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Background: Vagal nerve stimulation (VNS) can have a marked anti-inflammatory effect. We have previously shown that preinjury VNS prevented intestinal barrier breakdown and preserved epithelial tight junction protein expression. However, a pretreatment model has little clinical relevance for the care of the trauma patient. Therefore, we postulated that VNS conducted postinjury would also have a similar protective effect on maintaining gut epithelial barrier integrity., Methods: Male balb/c mice were subjected to a 30% total body surface area, full-thickness steam burn followed by right cervical VNS at 15, 30, 60, 90, 120, and 150 minutes postinjury. Intestinal barrier dysfunction was quantified by permeability to 4 kDa fluorescein isothiocyanate-Dextran, histologic evaluation, gut tumor necrosis factor-alpha (TNF-α) enzyme-linked immunosorbent assay, and expression of tight junction proteins (myosin light chain kinase, occludin, and ZO-1) using immunoblot and immunoflourescence., Results: Histologic examination documented intestinal villi appearance similar to sham if cervical VNS was performed within 90 minutes of burn insult. VNS done after injury decreased intestinal permeability to fluorescein isothiocyanate-Dextran when VNS was ≤90 minutes after injury. Burn injury caused a marked increase in intestinal TNF-α levels. VNS-treated animals had TNF-α levels similar to sham when VNS was performed within 90 minutes of injury. Tight junction protein expression was maintained at near sham values if VNS was performed within 90 minutes of burn, whereas expression was significantly altered in burn., Conclusion: Postinjury VNS prevents gut epithelial breakdown when performed within 90 minutes of thermal injury. This could represent a therapeutic window and clinically relevant strategy to prevent systemic inflammatory response distant organ injury after trauma.

Background: This study compares open tibia fractures in US Navy and US Marine Corps casualties from the current conflicts with those from a civilian Level I trauma center to analyze the effect of blast mechanism on limb-salvage rates., Methods: Data from the 28,646 records in the University of California San Diego Trauma Registry from 1985 to 2006 was compared with 2,282 records from the US Navy and US Marine Corps Combat Trauma Registry Expeditionary Medical Encounter Database for the period of March 2004 to August 2007. Injuries were categorized by Gustilo-Anderson (G-A) open fracture classification. Independent variables included age, gender, mechanism of injury including blast mechanisms, shock, blood loss, prehospital time, procedures, Injury Severity Score, length of stay, and Mangled Extremity Severity Score (MESS). Dependent variables included early or late amputation and mortality., Results: The civilian group had 850 open tibia fractures with 45 amputations; the military group had 21 amputation patients (3 bilateral) in 115 open tibia fractures. Military group patients were more severely injured, more likely have hypotension, and had a higher amputation rate for G-A IIIB and IIIC fractures then civilian group patients. Blast mechanism was seen in the majority of military group patients and was rare in the civilian group. MESS scores had poor sensitivity (0.46, 95% confidence interval: 0.29-0.64) in predicting the need for amputation in the civilian group; in the military group sensitivity was better (0.67, 95% confidence interval: 0.43-0.85), but successful limb salvage was still possible in most cases with an MESS score of ≥7 when attempted., Conclusion: Despite current therapy, limb salvage for G-A IIIB and IIIC grades are significantly worse for open tibia fractures as a result of blast injury when compared with typical civilian mechanisms. MESS scores do not adequately predict likelihood of limb salvage in combat or civilian open tibia fractures.

Objective: Conflicting data exist regarding pseudoaneurysm screening (PSA-S), initial angioembolization (IE), deep venous thrombosis prophylaxis (DVT-P), and activity limitation after hemodynamically stable blunt splenic injury (BSI). To determine whether there was consensus regarding BSI management, the multi-institutional trial committee of the American Association for the Surgery of Trauma (AAST) approved a survey of member practice patterns regarding BSI management., Methods: Over 2 months, AAST members were invited to participate in an online survey. Practice patterns and attitudes surrounding PSA-S, IE, DVT-P, and activity limitation after BSI were determined., Results: The response rate was 37.5%. Practice patterns varied by injury grade. Observation only was thought appropriate for grades I (94.4%) and II (84.6%) injuries. For grades III to V injuries, fewer and fewer respondents felt observation only was appropriate. PSA-S was the most commonly used strategy for grades IV and V injuries (32.7% and 28.2%), and IE was thought to be appropriate by 23.5% of respondents for grade IV injuries and 25.5% of respondents with grade V injuries. Thirty percent of respondents felt that no DVT-P was indicated for adult patients with BSI. Recommendations regarding return to full activity varied by perceived risk to the patient and by injury grade., Conclusions: There is considerable variation in the opinions of AAST members regarding BSI management, particularly for high-grade injuries. These results will aid in the design of prospective observational and random trials to determine optimal BSI management.

