A mixed-drug intoxication involving venlafaxine and verapamil

This case report describes the suicide of a 52-year-old woman whose cause of death was attributed to a mixed-drug intoxication involving venlafaxine and verapamil. Venlafaxine is prescribed for the treatment of depression and should be used with caution in patients with cardiovascular disease. Verapamil is a calcium channel blocker primarily used for treatment of cardiovascular disorders. The following drug concentrations were determined in postmortem fluids: verapamil--3.5 mg/L (femoral blood), 9.4 mg/L (subclavian blood), and 1.0 mg/L (vitreous fluid); norverapamil--1.0 mg/L (femoral blood), 2.1 mg/L (subclavian blood), and 0.20 mg/L (vitreous fluid); verapamil and norverapamil could not be detected in bile or urine due to the high levels of erythromycin present; venlafaxine--6.2 mg/L (femoral blood), 8.6 mg/L (subclavian blood), 5.3 mg/L (vitreous fluid), 54.0 mg/L (bile), and 72.3 mg/L (urine); and O-desmethylvenlafaxine--5.4 mg/L (femoral blood), 8.3 mg/L (subclavian blood), positive (vitreous fluid), 29.2 mg/L (bile), and 9.5 mg/L (urine). The cause of death was determined to be a mixed-drug intoxication resulting from an overdose of verapamil and venlafaxine. The manner of death was determined to be suicide.     

Suicide with acetylsalicylic acid

The authors report on a suicide of a 41-year-old man with acetylsalicylic acid. According to his own statement the man had taken about 200 tablets of Aspirin (65 g acetylsalicylic acid) and initially showed no symptoms of intoxication. 4-5 hours after ingestion he vomited twice, but clear intoxication symptoms like convulsions and cardiac arrhythmia occurred not earlier than 11 hours after ingestion. Resuscitation by the emergency physician was not successful. The chemical-toxicological analysis (HPLC-DAD) of blood samples taken in the hospital approximately 12 h after ingestion showed salicylate in concentrations of 475 mg/L to 557 mg/L. The post-mortem concentrations of salicylate were within the lethal-toxic range, i.e. 762 mg/L in heart blood and 215 mg/L in femoral blood. All tested organs contained equally lethal salicylate levels (e.g. 503 mg/L in the liver and 251 mg/L in the brain).     

Fatal bupivacaine intoxication following unusual erotic practices

A fatal drug overdose is described which involved unusual erotic practices. A 54-year-old male was discovered supine on the floor surrounded by sexual paraphernalia, syringes, and medications including three empty bottles of bupivacaine. Acute and chronic injection sites of the external genitalia with contusions, scarring, focal necrosis, and calcification were present at autopsy. Toxicology revealed femoral blood, heart blood, and vitreous bupivacaine concentrations of 3.8, 2.8 and 1.3 mg/L, respectively. The urine bupivacaine concentration was 11.4 mg/L. The cause of death was attributed to bupivacaine intoxication and the manner of death was accidental.     

Fatal intoxication by Remoxipride

The case history and toxicologic findings of a 23-year-old woman who committed suicide with Remoxipride are described. Remoxipride is a recently developed neuroleptic drug of the benzamide type. Remoxipride was detected in the liver, stomach content, blood, and urine. The concentration of Remoxipride in the blood was 230 mg/L. The recommended therapeutic level for Remoxipride should not exceed 7 to 8 mg/L. The victim had no blood alcohol, but an ethanol concentration of 0.048 g/100 L was detected in the urine. The mechanism of death from Remoxipride intoxication is not known. In clinical studies, sinus bradycardia and infrequent supraventricular and ventricular ectopic beats have been noted.     

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.     

Fulminant liver failure in a young child following repeated acetaminophen overdosing

Acetaminophen (paracetamol), a widely used analgetic drug, is well tolerated at therapeutic doses, but may cause severe hepatotoxicity when ingested in large overdose. Self-poisoning is still very popular in adults and accidental ingestion of one single overdose occurs occasionally in children. In contrast, lethal intoxication in children after repeated administration of therapeutic doses is a very rare event. This case report describes an iatrogenic acetaminophen overdosing in a 5-year-old child receiving 8.5 g acetaminophen in 48 h. Fulminant liver failure developed within 60 h. Autopsy findings included panlobular liver cell necrosis. Acetaminophen serum levels were rather low compared to cases with ingestion of one single overdose. Postmortem diagnosis of chronic acetaminophen intoxication as cause of death should include the clinical history as well as, if available, the calculated drug serum half-life.     

