Propofol (Monograph)

Brand name: Diprivan
Drug class: Non-barbiturates

Medically reviewed by Drugs.com on Jun 10, 2024. Written by ASHP.

Introduction

Sedative and hypnotic.¹ ² ²¹⁵

Uses for Propofol

Induction and Maintenance of Anesthesia

IV induction and maintenance of general anesthesia.¹ ² ⁶ ⁷ ⁸ ⁹ ¹⁰ ¹¹⁸ ¹⁹² ²¹⁶ ²¹⁷ ²¹⁸ ²²¹

FDA-labeled for use as an IV induction agent for general anesthesia in adults and pediatric patients ≥3 years of age and for maintenance anesthesia in adults and pediatric patients ≥2 months of age.¹ ²

IV induction with propofol is rapid and results in dose-related hypnotic effects (progressing from light sleep to unconsciousness) and anterograde amnesia; however, analgesic properties not conclusively demonstrated.¹ ⁵ ⁶ ⁸ ¹⁰ ¹⁷ ²⁰ ¹¹⁸ ²¹⁵ ²¹⁶ ²²⁸ Generally produces loss of consciousness in <1 minute (time required for one arm-brain circulation).¹ ⁹ Following induction, anesthesia can be maintained by continuous IV infusion or intermittent IV injections.¹ ² ⁵ ⁶ ⁹ ¹⁰ ¹¹⁸ ²¹⁶ Recovery from propofol anesthesia is rapid because of fast redistribution and clearance of the drug.¹ ²¹⁸

Usually associated with similar or faster time to recovery from anesthesia, more rapid recovery of psychomotor performance and time to discharge, and lower incidence of adverse effects (e.g., nausea, vomiting) compared with other IV anesthetic agents (e.g., etomidate, methohexital).⁶ ⁷ ⁹ ¹⁰ ¹¹⁸ ²¹⁵

Compared with inhalation anesthetics (e.g., sevoflurane, desflurane, isoflurane), propofol is associated with a consistent and clinically relevant lower incidence of postoperative nausea and vomiting.¹¹⁹ ¹²² ¹²⁴ ¹²⁵ ¹²⁶ ¹²⁷ ¹⁷⁸ ²¹⁷ ²¹⁸ ²²⁵

Procedural Sedation

Sedation in patients undergoing diagnostic or therapeutic procedures across various clinical settings (e.g., emergency department, cardiac catheterization laboratories, radiology suites, endoscopy suites, dental offices).¹ ⁶ ¹⁷⁰ ¹⁷¹ ²¹² ²¹³ ²¹⁴ ²¹⁵ ²¹⁹ ²²⁰ ²²¹ ²²² ²²³ ²²⁴ ²²⁶ ²²⁷ ²²⁸ ⁸²¹ ⁸²² ⁸²³ A preferred drug for this use because of rapid onset of effect, short duration, and rapid recovery.²²² ⁸²¹ ⁸²² ⁸²³

Generally used to provide moderate sedation (also referred to as conscious sedation) or deep sedation depending on the procedure, clinical setting, and patient requirements.²¹² ²¹³ ²¹⁴ ²¹⁹ ⁸²² ⁸²³ Because propofol can produce rapid and profound changes in the depth of sedation and lacks a reversal agent, the American Society of Anesthesiologists states that even if moderate sedation is intended, patients should receive the same level of care required for deep sedation.⁷⁵⁷

May be used with monitored anesthesia care (MAC) or in conjunction with local or regional anesthesia.¹ ²³ ⁴² ⁴³ ⁷⁵⁴ ⁷⁵⁵

Although not FDA-labeled for use in children,¹ propofol has been used widely for pediatric procedural sedation^{† [off-label]}.⁹⁹ ²¹⁴ ²²¹ ²²² ²²³ ²²⁶ ⁸²¹ ⁸²²

Monitored Anesthesia Care

Initiation and maintenance of MAC sedation (alone or in combination with an opiate analgesic and/or a benzodiazepine) in adults undergoing diagnostic or therapeutic procedures.¹ ² ⁶ ⁷ ¹⁵² ¹⁵³ ¹⁵⁴ ¹⁵⁵ ¹⁵⁶ ¹⁵⁷ ¹⁵⁸ ²¹³

MAC is a specific anesthesia service performed by a qualified anesthesia provider and does not refer to a specific level of sedation.⁷⁵⁴ ⁷⁵⁵ The MAC provider is focused exclusively on the patient's anesthetic needs and is prepared to manage any complications, including conversion to general anesthesia if necessary.⁷⁵⁴ ⁷⁵⁵

Factors to consider when determining whether MAC sedation is indicated include the nature of the procedure, patient's clinical condition, risk factors, and/or need for deeper levels of analgesia and sedation than can be provided by moderate sedation (including need to convert to general or regional anesthesia).²¹³ ⁷⁵⁴ ⁷⁵⁵

MAC sedation is distinguished from moderate sedation, which is a drug-induced depression of consciousness during which patients respond purposefully to verbal commands.⁷⁵⁴ ⁷⁵⁵

Sedation in Critical Care Settings

Sedation in intubated and mechanically ventilated adults in a critical care setting (e.g., ICU);¹ ² ⁵ ³³ ³⁴ ³⁵ ³⁶ ³⁷ ³⁹ ⁴⁰ ⁴¹ ⁴⁷ ⁶⁹ ¹³² ¹³³ ¹³⁵ ²³² ⁸⁰⁰ used alone or in combination with an opiate analgesic (e.g., morphine, fentanyl).¹ ² ⁵ ⁸ ³³ ³⁵ ³⁶ ³⁸ ³⁹ ⁴¹ ⁶⁹ ¹³² ¹³³ ¹³⁵ ¹³⁶ ¹⁵⁹ ¹⁶⁰ ¹⁶²

Appears to be as effective as dexmedetomidine and benzodiazepines (e.g., midazolam, lorazepam) for ICU sedation; however, because of some modest clinical benefits (e.g., reduced duration of mechanical ventilation, shorter time to extubation, reduced risk of delirium), some experts state that nonbenzodiazepine sedatives (dexmedetomidine or propofol) may be preferred to benzodiazepines in mechanically ventilated, critically ill adults.⁸⁰⁰ ⁸⁰¹ ⁸¹⁷ ⁸¹⁸ ⁸¹⁹ ⁸²⁰

When selecting an appropriate sedative agent, consider patient's individual sedation goals in addition to specific drug-related (e.g., pharmacology, pharmacokinetics, adverse effects, availability, cost) and patient-related (e.g., comorbid conditions such as anxiety, seizures, or alcohol or benzodiazepine withdrawal) factors.²³ ²⁴ ⁸⁰⁰ ⁸⁰¹

Because of its short duration of sedative effect, some experts state that propofol may be particularly useful in patients requiring frequent awakenings (e.g., for neurologic assessments) or undergoing daily sedation interruption protocols.⁸⁰¹

Seizures

Has been used in patients with refractory status epilepticus^{† [off-label]}.¹⁷ ⁴⁸ ⁴⁹ ¹³⁴ ¹³⁷ ¹⁶⁸ ¹⁶⁹ ²³³ ²³⁴

