Multimodal approach to control postoperative pathophysiology and rehabilitation. By Kehlet H. Br J Anaesth 1997; 78:606–17 Major surgery is still associated with undesirable sequelae such as pain, cardiopulmonary, infective and thromboembolic complications, cerebral dysfunction, nausea and gastrointestinal paralysis, fatigue, and prolonged convalescence. The key pathogenic factor in postoperative morbidity, excluding failures of surgical and anesthetic technique, is the surgical stress response with subsequent increased demands on organ function. These changes in organ function are thought to be mediated by trauma-induced endocrine metabolic changes and activation of several biologic cascade systems (cytokines, complement, arachidonic acid metabolites, nitric oxide, free oxygen radicals, among others). To understand postoperative morbidity, it is therefore necessary to understand the pathophysiologic role of the various components of the surgical stress response and to determine whether modification of such responses may improve surgical outcome. While no single technique or drug regimen has been shown to eliminate postoperative morbidity and mortality, multimodal interventions may lead to a major reduction in the undesirable sequelae of surgical injury with improved recovery and reduction in postoperative morbidity and overall costs.