My friend Jonathan Blatman asks the following question about naloxone (Narcan) on Facebook –
 

I’ve heard that PA (Pennsylvania) is looking to follow down the “Narcan for everyone” route, in allowing PD and BLS folks to give intranasal naloxone.^[1]

The problem is not that basic EMTs, or first responders, or police are stupid people.

The problem is that all people are stupid people.

Doctors, nurses, and paramedics do not understand naloxone, so we need to improve the understanding of pharmacology among doctors, nurses, and paramedics, before we increase the ranks of ignorant people inappropriately administering the drug.

Naloxone itself is very safe.

A quack once challenged me to take 1,000 times the dose of any medicine I chose, while he would do the same with some natural product. I accepted and chose naloxone, with the condition that he first take 1,000 time the daily recommended dose of one of something he considered completely safe and natural – water.

The quack had it pointed out to him that this dose of all natural water would be deadly. The quack backed out. Whether naloxone’s standard dose is 0.4 mg (it should not be more than this) or the dose more popular in areas with frequent fentanyl overdoses (2.0 mg) does not matter. Naloxone has been demonstrated to be relatively safe at massive doses.
 

Adult Patients
In one small study, volunteers who received 24 mg/70 kg did not demonstrate toxicity.
In another study, 36 patients with acute stroke received a loading dose of 4 mg/kg (10 mg/m2/min) of naloxone hydrochloride injection followed immediately by 2 mg/kg/hr for 24 hours. Twenty-three patients experienced adverse events associated with naloxone use, and naloxone was discontinued in seven patients because of adverse effects. The most serious adverse events were: seizures (2 patients), severe hypertension (1), and hypotension and/or bradycardia (3).^[2]

400 mg (0.4 mg dose x 1,000) or 2,000 mg (2.0 mg x 1,000) would be higher than the doses tested in these patients, but would still be much safer than 1,000 times the recommended daily dose of water, even though water is safe and essential for life. It does not matter if there is fluoride in the water for it to be lethal, but we should fluoridate water, because only conspiracy theorists think that fluoride is dangerous in drinking water.
 

We engage in magical thinking about the drugs we give.

The problem is not with the drug. The problem is with the actions of the people giving the drug – us.

We still have a big push for giving fibrinolytics (tPA – tissue Plasminogen Activator) to patients with acute ischemic stroke, even though most of the improvement may be due to the transience of stroke symptoms in some stroke patients (TIS – Transient Ischemic Attack). Fibrinolytics do not appear to be beneficial for acute ischemic stroke and there is no reason to give them for a TIA.

There is weak beneficial evidence in only two out of eleven studies (only 18% of studies) – and increases in death in most studies of fibrinolytics for acute ischemic stroke.^[3] The problem is not with the drug. The problem is with the actions of the people giving the drug. Most of the evidence shows death increased, but we ignore that.

Naloxone and tPA are both given based on a rush to treatment and a fear of not giving the standard of care – the Yuppie Nuremberg Defense.
 

Everyone’s got a mortgage to pay. [inner monologue] The Yuppie Nuremberg defense.^[4]

Will this be a matter of providing naloxone, rather than providing ventilations?
 

An epidemic of naloxone-resistant heroin overdoses due to fentanyl adulteration has led to significant morbidity and mortality throughout the central and eastern United States. According to records of the Philadelphia County Medical Examiner’s office, at least 250 overdose deaths have been associated with fentanyl between April 1, 2006, and March 1, 2007.^[5]

What about people who take more than one drug?

If the opioid is reversed, will there be problems?
 

All were initially lethargic and became agitated and combative after emergency medical service (EMS) personnel treated them with parenteral naloxone, which is routinely used for suspected heroin overdose to reverse the toxic effects of opioids (e.g., coma and respiratory depression). All patients received diazepam or lorazepam for sedation, and signs and symptoms resolved during the next 12-24 hours.^[6]

Will we identify the patients who have other medical conditions that may respond after naloxone, but not because of naloxone, such as hypoglycemia, stroke, seizures, clonidine overdose, arrhythmia, head trauma, dehydration, syncope, et cetera?
 

Six of the 25 complete responders to naloxone (24%) ultimately were proven to have had false-positive responses, as they were not ultimately given a diagnosis of opiate overdose. In four of these patients, the acute episode of AMS was related to a seizure, whereas in two, it was due to head trauma; in none of these cases did the ultimate diagnosis include opiates or any other class of drug overdose (which might have responded directly to naloxone). Thus, what was apparently misinterpreted as a response to naloxone in these cases appears in retrospect to have been due to the natural lightening that occurs with time during the postictal period or after head trauma.^[7]

The problem is not with the administration of naloxone, but with the faulty assumption that because a patient wakes up after naloxone, the patient woke up because of naloxone.

Doctors, nurses, and paramedics do not do a good job of identifying the difference currently. We need to educate them, rather than encourage others to replicate their mistakes.

Pharmacology is poorly understood by people with medical education.
 

The documented indication for nebulized naloxone administration was suspected opioid overdose in 70 patients (66.7%), altered mental status in 34 patients (32.3%), and respiratory depression in one patient (0.9%).^[8]

The indication for naloxone is respiratory depression.

The treatment for respiratory depression is to supplement oxygen and/or ventilations. We have decided to give naloxone in stead.

Naloxone was used appropriately in fewer than 1% of patients.

How good bad will our naloxone by everyone education be?

Don’t wait with bated breath – someone my administer naloxone.
 

Also read –

Should Basic EMTs Give Naloxone (Narcan)?