Background: An occult pneumothorax (OPTX) is found incidentally in 2% to 10% of all blunt trauma patients. Indications for intervention remain controversial. We sought to determine which factors predicted failed observation in blunt trauma patients., Methods: A prospective, observational, multicenter study was undertaken to identify patients with OPTX. Successfully observed patients and patients who failed observation were compared. Multivariate logistic regression was used to identify predictors of failure of observation. OPTX size was calculated by measuring the largest air collection along a line perpendicular from the chest wall to the lung or mediastinum., Results: Sixteen trauma centers identified 588 OPTXs in 569 blunt trauma patients. One hundred twenty-one patients (21%) underwent immediate tube thoracostomy and 448 (79%) were observed. Twenty-seven patients (6%) failed observation and required tube thoracostomy for OPTX progression, respiratory distress, or subsequent hemothorax. Fourteen percent (10 of 73) failed observation during positive pressure ventilation. Hospital and intensive care unit lengths of stay, and ventilator days were longer in the failed observation group. OPTX progression and respiratory distress were significant predictors of failed observation. Most patient deaths were from traumatic brain injury. Fifteen percentage of patients in the failed observation group developed complications. No patient who failed observation developed a tension PTX, or experienced adverse events by delaying tube thoracostomy., Conclusion: Most blunt trauma patients with OPTX can be carefully monitored without tube thoracostomy; however, OPTX progression and respiratory distress are independently associated with observation failure.

Background: Since the promulgation of emergency department (ED) thoracotomy>40 years ago, there has been an ongoing search to define when this heroic resuscitative effort is futile. In this era of health care reform, generation of accurate data is imperative for developing patient care guidelines. The purpose of this prospective multicenter study was to identify injury patterns and physiologic profiles at ED arrival that are compatible with survival., Methods: Eighteen institutions representing the Western Trauma Association commenced enrollment in January 2003; data were collected prospectively., Results: During the ensuing 6 years, 56 patients survived to hospital discharge. Mean age was 31.3 years (15-64 years), and 93% were male. As expected, survival was predominant in those with thoracic injuries (77%), followed by abdomen (9%), extremity (7%), neck (4%), and head (4%). The most common injury was a ventricular stab wound (30%), followed by a gunshot wound to the lung (16%); 9% of survivors sustained blunt trauma, 34% underwent prehospital cardiopulmonary resuscitation (CPR), and the presenting base deficit was >25 mequiv/L in 18%. Relevant to futile care, there were survivors of blunt torso injuries with CPR up to 9 minutes and penetrating torso wounds up to 15 minutes. Asystole was documented at ED arrival in seven patients (12%); all these patients had pericardial tamponade and three (43%) had good functional neurologic recovery at hospital discharge., Conclusion: Resuscitative thoracotomy in the ED can be considered futile care when (a) prehospital CPR exceeds 10 minutes after blunt trauma without a response, (b) prehospital CPR exceeds 15 minutes after penetrating trauma without a response, and (c) asystole is the presenting rhythm and there is no pericardial tamponade.

Introduction: An increasing proportion of trauma patients are on anticoagulation or antiplatelet therapy. Unlike warfarin, where measuring international normalized ratio can help direct management, measuring platelet inhibition from clopidogrel (Plavix) is not standardized. We report the use of a new P2Y12 point-of-care assay (VerifyNow; Accumetrics, San Diego, CA) to determine the magnitude of platelet inhibition in trauma patients using clopidogrel., Methods: Trauma patients in 2009 were queried for clopidogrel use by prehospital personnel and the trauma team. Blood was obtained on admission for patients reportedly taking clopidogrel and was assayed for platelet inhibition using the VerfiyNow-P2Y12 device that measures P2Y12 reaction units and photometrically determines platelet inhibition percentage within 30 minutes. Patient demographics including age, Injury Severity Score, mechanism of injury, and complications from hemorrhage were also analyzed., Results: In the time studied, 46 patients taking clopidogrel were assayed for platelet inhibition. The mean age was 75.9 years±11.8 years, and the most common mechanism of injury was fall (86.9%). Platelet inhibition ranged from 0% to 89%. There were no deaths, and only two patients, from the 0% and>30% inhibition group, had hemorrhagic complications (increased intracranial hemorrhage)., Conclusions: The P2Y12 point-of-care assay determined that a large percentage of patients had undetectable or low platelet inhibition despite reportedly being on clopidogrel therapy. These patients may be clopidogrel nonresponders or noncompliant. It is unlikely that clopidogrel reversal therapies, such as platelet transfusions or Desmopressin, would be beneficial in this group. Further studies stratifying the percent platelet inhibition needed to increase bleeding complications is warranted to optimize management strategies.

Background: Emergent endotracheal intubation (ETI) is considered the standard of care for patients with severe traumatic brain injury (TBI). However, recent evidence suggests that the procedure may be associated with increased mortality, possibly reflecting inadequate training, suboptimal patient selection, or inappropriate ventilation., Objective: To explore prehospital ETI in patients with severe TBI using a novel application of Trauma Score and Injury Severity Score methodology., Methods: Patients with moderate-to-severe TBI (head Abbreviated Injury Scale score 3+) were identified from our county trauma registry. Demographic information, pre-resuscitation vital signs, and injury severity scores were used to calculate a probability of survival for each patient. The relationship between outcome and prehospital ETI, provider type (air vs. ground), and ventilation status were explored using observed survival-predicted survival and the ratio of unexpected survivors/deaths., Results: A total of 11,000 patients were identified with complete data for this analysis. Observed and predicted survivals were similar for both intubated and nonintubated patients. The ratio of unexpected survivors/deaths increased and observed survival exceeded predicted survival for intubated patients with lower predicted survival values. Both intubated and nonintubated patients transported by air medical crews had better outcomes than those transported by ground. Both hypo- and hypercapnia were associated with worse outcomes in intubated but not in nonintubated patients., Conclusions: Prehospital intubation seems to improve outcomes in more critically injured TBI patients. Air medical outcomes are better than predicted for both intubated and nonintubated TBI patients. Iatrogenic hyper- and hypoventilations are associated with worse outcomes.

