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Propofol

Pronunciation

Pronunciation

(PROE po fole)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Emulsion, Intravenous:

Diprivan: 100 mg/10 mL (10 mL); 200 mg/20 mL (20 mL); 500 mg/50 mL (50 mL); 1000 mg/100 mL (100 mL) [contains edetate disodium, egg phospholipids (egg lecithin), glycerin, soybean oil]

Generic: 1000 mg/100 mL (100 mL); 200 mg/20 mL (20 mL); 500 mg/50 mL (50 mL)

Emulsion, Intravenous [preservative free]:

Fresenius Propoven: 200 mg/20 mL (20 mL); 500 mg/50 mL (50 mL); 1000 mg/100 mL (100 mL) [contains egg phosphatides, soybean oil]

Generic: 1000 mg/100 mL (100 mL); 200 mg/20 mL (20 mL); 500 mg/50 mL (50 mL)

Brand Names: U.S.

  • Diprivan
  • Fresenius Propoven

Pharmacologic Category

  • General Anesthetic

Pharmacology

Propofol is a short-acting, lipophilic intravenous general anesthetic. The drug is unrelated to any of the currently used barbiturate, opioid, benzodiazepine, arylcyclohexylamine, or imidazole intravenous anesthetic agents. Propofol causes global CNS depression, presumably through agonism of GABAA receptors and perhaps reduced glutamatergic activity through NMDA receptor blockade.

Distribution

Large volume of distribution; highly lipophilic; Vd:

Children 4 to 12 years: 5 to 10 L/kg

Adults: 2 to 10 L/kg; after a 10-day infusion, Vd approaches 60 L/kg; decreased in the elderly

Metabolism

Hepatic to water-soluble sulfate and glucuronide conjugates (~50%)

Excretion

Urine (~88% as metabolites, 40% as glucuronide metabolite); feces (<2%)

Onset of Action

Anesthetic: Bolus infusion (dose dependent): 9 to 51 seconds (average: 30 seconds)

Duration of Action

3 to 10 minutes depending on the dose, rate and duration of administration; with prolonged use (eg, 10 days ICU sedation), propofol accumulates in tissues and redistributes into plasma when the drug is discontinued, so that the time to awakening (duration of action) is increased; however, if dose is titrated on a daily basis, so that the minimum effective dose is utilized, time to awakening may be within 10 to 15 minutes even after prolonged use

Half-Life Elimination

Biphasic: Initial: 40 minutes; Terminal: 4 to 7 hours (after 10-day infusion, may be up to 1 to 3 days)

Protein Binding

97% to 99%

Special Populations: Elderly

With increasing age, the dose requirement decreases because of occurrence of higher peak plasma concentrations.

Use: Labeled Indications

Induction of anesthesia in patients ≥3 years of age; maintenance of anesthesia in patients >2 months of age; in adults, for monitored anesthesia care sedation during procedures; in adults, for sedation in intubated, mechanically-ventilated ICU patients

Note: Consult local regulations and individual institutional policies and procedures.

Use: Unlabeled

Postoperative antiemetic; Refractory delirium tremens (case reports)

Contraindications

Hypersensitivity to propofol or any component of the formulation; hypersensitivity to eggs, egg products, soybeans, or soy products; when general anesthesia or sedation is contraindicated

Note: Fresenius Propoven is also contraindicated in patients who are hypersensitive to peanuts. In July 2012, the FDA initiated temporary importation of Fresenius Propoven 1% (propofol) injection into the U.S. market to address a propofol shortage.

Dosing: Adult

Consult local regulations and individual institutional policies and procedures. Dosage must be individualized based on total body weight and titrated to the desired clinical effect. Wait at least 3 to 5 minutes between dosage adjustments to clinically assess drug effects. Smaller doses are required when used with opioids; the following are general dosing guidelines (see “Abbreviations, Acronyms, and Symbols” for explanation of ASA-PS classes):

General anesthesia: Note: Increase dose in patients with chronic alcoholism (Fassoulaki, 1993); decrease dose with acutely intoxicated (alcoholic) patients.

Induction of general anesthesia:

Healthy adults, ASA-PS 1 or 2, <55 years: IV: 2 to 2.5 mg/kg (~40 mg every 10 seconds until onset of induction)

Debilitated, ASA-PS 3 or 4: Refer to geriatric dosing.

