Sepsis Presenting in Hospitals versus Emergency Departments: Demographic, Resuscitation, and Outcome Patterns in a Multicenter Retrospective Cohort.

BACKGROUND: Differences between hospital-presenting sepsis (HPS) and emergency department-presenting sepsis (EDPS) are not well described. OBJECTIVES: We aimed to (1) quantify the prevalence of HPS versus EDPS cases and outcomes; (2) compare HPS versus EDPS characteristics at presentation; (3) compare HPS versus EDPS in process and patient outcomes; and (4) estimate risk differences in patient outcomes attributable to initial resuscitation disparities. DESIGN: Retrospective consecutive-sample cohort. SETTING: Nine hospitals from October 1, 2014, to March 31, 2016. PATIENTS: All hospitalized patients with sepsis or septic shock, as defined by simultaneous (1) infection, (2) ≥2 Systemic Inflammatory Response Syndrome (SIRS) criteria, and (3) ≥1 acute organ dysfunction criterion. EDPS met inclusion criteria while physically in the emergency department (ED). HPS met the criteria after leaving the ED. MEASUREMENTS: We assessed overall HPS versus EDPS contributions to case prevalence and outcomes, and then compared group differences. Process outcomes included 3-hour bundle compliance and discrete bundle elements (eg, time to antibiotics). The primary patient outcome was hospital mortality. RESULTS: Of 11,182 sepsis hospitalizations, 2,509 (22.4%) were hospital-presenting. HPS contributed 785 (35%) sepsis mortalities. HPS had more frequent heart failure (OR: 1.31, CI: 1.18-1.47), renal failure (OR: 1.62, CI: 1.38-1.91), gastrointestinal source of infection (OR: 1.84, CI: 1.48-2.29), euthermia (OR: 1.45, CI: 1.10-1.92), hypotension (OR: 1.85, CI: 1.65-2.08), or impaired gas exchange (OR: 2.46, CI: 1.43-4.24). HPS were admitted less often from skilled nursing facilities (OR: 0.44, CI: 0.32-0.60), had chronic obstructive pulmonary disease (OR: 0.53, CI: 0.36-0.78), tachypnea (OR: 0.76, CI: 0.58-0.98), or acute kidney injury (OR: 0.82, CI: 0.68-0.97). In a propensity-matched cohort (n = 3,844), HPS patients had less than half the odds of 3-hour bundle compliant care (17.0% vs 30.3%, OR: 0.47, CI: 0.40-0.57) or antibiotics within three hours (66.2% vs 83.8%, OR: 0.38, CI: 0.32-0.44) vs EDPS. HPS was associated with higher mortality (31.2% vs 19.3%, OR: 1.90, CI: 1.64-2.20); 23.3% of this association was attributable to differences in initial resuscitation (resuscitation-adjusted OR: 1.69, CI: 1.43-2.00). CONCLUSIONS: HPS differed from EDPS by admission source, comorbidities, and clinical presentation. These patients received markedly less timely initial resuscitation; this disparity explained a moderate proportion of mortality differences.

Predictors, Prevalence, and Outcomes of Early Crystalloid Responsiveness Among Initially Hypotensive Patients With Sepsis and Septic Shock.

