Issues surrounding lethal injection as a means of capital punishment.

Lethal injection as a method of state-sanctioned capital punishment was initially proposed in the United States in 1977 and used for the first time in 1982. Most lethal injection protocols use a sequential drug combination of sodium thiopental, pancuronium bromide, and potassium chloride. Lethal injection was originally introduced as a more humane form of execution compared with existing mechanical methods such as electrocution, toxic gassing, hanging, or firing squad. Lethal injection has not, however, been without controversy. Several states are considering whether lethal injection meets constitutional scrutiny forbidding cruel and unusual punishment. Recently in the case of Ralph Baze and Thomas C. Bowling, Petitioners, v John D. Rees, Commissioner, Kentucky Department of Corrections et al, the United States Supreme Court upheld the constitutionality of the lethal injection protocol as carried out in the Commonwealth of Kentucky. Most of the debate has surrounded the dosing and procedures used in lethal injection and whether the drug combinations and measures for administering the drugs truly produce a timely, pain-free, and fail-safe death. Many have also raised issues regarding the "medicalization" of execution and the ethics of health care professionals' participation in any part of the lethal injection process. As a result of all these issues, the future of lethal injection as a means of execution in the United States is under significant scrutiny. Outcomes of ongoing legislative and judicial reviews might result in cessation of lethal injection in totality or in alterations involving specific drug combinations or administration procedures.

Pancuronium bromide (Pavulon) isolation and identification in aged autopsy tissues and fluids.

The isolation and detection of pancuronium bromide was developed for aged autopsy samples to identify and confirm this compound in questioned tissue samples. A novel protocol was optimized for the isolation of the target drug in highly decomposed tissues. Solid-phase extraction (SPE) cartridges containing styrene-divinylbenzene were investigated. This polymer retained quaternary drugs and facilitated sequential elution upon washing with commonly available solvents. The semi-purified SPE samples were prescreened by pyrolysis GC-MS. A candidate specimen was then confirmed by microbore high-performance liquid chromatography/electrospray-ionization/mass spectrometry (microHPLC-ESI-MS/MS) with a triple-quadrupole mass spectrometer. The developed procedures provided a qualitative or semiquantitative (at best) basis for the investigation of difficult cases involving overdoses of polar drugs.

The application of pancuronium bromide (Pavulon) forensic analyses to tissue samples from an "Angel of Death" investigation.

The case report of a serial killer who worked at several hospitals as a respiratory therapist is presented. The suspect was initially labeled a benevolent Angel of Death who ended the suffering of elderly patients through mercy killing. However, his subsequently declared motive for homicide was very different from other similar cases in medical settings. The application of new analysis techniques for the detection of pancuronium bromide in a series of aged exhumation tissues gave positive results and led to the resultant conviction of the therapist.

Instability of pancuronium in postmortem blood and liver taken after a fatal intramuscular Pavulon injection.

The present study was designed to determine the stability of pancuronium in postmortem blood and liver during storage. Results were obtained using the method by Kerskes et al. [C.H.M. Kerskes, K.J. Lusthof, P.G.M. Zweipfenning, J.P. Franke, The detection and identification of quaternary nitrogen muscle relaxants in biological fluids and tissues by ion-trap LC-ESI-MS, J. Anal. Toxicol. 26 (2002) 29-34.], modified and validated in our laboratory. Target analytes were isolated after enzymatic hydrolysis followed by solid phase extraction (BondElut C18 column). Internal standardisation was carried out using laudanosine and the target ions were monitored by LC-ESI-MS (monitoring ions m/z 358 for IS and 286 for pancuronium). Materials were taken from a 46-year-old woman, who had been found dead. A syringe (2 ml) and an empty ampoule of Pavulon (4 mg/2 mL) were found in her hand. The residual volume of fluid in the syringe was 0.7 ml. An autopsy was performed six days after death. It revealed a needle mark on the left thigh. Postmortem materials (muscle from the injection site, blood and liver) and the syringe with fluid were stored for four months in a freezer at -20 degrees C. The initial pancuronium concentrations were 81 ng/mL in blood and 532 ng/g in liver. The analyte was stable when stored at -20 degrees C in blood even up to seven months. In liver samples its concentrations were variable. Pancuronium in blood stored at 20 degrees C underwent degradation very rapidly. After three months of storage these blood samples had concentrations not greater about 10% of the initial value. The degradation patterns of pancuronium depended on temperature and the biological matrix.

