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Background: Severe trauma and hemorrhagic shock lead to persistent anemia. Although biologic gender is known to modulate inflammatory responses after critical illness, the impact of gender on anemia recovery after injury remains unknown. The aim of this study was to identify gender-specific differences in anemia recovery after critical illness. Materials and Methods: Male and proestrus female Sprague-Dawley rats (n = 8-9 per group) were subjected to lung contusion and hemorrhagic shock (LCHS) or LCHS with daily chronic stress (LCHS/CS) compared with naïve. Hematologic data, bone marrow progenitor growth, and bone marrow and liver gene transcription were analyzed on day seven. Significance was defined as p < 0.05. Results: Males lost substantial weight after LCHS and LCHS/CS compared with naïve males, while female LCHS rats did not compared with naive counterparts. Male LCHS rats had a drastic decrease in hemoglobin from naïve males. Male LCHS/CS rats had reduced colony-forming units-granulocyte, -erythrocyte, -monocyte, -megakaryocyte (CFU-GEMM) and burst-forming unit-erythroid (BFU-E) when compared with female counterparts. Naïve, LCHS, and LCHS/CS males had lower serum iron than their respective female counterparts. Liver transcription of BMP4 and BMP6 was elevated after LCHS and LCHS/CS in males compared with females. The LCHS/CS males had decreased expression of bone marrow pro-erythroid factors compared with LCHS/CS females. Conclusions: After trauma with or without chronic stress, male rats demonstrated increased weight loss, substantial decrease in hemoglobin level, dysregulated iron metabolism, substantial suppression of bone marrow erythroid progenitor growth, and no change in transcription of pro-erythroid factors. These findings confirm that gender is an important variable that impacts anemia recovery and bone marrow dysfunction after traumatic injury and shock in this rat model.

Background: Post-injury inflammation and its correlation with anemia recovery after severe trauma is poorly described. Severe injury induces a systemic inflammatory response associated with critical illness and organ dysfunction, including disordered hematopoiesis, and anemia. This study sought to characterize the resolution of post-injury inflammation and anemia to identify risk factors associated with persistence of anemia. Patients and Methods: This single-institution study prospectively enrolled 73 trauma patients with an injury severity score >15, hemorrhagic shock, and a lower extremity long bone orthopedic injury. Blood was obtained at enrollment and after 14 days, one, three, and six months. Analytes were compared using Mann-Whitney U tests with correction for multiple comparisons. Results: Median age was 45 years and Injury Severity Score (ISS) was 27, with anemia rates of 97% at two weeks, 80% at one month, 52% at three months, and 30% at six months. Post-injury elevations in erythropoietin, interleukin-6, and C-reactive protein resolved by one month, three months, and six months, respectively. Median granulocyte colony-stimulating factor (G-CSF) and tumor necrosis factor (TNF)-α concentrations remained elevated throughout the six-month follow-up period. Patients with persistent anemia had longer intensive care unit and hospital lengths of stay, more infectious complications, and received more packed red blood cell transfusions compared to those with early anemia recovery. Conclusions: Severe trauma is associated with a prolonged inflammatory response, which is associated with increased transfusion requirements, lengths of stay, and persistent anemia. Further analysis is needed to identify correlations between prolonged inflammation and clinical outcomes after discharge.

