Expert consensus on the management of systemic sclerosis-associated interstitial lung disease.

BACKGROUND: Systemic sclerosis (SSc) is a rare, complex, connective tissue disorder. Interstitial lung disease (ILD) is common in SSc, occurring in 35-52% of patients and accounting for 20-40% of mortality. Evolution of therapeutic options has resulted in a lack of consensus on how to manage this condition. This Delphi study was initiated to develop consensus recommendations based on expert physician insights regarding screening, progression, treatment criteria, monitoring of response, and the role of recent therapeutic advances with antifibrotics and immunosuppressants in patients with SSc-ILD. METHODS: A modified Delphi process was completed by pulmonologists (n = 13) and rheumatologists (n = 12) with expertise in the management of patients with SSc-ILD. Panelists rated their agreement with each statement on a Likert scale from - 5 (complete disagreement) to + 5 (complete agreement). Consensus was predefined as a mean Likert scale score of ≤ - 2.5 or ≥ + 2.5 with a standard deviation not crossing zero. RESULTS: Panelists recommended that all patients with SSc be screened for ILD by chest auscultation, spirometry with diffusing capacity of the lungs for carbon monoxide, high-resolution computed tomography (HRCT), and/or autoantibody testing. Treatment decisions were influenced by baseline and changes in pulmonary function tests, extent of ILD on HRCT, duration and degree of dyspnea, presence of pulmonary hypertension, and potential contribution of reflux. Treatment success was defined as stabilization or improvement of signs or symptoms of ILD and functional status. Mycophenolate mofetil was identified as the initial treatment of choice. Experts considered nintedanib a therapeutic option in patients with progressive fibrotic ILD despite immunosuppressive therapy or patients contraindicated/unable to tolerate immunotherapy. Concomitant use of nintedanib with MMF/cyclophosphamide can be considered in patients with advanced disease at initial presentation, aggressive ILD, or significant disease progression. Although limited consensus was achieved on the use of tocilizumab, the experts considered it a therapeutic option for patients with early SSc and ILD with elevated acute-phase reactants. CONCLUSIONS: This modified Delphi study generated consensus recommendations for management of patients with SSc-ILD in a real-world setting. Findings from this study provide a management algorithm that will be helpful for treating patients with SSc-ILD and addresses a significant unmet need.

Risk Factors for and Outcomes Associated With Peri-Intubation Hypoxemia: A Multicenter Prospective Cohort Study.

BACKGROUND: Little is known about hypoxemia surrounding endotracheal intubation in the critically ill. Thus, we sought to identify risk factors associated with peri-intubation hypoxemia and its effects' on the critically ill. METHODS: Data from a multicenter, prospective, cohort study enrolling 1,033 critically ill adults who underwent endotracheal intubation across 16 medical/surgical ICUs in the United States from July 2015-January 2017 were used to identify risk factors associated with peri-intubation hypoxemia and its effects on patient outcomes. We defined hypoxemia as any pulse oximetry ≤ 88% during and up to 30 minutes following endotracheal intubation. RESULTS: In the full analysis (n = 1,033), 123 (11.9%) patients experienced the primary outcome. Five risk factors independently associated with our outcome were identified on multiple logistic regression: cardiac related reason for endotracheal intubation (OR 1.67, [95% CI 1.04, 2.69]); pre-intubation noninvasive ventilation (OR 1.66, [95% CI 1.09, 2.54]); emergency intubation (OR 1.65, [95% CI 1.06, 2.55]); moderate-severe difficult bag-mask ventilation (OR 2.68, [95% CI 1.72, 4.19]); and crystalloid administration within the preceding 24 hours (OR 1.24, [95% CI 1.07, 1.45]; per liter up to 4 liters). Higher baseline SpO2 was found to be protective (OR 0.93, [95% CI 0.91, 0.96]; per percent up to 97%). Consistent results were seen in a separate analysis on only stable patients (n = 921, 93 [10.1%]) (those without baseline hypoxemia ≤ 88%). Peri-intubation hypoxemia was associated with in-hospital mortality (OR 2.40, [95% CI 1.33, 4.31]; stable patients: OR 2.67, [95% CI 1.38, 5.17]) but not ICU length of stay (point estimate 0.9 days, [95% CI -1.0, 2.8 days]; stable patients: point estimate 1.5 days, [95% CI -0.4, 3.4 days]) after adjusting for age, body mass index, illness severity, airway related reason for intubation (i.e., acute respiratory failure), and baseline SPO2. CONCLUSIONS: Patients with pre-existing noninvasive ventilation and volume loading who were intubated emergently in the setting of hemodynamic compromise with bag-mask ventilation described as moderate-severe were at increased risk for peri-intubation hypoxemia. Higher baseline oxygenation was found to be protective against peri-intubation hypoxemia. Peri-intubation hypoxemia was associated with in-hospital mortality but not ICU length of stay. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02508948 and Registered Report Identifier: RR2-10.2196/11101.

