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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 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.

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.

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

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.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.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 (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.

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.

Background:The evolution of compliance and driving pressure in acute respiratory distress syndrome (ARDS) and the effects of time spent on noninvasive respiratory support prior to intubation has not been well studied. We conducted this study to assess the effect of the duration of noninvasive respiratory support prior to intubation (i.e., 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: Retrospective analysis of prospectively collected data from one university-affiliated academic medical center, one a rural magnet hospital, and three suburban community facilities. A total of 589 patients were included: 55 COVID-19 positive, 137 culture positive, and 397 culture negative patients. Static compliance and driving pressure were calculated at each 8-hour ventilator check. Results:Days of pre-intubation noninvasive respiratory support was associated with worse compliance and driving pressure but did not moderate any trajectory. COVID-19 positive patients showed non-statistically significant worsening compliance by 0.08-units per ventilator check (p = .241), whereas COVID-19 negative patients who were either culture positive or negative patients showed statistically significant improvement (0.12 and 0.18, respectively; both p < .05); a statistically similar but inverse pattern was observed for driving pressure. ConclusionIn contrast to non-COVID-19 ARDS, COVID-19 ARDS was associated with a more ominous trajectory with no improvement in static lung 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.

Disclaimer In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. 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, 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.

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.Is prolonged prehospital time an independent risk factor for pneumonia?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.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.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.

Ethylene glycol is a colorless, odorless, sweet-tasting liquid commonly found in antifreeze, as well as in industrial agents. It is regarded as one of the toxic alcohols. Ethylene glycol poisoning usually occurs due to ingestion, and its toxicity is mediated by its metabolites, glycolic acid, and oxalate. These metabolites can cause neurological symptoms, gastrointestinal symptoms, and/or renal failure if not diagnosed and treated promptly. The diagnosis can be very challenging as the test used to detect ethylene glycol in the blood may not be readily available or due to an inaccurate history. The treatment of ethylene glycol poisoning consists of supportive care, sodium bicarbonate, and the use of an antidote (ethanol or fomepizole) which inhibits alcohol dehydrogenase and thereby prevents the formation of toxic metabolites. Patients with advanced poisonings may also require dialysis. The diagnosis is usually suggested by a high anion gap metabolic acidosis and an elevated osmolal gap in the setting of a suspected ingestion. Rarely, the osmolal gap may be close to normal which can delay the diagnosis or lead to a misdiagnosis. We report a case of ethylene glycol ingestion with a near-normal osmolal gap.

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.

Supplemental Digital Content is available in the text., Objectives: Given perceived similarities between coronavirus disease 2019 pneumonia and the acute respiratory distress syndrome, we explored whether awake self-proning improved outcomes in coronavirus disease 2019-infected patients treated in a rural medical center with limited resources during a significant local coronavirus disease 2019 outbreak. Design: Retrospective analysis of prospectively collected clinical data. Setting: Single-center rural community-based medical center in Grand Island, NE. Patients: One hundred five nonintubated, coronavirus disease-infected patients. Interventions: None. Measurements and Main Results: After patients were educated on the benefits of awake self-proning, compliance was voluntary. The primary outcome was need for intubation during the hospital stay; secondary outcomes included serial peripheral capillary oxygen saturation measured by pulse oximetry to the Fio2 ratios, in-hospital mortality, and discharge disposition. Of 105 nonintubated, coronavirus disease-infected patients, 40 tolerated awake self-proning. Patients who were able to prone were younger and had lower disease severity. The risk of intubation was lower in proned patients after adjusting for disease severity using Sequential Organ Failure Assessment scores (adjusted hazard ratio, 0.30; 95% CI, 0.09–0.96; p = 0.043) or Acute Physiology and Chronic Health Evaluation II scores (adjusted hazard ratio, 0.30; 95% CI, 0.10–0.91; p = 0.034). No prone patient died compared with 24.6% of patients who were not prone (p < 0.001; number needed to treat = 5; 95% CI, 3–8). The probability of being discharged alive and peripheral capillary oxygen saturation measured by pulse oximetry to the Fio2 ratios were statistically similar for both groups. Conclusions: Awake self-proning was associated with lower mortality and intubation rates in coronavirus disease 2019-infected patients. Prone positioning appears to be a safe and inexpensive strategy to improve outcomes and spare limited resources. Prospective efforts are needed to better delineate the effect of awake proning on oxygenation and to improve patients’ ability to tolerate this intervention.

