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JAMA Feb 2024Sepsis is a leading cause of death among children worldwide. Current pediatric-specific criteria for sepsis were published in 2005 based on expert opinion. In 2016, the...
IMPORTANCE
Sepsis is a leading cause of death among children worldwide. Current pediatric-specific criteria for sepsis were published in 2005 based on expert opinion. In 2016, the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) defined sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection, but it excluded children.
OBJECTIVE
To update and evaluate criteria for sepsis and septic shock in children.
EVIDENCE REVIEW
The Society of Critical Care Medicine (SCCM) convened a task force of 35 pediatric experts in critical care, emergency medicine, infectious diseases, general pediatrics, nursing, public health, and neonatology from 6 continents. Using evidence from an international survey, systematic review and meta-analysis, and a new organ dysfunction score developed based on more than 3 million electronic health record encounters from 10 sites on 4 continents, a modified Delphi consensus process was employed to develop criteria.
FINDINGS
Based on survey data, most pediatric clinicians used sepsis to refer to infection with life-threatening organ dysfunction, which differed from prior pediatric sepsis criteria that used systemic inflammatory response syndrome (SIRS) criteria, which have poor predictive properties, and included the redundant term, severe sepsis. The SCCM task force recommends that sepsis in children be identified by a Phoenix Sepsis Score of at least 2 points in children with suspected infection, which indicates potentially life-threatening dysfunction of the respiratory, cardiovascular, coagulation, and/or neurological systems. Children with a Phoenix Sepsis Score of at least 2 points had in-hospital mortality of 7.1% in higher-resource settings and 28.5% in lower-resource settings, more than 8 times that of children with suspected infection not meeting these criteria. Mortality was higher in children who had organ dysfunction in at least 1 of 4-respiratory, cardiovascular, coagulation, and/or neurological-organ systems that was not the primary site of infection. Septic shock was defined as children with sepsis who had cardiovascular dysfunction, indicated by at least 1 cardiovascular point in the Phoenix Sepsis Score, which included severe hypotension for age, blood lactate exceeding 5 mmol/L, or need for vasoactive medication. Children with septic shock had an in-hospital mortality rate of 10.8% and 33.5% in higher- and lower-resource settings, respectively.
CONCLUSIONS AND RELEVANCE
The Phoenix sepsis criteria for sepsis and septic shock in children were derived and validated by the international SCCM Pediatric Sepsis Definition Task Force using a large international database and survey, systematic review and meta-analysis, and modified Delphi consensus approach. A Phoenix Sepsis Score of at least 2 identified potentially life-threatening organ dysfunction in children younger than 18 years with infection, and its use has the potential to improve clinical care, epidemiological assessment, and research in pediatric sepsis and septic shock around the world.
Topics: Humans; Child; Shock, Septic; Multiple Organ Failure; Consensus; Sepsis; Systemic Inflammatory Response Syndrome; Organ Dysfunction Scores
PubMed: 38245889
DOI: 10.1001/jama.2024.0179 -
World Journal of Pediatrics : WJP Oct 2023Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, with extremely high mortality. Notably, sepsis is a heterogeneous... (Review)
Review
BACKGROUND
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, with extremely high mortality. Notably, sepsis is a heterogeneous syndrome characterized by a vast, multidimensional array of clinical and biologic features, which has hindered advances in the therapeutic field beyond the current standards.
DATA SOURCES
We used PubMed to search the subject-related medical literature by searching for the following single and/or combination keywords: sepsis, heterogeneity, personalized treatment, host response, infection, epidemiology, mortality, incidence, age, children, sex, comorbidities, gene susceptibility, infection sites, bacteria, fungi, virus, host response, organ dysfunction and management.
RESULTS
We found that host factors (age, biological sex, comorbidities, and genetics), infection etiology, host response dysregulation and multiple organ dysfunctions can all result in different disease manifestations, progression, and response to treatment, which make it difficult to effectively treat and manage sepsis patients.
CONCLUSIONS
Herein, we have summarized contributing factors to sepsis heterogeneity, including host factors, infection etiology, host response dysregulation, and multiple organ dysfunctions, from the key elements of pathogenesis of sepsis. An in-depth understanding of the factors that contribute to the heterogeneity of sepsis will help clinicians understand the complexity of sepsis and enable researchers to conduct more personalized clinical studies for homogenous patients.
