Dieter Rixen

Impact of the Method of Initial Stabilization for Femoral Shaft Fractures in Patients With Multiple Injuries at Risk for Complications (Borderline Patients)

Objectives:The timing of definitive fixation for major fractures in patients with multiple injuries is controversial. To address this gap, we randomized patients with blunt multiple injuries to either initial definitive stabilization of the femur shaft with an intramedullary nail or an external fixateur with later conversion to an intermedullary nail and documented the postoperative clinical condition. Methods:Multiply injured patients with femoral shaft fractures were randomized to either initial (<24 hours) intramedullary femoral nailing or external fixation and later conversion to an intramedullary nail. Inclusion: New Injury Severity Score >16 points, or 3 fractures and Abbreviated Injury Scale score ≥2 points and another injury (Abbreviated Injury Scale score ≥2 points), and age 18 to 65 years. Exclusion: patients in unstable or critical condition. Patients were graded as stable or borderline (increased risk of systemic complications). Outcomes:Incidence of acute lung injuries. Results:Ten European Centers, 165 patients, mean age 32.7 ± 11.7 years. Group intramedullary nailing, n = 94; group external fixation, n = 71. Preoperatively, 121 patients were stable and 44 patients were in borderline condition. After adjusting for differences in initial injury severity between the 2 treatment groups, the odds of developing acute lung injury were 6.69 times greater in borderline patients who underwent intramedullary nailing in comparison with those who underwent external fixation, P < 0.05. Conclusion:Intramedullary stabilization of the femur fracture can affect the outcome in patients with multiple injuries. In stable patients, primary femoral nailing is associated with shorter ventilation time. In borderline patients, it is associated with a higher incidence of lung dysfunctions when compared with those who underwent external fixation and later conversion to intermedullary nail. Therefore, the preoperative condition should be when deciding on the type of initial fixation to perform in patients with multiple blunt injuries.

Prognoseabschätzung des Schwerverletzten – Eine Analyse von 2069 Patienten des Traumaregisters der DGU