Introduction: Severe injury can cause intestinal permeability through decreased expression of tight junction proteins, resulting in systemic inflammation. Activation of the parasympathetic nervous system after shock through vagal nerve stimulation is known to have potent anti-inflammatory effects; however, its effects on modulating intestinal barrier function are not fully understood. We postulated that vagal nerve stimulation improves intestinal barrier integrity after severe burn through an efferent signaling pathway, and is associated with improved expression and localization of the intestinal tight junction protein occludin., Methods: Male balb/c mice underwent right cervical vagal nerve stimulation for 10 minutes immediately before 30% total body surface area, full-thickness steam burn. In a separate arm, animals underwent abdominal vagotomy at the gastroesophageal junction before vagal nerve stimulation and burn. Intestinal barrier injury was assessed by permeability to 4 kDa FITC-dextran, histology, and changes in occludin expression using immunoblotting and confocal microscopy., Results: Cervical vagal nerve stimulation decreased burn-induced intestinal permeability to FITC-dextran, returning intestinal permeability to sham levels. Vagal nerve stimulation before burn also improved gut histology and prevented burn-induced changes in occludin protein expression and localization. Abdominal vagotomy abrogated the protective effects of cervical vagal nerve stimulation before burn, resulting in gut permeability, histology, and occludin protein expression similar to burn alone., Conclusion: Vagal nerve stimulation performed before injury improves intestinal barrier integrity after severe burn through an efferent signaling pathway and is associated with improved tight junction protein expression.

Background: Traumatic brain injury (TBI) causes gastrointestinal dysfunction and increased intestinal permeability. Regulation of the gut barrier may involve the central nervous system. We hypothesize that vagal nerve stimulation prevents an increase in intestinal permeability after TBI., Methods: Balb/c mice underwent a weight drop TBI. Selected mice had electrical stimulation of the cervical vagus nerve before TBI. Intestinal permeability to 4.4 kDa FITC-Dextran was measured 6 hours after injury. Ileum was harvested and intestinal tumor necrosis factor-alpha and glial fibrillary acidic protein (GFAP), a marker of glial activity, were measured., Results: TBI increased intestinal permeability compared with sham, 6 hours after injury (98.5 microg/mL +/- 12.5 vs. 29.5 microg/mL +/- 5.9 microg/mL; p < 0.01). Vagal stimulation prevented TBI-induced intestinal permeability (55.8 +/- 4.8 microg/mL vs. 98.49 microg/mL +/- 12.5; p < 0.02). TBI animals had an increase in intestinal tumor necrosis factor-alpha 6 hours after injury compared with vagal stimulation + TBI (45.6 +/- 8.6 pg/mL vs. 24.1 +/- 1.4 pg/mL; p < 0.001). TBI increased intestinal GFAP 6.2-fold higher than sham at 2 hours and 11.5-fold higher at 4 hours after injury (p < 0.05). Intestinal GFAP in vagal stimulation + TBI animals was also 6.7-fold higher than sham at 2 hours, however, intestinal GFAP was 18.0-fold higher at 4 hours compared with sham and 1.6-fold higher than TBI alone (p < 0.05)., Conclusion: In a mouse model of TBI, vagal stimulation prevented TBI-induced intestinal permeability. Furthermore, vagal stimulation increased enteric glial activity and may represent the pathway for central nervous system regulation of intestinal permeability.

Background: Fluid resuscitation can contribute to postshock inflammation and the development of end organ injury. We have previously observed an attenuation in pulmonary and ileal inflammation when hypertonic saline and pentoxifylline (HSPTX) were concomitantly administered after hemorrhage. We hypothesized that the attenuation in hepatic injury observed with HSPTX is associated with the reduction of transcription factor activation and proinflammatory mediator production when compared with Ringer's lactate (RL)., Methods: Male Sprague-Dawley rats were resuscitated with racemic RL (32 mL/kg) or HSPTX (4 mL/kg 7.5% NaCl + PTX 25 mg/kg) and killed at 4 hours and 24 hours after resuscitation. Liver injury was determined by histology and serum aminotransferases. Nitrite, tumor necrosis factor-alpha, interleukin (IL)-1beta, and IL-6 were measured with enzyme-linked immunosorbent assay. High mobility group box 1, inducible nitric oxide synthase, nuclear factor (NF)-kappaB phosphorylation, and signal transducers and activators of transcription-3 phosphorylation were determined by Western blot. Transcription factor activation was verified with Electrophoretic Mobility Shift Assay., Results: RL resuscitation led to significant increases all measured parameters when compared with control. In contrast, HSPTX did not induce elevations in histologic liver injury or alanine aminotransferase levels. HSPTX attenuated inducible nitric oxide synthase by 23% (p < 0.01), nitrite by 25% (p < 0.05), tumor necrosis factor-alpha by 25% (p < 0.05), IL-1 by 63% (p < 0.01), IL-6 by 35% (p < 0.05), and high mobility group box 1 by 39% (p < 0.05) when compared with RL. HSPTX reduced IkappaB-alpha phosphorylation by 34% (p < 0.05), NF-kappaB p65 phosphorylation by 75% (p < 0.01), and signal transducers and activators of transcription-3 phosphorylation by 52% (p < 0.01)., Conclusions: The reduction in liver injury observed with HSPTX resuscitation after hemorrhage is associated with attenuation transcription factor activation and proinflammatory mediators. HSPTX has the potential to be a superior resuscitation fluid with significant immunomodulatory properties.