BackgroundIntravenous (IV) acetaminophen is used in multimodal analgesia to reduce the amount and duration of opioid use in the postoperative setting.MethodsA systematic review of published randomized controlled trials was conducted to define the opioid-sparing effect of IV acetaminophen in different types of surgeries. Eligible studies included prospective, randomized, double-blind trials of IV acetaminophen compared with either a placebo- or active-treatment group in adult (age ≥18 years) patients undergoing surgery. Trials had to be published in English in a peer-reviewed journal.ResultsA total of 44 treatment cohorts included in 37 studies were included in the systematic analysis. Compared with active- or placebo-control treatments, IV acetaminophen produced a statistically significant opioid-sparing effect in 14 of 44 cohorts (32%). An opioid-sparing effect was more common in placebo-controlled comparisons. Of the 28 placebo treatment comparisons, IV acetaminophen produced an opioid-sparing effect in 13 (46%). IV acetaminophen produced an opioid-sparing effect in only 6% (one out of 16) of the active-control groups. Among the 16 active-control groups, opioid consumption was significantly greater with IV acetaminophen than the active comparator in seven cohorts and not significantly different than the active comparator in eight cohorts.ConclusionsThe results of this systematic analysis demonstrate that IV acetaminophen is not effective in reducing opioid consumption compared with other adjuvant analgesic agents in the postoperative patient. In patients where other adjuvant analgesic agents are contraindicated, IV acetaminophen may be an option.

Although resuscitation with IV fluids is the cornerstone of sepsis management, consensus regarding their association with improvement in clinical outcomes is lacking.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?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).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.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.

ObjectiveHypotension following endotracheal intubation in the ICU is associated with poor outcomes. There is no formal prediction tool to help estimate the onset of this hemodynamic compromise. Our objective was to derive and validate a prediction model for immediate hypotension following endotracheal intubation.MethodsA multicenter, prospective, cohort study enrolling 934 adults who underwent endotracheal intubation across 16 medical/surgical ICUs in the United States from July 2015-January 2017 was conducted to derive and validate a prediction model for immediate hypotension following endotracheal intubation. We defined hypotension as: 1) mean arterial pressure ResultsPost-intubation hypotension developed in 344 (36.8%) patients. In the full cohort, 11 variables were independently associated with hypotension: increasing illness severity; increasing age; sepsis diagnosis; endotracheal intubation in the setting of cardiac arrest, mean arterial pressure ConclusionsA novel multivariable risk score predicted post-intubation hypotension with accuracy in both unstable and stable critically ill patients.Study registrationClinicaltrials.gov identifier: NCT02508948 and Registered Report Identifier: RR2-10.2196/11101.

Objective: To evaluate the potential for drug interactions with oral inhaled medications (OIMs). OIMs include bronchodilators (β-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.

Clinicians have traditionally dichotomized bacteria as friendly commensals or harmful pathogens. However, the line separating the two has become blurred with the recognition that the intestinal microbiome is a complex entity in which species can shift sides—from friend to foe and back again—based on crucial factors in their local environment. Significant disruptions in the homeostasis of the microbiome, a phenomenon called dysbiosis, is increasingly associated with a host of untoward effects. Patients in the ICU are at high risk for dysbiosis given the high rate of antibiotic use, acute changes in diet, and the stress of critical illness. Probiotics are living microbes of human origin that when ingested in sufficient quantities, can colonize sites such as the oropharynx and GI tract and provide benefits to the host. In recent years, we have increasingly explored the utility of using probiotics to reverse the intestinal dysbiosis associated with critical illness, thereby reducing select ICU complications associated with increased morbidity and mortality. Although these preliminary efforts have demonstrated varying degrees of success, our present studies suffer from a host of limitations that hinder the strength of their conclusions and the generalizability of their results. Probiotic investigations have been further hobbled by current regulatory requirements, which were designed to serve as the framework for pharmaceutical research. Although such measures are intended to ensure patient safety, they inadvertently impose barriers that stifle innovation regarding nutraceuticals. This review strives to summarize the current evidence regarding the efficacy and safety of probiotics in the ICU as well as to provide an overview of the obstacles probiotic researchers face going forward.

