Rapid Rx Quiz: Opioid Overdose

Medscape

17-07-2025

Recent efforts in prevention, treatment, and harm reduction have led to encouraging signs of progress in the opioid epidemic. Increased public awareness, expanded access to naloxone, and evolving prescribing practices have all contributed to a decline in overdose deaths. However, due to the widespread availability of synthetic opioids (particularly fentanyl), clinicians must remain vigilant because overdose presentations are becoming increasingly complex and resistant to standard interventions. Effective management requires rapid clinical decision-making and a thorough understanding of opioid pharmacology and toxicity.
How much do you know about managing opioid overdose? Test yourself with this quick quiz.
Activation of cardiac opioid receptors during overdose leads to membrane hyperpolarization and increased vagal tone. These effects promote bradycardia and peripheral vasodilation, both of which can lead to hypotension. In addition, systemic histamine release can further intensify vasodilation and might result in profound hypotension.
Learn more about the pathophysiology of opioid toxicity.
According to ASAM guidelines, naloxone should be administered to all pregnant women experiencing an opioid overdose to prioritize maternal survival. Delaying or withholding naloxone during overdose due to concerns about fetal effects is not recommended. Although naloxone might precipitate opioid withdrawal, this risk is outweighed by the need to reverse potentially fatal respiratory depression.
Learn more about the presentation of opioid toxicity.
Buprenorphine has an exceptionally high affinity for the mu opioid receptor, making it difficult to displace with naloxone. A bolus dose of naloxone is recommended to achieve a high enough serum concentration to begin competitively binding at these receptor sites. Continuous infusion alone might be insufficient to rapidly reverse respiratory depression without an initial bolus.
Hemodialysis is not an effective treatment for buprenorphine overdose, and avoiding dialysis is not a relevant consideration. Although benzodiazepines are commonly co-ingested with buprenorphine and might contribute to respiratory depression, this does not explain the need for a naloxone bolus, because naloxone does not reverse benzodiazepine effects. Buprenorphine has a long half-life compared to many other opioid drugs, but this affects the duration of monitoring and the potential need for prolonged naloxone infusion, not the decision to administer a bolus dose.
Learn more about buprenorphine/naloxone toxicity.
Recommended criteria for emergency department discharge following 6-12 hours of observation after naloxone reversal of opioid overdose include an oxygen saturation ≥ 92% on room air. Other criteria include a Glasgow Coma Scale score of 15, a respiratory rate ≥ 10 breaths/min, and blood pressure between 110/90 mm Hg and 140/90 mm Hg. These parameters help confirm sustained clinical stability following naloxone reversal.
Learn more about emergency department care of opioid toxicity.
Fentanyl exhibits a biphasic plasma concentration profile, with an initial peak followed by a decline. However, in overdose, secondary plasma peaks might occur 45-60 minutes or even hours later, a phenomenon referred to as 'fentanyl rebound.' These delayed increases in fentanyl concentration have been linked to new or recurrent respiratory depression, sometimes requiring additional naloxone. Nalmefene injection or nalmefene intranasal are other options for treating fentanyl overdose. Nalmefene has a longer half-life than naloxone.
Despite rapid hepatic metabolism, fentanyl has a prolonged and variable duration of effect due to redistribution into peripheral tissues. Because fentanyl is highly lipophilic, it readily accumulates in tissues like muscle and fat, especially with repeated use.
Fentanyl-induced skeletal muscle rigidity, including the chest wall rigidity known as wooden chest syndrome, typically occurs within minutes of exposure. This complication can make airway management more difficult in overdose scenarios.
Learn more about fentanyl.