U. Obertacke

Epidemiology of the severely injured patient. A prospective assessment of preclinical and clinical management. AG Polytrauma of DGU

ZusammenfassungTrotz der großen medizinischen und sozioökonomischer Bedeutung der schweren Mehrfachverletzung existieren nur wenige aktuelle Daten zur Beschreibung dieses Kollektivs. Ziel der Untersuchung war es, die von 1993 – 1997 prospektiv und multizentrisch erfaßten 2069 Patienten des DGU-Traumaregisters epidemiologisch zu untersuchen. Es erfolgte eine deskriptive Analyse der Inzidenz der Verletzungen und Komplikationen im Patientenkollektiv und des Umfanges therapeutischer Maßnahmen. Der Verkehrsunfall war mit 56,7% die häufigste Unfallursache, das Durchschnittsalter betrug 38,5 ± 18,7 Jahre, das Verhältnis männlich zu weiblich 2,6:1. Bei einem “Injury Severity Score” (ISS) von durchschnittlich 22,2 ± 13,1 Punkten war bei fast ausschließlich stumpfen Verletzungen das Thoraxtrauma die häufigste relevante Verletzung (AIS der Region Thorax ≥ 3 Punkte, 44,5%). Das Schädel-Hirn-Trauma (SHT) mit einem AIS ≥ 3 (39,2%) beeinflußte die Frühletalität (Tod ≤ 24 h nach Trauma, 51,7% der Verstorbenen) und die Gesamtklinikletalität (18,6%); 68,9% der Patienten zeigten Extremitätenverletzungen; 71,7% der Patienten wurden im Bereitschaftsdienst aufgenommen (16–8 Uhr werktags, Wochenenden und Feiertage). Die Verletzten wurden Median 4 Tage beatmet, 6 Tage intensivstationär behandelt und verweilten 19 Tage im Krankenhaus. An Komplikationen wurden Organversagen (Lunge 22%, Kreislauf 18,7%, Leber 9,6%, Niere 3,1%) und Sepsis (11,6%) erfaßt. Die durchgeführte epidemiologische Analyse stellt eine umfassende Beschreibung eines großen Kollektivs schwer Mehrfachverletzter dar. Die aktuellen Daten des DGU-Traumaregisters sind nutzbar zur Beantwortung wissenschaftlicher, klinischer und ökonomischer Fragen zum Qualitätsmanagement.AbstractThe severe multiple trauma is of extraordinary medical and social and economical importance. Nevertheless there exist only a few german data to describe these patients. The aim of the study was an epidemiological analysis of 2069 patients of the Trauma Registry of the German Society of Trauma Surgery, recorded from 1993 – 1997. A descriptive kind of analysis of the incidence of injuries and complications of theis collective was done and the amount of therapeutic means examined. Most patients (56.7%) were traffic victims, almost all patients suffered from blunt trauma. The relation male to female was 2.6:1, the average Injury Severity Score 22.2 ± 13.1 points, the average age was 38.5 ± 18.7 years. Chest trauma was the most frequent significant injury (AIS ≥ 3 points, 44.5%), followed by severe head injury (39.2%) which was the most important reason for early lethality (death ≤ 24 h after trauma, 51.7% of all deceased) and the total hospital lethality (18.6%). 68.9% of the patients showed injuries of the extremities. Patients were admitted to hospital in 71.7% in times of stand-by service (between 4 p.m. and 8 a.m., weekends, holidays) and required (median) 4 days ventilation, 6 days ICU treatment and stayed in hospital 19 days. Complications recorded were organ failure (lung 22.0%, circulation 18.7%, liver 9.6%, kidney 3.1%) and sepsis (11.6%). The presented epidemiological analysis is comprehensive description of a large collective of multiple traumatized patients. The current data of the Trauma Registry of the German Trauma Society can be used to answer scientifical, clinical and economical questions and for quality management.

Sex differences in posttraumatic cytokine release of endotoxin-stimulated whole blood: relationship to the development of severe sepsis.

