Raminder Nirula

The effects of leukoreduced blood transfusion on infection risk following injury: a randomized controlled trial.

ABSTRACT Allogeneic blood transfusions in surgical patients have been associated with an increased risk of infectious complications and organ dysfunction. Residual leukocytes contaminating units of packed red blood cells have been incriminated through the induction of anergy and/or a potentiated inflammatory response, leading to the possibility that leukoreduced red blood cell transfusion might mitigate these effects. We set out to evaluate the effect of leukoreduced red cell transfusion on the risk of infections complications in patients requiring transfusion following injury. We conducted a single-center, double-blinded randomized controlled trial of leukoreduced versus standard, nonleukoreduced red blood cell transfusions in injured patients receiving transfusion within 24 hrs of injury. The primary endpoint was infectious complications within 28 days of randomization. Secondary end points were multiple organ failure, length of stay, febrile episodes, and mortality. Two hundred sixty eight subjects were eligible for analysis. Rates of infectious complications were similar in subjects receiving leukoreduced transfusions (30%) or standard transfusions (36%) ([RR], 0.84 [0.55-1.3]) and there was no statistically significant effect of leukoreduced blood transfusion on mortality [RR, 1.20 (0.74-1.9)], febrile episodes [RR, 1.01 (0.89-1.2)], or organ dysfunction scores (5.9 vs. 6.6; P = 0.29). Thus, pre-storage leukoreduction of allogeneic red blood cells had a small, but non-significant effect on the rate of infectious complication in this high-risk population requiring transfusion. There was no effect on the rates of febrile episodes, mortality, length of stay, or severity of organ dysfunction.

Propofol is associated with favorable outcomes compared with benzodiazepines in ventilated intensive care unit patients.

RATIONALE Mechanically ventilated intensive care unit (ICU) patients are frequently managed using a continuous-infusion sedative. Although recent guidelines suggest avoiding benzodiazepines for sedation, this class of drugs is still widely used. There are limited data comparing sedative agents in terms of clinical outcomes in an ICU setting. OBJECTIVES Comparison of propofol to midazolam and lorazepam in adult ICU patients. METHODS Data were obtained from a multicenter ICU database (2003-2009). Patient selection criteria included age greater than or equal to 18 years, single ICU admission with single ventilation event (>48 h), and treatment with continuously infused sedation (propofol, midazolam, or lorazepam). Propensity score analysis (1:1) was used and mortality measured. Cumulative incidence and competing risk methodology were used to examine time to ICU discharge and ventilator removal. MEASUREMENTS AND MAIN RESULTS There were 2,250 propofol-midazolam and 1,054 propofol-lorazepam matched patients. Hospital mortality was statistically lower in propofol-treated patients as compared with midazolam- or lorazepam-treated patients (risk ratio, 0.76; 95% confidence interval [CI], 0.69-0.82 and risk ratio, 0.78; 95% CI, 0.68-0.89, respectively). Competing risk analysis for 28-day ICU time period showed that propofol-treated patients had a statistically higher probability for ICU discharge (78.9% vs. 69.5%; 79.2% vs. 71.9%; P < 0.001) and earlier removal from the ventilator (84.4% vs. 75.1%; 84.3% vs. 78.8%; P < 0.001) when compared with midazolam- and lorazepam-treated patients, respectively. CONCLUSIONS In this large, propensity-matched ICU population, patients treated with propofol had a reduced risk of mortality and had both an increased likelihood of earlier ICU discharge and earlier discontinuation of mechanical ventilation.

Safety and Efficacy of Erythropoietin in Traumatic Brain Injury Patients: A Pilot Randomized Trial

Background. Erythropoietin (EPO) is a neuroprotective agent utilized in stroke patients. This pilot study represents the first randomized trial of EPO in traumatic brain injury (TBI) patients. Methods. Adult, blunt trauma patients with evidence of TBI were randomized to EPO or placebo within 6 hours of injury. Baseline and daily serum S-100B and Neuron Specific Enolase (NSE) levels were measured. Results. TBI was worse in the EPO (n = 11) group compared to placebo patients (n = 5). The use of EPO did not impact NSE (P = .89) or S100 B (P = .53) levels compared to placebo. Conclusions. At the dose used, EPO did not reduce neuronal cell death compared to placebo; however, TBI severity was worse in the EPO group while levels of NSE and S100-B were similar to the less injured placebo group making it difficult to rule out a treatment effect. A larger, balanced study is necessary to confirm a potential treatment effect.

