Metabolic resuscitation in pediatric sepsis: a narrative review
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SUBMITTER: Schlapbach L
PROVIDER: S-EPMC8578751 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveThe objective of this narrative review is to outline the current epidemiology and interventional research within the context of sepsis recovery, and to provide a summary of key priorities for future work in this area.BackgroundMorbidity and mortality secondary to sepsis disproportionately affects children, especially those in low- and middle-income countries (LMICs), where over 85% of global cases and deaths occur. These regions are plagued by poorly resilient health systems, widespread socio-economic deprivation and unique vulnerabilities such as malnutrition. Reducing the overall burden of sepsis will require a multi-pronged strategy that addresses all three important periods along the sepsis care continuum - pre-facility, facility and post-facility. Of these aspects, post-facility issues have been largely neglected in research, practice and policy, and are thus the focus of this review.MethodsRelevant data for this review was identified through a literature search using PubMed, through a review of the citations of select systematic reviews and from the personal repositories of articles collected by the authors. Data is presented within three sections. The first two sections on the short and long-term outcomes among sepsis survivors each outline the epidemiology as well as review relevant interventional research done. Where clear gaps exist, these are stated. The third section focuses on priorities for future research. This section highlights the importance of data (and data systems) and of innovative interventional approaches, as key areas to improve research of post-sepsis outcomes in children.ConclusionsDuring the initial post-facility period, mortality is high with as many children dying during this period as during the acute period of hospitalization, mostly due to recurrent illness (including infections) which are associated with malnutrition and severe acute disease. Long-term outcomes, often labelled as post-sepsis syndrome (PSS), are characterized by a lag in developmental milestones and suboptimal quality of life (QoL). While long-term outcomes have not been well characterized in resource limited settings, they are well described in high-income countries (HICs), and likely are important contributors to long-term morbidity in resource limited settings. The paucity of interventional research to improve post-discharge outcomes (short- or long-term) is a clear gap in addressing its burden. A focus on the development of improved data systems for collecting routine data, standardized definitions and terminology and a health-systems approach in research need to be prioritized during any efforts to improve outcomes during the post-sepsis phase.
| S-EPMC8578768 | biostudies-literature
Project description:BackgroundGrowing evidence associates organ dysfunction(s) with impaired metabolism in sepsis. Recent research has increased our understanding of the role of substrate utilization and mitochondrial dysfunction in the pathophysiology of sepsis-related organ dysfunction. The purpose of this review is to present this evidence as a coherent whole and to highlight future research directions.Main textSepsis is characterized by systemic and organ-specific changes in metabolism. Alterations of oxygen consumption, increased levels of circulating substrates, impaired glucose and lipid oxidation, and mitochondrial dysfunction are all associated with organ dysfunction and poor outcomes in both animal models and patients. The pathophysiological relevance of bioenergetics and metabolism in the specific examples of sepsis-related immunodeficiency, cerebral dysfunction, cardiomyopathy, acute kidney injury and diaphragmatic failure is also described.ConclusionsRecent understandings in substrate utilization and mitochondrial dysfunction may pave the way for new diagnostic and therapeutic approaches. These findings could help physicians to identify distinct subgroups of sepsis and to develop personalized treatment strategies. Implications for their use as bioenergetic targets to identify metabolism- and mitochondria-targeted treatments need to be evaluated in future studies.
| S-EPMC8254847 | biostudies-literature
Project description:Background and objectiveSepsis, characterized by an aberrant immune response to infection leading to acute organ dysfunction, impacts millions of individuals each year and carries a substantial risk of mortality, even with prompt care. Despite notable medical advancements, managing sepsis remains a formidable challenge for clinicians and researchers, with treatment options limited to antibiotics, fluid therapy, and organ-supportive measures. Given the heterogeneous nature of sepsis, the identification of distinct clinical phenotypes holds the promise of more precise therapy and enhanced patient care. In this review, we explore various phenotyping schemes applied to sepsis.MethodsWe searched PubMed with the terms "Clinical phenotypes AND sepsis" for any type of article published in English up to September 2023. Only reports in English were included, editorials or articles lacking full text were excluded. A review of clinical phenotypes of sepsis is provided.Key content and findingsWhile discerning clinical phenotypes may seem daunting, the application of artificial intelligence and machine learning techniques provides a viable approach to quantifying similarities among individuals within a sepsis population. These methods enable the differentiation of individuals into distinct phenotypes based on not only factors such as infectious diseases, infection sites, pathogens, body temperature changes and hemodynamics, but also conventional clinical data and molecular omics.ConclusionsThe classification of sepsis holds immense significance in improving clinical cure rates, reducing mortality, and alleviating the economic burden associated with this condition.