Introduction Diffuse alveolar hemorrhage (DAH) is bleeding into the alveolar space of the lungs. Pirfenidone is an antifibrotic agent that is approved for the treatment of idiopathic pulmonary fibrosis (IPF). The most commonly reported side effects include gastrointestinal and skin-related events. We present 3 cases of hemoptysis and DAH among patients on pirfenidone therapy for IPF. Case Summaries An 88-year-old female, a 75-year-old male, and a 73-year-old male all with IPF on pirfenidone presented with hemoptysis and chest computed tomography (CT) findings of usual interstitial pneumonia (UIP) with superimposed opacities. In 2 patients, DAH was confirmed with bronchoscopy. Corticosteroids were initiated and pirfenidone discontinued in all patients, and 2 patients improved while the third continued to deteriorate. Nintedanib was initiated in the remaining 2 patients at follow-up visit with no further issues. Discussion IPF is a chronic, progressive, fibrotic interstitial lung disease (ILD) which appears to be increasing in the United States and has a relatively short survival. Nintedanib and pirfenidone were the first Food and Drug Administration (FDA)-approved agents for the treatment of IPF in October 2014. We present 3 cases of DAH in patients with IPF receiving pirfenidone. Symptoms occurred within 2 months of pirfenidone initiation and resolved with discontinuation of pirfenidone and initiation of systemic corticosteroids in 2 patients; however, one case was complicated by concomitant discontinuation of aspirin. The mechanism by which DAH occurred in our patients remains unclear. Conclusion We report the first cases of possible pirfenidone-induced DAH. Further studies are warranted to explore this reaction, but prescribers should be cognizant of this potential issue when choosing to prescribe pirfenidone.

Objectives To report 2 cases of lipoid pneumonia. Summary Lipoid pneumonia is an inflammatory process in the lower airways due to the presence of lipid molecules in the alveoli. Exogenous lipoid pneumonia is due to the inhalation or aspiration of fat-containing substances. Historically, mineral oil is the most common medication cause but there have also been several reports of lipoid pneumonia associated with petroleum jelly, medicated vapor rub, and lip glosses. Two case reports are presented to illustrate the importance of identifying risk factors for lipoid pneumonia. Results Use of the Naranjo algorithm suggested that both cases of lipoid pneumonia were "possibly" due to aspiration of lipid-containing over-the-counter agents. The first case was associated with aspiration of mentholated topical ointment applied intranasally, whereas the second case was attributed to probable aspiration of mineral oil for management of chronic constipation. Conclusion Pharmacists in many practice settings can play an integral role in preventing this condition and screening for patients who may warrant a diagnostic workup. During medication reconciliation, pharmacists should identify all prescription and nonprescription medications used by patients. Patients should specifically be asked about lipid-based over-the-counter products and cosmetic agents.

