No

General Anesthetic

Induction or maintenance of anesthesia for inpatient or outpatient surgery; may be used (for patients >18 years of age who are intubated and mechanically ventilated) as an alternative to benzodiazepines for the treatment of agitation in the intensive care unit; pain should be treated with analgesic agents, propofol must be titrated separately from the analgesic agent; has demonstrated antiemetic properties in the postoperative setting

B

Absolute contraindications:

Patients with a hypersensitivity to propofol

Patients with a hypersensitivity to propofol's emulsion which contains soybean oil, egg phosphatide, and glycerol or any of the components

Patients who are not intubated or mechanically ventilated

Patients who are pregnant or nursing: Propofol is not recommended for obstetrics, including cesarian section deliveries. Propofol crosses the placenta and, therefore, may be associated with neonatal depression.

Relative contraindications:

Pediatric Intensive Care Unit patients: Safety and efficacy of propofol is not established

Patients with severe cardiac disease (ejection fraction <50%) or respiratory disease - propofol may have more profound adverse cardiovascular responses

Patients with a history of epilepsy or seizures

Patients with increased intracranial pressure or impaired cerebral circulation - substantial decreases in mean arterial pressure and subsequent decreases in cerebral perfusion pressure may occur

Patients with hyperlipidemia as evidenced by increased serum triglyceride levels or serum turbidity

Patients who are hypotensive, hypovolemic, or hemodynamically unstable

Use slower rate of induction in the elderly; transient local pain may occur during I.V. injection; perioperative myoclonia has occurred; do not administer with blood or blood products through the same I.V. catheter; not for obstetrics, including cesarean section deliveries. Safety and effectiveness has not been established in children. Abrupt discontinuation prior to weaning or daily wake up assessments should be avoided. Abrupt discontinuation can result in rapid awakening, anxiety, agitation, and resistance to mechanical ventilation; not for use in neurosurgical anesthesia.

>10%:

Cardiovascular: Hypotension, intravenous propofol produces a dose-related degree of hypotension and decrease in systemic vascular resistance which is not associated with a significant increase in heart rate or decrease in cardiac output

Local: Pain at injection site occurs at an incidence of 28.5% when administered into smaller veins of hand versus 6% when administered into antecubital veins

Respiratory: Apnea (incidence occurs in 50% to 84% of patients and may be dependent on premedication, speed of administration, dose and presence of hyperventilation and hyperoxia)

1% to 10%:

Anaphylaxis: Several cases of anaphylactic reactions have been reported with propofol

Central nervous system: Dizziness, fever, headache; although propofol has demonstrated anticonvulsant activity, several cases of propofol-induced seizures with opisthotonos have occurred

Gastrointestinal: Nausea, vomiting, abdominal cramps

Respiratory: Cough, apnea

Neuromuscular & skeletal: Twitching

Miscellaneous: Hiccups

Symptoms of overdose include hypotension, bradycardia, cardiovascular collapse

Treatment is symptomatic and supportive; hypotension usually responds to I.V. fluids and/or Trendelenburg positioning; parenteral inotropes may be needed

Increased toxicity:

Neuromuscular blockers:

Atracurium: Anaphylactoid reactions (including bronchospasm) have been reported in patients who have received concomitant atracurium and propofol

Vecuronium: Propofol may potentiate the neuromuscular blockade of vecuronium

Central nervous system depressants: Additive CNS depression and respiratory depression may necessitate dosage reduction when used with: Anesthetics, benzodiazepines, opiates, ethanol, narcotics, phenothiazines

Decreased effect: Theophylline: May antagonize the effect of propofol, requiring dosage increases

Do not use if there is evidence of separation of phases of emulsion

Store at room temperature 4°C to 22°C (40°F to 72°F), refrigeration is not recommended; protect from light

Propofol may be further diluted in dextrose 5% in water to a concentration greater than or equal to 2 mg/mL and is stable for 8 hours at room temperature

Y-site compatible with D₅LR, D₅NS, D₅W, LR, lidocaine

Soybean fat emulsion is used as a vehicle for propofol. This soybean fat emulsion contains no preservatives. Strict aseptic technique must be maintained in handling because this vehicle is capable of supporting rapid bacterial growth.

Propofol is a hindered phenolic compound with intravenous general anesthetic properties. The drug is unrelated to any of the currently used barbiturate, opioid, benzodiazepine, arylcyclohexylamine, or imidazole intravenous anesthetic agents.