| S-EPMC11320222 | biostudies-literature
Project description:Extracorporeal cardiopulmonary resuscitation (eCPR) is emerging as an effective, lifesaving resuscitation strategy for select patients with prolonged or refractory cardiac arrest. Currently, a paucity of evidence-based recommendations is available to guide clinical management of eCPR patients. Despite promising results from initial clinical trials, neurological injury remains a significant cause of morbidity and mortality. Neuropathology associated with utilization of an extracorporeal circuit may interact significantly with the consequences of a prolonged low-flow state that typically precedes eCPR. In this narrative review, we explore current gaps in knowledge about cerebral perfusion over the course of cardiac arrest and resuscitation with a focus on patients treated with eCPR. We found no studies which investigated regional cerebral blood flow or cerebral autoregulation in human cohorts specific to eCPR. Studies which assessed cerebral perfusion in clinical eCPR were small and limited to near-infrared spectroscopy. Furthermore, no studies prospectively or retrospectively evaluated the relationship between epinephrine and neurological outcomes in eCPR patients. In summary, the field currently lacks a comprehensive understanding of how regional cerebral perfusion and cerebral autoregulation are temporally modified by factors such as pre-eCPR low-flow duration, vasopressors, and circuit flow rate. Elucidating these critical relationships may inform future strategies aimed at improving neurological outcomes in patients treated with lifesaving eCPR.
| S-EPMC9877198 | biostudies-literature
Project description:ObjectivesSepsis is responsible for a substantial proportion of global childhood morbidity and mortality. However, evidence demonstrates major inaccuracies in the use of the term "sepsis" in clinical practice, coding, and research. Current and previous definitions of sepsis have been developed using expert consensus but the specific criteria used to identify children with sepsis have not been rigorously evaluated. Therefore, as part of the Society of Critical Care Medicine's Pediatric Sepsis Definition Taskforce, we will conduct a systematic review to synthesize evidence on individual factors, clinical criteria, or illness severity scores that may be used to identify children with infection who have or are at high risk of developing sepsis-associated organ dysfunction and separately those factors, criteria, and scores that may be used to identify children with sepsis who are at high risk of progressing to multiple organ dysfunction or death.Data sourcesWe will identify eligible studies by searching the following databases: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials.Study selectionWe will include all randomized trials and cohort studies published between January 1, 2004, and March 16, 2020.Data extractionData extraction will include information related to study characteristics, population characteristics, clinical criteria, and outcomes.Data synthesisWe will calculate sensitivity and specificity of each criterion for predicting sepsis and conduct a meta-analysis if the data allow. We will also provide pooled estimates of overall hospital mortality.ConclusionsThe potential risk factors, clinical criteria, and illness severity scores from this review which identify patients with infection who are at high risk of developing sepsis-associated organ dysfunction and/or progressing to multiple organ dysfunction or death will be used to inform the next steps of the Pediatric Sepsis Definition Taskforce.
| S-EPMC7314341 | biostudies-literature
Project description:In the five decades since its inception, brain death has become an accepted medical and legal concept throughout most of the world. There was initial reluctance to apply brain death criteria to children as they are believed more likely to regain neurologic function following injury. In spite of early trepidation, criteria for pediatric brain death certification were first proposed in 1987 by a multidisciplinary committee comprised of experts in the medical and legal communities. Protocols have since been developed to standardize brain death determination, but there remains substantial variability in practice throughout the world. In addition, brain death remains a topic of considerable ethical, philosophical, and legal controversy, and is often misrepresented in the media. In the present article, we discuss the history of brain death and the guidelines for its determination. We provide an overview of past and present challenges to its concept and diagnosis from biophilosophical, ethical and legal perspectives, and highlight differences between adult and pediatric brain death determination. We conclude by anticipating future directions for brain death as related to the emergence of new technologies. It is our position that providers should endorse the criteria for brain death diagnosis in children as proposed by the Society of Critical Care Medicine (SCCM), American Academy of Pediatrics (AAP), and Child Neurology Society (CNS), in order to prevent controversy and subjectivity surrounding what constitutes life versus death.
| S-EPMC8578760 | biostudies-literature
Project description:BackgroundIt has been estimated that 20% of the tests and therapies currently prescribed in North America are likely unnecessary, add no value, and may even cause harm. The Choosing Wisely (CW) campaign was launched in 2012 in the US and Canada to limit the overuse of medical procedures in adult and pediatric healthcare, to avoid overdiagnosis and overtreatment.MethodsIn this narrative review, we describe the birth and spread of the CW campaign all over the world, with emphasis on CW in pediatric healthcare.ResultsTo date, CW has spread to more than 25 countries and 80 organizations, with 700 recommendations published. The awareness of medication overuse also made its way into pediatrics. One year after the launch of the CW campaign, the American Academy of Pediatrics and the pediatric section of the Society of Hospital Medicine provided the first recommendations specifically aimed at pediatricians. Thereafter, many European pediatric societies also became active in the CW campaign and published specific top-5 recommendations, although there is not yet a common set of CW recommendations in Europe.DiscussionWe reviewed the main pediatric CW recommendations in medical and surgical fields and discussed how the recommendations have been produced, published, and disseminated. We also analyzed whether and how the CW recommendations impacted pediatric medical practice. Furthermore, we highlighted the common obstacles in applying CW recommendations, such as pressure from patients and families, diagnostic uncertainty, and worries about legal problems. Finally, we highlighted the necessity to foster the CW culture, develop an implementation plan, and measure the results in terms of overuse decline.
