Ketoconazole and pulmonary failure after esophagectomy: a prospective clinical trial

Thromboxane is a key mediator in pulmonary injury after esophageal resectio n. In this prospective trial we studied the clinical course and development of pulmonary alterations in patients undergoing esophagectomy and prophyla ctic treatment with a thromboxane synthase inhibitor. Thirty-eight consecut ive patients undergoing esophageal resection were treated pre- and perioper atively with 3 x 200 mg ketoconazole. The clinical course was studied and p ulmonary function was assessed according to the Murray score. A historical group of 118 patients undergoing esophagectomy for benign and malignant eso phageal diseases served as controls. Patients in both groups were similar i n terms of age, sex, and preoperative pulmonary function, as well as in the anesthetic and surgical procedures performed. However, in the ketoconazole group, more patients were at risk of pulmonary failure by receiving neoadj uvant radiochemotherapy (22/38) or undergoing thoracotomies (33/38) than co ntrol subjects (14/118 and 80/118, P < 0.05). Two out of 38 ketoconazole-tr eated patients developed acute lung injury after esophagectomy, as did 20/1 18 control patients (P < 0.05). This prospective non-randomized clinical st udy (in patients subjected to esophagectomy) provides further evidence that prophylactic thromboxane synthase inhibition by ketoconazole reduces the i ncidence of acute lung injury in patients at risk.