Lethal self-administration of propofol and atracurium: Two case reports and literature review

Abstract

Propofol is an intravenous anesthetic agent widely used in the induction and maintenance of general anesthesia. Acute intoxications with propofol are rare and remain primarily related to the acquisition of the product in hospital. If propofol can induce fatal respiratory depression alone, in a number of cases the clinical situation is exacerbated by the presence of other drugs like neuromuscular-blocking agents. Laudanosine, the circulating form of atracurium or cisatracurium, two non-depolarizing neuromuscular-blocking agents, is more frequently observed in toxicology. Such agents are widely used for tracheal intubations. Laudanosine has no pharmacological activity, which is exclusively due to the parent drugs. These agents can be fatal at any concentration, due to respiratory failure. Here, two cases of anesthesiologists’ suicide following self-administration of propofol-atracurium combination are reported. Case 1: a 48-years-old anesthesiologist was found without vital signs at his office. The drugs and paraphernalia used for delivery were discovered at the scene. Case 2: a 61-years-old anesthesiologist was found dead at home with a cannula connected to an infusion set at the bend of the elbow. Next to the body several empty ampoules of Diprivan ® and Atracurium besylate ® were found. For both cases, several biological specimens were collected for toxicological investigation. Comprehensive screenings of drugs and toxic compounds were performed using LC-DAD and GC-MS. Ethanol concentrations were determined using GC-FID. Laudanosine was quantified using LC-DAD. Propofol was quantified using GC-MS and LC-MS/MS. Propofol blood concentrations were 1 and 1.91 mg/L for case 1 and case 2, respectively (therapeutic range: 2–8 mg/L). Laudanosine blood concentrations were 0.13 and 1.18 mg/L for case 1 and case 2, respectively. Paroxetine, N-demethyldiazepam and ethanol were detected in the first case. Hydroxyzine was detected in the second case. In both cases, levels of these substances could not explain the death. Propofol related fatalities are rare, even more when combined with neuromuscular- blocking agents [1] . Propofol and atracurium concentrations documented here, are in agreement with those reported in the literature, these being characterized by a high inter-individual variability [2] . However, the concentrations observed in suicide cases compared to those observed in accidental fatalities (chronic abusers) appear to be much higher. In fact, three manners of death have been described with propofol: suicide, accidental overdose in chronic abusers, and more exceptionally, murder [3] . In the cases described here, circumstances and the use of atracurium suggest suicide. It should be noted that the concentrations of laudanosine and propofol observed here are in the usual anesthetic range. Albeit, it should be pointed out that for anesthetic agents, therapeutic concentrations are established for patients being supported respiratory-wise, while in non-supported or non-intubated patients such concentrations may be fatal. Therefore, the interpretation of the blood concentration in the forensic toxicological analysis must take into account the context and the circumstances of the death.