Without evidence of benefit, an intervention should not be presumed to be beneficial or safe.

- Rogue Medic

How Diagnostic is Narcan?

ResearchBlogging.org

At Resus.ME,[1] Dr. Reid suggests that one benefit of nebulized naloxone[2] is its diagnostic value. He asks –

Do you ever use naloxone diagnostically, and if so, do you think it’s worth knowing that the nebulised route is an option?

This has been studied.

our primary hypothesis was that response to naloxone in such patients is almost always predictable on the basis of easily determined clinical characteristics.[3]

For AMS (Altered Mental Status) patients, compared with a very simple exam, does naloxone improve our ability to identify the patients with opioid overdose?

Data collected included the patient’s response to naloxone as well as three specific clinical findings; these findings were respirations, pupil size, and presence or absence of circumstantial evidence of opiate abuse.[3]

Today, the circumstantial evidence is probably going to be present less often due to the increased percentage of abuse of prescription pain pills. If the pill container is not present, or the pill container is not the original labeled container, then this might not be helpful. Since there is less of a need to inject the opioids to produce the high, the presence of track marks, or a needle and a spoon, or other drug paraphernalia, may not be present.

Would that make much difference?

Even more accurate than response to naloxone is a respiratory rate of 12 or less.


Click on image to make it larger.

The hospital charts of all naloxone responders, partial responders, and the sample of nonresponders were reviewed by one of the physician authors to determine whether opiate overdose was included as a discharge diagnosis.[3]

If anything, the response to naloxone would bias the diagnosis toward including opioid overdose in the diagnosis, so the results should have made naloxone look better.

Does a response to naloxone mean that the emergency physician can safely rule out other causes of AMS?

How diagnostically useful is naloxone?

Final diagnoses at discharge from the ED, or the hospital if admitted, were obtained on all 25 responders, 26 of 32 partial responders, and 195 of 673 nonresponders.[3]

That is a lot of naloxone for very little response.

What about nebulized naloxone?
 


Image credit.

For the patients most likely to be breathing well enough to use a nebulizer for naloxone administration (≥13 breaths per minute), does naloxone provide any benefit?

The two patients with opiate overdose who were not identified by these clinical findings did not respond to naloxone,[3]

Only two patients were breathing faster than 12 times per minute, but neither patient responded to IV (IntraVenous) naloxone.

Should we expect them to respond to nebulized naloxone?

Are these two patients in any way representative of the patients breathing adequately enough to use nebulized naloxone?

We should not draw conclusions from such a small group 2 out of 730 patients, but the lack of response to naloxone in both of these patients is not exactly a recommendation for the diagnostic value of naloxone even in the group of patients most likely to receive naloxone by nebulizer.

The study indicates that there is no diagnostic benefit derived from the administration of naloxone to all AMS patients.[3]

This is probably not what Dr. Reid was suggesting, but it is disappointing to know that many of us have continued to give naloxone routinely to AMS (Altered Mental Status) patients, even though we have had good evidence that we could use diagnostic criteria to identify the patients most likely to respond to naloxone since 1991.

While the value of subsequent administration of naloxone in the ED has never been formally analyzed (and cannot be fairly evaluated on the basis of our data), allowing physicians to selectively decide which patients with AMS should receive this drug would undoubtedly retain many of the benefits demonstrated here while allowing medical judgment to determine if any other patients without clear-cut indications might still benefit from its use.[3]

I expect that Dr. Reid is not administering naloxone to every AMS patient he sees, but trying to limit the use to those patients most likely to respond.

If we give naloxone – nebulized, rectally, buccally, subcutaneously, intramuscularly, intravenously, or just massaged into the skin as part of a diagnostic massage – does naloxone diagnose anything?

If the patient is postictal and has an improvement in level of consciousness after naloxone, is that diagnostic?

If the patient had a TIA (Transient Ischemic Attack), or a stroke, and has an improvement in level of consciousness after naloxone, is that diagnostic?

If the patient is diabetic, but responding to dextrose (or to glucagon) slowly, and has an improvement in level of consciousness after naloxone, is that diagnostic? Yes, we should have a blood sugar, but if we are fixated on naloxone . . . .

If the patient had a clonidine overdose and has an improvement in level of consciousness after naloxone, is that diagnostic?

If the patient has consumed alcohol and has an improvement in level of consciousness after naloxone, is that diagnostic?

The answer to all of these appears to be No.

Also see –

Nebulised Naloxone at flobachrepublic.

Narcan Nebs – Why? New research doesn’t say.. at Mill Hill Ave Command.

