Propofol (Diprivan) and It’s Adverse Effect in Anesthesia Liu, Chih-Min

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Propofol (Diprivan) and It’s Adverse Effect in Anesthesia

  • Liu, Chih-Min

  • 2003-8-19



  • Indications: Anesthesia, general

  • Pregnancy Category B

  • FDA Approved 1989 Oct

  • 2,6-diisopropylphenol

  • molecular weight of 178.27.

  • isotonic

  • pH of 7-8.5

Mechanism of Action

  • The actual mechanism of action is unknown, but it is postulated that propofol mediates activity of the GABA receptors.

  • rapid sedation with minimal excitatory activity

  • no analgesic properties


  • eliminated by hepatic conjugation to inactive metabolites, excreted by the kidney

  • No dosage adjustments are needed for patients with renal or hepatic failure

  • Geriatrics

    • age-related decrease in volume of distribution
    • higher peak plasma concentrations
    • cardiorespiratory effects including hypotension, apnea, airway obstruction, and/or oxygen desaturation


  • induction and/or maintenance of anesthesia

  • in adult patients and pediatric patients greater than 3 years of age

  • not recommended for obstetrics

  • not recommended for use in nursing mothers

Pediatric Use

  • not recommended in:

    • induction of anesthesia in patients younger than 3 years of age
    • maintenance of anesthesia in patients younger than 2 months of age
    • not indicated for use in pediatric patients for ICU sedation

Cardiac Anesthesia

  • well-studied in coronary artery disease, but valvular or congenital heart disease is limited

  • decrease in blood pressure that is secondary to decreases in preload and afterload

  • lower heart rates possibly due to reduction of the sympathetic activity and/or resetting of the baroreceptor reflexes anticholinergic agents should be administered when increases in vagal tone are anticipated

Induction of General Anesthesia

  • Healthy Adults Less Than 55 Years of Age: 40 mg every 10 seconds until induction onset (2-2.5 mg/kg).

  • Elderly, Debilitated, or ASA III/IV Patients: 20 mg every 10 seconds until induction onset (1-1.5 mg/kg).

  • Cardiac Anesthesia: 20 mg every 10 seconds until induction onset (0.5-1.5 mg/kg).

  • Neurosurgical Patients: 20 mg every 10 seconds until induction onset (1-2 mg/kg).

  • Pediatric Patients - healthy, from 3-16 years of age: 2.5-3.5 mg/kg administered over 20-30 seconds.

Maintenance of General Anesthesia

  • Healthy Adults Less Than 55 Years of Age: 100-200 μg/kg/min (6-12 mg/kg/h).

  • Elderly, Debilitated, ASA III/IV Patients: 50-100 μg/kg/min (3-6 mg/kg/h).

  • Pediatric Patients - healthy, from 2 months to 16 years of age: 125-300 μg/kg/min (7.5-18 mg/kg/h)

  • Cardiac Anesthesia, Most Patients Require: Primary propofol injectable emulsion with secondary opioid: 100-150 μg/kg/min. Low-dose propofol injectable emulsion with primary opioid: 50-100 μg/kg/min.

  • Neurosurgical Patients: 100-200 μg/kg/min (6-12 mg/kg/h).


  • hypersensitivity to propofol injectable emulsion or its components, or when general anesthesia or sedation are contraindicated.

Beneficial Effects

  • Sedation

  • Amnesia

Adverse Effects

  • Airway

    • Copious secretions
    • Laryngospasm
  • Respiratory

    • Apnea, respiratory depression
    • Hiccough
    • Bronchospasm
  • Cardiovascular

    • Hypotension
    • Dysrhythmias, bradycardia or tachycardia

Adverse Effects

  • Central Nervous System

    • Headache
    • Dizziness, euphoria, confusion
    • Clonic/myoclonic movements
    • Seizures, disinhibition
  • Other

Adverse Effects

  • Incidence Greater Than 1%

    • Cardiovascular: Bradycardia; arrhythmia [Peds: 1.2%]; tachycardia nodal [Peds: 1.6%]; hypotension* [Peds: 17%] [hypertension Peds: 8%]
    • Central Nervous System: Movement* [Peds: 17%]
    • Injection Site: Burning/stinging or pain, 17.6% [Peds: 10%]
    • Respiratory: Apnea
    • Skin and Appendages: Rash [Peds: 5%]; pruritus [Peds: 2%]. Events without an * or % had an incidence of 1-3%. * Incidence of events 3-10%.

