Valproic Acid Protects Against Acute Kidney Injury in Hemorrhage and Trauma.

INTRODUCTION: Trauma is the leading cause of death among young people. These patients have a high incidence of kidney injury, which independently increases the risk of mortality. As valproic acid (VPA) treatment has been shown to improve survival in animal models of lethal trauma, we hypothesized that it would also attenuate the degree of acute kidney injury. METHODS: We analyzed data from two separate experiments where swine were subjected to lethal insults.  Model 1: hemorrhage (50% blood volume hemorrhage followed by 72-h damage control resuscitation). Model 2: polytrauma (traumatic brain injury, 40% blood volume hemorrhage, femur fracture, rectus crush and grade V liver laceration). Animals were resuscitated with normal saline (NS) +/- VPA 150 mg/kg after a 1-h shock phase in both models (n = 5-6/group). Serum samples were analyzed for creatinine (Cr) using colorimetry on a Liasys 330 chemistry analyzer. Proteomic analysis was performed on kidney tissue sampled at the time of necropsy. RESULTS: VPA treatment significantly (P < 0.05) improved survival in both models. (Model 1: 80% vs 20%; Model 2: 83% vs. 17%). Model 1 (Hemorrhage alone): Cr increased from a baseline of 1.2 to 3.0 in NS control animals (P < 0.0001) 8 h after hemorrhage, whereas it rose only to 2.1 in VPA treated animals (P = 0.004). Model 2 (Polytrauma): Cr levels increased from baseline of 1.3 to 2.5 mg/dL (P = 0.01) in NS control animals 4 h after injury but rose to only 1.8 in VPA treated animals (P = 0.02). Proteomic analysis of kidney tissue identified metabolic pathways were most affected by VPA treatment. CONCLUSIONS: A single dose of VPA (150 mg/kg) offers significant protection against acute kidney injury in swine models of polytrauma and hemorrhagic shock.

Multidisciplinary team approach to traumatic spinal cord injuries: a single institution's quality improvement project.

BACKGROUND: A stepwise multidisciplinary team (MDT) approach to the injured trauma patient has been reported to have an overall benefit, with reduction in mortality and improved morbidity. Based on clinical experience, we hypothesized that implementation of a dedicated Spinal Cord Injury Service (SCIS) would impact outcomes of a patient specific population on the trauma service. METHODS: The trauma center registry was retrospectively queried, from January 2011 through December 2015, for patients presenting with a spinal cord injury. In 2013, a twice weekly rounding SCIS MDT was initiated. This new multidisciplinary service, the post-SCIS, was compared to the 2011-2012 pre-SCIS. The two groups were compared across patient demographics, mechanism of injury, surgical procedures, and disposition at discharge. The primary outcome was mortality. Secondary endpoints also included the incidence of complications, hospital length of stay (HLOS), ICU LOS, ventilator free days, and all hospital-acquired infectious complications. Logistic regression and Student's t test were used to analyze data. RESULTS: Ninety-five patients were identified. Of these patients, 41 (43%) pre-SCIS and 54 (57%) post-SCIS patients were compared. Mean age was 46.9 years and 79% male. Overall, adjusted mortality rate between the two groups was significant with the implementation of the post-SCIS (p = 0.033). In comparison, the post-SCIS revealed shorter HLOS (23 vs 34.8 days, p = 0.004), increased ventilator free days (20.2 vs 63.3 days, p < 0.001), and less nosocomial infections (1.8 vs 22%, p = 0.002). While the post-SCIS mean ICU LOS was shorter (12 vs 17.9 days, p = 0.089), this relationship was not significant. CONCLUSIONS: The application of an SCIS team in addition to the trauma service suggests that a structured coordinated approach can have an expected improvement in hospital outcomes and shorter length of stays. We believe that this clinical collaboration provides distinct specialist perspectives and, therefore, optimizes quality improvement. Level of evidence Epidemiologic study, level III.

[Deployment and efficacy of ground versus helicopter emergency service for severely injured patients. Analysis of a nationwide Swiss trauma center]. / Status quo der Boden- und Luftrettung schwerverletzter Patienten. Analyse eines überregionalen Schweizer Traumazentrums.

The influence of the transport mode, i.e. Helicopter Emergency Medical Service (HEMS) versus ground-based Emergency Medical Service (EMS) on the mortality of multiple trauma patients is still controversially discussed in the literature. In this study a total of 333 multiple trauma patients treated over a 1-year period in a level I trauma center in Switzerland were analyzed. Using the newly established revised injury severity classification (RISC) score there was a tendency towards a better outcome for patients transported by HEMS (standardized mortality ratio 1.06 for HEMS versus 1.29 for EMS). Overall a short preclinical time and the presence of an emergency physician (EP) were associated with a better outcome.

