NPH insulin-dependent diabetics undergoing cardiac catheterization

Protamine is widely used for reversing systemic heparinization after cardiac catheterization. Although rare, major reactions to protamine that simulate anaphylaxis occasionally occur and have previously been associated only with an allergic reaction to fish. Because neutral protamine Hagedorn (NPH) insulin includes protamine, it might be anticipated that NPH insulin-dependent diabetic patients would develop sensitivity to protamine. Of 866 consecutive patients undergoing cardiac catheterization over a 20 month period, 651 received protamine for reversal of heparinization. Of these, 8.5% (56/651) were diabetics and 2.3% (15/651) were NPH insulin-dependent diabetics. During this period seven patients were observed immediately after administration of protamine to have major adverse reactions that required the administration of catecholamines. One death ensued. Of the seven major reactions, four occurred in NPH insulin-dependent diabetics and one occurred in a patient with an allergy to fish. The incidence of major protamine reactions was 27% (4/15) in the NPH insulindependent diabetics vs 0.5% (3/636) in those with no history of NPH insulin use (p < .001). This represents a 50-fold increased risk of a major reaction to protamine if the patient was receiving NPH insulin. Accordingly, we recommend that diabetics on NPH insulin and patients with allergies to fish undergo cardiac catheterization without the use of protamine or, when necessary, that protamine be administered cautiously in anticipation of a major adverse reaction. Circulation 70, No. 5, 788-792, 1984. SINCE its introduction in 1939, protamine has been used for reversal of the effects of heparin in situations requiring short-term anticoagulation.1 Its use in cardiac catheterizations performed with the femoral approach has become routine in many laboratories. Used according to established guidelines,2 protamine is a relatively safe and effective drug. However, severe reactions to intravenous protamine have been reported, documenting respiratory compromise, hypotension, and shock immediately after its administration.31-0 The only factor previously reported to predispose to such protamine reactions is a history of allergic reactions to ingestion of fish.9' '° Many insulin-dependent diabetic patients have had long-term exposure to protamine in the form of neutral protamine Hagedorn (NPH) insulin. The purpose of From the Evans Memorial Department of Clinical Research and the Department of Medicine, Division of Cardiology, Boston University Medical Center, Boston. Address for correspondence: Thomas J. Ryan, M.D., Section of Cardiology, University Hospital, 75 East Newton St., Boston, MA 02118. Received April 24, 1984; revision accepted June 21, 1984. *Current address: Massachusestts General Hospital, Cardiac Ultrasound Laboratory, Fruit St., Boston, MA 02114. 788 this study was to investigate the relationship between NPH insulin use and severe adverse reactions to intravenous protamine given in the course of cardiac catheterization.