BACKGROUND: Protamine sulfate (PS), used to neutralize the anticoagulant effect of heparin, is often associated with systemic hypotension. The present study was aimed to investigate the protective effects of calcium chloride (CaCl2) on adverse hemodynamic reactions to PS in patients undergoing open heart surgery. METHODS: After IRB approval, sixty-one patients undergoing open heart surgery were allocated randomly to receive either saline 10 ml (control group, n = 26), CaCl2 5 mg/kg (CaCl2 5 group, n = 18) or 10 mg/kg (CaCl2 10 group, n = 18), added to PS 3 mg/kg given over 3 min through the right atrium to reverse heparinization. Hemodynamic measurements, including systolic (SAP), diastolic (DAP), and mean arterial pressure (MAP), heart rate, and central venous pressure (CVP) were continuously recorded in a baseline condition and up to 10 minutes after PS infusion. Plasma Ca2+ level and arterial blood gas tension were also measured. RESULTS: PS caused immediate and significant decreases in SAP, DAP, and MAP in all three groups. However, the degree of hypotension was significantly less in the CaCl2 10 group than in the CaCl2 5 and control groups. Heart rate and CVP remained unchanged throughout the study in all groups. Intravenous CaCl2 5 and 10 mg/kg IV caused an increase in plasma Ca2 by 0.13 +/- 0.08 mM and 0.45 0.08 mM at 2 min after its injection, respectively. Arterial oxygen tension did not change significantly throughout the study in any group. CONCLUSIONS: These results suggest that simultaneous administration of 10 mg/kg CaCl2 attenuates the hypotensive effect of PS used to reverse heparin anticoagulation in patients undergoing open heart surgery. However, hypotensive reactions may still occur.