Background: We have previously demonstrated that postshock resuscitation with Hypertonic saline and Pentoxifylline (HSPTX) attenuates pulmonary and histologic gut injury when compared with Ringer's lactate (RL). In this study, we hypothesized that the decrease in gut injury observed with HSPTX is associated with the attenuation of inducible nitric oxide synthase (iNOS) activity and production of ileal proinflammatory mediators after hemorrhagic shock., Methods: In a rat model of hemorrhagic shock, resuscitation was conducted with RL (32 mL/kg; n = 7) or HSPTX (4 mL/kg 7.5% NaCl + PTX 25 mg/kg; n = 7). Sham animals that did not undergo shock were also studied. Four hours after resuscitation, the terminal ileum was collected for evaluation of nitrite, tumor necrosis factor (TNF)-alpha, Interleukin (IL)-6, and cytokine-induced neutrophil chemoattractant (CINC) by enzyme immunoassay. Heme oxygenase-1 (HO-1), iNOS, cytoplasmic inhibitor of kappa B (Ikappa B) phosphorylation, and nuclear factor (NF)kappa B p65 nuclear translocation were determined by Western blot., Results: HSPTX resuscitation resulted in a 49% decrease in iNOS when compared with RL (p < 0.05). Similar results were obtained when examining nitrite (882 +/- 59 vs. 1,435 +/- 177 micromol/L; p < 0.01), and HO-1 content (p < 0.05). RL resuscitation resulted in markedly higher levels of TNF-alpha (83 +/- 27 vs. 9 +/- 5 pg/mL; p < 0.01), IL-6 (329 +/- 58 vs. 118 +/- 43 pg/mL; p < 0.05), and CINC (0.43 +/- .06 vs. 0.19 +/- .08 ng/mL; p < 0.05) than HSPTX. The increase in cytokines observed with RL was also associated with an increase in I-kappaB phosphorylation (p < 0.01) and NF-kappaB p65 nuclear translocation (p < 0.001)., Conclusion: The attenuation in gut injury after postshock resuscitation with HSPTX is associated with downregulation of iNOS activity and subsequent proinflammatory mediator synthesis. HSPTX has the potential to be a superior resuscitation fluid with significant immunomodulatory properties.

Background: Injury is a leading cause of death and preventable morbidity in adolescents. Little is known about long-term quality of life (QoL) outcomes in injured adolescents. The objectives of the present report are to describe long-term QoL outcomes and compare posttrauma QoL to national norms for QoL in uninjured adolescents from the National Health Interview Survey (NHIS)., Methods: In all, 401 trauma patients aged 12 to 19 years were enrolled in the study. Enrollment criteria excluded spinal cord injury. QoL after trauma was measured using the Quality of Well-being (QWB) scale, a sensitive and well-validated functional index (range: 0 = death to 1.000 = optimum functioning). Patient outcomes were assessed at discharge, and 3, 6, 12, 18, and 24 months after discharge. NHIS data were based on 3 survey years and represent a population-based U.S. national random sample of uninjured adolescents., Results: Major trauma in adolescents was associated with significant and marked deficits in QoL throughout the 24-month follow-up period, compared with NHIS norms for this age group. Compared with NHIS norms for QoL in uninjured adolescents aged 12 to 19 years (N = 81,216,835; QWB mean = 0.876), injured adolescents after major trauma had striking and significant QoL deficits beginning at 3-month follow-up (QWB mean = 0.694, p < 0.0001), that continued throughout the long-term follow-up 24 months after discharge (6-month follow-up QWB mean = 0.726, p < 0.0001; 12-month follow-up QWB mean = 0.747, p < 0.0001; 18-month follow-up QWB mean = 0.758, p < 0.0001; 24-month follow-up QWB mean = 0.766, p < 0.0001). QoL deficits were also strongly associated with age (>or=15 years) and female sex. Other significant risk factors for poor QoL outcomes were perceived threat to life, pedestrian struck mechanism, and Injury Severity Scores >16., Conclusions: Major trauma in adolescents is associated with significant and marked deficits in long-term QoL outcomes, compared with U.S. norms for healthy adolescents. Early identification and treatment of risk factors for poor long-term QoL outcomes must become an integral component of trauma care in mature trauma care systems.

Background: Ringer's lactate (RL), the current standard resuscitation fluid, potentiates neutrophil activation and is associated with pulmonary inflammation. Resuscitation with hypertonic saline and pentoxifylline (HSPTX) has been shown to attenuate hemorrhagic shock-induced injury when compared with RL. Because the neutrophil plays a major role in postshock inflammation, we hypothesized that HSPTX reduces pulmonary inflammation after resuscitation in comparison to RL., Methods: Sprague-Dawley rats underwent controlled shock and were resuscitated with RL (32 mL/kg) or HSPTX (4 mL/kg 7.5% NaCl + pentoxifylline 25 mg/kg). Animals who did not undergo shock or resuscitation served as controls. After 24 hours, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. Cytokine induced neutrophil chemoattractant (CINC) was measured in BALF by enzyme-linked immunosorbent assay. Matrix metalloproteinases (MMP)-2 and -9 were measured by zymography. Hemeoxygenase-1 (HO-1) was assessed by Western blot and immunohistochemistry., Results: HSPTX resuscitation led to a 62% decrease in CINC levels compared with RL (p < 0.01). BALF MMP-2 expression was attenuated by 11% with HSPTX (p = 0.09). Lung MMP-2 and MMP-9 expression was reduced by 89% (p < 0.01) and 76%, respectively (p < 0.05). Lung HO-1 expression declined by 34% with HSPTX in comparison to RL (p < 0.01), indicating less oxidative injury. Lung immunohistochemistry localized HO-1 to neutrophils, macrophages, and airway epithelial cells., Conclusion: Collectively, the attenuation of pulmonary inflammation with HSPTX after shock when compared with RL is associated with downregulation of neutrophil activation, oxidative stress, and proinflammatory mediator production.

