Suicide with cisatracurium and thiopental: forensic and analytical aspects.

The suicide of a 43-year-old male by intravenous injection of cisatracurium, a non-depolarizing neuromuscular blocking agent, and thiopental, an ultra-short-acting barbiturate, is presented. Systematic toxicological screening by gas chromatography-mass spectrometry (GC-MS), liquid chromatography (LC)-diode-array detection, and LC-MS-MS confirmed the presence of thiopental. A large peak in the GC-MS chromatogram was matched by the Pfleger-Maurer library as corlumine, but neither atracurium neither its metabolite, laudanosine, were detected. To confirm the absence or the presence of laudanosine in the blood sample, an ultra-performance liquid chromatography-MS-MS method for cisatracurium and laudanosine quantification was developed. The calibration range was 2.5-500 ng/mL for laudanosine and 10-500 ng/mL for cisatracurium. The biases were lower than 12.3%. Intraday and interday precisions, expressed as coefficient of variation, were lower than 13.3%. This method allowed to confirm the presence of laudanosine and measurement of laudanosine in all samples. The femoral blood concentration was therapeutic (0.46 µg/mL). This case report documents a possible analytical pitfall and describes a simple and fast method for cisatracurium determination. Moreover, the purpose of this case report was to document the postmortem redistribution of cisatracurium and laudanosine, which could help make it possible to interpret tissue or cardiac blood concentrations in forensic cases where femoral blood is not available.

Twitch potentiation influences the time course of twitch depression in muscle relaxant studies: a pharmacokinetic-pharmacodynamic explanation.

The time course of twitch depression following neuromuscular blocking agent (NMBA) administration is influenced by the duration of control neuromuscular monitoring (twitch stabilization). The physiological mechanism for this interaction is not known. During twitch stabilization twitch response often increases to a plateau, this is known as twitch potentiation or the staircase phenomenon. Since twitch potentiation contributes to the observed twitch response it may also influence the time course of twitch depression following NMBA administration. Our objective was to estimate the degree that twitch potentiation influences the time course of twitch depression following NMBA administration under conditions typical for muscle relaxation studies. We used previousy described pharmacokinetic-pharmacodynamic (PK-PD) and twitch potentiation models to simulate twitch data. Simulations consisted of twitch stabilization followed by a NMBA bolus dose and subsequent onset and recovery from muscle relaxation. Twitch data were analyzed for onset and recovery characteristics and the results compared to clinical muscle relaxation studies in existing literature. We found that twitch potentiation likely plays a minor role in shortened onset time and increased duration of twitch depression observed with long periods of twitch stabilization.

Aconitine poisoning due to Chinese herbal medicines: a review.

Both "chuanwu", the main root of Aconitum carmichaeli, and "caowu", the root of A kusnezoffii, are believed to possess anti-inflammatory, analgesic and cardiotonic effects and have been used in Chinese materia medica mainly for the treatment of musculoskeletal disorders. They contain the highly toxic C19 diterpenoid alkaloids of aconitine, mesaconitine and hypaconitine. After ingestion, patients may present with signs and symptoms that are typical of aconitine poisoning. Death may occur from ventricular arrhythmias, which are most likely to occur within the first 24 h. Management of aconitine poisoning is essentially supportive. There are no adequate studies in humans to indicate the most effective treatment of the ventricular arrhythmias. All clinicians should be alerted to the potential toxicity of "chuanwu" and "caowu".

Severe hepatic failure occurring with T61 ingestion in an attempted suicide. Early recovery with the use of intravenous infusion of reduced glutathione.

A case of acute hepatic failure following ingestion of the veterinary euthanasia drug T61 is described. Presenting symptoms were drowsiness, disorientation, muscle hypertonia, and upper limb myoclonus, which faded within a few hours. Two days later, acute liver failure occurred, manifested as encephalopathy, jaundice, and a severe coagulopathy. The hepatic damage was thought to be due to the solvent dimethylformamide, which is the only known hepatotoxin included in the preparation utilized in the suicide attempt. High-dose (1.2 g/day) intravenous reduced glutathione was administered, with a rapid improvement of liver function. The patient was discharged after 17 days. Normalization of all liver function tests was achieved within two months. The favorable outcome in this case stands in contrast to the report of a previous case of lethal T61-induced hepatic failure. Although a different amount of dimethylformamide was ingested in each case (0.45 vs 0.60 ml/kg body wt) and individual differences in susceptibility to the effects of the hepatotoxic agent may have played a major role in these two cases, it is not unlikely that the infusion of high doses of glutathione to our patient contributed to her survival and hepatic recovery.

