A review on tramadol toxicity: mechanism of action, clinical presentation, and treatment

Abstract

Aims As an analgesic that acts upon the central nervous system (CNS), tramadol has gained popularity in treating moderate to severe pain. Recently, it has been increasingly reported as a drug of misuse with intentional overdoses or intoxications. This review focuses on tramadol intoxication in humans and its effects on different systems. Subject and method This narrative review provides a comprehensive view of the pharmacokinetics, mechanism of action, and incidence of tramadol toxicity with an in-depth look at its side effects. In addition, the main approaches to the management of tramadol poisoning are described. Results Tramadol poisoning can affect multiple organ systems: gastrointestinal, central nervous system (seizure, CNS depression, low-grade coma, anxiety, and over time anoxic brain damage), cardiovascular system (palpitation, mild hypertension to life-threatening complications such as cardiopulmonary arrest), respiratory system, renal system (renal failure with higher doses of tramadol intoxication), musculoskeletal system (rhabdomyolysis), endocrine system (hypoglycemia), as well as, cause serotonin syndrome. Seizure, a serious nervous disturbance, is more common in tramadol intoxication than with other opioids. Fatal tramadol intoxications are uncommon, except in ingestion cases concurrent with other medications, particularly CNS depressants, most commonly benzodiazepines, and ethanol. Conclusion With the increasing popularity of tramadol, physicians must be aware of its adverse effects, substantial abuse potential, and drug interactions, to weigh its risk–benefit ratio for pain management. Alternative therapies might be considered in patients with a previous overdose history to reduce risks for adverse outcomes.

Comparison of Online Patient Reviews and National Pharmacovigilance Data for Tramadol-Related Adverse Events: Comparative Observational Study

“…However, there is insufficient empirical evidence that tramadol is safer than other opioids. Recent systematic reviews have revealed that tramadol is more likely to induce severe adverse events (AEs) such as seizures and hypoglycemia than other opioids [ 9 - 11 ]. Some studies suggest that tramadol has a similar or higher risk of long-term opioid use than other short-acting opioids [ 12 , 13 ].…”

Molecular Network-Based Identification of Tramadol Metabolites in a Fatal Tramadol Poisoning

“…We applied the proposed workflow to comprehensively identify metabolites of tramadol, a widely prescribed central-acting analgesic. Based on data obtained using LC-HRMS/MS with polarity switching in DDA mode, we first studied the analytical features of tramadol and its demethylated metabolites, i.e., O-desmethyl tramadol, N-desmethyl tramadol, and N,O-desmethyl tramadol [ 19 , 20 ]. We then analyzed urine and plasma samples obtained from a severely tramadol-poisoned 32-year-old female managed in the intensive care unit two days after self-ingestion of 9 g tramadol in a suicide attempt [ 21 ].…”

“…We then analyzed urine and plasma samples obtained from a severely tramadol-poisoned 32-year-old female managed in the intensive care unit two days after self-ingestion of 9 g tramadol in a suicide attempt [ 21 ]. Plasma tramadol concentration on admission was 10.05 mg/L, a highly toxic concentration (toxic range, >1 mg/L) [ 19 , 20 ]. Despite optimal management, poisoning resulted in the patient’s death.…”

Tramadol intoxication in infants: experience at a tertiary care hospital in Dhaka, Bangladesh

“…8 Others include seizures, dizziness, confusion, nausea, vomiting, constipation, haemodynamic instability, headache and dry mouth. 3,[9][10][11][12] Blood glucose abnormality, hepatic injury and anaphylaxis are also evidenced. [12][13][14] Toxicity can be reversed by naloxone without significant adverse effects.…”

“…3,[9][10][11][12] Blood glucose abnormality, hepatic injury and anaphylaxis are also evidenced. [12][13][14] Toxicity can be reversed by naloxone without significant adverse effects. But there is evidence of seizure after naloxone.…”