Cytokine Liberation From Secondary Surgery in the Setting of the Second Hit Syndrome

There is still debate concerning the appropriate timing of stabilization of long bone fractures in patients with thoracic trauma2. While most surgeons agree that definitive stabilization within 24 hours of injury is optimal, this is sometimes not possible nor wise. When early definitive stabilization is not possible, there are differences between accepted practice between European and North American surgeons. European surgeons prefer to wait five days until definitive treatment, citing literature from Pape6 concerning the increased incidence of pulmonary complications and multi-system organ failure (MOF) which is purported to be higher in patients who undergo stabilization during the two to four day window. Pape postulates that this may be in part due to a "second hit" to the inflammatory system. He cites an increase in IL-6 and TNFα in patients who are operated during this window.

North American surgeons tend to operate whenever it is felt that the patient is stable enough to undergo surgical stabilization from a trauma surgery standpoint. Much less emphasis is placed on the "second hit" etiology of multi-system organ failure. More emphasis in this country is placed on the fat embolism theory of MOF.

There are several flaws in the European literature which leave North American surgeons unconvinced that delay is better in this population. First, Pape's large retrospective study which reported on 4313 patients treated between 1975 and 1999 did not take into account the dramatic changes in the management of critically ill patients which occurred during this time interval. The conclusion that patients treated later in the study with the concept of "damage control orthopaedics" may have had better outcomes because of improved ventilatory or resuscitative techniques, rather than because of the timing of secondary surgery. In another study, he made the conclusion that patients operated between days two and four had a worse outcome than those operated after four days. Patients with a poor outcome also correlated with elevated IL-6 levels on admission. This study was a prospective cohort study with patients selected for early versus delayed treatment based on the convenience of getting to the operating room and the patient's general condition. This study did not control for other surgical procedures which may have been performed during the time periods studied. While compelling, this study should be repeated using randomized controls.

There is considerable literature1,4,7-10 which suggests that MOF is related to an inflammatory mediated chain of events. Most inflammatory markers are elevated in trauma, and IL-6 seems to be one which may be of prime importance in this cascade of events. It has been shown that surgery of many kinds increases IL-6 levels.

Furthermore, there is evidence that there is a genetic predisposition3,5 toward producing high levels of cytokines.