OBJECTIVES: The prevalence of responsiveness to initial fluid challenge among hypotensive sepsis patients is unclear. To avoid fluid overload, and unnecessary treatment, it is important to differentiate these phenotypes. We aimed to 1) determine the proportion of hypotensive sepsis patients sustaining favorable hemodynamic response after initial fluid challenge, 2) determine demographic and clinical risk factors that predicted refractory hypotension, and 3) assess the association between timeliness of fluid resuscitation and refractoriness. DESIGN: Secondary analysis of a prospective, multisite, observational, consecutive-sample cohort. SETTING: Nine tertiary and community hospitals over 1.5 years. PATIENTS: Inclusion criteria 1) suspected or confirmed infection, 2) greater than or equal to two systemic inflammatory response syndrome criteria, 3) systolic blood pressure less than 90 mm Hg, greater than 40% decrease from baseline, or mean arterial pressure less than 65 mm Hg. MEASUREMENTS AND MAIN RESULTS: Sex, age, heart failure, renal failure, immunocompromise, source of infection, initial lactate, coagulopathy, temperature, altered mentation, altered gas exchange, and acute kidney injury were used to generate a risk score. The primary outcome was sustained normotension after fluid challenge without vasopressor titration. Among 3,686 patients, 2,350 (64%) were fluid responsive. Six candidate risk factors significantly predicted refractoriness in multivariable analysis: heart failure (odds ratio, 1.43; CI, 1.20-1.72), hypothermia (odds ratio, 1.37; 1.10-1.69), altered gas exchange (odds ratio, 1.33; 1.12-1.57), initial lactate greater than or equal to 4.0 mmol/L (odds ratio, 1.28; 1.08-1.52), immunocompromise (odds ratio, 1.23; 1.03-1.47), and coagulopathy (odds ratio, 1.23; 1.03-1.48). High-risk patients (≥ three risk factors) had 70% higher (CI, 48-96%) refractory risk (19% higher absolute risk; CI, 14-25%) versus low-risk (zero risk factors) patients. Initiating fluids in greater than 2 hours also predicted refractoriness (odds ratio, 1.96; CI, 1.49-2.58). Mortality was 15% higher (CI, 10-18%) for refractory patients. CONCLUSIONS: Two in three hypotensive sepsis patients were responsive to initial fluid resuscitation. Heart failure, hypothermia, immunocompromise, hyperlactemia, and coagulopathy were associated with the refractory phenotype. Fluid resuscitation initiated after the initial 2 hours more strongly predicted refractoriness than any patient factor tested.

Patterns and Outcomes Associated With Timeliness of Initial Crystalloid Resuscitation in a Prospective Sepsis and Septic Shock Cohort.

OBJECTIVES: The objectives of this study were to 1) assess patterns of early crystalloid resuscitation provided to sepsis and septic shock patients at initial presentation and 2) determine the association between time to initial crystalloid resuscitation with hospital mortality, mechanical ventilation, ICU utilization, and length of stay. DESIGN: Consecutive-sample observational cohort. SETTING: Nine tertiary and community hospitals over 1.5 years. PATIENTS: Adult sepsis and septic shock patients captured in a prospective quality improvement database inclusion criteria: suspected or confirmed infection, greater than or equal to two systemic inflammatory response criteria, greater than or equal to one organ-dysfunction criteria. INTERVENTIONS: The primary exposure was crystalloid initiation within 30 minutes or lesser, 31-120 minutes, or more than 120 minutes from sepsis identification. MEASUREMENTS AND MAIN RESULTS: We identified 11,182 patients. Crystalloid initiation was faster for emergency department patients (ß, -141 min; CI, -159 to -125; p < 0.001), baseline hypotension (ß, -39 min; CI, -48 to -32; p < 0.001), fever, urinary or skin/soft-tissue source of infection. Initiation was slower with heart failure (ß, 20 min; CI, 14-25; p < 0.001), and renal failure (ß, 16 min; CI, 10-22; p < 0.001). Five thousand three hundred thirty-six patients (48%) had crystalloid initiated in 30 minutes or lesser versus 2,388 (21%) in 31-120 minutes, and 3,458 (31%) in more than 120 minutes. The patients receiving fluids within 30 minutes had lowest mortality (949 [17.8%]) versus 31-120 minutes (446 [18.7%]) and more than 120 minutes (846 [24.5%]). Compared with more than 120 minutes, the adjusted odds ratio for mortality was 0.76 (CI, 0.64-0.90; p = 0.002) for 30 minutes or lesser and 0.76 (CI, 0.62-0.92; p = 0.004) for 31-120 minutes. When assessed continuously, mortality odds increased by 1.09 with each hour to initiation (CI, 1.03-1.16; p = 0.002). We observed similar patterns for mechanical ventilation, ICU utilization, and length of stay. We did not observe significant interaction for mortality risk between initiation time and baseline heart failure, renal failure, hypotension, acute kidney injury, altered gas exchange, or emergency department (vs inpatient) presentation. CONCLUSIONS: Crystalloid was initiated significantly later with comorbid heart failure and renal failure, with absence of fever or hypotension, and in inpatient-presenting sepsis. Earlier crystalloid initiation was associated with decreased mortality. Comorbidities and severity did not modify this effect.

