Head injuries, pentobarbital, and the determination of death.

The Bexar County Medical Examiner's Office in San Antonio, Texas, has encountered 3 cases within a 15-month period involving decedents who were pronounced dead by brain death or cardiac death examination and who had elevated, if not toxic concentrations of pentobarbital present at the time of examination. The elevated levels of pentobarbital were discovered during an autopsy examination performed for medicolegal reasons. The diagnosis of brain death and the implications of pentobarbital intoxication during a brain death examination are discussed.

Comparison of drug concentrations taken from clamped and unclamped femoral vessels.

Postmortem drug concentrations may vary depending on sampling site, volume of blood collected, and method of sampling, making it important to analyze specimens from different sites in the body to detect postmortem redistribution and avoid erroneous conclusions on cause and manner of death. Using a blind stick method to draw large amounts of blood from the femoral vessel may increase the likelihood of contamination with blood from more central sites. It has been suggested that clamping the femoral vessel before drawing the sample may eliminate possible contribution from central sites. Eight drugs from four different drug classes were evaluated to determine the difference between drug concentrations in clamped and blind stick femoral blood. Drug concentrations of three selective serotonin reuptake inhibitors, or SSRIs (sertraline, paroxetine, citalopram), two benzodiazepines (diazepam and alprazolam), two antihistamines (diphenhydramine and promethazine), and one opiate (hydrocodone) were evaluated in clamped femoral blood, blind stick femoral blood, and heart blood and compared using concentration ratios and linear regression analysis. Clamped femoral blood concentrations and blind stick femoral blood concentrations were found to have good predictability across all drug classes with ratios around 1.0, indicating good correlation between blind stick femoral and clamped femoral samples. Therefore, it can be concluded that a blind stick femoral blood sample does not have significant redistribution from central sites and is of equivalent quality to a clamped femoral sample.

Adverse events, including death, associated with the use of 1,4-butanediol.

BACKGROUND: 1,4-Butanediol is an industrial solvent that, when ingested, is converted to gamma-hydroxybutyrate, a drug of abuse with depressant effects, primarily on the central nervous system. After reports of toxic effects of gamma-hydroxybutyrate and its resultant regulation by the federal government, 1,4-butanediol and gamma-butyrolactone, another precursor of gamma-hydroxybutyrate and an industrial solvent, began to be marketed as dietary supplements. We investigated reports of toxic effects due to the ingestion of 1,4-butanediol and reviewed the related health risks. METHODS: From June 1999 through December 1999, we identified cases of toxic effects of 1,4-butanediol involving patients who presented to our emergency departments with a clinical syndrome suggesting toxic effects of gamma-hydroxybutyrate and a history of ingesting 1,4-butanediol and patients discovered through public health officials and family members. We used gas chromatography-mass spectrometry to measure 1,4-butanediol or its metabolite, gamma-hydroxybutyrate, in urine, serum, or blood. RESULTS: We identified nine episodes of toxic effects in eight patients who had ingested 1,4-butanediol recreationally, to enhance bodybuilding, or to treat depression or insomnia. One patient presented twice with toxic effects and had withdrawal symptoms after her second presentation. Clinical findings and adverse events included vomiting, urinary and fecal incontinence, agitation, combativeness, a labile level of consciousness, respiratory depression, and death. No additional intoxicants were identified in six patients, including the two who died. The doses of 1,4-butanediol ingested ranged from 5.4 to 20 g in the patients who died and ranged from 1 to 14 g in the nonfatal cases. CONCLUSIONS: The health risks of 1,4-butanediol are similar to those of its counterparts, gamma-hydroxybutyrate and gamma-butyrolactone. These include acute toxic effects, which may be fatal, and addiction and withdrawal.

Determination of volume of distribution for ethanol in male and female subjects.