Footnotes:

[1] Nebulised naloxone
May 14, 2012
by Cliff
Resus.ME
Article

[2] Can Nebulized Naloxone Be Used Safely and Effectively by Emergency Medical Services for Suspected Opioid Overdose?
Weber JM, Tataris KL, Hoffman JD, Aks SE, Mycyk MB.
Prehosp Emerg Care. 2011 Dec 22. [Epub ahead of print]
PMID: 22191727 [PubMed – as supplied by publisher]

[3] The empiric use of naloxone in patients with altered mental status: a reappraisal.
Hoffman JR, Schriger DL, Luo JS.
Ann Emerg Med. 1991 Mar;20(3):246-52.
PMID: 1996818 [PubMed – indexed for MEDLINE]

Hoffman JR, Schriger DL, & Luo JS (1991). The empiric use of naloxone in patients with altered mental status: a reappraisal. Annals of emergency medicine, 20 (3), 246-52 PMID: 1996818

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Comments

  1. Great points about the diagnostic usage of narcan. The end pretty much spells it out. While the patient improved the underlying cause needs to be understood. I’ve never been a fan of the coma cocktail and the reason is simply that you are treating a variety of things and not recognizing the route cause. Critical thinking before treating will most likely lead you down the right treatment.

    • Dave Aber,

      Great points about the diagnostic usage of narcan. The end pretty much spells it out. While the patient improved the underlying cause needs to be understood. I’ve never been a fan of the coma cocktail and the reason is simply that you are treating a variety of things and not recognizing the route cause. Critical thinking before treating will most likely lead you down the right treatment.

      Thank you.

      There will always be patients who are difficult to figure out.

      If we treat a seizure patient with naloxone, and the post-ictal period ends after the naloxone, and we leave him there to seize again, based on the assumption that he is just a junkie, we are not providing good medical care. The same is true for the stroke patient, or any other patient with symptoms that improve at some point near when naloxone was given.

      .

  2. While I understand, and support, your comment I do need to add my 2 cents. Confronted with any patient with altered mental state, diminished consciousness I was taught to exclude:
    1 Metabolic causes: i.e. hypo/hyperglycaemia
    2 Electrolyte imbalance: i.e. hypo/hypernatriemia
    3 Toxicity: i.e. drugs (both illegal and prescribed), uremia
    4 Neurological causes: i.e. CVA, epilepsy
    5 Infectious causes: i.e. meningitis, sepsis
    6 Cardiological causes: i.e. arrhythmia
    7 Psychiatric causes: i.e. catatonia

    In other words, Narcan would be usefull after you have excluded other causes, or if you are certain of opioid overdose (somebody was overly enthusiastic and administered too much morphine to the patient). As the sole diagnostic tool I would be hesitant to use it for the reasons you have specified.

    • Nescio,

      While I understand, and support, your comment I do need to add my 2 cents. Confronted with any patient with altered mental state, diminished consciousness I was taught to exclude:
      1 Metabolic causes: i.e. hypo/hyperglycaemia
      2 Electrolyte imbalance: i.e. hypo/hypernatriemia
      3 Toxicity: i.e. drugs (both illegal and prescribed), uremia
      4 Neurological causes: i.e. CVA, epilepsy
      5 Infectious causes: i.e. meningitis, sepsis
      6 Cardiological causes: i.e. arrhythmia
      7 Psychiatric causes: i.e. catatonia

      In other words, Narcan would be usefull after you have excluded other causes, or if you are certain of opioid overdose (somebody was overly enthusiastic and administered too much morphine to the patient). As the sole diagnostic tool I would be hesitant to use it for the reasons you have specified.

      I agree. I was pointing out that naloxone is not diagnostic.

      Just because something improves after naloxone, does not mean that it improves because of naloxone.

      The old post naloxone, propter naloxone fallacy.

      .

  3. If the patient is breathing good enough to use a nebulizer, why the heck would we give Narcan?

    • Scott Babbitt,

      If the patient is breathing good enough to use a nebulizer, why the heck would we give Narcan?

      Would these patients have had worse outcomes without the nebulized naloxone?

      Probably not, but there was no placebo group, so we can only speculate

      From Academic Life in Emergency Medicine

      Advantages:

      Nebulized naloxone does not require an IV, which is often difficult to establish in IV drug users.

      Instead of administering multiple doses of naloxone for long-acting opiates, nebulized naloxone can provide a steady, low maintenance dose similar to an IV drip but without needing an IV.

      Nebulized naloxone is a self-titrating medication because when the patient awakens, s/he often will pull off the mask.

      Having options is a good thing.

      Naloxone can be given by so many different routes, that there are a lot of options.

      .

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