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

Abstract

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, we will 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.

Naloxone for Opioid Overdose: Reply

“…Milas and Varon 2 for their interest and careful reading of our article on the use of naloxone in the reversal of an opioid overdose as might occur in the community setting in the United States. 3 Individuals that overdose are commonly found in a state of unconsciousness, and these overdose victims, as recently discussed in the general media, 4 are often positive for fentanyl as well as for other substances ( e.g. , methamphetamine, xylazine, cannabis, or gabapentin), that affect not only breathing but also the level of consciousness.…”

Acute opioid overdose in pediatric patients

“…The focus of treatment should be prompt recognition and activation of the emergency response system and administration of high‐quality cardiopulmonary resuscitation (CPR). It is reasonable to administer naloxone to a child in respiratory arrest with a pulse in addition to standard basic life support/pediatric advanced life support (BLS/PALS) care 76–81 . No studies demonstrate improved outcomes for administering naloxone during cardiac arrest and providing high‐quality CPR should be the initial focus of a child found to be in arrest.…”

“…It is reasonable to administer naloxone to a child in respiratory arrest with a pulse in addition to standard basic life support/pediatric advanced life support (BLS/PALS) care. [76][77][78][79][80][81] No studies demonstrate improved outcomes for administering naloxone during cardiac arrest and providing highquality CPR should be the initial focus of a child found to be in arrest.…”

Intranasal Naloxone Repeat Dosing Strategies and Fentanyl Overdose

“…[1][2][3] Following a rise in opioid overdoses and deaths, including from fentanyl and its derivatives (hereinafter, fentanyl), 4,5 the FDA approved specific naloxone products for use by laypersons as single-use autoinjectors and intranasal sprays. 1,6,7 Due to challenges in conducting clinical efficacy trials in the community setting, these approvals were based on demonstrating that naloxone plasma concentrations are comparable to or greater than those achieved by approved, labeled routes of administration. 8 Intranasal naloxone products are sold in packages with 2 single-use nasal sprays and are approved for administration as a single dose with repeat doses every 2 to 3 minutes if the patient does not respond.…”

“…Naloxone is a mu-opioid receptor antagonist approved by the US Food and Drug Administration (FDA) to reverse opioid-induced respiratory depression . Following a rise in opioid overdoses and deaths, including from fentanyl and its derivatives (hereinafter, fentanyl), the FDA approved specific naloxone products for use by laypersons as single-use autoinjectors and intranasal sprays .…”