Nausea and Vomiting

Has been used for the management of postoperative nausea and vomiting^{† [off-label]}.¹⁷ ⁵⁰

Has been used in combination with conventional antiemetics for the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy^{† [off-label]} .¹⁷ ⁵¹ ⁵²

Pruritus

Has been used effectively for relief of pruritus^{† [off-label]} associated with use of spinal opiates or with cholestasis.¹⁷ ⁵³ ⁵⁴ ⁵⁵ ⁵⁶

Propofol Dosage and Administration

General

Patient Monitoring

During administration of propofol, closely monitor patient's cardiorespiratory function.¹ ²²⁰ ⁷⁵⁷
In elderly, debilitated, or American Society of Anesthesiologists-Physical Status (ASA-PS) III or IV patients, continuously monitor for early signs of hypotension and/or bradycardia during administration of propofol.¹

Dispensing and Administration Precautions

Use strict aseptic technique when preparing and administering propofol to avoid microbial contamination and transmission of infections.¹ ² ²³¹
Due to the potential for rapid and profound changes in the depth of anesthesia and sedation, special precautions are required when administering propofol.⁷⁵⁷ The ASA states that even if moderate sedation is intended, patients receiving propofol should receive care consistent with that required for deep sedation.⁷⁵⁷
There are different considerations when propofol is used for sedation of intubated, ventilated patients in a critical care setting.⁷⁵⁷ Administration of propofol is regulated at the state, regional, and local levels; guidance from these areas should be consulted.²¹³ ⁷⁵⁷
When used for general anesthesia or monitored anesthesia care (MAC) sedation, propofol should be administered by individuals experienced in the use of general anesthesia who are not involved in the conduct of the surgical and/or diagnostic procedure.¹ ² ⁶ ⁷ ¹³¹ ⁷⁵⁴ Sedated patients should be constantly monitored and equipment necessary for intubation, assisted respiration, administration of oxygen, and cardiopulmonary resuscitation must be readily available.¹ ² ⁶ ⁷ ¹³¹ ¹⁹² ⁷⁵⁴
When used for sedation in intubated, mechanically ventilated patients in the ICU, propofol should be administered only by individuals qualified in the management of critically ill patients and trained in cardiovascular resuscitation and airway management.¹ ² ⁷ ¹⁹² Since excessively high blood concentrations of propofol may occur in patients receiving the drug for prolonged periods, the infusion rate should be reduced and titrated according to individual clinical response and sedation levels should be evaluated at least daily when the drug is used for long durations.¹ ² ¹³⁶ ¹⁸¹ Opioids and paralytic agents should be discontinued and respiratory function optimized prior to weaning patients from mechanical ventilation.¹ ² Abrupt discontinuance of propofol should be avoided since this may result in rapid awakening accompanied by anxiety, agitation, and resistance to mechanical ventilation.¹ ² Therefore, the manufacturers recommend that administration of propofol be continued to maintain a light level of sedation throughout the weaning process until about 10–15 minutes prior to extubation.¹ ²
Based on the Institute for Safe Medication Practices (ISMP), propofol is a high-alert medication that has a heightened risk of causing significant patient harm when used in error.¹¹⁶⁹

Administration

IV Administration

Administer by IV infusion or IV injection.¹ ² ⁶ ⁸ ⁹ ¹⁰ ¹¹⁸

When administered by IV infusion, a controlled-infusion device (e.g., syringe or volumetric pump) is recommended.¹ ² In patients undergoing magnetic resonance imaging (MRI), metered controlled devices may be used when mechanical pumps are not suitable.¹ ²

Propofol may be transferred to a syringe prior to administration.¹ ² ⁷ After cleaning the rubber stopper of the vial with 70% isopropyl alcohol, transfer contents into a sterile syringe immediately after vial is opened using a sterile vented spike.¹ ² ⁷ Label syringes with appropriate information, including date and time vial was opened.¹ ²

Shake well prior to administration.¹ ² 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 stability of the product has been compromised.¹ ² Slight creaming, which may be visible upon prolonged standing, should disappear after shaking.¹ ²

Filters

Clinical experience with use of inline filters is limited.¹ ² An inline membrane filter may be used; however, the mean pore diameter of the filter should be ≥5 µm unless it has been demonstrated that the filter does not restrict flow and/or cause breakdown of the emulsion.¹ ² ¹¹ Use filters with caution and only when clinically appropriate.¹ ² Monitor continuously for restricted flow and breakdown of the emulsion.¹ ²

Stability and Sterility Considerations

Manufacturers state that propofol should not be admixed with other drugs prior to administration.¹ ² ¹² Do not administer through the same catheter as blood, serum, or plasma.¹ ²

Use strict aseptic technique during preparation and administration.¹ ² ²³¹ Although commercially available preparations contain ingredients that retard growth of microorganisms (e.g., edetate disodium, sodium metabisulfite, sodium benzoate, benzyl alcohol), the emulsion may still support growth of microorganisms.¹ ² ²³¹ Vials are intended for single-patient use and single access only.¹ ² Discard unused drug within specified time limits.¹ ² Failure to observe strict aseptic technique has resulted in microbial contamination and transmission of infections.¹ ² Do not use if contamination is suspected.¹ ²

When used for general anesthesia or MAC sedation, start administration promptly and complete within 12 hours of opening vials.¹ ² ⁷ Prepare propofol for use immediately prior to initiation of each individual anesthetic/sedative procedure.¹ ² Discard any unused portion, reservoirs, dedicated administration tubing, and/or solutions containing propofol at the end of the anesthetic procedure or after 12 hours (whichever occurs sooner).¹ ² Flush the IV line every 12 hours (one manufacturer recommends flushing with 5% dextrose)¹⁹² and at the end of the procedure to remove residual propofol emulsion.¹ ² ¹⁸¹

When used for sedation in critical care settings, minimize manipulations of IV lines; start administration promptly and complete within 12 hours after inserting spike in vial.¹ ² ⁷ Use a sterile vent spike and sterile tubing.¹ ² Discard any unused portion and the IV tubing at the end of the procedure or after 12 hours.¹

Dilution

Commercially available 1% (10 mg/mL) injectable emulsion may be administered without dilution.¹ ²

If dilution is necessary, dilute with 5% dextrose injection only; do not dilute to a concentration less than 0.2% (2 mg/mL) in order to maintain the emulsion.¹ ² Do not use if there is evidence of separation of the emulsion.¹ ²

Standardize 4 Safety

Standardized concentrations for propofol have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care.²⁴⁹ ²⁵⁰ Multidisciplinary expert panels were convened to determine recommended standard concentrations.²⁴⁹ ²⁵⁰ Because recommendations from the S4S panels may differ from the manufacturer’s prescribing information, caution is advised when using concentrations that differ from labeling, particularly when using rate information from the label.²⁴⁹ ²⁵⁰ For additional information on S4S (including updates that may be available), see [Web].²⁴⁹ ²⁵⁰

Dosing units differ from concentration units

Table 1: Standardize 4 Safety Continuous Infusion Standards for Propofol249250
Patient Population	Concentration standard	Dosing units
Adults	10 mg/mL	mcg/kg/min
Pediatric patients (<50 kg)	10 mg/mL	mcg/kg/min

