Factors Associated With Prolonged Antibiotic Use in the Setting of Suspected Pneumonia and Negative Bronchoalveolar Lavage Cultures.

Background: Diagnostic criterion for pneumonia includes clinical data and bronchoalveolar lavage cultures (BALCx) to identify pathogens. Although ~60% of BALCx are negative, there may be reluctance to discontinue antibiotics, leading to prolonged antibiotic use (PAU). Objective: The purpose of this study is to compare outcomes of subjects with negative BALCx with PAU versus without prolonged antibiotic use (nPAU). Methods: A retrospective cohort study was conducted including subjects admitted to the intensive care unit (ICU), with suspected pneumonia, and negative BALCx. Data were compared based on length of exposure to antibiotics, PAU (antibiotics >4 days) versus nPAU (antibiotics <4 days). Results: A total of 128 subjects were included, 57 in the PAU group and 71 in the nPAU group. Baseline demographics were similar between groups. Severity of illness measured by multiple organ dysfunction scores at time of bronchoalveolar lavage (BAL) collection to final result showed a statistically significant decrease in the PAU group but not in the nPAU group. No differences were found in ICU days, ventilator-free days, or mortality; however, length of stay was longer for PAU (23 vs. 17, p = .04). In the PAU group, there were fewer BALCx results of "no growth" (23% vs. 45%, p = .04), more positive gram stains (83% vs. 60%, p = .01) and more positive non-BALCx (40% vs. 14%, p = .01). In a multivariate analysis, factors associated with PAU were positive BAL gram stains (adjusted odds ratio [aOR] 3.1, p = .037) and positive non-BALCx (aOR 4.7, p = .002). Conclusion: For subjects with suspected pneumonia and negative BALCx, positive non-BALCx and positive BALCx gram stain influenced the length of exposure of antibiotics.

Effect of Neuromuscular Blocking Agents on Sedation Requirements in Trauma Patients with an Open Abdomen.

The appropriate level of sedation in patients with an open abdomen following damage control laparotomy (DCL) is debated. Chemical paralysis with neuromuscular blocking agents (NMBAs) has been used to decrease time to abdominal closure. We sought to evaluate the effect of NMBA use on sedation requirements in patients with an open abdomen and to determine the effect of sedation on patient outcomes. A retrospective cohort study was conducted at an American College of Surgeons' verified level 1 trauma center. Adult trauma patients who underwent DCL between 2009 and 2015 were included. Patients with an intensive care unit length of stay of less than 48 hours and those who died before abdominal closure were excluded. The NMBA+ group received continuous NMBA within 24 hours of DCL; the NMBA- group did not. The primary outcome was cumulative sedation dose during the 7 days following DCL. Secondary outcomes included Richmond Agitation-Sedation Scale (RASS) score, mechanical ventilation-free days, and delirium-coma-free days. Delirium-coma-free days were analyzed with linear regression. A total of 222 patients were included (NMBA+ 125; NMBA- 97). Demographics were similar between groups including age, Injury Severity Score, and mechanism of injury. The median time to closure in the overall cohort was 2 days (interquartile range [IQR] 1-2 days). Propofol and fentanyl were the primary sedatives used. The NMBA+ group received higher cumulative doses of propofol (NMBA+ 5405 mg, IQR 3103-10,573 mg; NMBA- 3601 mg, IQR 1605-6887 mg; p=0.007), but not of fentanyl. Time to abdominal closure, but not NMBA use, was associated with a higher cumulative propofol dose on multivariate analysis. The NMBA+ group had significantly lower RASS scores on the first 3 days following DCL. Mechanical ventilation-free days (NMBA+ 20 days vs NMBA- 18 days, p=0.960) and delirium-coma-free days (NMBA+ 18 days vs NMBA- 18 days, p=0.610) were similar between the groups. On linear regression, cumulative propofol dose was associated with fewer delirium-coma-free days (ß-coefficient -0.007, 95% confidence interval -0.015 to -0.003). In trauma patients managed with DCL, higher cumulative sedative doses were administered in patients who received adjunctive NMBA, although NMBA therapy was not associated with a higher cumulative propofol dose on multivariate analysis. Consideration must be given to the potential effect of sedation on delirium and awakening following DCL.

Effectiveness and safety of continuous neuromuscular blockade in trauma patients with an open abdomen: A follow-up study.

