Fatal accidental enflurane intoxication

Among reported cases of abuse of volatile anesthetics there is only one of enflurane intoxication. We report another fatal enflurane intoxication. A 21-year-old man found dead seemed to have experimented with enflurane. Three and one-half days after death high amounts of enflurane were detected in blood, brain, and subcutaneous fat. Gas chromatographic quantification revealed the following high enflurane concentrations: blood: 130 mg/l-1, brain: 350 mg/l-1, and subcutaneous fat: 100 mg/l-1. Histologic signs of drug-induced damage were lacking. No suicide intentions became known. It was concluded that the young man died of an accidental intoxication while abusing enflurane.     

Driving under the influence of chlormethiazole

This article describes a case of driving under the influence of the sedative-hypnotic-anticonvulsant drug chlormethiazole. The suspect, who was a physician, was driving dangerously on a busy highway and caused a traffic collision. When apprehended by the police, the man had bloodshot and glazed eyes and pupil size was enlarged. He could not answer the questions properly and his gait was unsteady. A roadside breath-alcohol screening test was positive but an evidential breath-alcohol test conducted about one hour later was below the legal limit for driving of 0.10 mg/L (10 microg/100 mL or 0.021 g/210 L). Because of the special circumstances of the traffic crash and the man's appearance and behaviour, the police suspected that drugs other than alcohol were involved and obtained a venous blood sample for toxicological analysis. The blood contained 0.23 mg/g alcohol, which is above the legal limit for driving in Sweden 0.20 mg/g (20 mg/100 mL or 0.020 g/100 mL), and codeine was also present at a therapeutic concentration of 0.02 mg/L. The conflict between the clinical signs of impairment and the toxicology report prompted a reanalysis of the blood sample with major focus on sedative-hypnotic drugs. Analysis by capillary GC-NPD identified chlormethiazole at a concentration of 5mg/L, the highest so far encountered in traffic cases in Sweden. In 13 other impaired driving cases over 10 years the mean (median) and range of concentrations of chlormethiazole were 1.6 mg/L (1.6 mg/L) and 0.3-3.3 mg/L. This case report underscores the need to consider clinical observations and the person's behaviour in relation to the toxicology report when interpreting and testifying in drug-impaired driving cases.     

Relationship between the concentration of ethanol and methanol in blood samples from Swedish drinking drivers

Headspace gas chromatography was used to determine the concentration of ethanol and methanol in blood samples from 519 individuals suspected of drinking and driving in Sweden where the legal alcohol limit is 0.50 mg/g in whole blood (11 mmol/l). The concentration of ethanol in blood ranged from 0.01 to 3.52 mg/g with a mean of 1.83 +/- 0.82 mg/g (+/- S.D.). The frequency distribution was symmetrical about the mean but deviated from normality. A plot of the same data on normal probability paper indicated that it might be composed of two subpopulations (bimodal). The concentration of methanol in the same blood specimens ranged from 1 to 23 mg/l with a mean of 7.3 +/- 3.6 mg/l (+/- S.D.) and this distribution was markedly skew (+). The concentration of ethanol (x) and methanol (y) were positively correlated (r = 0.47, P less than 0.001) and implies that 22% (r2) of the variance in blood-methanol can be attributed to its linear regression on blood-ethanol. The regression equation was y = 3.6 + 2.1 x and the standard error estimate was 0.32 mg/l. This large scatter precludes making reliable estimates of blood-methanol concentration from measurements of blood-ethanol concentration and the regression equation. But higher blood-methanol concentrations are definitely associated with higher blood-ethanol in this sample of Swedish drinking drivers. Frequent exposure to methanol and its toxic products of metabolism, formaldehyde and formic acid, might constitute an additional health risk associated with heavy drinking in predisposed individuals. The determination of methanol in blood of drinking drivers in addition to ethanol could indicate long-standing ethanol intoxication and therefore potential problem drinkers or alcoholics.     

