Measurements of fentanyl and sufentanil in blood and urine after surgical application. Implication in detection of abuse.

An increase in cases of death from overdose and abuse from fentanyl or sufentanil is being encountered by the Bexar County Forensic Science Center in San Antonio, Texas. These drugs have been abused almost solely by health care professionals. The fentanyl derivatives cannot currently be detected by routine laboratory drug-screening programs. Forensic toxicology assays that identify the specific analyte must be used. We report a sensitive assay for detection of fentanyl and sufentanil with a detection limit of -0.5 ng/ml. In addition, results from the analysis of urine and blood samples obtained up to 72 h after drug administration to five patients undergoing cardiac bypass surgery who had received either fentanyl or sufentanil are described. The new procedure enables detection of these drugs more readily, in smaller amounts, and for a longer period of time after use than previously possible. We hope this will lead to intervention and treatment in those abusing the drugs.

Drug use among homicide victims. Changing patterns.

Complete toxicology screens were performed on Bexar County homicide victims in four recent representative years (1985, 1986, 1990, and 1991). A high positivity rate for drugs and/or alcohol, ranging from 66 to 73%, was found for each year. Alcohol was present in more than half of the cases, ranging from 54.2 to 60.3%. Detection of cocaine or cocaine metabolites increased drastically during this study period, from 1.6% of cases in 1985 to 18.7% in 1991. Heroin metabolites, indicative of recent heroin use, were detected in only 2-5% of the cases in each of the years studied. Drugs other than alcohol, cocaine, or heroin were detected in 7-25% of the cases.

A case of fatal ingestion of malathion.

We report a case of suicide due to organophosphate poisoning in an 80-year-old woman who ingested malathion mixed with a fruit drink. She presented with signs and symptoms of cholinergic crisis and initially improved with therapy. Her plasma cholinesterase (ChE) level remained low, her course progressively deteriorated with respiratory and renal failure, and she died 12 days after hospital admission. The antemortem blood malathion level of 23.9 mg/L is the highest reported in the literature, as determined by modern methods. Postmortem toxicologic analysis revealed still greatly reduced ChE activity.

Alcohol and motorcycle riders: a comparison of motorcycle and car/truck DWIs.

Alcohol's effects on balance and motor coordination would be expected to have greater consequences for motorcycle riders than car/truck drivers. Driving while intoxicated/under the influence (DWI) reports for 1984 and 1985 from the San Antonio, TX, Police Department were reviewed to evaluate motorcycle DWIs, and to compare them with car/truck DWIs. During the 2-y period there were 100 DWI reports involving motorcycle riders, which were compared to 100 involving car/truck drivers. Motorcycle riders were all male and younger (mean 26 y) than car/truck drivers (p less than 0.05). Initiation of the DWI investigation of motorcycle riders was more frequently due to excessive speed, and less likely due to an accident, when compared to car/truck investigations. Breath alcohol testing demonstrated a significantly lower blood alcohol concentration in motorcycle riders, 0.14 +/- 0.05 g/dL, than in car/truck drivers, 0.16 +/- 0.05 g/dL (p = 0.016). The results of this study suggest that alcohol influences motorcycle riders to a greater extent than it does car/truck drivers. Further data is needed to determine whether lower blood alcohol concentration limits should be considered for the definition of "driving while impaired" in motorcycle riders.

Eye injuries with metal missiles presenting to an emergency center: a three year study.

The authors retrospectively evaluated 33 eye injuries due to metal missiles in 31 patients presenting to our emergency center over the last 3 years. Injuries occurred most frequently when the patients were grinding metal or working on their cars. The type of metal involved in the injury often dictates the type of ophthalmic reaction that will occur. A discussion of intraocular metallic foreign bodies with an emphasis on electroretinograms and metal analysis is presented.

Skeletal muscle as an alternative specimen for alcohol and drug analysis.

In a random group of medical examiner cases, muscle tissue, as well as blood and vitreous humor, was analyzed for ethyl alcohol, and the results were compared. When the blood concentration was greater than 0.10 g/dL, the muscle to blood ratio was 1.00 or less (average 0.94), and when the blood concentration was less than 0.10 g/dL, this ratio was greater than 1.00 (average 1.48). The author proposes that this ratio is dependent upon the time course of absorption and distribution, as has been observed for vitreous humor, but with a more rapid equilibration. Muscle tissue was also analyzed in another group of cases found to be positive for one or more drugs in blood. The concentrations of the drugs in muscle varied from none detected to 6.5 times those in blood and seemed to be dependent on the time course between ingestion and death, as well as on the nature of the drug. For most common basic drugs, the ratios were often near unity. Muscle is proposed as a useful alternative specimen to postmortem blood.

Recovery of cyclic antidepressants with gastric lavage.

