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.

A Narrative Medicine Pilot Curriculum for Internal Medicine Residents.

Narrative medicine (NM) is the practice of reflecting on patient stories, which can improve physician empathy and has been linked to higher levels of well-being. We implemented a NM curriculum for a large internal medicine residency program and report the curriculum's positive effects.

TIME FROM HOSPITAL ADMISSION TO ONSET OF SEPTIC SHOCK IS ASSOCIATED WITH HIGHER IN-HOSPITAL MORTALITY.

ABSTRACT: Objective: Several studies have shown septic shock developing later during the hospital stay is associated with higher mortality. However, the precise point at which time from hospital admission to the onset of septic shock (admission-shock-onset-time) becomes an independent prognostic marker of mortality remains unknown. This study evaluated the association between admission-shock-onset-time and in-hospital mortality among patients with septic shock and the optimal cutoff period to categorize early- and late-onset septic shock. Method: We conducted a single-center retrospective, observational cohort study at a quaternary academic hospital comprising adult patients with septic shock admitted to a medical intensive care unit (ICU) from January 2011 to December 2020. A multivariable additive logistic regression model was developed to assess if log-transformed admission-shock-onset-time was associated with in-hospital mortality. The thin plate spline function was used to describe the nonlinear relationship between the log-transformed admission-shock-onset-time and in-hospital mortality. The primary outcome was in-hospital mortality, and the secondary outcome was ICU mortality. Results: Two thousand five hundred twenty patients met the inclusion criteria with an overall in-hospital mortality of 37.3%. The log-transformed admission-shock-onset-time was associated with higher in-hospital and ICU mortality even after adjusting for clinical variables. The odds ratio for in-hospital mortality continued to increase throughout the observation period. The adjusted odds ratio exceeded 2 in between 20.1 and 54.6 h, and it surpassed 3 in between 54.6 and 148.4 h of the time from the hospital admission to shock onset. Conclusion: In-hospital mortality continued to rise as admission-shock-onset-time increased in patients with septic shock. No clear dichotomization between early and late septic shock could be ascertained, and this categorization may limit our understanding of the temporal relationship of shock onset to mortality.

Factors Associated With Mortality Among Patients Managed for Large Volume Hemorrhage in a Medical Intensive Care Unit.

PURPOSE: Our goal was to describe resuscitation practices in critically ill medical patients with active hemorrhage requiring large volume resuscitation and identify factors associated with poor outcomes. PATIENTS AND METHODS: This was a single center retrospective observational cohort study. Patients admitted to the medical intensive care unit from 2011 to 2017 who received ≥5 units of packed red blood cells (pRBCs) within 24 h were included. Data including volume of blood products and crystalloid administered, baseline sequential organ failure assessment (SOFA) scores, and outcomes were abstracted. Univariate and multivariate analyses were performed to determine clinical factors associated with hospital mortality. RESULTS: Two hundred forty-six patients were identified. Mean volumes of 2,448 mL of pRBCs and 3.9L of crystalloid were transfused over 24 h. Inpatient mortality for the entire cohort was 48%. Multivariable analysis identified factors associated with hospital mortality; higher BMI (OR 1.047, 95% CI 1.013-1.083), higher ratio of fresh frozen plasma (FFP) to pRBCs (OR 2.744, 95% CI 1.1-6.844), and higher baseline SOFA scores (OR 1.3, 95% CI 1.175-1.437). CONCLUSION: In a cohort of critically ill medical patients undergoing resuscitation for hemorrhage, higher BMI, increased ratio of FFP to pRBCs, and higher SOFA scores were associated with increased mortality. Further studies are needed to clarify resuscitation practices associated with outcomes in this population.

The ED-SED Study: A Multicenter, Prospective Cohort Study of Practice Patterns and Clinical Outcomes Associated With Emergency Department SEDation for Mechanically Ventilated Patients.