Rate of Administration

Administer slowly to minimize adverse effects (e.g., hypotension, respiratory depression).¹ ² Cardiorespiratory depression is more likely to occur at higher propofol concentrations resulting from rapid IV (“bolus”) injection or rapid increases in the rate of infusion.¹ ²

For IV injection, administer in incremental doses.¹ ² ⁶ ⁸ ⁹ ¹⁰ ¹¹⁸

When administered as an IV infusion, adjust rate of infusion according to individual requirements; allow sufficient time between rate adjustments to assess clinical effect.¹ ² To avoid administering the drug at rates higher than clinically necessary, always titrate infusion rates downward in the absence of clinical signs of light anesthesia until a mild response to surgical stimulation is obtained.¹ ²

To optimize recovery times, manufacturers state that maintenance IV infusions usually should be administered at a rate of about 50–100 mcg/kg per minute in adults.¹ ²

Injection-site Pain

Pain on injection occurs frequently.¹ ²²¹ ²²⁹ ²³⁰ Minimize pain by using larger veins of the forearm or antecubital fossa (rather than hand veins) and administering IV lidocaine (either as pretreatment or admixed with propofol).¹ ² ¹⁴⁴ ²²¹ ²³⁰ Because lidocaine may cause instability of the propofol emulsion, manufacturers recommend administering 1 mL of 1% lidocaine hydrochloride solution 30–120 seconds prior to propofol administration or adding lidocaine to propofol immediately prior to administration in quantities not exceeding 20 mg of lidocaine per 200 mg of propofol.¹ ² ⁶ ⁸ ⁹ ¹⁴⁴

Administration Precautions

Due to potential for rapid and profound changes in the depth of anesthesia and sedation, special precautions are required when administering propofol.⁷⁵⁷ The American Society of Anesthesiologists (ASA) states that even if moderate sedation is intended, patients receiving propofol should receive care consistent with that required for deep sedation.⁷⁵⁷

During administration, monitor patients continuously to assess level of consciousness and identify early signs of hypotension, bradycardia, apnea, airway obstruction, and/or oxygen desaturation.²²⁰ ⁷⁵⁷ There are different considerations when propofol is used for ICU sedation.⁷⁵⁷ Administration of propofol is regulated at the state, regional, and local levels; such guidance should be consulted.²¹³ ⁷⁵⁷

Dosage

Individual response to propofol is variable; therefore, adjust dosage (including infusion rate or amount and frequency of incremental doses) according to individual requirements and response, age, weight, clinical status (e.g., ASA physical status, degree of debilitation), blood lipid profile, underlying pathologic conditions (e.g., shock, intestinal obstruction, malnutrition, anemia, burns, advanced malignancy, ulcerative colitis, uremia, alcoholism), and type and amount of premedication or concomitant medication(s) used.¹ ² ¹¹⁸ Use the smallest effective dosage.¹ ²

Pediatric Patients

Induction and Maintenance of General Anesthesia

IV

Induction of anesthesia in children 3–16 years of age: 2.5–3.5 mg/kg until induction onset, as determined by clinical response, in those with ASA physical status of I or II.¹ ² Within this dosage range, younger patients may require higher induction dosages than older patients.¹ ² A lower dosage is recommended for induction of anesthesia in patients with ASA physical status of III or IV.¹ ²

Maintenance of anesthesia in children 2 months to 16 years of age: May be given by IV infusion or intermittent bolus injection. IV infusion: 125–300 mcg/kg per minute (7.5–18 mg/kg per hour) administered concomitantly with inhaled 60–70% nitrous oxide and oxygen in those with ASA physical status of I or II.¹ ² Dosage of 200–300 mcg/kg per minute may be required for the first 30 minutes after induction, then decrease dosage to 125–150 mcg/kg per minute (unless clinical signs of light anesthesia develop) by titration, according to the patient’s response.¹ ² Within this dosage range, younger patients may require higher infusion rates than older patients.¹ ²

Intermittent IV bolus: 1–4 mg/kg initially, followed by administration of 0.5–2 mg/kg injections based on patient response.¹ ²

Procedural Sedation†

IV

Various dosage regimens have been used.⁹⁹ ²¹² ²²² ²²⁶ Individualize appropriate dose and depth of sedation based on the procedure and needs of the patient.²¹³

Has been given as an initial IV bolus injection followed by intermittent injections or by continuous IV infusion to maintain desired level of sedation.⁹⁹ ²¹² ²²²

In pediatric patients undergoing procedural sedation^†, an initial IV propofol dose of 1 mg/kg has been used.⁹⁹ ²²² ²²⁶ In one study, children 3–18 years of age undergoing an emergency orthopedic procedure received an initial IV propofol dose of 1 mg/kg, followed by smaller intermittent doses based on patient response.²²² ²²⁶ In another study in children ≥2 years of age who received propofol sedation for closed orthopedic reductions, the drug was given as an initial 1-mg/kg IV bolus dose over 2 minutes, followed by an IV infusion of 67–100 mcg/kg per minute until cast completion.⁹⁹ To maintain the desired level of sedation, additional IV bolus doses of 1 mg/kg were administered and/or the infusion rate was adjusted.⁹⁹

Adults

Induction and Maintenance of General Anesthesia

General Surgery

Induction of anesthesia in adults <65 years of age with ASA physical status of I or II: 2–2.5 mg/kg according to the patient’s response until the onset of induction.¹ ²

Maintenance of anesthesia in adults <65 years of age: Initially, 100–200 mcg/kg per minute (6–12 mg/kg per hour) administered concomitantly with inhaled 60–70% nitrous oxide and oxygen.¹ ² Higher IV infusion rates of 150–200 mcg/kg per minute may be required for the first 10–15 minutes after induction, then decrease the infusion rate by 30–50% during the first 30 minutes of maintenance anesthesia.¹ ² IV infusion rates of 50–100 mcg/kg per minute usually are used to optimize recovery times.¹

Alternatively, for maintenance of anesthesia in adults <65 years of age: 25–50 mg by intermittent IV injection in combination with inhaled nitrous oxide.¹ ² ¹⁹² These incremental boluses may be given, if necessary, as determined by clinical signs (increases in pulse rate, BP, sweating, and/or lacrimation) indicating a stress response to surgical stimulation or emergence from anesthesia.¹ ²

In geriatric (65 years of age and older), debilitated, or ASA III or IV physical status patients, lower induction doses of 1–1.5 mg/kg are usually required with a usual maintenance IV infusion rate of 50–100 mcg/kg per minute (3–6 mg/kg per hour).