Maintenance of general anesthesia:

Healthy adults, ASA-PS 1 or 2, <55 years:

IV infusion: Initial: 100 to 200 mcg/kg/minute (or 6 to 12 mg/kg/hour) for 10 to 15 minutes; usual maintenance infusion rate: 50 to 100 mcg/kg/minute (or 3 to 6 mg/kg/hour) to optimize recovery time.

IV intermittent bolus: 25 to 50 mg increments as needed

Debilitated, ASA-PS 3 or 4: IV Infusion: Refer to geriatric dosing.

Monitored anesthesia care sedation:

Healthy adults, ASA-PS 1 or 2, <55 years: Slow IV infusion: 100 to 150 mcg/kg/minute (or 6 to 9 mg/kg/hour) for 3 to 5 minutes or slow injection: 0.5 mg/kg over 3 to 5 minutes followed by IV infusion of 25 to 75 mcg/kg/minute (or 1.5 to 4.5 mg/kg/hour) or incremental bolus doses: 10 mg or 20 mg

Debilitated or ASA-PS 3 or 4 patients: Use 80% of healthy adult dose

ICU sedation in intubated mechanically-ventilated patients: Avoid rapid bolus injection; individualize dose and titrate to response.

Continuous infusion: Initial: 5 mcg/kg/minute (or 0.3 mg/kg/hour); increase by 5 to 10 mcg/kg/minute (or 0.3 to 0.6 mg/kg/hour) every 5 to 10 minutes until desired sedation level is achieved; usual maintenance: 5 to 50 mcg/kg/minute (or 0.3 to 3 mg/kg/hour); reduce dose after adequate sedation established and adjust to response (eg, evaluate frequently to use minimum dose for sedation). Daily interruption with retitration or a light target level of sedation is recommended to minimize prolonged sedative effects (Barr, 2013).

Elderly, debilitated, or ASA-PS 3 or 4 patients: Refer to geriatric dosing.

Postoperative nausea and vomiting (PONV), rescue therapy (off-label use): IV: 15 to 20 mg, may be repeated (Gan 2004; SAA [Gan 2007]; Unlugenc 2004).

Status epilepticus, refractory (off-label use): IV: Note: Mechanical ventilation and cardiovascular monitoring required; titrate dose to cessation of electrographic seizures or burst suppression (NCS [Brophy, 2012]).

Neurocritical Care Society recommendations (NCS [Brophy, 2012]):

Loading dose: 1 to 2 mg/kg with initiation of a continuous infusion.

Continuous infusion: Initial: 20 mcg/kg/minute (1.2 mg/kg/hour). If the patient experiences breakthrough status epilepticus while on continuous infusion, increase infusion rate by 5 to 10 mcg/kg/minute (0.3 to 0.6 mg/kg/hour) every 5 minutes (may also administer a 1 mg/kg bolus dose with continuous infusion titration); dosage range: 30 to 200 mcg/kg/minute (1.8 to 12 mg/kg/hour). Note: Use caution with doses >80 mcg/kg/minute (>4.8 mg/kg/hour) for >48 hours. Prior to withdrawal, a period of at least 24 to 48 hours of electrographic control is recommended; withdraw gradually to prevent recurrent status epilepticus.

Dosing: Geriatric

Consult local regulations and individual institutional policies and procedures. Dosage must be individualized based on total body weight and titrated to the desired clinical effect. Wait at least 3 to 5 minutes between dosage adjustments to clinically assess drug effects. Smaller doses are required when used with opioids; the following are general dosing guidelines (see “Abbreviations, Acronyms, and Symbols” for explanation of ASA-PS classes):

General anesthesia: Note: Increase dose in patients with chronic alcoholism (Fassoulaki, 1993); decrease dose with acutely intoxicated (alcoholic) patients.

Induction of general anesthesia: Elderly, debilitated, ASA-PS 3 or 4: IV: 1 to 1.5 mg/kg (~20 mg every 10 seconds until onset of induction)

Maintenance of general anesthesia: Elderly, debilitated, ASA-PS 3 or 4: IV infusion: 50 to 100 mcg/kg/minute (or 3 to 6 mg/kg/hour)

Monitored anesthesia care sedation: Elderly, debilitated, ASA-PS 3 or 4: IV: Use 80% of healthy adult dose

ICU sedation in intubated mechanically-ventilated patients: Avoid rapid bolus injection; individualize dose and titrate to response:

Continuous infusion: Elderly, debilitated, ASA-PS 3 or 4: Use 80% of healthy adult dose; reduce dose after adequate sedation established and adjust to response (eg, evaluate frequently to use minimum dose for sedation). Daily interruption with retitration or a light target level of sedation is recommended to minimize prolonged sedative effects (Barr, 2013).