Background: Necrotizing soft tissue infections (NSTIs) require prompt surgical debridement and antimicrobial therapy. Indicated antimicrobial therapy involves broad-spectrum coverage against common pathogens and toxin inhibition. Linezolid provides both methicillin-resistant Staphylococcus aureus (MRSA) coverage and toxin inhibition, however, there is limited evidence evaluating its role in empiric treatment. The purpose of this study was to evaluate the impact of empiric linezolid use for NSTIs on the total duration of MRSA-active therapy. Patients and Methods: This retrospective, single-center study included adult surgical intensive care unit (ICU) patients treated with empiric vancomycin and clindamycin or linezolid along with gram-negative and anaerobe coverage for NSTIs. The primary end point of this study was the duration of MRSA-active therapy. Secondary end points included ICU and hospital length of stay (LOS; days), new-onset acute kidney injury (AKI), and Clostridioides difficile infection (CDI). Results: There were 21 patients in the vancomycin/clindamycin cohort and 28 patients in the linezolid cohort. The average duration of vancomycin was 3.9 days versus 2.9 days of linezolid (p = 0.04). The average hospital LOS for the vancomycin/clindamycin cohort was somewhat longer than the linezolid cohort, although the difference was not statistically significant (p = 0.07), and the incidence of new-onset AKI during hospitalization was higher in the vancomycin/clindamycin cohort (38.1% vs. 0%; p < 0.001). No differences were observed for ICU LOS or CDI. Conclusions: Empiric linezolid use for NSTI was associated with one less day of MRSA-active therapy and lower incidence of new-onset AKI during hospitalization. Linezolid was a safe and effective alternative to vancomycin/clindamycin for empiric treatment of NSTIs.

Background: To determine whether degree of anemia at sepsis onset is predictive of inflammatory cytokine trajectory, erythropoietin response, and recovery. Patients and Methods: Critically ill patients with sepsis were stratified into three groups based on initial hemoglobin (Hgb): Hgb <8 g/dL (severe); 8-10 g/dL (moderate); and >10 g/dL (mild). Granulocyte colony stimulating factor (G-CSF), interferon (IFN)-γ, tumor necrosis factor (TNF)-α, C-reactive protein (CRP), erythropoietin (EPO), and Zubrod scores were measured serially. Results: Thirty-four percent had severe anemia (Hgb, 7.2 ± 0.7g/dL), 35% had moderate anemia (Hgb, 9.1 ± 0.6g/dL), and 31% had mild anemia (Hgb, 11.3 ± 1.1g/dL). All groups experienced persistently high EPO levels without resolution of anemia. IFN-γ and CRP was persistently elevated in all groups. At three, six, and 12 months, the severe anemia group had higher Zubrod scores. Conclusions: Degree of anemia at sepsis onset was not associated with a difference in proinflammatory cytokine trajectory but was associated with a worse functional outcome. Despite initial elevated EPO levels, it did not correlate with resolution of anemia.

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 10 4 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., Competing Interests: Author Disclosure Statement The authors have nothing to disclose.

Background: Haemophilus species bacteria (HSB) are known pathogens responsible for early pneumonia in intubated trauma patients. The primary goal of this study was to examine the incidence and extent of hypoxemia in intubated trauma patients who develop early ventilator-associated pneumonia (VAP) secondary to HSB. On the basis of our clinical experiences, we hypothesized that patients with Haemophilus species bacteria pneumonia (HSBP) would have a high rate of hypoxemia but that the effect would be transient., Methods: Retrospective review of intubated trauma patients from an urban level I trauma center with HSBP diagnosed by deep tracheal aspirate or bronchoalveolar lavage from April 2007 to November 2012. Collected variables included day of HSBP diagnosis; PaO2 to FIO2 ratio (P:F) at HSBP diagnosis as well as HSBP day three and HSBP day seven; injury severity score (ISS) and its component parts; admission Glasgow Coma Scale (GCS) score; and mortality. Hypoxemia was defined as P:F <200. χ(2) Tests were utilized to assess factors that differed between hypoxemic and non-hypoxemic patients; data are presented as median (interquartile range, IQR)., Results: Sixty-nine patients were identified (80% male; age, 35 y [range, 24-49]; ISS 27 [9-59]). Diagnosis of HSBP occurred early (hospital day 4 [range, 3-5]). Forty-three percent of patients had acute respiratory distress syndrome (ARDS) on HSBP day 1; this decreased to 26% on day three and to 30% on day seven. Forty patients (77%) had a tracheostomy performed. Patients with hypoxemia were significantly less likely to have a severe head injury (GCS<9), p<0.05. Patients with hypoxemia had similar hospital length of stay and mortality to patients who did not develop hypoxemia., Conclusion: Haemophilus species bacteria pneumonia in trauma patients is associated with high rates of transient hypoxemia and a high tracheostomy rate, although subsequent outcomes are not affected. Patients with head injuries had a lower incidence of hypoxemia from pneumonia.