Simultaneous hair testing for opiates, cocaine, and metabolites by GC-MS: a survey of applicants for driving licenses with a history of drug use

A sensitive GC-MS method for the simultaneous determination of opiates, cocaine, and metabolites in hair at a cut-off level of 0.1 ng/mg was adopted to assess past exposure to these drugs in applicants for driving licenses with a history of drug use. The sampling protocol consisted of collection of one hair (sample A, 5-cm length) and one urine sample. When hair and urine (EMIT Syva, cut-off levels: 0.3 mg/l for opiates, 0.15 mg/l for cocaine, GC-MS confirmation of positives) were both positive or negative the protocol was concluded. In the other cases, the assessment of 'current exposure' to drugs was carried out, in order to avoid seriated random urinalysis, by collecting a second hair sample (sample B) 6 weeks later and analysing the proximal 1-cm segment. Out of the 214 'A' hair samples analyzed, 14 (6.5%) tested positive for morphine and/or 6-acetylmorphine (6AM), and 26 (12%) for cocaine and/or benzoylecgonine (BE), whereas none of the samples tested positive for both drugs. Levels between 0.1 and 1 ng/mg of the single analytes were found in eight out of the 14 morphine-6AM positives (57%) and in 18 out of the 26 cocaine-BE positives (69%). The time course of positive cases showed a progressive decrease of morphine-6AM positives and a corresponding increase of cocaine-BE positives within the study period September 1995-February 1999. No cases with positive urine and negative hair were observed. Among the 40 positive cases, seven (four and three for opiates and cocaine, respectively) were found to be 'currently exposed to drug', four by urinalysis (three and one) and three by analysis of the hair sample B (1 and 2).     

A controlled study of the time-course of breath alcohol concentration after moderate ingestion of ethanol following a social drinking session

This paper evaluates the breath alcohol concentration (BrAC), nausea (feeling of being slightly intoxicated) and subjective driving performance after ingesting a moderate dose of alcohol in the presence of a light meal, which intends to approach a social drinking setting. 119 healthy individuals (69 males and 50 females, aged 21.7+/-3.0) ingested three glasses of wine (95mL each) and their BrAC was determined by an Alcotest 7410 at 15, 30, 45, 60, 90 and 120min post-drinking. 46% of females and no male subjects exceeded a BrAC of 0.25mg/L, the legal limit for driving fixed by some Western countries. 53% of the study population felt nausea during the experimental session and 20% self-reported impairment of their driving skills. In both cases these subjective effects were more pronounced in females. The major determinants of mean BrAC were time post-drinking, gender (male) and body mass index (BMI), all these variables being inversely associated. Females and individuals with a BMI lower than 22.5kg/m(2) were at an increased risk of exceeding the legal limit of BrAC. The feeling of nausea was significantly associated with gender (females), the ingestion of up to 2 drinks on weekdays, and having exceeded a BrAC of 0.25mg/L during the experimental study. The main predictor of self-perception of impaired driving skills was the feeling of nausea, followed by a BrAC in excess of 0.25mg/L. In conclusion, both females and subjects with lower BMI are at an increased risk of exceeding the legal limit of BrAC after moderate alcohol consumption resembling a social drinking setting.     

Detection of psilocin in body fluids

Active compounds of some mushrooms e.g. Psilocybe cubensis, Paneolus subalteatus or Stropharia coronilla, the psychotropic agents psilocybin and psilocin, have hallucinogenic effects. In one case of 'magic mushroom' intake, we had to analyse blood and urine. Psilocin was detected in the urine with REMEDi HS. Most of the psilocin was excreted as the glucuronide. Therefore an enzymatic hydrolysis should be the first step in analysis. Free psilocin was determined at a concentration of 0.23 mg/l while the total amount was 1.76 mg/l urine. The concentration of psilocin in serum was too low for detection with REMEDi HS. We proved a GC-MS-method with d(3)-morphine as internal standard and silylation with MSTFA. Similarly to urine, most of the psilocin in serum was found in the conjugated form. The concentration of free psilocin was 0.018 mg/l, that of total psilocin, 0.052 mg/l serum.     

Two tricyclic antidepressant poisonings: levels of amitriptyline, nortriptyline and desipramine in post-mortem biological samples

Two deaths due to amitriptyline and desipramine overdoses are reported. The first case deals with a 20-year-old Caucasian male who was found dead at his residence. Toxicological analysis of the blood, urine, liver and kidney revealed the presence of amitriptyline (1.7 mg/l, 0.13 mg/l, 36.0 mg/kg and 98.0 mg/kg) and nortriptyline (0.66 mg/l, 0.74 mg/l, 12.0 mg/kg and 37.0 mg/kg). The gastric content contained only 220 mg of amitriptyline. The urine also contained norverapamil, which was consistent with previous verapamil therapy. The second case involved a 19-year-old Caucasian male who attempted suicide earlier and was on desipramine medication. The blood, urine, liver and gastric content disclosed the presence of desipramine in the concentrations of 14.2 mg/l, 33.7 mg/l, 112.5 mg/kg and 180 mg, respectively. The levels of these tricyclics analyzed by high pressure liquid chromatography were in agreement with the levels reported in the literature. Though with the amitriptyline poisoning no significant anatomic changes were noted, the desipramine-caused death was further supported by the multisystem vascular congestion and ischemic changes consistent with cardiopulmonary failure.     

