propofol

Propofol is an intravenous anesthetic drug used to induce and maintain general anesthesia and sedation during surgical procedures. Propofol is also used for monitored anesthesia care (MAC), also known as procedural sedation or conscious sedation, and to sedate mechanically ventilated ICU patients.

Propofol is a rapid acting anesthetic that works by depressing the central nervous system. It is not entirely clear how exactly propofol works, but it is believed to induce sedation by enhancing the activity of gamma-aminobutyric acid (GABA) , the major inhibitory chemical messenger (neurotransmitter) in the brain. Propofol works by prolonging the inhibitory activity of GABA on GABA-A receptors on nerve cells (neurons).

Uses of propofol include:

Adult:

• Induction and maintenance of monitored anesthesia care
• Combined sedation and regional anesthesia
• Induction and maintenance of general anesthesia
• Sedation of intubated mechanically ventilated ICU patients

Pediatric:

• Induction and maintenance of general anesthesia

Off-label uses include:

• Refractory postoperative nausea and vomiting in adults
• Refractory status epilepticus, a prolonged seizure state (adults and children)

• Do not administer propofol to patients with known hypersensitivity to propofol or any of its components
• Do not administer propofol to patients with egg or soybean allergy; the emulsion used to deliver propofol contains egg and soybean fats
• Use of propofol has been associated with severe allergic reactions (anaphylactic and anaphylactoid) that can be life-threatening or fatal
• The emulsion used in the propofol formulation can support rapid growth of microorganisms; use proper aseptic technique
• Avoid leakage of propofol out of the vein (extravasation); can cause tissue death (necrosis)
• Vital signs of sedated patients must be continuously monitored
• Patients with anemia, impaired kidney or liver function or severe hypothyroidism (myxedema) must be monitored closely
• Propofol can lower blood pressure, use with caution in patients with low blood pressure (hypotension), low blood volume (hypovolemia), unstable blood pressure, abnormally low vascular tone or severe heart disease
• Prolonged infusion for ICU sedation is associated with propofol infusion syndrome, which causes several metabolic disturbances including severe acid buildup (metabolic acidosis), high potassium levels (hyperkalemia), high concentration of emulsified fats in blood (hyperlipemia) and organ system failures including muscle tissue breakdown (rhabdomyolysis), liver enlargement (hepatomegaly), renal failure, ECG changes and cardiac failure
• Use propofol with caution in patients with elevated intracranial pressure or impaired cerebral blood circulation
• Use with caution in patients with respiratory disease and history of epilepsy or seizures; seizure may occur during recovery
• Do not abruptly discontinue propofol; may result in rapid awakening, with associated anxiety, agitation and resistance to mechanical ventilation
• Propofol does not have pain-relieving (analgesic) properties; analgesics must be separately administered
• Propofol is associated with the risk of chills, fever and body aches
• Repeated or prolonged exposure to propofol can impair brain development in pediatric patients

Common side effects of propofol include:

• Injection site burning, stinging or pain
• Low blood pressure (hypotension)
• Reduced cardiac output
• Elevated blood pressure (hypertension)
• Pause in breathing (apnea) lasting 30-60 seconds
• Apnea lasting longer than 60 seconds
• Impaired ability of lungs to remove carbon dioxide (respiratory acidosis) during the weaning phase
• Impaired movement
• High level of emulsified fats in the blood (hyperlipidemia)
• High triglyceride level in blood (hypertriglyceridemia)

Less common side effects of propofol include:

• Irregular heart rhythm (arrhythmia)
• Slow heartbeat (bradycardia)
• Rapid heartbeat (tachycardia)
• Rash
• Itching (pruritus)
• Rare side effects of propofol include
• Severe allergic reaction (anaphylaxis)
• Arterial hypotension
• Abnormal ECG
• Atrial arrhythmia
• Absence of heartbeat (flatline/asystole)
• Cardiac arrest
• Fainting (syncope)
• Bronchospasm
• Fluid in the lungs (pulmonary edema)
• Involuntary muscle contractions (dystonia)
• Seizure
• Agitation
• Dizziness
• Drowsiness (somnolence)
• Delirium
• Flushing
• Excessive salivation (hypersalivation)
• Nausea
• Inflammation of the pancreas (pancreatitis)
• Inner ear reactions
• Abnormal vision
• Low magnesium levels (hypomagnesemia)
• Inflammation of the vein (phlebitis)
• Blood clot (thrombosis)
• Kidney damage (renal tubular toxicity)
• Cloudy or greenish urine

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug.

Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Injectable solution

• 10 mg/mL

Adult:

Anesthesia

Induction

• Adults under 55 years ASA I/II: 40 mg intravenously (IV) every 10 seconds until onset (2-2.5 mg/kg IV when not pre-medicated with oral benzodiazepines or intramuscular opioids)
• Adults over 55 years or debilitated or ASA III/IV: 20 mg IV every 10 seconds until onset (1-1.5 mg/kg); do not use rapid bolus because it will increase the likelihood of undesirable cardiorespiratory depression, including hypotension, apnea, airway obstruction, and/or oxygen desaturation

Maintenance

• Adults under 55 years ASA I/II: 0.1-0.2 mg/kg/minute intravenously (IV); administered in a variable rate infusion with nitrous oxide 60% to 70% and oxygen provides anesthesia for patients undergoing general surgery; maintenance infusion should immediately follow induction dose to provide satisfactory or continuous anesthesia during the induction phase
• Intermittent bolus: Increments of 25-50 mg (2.5-5 mL) may be administered with nitrous oxide in adults undergoing general surgery; administer incremental boluses when changes in vital signs indicate response to surgical stimulation or light anesthesia
• Adults over 55 years or debilitated or ASA III/IV: 0.05-0.1 mg/kg/minute intravenously (IV)

Monitored Anesthesia Care (MAC Sedation/Conscious Sedation)

Initiation

• 0.1-0.15 mg/kg/minute intravenously (IV) for 3-5 minutes; titrate to desired clinical effect; monitor respiratory function; administered as a slow infusion or slow injection while monitoring cardiorespiratory function
• Slow injection: 0.5 mg/kg administered over 3-5 minutes; titrate to clinical response
• Elderly: Do not use rapid bolus dose administration; administer over 3-5 minutes; reduce dose to approximately 80% of usual adult dose according to their condition, response, and changes in vital signs

Maintenance

• Variable-rate of infusion method preferable over intermittent bolus dose method
• Variable-rate infusion method: 0.025-0.075 mg/kg/minute intravenously (IV) during first 10-15 min sedation maintenance; subsequently decrease infusion rates overtime to 25 to 50 mcg/kg/minute and adjust clinical response; allow approximately 2 min for the onset of peak drug effect to titrate to clinical response; titrate downward in absence of clinical signs of light sedation until mild response to stimulation obtained to avoid sedative administration at rates higher than clinically necessary
• Intermittent bolus method: Administer 10-20 mg increments and titrate to the desired level of sedation
• Elderly: 0.02-0.06 mg/kg/minute IV; do not use rapid bolus dose administration; reduce the rate of administration to 80% of usual adult dose according to their condition, response, and changes in vital signs

Postoperative Nausea/Vomiting

• 20 mg intravenously (IV); may repeat

ICU Patient

• Initiation: 0.005 mg/kg/minute intravenously (IV) for at least 5 minutes; titrate to desired clinical effect; increase by 5-10 mcg/kg/minute over 5-10 minute intervals until desired sedation level achieved; allow a minimum of 5 minutes between adjustments for the onset of peak effect
• For medical ICU patients or patients who recovered from the effect of general anesthesia or deep sedation, a rate of administration of 50 mcg/kg/min or more may be required to achieve adequate sedation
• Maintenance: 0.005-0.05 mg/kg/minute intravenous (IV) individualized and titrated to clinical response; (0.005 mg/kg/minute increment increase every 5 minutes)
• Discontinuation: Avoid discontinuation prior to weaning or for daily evaluation of sedation levels; may result in rapid awakening with associated anxiety, agitation, and resistance to mechanical ventilation

Pediatric:

Anesthesia

Induction

• Children under 3 years: Not recommended
• 3-16 years ASA I/II: 2.5-3.5 mg/kg intravenously (IV) over 20-30 sec when not pre-medicated or when lightly pre-medicated with oral benzodiazepines or intramuscular opioids; younger patients may require higher induction doses than older children; lower dosage recommended for children ASA III/IV

Maintenance

• Children 2 months-16 years ASA I/II: 0.125-0.3 mg/kg/minute intravenously (IV); after 30 minutes, if clinical signs of light anesthesia are absent, decrease infusion rate; children 5 years or younger may require larger infusion rates compared to older children

• There are reports of the abuse of propofol for recreational and other improper purposes, which have resulted in fatalities and other injuries. Instances of self-administration of propofol by health care professionals have also been reported, which have resulted in fatalities and other injuries. Inventories of propofol should be stored and managed to prevent the risk of diversion, including restriction of access and accounting procedures as appropriate to the clinical setting.
• In case of overdosage, propofol administration should be discontinued immediately.
• Overdose can cause cardiorespiratory depression. Respiratory depression should be treated by artificial ventilation with oxygen.
• Cardiovascular depression may require repositioning of the patient by raising the patient's legs, increasing the flow rate of intravenous fluids, and administering pressor agents and/or anticholinergic agents.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Severe Interactions of propofol include:
  • None
• Propofol has serious interactions with at least 33 different drugs including:
  • ceritinib
  • doxapram
  • epinephrine
  • fentanyl
  • isocarboxazid
  • norepinephrine
  • phenelzine
  • phenylephrine
  • pirfenidone
  • selegiline
• Propofol has moderate interactions with at least 189 different drugs.
• Mild Interactions of propofol include:
  • amitriptyline
  • amoxapine
  • clomipramine
  • desipramine
  • doxepin
  • imipramine
  • lofepramine
  • nortriptyline
  • ruxolitinib
  • trazodone

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• There are no adequate and well-controlled studies for the use of propofol in pregnancy; use with caution if benefits outweigh risks.
• Animal studies indicate that propofol use in the third trimester may cause fetal harm and may affect brain development; avoid use.
• Propofol is not recommended for use in labor and delivery, including cesarean section deliveries; propofol may cause neonatal depression.
• Propofol has been reported to be excreted in breast milk; effects on the breastfed infant are not known; do not use in nursing mothers.