Suboptimal compliance with evidence-based guidelines in patients with traumatic brain injuries: Clinical article

OBJECT Evidence-based management (EBM) guidelines for severe traumatic brain injuries (TBIs) were promulgated decades ago. However, the extent of their adoption into bedside clinical practices is not known. The purpose of this study was to measure compliance with EBM guidelines for management of severe TBI and its impact on patient outcome. METHODS This was a retrospective study of blunt TBI (11 Level I trauma centers, study period 2008-2009, n = 2056 patients). Inclusion criteria were an admission Glasgow Coma Scale score ≤ 8 and a CT scan showing TBI, excluding patients with nonsurvivable injuries-that is, head Abbreviated Injury Scale score of 6. The authors measured compliance with 6 nonoperative EBM processes (endotracheal intubation, resuscitation, correction of coagulopathy, intracranial pressure monitoring, maintaining cerebral perfusion pressure ≥ 50 cm H2O, and discharge to rehabilitation). Compliance rates were calculated for each center using multivariate regression to adjust for patient demographics, physiology, injury severity, and TBI severity. RESULTS The overall compliance rate was 73%, and there was wide variation among centers. Only 3 centers achieved a compliance rate exceeding 80%. Risk-adjusted compliance was worse than average at 2 centers, better than average at 1, and the remainder were average. Multivariate analysis showed that increased adoption of EBM was associated with a reduced mortality rate (OR 0.88; 95% CI 0.81-0.96, p < 0.005). CONCLUSIONS Despite widespread dissemination of EBM guidelines, patients with severe TBI continue to receive inconsistent care. Barriers to adoption of EBM need to be identified and mitigated to improve patient outcomes.

Delay to Therapeutic Interventional Radiology Postinjury: Time Is of the Essence

OBJECTIVE Hemorrhage remains a leading cause of early death in injured patients, and definitive control of bleeding remains a fundamental principle of trauma management. Therapeutic interventional radiology (IR) procedures have increasingly become essential in the acute management of traumatic injury. The importance of time to control of hemorrhage for therapeutic IR procedures has not been adequately characterized. METHODS A retrospective analysis was performed by using data derived from the National Trauma Data Bank, version 7.1. Inclusion criteria included the following: adult, hypotensive patients, scene admission, patients who underwent early therapeutic IR vascular occlusive procedures within in 3 hours of admission at a level I or II designated trauma center (n = 1,748). Exclusion criteria included intracranial or venous occlusion procedures, patients who underwent any abdominal, thoracic, vascular, or intracranial operative procedures throughout their entire hospital stay. Logistic regression analysis was used to analyze the independent mortality risk associated with DELAY to IR procedures after controlling for important confounders. RESULTS The majority of patients who died did so within the first 48 hours from injury (80%). Regression analysis revealed that DELAY to IR was independently associated with more than a twofold higher risk of mortality (odds ratio 2.7, 95% confidence interval 1.6-4.9, p < 0.001). For every hour delay, the risk of mortality increased by 47%. These findings were independent of injury mechanism and most pertinent to level I trauma centers. CONCLUSION In hemodynamically unstable trauma patients undergoing therapeutic catheter-based IR procedures, delay to IR was independently associated with more than a twofold higher risk of mortality. These results suggest that therapeutic IR procedures should be performed as expeditiously as possible and held to the same dogma as applied to definitive operative control of hemorrhage.