Onset of anesthesia: Within 9-51 seconds (average 30 seconds) after bolus infusion (dose dependent)

Duration: 3-10 minutes depending on the dose and the rate of administration

Distribution: V_d: 2-6 mcg/mL during anesthesia; 1-2 mcg/mL upon awakening; large volume of distribution; highly lipophilic

Protein binding: 97% to 99%

Half-life, elimination (biphasic): Initial: 40 minutes; Terminal: 1-3 days

Metabolism: In the liver to water-soluble sulfate and glucuronide conjugates; total body clearance exceeds liver blood flow

Elimination: ~88% of a propofol dose is recovered in the urine as metabolites (40% as glucuronide metabolite) and <2% of a propofol dose is excreted in the feces

Dosage must be individualized based on total body weight and titrated to the desired clinical effect; however, as a general guideline:

Induction: I.V.:

Adults less than or equal to 55 years, and/or ASA I or II patients: 2-2.5 mg/kg of body weight (approximately 40 mg every 10 seconds until onset of induction)

Elderly, debilitated, hypovolemic, and/or ASA III or IV patients: 1-1.5 mg/kg of body weight (approximately 20 mg every 10 seconds until onset of induction)

Maintenance: I.V. infusion:

Adults less than or equal to 55 years, and/or ASA I or II patients: 0.1-0.2 mg/kg of body weight/minute (6-12 mg/kg of body weight/hour)

Elderly, debilitated, hypovolemic, and/or ASA III or IV patients: 0.05-0.1 mg/kg of body weight/minute (3-6 mg/kg of body weight/hour)

I.V. intermittent: 25-50 mg increments, as needed

ICU sedation: Rapid bolus injection should be avoided. Bolus injection can result in hypotension, oxyhemoglobin desaturation, apnea, airway obstruction, and oxygen desaturation. The preferred route of administration is slow infusion. Doses are based on individual need and titrated to response.

Recommended starting dose: 5 mcg/kg/minute (0.3-0.6 mg/kg/hour) over 5-10 minutes may be used until the desired level of sedation is achieved; infusion rate should be increased by increments of 5-10 mcg/kg/minute (0.3-0.6 mg/kg/hour) until the desired level of sedation is achieved; most adult patients require maintenance rates of 5-50 mcg/kg/minute (0.3-3 mg/kg/hour) or higher

Adjustments in dose can occur at 3- to 5-minute intervals. An 80% reduction in dose should be considered in elderly, debilitated, and ASA III or IV patients. Once sedation is established, the dose should be decreased for the maintenance infusion period and adjusted to response.

Do not use filter with <5 micron for administration

Cardiac monitor, blood pressure monitor, and ventilator required; serum triglyceride levels should be obtained prior to initiation of therapy (ICU setting) and every 3-7 days, thereafter

cholesterol (S); porphyrin (U); cortisol (S), but does not appear to inhibit adrenal responsiveness to ACTH

May cause dizziness

Concurrent use with psychotropics may produce additive CNS depression and respiratory depression; monitor and adjust dosages as needed

No information available to require special precautions

No effects or complications reported

Protect from light; shake well

Changes urine color to green; abrupt discontinuation of infusion may result in rapid awakening of the patient associated with anxiety, agitation, and resistance to mechanical ventilation, making weaning from mechanical ventilation difficult; use a light level of sedation throughout the weaning process until 10-15 minutes before extubation; titrate the infusion rate so the patient awakens slowly. Tubing and any unused portions of propofol vials should be discarded after 12 hours.

Injection: 10 mg/mL (20 mL, 50 mL, 100 mL)

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Bennett SN, McNeil MM, Bland LA, et al, "Postoperative Infections Traced to Contamination of an Intravenous Anesthetic, Propofol," N Engl J Med, 1995, 333(3):147-54.

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Langley MS and Heel RC, "Propofol: A Review of its Pharmacodynamic and Pharmacokinetic Properties and Use as an Intravenous Anaesthetic," Drugs, 1988, 35(4):334-72.

Merigian KS, Browning RG, and Leeper KV, "Successful Treatment of Amoxapine-Induced Refractory Status Epilepticus With Propofol," Acad Emerg Med, 1995, 2(2):128-33.

Mirenda J, "Prolonged Propofol Sedation in the Critical Care Unit," Crit Care Med, 1995, 23(7):1304.

Parke TJ, Stevens JE, Rice ASC, et al, "Metabolic Acidosis and Fatal Myocardial Failure After Propofol Infusion in Children: Five Case Reports," BMJ, 1992, 305(6854):613-6.

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