therefore, anticholinergic agents should be administered when increases in vagal tone are anticipated.
As with other anesthetic agents, propofol injectable emulsion reduces myocardial oxygen consumption. Further studies are needed to confirm and delineate the extent of these effects on the myocardium and the coronary vascular system.
Morphine premedication (0.15 mg/kg) with nitrous oxide 67% in oxygen has been shown to decrease the necessary propofol injectable emulsion maintenance infusion rates and therapeutic blood concentrations when compared to non-narcotic (lorazepam) premedication. The rate of propofol injectable emulsion administration should be determined based on the patient's premedication and adjusted according to clinical responses.
A rapid bolus induction should be avoided. A slow rate of approximately 20 mg every 10 seconds until induction onset (0.5 to 1.5 mg/kg) should be used. In order to assure adequate anesthesia, when propofol injectable emulsion is used as the primary agent, maintenance infusion rates should not be less than 100 mcg/kg/min and should be supplemented with analgesic levels of continuous opioid administration. When an opioid is used as the primary agent, propofol injectable emulsion maintenance rates should not be less than 50 mcg/kg/min, and care should be taken to ensure amnesia. Higher doses of propofol injectable emulsion will reduce the opioid requirements (see Table 4). When propofol injectable emulsion is used as the primary anesthetic, it should not be administered with the high-dose opioid technique as this may increase the likelihood of hypotension (see PRECAUTIONS, Cardiac Anesthesia).
TABLE 4. Cardiac Anesthesia TechniquesaOPIOID is defined in terms of fentanyl equivalents, i.e.,
1 mcg of fentanyl
= 5 mcg of alfentanil (for bolus)
= 10 mcg of alfentanil (for maintenance)
or
= 0.1 mcg of sufentanil
bCare should be taken to ensure amnesia.
Primary Agent Rate Secondary Agent/Rate
(Following Induction with Primary Agent) Propofol Injectable Emulsion OPIOIDa/0.05 to 0.075 mcg/kg/min (no bolus) Preinduction
Anxiolysis
25 mcg/kg/min Induction 0.5 to 1.5 mg/kg over 60 sec Maintenance (Titrated to Clinical Response) 100 to 150 mcg/kg/min OPIOIDb Propofol Injectable Emulsion/50 to 100 mcg/kg/min (no bolus) Induction 25 to 50 mcg/kg Maintenance 0.2 to 0.3 mcg/kg/min Maintenance of General AnesthesiaPropofol injectable emulsion has been used with a variety of agents commonly used in anesthesia such as atropine, scopolamine, glycopyrrolate, diazepam, depolarizing and nondepolarizing muscle relaxants, and opioid analgesics, as well as with inhalational and regional anesthetic agents.
In the elderly, debilitated, or ASA-PS III or IV patients, rapid bolus doses should not be used, as this will increase cardiorespiratory effects including hypotension, apnea, airway obstruction, and oxygen desaturation.
Adult PatientsIn adults, anesthesia can be maintained by administering propofol injectable emulsion by infusion or intermittent IV bolus injection. The patient's clinical response will determine the infusion rate or the amount and frequency of incremental injections.
Continuous InfusionPropofol injectable emulsion 100 to 200 mcg/kg/min administered in a variable rate infusion with 60% to 70% nitrous oxide and oxygen provides anesthesia for patients undergoing general surgery. Maintenance by infusion of propofol injectable emulsion should immediately follow the induction dose in order to provide satisfactory or continuous anesthesia during the induction phase. During this initial period following the induction dose, higher rates of infusion are generally required (150 to 200 mcg/kg/min) for the first 10 to 15 minutes. Infusion rates should subsequently be decreased 30% to 50% during the first half-hour of maintenance. Generally, rates of 50 to 100 mcg/kg/min in adults should be achieved during maintenance in order to optimize recovery times.
Other drugs that cause CNS depression (hypnotics/sedatives, inhalational anesthetics, and opioids) can increase the CNS depression induced by propofol.
Intermittent BolusIncrements of propofol injectable emulsion 25 mg (2.5 mL) to 50 mg (5 mL) may be administered with nitrous oxide in adult patients undergoing general surgery. The incremental boluses should be administered when changes in vital signs indicate a response to surgical stimulation or light anesthesia.
Pediatric PatientsPropofol injectable emulsion administered as a variable rate infusion supplemented with nitrous oxide 60% to 70% provides satisfactory anesthesia for most children 2 months of age or older, ASA-PS I or II, undergoing general anesthesia.
In general, for the pediatric population, maintenance by infusion of propofol injectable emulsion at a rate of 200 to 300 mcg/kg/min should immediately follow the induction dose. Following the first half-hour of maintenance, infusion rates of 125 to 150 mcg/kg/min are typically needed. Propofol injectable emulsion should be titrated to achieve the desired clinical effect. Younger pediatric patients may require higher maintenance infusion rates than older pediatric patients (see Table 2 Clinical Trials).
Monitored Anesthesia Care (MAC) Sedation Adult PatientsWhen propofol injectable emulsion is administered for MAC sedation, rates of administration should be individualized and titrated to clinical response. In most patients, the rates of propofol injectable emulsion administration will be in the range of 25 to 75 mcg/kg/min.
During initiation of MAC sedation, slow infusion or slow injection techniques are preferable over rapid bolus administration. During maintenance of MAC sedation, a variable rate infusion is preferable over intermittent bolus dose administration. In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation (see WARNINGS). A rapid bolus injection can result in undesirable cardiorespiratory depression including hypotension, apnea, airway obstruction, and oxygen desaturation.
Initiation of MAC SedationFor initiation of MAC sedation, either an infusion or a slow injection method may be utilized while closely monitoring cardiorespiratory function. With the infusion method, sedation may be initiated by infusing propofol injectable emulsion at 100 to 150 mcg/kg/min (6 to 9 mg/kg/h) for a period of 3 to 5 minutes and titrating to the desired clinical effect while closely monitoring respiratory function. With the slow injection method for initiation, patients will require approximately 0.5 mg/kg administered over 3 to 5 minutes and titrated to clinical responses. When propofol injectable emulsion is administered slowly over 3 to 5 minutes, most patients will be adequately sedated, and the peak drug effect can be achieved while minimizing undesirable cardiorespiratory effects occurring at high plasma levels.
In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation (see WARNINGS). The rate of administration should be over 3 to 5 minutes and the dosage of propofol injectable emulsion should be reduced to approximately 80% of the usual adult dosage in these patients according to their condition, responses, and changes in vital signs (see DOSAGE AND ADMINISTRATION).
Maintenance of MAC SedationFor maintenance of sedation, a variable rate infusion method is preferable over an intermittent bolus dose method. With the variable rate infusion method, patients will generally require maintenance rates of 25 to 75 mcg/kg/min (1.5 to 4.5 mg/kg/h) during the first 10 to 15 minutes of sedation maintenance. Infusion rates should subsequently be decreased over time to 25 to 50 mcg/kg/min and adjusted to clinical responses. In titrating to clinical effect, allow approximately 2 minutes for onset of peak drug effect.
