Question

The incidence of opioid-overdose-related deaths has clearly increased in the past decade, with recent estimates of up to 17% of OHCA being opioid-related in 2023. [1,2] The use of naloxone for opiate reversal in overdose is well-established, with reasonable inference but no formal proof that its use could help in opioid-associated out of hospital cardiac arrest (OA-OHCA). [3] The August publication of two trials [4,5] retrospectively examining naloxone administration in OHCA offers some perspectives…

• Patients receiving naloxone for OHCA are:
  • More often be younger, with fewer comorbidities, but more often unwitnessed than their non-naloxoned counterparts
  • More likely to have opioid OD as a presumed etiology

and

• Naloxone administration is associated with:
  • Increased rates/odds of ROSC and survival to hospital discharge, whether OD is suspected or not
  • And “early” naloxone (given prior to EMS IV/IO access) is associated with increased rates of DC with good neuro outcome in PEA compared to receipt after IV/IO access or none at all

[View “Visual Diagnosis” for slightly more detail on the referenced studies.]

Bottom Line: While prospective trials are absolutely needed to offer more definitive evidence regarding the use of empiric naloxone in nontraumatic OHCA, the rising incidence of OA-OHCA in the U.S. and current findings are convincing enough to encourage early naloxone administration, especially in populations with higher incidence of opioid use.

U.S. Mortality due to Opioid Overdose (CDC data)

Answer

Dillon et al, JAMA

• Restrospective cohort
• EMS adult patients with nontraumatic OHCA
• Received naloxone (14.2%) vs. didn't 
  • Naloxone group 
    • Younger, more likely to be male, fewer comorbidities
    • Given more in nonshockable OHCA and unwitnessed arrests
• Primary outcome = survival to DC (naloxone 15.9% vs. 9.7%)
• Secondary outcome = ROSC (naloxone 34.5% vs. 22.9%)
  • Improved outcomes whether EMS assumed drug-related or not

Strong et al, Resuscitation

• Retrospective cohort from EMS database
• Adult patients with nontraumatic nonshockable OHCA
• Received naloxone before IV/IO access ("early") versus after IV/IO or not at all
  • Early naloxone group
    • Younger, more often arrested outside the home, more often unwitnessed
    • More likely to have opioid OD as presumed etiology
• Primary outcome = ROSC on ED arrival (early 35.1% vs. 21.6%, p=0.022)
• Secondary outcomes 
  • Survival to admission (early 45.6 vs. 22.5%, p <0.001)
  • Survival to DC (early 14% vs. 3.3%, p<0.001)
  • Good neuro outcome (early 12.3% vs. 2.9%, p=0.002) – on stratification, this was seen in PEA but not asystole as initial rhythm

References

1. Wang RC, Montoy JCC, Rodriguez RM, et al. Trends in presumed drug overdose out-of-hospital cardiac arrests in San Francisco, 2015-2023. Resuscitation. 2024 May;198:110159. doi: 10.1016/j.resuscitation.2024.110159. 
2. Smith G, Beger S, Vadeboncoeur T, et al. Trends in overdose-related out-of-hospital cardiac arrest in Arizona. Resuscitation. 2019 Jan;134:122-126. doi: 10.1016/j.resuscitation.2018.10.019. 
3. van Lemmen M, Florian J, Li Z, et  al. 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. Erratum in: Anesthesiology. 2023 Dec 1;139(6):920. doi: 10.1097/ALN.0000000000004760.
4. Dillon DG, Montoy JCC, Nishijima DK, et al. Naloxone and Patient Outcomes in Out-of-Hospital Cardiac Arrests in California. JAMA Netw Open. 2024 Aug 1;7(8):e2429154. doi: 10.1001/jamanetworkopen.2024.29154. 
5. Strong NH, Daya MR, Neth MR, et al. The association of early naloxone use with outcomes in non-shockable out-of-hospital cardiac arrest. Resuscitation. 2024 Aug;201:110263. doi: 10.1016/j.resuscitation.2024.110263.

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