ZusammenfassungZum Zeitpunkt der Krankenhausaufnahme werden zahlreiche Variablen beim schwerverletzten Patienten erhoben. Die Wertigkeit dieser Variablen in Bezug auf ihre Fähigkeit der Prognoseabschätzung wird unterschiedlich beurteilt. Ziel ist es, bei Krankenhausaufnahme eine initiale Abschätzung des Outcomes schwerverletzter Patienten vornehmen zu k¨nnen. Dazu wurde ein multivariates Prognosemodell auf der Grundlage des Traumaregisters der DGU entwickelt. Patienten und Methode. Zum Zeitpunkt der Krankenhausaufnahme werden durch das DGU-Traumaregister mehr als 30 Variable prospektiv erfasst. Im 1. Schritt der zentral anonymisierten Auswertung wurden zur Vermeidung multipler statistischer Vergleiche diejenigen Variablen ausgewählt, die aufgrund der Literatur als klinische Prädiktoren für das Outcome angesehen werden. Im 2. Schritt erfolgte eine univariate Analyse dieser Variablen. Für alle primären Variablen mit univariater Signifikanz der Outcomevorhersage wurde im 3. Schritt, eine multivariate logistische Regression durchgeführt und ein multivariates Prognosemodell entwickelt. Ergebnisse. Vom 01.01.1993 bis 31.12.1997 wurden 2069 Patienten aus 20 Kliniken im Traumaregister prospektiv erfasst (Alter 39±19 Jahre; m.: 70,0%; ISS 22±13; 18,6% verstorben). Aus mehr als 30 bei Aufnahme erhobenen Variablen zeigten sich das Alter, der GCS, der ISS, der Base-Excess (BE) und der Quick-Wert als wichtigste Prognosefaktoren zur Abschätzung der Wahrscheinlichkeit zu versterben [P(Tod)]. Folgendes Prognosemodell wurde entwickelt: P(Tod)=1/1+e{−[k+β1(Alter)+β2(GCS)+β3(ISS)+β4(BE)+β5(Quick)]} wobei: k=−0,1551, β1=0,0438 mit p<0,0001, β2=−0,2067 mit p<0,0001, β3=0,0252 mit p=0,0071, β4=−0,0840 mit p<0,0001 und β5=−0,0359 mit p−0,0001.Jedes der 5 Variablen trägt signifikant zu dieser multifaktoriellen Gleichung bei. Schlussfolgerungen. Diese Daten zeigen, dass initiales Alter, GCS, ISS, Base-Excess und Quick-Wert frühzeitig verfügbare und potentiell wichtige Prädiktoren sind, um Traumapatienten mit einer hohen Sterbenswahrscheinlichkeit zu identifizieren. Mit Hilfe von Base-Excess und Quick-Wert, als einzige beeinflussbare Variablen dieser multifaktoriellen Gleichung, kann möglicherweise die frühzeitige, aggressive Therapie besser gesteuert werden.AbstractOn hospital admission numerous variables are documented from multiple trauma patients. The value of these variables to predict outcome are discussed controversially. The aim was the ability to initially determine the probability of death of multiple trauma patients. Thus, a multivariate probability model was developed based on data obtained from the trauma registry of the Deutsche Gesellschaft für Unfallchirurgie (DGU). Patients and methods. On hospital admission the DGU trauma registry collects more than 30 variables prospectively. In the first step of analysis those variables were selected, that were assumed to be clinical predictors for outcome from literature. In a second step a univariate analysis of these variables was performed. For all primary variables with univariate significance in outcome prediction a multivariate logistic regression was performed in the third step and a multivariate prognostic model was developed. Results. 2069 patients from 20 hospitals were prospectively included in the trauma registry from 01.01.1993–31.12.1997 (age 39±19 years; 70.0% males; ISS 22±13; 18.6% lethality). From more than 30 initially documented variables, the age, the GCS, the ISS, the base excess (BE) and the prothrombin time were the most important prognostic factors to predict the probability of death (P(death)). The following prognostic model was developed: P(death)=1/1+e{−[k+β1(age)+β2(GCS)+β3(ISS)+β4(BE)+β5(prothrombin time)]} where: k=minus;0.1551, β1=0.0438 with p<0.0001, β2=−0.2067 with p<0.0001, β3=0.0252 with p=0.0071, β4=−0.0840 with p<0.0001 and β5=−0.0359 with p<0.0001. Each of the five variables contributed significantly to the multifactorial model. Conclusions. These data show that the age, GCS, ISS, base excess and prothrombin time are potentially important predictors to initially identify multiple trauma patients with a high risk of lethality. With the base excess and prothrombin time value, as only variables of this multifactorial model that can be therapeutically influenced, it might be possible to better guide early and aggressive therapy.

The reliability of clinical examination in detecting pelvic fractures in blunt trauma patients: a meta-analysis.

IntroductionSeveral studies have recently questioned whether routine radiographic screening for pelvic fractures is necessary in the initial evaluation of blunt trauma patients. Therefore, we assessed how sensitive and specific the clinical examination is in detecting fractures of the pelvis.MethodsWe extensively searched various medical databases for studies that reported on the accuracy of pelvic examination in severely injured adults or children. Individual study results were summarized in a receiver operating characteristics (ROC) curve and pooled in a meta-analysis.ResultsTwelve studies with a total of 5454 patients met our inclusion criteria and provided data in sufficient detail. Pooled sensitivity and specificity were 0.90 (95% confidence interval: 0.85–0.93) and 0.90 (0.84–0.94), respectively. Results were better in those studies which excluded neurologically impaired patients [e.g., Glasgow Coma Scale (GCS) <13]. Among the 49 false negative cases whose fractures went undetected on clinical examination, the majority of patients had either altered consciousness or minor pelvic fracture only. Only 3 clinically relevant pelvic fractures were missed among 441 patients with fracture within a total population of 5235 patients.ConclusionIn stable and alert trauma patients, a thorough clinical examination will detect pelvic fractures with nearly 100% sensitivity, thus rendering initial radiography unnecessary in this group of patients.

