Debra L. Malone

Blood transfusion, independent of shock severity, is associated with worse outcome in trauma.

BACKGROUND We have previously shown that blood transfusion in the first 24 hours is an independent predictor of mortality, intensive care unit (ICU) admission, and increased ICU length of stay in the acute trauma setting when controlling for Injury Severity Score, Glasgow Coma Scale score, and age. Indices of shock such as base deficit, serum lactate level, and admission hemodynamic status (systolic blood pressure, heart rate) and admission hematocrit were considered potential confounding variables in that study. The objectives of this study were to evaluate admission anemia and blood transfusion within the first 24 hours as independent predictors of mortality, ICU admission, ICU length of stay (LOS), and hospital LOS, with serum lactate level, base deficit, and shock index (heart rate/systolic blood pressure) as covariates. METHODS Prospective data were collected on 15,534 patients admitted to a Level I trauma center over a 3-year period (1998-2000) and stratified by age, gender, race, Glasgow Coma Scale score, and Injury Severity Score. Admission anemia and blood transfusion were assessed as independent predictors of mortality, ICU admission, ICU LOS, and hospital LOS by logistic regression analysis, with base deficit, serum lactate, and shock index as covariates. RESULTS Blood transfusion was a strong independent predictor of mortality (odds ratio [OR], 2.83; 95% confidence interval [CI], 1.82-4.40; p < 0.001), ICU admission (OR, 3.27; 95% CI, 2.69-3.99; p < 0.001), ICU LOS (p < 0.001), and hospital LOS (Coef, 4.37; 95% CI, 2.79-5.94; p < 0.001) when stratified by indices of shock (base deficit, serum lactate, shock index, and anemia). Patients who underwent blood transfusion were almost three times more likely to die and greater than three times more likely to be admitted to the ICU. Admission anemia (hematocrit < 36%) was an independent predictor of ICU admission (p = 0.008), ICU LOS (p = 0.012), and hospital LOS (p < 0.001). CONCLUSION Blood transfusion is confirmed as an independent predictor of mortality, ICU admission, ICU LOS, and hospital LOS in trauma after controlling for severity of shock by admission base deficit, lactate, shock index, and anemia. The use of other hemoglobin-based oxygen-carrying resuscitation fluids (such as human or bovine hemoglobin substitutes) in the acute postinjury period warrants further investigation.

Abdominal wall hernias: risk factors for infection and resource utilization

BACKGROUND Abdominal wall hernia repairs are common surgical procedures. Several recent reports have studied the outcomes of elderly patients undergoing inguinal hernia repair and documented a morbidity rate ranging from 5-57% and a mortality rate ranging from 1.6-14%. However, there has been limited data documenting the risk factors associated with postoperative morbidity and mortality from abdominal wall hernia repairs in general. Therefore, we sought to investigate the incidence of complications in patients undergoing abdominal wall hernia repair and to evaluate the risk factors for infection and resource utilization in these patients. METHODS Prospective data (NSQIP) were collected on 6301 noncardiac surgical patients at the VA Maryland Healthcare System from 1995 to 2000. From this data set, 487 (7.7%) patients underwent abdominal wall hernia repairs and comprised the study cohort. Logistic and linear regression analyses were performed to identify risk factors for infection and hospital length of stay. RESULTS The mean age of the study cohort was 60 +/- 14 and the mean ASA class was 2.4 +/- 0.7. Descriptive data revealed 99% were male, 43% used tobacco, 8.4% were diabetic, 7.4% used alcohol, 6.3% had chronic obstructive pulmonary disease (COPD), 2.1% were malnourished (defined as >/= 10% weight loss over prior 6 months), 1.6% used steroids, 1.2% had ascites, and 0.2% had coronary artery disease (CAD). The mortality rate was low at 1% but the morbidity rate was higher with a 4.3% incidence of wound infections and a 15.1% incidence of recurrent hernias. The mean preoperative serum albumin level was 4.1 +/- 0.6 g/dL, and the mean hospital length of stay was 1.4 +/- 4.8 days. Multiple logistic and linear regression analyses documented that CAD, COPD, low preoperative serum albumin, and steroid use were independent risk factors for increased postoperative wound infections (P < 0.05) and increased hospital length of stay (P < 0.05). CONCLUSIONS Abdominal wall hernia repair is associated with significant morbidity in this predominantly elderly cohort but mortality rates were low. COPD and low preoperative serum albumin were independent predictors of wound infections and CAD, COPD, low preoperative serum albumin, and steroid use were independent predictors of increased hospital length of stay. Therefore, consideration should be given to optimizing patients cardiopulmonary and nutritional status before abdominal wall hernia repair.