Sepsis and the Obesity Paradox: Size Matters in More Than One Way.

OBJECTIVES: Multiple studies have demonstrated an obesity paradox such that obese ICU patients have lower mortality and better outcomes. We conducted this study to determine if the mortality benefit conferred by obesity is affected by baseline serum lactate and mean arterial pressure. DESIGN: Retrospective analysis of prospectively collected clinical data. SETTING: Five community-based and one academic medical center in the Omaha, NE. PATIENTS: 7,967 adults hospitalized with sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were categorized by body mass index as underweight, normal weight, overweight, or obese. Multivariable logistic regression models were used to estimate the odds of in-hospital death by body mass index category; two-way interactions between body mass index and each covariate were also evaluated. Subgroup and sensitivity analyses were conducted using an ICU cohort and Acute Physiology and Chronic Health Evaluation III scores, respectively. The overall unadjusted mortality rate was 12.1% and was consistently lower in higher body mass index categories (all comparisons, p < 0.007). The adjusted mortality benefit observed in patients with higher body mass index was smaller in patients with higher lactate levels with no mortality benefit in higher body mass index categories observed at lactate greater than 5 mmol/L. By contrast, the association between lower MAP and higher mortality was constant across body mass index categories. Similar results were observed in the ICU cohort. Finally, the obesity paradox was not observed after including Acute Physiology and Chronic Health Evaluation III scores as a covariate. CONCLUSIONS: Our retrospective analysis suggests that although patient size (i.e., body mass index) is a predictor of in-hospital death among all-comers with sepsis-providing further evidence to the obesity paradox-it adds that illness severity is critically important whether quantified as higher lactate or by Acute Physiology and Chronic Health Evaluation III score. Our results highlight that the obesity paradox is more than a simple association between body mass index and mortality and reinforces the importance of illness severity.

Role of B-Type Natriuretic Peptide in Predicting In-Hospital Outcomes in Acute Exacerbation of Chronic Obstructive Pulmonary Disease With Preserved Left Ventricular Function: A 5-Year Retrospective Analysis.

BACKGROUND: The role of B-type natriuretic peptide (BNP) is less understood in the risk stratification of patients with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD), especially in patients with normal left ventricular ejection fraction (LVEF). METHODS: This retrospective study from 2008 to 2012 evaluated all adult patients with AECOPD having BNP levels and available echocardiographic data demonstrating LVEF ≥40%. The patients were divided into groups 1, 2, and 3 with BNP ≤ 100, 101 to 500, and ≥501 pg/mL, respectively. A subgroup analysis was performed for patients without renal dysfunction. Outcomes included need for and duration of noninvasive ventilation (NIV) and mechanical ventilation (MV), NIV failure, reintubation at 48 hours, intensive care unit (ICU) and total length of stay (LOS), and in-hospital mortality. Two-tailed P < .05 was considered statistically significant. RESULTS: Of the total 1145 patients, 550 (48.0%) met our inclusion criteria (age 65.1 ± 12.2 years; 271 [49.3%] males). Groups 1, 2, and 3 had 214, 216, and 120 patients each, respectively, with higher comorbidities and worse biventricular function in higher categories. Higher BNP values were associated with higher MV use, NIV failure, MV duration, and ICU and total LOS. On multivariate analysis, BNP was an independent predictor of higher NIV and MV use, NIV failure, NIV and MV duration, and total LOS in groups 2 and 3 compared to group 1. B-type natriuretic peptide continued to demonstrate positive correlation with NIV and MV duration and ICU and total LOS independent of renal function in a subgroup analysis. CONCLUSION: Elevated admission BNP in patients with AECOPD and normal LVEF is associated with worse in-hospital outcomes and can be used to risk-stratify these patients.

