Effect of site of venous protamine administration, previously alleged risk factors, and preoperative use of aspirin on acute protamine-induced pulmonary vasoconstriction

Abstract

Objective: To determine whether the incidence of protamine-induced pulmonary vasoconstriction (PIPV) is influenced by central venous versus peripheral venous infusion of protamine and whether aspirin ingestion within a week of surgery would decrease the incidence of PIPV. Design: Single-institution, prospective, observational, randomized trial. Setting: University teaching hospital. Participants: One thousand four hundred ninety-seven consecutive patients undergoing cardiopulmonary bypass procedures. Intervention: Protamine neutralization of heparin by infusion pump via either central venous or peripheral venous route. Measurements and Main Results: Five previously suspected risk factors (valve surgery, prior protamine exposure, history of pulmonary hypertension, fish allergy, and vasectomy), aspirin ingestion within 7 days of surgery, and demographic information were recorded. PIPV was defined as an abrupt increase in mean PA pressure of 7 mmHg or more with associated right ventricular dysfunction as assessed by observation of the right ventricle in the field and regional wall motion abnormality by transesophageal echocardiogram and hypotension (systolic blood pressure ≤ 90 mmHg). Data were collected via continuous strip chart recording. A total of 10 patients (0.6%) developed PIPV during protamine infusion. The incidents were similar with respect to the site of venous administration. Prior exposure to protamine was associated with a greater incidence of PIPV (odds ratio 6.9; p < 0.01). Other previously suspected risk factors did not achieve statistical significance. None of the 766 patients who ingested aspirin experienced PIPV as opposed to 10 of the 731 patients who did not ingest aspirin (odds ratio 0.08; p < 0.001). Conclusions: Although the site of venous protamine administration does not influence incidence of PIPV, aspirin ingestion within 1 week of surgery may decrease it. These data also confirmed other studies suggesting that previous protamine administration predisposes to this protamine reaction.