Methylenedioxypyrovalerone (“Bath Salts”),Related Death: Case Report and Review of the Literature,

Cathinone derivatives (bath salts) have emerged as the latest drugs of abuse. 3,4‐methylenedioxypyrovalerone (MDPV) is the primary active ingredient in bath salts used in this country. This article presents the second reported cause of death by MDPV intoxication alone. In April 2011, a delusional man was emergently brought to a hospital, where he self‐reported bath salt usage. He became agitated, developed ventricular tachycardia, hyperthermia, and died. Comprehensive alcohol and drug testing was performed. Using the alkaline drug screen, heart blood contained 0.7 mg/L MDPV and peripheral blood contained 1.0 mg/L MDPV. His bizarre behavior with life‐threatening hyperthermia was consistent with an MDPV‐induced excited delirium state. MDPV is not yet found by routine immunoassay toxicology screens. Testing for MDPV should be considered in cases with a history of polysubstance abuse with stimulant type drugs, report of acute onset of psychogenic symptoms, excited delirium syndrome, or presentation in a hyperthermic state.     

Concentrations of zolpidem and zopiclone in venous blood samples from impaired drivers compared with femoral blood from forensic autopsies

The concentrations of zolpidem and zopiclone were determined in peripheral blood samples in two forensic materials collected over a 10-year period (2001-2010). The z-hypnotics were determined in venous blood from living subjects (impaired drivers) and in femoral blood from deceased persons (forensic autopsies), with the latter classified as intoxication or other causes of death. The z-hypnotics were determined in blood by capillary column gas chromatography (GC) with a nitrogen-phosphorous (N-P) detector after solvent extraction with n-butyl acetate. The analytical limit of quantitation (LOQ) was 0.02mg/L for zopiclone and 0.05mg/L for zolpidem and these have remained unchanged throughout the study. When death was attributed to drug intoxication (N=918), the median concentration of zopiclone in blood was 0.20mg/L compared with 0.06mg/L for other causes of death (N=1215) and 0.07mg/L in traffic offenders (N=691) (p<0.001). Likewise, a higher median concentration (0.30mg/L) was found in intoxication deaths involving zolpidem (N=357) compared with 0.13mg/L for other causes of death (N=397) or 0.19mg/L in impaired drivers (N=837) (p<0.001). Median concentration in blood of both z-hypnotics were appreciably higher in intoxication deaths when no other substances were identified; 0 70mg/L (N=12) for zopiclone and 1.35mg/L (N=12) for zolpidem. The median concentrations of z-hypnotics in blood decreased as the number of co-ingested substances increased for intoxication deaths but not other causes of death. The most prevalent co-ingested substances were ethanol in autopsy cases and diazepam in the motorists. This large compilation of forensic cases should prove useful when toxicologists are required to interpret concentrations of z-hypnotics in blood samples in relation to cause of death.     

Fatal overdose of zopiclone in an elderly woman with bronchogenic carcinoma

The death of a 72-year-old woman with respiratory debilitation due to bronchogenic carcinoma is described. She overdosed herself with probably 200 to 350 mg of zopiclone. Zopiclone, quantitated by HPLC in femoral postmortem blood, was found to be 1.9 mg/L (4.8 micromol/L). This level is higher than many other zopiclone fatalities reported. We report a case where only zopiclone was detected.     

Acute intoxication with guaifenesin, diphenhydramine, and chlorpheniramine.

Mixed drug reactions are frequently encountered in emergency department overdose cases and also in fatal intoxications. Assessment of the relative contribution of each drug in producing adverse effects is often compounded by lack of case history and the paucity of cases reported in the literature. This report describes a fatal intoxication with three common over-the-counter medications: guaifenesin, diphenhydramine, and chlorpheniramine. A 48-year-old woman was found dead in the attic bedroom of her residence. Specimens obtained at autopsy for toxicologic analysis included heart blood, urine, bile, gastric contents, vitreous humor, and cerebrospinal fluid. The over-the-counter drugs were identified and quantitated by acid/neutral or basic liquid-liquid extraction followed by gas chromatographic analysis with nitrogen phosphorus detection. Concentrations of guaifenesin, diphenhydramine, and chlorpheniramine detected in the heart blood were 27.4, 8.8, and 0.2 mg/L, respectively. The cause of death was determined to be acute intoxication by the combined effects of guaifenesin, diphenhydramine, and chlorpheniramine, and the manner of death was determined to be suicide. To our knowledge, the blood guaifenesin concentration in this case is the highest reported concentration to date associated with an acute intoxication.     

