Reversal Agents: Naloxone vs Flumazenil

September

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Coming soon

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One of the most common questions I receive at my courses relates to reversal agents. When and why would you use one versus the other? I love it when students ask this question because it opens the door to some very important topics that can save lives – literally.

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Two Keys

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There are two keys to understanding these medications: How do they work? What is happening to the patient that requires a reversal agent? Most people remember that these agents are given “to reverse an overdose”. While this is technically true, it’s overly simple and has led many providers to make mistakes. Let me explain these medications and their use from my perspective.

 Naloxone is an opioid antagonist. It binds to mu opioid receptors and keeps the narcotics from having their pain-relieving effects. In doing so, it also reverses the respiratory depression associated with too much narcotics. Naloxone is easily administered intramuscularly, intravenously, and even in nasal spray. It reverses narcotic effects very quickly with each of these administration routes.

 

Flumazenil is a benzodiazepine reversal agent. It is quite different from naloxone in that it is labeled for use as an intravenous agent. This is important because many providers are giving patients benzodiazepines orally and don’t place IVs. I have heard that some doctors are administering flumazenil intramuscularly or sublingual, but off-label use is sometimes complicated and risky.

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Benzodiazepines by themselves almost never cause respiratory depression. Don’t forget this!

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So, now to the nitty-gritty. Which one to choose and which situation? Let’s start with a phrase that I want burned into your mind: Benzodiazepines by themselves almost never cause respiratory depression. Don’t forget this! They DO, however, work in synergy with narcotics to amplify the effects of both drugs. Synergy. Synergy means that the combination of the drugs is more potent than either of them by themselves. This is how providers can make a mistake that costs time and sometimes worse.

 Here is a good example. You administer triazolam, a benzodiazepine, and the patient slows their breathing to only a few times a minute. Their oxygen saturation drops and you are having trouble waking them and getting them to breathe. Because you administered triazolam, you reach for the flumazenil. You try to give it off label intramuscularly. While the patient stirs a little, they continue to breathe very slowly and the saturation is in the 60s. This is a very common situation and I’ve been asked about this at almost every seminar I’ve given. What’s going on? Why didn’t the reversal work? The most likely reason is synergy with a narcotic. Remember that many patients take narcotics and often don’t mention them. In our example, if you administer naloxone intramuscularly, the patient would likely increase their respiratory rate in a minute or less.

 Perhaps the best way to think about reversal agents is a two-fold approach. 

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First, think about what problem the patient is having that you are trying to fix. If the patient has respiratory depression, consider naloxone right away. If they are breathing well but simply won’t wake up, consider reversing the benzodiazepine with flumazenil.

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Second, consider both the drugs you gave and the drugs they are already taking.

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Conclusion

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 Since respiratory depression from narcotics (or synergy with narcotics) is dangerous and certainly very likely in our patient population, I strongly suggest that all providers have naloxone available and be familiar with its use. I’m not suggesting that it is a silver bullet for all situations, but it certainly should be considered when dealing with any patient who isn’t breathing well!

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About the author, sethbarrus

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