Clinically Significant Food-Drug Interactions.

OBJECTIVE: Provide an up-to-date review for health care providers regarding clinically significant food-drug interactions and summarize recommendations for optimal medication administration in older adults and long-term care patients. DATA SOURCES: A literature search was performed using MEDLINE, PUBMED, and IPA abstracts to locate relevant articles published between January 1982 and July 2017. DAILYMED was used to identify manufacturer-specific medication administration recommendations. STUDY SELECTION AND DATA EXTRACTION: Articles were reviewed for inclusion based on their relevance to this subject matter and the integrity of the information provided. Additionally, the package labeling of included products was reviewed. DATA SYNTHESIS: The current recommendations for specific medication administration with regard to food are summarized descriptively. CONCLUSION: Clinically significant food-drug interactions are common and have been reported with multiple classes of medications. However, there are a limited number of studies examining food-drug interactions, and the majority of recommendations are made by product-specific manufacturers. Pharmacists should be aware of common food-drug interactions in the community, assisted living, long-term care, subacute care, and hospital settings. To optimize medication therapy and improve therapeutic outcomes, it is important for pharmacists and other health care providers to identify agents with potential for food-drug interactions and to understand the clinical relevance of such interactions.

Drug Interactions With Oral Inhaled Medications.

Objective: To evaluate the potential for drug interactions with oral inhaled medications (OIMs). OIMs include bronchodilators (ß-agonists and antimuscarinics), corticosteroids, combination products (2 or more agents combined within a single inhalation device), antibiotics, prostacyclins, anesthetics, acetylcysteine, mucolytics, insulin, antivirals, nitric oxide, and nicotine replacement. Data Sources: A systemic literature search (1980 to May 2018) was performed using PubMed and EBSCO to locate relevant articles. The MESH terms used included each specific medication available as an OIM as well as "drug interactions." DAILYMED was used for product-specific drug interactions. Study Selection and Data Extraction: The search was conducted to identify drug interactions with OIMs. The search was limited to those articles studying human applications with OIMs and publications using the English language. Case reports, clinical trials, review articles, treatment guidelines, and package labeling were selected for inclusion. Data Synthesis: Primary literature and package labeling indicate that OIMs are subject to pharmacokinetic and pharmacodynamics interactions. The most frequently identified clinically significant drug interaction is an inhaled corticosteroid when combined with a potent CYP 450 inhibitor such as a protease inhibitor or antifungal. Conclusions: The available literature indicates that OIMs are associated with clinically significant drug interactions and subsequent adverse reactions. Clinicians in all practice settings should be mindful of this potential to minimize adverse effects and optimize therapy.

Idiopathic Pulmonary Fibrosis: A Case Discussion.

OBJECTIVE: The purpose of this report is to describe the case of a 68-year-old man who was treated for idiopathic pulmonary fibrosis (IPF), a chronic and fatal lung disease that is characterized by progressive deterioration of pulmonary function. He was initially prescribed pirfenidone and developed significant gastric distress. The treatment was transitioned to nintedanib. This article will provide the pharmacist with a therapeutic overview of IPF, as well as review the unique process involved with drug acquisition, dosing, patient education, and monitoring of pirfenidone and nintedanib. SETTINGS: Community pharmacy, nursing facility pharmacy, consultant pharmacy practice. PRACTICE CONSIDERATIONS: Pirfenidone and nintedanib are the only medications in the United States approved to treat IPF. These treatments have distinctive properties that differ from past therapies for IPF. CONCLUSION: It is important for pharmacists to understand the treatment recommendations for IPF and to review the process for acquisition, dosing, and administration of pirfenidone and nintedanib to better assist physicians and patients and improve therapeutic outcomes.

