Time to Treatment and Mortality during Mandated Emergency Care for Sepsis.
ABSTRACT: BACKGROUND:In 2013, New York began requiring hospitals to follow protocols for the early identification and treatment of sepsis. However, there is controversy about whether more rapid treatment of sepsis improves outcomes in patients. METHODS:We studied data from patients with sepsis and septic shock that were reported to the New York State Department of Health from April 1, 2014, to June 30, 2016. Patients had a sepsis protocol initiated within 6 hours after arrival in the emergency department and had all items in a 3-hour bundle of care for patients with sepsis (i.e., blood cultures, broad-spectrum antibiotic agents, and lactate measurement) completed within 12 hours. Multilevel models were used to assess the associations between the time until completion of the 3-hour bundle and risk-adjusted mortality. We also examined the times to the administration of antibiotics and to the completion of an initial bolus of intravenous fluid. RESULTS:Among 49,331 patients at 149 hospitals, 40,696 (82.5%) had the 3-hour bundle completed within 3 hours. The median time to completion of the 3-hour bundle was 1.30 hours (interquartile range, 0.65 to 2.35), the median time to the administration of antibiotics was 0.95 hours (interquartile range, 0.35 to 1.95), and the median time to completion of the fluid bolus was 2.56 hours (interquartile range, 1.33 to 4.20). Among patients who had the 3-hour bundle completed within 12 hours, a longer time to the completion of the bundle was associated with higher risk-adjusted in-hospital mortality (odds ratio, 1.04 per hour; 95% confidence interval [CI], 1.02 to 1.05; P<0.001), as was a longer time to the administration of antibiotics (odds ratio, 1.04 per hour; 95% CI, 1.03 to 1.06; P<0.001) but not a longer time to the completion of a bolus of intravenous fluids (odds ratio, 1.01 per hour; 95% CI, 0.99 to 1.02; P=0.21). CONCLUSIONS:More rapid completion of a 3-hour bundle of sepsis care and rapid administration of antibiotics, but not rapid completion of an initial bolus of intravenous fluids, were associated with lower risk-adjusted in-hospital mortality. (Funded by the National Institutes of Health and others.).
Project description:Importance:The death of a pediatric patient with sepsis motivated New York to mandate statewide sepsis treatment in 2013. The mandate included a 1-hour bundle of blood cultures, broad-spectrum antibiotics, and a 20-mL/kg intravenous fluid bolus. Whether completing the bundle elements within 1 hour improves outcomes is unclear. Objective:To determine the risk-adjusted association between completing the 1-hour pediatric sepsis bundle and individual bundle elements with in-hospital mortality. Design, Settings, and Participants:Statewide cohort study conducted from April 1, 2014, to December 31, 2016, in emergency departments, inpatient units, and intensive care units across New York State. A total of 1179 patients aged 18 years and younger with sepsis and septic shock reported to the New York State Department of Health who had a sepsis protocol initiated were included. Exposures:Completion of a 1-hour sepsis bundle within 1 hour compared with not completing the 1-hour sepsis bundle within 1 hour. Main Outcomes and Measures:Risk-adjusted in-hospital mortality. Results:Of 1179 patients with sepsis reported at 54 hospitals (mean [SD] age, 7.2 [6.2] years; male, 54.2%; previously healthy, 44.5%; diagnosed as having shock, 68.8%), 139 (11.8%) died. The entire sepsis bundle was completed in 1 hour in 294 patients (24.9%). Antibiotics were administered to 798 patients (67.7%), blood cultures were obtained in 740 patients (62.8%), and the fluid bolus was completed in 548 patients (46.5%) within 1 hour. Completion of the entire bundle within 1 hour was associated with lower risk-adjusted odds of in-hospital mortality (odds ratio [OR], 0.59 [95% CI, 0.38 to 0.93], P?=?.02; predicted risk difference [RD], 4.0% [95% CI, 0.9% to 7.0%]). However, completion of each individual bundle element within 1 hour was not significantly associated with lower risk-adjusted mortality (blood culture: OR, 0.73 [95% CI, 0.51 to 1.06], P?=?.10; RD, 2.6% [95% CI, -0.5% to 5.7%]; antibiotics: OR, 0.78 [95% CI, 0.55 to 1.12], P?=?.18; RD, 2.1% [95% CI, -1.1% to 5.2%], and fluid bolus: OR, 0.88 [95% CI, 0.56 to 1.37], P?=?.56; RD, 1.1% [95% CI, -2.6% to 4.8%]). Conclusions and Relevance:In New York State following a mandate for sepsis care, completion of a sepsis bundle within 1 hour compared with not completing the 1-hour sepsis bundle within 1 hour was associated with lower risk-adjusted in-hospital mortality among patients with pediatric sepsis and septic shock.