Influence of access to an integrated trauma system on in-hospital mortality and length of stay.

BACKGROUND: Few data are available on population-based access to specialised trauma care and its influence on patient outcomes in an integrated trauma system. We aimed to evaluate the influence of access to an integrate trauma system on in-hospital mortality and length of stay (LOS). METHODS: All adults admitted to acute care hospitals for major trauma [International Classification of Diseases Injury Severity Score (ICISS<0.85)] in a Canadian province with an integrated trauma system between 2006 and 2011 were included using an administrative hospital discharge database. The influence of access to an integrated trauma system on in-hospital mortality and LOS was assessed globally and for critically injured patients (ICISS<0.75), according to the type of injury [traumatic brain injury (TBI), abdominal/thoracic, spine, orthopaedic] using logistic and linear multivariable regression models. RESULTS: We identified 22,749 injury admissions. In-hospital mortality was 7% and median LOS was 9 days for all injuries. Overall, 92% of patients were treated within the trauma system. Globally, patients who did not have access had similar mortality and LOS compared to patients who had access. However, we observed a 62% reduction in mortality for critical abdominal/thoracic injuries (odds ratio=0.38; 95% CI, 0.16-0.92) and an 8% increase in LOS for TBI patients (geometric mean ratio=1.08; 95% CI, 1.02-1.14) treated within the trauma system. CONCLUSIONS: Results provides evidence that in a health system with an integrated mature trauma system, access to specialised trauma care is high and the small proportion of patients treated outside the system, have similar mortality and LOS compared to patients treated within the system. This study suggests that the Québec trauma system performs well in its mandate to offer appropriate treatment to victims of injury that require specialised care.

[Quality of life after multiple trauma]. / Lebensqualität nach Polytrauma.

BACKGROUND: Multiple trauma is an independent injury pattern which, because of its complexity, is responsible for 25 % of the costs for the treatment of all injured patients. Because of the often long-lasting physical impairment and the high incidence of residual permanent handicaps, it is apparent that multiple trauma can lead to a reduction in patient quality of life. OBJECTIVES: The aim of this study was to give an overview of the known data concerning the change in quality of life for multiple trauma patients. Furthermore, predictors for the reduction of quality of life after multiple trauma will be identified. MATERIALS AND METHODS: A MedLine search was performed to identify studies dealing with the outcome after multiple trauma. RESULTS: In addition to functional outcome parameters, the term quality of life has become more important in recent years when it comes to evaluating the outcome following injury. While the mortality after multiple trauma could be significantly reduced over the years, there is no comparable effect on the quality of life. Predictors for a worse quality of life after multiple trauma are female gender, high age, low social status, concomitant head injuries and injury to the lower extremities. CONCLUSION: The fact that mortality after multiple trauma has decreased but not impairment of the quality of life makes it clear that in addition to the acute medical treatment, a follow-up treatment including not only physiotherapy but also psychotherapy is crucial for multiple trauma patients.

Testing of blood products in a polytrauma model: results of a multi-institutional randomized preclinical trial.

INTRODUCTION: Trauma-induced coagulopathy, acidosis, and hypothermia form a "lethal triad" that is difficult to treat and is associated with extremely high mortality. This study was performed at three academic centers to evaluate whether resuscitation with blood components could reverse the coagulopathy in a complex polytrauma model. METHODS: Yorkshire swine (40 +/- 5 kg) were subjected to a three-phase protocol: (a) "Prehospital" phase = femur fracture, hemorrhage (60% blood volume), and 30 minutes shock + infusion of saline (3x shed blood) + induction of hypothermia (33 degrees C); (b) "Early hospital" phase = grade V liver injury; and (c) "Operative" phase= liver packing. After liver packing, the animals (n = 60) were randomized to the following groups: (1) Sham-instrumentation and anesthesia without hemorrhage/injuries, (2) fresh whole blood (FWB), (3) 6% hetastarch (Hextend), (4) fresh frozen plasma/packed RBCs in 1:1 ratio (1:1 FFP/PRBC), and (5) FFP alone. Treatment volumes were equal to the volume of shed blood. Hemodynamic and physiologic parameters and coagulation profile (thrombelastography, prothrombin time, activated partial thromboplastin time, international normalized ratio, and platelets) were monitored during the experiment and for 4 hours posttreatment. RESULTS: At the end of prehospital phase, animals had developed significant acidosis (lactate >5 mmol/L and base deficit >9 mmol/L) and coagulopathy. Posttreatment mortality rates were 85% and 0% for the Hextend and blood component treated groups, respectively (p < 0.05). Hemodynamic parameters and survival rates were similar in groups that were treated with blood products (FWB, FFP, and FFP:PRBC). Animals treated with FFP and Hextend had significant anemia compared with the groups that received red blood cells (FWB and FFP:PRBC). Treatment with FFP and FFP:PRBC corrected the coagulopathy as effectively as FWB, whereas Hextend treatment worsened coagulopathy. CONCLUSIONS: In this reproducible model, we have shown that trauma-associated coagulopathy is made worse by hetastarch, but it can be rapidly reversed with the administration of blood components. Impressively, infusion of FFP, even without any red blood cells, can correct the coagulopathy and result in excellent early survival.

