Bernd Maier

Early versus late onset of multiple organ failure is associated with differing patterns of plasma cytokine biomarker expression and outcome after severe trauma.

Although multiple organ failure (MOF) remains the leading cause of death after trauma, the pathogenic cellular and molecular mechanisms underlying MOF are poorly understood. In addition to proinflammatory and anti-inflammatory mediator cascades, the temporal onset of MOF has generated recent interest because the organ systems involved into MOF seem to deteriorate in a time-dependent fashion after trauma. We therefore investigated the temporal course of MOF in traumatized human patients and evaluated and compared the distribution patterns of cytokine expression, including interleukin (IL) 6, IL-8, IL-10, and the soluble tumor necrosis factor-α receptors sTNF-R p55 and sTNF-R p75 in early-onset versus late-onset MOF. In addition, we analyzed the predictive value of cytokine biomarkers of MOF and lethal outcome. In a prospective observational cohort study conducted at three trauma centers, all patients (n = 352) admitted to two level 1 trauma centers in Germany were enrolled in the study based on the following inclusion criteria: severe traumatic brain injury (TBI) with a Glasgow Coma Scale (GCS) score of 8 or lower and/or distinct changes in cranial computed tomography and/or multiple injuries (MT) to the body (at least two regions had Abbreviated Injury Scale score of 3 or higher). The incidence of MOF was evaluated using the modified Goris-MOF score. The temporal onset of MOF was divided into early-onset MOF (EMOF, developing on days 0-3), late-onset MOF (LMOF, developing on days 4-10), combined early-onset and late-onset MOF (CMOF), and patients never showing signs of MOF during the observation period. In addition, the levels of the serum cytokine markers IL-6, IL-8, IL-10, sTNF-R p55, and sTNF-R p75 were analyzed at specific posttraumatic time points using established enzyme-linked immunosorbent assay techniques. A total of 352 patients (274 men and 78 women; TBI, 101; TBI + MT, 125; MT, 126) were enrolled into the study. Patients assigned to the EMOF group showed specific disruption of pulmonary and cardiocirculatory function, whereas LMOF was significantly associated with hepatic failure. The patients without signs of MOF and the EMOF patients had the same risk of lethal outcome (8.2% vs. 7.5%); LMOF and CMOF were found to be associated with a 3- to 4-fold increase in mortality (38.5% vs. 30.6%, respectively). Analysis of cytokine serum biomarkers revealed that patients with LMOF showed a biphasic elevation of IL-6 and significantly higher sTNF-R concentrations than did all other subgroups (P < 0.001). In addition, the initial values (days 0-1) of sTNF-R p55 and sTNF-R p75 expression levels had a good predictive capacity for the development of LMOF (p55, 0.75; p75, 0.72); values greater than 0.65 were accepted to have a predictive capacity. These results demonstrate that mortality differs significantly between the development of EMOF and LMOF after traumatic injury. Our results also suggest that serum cytokine measurements may be important early biochemical markers for predicting the development of delayed MOF.

Differential release of interleukines 6, 8, and 10 in cerebrospinal fluid and plasma after traumatic brain injury.

Traumatic brain injury (TBI) is characterized by a high mortality which is largely determined by the initial cerebral trauma, secondary brain injury or indirectly during a Multiple Organ Dysfunction Syndrome (MODS). Therefore, we analyzed IL-6, IL-8, and IL-10 in cerebrospinal fluid (CSF) and in plasma with respect to blood-brain barrier (BBB) integrity in 29 patients suffering from isolated TBI. IL-6 and IL-8 were significantly increased compared to baseline levels early after trauma in CSF and plasma. In all patients CSF IL-6 and IL-8 were found to be higher than corresponding plasma levels. IL-10 in plasma was significantly increased above control plasma values, however, without a significant difference to the corresponding CSF values. BBB dysfunction was temporary present in 23 patients. Significant correlations between BBB dysfunction and cytokines were not found. Thus, alterations of the BBB seems not to influence the distribution pattern of interleukines in CSF and plasma after trauma.

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.

Delayed elevation of soluble tumor necrosis factor receptors p75 and p55 in cerebrospinal fluid and plasma after traumatic brain injury.

