Anaphylactoid reactions to protamine: An often lethal complication in insulin-dependent diabetic patients undergoing vascular surgery
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Protamine is used routinely at our institution during arterial surgery to reverse the anticoagulant effect of heparin. Adverse fatal reactions to protamine are generally believed to be rare. However, major anaphylactoid reactions occurred in 11 of the last 1150 patients receiving this drug at our institution. Nine of these reactions occurred in 325 insulin-dependent diabetic patients (incidence, 3%), whereas only two occurred in the 825 patients not receiving insulin (incidence, 0.2%) (p less than 0.001). Ten of these reactions occurred within 10 minutes of protamine administration (15 to 35 mg), whereas one reaction occurred immediately after administration of a 5 mg test dose of protamine. Systolic blood pressure fell below 60 mm Hg in all of the 11 patients, and three patients had to be resuscitated with closed-chest massage. Initial treatment with epinephrine and steroids was successful in seven cases. Four patients required further resuscitative measures, including closed-chest massage. However, one of the patients died as a result of ventricular fibrillation resistant to treatment. Ten of the 11 patients, including the patient who died, had significant preexisting cardiac disease; six of the surviving 10 patients (60%) had perioperative myocardial infarctions and three died. Thus the total mortality rate was 36% (4/11). These data support the implication that neutral protamine Hagedorn (NPH) insulin produces an adverse reaction through immunologic presensitization of the patient. These data also show that, in the older vascular surgery population with a high incidence of significant cardiac disease, protamine reactions can be potentially lethal. Thus routine use of protamine should be avoided in diabetic patients receiving insulin.