Influence of Left Ventricular Hypertrophy on In-Hospital Outcomes in Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Left ventricular hypertrophy (LVH) is associated with worse outcomes in chronic obstructive pulmonary disease (COPD); however, its role in an acute exacerbation of COPD (AECOPD) has not been reported. This was a retrospective cohort study during 2008-2012 at an academic medical center. AECOPD patients >18 years with available echocardiographic data were included. LVH was defined as LV mass index (LVMI) >95 g/m2 (women) and >115g/m2 (men). Relative wall thickness was used to classify LVH as concentric (>0.42) or eccentric (<0.42). Outcomes included need for and duration of non-invasive ventilation (NIV) and mechanical ventilation (MV), NIV failure, intensive care unit (ICU) and total length of stay (LOS), and in-hospital mortality. Two-tailed p < 0.05 was considered statistically significant. Of 802 patients with AECOPD, 615 patients with 264 (42.9%) having LVH were included. The LVH cohort had higher LVMI (141.1 ± 39.4 g/m2 vs. 79.7 ± 19.1 g/m2; p < 0.001) and lower LV ejection fraction (44.5±21.9% vs. 50.0±21.6%; p ≤ 0.001). The LVH cohort had statistically non-significant longer ICU LOS, and higher NIV and MV use and duration. Of the 264 LVH patients, concentric LVH (198; 75.0%) was predictive of greater NIV use [82 (41.4%) vs. 16 (24.2%), p = 0.01] and duration (1.0 ± 1.9 vs. 0.6 ± 1.4 days, p = 0.01) compared to eccentric LVH. Concentric LVH remained independently associated with NIV use and duration. In-hospital outcomes in patients with AECOPD were comparable in patients with and without LVH. Patients with concentric LVH had higher NIV need and duration in comparison to eccentric LVH.

Use of Quantitative CT Imaging to Identify Bronchial Thermoplasty Responders.

BACKGROUND: Bronchial thermoplasty (BT) is a treatment for patients with poorly controlled, severe asthma. However, predictors of treatment response to BT are defined poorly. RESEARCH QUESTION: Do baseline radiographic and clinical characteristics exist that predict response to BT? STUDY DESIGN AND METHODS: We conducted a longitudinal prospective cohort study of participants with severe asthma receiving BT across eight academic medical centers. Participants received three separate BT treatments and were monitored at 3-month intervals for 1 year after BT. Similar to prior studies, a positive response to BT was defined as either improvement in Asthma Control Test results of ≥ 3 or Asthma Quality of Life Questionnaire of ≥ 0.5. Regression analyses were used to evaluate the association between pretreatment clinical and quantitative CT scan measures with subsequent BT response. RESULTS: From 2006 through 2017, 88 participants received BT, with 70 participants (79.5%) identified as responders by Asthma Control Test or Asthma Quality of Life Questionnaire criteria. Responders were less likely to undergo an asthma-related ICU admission in the prior year (3% vs 25%; P = .01). On baseline quantitative CT imaging, BT responders showed less air trapping percentage (OR, 0.90; 95% CI, 0.82-0.99; P = .03), a greater Jacobian determinant (OR, 1.49; 95% CI, 1.05-2.11), greater SD of the Jacobian determinant (OR, 1.84; 95% CI, 1.04-3.26), and greater anisotropic deformation index (OR, 3.06; 95% CI, 1.06-8.86). INTERPRETATION: To our knowledge, this is the largest study to evaluate baseline quantitative CT imaging and clinical characteristics associated with BT response. Our results show that preservation of normal lung expansion, indicated by less air trapping, a greater magnitude of isotropic expansion, and greater within-lung spatial variation on quantitative CT imaging, were predictors of future BT response. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01185275; URL: www. CLINICALTRIALS: gov.

Effects of adherence to ventilator-associated pneumonia treatment guidelines on clinical outcomes.

Two guidelines are currently available to guide Japanese clinicians caring for patients with ventilator-associated pneumonia (VAP): the 2005 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines or the 2008 Japanese Respiratory Society (JRS) guidelines. We aimed to measure compliance with guideline recommendations for VAP in Japanese intensive care units (ICUs) and to assess the effects of guideline-compliant treatment on outcomes. We retrospectively reviewed the records of all patients with microbiologically confirmed VAP in five Japanese ICUs between January 1, 2006, and December 31, 2009. We evaluated whether empiric antibiotic prescriptions were guideline compliant and correlated compliance with clinical outcomes. Among the 95 patients with VAP who were included, 85 patients received empiric antibiotics. Of these, therapy of 62 patients (73 %) was appropriate based on in vitro sensitivity testing. Using ATS/IDSA criteria, 16 patients (19 %) received guideline-compliant therapy and 69 patients (81 %) received noncompliant treatment. Using JRS criteria, 24 patients (28 %) received guideline-compliant therapy and 61 patients (72 %) received noncompliant treatment. All-cause 28-day mortality was 24 %. When compared to patients who received noncompliant therapy, there were no differences in 28-day mortality rates for patients who received ATS/IDSA guideline-compliant regimens (25 vs. 25 %, p = 1.00) or JRS guideline-compliant regimens (21 vs. 26 %, p = 0.78). Our study demonstrates poor compliance with guideline-recommended antibiotic therapy for VAP in Japanese ICUs. Compliance with current VAP guidelines was not associated with increased rates of appropriate antibiotic treatment or improved 28-day mortality.