Ten nonalcoholic subjects gave written informed consent. Six men (aged 25-43) and four women (aged 25-35) were hydrostatically weighed to determine their percentage of body fat and lean weight. Each subject fasted for at least 10 h and then received an oral dose of alcohol (0.9 g per kilogram of lead body weight) calculated to yield a peak alcohol concentration of 0.100 g/210-L breath. Breath alcohol measurements were conducted at 20-min intervals until each subject's alcohol concentration returned to 0.000 g/210-L breath. All alcohol analyses were conducted on the Intoxilyzer 5000 and reported as g/210-L breath. Female subjects on average reached a lower peak alcohol concentration (mean, 0.086; range, 0.074-0.091 g/210 L) than male subjects (mean, 0.096; range, 0.093-0.101 g/210 L). Females demonstrated a higher average rate of elimination (mean, 0.017; range, 0.014-0.021 g/210 L) than males (mean, 0.015; range, 0.013-0.017 g/210 L). Female subjects on average had a higher percentage of body fat (mean, 26.0; range, 16.7-36.8%) than males (mean, 18.0; range, 10.2-25.3%). The average volume of distribution (Vd), as calculated from percentage of body fat, for the women (mean, 0.63; range, 0.54-0.71) was less than for the men (mean, 0.69; range, 0.63-0.76). The average Vd as calculated from linear regression of the alcohol concentration curve, for the women (mean 0.64, range, 0.56-0.71) was also less than for the men (mean, 0.72; range, 0.67-0.77). The data from this limited study indicate that hydrostatic weighing is an acceptable way of determining Vd for both men and women.

The response of the Intoxilyzer 4011AS-A to a number of possible interfering substances.

Five Intoxilyzer 4011AS-As were tested for their response to eleven chemicals and one mixture of chemicals. The air/water partition ratios were also determined for these eleven chemicals and one mixture. The chemicals tested and their approximate partition ratios were the following: acetaldehyde (190:1), acetone (341:1), acetonitrile (578:1), isoprene (1:1), isopropanol (1671:1), methanol (3229:1), methylene chloride (11:1), methyl ethyl ketone (229:1), toluene (5.5:1), 1,1,1-trichloroethane (14:1), trichloroethylene (20:1), and a 50:50 mixture of 1,1,1-trichloroethane and trichloroethylene (14:1). Of the eleven chemicals and one mixture studied during this experiment, only three, isopropanol, toluene, and methyl ethyl ketone, could reasonably interfere with the test, and then only under unusual circumstances--those circumstances being a slight additive effect to a breath ethanol concentration near the level required for prosecution. Any substantial additive effect from these three substances would illuminate the interference light which invalidates the test. The mean illumination point of the interference light was 0.0286 g/210 L for methyl ethyl ketone, 0.0294 for toluene, and between 0.0116 and 0.0292 for the apparent alcohol concentration for isopropanol, depending on the amount of isopropanol metabolized to acetone. Even with these unusual circumstances considered, the Intoxilyzer 4011AS-A must be viewed as an effective way of determining the ethanol concentration in human breath for evidential purposes.

Preliminary evaluation of the Abbott TDx for benzoylecgonine and opiate screening in whole blood.

A method for the detection of benzoylecgonine (cocaine metabolite) and opiates in whole blood is described. This method employs the Abbott TDx fluorescence polarization immunoassay technique, which was designed for urine analysis. Drug-free whole blood was spiked with varying concentrations of benzoylecgonine, morphine, and codeine. Samples were prepared for analysis by adding 300 microL of 10% trichloroacetic acid to 300 microL of blood. Specimens were vortexed and centrifuged with 50 microL of supernatant required per assay. Precision studies of six replicate samples spiked with benzoylecgonine at 0.5 mg/L gave a within-run CV of 4.7% and a between-run CV of 4.7% with a detection limit of 0.1 mg/L. Within-run CVs for morphine at 0.5 mg/L and 0.1 mg/L were 1.7% and 7.9% respectively. The detection limits for morphine and codeine were 0.05 mg/L. Correlation coefficients for spiked whole blood calibration curves of benzoylecgonine, morphine, and codeine were 0.984, 0.999, and 0.997 respectively. This preliminary evaluation demonstrates a potential application of the TDx fluorescence polarization immunoassay technique to the analysis of drugs in whole blood.

Matrix modification for furnace atomic absorption spectrometric determination of arsenic in whole human blood.

A method for the determination of arsenic in whole human blood is presented. To decrease the matrix effects from this complex sample, the blood was prediluted with a matrix modifier solution. The modifier solution contained a surfactant, Triton X-100, which homogenized the sample and allowed accurate pipetting by an autosampler. The modifier also contained nickel nitrate which stabilized the arsenic and allowed ash temperatures of 1400 degrees C without loss of the arsenic. The method exhibited a sensitivity of 5 micrograms/L (concentration/1% absorption) which was sufficient for the forensic evaluation of elevated arsenic levels in the blood.