Cardiac Anesthesia

Induction of anesthesia: 0.5–1.5 mg/kg until the onset of induction, as determined by the clinical response of the patient.¹ ² ¹⁹² Maintenance dose of propofol in adult cardiac patients: 25-100 mcg/kg/min, adjusted according to the patient’s sedation level and clinical response.¹ ²

Neurosurgery

Induction of anesthesia: 1–2 mg/kg until the onset of induction, as determined by the clinical response of the patient.¹ ²

Maintenance of anesthesia: 100–200 mcg/kg per minute (6–12 mg/kg per hour).¹ ²

Procedural Sedation

Various dosage regimens have been used.²¹² ²¹³ ²²² ²²⁴ ²²⁷ ²²⁸ Individualize appropriate dose and depth of sedation based on the procedure and needs of the patient.²¹³ Usually given as an initial IV bolus injection followed by intermittent injections or continuous IV infusion to maintain desired level of sedation; also has been given by IV infusion throughout the procedure.²¹² ²¹³ ²²² ²²⁴ ²²⁷ ²²⁸ Administration by IV infusion may allow for more precise control of the level of sedation compared with a repeated bolus technique.²²⁸

In clinical studies, an IV propofol dose of 1 mg/kg was commonly used to achieve initial sedation in adults undergoing a diagnostic or therapeutic procedure; however, lower (e.g., 0.5 mg/kg) or higher (e.g., 1.5 mg/kg) initial doses also have been used.²²² ²²⁴ ²²⁷ ⁸²² To maintain the desired level of sedation, additional doses (e.g., 0.25-0.5 mg/kg by intermittent IV injection) usually are administered as needed.²²² ²²⁴ ²²⁷

Monitored Anesthesia Care

IV

Initiation of MAC sedation in healthy adults <65 years of age: Infusion of 100–150 mcg/kg per minute (6–9 mg/kg per hour) for 3–5 minutes; alternatively, injection of 0.5 mg/kg over 3–5 minutes.¹ ² Slow rate of infusion or injection recommended to reduce the risk of apnea and hypotension.¹ ²

Maintenance dosage in healthy adults <65 years of age: Infusion of 25–75 mcg/kg per minute (1.5–4.5 mg/kg per hour) for the first 10–15 minutes, then decrease the infusion rate to 25–50 mcg/kg per minute.¹ ² Adjust dosage according to clinical effect, allowing approximately 2 minutes for onset of peak drug response.¹ ²

Alternatively, for maintenance therapy, administer intermittent IV injections of 10 or 20 mg; however, a variable-rate IV infusion is preferred.¹ ²

In geriatric, debilitated, ASA III or IV physical status, or neurosurgical patients, reduce maintenance dosage by 20%.¹ ² Rapid IV injection is not recommended in these patients because of an increased risk of adverse cardiorespiratory effects.¹ ²

Sedation in Critical Care Settings

IV

Individualize dosage and titrate to the desired level of sedation; in most cases, a light rather than deep level of sedation is recommended in critically ill, mechanically ventilated adults because of improved clinical outcomes (e.g., shortened duration of mechanical ventilation, reduced ICU length of stay).⁸⁰⁰ ⁸⁰¹ Assess depth and quality of sedation frequently using a validated and reliable assessment tool (e.g., Richmond Agitation-Sedation Scale [RASS], Sedation-Agitation Scale [SAS]).⁸⁰¹

Initiate slowly with a continuous IV infusion to minimize risk of hypotension.¹ ² ⁵ ⁷ ¹⁰ ³³ ³⁶ ³⁸ ⁴¹ ⁴⁷ ¹³³ ¹³⁴ ¹³⁶ Because most patients will have residual effects from previous anesthetic or sedative agents, manufacturers recommend an initial infusion rate of 5 mcg/kg per minute (0.3 mg/kg per hour) for at least 5 minutes.¹ ² ⁵ Increase infusion rate slowly in increments of 5–10 mcg/kg per minute (0.3–0.6 mg/kg per hour) until desired level of sedation is achieved; allow a minimum period of 5 minutes between dosage adjustments to assess clinical effects.¹ ² ⁵

For maintenance of sedation, most adults require 5–50 mcg/kg per minute (0.3–3 mg/kg per hour); higher maintenance infusion rates occasionally required (e.g., patients who have recovered from general anesthesia or deep sedation).¹ ² ⁵ However, manufacturers state that infusion rate should not exceed 4 mg/kg per hour unless benefits outweigh risks.¹ ² Infusion rates >4 mg/kg per hour associated with propofol infusion syndrome.⁷⁵⁹

Rapid IV (“bolus”) administration of 10- or 20-mg doses may be used to rapidly increase depth of sedation in patients in whom development of hypotension is unlikely.¹ ²

Assess level of sedation and CNS function at regular intervals (at least daily during maintenance sedation); adjust infusion rate accordingly to ensure adequate titration of the sedation level.¹ ² ¹³⁶ ¹⁸¹ ¹⁹²

Do not abruptly discontinue propofol prior to weaning or for daily evaluation of sedation levels.¹ ²

Do not administer Diprivan injectable emulsion as a continuous IV infusion for >5 days without a drug-free interval to allow replacement of estimated or measured urinary zinc losses.¹ ² ¹³⁶

Some tolerance to the drug’s sedative effects may occur during long-term (>7 days) therapy; increasing the infusion rate may be necessary.⁵ ⁶⁴ However, such effects also may be associated with changes in drug elimination or an improved health status of the patient.⁶⁴

Seizures†

Refractory Status Epilepticus†

Initially, 1- to 2-mg/kg doses by IV injection over 5 minutes; repeat when seizure activity no longer is adequately controlled.¹³⁷ Maintenance infusion of 2–10 mg/kg per hour; adjust the infusion rate until the lowest rate of infusion needed to suppress epileptiform activity is achieved.¹³⁷ Gradually decrease the dosage to prevent withdrawal seizures.¹³⁷

Nausea and Vomiting†

Postoperative Nausea and Vomiting†

Doses of 10–15 mg have been used.¹⁷ ⁵⁰

Prevention of Nausea and Vomiting Associated with Emetogenic Cancer Chemotherapy†

Dosage of 1 mg/kg per hour as a continuous IV infusion has been used.¹⁷ ⁵¹ ⁵²

Pruritus†

Pruritus Associated with Use of Spinal Opiates†

Doses of 10 mg administered by direct IV injection have been used; alternatively, IV infusions of 0.5–1 mg/kg per hour have been used.¹⁷ ⁵³ ⁵⁴

Pruritus Associated With Cholestasis†

Doses of 15 mg administered by direct IV injection have been used; alternatively, IV infusions of 1–1.5 mg/kg per hour have been used.¹⁷ ⁵³ ⁵⁴

Special Populations

Hepatic Impairment

The manufacturer makes no specific dosage recommendations for patients with hepatic impairment.¹

Renal Impairment

The manufacturer makes no specific dosage recommendations for patients with renal impairment.¹

Geriatric Patients

Lower doses are recommended for initiation and maintenance of sedation and anesthesia in geriatric patients.¹ ²

Cautions for Propofol

Contraindications

Known hypersensitivity to propofol or any ingredient in the formulation.¹ ²
Known hypersensitivity to eggs, egg products, soybeans, or soy products.¹ ²

Warnings/Precautions

Warnings

Anaphylactic and Anaphylactoid Reactions

Anaphylactoid and/or anaphylactic reactions (e.g., angioedema, bronchospasm, erythema, hypotension) reported rarely following propofol administration; may be fatal or life-threatening.¹ ² ⁶

Sulfite Sensitivity

Some formulations contain sulfites that may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.³ ¹⁶³

