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BACKGROUND: Sepsis has a high prevalence within intensive care units, with elevated rates of morbidity and mortality, and high costs. Data on sepsis costs are scarce in the literature, and in developing countries such as Brazil these data are largely unavailable. Enrolled patients were assessed daily in terms of cost-related expenditures such as hospital fees, operating room fees, gas therapy, physiotherapy, blood components transfusion, medications, renal replacement therapy, laboratory analysis and imaging. Standard unit costs (year 2006 values) were based on the Brazilian Medical Association (AMB) price index for medical procedures and the BRASINDICE price index for medications, solutions and hospital consumables. Medical resource utilization was also assessed daily using the Therapeutic Intervention Scoring System (TISS-28). Indirect costs were not included. The median total cost of sepsis was $US9632 (interquartile range [IQR] 4583–18 387; 95% CI 8657, 10 672) per patient, while the median daily ICU cost per patient was $US934 (IQR 735–1170; 95% CI 897, 963). The median daily ICU cost per patient was significantly higher in non-survivors than in survivors, i.e. $US1094 (IQR 888–1341; 95% CI 1058, 1157) and $US826 (IQR 668–982; 95% CI 786, 854), respectively (p < 0.001). For patients admitted to public and private hospitals, we found a median SOFA score at ICU admission of 7.5 and 7.1, respectively (p = 0.02), and the mortality rate was 49.1% and 36.7%, respectively (p = 0.006). Patients admitted to public and private hospitals had a similar length of stay of 10 (IQR 5–19) days versus 9 (IQR 4–16) days (p = 0.091), and the median total direct costs for public ($US9773; IQR 4643–19 221; 95% CI 8503, 10 818) versus private ($US9490; IQR 4305–17 034; 95% CI 7610, 11 292) hospitals did not differ significantly (p = 0.37). OBJECTIVES: To assess the standard direct costs of sepsis management in Brazilian intensive care units (ICUs) and to disclose factors that could affect those costs. Enrolled patients were assessed daily in terms of cost-related expenditures such as hospital fees, operating room fees, gas therapy, physiotherapy, blood components transfusion, medications, renal replacement therapy, laboratory analysis and imaging. Standard unit costs (year 2006 values) were based on the Brazilian Medical Association (AMB) price index for medical procedures and the BRASINDICE price index for medications, solutions and hospital consumables. Medical resource utilization was also assessed daily using the Therapeutic Intervention Scoring System (TISS-28). Indirect costs were not included. The median total cost of sepsis was $US9632 (interquartile range [IQR] 4583–18 387; 95% CI 8657, 10 672) per patient, while the median daily ICU cost per patient was $US934 (IQR 735–1170; 95% CI 897, 963). The median daily ICU cost per patient was significantly higher in non-survivors than in survivors, i.e. $US1094 (IQR 888–1341; 95% CI 1058, 1157) and $US826 (IQR 668–982; 95% CI 786, 854), respectively (p < 0.001). For patients admitted to public and private hospitals, we found a median SOFA score at ICU admission of 7.5 and 7.1, respectively (p = 0.02), and the mortality rate was 49.1% and 36.7%, respectively (p = 0.006). Patients admitted to public and private hospitals had a similar length of stay of 10 (IQR 5–19) days versus 9 (IQR 4–16) days (p = 0.091), and the median total direct costs for public ($US9773; IQR 4643–19 221; 95% CI 8503, 10 818) versus private ($US9490; IQR 4305–17 034; 95% CI 7610, 11 292) hospitals did not differ significantly (p = 0.37).… [ABSTRACT FROM AUTHOR]

Background: The sepsis burden on acute care services in middle-income countries is a cause for concern. We estimated incidence, prevalence, and mortality of sepsis in adult Brazilian intensive care units (ICUs) and association of ICU organisational factors with outcome.Methods: We did a 1-day point prevalence study with follow-up of patients in ICU with sepsis in a nationally representative pseudo-random sample. We produced a sampling frame initially stratified by geographical region. Each stratum was then stratified by hospitals' main source of income (serving general public vs privately insured individuals) and ICU size (ten or fewer beds vs more than ten beds), finally generating 40 strata. In each stratum we selected a random sample of ICUs so as to enrol the total required beds in 1690 Brazilian adult ICUs. We followed up patients until hospital discharge censored at 60 days, estimated incidence from prevalence and length of stay, and generated national estimates. We assessed mortality prognostic factors using random-effects logistic regression models.Findings: On Feb 27, 2014, 227 (72%) of 317 