Early sepsis bundle compliance for non-hypotensive patients with intermediate versus severe hyperlactemia.

OBJECTIVE: To compare the association of 3-h sepsis bundle compliance with hospital mortality in non-hypotensive sepsis patients with intermediate versus severe hyperlactemia. METHODS: This was a cohort study of all non-hypotensive, hyperlactemic sepsis patients captured in a prospective quality-improvement database, treated October 2014 to September 2015 at five tertiary-care centers. We defined sepsis as 1) infection, 2) ≥2 SIRS criteria, and 3) ≥1 organ dysfunction criterion. "Time-zero" was the first time a patient met all sepsis criteria. INCLUSION CRITERIA: systolic blood pressure>90 mmHg, mean arterial pressure>65 mmHg, and serum lactate≥2.2 mmol/L. Primary exposures: 1) intermediate(2.2-3.9 mmol/L) versus severe(≥4.0 mmol/L) hyperlactemia and 2) full 3-h bundle compliance. Bundle elements: The primary outcome was 60-day in-hospital mortality. RESULTS: 2417 patients met inclusion criteria. 704(29%) had lactate≥4.0 mmol/L versus 1775 patients with lactate 2.2-3.9 mmol/L. Compliance was 75% for antibiotics and 53% for fluids. Full-compliance was comparable between lactate groups (n=200(29%) and 488(28%), respectively). We observed 424(17.5%) mortalities: intermediate/non-compliant - 182(14.9%), intermediate/compliant - 41(8.4%), severe/non-compliant - 147(29.2%), severe/compliant - 54(27.0%) [difference-of-differences=4.3%, CI=2.6-5.9%]. In multivariable regression, mortality predictors included severe hyperlactemia (OR=1.99, CI=1.51-2.63) and bundle compliance (OR=0.62, CI=0.42-0.90), and their interaction was significant: p(interaction)=0.022. CONCLUSION: We observed a significant interaction between 3-h bundle compliance and initial hyperlactemia. Bundle compliance may be associated with greater mortality benefit for non-hypotensive sepsis patients with less severe hyperlactemia.

Survival Benefit and Cost Savings From Compliance With a Simplified 3-Hour Sepsis Bundle in a Series of Prospective, Multisite, Observational Cohorts.