Fatal cardiac arrhythmia after repeated exposure to 1,1-difluoroethane (DFE)

A 42-year-old man was found dead after repeated exposure to 1,1-difluoroethane (DFE, Freon 152a), a propellant found in CRC Duster, a product intended for the removal of dust and lint. Toxicologic analysis detected DFE in femoral blood 136.3 mg/L, brain 117.5 mg/kg, liver 87.6 mg/kg, lung 60.3 mg/kg, adipose 235.7 mg/kg, and vitreous fluid 25.1 mg/L. The cause of death was determined to be a fatal cardiac arrhythmia due to intoxication with 1,1-difluoroethane. After comparison to previously published cases involving DFE, we suggest that analysis of adipose tissue for DFE and similar compounds, along with blood and other tissues, may be useful in distinguishing between acute versus chronic exposure. Adipose may also be a valuable alternate specimen for detection in cases where loss or elimination from blood is likely to have occurred.     

A fatality involving metaxalone

A case is presented of a 54-year-old white female found dead in a secured apartment. Postmortem toxicologic analysis of the heart blood identified acetaminophen (97 mg/L), citalopram (0.4 mg/L), gabapentin (24 mg/L) and metaxalone (21 mg/L). The metaxalone concentration is within the range of previously reported fatalities involving metaxalone. The medical examiner ruled that the cause of death was metaxalone and gabapentin intoxication and the manner of death was suicide.     

Fatality due to methyl acetylene-propadiene (MAPP) inhalation

A 33-year-old man died after intentionally inhaling a gaseous mix of methyl acetylene (propyne) and propadiene (allene) commonly known as MAPP, which is used for soldering and welding. He was found with a plastic bag securely placed over his head and a cylinder of MAPP alongside his head. The cylinder had been vented into the bag using a flexible hose. A comprehensive toxicological analysis revealed only a trace of diphenhydramine in the liver and 0.02 mg/L of morphine in the urine. Analysis of blood by headspace gas chromatography (HS-GC) detected two unknown peaks. These were determined to be the components of MAPP gas. MAPP was quantitated in femoral blood (59.6 mg/L) and brain (43.6 mg/kg) using a HS-GC method. The cause of death was attributed to acute MAPP intoxication, and the manner was determined to be suicide. A discussion on the analytical and interpretive considerations commonly encountered when analyzing volatile compounds is also presented.     

Tissue distribution of olanzapine in a postmortem case

Olanzapine is a relatively new antipsychotic drug used in the United States for the treatment of schizophrenia. Since its release in the United States market in 1996, few cases of fatal acute intoxication have been reported in the literature. This article describes the case of a 25-year-old man found dead at home who had been prescribed olanzapine for schizophrenia. This case is unique because of the measurement of olanzapine in brain tissue obtained from seven regions in addition to the commonly collected biologic matrices. Olanzapine was detected and quantitated by basic liquid-liquid extraction followed by dual-column gas chromatographic analysis with nitrogen phosphorus detection. The assay had a limit of detection of 0.05 mg/L and an upper limit of linearity of 2 mg/L. The presence of olanzapine was confirmed by gas chromatography-mass spectrometry by use of electron impact ionization. The concentrations of olanzapine measured in this case were as follows (mg/L or mg/kg): 0.40 (heart blood), 0.27 (carotid blood), 0.35 (urine), 0.61 (liver), negative (cerebrospinal fluid), 0.33 mg in 50 ml (gastric contents). In the brain, the following distribution of olanzapine was determined (mg/kg): negative (cerebellum), 0.22 (hippocampus), 0.86 (midbrain), 0.16 (amygdala), 0.39 (caudate/putamen), 0.17 (left frontal cortex), and 0.37 (right frontal cortex). The cause of death was determined to be acute intoxication by olanzapine, and the manner of death was accidental.     

Case report of a fatal intoxication by citalopram

Citalopram is an antidepressant drug within the group of the selective serotonin reuptake inhibitors (SSRI). It is widely prescribed both in Europe and in United States, and it has always been considered a "safe" drug as pure intoxication with lethal outcome is rare, and most cases of overdose, even with high doses of citalopram ingested, are reported to have an uneventful course.We report the case of a young woman found dead at home. She had been prescribed citalopram by her family doctor 3 weeks before her death for a depressive syndrome. Police found in her house 3 empty blister packages of 28 citalopram tablets (20 mg) and 2 bottles of citalopram oral solution (4%, 15 mL each). The autopsy findings were unremarkable. Nasal swabs, blood from femoral vein, urine, bile and tissue samples were collected for toxicologic investigation. Citalopram separation was performed by solid/liquid method, using Bond-Elute columns. The extracts were analyzed by GLC and GC/MS methods. The toxicologic analysis showed high levels of citalopram in all the examined fluids and tissue samples (blood concentration: 11.60 mg/L). No other drugs and alcohol were detected. Our data confirm that if no other drug is involved, fatal complications occur only after ingestion of very high doses. However, there is no predefined "toxic dose," and the conditions under which the overdose occurs can be very important. We report the exact concentrations of the citalopram in the organs, and wethink that this can be useful in the cases where the blood samples were not available (ie, carbonized or decomposed body).     