Das schwere Schädel-Hirn-Trauma bei Mehrfachverletzten Eine Bestandsaufnahme zur Interaktion lokaler und systemischer Mediatorwirkungen

ZusammenfassungDas isolierte oder mit weiteren Verletzungen kombinierte Schädel-Hirn-Trauma (SHT) ist ein Hauptprognosefaktor für Morbidität und Mortalität nach einem Unfallereignis. Die Prognose des Patienten ist sowohl von der primären, mechanischen Hirnschädigung als auch von der Entwicklung sekundärer Hirnschäden abhängig. Als Ursachen einer sekundären Hirnschädigung werden neben der intrakraniellen Raumforderung aufgrund posttraumatischer Blutungen und Ödembildungen, sowie der daraus resultierenden Ischämie, Entzündungsprozesse diskutiert. Sowohl beim isolierten SHT als auch nach Polytrauma mit und ohne Hirnschädigung kann eine inflammatorische “Systemreaktion” (SIRS) unter der Beteiligung von Zytokinen und anderen Entzündungsmediatoren zu einem Ein- oder Multiorganversagen (MOF) führen. Dabei sind einzelne Verletzungskomponenten und Funktionsstörungen meistens überlebbar, können jedoch in Ihrer Kombination und Kumulation tödlich enden. Hypermetabolische Zustände nach einem SHT werden auch als Interaktionen des ZNS mit dem Gesamtorganismus unter Beteiligung der neuroendokrinen Achse aufgefaßt. Diesen Auswirkungen eines SHT auf den übrigen Organismus ist der Einfluß multipler Verletzungen eines polytraumatisierten Verletzten auf die Hirnfunktion gegenüberzustellen, wobei schockbedingte Perfusionsstörungen eine prognoselimitierende Hypoxie des Gehirns verursachen können. Darüber hinaus beeinflußt die generalisierte “Ganzkörperentzündungsreaktion” Blutgerinnung, Stoffwechsel und Frakturheilung. Die Kenntnisse der traumainduzierten, bidirektionalen, inflammatorischen Interaktionen zwischen Gehirn und Gesamtorganismus, sowie der Einfluß der derzeit angewendeten Therapiemaßnahmen sind bisher noch unzureichend und bedürfen weiterer Aufklärung. Letztendlich muß aus dieser Sicht auch die Wahl des richtigen Zeitpunktes für sekundäre Eingriffe, die nicht unmittelbar der Lebenserhaltung dienen und zu einer zusätzlichen Belastung des Patienten durch das Operationstrauma führen, überdacht werden. Diese Arbeit versucht wichtige Aspekte auf diesem Gebiet zusammenzufassen.SummaryIsolated severe head trauma (SHT) or SHT in combination with multiple injuries are important factors for the prognosis of morbidity and mortality in patients suffering from the consequences of accidents. The prognosis mainly depends on the presence of primary mechanic brain injury and the development of secondary brain damage. Causes for the development of secondary brain damage are the intracranial space demand after traumatic injury and edema formation which may result in iscemia, as well as inflammatory processes. Both isolated SHT and polytrauma with or without brain damage may result in a systemic inflammatory response syndrome (SIRS) due to the synthesis of cytokines and other inflammatory mediators which may cause a single or multiple organ failure (MOF). Often the organism is able to survive isolated traumatic injuries and functional disturbances, but in combination or cumulation they may be lethal. The hypermetabolism after SHT is often regarded as an interaction between the central nervous system and the whole organism by the activation of the neuroendocrine axis. In contrast to the consequences of SHT for the whole organism, multiple injuries after polytrauma may affect brain functions, such as the shock dependent disturbance of the brain perfusion accompanied by brain hypoxia which may lead to an aggravated prognosis. Moreover, coagulation, metabolism and fracture healing are influenced by the onset of SIRS as well. Our knowledge about the bidirectional inflammatory interaction between brain and whole organism is still limited. In this context, the effects of secondary surgical interventions which may additionally stress a traumatized body have to be considered and are the subject for actual clinical discussions and experimental studies. This article tries to summarize some important aspects on this topic.

[Management strategies in the first operative phase after long-bone injury of the lower extremity in multiple-injured patients. A systematic literature review].