Project description:BACKGROUND: There is ample literature available on the association between both time to antibiotics and appropriateness of antibiotics and clinical outcomes from sepsis. In fact, the current state of debate surrounds the balance to be struck between prompt empirical therapy and care in the choice of appropriate antibiotics (both in terms of the susceptibility of infecting organism and minimizing resistance arising from use of broad-spectrum agents). The objective of this study is to determine sepsis bundle compliance and the appropriateness of antimicrobial therapy in patients with severe sepsis and septic shock and its impact on outcomes. MATERIAL: This study was conducted in the ICU of a tertiary care, private hospital in São Paulo, Brazil. A retrospective cohort study was conducted from July 2005 to December 2012 in patients with severe sepsis and septic shock. RESULTS: A total of 1,279 patients were identified with severe sepsis and septic shock, of which 358 (32.1%) had bloodstream infection (BSI). The inpatient mortality rate was 29%. In evaluation of the sepsis bundle, over time there was a progressive increase in serum arterial lactate collection, obtaining blood cultures prior to antibiotic administration, administration of broad-spectrum antibiotics within 1 hour, and administration of appropriate antimicrobials, with statistically significant differences in the later years of the study. We also observed a significant decrease in mortality. In patients with bloodstream infection, after adjustment for other covariates the administration of appropriate antimicrobial therapy was associated with a decrease in mortality in patients with severe sepsis and septic shock (p?=?0.023). CONCLUSIONS: The administration of appropriate antimicrobial therapy was independently associated with a decline in mortality in patients with severe sepsis and septic shock due to bloodstream infection. As protocol adherence increased over time, the crude mortality rate decreased, which reinforces the need to implement institutional guidelines and monitor appropriate antimicrobial therapy compliance.
Project description:Delayed antimicrobials are associated with poor outcomes in adult sepsis, but data relating antimicrobial timing to mortality and organ dysfunction in pediatric sepsis are limited. We sought to determine the impact of antimicrobial timing on mortality and organ dysfunction in pediatric patients with severe sepsis or septic shock.Retrospective observational study.PICU at an academic medical center.One hundred thirty patients treated for severe sepsis or septic shock.None.We determined if hourly delays from sepsis recognition to initial and first appropriate antimicrobial administration were associated with PICU mortality (primary outcome); ventilator-free, vasoactive-free, and organ failure-free days; and length of stay. Median time from sepsis recognition to initial antimicrobial administration was 140 minutes (interquartile range, 74-277 min) and to first appropriate antimicrobial was 177 minutes (90-550 min). An escalating risk of mortality was observed with each hour delay from sepsis recognition to antimicrobial administration, although this did not achieve significance until 3 hours. For patients with more than 3-hour delay to initial and first appropriate antimicrobials, the odds ratio for PICU mortality was 3.92 (95% CI, 1.27-12.06) and 3.59 (95% CI, 1.09-11.76), respectively. These associations persisted after adjustment for individual confounders and a propensity score analysis. After controlling for severity of illness, the odds ratio for PICU mortality increased to 4.84 (95% CI, 1.45-16.2) and 4.92 (95% CI, 1.30-18.58) for more than 3-hour delay to initial and first appropriate antimicrobials, respectively. Initial antimicrobial administration more than 3 hours was also associated with fewer organ failure-free days (16 [interquartile range, 1-23] vs 20 [interquartile range, 6-26]; p = 0.04).Delayed antimicrobial therapy was an independent risk factor for mortality and prolonged organ dysfunction in pediatric sepsis.