Efeito da ingestão protéica nos marcadores nutricionais e complicações clínicas em pacientes politraumatizados / Efecto de la ingesta de proteínas en los marcadores nutricionales y las complicaciones clínicas en los pacientes politraumatizados / Effect of protein intake on nutritional markers and clinical complications in polytrauma patients

Objetivo: Avaliar o efeito da ingestão protéica nos níveis de albumina sérica, na prevalência de complicações clínicas relacionadas à dieta, no estado nutricional e na mortalidade de pacientes politraumatizados. Método: Pacientes politraumatizados atendidos na Unidade de Terapia Intensiva entre janiero e setembro de 2006 foram divididos em 2 grupos, sendo o grupo 1 composto por aqueles que ingeriram diariamente quantidade de proteínas=1g/kg e o grupo 2 por aqueles que ingeriram diariamente quantidade de proteínas>1g/Kg, com suplementação protéica. Foram coletados semanalmente albumina sérica, leucócitos e bastonetes, dados clínicos das fichas médicas, e escore da avaliação subjetiva global, e compararam-se os dados iniciais e finais. Resultados: Pacientes do grupo 2 demonstraram tendência em apresentar níveis mais elevados de albumina sérica do que os indivíduos do grupo 1. As complicações clínicas relacionadas à dieta apresentadas pelos pacientes dos grupos 1 e 2, respectivamente, foram diarréia (41,37% vs. 30%; p>0,05), hiperglicemia (68,96% vs. 55%;p>0,05) e estase gástrica (58,6% vs.25%; p=0,04), sendo somente a última com diferença estatística significativa entre os grupos. No grupo 1,8% dos pacientes apresentaram desnutrição grave, e a prevalência de infecção foi maior que no grupo 2 (18,7% vs. 11,1%, respectivamente; p=0,02). Conclusões: Este estudo sugere que a ingestão protéica acima de 1g/kg/dia, associada à quantidades adequadas de energia, diminui a suscetibilidade às infecções, e pode estar relacionada com melhora do estado nutricional e dos níveis séricos de albumina.

Objetivo: Evaluar el efecto de la ingesta de proteínas de suero de los niveles de albúmina, la prevalencia de complicaciones clínicas relacionadas con la dieta, el estado nutricional y la mortalidad de los pacientes politraumatizados. Método: Los pacientes politraumatizados atendidos en la Unidad de Cuidados Intensivos entre septiembre de 2006 y Janiero se dividieron en dos grupos, un grupo que está compuesto por aquellos que consumían la cantidad diaria de proteínas y el grupo 2 = 1g/kg por los que tomaron la cantidad diaria de proteínas > 1g/kg con suplementos de proteína. Semanalmente, se recolectaron suero leucocitos albúmina, y las barras, los datos clínicos de los registros médicos, y la puntuación subjetiva de evaluación global, y compararon los datos iniciales y finales. Resultados: Los pacientes en el grupo 2 tienden a presentar niveles más altos de albúmina de suero de los pacientes en el grupo 1. La dieta de complicaciones relacionadas con la clínica que presentan los pacientes en los grupos 1 y 2, respectivamente, fueron: diarrea (41,37% frente al 30%, p> 0,05), hiperglucemia (68,96% frente al 55%, p> 0 , 05) y la estasis gástrica (58,6% vs.25%, p = 0,04), y sólo este último con una diferencia estadísticamente significativa entre los grupos. En el grupo de 1,8% de los pacientes padecían de desnutrición severa, y la prevalencia de infección fue superior en el grupo 2 (18,7% vs 11,1%, respectivamente, p = 0,02). Conclusiones: Este estudio sugiere que la ingesta de proteínas por encima de 1g/kg/day, junto con cantidades adecuadas de energía, disminuye la susceptibilidad a las infecciones, y pueden estar relacionados con la mejora del estado nutricional y la albúmina sérica.