Fatal intoxication following self-administration of a massive dose of buprenorphine

Several drug packages, including Subutex (high-dose buprenorphine, as sublingual tablets) boxes, were found near the corpse of a 25-year-old male drug addict, who apparently had committed suicide. The autopsy revealed a fatal respiratory depression. The toxicological investigations concluded that death resulted from massive burpienorphine intoxication. The determination of buprenorphine (BU) and norbuprenorphine (NBU) in all biological specimens was performed by liquid chromatography-electrospray mass spectrometry (LC-ES-MS) after hydrolysis (for solid tissues), deproteinization of the matrices, and solid-phase extraction of the compounds. Exceptionally high concentrations of BU and NBU were found in blood (3.3 and 0.4 mg/L, respectively), urine (3.4 and 0.6 mg/L), bile (2035 and 536 mg/L and brain (6.4 a nd 3.9 microg/g). The high concentration of BU (899 mg/L) and the absence of NBU in gastric liquid suggested oral intake. High concentrations of amino-7-flunitra/epam, the main metabolite of flunitra/epam, were also found in blood, urine and gastric liquid. This benzodiazepine may have been a co-factor in the toxic effects of BU.     

Postmortem diffusion of drugs from the bladder into femoral venous blood.

We describe significantly elevated drug concentrations in the femoral venous blood due probably to postmortem diffusion from the bladder. A 16-year-old deceased male was found in a shallow ditch in winter. The estimated postmortem interval was 9 days and putrefaction was not advanced. The cardiac chambers contained fluid and coagulated blood and a small amount of buffy coat clots. Diffused hemorrhages were found in the gastric mucosa. The bladder contained approximately 600 ml of clear urine. Gas chromatographic-mass spectrometric analysis of the urine disclosed allylisopropylacetylurea (a fatty acid ureide sedative), diphenhydramine, chlorpheniramine and dihydrocodeine. The cause of death was considered to be drowning due to a drug overdose and cold exposure. The concentrations of diphenhydramine, free dihydrocodeine and total dihydrocodeine in the femoral venous blood (1.89, 3.27 and 3.30 microg/ml, respectively) were much higher than those in blood from the right cardiac chambers (0.294, 0.237 and 0.240 microg/ml, respectively). Urine concentrations of diphenhydramine, free dihydrocodeine and total dihydrocodeine were 22.6, 37.3 and 43.1 microg/ml, respectively. The stomach contained negligible amounts of diphenhydramine, free dihydrocodeine and total dihydrocodeine (0.029, 0.018 and 0.024 mg, respectively); concentrations of these drugs in the femoral muscle were 0.270, 0.246 and 0.314 microg/g, respectively. These results indicate that postmortem diffusion of diphenhydramine and dihydrocodeine from the bladder resulted in the elevated concentrations of these drugs in the femoral venous blood. Not only high urinary drug concentrations but also a large volume of urine in the bladder might accelerate the postmortem diffusion.     

Polydrug fatality involving metaxalone

A 29-year old female with a history of depression was found dead in a hotel room. The death scene investigation found empty pill bottles and an empty liter bottle of wine. Metaxalone, a centrally acting muscle relaxant, along with citalopram, ethanol, and chlorpheniramine were identified in the postmortem samples and quantitated by gas chromatography-mass spectrometry. The concentration of metaxalone in femoral vein blood was 39 mg/L. The heart blood concentration was 54 mg/L. Femoral vein blood concentrations of citalopram and chlorpheniramine were 0.77 mg/L and 0.04 mg/L, respectively. Ethanol levels were 0.13 g/dL in vitreous and 0.08 g/dL in heart blood. Other tissue samples were also analyzed. The authors consider the metaxalone concentrations toxic and potentially fatal. The citalopram concentrations were lower than those reported in fatal cases for this drug alone. Death was ascribed to polydrug abuse/overdose with metaxalone a major contributor. This represents the first reported case to our knowledge in which a metaxalone overdose significantly contributed to death.