Back to basics : Validation of the admission systemic inflammatory response syndrome score in predicting outcome in trauma

BACKGROUND We have previously documented that the admission systemic inflammatory response syndrome (SIRS) score, calculated with four variables-temperature, heart rate, neutrophil count, and respiratory rate-is a significant predictor of outcome in trauma (n = 4,887). The objective of this current study was to validate our previous findings in a larger trauma patient population, to analyze the predictive accuracy of the four individual components of the SIRS score (temperature, heart rate, neutrophil count, and respiratory rate), and to assess whether the admission SIRS score is an accurate predictor of intensive care unit (ICU) resource use in trauma. METHODS Prospective data were collected on 9,539 patients admitted to a Level I trauma center over a 30-month period (January 1997-July 1999). Patients were stratified by age, sex, race, and Injury Severity Score (ISS). SIRS score was calculated at admission, and SIRS was defined as a SIRS score > or = 2. RESULTS SIRS score was validated as a significant independent predictor of outcome in trauma by logistic regression analysis after controlling for age and ISS. Of the four SIRS variables, hypothermia (temperature < 36 degrees C) was the most significant predictor of mortality after controlling for age and ISS. Leukocytosis (neutrophil count > 12,000/mm3) was the most significant predictor of total hospital length of stay. SIRS scores of > or = 2 were increasingly predictive of mortality and ICU admission by logistic regression analysis (p < 0.001). CONCLUSION These data provide further validation that an admission SIRS score of > or = 2 is a significant independent predictor of outcome and ICU resource use in trauma. Temperature (hypothermia) is the individual component of the SIRS score with the greatest predictive accuracy. SIRS score should be calculated on all trauma admissions.

Reduction of IL-10 and nitric oxide synthesis by SR31747A (sigma ligand) in RAW murine macrophages.

BACKGROUND There are several subtypes of sigma receptor, one of which is found throughout the immune system. SR31747A is a unique sigma ligand that possesses potent immune modulatory properties. Previous in vivo studies have documented that administration of SR31747A in murine models of sepsis resulted in decreased proinflammatory (IL-1, IL-6, TNF-alpha) and increased anti-inflammatory (IL-10) response (serum, splenocyte). Studies regarding the effect of this sigma ligand on purified macrophages are lacking. We therefore sought to investigate the effect of SR31747A in LPS-stimulated murine macrophages (RAW 264.7). METHODS RAW cells were incubated at 2.5 x 10(5) cells/well; controls were incubated with media alone, experimental groups contained LPS (0.01 microg) and SR31747A (1 nM, 10 nM, 100 nM, 1 microM, 10 microM). Supernatant and cells were harvested at 24 and 48 h. Concentrations of nitric oxide (Greiss reaction) and IL-10 were determined in the supernatant; cellular IL-10 mRNA was assessed. RESULTS SR31747A induced a dose-dependent reduction in NO and IL-10 protein release in LPS-stimulated murine macrophages. The decrease in IL-10 protein synthesis was paralleled by a significant dose-dependent reduction in IL-10 mRNA. CONCLUSION SR31747A is a novel immunomodulator that down regulates nitric oxide and IL-10 protein and mRNA expression. This in vitro reduction of IL-10 protein and mRNA expression is in contrast to previous in vivo murine studies. These data suggest that peripheral macrophages are not the source of the increased anti-inflammatory (IL-10) response induced by SR31747A.

Clinical relevance of mold culture positivity with and without recurrent wound necrosis following combat-related injuries