Project description:BACKGROUND:Early recognition of sepsis is critical for timely initiation of treatment. The first objective of this study was to assess the timeliness of diagnostic procedures for recognizing sepsis in emergency departments. We define diagnostic procedures as tests used to help diagnose the condition of patients. The second objective was to estimate associations between diagnostic procedures and time to antibiotic treatment, and to estimate associations between time to antibiotic treatment and mortality. METHODS:This observational study from 24 emergency departments in Norway included 1559 patients with infection and at least two systemic inflammatory response syndrome criteria. We estimated associations using linear and logistic regression analyses. RESULTS:Of the study patients, 72.9% (CI 70.7-75.1) had documented triage within 15 minutes of presentation to the emergency departments, 44.9% (42.4-47.4) were examined by a physician in accordance with the triage priority, 44.4% (41.4-46.9) were adequately observed through continual monitoring of signs while in the emergency department, and 25.4% (23.2-27.7) received antibiotics within 1 hour. Delay or non-completion of these key diagnostic procedures predicted a delay of more than 2.5 hours to antibiotic treatment. Patients who received antibiotics within 1 hour had an observed 30-day all-cause mortality of 13.6% (10.1-17.1), in the timespan 2 to 3 hours after admission 5.9% (2.8-9.1), and 4 hours or later after admission 10.5% (5.7-15.3). CONCLUSIONS:Key procedures for recognizing sepsis were delayed or not completed in a substantial proportion of patients admitted to the emergency department with sepsis. Delay or non-completion of key diagnostic procedures was associated with prolonged time to treatment with antibiotics. This suggests a need for systematic improvement in the initial management of patients admitted to emergency departments with sepsis.
Project description:OBJECTIVES:Sepsis, the acute organ dysfunction caused by a dysregulated host response to infection, poses a serious public health burden. Current management includes early detection, initiation of antibiotics and fluids, and source control as necessary. Although observational data suggest that delays of even a few hours in the initiation of antibiotics or IV fluids is associated with survival, these findings are controversial. There are no randomized data in humans, and prior animal studies studied time from experimental manipulation, not from the onset of clinical features of sepsis. Using a recently developed murine cecal ligation and puncture model that precisely monitors physiologic deterioration, we hypothesize that incremental hourly delays in the first dose of antibiotics, in the first bolus of fluid resuscitation, or a combination of the two at a clinically relevant point of physiologic deterioration during polymicrobial sepsis will shorten survival. DESIGN:Randomized laboratory animal experimental trial. SETTING:University basic science laboratory. SUBJECTS:Male C57BL/6J, female C57BL/6J, aged (40-50?wk old) male C57BL/6J, and BALB/C mice. INTERVENTIONS:Mice (n = 200) underwent biotelemetry-enhanced cecal ligation and puncture and were randomized after meeting validated criteria for acute physiologic deterioration. Treatment groups consisted of a single dose of imipenem/cilastatin, a single bolus of 30?mL/kg fluid resuscitation, or a combination of the two. Mice were allocated to receive treatment at the time of meeting deterioration criteria, after a 2-hour delay or after a 4-hour delay. MEASUREMENTS AND MAIN RESULTS:Hourly delays in the initiation of antibiotic therapy led to progressively shortened survival in our model (p < 0.001). The addition of fluid resuscitation was unable to rescue animals, which received treatment 4 hours after meeting enrollment criteria. Systemic inflammation was increased, and host physiology was increasingly deranged with hourly delays to antibiotics. CONCLUSIONS:We conclude that antibiotic therapy is highly time sensitive, and efforts should be made to deliver this critical therapy as early as possible in sepsis, perhaps extending into the first point of medical contact outside the hospital.
