Protamine-induced hypotension in heart operations: application of the concept of ventricular-arterial coupling

Protamine sulfate often causes hypotension during heparin neutralization. The concept of ventricular-arterial coupling was applied to determine whether a negative inotropic effect or a vasodilating effect of protamine was the major contributing factor to this hypotension. Thirty-five patients who underwent cardiac operations were studied during operation by measuring instantaneous left ventricular pressure and aortic flow to examine the end-systolic pressure-volume relationship. We obtained end-systolic elastance and effective arterial elastance values in a beat-to-beat fashion with a single-beat estimation method. In 28 of the 35 patients (80%), mean arterial pressure decreased more than 10 mm Hg with protamine infusion. Parameters were compared at the following three points: before a decrease in mean arterial pressure (control), at maximally decreased mean arterial pressure (maximum), and at a middle point between control and maximum values (midpoint). At both midpoint and maximum, mean arterial pressure decreased significantly (control 79.6 +/- 12.6 mm Hg, midpoint 66.5 +/- 10.8 mm Hg, maximum 52.7 +/- 9.9 mm Hg; p < 0.01). Similar changes were observed in effective arterial elastance (control 2.00 +/- 0.75 mm Hg/ml, midpoint 1.60 +/- 0.53 mm Hg/ml, maximum 1.31 +/- 0.46 mm Hg/ml; p < 0.01). Although the decrease in end-systolic elastance at midpoint (control 3.08 +/- 1.61 mm Hg/ml, midpoint 2.92 +/- 1.68 mm Hg/ml) did not reach statistical significance, end-systolic elastance significantly decreased at maximum (2.63 +/- 1.46 mm Hg/ml; p < 0.01). Continuous measurements showed that the decreases in mean arterial pressure and effective arterial elastance always preceded the depression of end-systolic elastance and that afterload reduction by vasodilating effect of protamine was the mechanism most likely to have initiated the hypotension. Delayed decrease in contractility may be ascribed to reduced coronary perfusion pressure caused by vasodilation or to a direct effect of protamine.