Hospital-Onset Sepsis Warrants Expanded Investigation and Consideration as a Unique Clinical Entity.

Sepsis causes more than a quarter million deaths among hospitalized adults in the United States each year. Although most cases of sepsis are present on admission, up to one-quarter of patients with sepsis develop this highly morbid and mortal condition while hospitalized. Compared with patients with community-onset sepsis (COS), patients with hospital-onset sepsis (HOS) are twice as likely to require mechanical ventilation and ICU admission, have more than two times longer ICU and hospital length of stay, accrue five times higher hospital costs, and are twice as likely to die. Patients with HOS differ from those with COS with respect to underlying comorbidities, admitting diagnosis, clinical manifestations of infection, and severity of illness. Despite the differences between these patient populations, patients with HOS sepsis are understudied and warrant expanded investigation. Here, we outline important knowledge gaps in the recognition and management of HOS in adults and propose associated research priorities for investigators. Of particular importance are questions regarding standardization of research and clinical case identification, understanding of clinical heterogeneity among patients with HOS, development of tailored management recommendations, identification of impactful prevention strategies, optimization of care delivery and quality metrics, identification and correction of disparities in care and outcomes, and how to ensure goal-concordant care for patients with HOS.

Association between emergency department sepsis order set design and delay to second dose piperacillin-tazobactam administration.

BACKGROUND: Delay to first antibiotic dose in patients with sepsis has been associated with increased mortality. Second dose antibiotic delay has also been linked to worsened patient outcomes. Optimal methods to decrease second dose delay are currently unclear. The primary objective of this study was to evaluate the association between updating an emergency department (ED) sepsis order set design from one-time doses to scheduled antibiotic frequencies and delay to administration of second piperacillin-tazobactam dose. METHODS: This retrospective cohort study was conducted at eleven hospitals in a large, integrated health system and included adult patients treated in the ED with at least one dose of piperacillin-tazobactam ordered through an ED sepsis order set over a two year period. Patients were excluded if they received less than two doses of piperacillin-tazobactam. Midway through the study period, the enterprise-wide ED sepsis order set was updated to include scheduled antibiotic frequencies. Two patient cohorts receiving piperacillin-tazobactam were compared: those in the year before the order set update and those in the year post-update. The primary outcome was major delay, defined as an administration delay >25% of the recommended dosing interval, which was evaluated with multivariable logistic regression and interrupted time series analysis. RESULTS: 3219 patients were included: 1222 in the pre-update group and 1997 in the post-update group. The proportion of patients who experienced major second dose delay was significantly lower in the post-update group (32.7% vs 25.6%, p < 0.01; adjusted OR 0.64, 95% CI 0.52 to 0.78). No between-group difference was detected in the slope of monthly major delay frequency, but there was a significant level change (post-update change -10%, 95% CI -17.9% to -1.9%). CONCLUSIONS: Including scheduled antibiotic frequencies in ED sepsis order sets is a pragmatic mechanism to decrease delays in second antibiotic doses.

Practice Patterns and Outcomes Associated With Early Sedation Depth in Mechanically Ventilated Patients: A Systematic Review and Meta-Analysis.

OBJECTIVES: Emerging data suggest that early deep sedation may negatively impact clinical outcomes. This systematic review and meta-analysis defines and quantifies the impact of deep sedation within 48 hours of initiation of mechanical ventilation, as described in the world's literature. The primary outcome was mortality. Secondary outcomes included hospital and ICU lengths of stay, mechanical ventilation duration, and delirium and tracheostomy frequency. DATA SOURCES: The following data sources were searched: MEDLINE, EMBASE, Scopus, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews and Effects, Cochrane Database of Systematic Reviews databases, ClinicalTrials.gov, conference proceedings, and reference lists. STUDY SELECTION: Randomized controlled trials and nonrandomized studies were included. DATA EXTRACTION: Two reviewers independently screened abstracts of identified studies for eligibility. DATA SYNTHESIS: Nine studies (n = 4,521 patients) published between 2012 and 2017 were included. A random effects meta-analytic model revealed that early light sedation was associated with lower mortality (9.2%) versus deep sedation (27.6%) (odds ratio, 0.34 [0.21-0.54]). Light sedation was associated with fewer mechanical ventilation (mean difference, -2.1; 95% CI, -3.6 to -0.5) and ICU days (mean difference, -3.0 (95% CI, -5.4 to -0.6). Delirium frequency was 28.7% in the light sedation group and 48.5% in the deep sedation group, odds ratio, 0.50 (0.22-1.16). CONCLUSIONS: Deep sedation in mechanically ventilated patients, as evaluated in a small number of qualifying heterogeneous randomized controlled trials and observational studies, was associated with increased mortality and lengths of stay. Interventions targeting early sedation depth assessment, starting in the emergency department and subsequent ICU admission, deserve further investigation and could improve outcome.

Practice patterns and outcomes associated with early sedation depth in mechanically ventilated patients: a systematic review protocol.