Infusion rates should always be titrated downward in the absence of clinical signs of light sedation until mild responses to stimulation are obtained in order to avoid sedative administration of propofol injectable emulsion at rates higher than are clinically necessary.
If the intermittent bolus dose method is used, increments of propofol injectable emulsion 10 mg (1 mL) or 20 mg (2 mL) can be administered and titrated to desired clinical effect. With the intermittent bolus method of sedation maintenance, there is increased potential for respiratory depression, transient increases in sedation depth, and prolongation of recovery.
In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation (see WARNINGS). The rate of administration and the dosage of propofol injectable emulsion should be reduced to approximately 80% of the usual adult dosage in these patients according to their condition, responses, and changes in vital signs (see DOSAGE AND ADMINISTRATION).
Propofol injectable emulsion can be administered as the sole agent for maintenance of MAC sedation during surgical/diagnostic procedures. When propofol injectable emulsion sedation is supplemented with opioid and/or benzodiazepine medications, these agents increase the sedative and respiratory effects of propofol injectable emulsion and may also result in a slower recovery profile (see PRECAUTIONS, Drug Interactions).
ICU Sedation(See WARNINGS and DOSAGE AND ADMINISTRATION, Handling Procedures.)
Abrupt discontinuation of propofol injectable emulsion prior to weaning or for daily evaluation of sedation levels should be avoided. This may result in rapid awakening with associated anxiety, agitation, and resistance to mechanical ventilation. Infusions of propofol injectable emulsion should be adjusted to assure a minimal level of sedation is maintained throughout the weaning process and when assessing the level of sedation (see PRECAUTIONS).
Adult PatientsFor intubated, mechanically ventilated adult patients, Intensive Care Unit (ICU) sedation should be initiated slowly with a continuous infusion in order to titrate to desired clinical effect and minimize hypotension (see DOSAGE AND ADMINISTRATION).
Most adult ICU patients recovering from the effects of general anesthesia or deep sedation will require maintenance rates of 5 to 50 mcg/kg/min (0.3 to 3 mg/kg/h) individualized and titrated to clinical response (see DOSAGE AND ADMINISTRATION). With medical ICU patients or patients who have recovered from the effects of general anesthesia or deep sedation, the rate of administration of 50 mcg/kg/min or higher may be required to achieve adequate sedation. These higher rates of administration may increase the likelihood of patients developing hypotension. Administration should not exceed 4 mg/kg/hour unless the benefits outweigh the risks (see WARNINGS).
Dosage and rate of administration should be individualized and titrated to the desired effect, according to clinically relevant factors including the patient's underlying medical problems, preinduction and concomitant medications, age, ASA-PS classification, and level of debilitation of the patient. The elderly, debilitated, and ASA-PS III or IV patients may have exaggerated hemodynamic and respiratory responses to rapid bolus doses (see WARNINGS).
Propofol injectable emulsion should be individualized according to the patient's condition and response, blood lipid profile, and vital signs (see PRECAUTIONS, Intensive Care Unit Sedation). For intubated, mechanically ventilated adult patients, Intensive Care Unit (ICU) sedation should be initiated slowly with a continuous infusion in order to titrate to desired clinical effect and minimize hypotension. When indicated, initiation of sedation should begin at 5 mcg/kg/min (0.3 mg/kg/h). The infusion rate should be increased by increments of 5 to 10 mcg/kg/min (0.3 to 0.6 mg/kg/h) until the desired level of sedation is achieved. A minimum period of 5 minutes between adjustments should be allowed for onset of peak drug effect. Most adult patients require maintenance rates of 5 to 50 mcg/kg/min (0.3 to 3 mg/kg/h) or higher. Administration should not exceed 4 mg/kg/hour unless the benefits outweigh the risks (see WARNINGS). Dosages of propofol injectable emulsion should be reduced in patients who have received large dosages of narcotics. The propofol injectable emulsion dosage requirement may also be reduced by adequate management of pain with analgesic agents. As with other sedative medications, there is interpatient variability in dosage requirements, and these requirements may change with time (see SUMMARY OF DOSAGE GUIDELINES). Evaluation of level of sedation and assessment of CNS function should be carried out daily throughout maintenance to determine the minimum dose of propofol injectable emulsion required for sedation (see Clinical Trials, Intensive Care Unit (ICU) Sedation). Bolus administration of 10 or 20 mg should only be used to rapidly increase depth of sedation in patients where hypotension is not likely to occur. Patients with compromised myocardial function, intravascular volume depletion, or abnormally low vascular tone (e.g., sepsis) may be more susceptible to hypotension (see PRECAUTIONS).
-
Hospira, Inc.
Propofol | Hospira, Inc.
NOTE: CONTAINS BENZYL ALCOHOL (See PRECAUTIONS section.)
Propofol blood concentrations at steady state are generally proportional to infusion rates, especially in individual patients. Undesirable effects such as cardiorespiratory depression are likely to occur at higher blood concentrations which result from bolus dosing or rapid increases in the infusion rate. An adequate interval (3 to 5 minutes) must be allowed between dose adjustments to allow for and assess the clinical effects.
When administering propofol injectable emulsion by infusion, syringe or volumetric pumps are recommended to provide controlled infusion rates. When infusing propofol injectable emulsion to patients undergoing magnetic resonance imaging, metered control devices may be utilized if mechanical pumps are impractical.
Changes in vital signs indicating a stress response to surgical stimulation or the emergence from anesthesia may be controlled by the administration of 25 mg (2.5 mL) to 50 mg (5 mL) incremental boluses and/or by increasing the infusion rate of propofol injectable emulsion.
For minor surgical procedures (e.g., body surface) nitrous oxide (60% to 70%) can be combined with a variable rate propofol injectable emulsion infusion to provide satisfactory anesthesia. With more stimulating surgical procedures (e.g., intra-abdominal), or if supplementation with nitrous oxide is not provided, administration rate(s) of propofol injectable emulsion and/or opioids should be increased in order to provide adequate anesthesia.
Infusion rates should always be titrated downward in the absence of clinical signs of light anesthesia until a mild response to surgical stimulation is obtained in order to avoid administration of propofol injectable emulsion at rates higher than are clinically necessary. Generally, rates of 50 to 100 mcg/kg/min in adults should be achieved during maintenance in order to optimize recovery time.
Other drugs that cause CNS depression (hypnotics/sedatives, inhalational anesthetics, and opioids) can increase CNS depression induced by propofol. Morphine premedication (0.15 mg/kg) with nitrous oxide 67% in oxygen has been shown to decrease the necessary propofol injection maintenance infusion rate and therapeutic blood concentrations when compared to non-narcotic (lorazepam) premedication.
