Secondary hypoxia is a known contributor to adverse outcomes in patients with traumatic brain injury (TBI). Based on the evidence that hypoxia and TBI in isolation induce neuroinflammation, we investigated whether TBI combined with hypoxia enhances cerebral cytokine production. We also explored whether increased concentrations of injury biomarkers discriminate between hypoxic (Hx) and normoxic (Nx) patients, correlate to worse outcome, and depend on blood-brain barrier (BBB) dysfunction. Forty-two TBI patients with Glasgow Coma Scale ≤8 were recruited. Cerebrospinal fluid (CSF) and serum were collected over 6 days. Patients were divided into Hx (n=22) and Nx (n=20) groups. Eight cytokines were measured in the CSF; albumin, S100, myelin basic protein (MBP) and neuronal specific enolase (NSE) were quantified in serum. CSF/serum albumin quotient was calculated for BBB function. Glasgow Outcome Scale Extended (GOSE) was assessed at 6 months post-TBI. Production of granulocye macrophage-colony stimulating factor (GM-CSF) was higher, and profiles of GM-CSF, interferon (IFN)-γ and, to a lesser extent, tumor necrosis factor (TNF), were prolonged in the CSF of Hx but not Nx patients at 4-5 days post-TBI. Interleukin (IL)-2, IL-4, IL-6, and IL-10 increased similarly in both Hx and Nx groups. S100, MBP, and NSE were significantly higher in Hx patients with unfavorable outcome. Among these three biomarkers, S100 showed the strongest correlations to GOSE after TBI-Hx. Elevated CSF/serum albumin quotients lasted for 5 days post-TBI and displayed similar profiles in Hx and Nx patients. We demonstrate for the first time that post-TBI hypoxia is associated with prolonged neuroinflammation, amplified extravasation of biomarkers, and poor outcome. S100 and MBP could be implemented to track the occurrence of post-TBI hypoxia, and prompt adequate treatment.

BACKGROUNDIt is unclear whether decompressive craniectomy improves the functional outcome in patients with severe traumatic brain injury and refractory raised intracranial pressure.METHODSFrom December 2002 through April 2010, we randomly assigned 155 adults with severe diffuse traumatic brain injury and intracranial hypertension that was refractory to first-tier therapies to undergo either bifrontotemporoparietal decompressive craniectomy or standard care. The original primary outcome was an unfavorable outcome (a composite of death, vegetative state, or severe disability), as evaluated on the Extended Glasgow Outcome Scale 6 months after the injury. The final primary outcome was the score on the Extended Glasgow Outcome Scale at 6 months.RESULTSPatients in the craniectomy group, as compared with those in the standard-care group, had less time with intracranial pressures above the treatment threshold (P<0.001), fewer interventions for increased intracranial pressure (P<0.02 for all comparisons), and fewer days in the intensive care unit (ICU) (P<0.001). However, patients undergoing craniectomy had worse scores on the Extended Glasgow Outcome Scale than those receiving standard care (odds ratio for a worse score in the craniectomy group, 1.84; 95% confidence interval [CI], 1.05 to 3.24; P=0.03) and a greater risk of an unfavorable outcome (odds ratio, 2.21; 95% CI, 1.14 to 4.26; P=0.02). Rates of death at 6 months were similar in the craniectomy group (19%) and the standard-care group (18%).CONCLUSIONSIn adults with severe diffuse traumatic brain injury and refractory intracranial hypertension, early bifrontotemporoparietal decompressive craniectomy decreased intracranial pressure and the length of stay in the ICU but was associated with more unfavorable outcomes. (Funded by the National Health and Medical Research Council of Australia and others; DECRA Australian Clinical Trials Registry number, ACTRN012605000009617.).

Progressive neurodegeneration following traumatic brain injury (TBI) involves the Fas and TNF-receptor1 protein systems which have been implicated in mediating delayed cell death. In this study, we used two approaches to assess whether inhibition of these pathways reduced secondary brain damage and neurological deficits after TBI. Firstly, we investigated whether the expression of non-functional Fas in lpr mice subjected to TBI altered tissue damage and neurological outcome. Compared to wild-type, lpr mice showed improved neurological deficit (p = 0.0009), decreased lesion volume (p = 0.017), number of TUNEL+ cells (p = 0.011) and caspase-3+ cells (p = 0.007). Changes in cellular inflammation and cytokine production were also compared between mouse strains. Accumulation of macrophages/microglia occurred earlier in lpr mice, likely due to enhanced production of the chemotactic mediators IL-12(p40) and MCP-1 (p < 0.05). Cortical production of IL-1α and IL-6 increased after injury to a similar extent regardless of strain (p < 0.05), while TNF and G-CSF were significantly higher in lpr animals (p < 0.05). Secondly, we assessed whether therapeutic inhibition of FasL and TNF via intravenous injection of neutralizing antibodies in wild-type mice post-TBI could reproduce the beneficial effects observed in lpr animals. No differences were found with this approach in animals treated with anti-FasL and anti-TNF antibodies alone or the combination of both. Altogether, reduced neurological deficits and lesion volume in lpr mice was associated with altered cellular and humoral inflammation, possibly contributing to neuroprotection, whereas neutralization of FasL and TNF had no effect. In future studies, the lpr mouse strain may be utilized as a model to further characterize molecular and cellular mechanisms protecting against secondary brain damage after TBI.