INTRODUCTION: Mechanical ventilation is a commonly performed intervention in critically ill patients. Frequently, these patients experience deep sedation early in their clinical course. Emerging data suggest that the practice of early deep sedation may negatively impact patient outcomes. The purpose of this review is to assess the world's literature to describe and determine the impact of early deep sedation on the outcomes of mechanically ventilated patients. METHODS AND ANALYSIS: Randomised controlled trials and non-randomised studies will be eligible for inclusion in this systematic review. With the assistance of a medical librarian, we will comprehensively search MEDLINE, Embase, Scopus, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews and Effects, and Cochrane Database of Systematic Reviews for peer-reviewed literature. Grey literature from appropriate professional society conferences, held from 2010 to 2017, will be reviewed manually. Two authors will independently review all search results, and disagreements will be resolved through arbitration by a third author. If appropriate, meta-analysis will be used for quantitative analysis of the data. Heterogeneity between studies will be assessed using the I2 statistic. ETHICS AND DISSEMINATION: The proposed systematic review will not collect data that are associated with individual patients and does not require ethical approval. Results of this study will contribute to the understanding of early sedation, identify future research targets and guide early care in mechanically ventilated patients. TRIAL REGISTRATION NUMBER: This systematic review has been registered in the international prospective register of systematic reviews (PROSPERO #CRD42017057264).

Prognostic Factors for Long-Term Mortality in Critically Ill Patients Treated With Prolonged Mechanical Ventilation: A Systematic Review.

OBJECTIVES: Long-term survival for patients treated with prolonged mechanical ventilation is generally poor; however, patient-level factors associated with long-term mortality are unclear. Our objective was to systematically review the biomedical literature and synthesize data for prognostic factors that predict long-term mortality in prolonged mechanical ventilation patients. DATA SOURCES: We searched PubMed, CINAHL, and Cochrane Library from 1988 to 2015 for studies on prolonged mechanical ventilation utilizing a comprehensive strategy without language restriction. STUDY SELECTION: We included studies of adults 1) receiving mechanical ventilation for more than or equal to 14 days, 2) admitted to a ventilator weaning unit, or 3) received a tracheostomy for acute respiratory failure. We analyzed articles that used a multivariate analysis to identify patient-level factors associated with long-term mortality (≥ 6 mo from when the patient met criteria for receiving prolonged mechanical ventilation). DATA EXTRACTION: We used a standardized data collection tool and assessed study quality with a customized Newcastle-Ottawa Scale. We abstracted the strength of association between each prognostic factor and long-term mortality. Individual prognostic factors were then designated as strong, moderate, weak, or inconclusive based on an a priori previously published schema. DATA SYNTHESIS: A total of 7,411 articles underwent relevance screening; 419 underwent full article review. We identified 14 articles that contained a multivariate analysis. We abstracted 19 patient-level factors that showed association with long-term mortality. Six factors demonstrated strong strength of evidence for association with the primary outcome: age, vasopressor requirement, thrombocytopenia, preexisting kidney disease, failed ventilator liberation, and acute kidney injury ± hemodialysis requirement. All factors, except preexisting kidney disease and failed ventilator liberation, were measured at the time the patients met criteria for prolonged mechanical ventilation. CONCLUSIONS: Despite the magnitude of the public health challenge posed by the prolonged mechanical ventilation population, only 14 articles in the biomedical literature have tested patient-level factors associated with long-term mortality. Further research is needed to inform optimal patient selection for prolonged mechanical ventilation.

The use of etomidate for rapid sequence induction in septic patients.

There is continued debate about the clinical ramifications of single-dose etomidate for rapid sequence induction (RSI) in patients with sepsis. This history of this debate includes early studies identifying an association between etomidate infusions and mortality with adrenal suppression as a hypothesized mechanism. More recent data describing the high prevalence of adrenal insufficiency in patients with sepsis has prompted additional investigation as to the clinical effects of single-dose etomidate when utilized as an agent in RSI. Acknowledging the small number and heterogeneity of studies on this topic, we feel that the recent meta-analysis by Gu et al. provides an accurate and complete assessment of the existing literature on this topic. We continue to utilize etomidate for the purposes of RSI in this critically ill patient population and feel that the current data supports this position.

Sepsis-associated pulmonary complications in emergency department patients monitored with serial lactate: An observational cohort study.

PURPOSE: Patients with severe sepsis and septic shock are at high risk for development of pulmonary complications, including acute respiratory distress syndrome (ARDS). Serial lactate monitoring is a useful tool to gauge global tissue hypoxia in emergency department (ED) patients with sepsis. We hypothesized that patients undergoing serial lactate monitoring (SL) would demonstrate a decreased incidence of pulmonary complications. METHODS: This is a retrospective observational cohort study of adult severe sepsis and septic shock patients with elevated lactate presenting to a large academic ED. A total of 243 patients were assigned to SL (n=132) or no serial lactate monitoring (NL; n=111). The primary outcome was a composite of pulmonary complications: (1) ARDS development and (2) respiratory failure. RESULTS: Twenty-eight patients (21%) in the SL group and 37 patients (33%) in the NL group developed the primary outcome (P=.03). Multivariate analysis demonstrated an association between the NL group and development of pulmonary complications (adjusted odds ratio [aOR], 2.1; confidence interval [CI], 1.15-3.78). Emergency department mechanical ventilation was independently associated with development of ARDS (aOR, 3.5; 1.8-7.0). In the a priori subgroup of patients mechanically ventilated in the ED (n=97), those who developed ARDS received higher tidal volumes compared to patients who did not develop ARDS (8.7 mL/kg predicted body weight [interquartile range, 7.6-9.5] vs 7.6 [interquartile range, 6.8-9.0]; P<.01). CONCLUSIONS: Serial lactate monitoring is associated with a decrease in major pulmonary complications in severe sepsis and septic shock. Acute respiratory distress syndrome incidence is also influenced by ED-based mechanical ventilation. These results provide 2 potentially modifiable variables to be targeted in future studies to prevent pulmonary complications in this patient subset.