Objective: To evaluate the effect of protein intake on serum albumin levels, the prevalence of clinical complications related to diet, nutritional status and mortality of polytrauma patients. Method: polytrauma patients treated at the Intensive Care Unit between September 2006 and janiero were divided into two groups, one group being composed of those who ate the daily amount of protein and group 2 = 1g/kg by those who took daily amount of protein > 1g/kg with protein supplementation. Were collected weekly serum albumin, leukocytes and rods, clinical data from medical records, and subjective global assessment score, and compared the initial and final data. Results: Patients in group 2 tended to present higher levels of serum albumin than patients in group 1. The diet-related clinical complications presented by patients in groups 1 and 2, respectively, were diarrhea (41.37% vs. 30%, p> 0.05), hyperglycemia (68.96% vs. 55%, p> 0 , 05) and gastric stasis (58.6% vs.25%, p = 0.04), and only the latter with a statistically significant difference between groups. In group 1.8% of patients had severe malnutrition, and prevalence of infection was higher than in group 2 (18.7% vs. 11.1%, respectively, p = 0.02). Conclusions: This study suggests that protein intake above 1g/kg/day, coupled with adequate amounts of energy, decreases the susceptibility to infections, and may be related with improvement of nutritional status and serum albumin.

Comparison of mortality due to severe multiple trauma in two comprehensive models of emergency care: Atlantic Pyrenees (France) and Navarra (Spain).

BACKGROUND: Injury due to external causes is an important health problem in our society today. Emergency care systems based on the concept of "comprehensive care" can prevent deaths and disabilities as well as limit the severity and pain caused by trauma. OBJECTIVE: To investigate the frequency and characteristics of different mechanisms of injury and to estimate mortality, comparing two comprehensive emergency systems: Atlantic Pyrenees (AP) in France and Navarra (NA) in Spain. MATERIAL AND METHODS: A prospective cohort study of severe multiple-injury patients attended to by the comprehensive emergency care systems of AP and NA from April 1, 2001 to March 31, 2002. Data were collected from personal patient data, the emergency coordination center "112," pre-hospital and hospital health care levels, and discharge data. Bivariate statistical analysis and multivariate logistic regression models were employed for statistical management. RESULTS: There were 614 severe multiple trauma patients recorded, 278 in AP and 336 in NA. Significant differences were observed in arrival time, pre-hospitalization care, pre-hospital Revised Trauma Score (RTS), Injury Severity Score (ISS) at the intensive care unit, and procedures used (intubation, administration of fluids, immobilization, and diagnostic methods). Logistic regression showed significant differences in patient death, age (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.01-1.03), penetrating or accidental injuries, (OR 3.85, 95% CI 1.1-13.1), RTS (OR 0.58, 95% CI 0.5-0.7), and ISS score (OR 1.05, 95% CI 1.0-1.1). CONCLUSION: Despite a more aggressive approach and employment of greater resources, the French comprehensive trauma system does not show greater survival rates among injured patients compared to Navarra, even when controlling for confounding factors like age, injury mechanism, RTS, ISS, and others.

Frequent intravenous pulses of growth hormone together with glutamine supplementation in prolonged critical illness after multiple trauma: effects on nitrogen balance, insulin resistance, and substrate oxidation.

OBJECTIVES: To estimate the efficacy and metabolic effects of growth hormone substitution as intravenous pulses together with alanyl-glutamine supplementation and tight blood glucose control in prolonged critical illness. DESIGN: Prospective double-blind, randomized trial with open-label control arm. SETTING: Intensive care unit of tertiary level hospital. PATIENTS: Thirty multiple trauma patients (median Injury Severity Score 34). INTERVENTIONS: Patients were randomized, at day 4 after trauma, to receive intravenous alanyl-glutamine supplementation (0.3 g/kg x day(-1) from day 4 until day 17) and intravenous growth hormone (administered days 7-17, full dose 50 microg/kg x day(-1) from day 10 onward) (group 1, n = 10) or alanyl-glutamine and placebo (group 2, n = 10). Group 3 (n = 10) received isocaloric isonitrogenous nutrition (proteins 1.5 g/kg x day(-1)) without alanyl-glutamine. MEASUREMENTS AND MAIN RESULTS: Cumulative nitrogen balance for the whole study period was -97 +/- 38 g of nitrogen for group 1, -193 +/- 50 g of nitrogen for group 2, and -198 +/- 77 g of nitrogen for group 3 (p < .001). This represents a daily saving of 300 g of lean body mass in group 1. Insulin-mediated glucose disposal, during euglycemic clamp, as a measure of insulin sensitivity, significantly worsened between days 4 and 17 in group 1 but improved in groups 2 and 3. Group 1 required significantly more insulin to control blood glucose, resulting in higher insulinemia (approximately 70 mIU in group 1 vs. approximately 25 mIU in groups 2 and 3). Despite this, growth hormone treatment caused an increase in plasma nonesterified fatty acid (approximately 0.5-0.6 mM in group 1 in comparison with approximately 0.2-0.3 mM in groups 2 and 3) but did not influence lipid oxidation. There were no differences in morbidity, mortality, or 6-month outcome among the groups. CONCLUSIONS: Treatment with frequent intravenous pulses of low-dose growth hormone together with alanyl-glutamine supplementation improves nitrogen economy in patients with prolonged critical illness after multiple trauma but worsens insulin sensitivity. Tight blood glucose control is possible but requires higher doses of insulin.