Induction of General Anesthesia
Adult Patients: Most adult patients under 55 years of age and classified as ASA-PS I or II require 2 to 2.5 mg/kg of propofol injectable emulsion for induction when unpremedicated or when premedicated with oral benzodiazepines or intramuscular opioids. For induction, propofol injectable emulsion should be titrated (approximately 40 mg every 10 seconds) against the response of the patient until the clinical signs show the onset of anesthesia. As with other sedative-hypnotic agents, the amount of intravenous opioid and/or benzodiazepine premedication will influence the response of the patient to an induction dose of propofol injectable emulsion.
Elderly, Debilitated, or ASA-PS III or IV Patients: It is important to be familiar and experienced with the intravenous use of propofol injectable emulsion before treating elderly, debilitated, or ASA-PS III or IV patients. Due to the reduced clearance and higher blood concentrations, most of these patients require approximately 1 to 1.5 mg/kg (approximately 20 mg every 10 seconds) of propofol injectable emulsion for induction of anesthesia according to their condition and responses. A rapid bolus should not be used, as this will increase the likelihood of undesirable cardiorespiratory depression including hypotension, apnea, airway obstruction, and/or oxygen desaturation. (See DOSAGE AND ADMINISTRATION.)
Pediatric Patients: Most patients aged 3 years through 16 years and classified ASA-PS I or II require 2.5 to 3.5 mg/kg of propofol injectable emulsion for induction when unpremedicated or when lightly premedicated with oral benzodiazepines or intramuscular opioids. Within this dosage range, younger pediatric patients may require higher induction doses than older pediatric patients. As with other sedative-hypnotic agents, the amount of intravenous opioid and/or benzodiazepine premedication will influence the response of the patient to an induction dose of propofol injectable emulsion. A lower dosage is recommended for pediatric patients classified as ASA-PS III or IV. Attention should be paid to minimize pain on injection when administering propofol injectable emulsion to pediatric patients. Boluses of propofol injectable emulsion may be administered via small veins if pretreated with lidocaine or via antecubital or larger veins. (See PRECAUTIONS - General.)
Neurosurgical Patients: Slower induction is recommended using boluses of 20 mg every 10 seconds. Slower boluses or infusions of propofol injectable emulsion for induction of anesthesia, titrated to clinical responses, will generally result in reduced induction dosage requirements (1 to 2 mg/kg). (See PRECAUTIONS and DOSAGE AND ADMINISTRATION.)
Cardiac Anesthesia: Propofol injectable emulsion has been well-studied in patients with coronary artery disease, but experience in patients with hemodynamically significant valvular or congenital heart disease is limited. As with other anesthetic and sedative-hypnotic agents, propofol injectable emulsion in healthy patients causes a decrease in blood pressure that is secondary to decreases in preload (ventricular filling volume at the end of the diastole) and afterload (arterial resistance at the beginning of the systole). The magnitude of these changes is proportional to the blood and effect site concentrations achieved. These concentrations depend upon the dose and speed of the induction and maintenance infusion rates.
In addition, lower heart rates are observed during maintenance with propofol injectable emulsion, possibly due to reduction of the sympathetic activity and/or resetting of the baroreceptor reflexes. Therefore, anticholinergic agents should be administered when increases in vagal tone are anticipated.
As with other anesthetic agents, propofol injectable emulsion reduces myocardial oxygen consumption. Further studies are needed to confirm and delineate the extent of these effects on the myocardium and the coronary vascular system.
Morphine premedication (0.15 mg/kg) with nitrous oxide 67% in oxygen has been shown to decrease the necessary propofol injectable emulsion maintenance infusion rates and therapeutic blood concentrations when compared to non-narcotic (lorazepam) premedication. The rate of propofol injectable emulsion administration should be determined based on the patient’s premedication and adjusted according to clinical responses.
A rapid bolus induction should be avoided. A slow rate of approximately 20 mg every 10 seconds until induction onset (0.5 to 1.5 mg/kg) should be used. In order to assure adequate anesthesia, when propofol injectable emulsion is used as the primary agent, maintenance infusion rates should not be less than 100 mcg/kg/min and should be supplemented with analgesic levels of continuous opioid administration. When an opioid is used as the primary agent, propofol injectable emulsion maintenance rates should not be less than 50 mcg/kg/min, and care should be taken to ensure amnesia. Higher doses of propofol injectable emulsion will reduce the opioid requirements (see TABLE 4). When propofol injectable emulsion is used as the primary anesthetic, it should not be administered with the high-dose opioid technique as this may increase the likelihood of hypotension (see PRECAUTIONS - Cardiac Anesthesia).
TABLE 4. CARDIAC ANESTHESIA TECHNIQUES a OPIOID is defined in terms of fentanyl equivalents, i.e.,
1 mcg of fentanyl = 5 mcg of alfentanil (for bolus)
= 10 mcg of alfentanil (for maintenance)
OR
= 0.1 mcg of sufentanil
b Care should be taken to ensure amnesia.Primary Agent
Rate
Secondary Agent/Rate
(Following Induction with Primary Agent)Propofol Injectable Emulsion
OPIOIDa/0.05 - 0.075 mcg/kg/min (no bolus)
Preinduction
Anxiolysis
25 mcg/kg/min
Induction
0.5 - 1.5 mg/kg
Over 60 sec
Maintenance
(Titrated to Clinical Response)
100 - 150 mcg/kg/min
OPIOIDb
Propofol Injectable Emulsion/50 - 100 mcg/kg/min (no bolus)
Induction
25 - 50 mcg/kg
Maintenance
0.2 - 0.3 mcg/kg/min
Maintenance of General Anesthesia
Adult Patients: In adults, anesthesia can be maintained by administering propofol injectable emulsion by infusion or intermittent I.V. bolus injection. The patient’s clinical response will determine the infusion rate or the amount and frequency of incremental injections.
Continuous Infusion: Propofol injectable emulsion 100 to 200 mcg/kg/min administered in a variable rate infusion with 60% to 70% nitrous oxide and oxygen provides anesthesia for patients undergoing general surgery. Maintenance by infusion of propofol injectable emulsion should immediately follow the induction dose in order to provide satisfactory or continuous anesthesia during the induction phase. During this initial period following the induction dose, higher rates of infusion are generally required (150 to 200 mcg/kg/min) for the first 10 to 15 minutes. Infusion rates should subsequently be decreased 30% to 50% during the first half-hour of maintenance. Generally, rates of 50 to 100 mcg/kg/min in adults should be achieved during maintenance in order to optimize recovery times.
Other drugs that cause CNS depression (hypnotics/sedatives, inhalational anesthetics, and opioids) can increase the CNS depression induced by propofol.
Intermittent Bolus: Increments of propofol injectable emulsion 25 mg (2.5 mL) to 50 mg (5 mL) may be administered with nitrous oxide in adult patients undergoing general surgery. The incremental boluses should be administered when changes in vital signs indicate a response to surgical stimulation or light anesthesia.