Potential for Microbial Contamination

Potential for microbial contamination of the injection and consequent development of fever, infection, sepsis, other life-threatening illness, or death with improper aseptic technique when handling propofol.¹ ² ¹⁰³ ¹⁹⁵ ²³¹ In addition, transmission of bloodborne pathogens (e.g., hepatitis B, hepatitis C, HIV) reported from unsafe injection practices and use of propofol vials intended for single use on multiple patients.¹ ²

Although commercially available preparations contain ingredients that retard growth of microorganisms, they are not considered antimicrobially preserved products by USP standards.¹ ² ¹⁰³ Contamination of propofol with even very small numbers of microorganisms may result in clinical disease;¹⁹⁷ strict aseptic technique and strict adherence to the manufacturer’s preparation and handling instructions are required.¹ ² ¹⁰³ ¹¹³ ¹⁹⁵ ¹⁹⁷ ¹⁹⁸ ¹⁹⁹

Do not use if contamination is suspected; discard unused portions of the drug as recommended by the manufacturers.¹ ²

Respiratory and Cardiovascular Effects

Risk of respiratory depression;¹ ² ⁵ ⁶ ⁸ ⁹ apnea and airway obstruction can occur, especially following rapid bolus injection and/or administration of larger doses such as those used for induction of anesthesia.¹ ² ⁶ ⁸ ⁹ ¹⁰ ¹¹⁸ ²²⁸

Cardiovascular depressant¹ ² ⁵ ⁶ ⁷ ⁸ ⁹ ¹⁰ ¹¹⁸ with effects greater than or equal to those associated with other IV induction agents.⁶ ⁸ ⁹ ¹⁰ ¹¹⁸ The main adverse cardiovascular effect during induction of anesthesia is hypotension, with ≥30% decreases in systolic and diastolic BP.¹ ² ⁶ ⁷ ¹¹⁸

Patients with impaired myocardial function, intravascular volume depletion, or abnormally low vascular tone (sepsis) may be more susceptible to hypotension.¹ ²

Management of hypotension may include discontinuance of propofol, increasing the rate of IV fluid administration (except when additional fluid therapy is contraindicated), elevation of the lower extremities, and/or use of vasopressors.¹ ²

Possible bradycardia, asystole, and rarely, cardiac arrest, especially in pediatric patients receiving fentanyl concomitantly.¹ ² Consider intervention with anticholinergic agents (e.g., atropine, glycopyrrolate) to modify potential increases in vagal tone associated with surgical stimuli or concomitant use of certain drugs (e.g., succinylcholine).¹ ²

Pulmonary edema reported rarely; causal relationship not established.¹ ²

Monitor sedated patients continuously for early signs of hypotension and bradycardia;¹ ² also monitor for adverse respiratory effects (e.g., apnea, airway obstruction, oxyhemoglobin desaturation), especially in those undergoing MAC sedation.¹ ²

Cardiorespiratory effects are more likely to occur following administration of rapid IV (“bolus”) injections, especially in patients with ASA physical status of III or IV and in geriatric or debilitated patients.¹ ²

Facilities necessary for intubation, assisted respiration, administration of oxygen, and cardiopulmonary resuscitation should be readily available.¹ ² ⁶ ⁷ ¹³¹ ¹⁹²

Seizures

Propofol appears to be associated with both anticonvulsant activity and excitatory effects (e.g., seizures, myoclonus, opisthotonos) on the nervous system.⁵ ⁶ ¹⁷ ¹¹⁷ ¹¹⁸

Patients with a history of seizure disorders who are receiving propofol are at increased risk of developing seizures during the recovery phase of anesthesia.¹ ²

Neurosurgical Anesthesia

Avoid substantial decreases in mean arterial pressure (because of the resultant decreases in cerebral perfusion pressure) in patients with increased intracranial pressure or impaired cerebral circulation who are undergoing neurosurgery.¹ ² To avoid substantial hypotension and decreases in cerebral perfusion pressure, administer by IV infusion or slow IV injection.¹ ²

If increased intracranial pressure is suspected, administer in combination with hyperventilation and hypocarbia.¹

Cardiac Anesthesia

Use slower rates of IV administration in patients undergoing cardiac surgery who received premedication and in those with recent fluid imbalance or those who are hemodynamically unstable.¹ ² ¹⁸¹ ¹⁹² Correct fluid depletion prior to administration of propofol.¹ ²

If additional fluid therapy is contraindicated, management of hypotension may include discontinuance of propofol, elevation of the lower extremities, and/or use of vasopressors.¹ ²

Studied extensively in patients with CAD and in those with valvular or congenital heart disease.¹ ²

Critical Care Sedation

Failure to reduce the infusion rate during prolonged therapy may result in excessively high blood concentrations of propofol; titrate according to individual clinical response.¹ ² ¹³⁶ ¹⁸¹ Evaluate sedation levels at least daily.¹ ² ¹³⁶ ¹⁸¹

Prior to weaning patients from mechanical ventilator assistance, discontinue neuromuscular blocking agents¹ ² or reverse neuromuscular blockade¹⁸¹ and discontinue opiate therapy¹ ² or adjust the dosage¹⁸¹ to optimize respiratory function and/or to maintain a light level of sedation.¹ ² If respiratory depression does not develop, maintain this level of sedation during the weaning process since abrupt withdrawal has been associated with rapid awakening accompanied by anxiety, agitation, and resistance to mechanical ventilation, thus making the weaning process difficult.¹ ² Therefore, the manufacturers recommend that administration of propofol be continued to produce a light level of sedation until about 10–15 minutes prior to extubation.¹ ²

Propofol Infusion Syndrome

Propofol infusion syndrome reported in patients receiving propofol for sedation in a critical care setting.¹ ² ²¹¹ Characterized by severe metabolic acidosis, hyperkalemia, lipidemia, rhabdomyolysis, hepatomegaly, and cardiac, renal, or circulatory failure.¹ ² ²¹¹ Occurs most frequently in patients receiving prolonged, high-dose infusions (>5 mg/kg per hour for >48 hours) but has occurred following short-term, high-dose infusions during surgical anesthesia.¹ ² ²¹¹

Closely monitor patients for development of unexplained acidosis, rhabdomyolysis, and cardiac or renal failure.²¹¹ Consider alternate means of sedation in the setting of prolonged need for sedation, increasing propofol dosage requirements to maintain a constant level of sedation, or onset of metabolic acidosis during propofol infusion.¹ ²

Effects on Lipids

Commercial propofol preparations are oil-in-water emulsions; use with caution in patients with disorders of lipid metabolism (e.g., primary hyperlipoproteinemia, diabetic hyperlipemia, pancreatitis).¹ ²

Prolonged administration may result in increased serum lipid concentrations (e.g., hypertriglyceridemia); monitor patients undergoing sedation in a critical care setting who are at risk of developing hyperlipidemia for increases in serum triglyceride concentrations or serum turbidity.¹ ²

Reduce the quantity of concurrently administered lipids (e.g., fat emulsions for parenteral nutrition) in these patients in order to compensate for the amount of lipids contained in the propofol formulation (1 mL of propofol injectable emulsion contains 0.1 g of fat [1.1 kcal]).¹ ²

Zinc Loss

Certain formulations (e.g., Diprivan) contain edetate disodium, a strong chelator of trace metal, including zinc.¹ ¹³⁶