Synbiotics, prebiotics, glutamine, or peptide in early enteral nutrition: a randomized study in trauma patients.

BACKGROUND: Since the hepatosplanchnic region plays a central role in development of multiple-organ failure and infections in critically ill trauma patients, this study focuses on the influence of glutamine, peptide, and synbiotics on intestinal permeability and clinical outcome. METHODS: One hundred thirteen multiple injured patients were prospectively randomized into 4 groups: group A, glutamine; B, fermentable fiber; C, peptide diet; and D, standard enteral formula with fibers combined with Synbiotic 2000 (Synbiotic 2000 Forte; Medifarm, Sweden), a formula containing live lactobacilli and specific bioactive fibers. Intestinal permeability was evaluated by measuring lactulose-mannitol excretion ratio on days 2, 4, and 7. RESULTS: No differences in days of mechanical ventilation, intensive care unit stay, or multiple-organ failure scores were found between the patient groups. A total of 51 infections, including 38 pneumonia, were observed, with only 5 infections and 4 pneumonias in group D, which was significantly less than combined infections (p = .003) and pneumonias (p = .03) in groups A, B, and C. Intestinal permeability decreased only in group D, from 0.148 (0.056-0.240) on day 4 to 0.061 (0.040-0.099) on day 7; (p < .05). In group A, the lactulose-mannitol excretion ratio increased significantly (p < .02) from 0.050 (0.013-0.116) on day 2 to 0.159 (0.088-0.311) on day 7. The total gastric retention volume in 7 days was 1150 (785-2395) mL in group D, which was significantly more than the 410 (382-1062) mL in group A (p < .02), and 620 (337-1190) mL in group C (p < .03). CONCLUSIONS: Patients supplemented with synbiotics did better than the others, with lower intestinal permeability and fewer infections.

[Interdisciplinary quality management in the treatment of severely injured patients. Validation of a QM system for the diagnostic and therapeutic process in early clinical management]. / Interdisziplinäres Qualitätsmanagement in der Behandlung schwerverletzter Patienten. Validierung eines QM-Systems für den diagnostischen und therapeutischen Ablauf der frühklinischen Versorgung.

A multidisciplinary quality management system (QMS) for the early treatment of severely injured patients was validated in a trauma center in Germany. In the presented prospective study a QMS developed at another trauma center was implemented at the department of trauma surgery of the University of Essen for the presented study. The essential elements of the QMS were the establishment of (1) an adequate protocol for documentation, (2) 20 criteria for the assessment of treatment quality, (3) regular statistical analysis of treatment quality and (4) a quality circle comprising all medical specialties for data discussion. From 5/98-9/99 a cohort of 447 patients with an average injury severity score (ISS) of 22 +/- 17 was treated in the emergency department. The impact of the QMS was assessed in 4 periods (1: 5/1998-8/1998; 2: 9-12/1998; 3: 1-4/1999; 4: 5-8/1999). The quality circle met 8 times. For the improvement of the process 16 long-term changes were introduced. In 60% (n = 12) of the 20 assessment criteria significant improvements were detected. In diagnostics there were significant reductions of the time needed for basic radiological and sonographic check-up (from 24 +/- 12 min in the first to 14 +/- 8 min in the last period) and of the duration until performance of a cranial computed tomography in severe traumatic brain injury (sTBI; from 45 +/- 22 to 28 +/- 8 min). The rate of delayed diagnoses remained low (4% in the first, 5% in the last period). Further positive changes were the time savings in transfusion (from 35 +/- 20 to 20 +/- 4 min) and emergency operations (from 67 +/- 20 to 48 +/- 4 min) in hemorrhagic shock as well as for craniotomies (77 +/- 41 to 54 +/- 19 min) in sTBI. Apart from the significant time reductions other improvements were found. Overall mortality was diminished from 17% in the first to 10% in the last observation period. In conclusion the study revealed that the quality of the early therapy of severely injured patients was significantly improved by implementation of a multidisciplinary quality management system especially with respect to treatment efficiency.

Traditional injury scoring underestimates the relative consequences of orthopedic injury.