Hemolysis and hyperkalemia complicate malignant hyperpyrexia during anesthetic death

A healthy, 15-year-old male received a thiopental, nitrous oxide, oxygen, enflurane anesthetic for appendectomy. Cardiac arrest, following succinylcholine administration, was associated with marked hyperkalemia (potassium levels 8.7 to 11.6 meq), hemolysis (hematocrit fall from 41.7 to 26.6%, plasma hemoglobin 27 mg/dL), and creatine phosphokinase (CPK) elevation (8900 units). Vigorous resuscitative therapy including dantrolene was unsuccessful. The diagnosis of malignant hyperthermia was made by the marked CPK elevation on blood samples drawn during resuscitation and analyzed by the Medical Examiner's Office.     

Quantitative determination of strychnine in blood and urine by gas chromatography with mass-selective detector

A method for the quantitative determination of strychnine in biological fluids by gas chromatography--mass spectrometry is proposed. The preparation of samples for the analysis included extraction of strychnine from blood and urine with the use of AccuBond(II) EVIDEX cartridges for solid-phase extraction and SPEC MP3 disks respectively. The efficiency of extraction was estimated at 0.05 mg/l for blood and 0.02 mg/l for urine. The detection limit was 0.10 mg/l in blood and 0.05 mg/l in urine.     

Forensic cases involving the use of GHB in The Netherlands

In this study, forensic cases involving the use of Gamma Hydroxy Butyric acid (GHB) from the second half of 1999 through the second half of 2001 in The Netherlands (blood >5mg/l and urine >10mg/l) are described. GHB was analysed by GC-MS after lactone formation and using GHB-d6 as internal standard. The results are divided into three groups: cases of chemical submission, cases of driving under the influence and cases of unknown causes of death.GHB was found in six cases of possible chemical submission. In these cases, relatively low concentrations of GHB were found. The results show that in cases of chemical submission, urine should be analyzed, because GHB is present longer in urine than in blood. The police should collect the samples in containers that do not contain citrate as anticoagulant. Especially at low levels of GHB, the formation of GHB in these tubes hampers an interpretation of the results.GHB was found in 13 cases of driving under the influence. In contrast to the cases of chemical submission, high concentrations of GHB were found, corresponding with observations of extreme sleepiness or temporary loss of consciousness.GHB was found in 16 cases of unexplained death: the measured range of GHB concentrations in blood might correspond to effects such as drowsiness, but not to serious toxicity of GHB. In 4 of these 16 cases, the role of GHB could be excluded. In the remaining cases, the role of GHB remains unclear; more research into "background" concentrations of GHB in post-mortem material is required.The incidence of the use of GHB in The Netherlands cannot be derived from these toxicological data. As GHB is not routinely found during systematical toxicological analyses, these data may seriously underestimate the use of GHB. Therefore, information from the police to the forensic institute is essential.     

A survey of extraction techniques for drugs of abuse in urine

Sixty nine participants in the United Kingdom national external quality assessment scheme for drugs of abuse in urine reported details of their sample extraction technique by questionnaire. Laboratories were categorised by differences in technique and their analytical test results compared for samples containing D-amfetamine 0.4 (4) and 0.8 (3) mg/l, morphine 0.4 (4) and 0.8 (4)mg/l, and benzoylecgonine 0.15/0.2 (2) and 0.45/0.5 (4) mg/l. Values in parentheses are numbers of samples. For amfetamine, there was no significant difference in the frequency of true positive results between liquid-liquid or solid phase extraction and the Toxi-Lab A system at 0.8 mg/l. Toxi-Lab A gave significantly fewer positives when operating below its specified threshold at 0.4 mg/l. Paradoxically, laboratories using >5 ml urine volume performed less well. Acidification of the extract before volume reduction gave significantly more true positives. For extraction of morphine, solid phase systems significantly outperformed both liquid-liquid and the Toxi-Lab A system at both 0.8 and 0.4 mg/l. No significant differences between extraction techniques were demonstrated for analysis of benzoylecgonine.     

