An Adjusted Calculation Model Allows for Reduced Protamine Doses without Increasing Blood Loss in Cardiac Surgery

Abstract

Background Heparin dosage for anticoagulation during cardiopulmonary bypass (CPB) is commonly calculated based on the patient's body weight. The protamine-heparin ratio used for heparin reversal varies widely among institutions (0.7-1.3 mg protamine/100 IU heparin). Excess protamine may impair coagulation. With an empirically developed algorithm, the HeProCalc program, heparin, and protamine doses are calculated during the procedure. The primary aim was to investigate whether HeProCalc-based dosage of heparin could reduce protamine use compared with traditional dosages. The secondary aim was to investigate whether HeProCalc-based dosage of protamine affected postoperative bleeding. Patients and Methods We consecutively randomized 40 patients into two groups. In the control group, traditional heparin and protamine doses, based on body weight alone, were given. In the treatment group, the HeProCalc program was used, which calculated the initial heparin bolus dose from weight, height, and baseline activated clotting time and the protamine dose at termination of CPB. Results We analyzed the results from 37 patients, after exclusion of three patients. Equal doses of heparin were given in both groups, whereas significantly lower mean doses of protamine were given in the treatment group versus control group (211 ± 56 vs. 330 ± 61 mg, p < 0.001). Postoperative bleeding was less in the HeProCalc group (280 ± 229 mL) as compared with the control group (649 ± 279 mL). However, this difference was not found statistically significant (p = 0.074). Conclusion HeProCalc-based dosage of heparin and protamine allowed for reduced protamine use after CPB compared with when conventional calculations were used. Furthermore, HeProCalc-based regimen for heparin reversal suggested less postoperative bleeding, although the difference between the groups was not statistically significant.

The effect of heparins on plasma concentration of heparin-binding protein: a pilot study

“…During ECC, the plasma HBP concentration gradually increased to a peak of 248 (190–374) ng ml −1 just before the initial dose of protamine was given, when the patients had just been taken off the ECC. During ECC, seven patients received extra heparin according to a local protocol based on the patient's age, sex, height, weight, and measurements of activated clotting time 29 : five patients needed heparin repeatedly ( Supplementary Table S1 ). However, the increase in HBP concentration during ECC did not differ between these seven patients and the three patients not receiving extra heparin (Δ211 (136–421) vs Δ232 (195–255) ng ml −1 , respectively).…”

“…While on ECC, patients were given extra doses of heparin according to the local practice with the help of the HeProCalc perfusion system algorithm. 29 The HBP concentrations were also measured just before the patients were given protamine sulfate, and then 3 and 15 min after the whole protamine dose was given. The protamine was given over a median time of 16 min.…”

Protamine, Platelet Function and Coagulation in Cardiac Surgery

“…The most common methods to dose protamine for the reversal of heparin are either using a fixed protamine to heparin ratio (for example 0.8 mg/100 U, 65 1 mg/100 U, 66-68 1.3 mg/100 U 69 ), or a mathematical calculation of heparin left in the circulation at the time of reversal 69,70 or a titration method using a dose response curve such as Hepcon® (HMS Plus, Medtronic, Minneapolis, USA). [71][72][73][74][75][76][77][78] The usage of a dose response titration method generally results in a lower protamine/heparin ratio than the other methods.…”

Optimal protamine dosing after cardiopulmonary bypass: The PRODOSE adaptive randomised controlled trial

“…Pharmacokinetic algorithms have been promoted as a cheaper, more readily accessible alternative. Previous retrospective observational [13,28], prospective observational [12,[29][30][31], and pilot randomised controlled trials [32,33] have examined different mathematical models for determining heparin concentration following CPB. Kjellberg and colleagues have performed the sole, adequately powered randomised trial in the literature that compares such a model to a fixed ratio approach [10].…”