A multicenter, randomized clinical trial of IV iron supplementation for anemia of traumatic critical illness*.

OBJECTIVE: To evaluate the efficacy of IV iron supplementation of anemic, critically ill trauma patients. DESIGN: Multicenter, randomized, single-blind, placebo-controlled trial. SETTING: Four trauma ICUs. PATIENTS: Anemic (hemoglobin < 12 g/dL) trauma patients enrolled within 72 hours of ICU admission and with an expected ICU length of stay of more than or equal to 5 days. INTERVENTIONS: Randomization to iron sucrose 100 mg IV or placebo thrice weekly for up to 2 weeks. MEASUREMENTS AND MAIN RESULTS: A total of 150 patients were enrolled. Baseline iron markers were consistent with functional iron deficiency: 134 patients (89.3%) were hypoferremic, 51 (34.0%) were hyperferritinemic, and 64 (42.7%) demonstrated iron-deficient erythropoiesis as evidenced by an elevated erythrocyte zinc protoporphyrin concentration. The median baseline transferrin saturation was 8% (range, 2-58%). In the subgroup of patients who received all six doses of study drug (n = 57), the serum ferritin concentration increased significantly for the iron as compared with placebo group on both day 7 (808.0 ng/mL vs 457.0 ng/mL, respectively, p < 0.01) and day 14 (1,046.0 ng/mL vs 551.5 ng/mL, respectively, p < 0.01). There was no significant difference between groups in transferrin saturation, erythrocyte zinc protoporphyrin concentration, hemoglobin concentration, or packed RBC transfusion requirement. There was no significant difference between groups in the risk of infection, length of stay, or mortality. CONCLUSIONS: Iron supplementation increased the serum ferritin concentration significantly, but it had no discernible effect on transferrin saturation, iron-deficient erythropoiesis, hemoglobin concentration, or packed RBC transfusion requirement. Based on these data, routine IV iron supplementation of anemic, critically ill trauma patients cannot be recommended (NCT 01180894).

Review article: drug-induced liver injury in the context of nonalcoholic fatty liver disease - a physiopathological and clinical integrated view.

BACKGROUND: Nonalcoholic fatty disease (NAFLD) is the most common liver disease, since it is strongly associated with obesity and metabolic syndrome pandemics. NAFLD may affect drug disposal and has common pathophysiological mechanisms with drug-induced liver injury (DILI); this may predispose to hepatoxicity induced by certain drugs that share these pathophysiological mechanisms. In addition, drugs may trigger fatty liver and inflammation per se by mimicking NAFLD pathophysiological mechanisms. AIMS: To provide a comprehensive update on (a) potential mechanisms whereby certain drugs can be more hepatotoxic in NAFLD patients, (b) the steatogenic effects of drugs, and (c) the mechanism involved in drug-induced steatohepatitis (DISH). METHODS: A language- and date-unrestricted Medline literature search was conducted to identify pertinent basic and clinical studies on the topic. RESULTS: Drugs can induce macrovesicular steatosis by mimicking NAFLD pathogenic factors, including insulin resistance and imbalance between fat gain and loss. Other forms of hepatic fat accumulation exist, such as microvesicular steatosis and phospholipidosis, and are mostly associated with acute mitochondrial dysfunction and defective lipophagy, respectively. Drug-induced mitochondrial dysfunction is also commonly involved in DISH. Patients with pre-existing NAFLD may be at higher risk of DILI induced by certain drugs, and polypharmacy in obese individuals to treat their comorbidities may be a contributing factor. CONCLUSIONS: The relationship between DILI and NAFLD may be reciprocal: drugs can cause NAFLD by acting as steatogenic factors, and pre-existing NAFLD could be a predisposing condition for certain drugs to cause DILI. Polypharmacy associated with obesity might potentiate the association between this condition and DILI.

RibScore: A novel radiographic score based on fracture pattern that predicts pneumonia, respiratory failure, and tracheostomy.

BACKGROUND: There is currently no scoring system for rib fractures that relates detailed anatomic variables to patient outcomes. Our objective was to develop and validate a radiographic rib fracture scoring system based on computed tomographic chest findings. METHODS: We reviewed our trauma registry from September 2012 to April 2014 for all blunt trauma patients with one or more rib fractures visualized on chest computed tomography. We identified the following six candidate radiographic variables and tested their individual associations with pneumonia, respiratory failure, and tracheostomy: (1) six or more rib fractures, (2) bilateral fractures, (3) flail chest, (4) three or more severely (bicortical) displaced fractures, (5) first rib fracture, and (6) at least one fracture in all three anatomic areas (anterior, lateral, and posterior). We developed the "RibScore" by assigning 1 point for each variable, which was validated among the sample using univariate analyses, test performance characteristics, and the receiver operating characteristic area under the curve c statistic. RESULTS: A total of 385 patients with one or more rib fractures were identified; 274 (71.2%) were males, median age was 48 years, and median Injury Severity Score (ISS) was 17. Of these patients, 156 had six or more rib fractures, 120 had bilateral fractures, 46 had flail chest, 32 had three or more severely displaced fractures, 91 had a first rib fracture, and 58 had fractures in all three anatomic areas. Each RibScore component variable was associated with the three pulmonary outcomes by univariate analysis (p < 0.05). The median RibScore was 1 (range, 0-6). The distribution of the RibScore was as follows: score of 0, 41.9%); score of 1, 23.9%; score of 2, 15.4%; score of 3, 9.9%; score of 4, 7.6%; and score of five, 1.3%. RibScore was linearly associated with pneumonia (p < 0.01), acute respiratory failure (p < 0.01), and tracheostomy (p < 0.01). The receiver operating characteristic areas under the curve for the outcomes were 0.71, 0.71, and 0.75, respectively. CONCLUSION: The RibScore predicts adverse pulmonary outcomes and represents a standardized assessment of fracture severity that may be used for communication and prognostication of the severely injured trauma patient. LEVEL OF EVIDENCE: Prognostic study, level III.

