The conundrum of polysubstance overdose

Abstract

What is known and objective: Treating an opioid overdose using an opioid receptor antagonist (such as naloxone) makes mechanistic sense and can be effective.Unfortunately, the majority of current drug overdose deaths involve polysubstance use (i.e., an opioid plus a non-opioid).Comment: Respiratory depression induced by opioids results from excessive opioid molecules binding to opioid receptors. This effect can be reversed by an opioid receptor antagonist. However, the respiratory depression induced by non-opioid drugs is not due to action at opioid receptors; thus, an opioid receptor antagonist is ineffective in many of these cases. For respiratory depression induced by non-opioids, receptor antagonists are either not available (e.g., for propofol overdose) or there may be attendant risks with their use (e.g., seizures with flumazenil). This gives rise to a need for more effective ways to treat polysubstance overdose. What is new and conclusion:A new approach to treating opioid-induced respiratory depression due to drug overdose focuses on agents that stimulate respiratory drive rather than competing for opioid receptors. Such an approach is "agnostic" to the cause of the respiratory depression, so might be a potential way to treat polysubstance overdose.

Old Drugs and New Challenges: A Narrative Review of Nitazenes

“…Polysubstance abuse is increasingly prevalent [17], and the use of multiple drugs and/or alcohol concomitantly can result in a synergistic respiratory depression, with consequent decrease in oxygen saturation in the body, culminating in cerebral hypoxia [18,19]. While overdose toxicity is typically described as being either fatal or nonfatal with the implication that nonfatal overdoses cause no harm, opioid overdose is better thought of as occurring on a spectrum.…”

Use of Extracorporeal Membrane Oxygenation in Acutely Poisoned Pediatric Patients in United States: A Retrospective Analysis of the Extracorporeal Life Support Registry From 2003 to 2019

“…On the other hand, we observed a significantly higher survival rate in cases with single-agent exposure (72.2% vs 28.6%; p = 0.005) compared to the findings from the National Poison Data System (3). It is reasonable to surmise that multiple substance exposure may have resulted in more severe multiple organ dysfunction, decreasing the chance of patients’ recovery (23). Survival rate between two age groups (≤ 3 and 13–17 yr) were similar in our study, although the indication for ECMO was different.…”