Review of the Multicenter Trial Committee Report: A Prospective, Randomized Study on the Prophylaxis of Postoperative Deep Venous Thrombosis

The etiology of postoperative deep venous thrombosis (DVT) is thought to be due to a combination of factors including stasis, a hypercoagulable state and venous endothelial damage. Methods of prophylaxis are directed toward correcting one or more of these pathologic events. Methods counteracting more than one of these factors can be expected to be even more effective. The combination of dihydroergotamine (DHE) and heparin was anticipated to minimize stasis and the hypercoagulable state respectively. Based upon current experimental evidence and current theory, an additional benefit might include minimizing venous endothelial injury by controlling venomotor tone. A prospective, randomized, double‐blind, multicenter trial was designed and performed in the United States evaluating the prophylactic efficacy of DHE 0.5 mg plus heparin 5000 U, DHE 0.5 mg plus heparin 2500 U, heparin 5000 U, and DHE 0.5 mg versus placebo. General surgical patients including those undergoing noncardiac thoracic and pelvic operations who were identified at moderate to high risk for postop DVT were included. Study medications were injected subcutaneously two hours preoperatively and every 12 hours postoperatively for 5–7 days or until the 125 I‐fibrinogen‐uptake test (RFUT) became positive. Eight hundred and eighty eight patients were entered into this trial and 744 (85%) completed the study. Results showed a statistically significant benefit from DHE/Hep 5000 compared to placebo (p < 0.01) and compared to other active agents (p < 0.05). None of the other active agents showed a statistically significant prophylactic benefit. This was most likely due to sample size. Intraoperative blood loss, postoperative blood loss, and the amount of blood replaced were monitored and were similar for all treatment groups and placebo. There was no significant difference in incidence of wound hematomas or injection site hematomas. The side effects were similar throughout all treatment groups and placebo. Ths US Multi‐center Trial suggests that general surgical patients who are at high risk for developing postoperative DVT can be offered safe and effective prophylaxis with the combination of DHE/heparin 5000.