Clinical treatment strategies and experimental studies in polytrauma

Abstract

This thesis describes the clinical treatment of polytrauma patients and the underlying pathophysiological mechanisms causing injury-induced inflammatory response. Even though the treatment of polytrauma patients has improved over the years, trauma is still the leading cause of death worldwide.Classically, the epidemiology of traumatic deaths was described as a trimodal distribution (immediate deaths, early hospital deaths, late deaths). With improved trauma care, we have revaluated this and discovered that the classical trimodal death distribution nowadays is much more skewed towards early deaths. Death by exsanguination has become as frequent as lethal head injuries, but the incidence of fatal multiple organ failure is lower than reported earlier. Although the introduction of the damage control surgery strategy in the 1990s has decreased the mortality of trauma patients, morbidity rates have increased, leading to new challenges such as abdominal compartment syndrome (ACS). Recognition, treatment and prevention have decreased the incidence of ACS in the last decade. Further, attenuation of the deadly ACS to a less deleterious intra-abdominal hypertension is considered a success of the last decade in trauma and critical care. The increased popularity of damage control surgery and increased ACS recognition has led to a raised incidence of abdomens left open after surgery. Even though opening an abdomen in ACS is life-saving, morbidity rates are high. Several techniques have been described for temporary closure of an open abdomen. To date, however, there is no perfect method to cover an open abdomen. A special group of polytrauma patients are those with open pelvic fractures. Up to half of them die due to pelvic injuries (acute hemorrhage and late sepsis).The open nature of the injury increases the chances of significant fracture site uncontrolled bleeding and pelvic contamination. Historically, faecal diversion has been regarded as an obligatory procedure to minimize infectious complications. With novel wound management techniques available we suggest that a diverting stoma is only warranted in patients with transmural rectal lacerations and/or extensive soft tissue injuries in the perineum. Trauma leads to immune activation after which immune mediators and inflammatory cells are released. This immune response promotes wound healing and increases the protection against bacteria. Sometimes, however, the immune system will become hyperactive, inducing (extra) tissue damage leading to organ failure.In the second part of this thesis experimental studies are described investigating the role of neutrophils (white blood cell important for the immune response) on the development of an inflammatory response after several types of trauma (hemorrhagic shock (HS), mechanical ventilation, septic shock). It was noted that HS alone had minimal effect on the development of systemic inflammation. Mechanical ventilation (alone or in combination with HS) is the determining factor in inducing an inflammatory response. These results emphasize the importance of local (pulmonary) ventilation-induced damage in the development of systemic inflammation. Further, experiments have shown that HS and septic shock show different neutrophil phenotypes in the circulation, suggesting theyinduce an inflammatory response via at least a partially different pathway