Laparoscopic versus open repair of perforated gastroduodenal ulcer: a National Surgical Quality Improvement Program analysis

BACKGROUND Surgical repair of perforated gastroduodenal ulcers remains a common indication for emergent surgery. The aim of this study was to test the hypothesis that the laparoscopic approach (LA) would be associated with reduced length of stay compared to the open approach. METHODS Patients with acute, perforated gastroduodenal ulcer were identified in the National Surgical Quality Improvement Program database, of whom 50 had the LA. One-to-one case/control matching on the basis of age, American Society of Anesthesiologists class, gender, and cardiac disease was evaluated for outcome analysis. RESULTS After matching, the 2 groups had similar characteristics. The rates of wound complications, organ space infections, prolonged ventilation, postoperative sepsis, return to the operating room, and mortality tended to be lower for the LA, although not significantly. Length of hospital stay was, however, significantly shorter for the LA by an average of 5.4 days. CONCLUSIONS The LA appears to be safe in mild to moderately ill patients with perforated peptic ulcer disease and is associated with reduced use of hospital resources.

Multicenter validation of American Association for the Surgery of Trauma grading system for acute colonic diverticulitis and its use for emergency general surgery quality improvement program

BACKGROUND The American Association for the Surgery of Trauma (AAST) has developed a new grading system for uniform description of anatomic severity of emergency general surgery (EGS) diseases, ranging from Grade I (mild) to Grade V (severe). The purpose of this study was to determine the relationship of AAST grades for acute colonic diverticulitis with patient outcomes. A secondary purpose was to propose an EGS quality improvement program using risk-adjusted center outcomes, similar to National Surgical Quality Improvement Program and Trauma Quality Improvement Program methodologies. METHODS This was a retrospective study of 1,105 patients (one death) from 13 centers. At each center, two reviewers (blinded to each others assignments) assigned AAST grades. Interrater reliability was measured using &kgr; coefficient. Relationship between AAST grade and clinical events (complications, intensive care unit use, surgical intervention, and 30-day readmission) as well as length of stay was measured using regression analyses to control for age, comorbidities, and physiologic status at the time of admission. Final model was also used to calculate observed-to-expected (O-E) ratios for adverse outcomes (death, complications, readmissions) for each center. RESULTS Median age was 54 years, 52% were males, 43% were minorities, and 22% required a surgical intervention. Almost two thirds had Grade I or II disease. There was a high level of agreement for grades between reviewers (&kgr; = 0.81). Adverse events increased from 13% for Grade I, to 18% for Grade II, 28% for Grade III, 44% for Grade IV, and 50% for Grade V. Regression analysis showed that higher disease grades were independently associated with all clinical events and length of stay, after adjusting for age, comorbidities, and physiology. O-E ratios showed statistically insignificant variations in risk of death, complications, or readmissions. CONCLUSION AAST grades for acute colonic diverticulitis are independently associated with clinical outcomes and resource use. EGS quality improvement program methodology that incorporates AAST grade, age, comorbidities, and physiologic status may be used for measuring quality of EGS care. High-quality EGS registries are essential for developing meaningful quality metrics. LEVEL OF EVIDENCE Prognostic study, level V.

American College of Surgeons Guidelines Program: a process for using existing guidelines to generate best practice recommendations for central venous access.

BACKGROUND Many professional organizations help their members identify and use quality guidelines. Some of these efforts involve developing new guidelines, and others assess existing guidelines for their clinical usefulness. The American College of Surgeons Guidelines Program attempts to recognize useful surgical guidelines and develop research questions to help clarify existing clinical guidelines. We used existing guidelines about central venous access to develop a set of summary recommendations that could be used by practitioners to establish local best practices. STUDY DESIGN A comprehensive literature search identified existing clinical guidelines for short-term central venous access. Two reviewers independently rated the guidelines using the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument. Highly scored guidelines were analyzed for content, and their recommendations were compiled into a summary table. The summary table was reviewed by an independent panel of experts for clinical utility. RESULTS Thirty-two guidelines were identified, and 23 met inclusion criteria. The AGREE rating resulted in four guidelines that were strongly recommended and five that were recommended with alterations. Three comprehensive tables of recommendations were produced: procedural, maintenance, and infectious assessment. A panel of experts came to consensus agreement on the final format of the best practice recommendations, which included 30 summary recommendations. CONCLUSIONS Our process combined assessing existing guidelines methodology with expert opinion to produce a best practice list of guidelines that could be fashioned into local care routines by practicing physicians. The American College of Surgeons guidelines program believes this process will help validate the clinical utility of existing guidelines and identify areas needing further investigation to determine practical validity.

