DrugindexOnline^{2nd edition}

Pronouncation: (PRO-puh-FOLE)
Class: General anesthetic

Trade Names:
Diprivan
- Injection 10 mg/mL

Mechanism of Action

Pharmacology

Produces sedation/hypnosis rapidly (within 40 sec) and smoothly with minimal excitation; decreases intraocular pressure and systemic vascular resistance; rarely is associated with malignant hyperthermia and histamine release; suppresses cardiac output and respiratory drive.

Pharmacokinetics

Absorption

Rapidly and extensively distributed. Vd is approximately 60 L/kg (10-day infusion), highly lipophilic. Crosses blood brain barrier and placenta; distributes into breast milk. Protein binding is 95% to 99%.

Metabolism

Liver conjugation to inactive metabolites.

Elimination

50% of dose is excreted in the kidney (metabolites). Clearance is 23 to 50 mL/kg/min. Terminal t _1/2 is 1 to 3 days (10-day infusion). T _1/2 of rapid distribution is 2 to 4 min. T _1/2 of slower distribution is 30 to 64 min.

Onset

Rapid onset, usually within 40 sec from start of injection.

Duration

3 to 5 min (single bolus).

Special Populations

Elderly

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

Indications and Usage

Induction and maintenance of anesthesia in adults; induction anesthesia in children at least 3 yr; maintenance anesthesia in pediatric patients at least 2 mo; initiation and maintenance of monitored anesthesia care sedation in adults; sedation in intubated or respiratory-controlled adult ICU patients.

Contraindications

Situations in which general anesthesia or sedation are contraindicated.

Dosage and Administration

Anesthesia
Adults under 55 yr

IV Induction 40 mg q 10 sec until onset. Usual dose is 2 to 2.5 mg/kg total. For maintenance infusion, titrate to 100 to 200 mcg/kg/min (6 to 12 mg/kg/hr). For maintenance intermittent bolus, use 25 to 50 mg increments, as needed.

Elderly, Debilitated, or ASA III/IV

(American Society of Anesthesiologists classification of heart disease, cardiac function, angina, and physical status used to assign risk for anesthesia.) IV 20 mg q 10 sec until onset. Usual dose is 1 to 1.5 mg/kg. For maintenance infusion, titrate to 50 to 100 mcg/kg/min (3 to 6 mg/kg/hr).

Neurosurgical patients

IV Induction 20 mg q 10 sec until onset. Usual dose is 1 to 2 mg/kg. For maintenance infusion, use 100 to 200 mcg/kg/min (6 to 12 mg/kg/hr).

Children at least 3 yr

IV Induction 2.5 to 3.5 mg/kg over 20 to 30 sec. For maintenance infusion (at least 2 mo), use 200 to 300 mcg/kg/min immediately following the induction dose, then, after the first 30 min of maintenance, use infusion rates of 125 to 150 mcg/kg/min titrated to achieve the desired clinical effect, are typically needed.

Sedation
Adults under 55 yr

IV Initiation 100 to 150 mcg/kg/min (6 to 9 mg/kg/hr) for 3 to 5 min (preferred method) or slow injection of 0.5 mg/kg over 3 to 5 min; follow by maintenance infusion. For maintenance, use 25 to 75 mcg/kg/min (1.5 to 4.5 mg/kg/hr) (preferred method) or incremental bolus doses of 10 to 20 mg.

Elderly, Debilitated, or ASA III/IV

IV Initiation Same as adults; not as rapid bolus. For maintenance, use 20% reduction of adult dose; avoid rapid bolus doses.

ICU Sedation
Adults

IV Initiation 5 mcg/kg/min (0.3 mg/kg/hr) for at least 5 min; increments of 5 to 10 mcg/kg/min (0.2 to 0.6 mg/kg/hr) over 5 to 10 min may be used until desired level of sedation is achieved. For maintenance, use 5 to 50 mcg/kg/min (0.3 to 3 mg/kg/hr) or higher may be required; use minimum dose required for sedation.

General Advice

• Should be administered only by personnel who are trained in administration of general anesthesia and familiar with drug.
• Administer only in settings in which resuscitation equipment is immediately available.
• Shake well before use. Do not use if there is evidence of separation of phases of emulsion.
• Maintain strict aseptic technique in handling; rapid growth of organisms may occur if contaminated.
• Dilute with 5% Dextrose Injection, but do not dilute to concentration less than 2 mg/mL. Drug is compatible with 5% Dextrose; Lactated Ringer's Injection; Lactated Ringer's and 5% Dextrose Injection; 5% Dextrose and 0.45% Sodium Chloride Injection; 5% Dextrose and 0.2% Sodium Chloride Injection.
• Minimize pain associated with administration by infusing into larger veins.
• Discard any unused portions of drug or solution at end of anesthetic procedure; do not keep for more than 6 hr.
• In ICU sedation discard after 12 hr if administered directly from vial or after 6 hr if transferred to syringe or other container.

Storage/Stability

Store between 40° and 72°F. Do not freeze. Protect from light.

Drug Interactions

CNS depressants (eg, barbiturates, benzodiazepines, narcotics)

Increased CNS depression.

Incompatibility

For IV, do not mix with other therapeutic agents prior to administration. Avoid mixing blood or plasma in same IV catheter.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Myocardial ischemia; hypotension; bradycardia; decreased cardiac output; hypertension (especially in children).

CNS

Amorous behavior; movement hypotonia; hallucinations; neuropathy; opisthotonos.

Dermatologic

Rash.

EENT

Conjunctival hyperemia; nystagmus.

Metabolic

Hyperlipidemia.

Respiratory

Apnea; cough; respiratory acidosis during weaning.

Miscellaneous

Asthenia; burning, stinging, or pain at injection site; fever.

Precautions

Pregnancy

Category B .

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established for induction anesthesia in children under 3 yr or maintenance anesthesia in children under 2 mo.

Labor and Delivery

Not recommended for obstetrical anesthesia (neonatal depression).

Special Risk Patients

Use lower induction and maintenance doses in elderly, debilitated, and ASA III/IV patients, and monitor continuously for sign of hypotension or bradycardia. Use with caution in patients with lipid metabolism disorders, because propofol is an emulsion. Epileptics may be at risk of convulsions during recovery phase. Avoid significant decreases in mean arterial pressure (and cerebral perfusion) in patients with increased intracranial pressure or impaired cerebral circulation.

Anaphylaxis

Has occurred rarely; relationship to drug has not been established.

Overdosage

Symptoms

Cardiorespiratory and cardiovascular depression.

Patient Information

• Advise patient that mental alertness, coordination, and physical dexterity may be impaired for some time after administration.