Bas de Groot

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

IntroductionIn 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.MethodsThis 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.ResultsOf 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).ConclusionsIn 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.

High-sensitivity cardiac troponin T is an independent predictor of inhospital mortality in emergency department patients with suspected infection: a prospective observational derivation study

Introducion To assess the prognostic and discriminative accuracy of high-sensitivity cardiac troponin T (hs-cTnT) for prediction of inhospital mortality in emergency department (ED) patients with suspected infection. Methods Prospective observational derivation study in ED patients with suspected infection. Prognostic performance of hs-cTnT (divided in four quartiles because of non-linearity) for prediction of inhospital mortality was assessed using multivariable logistic regression, correcting for predisposition, infection, response and organ failure (PIRO) score as a measure of illness severity and quality of ED treatment as quantified by the number of ‘Surviving Sepsis Campaign’ goals achieved. Discriminative power of hs-cTnT was assessed by receiver operator characteristics with area under the curve (AUC) analysis. Results Hs-cTnT (median (IQR) was 57 (25–90) ng/L (n=23) in non-survivors, significantly higher than the 15 (7–28) ng/L in survivors (n=269, p<0.001). Additionally, the lowest quartile of hs-cTnT was a perfect predictor of survival because zero death occurred. Therefore, the second quartile was used as a reference category in the multivariable logistic regression analysis showing that hs-cTnT was an independent predictor of inhospital mortality: Corrected ORs were 2.2 (95% CI 0.4 to 12.1) and 5.8 (1.2 to 27.3) for the 3rd and 4th quartile compared with the 2nd hs-cTnT quartile. The AUCs of hs-TnT was 0.81 (0.74 to 0.88), similar to the AUC of 0.78 (0.68 to 0.87) of the PIRO score (p>0.05). Overall negative predictive value of hs-cTnT was 99%. Conclusions In ED patients with suspected infection, the routinely used biomarker hs-cTnT is an independent predictor of inhospital mortality with excellent discriminative performance. Future studies should focus on the additional value of hs-cTnT to existing risk stratification tools.

Lack of clinically evident signs of organ failure affects ED treatment of patients with severe sepsis

BackgroundIt is not known whether lack of recognition of organ failure explains the low compliance with the “Surviving Sepsis Campaign” (SSC) guidelines. We evaluated whether compliance was higher in emergency department (ED) sepsis patients with clinically recognizable signs of organ failure compared to patients with only laboratory signs of organ failure.MethodsThree hundred twenty-three ED patients with severe sepsis and septic shock were prospectively included. Multivariable binary logistic regression was used to assess if clinical and biochemical signs of organ failure were associated with compliance to a SSC-based resuscitation bundle. In addition, two-way analysis of variance was used to investigate the relation between the predisposition, infection, response and organ failure (PIRO) score (3 groups: 1–7, 8–14, 15–24) as a measure of illness severity and time to antibiotics with disposition to ward or ICU as effect modifier.ResultsOne hundred twenty-five of 323 included sepsis patients with new-onset organ failure were admitted to the ICU, and in all these patients the SSC resuscitation bundle was started. Respiratory difficulty, hypotension and altered mental status as clinically recognizable signs of organ failure were independent predictors of 100% compliance and not illness severity per se. Corrected ORs (95% CI) were 3.38 (1.08–10.64), 2.37 (1.07–5.23) and 4.18 (1.92–9.09), respectively. Septic ED patients with clinically evident organ failure were more often admitted to the ICU compared to a ward (125 ICU admissions, P < 0.05), which was associated with shorter time to antibiotics [ward: 127 (113–141) min; ICU 94 (80–108) min (P = 0.005)].ConclusionsThe presence of clinically evident compared to biochemical signs of organ failure was associated with increased compliance with a SSC-based resuscitation bundle and admission to the ICU, suggesting that recognition of severe sepsis is an important barrier for successful implementation of quality improvement programs for septic patients. In septic ED patients admitted to the ICU, the time to antibiotics was shorter compared to patients admitted to a normal ward.

Impact of the diagnostic process on the accuracy of source identification and time to antibiotics in septic emergency department patients.