Tailoring the operative approach for appendicitis to the patient: a prediction model from national surgical quality improvement program data.

BACKGROUND Laparoscopic appendectomy (LA) is increasingly being performed in the United States, despite controversy about differences in infectious complication rates compared with open appendectomy (OA). Subpopulations exist in which infectious complication rates, both surgical site and organ space, differ with respect to LA compared with OA. STUDY DESIGN All appendectomies in the National Surgical Quality Improvement Program database were analyzed with respect to surgical site infection (SSI) and organ space infection (OSI). Multivariate logistic regression analysis identified independent predictors of SSI or OSI. Probabilities of SSI or OSI were determined for subpopulations to identify when LA was superior to OA. RESULTS From 2005 to 2009, there were 61,830 appendectomies performed (77.5% LA), of which 9,998 (16.2%) were complicated (58.7% LA). The risk of SSI was considerably lower for LA in both noncomplicated and complicated appendicitis. Across all ages, body mass index, renal function, and WBCs, LA was associated with a lower probability of SSI. The risk of OSI was considerably greater for LA in both noncomplicated and complicated appendicitis. In complicated appendicitis, OA was associated with a lower probability of OSI in patients with WBC >12 cells × 10(3)/μL. In noncomplicated appendicitis, OA was associated with a lower probability of OSI in patients with a body mass index <37.5 when compared with LA. CONCLUSIONS Subpopulations exist in which OA is superior to LA in terms of OSI, however, SSI is consistently lower in LA patients.

Novel oral anticoagulants and trauma: The results of a prospective American Association for the Surgery of Trauma Multi-Institutional Trial.

BACKGROUND The number of anticoagulated trauma patients is increasing. Trauma patients on warfarin have been found to have poor outcomes, particularly after intracranial hemorrhage (ICH). However, the effect of novel oral anticoagulants (NOAs) on trauma outcomes is unknown. We hypothesized that patients on NOAs would have higher rates of ICH, ICH progression, and death compared with patients on traditional anticoagulant and antiplatelet agents. METHODS This was a prospective observational trial across 16 trauma centers. Inclusion criteria was any trauma patient admitted on aspirin, clopidogrel, warfarin, dabigatran, rivaroxaban, or apixaban. Demographic data, admission vital signs, mechanism of injury, injury severity scores, laboratory values, and interventions were collected. Outcomes included ICH, progression of ICH, and death. RESULTS A total of 1,847 patients were enrolled between July 2013 and June 2015. Mean age was 74.9 years (SD ± 13.8), 46% were female, 77% were non-Hispanic white. At least one comorbidity was reported in 94% of patients. Blunt trauma accounted for 99% of patients, and the median Injury Severity Score was 9 (interquartile range, 4–14). 50% of patients were on antiplatelet agents, 33% on warfarin, 10% on NOAs, and 7% on combination therapy or subcutaneous agents. Patients taking NOAs were not at higher risk for ICH on univariate (24% vs. 31%) or multivariate analysis (incidence rate ratio, 0.78; confidence interval 0.61–1.01, p = 0.05). Compared with all other agents, patients on aspirin (90%, 81 mg; 10%, 325 mg) had the highest rate (35%) and risk (incidence rate ratio, 1.27; confidence interval, 1.13–1.43; p < 0.001) of ICH. Progression of ICH occurred in 17% of patients and was not different between medication groups. Study mortality was 7% and was not significantly different between groups on univariate or multivariate analysis. CONCLUSION Patients on NOAs were not at higher risk for ICH, ICH progression, or death. LEVEL OF EVIDENCE Prognostic/epidemiologic study, level III.