A prospective, controlled clinical evaluation of surgical stabilization of severe rib fractures.

BACKGROUND: Previous studies of surgical stabilization of rib fractures (SSRF) have been limited by small sample sizes, retrospective methodology, and inclusion of only patients with flail chest. We performed a prospective, controlled evaluation of SSRF as compared with optimal medical management for severe rib fracture patterns among critically ill trauma patients. We hypothesized that SSRF improves acute outcomes. METHODS: We conducted a 2-year clinical evaluation of patients with any of the following rib fracture patterns: flail chest, three or more fractures with bicortical displacement, 30% or greater hemithorax volume loss, and either severe pain or respiratory failure despite optimal medical management. In the year 2013, all patients were managed nonoperatively. In the year 2014, all patients were managed operatively. Outcomes included respiratory failure, tracheostomy, pneumonia, ventilator days, tracheostomy, length of stay, daily maximum incentive spirometer volume, narcotic requirements, and mortality. Univariate and multivariable analyses were performed. RESULTS: Seventy patients were included, 35 in each group. For the operative group, time from injury to surgery was 2.4 day, operative time was 1.5 hours, and the ratio of ribs fixed to ribs fractured was 0.6. The operative group had a significantly higher RibScore (4 vs. 3, respectively, p < 0.01) and a significantly lower incidence of intracranial hemorrhage (5.7% vs. 28.6%, respectively, p = 0.01). After controlling for these differences, the operative group had a significantly lower likelihood of both respiratory failure (odds ratio, 0.24; 95% confidence interval, 0.06-0.93; p = 0.03) and tracheostomy (odds ratio, 0.18; 95% confidence interval, 0.04-0.78; p = 0.03). Duration of ventilation was significantly lower in the operative group (p < 0.01). The median daily spirometry value was 250 mL higher in the operative group (p = 0.04). Narcotic requirements were comparable between groups. There were no mortalities. CONCLUSION: In this evaluation, SSRF as compared with the best medical management improved acute outcomes among a group of critically ill trauma patients with a variety of severe fracture patterns. LEVEL OF EVIDENCE: Therapeutic study, level II.

Screening for Ventilator-Associated Pneumonia in the Surgical Intensive Care Unit: A Single-Institution Analysis of 1,013 Lower Respiratory Tract Cultures.

BACKGROUND: Refinement of criteria for both screening and initiation of empiric therapy in ventilator-associated pneumonia (VAP) will minimize antibiotic overuse. We hypothesized that variables within the commonly used Clinical Pulmonary Infection Score (CPIS) have unfavorable test performance characteristics. METHODS: Consecutive bronchoalveolar lavage (BAL) cultures obtained from surgical intensive care unit patients were abstracted (2009-2012). Ventilator-associated pneumonia was defined as ≥10(5) cfu/mL. The CPIS both without (CPISclinical) and with (CPISclinical+GS) the result of gram stain (GS) was calculated. Test performance characteristics for the sample, as well as several subgroups, were compared. RESULTS: One thousand thirteen lower respiratory tract cultures from 492 patients were analyzed; 438 (43.2%) of cultures were classified as VAP, and 310 of 492 patients (62.4%) had ≥1 episode of VAP. Both CPISclinical and CPISclinical+GS had poor discrimination for VAP (Receiver-operating characteristic area under the curve=0.55 and 0.66, respectively). Sensitivity of CPISclinical using a threshold of >6 was 21%; the lowest threshold for CPISclinical for which the sensitivity was at least 85% was 3. The highest sensitivity among the individual CPIS components was new CXR infiltrate (91.1%). Among the subset of cultures sent during the early VAP window (days intubated 2-5), organisms on GS had a sensitivity of 93.3%. The CPISclinical, CPISclinical+GS, organisms, and neutrophils on GS parameters all became less accurate in both the late VAP window and when screening for recurrent VAP. Every case of VAP had at least one of the following: 1) fever; 2) new CXR infiltrate, or 3) organisms on GS. CONCLUSION: In this series of BALs, traditional screening tools for VAP missed the majority of microbiological confirmed cases. Screening based on either new CXR infiltrate or fever yielded an acceptably high sensitivity. The only scenario identified in which empiric antibiotics could be withheld safely was the absence of organisms on GS in the early VAP window.