BACKGROUND: Neuromuscular blocking agents (NMBA) have been associated with decreased time to fascial closure following damage control laparotomy (DCL). Changes in resuscitation over the last decade bring this practice into question. METHODS: A retrospective cohort study of adults who underwent DCL between 2009 and 2015 was conducted at an ACS-verified level 1 trauma center. The study group (NMBA+) received continuous NMBA within 24 h of DCL. Data collected included demographics, resuscitative fluids, mortality, and complications. The primary outcome was time to fascial closure. Factors associated with abdominal closure were determined by ordinal logistic regression. RESULTS: There were 222 patients included (NMBA+ 125; NMBA- 97). Demographics were similar, including median age (NMBA+ 36; NMBA- 39 years) and ISS (NMBA+ 29; NMBA- 34). There was no difference in median time to closure (NMBA+ 2; NMBA- 2 days) or the incidence of complications (NMBA+ 64%; NMBA- 59%). In a regression model, NMBA exposure was not associated with time to abdominal closure. CONCLUSIONS: In adult trauma patients requiring DCL, continuous NMBA did not affect the time to abdominal closure.

Antioxidant supplementation and atrial arrhythmias in critically ill trauma patients.

BACKGROUND: The purpose of this study is to determine if antioxidant supplementation influences the incidence of atrial arrhythmias in trauma intensive care unit (ICU) patients. MATERIALS AND METHODS: In this retrospective pre-post study, critically ill injured patients aged ≥18 years, admitted to a single-center trauma ICU for ≥48 hours were eligible for inclusion. The control group consists of patients admitted from January 2000 to September 2005, before routine antioxidant supplementation in our ICU. The antioxidant group consists of patients admitted from October 2005 to June 2011 who received an antioxidant protocol for ≥48 hours. The primary outcome is the incidence of atrial arrhythmias in the first 2 weeks of hospitalization or before discharge. RESULTS: Of the 4699 patients, 1622 patients were in the antioxidant group and 2414 patients were in the control group. Adjusted for age, sex, year, injury severity, past medical history, and medication administration, the unadjusted incidence of atrial arrhythmias was 3.02% in the antioxidant group versus 3.31% in the control group, with no adjusted difference in atrial arrhythmias among those exposed to antioxidants (odds ratio: 1.31 [95% confidence interval: 0.46, 3.75], P = 0.62). Although there was no change in overall mortality, the expected adjusted survival of patients in those without antioxidant therapy was lower (odds ratio: 0.65 [95% confidence interval: 0.43, 0.97], P = 0.04). CONCLUSIONS: ICU antioxidant supplementation did not decrease the incidence of atrial arrhythmias, nor alter the time from admission to development of arrhythmia. A longer expected survival time was observed in the antioxidant group compared with the control group but without a change in overall mortality between groups.

Beta-blockers and Traumatic Brain Injury: A Systematic Review, Meta-analysis, and Eastern Association for the Surgery of Trauma Guideline.

OBJECTIVE: To determine if beta-(ß)-blockers improve outcomes after acute traumatic brain injury (TBI). BACKGROUND: There have been no new inpatient pharmacologic therapies to improve TBI outcomes in a half-century. Treatment of TBI patients with ß-blockers offers a potentially beneficial approach. METHODS: Using MEDLINE, EMBASE, and CENTRAL databases, eligible articles for our systematic review and meta-analysis (PROSPERO CRD42016048547) included adult (age ≥ 16 years) blunt trauma patients admitted with TBI. The exposure of interest was ß-blocker administration initiated during the hospitalization. Outcomes were mortality, functional measures, quality of life, cardiopulmonary morbidity (e.g., hypotension, bradycardia, bronchospasm, and/or congestive heart failure). Data were analyzed using a random-effects model, and represented by pooled odds ratio (OR) with 95% confidence intervals (CI) and statistical heterogeneity (I). RESULTS: Data were extracted from 9 included studies encompassing 2005 unique TBI patients with ß-blocker treatment and 6240 unique controls. Exposure to ß-blockers after TBI was associated with a reduction of in-hospital mortality (pooled OR 0.39, 95% CI: 0.27-0.56; I = 65%, P < 0.00001). None of the included studies examined functional outcome or quality of life measures, and cardiopulmonary adverse events were rarely reported. No clear evidence of reporting bias was identified. CONCLUSIONS: In adults with acute TBI, observational studies reveal a significant mortality advantage with ß-blockers; however, quality of evidence is very low. We conditionally recommend the use of in-hospital ß-blockers. However, we recommend further high-quality trials to answer questions about the mechanisms of action, effectiveness on subgroups, dose-response, length of therapy, functional outcome, and quality of life after ß-blocker use for TBI.

Method of Hypertonic Saline Administration: Effects on Osmolality in Traumatic Brain Injury Patients.

