Tramadol as a fentanyl adulterant: Prevalence and management in a ToxIC Fentalog study prospective cohort

Background: Tramadol is an adulterant of illicit opioids. As it is a serotonin-norepinephrine reuptake inhibitor as well as a μ-opioid agonist, tramadol adulteration may worsen overdose signs and symptoms or affect the amount of naloxone patients receive.

Methods: This is a multicenter, prospective cohort of adult patients with suspected opioid overdoses who presented to one of eight United States emergency departments and were included in the Toxicology Investigators Consortium's Fentalog Study. Patient serum was analyzed via liquid chromatography quadrupole time-of-flight mass spectroscopy to detect opioids, novel psychoactive substances, and adulterants. Patients were separated into groups of those with tramadol detected versus no tramadol detected. Differences in naloxone administration, intubation, performance of cardiopulmonary resuscitation (CPR), or death between those exposed or not exposed to tramadol were evaluated.

Results: From September 21, 2020 - October 31, 2021; 2298 patients were screened and 537 met inclusion criteria. Eighty-one patients (15 %) tested positive for tramadol. There was no significant difference found between those who reported chronic prescription opioid use (p = 0.81) or reported chronic pain (p = 0.27). Additionally, no difference was found between groups in the number of patients receiving a single, second, or third dose of naloxone (p = 0.25; 0.92; 0.59) or the proportion initiated on a naloxone infusion (p = 0.84). Similarly, there was no difference in outcomes of intubation, CPR, or death (p = 0.26; 0.75; 0.29).

Conclusions: Tramadol was identified in a subset of patients presenting to the Emergency Department with opioid overdoses suggesting adulteration of illicitly manufactured fentanyl with tramadol. Its presence was not associated with a lack of treatment response, difference in severity of overdose, or increased risk of complications.