Background: The purpose of this study is to describe practice patterns and outcomes of posttraumatic retrievable inferior vena caval filters (R-IVCF)., Methods: A retrospective review of R-IVCFs placed during 2004 at 21 participating centers with follow up to July 1, 2005 was performed. Primary outcomes included major complications (migration, pulmonary embolism [PE], and symptomatic caval occlusion) and reasons for failure to retrieve., Results: Of 446 patients (69% male, 92% blunt trauma) receiving R-IVCFs, 76% for prophylactic indications and 79% were placed by interventional radiology. Excluding 33 deaths, 152 were Gunter-Tulip (G-T), 224 Recovery (R), and 37 Optease (Opt). Placement occurred 6 +/- 8 days after admission and retrieval at 50 +/- 61 days. Follow up after discharge (5.7 +/- 4.3 months) was reported in 51%. Only 22% of R-IVCFs were retrieved. Of 115 patients in whom retrieval was attempted, retrieval failed as a result of technical issues in 15 patients (10% of G-T, 14% of R, 27% of Opt) and because of significant residual thrombus within the filter in 10 patients (6% of G-T, 4% of R, 46% Opt). The primary reason R-IVCFs were not removed was because of loss to follow up (31%), which was sixfold higher (6% to 44%, p = 0.001) when the service placing the R-IVCF was not directly responsible for follow up. Complications did not correlate with mechanism, injury severity, service placing the R-IVCF, trauma volume, use of anticoagulation, age, or sex. Three cases of migration were recorded (all among R, 1.3%), two breakthrough PE (G-T 0.6% and R 0.4%) and six symptomatic caval occlusions (G-T 0, R 1%, Opt 11%) (p < 0.05 Opt versus both G-T and R)., Conclusion: Most R-IVCFs are not retrieved. The service placing the R-IVCF should be responsible for follow up. The Optease was associated with the greatest incidence of residual thrombus and symptomatic caval occlusion. The practice patterns of R-IVCF placement and retrieval should be re-examined.

Background: Age has been shown to be a primary determinant of survival following isolated traumatic brain injury (TBI). We have previously reported that patients > or =65 years who survived mild TBI have decreased functional outcome at 6 months compared with younger patients. The purpose of this study was to further investigate the effect of age on outcome at 1 year in all patients surviving isolated TBI., Methods: The Western Trauma Association multicenter prospective study included all patients sustaining isolated TBI defined as Abbreviated Injury Scale score for Head > or = 3 with an Abbreviated Injury Scale score in any other body area < or = 1. Outcome data included discharge disposition, Glasgow Outcome Scale score (1 = dead to 5= full recovery) and modified Functional Independence Measure (FIM) score measuring feeding, expression, and locomotion (1 = total dependence to 4 = total independence) for each component at discharge and 1 year., Results: In all, 295 patients were enrolled with a follow-up of 82%, resulting in 241 study patients. An additional five patients died from non-TBI causes and were excluded. The mean and median times for the last follow-up in the 236 remaining patients were 307 and 357 days, respectively. Patients were divided into four age ranges: 18 to 29 years (n = 66), 30 to 44 years (n = 54), 45 to 59 years (n = 50), and > or =60 years (n = 65). More severe TBIs, as measured by admitting Glasgow Coma Scale (GCS), were observed in the youngest group compared with all others but there were no differences in mean GCS between the remaining three groups. There were no differences in neurosurgical intervention between the groups. Age was a major determinant in the outcome at discharge and last follow-up. Patients over 60 years discharged with a GOS < or =4 were less likely to improve at 1 year than all other groups (37% versus 63 to 85%; p < or = 0.05). Patients between 18 and 29 years of age had the lowest mean Glasgow Outcome Scale and discharge FIM scores, which correlated with the low admission GCS. Despite the increased severity of TBI, this group had the best FIM score at 1 year. In contrast, patients older than 60 years had the least improvement and had a significantly lower final FIM score at 1 year compared with all other groups., Conclusion: Older patients following isolated TBI have poorer functional status at discharge and make less improvement at 1 year compared with all other patients. These worse outcomes occur despite what appears to be less severe TBI as measured by a higher GCS upon admission. Differences in outcome begin to appear even in patients between 45 and 59 years. Further investigations with more detailed outcome instruments are required to better understand the qualitative limitations of a patient's recovery and to devise strategies to maximize functional improvement following TBI. Age is an exceedingly important parameter affecting recovery from isolated TBI.