A Retrospective Analysis of the Effects of Time on Compliance and Driving Pressures in ARDS.

BACKGROUND: The evolution of compliance and driving pressure in ARDS and the effects of time spent on noninvasive respiratory support prior to intubation have not been well studied. We conducted this study to assess the effect of the duration of noninvasive respiratory support prior to intubation (ie, noninvasive ventilation [NIV], high-flow nasal cannula [HFNC], or a combination of NIV and HFNC) on static compliance and driving pressure and retrospectively describe its trajectory over time for COVID-19 and non-COVID-19 ARDS while on mechanical ventilation. METHODS: This is a retrospective analysis of prospectively collected data from one university-affiliated academic medical center, one rural magnet hospital, and 3 suburban community facilities. A total of 589 subjects were included: 55 COVID-19 positive, 137 culture positive, and 397 culture-negative subjects. Static compliance and driving pressure were calculated at each 8-h subject-ventilator assessment. RESULTS: Days of pre-intubation noninvasive respiratory support were associated with worse compliance and driving pressure but did not moderate any trajectory. COVID-19-positive subjects showed non-statistically significant worsening compliance by 0.08 units per subject-ventilator assessment (P = .24), whereas COVID-19-negative subjects who were either culture positive or negative showed statistically significant improvement (0.12 and 0.18, respectively; both P < .05); a statistically similar but inverse pattern was observed for driving pressure. CONCLUSIONS: In contrast to non-COVID-19 ARDS, COVID-19 ARDS was associated with a more ominous trajectory with no improvement in static compliance or driving pressures. Though there was no association between days of pre-intubation noninvasive respiratory support and mortality, its use was associated with worse overall compliance and driving pressure.

Synbiotics and probiotics in the critically ill after the PROPATRIA trial.

PURPOSE OF REVIEW: Recent clinical trials have furthered our understanding of the role of probiotic and synbiotic therapy across a variety of diverse diseases including antibiotic-associated diarrhea, Clostridium difficile associated diarrhea, acute pancreatitis, ventilator-associated pneumonia, and sepsis among others. Although each of these conditions has implications for critically ill patients, relatively few studies have specifically studied this vulnerable population. RECENT FINDINGS: One recent clinical trial studying probiotics in severe pancreatitis (the PROPATRIA trial) found an unexpected increase in mortality in probiotic-treated patients. These results stimulated an immediate, extensive, and badly overdue discussion focused on the need for improved safety monitoring during the execution of all clinical trials using probiotics. However, issues with the design, execution, and analysis of PROPATRIA ultimately created more questions than it answered. SUMMARY: Regardless of technical issues with the study, the increased mortality seen with probiotics cannot be ignored. As a result, various regulatory agencies have clarified their stance on the safety of probiotic research and the legacy of PROPATRIA is increasingly stringent regulation of this fledgling niche.

Probiotic, prebiotic, and synbiotic use in critically ill patients.

PURPOSE OF REVIEW: To summarize the existing data regarding the use of probiotics, prebiotics, and synbiotics in select disorders encountered in the intensive care unit setting. RECENT FINDINGS: Recent systematic reviews and meta-analyses have more rigorously aggregated the fragmented primary data which suffers from multiple limitations. SUMMARY: Probiotics are living microorganisms which, when ingested in adequate amounts, provide health benefits to the host. The mechanisms of these benefits include improved gastrointestinal barrier function, modification of the gut flora by inducing host cell antimicrobial peptides, releasing probiotic antimicrobial factors, competing for epithelial adherence, and immunomodulation to the advantage of the host. In the intensive care unit, probiotics appear to provide benefits in antibiotic-associated diarrhea, ventilator-associated pneumonia, and necrotizing enterocolitis. With increasing rates of antibiotic resistance among common nosocomial pathogens and fewer new antibiotics in the research pipeline, increasing attention has been placed on nonantibiotic approaches to the prevention and treatment of nosocomial infections. Existing studies of probiotics in critically ill patients are limited by heterogeneity in probiotic strains, dosages, duration of administration, and small sample sizes. Although probiotics are generally well tolerated and adverse events are very rare, the results of the PROPATRIA (Probiotics Prophylaxis in Patients with Predicted Severe Acute Pancreatitis) trial highlight the need for meticulous attention to safety monitoring. Better identification of the ideal characteristics of effective probiotics coupled with improved understanding of mechanisms of action will help to delineate the true beneficial effects of probiotics in various disorders.