A proportion of patients with interstitial lung diseases (ILDs) are at risk of developing a progressive-fibrosing phenotype, which is associated with a deterioration in lung function and early mortality. In addition to idiopathic pulmonary fibrosis (IPF), fibrosing ILDs that may present a progressive phenotype include idiopathic nonspecific interstitial pneumonia, connective tissue disease-associated ILDs, hypersensitivity pneumonitis, unclassifiable idiopathic interstitial pneumonia, ILDs related to other occupational exposures and sarcoidosis. Corticosteroids and/or immunosuppressive therapies are sometimes prescribed to patients with these diseases. However, this treatment regimen may not be effective, adequate on its own or well tolerated, suggesting that there is a pressing need for efficacious and better tolerated therapies. Currently, the only approved treatments to slow disease progression in patients with IPF are nintedanib and pirfenidone. Similarities in pathobiological mechanisms leading to fibrosis between IPF and other ILDs that may present a progressive-fibrosing phenotype provide a rationale to suggest that nintedanib and pirfenidone may be therapeutic options for patients with the latter diseases.This review provides an overview of the therapeutic options currently available for patients with fibrosing ILDs, including fibrosing ILDs that may present a progressive phenotype, and explores the status of the randomised controlled trials that are underway to determine the efficacy and safety of nintedanib and pirfenidone.

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.

To identify preoperative factors associated with an increased risk of postoperative pneumonia and subsequently develop and validate a risk calculator.The American College of Surgeons' National Surgical Quality Improvement Program, a multicenter, prospective data set (2007-2008) was used. Univariate and multivariate logistic regression analyses were performed. The 2007 data set (N=211,410) served as the training set, and the 2008 data set (N=257,385) served as the validation set.In the training set, 3825 patients (1.8%) experienced postoperative pneumonia. Patients who experienced postoperative pneumonia had a significantly higher 30-day mortality (17.0% vs 1.5%; P.001). On multivariate logistic regression analysis, 7 preoperative predictors of postoperative pneumonia were identified: age, American Society of Anesthesiologists class, chronic obstructive pulmonary disease, dependent functional status, preoperative sepsis, smoking before operation, and type of operation. The risk model based on the training data set was subsequently validated on the validation data set, with model performance being very similar (C statistic: 0.860 and 0.855, respectively). The high C statistic indicates excellent predictive performance. The risk model was used to develop an interactive risk calculator.Preoperative variables associated with an increased risk of postoperative pneumonia include age, American Society of Anesthesiologists class, chronic obstructive pulmonary disease, dependent functional status, preoperative sepsis, smoking before operation, and type of operation. The validated risk calculator provides a risk estimate for postoperative pneumonia and is anticipated to aid in surgical decision making and informed patient consent.

Background There are few data on dose optimization and clinical outcomes of antimicrobial agents based on patients' weight, despite the rising prevalence of obesity. Because there are physiologic, pharmacologic, and dosing differences related to weight, it is important to evaluate the impact of weight on antimicrobial agents to optimize clinical outcomes. Objectives This study compared effects of weight on efficacy and safety in patients treated with linezolid or vancomycin for complicated skin and skin structure infections (cSSSIs) and nosocomial pneumonia (NP) caused by methicillin-resistant Staphylococcus aureus (MRSA). Methods We analyzed data from 2 clinical trials of patients randomized to receive a fixed dose of linezolid or weight-based dosing of vancomycin for the treatment of cSSSIs or NP caused by MRSA. For each study, patients were stratified into quartiles (Q1–4 [lowest to highest weight, respectively]). Clinical success, microbiologic success, and adverse events (AEs) were evaluated. Results The analysis included 632 patients with cSSSIs (linezolid, n=316; vancomycin, n=316) and 447 patients with NP (linezolid, n=224; vancomycin, n=223). Among patients with cSSSIs, clinical success rates at the study end with fixed-dose linezolid were similar across all weight quartiles and similar to weight-based dosing of vancomycin for Q1–3. Among Q4 (the highest weight quartile [97–295 kg]), clinical success with vancomycin was significantly lower compared with linezolid (69.5% vs 86.2%; P = 0.03). Among patients with NP, no significant differences in success rates between fixed-dose linezolid and weight-based dosing of vancomycin were observed across all quartiles. Frequencies of AEs were consistent across the quartiles for both indications and by treatment. Conclusions Except for Q4 within the vancomycin-treated patients for MRSA cSSSI, the efficacy of fixed-dosed linezolid and weight-based dosing of vancomycin was maintained across all weight quartiles and MRSA infection types. The AEs were consistent with the known safety profiles of each drug regardless of weight quartile. ClinicalTrials.gov identifiers: NCT00087490 and NCT00084266.

