Abstract
Importance: Opioid overdose is the commonest cause of drug-related deaths worldwide. Naloxone is an effective treatment when instituted early. The emergence of highly potent novel synthetic opioids such as nitazenes and fentanyl analogues has led to a systematic reappraisal of the evidence on management of opioid toxicity with naloxone and development of evidence-based clinical guidelines to reduce opioid-related deaths.
Observations: Guidelines on management of opioid-associated out-of-hospital cardiac arrest recommend standard resuscitation alone in pulseless patients and administration of naloxone if there is uncertainty about the presence of a pulse. For pre-hospital and in-hospital reversal of respiratory depression, intravenous or intranasal naloxone is recommended. Current guidelines recommend a titrated dosing strategy in hospital to reduce the risk of opioid withdrawal. New formulations of intranasal naloxone have been approved to facilitate take-home naloxone and community-based naloxone distribution programmes to reduce opioid-related deaths. Nalmefene and buprenorphine are existing licensed drugs which are being considered as alternatives to naloxone for toxicity from long-acting opioids. Several new experimental antidotes are currently in development to counter the threat from novel synthetic opioids.
Conclusions: Naloxone remains the gold standard antidote for opioid toxicity, both for pre-hospital and hospital use. Further research is required to determine the optimal dose and route of administration. New antidotes are in development but require randomised clinical trials to test their safety and efficacy before they can be implemented in clinical practice.