Background & Prevalence

The physician William Osler first described narcotic-related pulmonary edema during an autopsy in 1880 [1,2]. Its presentation and clinical course was not appreciated until the 1950s-60s. The prevalence of opioid-related NCPE is about 2-10% of heroin overdoses [1,2]. It is most commonly seen in heroin overdose but has been reported with other opioids.

Presentation & Clinical Course

Opioid-related NCPE typically presents as dyspnea accompanied by development of pink, frothy pulmonary secretions associated with ongoing hypoxia despite reversal of respiratory depression with an opioid antagonist (i.e. naloxone). It often presents immediately after reversal but can be slightly delayed, up to four hours [1]. Most cases will resolve within 24-36 hours, but up to one-third of cases will require aggressive respiratory support [1,2]. If left untreated, it can progress to complete hypoxic respiratory failure, hypoxic end-organ injury, and cardiac arrest.

Pathophysiology

The mechanism of opioid-related NCPE is poorly understood, in part because there are a variety of drugs involved, including the opioid antagonist naloxone. There are several published theories. Perhaps the most popular theory is increased pulmonary capillary permeability related to hypoxia and/or histamine release [1,2]. Heroin in particular is prone to causing excessive histamine release, causing leaky pulmonary vasculature. Morphine is another drug known to do this.

Other theories blame naloxone. A patient who is opioid dependent, overdoses, and who is rapidly reversed with a high dose of naloxone subsequently experiences a catecholamine surge, particularly in those with concomitant cocaine use. [2] A second theory blaming naloxone is that following a prolonged period of near or complete apnea, reversal that results in inspiratory effort prior to complete opening of the glottis can result in excessive negative pressure within the lung, drawing in fluid from the pulmonary vasculature. Administering positive pressure ventilation prior to naloxone therapy may mitigate this. It is likely that opioid-related NCPE is multifactorial, with both the opioid agent and naloxone contributing. Regardless of the underlying etiology, treatment remains the same.

Management

The treatment of opioid-related NCPE is supportive and focused on correcting hypoxemia. Initial measures include application of supplemental oxygen, preferably via a non-rebreather mask. Patients with hypoxia refractory to high flow O2 warrant assisted ventilations. Paramedics should have a low threshold for initiating CPAP therapy in the patient experiencing opioid-related pulmonary edema. Hypoxemia or distress refractory to CPAP therapy may warrant endotracheal intubation and invasive ventilation to correct hypoxemia. There has been no identified role for nitroglycerin or other medications in treating opioid-related NCPE.

Back to the case:

The medic recognizes that this patient is experiencing opioid-related NCPE. Only 8 minutes from the nearest emergency department, RSI is deferred in favor of immediate transport. CPAP is placed onto the patient at a pressure of 5 cm H20. The patient tolerates CPAP well, and oxygenation is improved to 90% on arrival at the emergency department, where care is transferred. The patient continues to improve on CPAP and is admitted for further monitoring.

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