Dosing: Pediatric

Consult local regulations and individual institutional policies and procedures. Dosage must be individualized based on total body weight and titrated to the desired clinical effect. Wait at least 3 to 5 minutes between dosage adjustments to clinically assess drug effects. Smaller doses are required when used with opioids; the following are general dosing guidelines (see “Abbreviations, Acronyms, and Symbols” for explanation of ASA-PS classes):

General anesthesia: Note: Increase dose in patients with chronic alcoholism (Fassoulaki, 1993); decrease dose with acutely intoxicated (alcoholic) patients.

Induction of general anesthesia: IV: Healthy children 3 to 16 years, ASA-PS 1 or 2: 2.5 to 3.5 mg/kg over 20 to 30 seconds; use a lower dose for children ASA-PS 3 or 4

Maintenance of general anesthesia: IV infusion: Healthy children 2 months to 16 years, ASA-PS 1 or 2: 125 to 300 mcg/kg/minute (or 7.5 to 18 mg/kg/hour); after 30 minutes, if clinical signs of light anesthesia are absent, decrease the infusion rate. Children ≤5 years may require larger infusion rates compared to older children.

Status epilepticus, refractory (off-label use): IV: Note: Mechanical ventilation and cardiovascular monitoring required; titrate dose to cessation of electrographic seizures or burst suppression (NCS [Brophy, 2012]).

Neurocritical Care Society recommendations (NCS [Brophy, 2012]):

Loading dose: 1 to 2 mg/kg with initiation of a continuous infusion.

Continuous infusion: Initial: 20 mcg/kg/minute (1.2 mg/kg/hour). If the patient experiences breakthrough status epilepticus while on continuous infusion, increase infusion rate by 5 to 10 mcg/kg/minute (0.3 to 0.6 mg/kg/hour) every 5 minutes (may also administer a 1 mg/kg bolus dose with continuous infusion titration); dosage range: 30 to 200 mcg/kg/minute (1.8 to 12 mg/kg/hour). Note: Use caution with doses >80 mcg/kg/minute (>4.8 mg/kg/hour) for >48 hours. Prior to withdrawal, a period of at least 24 to 48 hours of electrographic control is recommended; withdraw gradually to prevent recurrent status epilepticus.

Dosing: Renal Impairment

No dosage adjustment necessary.

Dosing: Hepatic Impairment

No dosage adjustment necessary.

Reconstitution

Does not need to be diluted; however, propofol may be further diluted in 5% dextrose in water to a concentration of ≥2 mg/mL.

Administration

Consult local regulations and individual institutional policies and procedures. Strict aseptic technique must be maintained in handling although a preservative has been added. Do not use if contamination is suspected. Do not administer through the same IV catheter with blood or plasma. Tubing and any unused portions of propofol vials should be discarded after 12 hours.

To reduce pain associated with injection, use larger veins of forearm or antecubital fossa; lidocaine IV (1 mL of a 1% solution) may also be used prior to administration or it may be added to propofol immediately before administration in a quantity not to exceed 20 mg lidocaine per 200 mg propofol. Do not use filter <5 micron for administration.

Dietary Considerations

Propofol is formulated in an oil-in-water emulsion. If on parenteral nutrition, may need to adjust the amount of lipid infused. Propofol emulsion contains 1.1 kcal/mL. Soybean fat emulsion is used as a vehicle for propofol. Formulations also contain egg phosphatide and glycerol.

Compatibility

Stable in D5LR, D51/4NS, D51/2NS, D5W, LR. Do not mix with other therapeutic agents prior to administration.

Y-site administration: Incompatible with amikacin, amphotericin B, atracurium, calcium chloride, diazepam, doripenem, gentamicin, levofloxacin, methotrexate, methylprednisolone sodium succinate, minocycline, mitoxantrone, pantoprazole, phenytoin, tobramycin.

