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

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

• Liu, Chih-Min

• 2003-8-19

2,6-diisopropylphenol

Propofol

• 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

Pharmacokinetics

• 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

INDICATIONS AND USAGE:

• 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).

CONTRAINDICATIONS

• 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

• Pain or burning at the injection site is common especially when the IV is in a small peripheral vein
• Green urine

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

DRUG INTERACTIONS:

• 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

DRUG INTERACTIONS:

• 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

• CONCLUSIONS:

• 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

• CONCLUSIONS:

• 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
• CONCLUSION—
• 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.

• CONCLUSIONS:

• 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.

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