Item does not contain fulltext BACKGROUND: Estimating attributable mortality of ventilator-associated pneumonia has been hampered by confounding factors, small sample sizes, and the difficulty of doing relevant subgroup analyses. We estimated the attributable mortality using the individual original patient data of published randomised trials of ventilator-associated pneumonia prevention. METHODS: We identified relevant studies through systematic review. We analysed individual patient data in a one-stage meta-analytical approach (in which we defined attributable mortality as the ratio between the relative risk reductions [RRR] of mortality and ventilator-associated pneumonia) and in competing risk analyses. Predefined subgroups included surgical, trauma, and medical patients, and patients with different categories of severity of illness scores. FINDINGS: Individual patient data were available for 6284 patients from 24 trials. The overall attributable mortality was 13%, with higher mortality rates in surgical patients and patients with mid-range severity scores at admission (ie, acute physiology and chronic health evaluation score [APACHE] 20-29 and simplified acute physiology score [SAPS 2] 35-58). Attributable mortality was close to zero in trauma, medical patients, and patients with low or high severity of illness scores. Competing risk analyses could be done for 5162 patients from 19 studies, and the overall daily hazard for intensive care unit (ICU) mortality after ventilator-associated pneumonia was 1.13 (95% CI 0.98-1.31). The overall daily risk of discharge after ventilator-associated pneumonia was 0.74 (0.68-0.80), leading to an overall cumulative risk for dying in the ICU of 2.20 (1.91-2.54). Highest cumulative risks for dying from ventilator-associated pneumonia were noted for surgical patients (2.97, 95% CI 2.24-3.94) and patients with mid-range severity scores at admission (ie, cumulative risks of 2.49 [1.81-3.44] for patients with APACHE scores of 20-29 and 2.72 [1.95-3.78] for those with SAPS 2 scores of 35-58). INTERPRETATION: The overall attributable mortality of ventilator-associated pneumonia is 13%, with higher rates for surgical patients and patients with a mid-range severity score at admission. Attributable mortality is mainly caused by prolonged exposure to the risk of dying due to increased length of ICU stay. FUNDING: None.

Clostridium difficile is a leading cause of hospital-associated infection in the United States. The purpose of this study is to assess the prevalence of C. difficile infection among mechanically ventilated patients within the ICUs of three academic hospitals and secondarily describe the influence of C. difficile infection on the outcomes of these patients.A retrospective cohort study.ICUs at three teaching hospitals: Barnes-Jewish Hospital, Mayo Clinic, and Creighton University Medical Center over a 2-year period.All hospitalized patients requiring mechanical ventilation for greater than 48 hours within an ICU were eligible for inclusion.None.A total of 5,852 consecutive patients admitted to the ICU were included. Three hundred eighty-six (6.6%) patients with development of C. difficile infection while in the hospital (5.39 cases/1,000 patient days). Septic shock complicating C. difficile infection occurred in 34.7% of patients. Compared with patients without C. difficile infection (n = 5,466), patients with C. difficile infection had a similar hospital mortality rate (25.1% vs 26.3%, p = 0.638). Patients with C. difficile infection were significantly more likely to be discharged to a skilled nursing or rehabilitation facility (42.4% vs 31.9%, p0.001), and the median hospital (23 d vs 15 d, p0.001) and ICU length of stay (12 d vs 8 d, p0.001) were found to be significantly longer in patients with C. difficile infection.Clostridium difficile infection is a relatively common nosocomial infection in mechanically ventilated patients and is associated with prolonged length of hospital and ICU stay, and increased need for skilled nursing care or rehabilitation following hospital discharge.