Hypertonic saline (HTS) is an effective therapy for reducing intracranial pressure (ICP). The ideal method of administration is unknown. The purpose of this study was to evaluate the method of HTS infusion and time to goal osmolality. A retrospective cohort analysis was conducted in severe TBI patients with ICP monitoring in place who received 2 doses of HTS. Patients were divided into bolus versus continuous infusion HTS cohorts. The primary outcome was median time to goal osmolality. Secondary outcomes included percentage of patients reaching goal osmolality, percent time at goal osmolality, mean cerebral perfusion pressure (CPP) and ICP, ICU length of stay, and mortality. Safety outcomes included rates of hyperchloremia, hypernatremia, and acute kidney injury (AKI). 162 patients were included with similar baseline characteristics. Time to goal osmolality was similar between cohorts (bolus 9.78h vs. continuous 11.4h, p=0.817). A significant difference in the percentage of patients reaching goal osmolality favoring the continuous group was found (93.9% vs 73.3%, p=0.003). The continuous group was maintained at goal osmolality for a higher percentage of osmolality values after reaching goal (80% vs. 50%, p=0.032). No difference was seen in CPP, ICP, length of stay and mortality. Rates of hypernatremia were similar, but significant higher rates of hyperchloremia (0.77vs 1.58 events per HTS days, p<0.001) and AKI (0% vs 12.9%, p=0.025) were observed in the continuous cohort. Although no difference in time to goal osmolality was observed, continuous HTS was associated with a higher percentage of patients achieving goal osmolality.

Use of an evidence-based algorithm for patients with traumatic hemothorax reduces need for additional interventions.

BACKGROUND: Concerted management of the traumatic hemothorax is ill-defined. Surgical management of specific hemothoraces may be beneficial. A comprehensive strategy to delineate appropriate patients for additional procedures does not exist. We developed an evidence-based algorithm for hemothorax management. We hypothesize that the use of this algorithm will decrease additional interventions. METHODS: A pre-/post-study was performed on all patients admitted to our trauma service with traumatic hemothorax from August 2010 to September 2013. An evidence-based management algorithm was initiated for the management of retained hemothoraces. Patients with length of stay (LOS) less than 24 hours or admitted during an implementation phase were excluded. Study data included age, Injury Severity Score, Abbreviated Injury Scale chest, mechanism of injury, ventilator days, intensive care unit (ICU) LOS, total hospital LOS, and interventions required. Our primary outcome was number of patients requiring more than 1 intervention. Secondary outcomes were empyema rate, number of patients requiring specific additional interventions, 28-day ventilator-free days, 28-day ICU-free days, hospital LOS, all-cause 6-month readmission rate. Standard statistical analysis was performed for all data. RESULTS: Six hundred forty-two patients (326 pre and 316 post) met the study criteria. There were no demographic differences in either group. The number of patients requiring more than 1 intervention was significantly reduced (49 pre vs. 28 post, p = 0.02). Number of patients requiring VATS decreased (27 pre vs. 10 post, p < 0.01). Number of catheters placed by interventional radiology increased (2 pre vs. 10 post, p = 0.02). Intrapleural thrombolytic use, open thoracotomy, empyema, and 6-month readmission rates were unchanged. The "post" group more ventilator-free days (median, 23.9 vs. 22.5, p = 0.04), but ICU and hospital LOS were unchanged. CONCLUSION: Using an evidence-based hemothorax algorithm reduced the number of patients requiring additional interventions without increasing complication rates. Defined criteria for surgical intervention allows for more appropriate utilization of resources. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Intrapleural tissue plasminogen activator for the treatment of parapneumonic effusion.

Intrapleural tissue plasminogen activator (t-PA) has emerged over the past several years as a treatment option for patients with complicated parapneumonic effusion that does not respond to medical management and drainage. Fibrinolytics are thought to dissolve fibrin deposits and loculations within the pleural space, facilitating drainage of the trapped pleural fluid surrounding the lungs. Whereas older fibrinolytics (streptokinase and urokinase) have been studied for intrapleural use with conflicting results, t-PA is currently the agent most commonly used in adults for this indication. However, the literature describing t-PA therapy for complicated parapneumonic effusion and empyema is sparse, and studies have been highly variable in their methods. Several articles report use of this drug at doses ranging from 2-100 mg at daily intervals or more frequently. Surgical treatment options associated with good outcomes are also available to these patients. As a result, the indications for intrapleural t-PA (especially compared with surgical management) in patients with effusions resistant to conventional drainage are not fully clear. The usefulness of t-PA in all patients with resistant parapneumonic effusions or empyema before surgical intervention remains undetermined, but several studies have taken this approach. Sufficient evidence is available to indicate that this therapy does have potential in patients for whom surgery is not a safe or desired option. Further study is needed to better understand the role of t-PA and its optimal dosage in patients with complicated parapneumonic effusion.