BACKGROUND Invasive fungal wound infections (IFIs) are a recognized threat for personnel who sustain combat-related blast trauma in Afghanistan. Blast trauma, particularly when dismounted, has wounds contaminated with organic debris and potential for mold infection. Trauma-associated IFI is characterized by recurrent wound necrosis on serial debridement with histologic evidence of invasive molds and/or fungal culture growth. Wounds with mold growth but lacking corresponding recurrent necrosis present a clinical dilemma of whether to initiate antifungal treatment. Our objective was to assess the clinical significance of fungal culture growth without recurrent wound necrosis. METHODS US military personnel wounded during combat in Afghanistan (June 2009 to August 2011) were assessed for growth of mold from wound cultures and/or histopathologic evidence of IFI. Identified patients were stratified based on clinical wound appearance (with/without recurrent necrosis), and the resultant groups were compared for injury characteristics, clinical management, and outcomes. RESULTS A total of 96 patients were identified: 77 with fungal elements on histopathology and/or fungal growth plus recurrent wound necrosis and 19 with fungal growth on culture but no wound necrosis after initial debridements. Injury patterns and severity were similar between the groups. Patients with recurrent necrosis had more frequent fevers and leukocytosis during the first 2 weeks after injury, and the majority received antifungal therapy compared with only three patients (16%) without recurrently necrotic wounds. Overall, patients without recurrent wound necrosis had significantly less operative procedures (p = 0.02), shorter stay in the intensive care unit (p < 0.01), and lower rates of high-level amputations (5% vs. 20%) and deaths (none vs. 8%) despite no or infrequent antifungal use. CONCLUSION The finding of molds on wound culture among patients with blast trauma in the absence of recurrently necrotic wounds on serial debridement does not require systemic antifungal chemotherapy. LEVEL OF EVIDENCE Therapeutic study, level IV. Prognosti/epidemiologic study, level III.

Brain hypoxia is exacerbated in hypobaria during aeromedical evacuation in swine with traumatic brain injury.

BACKGROUND There is inadequate information on the physiologic effects of aeromedical evacuation on wounded war fighters with traumatic brain injury (TBI). At altitudes of 8,000 ft, the inspired oxygen is lower than standard sea level values. In troops experiencing TBI, this reduced oxygen may worsen or cause secondary brain injury. We tested the hypothesis that the effects of prolonged aeromedical evacuation on critical neurophysiologic parameters (i.e., brain oxygenation [PbtO2]) of swine with a fluid percussion injury/TBI would be detrimental compared with ground (normobaric) transport. METHODS Yorkshire swine underwent fluid percussion injury/TBI with pretransport stabilization before being randomized to a 4-hour aeromedical transport at simulated flight altitude of 8,000 ft (HYPO, n = 8) or normobaric ground transport (NORMO, n = 8). Physiologic measurements (i.e., PbtO2, cerebral perfusion pressure, intracranial pressure, regional cerebral blood flow, mean arterial blood pressure, and oxygen transport variables) were analyzed. RESULTS Survival was equivalent between groups. Measurements were similar in both groups at all phases up to and including onset of flight. During the flight, PbtO2, cerebral perfusion pressure, and mean arterial blood pressure were significantly lower in the HYPO than in the NORMO group. At the end of flight, regional cerebral blood flow was lower in the HYPO than in the NORMO group. Other parameters such as intracranial pressure, cardiac output, and mean pulmonary artery pressure were not significantly different between the two groups. CONCLUSION A 4-hour aeromedical evacuation at a simulated flight altitude of 8,000 ft caused a notable reduction in neurophysiologic parameters compared with normobaric conditions in this TBI swine model. Results suggest that hypobaric conditions exacerbate cerebral hypoxia and may worsen TBI in casualties already in critical condition.

Treatment of Suspected Invasive Fungal Infection in War Wounds

Invasive fungal wound infections (IFIs) were an unexpected complication associated with blast-related wounds during Operation Enduring Freedom. Between 2010 and 2012, IFI incidence rates were as high as 10-12% for patients injured during Operation Enduring Freedom and admitted to the intensive care unit at the Landstuhl Regional Medical Center. Independent risk factors for the development of IFIs include dismounted blast injuries, above knee amputations and massive (>20 units) packed red blood cell transfusions within 24 hours after injury. The Joint Trauma System developed a Clinical Practice Guideline on IFI prevention, identification and management. Aggressive and frequent surgical debridement remains the primary therapy accompanied by topical antifungal therapy (e.g., Dakins solution). Empiric systemic antifungal therapy with both liposomal amphotericin B and an intravenous broad-spectrum triazole (e.g., voriconazole or posaconazole) should be administered when there is strong suspicion of IFI based on the occurrence of recurrent wound necrosis following serial surgical debridements, since many cases involve multiple fungal species. Other recommendations include: (1) early tissue sampling for wound histopathology and fungal cultures, (2) early consultation with infectious disease specialists, and (3) coordination with surgical pathology and clinical microbiology.