Negative pressure pulmonary hemorrhage

Educational aims 

A 26-year-old male prisoner was brought to the emergency department for frank hemoptysis of one-day duration. He described coughing about 4–5 tablespoons of bright red blood in 24h. He reported increasing dyspnea associated with the hemoptysis, but denied fevers, chills, or night sweats. The day prior to presentation, he was partially strangulated during an altercation with a prison guard. He passed out for a few minutes, then developed shortness of breath and hemoptysis immediately afterwards. He was an active smoker, denied any recent drug use, and was not on any medications.

On hospital admission, he had a temperature of 37.8°C. Heart rate was 85beats/min. He was normotensive. Respiratory rate was 18breaths/min. Oxygen saturation was 94% on room air, which was an improvement from several hours earlier when he was requiring 3L oxygen by nasal cannula to keep his oxygen saturation above 92%. His head and neck exam revealed no palpable lymph nodes and no mouth lesions. The cardiac exam demonstrated a regular rate and rhythm with no murmurs. On chest exam, coarse breath sounds were heard diffusely. His abdomen was soft and non-tender without organomegaly. The extremity, skin, and neurologic examinations were non-revealing.

WBC count was 16,000/μl, with manual differential showing 83% neutrophils. Hemoglobin was 14g/dl. Platelets were 176,000/μl. Activated partial thromboplastin time was normal. INR was slightly elevated at 1.2. Electrolytes and liver function tests were normal. Creatinine was 1.2mg/dl. Urinalysis was bland with no protein, red blood cells, hemoglobin, or casts detected. Urine drug screen was negative for illicit drugs. The electrocardiogram showed normal sinus rhythm. Admission chest X-ray demonstrated diffuse bilateral alveolar and interstitial opacities (Fig. 1). A CT scan of the chest was subsequently done revealing diffuse patchy bilateral alveolar opacities (Fig. 2). Further testing included the following: erythrocyte sedimentation rate: 3mm/h (0–15mm/h); HIV antibody (ELISA): non-reactive; Anti-glomerular basement membrane, and antineutrophil cytoplasmic antibodies: negative; hepatitis B and C serologies and hepatitis B surface antigen: negative; histoplasma complement fixation titers, and urine histoplasma antigen: negative.

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Fig. 1 Chest radiograph on presentation showing diffuse alveolar and interstitial opacities.

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Fig. 2 Chest CT scan on presentation showing diffuse central patchy alveolar opacities in a uniform distribution, sparing the periphery.

Based on the patient's laboratory results, X-rays, and history, we suspected the diagnosis of negative pressure pulmonary edema leading to alveolar hemorrhage. We opted to admit him to the hospital for observation and supportive care, which is the standard of care for the treatment of negative pressure pulmonary edema. The patient's symptoms and infiltrates resolved 48h after admission, and his oxygen saturation was 99% on room air the day of discharge. Figs. 3 and 4 show the chest X-rays 24h and 48h after admission respectively.

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Fig. 3 Chest radiograph 24h after admission showing partial resolution of the alveolar opacities.

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Fig. 4 Chest radiograph 48h after admission showing complete resolution of the alveolar opacities.

2. Discussion 

Negative pressure pulmonary edema is a well-described and dangerous complication of acute upper airway obstruction.1 It typically occurs in young healthy muscular people who experience acute upper airway obstruction.2 It is characterized by rapid onset and resolution of pulmonary edema after an episode of upper airway obstruction. Resolution takes place within 12–48h.3 Various causes of upper airway obstruction have been linked to this entity. These are shown below (Table 1).2, 3, 4, 5, 6, 7, 8, 9, 10

Table 1. Causes of upper airway obstruction leading to negative pressure pulmonary edema.

	Post-extubation laryngospasm2
	Hanging4, 5
	Strangulation4, 6
	Foreign body obstruction4, 7
	Laryngeal tumor4
	Sleep apnea4
	Biting down on the endotracheal tube or laryngeal mask while intubated8
	Croup and epiglottitis in children9
	Post thyroidectomy10

The etiology of negative pressure pulmonary edema is related to generation of markedly negative intrathoracic pressure due to forced inspiration against a closed glottis. Negative intrathoracic pressure causes a decreased right atrial pressure and increased venous return to the right ventricle. The right ventricle is therefore distended shifting the intraventricular septum to the left side. This decreases left ventricular compliance, and combined with increased afterload, results in increased left ventricular end-diastolic pressure and pulmonary capillary wedge pressure. The resulting elevation of the pulmonary capillary transmural pressure leads to extravasation of fluid into the alveoli causing pulmonary edema and hypoxia. Hypoxia leads to pulmonary vasoconstriction, and also results in a massive sympathetic discharge, which causes systemic vasoconstriction, increasing left ventricular afterload. This results in further elevation of the pulmonary capillary transmural pressure, which increases stress on the pulmonary capillaries, and promotes additional extravasation of fluid into the alveolar spaces. Fluid resorption subsequently takes place at a fast rate with re-absorption of most of the edema fluid within 48h of the insult.3, 11

The pulmonary capillary blood-gas barrier is formed by the capillary endothelium, extracellular matrix, mostly composed of a thin layer of type IV collagen, and the alveolar epithelium. Increased pulmonary capillary transmural pressure causes circumferential stress on the blood-gas barrier and pulmonary capillary wall. This is a result of Laplace's law and is shown below (Fig. 5). Markedly increased transmural pressures ultimately lead to stress failure of the blood-gas barrier causing breaks in the epithelial and endothelial surfaces. Extravasation of blood in addition to fluid ensues producing alveolar hemorrhage as seen in the present patient. Negative pressure pulmonary hemorrhage has been reported previously, and a similar mechanism may be responsible for the alveolar hemorrhage seen in cases of pulmonary edema related to high altitude and peak exercise.3, 11, 12, 13, 14

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Fig. 5 Pulmonary capillary blood-gas barrier. Increased pulmonary capillary hydrostatic pressure causes increased pulmonary capillary wall tension, which could lead to stress failure of the blood-gas barrier. T=tension; P=Transmural pressure; r=radius of the capillary; t=thickness of the blood-gas barrier; ECM=Extracellular matrix.

Conflict of interest statement 

Dr. Diab and Dr. Noor have no conflicts of interest to disclose in relation to this work.