| S-EPMC9871764 | biostudies-literature
Project description:We reviewed the literature to investigate the relationship between depression and metabolic syndrome. Major depressive disorder is characterized by a low mood or a loss of interest for longer than two weeks. Metabolic syndrome describes multiple metabolic risk factors including obesity, insulin resistance, dyslipidemia, and hypertension. We divided our findings into environmental, genetic, epigenetic, and biological pathway links between depression and the different aspects of metabolic syndrome. We found various sources linking obesity and metabolic syndrome genetically, environmentally, biological pathway-wise, and, while not fully explored, epigenetically. Diabetes and depression were also found to be linked environmentally with both conditions increasing the risk of the other. Depression was also shown to be linked to cardiovascular complications as it increased the risk of occurrence of such complications in healthy people. These findings have led us to believe that there is a link between depression and metabolic syndrome on various levels, especially obesity.
| S-EPMC8920832 | biostudies-literature
Project description:Clinicians face challenges in the timely diagnosis and management of pediatric sepsis. Pediatric heart rate has been incorporated into early warning systems and studied as a predictor for critical illness. We aim to review: (I) the role of heart rate in pediatric warning systems and (II) the role of heart rate variability (HRV) in adult and neonatal sepsis, with a focus on its potential applications in pediatrics. We conducted a literature search for papers published up to December 2019 on the utility of heart rate and HRV analysis in the diagnosis and management of sepsis, using four medical databases: PubMed, Google Scholar, EMBASE and Web of Science. This review demonstrates that the clinical utility of pediatric heart rate in predicting clinical deterioration is limited by the lack of consensus among warning systems, consensus-based guidelines, and evidence-based studies as to what constitutes abnormal heart rate in the pediatric age group. Current studies demonstrate that abnormal heart rate itself does not adequately discriminate children with sepsis from those without. HRV analysis provides a quick and non-invasive method of assessment and can provide more information than traditional heart rate. HRV analysis has the potential to add value in identification and prognostication of adult and neonatal sepsis. With further studies to explore its role, HRV analysis has the potential to add to current tools in the diagnosis and prognosis of pediatric sepsis.
| S-EPMC7333166 | biostudies-literature
Project description:ObjectiveTo determine the associations of demographic, clinical, laboratory, organ dysfunction, and illness severity variable values with: 1) sepsis, severe sepsis, or septic shock in children with infection and 2) multiple organ dysfunction or death in children with sepsis, severe sepsis, or septic shock.Data sourcesMEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from January 1, 2004, and November 16, 2020.Study selectionCase-control studies, cohort studies, and randomized controlled trials in children greater than or equal to 37-week-old postconception to 18 years with suspected or confirmed infection, which included the terms "sepsis," "septicemia," or "septic shock" in the title or abstract.Data extractionStudy characteristics, patient demographics, clinical signs or interventions, laboratory values, organ dysfunction measures, and illness severity scores were extracted from eligible articles. Random-effects meta-analysis was performed.Data synthesisOne hundred and six studies met eligibility criteria of which 81 were included in the meta-analysis. Sixteen studies (9,629 patients) provided data for the sepsis, severe sepsis, or septic shock outcome and 71 studies (154,674 patients) for the mortality outcome. In children with infection, decreased level of consciousness and higher Pediatric Risk of Mortality scores were associated with sepsis/severe sepsis. In children with sepsis/severe sepsis/septic shock, chronic conditions, oncologic diagnosis, use of vasoactive/inotropic agents, mechanical ventilation, serum lactate, platelet count, fibrinogen, procalcitonin, multi-organ dysfunction syndrome, Pediatric Logistic Organ Dysfunction score, Pediatric Index of Mortality-3, and Pediatric Risk of Mortality score each demonstrated significant and consistent associations with mortality. Pooled mortality rates varied among high-, upper middle-, and lower middle-income countries for patients with sepsis, severe sepsis, and septic shock (p < 0.0001).ConclusionsStrong associations of several markers of organ dysfunction with the outcomes of interest among infected and septic children support their inclusion in the data validation phase of the Pediatric Sepsis Definition Taskforce.
| S-EPMC8670345 | biostudies-literature