Background: Injury is the leading cause of death and functional disability in adolescent children. Little is known about quality of life and psychological outcomes after trauma in adolescents. The Trauma Recovery Project in Adolescents is a prospective epidemiologic study designed to examine multiple outcomes after major trauma in adolescents aged 12 to 19 years, including quality of life (QoL) and psychological sequelae such as acute stress disorder (ASD) and posttraumatic stress disorder (PTSD). The specific objectives of the present report are to examine ASD rates and the association of ASD with QoL outcomes in injured adolescents., Methods: Between April 26, 1999, and November 13, 2002, 401 eligible trauma patients aged 12 to 19 years triaged to five participating trauma center hospitals in a regionalized trauma system were enrolled in the study. The admission criteria for patients were as follows: (1) age 12 to 19 years and (2) injury diagnoses excluding severe traumatic brain injury (TBI) or spinal cord injury. QoL after trauma was measured using the Quality of Well-being (QWB) scale, a sensitive and well-validated functional index (range, 0 = death to 1.000 = optimum functioning). ASD (before discharge) was diagnosed with the Impact of Events Scale-Revised. Scores of 24+ were used to diagnose ASD. Patient outcomes were assessed at discharge and at 3, 6, 12, 18, and 24 months after discharge., Results: ASD before discharge was diagnosed in 40% of adolescent trauma survivors. ASD status was associated with large QoL deficits during follow-up, as follows: 3-month, ASD-positive QWB score = 0.667 vs. ASD-negative QWB score = 0.710, p < 0.01; 6-month, ASD-positive QWB score = 0.704 vs. ASD-negative QWB score = 0.742, p < 0.001; 12-month: ASD-positive QWB score = 0.718 vs. ASD-negative QWB score = 0.757, p < 0.01; 24-month, ASD-positive QWB score = 0.725 vs. ASD-negative QWB score = 0.769, p < 0.01. Female sex and violent mechanism predicted ASD risk (47% female vs. 36% male; odds ratio, 1.6; p < 0.05; violence 54% vs. 38%; odds ratio, 1.9; p < 0.01)., Conclusions: Adolescent trauma survivors have high rates of ASD. ASD severely impacts QoL outcomes and is associated with female sex and mechanism of injury in adolescents. Early recognition and treatment of ASD in seriously injured adolescents will improve QoL outcomes.

Background: Little is known about long-term psychological outcomes after major trauma in adolescents, a leading cause of death and preventable morbidity in this age group. A prospective epidemiologic study was conducted to examine quality of life (QoL) and posttraumatic stress disorder (PTSD) outcomes in injured adolescents. The specific objectives of the present report are to describe long-term PTSD and to identify risk factors for long-term PTSD and the impact of PTSD on QoL., Methods: Between April 26, 1999, and November 13, 2002, 401 eligible trauma patients aged 12 to 19 years triaged to five participating trauma center hospitals in a regionalized trauma system were enrolled in the study. The admission criteria for patients were as follows: age 12 to 19 years and injury diagnoses excluding severe traumatic brain injury or spinal cord injury. PTSD was diagnosed with the Impact of Events Scale-Revised; scores of 24+ were used to diagnose PTSD. QoL after trauma was measured using the Quality of Well-Being scale, a sensitive and well-validated functional index (range: 0 = death to 1.000 = optimum functioning). Patient outcomes were assessed at discharge and at 3, 6, 12, 18, and 24 months after discharge., Results: The rate of long-term PTSD was 27%, with high rates over the follow-up period. Risk factors for long-term PTSD were perceived threat to life (odds ratio [OR], 2.2; p < 0.001.); death of a family member at the scene (OR, 4.7; p < 0.001); no control over injury event (OR, 1.7; p < 0.05), and violence-related injury (OR, 2.2; p < 0.05). PTSD in adolescents was significantly and strongly associated with female gender, older age, low socioeconomic status, drug and alcohol abuse, and other adolescent behavioral problems. Long-term PTSD was also associated with marked and significant QoL deficits throughout the 24-month follow-up interval., Conclusion: High rates of long-term PTSD persist after major trauma in adolescents. Injury events such as perceived threat to life and control over the event are strongly associated with PTSD risk. Prolonged PTSD severely impacts QoL outcomes. Early identification and treatment of risk factors for long-term PTSD will be important to improve outcomes in injured adolescents.

Background: Excessive production of reactive oxygen species by PMN is associated with tissue damage during inflammation. LPS interacts with the cell surface receptor CD14, which generates transmembrane signals through Toll-like protein 4 leading to mitogen activated protein kinase (MAPK) p38 activation, cytokine synthesis, PMN beta2-integrin expression and oxidative burst. Phosphodiesterase inhibition decreases proinflammatory cytokine production and tissue injury after LPS challenge. Its effects on PMN function after LPS stimulation, however, have not been fully investigated. We hypothesized that LPS-induced TNF-alpha synthesis and subsequent PMN beta2-integrin expression and oxidative burst are downregulated by concomitant treatment with the non-specific phosphodiesterase inhibitor pentoxifylline (PTX)., Methods: Whole blood was incubated with HBSS (control), LPS (100 microg/mL), fMLP (1 micromol/L), LPS+PTX (2 mmol/L) and fMLP+PTX for different time intervals at 37C. Oxidative burst, CD14, and CD-11b expression were measured by flow cytometry. Serum TNF-alpha levels were measured by ELISA. In an attempt to localize the site of action of PTX (proximal or distal to PKC) cell surface receptors were bypassed by PMA stimulation (1 microg/mL) and oxidative burst was measured with and without PTX., Results: Up-regulation of CD14 expression was similar in LPS and LPS+PTX groups. LPS stimulation caused a significant increase in PMN oxidative burst, CD11b expression, and TNF-alpha serum levels. In addition, PMA and fMLP stimulation also caused significant increase in oxidative burst compared with controls. Concomitant addition of PTX to LPS led to a significant decrease in PMN oxidative burst (65%; p < 0.0001), PMN CD11b expression (20%; p = 0.012), and TNF-alpha levels (93%; p < 0.0001). Also, PMA- and fMLP-induced PMN oxidative burst were significantly decreased by PTX [77.5% (p < 0.0001) and 50% (p < 0.01), respectively]., Conclusions: These results suggest that PTX-inhibition of oxidative burst occurs distal to PKC and may be either due to direct inhibition of NADPH oxidase or inhibition of MAPK phosphorylation, leading to decreased adhesion molecule expression and TNF-alpha synthesis. Its use in clinical scenarios in which PMN are primed may be of clinical relevance.

