Although analysis for the detection of propofol follows standard procedures, the toxicological and medico-legal determination of the contribution of propofol to a fatality is often complicated by wide variability of propofol plasma concentrations and the concomitant abuse of other drugs.
The recent cases of fatal prescription drug overdoses by celebrities (Heath Ledger, Michael Jackson) have resulted in a new set of analytical challenges for forensic toxicology laboratories. Although the abuse of benzodiazepines is widely accepted, it has also been noted that injectable short-term general anesthetics such as propofol, ketamine, and the barbiturates thiopental and methohexital are being frequently abused by healthcare professionals such as nurses and physicians1-3 and has now spread to wider populations as well.This article provides a brief review of propofol with regard to its abuse, toxicological analysis, and medico-legal challenges.
Mechanism of Action and Pharmacokinetics
Propofol is a phenol derivative and is one of the most commonly used injectable anesthetics for the induction of anesthesia as well as maintenance of short-term anesthesia. It was introduced in 1989 under the trade name Diprivan® and surpassed other injectable anesthetics in frequency of use due to its favorable side effects profile with fewer incidences of nausea and vomiting as well as postoperative drowsiness.1 Propofol acts on γ-aminobutyric acid A(GABAA) receptors as an enhancer as well as an antagonist at glutamatergic NMDA (N-methyl-D-aspartate) receptors3,4 thereby causing central nervous system(CNS) depression leading to rapid induction of unconsciousness and muscle relaxation necessary for anesthesia during surgical processes. Propofol is highly lipid soluble and intravenous administration therefore requires a 1-2% propofol solution in a soybean oil emulsion which can cause allergic reactions as well as contamination and growth of bacteria once the sterile seal has been broken.4
Propofol dependence had not been recognized until 1992 but has gained considerable attention in recent years. Most abusers favor the fast onset of propofol and the short duration of action, creating a short ecstatic and euphoric feeling without many of the side effects that are associated with other drugs.2 However, propofol is a potent CNS and respiratory depressant which may lead to lethal overdosing with resulting respiratory failure as well as cardiac complications.3