Drug shortages are a frequent challenge in current clinical practice. Certain drugs (e.g., protamine) lack alternatives, and inadequate supplies can limit access to services. Conventional protamine dosing uses heparin ratio-based calculations for heparin reversal after cardiopulmonary bypass and may result in excess protamine utilization and potential harm due to its intrinsic anticoagulation. This study hypothesized that a fixed 250-mg protamine dose would be comparable, as measured by the activated clotting time, to a 1:1 (1 mg for every 100 U) protamine-to-heparin ratio-based strategy for heparin reversal and that protamine would be conserved.

In a single-center, double-blinded trial, consenting elective adult cardiac surgical patients without preexisting coagulopathy or ongoing anticoagulation and a calculated initial heparin dose greater than or equal to 27,500 U were randomized to receive, after cardiopulmonary bypass, protamine as a fixed dose (250 mg) or a ratio-based dose (1 mg:100 U heparin). The primary outcome was the activated clotting time after initial protamine administration, assessed by Student’s t test. Secondary outcomes included total protamine, the need for additional protamine, and the cumulative 24-h chest tube output.

There were 62 and 63 patients in the fixed- and ratio-based dose groups, respectively. The mean postprotamine activated clotting time was not different between groups (−2.0 s; 95% CI, −7.2 to 3.3 s; P = 0.47). Less total protamine per case was administered in the fixed-dose group (−2.1 50-mg vials; 95% CI, −2.4 to −1.8; P < 0.0001). There was no difference in the cumulative 24-h chest tube output (difference, −77 ml; 95% CI, 220 to 65 ml; P = 0.28).

A 1:1 heparin ratio-based protamine dosing strategy compared to a fixed 250-mg dose resulted in the administration of a larger total dose of protamine but no difference in either the initial activated clotting time or the amount postoperative chest-tube bleeding.