Chemokines and their receptors have crucial roles in the trafficking of leukocytes, and are of particular interest in the context of the unique immune responses elicited in the central nervous system (CNS). The chemokine system CC ligand 2 (CCL2) with its receptor CC receptor 2 (CCR2), as well as the receptor CXCR2 and its multiple ligands CXCL1, CXCL2 and CXCL8, have been implicated in a wide range of neuropathologies, including trauma, ischemic injury and multiple sclerosis. This review aims to overview the current understanding of chemokines as mediators of leukocyte migration into the CNS under neuroinflammatory conditions. We will specifically focus on the involvement of two chemokine networks, namely CCL2/CCR2 and CXCL8/CXCR2, in promoting macrophage and neutrophil infiltration, respectively, into the lesioned parenchyma after focal traumatic brain injury. The constitutive brain expression of these chemokines and their receptors, including their recently identified roles in the modulation of neuroprotection, neurogenesis, and neurotransmission, will be discussed. In conclusion, the value of evidence obtained from the use of Ccl2- and Cxcr2-deficient mice will be reported, in the context of potential therapeutics inhibiting chemokine activity which are currently in clinical trial for various inflammatory diseases.

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Background:Flail chest is a serious injury in trauma with a significant mortality rate, and long-term pain and disability. Traditionally, management has consisted of internal pneumatic splinting, leading to prolonged periods of mechanical ventilation, and its attendant complications. The aim of this study was to assess the safety of operative fixation of broken ribs in flail chest using absorbable prostheses.Methods:Thirteen consecutive patients with severe flail chest injury were enrolled in this pilot study. Surgery was planned after viewing three-dimensional reconstructions of the computed tomography scans of the chest. The plates were applied to the external cortical surface of the rib after reducing the fracture. Segmentally fractured ribs were usually plated only once to convert the flail segment to simple fractured ribs and correct the paradoxical wall motion abnormality.Results:All patients had a good surgical result. On average, four ribs were fixed per patient. All patients were able to be weaned from mechanical ventilation and all patients were discharged from the hospital. There were no deaths. No plates had to be removed. In all patients, the flail chest was successfully stabilized and paradoxical chest wall movement was eliminated.Conclusion:This pilot study of operative fixation of broken ribs in patients with flail chest, using absorbable plates and screws, has shown the technique to be safe and effective. On the basis of these results, a prospective randomized trial has commenced at The Alfred Hospital, comparing this management strategy with conservative management.

The incidence of blunt bowel and mesenteric injury (BBMI) has increased recently in blunt abdominal trauma, possibly due to an increasing number of high-speed motor accidents and the use of seat belts.

AimsTo comprehensively examine the inter-hospital transfer of major trauma patients—including the reason for transfer, duration, escorts, interventions and unexpected events.MethodsThis was an detailed study of the transfer of major trauma cases in the State of Victoria, Australia, between April 16, 2003 and December 31, 2004. Twenty-three hospitals and seven transfer/retrieval services participated. Defined major trauma cases that were transferred between participating hospitals for the purpose of definitive care were eligible for enrolment. The transfer phase extended from 30min before until 30min after the transfer. The transferring and receiving hospitals and the transfer escorts were asked to record data on a specifically designed data collection form.ResultsA total of 451 cases were enrolled (mean Injury Severity Score 22.2). Transfers originated mainly from Regional Trauma (42.8%) and Metropolitan Trauma (31.3%) Services and most (90.5%) terminated at a Major Trauma Service. Median time from injury to arrival at the receiving hospital was 8h 30min. Median time from arrival at referring hospital to request for transfer was 3h 25min.Escorts comprised ambulance and medical/nursing staff in 67.0% and 30.4% of cases, respectively. Metropolitan retrieval services were involved in only 10% of cases. Medical escorts were mainly (62.9%) from the referring hospital and the majority of these were registrars (49.4%) and hospital medical officers (HMOs, 16.9%).Overall mortality was 6.2%. Mortality rates for cases escorted by referring hospital doctors, Mobile Intensive Care Ambulance (MICA), non-MICA and any other escorts were 14.5%, 6.0%, 2.6% and 4.3%, respectively. HMO escorts had the highest mortality risk (OR 3.67, 95%CI 1.00–13.49, p<0.001).Mortality risk was greatest for cases that required administration of vasopressor drugs (OR 11.4, 95%CI 3.78–34.36, p<0.001), intubation prior to arrival at the referring hospital (OR 10.36, 95%CI 3.51–30.52, p<0.001), any interventions at the referring hospital (OR 8.3, 95%CI 3.1–22.2, p<0.001), administration of blood at the receiving hospital (OR 4.91, 95%CI 1.5–16.1, p=0.01), and cases using escorts from the referring hospital (OR 3.8, 95%CI 1.69–8.39, p=0.001).ConclusionConsiderable variability in request for transfer and transfer times, transfer escorts and mortality risk exist. The single greatest issue identified that most severely injured group were escorted by the most junior doctors (HMOs) and had the highest mortality. This crucial issue must be addressed by the State Trauma System and by any redesigned retrieval service in Victoria. A detailed review of activation and responsiveness criteria and the nature of the transfer escort is indicated. The establishment of Adult Retrieval Victoria may address many of the concerns raised by this study.