Management of patients with fibrosing interstitial lung diseases.

PURPOSE: This article summarizes the appropriate use and pharmacology of treatments for fibrosing interstitial lung diseases, with a specific focus on the antifibrotic agents nintedanib and pirfenidone. SUMMARY: The interstitial lung diseases are a heterogenous group of parenchymal lung disorders with a common feature-infiltration of the interstitial space with derangement of the normal capillary-alveolar anatomy. Diseases characterized by fibrosis of the interstitial space are referred to as the fibrosing interstitial lung diseases and often show progression over time: idiopathic pulmonary fibrosis is the most common fibrotic interstitial lung disease. Historically, therapies for fibrosing lung diseases have been limited in number, questionable in efficacy, and associated with potential harms. Food and Drug Administration (FDA) approval of the antifibrotic agents nintedanib and pirfenidone for idiopathic pulmonary fibrosis in 2014 heralded an era of reorganization of therapy for the fibrotic interstitial lung diseases. Subsequent investigations have led to FDA approval of nintedanib for systemic sclerosis-associated interstitial lung disease and interstitial lung diseases with a progressive phenotype. Although supportive care and pulmonary rehabilitation should be provided to all patients, the role(s) of immunomodulators and/or immune suppressing agents vary by the underlying disease state. Several agents previously used to treat fibrotic lung diseases (N-acetylcysteine, anticoagulation, and pulmonary vasodilators) lack efficacy or cause harm. CONCLUSION: With the introduction of effective pharmacotherapy for fibrosing interstitial lung disease, pharmacists have an increasingly important role in the interdisciplinary team managing these patients.

Prolonged Prehospital Time Is a Risk Factor for Pneumonia in Trauma (the PRE-TRIP Study): A Retrospective Analysis of the United States National Trauma Data Bank.

BACKGROUND: Although multiple risk factors for development of pneumonia in patients with trauma sustained in a motor vehicle accident have been studied, the effect of prehospital time on pneumonia incidence post-trauma is unknown. RESEARCH QUESTION: Is prolonged prehospital time an independent risk factor for pneumonia? STUDY DESIGN AND METHODS: We retrospectively analyzed prospectively collected clinical data from 806,012 motor vehicle accident trauma incidents from the roughly 750 trauma hospitals contributing data to the National Trauma Data Bank between 2010 and 2016. RESULTS: Prehospital time was independently associated with development of pneumonia post-motor vehicle trauma (P < .001). This association was primarily driven by patients with low Glasgow Coma Scale scores. Post-trauma pneumonia was uncommon (1.5% incidence) but was associated with a significant increase in mortality (P < .001, 4.3% mortality without pneumonia vs 12.1% mortality with pneumonia). Other pneumonia risk factors included age, sex, race, primary payor, trauma center teaching status, bed size, geographic region, intoxication, comorbid lung disease, steroid use, lower Glasgow Coma Scale score, higher Injury Severity Scale score, blood product transfusion, chest trauma, and respiratory burns. INTERPRETATION: Increased prehospital time is an independent risk factor for development of pneumonia and increased mortality in patients with trauma caused by a motor vehicle accident. Although prehospital time is often not modifiable, its recognition as a pneumonia risk factor is important, because prolonged prehospital time may need to be considered in subsequent decision-making.

Reoperative antireflux surgery for dysphagia.