Pediatric Patients: Propofol injectable emulsion administered as a variable rate infusion supplemented with nitrous oxide 60% to 70% provides satisfactory anesthesia for most children 2 months of age or older, ASA-PS I or II, undergoing general anesthesia.
In general, for the pediatric population, maintenance by infusion of propofol injectable emulsion at a rate of 200 to 300 mcg/kg/min should immediately follow the induction dose. Following the first half-hour of maintenance, infusion rates of 125 to 150 mcg/kg/min are typically needed. Propofol injectable emulsion should be titrated to achieve the desired clinical effect. Younger pediatric patients may require higher maintenance infusion rates than older pediatric patients. (See Clinical Trials - TABLE 2.)
Propofol injectable emulsion has been used with a variety of agents commonly used in anesthesia such as atropine, scopolamine, glycopyrrolate, diazepam, depolarizing and nondepolarizing muscle relaxants, and opioid analgesics, as well as with inhalational and regional anesthetic agents.
In the elderly, debilitated, or ASA-PS III or IV patients, rapid bolus doses should not be used, as this will increase cardiorespiratory effects including hypotension, apnea, airway obstruction, and oxygen desaturation.
Monitored Anesthesia Care (MAC) Sedation
Adult Patients: When propofol injectable emulsion is administered for MAC sedation, rates of administration should be individualized and titrated to clinical response. In most patients, the rates of propofol injectable emulsion administration will be in the range of 25 to 75 mcg/kg/min.
During initiation of MAC sedation, slow infusion or slow injection techniques are preferable over rapid bolus administration. During maintenance of MAC sedation, a variable rate infusion is preferable over intermittent bolus dose administration. In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation. (See WARNINGS.) A rapid bolus injection can result in undesirable cardiorespiratory depression including hypotension, apnea, airway obstruction, and oxygen desaturation.
Initiation of MAC Sedation: For initiation of MAC sedation, either an infusion or a slow injection method may be utilized while closely monitoring cardiorespiratory function. With the infusion method, sedation may be initiated by infusing propofol injectable emulsion at 100 to 150 mcg/kg/min (6 to 9 mg/kg/h) for a period of 3 to 5 minutes and titrating to the desired clinical effect while closely monitoring respiratory function. With the slow injection method for initiation, patients will require approximately 0.5 mg/kg administered over 3 to 5 minutes and titrated to clinical responses. When propofol injectable emulsion is administered slowly over 3 to 5 minutes, most patients will be adequately sedated, and the peak drug effect can be achieved while minimizing undesirable cardiorespiratory effects occurring at high plasma levels.
In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation. (See WARNINGS.) The rate of administration should be over 3-5 minutes and the dosage of propofol injectable emulsion should be reduced to approximately 80% of the usual adult dosage in these patients according to their condition, responses, and changes in vital signs. (See DOSAGE AND ADMINISTRATION.)
Maintenance of MAC Sedation: For maintenance of sedation, a variable rate infusion method is preferable over an intermittent bolus dose method. With the variable rate infusion method, patients will generally require maintenance rates of 25 to 75 mcg/kg/min (1.5 to 4.5 mg/kg/h) during the first 10 to 15 minutes of sedation maintenance. Infusion rates should subsequently be decreased over time to 25 to 50 mcg/kg/min and adjusted to clinical responses. In titrating to clinical effect, allow approximately 2 minutes for onset of peak drug effect.
Infusion rates should always be titrated downward in the absence of clinical signs of light sedation until mild responses to stimulation are obtained in order to avoid sedative administration of propofol injectable emulsion at rates higher than are clinically necessary.
If the intermittent bolus dose method is used, increments of propofol injectable emulsion 10 mg (1 mL) or 20 mg (2 mL) can be administered and titrated to desired clinical effect. With the intermittent bolus method of sedation maintenance, there is increased potential for respiratory depression, transient increases in sedation depth, and prolongation of recovery.
In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation. (See WARNINGS.) The rate of administration and the dosage of propofol injectable emulsion should be reduced to approximately 80% of the usual adult dosage in these patients according to their condition, responses, and changes in vital signs. (See DOSAGE AND ADMINISTRATION.)
Propofol injectable emulsion can be administered as the sole agent for maintenance of MAC sedation during surgical/diagnostic procedures. When propofol injectable emulsion sedation is supplemented with opioid and/or benzodiazepine medications, these agents increase the sedative and respiratory effects of propofol injectable emulsion and may also result in a slower recovery profile. (See PRECAUTIONS - Drug Interactions.)
ICU Sedation: (See WARNINGS and DOSAGE AND ADMINISTRATION - Handling Procedures.)
Abrupt discontinuation of propofol injectable emulsion prior to weaning or for daily evaluation of sedation levels should be avoided. This may result in rapid awakening with associated anxiety, agitation, and resistance to mechanical ventilation. Infusions of propofol injectable emulsion should be adjusted to assure a minimal level of sedation is maintained throughout the weaning process and when assessing the level of sedation. (See PRECAUTIONS.)
Adult Patients: For intubated, mechanically ventilated adult patients, Intensive Care Unit (ICU) sedation should be initiated slowly with a continuous infusion in order to titrate to desired clinical effect and minimize hypotension. (See DOSAGE AND ADMINISTRATION.)
Most adult ICU patients recovering from the effects of general anesthesia or deep sedation will require maintenance rates of 5 to 50 mcg/kg/min (0.3 to 3 mg/kg/h) individualized and titrated to clinical response. (See DOSAGE AND ADMINISTRATION.) With medical ICU patients or patients who have recovered from the effects of general anesthesia or deep sedation, the rate of administration of 50 mcg/kg/min or higher may be required to achieve adequate sedation. These higher rates of administration may increase the likelihood of patients developing hypotension.
Dosage and rate of administration should be individualized and titrated to the desired effect, according to clinically relevant factors including the patient’s underlying medical problems, preinduction and concomitant medications, age, ASA-PS classification, and level of debilitation of the patient. The elderly, debilitated, and ASA-PS III or IV patients may have exaggerated hemodynamic and respiratory responses to rapid bolus doses. (See WARNINGS.)
Propofol injectable emulsion should be individualized according to the patient’s condition and response, blood lipid profile, and vital signs. (See PRECAUTIONS - Intensive Care Unit Sedation.) For intubated, mechanically ventilated adult patients, Intensive Care Unit (ICU) sedation should be initiated slowly with a continuous infusion in order to titrate to desired clinical effect and minimize hypotension. When indicated, initiation of sedation should begin at 5 mcg/kg/min (0.3 mg/kg/h). The infusion rate should be increased by increments of 5 to 10 mcg/kg/min (0.3 to 0.6 mg/kg/h) until the desired level of sedation is achieved. A minimum period of 5 minutes between adjustments should be allowed for onset of peak drug effect. Most adult patients require maintenance rates of 5 to 50 mcg/kg/min (0.3 to 3 mg/kg/h) or higher. Dosages of propofol injectable emulsion should be reduced in patients who have received large dosages of narcotics. Conversely, the propofol injectable emulsion dosage requirement may be reduced by adequate management of pain with analgesic agents. As with other sedative medications, there is interpatient variability in dosage requirements, and these requirements may change with time. (See SUMMARY OF DOSAGE GUIDELINES.) Evaluation of level of sedation and assessment of CNS function should be carried out daily throughout maintenance to determine the minimum dose of propofol required for sedation (see Clinical Trials - Intensive Care Unit (ICU) Sedation). Bolus administration of 10 or 20 mg should only be used to rapidly increase depth of sedation in patients where hypotension is not likely to occur. Patients with compromised myocardial function, intravascular volume depletion, or abnormally low vascular tone (e.g., sepsis) may be more susceptible to hypotension. (See PRECAUTIONS.)