ICUs that were randomly selected provided data on 2632 patients, of whom 794 had sepsis (30·2 septic patients per 100 ICU beds, 95% CI 28·4-31·9). The ICU sepsis incidence was 36·3 per 1000 patient-days (95% CI 29·8-44·0) and mortality was observed in 439 (55·7%) of 788 patients (95% CI 52·2-59·2). Low availability of resources (odds ratio [OR] 1·67, 95% CI 1·02-2·75, p=0·045) and adequacy of treatment (OR 0·56, 0·37-0·84, p=0·006) were independently associated with mortality. The projected incidence rate is 290 per 100 000 population (95% CI 237·9-351·2) of adult cases of ICU-treated sepsis per year, which yields about 420 000 cases annually, of whom 230 000 die in hospital.Interpretation: The incidence, prevalence, and mortality of ICU-treated sepsis is high in Brazil. Outcome varies considerably, and is associated with access to adequate resources and treatment. Our results show the burden of sepsis in resource-limited settings, highlighting the need to establish programmes aiming for sepsis prevention, early diagnosis, and adequate treatment.Funding: Fundação de Apoio a Pesquisa do Estado de São Paulo (FAPESP). [ABSTRACT FROM AUTHOR]

Competing Interests: Dr. Evans’ institution received funding from the National Institute of Child Health and Human Development; he received support for article research from the National Institutes of Health. Dr. Argent received funding for provision of medical expert opinions and guest speaker fees. Dr. Menon disclosed they are Children’s Hospital of Eastern Ontario Foundation Research Chair in Pediative Intensive Care. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Paediatric critical care units are designed for children at a vulnerable stage of development, yet the evidence base for practice and policy in paediatric critical care remains scarce. In this Health Policy, we present a roadmap providing strategic guidance for international paediatric critical care trials. We convened a multidisciplinary group of 32 paediatric critical care experts from six continents representing paediatric critical care research networks and groups. The group identified key challenges to paediatric critical care research, including lower patient numbers than for adult critical care, heterogeneity related to cognitive development, comorbidities and illness or injury, consent challenges, disproportionately little research funding for paediatric critical care, and poor infrastructure in resource-limited settings. A seven-point roadmap was proposed: (1) formation of an international paediatric critical care research network; (2) development of a web-based toolkit library to support paediatric critical care trials; (3) establishment of a global paediatric critical care trial repository, including systematic prioritisation of topics and populations for interventional trials; (4) development of a harmonised trial minimum set of trial data elements and data dictionary; (5) building of infrastructure and capability to support platform trials; (6) funder advocacy; and (7) development of a collaborative implementation programme. Implementation of this roadmap will contribute to the successful design and conduct of trials that match the needs of globally diverse paediatric populations., Competing Interests: Declaration of interests LJS received grants from the Swiss Personalized Health Network, Personalized Health-Related Technologies Switzerland, Nomis Foundation, Thomas & Doris Ammann Foundation, National Institutes of Health (NIH), National Health and Medical Research Council, and Medical Research Future Funds. KSG received support from a National Health and Medical Research Council Emerging Leader Fellowship. BMM received grants from EuroQoL and the Society of Critical Care Medicine; and serves as President of the World Federation of Pediatric Intensive and Critical Care Societies and the Critical Care Society of South Africa. NN received grants from Actuated Medical and Philips Respironics. AA received travel support from the WHO. JHL received grants from the Thrasher Foundation (USA) and the National Research Medical Council (Singapore). MJP received grants from the National Institute for Health and Care Research Health Technology Assessment and serves on the general funding committee. JF-S received grants from the Universidad de La Sabana. HRF received a grant from NIH. PF received grants from the Canadian Institutes of Health Research. MCJK received a grant from NIH and consultancy fees from Metran. KM received funding from the Children's Hospital of Eastern Ontario Foundation; and is chair of the Canadian Critical Care Trials Group., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Abstract: Early recognition of septic shock and its treatment are key factors for limiting progression to multiple