Education  |   May 2018
Averting Opioid-induced Respiratory Depression without Affecting Analgesia
Author Notes
  • From the Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands.
  • This is a 2017 Frontiers in Opioid Pharmacotherapy Symposium article.
    This is a 2017 Frontiers in Opioid Pharmacotherapy Symposium article.×
  • Submitted for publication November 8, 2017. Accepted for publication February 20, 2018.
    Submitted for publication November 8, 2017. Accepted for publication February 20, 2018.×
  • Address correspondence to Dr. Dahan: Leiden University Medical Center, H5-22, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. a.dahan@lumc.nl. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Education / Review Article / Central and Peripheral Nervous Systems / Pain Medicine / Pharmacology / Respiratory System / Opioid
Education   |   May 2018
Averting Opioid-induced Respiratory Depression without Affecting Analgesia
Anesthesiology 5 2018, Vol.128, 1027-1037. doi:10.1097/ALN.0000000000002184
Anesthesiology 5 2018, Vol.128, 1027-1037. doi:10.1097/ALN.0000000000002184
Abstract

The ventilatory control system is highly vulnerable to exogenous administered opioid analgesics. Particularly respiratory depression is a potentially lethal complication that may occur when opioids are overdosed or consumed in combination with other depressants such as sleep medication or alcohol. Fatalities occur in acute and chronic pain patients on opioid therapy and individuals that abuse prescription or illicit opioids for their hedonistic pleasure. One important strategy to mitigate opioid-induced respiratory depression is cotreatment with nonopioid respiratory stimulants. Effective stimulants prevent respiratory depression without affecting the analgesic opioid response. Several pharmaceutical classes of nonopioid respiratory stimulants are currently under investigation. The majority acts at sites within the brainstem respiratory network including drugs that act at α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (ampakines), 5-hydroxytryptamine receptor agonists, phospodiesterase-4 inhibitors, D1-dopamine receptor agonists, the endogenous peptide glycyl-glutamine, and thyrotropin-releasing hormone. Others act peripherally at potassium channels expressed on oxygen-sensing cells of the carotid bodies, such as doxapram and GAL021 (Galleon Pharmaceuticals Corp., USA). In this review we critically appraise the efficacy of these agents. We conclude that none of the experimental drugs are adequate for therapeutic use in opioid-induced respiratory depression and all need further study of efficacy and toxicity. All discussed drugs, however, do highlight potential mechanisms of action and possible templates for further study and development.