BACKGROUND: Troublesome dysphagia is a common indication for redo antireflux surgery (Re-ARS). This study is aimed to analyze the efficacy of Re-ARS in resolving dysphagia and to identify risk factors for persistent or new-onset dysphagia after Re-ARS. METHODS: A prospectively maintained database was retrospectively reviewed to identify patients after Re-ARS. Dysphagia severity was graded on a scale of 0 to 3 before and after Re-ARS based on responses to a standardized questionnaire. Patients reporting grade 2 or 3 symptoms were considered to have significant dysphagia. Satisfaction was graded using a 10-point analog scale. RESULTS: Between December 2003 and July 2008, 106 patients underwent Re-ARS. Significant preoperative dysphagia was reported by 54 patients, and impaired esophageal motility was noted in 31 patients. Remedial surgery included redo fundoplication (n = 87), Collis gastroplasty with redo fundoplication (n = 16), and takedown of the fundoplication or hiatal closure alone (n = 3). At least 1 year follow-up period (mean 21.8 months) was available for 92 patients. For patients with significant preoperative dysphagia (n = 46), the mean symptom score declined from 2.35 to 0.78 (p < 0.0001). Persistent dysphagia was reported by 13 patients and new-onset dysphagia by 4 patients. No patients reported grade 3 dysphagia after Re-ARS. Dilations were used to treat 11 patients. Multivariate logistic regression analysis identified Collis gastroplasty (p = 0.03; adjusted odds ratio [OR], 5.74) and preoperative dysphagia (p = 0.01; adjusted OR, 6.80) as risk factors for significant postoperative dysphagia. The overall satisfaction score was 8.3, but certain subsets had significantly lower satisfaction scores. These subsets included patients with esophageal dysmotility (7.1; p = 0.04), patients who required Collis gastroplasty (7.0; p = 0.09), and patients with esophageal dysmotility who required Collis gastroplasty (5.0; p < 0.01). CONCLUSION: Although dysphagia is a common symptom among patients requiring Re-ARS, intervention provides a significant benefit. Patients with preoperative dysphagia, especially those requiring Collis gastroplasty, are at increased risk for persistent dysphagia and decreased satisfaction after Re-ARS.

Probiotic prophylaxis of ventilator-associated pneumonia: a blinded, randomized, controlled trial.

RATIONALE: Enteral administration of probiotics may modify the gastrointestinal environment in a manner that preferentially favors the growth of minimally virulent species. It is unknown whether probiotic modification of the upper aerodigestive flora can reduce nosocomial infections. OBJECTIVES: To determine whether oropharyngeal and gastric administration of Lactobacillus rhamnosus GG can reduce the incidence of ventilator-associated pneumonia (VAP). METHODS: We performed a prospective, randomized, double-blind, placebo-controlled trial of 146 mechanically ventilated patients at high risk of developing VAP. Patients were randomly assigned to receive enteral probiotics (n = 68) or an inert inulin-based placebo (n = 70) twice a day in addition to routine care. MEASUREMENTS AND MAIN RESULTS: Patients treated with Lactobacillus were significantly less likely to develop microbiologically confirmed VAP compared with patients treated with placebo (40.0 vs. 19.1%; P = 0.007). Although patients treated with probiotics had significantly less Clostridium difficile-associated diarrhea than patients treated with placebo (18.6 vs. 5.8%; P = 0.02), the duration of diarrhea per episode was not different between groups (13.2 ± 7.4 vs. 9.8 ± 4.9 d; P = 0.39). Patients treated with probiotics had fewer days of antibiotics prescribed for VAP (8.6 ± 10.3 vs. 5.6 ± 7.8 d; P = 0.05) and for C. difficile-associated diarrhea (2.1 ± 4.8 SD d vs. 0.5 ± 2.3 d; P = 0.02). No adverse events related to probiotic administration were identified. CONCLUSIONS: These pilot data suggest that L. rhamnosus GG is safe and efficacious in preventing VAP in a select, high-risk ICU population. Clinical trial registered with www.clinicaltrials.gov (NCT00613795).

Sympathetic stimulation increases serum lactate concentrations in patients admitted with sepsis: implications for resuscitation strategies.