SUMMARY OF DOSAGE GUIDELINESDosages and rates of administration in the following table should be individualized and titrated to clinical response. Safety and dosing requirements for induction of anesthesia in pediatric patients have only been established for children 3 years of age or older. Safety and dosing requirements for the maintenance of anesthesia have only been established for children 2 months of age and older.
For complete dosage information, see DOSAGE AND ADMINISTRATION.
INDICATION
DOSAGE AND ADMINISTRATION
Induction of General Anesthesia
Healthy Adults Less Than 55 Years of Age: 40 mg every 10 seconds until induction onset (2 to 2.5 mg/kg).
Elderly, Debilitated, or ASA-PS III or IV Patients: 20 mg every 10 seconds until induction onset (1 to 1.5 mg/kg).
Cardiac Anesthesia: 20 mg every 10 seconds until induction onset (0.5 to 1.5 mg/kg).
Neurosurgical Patients: 20 mg every 10 seconds until induction onset (1 to 2 mg/kg).
Pediatric Patients - healthy, from 3 years to 16 years of age: 2.5 to 3.5 mg/kg administered over 20 to 30 seconds.
(See PRECAUTIONS - Pediatric Use and CLINICAL PHARMACOLOGY - Pediatrics.)
Maintenance of General Anesthesia: Infusion
Healthy Adults Less Than 55 Years of Age: 100 to 200 mcg/kg/min (6 to 12 mg/kg/h).
Elderly, Debilitated, ASA-PS III or IV Patients: 50 to 100 mcg/kg/min (3 to 6 mg/kg/h).
Cardiac Anesthesia: Most patients require:
Primary Propofol Injectable Emulsion with Secondary Opioid -100 to 150 mcg/kg/min.
Low-dose Propofol Injectable Emulsion with Primary Opioid - 50 to 100 mcg/kg/min. (See DOSAGE AND ADMINISTRATION, TABLE 4.)
Neurosurgical Patients: 100 to 200 mcg/kg/min (6 to 12 mg/kg/h).
Pediatric Patients - healthy, from 2 months of age to 16 years of age: 125 to 300 mcg/kg/min (7.5 to 18 mg/kg/h).
Following the first half hour of maintenance, if clinical signs of light anesthesia are not present, the infusion rate should be decreased. (See PRECAUTIONS - Pediatric Use and CLINICAL PHARMACOLOGY - Pediatrics.)
Maintenance of General Anesthesia: Intermittent Bolus
Healthy Adults Less Than 55 Years of Age: Increments of 20 to 50 mg as needed.
Initiation of MAC Sedation
Healthy Adults Less Than 55 Years of Age: Slow infusion or slow injection techniques are recommended to avoid apnea or hypotension. Most patients require an infusion of 100 to 150 mcg/kg/min (6 to 9 mg/kg/h) for 3 to 5 minutes or a slow injection of 0.5 mg/kg over 3 to 5 minutes followed immediately by a maintenance infusion.
Elderly, Debilitated, Neurosurgical, or ASA-PS III or IV Patients: Most patients require dosages similar to healthy adults. Rapid boluses are to be avoided. (See WARNINGS.)
Maintenance of MAC Sedation
Healthy Adults Less Than 55 Years of Age: A variable rate infusion technique is preferable over an intermittent bolus technique. Most patients require an infusion of 25 to 75 mcg/kg/min (1.5 to 4.5 mg/kg/h) or incremental bolus doses of 10 mg or 20 mg.
In Elderly, Debilitated, Neurosurgical, or ASA-PS III/IV Patients: Most patients require 80% of the usual adult dose. A rapid (single or repeated) bolus dose should not be used. (See WARNINGS.)
Initiation and Maintenance of ICU Sedation in Intubated, Mechanically Ventilated
Adult Patients – Because of the residual effects of previous anesthetic or sedative agents, in most patients the initial infusion should be 5 mcg/kg/min (0.3 mg/kg/h) for at least 5 minutes. Subsequent increments of 5 to 10 mcg/kg/min (0.3 to 0.6 mg/kg/h) over 5 to 10 minutes may be used until desired clinical effect is achieved. Maintenance rates of 5 to 50 mcg/kg/min (0.3 to 3 mg/kg/h) or higher may be required.
Evaluation of clinical effect and assessment of CNS function should be carried out daily throughout maintenance to determine the minimum dose of propofol injectable emulsion required for sedation.
The tubing and any unused portions of propofol injectable emulsion should be discarded after 12 hours because propofol injectable emulsion contains no preservatives and is capable of supporting growth of microorganisms. (See WARNINGS and DOSAGE AND ADMINISTRATION.)
Administration with Lidocaine: If lidocaine is to be administered to minimize pain on injection of propofol, it is recommended that it be administered prior to propofol administration or that it be added to propofol immediately before administration and in quantities not exceeding 20 mg lidocaine/200 mg propofol.
Compatibility and Stability: Propofol injectable emulsion should not be mixed with other therapeutic agents prior to administration.
Dilution Prior to Administration: Propofol injectable emulsion is provided as a ready-to-use formulation. However, should dilution be necessary, it should only be diluted with 5% Dextrose Injection, USP, and it should not be diluted to a concentration less than 2 mg/mL because it is an emulsion. In diluted form it has been shown to be more stable when in contact with glass than with plastic (95% potency after 2 hours of running infusion in plastic).
Administration with Other Fluids: Compatibility of propofol injectable emulsion with the coadministration of blood/serum/plasma has not been established. (See WARNINGS.) When administered using a y-type infusion set, propofol injectable emulsion has been shown to be compatible with the following intravenous fluids.
– 5% Dextrose Injection, USP
– Lactated Ringers Injection, USP
– Lactated Ringers and 5% Dextrose Injection
– 5% Dextrose and 0.45% Sodium Chloride Injection, USP
– 5% Dextrose and 0.2% Sodium Chloride Injection, USPHandling Procedures
General
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
Clinical experience with the use of in-line filters and propofol injectable emulsion during anesthesia or ICU/MAC sedation is limited. Propofol injectable emulsion should only be administered through a filter with a pore size of 5 micron or greater unless it has been demonstrated that the filter does not restrict the flow of propofol injectable emulsion and/or cause the breakdown of the emulsion. Filters should be used with caution and where clinically appropriate. Continuous monitoring is necessary due to the potential for restricted flow and/or breakdown of the emulsion.