Do not administer IV infusions of propofol for longer than 5 days without a drug-free interval to replace urine zinc losses.¹

In patients who are predisposed to zinc deficiency (e.g., those with burns, diarrhea, major sepsis), consider the need for supplemental zinc during prolonged therapy with edetate disodium-containing formulations.¹

Renal toxicity reported rarely in patients receiving high dosages (2–3 g daily) of edetate disodium; however, decreased renal function has not been observed in clinical studies to date in patients with normal or impaired renal function receiving propofol (Diprivan).¹ Manufacturer of Diprivan recommends that laboratory analysis of urine (including urine sediment) be performed prior to sedation and every other day during therapy in patients at risk for developing renal impairment.¹

Use in Debilitated, Elderly, or ASA-PS III or IV Patients

Use a lower induction dose and slower maintenance rate of administration in elderly, debilitated, or ASA-PS III or IV patients.¹ Continuously monitor patients for early signs of hypotension and/or bradycardia.¹ Apnea requiring ventilatory support often occurs during induction and may persist for more than 60 seconds.¹

Local Effects

Pain at the injection site occurs in up to 70% of patients¹⁴⁴ following peripheral IV administration.¹ ⁵ ⁶ ⁷ ⁸ ⁹ ⁸⁹ ¹¹⁸ ¹⁴⁴ Thrombosis or phlebitis reported rarely.¹ ²

Pain, but no evidence of major sequelae, reported following inadvertent intra-arterial injection.¹ ² ⁸ ¹¹⁸ Local pain, swelling, blisters, and/or tissue necrosis reported rarely following inadvertent extravasation.¹ ²

To minimize pain at injection site, use larger veins of the forearm or antecubital fossa rather than hand veins; may also administer lidocaine prior to propofol administration or add lidocaine to propofol immediately before administration in a quantity not exceeding 20 mg of lidocaine per 200 mg of propofol.¹ ² ⁶ ⁸ ⁹ ¹⁴⁴ Other methods that may be beneficial include prior administration of low-dose opiates or other analgesic agents and venous occlusion with a tourniquet.²²¹ ²³⁰

Risk of Aggregation if Administered through the Same Intravenous Catheter with Blood or Plasma

Propofol should not be administered through the same catheter as blood or plasma because compatibility not established.¹ ² Aggregates of the globular component of the vehicle containing propofol may form when the drug is in contact with blood, serum, or plasma.¹ ² Clinical importance of these effects not known.¹ ²

Postoperative Effects

Associated rarely with a period of postoperative unconsciousness (sometimes preceded by a brief period of wakefulness), which may be accompanied by increased muscle tone; recovery has been spontaneous.¹ ²

Perioperative Myoclonia

Perioperative myoclonia, rarely including convulsions and opisthotonos, reported.¹

Pulmonary Edema

Pulmonary edema reported rarely in temporal relationship to administration of propofol, although causal relationship not established.¹

Pancreatitis

Pancreatitis (sometimes requiring hospitalization) reported in adults undergoing induction of anesthesia¹ ² ⁸⁵ ⁸⁶ ⁸⁷ ⁸⁸ ¹⁶⁷ or prolonged sedation with propofol in a critical care setting.⁸⁴ ⁸⁷ ¹⁶⁷ Causal relationship with propofol not established; consider the possibility of pancreatitis in patients receiving propofol.⁸⁵ ⁸⁶ ¹⁸¹ ¹⁹²

Dependence, Tolerance, and Abuse

Dependence and abuse, sometimes resulting in death, have been reported.⁵⁷ ⁸³ ¹⁰⁹ ²⁰⁰ ²⁰¹ ²⁰² ²⁰³ ²⁰⁴ ²⁰⁶ ²⁰⁷ ²⁰⁸ ²⁰⁹ Most reported cases have involved healthcare professionals (principally anesthesiology personnel),⁵⁷ ⁶⁵ ⁶⁶ ¹⁰⁹ ²⁰¹ ²⁰² ²⁰³ ²⁰⁴ ²⁰⁹ but abuse by lay persons also reported.²⁰⁰ ²⁰⁶ ²⁰⁸ ²⁰⁹

Currently not subject to control under the Federal Controlled Substances Act of 1970; however, some clinicians have suggested such control or some other means of ensuring greater accountability (e.g., restriction of access, drug accounting procedures, routine testing for propofol in drug screenings of at-risk individuals).¹ ² ⁶⁵ ⁶⁷ ⁸³ ²⁰⁴ ²⁰⁵ Prevalence of abuse and related deaths appears to be greater at institutions with no established system to control or monitor propofol use.²⁰⁴ ²⁰⁵

Psychological dependence (e.g., intense craving for the drug, loss of control over amount and frequency of use) reported in cases of propofol abuse.⁵⁷ ²⁰⁰ ²⁰² ²⁰⁶ ²⁰⁷ Withdrawal symptoms (e.g., insomnia, anxiety, difficulty concentrating), suggesting physical dependence, observed rarely.²⁰² Signs of tolerance also observed.¹⁰⁹ ²⁰⁰ ²⁰⁶

General Precautions

CNS Effects

Performance of activities requiring mental alertness (e.g., driving, operating machinery, signing legal documents) may be impaired for some time after general anesthesia or sedation with propofol.¹ ² Concomitant use of opiate analgesics and benzodiazepines can increase the risk of CNS effects.¹ ²

Monitored Anesthesia Care

A variable infusion rate is preferred to intermittent bolus administration for maintenance of MAC sedation in healthy adults because the risk of hypotension may be lower.¹ ² ¹⁹² If intermittent IV injections are given, consider the possibility of respiratory depression, transient increases in sedation depth, and/or prolongation of recovery.¹ ²

Specific Populations

Pregnancy

No adequate and controlled studies in pregnant women.¹ ² Not recommended for obstetric surgery (e.g., cesarean section).¹ ²

In animal reproduction studies, decreased pup survival and increased postimplantation loss observed.¹

Based on animal data, repeated or prolonged use of general anesthetics and sedation drugs, including propofol, during the third trimester of pregnancy may result in adverse neurodevelopmental effects in the fetus.⁷⁵⁰ ⁷⁵³

Lactation

Distributed into milk;¹ ² ⁶ ¹⁹ use not recommended by manufacturers.¹ ²

Some clinicians state that nursing women undergoing surgery may receive usual anesthetic induction doses of propofol;¹¹⁸ however, since trace amounts of the drug may be present in milk, drowsiness of nursing infants may occur on the day of the procedure.¹¹⁸

Pediatric Use

Manufacturer states safety and efficacy for induction of general anesthesia not established in children <3 years of age; safety and efficacy for maintenance of general anesthesia not established in children <2 months of age.¹

The manufacturers state that propofol is not recommended for sedation in critical care settings or for use in combination with regional anesthesia in children <16 years of age¹ ² ¹⁹² because safety for these uses in this patient population has not been established.¹ ² ⁹⁰ ¹⁴⁶ ¹⁹² Severe, progressive metabolic (e.g., lactic) acidosis syndrome (that may progress to death) has been reported in several ventilated children (mainly with respiratory infections) receiving propofol for sedation in critical care settings.¹ ² ⁵ ⁹⁰ ⁹¹ ¹⁴⁰ ¹⁴² ¹⁴³ ¹⁴⁶ ¹⁴⁷