organ dysfunction and death. Lactate, a byproduct of metabolic pathways, is usually elevated in tissue hypoperfusion and shock and is associated with poor prognosis in sepsis. As a biomarker, it may help the clinician in risk stratification, and the identification and treatment of sepsis. In this article, we provide an update on lactate's pathophysiology and role in diagnosis, treatment, and prognosis in children with sepsis and septic shock., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Sepsis is a major contributor to poor child health outcomes around the world. The high morbidity, mortality, and societal cost associated with paediatric sepsis render it a global health priority, as summarised in Paper 1 of this Series. Sepsis is characterised by a dysregulated host response to infection that manifests as organ failure, and children are uniquely susceptible to sepsis, as discussed in Paper 2. The focus of this third Series paper is quality improvement in paediatric sepsis. The 2017 WHO resolution on sepsis outlined key aims to reduce the burden of sepsis. As of 2024, only a small number of countries have implemented systematic, paediatric-focused quality improvement programmes to raise sepsis awareness, enhance recognition of sepsis, promote timely treatment, and provide long-term support for paediatric sepsis survivors. We examine programme successes and systematic barriers to quality improvement targeting paediatric sepsis. We highlight the need for programme design to consider the entire patient journey, starting with prevention, caregiver awareness, recognition at home, education of the health-care workforce, development of health-care systems, and establishment of long-term family and survivor support extending beyond the intensive care unit. Building on lessons learnt from existing quality improvement programmes, we outline implementation strategies and measures to enable benchmarking. Ultimately, quality improvement on a global scale can only be accelerated through a global learning platform focusing on paediatric sepsis., Competing Interests: Declaration of interests LJS received grants from the Swiss Personalized Health Network, Australian National Health and Medical Research Council, Medical Research Future Fund, and US National Institutes of Health (R01HD105939). All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Septic shock is a leading cause of hospitalisation, morbidity, and mortality for children worldwide. In 2020, the paediatric Surviving Sepsis Campaign (SSC) issued evidence-based recommendations for clinicians caring for children with septic shock and sepsis-associated organ dysfunction based on the evidence available at the time. There are now more trials from multiple settings, including low-income and middle-income countries (LMICs), addressing optimal fluid choice and amount, selection and timing of vasoactive infusions, and optimal monitoring and therapeutic endpoints. In response to developments in adult critical care to trial personalised haemodynamic management algorithms, it is timely to critically reassess the current state of applying SSC guidelines in LMIC settings. In this Viewpoint, we briefly outline the challenges to improve sepsis care in LMICs and then discuss three key concepts that are relevant to management of children with septic shock around the world, especially in LMICs. These concepts include uncertainties surrounding the early recognition of paediatric septic shock, choices for initial haemodynamic support, and titration of ongoing resuscitation to therapeutic endpoints. Specifically, given the evolving understanding of clinical phenotypes, we focus on the controversies surrounding the concepts of early fluid resuscitation and vasoactive agent use, including insights gained from experience in LMICs and high-income countries. We outline the key components of sepsis management that are both globally relevant and translatable to low-resource settings, with a view to open the conversation to the large variety of treatment pathways, especially in LMICs. We emphasise the role of simple and easily available monitoring tools to apply the SSC guidelines and to tailor individualised support to the patient's cardiovascular physiology., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Public hospitals in emerging countries pose a challenge to quality improvement initiatives in sepsis. Our objective was to evaluate the results of a quality improvement initiative in sepsis in a network of public institutions and to assess potential differences between institutions that did or did not achieve a reduction in mortality., Methods: We conducted a prospective study of patients with sepsis or septic shock. We collected baseline data on compliance with the Surviving Sepsis