Topics: Child; Humans; Multiple Organ Failure; Sepsis
PubMed: 36735197
DOI: 10.1007/s12519-023-00689-8 -
Nephrology, Dialysis, Transplantation :... Dec 2023Sepsis is a host's deleterious response to infection, which could lead to life-threatening organ dysfunction. Sepsis-associated acute kidney injury (SA-AKI) is the most... (Review)
Review
Sepsis is a host's deleterious response to infection, which could lead to life-threatening organ dysfunction. Sepsis-associated acute kidney injury (SA-AKI) is the most frequent organ dysfunction and is associated with increased morbidity and mortality. Sepsis contributes to ≈50% of all AKI in critically ill adult patients. A growing body of evidence has unveiled key aspects of the clinical risk factors, pathobiology, response to treatment and elements of renal recovery that have advanced our ability to detect, prevent and treat SA-AKI. Despite these advancements, SA-AKI remains a critical clinical condition and a major health burden, and further studies are needed to diminish the short and long-term consequences of SA-AKI. We review the current treatment standards and discuss novel developments in the pathophysiology, diagnosis, outcome prediction and management of SA-AKI.
Topics: Adult; Humans; Multiple Organ Failure; Acute Kidney Injury; Kidney; Prognosis; Sepsis; Critical Illness
PubMed: 37401137
DOI: 10.1093/ndt/gfad142 -
Critical Care Clinics Jan 2024Cardiogenic shock (CS) is a life-threatening circulatory failure syndrome which can progress rapidly to irreversible multiorgan failure through self-perpetuating... (Review)
Review
Cardiogenic shock (CS) is a life-threatening circulatory failure syndrome which can progress rapidly to irreversible multiorgan failure through self-perpetuating pathophysiological processes. Recent developments in CS classification have highlighted its etiologic, mechanistic, and hemodynamic heterogeneity. Optimal CS management depends on early recognition, rapid reversal of the underlying cause, and prompt initiation of hemodynamic support.
Topics: Humans; Shock, Cardiogenic; Myocardial Infarction; Multiple Organ Failure; Hemodynamics; Treatment Outcome
PubMed: 37973356
DOI: 10.1016/j.ccc.2023.05.001 -
Molecular Medicine Reports Dec 2023Sepsis is a manifestation of the immune and inflammatory response to infection, which may lead to multi‑organ failure. Health care advances have improved outcomes in... (Review)
Review
Sepsis is a manifestation of the immune and inflammatory response to infection, which may lead to multi‑organ failure. Health care advances have improved outcomes in critical illness, but it still remains the leading cause of death. Septic cardiomyopathy is heart dysfunction brought on by sepsis. Septic cardiomyopathy is a common consequence of sepsis and has a mortality rate of up to 70%. There is a lack of understanding of septic cardiomyopathy pathogenesis; knowledge of its pathogenesis and the identification of potential therapeutic targets may reduce the mortality rate of patients with sepsis and lead to clinical improvements. The present review aimed to summarize advances in the pathogenesis of cardiac dysfunction in sepsis, with a focus on mitochondrial dysfunction, metabolic changes and cell death modalities and pathways. The present review summarized diagnostic criteria and outlook for sepsis treatment, with the goal of identifying appropriate treatment methods for this disease.
Topics: Humans; Sepsis; Heart Diseases; Cardiomyopathies; Multiple Organ Failure
PubMed: 37859613
DOI: 10.3892/mmr.2023.13114 -
JAMA Feb 2024The Society of Critical Care Medicine Pediatric Sepsis Definition Task Force sought to develop and validate new clinical criteria for pediatric sepsis and septic shock...
IMPORTANCE
The Society of Critical Care Medicine Pediatric Sepsis Definition Task Force sought to develop and validate new clinical criteria for pediatric sepsis and septic shock using measures of organ dysfunction through a data-driven approach.
OBJECTIVE
To derive and validate novel criteria for pediatric sepsis and septic shock across differently resourced settings.
DESIGN, SETTING, AND PARTICIPANTS
Multicenter, international, retrospective cohort study in 10 health systems in the US, Colombia, Bangladesh, China, and Kenya, 3 of which were used as external validation sites. Data were collected from emergency and inpatient encounters for children (aged <18 years) from 2010 to 2019: 3 049 699 in the development (including derivation and internal validation) set and 581 317 in the external validation set.
EXPOSURE
Stacked regression models to predict mortality in children with suspected infection were derived and validated using the best-performing organ dysfunction subscores from 8 existing scores. The final model was then translated into an integer-based score used to establish binary criteria for sepsis and septic shock.
MAIN OUTCOMES AND MEASURES
The primary outcome for all analyses was in-hospital mortality. Model- and integer-based score performance measures included the area under the precision recall curve (AUPRC; primary) and area under the receiver operating characteristic curve (AUROC; secondary). For binary criteria, primary performance measures were positive predictive value and sensitivity.
