Incidence, Reversal, and Prevention of Opioid-induced Respiratory Depression

Abstract

Opioid treatment of pain is generally safe with 0.5% or less events from respiratory depression. However, fatalities are regularly reported. The only treatment currently available to reverse opioid respiratory depression is by naloxone infusion. The efficacy of naloxone depends on its own pharmacological characteristics and on those (including receptor kinetics) of the opioid that needs reversal. Short elimination of naloxone and biophase equilibration half-lives and rapid receptor kinetics complicates reversal of high-affinity opioids. An opioid with high receptor affinity will require greater naloxone concentrations and/or a continuous infusion before reversal sets in compared with an opioid with lower receptor affinity. The clinical approach to severe opioid-induced respiratory depression is to titrate naloxone to effect and continue treatment by continuous infusion until chances for renarcotization have diminished. New approaches to prevent opioid respiratory depression without affecting analgesia have led to the experimental application of serotinine agonists, ampakines, and the antibiotic minocycline.

Review article: Practical current issues in perioperative patient safety

“…This issue has received considerable attention, [26][27][28][29] and an appreciable number of preventable catastrophic accidents continue to occur. However, while increased monitoring of at-risk patients (particularly when patient-controlled analgesia is used) seems indicated, consensus has not been achieved regarding a ''get to zero'' approach of eliminating these mishaps.…”

Changes in the hemodynamic and thyroid functions of rats treated by opium

“…Studies indicated that opioid drugs can lead to respiratory depression and acidaemia [7]. Aguiler et al, [2000] postulated that acidaemia decreases the binding of calcium to plasma protein with subsequent increases in the ionized calcium [23].…”

Opioids: a two-faced Janus

“…Whilst respiratory depression can be effectively treated by the opioid antagonists naloxone and naltrexone, analgesic efficacy is also reduced. Agents such as the a-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid (AMPA) receptor agonists (ampakines) and minocycline have been shown to suppress opioid-induced respiratory depression without affecting analgesic efficacy 81,82 . Serotonin (5-hydroxy tryptamine,5-HT) agonists, by virtue of the role of 5-HT neurones in the maintenance of respiratory drive, have also been evaluated for the suppression of opioid-induced respiratory depression, but not found to be effective 82 .…”

“…Agents such as the a-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid (AMPA) receptor agonists (ampakines) and minocycline have been shown to suppress opioid-induced respiratory depression without affecting analgesic efficacy 81,82 . Serotonin (5-hydroxy tryptamine,5-HT) agonists, by virtue of the role of 5-HT neurones in the maintenance of respiratory drive, have also been evaluated for the suppression of opioid-induced respiratory depression, but not found to be effective 82 . In contrast to the approaches designed to mitigate the adverse effects of classical opioids outlined above, novel non-classical molecules with similar efficacy but reduced side effects are in clinical development.…”