Opioid Overdose: Limitations in Naloxone Reversal of Respiratory Depression and Prevention of Cardiac Arrest

Anesthesiology. 2023 Sep 1;139(3):342-353. doi: 10.1097/ALN.0000000000004622.


Opioids are effective analgesics, but they can have harmful adverse effects, such as addiction and potentially fatal respiratory depression. Naloxone is currently the only available treatment for reversing the negative effects of opioids, including respiratory depression. However, the effectiveness of naloxone, particularly after an opioid overdose, varies depending on the pharmacokinetics and the pharmacodynamics of the opioid that was overdosed. Long-acting opioids, and those with a high affinity at the µ-opioid receptor and/or slow receptor dissociation kinetics, are particularly resistant to the effects of naloxone. In this review, the authors examine the pharmacology of naloxone and its safety and limitations in reversing opioid-induced respiratory depression under different circumstances, including its ability to prevent cardiac arrest.

Publication types

  • Review

MeSH terms

  • Analgesics, Opioid / adverse effects
  • Drug Overdose* / drug therapy
  • Heart Arrest* / chemically induced
  • Heart Arrest* / drug therapy
  • Heart Arrest* / prevention & control
  • Humans
  • Naloxone / pharmacology
  • Naloxone / therapeutic use
  • Narcotic Antagonists / pharmacology
  • Narcotic Antagonists / therapeutic use
  • Opiate Overdose* / drug therapy
  • Respiratory Insufficiency* / chemically induced
  • Respiratory Insufficiency* / drug therapy
  • Respiratory Insufficiency* / prevention & control


  • Naloxone
  • Analgesics, Opioid
  • Narcotic Antagonists