Compatibility in syringe: Incompatible with ceftriaxone.

Storage

Store between 4°C to 22°C (40°F to 72°F); refrigeration is not required. Do not freeze. If transferred to a syringe or other container prior to administration, use within 6 hours. If used directly from vial/prefilled syringe, use within 12 hours. If diluted in 5% dextrose stable for 8 hours at room temperature. Shake well before use. Do not use if there is evidence of separation of phases of emulsion.

Drug Interactions

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy

Alfentanil: May enhance the adverse/toxic effect of Propofol. Specifically the development of opisthotonus (severe hyperextension and spasticity resulting in arching or bridging position) and/or grand mal seizures. Monitor therapy

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy

ARIPiprazole: CYP2D6 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy modification

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Exceptions: Levocabastine (Nasal). Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

Hydrocodone: CNS Depressants may enhance the CNS depressant effect of Hydrocodone. Management: Consider starting with a 20% to 30% lower hydrocodone dose when using together with any other CNS depressant. Dose reductions in the other CNS depressant may also be warranted. Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy

Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Consider therapy modification

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification

Metyrosine: CNS Depressants may enhance the sedative effect of Metyrosine. Monitor therapy

Midazolam: May increase the serum concentration of Propofol. Propofol may increase the serum concentration of Midazolam. Monitor therapy

Mifepristone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying). Management: Though the drugs listed here have uncertain QT-prolonging effects, they all have some possible association with QT prolongation and should generally be avoided when possible. Consider therapy modification

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Monitor therapy

Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: When oxycodone is combined with another CNS depressant, a dose reduction of one or both agents should be considered. The extended release oxycodone starting dose should be reduced 50% to 67% when initiated in patients already receiving CNS depressants. Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Avoid combination

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Rifampin: May enhance the hypotensive effect of Propofol. Management: Note that use of propofol in a patient who has been taking rifampin may result in clinically significant hypotension. If possible, avoid use of this combination. Consider therapy modification

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

Ropivacaine: Propofol may increase the serum concentration of Ropivacaine. Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Start tapentadol at a dose of one-third to one-half of the normal dose if being initiated in a patient who is taking another drug with CNS depressant effects. Monitor closely for evidence of excessive CNS depression. Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Thiotepa: May increase the serum concentration of CYP2B6 Substrates. Monitor therapy

TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use cannot be avoided, initiate tizanidine at an adult dose of 2 mg and increase in 2-4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification

Adverse Reactions

>10%:

Cardiovascular: Hypotension (children 17%; adults 3% to 26%)

Central nervous system: Movement (children 17%; adults 3% to 10%)

Local: Injection site burning, stinging, or pain (children 10%; adults 18%)

Respiratory: Apnea lasting 30-60 seconds (children 10%; adults 24%), apnea lasting >60 seconds (children 5%; adults 12%)

1% to 10%:

Cardiovascular: Hypertension (children 8%), arrhythmia (1% to 3%), bradycardia (1% to 3%), cardiac output decreased (1% to 3%; concurrent opioid use increases incidence), tachycardia (1% to 3%)

Dermatologic: Pruritus (1% to 3%), rash (children 5%; adults 1% to 3%)

Endocrine & metabolic: Hypertriglyceridemia (3% to 10%)

Respiratory: Respiratory acidosis during weaning (3% to 10%)

<1% (Limited to important or life-threatening): Agitation, amblyopia, anaphylaxis, anaphylactoid reaction, anticholinergic syndrome, asystole, atrial arrhythmia, bigeminy, cardiac arrest, chills, cough, dizziness, delirium, discoloration (green [urine, hair, or nailbeds]), extremity pain, fever, flushing, hemorrhage, hypersalivation, hypertonia, hypomagnesemia, hypoxia, infusion site reactions (including pain, swelling, blisters and/or tissue necrosis following accidental extravasation); laryngospasm, leukocytosis, lung function decreased, myalgia, myoclonia (rarely including convulsions and opisthotonos), nausea, pancreatitis, paresthesia, phlebitis, postoperative unconsciousness with or without increase in muscle tone, premature atrial contractions, premature ventricular contractions, pulmonary edema, propofol-related infusion syndrome, rhabdomyolysis, somnolence, syncope, thrombosis, urine cloudy, vision abnormality, wheezing

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylaxis/hypersensitivity reactions: May rarely cause hypersensitivity, anaphylaxis, anaphylactoid reactions, angioedema, bronchospasm, and erythema; medications for the treatment of hypersensitivity reactions should be available for immediate use. Use with caution in patients with history of hypersensitivity/anaphylactic reaction to peanuts; a low risk of crossreactivity between soy and peanuts may exist. Use is contraindicated in patients who are hypersensitive to eggs, egg products, soybeans, or soy products.