BACKGROUNDnIn experimental trauma-hemorrhage and sepsis, a sexual dimorphism of cell-mediated immune functions has been described, which has been related to higher susceptibility to and mortality from sepsis in males. Therefore, in the present study, sex differences with regard to cytokine release of endotoxin stimulated whole blood and its relation to the development of severe posttraumatic sepsis were investigated in blunt trauma patients with multiple injuries.nnnMETHODSnEighty-four patients (25 female; 59 male) sustaining blunt injuries with an Injury Severity Score > 16 were enrolled in the study. Whole blood and serum were obtained during a 14-day period of hospitalization. The capacity of peripheral blood mononuclear cells to produce cytokines (tumor necrosis factor-alpha, interleukin [IL]-6, IL-8) was tested by using a whole blood assay. Serum samples were assayed for anti-inflammatory cytokines (IL-4, IL-10, and transforming growth factor beta1) and sex hormones (testosterone, estradiol, progesterone). Patients were monitored daily for sepsis criteria according to the ACCP/ SCCM consensus conference 1992.nnnRESULTSnWithin the entire patient population, sex differences in posttraumatic cytokine release were not detectable. Male trauma patients developing severe sepsis (n = 16) presented with a significantly increased cytokine producing capacity in the early posttraumatic period (< or = 24 hours after admission to the emergency room) when compared with males with an uncomplicated recovery. In females, differences between the subgroups of patients with (n = 7) and without development of severe sepsis were not detectable. There were no differences in systemic levels of anti-inflammatory cytokines within the early posttraumatic period between the subgroups of male and female patients with and without development of severe sepsis. In females, differences in sex hormone levels were not detectable, whereas in males, development of severe sepsis later was found to coincide with significantly decreased testosterone and increased estradiol serum levels.nnnCONCLUSIONnThe present study demonstrates a sex-specific regulation of leukocyte function in patients with multiple injuries within the early posttraumatic period. In male patients with multiple injuries, increased cytokine-producing capacities may correspond to enhanced inflammatory responses, which increase susceptibility to sepsis, whereas in female patients, other regulatory mechanisms may be involved.

Intermittent prone positioning in the treatment of severe and moderate posttraumatic lung injury.

OBJECTIVEnSevere posttraumatic lung injury is characterized by impairment of gas exchange and pulmonary densities. The influence of intermittent prone positioning on pulmonary gas exchange and parenchymal densities was investigated prospectively in patients with pulmonary injury after multiple trauma with blunt chest trauma.nnnSETTINGnA six-bed trauma intensive care unit in a university hospital.nnnDESIGNnProspective, descriptive study.nnnPATIENTSnTwenty-two consecutive patients with pulmonary injury after multiple trauma with blunt chest trauma and acute lung injury (n = 11) or severe acute respiratory distress syndrome (ARDS) (n = 11) according to the definitions of the consensus conference on ARDS.nnnINTERVENTIONSnPulmonary densities were calculated planimetrically from computed tomographic scans of the chest before the first and after the last cycle of prone positioning. Indications for prone positioning were a) mechanical ventilation with FIO2 >0.5 at positive end-expiratory pressure >10 cm H2O for >24 hrs; or b) pulmonary densities in two or more quadrants being constant or increasing within 48 hrs. Arterial blood gas analysis was performed every 2 hrs. Intrapulmonary right-to-left shunt (Qs/Qt) and alveolar-arterial PO2 difference were calculated 2 hrs after the beginning and end of every prone and supine cycle, respectively. Patients were ventilated in the prone position for 8 hrs each day.nnnMEASUREMENTS AND MAIN RESULTSnEvery single posture change from the supine to the prone position resulted in a significant average increase in the oxygenation index of 28+/-8 torr (3.7+/-1.1 kPa) (p<.0001). There was a significant improvement in oxygenation (4.3+/-0.8 torr [0.57+/-0.11 kPa]) with time between two consecutive measurements in the prone as well as the supine position (p<.0001). Alveolar-arterial PO2 difference and Qs/Qt showed a significant decrease of 25+/-7 torr (3.3+/-0.9 kPa) and 1.1+/-0.46%, respectively, for every cycle of prone positioning. Statistical analysis revealed no significant alteration of gas exchange within every prone and supine cycle. Total static lung compliance improved significantly over time (p<.001). However, ventilation of patients in the prone position demonstrated a mean decrease in compliance of 2.1+/-0.72 mL/cm H2O. The response to prone positioning was similar in patients with ARDS and acute lung injury and revealed no significant difference. In both groups, the course of the oxygenation index and Qs/Qt over time was almost parallel. Posture changes were continued for 9.0+/-1.1 days. The oxygenation index showed an overall increase of 129+/-20 torr (17.2+/-2.7 kPa) from baseline supine at the end of prone positioning (p<.0001). Pulmonary densities were reduced significantly from 31.1+/-2.5% to 3.8+/-0.81%, Qs/Qt was reduced from 24.9+/-1.5% to 11.7+/-0.32%, and FIO2 was reduced from 0.43+/-0.04 to 0.26+/-0.02 (p<.01). Gas exchange improved in all patients, and no patient died immediately as a result of respiratory failure.nnnCONCLUSIONnRepeated prone positioning recruits collapsed lung tissue and improves gas exchange in trauma patients with blunt chest trauma and severe ARDS as well as in trauma patients with acute lung injury.