The role of lavage fluid volume in recovery of cyclic antidepressant with gastric lavage was determined in 13 patients treated for moderate to severe cyclic antidepressant intoxication. An orogastric tube was placed, gastric contents aspirated, and gastric lavage performed with 60 to 180 mL aliquots of tap water or 0.9% NaCl for irrigation. A volume of 12.8 +/- 4.4 liters of lavage fluid was instilled, and 97.6 +/- 6.9% of this volume was recovered. The recovered aspirate and lavage fluid were inspected for the presence of particulate matter and saved in 4 to 5 liter collections. Determination of cyclic antidepressant and metabolite concentrations was performed using gas chromatography-mass spectrometry, and the amount of cyclic antidepressant recovered was calculated. The mean total amount recovered was 110 mg and ranged from 2.4 mg to 342 mg. Of the total amount recovered, 88% +/- 13% was recovered in the first 4 to 5 liters of lavage fluid. An estimate of the dose ingested was available in 7 patients, with 8.7% (0.4% to 21.7%) of the estimated dose recovered by lavage. There were no cases of significant drug recovery in clear lavage fluid. We conclude that if gastric lavage is undertaken in cyclic antidepressant intoxications, it should utilize 5 liters initially and then continue only if particulate matter is seen.

Three fatal sodium azide poisonings.

We report 3 cases and review the published literature on sodium azide ingestion. A 38-year-old man intentionally ingested 2 tablespoonsful of sodium azide in water and developed seizures, coma, hypotension and fatal ventricular arrhythmias within 2 hours. A 33-year-old male ingested an unknown quantity of sodium azide. In the emergency department he was unconscious and underwent immediate intubation and gastric lavage. Nitrite therapy was instituted without improvement. He remained acidotic despite bicarbonate therapy and developed hypotension which was unresponsive to pressor agents. He died approximately 8 hours after admission despite resuscitative efforts. A 52-year-old male ingested 1.5 to 2g of sodium azide and survived for 40 hours. Nitrite therapy was ineffective. The role of sodium nitrite in treating sodium azide toxicity by producing methaemoglobin which complexes with azide is discussed.

A sensitive thin-layer chromatographic procedure for the detection of urinary 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid.

A sensitive high-performance thin-layer chromatographic (HPTLC) procedure for the detection of 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH), the major urinary metabolite of delta 9-tetrahydrocannabinol (THC), is described. After alkaline hydrolysis, the THC-COOH is extracted from acidified urine into hexane. The hexane is evaporated and the residue spotted onto an HPTLC plate. Chromatography time is 11 min with heptane/butanol/acetic acid (90:9:1) as mobile phase. The cannabinoids are visualized by sequentially dipping the thin-layer plate in diethylamine then in 0.1% Fast Blue BB. The limit of detection for THC-COOH is 5 ng/mL when 2 mL of urine is used. Extraction efficiencies averaged 71% over the 10-400 ng/mL range. No drugs, drug metabolites, or endogenous urinary substances interfere with the procedure.

A fatal poisoning from Nicotiana glauca.

A young adult male was found dead in a field. No cause of death was apparent at autopsy, and the only positive toxicological finding was the presence of a nicotine-like alkaloid isolated from the liver. Anabasine, the major, highly toxic alkaloid of the shrub, Nicotiana glauca (tree tobacco) was subsequently identified in all body specimens examined using gas chromatography/mass spectrometry. Concentrations of anabasine in blood, urine and other body organs are reported.

Detection of cannabinoids in homicide victims and motor vehicle fatalities.

A gas chromatographic/mass spectrometric (GC/MS) procedure is described for the detection and measurement of delta 9-tetrahydrocannabinol, 11-hydroxy-delta 9-tetrahydrocannabinol, and 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid in blood, or 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid in urine. About 50% of all homicide victims and motor vehicle drivers killed in Bexar County in 1985 were tested for the presence of cannabinoids. Of 130 homicides and 69 drivers tested, blood was analyzed primarily in all but 15 and 3 cases, respectively. In these latter cases, blood analyzed after urine was found to be positive. Of the homicide victims, 44 (34%), and of all drivers, 19 (28%), tested were positive for one or more of the cannabinoids. As a separate group, 16 motorcycle drivers tested had 38% positive as compared with 25% of the other vehicle drivers. Ethyl alcohol was present in 55% of the drivers, and in 63% of the homicide victims. Drugs other than alcohol or cannabinoids were found in 10% of the drivers, and in 12% of the homicide victims.

Blood pentobarbital concentrations during thiopental therapy.

The desulfuration of thiopental to pentobarbital has previously been shown to be a relatively minor pathway of thiopental metabolism. In two cases, we observed significant conversion, resulting in blood pentobarbital concentrations up to 50 percent of total blood barbiturate (thiopental and pentobarbital) concentrations. Both patients received continuous infusions of thiopental and had present a condition (hypothermia) or drug (cimetidine) known to inhibit hepatic microsomal enzyme activity. It is suggested that inhibition of hepatic microsomal enzyme activity may prevent thiopental's metabolism to its major metabolite, a carboxylic acid analogue, and increase the amount of thiopental desulfurated to pentobarbital. Inhibition of hepatic microsomal metabolism also decreases the metabolism of pentobarbital. Until further elucidation of the causes of altered thiopental metabolism is available to identify patients more likely to have elevated concentrations of pentobarbital, monitoring of blood drug concentrations in patients receiving thiopental should include determination of both thiopental and pentobarbital concentrations.