Project description:Background: Patients with cancer are at high risk for severe sepsis and septic shock (SS/SSh), and a delay in receiving effective antibiotics is strongly associated with mortality. Delays are due to logistics of clinic flow and drug delivery. In an era of increasing antimicrobial resistance, combination therapy may be superior to monotherapy for patients with SS/SSh. Patients and Methods: At the Seattle Cancer Care Alliance, we implemented the Sepsis STAT Pack (SSP) program to simplify timely and effective provision of empiric antibiotics and other resuscitative care to outpatients with cancer with suspected SS/SSh before hospitalization. Over a 49-month period from January 1, 2008, through January 31, 2012, a total of 162 outpatients with cancer received the intervention. A retrospective cohort study was conducted to determine outcomes, including mortality and adverse events associated with the use of a novel care bundle designed for compatibility of broad-spectrum antibiotics and other supportive care administered concurrently via rapid infusion at fixed doses. Results: Of 162 sequential patients with cancer and suspected SS/SSh who received the SSP, 71 (44%) were diagnosed with SS/SSh. Median age was 53 years and 65% were men; 141 (87%) had hematologic malignancies, 77 (48%) were transplant recipients, and 80 (49%) were neutropenic. Median time to completion of antibiotics was 111 minutes (interquartile range, 60-178 minutes). A total of 71 patients (44%) had bacteremia and 17% of 93 isolates were multidrug-resistant. Possibly related nephrotoxicity occurred in 7 patients, and 30-day mortality occured in 6 of 160 patients (4%), including 3 of 71 (4%) with SS/SSh. Risk of developing SSh or death within 30 days increased 18% (95% CI, 4%-34%) for each hour delay to completion of antibiotics (P=.01). Conclusions: Rapidly administered combination antibiotics and supportive care delivered emergently to ambulatory patients with cancer with suspected SS/SSh was well-tolerated and associated with excellent short-term survival.
Project description:OBJECTIVES:To determine if time to initial antimicrobial is associated with progression of severe sepsis to septic shock. DESIGN:Retrospective cohort. SETTING:Six hundred fifty-six bed urban academic medical center. PATIENTS:Emergency department patients greater than or equal to 18 years old with severe sepsis and/or septic shock and antimicrobial administration within 24 hours. Patients with shock on presentation were excluded. INTERVENTIONS:Not available. MEASUREMENTS AND MAIN RESULTS:We identified 3,929 severe sepsis patients, with overall mortality 12.8%. Nine hundred eighty-four patients (25.0%) progressed to septic shock. The median time to antimicrobial was 3.77 hours (interquartile range = 1.96-6.42) in those who progressed versus 2.76 hours (interquartile range = 1.60-4.82) in those who did not (p < 0.001). Multivariate logistic regression demonstrated that male sex (odds ratio = 1.18; 95% CI, 1.01-1.36), Charlson Comorbidity Index (odds ratio = 1.18; 95% CI, 1.11-1.27), number of infections (odds ratio = 1.05; 95% CI, 1.02-1.08), and time to first antimicrobial (odds ratio = 1.08; 95% CI, 1.06-1.10) were associated with progression. Each hour until initial antimicrobial administration was associated with a 8.0% increase in progression to septic shock. Additionally, time to broad-spectrum antimicrobial was associated with progression (odds ratio = 1.06; 95% CI, 1.05-1.08). Time to initial antimicrobial was also associated with in-hospital mortality (odds ratio = 1.05; 95% CI, 1.03-1.07). CONCLUSIONS:This study emphasizes the importance of early, broad-spectrum antimicrobial administration in severe sepsis patients admitted through the emergency department, as longer time to initial antimicrobial administration is associated with increased progression of severe sepsis to septic shock and increased mortality.
Project description:It has been shown that completion of the "Sepsis 6" within 1 hour reduces mortality (1). This project aims to assess compliance with this standard and evaluate the effectiveness of a sepsis improvement plan in a district general hospital in the UK. A baseline audit was performed, examining case notes of "septic patients" retrospectively (those on intravenous antibiotics). Compliance with each element of the sepsis six plus time to first antibiotic (TTFA) was assessed. A sepsis improvement plan was introduced consisting of staff education, reinforcing vigilance, regular multidisciplinary meetings and incorporating a standardised approach through the use of a sepsis proforma. Following the introduction of this, and after some refinement, the average time to antibiotic fell from 6 hours to 1.4 hours. In conclusion, an educational drive along with a systematic change in processes has seen reduced TTFA along with enhanced compliance with most elements of the sepsis 6. Through continued assessment and further improving upon systematic processes with continued education we would anticipate consistent improvement in the management of septic patients.