Adverse Effects

  • postoperative unconsciousness

  • Transient local pain: larger veins; prior injection of IV lidocaine (1 ml of a 1% solution)

  • rare reports of pulmonary edema

  • unexplained postoperative pancreatitis

Adverse Effects

  • Pediatric patients

    • no vagolytic activity
    • Reports of bradycardia, asystole, and rarely, cardiac arrest have been associated with propofol
    • particularly when fentanyl is given
    • anticholinergic agents


  • dose requirements redused:

    • Premedication with narcotics (e.g., morphine, meperidine, and fentanyl, etc.)
    • In pediatric patients, administration of fentanyl concomitantly with propofol may result in serious bradycardia
    • combinations of opioids and sedatives (e.g., benzodiazepines, barbiturates, chloral hydrate, droperidol, etc.)
    • more pronounced decreases in systolic, diastolic, and mean arterial pressures and cardiac output


    • reduced in the presence nitrous oxide
    • inhalational agents (e.g., isoflurane, enflurane, and halothane) has not been extensively evaluated
    • does not cause a clinically significant change in onset, intensity or duration of action of the commonly used neuromuscular blocking agents (e.g., succinylcholine and nondepolarizing muscle relaxants).

A small dose of midazolam decreases the time to achieve hypnosis without delaying emergence during short-term propofol anesthesia. Journal of Clinical Anesthesia Volume 13 • Number 4 • June 2001 Copyright © 2001 Elsevier


    • Coadministration of 10 microg kg(-1)midazolam decreases the dose and time required to achieve hypnosis with propofol induction without delaying emergence from anesthesia.
    • Additional administration of flumazenil further shortens the time to emerge from midazolam-propofol anesthesia.

Seizure-like phenomena and propofol: a systematic review. Neurology Volume 58 • Number 9 • May 14, 2002 Copyright © 2002 American Academy of Neurology

  • a change in cerebral concentration of propofol may be causal

  • a drug-induced excitation of the CNS, [9] including seizures in susceptible patients

  • warned about the use of propofol in patients with epilepsy

The interaction between fentanyl and propofol during emergence from anesthesia: monitoring with the EEG-Bispectral index. Journal of Clinical Anesthesia Volume 15 • Number 2 • March 2003 Copyright © 2003 Elsevier


    • The plasma levels of fentanyl affect the concentrations of propofol required for patients to regain consciousness.
    • The BIS values for wakefulness are unaltered at the different combinations of propofol and fentanyl concentrations. Thus, the BIS appears to be a useful and consistent indicator for level of consciousness during emergence from propofol/fentanyl intravenous anesthesia

Death related to propofol use in an adult patient. Critical Care Medicine Volume 28 • Number 8 • August 2000 Copyright © 2000 Lippincott Williams & Wilkins

    • several reports linking propofol to the development of metabolic acidosis and cardiac dysrhythmias in pediatric patients
    • Arrhythmias, metabolic acidosis, cardiac failure, and death related to propofol use can occur in adults as well as in children

Metabolic acidosis and fatal myocardial failure after propofol infusion in children: five case reports BMJ 1992; 305:613–616  

    • increasing metabolic acidosis was associated with brady-arrhythmia and progressive myocardial failure, which did not respond to resuscitative measures
      • Although the exact cause of death in these children could not be defined, propofol may have been a contributing factor.

Morphologic changes in the upper airway of children during awakening from propofol administration. Anesthesiology Volume 96 • Number 3 • March 2002 Copyright © 2002 American Society of Anesthesiologists, Inc.


    • The dimensions of the upper airways of children change shape significantly on awakening from propofol sedation.
    • When sedated, the upper airway is oblong shaped, with the A-P diameter larger than the transverse diameter.
    • On awakening, the shape of the upper airway in most children changed such that the transverse diameter was larger. Cross-sectional areas between sedated and awakening states were unchanged.
    • These changes may reflect the differential effects of propofol on upper airway musculature during awakening

A comparison of ketamine and lidocaine spray with propofol for the insertion of laryngeal mask airway in children: a double-blinded randomized trial. Anesth Analg - 01-DEC-2002; 95(6): 1586-9

    • Ketamine and lidocaine spray appear to be appropriate for laryngeal mask airway (LMA) insertion in children.
    • apnea and airway obstruction, the two most serious and frequent complications of propofol, can be avoided during LMA insertion.

Thanks for your attention!

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