Background: Ventilator-associated pneumonia (VAP) is a well-known complication of mechanical ventilation in severely injured patients. A subset of patients with VAP develop an associated bacteremia (B-VAP), but the risk factors, microbiology, morbidity, and mortality in this group are not well described. The goal of this study was to examine the incidence, predictors, and outcome of B-VAP in adult trauma patients., Methods: We conducted a retrospective review of trauma patients who developed VAP or B-VAP from January 2007 to December 2009 at a single, university-affiliated medical center. Ventilator-associated pneumonia was defined as a clinician-documented instance of VAP together with confirmed positive respiratory cultures (bronchoalveolar lavage [BAL] fluid specimen with ≥10(4) colony forming units (CFU)/mL or tracheal aspirate with moderate-to-many organisms and polymorphonuclear neutrophils [PMN]). Bacteremia associated with VAP (B-VAP) was defined as the blood culture of an organism that matched the pulmonary pathogen in a case of VAP. We reviewed the demographic data, injury severity, transfusion data, and microbiology of patients who developed VAP and B-VAP. Outcome data included the number of days of care in the intensive care unit (ICU) and hospital length of stay, number of days of mechanical ventilation, and survival. A Student t-test, χ(2) test, or logistic regression was used as appropriate for data analysis., Results: During the 36-mo period of the study, 4,018 adult patients were admitted to the hospital. Ventilator-associated pneumonia was diagnosed in 206 (5%) of these patients, and 26 of these latter patients (13%) had an associated bacteremia. The mean time from admission to the development of VAP was 5 d (95% CI 4.6-5.8). Patients who had B-VAP received significantly more units of red blood cell concentrates (PRBC) than those who did not have B-VAP (23 units vs. 9 units of PRBC, respectively, p<0.05). Patients with B-VAP also had higher rates of simultaneous non-pulmonary infections than those with VAP alone (69% vs. 38%, respectively), a greater number of days of mechanical ventilator support (24 d vs. 14 d, respectively, p<0.05), a greater number of days in the ICU (26 d vs. 17 d, respectively, p<0.05), and a greater hospital length of stay (50 d vs. 30 d, respectively, p<0.05). Patients with B-VAP showed a trend toward lower survival than those without B-VAP, but B-VAP was not an independent predictor of mortality., Conclusions: Trauma patients with B-VAP have a similar mortality but greater morbidity than those with VAP alone. The number of PRBC received is the most significant risk factor for developing B-VAP. More than two-thirds of patients with B-VAP have contemporaneous extra-pulmonic infections. Trauma patients with B-VAP may benefit from increased surveillance for additional concomitant infections and from more aggressive empiric antimicrobial coverage.

Background: Prolonged courses of broad-spectrum antibiotics are often cited as standard care for the prevention of infectious complications in thoracolumbar or sacral (TLS) fractures following penetrating abdominal trauma. Perforation of a hollow viscus in addition to a TLS fracture is believed to be associated with a high incidence of spine infection. Because over use of antibiotics is associated with an increasing prevalence of multi-drug-resistant organisms, this study seeks to define the actual risk of infection of the spine and need for antibiotics in patients with TLS fractures and intraperitoneal injuries following penetrating trauma., Methods: A retrospective review of 67 patients with penetrating abdominal trauma and concomitant TLS fracture was performed. Demographics, level of TLS fracture, associated spinal cord injury (SCI), need for operative intervention, presence of concomitant hollow viscus injury, and type and duration of antibiotic coverage were collected. In addition, associated infectious complications were reviewed. Spine infections were defined as spinal or paraspinal abscess, osteomyelitis of the spine, or meningitis. Intraabdominal infections were defined with imaging studies or positive peritoneal cultures., Results: Sixty-seven patients (mean age of 27 ± 9 years) had an exploratory laparotomy and one or more TLS fractures. Four patients died within 24 h and were excluded from further study. Thirty-eight patients (60%) had one or more hollow viscus injuries, 13 (21%) had solid organ injuries alone and 12 (19%) had a non-therapeutic laparotomy. All patients received perioperative antibiotics; 92% received 48 h or less of antibiotic prophylaxis and 62% received only 24 h of antibiotics. In one patient with an isolated solid organ injury there was a spine infection (1%)., Conclusions: In this study, 92% of patients received antibiotics for 48 h or less with no increased incidence of spine infections. Bacterial colonization of the vertebrae was not higher in patients with penetrating gastrointestinal injury. There is insufficient evidence to support the use of prolonged antibiotic prophylaxis to prevent spine infection in patients with penetrating abdominal trauma and TLS fracture.

