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