Do not use if there is evidence of separation of the phases of the emulsion.
Rare cases of self-administration of propofol injectable emulsion, by health care professionals have been reported, including some fatalities. (See DRUG ABUSE AND DEPENDENCE.)
Strict aseptic technique must always be maintained during handling. Propofol injectable emulsion is a single-use parenteral product which contains benzyl alcohol 1.5 mg/mL and sodium benzoate 0.7 mg/mL to inhibit the rate of growth of microorganisms, up to 12 hours, in the event of accidental extrinsic contamination. However, propofol injectable emulsion can still support the growth of microorganisms as it is not an antimicrobially preserved product under USP standards. Accordingly, strict aseptic technique must still be adhered to. Do not use if contamination is suspected. Discard unused portions as directed within the required time limits (see DOSAGE AND ADMINISTRATION – Handling Procedures). There have been reports in which failure to use aseptic technique when handling propofol injectable emulsion was associated with microbial contamination of the product and with fever, infection/sepsis, other life-threatening illness, and/or death.
Propofol injectable emulsion, with benzyl alcohol, inhibits microbial growth for up to 12 hours, as demonstrated by test data for representative USP microorganisms.
Guidelines for Aseptic Technique for General Anesthesia/MAC Sedation
Propofol should be prepared for use just prior to initiation of each individual anesthetic/sedative procedure. The vial rubber stopper should be disinfected using 70% isopropyl alcohol. Propofol should be drawn into sterile syringes immediately after vials are opened. When withdrawing propofol from vials, a sterile vent spike should be used. The syringe(s) should be labeled with appropriate information including the date and time the vial was opened. Administration should commence promptly and be completed within 12 hours after the vials have been opened.
Propofol injectable emulsion should be prepared for single-patient use only. Any unused portions of propofol injectable emulsion, reservoirs, dedicated administration tubing and/or solutions containing propofol injectable emulsion must be discarded at the end of the anesthetic procedure or at 12 hours, whichever occurs sooner. The I.V. line should be flushed every 12 hours and at the end of the anesthetic procedure to remove residual propofol injectable emulsion.
Guidelines for Aseptic Technique for ICU Sedation
Propofol injectable emulsion should be prepared for single-patient use only. When propofol injectable emulsion is administered directly from the vial, strict aseptic techniques must be followed. The vial rubber stopper should be disinfected using 70% isopropyl alcohol. A sterile vent spike and sterile tubing must be used for administration of propofol injectable emulsion. As with other lipid emulsions, the number of I.V. line manipulations should be minimized. Administration should commence promptly and must be completed within 12 hours after the vial has been spiked. The tubing and any unused portions of propofol injectable emulsion must be discarded after 12 hours.
If propofol injectable emulsion is transferred to a syringe or other container prior to administration, the handling procedures for General Anesthesia/MAC Sedation should be followed and the product should be discarded and administration lines changed after 12 hours.
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General Injectables And Vaccines, Inc
Propofol | General Injectables And Vaccines, Inc
NOTE: CONTAINS BENZYL ALCOHOL. (See PRECAUTIONSsection.)
Propofol blood concentrations at steady state are generally proportional to infusion rates, especially in individual patients. Undesirable effects such as cardiorespiratory depression are likely to occur at higher blood concentrations which result from bolus dosing or rapid increases in the infusion rate. An adequate interval (3 to 5 minutes) must be allowed between dose adjustments to allow for and assess the clinical effects.
When administering propofol injectable emulsion by infusion, syringe or volumetric pumps are recommended to provide controlled infusion rates. When infusing propofol injectable emulsion to patients undergoing magnetic resonance imaging, metered control devices may be utilized if mechanical pumps are impractical.
Changes in vital signs indicating a stress response to surgical stimulation or the emergence from anesthesia may be controlled by the administration of 25 mg (2.5 mL) to 50 mg (5 mL) incremental boluses and/or by increasing the infusion rate of propofol injectable emulsion.
For minor surgical procedures (e.g., body surface) nitrous oxide (60% to 70%) can be combined with a variable rate propofol injectable emulsion infusion to provide satisfactory anesthesia. With more stimulating surgical proce4dures (e.g., intra-abdominal), or if supplementation with nitrous oxide is not provided, administration rate(s) of propofol injectable emulsion and/or opioids should be increased in order to provide adequate anesthesia.
Infusion rates should always be titrated downward in the absence of clinical signs of light anesthesia until a mild response to surgical stimulation is obtained in order to avoid administration of profofol injection emulsion at rates higher than are clinically necessary. Generally, rates of 50 to 100 mcg/kg/min in adults should be achieved during maintenance in order to optimize recovery time.
Other drugs that cause CNS depression (hypnotics/sedatives, inhalational anesthetics, and opioids) can increase CNS depression induced by propofol. Morphine premedication (0.15 mg/kg) with nitrous oxide 67% in oxygen has been shown to decrease the necessary propofol injection maintenance infusion rate and therapeutic blood concentrations when compared to non-narcotic (lorazepam) premedication.
Induction of General Anesthesia
Adult Patients: Most adult patients under 55 years of age and classified as ASA-PS I or II require 2 to 2.5 mg/kg of propofol injectable emulsion for induction when unpremedicated or when premedicated with oral benzodiazepines or intramuscular opioids. For induction, propofol injectable emulsion should be titrated (approximately 40 mg every 10 seconds) against the response of the patient until the clinical signs show the onset of anesthesia. As with other sedative-hypnotic agents, the amount of intravenous opioid and/or benzodiazepine premedication will influence the response of the patient to an induction dose of propofol injectable emulsion.
Elderly, Debilitated, or ASA-PS III or IV Patients: It is important to be familiar and experienced with the intravenous use of propofol injectable emulsion before treating elderly, debilitated, or ASA-PS III or IV patients. Due to the reduced clearance and higher blood concentrations, most of these patients require approximately 1 to 1.5 mg/kg (approximately 20 mg every 10 seconds) of propofol injectable emulsion for induction of anesthesia according to their condition and responses. A rapid bolus should not be used, as this will increase the likelihood of undesirable cardiorespiratory depression including hypotension, apnea, airway obstruction, and/or oxygen desaturation. (See DOSAGE AND ADMINISTRATION.)
Pediatric Patients: Most patients aged 3 years through 16 are classified ASA-PS I or II require 2.5 to 3.5 mg/kg of propofol injectable emulsion for induction when unpremedicated or when lightly premedicated with oral benzodiazepines or intramuscular opioids. Within this dosage range, younger pediatric patients may require higher induction doses than older pediatric patients. As with other sedative-hypnotic agents, the amount of intravenous opioid and/or benzodiazepine premedication will influence the response of the patient to an induction dose of propofol injectable emulsion. A lower dosage is recommended for pediatric patients classified as ASA-PS III or IV. Attention should be paid to minimize pain on injection when administering propofol injectable emulsion to pediatric patients. Boluses of propofol injectable emulsion may be administered via small veins if pretreated with lidocaine or via antecubital or larger veins. (See PRECAUTIONS - General.)