The extent of traumatic damage determines a graded depression of the endotoxin responsiveness of peripheral blood mononuclear cells from patients with blunt injuries.

OBJECTIVEnTo study whether the endotoxin responsiveness of peripheral blood mononuclear cells correlates with the severity of injury in trauma patients.nnnDESIGNnProspective, observational study.nnnSETTINGnUniversity trauma center.nnnPATIENTSnFifty-nine patients with blunt trauma (Injury Severity Score [ISS] 4 to 57 points).nnnINTERVENTIONSnStandard emergency department care, surgical care, and postoperative intensive care unit treatment.nnnMEASUREMENTS AND MAIN RESULTSnWhole blood and serum were obtained 94+/-89 (SD) mins post trauma (day 0) and during a 14-day period postinjury. Endotoxin-induced tumor necrosis factor-alpha (TNF-alpha) synthesis of peripheral blood mononuclear cells ex vivo was tested using a whole blood assay. Serum samples were assayed for TNF-alpha concentrations. A reduced capacity of whole blood to produce TNF-alpha ex vivo with endotoxin treatment was found to be closely correlated with the ISS. The capacity to produce TNF-alpha on endotoxin stimulation of whole blood from patients with an ISS > or =16 points was depressed immediately after trauma and did not reach normal values during the observation period. In patients with an ISS >22 points, maximum depression of the capacity of whole blood to produce TNF-alpha occurs within 100 mins post injury. In contrast, in patients with an ISS <22 points, maximal depression of whole blood TNF-alpha production occurs with a delay of 24 to 48 hrs after trauma. Based on pre- and postoperative values, primary surgical intervention caused a decrease of the endotoxin-stimulated TNF-alpha production of whole blood in the latter patient subgroup, as well as in the entire patient population (ISS 4 to 57) when secondary surgical treatment was necessary 5 to 13 days after trauma.nnnCONCLUSIONSnThe extent of traumatic tissue damage leads to a graded depression of immunocyte function and appears to be amplified by surgical treatment. The endotoxin responsiveness of peripheral blood mononuclear cells displays a functional marker of the anatomically defined severity of injury and gives insights into the regulation of immunocyte function after severe blunt trauma.

Altered pulmonary surfactant in uncomplicated and septicemia-complicated courses of acute respiratory failure.