The Myth that Narcan Reverses Cardiac Arrest

To Narcan or not Narcan

What About Nebulized Naloxone (Narcan) – Part I

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Footnotes:

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^[1] I’ve heard that PA is looking to follow down the “Narcan for everyone” route, in allowing PD and BLS folks to give intranasal naloxone. . . .
Facebook
Narcan post

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^[2] NALOXONE HYDROCHLORIDE injection, solution
[Hospira, Inc.]
DailyMed
Adverse reactions
Overdosage
FDA Label

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^[3] The Guideline, The Science, and The Gap
Wednesday, April 17, 2013
Dr. David Newman browngorilla540
Smart EM
Article

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^[4] Thank You for Smoking
Movie, based on the book by Christopher Buckley
Wikiquote
Quote page

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^[5] Heroin: what’s in the mix?
Muller AA, Osterhoudt KC, Wingert W.
Ann Emerg Med. 2007 Sep;50(3):352-3.
PMID: 17709054 [PubMed – indexed for MEDLINE]

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^[6] Scopolamine Poisoning among Heroin Users — New York City, Newark, Philadelphia, and Baltimore, 1995 and 1996
MMWR (Morbidity and Mortality Weekly Report).
Vol 45, No 22;457;
Free Full Text from the Centers for Disease Control and prevention.

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^[7] 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]

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^[8] 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. 2012 Apr-Jun;16(2):289-92. doi: 10.3109/10903127.2011.640763. Epub 2011 Dec 22.
PMID: 22191727 [PubMed – indexed for MEDLINE]

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Image credit.
 

EMSDoc911 writes about whether naloxone (Narcan) is a good idea for a specific patient presentation.
 

Dispatched for a 50ish yo witnessed cardiac arrest, CPR in progress on my arrival.

The pt was pulseless in brady..ish PEA with agonal respirations. He received ~2min of CPR by us when we got a pulse back. Intubated, IV, no code meds as we never got around to it. Per bystanders, the pt “started crying, then collapsed into a code… we got there in <5min.

As I started doing my secondary assessment in the truck, I noticed on my neuro exam that the pt has pinpoint pupils. So to Narcan or NOT Narcan???

Note: the pt is 250+ lbs, intubated, with IV, yada yada yada… we are 12min from ED, and it is just me & a firefighter in the back.^[1]

Should we give this patient naloxone?

We should only be giving drugs when they are indicated.

1. Is there any benefit to the patient?

2. Is there any harm?

3. How much uncertainty is there about what will happen?

There is always uncertainty, but never certainty. We need to understand how uncertain we are.

Certainty would imply that we never make mistakes.

Some people do claim to never make mistakes. These are people who never make any decisions (I would call that a mistake) and liars. If you are in EMS and you tell me that you have never made a mistake, then you are either brand new and do not have enough experience to recognize mistakes or you are a liar.
 

1. What are the possible benefits from giving naloxone to this patient?

We do not have to squeeze the bag.

We can extubate the patient in the field. This is also one of the possible harms, because extubation does not always go as planned – just ask a doctor who extubates a lot of patients.

We have a better idea of what happened.

In other words – not much benefit.
 

2. What are the possible harms from giving naloxone to this patient?

A. If this actually is an opioid overdose –

He has some stimulants on board and becomes combative.

He has some stimulants on board and the catecholamine surge puts him back into cardiac arrest.

If the patient has taken an opioid and that is keeping stimulants, this is about the same as deciding if we should give a bolus of epinephrine to a resuscitated patient.

We may end up fighting with the patient in the back. Not good for the resuscitated patient and not good for us.

B. If this is not an opioid overdose –

Should we be giving drugs to someone on a hunch?

The naloxone with wipe out the protective effect of endorphins – the body’s natural opioids.

Block the effect of endorphins and we cannot safely use opioids. Naloxone is a competitive antagonist, but what is an effective dose of morphine, or fentanyl, after giving naloxone? How do we know?

Can we really titrate naloxone that accurately that we can stop before any adverse effects cause problems?

If we answer Yes – we are lying to ourselves. Sometimes this will work, but other times it will not – and that is just in giving naloxone, not in giving morphine to a patient who has already received naloxone to treat a potential overdose of heroin, or fentanyl, or methadone, or tramadol, or hydromorphone, or any of the other opioids used on the street, whether smoked, or injected, or swalloed, taken as a transdermal patch, or rubbed on the gums, or something else.
 

3. How much uncertainty is there when giving naloxone to this patient?

Has the patient taken something that will respond to naloxone?

Will the patient be able to tolerate the expected catecholamine surge if the naloxone has a clear effect.

The adverse reactions section of the FDA (Food and Drug Administration) label includes the following –
 

pulmonary edema, cardiac arrest or failure, tachycardia, ventricular fibrillation, and ventricular tachycardia. Death, coma, and encephalopathy^[2]

Those are just the cardiovascular adverse events.

While the risk of these adverse reactions is small, it may be larger in the intubated patient, or in the post-arrest patient. The possible benefits are tiny, while the possible harms are the kind that

The uncertainty is huge.

Is the significant risk justified by the tiny possible benefit?

Go read what EMSDoc911 wrote, but remember that a good outcome does not mean that the decision was the right decision. If that were the case, betting my paycheck on the flip of a coin would be a good decision if I win, but only a bad decision if I lose.

We cannot justify our decisions based only on the knowledge of the outcome, because we don’t know the outcome until after we have taken the risk.

 
Also see – The Myth that Narcan Reverses Cardiac Arrest

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Footnotes:

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^[1] To Narcan or not Narcan
EMSDoc911
Dec 11, 2012
Article

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^[2] NALOXONE HYDROCHLORIDE injection, solution
[Hospira, Inc.]
DailyMed
FDA Label
Adverse Reactions

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