Anemia and blood transfusion in elderly trauma patients.

BACKGROUND: The natural history of postinjury among elderly trauma patients has not been well described. We hypothesized that elderly trauma patients would have lower admission hemoglobin (Hb) levels, higher transfusion rates, and worse outcomes than young trauma patients. METHODS: We performed a propensity-matched retrospective cohort analysis comparing elderly (age ≥65 y) to young (age 18-64) trauma patients matched by sex, mechanism of injury, Injury Severity Score, base deficit, comorbidities, operative blood loss, and phlebotomy blood loss (n = 41/group). Outcomes included Hb trends, packed red blood cell (PRBC) transfusion, length of stay, and mortality. RESULTS: Elderly patients had lower admission Hb (11.3 versus 10.2 g/dL, P = 0.012), received more PRBC transfusions within 24 h (3.6 versus 1.8 units, P = 0.046), and during admission (6.9 versus 4.3 units, P = 0.008). Despite receiving more PRBC transfusions and having similar operative and phlebotomy blood loss, elderly subjects had lower discharge Hb (9.0 versus 9.7 g/dL, P = 0.013). Elderly subjects had fewer ICU-free days (2.0 versus 6.0 d, P < 0.001) and higher in-hospital mortality (15% versus 0%, P = 0.026). CONCLUSIONS: Elderly trauma patients had lower admission Hb, received more transfusions, and had persistently lower Hb on discharge when controlling for injury severity, comorbid conditions, and blood loss. Aging may have a negative impact on postinjury anemia.

Dr. Jekyll and Mr. Hyde: Oxidizable phenol-generated reactive oxygen species enhance sulforaphane's antioxidant response element activation, even as they suppress Nrf2 protein accumulation.

The transcription factor Nrf2 is a master regulator of antioxidant and cytoprotective genes, binding to antioxidant response elements (AREs) in their promoter regions. Due to the therapeutic role of the Nrf2/ARE system in oxidative homeostasis, its activation has been investigated in many pre-clinical and clinical trials for common chronic diseases. One of the most promising Nrf2 activators is sulforaphane, the subject of over 50 clinical trials. In this work, we examine the effect of reactive oxygen species (ROS) on sulforaphane's Nrf2/ARE activation in the non-tumorigenic keratinocyte cell line HaCaT, with the non-arylating oxidizable phenol, 2,5-di-tert-butylhydroquinone (dtBHQ), as the source of ROS. We find that, in combination with 2.5 µM sulforaphane, dtBHQ markedly enhances ARE-regulated gene expression, including expression of the cytoprotective proteins aldo-keto reductase family 1 member C1 (AKR1C1) and heme oxygenase-1 (HO-1). Additionally, sulforaphane's therapeutic window is widened by 12.5 µM dtBHQ. Our data suggest that H2O2 generated by dtBHQ oxidation is responsible for these effects, as shown by inclusion of catalase and by co-treatment with sulforaphane and H2O2. While sulforaphane treatment causes Nrf2 protein to accumulate as expected, interestingly, dtBHQ and H2O2 appear to act on targets downstream of Nrf2 protein accumulation to enhance sulforaphane's ARE-regulated gene expression. Inclusion of dtBHQ or H2O2 with sulforaphane does not increase Nrf2 protein levels, and catalase has little effect on Nrf2 protein levels in the presence of sulforaphane and dtBHQ. Surprisingly, dtBHQ suppresses Nrf2 protein synthesis. Inclusion of a superoxide dismutase mimetic with sulforaphane and dtBHQ partly rescues Nrf2 suppression and significantly further increases sulforaphane's efficacy for ARE-reporter expression. Thus, there is a "Dr. Jekyll and Mr. Hyde" effect of ROS: ROS enhance sulforaphane's ARE-regulated gene expression even as they also inhibit Nrf2 protein synthesis. This unexpected finding reveals the degree to which targets in the ARE pathway downstream of Nrf2 protein accumulation contribute to gene expression. The results presented here provide a model system for significant enhancement of sulforaphane's potency with small molecule co-treatment.

The effects of red cell transfusion donor age on nosocomial infection among trauma patients.