Toxicological findings in a multi-drug death involving propoxyphene, caffeine, phenacetin, acetaminophen and salicylate

The toxicological findings of a multi-drug related fatal poisoning are described here. A 35-year-old Caucasian male found dead on the kitchen floor was a known user of abused drugs and had been taking aspirin alone or in combination with phenacetin and caffeine for the relief of joint pains. The gross examination of the organs at autopsy revealed slight grooving of the uncus and various stages of necrosis in the renal papillae. Histological examination confirmed the gross appearance of pulmonary congestion and edema, cerebral edema and interstitial nephritis of the tubules. Toxicological evaluation of the blood and urine samples disclosed the presence of propoxyphene (51 and 250 mg/l), salicylate (185 and 2750 mg/l), caffeine (16 and 37 mg/l), and phenacetin (9.6 and 20 mg/l). Furthermore, acetaminophen also was present in the plasma (54 mg/l) and urine. A gas liquid chromatographic method for simultaneous analysis of phenacetin and caffeine utilizing a nitrogen phosphorus detector was proposed.     

论道路交通事故与驾驶员血中酒精含量关系

目的探讨道路交通事故与饮酒驾车血中酒精含量关系及其法医学意义,为预防、控制道路交通事故提供重要依据。方法对2005份道路交通事故肇事驾驶员血酒精鉴定资料进行系统分析性研究。结果饮酒驾车以男性为主,女性饮酒驾车出现醉酒驾车的比例与男性无差别。市区驾驶员醉酒驾车高于郊区。驾驶员BAC<20mg/100mL肇事导致死亡的比例高于饮酒驾车肇事组(BAC20￣79mg/100ML),而BAC≥80mg/100mL则低于饮酒驾车肇事组。结论应降低饮酒驾车和醉酒驾车BAC标准,以利于减少交通事故肇事死亡率。     

The Effects of Dextromethorphan on Driving Performance and the Standardized Field Sobriety Test

Dextromethorphan (DXM) is abused most commonly among adolescents as a recreational drug to generate a dissociative experience. The objective of the study was to assess driving with and without DXM ingestion. The effects of one‐time maximum daily doses of DXM 120 mg versus a guaifenesin 400 mg dose were compared among 40 healthy subjects using a crossover design. Subjects’ ability to drive was assessed by their performance in a driving simulator (STISIM^® Drive driving simulator software) and by conducting a standardized field sobriety test (SFST) administered 1‐h postdrug administration. The one‐time dose of DXM 120 mg did not demonstrate driving impairment on the STISIM^® Drive driving simulator or increase SFST failures compared to guaifenesin 400 mg. Doses greater than the currently recommended maximum daily dose of 120 mg are necessary to perturb driving behavior.     

Interpretation of GC-MS opiate results in the presence of pholcodine

Although the cross reactivity of pholcodine with opiate immunoassays has been well documented there is little published information the potential for pholcodine interference with chromatographic analyses. Wilson and Smith [Ann. Clin. Biochem. 36 (1999) 592] recently described the 'misidentification' of morphine in quality control specimens that had been spiked with pholcodine. This report describes a sensitive, rapid gas chromatography-mass spectrometry (GC-MS) method for the detection and quantitation of pholcodine and morphine, together with 6-monoacetylmorphine (6-MAM), codeine and dihydrocodeine in urine. This method was used to analyse urine specimens collected from volunteers given single and multiple doses of pholcodine to establish the significance this drug on the analytical results obtained when performing drug screening according to the proposed UK and EU legally defensible workplace drug testing guidelines. The maximum urinary free morphine concentration achieved following a single 10mg oral dose of pholcodine was 1.39 mg/l at 2-4h post dose. Following multiple 10mg oral doses of pholcodine the maximum urinary free morphine concentration was determined as 0.4 mg/l at 170 h after the final dose was administered. This apparent anomaly in the morphine concentrations obtained following single and multiple pholcodine doses can be explained in part by differences in the concentration of the specimens, and may be overcome by applying a correction factor for specimen dilution using their creatinine concentration. The data from this study suggests that even following one single 10mg dose of pholcodine, free morphine concentrations greater than both the proposed UK workplace drug testing guidelines threshold of 0.3mg/l total morphine and the proposed European Union threshold of 0.2mg/l total morphine can be achieved. This highlights the need for caution when interpreting confirmatory opiate data, especially in medicolegal and clinical cases, and in cases where the use of pholcodine is suspected.     