• ECG effects: In most cases, propofol does not significantly affect the QT interval (Staikou, 2014). However, prolongation of the QT interval, usually within normal limits, has occurred in case reports and small prospective studies and may be dose dependent (Hume-Smith, 2008; Kim, 2008; McConachie, 1989; Saarnivaara, 1990; Saarnivaara, 1993; Sakabe, 2002). Shortening of the QT interval has also occurred (Erdil, 2009; Tanskanen, 2002).

• Hypertriglyceridemia: Because propofol is formulated within a 10% fat emulsion, hypertriglyceridemia is an expected side effect. Patients who develop hypertriglyceridemia (eg, >500 mg/dL) are at risk of developing pancreatitis. Serum triglyceride levels should be obtained prior to initiation of therapy and every 3 to 7 days thereafter. Monitoring of serum triglycerides should especially be considered with therapy >48 hours with doses exceeding 50 mcg/kg/minute (Devlin, 2005). An alternative sedative agent should be employed if significant hypertriglyceridemia occurs. Use with caution in patients with preexisting hyperlipidemia as evidenced by increased serum triglyceride levels or serum turbidity.

• Hypotension: The major cardiovascular effect of propofol is hypotension especially if patient is hypovolemic or if bolus dosing is used. Hypotension may be substantial with a reduction in mean arterial pressure occasionally exceeding 30%. Use with caution in patients who are hemodynamically unstable, hypovolemic, or have abnormally low vascular tone (eg, sepsis).

• Injection-site reaction: Transient local pain may occur during IV injection; lidocaine 1% solution may be administered prior to administration or may be added to propofol immediately prior to administration to reduce pain associated with injection (see Administration).

• Myoclonus: Perioperative myoclonus (eg, convulsions and opisthotonos) has occurred with administration.

• Propofol-related infusion syndrome (PRIS): PRIS is a serious side effect with a high mortality rate (up to 33%) characterized by dysrhythmia (eg, bradycardia or tachycardia), heart failure, hyperkalemia, lipemia, metabolic acidosis, and/or rhabdomyolysis or myoglobinuria with subsequent renal failure. Risk factors include poor oxygen delivery, sepsis, serious cerebral injury, and the administration of high doses of propofol (usually doses >83 mcg/kg/minute or >5 mg/kg/hour for >48 hours), but has also been reported following large dose, short-term infusions during surgical anesthesia. PRIS has also been reported with lower-dose infusions (Chukwuemeka, 2006; Merz, 2006). The onset of the syndrome is rapid, occurring within 4 days of initiation. The mechanism of the syndrome has yet to be determined. Alternate sedative therapy should be considered for patients with escalating doses of vasopressors or inotropes, when cardiac failure occurs during high-dose propofol infusion, when metabolic acidosis is observed, or in whom lengthy and/or high-dose sedation is needed (Barr, 2013; Corbett, 2008).

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with severe cardiac disease (ejection fraction <50%) or hypotension; may have more profound adverse cardiovascular responses to propofol.

• Increased intracranial pressure: Use with caution in patients with increased intracranial pressure or impaired cerebral circulation; substantial decreases in mean arterial pressure and subsequent decreases in cerebral perfusion pressure may occur; consider continuous infusion or administer as a slow bolus.

• Infection risk: Propofol vials and prefilled syringes have the potential to support the growth of various microorganisms despite product additives intended to suppress microbial growth. To limit the potential for contamination, strictly adhere to recommendations in product labeling for handling and administering propofol.

• Pancreatitis: Use with caution in patients with preexisting pancreatitis; use of propofol may exacerbate this condition.

• Respiratory disease: Use with caution in patients with respiratory disease.

• Seizure disorder: Use with caution in patients with a history of epilepsy or seizures; seizure may occur during recovery phase.

