Tramadol (Ultram®) Concentrations in Death Investigation and Impaired Driving Cases and Their Significance

Abstract

We reviewed a series of 66 deaths in Washington State between 1995–2000 in which tramadol (Ultram® and Ultracet®, Ortho-McNeil) was detected in the decedent's blood, in order to assess the role tramadol was determined to have played. Additionally, we reviewed a series of 83 impaired driving cases in which tramadol was detected in order to establish a non-lethal blood tramadol concentration reference range. In both populations, tramadol was consistently found together with other analgesic, muscle relaxant, and CNS depressant drugs. Death was rarely attributable to tramadol alone. However, tramadol may be a significant contributor to lethal intoxication when taken in excess with other drugs, via the potential interaction with serotonergic antidepressant medications, as well as the potential for increased CNS depression. Although the incidence of tramadol detection has increased consistently over the last eight years, there is no evidence of a corresponding increase in the number of cases in which death was attributed solely to tramadol. Blood drug concentrations in many deaths exceeded the therapeutic serum range of 0.28–0.61 mg/L (1); however, the concentrations overlapped almost completely with the range identified in living subjects arrested for impaired driving. These findings suggest caution in the interpretation of blood tramadol concentrations outside of the recognized therapeutic range. It also suggests that the drug, even when used in moderate excess, is not a principle cause of death in suicidal or accidental deaths.

Fatal unintentional intoxications with tramadol during 1995–2005

“…According to our knowledge previous studies have not investigated the presence or absence of intention among the cases of tramadol intoxications. A comparable forensic US study concluded that despite increased detection of tramadol in forensic investigations, no corresponding increase occurred in the number of deaths solely attributable to tramadol [16]. This has been confirmed by the FDA [21] and the manufacturer Johnson & Johnson [11].…”

“…Using forensic materials, Clarkson et al [16] reported that tramadol might be a significant contributor to lethal intoxication when taken in excess with other drugs that depress central nervous functions, such as analgesics, muscle relaxants and antidepressants.…”

Severe acute lactic acidosis and hypoglycemia due to isolate tramadol poisoning

“…A frozen vial of the patient's blood was then sent to a specialized laboratory for assessment of tramadol and O-demethyl-tramadol (the main metabolite), which yielded blood concentrations of 26.1 mg/dL of tramadol (largely exceeding the serum therapeutic ranhe of 0.28-0.61 mg/dL) and 5.3 mg/dL of O-demethyltramadol, respectively. 19 Interestingly, it was lately found that the patient had obtained the tramadol bottles by another jailed man, who was using the drug for chronic post-traumatic pain.…”

Psychoactive prescription drug use disorders, misuse and abuse : Pharmacoepidemiological aspects

“…These have shown that tramadol may induce physical dependence and withdrawal reactions, and is implicated in misuse, abuse and diversion (143), as well as intoxications, emergency department visits (185), and drug-related deaths (186,187). Yet, the addictive properties of tramadol are considered to be low (188)(189)(190). Notably, due to other drugrelated problems including some adverse reactions the benefit-risk profile of tramadol at the effective dose is a matter of debate (191).…”