The detection and identification of quaternary nitrogen muscle relaxants in biological fluids and tissues by ion-trap LC-ESI-MS.

Quaternary nitrogen muscle relaxants pancuronium, rocuronium, vecuronium, gallamine, suxamethonium, mivacurium, and atracurium and its metabolites were extracted from whole blood and other biological fluids and tissues by using a solid-phase extraction procedure. The extracts were examined by using high-performance liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS). The drugs were separated on a ODS column in a gradient of ammonium acetate buffer (pH 5.0) and acetonitrile. Full-scan mass spectra of the compounds showed molecular ions, and MS-MS spectra showed fragments typical of the particular compounds. LC-ESI-MS allowed an unequivocal differentiation of all muscle relaxants involved. The method was applied in a case of rocuronium and suxamethonium administration in a Caesarian section and in a case of intoxication by pancuronium injection. In both cases, the administered drugs could be detected and identified in the supplied samples.

[A case of suicide by an intravenous injection of pancuronium].

A 25-year-old male anesthesiologist was found dead in his room with an intravenous drip line connected with his leg. There were several empty ampules of pancuronium, midazolam and buprenorphine around him. Pancuronium and midazolam in the blood and urine samples collected at postmortem examination were detected by spectrofluorometry and ECD-gas chromatography, respectively. The concentrations of pancuronium and midazolam were 0.3 micrograms/g and 0.12 micrograms/g in the blood, respectively; 0.9 micrograms/g and 0.05 micrograms/g in the urine, respectively. The cause of death was determined to be asphyxia due to respiratory muscle paralysis caused by pancuronium.

Attempted murder with pancuronium.

A nurse was accused of attempting to murder her anesthesiologist husband on two occasions by administering to him a neuromuscular blocking agent. In both episodes, urine specimens were obtained from the victim shortly after the suspected assaults. The samples were initially tested fluorometrically using Rose Bengal dye as a pairing agent. Both were presumptively positive for pancuronium. Confirmation of these results was achieved by pairing the drug with potassium iodide, extracting the complex, and submitting the extract to thin-layer chromatography (TLC) cleanup, elution at the appropriate retardation factor (Rf), and, finally, gas chromatography/mass spectrometry (GC/MS) analysis in the selected-ion monitoring mode. The two quaternary amines of pancuronium appear to undergo pyrolytic N-demethylation in the injection port to yield an entity amenable to capillary column gas chromatography. The mass spectrum of the compound consists of a base peak of m/z 322, with additional fragments of 292, 323, 338, and 397 m/z, each of which was monitored. The confirmed positive findings were instrumental in adjudicating the case.

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.

A suicide by pancuronium bromide injection: evaluation of the fluorometric determination of pancuronium in postmortem blood, serum and urine.

A fatal case of suicidal injection of pancuronium bromide is presented. Pancuronium was detected in blood and urine by ion-pair extraction and fluorometry. An evaluation of the fluorometric procedure for the determination of pancuronium in postmortem blood, serum and urine is presented. Stability of the extracted ion-pair, possible interferences from other drugs, and the effects of specimen storage were studied.

Denying the incredible: unexplained deaths in a Veterans Administration hospital.

During July and August 1975 a large number of patients at the Ann Arbor Veterans Administration Hospital experienced unexplained respiratory arrests, and there were six deaths. These were later shown to be due to the deliberate injection of pancuronium bromide, a muscle relaxant. A questionnaire survey of the reactions of the hospital patients and staff to the deaths revealed that the patients had more confidence in the hospital and their medical treatment than did the staff, and those patients who were theoretically most vulnerable used denial to cope with the unprecedented and frightening situation.

An epidemic of mysterious cardiopulmonary arrests.

Over a six-week period, a striking increase in the incidence of cardiopulmonary arrests occurred at the Ann Arbor Veterans Administration Hospital, Criminal administration of a muscle-paralyzing agent was implicated. An epidemiologic investigation les to a description of the classic features of an epidemic; time, place, person, agent and mode of transmission. Control of the agent and susceptible patients led to cessation of the epidemic. Although the perpetrator was not specifically identified, the concurrent criminal investigation was aided by the data developed in the medical investigation. On the basis of this experience, we propose a surveilliance mechanism for early detection of increased critical incidents, such as cardiopulmonary arrests, and a scheme for systematically examining similar events.