BACKGROUND: Diametrically opposed positions exist regarding the deleterious effects of elevated lactate. There are data suggesting that it is a detrimental proxy for tissue hypoperfusion and anaerobic metabolism in sepsis and an alternative viewpoint is that some of the hyperlactatemia produced maybe adaptive. This study was conducted to explore the relationship between serum lactate levels, mean arterial blood pressure (MAP), and sympathetic stimulation in patients with sepsis. METHODS: Retrospective analysis of prospectively collected clinical data from four community-based hospitals and one academic medical center. 8173 adults were included. Heart rate (HR) was used as a surrogate marker of sympathetic stimulation. HR, MAP, and lactate levels were measured upon presentation. RESULTS: MAP and HR interacted to affect lactate levels with the highest levels observed in patients with low MAP and high HR (3.6 mmol/L) and the lowest in patients with high MAP and low HR (2.2 mmol/L). The overall mortality rate was 12.4%. Each 10 beats/min increase in HR increased the odds of death 6.0% (95% CI 2.6% to 9.4%), each 1 mmol/L increase in lactate increased the odds of death 20.8% (95% CI 17.4% to 24.2%), whereas each 10 mmHg increase in MAP reduced the odds of death 12.3% (95% CI 9.2% to 15.4%). However, HR did not moderate or mediate the association between lactate and death. CONCLUSIONS: In septic patients, lactate production was associated with increased sympathetic activity (HR ≥ 90) and hypotension (MAP < 65 mmHg) and was a significant predictor of mortality. Because HR, lactate, and MAP were associated with mortality, our data support the present strategy of using these measurements to gauge severity of illness upon presentation. Since HR did not moderate or mediate the association between lactate and death, criticisms alleging that lactate caused by sympathetic stimulation is adaptive (i.e., less harmful) do not appear substantiated.

Sepsis, the Administration of IV Fluids, and Respiratory Failure: A Retrospective Analysis-SAIFR Study.

BACKGROUND: Although resuscitation with IV fluids is the cornerstone of sepsis management, consensus regarding their association with improvement in clinical outcomes is lacking. RESEARCH QUESTION: Is there a difference in the incidence of respiratory failure in patients with sepsis who received guideline-recommended initial IV fluid bolus of 30 mL/kg or more conservative resuscitation of less than 30 mL/kg? STUDY DESIGN AND METHODS: This was a retrospective analysis of prospectively collected clinical data conducted at an academic medical center in Omaha, Nebraska. We abstracted data from 214 patients with sepsis admitted to a single academic medical center between June 2017 and June 2018. Patients were stratified by receipt of guideline-recommended fluid bolus. The primary outcome was respiratory failure defined as an increase in oxygen flow rate or more intense oxygenation and ventilation support; oxygen requirement and volume were measured at admission, 6 h, 12 h, 24 h, and at discharge. Subgroup analyses were conducted in high-risk patients with congestive heart failure (CHF) as well as those with chronic kidney disease (CKD). RESULTS: A total of 62 patients (29.0%) received appropriate bolus treatment. The overall rate of respiratory failure was not statistically different between patients who received appropriate bolus or did not (40.3% vs 36.8%; P = .634). Likewise, no differences were observed in time to respiratory failure (P = .645) or risk of respiratory failure (adjusted hazard ratio, 1.1 [95% CI, 0.7-1.7]; P = .774). Results were similar within the high-risk CHF and CKD subgroups. INTERPRETATION: In this single-center retrospective study, we found that by broadly defining respiratory failure as an increase in oxygen requirements, a conservative initial IV fluid resuscitation strategy did not correlate with decreased rates of hypoxemic respiratory failure.

Recognition and prevention of nosocomial pneumonia in the intensive care unit and infection control in mechanical ventilation.

Nosocomial pneumonia (NP) is a difficult diagnosis to establish in the critically ill patient due to the presence of underlying cardiopulmonary disorders (e.g., pulmonary contusion, acute respiratory distress syndrome, atelectasis) and the nonspecific radiographic and clinical signs associated with this infection. Additionally, the classification of NP in the intensive care unit setting has become increasingly complex, as the types of patients who develop NP become more diverse. The occurrence of NP is especially problematic as it is associated with a greater risk of hospital mortality, longer lengths of stay on mechanical ventilation and in the intensive care unit, a greater need for tracheostomy, and significantly increased medical care costs. The adverse effects of NP on healthcare outcomes has increased pressure on clinicians and healthcare systems to prevent this infection, as well as other nosocomial infections that complicate the hospital course of patients with respiratory failure. This manuscript will provide a brief overview of the current approaches for the diagnosis of NP and focus on strategies for prevention. Finally, we will provide some guidance on how standardized or protocolized care of mechanically ventilated patients can reduce the occurrence of and morbidity associated with complications like NP.