Has been used in children undergoing MAC sedation for surgical, diagnostic, and other procedures (e.g., lumbar puncture with intrathecal chemotherapy, bone marrow aspiration and biopsy, central venous catheter placement, transesophageal echocardiogram, cardiac catheterization, radiologic examinations, orthopedic manipulations);⁹⁴ ⁹⁵ however, the manufacturers state that propofol should not be used for MAC sedation in children because safety and efficacy have not been established.¹ ²

Abrupt discontinuance following prolonged IV infusion in children may result in flushing of the hands and feet, agitation, tremulousness, hyperirritability, increased incidence of bradycardia, agitation, or jitteriness.¹

Repeated or prolonged use of general anesthetics and sedation drugs, including propofol, in children <3 years of age or during the third trimester of pregnancy may adversely affect neurodevelopment.⁷⁵⁰ ⁷⁵³ In animals, use for >3 hours of anesthetic and sedation drugs that block N-methyl-d-aspartic acid (NMDA) receptors and/or potentiate GABA activity leads to widespread neuronal apoptosis in the brain and long-term deficits in cognition and behavior;⁷⁵⁰ ⁷⁵¹ ⁷⁵² ⁷⁵³ clinical relevance to humans is unknown.⁷⁵⁰ Some evidence suggests similar deficits may occur in children following repeated or prolonged exposure to anesthesia early in life.⁷⁵⁰ ⁷⁵² Some evidence also indicates that a single, relatively brief exposure to general anesthesia in generally healthy children is unlikely to cause clinically detectable deficits in global cognitive function or serious behavioral disorders.⁷⁵⁰ ⁷⁵¹ ⁷⁵² Most studies to date have substantial limitations; further research needed to fully characterize effects, particularly for prolonged or repeated exposures and in more vulnerable populations (e.g., less healthy children).⁷⁵⁰ Consider benefits and potential risks when determining the timing of elective procedures requiring anesthesia.⁷⁵⁰ FDA states that medically necessary procedures should not be delayed or avoided.⁷⁵⁰ ⁷⁵³

Geriatric Use

Lower dosages may be required for anesthesia and other indications.¹ ²

Avoid rapid (single or repeated) IV (“bolus”) administration during general anesthesia or MAC sedation to minimize the risk of adverse effects, including cardiorespiratory depression (e.g., hypotension, apnea, airway obstruction, oxyhemoglobin desaturation).¹ ²

Hepatic Impairment

Long-term propofol therapy not evaluated to date.¹ ²

Renal Impairment

Long-term propofol therapy not evaluated to date.¹ ²

Common Adverse Effects

Common adverse reactions (>1%): bradycardia, arrhythmia, tachycardia, hypotension, hypertension, decreased cardiac output, movement, apnea, respiratory acidosis during weaning, rash, pruritus, burning/stinging or pain at injection site, hyperlipemia.¹

Drug Interactions

Metabolized mainly by CYP2B6 and to a lesser extent by CYP2C9.¹⁷⁹

Inhibits CYP isoenzymes 1A1, 1A2, 2B1, 2C9, 2D6, 2E1, and 3A4.⁷² ⁷³

Drugs Metabolized by or Affecting Hepatic Microsomal Enzymes

Possibility of interactions; however, because of the increased value for hepatic extraction (50 µM) of propofol,¹⁷⁹ there have been relatively few clinically important interactions with drugs metabolized by or affecting CYP isoenzymes.⁷¹ ¹⁹²

Specific Drugs

Drug	Interaction	Comments
Anticoagulants (e.g., warfarin)	IV administration of lipids (e.g., those contained in the propofol emulsion) may decrease response to warfarin in patients with malabsorptive states (e.g., Crohn’s disease)⁷⁰	Use heparin for initial anticoagulation in patients with malabsorptive states receiving high-dose lipid emulsions;⁷⁰ if warfarin is given, monitor INR daily⁷⁰
CNS depressants (e.g., benzodiazepines, opiates, inhalation anesthetics [e.g., nitrous oxide, isoflurane])	Increased sedative, anesthetic, and cardiorespiratory depressant effects of propofol¹ ²	Reduce induction dose of propofol in patients receiving premedication with IV or IM opiates or in those receiving opiates in combination with sedatives (e.g., benzodiazepines, barbiturates, chloral hydrate, droperidol)¹ ² Reduce infusion rate of propofol during maintenance of anesthesia or sedation in those receiving CNS depressants concomitantly¹ ²
Droperidol	Increased frequency of postoperative nausea and vomiting reported⁷⁴
Fentanyl	Possibility of severe bradycardia in pediatric patients¹ ²
Midazolam	Synergistic effect (possibly at GABA_A receptors in the brain), producing induction of anesthesia and sedation⁷⁸ ⁷⁹ ⁸⁰ Free plasma concentrations of midazolam increased by about 20%; no apparent effect on free concentrations of propofol⁷⁹
Neuromuscular blocking agents (e.g., succinylcholine, nondepolarizing skeletal muscle relaxants)	No clinically important changes in the onset, intensity, or duration of action of commonly used neuromuscular blocking agents¹ ² ⁸
Opiate agonists	May increase the anesthetic/sedative and cardiorespiratory effects of propofol¹ In pediatric patients, concomitant administration of fentanyl and propofol may result in serious bradycardia¹ Blood concentrations of opiates increased by 10–20%⁷⁵ Blood concentrations of propofol increased by up to 22% with alfentanil use⁷⁵	Variations in blood concentrations of propofol and opiates are unlikely to be clinically important;⁷⁵ however, sedation and analgesia may be greater with the combination than with either agent alone⁷⁶

Propofol Pharmacokinetics

Absorption

Onset

Following a single IV injection, onset as determined by time to unconsciousness (i.e., loss of response to voice command) usually ranges from 15–30 seconds and depends on the administration rate.⁶ ¹⁸ ²⁰ ¹¹⁷

Duration

Following a single rapid IV injection, duration of action usually is about 5–10 minutes.²⁰ ¹¹⁷

Plasma Concentrations

Following a single rapid IV injection, most patients will awaken as blood propofol concentrations decline to approximately 1 mcg/mL; improvement of psychomotor performance (as measured by patient response to verbal command) usually occurs at concentrations of 0.5–0.6 mcg/mL.⁹

Distribution

Extent

Highly lipophilic; rapidly distributed from plasma into body tissues, including the CNS.⁵ ⁶ ⁹ ¹⁰ ¹¹⁷ Following IV administration, widely distributed, initially to highly perfused tissues (e.g., brain), then to lean muscle tissue, and finally to fat tissue.⁵ ⁶ ⁷ ⁹ ¹¹⁷ Equilibration between blood and CSF occurs within about 2–3 minutes.⁵ ⁶ ⁹ ¹⁰ ¹¹⁷

Readily crosses the placenta.¹ ² ⁶ ¹⁹ ³¹ ³²

Distributed into milk in low concentrations.¹ ² ⁶ ¹⁹

Plasma Protein Binding

Approximately 95–99% (mainly albumin and hemoglobin).⁵ ⁶ ⁹ ¹⁸ Binding appears to be independent of plasma propofol concentration.⁶