OBJECTIVE: To demonstrate that patients with multiple injuries who have orthopedic injuries (ORTHO) face greater challenges regarding functional outcome than those without, to identify domains of postinjury dysfunction, and to illustrate the increasing discordance of functional recovery over time for ORTHO patients in relation to nonORTHO patients. METHODS: A convenience sample of adult blunt force trauma patients admitted to a Level I trauma center was evaluated at admission, and at 6 and 12 months after injury. Data were collected from the trauma registry (Trauma One), chart review, and interviews. Mailed surveys were completed 6 and 12 months after injury. The Short Form 36 (SF36) general health survey and the Sickness Impact Profile work scale (SIPw) were administered at both time points. Data are presented as mean +/- SEM or percent (%). To compare means, t tests were conducted, and Injury Severity Score (ISS) was controlled by linear regression before the evaluation of the role of ORTHO injury pattern on outcome measures. Significance is noted at the 95% confidence level (p < 0.05). RESULTS: The 165 patients studied averaged 37.2 +/- 1.1 years in age and were 67% men. The mean ISS was 14.4 +/- 0.6 and 61% had ORTHO injury. ORTHO patients were no different from nonORTHO in any measure of baseline status including the SIPw score and all domains of the SF36, except that the ISS was greater in the ORTHO group (15.6 +/- 0.96 vs. 12.7 +/- 0.73, p = 0.017). Baseline SF36 values were similar to national norms. Follow-up was 75% at 6 months, and 51% at 12 months. Those lost to follow-up differed only in that they were more likely to be men. Sixty-four percent had returned to work 12 months after injury. After controlling for ISS with linear regression, the ORTHO patients had worse scores on all physical measures of the SF36 (bodily pain, physical function, and role-physical). By 12 months after injury, the relative dysfunction of the ORTHO patients had expanded to include the SIPw score (p = 0.016) and six of eight SF36 domains (bodily pain, physical function, role-physical, mental health, role-emotional, and social function, all p < 0.05). CONCLUSION: Injury severity affects both mortality and the potentially more consequential issues of long-term morbidity. Patients with ORTHO injury have relatively worse functional recovery, and this worsens with time. As trauma centers approach the limits of achievable survival, new advances in trauma care can be directed more toward the quality of recovery for our patients. This will be contingent on further development of screening, scoring, and treatment systems designed to address issues of functional outcome across injury boundaries for those who survive.

[Significance of selenium in regulation of inflammatory response by transcription factors in polytrauma patients. A clinical study]. / Bedeutung von Selen in der Regulierung der inflammatorischen Antwort durch Transkriptionsfaktoren bei Polytraumapatienten. Eine klinische Studie.

The authors have investigated the relationship between selenium and transcription factors (NF-kappa B and AP-1) in the field of pathogenesis of polytrauma. Correlations between plasma selenium content and transcription factor binding activity have been found. The measured connecting capacitances of transcription factors have been associated with the severity of disease. To harden the results of this research a randomized double blind study with sodium selenite substitution is necessary next. This study will be to establish the therapy with sodium selenite in the treatment of polytrauma.

[Low T3 syndrome in multiple trauma patients--a phenomenon or important pathogenetic factor?]. / Low-T3-Syndrom bei Polytraumapatienten--Phänomen oder wichtiger pathogenetischer Faktor?

BACKGROUND: Many nonthyroidal illnesses, such as major trauma, severe burn injury, sepsis or immune deficiency are associated with a reduced T3 concentration without increased serum TSH secretion. The pathopysiologic meaning of this phenomenon was controversely discussed since its investigation 20 years ago. The identification of the Type I 5-iodthyronine-deiodinase as a selenoenzyme brought many new aspects into this discussion. PATIENTS AND METHODS: To investigate the correlation of T3 blood levels and the selenium concentrations in consideration of the severity of the nonthyroidal illness 20 patients with major trauma where included in this study. In all these patients frequently T3, T4, fT3, fT4, TSH, Se (whole blood), Se (plasma) and Glasgow-Coma-Scale (GCS), APACHE II and MOF-Score where measured until the 28th day of illness. RESULTS: Five patients (20%) died during the study until the 8th day of measurement. Survivors and nonsurvivors initial showed a low T3 and fT3 level in serum. While the T3 serum concentrations of nonsurvivors remained on a low level the thyronine concentrations of survivors distinctly increased. The measured thyroid hormone concentrations were significantly correlated with MOF-score, APACHE II and inversely with GCS. There was no significant correlation between low T3/fT3 blood levels and low selenium concentrations in all observed patients. CONCLUSION: The selenium deficiency in all patients with major trauma seems to be not the single cause of the low T3 syndrome. The distinctly suppression of TSH could be caused by the action of various cytokines such as IL-6 and TNF-alpha. Further investigations should improve the effectivity of substitution of selenium and/or thyroid hormones in the therapy of patients with severe nonthyroidal illness.

[Clinical effects of supplemental enteral nutrition solution in severe polytrauma]. / Klinische Auswirkungen einer supplementierten enteralen Nährlösung beim schweren Polytrauma.