Pulmonary surfactant, which is crucial for alveolar stability, may also be involved in endogenous defense mechanisms of the lungs. Thus, alterations in pulmonary surfactant may promote infections, including pneumonia and septicemia. Because patients who have acute respiratory failure often develop pneumonia, thus septicemia, we investigated when surfactant is altered in these patients and whether there is a specific pattern of changes in surfactant phospholipid composition associated with septicemia in these patients. To answer these questions, we determined the phospholipid content and composition in lung washings obtained from alveolar sites (by bronchoalveolar lavage) and from tracheal sites (by aspiration). Both techniques were performed serially over a period of 18 days in 30 patients who had acute respiratory failure resulting from polytrauma, 18 of whom developed septicemia caused by pneumonia. We found that in lung washings obtained from the alveolar sites from all patients, the phosphatidylglycerol content was decreased and the phosphatidylinositol content was increased as early as 6 hr after trauma and normalized during recovery of the patients. In addition, alveolar phosphatidylcholine content was decreased 24 hr after trauma. In patients who developed septicemia during the observation time, but not in patients who had uncomplicated courses of acute respiratory failure, the concentrations of alveolar phosphatidylethanolamine (normally 4.8% of total phospholipids) and alveolar phosphatidylcholine (normally 62.8%) both approached the proportions found in the trachea (phosphatidylethanolamine 33.4%, phosphatidylcholine 35.6%), suggesting that surfactant phospholipid pool size had progressively decreased. Our results indicate that in patients who have acute respiratory failure, pulmonary surfactant is altered very early, and that when septicemia complicates the course of acute respiratory failure, the surfactant phospholipid pool size decreases progressively.(ABSTRACT TRUNCATED AT 250 WORDS)

Nailing versus plating in thoracic trauma : An experimental study in sheep

In this study, femoral intramedullary pressure, fat embolization, and pulmonary response were measured during reamed and unreamed nailing and plating of femoral fractures after blunt thoracic trauma. Intramedullary peak pressures of 425 mm Hg (mean 205 mm Hg) occurred in the reamed nail group (group I) during reaming with the 9-mm reamer, while in the unreamed nail group (group II) peak values were seen during nail insertion (330 mm Hg) with a mean of 203 mm Hg. Plating never led to a pressure rise over 67 mm Hg (mean 37 mm Hg). In reamed nailing, the most intense embolism was identified under ultrasound imaging with the large awl and with the 9.0-mm reamer (mean 2.2) and in the unreamed nail group during nail insertion (mean 2.8). Minimal echoes appeared during plating. The pulmonary arterial pressure did not vary significantly postoperatively between the three groups (p < 0.08). Our findings indicate that intramedullary fracture fixation causes a higher increase of intramedullary pressure and more fat and bone marrow embolization than extramedullary ones. Nevertheless, only minimal differences in the pulmonary hemodynamic response (pulmonary arterial pressure) were noted even in the presence of thoracic trauma.

Whole blood tumor necrosis factor-alpha production and its relation to systemic concentrations of interleukin 4, interleukin 10, and transforming growth factor-beta1 in multiply injured blunt trauma victims.

