Noncardiogenic pulmonary edema immediately following rapid protamine administration

To report the case of a rare, potentially preventable, immediate noncardiogenic pulmonary edema reaction to the rapid administration of protamine during coronary artery bypass graft (CABG) surgery.

A 74-year-old white man was administered a 250-mg bolus of protamine sulfate toward the end of CABG surgery to reverse the heparin anticoagulation. Immediately following the administration of protamine, oxygen saturation declined, pink frothy sputum was suctioned from the trachea, and 1500 mL of serous fluid was removed from the airway. The patient was stabilized, but the surgeons were unable to close his chest because of the profound edema. Chest closure occurred on hospital day 6, with discharge from the intensive care unit on hospital day 28.

Noncardiogenic pulmonary edema is a rare adverse event that occurs in 0.2% of cardiopulmonary bypass patients, with mortality rates approaching 30%. Complement activation or direct pharmacologic release of histamine by high concentrations of protamine is the suspected cause. High concentrations of protamine in the lungs may directly release histamine, with significant vasodilating effects.

Immediate reversal of heparin anticoagulation with protamine is necessary to control bleeding; however, rapid protamine injection can be associated with life-threatening pulmonary edema. Slower, cautious administration and accurate calculation of protamine doses may prevent such an event.