OBJECTIVES: To characterize emergency department sedation practices in mechanically ventilated patients, and test the hypothesis that deep sedation in the emergency department is associated with worse outcomes. DESIGN: Multicenter, prospective cohort study. SETTING: The emergency department and ICUs of 15 medical centers. PATIENTS: Mechanically ventilated adult emergency department patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All data involving sedation (medications, monitoring) were recorded. Deep sedation was defined as Richmond Agitation-Sedation Scale of -3 to -5 or Sedation-Agitation Scale of 2 or 1. A total of 324 patients were studied. Emergency department deep sedation was observed in 171 patients (52.8%), and was associated with a higher frequency of deep sedation in the ICU on day 1 (53.8% vs 20.3%; p < 0.001) and day 2 (33.3% vs 16.9%; p = 0.001), when compared to light sedation. Mean (SD) ventilator-free days were 18.1 (10.8) in the emergency department deep sedation group compared to 20.0 (9.8) in the light sedation group (mean difference, 1.9; 95% CI, -0.40 to 4.13). Similar results according to emergency department sedation depth existed for ICU-free days (mean difference, 1.6; 95% CI, -0.54 to 3.83) and hospital-free days (mean difference, 2.3; 95% CI, 0.26-4.32). Mortality was 21.1% in the deep sedation group and 17.0% in the light sedation group (between-group difference, 4.1%; odds ratio, 1.30; 0.74-2.28). The occurrence rate of acute brain dysfunction (delirium and coma) was 68.4% in the deep sedation group and 55.6% in the light sedation group (between-group difference, 12.8%; odds ratio, 1.73; 1.10-2.73). CONCLUSIONS: Early deep sedation in the emergency department is common, carries over into the ICU, and may be associated with worse outcomes. Sedation practice in the emergency department and its association with clinical outcomes is in need of further investigation.

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.

The impact of cardiac dysfunction on acute respiratory distress syndrome and mortality in mechanically ventilated patients with severe sepsis and septic shock: an observational study.

PURPOSE: Acute respiratory distress syndrome (ARDS) is associated with significant mortality and morbidity in survivors. Treatment is only supportive, therefore elucidating modifiable factors that could prevent ARDS could have a profound impact on outcome. The impact that sepsis-associated cardiac dysfunction has on ARDS is not known. MATERIALS AND METHODS: In this retrospective observational cohort study of mechanically ventilated patients with severe sepsis and septic shock, 122 patients were assessed for the impact of sepsis-associated cardiac dysfunction on incidence of ARDS (primary outcome) and mortality. RESULTS: Sepsis-associated cardiac dysfunction occurred in 44 patients (36.1%). There was no association of sepsis-associated cardiac dysfunction with ARDS incidence (p= 0.59) or mortality, and no association with outcomes in patients that did progress to ARDS after admission. Multivariable logistic regression demonstrated that higher BMI was associated with progression to ARDS (adjusted OR 11.84, 95% CI 1.24 to 113.0, p= 0.02). CONCLUSIONS: Cardiac dysfunction in mechanically ventilated patients with sepsis did not impact ARDS incidence, clinical outcome in ARDS patients, or mortality. This contrasts against previous investigations demonstrating an influence of nonpulmonary organ dysfunction on outcome in ARDS. Given the frequency of ARDS as a sequela of sepsis, the impact of cardiac dysfunction on outcome should be further studied.

The impact of serial lactate monitoring on emergency department resuscitation interventions and clinical outcomes in severe sepsis and septic shock: an observational cohort study.