Background and Purpose: Ventilator-associated pneumonia (VAP) in the surgical intensive care unit (ICU) is associated with substantial morbidity and mortality. Affected patients are at higher risk for infection with multi-drug-resistant (MDR) pathogens, often necessitating therapeutic regimens of two parenteral antibiotics. Aerosolized antibiotics achieve high alveolar concentrations and have been reported anecdotally to have value in the treatment of VAP. This study examined the role of aerosolized aminoglycosides in the treatment of VAP in surgical ICU patients., Methods: We reviewed retrospectively the medical records of 22 patients who received aerosolized aminoglycosides in conjunction with parenteral antibiotics for VAP in the surgical ICU. Sixteen patients received inhaled tobramycin, and six received inhaled amikacin. Demographic information and data on the length of stay (LOS), mortality rate, days of antibiotic therapy, days of mechanical ventilation, and recurrence of VAP were collected. Results of bronchoscopic and sputum cultures were reviewed to identify bacterial pathogens and antimicrobial susceptibilities., Results: The average duration of mechanical ventilation was 31 +/- 12 days, the mean ICU LOS was 41 +/- 13 days, and the mean hospital LOS was 71 +/- 25 days. There were three deaths. The average duration of mechanical ventilation after initiation of aerosolized antibiotics was 4.3 days. Seven patients (40%) developed recurrent pneumonia with the same pathogen, but only one had a change in antibiotic susceptibility pattern. There were no renal or pulmonary complications of aminoglycoside treatment., Conclusions: Ventilator-associated pneumonia in critically ill patients is associated with substantial morbidity, longer ICU stays, and prolonged mechanical ventilation. Along with systemic therapy, aerosolized aminoglycosides are valuable adjuncts in select patients with minimal risk of antibiotic resistance.

Background: Severe trauma leads to hematopoietic failure and bone marrow (BM) dysfunction that manifests clinically as a persistent anemia and leukopenia. The impact of severe trauma and its associated hyperadrenergic state on erythropoiesis has not been described. The aim of this study was to demonstrate the effects of adrenergic agonists and antagonists on erythropoiesis, both in normal bone marrow mononuclear cells (BMNC) and stroma-depleted BM., Methods: Urine epinephrine (EPI) and norepinephrine (NE) excretion from severely injured patients was assessed via enzyme-linked immunoadsorbent assay (ELISA). Erythropoiesis was assessed by the growth of erythroid progenitors-erythroid burst forming units and colony forming units (BFU-E and CFU-E)-in normal human BM in the presence of adrenergic agonists and antagonists at varying concentrations. Parallel cultures, depleted of BM stroma by passage through nylon wool columns, were compared., Results: Urine NE excretion was elevated in all samples from days 1 to 10 following injury (average 139 +/- 59 mcg/day vs. control 35 +/- 9 mcg/day). In vitro doses of NE, EPI, and isoproterenol (ISO) exerted a stimulatory effect on BFU-E colony growth in BMNCs (expressed as percentage of control: 324 +/- 30, 272 +/- 16, 212 +/- 95, vs. 100%), but had no effect on stroma-depleted BM., Conclusions: There is a substantial and persistent hyperadrenergic state seen after severe injury that may last for up to a week. Adrenergic agonists have a clear stimulatory effect on the growth of primitive erythroid precursors in normal BM. The adrenergic stimulus appears to be mediated via BM stroma.