Distribution of embutramide and mebezonium iodide in a suicide after tanax injection.

Tanax is a veterinary formulation for euthanasia comprising embutramide, mebezonium iodide and tetracaine. A 37-year-old female was found dead on her bed, with three empty used syringes and a bottle of Tanax beside her body. Three needle puncture marks were observed on the body. The aim of this study was to evaluate the distribution of embutramide and mebezonium iodide in different biological matrices (femoral and cardiac blood, liver, muscle and vitreous humor) using a chromatographic method for the simultaneous determination of the two drugs. A direct and sensitive liquid chromatography-tandem mass spectrometry method was developed in multiple reaction monitoring mode with positive ionization. Lidocaine was used as an internal standard. Limits of detection and quantitation of 0.01 and 0.05 mg/L, respectively, were reached for both compounds. Embutramide levels ranged from 2.74 mg/L in vitreous humor to 5.06 mg/L in femoral blood, while mebezonium iodide was found at widely differing concentrations (ranging from 2.80 mg/kg in muscle to 24.80 mg/kg in liver). The chromatographic method developed for this study provides a very simple and sensitive means for the simultaneous determination of embutramide and mebezonium iodide, the emetic concentrations of which were consistent with suicides reported in the literature.

Dimethylformamide metabolism following self-harm using a veterinary euthanasia product.

BACKGROUND: A veterinary euthanasia drug containing embutramide, mebezonium, tetracaine, and dimethylformamide (DMF; T-61® or Tanax®) may cause serious manifestations or even fatalities after self-poisoning. Immediate toxicity is mainly due to a general anesthetic and due to a neuromuscular blocking agent, while delayed hepatotoxicity seems related to the solvent DMF. The protective role of N-acetylcysteine (NAC) administration remains debatable. MATERIAL AND METHODS: Two male veterinarians (50- and 44-year-old) attempted suicide by injecting T-61 in the precordial area for the first one, and by ingesting 50 mL for the second. Both received NAC (for 14 days in the first case and only for 20 h in the second). Urine was collected for the serial determination of DMF, N-methylformamide (NMF), and N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC). RESULTS: Both patients developed only mild signs of liver injury. The metabolite of DMF, NMF, appeared rapidly in the urine, while a further delay was necessary for AMCC excretion. The kinetics of elimination of DMF and DMF metabolites were slightly slower than those reported in exposed workers. CONCLUSIONS: While both patients had a favorable outcome, there is no clear evidence that NAC could directly influence NMF and AMCC excretion. Further investigations of NMF and AMCC excretion, with and without NAC, would be indicated.

A rapid and sensitive high-performance liquid chromatography method for determination of embutramide (a Tanax or T61 component) in human blood with photodiode-array UV detection.

Tanax or T61 is an euthanasia solution commonly used in veterinary medicine. Embutramide is one of the three components. In accidental intoxication, suicide, or suicide attempt, the determination of embutramide is needed to confirm the hypothesis of intoxication. Because the amount of sample is sometimes limited in forensic cases, a new rapid and sensitive high-performance liquid chromatography method using only 0.1 mL of blood has been developed with liquid-liquid extraction. The eluate was monitored with a photodiode-array detector with a fixed wavelength at 273 nm. The method provided extraction recoveries greater than 83%. The detection limit was 0.2 mg/L, and the limit of quantitation was 0.6 mg/L. The linearity of standards was excellent (r > 0.997). Intra- and interday precisions were acceptable with a coefficient of variation

Blood investigation in a fatality involving the veterinary drug T-61.

A case involving an acute fatality resulting from self-administration of about 30 mL of T-61, a euthanasia solution, consisting of a mixture of embutramide, mebezonium, and tetracaine, in a 58-year-old veterinarian is presented. Forensic investigations consisted of an external body examination, during which 5 mL of fluorinated femoral blood was collected. Embutramide and tetracaine were quantitated using gas chromatography coupled to mass spectrometry after extraction with chloroform/isopropanol/n-heptane (50:17:33, v/v) at pH 9.5 and separation on an HP5-MS capillary column. Mebezonium was quantitated using liquid chromatography coupled to mass spectrometry after ion-pair extraction (saturated KI solution) with methylene chloride at pH 5.4 and separation on a 5-mm Nucleosil C18 column. Blood concentrations were 43.0, 6.5, and 0.21 mg/L for embutramide, mebezonium, and tetracaine, respectively. No other drugs, including ethanol, were detected.