Objective Timely administration of effective antibiotics is important in sepsis management. Source-targeted antibiotics are believed to be most effective, but source identification could cause time delays. Objectives: First, to describe the accuracy/time delays of a diagnostic work-up and the association with time to antibiotics in septic emergency department (ED) patients. Second, to assess the fraction in which source-targeted antibiotics could have been administered solely on the basis of patient history and physical examination. Methods Secondary analysis of the prospective observational study on septic ED patients was carried out. The time to test result availability was associated with time to antibiotics. The accuracy of the suspected source of infection in the ED was assessed. For patients with pneumosepsis, urosepsis, and abdominal sepsis, combinations of signs and symptoms were assessed to achieve a maximal positive predictive value for the sepsis source, identifying a subset of patients in whom source-targeted antibiotics could be administered without waiting for diagnostic test results. Results The time to antibiotics increased by 18 (95% confidence interval: 12–24) min/h delay in test result availability (n=323). In 38–79% of patients, antibiotics were administered after additional tests, whereas the ED diagnosis was correct in 68–85% of patients. The maximal positive predictive value of signs and symptoms was 0.87 for patients with pneumosepsis and urosepsis and 0.75 for those with abdominal sepsis. Use of signs and symptoms would have led to correct ED diagnosis in 33% of patients. Conclusion Diagnostic tests are associated with delayed administration of antibiotics to septic ED patients while increasing the diagnostic accuracy to only 68–85%. In one-third of septic ED patients, the choice of antibiotics could have been accurately determined solely on the basis of patient history and physical examination.

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.

Early prediction of hospital admission for emergency department patients: a comparison between patients younger or older than 70 years

Objective The aim of this study was to develop models that predict hospital admission to ED of patients younger and older than 70 and compare their performance. Methods Prediction models were derived in a retrospective observational study of all patients≥18 years old visiting the ED of a university hospital during the first 6 months of 2012. Patients were stratified into two age groups (<70 years old and ≥70 years old). Multivariable logistic regression analysis was used to identify predictors of hospital admission among factors available immediately after patient arrival to the ED. Validation of the prediction models was performed on patients presenting to the ED during the second half of the year 2012. Results 10 807 patients were included in the derivation and 10 480 in the validation cohorts. The strongest independent predictors of hospital admission among the 8728 patients <70 years old were age, sex, triage category, mode of arrival, performance of blood tests, chief complaint, ED revisit, type of specialist, phlebotomised blood sample and all vital signs. The area under the curve (AUC) of the validation cohort for those <70 years old was 0.86 (95% CI 0.85 to 0.87). Among the 2079 patients ≥70 years, the same factors were predictive, except for gender, type of specialist and heart rate; the AUC was 0.77 (95% CI 0.75 to 0.79). The prediction models could identify a group of 10% of patients with the highest risk in whom hospital admission was predicted at ED triage, with a positive predictive value (PPV) of 71% (95% CI 68% to 74%) in younger patients and PPV of 87% (95% CI 81% to 92%) in older patients. Conclusion Demographic and clinical factors readily available early in the ED visit can be useful in identifying patients who are likely to be admitted to the hospital. While the model for the younger patients had a higher AUC, the model for older patients had a higher PPV in identifying the patients at highest risk for admission. Of note, heart rate was not a useful predictor in the older patients.

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.

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

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.

Emergency Department Management and Follow-up of Children with Bicycle Spoke Injuries

BACKGROUND Evidence for a standard x-ray study and cast immobilization in emergency department (ED) management and follow-up of children with bicycle spoke injury (BSI) is absent. OBJECTIVE To describe the injury pattern and outpatient follow-up and care of ED patients with BSI. In addition, patient characteristics predicting the presence of a fracture and long-term follow-up were assessed. METHODS This was a retrospective study including BSI patients < 9 years of age. Kruskal-Wallis test was used to compare groups with a fracture, soft tissue injury, and mild skin abrasion. Multivariable logistic regression analysis was used to identify independent predictors of a fracture and long-term outpatient follow-up. RESULTS Twenty-three percent of 141 included patients had a fracture, with a median (interquartile range) follow-up of 27 (23-40) days. For soft tissue injury and mild abrasions this was 9 (6-14) and 7 (5-9) days, respectively (p < 0.001). No clinical variables could predict a fracture. Fifty-six (40%) patients required no further care after the first outpatient visit at ∼1 week. Triage category yellow and swelling were independent predictors for more than one outpatient visit, besides presence of fracture. Corrected odds ratios (95% confidence interval) were 2.42 (0.99-5.88) and 4.76 (1.38-16.39), respectively. Only 12% of 141 patients had none of these predictors at ED presentation. CONCLUSIONS A quarter of ED patients with BSI have a fracture with no clinical signs that could predict the presence of a fracture, justifying a standard x-ray study in ED management. Only 12% of ED patients with BSI have no fracture and no signs that predict long-term follow-up. In this group, further studies are warranted to investigate the benefit of cast immobilization for fractures and soft tissue injury.

Predictors and Outcomes of Revisits in Older Adults Discharged from the Emergency Department: Predictors and outcomes of ED revisits

To study predictors of emergency department (ED) revisits and the association between ED revisits and 90‐day functional decline or mortality.