Adverse reactions to protamine sulfate during cardiac surgery in diabetic and non-diabetic patients

The incidence of adverse reactions to protamine sulfate range from 0.06% to 27% and vary from mild urticaria to anaphylactic shock and death. In a retrospective analysis of 2996 patients, only four subjects experienced an adverse reaction due to protamine. Two individuals were NPH-insulin-dependent diabetics and two patients had exposure to protamine only during cardiac catheterization. Skin test titrations to protamine were done in three of four patients. One patient had a positive reaction at a 100-micrograms/mL dilution whereas the other two patients had positive reactions at 1000 micrograms/mL. In a comparable number of normal subjects, the threshold for a positive immediate skin response was 1000 micrograms/mL. Since the observed incidence of adverse reactions was 2.9% in NPH-insulin-dependent diabetics and 0.07% in non-diabetics, this represents a nearly 40-fold increased risk for diabetic patients (P less than .005). Skin testing appears to have limited applicability in the assessment of protamine sensitivity.