The association between intravenous fluid resuscitation and mortality in older emergency department patients with suspected infection.

OBJECTIVE: Recent studies suggest that hypotension thresholds in current guidelines might be too low for older patients due to arterial stiffening, possibly leading to insufficient fluid resuscitation. We compared intravenous (IV) fluid volumes that older (≥ 70 years) and younger (< 70 years) patients with suspected infection with similar initial systolic blood pressure (SBP) received in the emergency department (ED) and investigated whether this was associated with in-hospital mortality in older patients. METHODS: This was an observational multicenter study using an existing database in which consecutive ED patients hospitalized with suspected infection were prospectively included. We first compared the fluid volumes older and younger ED patients received per initial SBP category. Patients were then stratified into two SBP categories (≤ or > 120 mmHg; 120 has been suggested to be a better threshold) and thereafter into three fluid volume categories: 0-1 L, 1-2 L, or > 2 L. In each SBP and fluid category, case-mix-adjusted in-hospital mortality was compared between older and younger patients, using multivariable logistic regression analysis. RESULTS: The included 981 (37%) older and 1678 (63%) younger ED patients received similar IV fluid volumes per initial SBP category. Older patients with an initial SBP > 120 mmHg had a higher adjusted OR of 2.06 (95% CI 1.02-4.16), in the 0-1 L category, while this association was not found in the higher fluid categories of 1-2 L or > 2 L. In the SBP ≤ 120 mmHg category, this association was also absent. CONCLUSION: This hypothesis-generating study suggests that older patients with suspected infection may need higher fluid volumes than younger patients, when having a seemingly normal initial SBP.

The association between systolic blood pressure and in-hospital mortality in older emergency department patients who are hospitalised with a suspected infection.

OBJECTIVE: In existing risk stratification and resuscitation guidelines for sepsis, a hypotension threshold of systolic blood pressure (SBP) below 90-100 mmHg is typically used. However, for older patients, the clinical relevance of a SBP in a seemingly 'normal' range (>100 mmHg) is still poorly understood, as they may need higher SBP for adequate tissue perfusion due to arterial stiffening. We therefore investigated the association between SBP and mortality in older emergency department (ED) patients hospitalised with a suspected infection. METHODS: In this observational multicentre study in the Netherlands, we interrogated an existing prospective database of consecutive ED patients hospitalised with a suspected infection between 2011 and 2016. We investigated the association between SBP categories (≤100, 101-120, 121-139, ≥140 mmHg) and in-hospital mortality in patients of 70 years and older. We adjusted for demographics, comorbidity, disease severity and admission to ward/intensive care using multivariable logistic regression. RESULTS: In the 833 included older patients, unadjusted in-hospital mortality increased from 4.7% (n=359) in SBP ≥140 mmHg to 20.8% (n=96) in SBP ≤100 mmHg. SBP categories were linearly associated with case-mix-adjusted in-hospital mortality. The adjusted ORs (95% CI) for ≤100, 101-120 and 121-139 mmHgcompared with the reference of ≥140 mmHg were 3.8 (1.8 to 7.8), 2.8 (1.4 to 5.5) and 1.9 (0.9 to 3.7), respectively. CONCLUSION: In older ED patients hospitalised with a suspected infection, we found an inverse linear association between SBP and case-mix-adjusted in-hospital mortality. Our data suggest that the commonly used threshold for hypotension is not clinically meaningful for risk stratification of older ED patients with a suspected infection.

Lactate ≥2 mmol/L plus qSOFA improves utility over qSOFA alone in emergency department patients presenting with suspected sepsis.

OBJECTIVE: The Sepsis-3 task force recommends the use of the quick Sequential Organ Failure Assessment (qSOFA) score to identify risk for adverse outcomes in patients presenting with suspected infection. Lactate has been shown to predict adverse outcomes in patients with suspected infection. The aim of the study is to investigate the utility of a post hoc lactate threshold (≥2 mmol/L) added qSOFA score (LqSOFA(2) score) to predict primary composite adverse outcomes (mortality and/or ICU stay ≥72 h) in patients presenting to ED with suspected sepsis. METHODS: Retrospective cohort study was conducted on a merged dataset of suspected or proven sepsis patients presenting to ED across multiple sites in Australia and The Netherlands. Patients are identified as candidates for quality improvement initiatives or research studies at respective sites based on local screening procedures. Data-sharing was performed across sites of demographics, qSOFA, SOFA, lactate thresholds and outcome data for included patients. LqSOFA(2) scores were calculated by adding an extra point to qSOFA score in patients who met lactate thresholds of ≥2 mmol/L. RESULTS: In a merged dataset of 12 555 patients where a full qSOFA score and outcome data were available, LqSOFA(2) ≥2 identified more patients with an adverse outcome (sensitivity 65.5%, 95% confidence interval 62.6-68.4) than qSOFA ≥2 (sensitivity 47.6%, 95% confidence interval 44.6- 50.6). The post hoc addition of lactate threshold identified higher proportion of patients at risk of adverse outcomes. CONCLUSIONS: The lactate ≥2 mmol/L threshold-based LqSOFA(2) score performs better than qSOFA alone in identifying risk of adverse outcomes in ED patients with suspected sepsis.

