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Tube thoracostomy is usually sufficient treatment for traumatic hemothorax. Occasionally, significant residual collections remain undrained. Open thoracotomy and video-assisted thoracoscopic surgery (VATS) have been used to manage undrained traumatic hemothoraces (UTHs). Both techniques are invasive and harbor risks. More recently, intrapleural administration of thrombolytic agents (streptokinase and urokinase) has been reported as an effective nonoperative treatment of residual collections caused by a variety of diseases. The role of intrapleural thrombolysis (IT) for the treatment of an UTH is inadequately explored.Patients with an UTH, defined as more than 300 mL of intrathoracic blood estimated by computed tomographic scan on the third day after chest tube insertion, were followed prospectively for 16 months. IT was instituted according to a standardized protocol using streptokinase or urokinase. IT effectiveness, defined by the incidence of successful resolution of the UTH, and IT safety, defined by the incidence of uncomplicated therapy, was calculated.Of 203 patients with a traumatic hemothorax, managed by tube thoracostomy, 25 (12.3%) developed an UTH. Successful resolution of the UTH was achieved in 23 (92%) patients within 3.4 ± 1.4 days. No bleeding or other significant complications related to IT were recorded.IT should be the initial treatment of choice for the management of an UTH.