[The use of drugs for euthanasia and assisted suicide in family practice]. / Het gebruik van middelen bij euthanasie en hulp bij zelfdoding in de huisartspraktijk.

An exploratory, descriptive, retrospective study was carried out concerning the use of means for euthanasia or assisted suicide, primarily regarding the period 1986-1989. Data were collected via an anonymous written inquiry among a random sample of family physicians in North Holland (n = 521) and family physicians in the rest of the Netherlands (n = 521). The inquiry contained among others questions about the last case they had encountered. In addition, police reports of euthanasia or assisted suicide administered by family physicians in North Holland (n = 263) were analysed. The response to the inquiry was 67%; (non-respondents did not differ from respondents): 388 cases could be analysed. The use of euthanatics by family physicians in North Holland and those in the rest of the Netherlands was identical. More than 40 different euthanatics were used, most of them incidentally. The most frequently used (combination of) means were a benzodiazepine with a neuromuscular relaxant (23%), a barbiturate with a neuromuscular relaxant (20%), barbiturates (15%) and opioids (12%). Most euthanatics were given intravenously (61%, of which 5% by infusion), orally 21%, intramuscularly 12%, rectally 3% and subcutaneously 2%. The quantities applied varied greatly. The average length of time from the start of the procedure till decrease was 3.8 hours (less than or equal to 1 minute-72 hours). In 12% of the cases complications or unintended effects were reported. Comparison of inquiry and police reports showed some differences.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of HLö-7 and pyrimidoxime as antidotes of nerve agent poisoning in mice.

The toxicity and efficacy of two oximes, HLö-7 and pyrimidoxime, were evaluated in mice and compared to those obtained with HI-6. HLö-7 and pyrimidoxime produced 24 h LD50 values of 356 and 291 mg/kg (i.p.), respectively. In combination with atropine (17.4 mg/kg, i.p.), HLö-7 was a very efficient therapy against poisoning by 3 x LD50 dose of soman, sarin and GF and 2 x LD50 dose of tabun with ED50 values of 12.4, 0.31, 0.32 and 25.2 mg/kg, respectively. In contrast, pyrimidoxime was a relatively poor therapy which resulted in ED50 values of greater than 150, 5.88, 100 and 71 mg/kg against poisoning by soman, sarin, GF and tabun, respectively. HLö-7 produced significant (p less than 0.05) reactivation of phosphorylated acetylcholinesterase, in vivo, resulting in 47, 38, 27 and 10% reactivation of sarin, GF, soman and tabun inhibited mouse diaphragm acetylcholinesterase, respectively. HLö-7 also antagonized sarin-induced hypothermia in mice suggesting that it reactivated central acetylcholinesterase. The potential of HLö-7 as a replacement oxime for the treatment of nerve agent poisoning is discussed.

A suicide with neuromuscular blocker.

We experienced an autopsy case in which a 29-year-old woman committed suicide by parenteral application of a neuromuscular blocker combined with thiobarbital. These medicines were easily accessible to the victim who was an anesthesiologist in a hospital. Paralyzing the respiratory muscles the usual dose of neuromuscular blockers can cause death unless a breathing apparatus is used. Unusual medicines given in small doses are difficult to detect in the autopsy materials. In our case in the course of forensic investigation we successfully identified the traces of a neuromuscular blocker by mass spectrometry.

Detection of overdosage of sedation in a patient with renal failure by the absence of lower oesophageal motility.

We report an accidental overdosage of morphine and midazolam in a patient with renal failure receiving haemofiltration detected by the absence of oesophageal motility. This situation demonstrates the difficulties of assessing the level of sedation as well as the dosage requirements in this type of patient.