RESULTS
Among the 172 984 children with suspected infection in the first 24 hours (development set; 1.2% mortality), a 4-organ-system model performed best. The integer version of that model, the Phoenix Sepsis Score, had AUPRCs of 0.23 to 0.38 (95% CI range, 0.20-0.39) and AUROCs of 0.71 to 0.92 (95% CI range, 0.70-0.92) to predict mortality in the validation sets. Using a Phoenix Sepsis Score of 2 points or higher in children with suspected infection as criteria for sepsis and sepsis plus 1 or more cardiovascular point as criteria for septic shock resulted in a higher positive predictive value and higher or similar sensitivity compared with the 2005 International Pediatric Sepsis Consensus Conference (IPSCC) criteria across differently resourced settings.
CONCLUSIONS AND RELEVANCE
The novel Phoenix sepsis criteria, which were derived and validated using data from higher- and lower-resource settings, had improved performance for the diagnosis of pediatric sepsis and septic shock compared with the existing IPSCC criteria.
Topics: Humans; Child; Shock, Septic; Multiple Organ Failure; Retrospective Studies; Organ Dysfunction Scores; Sepsis; Hospital Mortality
PubMed: 38245897
DOI: 10.1001/jama.2024.0196 -
Antibiotics (Basel, Switzerland) Jan 2024Toxic shock syndrome (TSS) is a rare, life-threatening, toxin-mediated infectious process linked, in the vast majority of cases, to toxin-producing strains of or . The... (Review)
Review
Toxic shock syndrome (TSS) is a rare, life-threatening, toxin-mediated infectious process linked, in the vast majority of cases, to toxin-producing strains of or . The pathophysiology, epidemiology, clinical presentation, microbiological features, management and outcome of TSS are described in this review. Bacterial superantigenic exotoxins induces unconventional polyclonal lymphocyte activation, which leads to rapid shock, multiple organ failure syndrome, and death. The main described superantigenic exotoxins are toxic shock syndrome toxin-1 (TSST-1) and enterotoxins for and exotoxins (SpE) A, B, and C and streptococcal superantigen A (SsA) for . Staphylococcal TSS can be menstrual or nonmenstrual. Streptococcal TSS is linked to a severe group A streptococcal infection and, most frequently, to a necrotizing soft tissue infection. Management of TSS is a medical emergency and relies on early detection, immediate resuscitation, source control and eradication of toxin production, bactericidal antibiotic treatment, and protein synthesis inhibiting antibiotic administration. The interest of polyclonal intravenous immunoglobulin G administration as an adjunctive treatment for TSS requires further evaluation. Scientific literature on TSS mainly consists of observational studies, clinical cases, and in vitro data; although more data on TSS are required, additional studies will be difficult to conduct due to the low incidence of the disease.
PubMed: 38247655
DOI: 10.3390/antibiotics13010096 -
Hematology. American Society of... Dec 2023Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of excessive and maladaptive inflammation. Primary HLH is most frequently encountered in young children, and,...
Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of excessive and maladaptive inflammation. Primary HLH is most frequently encountered in young children, and, without timely recognition and therapy, can lead to multiorgan failure and death. It is most often diagnosed using the HLH-2004 criteria and by identifying pathological mutations. However, the HLH-2004 criteria are not specific for HLH, and patients can easily fulfill these diagnostic criteria in other proinflammatory states in which HLH-therapy would not be indicated, including hematologic malignancies, infections, and rheumatologic disease. Therefore, great care must be taken to ensure that the specific disease associated with features of HLH is accurately recognized, as consequences of improper treatment can be catastrophic. We propose a diagnostic pathway for patients for whom HLH is on the differential (visual abstract). Importantly, in situations in which the initial diagnostic workup is equivocal or unrevealing, reevaluation for occult malignancy, infection, or rheumatologic disease would be prudent, as occult presentations may be missed on primary evaluation. Temporizing medications can be used in critically ill patients while awaiting secondary evaluation. By using this framework, clinicians will be able to more reliably discern primary HLH from other pro-inflammatory states and thus provide timely, appropriate disease-specific therapy.
Topics: Child; Humans; Child, Preschool; Lymphohistiocytosis, Hemophagocytic; Multiple Organ Failure; Syndrome; Hematologic Neoplasms; Arthritis, Rheumatoid
PubMed: 38066877
DOI: 10.1182/hematology.2023000463 -
British Journal of Anaesthesia Sep 2023Preventing postoperative organ dysfunction is integral to the practice of anaesthesia. Although intraoperative hypotension is associated with postoperative end organ...
Preventing postoperative organ dysfunction is integral to the practice of anaesthesia. Although intraoperative hypotension is associated with postoperative end organ dysfunction, there remains ambiguity with regards to its definition, targets, thresholds for initiating treatment, and ideal treatment modalities.
Topics: Humans; Arterial Pressure; Multiple Organ Failure; Intraoperative Complications; Postoperative Complications; Hypotension
PubMed: 37419749
DOI: 10.1016/j.bja.2023.05.027