ZusammenfassungFragestellungVerletzungen der unteren Extremität haben einen wesentlichen Anteil im Verletzungsmuster polytraumatisierter Patienten. Das Ziel dieser systematischen Literaturanalyse ist es, einen Überblick über die Evidenzlevel (EL) unterschiedlicher Versorgungsstrategien von Frakturen der unteren Extremität beim Polytrauma in der ersten operativen Phase zu erstellen und hieraus entweder (bei genügender Evidenz) klinische Behandlungskorridore abzuleiten oder aber (bei ungenügender Evidenz) die Notwendigkeit wissenschaftlicher Überprüfung zu dokumentieren.MethodikKlinische Studien wurden über systematische Suchen (Medline, Cochrane und Handsuchen) und Klassifikation nach Evidenzlevel (EL1–5 nach Oxforder Schema) zusammengetragen.ErgebnisseDie Notwendigkeit einer primär- vs. sekundär-definitiven Osteosynthese von Schaftfrakturen des Femurs/der Tibia beim Polytrauma ist derzeit noch nicht hinreichend geklärt. Das Operationsverfahren der Wahl zur definitiven Versorgung einer Femurschaftfraktur ist die Marknagelung. Der Stellenwert der Stabilisierung von proximalen und distalen Femur- sowie Tibiafrakturen beruht größtenteils auf Expertenmeinung. Nach der Literatur ist eine perioperative Antibiotikaprophylaxe bei der operativen Frakturversorgung indiziert.SchlussfolgerungenZu Versorgungsstrategien in der ersten operativen Phase nach Verletzungen langer Röhrenknochen der unteren Extremität beim Polytrauma liegen eine Vielzahl vergleichender Untersuchungen (EL2) vor, randomisierte Studien existieren jedoch wenige. Anhand der Datenlage ist eine wissenschaftlich begründete Behandlung dieser Patienten in weiten Bereichen möglich.AbstractObjectiveLower extremity injuries make up a substantial proportion of the injuries in multiply injured patients. The aim of this systematic literature analysis was to give an overview of the levels of evidence for different management strategies in the first operative phase after long-bone injuries of the lower extremity in multiply injured patients to enable, in the presence of adequate evidence, the development of clinical management corridors or, if the evidence was found to be inadequate, to document the necessity for scientific proof.MethodsClinical trials were systematically collected (Medline, Cochrane and hand searches) and classified into evidence levels (EL 1 to 5 according to the Oxford system).ResultsThe necessity for primary or secondary definitive osteosynthesis of femur/tibia shaft fractures is still a matter of discussion. Intramedullary nailing is the preferred operative procedure for definitive treatment of femur shaft fractures. Stabilization of proximal and distal femur and tibia fractures is predominantly based on expert opinion. According to the literature, perioperative antibiotic prophylaxis is essential in fracture treatment.ConclusionNumerous comparative studies (EL 2) dealing with management strategies in the first operative phase after long-bone injuries of the lower extremity in multiply injured patients are available, but there are only a few randomized studies. Based on the available data, it is possible to develop a rational therapy for this patient population.

Histamine release in sepsis : A prospective, controlled, clinical study

OBJECTIVE To determine if histamine release occurs in clinical sepsis. DESIGN Prospective, controlled, clinical study. SETTING Interdisciplinary intensive care unit and trauma ward. PATIENTS Sepsis was confirmed in 20 patients (test group) by the criteria of the Veterans Administration Systemic Sepsis Cooperative Study Group (1987) and was verified by positive blood culture. In addition, patients were scored by the Elebute and Stoner Sepsis Score (1983), as modified by Dionigi et al (1985). A concomitant control group consisted of 20 postoperative patients with non-life-threatening trauma to the extremities and without signs of local or systemic infection. INTERVENTIONS Observational study. Blood samples were collected for determination of plasma histamine concentrations in both groups at the time of study entry and on five succeeding days. MEASUREMENTS AND MAIN RESULTS The patients were well matched, and the groups were not significantly different for all criteria known to influence histamine release. Comparison of the median values of each group on days 1 through 5 demonstrated significantly higher plasma histamine values in the test group on days 1 through 4, but these values were no longer significantly higher on day 5. While none of the nonseptic control patients achieved a plasma histamine concentration of > 1 ng/mL (the concentration of which was considered to be the pathologic cutoff point representing histamine release), these values (i.e., > 1 ng/ mL) were found in nine of 20 test group patients. In the test group, nonsurvivors (n = 9) had significantly higher plasma histamine concentrations than survivors (n = 11) throughout the whole study and eight of nine nonsurvivors showed a plasma histamine concentration of > 1 ng/mL. Correlation of plasma histamine concentrations on day 1 to sepsis severity (initial Sepsis Score) showed that all but one patient with a combined low Sepsis Score (< 20 points) and histamine concentration of < 1 ng/mL survived, while all patients with a Sepsis Score of > 20 points and histamine release (plasma histamine concentration of > 1 ng/mL) died. CONCLUSION Increased histamine concentrations were shown to be causally associated (contributory determinant) with sepsis.