Monitoring in the setting of critical illness must be linked to beneficial therapy to affect clinical outcome. Elevated serum lactate is associated with an increase in mortality in emergency department (ED) patients with severe sepsis and septic shock. The reduction of lactate levels toward normal during acute resuscitation is associated with improved clinical outcomes. The majority of data demonstrating the interventions used to achieve a reduction in lactate levels and the associated clinical outcomes have been obtained during protocolized randomized trials. We therefore conducted a retrospective observational cohort study of 243 adult patients with severe sepsis and septic shock to assess the interventions associated with nonprotocolized serial lactate monitoring and to assess clinical outcomes. A multivariable model was used to assess outcome differences between the serial lactate (SL) and no serial lactate (NL) cohorts. The SL group received more crystalloid resuscitation (3.6 L vs. 2.5 L; P < 0.01), central venous oxygen saturation monitoring (30% vs. 12%; P < 0.01), and central venous pressure monitoring (23.5% vs. 11.8%; P = 0.02). By day 28, a total of 31 patients in the SL group (23.5%) and 44 in the NL group (39.6%) had died. Multivariable logistic regression analysis demonstrated that the lack of serial lactate monitoring was independently associated with mortality (adjusted odds ratio, 2.09; 95% confidence interval [CI], 1.12 - 3.89; P = 0.02). The SL group also showed greater improvement in 24-h Sequential Organ Failure Assessment scores (1.16 vs. 0.19; P = 0.03), decreased intensive care unit length of stay in days (4.6 vs. 6.0; P = 0.04), and more ventilator-free (19.9 vs. 16; P = 0.05) and vasopressor-free (21.6 vs. 17.9; P = 0.02) days. In the setting of routine clinical care, serial lactate monitoring is associated with an increase in crystalloid administration, resuscitation interventions, and improved clinical outcomes in ED patients with severe sepsis and septic shock. This suggests that serial lactate monitoring, targeting a reduction in lactate levels to normal, is a generalizable resuscitation target in the ED.

Mechanical ventilation and acute lung injury in emergency department patients with severe sepsis and septic shock: an observational study.

OBJECTIVES: The objectives were to characterize the use of mechanical ventilation in the emergency department (ED), with respect to ventilator settings, monitoring, and titration and to determine the incidence of progression to acute lung injury (ALI) after admission, examining the influence of factors present in the ED on ALI progression. METHODS: This was a retrospective, observational cohort study of mechanically ventilated patients with severe sepsis and septic shock (June 2005 to May 2010), presenting to an academic ED with an annual census of >95,000 patients. All patients in the study (n = 251) were analyzed for characterization of mechanical ventilation use in the ED. The primary outcome variable of interest was the incidence of ALI progression after intensive care unit (ICU) admission from the ED and risk factors present in the ED associated with this outcome. Secondary analyses included ALI present in the ED and clinical outcomes comparing all patients progressing to ALI versus no ALI. To assess predictors of progression to ALI, significant variables in univariable analyses at a p ≤ 0.10 level were candidates for inclusion in a bidirectional, stepwise, multivariable logistic regression analysis. RESULTS: Lung-protective ventilation was used in 68 patients (27.1%) and did not differ based on ALI status. Delivered tidal volume was highly variable, with a median tidal volume delivered of 8.8 mL/kg ideal body weight (IBW; interquartile range [IQR] = 7.8 to 10.0) and a range of 5.2 to 14.6 mL/kg IBW. Sixty-nine patients (27.5%) in the entire cohort progressed to ALI after admission to the hospital, with a mean (±SD) onset of 2.1 (±1) days. Multivariable logistic regression analysis demonstrated that a higher body mass index (BMI), higher Sequential Organ Failure Assessment (SOFA) score, and ED vasopressor use were associated with progression to ALI. There was no association between ED ventilator settings and progression to ALI. Compared to patients who did not progress to ALI, patients progressing to ALI after admission from the ED had an increase in mechanical ventilator duration, vasopressor dependence, and hospital length of stay (LOS). CONCLUSIONS: Lung-protective ventilation is uncommon in the ED, regardless of ALI status. Given the frequency of ALI in the ED, the progression shortly after ICU admission, and the clinical consequences of this syndrome, the effect of ED-based interventions aimed at reducing the sequelae of ALI should be investigated further.