Project description:<h4>Background</h4>The aim of this study was to compare completion of the Surviving Sepsis Campaign 3-hour treatment recommendations and patient-centered outcomes between patients with severe sepsis who received a sepsis-specific diagnosis code with those who did not.<h4>Methods</h4>This was a retrospective cohort analysis of adult patients admitted through an academic medical center ED who received an antibiotic and met criteria for severe sepsis. We measured and compared the Surviving Sepsis Campaign 3-hour treatment recommendations along with patient-centered outcomes in patients who were diagnosed with severe sepsis and those who were not.<h4>Results</h4>A total of 5,631 patients were identified (60.6 ± 17.2 years of age; 48.9% women). Less than half (32.8%) received an International Classification of Diseases, ninth revision, diagnosis code of 995.92. Completion of all four bundle components in < 3 hours was low for all patients (8.72%). Therapeutic components (a broad-spectrum antibiotic and IV fluids) were completed more often (31.3%). Those with a diagnosis code received all four bundle components (10.2% vs 7.9%; P < .005), as well as therapeutic components at a higher frequency (36.0% vs 29.0%; P < .001). Patients with a diagnosis code had higher mortality (6.3% vs 2.3%), more frequent ICU admissions (44.7% vs 22.5%), and longer hospitalizations (9.2 ± 6.9 days vs 6.9 ± 6.7 days) than did patients with severe sepsis with no diagnosis code (all P < .001).<h4>Conclusions</h4>Severe sepsis continues to be an underdiagnosed and undertreated condition. Patients who were diagnosed had higher treatment rates yet experienced worse outcomes. Continued investigation is needed to identify factors contributing to diagnosis, treatment, and outcomes in patients with severe sepsis.
Project description:The global incidence of sepsis is increasing, and mortality remains high. The mortality is even higher in resource-poor countries where facilities and equipment are limited. The Surviving Sepsis Campaign (SSC) recommends an updated hour-1 bundle based on the evidence from the International Guidelines for Management of Sepsis and Septic Shock 2018. To reduce mortality from sepsis, compliance with the "bundle" is essential. Data from developing countries like Sri Lanka on the management of sepsis according to the SSC guidelines are not available. Hence, this study looks at the patient characteristics and management of septic patients at a tertiary care hospital in Sri Lanka. Patients admitted to the University Medical Unit of Colombo South Teaching Hospital from January to August 2019 fulfilling the inclusion criteria were included. The hour-1 sepsis bundle adherence, demographic data, and management were recorded. There were 387 patients: 163 males and 224 females. The age range was 15-95 with a mean age of 63. 83.7% were direct admissions while 16.3% were transfers from a peripheral hospital. The most common source of infection was urine (82 (21.2%)) followed by blood stream (105 (27.1%)) and skin and soft tissue (114 (29.5%)). One-hour SSC bundle compliance is as follows: administration of intravenous fluids: 42 (10.9%), blood cultures before antibiotics: 225 (58.1%), first dose antibiotic: 15 (3.9%), and arterial blood gas: 60 (15.5%). Staffing capacity did not make a difference to adherence to the bundle. The study mortality rate was 37 (9.6%). Binary logistic regression indicates that quick sequential organ failure assessment (qSOFA) score is a significant predictor of mortality (chi-square = 35.08, df = 3, and p = 0.001 (<0.05)) with an odds ratio (OR) of 7.529 (95% CI 3.597-14.323). The other predictors, age, sex, adherence to sepsis care bundle, and comorbidities, were not significant. In conclusion, mortality of sepsis is high and adherence to sepsis care bundle is poor in Sri Lanka even at a tertiary care hospital. Education and training of staff are needed to boost adherence. This will in turn improve quality of care and outcomes of septic patients in resource-poor countries.