Elimination

Metabolism

Rapidly and extensively metabolized in the liver¹ ² ⁵ ⁶ ⁸ ⁹ ²⁰ ¹⁷⁹ by CYP2B6 and to a lesser extent by CYP2C9.¹⁷⁹

Elimination Route

Excreted mainly in urine, principally as sulfate and/or glucuronide conjugates;⁶ ⁹ ¹⁰ ²⁰ <0.3% of a dose is eliminated unchanged in urine,⁵ ⁶ ⁹ ¹⁰ and <2% of a dose is eliminated in feces.⁸

Half-life

Triphasic;¹ ² ⁵ ⁶ ¹⁰ ⁴⁵ following a single rapid injection or a continuous infusion, half-life averages 1.8–9.5 minutes in the initial distribution phase, 21–70 minutes in the second redistribution phase, and 1.5–31 hours in the terminal elimination phase.⁵ ⁶ ⁸ ⁹ ⁴⁵ ⁴⁶

Terminal plasma half-life may not affect clinical outcome as substantially as the distribution half-life does, since rapid awakening from anesthesia occurs once blood propofol concentrations decrease below the range required for hypnosis.⁶ ⁷

Special Populations

In geriatric patients, clearance may be reduced substantially,⁵ ⁶ ⁸ ⁹ ¹⁰ ¹⁸ ¹⁰⁶ possibly because of decreased hepatic metabolism resulting from decreased hepatic blood flow.⁶

Obese patients have a substantially higher clearance than leaner individuals; mean total body clearance appears to be proportional to body weight.⁵ ⁶ ¹⁸⁰ ¹⁹²

Chronic renal failure or chronic hepatic cirrhosis does not appear to affect pharmacokinetics of propofol;¹ ² ⁵ ⁶ ⁷ ⁸ ⁹ ¹⁰ not studied in patients with acute renal or hepatic failure.¹

Stability

Storage

Parenteral

Injectable Emulsion

4–25°C depending on the preparation.¹ ² ³ Do not freeze.¹

Actions

Effects appear to be related, at least partially, to propofol’s ability to enhance the activity of GABA⁶ ¹¹⁶ ¹⁴⁵ by interacting with the GABA_A receptor complex at spinal and supraspinal synapses.⁶ ¹⁷ ¹¹⁶ ¹⁴⁵ ¹⁸¹ ¹⁹² Also may interact with other neurotransmitter sites (e.g., glycine, nicotinic, glutamate, G-protein coupled receptors) and inhibit sodium channels.⁶ ¹⁴⁵
Capable of producing all levels of CNS depression—from light sleep to deep coma—depending on the dosage.⁵ ¹¹⁷
Associated with both anticonvulsant activity and excitatory effects on the nervous system.⁵ ⁶ ¹⁷ ¹¹⁷ ¹¹⁸ ²¹⁰
Anesthetic doses may increase cerebral vascular resistance and decrease cerebral blood flow and cerebral metabolic rate for oxygen and glucose.¹ ² ⁵ ⁶ ⁷ ⁸ ¹⁰ ¹¹⁷ ¹¹⁸ May slightly decrease intracranial pressure in patients undergoing intracranial surgery⁶ ⁸ ¹⁰ or in those undergoing sedation in a critical care setting.⁵
Hypnotic doses may be associated with analgesic effects; responses to subhypnotic doses vary from analgesia to hyperalgesia.⁵ ⁶ ¹⁰ ¹⁸ Subhypnotic doses may have anxiolytic effects comparable to those of midazolam or methohexital.¹⁷ ¹⁹² Amnesic effects are less than those of the benzodiazepines.⁵ ⁶ ⁷ ⁹ ³⁶ ⁴³ ¹³⁶
Propofol anesthesia associated with substantial (30–60%) reductions in intraocular pressure in patients undergoing ophthalmic surgery.¹ ² ⁶ ⁹ ¹⁰ ¹¹⁸
May have direct antiemetic properties; however, mechanism not established.¹⁷

Advice to Patients

Inform patients that their ability to perform activities requiring mental alertness (e.g., driving, operating machinery, signing legal documents) may be impaired for some time after undergoing general anesthesia or sedation.¹ ²
When procedures requiring general anesthetics or sedation drugs, including propofol, are considered for young children or pregnant women, importance of discussing with the patient, parent, or caregiver the benefits, risks (including potential risk of adverse neurodevelopmental effects), and appropriate timing and duration of the procedure.¹ ⁷⁵⁰ ⁷⁵³
Advise patients to inform their clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.¹
Advise women to inform their clinicians if they are or plan to become pregnant or plan to breast-feed.¹
Inform patients of other important precautionary information.¹

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Propofol
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injectable emulsion, for IV use	10 mg/mL*	Diprivan Emulsion (available as ready-to-use single patient vials)	Fresenius Kabi
			Propofol Injectable Emulsion

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

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179. Court MH, Duan SX, Hesse LM et al. Cytochrome P-450 2B6 is responsible for interindividual variability of propofol hydroxylation by human liver microsomes. Anesthesiology. 2001; 94:110-19. http://www.ncbi.nlm.nih.gov/pubmed/11135730?dopt=AbstractPlus

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191. Chao TC, Lo DS, Chui PP et al. The first fatal 2,6-di-isopropylphenol (propofol) poisoning in Singapore: a case report. Forensic Sci Int. 1994; 25:1-7.

192. AstraZeneca, Wilmington, DE. Personal communication.

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198. Fukada T, Ozaki M. Microbial growth in propofol formulations with disodium edetate and the influence of venous access system dead space. Anaesthesia. 2007; 62:575-80. http://www.ncbi.nlm.nih.gov/pubmed/17506735?dopt=AbstractPlus

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203. Riezzo I, Centini F, Neri M et al. Brugada-like EKG pattern and myocardial effects in a chronic propofol abuser. Clin Toxicol. 2009; 47:358-63.

204. Wischmeyer PE, Johnson BR, Wilson JE et al. A survey of propofol abuse in academic anesthesia programs. Anesth Analg. 2007; 105:1066-71. http://www.ncbi.nlm.nih.gov/pubmed/17898389?dopt=AbstractPlus

205. Dexter F. Detecting diversion of anesthetic drugs by providers. Anesth Analg. 2007; 105:897-8. http://www.ncbi.nlm.nih.gov/pubmed/17898362?dopt=AbstractPlus

206. Fritz G, Niemczyk W. Propofol dependency in a lay person. Anaesthesiology. 2002; 96:505-6.

207. Schneider U, Rada D, Rollnik JD et al. Propofol dependency after treatment of tension headache. Addict Biol. 2001; 6:263-5. http://www.ncbi.nlm.nih.gov/pubmed/11900605?dopt=AbstractPlus

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756. US Food and Drug Administration. Guidance document: temporary policy on repackaging or combining propofol drug products during the COVID-19 public health emergency guidance for industry. Silver Spring, MD; 2020 Apr. From FDA website. https://www.fda.gov/media/137224/download

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More about propofol

Drug Status

Availability Prescription only Rx

Pregnancy & Lactation Risk data available

CSA Schedule* Not a controlled drug N/A

Approval History Drug history at FDA

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410 Reviews