Previous studies in critically ill patients have shown the beneficial effects of early enteral nutrition supplemented with arginine, omega-3 fatty acids and nucleotides (Impact) on immunological response, infection rate and length of stay in hospital. No specific data exist for patients with severe multiple injury, who represent a high risk group for systemic inflammatory response syndrome (SIRS), septic complications and multiple organ failure (MOF). In this prospective, randomized, double-blind controlled clinical study on patients after severe trauma (ISS ca. 40) the primary study endpoints were incidence of SIRS and MOF [definitions according to Am Soc Crit Care Med (5) and Goris (23), Sauaia (43)]. Thirty-two patients enrolled in the study, and 29 were eligible for analysis: test (Impact) (n = 16), control (n = 13). Both groups were comparable according to age, body mass index and severity of trauma (PTS-test: 38.8 +/- 12.5, PTS-control: 40.8 +/- 15.5, ISS-test: 39.6 +/- 11.4, ISS-control: 40.5 +/- 9.2). Patients were randomized to receive either Impact (test) or an isonitrogenous isocaloric diet (control). Feeding was started on the 2nd day after trauma via endoscopically placed nasoduodenal or jejunal feeding tubes. The experimental diet was safe and well tolerated. During the 1st week the enteral feeding amount was about 2000 ml without significant difference. Test-fed patients developed SIRS significantly less frequently between day 1 and day 28 (8 vs 13.3; P < 0.05) and especially between day 8 and day 14 (3 vs 6.2; P < 0.001). In the control group the Goris score was significantly worse (P < 0.05) on days 3, 4, 6, 7, 10, 11, 16 and 17 and the Sauaia score on days 8, 9, 10 and 11 (P < 0.05; P < 0.01). Mortality rate did not significantly differ (test 2/16, control 4/13), nor did length of ICU or hospital stay. With regard to the acute-phase response, C-reactive protein was significantly lower on day 4 in the test group (test: 131 +/- 67 mg/l, control: 221 +/- 110 mg/l) as was fibrinogen on day 12 (6.6 +/- 1.4 vs 7.5 +/- 1.4 g/l) and day 14 (7.1 +/- 1.3 vs 7.8 +/- 0.8 g/l). No significant difference could be observed for CD4/CD8 ratio, CD45 isotope on activated T-cells and lymphocytic interleukin (II)-2-receptor- and II-6 level. However, HLA-DR antigen presentation on peripheral monocytes was significantly elevated on day 7 in the test group (P < 0.05). According to the results, arginine, omega-3 fatty acids and nucleotides-enriched diet during early enteral feeding leads to reduction of SIRS after severe multiple injury. There is evidence for improvement of post-traumatic immunological response which helps to overcome the immunological depression after trauma.

[Changes in the plasma concentration of vitamin A, vitamin E and beta-carotene in polytrauma patients and in patients with osteitis in relation to course of illness]. / Veränderungen in der Plasmakonzentration von Vitamin A, Vitamin E und beta-Karotin bei Polytraumatisierten und Patienten mit Osteitis in Abhängigkeit vom Krankheitsverlauf.

In 17 patients with osteitis and 16 polytraumatized patients changes in the plasma levels of vitamin A, vitamin E and beta-carotene were investigated. Plasma samples taken preoperatively, daily during the first three days and then twice a week postoperatively were analysed for fat-soluble vitamins by high performance liquid chromatography (HPLC). Significant changes in plasma levels of all three components depending on the outcome of injury were found in all patients. Increased levels were observed in patients that survived the injury, while in those who died a significant decrease was observed. Recommendations regarding the supplementation with these vitamins in clinical practice can not be made based on these results, but substitute might prove beneficial for vitamin E in certain types of injury.

[Is modification of systemic inflammatory response syndrome and multiple organ failure by parenteral feeding possible?]. / Ist eine Beeinflussung von SIRS und MOV durch Ernährungstherapie möglich?

In this prospective, randomized, double-blind controlled clinical study, 29 patients after severe trauma (ISS about 40) were randomized to receive either IMPACT (Test) or an isonitrogenous isocaloric diet (Control). The primary study endopoints were the incidence of SIRS and MOF (definitions according to Bone, Goris and Sauaia). Test-fed patients developed significantly less SIRS between days 1 and 28 (8 vs 13.3, P < 0.05) and especially between days 8 and 14 (3 vs 6.2, P < 0.001). In the control group the Goris score was significantly worse (P < 0.05) on days 3, 4, 6, 7, 10, 11, 16, 17 and the Sauaia score on days 8, 9, 10, 11 (P < 0.05, P < 0.01). According to the results, an arginine, omega-3-fatty acids and nucleotide-enriched diet during early enteral feeding leads to reduction of SIRS and MOF scores after severe multiple injury.

Effects of an immune-enhancing diet in critically injured patients.