Campaign 6-h bundles and mortality. Afterward, we initiated a multifaceted quality improvement initiative for patients with sepsis or septic shock in all hospital sectors. The primary outcome was hospital mortality over time. The secondary outcomes were the time to sepsis diagnosis and compliance with the entire 6-h bundles throughout the intervention. We defined successful institutions as those where the mortality rates decreased significantly over time, using a logistic regression model. We analyzed differences over time in the secondary outcomes by comparing the successful institutions with the nonsuccessful ones. We assessed the predictors of in-hospital mortality using logistic regression models. All tests were two-sided, and a p value less than 0.05 indicated statistical significance., Results: We included 3435 patients from the emergency departments (50.7%), wards (34.1%), and intensive care units (15.2%) of 9 institutions. Throughout the intervention, there was an overall reduction in the risk of death, in the proportion of septic shock, and the time to sepsis diagnosis, as well as an improvement in compliance with the 6-h bundle. The time to sepsis diagnosis, but not the compliance with bundles, was associated with a reduction in the risk of death. However, there was a significant reduction in mortality in only two institutions. The reduction in the time to sepsis diagnosis was greater in the successful institutions. By contrast, the nonsuccessful sites had a greater increase in compliance with the 6-h bundle., Conclusions: Quality improvement initiatives reduced sepsis mortality in public Brazilian institutions, although not in all of them. Early recognition seems to be a more relevant factor than compliance with the 6-h bundle.

Importance: The effectiveness of checklists, daily goal assessments, and clinician prompts as quality improvement interventions in intensive care units (ICUs) is uncertain., Objective: To determine whether a multifaceted quality improvement intervention reduces the mortality of critically ill adults., Design, Setting, and Participants: This study had 2 phases. Phase 1 was an observational study to assess baseline data on work climate, care processes, and clinical outcomes, conducted between August 2013 and March 2014 in 118 Brazilian ICUs. Phase 2 was a cluster randomized trial conducted between April and November 2014 with the same ICUs. The first 60 admissions of longer than 48 hours per ICU were enrolled in each phase., Interventions: Intensive care units were randomized to a quality improvement intervention, including a daily checklist and goal setting during multidisciplinary rounds with follow-up clinician prompting for 11 care processes, or to routine care., Main Outcomes and Measures: In-hospital mortality truncated at 60 days (primary outcome) was analyzed using a random-effects logistic regression model, adjusted for patients' severity and the ICU's baseline standardized mortality ratio. Exploratory secondary outcomes included adherence to care processes, safety climate, and clinical events., Results: A total of 6877 patients (mean age, 59.7 years; 3218 [46.8%] women) were enrolled in the baseline (observational) phase and 6761 (mean age, 59.6 years; 3098 [45.8%] women) in the randomized phase, with 3327 patients enrolled in ICUs (n = 59) assigned to the intervention group and 3434 patients in ICUs (n = 59) assigned to routine care. There was no significant difference in in-hospital mortality between the intervention group and the usual care group, with 1096 deaths (32.9%) and 1196 deaths (34.8%), respectively (odds ratio, 1.02; 95% CI, 0.82-1.26; P = .88). Among 20 prespecified secondary outcomes not adjusted for multiple comparisons, 6 were significantly improved in the intervention group (use of low tidal volumes, avoidance of heavy sedation, use of central venous catheters, use of urinary catheters, perception of team work, and perception of patient safety climate), whereas there were no significant differences between the intervention group and the control group for 14 outcomes (ICU mortality, central line-associated bloodstream infection, ventilator-associated pneumonia, urinary tract infection, mean ventilator-free days, mean ICU length of stay, mean hospital length of stay, bed elevation to ≥30°, venous thromboembolism prophylaxis, diet administration, job satisfaction, stress reduction, perception of management, and perception of working conditions)., Conclusions and Relevance: Among critically ill patients treated in ICUs in Brazil, implementation of a multifaceted quality improvement intervention with daily checklists, goal setting, and clinician prompting did not reduce in-hospital mortality., Trial Registration: clinicaltrials.gov Identifier: NCT01785966.