Versorgungsstrategien in der ersten operativen Phase nach Verletzung langer Röhrenknochen der unteren Extremität beim Polytrauma

ZusammenfassungFragestellungVerletzungen der unteren Extremität haben einen wesentlichen Anteil im Verletzungsmuster polytraumatisierter Patienten. Das Ziel dieser systematischen Literaturanalyse ist es, einen Überblick über die Evidenzlevel (EL) unterschiedlicher Versorgungsstrategien von Frakturen der unteren Extremität beim Polytrauma in der ersten operativen Phase zu erstellen und hieraus entweder (bei genügender Evidenz) klinische Behandlungskorridore abzuleiten oder aber (bei ungenügender Evidenz) die Notwendigkeit wissenschaftlicher Überprüfung zu dokumentieren.MethodikKlinische Studien wurden über systematische Suchen (Medline, Cochrane und Handsuchen) und Klassifikation nach Evidenzlevel (EL1–5 nach Oxforder Schema) zusammengetragen.ErgebnisseDie Notwendigkeit einer primär- vs. sekundär-definitiven Osteosynthese von Schaftfrakturen des Femurs/der Tibia beim Polytrauma ist derzeit noch nicht hinreichend geklärt. Das Operationsverfahren der Wahl zur definitiven Versorgung einer Femurschaftfraktur ist die Marknagelung. Der Stellenwert der Stabilisierung von proximalen und distalen Femur- sowie Tibiafrakturen beruht größtenteils auf Expertenmeinung. Nach der Literatur ist eine perioperative Antibiotikaprophylaxe bei der operativen Frakturversorgung indiziert.SchlussfolgerungenZu Versorgungsstrategien in der ersten operativen Phase nach Verletzungen langer Röhrenknochen der unteren Extremität beim Polytrauma liegen eine Vielzahl vergleichender Untersuchungen (EL2) vor, randomisierte Studien existieren jedoch wenige. Anhand der Datenlage ist eine wissenschaftlich begründete Behandlung dieser Patienten in weiten Bereichen möglich.AbstractObjectiveLower extremity injuries make up a substantial proportion of the injuries in multiply injured patients. The aim of this systematic literature analysis was to give an overview of the levels of evidence for different management strategies in the first operative phase after long-bone injuries of the lower extremity in multiply injured patients to enable, in the presence of adequate evidence, the development of clinical management corridors or, if the evidence was found to be inadequate, to document the necessity for scientific proof.MethodsClinical trials were systematically collected (Medline, Cochrane and hand searches) and classified into evidence levels (EL 1 to 5 according to the Oxford system).ResultsThe necessity for primary or secondary definitive osteosynthesis of femur/tibia shaft fractures is still a matter of discussion. Intramedullary nailing is the preferred operative procedure for definitive treatment of femur shaft fractures. Stabilization of proximal and distal femur and tibia fractures is predominantly based on expert opinion. According to the literature, perioperative antibiotic prophylaxis is essential in fracture treatment.ConclusionNumerous comparative studies (EL 2) dealing with management strategies in the first operative phase after long-bone injuries of the lower extremity in multiply injured patients are available, but there are only a few randomized studies. Based on the available data, it is possible to develop a rational therapy for this patient population.

