During the past century explosive developments have taken place in the field of molecular medicine and genetics, vastly expanding our understanding of the normal physiological response to injury. We have been able to characterise specific molecular and cell biological processes and apply some of this knowledge to the treatment of multiply injured patients. Despite the significant steps we have made, there still remains much work to be done in this area. This review article highlights the current concepts of post-traumatic immunological changes and their impact in the management of trauma patients.

Current concepts of the inflammatory response after major trauma: an update

In this book current knowledge of the pathophysiology of shock, sepsis and multi organ failure is presented. The rapid progress which has been made and the results achieved in intensive care medicine are based on sound basic research, which is duly reflected in these chapters. Multiorgan failure is the foremost cause of postoperative and posttraumatic death and many complex mechanisms are involved. Only with a good foundation of basic research can abnormalities in the physiological, biochemical, and morphological course of shock be recognized and the necessary conclusions for treatment drawn. Therapy must proceed from profound knowledge of the multi variant physiological events in order to influence shock, sepsis and organ failure. Although numerous possibilities for therapy have arisen from pharmaceutical research in recent years, they are beyond the scope of this book and are not discussed here. To gain a better understanding of the pathophysiological events it was necessary to examine and to describe different models that simulate and reproduce these events. Here we describe the causative agents (shock) and the consequences (sepsis, organ failure) in two main sections, divided on the basis of their pathophysiology.

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Pathophysiology of shock, sepsis, and organ failure

Inflammatory cells, particularly neutrophil granulocytes, have been implicated in the pathogenesis of the adult respiratory distress syndrome (ARDS). In this study, we investigated whether a relationship exists between neutrophil elastase in the plasma of multiple-trauma patients on initial hospital presentation and the subsequent development of lung injury and ARDS. Sixty-one multiple-trauma patients were enrolled prospectively. Neutrophil elastase was measured by a specific radioimmunoassay, and analysis was performed by nonparametric statistical methods. A highly significantly elevated plasma elastase level was found in patients who progressed to ARDS (median 217 ng/ml, range 127 to 480) (n = 8) compared with those who did not (median 117 ng/ml, range 21.4 to 685) (n = 53) (p = 0.009). Significant correlation was found between initial elastase values and subsequent requirement for mechanical ventilation (p = 0.01), lowest arterial oxygen saturation/oxygen supplementation recorded (p = 0.003), and organ failure score (p = 0.006). This study shows that within minutes of the initiating trauma event, there is evidence of enhanced neutrophil degranulation as manifested by elevated levels of immunoreactive neutrophil elastase in the peripheral blood. The level of this enzyme correlates with the degree of subsequent lung injury and ARDS. These findings reinforce the importance of neutrophils and their secretory products in early ARDS disease pathogenesis.

Plasma Elastase Levels and the Development of the Adult Respiratory Distress Syndrome

Almitrine improves ventilation/perfusion relationships (VA/Q) in COPD, but its effects in ARDS, in which VA/Q mismatching is the cause of severe hypoxemia, are not known. The effects of almitrine on pulmonary gas exchange and circulation were assessed in 9 patients with ARDS who were sedated, paralyzed, and mechanically ventilated at constant FlO2 (range, 0.48 to 0.74). Systemic and pulmonary hemodynamics, conventional gas exchange, and the VA/Q distribution by the multiple inert gas elimination technique (MIGT) were measured before (baseline), during (ALM 15), at the end of (ALM 30), and at 30-min intervals after (POSTALM 30, 60, and 90) the intravenous infusion of 0.5 mg/kg body weight of almitrine over 30 min. Almitrine significantly increased PaO2 from 78 +/- 15 mm Hg to 140 +/- 49 at ALM 15 and 138 +/- 52 at ALM 30. AaPO2 and QS/QT decreased during the administration of the drug. The MIGT showed that almitrine redistributed pulmonary blood flow from shunt areas (reduction from 29 +/- 11 to 17 +/- 11% of QT) to lung units with normal VA/Q ratios (increase from 63 +/- 9 to 73 +/- 6% of QT). The Ppa increased from 26 +/- 5 to 30 +/- 5 mm Hg without changes in QT. Changes were transient, returning toward baseline 30 min after stopping the infusion of the drug. Almitrine significantly reduced the VA/Q inequalities present in ARDS and may be useful in the management of those patients.

Effect of Almitrine on Ventilation-Perfusion Distribution in Adult Respiratory Distress Syndrome

Intramedullary nailing is the preferred treatment for stabilizing femoral diaphyseal fractures. Despite the superior biomechanical advantages over other implants, its use especially in some selected groups of patients, has been questioned because of possible harmful systemic effects of intramedullary reaming. The lung seems to be the primary target for fat embolization and for mediated effects by inflammatory reactions. The latter are initiated in the immediate aftermath after injury, and femoral nailing can amplify these responses. The role of reaming in the context of early femoral fracture fixation in the patient experiencing trauma is debatable. This review article focuses on the evidence that has emerged during the past century regarding the systemic effects of femoral nailing.

Lynne M. Zheutlin

Papers

Plasma elastase levels in the adult respiratory distress syndrome

C3A DES ARG and elastase-alpha 1-protease inhibitor levels in lavage fluid from patients with adult respiratory distress syndrome