Prehospital Naloxone and Emergency Department Adverse Events: A Dose-Dependent Relationship

Maloney, Lauren; Alptunaer, Timur; Coleman, G.; Ismael, Suleiman; McKenna, Peter; Marshall, R. T.; Hernández, Cristina Sánchez; Williams, Daryl W.

doi:10.1016/j.jemermed.2020.07.009

Cited by 5 publications

(10 citation statements)

References 25 publications

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“…In the event of an opioid overdose, naloxone may have adverse effects, albeit clinical data indicate that serious events are rare. 3,[41][42][43][44][45][46] In case of individuals with an opioid use disorder, withdrawal symptoms may become apparent after naloxone administration; symptoms include tachycardia, mild agitation or anxiety, hypertension abdominal pain, malaise, and insomnia. 2,3,41 In extremely rare cases, abrupt reversal of opioid-induced respiratory depression by naloxone has been followed by seizures, pulmonary edema, cardiac dysrhythmias, hypertension, and cardiac arrest.…”

Section: Naloxone Safetymentioning

confidence: 99%

“…2,3,41 In extremely rare cases, abrupt reversal of opioid-induced respiratory depression by naloxone has been followed by seizures, pulmonary edema, cardiac dysrhythmias, hypertension, and cardiac arrest. 3,[42][43][44][45] While a direct dose and effect relationship has not been established, the cardiopulmonary complications may be secondary to a sudden release of catecholamines after highdose or rapidly injected naloxone. Vasoconstriction and an increase in blood pressure and the occurrence of tachyarrhythmias may be the basis of these complications, with pulmonary edema arising from a rapid fluid shift or from inspiration against a closed glottis (negative pressure pulmonary edema).…”

Section: Naloxone Safetymentioning

confidence: 99%

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

Lemmen

Florian

et al. 2023

Anesthesiology

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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.

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Section: Naloxone Safetymentioning

confidence: 99%

Section: Naloxone Safetymentioning

confidence: 99%

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

Lemmen

Florian

et al. 2023

Anesthesiology

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“…Finally, the third study utilizing EMS and ED data from a suburban academic tertiary care center between 2014 to 2017 found 160 of 513 (31%) patients received !2 naloxone administrations in the prehospital setting, while 41 (54%) received multiple doses in the ED. 21 It is noted that in each of these combined EMS/ED studies, sample sizes were relatively modest, participants were treated at either 1 or 2 tertiary care centers representing a relatively confined geographic area and generally did not include those who refused transport to the hospital upon ambulance arrival, thereby potentially limiting generalizability. It is also notable that MNA rates in studies utilizing EMS or combined EMS/ED data were generally low relative to bystander-based MNA rates in this review.…”

Section: Resultsmentioning

confidence: 99%

“…Only 5 studies in this review documented OWS or other adverse events related to naloxone and reported a range from 0.6% to 38%. 20,21,24,27,31 A recent systematic literature review evaluating naloxone dosing and adverse events (AEs) found that only half of the reviewed studies (86/174) reported AEs, and among these, 11% of patients experienced OWS. 38 The lack of documented cases of OWS following increased naloxone dosing reported could suggest that the risk is low, but it may also reflect the difficulty in capturing this metric, thus more research is needed to better understand the likelihood of OWS with increased naloxone dosing.…”

Section: Opioid Withdrawal Syndrome (Ows)mentioning

confidence: 99%

“…With the increase of synthetic opioids and the rapid onset of effect, evidence is emerging suggesting the need for increased doses of naloxone to reverse opioid toxicity. Numerous studies have been published examining the occurrence of multiple naloxone administrations (MNA) in opioid overdose reversals, [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] however, these studies have varied in study design, scientific rigor, sample size and geographic locations, making it difficult to obtain a comprehensive understanding of the frequency and trends of MNA occurrence in the US.…”

Section: Introductionmentioning

confidence: 99%

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The Need for Multiple Naloxone Administrations for Opioid Overdose Reversals: A Review of the Literature

Abdelal¹,

Banerjee²,

Carlberg-Racich

et al. 2022

Substance Abuse

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Background A growing challenge in the opioid epidemic is the rise of highly potent synthetic opioids, (i.e., illicitly manufactured fentanyl [IMF]) entering the US non-prescription opioid market. Successful reversal may require multiple doses of naloxone, the standard of care for opioid overdose. We conducted a narrative literature review to summarize the rates of multiple naloxone administrations (MNA) for opioid overdose reversal. Methods: A MEDLINE search was conducted for published articles using MESH search terms: opioid overdose, naloxone and multiple naloxone administration. Of the 2,101 studies identified, articles meeting inclusion/exclusion criteria were reviewed, categorized by primary and secondary outcomes of interest and summarized by data source and study design. Results: A total of 24 articles meeting eligibility criteria were included. Among EMS-based studies, MNA rates ranged from 9% to 53%; in general, bystander-reported studies were notably higher, from 16% to 89%. Variation in study design, data sources, year and geography, may have contributed to these ranges. Three studies that included longitudinal results reported a significant percent increase between 26% and 43% in annual MNA rates or a significant increase in mean naloxone doses over time (p < .001). Conclusions: This summary found that multiple naloxone administrations during opioid overdose encounters vary widely, have occurred in up to 89% of all opioid overdoses, and have significantly increased over time. Higher naloxone formulations may fulfill an unmet need in opioid overdose reversals, given the rising rates of overdoses involving IMF. Further studies are needed to gain a better understanding of MNA during opioid overdose encounters, particularly across a wider geographic region in the US in order to inform continuing efforts to combat the opioid epidemic.

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Adverse Effects After Prehospital Administration of Naloxone by Bystanders: A Preliminary Study

Du Pont,

Fenderson,

Hunter

et al. 2024

Prehosp. Disaster med.

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Objective: Opioid use disorder is a cause of significant morbidity and mortality. In order to reverse opioid overdose as quickly as possible, many institutions and municipalities have encouraged people with no professional medical training to carry and administer naloxone. This study sought to provide preliminary data for research into the rates of adverse effects of naloxone when administered by bystanders compared to Emergency Medical Services (EMS) personnel, since this question has not been studied previously. Methods: This was a retrospective cohort study performed at an urban, tertiary, academic medical center that operates its own EMS service. A consecutive sample of patients presenting to EMS with opioid overdose requiring naloxone was separated into two groups based on whether naloxone was administered by bystanders or by EMS personnel. Each group was analyzed to determine the incidence of four pre-specified adverse events. Results: There was no significant difference in the rate of adverse events between the bystander (19%) and EMS (16%) groups (OR = 1.23; 95% CI, 0.63 - 2.32; P = .499) in this small sample. Based on these initial results, a study would need a sample size of 6,188 in order to reach this conclusion with 80% power. Similarly, there were no significant differences in the rates of any of the individual adverse events. Secondary analysis of patients’ demographics showed differences between the two groups which generate hypotheses for further investigation of disparities in naloxone administration. Conclusions: This preliminary study provides foundational data for further investigation of naloxone administration by bystanders. Adverse events after the prehospital administration of naloxone are rare, and future studies will require large sample sizes. These preliminary data did not demonstrate a statistically significant difference in adverse event rates when comparing naloxone administration by bystanders and EMS clinicians. This study provides data that will be useful for conducting further research on multiple facets of this topic.

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Prehospital Naloxone and Emergency Department Adverse Events: A Dose-Dependent Relationship

Cited by 5 publications

References 25 publications

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

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

The Need for Multiple Naloxone Administrations for Opioid Overdose Reversals: A Review of the Literature

Adverse Effects After Prehospital Administration of Naloxone by Bystanders: A Preliminary Study

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