Pulmonary vasoconstriction protamine

When given rapidly, protamine causes hypotension due to a decrease in vascular resistance, possibly linked to the release of nitric oxide from endothelium. Flypotension can be minimised by slow administration over 10-15 minutes. Protamine does not affect myocardial contractility. In some patients, systemic hypotension occurs in conjunction with pulmonary hypertension and, in severe cases, right ventricular failure. The mechanism is activation of the complement pathways by the heparin-protamine complex leading to release of thromboxane A2, which mediates pulmonary vasoconstriction. Unlike in anaphylaxis, plasma histamine concentrations are not increased. When this syndrome develops protamine administration should be stopped, and some have recommended giving heparin in an attempt to reduce the size of the heparin-protamine complex. 

Severe acute pulmonary vasoconstriction with cardiovascular collapse was identified in 1983 and subsequent studies showed that the incidence of protamine-induced pulmonary artery vasoconstriction was about 1.5% after cardiac surgery (3). Protamine-induced pulmonary artery vasoconstriction is accompanied by generation of large quantities of thromboxane A2, a potent vasoconstrictor (3). 

Anaphylactic reactions occur in 1% of patients with diabetes mellitus who have received protamine-containing insulin NPFl insulin or protamine zinc insulin) but are not limited to this group. A less common reaction consisting of pulmonary vasoconstriction, right ventricular dysfunction, systemic hypotension, and transient neutropenia also may occur after protamine administration. 

Life-threatening pulmonary vasoconstriction occurred in a 62-year-old male chronic smoker with long-standing systemic hypertension and hypercholesterolemia within 10 minutes of an intravenous infusion of protamine 4 mg/kg after coronary artery bypass graft surgery the authors attributed this to the formation of large heparin-protamine complexes after rapid infusion of protamine [213"°"]. In another case acute pulmonary hypertension induced by protamine during elective coronary artery... 

Hiong YT, Tang YK, Chui WH, Das SR. A case of catastrophic pulmonary vasoconstriction after protamine administration in cardiac surgery role of intraoperative transesophageal echocardiography. J Cardiothorac Vase Anesth 2008 22(5) 727-31. 

Fratacci, M.-D., Frostell, C., Chen, T.-Y., Wain, J. C., Robinson, D. R., and Zapol, W. M. (1991). Inhaled nitric oxide A selective pulmonary vasodilator of heparin-protamine vasoconstriction in sheep. Anesthesiology 75, 990-999. 

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