Background Although COPD affects large sections of the population, its effects on postoperative outcomes have not been rigorously studied. The objectives of this study were to describe the prevalence of COPD in patients undergoing surgery and to analyze the associations between COPD and postoperative morbidity, mortality, and hospital length of stay. Methods Patients with COPD who underwent surgery were identified from the National Surgical Quality Improvement Program database (2007-2008). Univariate and multivariate analyses were performed on this multicenter, prospective data set (N = 468,795). Results COPD was present in 22,576 patients (4.82%). These patients were more likely to be older, men, white, smokers, and taking corticosteroids and had a lower BMI ( P P P P 50 comorbidities through logistic regression modeling, COPD was independently associated with higher postoperative morbidity (OR, 1.35; 95% CI, 1.30-1.40; P P P Conclusions COPD is common among patients undergoing surgery and is associated with increased morbidity, mortality, and length of stay.

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.

Clinicians have traditionally dichotomized bacteria as friendly commensals or harmful pathogens. However, the line separating the two has become blurred with the recognition that the intestinal microbiome is a complex entity in which species can shift sides-from friend to foe and back again-based on crucial factors in their local environment. Significant disruptions in the homeostasis of the microbiome, a phenomenon called dysbiosis, is increasingly associated with a host of untoward effects. Patients in the ICU are at high risk for dysbiosis given the high rate of antibiotic use, acute changes in diet, and the stress of critical illness. Probiotics are living microbes of human origin that when ingested in sufficient quantities, can colonize sites such as the oropharynx and GI tract and provide benefits to the host. In recent years, we have increasingly explored the utility of using probiotics to reverse the intestinal dysbiosis associated with critical illness, thereby reducing select ICU complications associated with increased morbidity and mortality. Although these preliminary efforts have demonstrated varying degrees of success, our present studies suffer from a host of limitations that hinder the strength of their conclusions and the generalizability of their results. Probiotic investigations have been further hobbled by current regulatory requirements, which were designed to serve as the framework for pharmaceutical research. Although such measures are intended to ensure patient safety, they inadvertently impose barriers that stifle innovation regarding nutraceuticals. This review strives to summarize the current evidence regarding the efficacy and safety of probiotics in the ICU as well as to provide an overview of the obstacles probiotic researchers face going forward.

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 (2 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.

BACKGROUND: Although tobacco practices and the effects of tobacco use among the general American population are well described, minimal data exist regarding tobacco use and barriers to smoking cessation among homeless individuals. METHODS: Anonymous, voluntary surveys based on a previously implemented instrument were completed by 100 smoking individuals residing at a homeless shelter. These surveys assessed high-risk smoking behaviors and respondents9 perceived barriers to long-term smoking cessation. RESULTS: Ninety percent of study participants reported engaging in at least one of the high-risk tobacco practices. Nicotine replacement therapy was perceived by respondents to be the most desired form of smoking cessation aid. Excessive stress with use of tobacco smoking to alleviate stress and anxiety was the most significant self-perceived barrier to smoking cessation. CONCLUSIONS: High-risk tobacco practices are remarkably common among smoking homeless individuals. Despite literature consistently showing that non-nicotine tobacco cessation pharmacotherapies (varenicline, buproprion) have higher smoking cessation rates, nicotine replacement monotherapy was perceived as more valuable by survey respondents. Although lack of financial resources was expected to be the biggest barrier to successful cessation, social stressors and the use of smoking to cope with homelessness were perceived as a greater obstacle in this cohort. Given the paucity of data on the long-term effects of the high-risk tobacco behaviors reported by these homeless smokers, this study highlights the need for further investigations regarding tobacco use and tobacco cessation in this vulnerable population.

Patients who require intensive care are a uniquely vulnerable population. Their concurrent comorbidities, altered nutrition, required medications, and impaired barrier function predisposes them to a host of complications including nosocomial infections. Unfortunately, such intensive care unit-acquired infections are increasingly caused by resistant pathogens, further complicating their optimal care. As such, nonantibiotic prophylaxis and/or treatment strategies are particularly appealing in this subset of patients. An increasing amount of literature, both basic science and clinical in nature. suggests that probiotic, prebiotic, and synbiotic therapies may be effective in reducing nosocomial infection rates and the adverse implications of these infections. Although existing synbiotic studies in critically ill populations often suffer from small sample sizes and methodologic limitations, our current collective knowledge suggests that synbiotic therapy is safe and viable across an array of disease states. This review summarizes our current knowledge in this area, including limitations to our current investigations.