Zolpidem and driving impairment

Zolpidem, a non-benzodiazepine hypnotic, was identified in the blood of 29 subjects arrested for impaired driving. Zolpidem concentrations ranged from 0.05 to 1.4 mg/L (mean 0.29 mg/L, median 0.19 mg/L). In the subjects whose cases we reviewed where zolpidem was present with other drugs and/or alcohol, symptoms reported were generally those of CNS depression. Symptoms included slow movements and reactions, slow and slurred speech, poor coordination, lack of balance, flaccid muscle tone, and horizontal and vertical gaze nystagmus. In five separate cases, where zolpidem was the only drug detected (0.08-1.40 mg/L, mean 0.65 mg/L, median 0.47 mg/L), signs of impairment included slow and slurred speech, slow reflexes, disorientation, lack of balance and coordination, and "blacking out." Although no quantitative relationship between blood concentrations and degree of driving impairment is currently possible, it is reasonable to conclude that because of its specific activity as a sleep inducer, blood concentrations consistent with therapeutic doses of zolpidem have the potential to affect driving in a negative way, and that concentrations above the normal therapeutic range would further impair a person's level of consciousness and driving ability.     

Suicidal poisoning with barium chloride

A 49-year-old male pharmacist suffering from depression phoned the emergency services telling of how he had ingested barium chloride. He was found semicomatose in bed and resuscitation attempts were to no avail and he died at the scene. A white plastic container labelled "Barium chloride... Poison", and a book with a writing on a blank page... "give sulphate... SO(4)" were found.At autopsy, 1l of whitish-yellow fluid was found in the stomach.Autopsy barium levels were: blood 9.9mg/l; bile 8.8mg/l; urine 6.3mg/l; gastric 10.0g/l.Cause of death was given as cardiorespiratory arrest due to barium chloride poisoning.The issue of barium toxicity in a variety of itatrogenic and non itatrogenic situation is discussed together with the two only other cases of suicidal barium ingestion, and the feasibility of early intervention at the scene by an emergency team.     

Demographic, pathologic, and toxicological profiles of 127 decedents testing positive for ephedrine alkaloids

The relative toxicity of ephedra-containing dietary supplements is disputed. In order to ascertain the magnitude of the problem, we reviewed all autopsies in our Medical Examiner's jurisdiction, from 1994 to 2001, where ephedrine or any its isomers (E+) were detected. Toxicology testing results were tabulated and anatomic findings in E+ cases were compared to those in a control group of drug-free trauma victims. Of 127 E+ cases identified, 33 were due to trauma. Decedents were mostly male (80.3%) and mostly Caucasian (59%). Blood ephedrine concentrations were <0.49 mg/l in 50% of the cases, range 0.07-11.73 mg/l in trauma victims, and 0.02-12.35 mg/l in non-trauma cases. Norephedrine (NE) was present in the blood of 22.8% (mean of 1.81 mg/l, S.D.=3.14 mg/l) and in the urine of 36.2% (mean of 15.6 mg/l, S.D.=21.50mg/l). Pseudoephedrine (PE) was present in the blood of 6.3% (8/127). More than 88% (113/127) of the decedents also tested positive for other drugs, the most common being cocaine (or its metabolites) and morphine. The most frequent pathologic diagnoses were hepatic steatosis (27/127) and nephrosclerosis (22/127). Left ventricular hypertrophy was common, and coronary artery disease (CAD) detected in nearly one third of the cases. The most common findings in E+ deaths are those generally associated with chronic stimulant abuse, and abuse of other drugs was common in those with CAD. There were no cases of heat stroke or rhabdomyolysis. In most cases, norephedrine was not detected, suggesting it plays no role in ephedrine toxicity.     

Fatality caused by a combined trimipramine-citalopram intoxication

A 53-year-old woman who was diagnosed as suffering from depression was found dead in her bed. The autopsy revealed no morphological changes sufficient to explain death. Toxicological analysis was performed and the drugs trimipramine (2.33 mg/l), citalopram (4.81 mg/l) and zolpidem (0.07 mg/l) were identified in the femoral blood. A combined drug intoxication resulting in synergistic effects to cardiovascular disorders was proposed as the cause of death. An acute overdose and suicide was suggested by calculation of the parent drug to main metabolite ratios in femoral blood and liver tissue. The trimipramine to desmethyltrimipramine ratios were calculated to be 2.06 and 3.18, the citalopram to desmethylcitalopram ratios were 1.96 and 2.02.