ABSTRACT Recent studies have reported a significant inflammatory reaction in the brain and the systemic circulation after traumatic brain injury (TBI). Although there is growing knowledge and understanding of the mechanisms and mediators involved in the proinflammatory reaction, little is known about the anti-inflammatory mediators in the brain. As tumor necrosis factor &agr; (TNF-&agr;) plays a detrimental role in the initiation and promotion of the proinflammatory reactions after TBI, the endogenous scavenger system, represented by the soluble TNF receptors (sTNFRs) p55 and p75, seems to have an important anti-inflammatory capacity by binding to circulating TNF-&agr;. To evaluate this potentially anti-inflammatory response to trauma, we analyzed sTNFR p55 and p75 in paired plasma/cerebrospinal fluid (CSF) samples of 29 patients who encountered TBI. Values were compared with reference values obtained from healthy volunteers (n = 91). Patients with TBI showed significantly (P < 0.001) elevated sTNFR p55 and p75 values starting from day 2 and lasting until day 10 if compared with reference values. In contrast to the early increased plasma values p55 and p75 showed slowly increasing CSF values starting on day 4 and 3, respectively. Significantly (P < 0.001) increased CSF values of p 55 were determined on days 4 to 6 and day 9. p75 showed significantly (P < 0.001) elevated values if compared with control values on days 7 and 9. The sTNFR p55 and p75 show a distinct and long-lasting elevation in plasma of patients after TBI. In contrast, CSF values display a delayed and less intense elevation of both receptors in patients with TBI. These findings are suggestive of an imbalance of the proinflammatory and anti-inflammatory reactions of the central nervous system after trauma, with an emphasis on the proinflammatory mechanisms and a slow increase of potentially anti-inflammatory mediators such as the soluble TNFRs after TBI.

Interventional emergency embolization for severe pelvic ring fractures with arterial bleeding. Integration into the early clinical treatment algorithm

OBJECTIVE Presentation of our own experiences and results of an early clinical algorithm for treatment integrating emergency embolization (TAE) in cases of unstable pelvic ring fractures with arterial bleeding. METHOD Consecutive patient series from April 2002 to December 2006 at a level 1 trauma center. The data of the online shock room documentation (Traumawatch) of patients with a pelvic fracture and arterial bleeding detected on multislice computed tomography (MSCT) were examined for the following parameters: demographic data, injury mechanism, fracture classification according to Tile/AO and severity of the pelvic injury assessed with the Abbreviated Injury Score (AIS), accompanying injuries with elevation of the cumulative injury severity according to the Injury Severity Score (ISS), physiological admission parameters (circulatory parameters and initial Hb value) as well as transfusion requirement during treatment in the shock room, time until embolization, duration of embolization, and source of bleeding. RESULTS Of a total of 162 patients, arterial bleeding was detected in 21 patients by contrast medium extravasation on MSCT, 12 of whom were men and 9 women with an average age of 45 (14-80) years. The mechanism of injury was high energy trauma in all cases. In 33% it involved type B pelvic fractures and in 67% type C fractures with an average AIS pelvis of 4.4 points (3-5) and a total severity of injury with the ISS of 37 points (21-66). Upon admission 47.6% presented hemodynamic instability with an average Hb value of 7.8 g/dl (3.2-12.4) and an average transfusion requirement of 6 red blood cell units (4-13). The time until the TAE was started was on average 62 min (25-115) with a duration period of the TAE of 25 min (15-67). Branches of the internal iliac artery were identified as the sole source of bleeding. The success rate of TAE amounted to over 90%. CONCLUSION Interventional TAE represents an effective as well as a fast procedure for hemostasis of arterial bleeding detected on MSCT in patients with pelvic fractures. If an experienced radiologist on 24-h stand-by is assured and the infrastructure is efficient, this can be performed shortly after hospital admission and therefore should be integrated into the early clinical treatment protocol.

Interventionelle Notfallembolisation bei schweren Beckenfrakturen mit arterieller Blutung

OBJECTIVE Presentation of our own experiences and results of an early clinical algorithm for treatment integrating emergency embolization (TAE) in cases of unstable pelvic ring fractures with arterial bleeding. METHOD Consecutive patient series from April 2002 to December 2006 at a level 1 trauma center. The data of the online shock room documentation (Traumawatch) of patients with a pelvic fracture and arterial bleeding detected on multislice computed tomography (MSCT) were examined for the following parameters: demographic data, injury mechanism, fracture classification according to Tile/AO and severity of the pelvic injury assessed with the Abbreviated Injury Score (AIS), accompanying injuries with elevation of the cumulative injury severity according to the Injury Severity Score (ISS), physiological admission parameters (circulatory parameters and initial Hb value) as well as transfusion requirement during treatment in the shock room, time until embolization, duration of embolization, and source of bleeding. RESULTS Of a total of 162 patients, arterial bleeding was detected in 21 patients by contrast medium extravasation on MSCT, 12 of whom were men and 9 women with an average age of 45 (14-80) years. The mechanism of injury was high energy trauma in all cases. In 33% it involved type B pelvic fractures and in 67% type C fractures with an average AIS pelvis of 4.4 points (3-5) and a total severity of injury with the ISS of 37 points (21-66). Upon admission 47.6% presented hemodynamic instability with an average Hb value of 7.8 g/dl (3.2-12.4) and an average transfusion requirement of 6 red blood cell units (4-13). The time until the TAE was started was on average 62 min (25-115) with a duration period of the TAE of 25 min (15-67). Branches of the internal iliac artery were identified as the sole source of bleeding. The success rate of TAE amounted to over 90%. CONCLUSION Interventional TAE represents an effective as well as a fast procedure for hemostasis of arterial bleeding detected on MSCT in patients with pelvic fractures. If an experienced radiologist on 24-h stand-by is assured and the infrastructure is efficient, this can be performed shortly after hospital admission and therefore should be integrated into the early clinical treatment protocol.

