Non-cardiogenic Pulmonary Edema…

John W. Severinghaus, M.D.

To the Editor

In reporting a case of non-cardiogenic pulmonary edema related to difficult intubation (and extubation with laryngospasm), Ohn describes the several theses about its cause.(1) He mentions the movement of blood from peripheral veins into the thorax, partly due to sympathetic vasoconstriction and partly due to negative intrathoracic pressure. I write to further emphasize the major importance of the latter in translocating blood into the right heart, causing overdistention, endothelial damage and leakage of large pulmonary arteries, comparable to the putative site of injury in high altitude pulmonary edema (HAPE).(2)


The muscles of respiration can act as a blood pump even during cardiac arrest, inspiratory effort pulling central venous blood into the right heart, and expiratory effort forcing blood from the left ventricle into the aorta. Similar pumping action occurs when the heart is beating. Vigorous inspiratory efforts against a closed glottis can easily develop as much as -80 cmH2O or more pressure within the thorax. This negative pressure has no instantaneous effect on trans-mural pressures within the thorax since it is transmitted to all intrathoracic structures. However, it causes peripheral venous blood to flow into the thorax from the IVC and SVC. Blood “pours” down this 80 cmH2O pressure waterfall, overfilling the right heart, pulmonary arteries, capillaries and veins. The distended right ventricle then ejects an increased stroke volume.


The target of consideration should be pulmonary arteries, not capillaries. Both the passive influx of venous blood and the higher stroke volume over- distend pulmonary arteries. The normally very compliant pulmonary arteries double their volume with only a 20 torr pressure rise.(3) Damage appears to be primarily to the walls of the major arteries, not the capillaries. Evidence includes the x-ray pattern. As Ohn notes, and as most other authors have also reported, edema is seen as a perihilar, usually bilateral, “butterfly” pattern, markedly differing from the basal, peripheral cardiogenic edema. The major arteries are often noted to have diffuse or fuzzy edges due to periarterial edema. X-ray shows bilateral alveolar infiltrates, mostly around the hilum.(4) Halow and Ford(5) collected 19 reported cases of pulmonary edema after postoperative laryngospasm, (3 female, 16 male, aged 3 months to 60 years). Onset of edema was less than 3 minutes in 12 patients; chest roentgenograms showed edema in 17 patients. Cascade, Alexander and Mackie(6) reported eight patients with laryngospasm-induced negative- pressure pulmonary edema after endotracheal intubation. Radiologically, seven showed bilateral centralized patterns. The mean vascular pedicle width was 67 mm 12, a value 40% higher than the normal mean of 48 mm. Large athletic males with ample central blood volume are most susceptible.

Ohn writes, “Pulmonary arteriolar constriction increases pulmonary capillary pressure.” Neither evidence nor logic support this statement. Hypoxic constriction, which is largely confined to the small arterioles, less than 0.2 mm diameter, does raise the pressure upstream and dilates the larger arteries, but, if flow is constant, has no effect on capillary pressure.

In all cases, as Ohn notes, hypoxically driven sympathetic peripheral vasoconstriction and cardiac stimulation presumably are of great importance. Similar trans-arterial edema may be seen after death from heroin overdose, with drowning (often without aspiration), and perhaps after disconnection of a ventilator in a paralyzed patient. The characteristic edema is pink and frothy, and like that found in HAPE, is high in protein due to leakage through damaged endothelial junctions. HAPE is also typically perihilar and patchy, and is effectively treated and prevented by reducing pulmonary arterial pressure with nifedipine.(7)

John W. Severinghaus, M.D. Department of Anesthesia University of California San Francisco, CA


  1. Ohn JKC: Non-cardiogenic pulmonary edema after difficult intubation. APSF Newsletter 10(2): 22, 1995.
  2. Severinghaus JW: Transarterial Leakage: A Possible Mechanism of High Altitude Pulmonary Edema. Ciba Symposium on High Altitude Physiology: Cardiac and Respiratory Aspects. Edited by Porter R, Knight J. 1971, pp 61-77.
  3. Severinghaus JW: Pulmonary vascular function. Am Rev of Resp Disease 115:149-158, 1977.
  4. Rubio PP, Martin BP, Abades AJ: Ann Fr Anesth Reanim 7: 506-508, 1988.
  5. Halow KD, Ford EG: Pulmonary edema following postoperative laryngospasm: a case report and review of the literature. Am Surg 59: 443-447, 1993.
  6. Cascade PN, Alexander GD, Mackie DS: Negative-pressure pulmonary edema after endotracheal intubation. Radiology 186: 671-675, 1993.
  7. Bartsch P, Maggiorini M, Ritter M, Noti C, Vock P, Oelz O: Prevention of high-altitude pulmonary edema by nifedipine. N Engl J Med 325: 1284-1289, 1991.