Five cases of fatal overdose from caffeine-containing "look-alike" drugs.

Five cases of death from ingestion of "look-alike" dose forms are reported. "Look-alikes" are widely used non-prescription drugs sold as appetite suppressants or stimulants. Three of the cases had taken caffeine/ephedrine combinations, and two had taken caffeine only. All had lethal concentrations of caffeine detected in the blood (130 to 344 mg/L), and three had high ephedrine concentrations from 3.5 to 20.5 mg/L. Caffeine and ephedrine were measured in body fluids and tissues (when available) by SIM gas chromatography/mass spectrometry (GC/MS) after extraction with diethyl ether.

A death from fentanyl overdose.

A case of death from self-injection of fentanyl and a method for its detection in autopsy specimens are reported. Fentanyl was measured by extraction of biological samples with ethyl acetate, partitioning into 0.1N HCl, then reextracting into ethyl acetate after alkalinization of the acid phase. After reducing to a residue, the fentanyl was measured by selective ion monitoring gas chromatography/mass spectrometry. Concentrations of 4.8, 6.3, and 4.7 micrograms/L were found in blood, urine, and bile, respectively.

Metabolism of acetone to isopropyl alcohol in rats and humans.

Isopropyl alcohol and acetone have been detected in autopsy blood samples of individuals not previously exposed to these compounds. Since some of these individuals had a history of diabetes mellitus, it has been suggested that in these cases, reduction of acetone to isopropyl alcohol might be a metabolic pathway for its production. This hypothesis was investigated in a study of normal and diabetic rats. Acute administration of acetone resulted in measureable levels of isopropyl alcohol in blood. Metabolism of acetone to isopropyl alcohol was different in normal and diabetic animals. Blood levels of isopropanol reached a maximum at the second highest dose in normal rats, but there was a two-phase response in diabetic rats. In a second series of experiments, acetone was administered on alternate days for a week. In spite of this chronic administration (and persistence of high blood acetone), there was no enhancement of acetone metabolism to isopropyl alcohol. These experiments indicate that high levels of blood acetone could result in transformation to isopropyl alcohol.

Two cases of death involving dicyclomine in infants. Measurement of therapeutic and toxic concentrations in blood.

In two deaths of infants investigated by the Medical Examiner, high levels of dicyclomine were detected in blood. In one of the cases, a level of 0.505 micrograms/ml was found, nearly 10 times reported adult therapeutic blood concentrations, and death was ascribed to an overdose of dicyclomine. Gas chromatography/mass spectrometry was used for the analysis of biological specimens.

Chronic acetazolamide intoxication.

Severe acidosis associated with acetazolamide therapy is rare. We report the first case in which plasma and whole blood acetazolamide concentrations were measured. A 61 year-old patient receiving oral acetazolamide for treatment of glaucoma presented with a 7 day history of declining mental status. The patient was lethargic and oriented only to name. The respiratory rate was 36 per minute in a Kussmaul pattern with arterial blood gases revealing a pH of 7.23, pO2 68 mmHg, paCO2 14 mmHg and bicarbonate 6 mEq/L. Serum creatinine was 3.1 mg%, Cl 126 mEq/L, and anion gap 15. Urine pH was 6.0. Infection and other causes of acidosis and bicarbonate loss were excluded, and he was discharged with normal mental status and improving acid-base balance 18 days after admission. Acetazolamide concentrations four days after the last dose were 26.38 mcg/ml and 38.84 mcg/ml in serum and whole blood, respectively. The serum half-life was 34 hours, compared to a range of 1.5 to 6 hours in subjects with normal renal function. Monitoring acetazolamide concentrations may be useful in adjusting dosage and preventing toxicity in patients with decreased renal function.

A fatal case of lead poisoning due to a retained bullet.

Lead poisoning from a retained bullet or missile is rare and is usually dependent on the location of the missile in a bone or immediately adjacent to a joint. A review of the literature revealed only 14 cases in which there was adequate laboratory documentation of plumbism caused by a retained bullet or missile. Only one of these previously reported cases resulted in death. We report a second death due to lead poisoning from a retained bullet with elevated blood lead levels documented by toxicologic analysis.

Detection of marihuana use by GC/MS analysis of mouth swabs.

A relatively simple and rapid test for detection of the components of Cannabis sativa (marihuana) after smoking consists of swabbing the exposed areas with an alcohol-containing swab, then concentrating the extract from the swab for direct analysis by Gas Chromatography-Mass Spectrometry. This test is now performed in several medical examiner's offices. This study was performed to evaluate this test using volunteer marihuana-smoking subjects. Caution must be used in interpreting the results obtained because of the transient nature of the intoxication, and because of the possibility of obtaining false-positive results. The time response and other parameters concerning the procedure are also discussed.