OBJECTIVES: To determine mortality and costs associated with adherence to an aggressive, 3-hour sepsis bundle versus noncompliance with greater than or equal to one bundle element for severe sepsis and septic shock patients. DESIGN: Prospective, multisite, observational study following three sequential, independent cohorts, from a single U.S. health system, through their hospitalization. SETTING: Cohort 1: five tertiary and six community hospitals. Cohort 2: single tertiary, academic medical center. Cohort 3: five tertiary and four community hospitals. PATIENTS: Consecutive sample of all severe sepsis and septic shock patients (defined: infection, ≥ 2 systemic inflammatory response syndrome, and hypoperfusive organ dysfunction) identified by a quality initiative. The exposure was full 3-hour bundle compliance. Bundle elements are as follows: 1) blood cultures before antibiotics; 2) parenteral antibiotics administered less than or equal to 180 minutes from greater than or equal to two systemic inflammatory response syndrome "and" lactate ordered, or less than or equal to 60 minutes from "time-zero," whichever occurs earlier; 3) lactate result available less than or equal to 90 minutes postorder; and 4) 30 mL/kg IV crystalloid bolus initiated less than or equal to 30 minutes from "time-zero." Main outcomes were in-hospital mortality (all cohorts) and total direct costs (cohorts 2 and 3). MEASUREMENTS AND MAIN RESULTS: Cohort 1: 5,819 total patients; 1,050 (18.0%) bundle compliant. Mortality: 604 (22.6%) versus 834 (26.5%); CI, 0.9-7.1%; adjusted odds ratio, 0.72; CI, 0.61-0.86; p value is less than 0.001. Cohort 2: 1,697 total patients; 739 (43.5%) bundle compliant. Mortality: 99 (13.4%) versus 171 (17.8%), CI, 1.0-7.9%; adjusted odds ratio, 0.60; CI, 0.44-0.80; p value is equal to 0.001. Mean costs: $14,845 versus $20,056; CI, -$4,798 to -5,624; adjusted ß, -$2,851; CI, -$4,880 to -822; p value is equal to 0.006. Cohort 3: 7,239 total patients; 2,115 (29.2%) bundle compliant. Mortality: 383 (18.1%) versus 1,078 (21.0%); CI, 0.9-4.9%; adjusted odds ratio, 0.84; CI, 0.73-0.96; p value is equal to 0.013. Mean costs: $17,885 versus $22,108; CI, -$2,783 to -5,663; adjusted ß, -$1,423; CI, -$2,574 to -272; p value is equal to 0.015. CONCLUSIONS: In three independent cohorts, 3-hour bundle compliance was associated with improved survival and cost savings.

Association of Fluid Resuscitation Initiation Within 30 Minutes of Severe Sepsis and Septic Shock Recognition With Reduced Mortality and Length of Stay.

STUDY OBJECTIVE: We evaluate the association of intravenous fluid resuscitation initiation within 30 minutes of severe sepsis or septic shock identification in the emergency department (ED) with inhospital mortality and hospital length of stay. We also compare intravenous fluid resuscitation initiated at various times from severe sepsis or septic shock identification's association with the same outcomes. METHODS: This was a review of a prospective, observational cohort of all ED severe sepsis or septic shock patients during 13 months, captured in a performance improvement database at a single, urban, tertiary care facility (90,000 ED visits/year). The primary exposure was initiation of a crystalloid bolus at 30 mL/kg within 30 minutes of severe sepsis or septic shock identification. Secondary analysis compared intravenous fluid initiated within 30, 31 to 60, or 61 to 180 minutes, or when intravenous fluid resuscitation was initiated at greater than 180 minutes or not provided. RESULTS: Of 1,866 subjects, 53.6% were men, 72.5% were white, mean age was 72 years (SD 16.6 years), and mean initial lactate level was 2.8 mmol/L. Eighty-six percent of subjects were administered intravenous antibiotics within 180 minutes; 1,193 (64%) had intravenous fluid initiated within 30 minutes. Mortality was lower in the within 30 minutes group (159 [13.3%] versus 123 [18.3%]; 95% confidence interval [CI] 1.4% to 8.5%), as was median hospital length of stay (6 days [95% CI 6 to 7] versus 7 days [95% CI 7 to 8]). In multivariate regression that included adjustment for age, lactate, hypotension, acute organ dysfunction, and Emergency Severity Index score, intravenous fluid within 30 minutes was associated with lower mortality (odds ratio 0.63; 95% CI 0.46 to 0.86) and 12% shorter length of stay (hazard ratio=1.14; 95% CI 1.02 to 1.27). In secondary analysis, mortality increased with later intravenous fluid resuscitation initiation: 13.3% (≤30 minutes) versus 16.0% (31 to 60 minutes) versus 16.9% (61 to 180 minutes) versus 19.7% (>180 minutes). Median hospital length of stay also increased with later intravenous fluid initiation: 6 days (95% CI 6 to 7 days) versus 7 days (95% CI 6 to 7 days) versus 7 days (95% CI 6 to 8 days) versus 8 days (95% CI 7 to 9 days). CONCLUSION: The time of intravenous fluid resuscitation initiation was associated with improved mortality and could be used as an easier obtained alternative to intravenous fluid completion time as a performance indicator in severe sepsis and septic shock management.