Neurosurgical Patients: Slower induction in recommended using boluses of 20 mg every 10 seconds. Slower boluses or infusions or propofol injectable emulsion for induction of anesthesia, titrated to clinical responses, will generally result in reduced induction dosage requirements (1 to 2 mg/kg). (See PRECAUTIONSand DOSAGE AND ADMINISTRATION.)
Cardiac Anesthesia: Propofol injectable emulsion has been well-studied in patients with coronary artery disease, but experience in patients with hemodynamically significant valvular or congenital heart disease is limited. As with other anesthetic and sedative-hypnotic agents, propofol injectable emulsion in healthy patients causes a decrease in blood pressure that is secondary to decreases in preload (ventricular filling volume at the end of the diastole) and afterload (arterial resistance at the beginning of the systole). The magnitude of these changes is proportional to the blood and effect site concentrations achieved. These concentrations depend upon the dose and speed of the induction and maintenance infusion rates.
In addition, lower heart rates are observed during maintenance with propofol injectable emulsion, possibly due to reduction of the sympathetic activity and/or resetting of the baroreceptor reflexes. Therefore, anticholinergic agents should be administered when increases in vagal tone are anticipated.
As with other anesthetic agents, propofol injectable emulsion reduces myocardial oxygen consumption. Further studies are needed to confirm and delineate the extent of these effects on the myocardium and the coronary vascular system.
Morphine premedication (0.15 mg/kg) with nitrous oxide 67% in oxygen has been shown to decrease the necessary propofol injectable emulsion maintenance infusion rates and therapeutic blood concentrations when compared to non-narcotic (lorazepam) premedication. The rate of propofol injectable emulsion administration should be determined based on the patient's premedication and adjusted according to clinical responses.
A rapid bolus induction should be avoided. A slow rate of approximately 20 mg every 10 seconds until induction onset 0.5 to 1.5 mg/kg) should be used. In order to assure adequate anesthesia, when propofol injectable emulsion is used as the primary agent, maintenance infusion rates should not be less than 100 mcg/kg/min and should be supplemented with analgesic levels of continuous opioid administration. When an opioid is used as the primary agent, propofol injectable emulsion maintenance rates should not be less than 50 mcg/kg/min, and care should be taken to ensure amnesia. Higher doses of propofol injectable emulsion will reduce the opioid requirements (see TABLE 4). When propofol injectable emulsion is used as the primary anesthetic, it should not be administered with the high-dose opioid technique as this may increase the likelihood of hypotension (see PRECAUTIONS- Cardiac Anesthesia).
Maintenance of General Anesthesia
Adult Patients: In adults, anesthesia can be maintained by administering propofol injectable emulsion or infusion or intermittent I.V. bolus injection. The patient's clinical response will determine the infusion rate or the amount and frequency of incremental injections.
Continuous Infusion: Propofol injectable emulsion 100 to 200 mcg/kg/min administered in a variable rate infusion with 60% to 70% nitrous oxide and oxygen provides anesthesia for patients undergoing general surgery. Maintenance by infusion of propofol injectable emulsion should immediately follow the induction dose in order to provide satisfactory or continuous anesthesia during the induction phase. During this initial period following the induction dose, higher rates of infusion are generally required (150 to 200 mcg/kg/min) for the first 10 to 15 minutes. Infusion rates should subsequently be decreased 30% to 50% during the first half-hour of maintenance. Generally, rates of 50 to 100 mcg/kg.min in adults should be achieved during maintenance in order to optimize recovery times.
Other drugs that cause CNS depression (hypnotics/sedatives, inhalational anesthetics, and opioids) can increase the CNS depression induced by propofol.
Intermittent Bolus: Increments of propofol injectable emulsion 25 mg (2.5 mL) to 50 mg (5 mL) may be administered with nitrous oxide in adult patients udergoing general surgery. The incremental boluses should be administered when changes in vital signs indicated a response to surgical stimulation or light anesthesia.
Pediatric Patients: Propofol injectable emulsion administered as a variable rate infusion supplemented with nitrous oxide 60% to 70% provides satisfactory anesthesia for most children 2 months of age or older, ASA-PS I or II, undergoing general anesthesia.
In general, for the pediatric population, maintenance by infusion of propofol injectable emulsion at a rate of 200 to 300 mcg/kg/min should immediately follow the induction dose. Following the first half-hour of maintenance, infusion rates of 125 to 150 mcg/kg/min are typically needed. Propofol injectable emulsion should be titrated to achieve the desired clinical effect. Younger pediatric patients may require higher maintenance infusion rates than older pediatric patients. (See Clinical Trials - TABLE 2.)
Propofol injectable emulsion has been used with a variety of agents commonly used in anesthesia such as atropine, scopolamine, glycopyrrolate, diazepam, depolarizing and nondepolarizing muscle relaxants, and opioid analgesics, as well as with inhalational and regional anesthetic agents.
In the elderly, debilitated, or ASA-PS III or IV patients, rapid bolus doses should not be used, as this will increase cardiorespiratory effects including hypotension, apnea, airway obstruction, and oxygen desaturation.
Monitored Anesthesia Care (MAC) Sedation
Adult Patients: When propofol injectable emulsion is administered for MAC sedation, rates of administration should be individualized and titrated to clinical response. In most patients, the rates of propofol injectable emulsion administration will be in the range of 25 to 75 mcg/kg/min.
During initiation of MAC sedation, slow infusion or slow injection techniques are preferable over rapid bolus administration. During maintenance of MAC sedation, a variable rate infusion is preferable over intermittent bolus dose administration. In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation. (See WARNINGS.) A rapid bolus injection can result in undesirable cardiorespiratory depression including hypotension, apnea, airway obstruction, and oxygen desaturation.
Initiation of MAC Sedation: For initiation of MAC sedation, either an infusion or a slow injection method may be utilized while closely monitoring cardiorespiratory function. With the infusion method, sedation may be initiated by infusing propofol injectable emulsion at 100 to 150 mcg/kg/min (6 to 9 mg/kg/h) for a period of 3 to 5 minutes and titrating to the desired clinical effect while closely monitoring respiratory function. With the slow injection method for initiation, patients will require approximately 0.5 mg/kg administered over 3 to 5 minutes and titrated to clinical responses. When propofol injectable emulsion is administered slowly over 3 to 5 minutes, most patients will be adequately sedated, and the peak drug effect can be achieved while minimizing undesirable cardiorespiratory effects occurring at high plasma levels.
