Pulmonary Edema After Receiving Narcan

[Tony Held]

There is no definitive answer for why a patient may develop pulmonary edema secondary to receiving Narcan for opiate overdose reversal.  The incidence of this phenomenon is surprisingly low (0.2% to 3.6%).  There is an excellent article about this topic here.

Currently, it is assumed to be of multi-factorial cause:

A rapid increase in sympathetic response - This was the suggestion that got me to looking.  It made sense.  Rapid surge in catecholamines results in monstrous afterload, creates an impossible task for the left ventricle, pressure builds in the pulmonary artery and vein, and you have a reverse in osmotic pressure at the alveolar capillary membrane.  This is the physiology noted in the Sympathetic Crashing Acute Pulmonary Edema (SCAPE) patient.  Read more about that here and listen to a podcast about it here.  Unfortunately, there are several recorded instances of patients developing pulmonary edema without receiving Narcan at all.

Leaking of pulmonary capillaries - "This leads to accumulation of pulmonary fluid with higher concentrations of protein, and may be related to the release of histamine within the lung tissue and vasculature."  My only gripe here is that in the handful of instances I've witnessed, it was a rapid development of pulmonary edema.  This doesn't seem to be an element that would lend itself to a rapid shift in fluid.  This is likely the reason that pulmonary edema develops in those that didn't receive Narcan. Histamine release from narcotics such as Morphine create a gradual shift that should be noticeable to the provider upon initial assessment. 

Acutely generated negative pulmonary pressures - This makes some sense as we're dealing with a severely altered pressure gradient.  Once the Narcan is administered, the patient rapidly regains their desire to breathe.  This is fine as long as their airway isn't obstructed,  As gases try to normalize in concentration and have a vacuum on the other side of the alveolar capillary membrane, fluid will shift in order to normalize that gradient.

This condition is of particular interest now that first-responder agencies and pharmacies have begun stocking this medication.  0.2% to 3.6% is not a massive number, but it is enough to be on the lookout for this condition.  Shortly after a friend saves our beloved heroin addict, they may still need to call 911 for the acute pulmonary edema they're now experiencing.


References:

Incidence of Naloxone-Related Pulmonary Edema After Reversal of Opioid Overdose
Anthony J. Busti, MD, PharmD, FNLA, FAHA, Jeremiah Hinson, MD, PhD, Linda Regan, MD, FACEP, FAAEM
www.ebmconsult.com/articles/incidence-naloxone-pulmonary-edema-after-reversal-opioid-heroin-overdose

Mechanism for Naloxone-Related Pulmonary Edema in Opiate or Opioid Overdose Reversal
Anthony J. Busti, MD, PharmD, FNLA, FAHA, Jeremiah Hinson, MD, PhD, Linda Regan, MD, FACEP, FAAEM
www.ebmconsult.com/articles/mechanism-naloxone-related-pulmonary-edema-opiate-opioid-overdose-reversal

Sympathetic crashing acute pulmonary edema
Naman Agrawal, Akshay Kumar, Praveen Aggarwal, Nayer Jamshed
Department of Emergency Medicine, All India Institute of Medical Sciences, New Delhi, India
www.ijccm.org/article.asp?issn=0972-5229;year=2016;volume=20;issue=12;spage=719;epage=723;aulast=Agrawal

EMCrit Podcast 1 – Sympathetic Crashing Acute Pulmonary Edema (SCAPE)
April 25, 2009 by Scott Weingart
emcrit.org/podcasts/scape/

[Kris Thompson]

Thanks for this summary, Tony. Definitely an interesting phenomena and something we should think about as naloxone is being given more and more by non-medical personnel.

Looking at treatment of this condition, it seems like we should focus on nitroglycerin administration and non-invasive ventilation (CPAP or BiPap). If you have IV nitroglycerin, boluses of 100-1000 mcg IV push (over 1-2 minutes) are probably appropriate, followed by continuous infusion of 50-200 mcg/min quickly titrated up or down as needed. If you don't have the IV form, give sublingual doses of 400 mcg every 2-3 min (or as soon as last one is absorbed) until symptoms improve or hypotension ensues (no limit to number of doses).

As this could be partly caused by SCAPE, loop diuretics are contraindicated due to stimulation of the RAAS and sympathetic nervous system (Agrawal, et. al). Morphine has shown to cause harm in CHF and NSTEMI/ACS patients, so I would personally avoid it.