Objective: Trauma registries are integral to trauma systems, but reliance on mortality as the primary outcome measure remains a limitation. Some registries have included measures of discharge function, usually the modified Functional Independence Measure (FIM) or the Glasgow Outcome Scale (GOS), with the potential benefit being the ability to identify patients at risk for poor outcome. This study investigates the ability of these measures to predict longer term outcomes.Methods: Two hundred forty-three blunt major trauma patients participated. Data were captured from the trauma registry and discharge function was assessed using the modified FIM, FIM, and GOS. At 6 months postinjury, the GOS, FIM, modified FIM, return to work/study, and other outcome measures were collected by telephone inter-view. Multivariate analyses were used to assess the performance of discharge functional measures as predictors of 6-month outcomes.Results: Two hundred thirty-six (97.1%) participants were followed at 6 months postinjury. Disability was prevalent at 6 months; 42% had not returned to work/study, and only 32% were categorized as a "good recovery" by the GOS. Neither the GOS nor modified FIM at discharge were independent predictors of 6-month outcomes, whereas the FIM score and the FIM motor score were independent predictors of functional recovery (adjusted odds ratios 0.97; 95% confidence intervals: 0.96-0.99) and return to work/study (adjusted odds ratios 1.03, 95% confidence intervals: 1.01-1.04), respectively.Conclusions: For trauma registries to compare outcomes between regions and improvements over time, it is important that survivors with poor long-term outcomes are identified. Present measurement of discharge outcomes for trauma patients is inadequate for this purpose.

Background:Despite the high incidence of major trauma, few studies have directly compared the performance of trauma systems. This study compared the trauma system performance in Victoria, Australia, (VIC) and Hong Kong, China (HK). Methods:Prospectively collected data over 5 years from January 2001 from the 2 trauma systems were compared using univariate analysis. Variables were then entered into a multivariate logistic regression to assess differences in outcome between the systems and adjusted for effects of clinically important factors. Results:Five thousand five thirty-six cases from VIC and 580 cases from HK were taken for analysis. The HK group was older, but mechanisms of injury were similar in both systems. Thoracic and abdominal trauma was more common in VIC, compared with more head injuries in HK. More patients were admitted to intensive care in VIC and patients stayed in intensive care 1 day longer on average, despite more comorbidity in HK patients. Overall mortality was 20.2% for HK and 11.9% for VIC (X21 = 32.223, P < 0.001). Conclusion:The performance of the HK trauma system was comparable to international standards, but there was a significant difference in the probability of survival of major trauma between the 2 systems. Possible modifiable factors may include criteria for activation of trauma calls and improved ICU utilization.

Hemorrhage-related mortality (HRM) associated with pelvic fractures continues to challenge trauma care. This study describes the management and outcome of hemodynamically unstable patients with a pelvic fracture, with emphasis on primary intervention for hemorrhage control and HRM.

Oxidative stress plays a significant role in secondary damage after severe traumatic brain injury (TBI); and melatonin exhibits both direct and indirect antioxidant effects. Melatonin deficiency is deleterious in TBI animal models, and its administration confers neuroprotection, reducing cerebral oedema, and improving neurobehavioural outcome. This study aimed to measure the endogenous cerebrospinal fluid (CSF) and serum melatonin levels post-TBI in humans and to identify relationships with markers of oxidative stress via 8-isoprostaglandin-F2alpha (isoprostane), brain metabolism and neurologic outcome. Cerebrospinal fluid and serum samples of 39 TBI patients were assessed for melatonin, isoprostane, and various metabolites. Cerebrospinal fluid but not serum melatonin levels were markedly elevated (7.28+/-0.92 versus 1.47+/-0.35 pg/mL, P<0.0005). Isoprostane levels also increased in both CSF (127.62+/-16.85 versus 18.28+/-4.88 pg/mL, P<0.0005) and serum (562.46+/-50.78 versus 126.15+/-40.08 pg/mL (P<0.0005). A strong correlation between CSF melatonin and CSF isoprostane on day 1 after injury (r=0.563, P=0.002) suggests that melatonin production increases in conjunction with lipid peroxidation in TBI. Relationships between CSF melatonin and pyruvate (r=0.369, P=0.049) and glutamate (r=0.373, P=0.046) indicate that melatonin production increases with metabolic disarray. In conclusion, endogenous CSF melatonin levels increase after TBI, whereas serum levels do not. This elevation is likely to represent a response to oxidative stress and metabolic disarray, although further studies are required to elucidate these relationships.

