The Role of Danavorexton for Perioperative Opioid-Induced Respiratory Depression and Sedation: A Narrative Review

Alexia J Enache,1 Collin J Harris,1 Toluwanimi I Atewogbola,1 Aiden B De Witt,2 Shahab Ahmadzadeh,2 David W McGregor Jnr,2 Sahar Shekoohi,2 Alan D Kaye2 1School of Medicine, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA, USA; 2Department of Anesthesiology, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA, USACorrespondence: Sahar Shekoohi, Department of Anesthesiology, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA, 71103, USA, Email sahar.shekoohi@lsuhs.eduAbstract: Opioid-induced respiratory depression (OIRD) and sedation are significant perioperative complications that limit safe and effective use of opioid analgesia. Current reversal agents, such as naloxone, are effective at treating OIRD but may negatively affect pain management, leaving a critical clinical gap in perioperative pain management. The orexin system has a pivotal role in wakefulness and respiratory drive. Danavorexton is a selective orexin-2 receptor agonist that targets this system to promote arousal and respiratory function. It has emerged as a pharmacological option for OIRD and reversal for opioid sedation without compromising analgesia. Additionally, studies have shown that danavorexton can enhance tidal volume and minute ventilation in patients who are being managed with opioids. This narrative review discusses the pathophysiology of OIRD, current reversal strategies, and the emerging evidence supporting the use of Danavorexton in perioperative care. Danavorexton represents a novel and potentially transformative adjunct that could improve postoperative recovery, reduce adverse opioid-related events, and enhance patient safety in the surgical setting.Keywords: opioid-induced respiratory depression, danavorexton, orexin receptor agonist, perioperative sedation, opioid analgesia