Initial disease severity and quality of care of emergency department sepsis patients who are older or younger than 70 years of age.

OBJECTIVE: Due to atypical symptom presentation older patients are more prone to delayed sepsis recognition. We investigated whether initial disease severity before emergency department (ED) treatment (including treatable acute organ dysfunction), quality of ED sepsis care and the impact on mortality was different between patients older and younger than 70 years. If differences exist, improvements are needed for ED management of older patients at risk for sepsis. METHODS: In this observational multicenter study, ED patients who were hospitalized with a suspected infection were stratified by age <70 and ≥70 years. The presence of treatable and potentially reversible acute organ dysfunction was measured by the RO components of the Predisposition, Infection, Response and Organ dysfunction (PIRO) score, reflecting acute sepsis-related organ dysfunction developed before ED presentation. Quality of care, as assessed by the full compliance with nine quality performance measures and the standardized mortality ratio (SMR: observed/expected in-hospital mortality), was compared between older and younger patients. RESULTS: The RO-components of the PIRO score were 8 (interquartile range; 4-9) in the 833 older patients, twice as high as the 4 (2-8; P<0.001) in the 1537 younger patients. However, full compliance with all nine quality performance measures was achieved in 34.2 (31.0-37.4)% of the older patients, not higher than the 33.0 (30.7-35.4)% in younger patients (P = 0.640). In-hospital mortality was 9.2% (95%-CI, 7.3-11.2) in patients ≥70, twice as high as the 4.6% (3.6-5.6) in patients <70 years, resulting in an SMR (in study period) of ~0.7 in both groups (P>0.05). CONCLUSION: Older sepsis patients are sicker at ED presentation but are not treated more expediently or reliably despite their extra acuity The presence of twice as much treatable acute organ dysfunction before ED treatment suggests that acute organ dysfunction is recognized relatively late by general practitioners or patients in the out of hospital setting.

The most commonly used disease severity scores are inappropriate for risk stratification of older emergency department sepsis patients: an observational multi-centre study.

BACKGROUND: Sepsis recognition in older emergency department (ED) patients is difficult due to atypical symptom presentation. We therefore investigated whether the prognostic and discriminative performance of the five most commonly used disease severity scores were appropriate for risk stratification of older ED sepsis patients (≥70 years) compared to a younger control group (<70 years). METHODS: This was an observational multi-centre study using an existing database in which ED patients who were hospitalized with a suspected infection were prospectively included. Patients were stratified by age < 70 and ≥70 years. We assessed the association with in-hospital mortality (primary outcome) and the area under the curve (AUC) with receiver operator characteristics of the Predisposition, Infection, Response, Organ dysfunction (PIRO), quick Sequential Organ Failure Assessment (qSOFA), Mortality in ED Sepsis (MEDS), and the Modified and National Early Warning (MEWS and NEWS) scores. RESULTS: In-hospital mortality was 9.5% ((95%-CI); 7.4-11.5) in the 783 included older patients, and 4.6% (3.6-5.7) in the 1497 included younger patients. In contrast to younger patients, disease severity scores in older patients associated poorly with mortality. The AUCs of all disease severity scores were poor and ranged from 0.56 to 0.64 in older patients, significantly lower than the good AUC range from 0.72 to 0.86 in younger patients. The MEDS had the best AUC (0.64 (0.57-0.71)) in older patients. In older and younger patients, the newly proposed qSOFA score (Sepsis 3.0) had a lower AUC than the PIRO score (sepsis 2.0). CONCLUSION: The prognostic and discriminative performance of the five most commonly used disease severity scores was poor and less useful for risk stratification of older ED sepsis patients.

Inclusion of emergency department patients in early stages of sepsis in a quality improvement programme has the potential to improve survival: a prospective dual-centre study.