In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation. (See WARNINGS.) The rate of administration should be over 3 to 5 minutes and the dosage of propofol injectable emulsion should be reduced to approximately 80% of the usual adult dosage in these patients according to their condition, responses, and changes in vital signs. (See DOSAGE AND ADMINISTRATION.)
Maintenance of MAC Sedation: For maintenance of sedation, a variable rate infusion method is preferable over an intermittent bolus dose method. With the variable rate infusion method, patients will generally require maintenance rates of 25 to 75 mcg/kg/min (1.5 to 4.5 mg/kg/h) during the first 10 to 15 minutes of sedation maintenance. Infusion rates should subsequently be decreased over time to 25 to 50 mcg/kg/min and adjusted to clinical responses. In titrating to clinical effect, allow approximately 2 minutes for onset of peak drug effect.
Infusion rates should always be titrated downward in the absence of clinical signs of light sedation until mild responses to stimulation are obtained in order to avoid sedative administration of propofol injectable emulsion at rates higher than are clinically necessary.
If the intermittent bolus dose method is used, increments of propofol injectable emulsion 10 mg (1 mL) or 20 mg (2 mL) can be administered and titrated to desired clinical effect. With the intermittent bolus method of sedation maintenance, there is increased potential for respiratory depression, transient increases in sedation depth, and prolongation of recovery.
In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation. (See WARNINGS.) The rate of administration and the dosage of propofol injection emulsion should be reduced to approximately 80% of the usual adult dosage in these patients according to their condition, responses, and changes in vital signs. (See DOSAGE AND ADMINISTRATION.)
Propofol injectable emulsion can be administered as the sole agent for maintenance of MAC sedation during surgical/diagnostic procedures. When propofol injectable emulsion sedation is supplemented with opioid and/or benzodiazepine medications, these agents increase the sedative and respiratory effects of propofol injectable emulsion and may also result in a slower recovery profile. (See PRECAUTIONS -Drug Interactions.)
ICU Sedation: (See WARNINGS andDOSAGE AND ADMINISTRATION - Handling Procedures.)
Abrupt discontinuation of propofol injectable emulsion prior to weaning or for daily evaluation of sedation levels should be avoided. This may result in rapid awakening with associated anxiety, agitation, and resistance to mechanical ventilation. Infusions of propofol injectable emulsion should be adjusted to assure a minimal level of sedation is maintained throughout the weaning process and when assessing the level of sedation. (See PRECAUTIONS).
Administration with Lidocaine: If lidocaine is to be administered to minimize pain on injection of propofol, it is recommended that it be administered prior to propofol administration or that it be added to propofol immediately before administration and in quantities not exceeding 20 mg lidocaine/200 mg propofol.
Compatibility and Stability: Propofol injectable emulsion should not be mixed with other therapeutic agents prior to administration.
Dilution Prior to Administration: Propofol injectable emulsion is provided as a ready-to-use formulation. However, should dilution be necessary, it should only be diluted with 5% Dextrose Injection, USP, and it should not be diluted to a concentration less than 2 mg/mL because it is an emulsion. In diluted form it has been shown to be more stable when in contact with glass than with plastic (95% potency after 2 hours of running infusion in plastic).
Administration with Other Fluids: Compatibility of propofol injectable emulsion with the coadministration of blood/serum/plasma has not been established. (See WARNINGS.)
When administered using a y-type infusion set, propofol injectable emulsion has been shown to be compatible with the following intravenous fluids.
- 5% Dextrose Injection, USP
-Lactated Ringers Injection, USP
- Lactated Ringers and 5% Dextrose Injection
- 5% Dextrose and 0.45% Sodium Chloride Injection, USP
- 5% Dextrose and 0.2% Sodium Chloride Injection, USP
Handling Procedures
General
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
Clinical experience with the use of in-line filters and propofol injectable emulsion during anesthesia or ICU/MAC sedation is limited. Propofol injectable emulsion should only be administered through a filter with a pore size of 5 micron or greater unless it has been demonstrated that the filter does not restrict the flow of propofol injectable emulsion and/or cause the breakdown of the emulsion. Filters should be used with caution and where clinically appropriate. Continuous monitoring is necessary due to the potential for restricted flow and/or breakdown of the emulsion.
Rare cases of self-administration of propofol injectable emulsion, by health care professionals have been reported, including some fatalities. (See DRUG ABUSE AND DEPENDENCE.)
Strict aseptic technique must always be maintained during handling. Propofol injectable emulsion is a single-use parenteral product which contains benzyl alcohol 1.5 mg/mL and sodium benzoate 0.7 mg/mL to inhibit the rate of growth of microorganisms, up to 12 hours, in the event of accidental extrinsic contamination. However, propofol injectable emulsion can still support the growth of microorganisms as it is not an antimicrobially preserved product under USP standards. Accordingly, strict aseptic technique must still be adhered to. Do not use if contamination is suspected. Discard unused portions as directed within the required time limits (see DOSAGE AND ADMINISTRATION - Handling Procedures). There have been reports in whicch failure to use aseptic technique when handling propofol injectable emulsion was associated with microbial contamination of the product and with fever, infection/sepsis, other life-threatening illness, and/or death.
Propofol injectable emulsion, with benzyl alcohol, inhibits microbial growth for up to 12 hours, as demonstrated by test data for representative USP microorganisms.
Guidelines for Aseptic Technique for General Anesthesia/MAC Sedation
Propofol should be prepared for use just prior to initiation of each individual anesthetic/sedative procedure. The vial rubber stopper should be disinfected using 70% isopropyl alcohol. Propofol should be drawn into sterile syringes immediately after vials are opened. When withdrawing propofol from vials, a sterile vent spike should be used. The syringe(s) should be labeled with appropriate information including the date and time the vial was opened. Administration should commence promptly and be completed within 12 hours after the vials have been opened.
Propofol injectable emulsion should be prepared for single-patient use only. Any unused portions of propofol injectable emulsion, reservoirs, dedicated administration tubing and/or solutions containing propofol injectable emulsion must be idscarded at the end of the anesthetic procedure or at 12 hours, whichever occurs sooner. The I.V. line should be flushed every 12 hours at the end of the anesthetic procedure to remove residual propofol injectable emulsion.
Guidelines for Aseptic Technique for ICU Sedation
Propofol injectable emulsion should be prepared for single-patient use only. When propofol injectable emulsion is administered directly from the vial, strict aseptic techniques must be followed. The vial rubber stopper should be disinfected using 70% isopropyl alcohol. A sterile vent spike and sterile tubing must be used for administration of propofol injectable emulsion. As with other lipid emulsions, the number of I.V. line manipulations should be minimized. Adminstration should commence propltly and must be completed within 12 hours after the vial has been spiked. The tubing and any nused portions of propofol injectable emulsion must be discarded after 12 hours.
If propofol injectable emulsion is transferred to a syringe or other container prior to administration, the handling procedures for General Anesthesia/MAC Sedation should be followed and the product should be discarded and administration lines changed after 12 hours.
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