[Rescue and prevention of serious systemic toxicity following local anesthesia to mucous membranes of tetracaine].

Tetracaine remains a popular agent in clinical for the purpose of local anesthesia to mucous membranes. Its potential for systemic absorption and resulting toxicity has been seldom emphasized. One case of fatality from tetracaine pharyngeal local anesthesia for fibro-laryngoscopic procedure is described. The pharmacologic basis, clinical features, rescue and prevention for systemic toxicity is discussed.

Hepatotoxicity of N, N-dimethylformamide (DMF) in acute poisoning with the veterinary euthanasia drug T-61.

1. We report on a patient who was resuscitated after a suicide attempt with the veterinary euthanasia product T-61 and treated with N-acetylcysteine (NAC) to prevent hepatotoxicity from N,N-dimethylformamide (DMF), the solvent of T-61. 2. Serum concentrations of DMF were high as compared with values published on occupational exposure. 3. The patient showed only a transient increase in liver enzymes with eventually a full recovery. 4. The hepatoprotective effect of NAC was studied in a rat model using the rise in serum sorbitol dehydrogenase (SDH) as a marker for DMF-induced hepatotoxicity. 5. Four series of randomized, controlled and double-blind experiments were carried out and consistently showed a lower increase in SDH in NAC-treated animals in each series. The difference was statistically significant only when the data of the 4 series were pooled. This is probably due to the large interindividual variations in the effect of DMF. 6. We hypothesize that in the rat NAC may have a protective effect. Whether NAC is also protective in patients, in which it is administered after exposure to DMF, cannot be concluded from the present experiments.

Intracardiac injection of T-61, a veterinary euthanasia drug.

CASE REPORT: We report a suicidal attempt by intracardiac injection of T-61, a veterinary euthanasia drug containing embutramide, mebezonium and tetracaine in dimethylformamide. The main complications were reversible acute renal failure and pericardial effusion. There was a delayed abnormality of the liver function tests possibly related to the dimethylformamide solvent. A liver biopsy on day 16 showed a normal hepatic architecture with lipid-containing lysosomes and prominent vesicular endoplasmic reticulum noted on electron microscopy.

Severe hepatic failure occurring with T61 ingestion in an attempted suicide. Early recovery with the use of intravenous infusion of reduced glutathione.

A case of acute hepatic failure following ingestion of the veterinary euthanasia drug T61 is described. Presenting symptoms were drowsiness, disorientation, muscle hypertonia, and upper limb myoclonus, which faded within a few hours. Two days later, acute liver failure occurred, manifested as encephalopathy, jaundice, and a severe coagulopathy. The hepatic damage was thought to be due to the solvent dimethylformamide, which is the only known hepatotoxin included in the preparation utilized in the suicide attempt. High-dose (1.2 g/day) intravenous reduced glutathione was administered, with a rapid improvement of liver function. The patient was discharged after 17 days. Normalization of all liver function tests was achieved within two months. The favorable outcome in this case stands in contrast to the report of a previous case of lethal T61-induced hepatic failure. Although a different amount of dimethylformamide was ingested in each case (0.45 vs 0.60 ml/kg body wt) and individual differences in susceptibility to the effects of the hepatotoxic agent may have played a major role in these two cases, it is not unlikely that the infusion of high doses of glutathione to our patient contributed to her survival and hepatic recovery.

Suicide by ingestion of T-61.

T-61 is an agent used for euthanasia of animals and is primarily administered by iv injection. When so used it rapidly induces deep anesthesia and cerebral death. We report our findings in a case of ingestion of T-61 with suicidal intent. The coroner's report stated that the individual survived for 20 to 30 min and that death was due to cardio-respiratory failure. Levels of embutramide in the blood and liver are comparable to those reported in a number of animal species following the traditional routes of administration.

Fatality secondary to misuse of TAC solution.

The death of a 7 1/2-month-old girl from the misuse of tetracaine/adrenalin/cocaine solution for wound anesthesia is reported. Ten milliliters of the solution inappropriately came into contact with nasal mucous membranes, causing excessive drug absorption. The patient's death probably was due to cocaine toxicity (post-mortem blood level, 11.9 mg/L).

Veterinary euthanasia drugs as suicide agents.

We report three cases in which pentobarbital and T-61 were used or their use was threatened in suicide attempts. One patient died after IV injection of a pentobarbital solution. Another threatened suicide by the same method. A third patient survived the ingestion of both pentobarbital and T-61. Supportive care forms the mainstay of therapy when these agents are used in suicide attempts.