T. Hensler

Association between injury pattern of patients with multiple injuries and circulating levels of soluble tumor necrosis factor receptors, interleukin-6 and interleukin-10, and polymorphonuclear neutrophil elastase.

BACKGROUND Our knowledge about the bidirectional interactions between brain and whole organism after trauma is still limited. It was the purpose of this prospective clinical study to determine the influence of severe head trauma (SHT) as well as trauma in different anatomic injury regions on posttraumatic inflammatory mediator levels from patients with multiple injuries. METHODS Thirty-five healthy controls, 33 patients with an isolated SHT, 47 patients with multiple injuries without SHT, and 45 patients with both SHT and multiple injuries were studied. The posttraumatic plasma levels of soluble tumor necrosis factor receptors p55 and p75, interleukin (IL)-6, IL-10, and polymorphonuclear neutrophil (PMN) elastase were monitored using enzyme-linked immunosorbent assay technique. The influence of head injuries as well as thorax, abdomen, and extremity injuries on the mediator release from patients with multiple injuries was investigated by multivariate linear regression models. RESULTS The soluble tumor necrosis factor receptor p55/p75 ratio was significantly elevated within 3 hours of trauma in all three injury groups and returned to reference ratios after 12 hours. The lowest increase was found in patients suffering from an isolated SHT. Lowest mediator levels in this patient population were also found for IL-6, IL-10, and PMN elastase during the first 36 hours after trauma. Additional injuries to the head, thorax, abdomen, and extremity modulated mediator levels to a different degree. No specific effect was found for SHT when compared with other injury groups. Thorax injuries caused the quickest rise in mediator levels, whereas abdominal injuries significantly increased PMN elastase levels 12 to 24 hours after trauma. CONCLUSION Traumatic injuries cause the liberation of various mediators, without any specific association between anatomic injury pattern and the pattern of mediator release.

The clinical value of procalcitonin and neopterin in predicting sepsis and organ failure after major trauma

We examined whether procalcitonin (PCT) or neopterin (NT) are useful in predicting sepsis, multiple organ failure (MOF), or death after multiple trauma (MT). In a prospective clinical study, a total of 137 consecutive trauma patients (mean age 39 years, median injury severity score [ISS] 27 points) and 34 healthy volunteers were enrolled. Blood samples were collected on arrival in the emergency room until day 28 after trauma. Plasma NT was detected by enzyme-linked immunoassay and PCT plasma levels were determined using an immunoluminometric assay. The incidence of sepsis was 65%, MOF 48%, and death in hospital within 28 days 11%. After adjustment for age, gender, and ISS, PCT and NT levels during the first 2 days after injury were unable to differentiate between patients who developed sepsis or not. On the contrary, patients who developed MOF had higher PCT plasma levels on day 0 (0.60 vs. 0.15 ng/mL), and on days 1 and 2 combined (1.95 vs. 0.32 ng/mL). This difference remained significant in multivariate logistic regression (P = 0.01) and additional subgroup analyses for early and late MOF (P = 0.048 and 0.002). For NT, smaller differences were observed (4.39 vs. 3.68 nmol/L, and 7.20 vs. 5.79 nmol/L), which lost significance in multivariate analysis. On the basis of PCT, ISS, and age, a MOF prediction rule was developed and had a good predictive power (area under the curve: 0.77; P < 0.001). These findings demonstrate that high plasma concentrations of PCT in the early posttraumatic phase are an independent predictor of MOF but not of sepsis.

Immunologic alterations associated with high blood transfusion volume after multiple injury: effects on plasmatic cytokine and cytokine receptor concentrations.

The initial transfusion therapy after trauma has been identified as an independent risk factor for the incidence of multiple organ failure (MOF). Late occurrence of MOF in severely injured patients may be a clinical consequence of disturbed mediator homeostasis. For this reason, levels of interleukin (IL)-6, IL-10, and soluble tumor necrosis factor receptors (sTNFR) p55 and p75 were analyzed in the plasma of patients with comparable injury severity but with a different supply of packed red blood cells (PRBC). Thirty-eight multiple trauma patients with an injury severity score range of 25–54 points were separated into two groups according to their PRBC supply within the first 24 h after trauma. Patients who received at least 15 units of PRBC were analyzed in group 2 (n = 11); the remaining patients (n = 27) were assigned to group 1. The incidence of MOF was higher (P < 0.05) in group 2 patients. Correspondingly, levels of all assayed mediators were found significantly elevated at several time points in this patient group. We conclude that increases in mediator concentrations may be causally related to the extent of blood transfusion therapy itself or to the conditions for which it was needed.

