Modeling Supports Combinatorial Effects Between Pharmacological and Non-Pharmacological Interventions to Prevent Opioid-Induced Cardiac Arrest.

Few studies have quantified the effects of non-pharmacological interventions (e.g., rescue breathing) in the setting of community opioid overdose. We extended a previously validated model for opioid antagonists by incorporating the mechanism of rescue breathing, and quantified combinatorial effects between rescue breathing and various formulations of naloxone under different fentanyl overdose scenarios in a virtual patient population suffering from opioid-induced respiratory failure. We defined successful reversal of an overdose as fewer than 5% of the virtual population experiencing cardiac arrest after intervention. Our model showed that timely rescue breathing reduced the naloxone dose needed for successful overdose reversal from greater than 8 mg (intranasal) to less than 2 mg (intramuscular) and extended the naloxone rescue window to 10 minutes under a median fentanyl intravenous overdose scenario. Administration of 4 mg naloxone intranasally reduced the duration of rescue breathing needed from 11 hours to 5 minutes under a median fentanyl transmucosal overdose scenario. High-quality (as delivered by well-trained rescuers), but not low-quality (as delivered by laypersons), rescue breathing could successfully rescue severe opioid overdose scenarios. Even in cases where virtual subjects survived without naloxone, 4 mg intranasal naloxone provided benefit by shortening the time to recovery of spontaneous. Our results highlight the importance of utilizing both pharmacological and non-pharmacological interventions in reversal of overdose.