In Brief Background: Despite the high incidence of major trauma, few studies have directly compared the performance of trauma systems. This study compared the trauma system performance in Victoria, Australia, (VIC) and Hong Kong, China (HK). Methods: Prospectively collected data over 5 years from January 2001 from the 2 trauma systems were compared using univariate analysis. Variables were then entered into a multivariate logistic regression to assess differences in outcome between the systems and adjusted for effects of clinically important factors. Results: Five thousand five thirty-six cases from VIC and 580 cases from HK were taken for analysis. The HK group was older, but mechanisms of injury were similar in both systems. Thoracic and abdominal trauma was more common in VIC, compared with more head injuries in HK. More patients were admitted to intensive care in VIC and patients stayed in intensive care 1 day longer on average, despite more comorbidity in HK patients. Overall mortality was 20.2% for HK and 11.9% for VIC (X21 = 32.223, P < 0.001). Conclusion: The performance of the HK trauma system was comparable to international standards, but there was a significant difference in the probability of survival of major trauma between the 2 systems. Possible modifiable factors may include criteria for activation of trauma calls and improved ICU utilization. This study compared the trauma system performance in Victoria, Australia, (VIC) and Hong Kong, China (HK). The performance of the HK trauma system was comparable to international standards, but there was a significant difference in the probability of survival of major trauma between the 2 systems. Possible modifiable factors may include criteria for activation of trauma calls and improved intensive care unit utilization.

This review examines pleural decompression and drainage during initial hospital adult trauma reception and resuscitation, when it is indicated for haemodynamically unstable patients with signs of pneumothorax or haemothorax. The relevant historical background, techniques, complications and current controversies are highlighted. Key findings of this review are that: 1. Needle thoracocentesis is an unreliable means of decompressing the chest of an unstable patient and should only be used as a technique of last resort. 2. Blunt dissection and digital decompression through the pleura is the essential first step for pleural decompression, as decompression of the pleural space is a primary goal during reception of the haemodynamically unstable patient with a haemothorax or pneumothorax. Drainage and insertion of a chest tube is a secondary priority. 3. Techniques to prevent tube thoracostomy (TT) complications include aseptic technique, avoidance of trocars, digital exploration of the insertion site and guidance of the tube posteriorly and superiorly during insertion. 4. Whenever possible, blunt thoracic trauma patients should undergo definitive CT imaging after TT to check for appropriate tube position.

Despite the fact that traumatic brain injury (TBI) is a silently growing epidemic, we are yet to understand its multifaceted pathogenesis, where various cellular pathways are initiated in response to both the primary mechanical insult and secondary physiologically mediated injury. Although the brain has traditionally been considered an immunologically privileged site, evidence to the contrary exists in studies of central nervous system (CNS) pathology, in particular TBI. Transmigration of leukocytes following blood brain barrier (BBB) disruption results in activation of resident cells of the CNS, such as microglia and astrocytes, to possess immunological function. Both infiltrating peripheral immune cells and activated resident cells subsequently engage in the intrathecal production of cytokines, important indicators of the presence of neuroinflammation. Cytokines can either promote this neurotoxicity, by encouraging excitotoxicity and propagating the inflammatory response, or attenuate the damage through neuroprotective and neurotrophic mechanisms, including the induction of cell growth factors. Certain cytokines perform both functions, for example, interleukin-6 (IL-6). This review article discusses the notion that the inflammatory response to TBI is no longer a peripherally mediated phenomenon, and that the CNS significantly influences the immunological sequence of events in the aftermath of injury.

A 19-year-old woman with multiple fractures and mild brain injury developed severe cerebral fat embolism syndrome after “damage control” orthopaedic surgery. Acetazolamide therapy to manage ocular trauma, in association with hyperchloraemia, caused a profound metabolic acidosis with appropriate compensatory hypocapnia. During ventilator weaning, unexpected brainstem coning followed increased sedation and brief normalisation of arterial carbon dioxide concentration. Autopsy found severe cerebral fat embolism and brain oedema.