BACKGROUND: We hypothesized that packed red blood cell (PRBC) transfusions from older donors would be associated with fewer nosocomial infections among trauma patients. METHODS: We performed a four-year retrospective analysis of 264 consecutive adult trauma patients who received ≥1 PRBC transfusion during admission. The capacity of donor age to predict nosocomial infection was assessed by logistic regression. RESULTS: Thirty-three percent of all patients developed a nosocomial infection. Donor age was significantly higher among patients with nosocomial infection (40.3 vs. 37.6 years, p = 0.035), and the incidence of infection was directly proportional to donor age. The association between donor age and infection was strongest among recipients age ≥60 years, and was significant on multivariate regression for this cohort (OR 1.07 (95% CI 1.01-1.13), p = 0.024). CONCLUSIONS: Among trauma patients receiving PRBC transfusions, blood from older donors may be associated with increased risk for nosocomial infection.

Early bronchoalveolar lavage for intubated trauma patients with TBI or chest trauma.

PURPOSE: To evaluate the efficacy of an early bronchoalveolar lavage (E-BAL) protocol. BAL was performed within 48 h for intubated patients with traumatic brain injury or chest trauma. We hypothesized that E-BAL would decrease antibiotic use and improve outcomes compared to late BAL (L-BAL) triggered by clinical signs of pneumonia. METHODS: Retrospective cohort analysis of 132 patients with quantitative BAL and ≥1 risk factor: head Abbreviated Injury Score ≥2, ≥3 rib fractures, or radiographic signs of aspiration or pulmonary contusion. E-BAL (n=71) was compared to L-BAL (n=61). Pneumonia was defined as ≥104 organisms on BAL or Clinical Pulmonary Infection Score >6. RESULTS: There were no significant differences in age, injury severity, initial Pao2:Fio2, or smoking status between E-BAL and L-BAL groups. 52% and 61% of the E-BAL and L-BAL cultures were positive, respectively. E-BAL patients had fewer antibiotic days (7.3 vs 9.2, P=.034), ventilator days (11 vs 15, P=.002), tracheostomies (49% vs 75%, P=.002), and shorter intensive care unit and hospital length of stay (13 vs 17 days (P=.007), 18 vs 22 days (P=.041)). CONCLUSIONS: More than half of all E-BAL patients had pneumonia present early after admission. E-BAL was associated with fewer days on antibiotics and better outcomes than L-BAL.

Intubated Trauma Patients Receiving Prolonged Antibiotics for Pneumonia despite Negative Cultures: Predictors and Outcomes.

BACKGROUND: Despite the excellent negative predictive value of sterile respiratory cultures, antibiotics often are continued after negative endotracheal aspirate (ETA) or bronchoalveolar lavage (BAL) for critically ill trauma patients. We hypothesized that persistent elevation of the Clinical Pulmonary Infection Score (CPIS) would predict continued antibiotic therapy after a negative respiratory culture for intubated trauma patients, and that prolonged antibiotics would provide no benefit. METHODS: We performed a four-year retrospective cohort analysis (May 1, 2011-September 30, 2015), including patients from our trauma database with ETA or BAL, excluding patients with any infection other than pneumonia or bacteremia. Cultures with <2+ organisms on gram stain and <2+ or 104 organisms on culture were considered negative. The CPIS was assessed at the time of culture and five days later, when all cultures were final. Multiple logistic regression was used to identify predictors of long-term antibiotic therapy. RESULTS: A series of 106 patients with negative cultures were included, of whom 61 had ≤5 d of antibiotics and 45 had >5 d of antibiotics. There were no differences in injury severity, head or chest trauma, initial CPIS, or subsequent culture results between the groups. Long-term antibiotic therapy did not affect intensive care unit (ICU) length of stay (LOS), ventilator days, hospital LOS, or death. Factors predicting long-term antibiotic therapy included development of a localized chest radiograph infiltrate (odds ratio [OR] 6.8; 95% confidence interval [CI] 1.7-28), CPIS >5 five days after culture (OR 6.1; 95% CI 1.2-32), and a colonized culture (OR 3.3; 95% CI 1.3-8.3). CONCLUSIONS: Long-term antibiotic therapy for intubated trauma patients with negative respiratory cultures provided no benefit and was predicted by development of a localized chest radiograph infiltrate, persistently elevated CPIS, and a contaminated/colonized culture. Although long-term antibiotic use did not worsen outcomes, better strategies are needed to diagnose pneumonia accurately and ensure timely discontinuation of antibiotics when appropriate.