Postoperative pneumonia (PP) and respiratory failure (PRF) are known to be the most common nonwound complications after bariatric surgery. Our objective was to identify their current prevalence after bariatric surgery and to study the preoperative factors associated with them using data from the American College of Surgeons' National Surgical Quality Improvement Program.Patients undergoing bariatric surgery were identified from the National Surgical Quality Improvement Program (2006-2008), a multicenter, prospective database. Univariate analysis and multivariate logistic regression analysis were performed.Of 32,889 patients, PP was diagnosed in 187 patients (.6%) and PRF in 204 patients (.6%). The overall 30-day morbidity rate was 6.4%, with PP and PRF accounting for 18.7%. The 30-day mortality rate was greater for the patients with PP and PRF than those without (4.3% versus .16% and 13.7% versus .10%, P.0001). The hospital length of stay was also longer in patients with PP/PRF (P.0001). On multivariate analysis, congestive heart failure (odds ratio 5.3, 95% confidence interval 1.20-23.26) and stroke (odds ratio 4.1, 95% confidence interval 1.42-11.49) were the greatest preoperative risk factors for PP. Previous percutaneous coronary intervention (odds ratio 2.8, 95% confidence interval 1.64-4.74) and dyspnea at rest (odds ratio 2.64, 95% confidence interval 1.13-6.13) were the factors most strongly associated with PRF. Bleeding disorder, age, chronic obstructive pulmonary disease, and type of surgery were risk factors for both (P.05). Smoking also predisposed to PP, and diabetes mellitus, anesthesia time, and increasing weight also predisposed to PRF (P.05 for all).Although PP and PRF are infrequent, they account for one fifth of the postoperative morbidity and are associated with significantly increased 30-day mortality. They can be predicted by various risk factors, emphasizing the importance of patient optimization and careful selection before bariatric surgery.

The focus of this case is a 70-year-old female who was admitted to an assisted living community following a hospitalization for a severe asthma exacerbation. The diagnosis of asthma in the geriatric patient is often under-recognized, misdiagnosed, and improperly managed. Several factors may explain the misclassification and the undertreatment of asthma in the older patient. This case discusses the pharmacotherapeutic management of asthma in the geriatric patient and differentiates the clinical features of asthma from that of chronic obstructive lung disease. The comprehensive management of asthma should include an interprofessional approach because the consultant pharmacist is an essential member of the health care team.

Probiotics are living microorganisms that, when ingested in adequate amounts, provide benefits to the host. The benefits include either a shortened duration of infections or decreased susceptibility to pathogens. Proposed mechanisms of beneficial effects include improving gastrointestinal barrier function, modification of the gut flora by inducing host cell antimicrobial peptides and/or local release of probiotic antimicrobial factors, competition for epithelial adherence, and immunomodulation. With increasing intensive care unit (ICU) antibacterial resistance rates and fewer new antibiotics in the research pipeline, focus has been shifted to non-antibiotic approaches for the prevention and treatment of nosocomial infections. Probiotics offer promise to ICU patients for the prevention of antibiotic-associated diarrhea, Clostridium difficile infections, multiple organ dysfunction syndrome, and ventilator-associated pneumonia. Our current understanding of probiotics is confounded by inconsistency in probiotic strains studied, optimal dosages, study durations, and suboptimal sample sizes. Although probiotics are generally safe in the critically ill, adverse event monitoring must be rigorous in these vulnerable patients. Delineation of clinical differences of various effective probiotic strains, their mechanisms of action, and optimal dosing regimens will better establish the role of probiotics in various disorders. However, probiotic research will likely be hindered in the future given a recent ruling by the U.S. Food and Drug Administration.

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.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.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.

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. 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. 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