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• W2936106308 abstract "To the Editor: We appreciate the insights of Dr. Koons and colleagues in response to our study “Hospital Observation Upon Reversal (HOUR) with Naloxone: A Prospective Clinical Prediction Rule Validation Study.” As they noted, a majority (85.4%) of our patients received intranasal (IN) naloxone rather than parenteral (IV) naloxone. This finding mirrors the national trend of increasing IN naloxone utilization.1 IN naloxone has many potential advantages over IV naloxone, especially when administered by individuals without formal medical training.2 We agree that it is ideal to administer a low initial dose of naloxone followed by a slow-dose titration to achieve reversal of respiratory depression, and we encourage trained medical professionals to follow this approach. However, this is not practical for EMTs, law enforcement officers, firefighters, or laypersons who generally have less training than paramedics, but who are more ubiquitous and more likely to be the first to encounter a patient who has overdosed. This is especially true for responders who do not have training in supportive airway management. In these scenarios, it is imperative to rapidly administer a dose of naloxone that will reverse the patient's respiratory depression while awaiting emergency medical services. Although larger doses may precipitate opioid withdrawal, the minor risks associated with this are far outweighed by the benefits of a restored respiratory drive.3 It is important to consider the pharmacokinetic differences of IN naloxone. However, the clinical implications of these differences are not well established. The absorption and onset of action of IN naloxone are similar to intramuscular (IM) naloxone, but are slower than IV naloxone.4 The delayed onset can create a false impression that the dose was inadequate and may result in unnecessary redosing and opioid withdrawal symptoms.5 The prolonged absorption of IN naloxone also contributes to a higher area under the curve when compared to IV naloxone. This means that although administering 4 mg of IN naloxone and 0.4 mg of IV naloxone results in nearly identical peak serum levels, IN naloxone maintains a higher concentration in the blood than IV naloxone over a 120-minute period.6 Although these data support that IN naloxone remains in circulation for a longer time than IV naloxone, it does not provide any evidence that there is a difference in the pharmacodynamics (the duration of naloxone's clinical effect) after IN or IV administration. Although pharmacokinetics can be helpful in guiding patient care, it is important to recognize that they do not always correlate to the duration of a drug's clinical effects (pharmacodynamics).7, 8 This clinical prediction rule is designed to inform the discussion about the risks of recurrent toxicity during the shared decision-making process, but it is just one piece of the puzzle. We strongly agree with Dr. Koons and colleagues that initiating medication assisted treatment, establishing linkage to care, reviewing high-risk opioid behaviors (using opioids alone or in combination with other central nervous system depressants), and providing take-home naloxone are important components of appropriate patient care. Emergency physicians should not rush to discharge patients until all of these pieces are addressed." @default.
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• W2936106308 date "2019-05-23" @default.
• W2936106308 modified "2023-09-27" @default.
• W2936106308 title "Pharmacokinetics and Pharmacodynamics of Naloxone" @default.
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• W2936106308 doi "https://doi.org/10.1111/acem.13768" @default.
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