The Prognostic Value of Prothrombin Time in Predicting Survival after Major Trauma: a Prospective Analysis of 1,351 Patients from the German Trauma Registry

Background: Early assessment of the individual trauma load in major trauma patients is difficult. A simple and reliable prognostic factor already available in the emergency room would help the emergency physician to make appropriate therapeutic decisions, e. g., when and how to operate on major fractures. The aim of the study was to evaluate the prognostic value of prothrombin time (PT). Patients and Methods: The German Trauma Registry is a prospective, standardized and anonymous documentation of severely injured patients. 3,814 patients were included in the registry. 1,351 patients with an Injury Severity Score (ISS) ≤ 16 and complete data for specific variables (PT, Trauma Score + Injury Severity Score [TRISS], survival until discharge) were included in the study. The PT was measured on the patients arrival in the emergeny room. Three different analyses were performed. 1. According to clinical judgment, three groups of patients were compared (PT ≥ 60%, PT 40–59%, PT < 40%). A univariate analysis compared therapeutic interventions and outcome variables between the three groups. 2. A receiver-operator-characteristic (ROC) curve analysis compared the performance of PT with the prognostic standard TRISS. 3. A multivariate logistic regression was performed in order to evaluate PT as an independent prognostic variable. Results: PT values showed a good inverse correlation with the severity of injury and the level of therapeutic interventions. The ROC analysis as well as the regression revealed PT as a significant prognostic factor although it showed a slightly worse performance compared to TRISS. Conclusions: As PT, in contrast to TRISS, is readily available already in the emergency room, it can be used as a screening variable for the assessment of a patients trauma load and thereby help in the decision-making for further operative treatment of major trauma patients.

Beneficial effect of H2-agonism and H1-antagonism in rat endotoxic shock.

Although histamine release is generally considered harmful in endotoxic shock, several data exist to doubt this view. Own previous studies in rats let us assume a possible beneficial effect only with H1−antagonists, however a detrimental effect on survival with H2−antagonists. Consequently H1− and H2−agonists and antagonists were studied to prove the hypothesis of a beneficial H2−agonistic and H1−antagonistic effect. Two randomized studies were performed in a standardized rat endotoxic shock model (45 mg of Escherichia coli endotoxin/kg body weight (b.w.)). In both, methylprednisolone (50 mg/kg b.w.) and saline were used as positive and negative controls, respectively. Study I compared the effects of H1− and H2−agonists (betahistine, .1 mg/kg/h, and impromidine, 100 μg/kg/h) with H1− and H2−antagonists (astemizole and famotidine both 1 mg/kg b.w.; 20 rats/dose). Study II was performed to estimate the dose-response relationship of a new, highly potent H2−agonist with additional H1−antagonistic features (BU-E 75: .01, .1, 1.0, 10, and 100 μg/kg/h; 20 rats/dose). Animals receiving impromidine or BU-E 75 all received omeprazole (1 μol/kg b.w.) to suppress gastric acid secretion. In study I impromidine significantly increased the survival-time and -course compared to famotidine treated animals (p = .01 and p < .05). Study II showed a positive dose-response relationship of BU-E 75 with an increase in survival rates from 30% (.01 μg/kg/h) to 70% (100 μg/kg/h). These data strongly support the hypothesis of a beneficial effect of H2−agonism and H1−antagonism on survival parameters in rat endotoxic shock.

Time sequence of histamine release and formation in rat endotoxic shock.

Increased histamine release and formation (induced histamine) are two hypotheses considered in the pathogenesis of endotoxic shock development. To prove both hypotheses a sequence of four randomized controlled studies in rats was performed. Histamine release was measured indirectly as a decrease in tissue-histamine contents (lung, liver, spleen, stomach); histamine formation was estimated directly as an increase in histidine decarboxylase (HDC) activity in the same organs. Changes in contents and enzymatic activities were determined 4 and 8 h after shock induction; in addition, at the time of death, the activity of HDC was measured in heart, kidney, and small intestine. 4 h after shock induction, there was a significant decrease in the tissue-histamine content as measured only in the liver, with the same trend in lung and spleen. 8 h after endotoxin application, however, histamine concentration increased in the liver (significantly p < .05) and lung compared to the NaCl control group. The manifestation of changes in HDC activity in various organs was selective (i.e., not all organs showed alterations), not uniform (decreased as well as increased activities were measured), and time-dependent (no increase in HDC activity in animals dying at < 20 h). At 4 and 8 h, only the liver showed a strong increase in HDC activity which can explain the increase in histamine content. In lung, spleen, and stomach, a significant decrease occurred. The results on histamine release and formation let us conclude that histamine is involved in the pathogenesis of endotoxic shock development.