Concurrent drug therapy issues:

• Opioids: Concomitant use may lead to increased sedative or anesthetic effects of propofol, more pronounced decreases in systolic, diastolic, and mean arterial pressures and cardiac output; lower doses of propofol may be needed. In addition, fentanyl may cause serious bradycardia when used with propofol in pediatric patients. Alfentanil use with propofol has precipitated seizure activity in patients without any history of epilepsy.

Special populations:

• ASA-PS (American Society of Anesthesiologists - Physical Status) 3/4 patients: Use a lower induction dose, a slower maintenance rate of administration, and avoid rapidly delivered boluses in ASA-PS 3/4 patients to reduce the incidence of unwanted cardiorespiratory depressive events.

• Debilitated patients: Use a lower induction dose, a slower maintenance rate of administration, and avoid rapidly delivered boluses in debilitated patients to reduce the incidence of unwanted cardiorespiratory depressive events.

• Elderly: Use a lower induction dose, a slower maintenance rate of administration, and avoid rapidly delivered boluses in elderly patients to reduce the incidence of unwanted cardiorespiratory depressive events.

• Pediatric: Safety and efficacy have not been established in pediatric intensive care unit patients; concurrent use of fentanyl and propofol in pediatric patients may result in bradycardia.

• Pregnancy: Propofol should only be used in pregnancy if clearly needed. Not recommended for use in obstetrics, including cesarean section deliveries.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors, 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer’s labeling.

• Edetate disodium: Some formulations contain edetate disodium which may lead to decreased zinc levels in patients with prolonged therapy (>5 days) or a predisposition to zinc deficiency (eg, burns, diarrhea, or sepsis). A holiday from propofol infusion should take place after 5 days of therapy to allow for evaluation and necessary replacement of zinc.

• Sulfites: Some formulations may contain sulfites.

Other warnings/precautions:

• Abrupt discontinuation: Avoid abrupt discontinuation prior to weaning or daily wake up assessments. Abrupt discontinuation can result in rapid awakening, anxiety, agitation, and resistance to mechanical ventilation; wean the infusion rate so the patient awakens slowly. Discontinue opioids and paralytic agents prior to weaning. Long-term infusions can result in some tolerance; taper propofol infusions to prevent withdrawal.

• Analgesic supplementation: Propofol lacks analgesic properties; pain management requires specific use of analgesic agents, at effective dosages, propofol must be titrated separately from the analgesic agent.

• Experienced personnel: Use requires careful patient monitoring, should only be used by experienced personnel who are not actively engaged in the procedure or surgery. If used in a nonintubated and/or non–mechanically ventilated patient, qualified personnel and appropriate equipment for rapid institution of respiratory and/or cardiovascular support must be immediately available. Use to induce moderate (conscious) sedation in patients warrants monitoring equivalent to that seen with deep anesthesia. Consult local regulations and individual institutional policies and procedures.

Monitoring Parameters

Cardiac monitor, blood pressure, oxygen saturation (during monitored anesthesia care sedation), arterial blood gas (with prolonged infusions). With prolonged infusions (eg, ICU sedation), monitor for metabolic acidosis, hyperkalemia, rhabdomyolysis or elevated CPK, hepatomegaly, and progression of cardiac and renal failure.

ICU sedation: Assess and adjust sedation according to scoring system (Richmond Agitation-Sedation Scale [RASS] or Sedation-Agitation Scale [SAS]) (Barr, 2013); assess CNS function daily. Serum triglyceride levels should be obtained prior to initiation of therapy and every 3-7 days thereafter, especially if receiving for >48 hours with doses exceeding 50 mcg/kg/minute (Devlin, 2005); use intravenous port opposite propofol infusion or temporarily suspend infusion and flush port prior to blood draw.

Diprivan®: Monitor zinc levels in patients predisposed to deficiency (burns, diarrhea, major sepsis) or after 5 days of treatment.

Pregnancy Risk Factor

B

Pregnancy Considerations

Propofol crosses the placenta and may be associated with neonatal CNS and respiratory depression. Propofol is not recommended by the manufacturer for obstetrics, including cesarean section deliveries.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience fatigue. Have patient report immediately to prescriber severe dizziness, syncope, dyspnea, bradycardia, angina, difficulty with motor activity, fasciculations, change in balance, dysphagia, difficulty speaking, vision changes, significant injection site pain or irritation, rigidity, or signs of propofol infusion syndrome (rare) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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