Objective: Elderly patients (aged 60 years and older) have been demonstrated to have an increased mortality after isolated traumatic brain injury (TBI); however, the prognosis of those patients surviving their hospitalization is unknown. We hypothesized that surviving elderly patients would also have decreased functional outcome, and this study examined the functional outcome of patients with isolated TBI at discharge and at 6 months posthospitalization., Methods: This was a multicenter prospective study of all patients with isolated moderate to severe TBI defined as Head Abbreviated Injury Scale score of 3 with an Abbreviated Injury Scale score in any other body area of 1. Patients surviving to discharge gave their consent and were enrolled. Data collected included demographics, Glasgow Coma Scale (GCS) score at admission, and neurosurgical interventions. Outcome data included discharge disposition and Glasgow Outcome Scale score and modified Functional Independence Measure (FIM) score at discharge and at 6 months., Results: Two hundred thirty-five patients were enrolled, with 44 (19%) aged greater than or equal to 65 years. Mechanisms of injury were falls (34%), assaults (28%), motor vehicle collisions (14%), pedestrian (11%), and other (12%). Falls were more common in the older patients and assaults in the younger group. The mean admitting GCS score was 12.8 (95% confidence interval [CI], 12.4-13.3), with older patients having a higher mean GCS score, 14.1 (95% CI, 13.6-14.6) versus 12.5 (95% CI, 12.0-13.1; p = 0.03). There were no differences in the percentage of patients admitted to the intensive care unit or requiring neurosurgical intervention between younger and older patients. Because there were few elderly patients with low GCS scores who survived to discharge, outcome measures focused on those patients with GCS scores of 13 to 15. A greater percentage of elderly were discharged to rehabilitation (28% vs. 16%, p =0.08). The mean discharge FIM score was 10.4 (95% CI, 9.8-11.0) for the elderly versus 11.4 (95% CI, 11.1-11.7) for the young (p =0.001), with 68% elderly and 89% young discharged with total independent scores of 11 to 12. At 6 months, the difference narrowed, but the mean FIM score was still greater for the young group, 11.7 (95% CI, 11.6-11.9) versus 11.0 (95% CI, 10.6-11.4; p < 0.001)., Conclusion: Functional outcome after isolated mild TBI as measured by the Glasgow Outcome Scale and modified FIM is generally good to excellent for both elderly and younger patients. Older patients required more inpatient rehabilitation and lagged behind their younger counterparts but continued to recover and improve after discharge. Although there were statistically significant differences in the FIM score at both discharge and 6 months, the clinical importance of these small differences in the mean FIM score to the patient's quality of life is less clear. Measurable improvement in functional status during the first 6 months after injury is observed in both groups. Aggressive management and care of older patients with TBI is warranted, and efforts should be made to decrease inpatient mortality. Continued follow-up is ongoing to determine whether these outcomes persist at 12 months.

Background: The gut origin of the inflammatory response in trauma patients has been difficult to define. "In vivo" generation of neutrophil-activating factors by gut proteases may be a cause of multiorgan failure after hemorrhagic shock, and can be prevented with the serine protease inhibitor nafamostat mesilate (Futhan). The objective of this study was to determine the effect of nafamostat mesilate given by enteroclysis on enteric serine protease activity, neutrophil activation, and transfusion requirements during hemorrhagic shock., Methods: Sixteen pigs weighing 21 to 26 kg were divided into control and treatment groups. A laparotomy was performed under anesthesia, and catheters were placed in the duodenum, midjejunum, and terminal ileum. Pigs were bled 30 mL/kg over 30 minutes and maintained at a mean arterial pressure of 30 mm Hg for 60 minutes. Shed blood was then used to maintain a mean arterial pressure of 45 mm Hg for another 3 hours. Treated animals received 100 mL/kg of 0.37 mmol/L nafamostat mesilate in GoLYTELY through the duodenal catheter at 1 L/h. Control animals received GoLYTELY only. Samples of enteral content and blood were taken at baseline, after shock, and at 30-minute intervals during resuscitation. Animals were killed after 3 hours of resuscitation. Enteral trypsin-like activity at the three gut sites was measured by spectrophotometry. Activation of naive human neutrophils by pig plasma was measured by the percentage of cells having pseudopods larger than 1 microm on microscopy. Lung, liver, and small bowel were analyzed by histology and myeloperoxidase assay., Results: Both control and nafamostat mesilate-treated groups had significant reductions in protein and protease levels in the duodenum during enteroclysis; however, only nafamostat mesilate-treated animals had persistent suppression of protease activity throughout the experiment. Nafamostat mesilate-treated animals had a lower transfusion requirement of shed blood, 18.1 +/- 4.5 mL/kg versus 30 +/- 0.43 mL/kg (p = 0.002). Nafamostat mesilate-treated animals had significantly less neutrophil activation than controls at 150 minutes after resuscitation (33.7 +/- 6.48% vs. 42.4 +/- 4.57%,p = 0.01) and 180 minutes after resuscitation (31.1 +/- 3.31% vs. 46.9 +/- 4.53%, p = 0.0002). Lung myeloperoxidase activity was lower in nafamostat mesilate-treated animals (0.31 +/- 0.14) than in control animals (0.16 +/- 0.04, p = 0.04). Histology of liver and small intestine showed less injury in nafamostat mesilate-treated animals., Conclusion: Nafamostat mesilate given by means of enteroclysis with GoLYTELY significantly reduces enteral protease levels, leukocyte activation, and transfusion requirements during resuscitation from hemorrhagic shock. This strategy may have clinical promise.