OBJECTIVE: To determine the effects of an immune-enhancing experimental diet (XD = supplemental arginine, trace elements, and increased omega-3 fatty acids) versus standard diet (SD), on immune cell function and clinical outcome of critically injured patients. DESIGN: Prospective randomized clinical trial of patients admitted to the surgical intensive care unit after trauma (Injury Severity Score > 13). MATERIALS AND METHODS: Patients received early enteral nutrition with either XD or SD for a minimum of 5 days. MEASUREMENTS: Mortality, intensive care unit, ventilator, and hospital days, as well as incidence of adult respiratory distress syndrome (ARDS) and infectious complications were recorded. Nutritional parameters were also studied. Peripheral blood leukocytes were isolated from normal volunteers and from patients on days 1, 6, and 10 of feeding. MAIN RESULTS: Demographics and injury severity were similar in both groups. Both SD (n = 21) and XD (n = 22) groups revealed depressed monocyte function (tumor necrosis factor, prostaglandin E2, and procoagulant activity) on day 1 compared with a reference group (p < 0.05). However, monocytes from XD patients began to "normalize" their response (tumor necrosis factor, prostaglandin E2, and procoagulant activity) by day 6. Although ARDS occurred more frequently in the XD group (45 vs. 19%), the majority of ARDS in both groups occurred very early, with only three patients in the XD (13.6%) and one patient in the SD (4.7%) groups developing ARDS after study entry. XD patients remained on the ventilator longer (16.4 vs. 9.7 days) and in the hospital longer (32.9 vs. 22 days) compared with the SD group, but overall mortality was nearly identical (4.5 vs. 5%). CONCLUSION: The exact role and timing for diets with immune-enhancing effects has yet to be defined.

Nutritional antioxidants and the modulation of inflammation: theory and practice.

Highly potent substances are produced by the immune system. These substances include cytokines and oxidant molecules, such as hydrogen peroxide, free radicals, and hypochlorous acid. The purpose of immune cell products is to destroy invading organisms and damaged tissue, bringing about recovery. However, oxidants and cytokines can damage healthy tissue. Excessive or inappropriate production of these substances is associated with mortality and morbidity after infection and trauma, and in inflammatory diseases. Oxidants enhance interleukin-1, interleukin-8, and tumor necrosis factor production in response to inflammatory stimuli by activating the nuclear transcription factor, NF kappa B. Sophisticated antioxidant defenses directly and indirectly protect the host against the damaging influence of cytokines and oxidants. Indirect protection is afforded by antioxidants, which reduce activation of NF kappa B, thereby preventing up-regulation of cytokine production by oxidants. Cytokines increase both oxidant production and antioxidant defenses, thus minimizing damage to the host. While antioxidant defenses interact when a component is compromised, the nature and extent of the defenses are influenced by dietary intake of sulfur amino acids, for glutathione synthesis, and vitamins E and C. In animal studies, in vivo and in vitro responses to inflammatory stimuli are influenced by dietary intake of copper, zinc, selenium, N-acetylcysteine, cysteine, methionine, taurine, and vitamin E. Information from animal studies has yet to be fully translated into a clinical context. However, N-acetylcysteine, vitamin E, and a cocktail of antioxidant nutrients have reduced inflammatory symptoms in inflammatory joint disease, acute and chronic pancreatitis, and adult respiratory distress syndrome. Impaired antioxidant defenses may contribute to disease progression after infection with human immunodeficiency virus. Powerful arguments have been advanced for treatment with antioxidants to slow progression of acquired immunodeficiency syndrome.

Routine prophylactic antifungal agents (clotrimazole, ketoconazole, and nystatin) in nontransplant/nonburned critically ill surgical and trauma patients.

A prospective, randomized study was conducted to determine if prophylactic antifungal agents prevented yeast colonization (YC) or yeast sepsis (YS), or if they diminished mortality in 292 critically ill adult (nontransplant/nonburned) surgical and trauma patients admitted to the SICU for 48 hours or longer. Patients were randomized to receive (group I) no therapy, (group II) clotrimazole 10 mg three times a day, (group III) ketoconazole 200 mg per day, or (group IV) nystatin 2 million units every 6 hours. For comparison patients were stratified by the criteria of Slotman and Burchard into high risk (> or = 3 risk factors) and low risk (< 3 risk factors). Fifty patients (17%) had yeast colonization, nine (3.1%) had yeast sepsis, and 41 (14%) died. Stepwise logistic regression analysis of yeast colonization and sepsis using the variables APACHE II scores > 10, need for ventilator support > 48 hours, and 14 risk factors (Slotman and Burchard) showed that treatment with three or more antibiotics, APACHE II > 10, and ventilatory support > 48 hours were the only three variables that were significant predictors of yeast colonization and sepsis. There was no significant difference between the four groups with regard to YC (23%, 18%, 12%, and 15%, respectively), YS (3%, 1%, 2%, and 7%, respectively), or mortality (15%, 14%, 6%, and 20%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)