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.

The effect of additional brain injury on systemic interleukin (IL)-10 and IL-13 levels in trauma patients

Abstract:Objective: Besides interleukin (IL)-10, accumulating evidence from in vitro studies has indicated a strong antiinflammatory capacity for IL-13. A prospective clinical study was undertaken to assess the influence of additional brain injury on systemic IL-10 and IL-13 levels as markers for the antiinflammatory state in trauma patients.¶Material and methods: The course of IL-10 and IL-13 plasma levels from 32 patients with an isolated severe head trauma (SHT), 50 patients with multiple injuries and additional SHT and 39 patients with multiple injuries without SHT was detected using ELISA-technique. Blood samples from 37 healthy blood donors were analysed for control.¶Results: IL-10 levels were significantly elevated in all 3 injury groups within 3 h after trauma. The lowest initial release was detected in patients with an isolated SHT (Injury severity score; ISS: 18.1 ± 5.6). No difference could be demonstrated for the IL-10 levels from multiple injured patients with (ISS: 35.3 ± 9.6) or without additional SHT (ISS: 25.5 ± 11.7), though there were relevant differences in the ISS. In contrast, the IL-13 plasma levels were not elevated systemically after trauma.¶Conclusions: IL-10 but not IL-13 is a detectable antiinflammatory marker in trauma patients with or without brain injury and to a minor degree in patients with an isolated SHT.¶

Plasma Levels of Procalcitonin and Neopterin in Multiple Trauma Patients with or without Brain Injury

Clinical and experimental evidence suggests that traumatic brain injury (TBI) leads to a systemic immune response. To examine whether TBI causes a release of procalcitonin (PCT) or neopterin (NT) into the circulation, we compared plasmatic mediator levels among multiple injured patients with or without TBI. In total, 98 trauma patients (24 with TBI only, 39 with extracranial injuries excluding TBI, and 35 with combined injuries) and 35 healthy volunteers were studied. Blood was sampled at 15 predefined time points within 132 h after injury and analysed for NT and PCT. Multivariate statistical comparisons were adjusted for different severity of head, thorax, abdomen and extremity injuries, as quantified by the Abbreviated Injury Scale (AIS). PCT was normal 3 h after trauma, but 24 h after extracranial injuries a massive release (median 3 ng/mL) was observed. Significant positive associations between injury severity and posttraumatic PCT levels were found for abdominal and extremity, but not for cranial or thoracic injuries. Only modest changes of marginal statistical significance were detected for NT. The maximum increase per AIS point was 9% (95% confidence intervals [CI]: 3-16%). The effect of TBI on NT release was significant only at 108 h posttrauma with a 5% (95% CI: 1-10%) increase per AIS point. TBI induces a release of PCT and NT into the plasma, but this effect seems to be smaller for intra- than for extracranial injuries, probably due to more extensive surgery for abdominal and extremity injuries.

Pneumonia in multiple injured patients: a prospective controlled trial on early prediction using clinical and immunological parameters.

Abstract. Objective and design: In a prospective trial 266 multiple injured patients were included to evaluate clinical risk factors and immune parameters related to pneumonia.¶Methods: Clinical and humoral parameters were assessed and multivariate analysis performed.¶Results: The multivariate analysis (odds ratio with 95% confidence interval (CI)) revealed male gender (3.65), traumatic brain injury (TBI) (2.52), thorax trauma (AISthorax≤ 3) (2.05), antibiotic prophylaxis (1.30), injury severity score (ISS) (1.03 per ISS point) and the age (1.02 per year) as risk factors for pneumonia. The main pathogens were Acinetobacter Baumannii (40%) and Staphylococcus aureus (25%). A tendency towards higher Procalcitonin (PCT) and Interleukin (IL)-6 levels two days after trauma was observed for pneumonia patients.¶Conclusion: The immune parameters (PCT, IL-6, IL-10, soluble tumor necrosis factor p-55 and p-75) could not confirm the diagnosis of pneumonia earlier than the clinical parameters.