Background: Analysis of the mechanism and severity of injury over time may permit a more focused planning of acute care and trauma prevention programs., Methods: A retrospective, population-based study examining severe traumatic injury in a single county was undertaken. Three overlapping data sets were used to form a composite injury data set., Results: There were 55,664 patients included in the study. A total of 40,897 (73.5%) patients survived and 14,767 (26.5%) died. Of those patients who died, 8,910 (60.3%) died in the field and were not transported to a trauma center. There was an increase in the mean age of all trauma victims (3 years) and an increase of 5 years in fatally injured patients. The mean Injury Severity Score decreased from 14.7 to 11.6 (p < 0.01); however, Injury Severity Score for fatal patients remained constant (39.7). The overall injury rate remained unchanged (195 per 10(5)), whereas the fatal injury rate decreased by 22% (45.9 per 10(5)) over the 11-year study period. The leading cause of injury was motor vehicle crash, followed by assault. The leading cause of fatal injury was suicide, followed by homicide., Conclusion: A combination of three independent injury data sources generated a composite data set of serious and fatal injury. This regional injury analysis was the most comprehensive overview of injury in our region. Important observations included the following: there has been no change in the overall incidence of severe injury within our county; the incidence of fatal traumatic injury has significantly decreased; the leading causes of nonfatal injury do not correlate with the rank order of fatal injury; intentional injury was the leading cause of injury deaths; and scene fatalities represent a poorly studied group of patients who may benefit from primary prevention and injury control research.

Background: The protective effect of female gender on posttraumatic mortality or acute complications after traumatic brain injury (TBI) has been postulated. This effect might be seen if TBIs were analyzed by severity. To assess potential gender effects, we performed a retrospective case-controlled study matching female patients to male counterparts for overall injury severity; hemodynamic status at admission; and head, chest, and abdomen Abbreviated Injury Scale score., Methods: All female patients sustaining TBI admitted over 6.5 years were reviewed. An overall comparison between women (n = 914) and their male matched counterparts (n = 916) was performed. Patients were then stratified according to the severity of head injury on the basis of admission Glasgow Coma Scale (GCS) score into three groups: group 1, GCS score of 13 to 15 (788 female patients, 769 male patients); group 2, GCS score of 9 to 12 (40 female patients, 42 male patients); and group 3, GCS score < 9 (63 female patients, 87 male patients). Cohorts were compared for mortality or the development of acute respiratory distress syndrome, pneumonia, and systemic sepsis using standard definitions. A subset analysis was performed excluding patients with age above 50 years (789 women, 811 men) to exclude the effects of menopause on the results., Results: There was no statistically significant difference in outcome overall or in subset analysis of mild (group 1), moderate (group 2), or severe (group 3) TBI. The exclusion of patients older than 50 years showed no protective effect of female gender on outcome., Conclusion: Gender does not play a role in posttraumatic mortality or in the incidence of acute complications after any degree of TBI.

Objectives: Endotoxin induced suppression of cellular immune function is thought to contribute to septic complications in trauma patients. A rabbit model of endotoxemia was used to determine the relative roles of the anti-inflammatory factors interleukin-4 (IL-4), interleukin-10 (IL-10), transforming growth factor beta1 (TGFbeta1), and prostaglandin E2 (PGE2) in addition to other factors, in inducing immunosuppression., Design: T-cell suppressive factors (TSF) in serum ultrafiltrates were separated and tested for the presence of the known suppressive factors PGE2, IL-4, IL-10, and TGFbeta1., Material and Methods: New Zealand rabbits were injected with 50 microg/kg of purified Escherichia coli lipopolysaccharide. Animals were exsanguinated after 48 hours and serum was separated by ultrafiltration (cutoff 50 kd), TSK HW-40 size exclusion chromatography, and Q-Sepharose anion exchange chromatography. TSF activities of chromatographic fractions and serum samples were measured with a mitogen induced in vitro T-cell proliferation assay. Levels of PGE2, IL-4, IL-10, and TGFbeta1 were measured with enzyme immunoassays., Measurements and Main Results: Serum TSF activity, and levels of PGE2, IL-4, IL-10, and TGFbeta1 were increased after endotoxemia. Size exclusion chromatography revealed three major fractions (TSF1-3) with up to 600 times more TSF activity compared with controls. IL-4 and IL-10 were found in TSF1 and TSF3. Further separation of TSF1 by anion exchange chromatography revealed a total of eight different T-cell suppressive factors. TGFbeta1 probably remained in the retentate after ultrafiltration, while PGE2 eluted at a higher retention time. The known anti-inflammatory factors TGFbeta1, IL-10, IL-4, and PGE2 only accounted for 13% of the total serum TSF activity of 614 U/mL., Conclusions: Lipopolysaccharide shock results in the release of multiple T-cell suppressive factors in addition to known immunosuppressive factors, all of which contribute to the anti-inflammatory response.