Case Report
Fatality due to ingestion of tramadol alone

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Abstract

A rare case of a fatal intoxication in an adult with tramadol alone is reported. In the peripheral blood, tramadol was measured in a concentration of 9.6 mg/l exceeded at least 30-times the normal therapeutic range of 0.1–0.3 mg/l. The concentration of tramadol in liver and kidney, in relation to blood, failed to suggest a major sequestration of drug in either specimen which is consistent with the volume of distribution of 3 l/kg. The concentration of tramadol in the heart and peripheral blood specimens did not suggest a major difference (ratio of 1.36). Similar to morphine tramadol was accumulated significantly in the bile.

Introduction

Tramadol is a centrally acting analgesic used for the treatment of moderate to severe pains. The drug has a weak affinity for the μ-opioid receptor and inhibits the reuptake of norepinephrine and serotonin. Side effects from tramadol use include seizures and respiratory depression [1].

Recently, Michaud et al. reported in this journal about a case of a 30-year-old woman with history of depression, found dead after the ingestion of alprazolam, tramadol, and alcohol [2]. In the peripheral blood, alprazolam was detected in a concentration of 0.21 mg/l, the tramadol concentration was determined as 38.3 mg/l, and the blood alcohol concentration was 1.29 g/kg. The tramadol concentration exceeded at least 100-times the normal therapeutic range of 0.1–0.3 mg/l. Nevertheless, the authors could not ascribe the death only to tramadol because of high levels of ethanol and alprazolam. Death attributed only to tramadol intoxication are rarely described until now [3], [4]. We know about one case concerning a 6-month-old child with a blood concentration of tramadol of 2 mg/l [5], a suicide by tramadol overdose with a whole blood concentration of 13 mg/l (additionally, 7-aminoflunitrazepam was determined in a concentration too low to have contributed to death) [6], and a tramadol overdose fatality with a blood concentration of 15.1 mg/l [7]. We report about a further case of a fatal intoxication in an adult with tramadol alone. Additionally, we determined the tissue distribution of the drug.

Section snippets

Case history

A 26-year-old male nurse (body weight 70 kg, body length 191 cm) of an intensive care unit arrived at home at 6:30 a.m. from a night duty. He told his girl friend who was going to work that he is tired and would go to bed. At 7:30 p.m., the woman found the man dead lying face down on the bed. Rigor mortis had already established. In his trouser pockets a bottle of Tramal® (tramadol) was found. Until 1 year ago the male nurse had consumed Rohypnol® (flunitrazepam) which he had stolen from the

Toxicological analysis

Various body fluids and organ tissues were assayed for ethanol and drugs of abuse (acidic, basic and neutral organic drugs) using routine methods including immunochemical procedures and liquid–liquid as well as solid-phase extraction procedures with further analysis by gas chromatography/mass spectrometry (GC/MS) and high performance liquid chromatography with diode array detection (HPLC/DAD), the latter was used for quantitative determination of tramadol.

Results

Following standard extraction procedures tramadol, N-desmethyltramadol, and O-desmethyltramadol were identified in the urine sample by GC/MS by comparison of their mass spectra with reference libary spectra and reference material. A quantitative determination of tramadol was made by HPLC/DAD. The results are shown in Table 1. All other tests for ethanol and drugs of abuse were negative. Especially, nor flunitrazepam neither 7-aminoflunitrazepam were detected.

Discussion

Tramadol peripheral blood concentration of 9.6 mg/l exceeded at least 30-times the normal therapeutic range. Highest concentrations were measured in urine and bile. The concentration of tramadol in liver and kidney, in relation to blood, failed to suggest a major sequestration of drug in either specimen. This was consistent with the reported volume of distribution (Vds) of 3 l/kg. The concentration of tramadol in the heart and peripheral blood specimens did not suggest a major difference (ratio

References (9)

  • K. Michaud et al.

    Fatal overdose of tramadol and alprazolam

    Forensic Sci. Int.

    (1999)
  • B. Levine et al.

    Tramadol distribution in four postmortem cases

    Forensic Sci. Int.

    (1997)
  • C.R. Lee et al.

    Tramadol: a preliminary review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic potential in acute and chronic pain states

    Drugs

    (1993)
  • K.E. Goeringer et al.

    Identification of tramadol and ist metabolites in blood from drug-related deaths and drug impaired drivers

    J. Anal. Toxicol.

    (1997)
There are more references available in the full text version of this article.

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