Risk factors for the development of pneumonia in multiple injured patients. Results of a prospective clinical trial

ZusammenfassungDie Pneumonie ist die häufigste infektiöse Komplikation beim mehrfachverletzten Patienten. In einer prospektiven klinischen Kohortenstudie wurden 266 polytraumatisierte Patienten hinsichtlich ihrer posttraumatischen Pneumonieentwicklung untersucht. Verschiedene Risikofaktoren wurden univariat und multivariat analysiert.Dabei wurden drei unterschiedliche Pneumoniedefinitionen verwendet, um die Abhängigkeit der Ergebnisse von der jeweiligen Definition zu überprüfen. Die Inzidenz von Pneumonien (primär 41%) variierte je nach Definition zwischen 30 und 50%.Verletzungen von Thorax, Schädel und Abdomen waren mit einem signifikant erhöhtem Risiko einer Pneumonie assoziiert (adjustierte relative Risiken: 1,77, 1,97 bzw. 1,52). Ein höheres Lebensalter erhöhte ebenfalls signifikant das Pneumonierisiko.Obwohl sich in der Hauptanalyse ein erhöhtes Pneumonierisiko männlicher Patienten fand (relatives Risiko 2,23;95%-Konfidenzintervall 1,43–3,05), ließ sich dieses Ergebnis bei Verwendung anderer Pneumoniedefinitionen nicht sicher reproduzieren.Schwere Verletzungen des Körperstamms und Kopfes sowie das Alter des Patienten sind sichere Risikofaktoren für eine posttraumatische Pneumonie.Der Zusammenhang zwischen männlichem Geschlecht und infektiösen Komplikationen blieb fraglich.AbstractPneumonia is the most common infectious complication in multiple trauma patients. In a prospective clinical cohort study, 266 multiply injured patients were examined for the development of pneumonia.Various risk factors were tested in uni- and multivariate analyses.Three different definitions of pneumonia were used in order to examine how results depended on definition.The incidence of pneumonia was 41%, but varied with definition (30–50%). Injuries to the thorax, head,and abdomen were associated with a significantly increased risk of pneumonia (adjusted relative risk: 1.77, 1.97,and 1.52, respectively).Furthermore, increasing age led to a higher risk of pneumonia. Although the primary analysis revealed a higher pneumonia risk in male patients (adjusted relative risk: 2.23; 95% CI: 1.43–3.05), this result could not be consistently reproduced when using other definitions of pneumonia. Trunk and head injuries and age are proven risk factors for developing posttraumatic pneumonia.The association between male gender and an increased rate of infectious complications remained questionable.

Die Pneumonie als Komplikation bei Polytraumapatienten

Von 74 Polytraumapatienten (ISS: 27,5 ± 8,9) wurden Il-6, Il-10, TNFP55 and P75 innerhalb der ersten 24 h 6-stundig, danach am Tag 2–10, 14, 21 und 28 analysiert. 35% der Patienten entwickelten eine Pneumonie innerhalb der ersten 14 Tage. Von 38 Patienten mit Thoraxtrauma (ISS 34 ± 10) erlitten 50% (n=19) posttraumatisch eine Pneumonie, von den 36 Patienten ohne Thoraxtrauma (ISS 20 ± 7,5) bekamen mit 19% (n = 7) signifikant weniger eine Pneumonie (χ 2-Test: α < 0,05). Von den 38 Patienten mit Thoraxtrauma erhielten 25 eine AB-Prophylaxe (ISS 35 ± 10) und 13 (ISS 32 ± 10) keine. Trotz AB-Prophylaxe entwickelten 56% eine Pneumonie; die Patienten ohne AB-Prophylaxe nur zu 38%. Das Il-6, −10 und die TNFP55 und P75 Rezeptoren zeigten einen Anstieg wahrend der Pneumonie. Il-6 und −10 zeigten am ersten Pneumonietag einen Peak. Die AB-Prophylaxe kann in uber 50% eine Pneumonie nicht verhindern. Il-6, −10, TNFP55 und P75 kommen als pradiktive Faktoren fur eine drohende Pneumonie nicht in Frage.