Naloxone-associated pulmonary edema following recreational opioid overdose

Kummer, Rebecca L.; Kempainen, Robert R.; Olives, Travis D.; Leatherman, James W.; Prekker, Matthew E.

doi:10.1016/j.ajem.2021.12.030

Cited by 13 publications

(15 citation statements)

References 15 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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“…Naloxone-induced non-cardiogenic pulmonary edema is a rare event that can occur following naloxone administration for reversing an opioid overdose ( 75 – 78 ). A proposed mechanism is that naloxone, by producing a rapid increase in catecholamines, produces an adrenergic crisis ( 79 , 80 ), causing shifts in blood volume from the systemic bed to the pulmonary bed, thereby increasing permeability and inducing pulmonary edema ( 81 ).…”

Section: Concerns Over High-dose Naloxonementioning

confidence: 99%

Fact vs. fiction: naloxone in the treatment of opioid-induced respiratory depression in the current era of synthetic opioids

Dahan,

Franko,

Carroll

et al. 2024

Front. Public Health

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Opioid-induced respiratory depression (OIRD) deaths are ~80,000 a year in the US and are a major public health issue. Approximately 90% of fatal opioid-related deaths are due to synthetic opioids such as fentanyl, most of which is illicitly manufactured and distributed either on its own or as an adulterant to other drugs of abuse such as cocaine or methamphetamine. Other potent opioids such as nitazenes are also increasingly present in the illicit drug supply, and xylazine, a veterinary tranquilizer, is a prevalent additive to opioids and other drugs of abuse. Naloxone is the main treatment used to reverse OIRD and is available as nasal sprays, prefilled naloxone injection devices, and generic naloxone for injection. An overdose needs to be treated as soon as possible to avoid death, and synthetic opioids such as fentanyl are up to 50 times more potent than heroin, so the availability of new, higher-dose, 5-mg prefilled injection or 8-mg intranasal spray naloxone preparations are important additions for emergency treatment of OIRDs, especially by lay people in the community. Higher naloxone doses are expected to reverse a synthetic overdose more rapidly and the current formulations are ideal for use by untrained lay people in the community. There are potential concerns about severe withdrawal symptoms, or pulmonary edema from treatment with high-dose naloxone. However, from the perspective of first responders, the balance of risks would point to administration of naloxone at the dose required to combat the overdose where the risk of death is very high. The presence of xylazines as an adulterant complicates the treatment of OIRDs, as naloxone is probably ineffective, although it will reverse the respiratory depression due to the opioid. For these patients, hospitalization is particularly vital. Education about the benefits of naloxone remains important not only in informing people about how to treat emergency OIRDs but also how to obtain naloxone. A call to emergency services is also essential after administering naloxone because, although the patient may revive, they may overdose again later because of the short half-life of naloxone and the long-lasting potency of fentanyl and its analogs.

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“…More serious complications, including cardiac events in the setting of catecholamine surge due to opioid withdrawal and pulmonary edema, are rare and have been reported in case series; prevalence data are not available. 7 Naloxone-induced pulmonary edema can be difficult to distinguish from opioid-induced pulmonary edema. 8 Adverse effects are mitigated by administering the minimum dose necessary to restore breathing and calling 911 for transport to emergency care.…”

Section: Safetymentioning

confidence: 99%

“…The potential risks of naloxone administration are rarely life-threatening and include opioid withdrawal symptoms such as nausea, vomiting, agitation, tachycardia, and hypertension. More serious complications, including cardiac events in the setting of catecholamine surge due to opioid withdrawal and pulmonary edema, are rare and have been reported in case series; prevalence data are not available . Naloxone-induced pulmonary edema can be difficult to distinguish from opioid-induced pulmonary edema .…”

Section: Safetymentioning

confidence: 99%