STUDY OBJECTIVE: Sepsis quality improvement programmes typically focus on severe sepsis (ie, with acute organ failure). However, quality of ED care might be improved if these programmes included patients whose progression to severe sepsis could still be prevented (ie, infection without acute organ failure). We compared the impact on mortality of implementing a quality improvement programme among ED patients with a suspected infection with or without acute organ failure. METHODS: This prospective observational study among ED patients hospitalised with suspected infection was conducted in two hospitals in the Netherlands. After stratification by sepsis category (with or without organ failure), in-hospital mortality was compared between a full compliance (all quality performance measures achieved) and an incomplete compliance group. Multivariable logistic regression analysis was used to quantify the impact of full compliance on in-hospital mortality, adjusting for disease severity, disposition and hospital. RESULTS: There were 1732 ED patients and 130 deaths. Full compliance was independently associated with approximately two-thirds reduction in the odds of hospital mortality (adjusted OR of 0.30 (95% CI 0.19 to 0.47), which was similar in patients with and without organ failure. Among the 1379 patients with suspected infection without acute organ failure, there were 64 deaths, 15 (1.1%) in the full compliance group and 49 (3.6%) in the incomplete compliance group (mortality difference 2.5% (95% CI 1.6% to 3.3%)). Among 353 patients with organ failure, there were 66 deaths, 12 (3.4%) in the full compliance compared with 54 (15.3%) in the incomplete compliance group (mortality difference 11.9% (95% CI 8.5% to 15.3%)). Thus, there was a difference of 76 deaths between full and incomplete compliance groups, and 34 (45%) who benefited were those without acute organ failure. CONCLUSIONS: Sepsis quality improvement programmes should incorporate ED patients in earlier stages of sepsis given the potential to reduce in-hospital mortality among this population.

Independent predictors of major adverse cardiovascular events in emergency department patients who are hospitalised with a suspected infection: a retrospective cohort study.

OBJECTIVE: Emergency department (ED) patients hospitalised with a suspected infection have an increased risk for major adverse cardiovascular events (MACE). This study aims to identify independent predictors of MACE after hospital admission which could be used for identification of high-risk patients who may benefit from preventive strategies. SETTING: Dutch tertiary care centre and urban hospital. PARTICIPANTS: Consecutive, hospitalised, ED patients with a suspected infection. DESIGN: This was a secondary analysis using an existing database in which consecutive, hospitalised, ED patients with a suspected infection were prospectively enrolled. Potential independent predictors, including illness severity, as assessed by the Predisposition, Infection, Response, Organ failure (PIRO) score, and classic cardiac risk factors were analysed by multivariable binary logistic regression. Prognostic and discriminative performance of the model was quantified by the Hosmer-Lemeshow test and receiver operator characteristics with area under the curve (AUC) analyses, respectively. Maximum sensitivity and specificity for identification of MACE were calculated. PRIMARY OUTCOME: MACE within 90 days after hospital admission. RESULTS: 36 (2.1%) of the 1728 included patients developed MACE <90 days after ED presentation. Independent predictors of MACE were the RO components of the PIRO score, reflecting acute organ failure, with a corrected OR (OR (95% CI) 1.1 (1.0 to 1.3) per point increase), presence of atrial fibrillation/flutter; OR 3.9 (2.0 to 7.7) and >2 classic cardiovascular risk factors; 2.2 (1.1 to 4.3). The AUC was 0.773, and the goodness-of-fit test had a p value of 0.714. These predictors identified MACE with 75% sensitivity and 70% specificity. CONCLUSIONS: Besides the classical cardiovascular risk factors, atrial fibrillation and signs of acute organ failure were independent risk factors of MACE in ED patients hospitalised with a suspected infection. Future studies should investigate whether preventive measures like antiplatelet therapy should be initialised in hospitalised ED patients with suspected infection and high risk for MACE.

The association between time to antibiotics and relevant clinical outcomes in emergency department patients with various stages of sepsis: a prospective multi-center study.

INTRODUCTION: In early sepsis stages, optimal treatment could contribute to prevention of progression to severe sepsis. Therefore, we investigated if there was an association between time to antibiotics and relevant clinical outcomes in hospitalized emergency department (ED) patients with mild to severe sepsis stages. METHODS: This is a prospective multicenter study in three Dutch EDs. Patients were stratified into three categories of illness severity, as assessed by the predisposition, infection, response, and organ failure (PIRO) score: PIRO score 1 to 7, 8 to 14 and >14 points, reflected low, intermediate, and high illness severity, respectively. Consecutive hospitalized ED patients with a suspected infection who were treated with intravenous antibiotics were eligible to participate in the study. The primary outcome measure was the number of surviving days outside the hospital at day 28 which was used as an inverse measure of hospital length of stay (LOS). The secondary outcome measure was 28-day mortality, taking into account the time to mortality. Multivariable Cox regression analysis was used to estimate the association between time to antibiotics and the primary and secondary outcome measures corrected for confounders, including appropriateness of antibiotics and initial ED resuscitation, in three categories of illness severity. RESULTS: Of the 1,168 included patients, 112 died (10%), while 85% and 95% received antibiotics within three and six hours, respectively. No association between time to antibiotics and surviving days outside the hospital or mortality was found. Only in PIRO group 1 to 7 was delayed administration of antibiotics (>3 hours) associated with an increase in surviving days outside the hospital at day 28 (hazard ratio: 1.46, 95% confidence interval: 1.05 to 2.02 after correction for potential confounders). CONCLUSIONS: In ED patients with mild to severe sepsis who received antibiotics within six hours after ED presentation, a reduction in time to antibiotics was not found to be associated with an improvement in relevant clinical outcomes.