Case:
23 y/o male who is unresponsive found by his friends in an ally. Policearrive
on scene first and find the patient to have a respiratory rate of four andpinpoint
pupils. The decision is made to give 0.4 mg of intranasal Naloxone. The
respiratory rate has improved to six per minute however his pupilsremain
pinpoint and oxygen saturation is only 88% on room air. You administer
an additional 0.4 mg IV and place the patient on a non-rebreather mask
and shortly after the patient is alert and oriented to person, place, time, and
situation. The patient becomes tachypneic to a rate of 30, is saturating at 90%
on non-rebreather, is coughing up pink frothy sputum, has crackles diffusely
on exam and is now in severe respiratory distress. The patient denies a
history of hypertension, cardiac disease, or respiratory disease. Wha thappened?
The
safety of naloxone has been questioned over many years however with its more
controversial accessibility to non-medically trained personnel such as law
enforcement officers and family members of potential victims one of the more
life threatening questionable side effects has raised some concern. Does the
administration of naloxone cause pulmonary edema?
A
widely accepted mechanism of how naloxone causes pulmonary edema is adrenergic
overload. The sudden reversal causes catecholamine release that increases
stroke volume, blood pressure, pulse strength, cardiac index, and plasma
concentrations of epinephrine. These catecholamines also result in increased
pulmonary-capillary hydrostatic pressure causing increased permeability.
A
confusing aspect of this is that opioids alone can cause pulmonary edema. Sir
William Osler in 1880 noted in an autopsy of a patient who died of narcotic overdose
had pulmonary edema which was much earlier than the development
of naloxone. One proposed mechanism is that histamine release secondary
to opioid use causes secretion of proteinaceous material from lung capillaries
resulting in accumulation of fluid. A second is that with respiratory suppression
there is a rapid increase in negative pulmonary pressure from the upper
airway obstruction leading to the movement of fluid out of the pulmonary
capillaries and into the interstitial and alveolar space.
So
did the patient in our case have pulmonary edema as a result of using the opioid
or naloxone was administered?
According
to Boyer et al. naloxone has been mistakenly implicated as a cause of
pulmonary edema. Boyer notes that studies have shown that pulmonary edema
is not secondary to large doses of naloxone nor by means of continuous infusion
as in a naloxone drip and that auscultatory signs of pulmonary edema,
which are difficult to auscultate in an apneic patient, become apparent only
after naloxone restores ventilation.
The
development of non-cardiogenic pulmonary edema, more correctly identified
as acute lung injury (ALI) is multifactorial and cannot be predicted. The
overall incidence is low with rates ranging from 0.2% - 3.6% and studies suggest
that patients who develop pulmonary edema following opiate overdose
and naloxone administration usually do so within 4 hours however it
has been seen in one case up to 8 hours.
So
does Narcan cause pulmonary edema? There is no convincing evidence suggesting
that it does. There is data and evidence supporting theories of the patient
developing pulmonary edema because of using opioids as well as for naloxone
potentiating a physiologic cascade of events that causes the edema. There
have been may case reports of naloxone being suspected as causing non-cardiogenic
pulmonary edema in both hospital and prehospital settings but
to this date, there has been no trial published. Subsequently, naloxone induced
pulmonary edema remains unproven.
1.
Kienbaum P et al. Profound increase in epinephrine concentration in
plasma and cardiovascular stimulation after mu-opioid receptor blockade
in opioid-addicted patients during barbiturate-induced anesthesia
for acute detoxification. Anesthesiology 1998;88(5):1154-61.
PubMed
2.
Busti, A. J., Hinson, J., & Regan, L. (Eds.). (2015, August).
Mechanism
for Naloxone-Related Pulmonary Edema in Opiate or Opioid
Overdose
Reversal. Retrieved August 01, 2017, from
https://www.ebmconsult.com/articles/mechanism-naloxone-relatedpulmonary-
edema-opiate-opioid-overdose-reversal
3.
Sporer, K. A., & Dorn, E. (2001). Heroin-Related Noncardiogenic Pulmonary
Edema. Chest, 120(5), 1628-1632.
doi:10.1378/chest.120.5.1628
4.
Bhaskar B, Fraser JF. Negative pressure pulmonary edemarevisited:
Pathophysiology and review of management. Saudi J Anaesth.
2011;5(3):308-13
5.
Boyer EW. Management of opioid analgesic overdose. N Engl J
Med.
2012;367(2): 146-55
6.
Busti, A. J., Hinson, J., & Regan, L. (Eds.). (2015, August). Incidence of
Naloxone-Related Pulmonary Edema After Reversal of Opioid Overdose.
Retrieved August 1, 2017, from
https://www.ebmconsult.com/articles/incidence-naloxone-pulmonaryedema-
after-reversal-opioid-heroin-overdose
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