Objective To study the relation of whole blood endotoxin responsiveness to inhibitory mediators systemically released after severe blunt trauma. Design Prospective, observational study. Setting University trauma center. Patients Thirty-two patients with blunt trauma (mean injury severity score, 33 points). Interventions Standard emergency department, surgical care, and postoperative intensive care unit treatment. Measurements and Main Results Whole blood and serum were obtained immediately after admission to the emergency department (<8 hrs after trauma, denoted day 0) and on days 1, 2, 4, 6, 8, and 14 after trauma. Whole blood specimens were assayed for endotoxin-induced tumor necrosis factor (TNF)-&agr; synthesis ex vivo and serum specimen were assayed for interleukin (IL)-4, IL-10, and transforming growth factor (TGF)-&bgr;1 concentrations. Moreover, the TNF-&agr; inhibitory capacity of recombinant human (rh) IL-4, rhIL-10, and TGF-&bgr;1 as well as the inhibitory capacity of patients’ serum from days 0, 1, 2, 4, 6, 8, and 14 were tested on uninjured donors’ whole blood. Cytokines were determined by ELISA. Whole blood endotoxin responsiveness in multiply injured patients was significantly reduced during the observation period and was found to be significantly related to the total inhibitory activity detected in the corresponding sera. Exchange of patients’ serum for uninjured donors’ or recovered patients’ serum restored TNF-&agr; production of peripheral blood mononuclear cells from multiply injured patients. Serum levels of IL-4 and IL-10 were not related to trauma patients’ whole blood TNF-&agr; production upon endotoxin stimulation, whereas TGF-&bgr;1 concentrations were positively related. Compared with the apparent half-maximal inhibition concentrations determined, serum levels of TGF-&bgr;1, IL-10, and IL-4 were 20- to 20,000-fold below the quantities required to explain the inhibitory serum activity in multiply injured patients on day 0. Conclusions Whole blood hyporesponsiveness to endotoxin in multiply injured patients is caused by soluble serum factors systemically released after trauma, whereas the intrinsic leukocyte function appears unaffected. Inhibitory mediators other than IL-4, IL-10, or TGF-&bgr;1 are supposed to be of major biological relevance for the posttraumatic regulation of leukocyte function. Characterization of the causative suppressive mediators is supposed as a prerequisite for the development of immunologically based therapeutic approaches in critically ill patients.

Surfactant abnormalities and adult respiratory failure

Surfactant abnormalities have been implicated in the development of the acute respiratory distress syndrome in adults. Experimental studies show that surfactant inhibition by protein-leak into the alveolar space is of major importance under these circumstances. Fibrin(ogen)-surfactant-interaction appears to contribute to disturbances of surfactant function with subsequent alveolar instability and ventilation-perfusion-mismatch. In a prospective study in severely injured patients, the surfactant in serially obtained bronchoalveolar lavage fluids was investigated. An early leakage of plasma proteins into the alveolar space was noted in those patients, who developed severe ARDS. Moreover, deterioration of surfactant function was markedly more pronounced in those patients than in trauma victims who developed only mild pulmonary dysfunction. In addition to the protein-leakage, a progressive decrease of the surfactant-specific dipalmitoyl-phosphatidylcholine was noted, significantly correlated with the deterioration of surfactant function and the severity of respiratory failure. In conclusion, experimental and clinical studies show surfactant abnormalities in the adult respiratory distress syndrome. Plasma protein-leakage and progressive alteration of alveolar type II surfactant secretion appear to be of major importance.

Does lung contusion affect both the traumatized and the noninjured lung parenchyma? A morphological and morphometric study in the pig.

Isolated unilateral lung contusion (LC) was induced in 12 pigs to determine the pathophysiological role of LC in the high mortality after multiple injury. The Horovitz quotient, pulmonary vascular resistance, mean pulmonary artery pressure, mixed venous oxygen consumption, inspiratory pressure and compliance were significantly decreased in the LC group as compared to controls. The number of polymorphonuclear granulocytes, the microvascular permeability of albumine and the Wilhelmy balance as determined by bronchoalveolar lavage were significantly increased after lung contusion. As indicators of a systemic reaction we found elevated plasma levels of the terminal complement complex and decreased levels of the complement factor 3a after LC. The morphological assessment revealed changes such as those encountered during the early phase of adult respiratory distress syndrome, with granulocyte sticking, endothelial cell adhesion and transendothelial diapedesis. Morphometric analysis demonstrated a significant decrease in alveolar diameter in both the injured and the contralateral lung due to impaired surfactant surface activity. A distinct increase in septal diameter, related to edema and caused by increased microvascular permeability, was found in the injured lungs. These findings emphasize that LC leads to a generalized impairment of the entire lung, which may lead to progressive lung failure.

Kostenanalyse der Primärversorgung und intensivmedizinischen Behandlung polytraumatisierter Patienten

Treatment costs of emergency therapy, surgery and intensive care were analysed in 20 randomly chosen, representative patients with severe multiple trauma (mean ISS 32 p). For an average stay of about 22.5 days in the ICU, the total costs were DM 106,924.36 (about 70,000 US