S010: EVALUATION OF ACTIVATED CLOTTING TIMES WITH A HEPARIN REVERSAL PROTOCOL DESIGNED TO CONSERVE PROTAMINE DURING DRUG SHORTAGES: A RETROSPECTIVE, COHORT STUDY
Michael Fabbro II, DO, MBA; Alejandra Silva-De Las Salas, MD; Joseph Lamelas, MD; Richard H Epstein, MD, FASA; Kristin N Parker, BS; Kabir Bedi, BS; University of Miami, Miller School of Medicine
Introduction: Widespread shortages of many medications due to manufacturing and supply chain disruptions have had a critical impact on clinical operations. With no Food and Drug Administration-approved alternative heparin-reversal agents, protamine is an essential medication during surgery involving cardiopulmonary bypass. As such, shortages of protamine can limit community access to cardiac surgical services. In this study, we investigated a protamine conservation approach to heparin reversal we followed during times of critical shortages. In this approach, patients received a fixed 250 mg protamine dose following termination of bypass with additional doses reserved to only when clinically indicated.
Methods: We retrospectively analyzed 801 cardiac surgical patients who received ≥ 30,000 units of heparin before cardiopulmonary bypass. Primary analysis was limited to two groups for comparison. The first group (Low Dose group) comprised patients who received an initial fixed protamine dose of 250mg (n=436), and the second group (Conventional Dose group) received protamine in a ratio-based dose between 0.9 and 1.1 mg protamine / 100 Units heparin. The primary hypothesis was there would be no difference in the first ACT following the initial dose of protamine. Additional analyses compared total protamine doses and vials used between the groups, as well as final ACT values. Quantitative data were analyzed using Student-t tests, and proportions compared using the binomial test. Results with P < .01 were considered as statistically significant.
Results: The first ACT values measured after initial protamine administration were not different between the Low and Conventional Dose groups (122.3s vs 120.6s, 1.47s, 99% CI -1.47 to 4.94, P = 0.16) The total amount of protamine administered in the Low Dose group was substantively less than that in the Conventional Dose group (-100.5 mg, 99% CI -110.0 to -91.0, P < .0001) as were the number of 250 mg vials used per case (-0.69, 99% CI -0.75 to -0.63, P < .0001). When calculations were based on 50 mg vials, the number of vials used per case in the Low Dose group was even less (-2.16, 99% CI -2.36 to -1.97, P < .0001).) The proportions of cases in which the ACT returned to within the upper limit of the normal range for the i-STAT ACT, or within 120% or 110% of baseline, and the final ACT were not different between the 2 groups.
Conclusions: Conservation measures regarding critical medications and supplies during times of shortages can maintain access to important services within a community. These measures may have little clinical impact when compared to standard practices. Our investigation demonstrated that such is the case with protamine administration.