Computer-assisted, fluoroscopy-based ventral spondylodesis of thoracolumbar fractures

Sports Medicine as an apparent sub-class of medicine has developed apace over the past 30 years. Its recent trajectory has been evidenced by the emergence of specialist international research journals, standard texts, annual conferences, academic appointments and postgraduate courses. Although this field of enquiry and practice lays claim to the title ‘sports medicine’ this paper queries the legitimacy of that claim. Depending upon how ‘sports medicine’ and ‘medicine’ are defined, a plausible-sounding case can be made to show that sports medicine is not in fact a branch of medicine. Rather, it is sometimes closer to practices such as non-therapeutic cosmetic surgery. The argument of the paper is as follows. It begins with a brief statement concerning methodology. We then identify and subscribe to a plausible defining goal of medicine taken from a recognised authority in the field. Then two representative, authoritative, definitions of sports medicine are discussed. It is then shown that acceptance of these definitions of sports medicine generates a problem in that if they are accepted, no necessary commitment to the defining goal of medicine is present within sports medicine. It seems to follow that sports medicine is not medicine. In the final part of the paper a critical response to that conclusion is presented and rebutted. The response is one which rejects the identification of the defining goal of medicine upon which our argument rests.

Distribution of spinal and associated injuries in multiple trauma patients

Injury to the spinal column and cord are often part of life-threatening multiple trauma. Epidemiological data could help to establish an evidence-based assessment and therapy of these patients. We present a retrospective chart analysis of 590 multiple traumatized patients admitted within a 4-year-period. Patients suffering from injuries of the spinal column were analysed regarding mechanism and distribution of their injuries to all body regions. Thirty-one percent (n = 183) of polytraumatized patients displayed a spine injury. Distribution analysis showed peaks in the cervical spine and the thoraco-lumbar junction. The risk of relevant associated injuries is mainly influenced from anatomical vicinity to the injured spinal segment. Injuries to the spinal column are frequent in the multiple trauma patients population. Diagnosed injuries to distinct body regions should make the trauma team suspicious of injury to the nearby spinal column. Appropriate treatment includes thorough assessment of all injuries to clarify the damage and carry on special protection of these spinal regions preventing from deterioration.

Biphasic elevation in cerebrospinal fluid and plasma concentrations of endothelin 1 after traumatic brain injury in human patients.

Severe traumatic brain injury (TBI) is characterized by a high mortality and poor outcome. The pathomechanisms involved are cytokine-mediated proinflammatory and anti-inflammatory reactions and significant cerebral microcirculatory disorders. The role of endothelin 1 (ET-1), a very potent vasoconstrictive peptide, in the deterioration of cerebral perfusion after trauma is still unclear. The presented study investigated the changes in ET-1 in the cerebrospinal fluid (CSF) and plasma after TBI in humans, with special regard to the presence of subarachnoid hemorrhage (SAH) and clinical outcome. Twenty patients with TBI were consecutively enrolled into the study, 10 patients without SAH (TBI group) and 10 patients with SAH (TBI-H group). Paired samples of plasma and CSF were collected for 10 days after trauma. Analysis of the ET-1 concentrations showed that TBI is associated with initially increased ET-1 values in plasma (TBI, day 1; TBI-H, days 2-3) and significantly increased (P < 0.05, vs. control) CSF concentrations (TBI, days 1-2; TBI-H, days 1-3) in the first days after trauma. In the further time course, ET-1 values declined in both groups, reaching reference values in plasma. The CSF values remained significantly (P < 0.05 vs. control) elevated. Both groups showed a second peak on the beginning of the second week after trauma in plasma and CSF. Whereas plasma concentrations failed to reach significance, CSF values showed a significant peak on day 7 in both groups. The TBI-H patients had significantly (P < 0.05) higher values in the secondary peak compared with patients of the TBI group. The kinetics of traumatic SAH-dependent ET-1 needs to be assessed in further investigations.

Treatment of severe osteitis after elastic intramedullary nailing of a radial bone shaft fracture by using cancellous bone graft in Masquelet technique in a 13-year-old adolescent girl

We present here an unfortunate long-lasting case of sever osteitis after elastic intramedullary nailing of a radial bone shaft fracture in a 13-year-old adolescent girl and the final treatment by using a modified Masquelet technique (Palacos spacer and cancellous bone graft in a second session in addition to a plate osteosynthesis) to reconstruct the severely destroyed proximal radial bone.