Ketoconazole and pulmonary failure after esophagectomy: a prospective clinical trial

Thromboxane is a key mediator in pulmonary injury after esophageal resection. In this prospective trial we studied the clinical course and development of pulmonary alterations in patients undergoing esophagectomy and prophylactic treatment with a thromboxane synthase inhibitor. Thirty-eight consecutive patients undergoing esophageal resection were treated pre- and perioperatively with 3 x 200 mg ketoconazole. The clinical course was studied and pulmonary function was assessed according to the Murray score. A historical group of 118 patients undergoing esophagectomy for benign and malignant esophageal diseases served as controls. Patients in both groups were similar in 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 neoadjuvant radiochemotherapy (22/38) or undergoing thoracotomies (33/38) than control subjects (14/118 and 80/118, P < 0.05). Two out of 38 ketoconazole-treated patients developed acute lung injury after esophagectomy, as did 20/118 control patients (P < 0.05). This prospective non-randomized clinical study (in patients subjected to esophagectomy) provides further evidence that prophylactic thromboxane synthase inhibition by ketoconazole reduces the incidence of acute lung injury in patients at risk.