Extracorporeal Therapy in Sepsis.
Ontology highlight
ABSTRACT:
SUBMITTER: Govil D
PROVIDER: S-EPMC7347068 | biostudies-literature | 2020 Apr
REPOSITORIES: biostudies-literature
Publications
Extracorporeal Therapy in Sepsis.
Govil Deepak D Kumar G Praveen GP
Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine 20200401 Suppl 3
<b>How to cite this article:</b> Govil D, Kumar GP. Extracorporeal Therapy in Sepsis. Indian J Crit Care Med 2020;24(Suppl 3):S117-S121. ...[more]
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Project description:Vitamins are essential micronutrients with key roles in many biological pathways relevant to sepsis. Some of these relevant biological mechanisms include antioxidant and anti-inflammatory effects, protein and hormone synthesis, energy generation, and regulation of gene transcription. Moreover, relative vitamin deficiencies in plasma are common during sepsis and vitamin therapy has been associated with improved outcomes in some adult and pediatric studies. High-dose intravenous vitamin C has been the vitamin therapy most extensively studied in adult patients with sepsis and septic shock. This includes three randomized control trials (RCTs) as monotherapy with a total of 219 patients showing significant reduction in organ dysfunction and lower mortality when compared to placebo, and five RCTs as a combination therapy with thiamine and hydrocortisone with a total of 1134 patients showing no difference in clinical outcomes. Likewise, the evidence for the role of other vitamins in sepsis remains mixed. In this narrative review, we present the preclinical, clinical, and safety evidence of the most studied vitamins in sepsis, including vitamin C, thiamine (i.e., vitamin B1), and vitamin D. We also present the relevant evidence of the other vitamins that have been studied in sepsis and critical illness in both children and adults, including vitamins A, B2, B6, B12, and E. IMPACT: Vitamins are key effectors in many biological processes relevant to sepsis. We present the preclinical, clinical, and safety evidence of the most studied vitamins in pediatric sepsis. Designing response-adaptive platform trials may help fill in knowledge gaps regarding vitamin use for critical illness and association with clinical outcomes.
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Project description:BackgroundThe benefits of extracorporeal membrane oxygenation (ECMO) in children with sepsis remain controversial. Current guidelines on management of septic shock in children recommend consideration of ECMO as salvage therapy. We sought to review peer-reviewed publications on effectiveness of ECMO in children with sepsis.MethodsStudies reporting on mortality in children with sepsis supported with ECMO, published in PubMed, Scopus and Embase from 1972 till February 2020, were included in the review. This study was done in adherence to Preferred Reporting Items for Systematic Review and Meta-Analysis statement after registering the review protocol with PROSPERO. Study eligibility was independently assessed by two authors and disagreements resolved by a third author. Publications were reviewed for quality using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Random-effects meta-analyses (DerSimonian and Laird) were conducted, and 95% confidence intervals were computed using the Clopper-Pearson method. Outliers were identified by the Baujat plot and leave-one-out analysis if there was considerable heterogeneity. The primary outcome measure was survival to discharge. Secondary outcome measures included hospital length of stay, subgroup analysis of neonatal and paediatric groups, types and duration of ECMO and complications .ResultsOf the 2054 articles screened, we identified 23 original articles for systematic review and meta-analysis. Cumulative estimate of survival (13 studies, 2559 patients) in the cohort was 59% (95%CI: 51-67%). Patients had a median length of hospital stay of 28.8 days, median intensive care unit stay of 13.5 days, and median ECMO duration of 129 h. Children needing venoarterial ECMO (9 studies, 208 patients) showed overall pooled survival of 65% (95%CI: 50-80%). Neonates (< 4 weeks of age) with sepsis needing ECMO (7 studies, 85 neonates) had pooled survival of 73% (95%CI: 56- 87%). Gram positive organisms were the most common pathogens (47%) in septic children supported with ECMO.ConclusionSurvival rates of children with sepsis needing ECMO was 59%. Neonates had higher survival rates (73%); gram positive organisms accounted for most common infections in children needing ECMO. Despite limitations, pooled survival data from this review indicates consideration of ECMO in refractory septic shock for all pediatric age groups.
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Project description:BackgroundThe surviving sepsis campaign recommends consideration for extracorporeal membrane oxygenation (ECMO) in refractory septic shock. We aimed to define the benefit threshold of ECMO in pediatric septic shock.MethodsRetrospective binational multicenter cohort study of all ICUs contributing to the Australian and New Zealand Paediatric Intensive Care Registry. We included patients < 16 years admitted to ICU with sepsis and septic shock between 2002 and 2016. Sepsis-specific risk-adjusted models to establish ECMO benefit thresholds with mortality as the primary outcome were performed. Models were based on clinical variables available early after admission to ICU. Multivariate analyses were performed to identify predictors of survival in children treated with ECMO.ResultsFive thousand sixty-two children with sepsis and septic shock met eligibility criteria, of which 80 (1.6%) were treated with veno-arterial ECMO. A model based on 12 clinical variables predicted mortality with an AUROC of 0.879 (95% CI 0.864-0.895). The benefit threshold was calculated as 47.1% predicted risk of mortality. The observed mortality for children treated with ECMO below the threshold was 41.8% (23 deaths), compared to a predicted mortality of 30.0% as per the baseline model (16.5 deaths; standardized mortality rate 1.40, 95% CI 0.89-2.09). Among patients above the benefit threshold, the observed mortality was 52.0% (13 deaths) compared to 68.2% as per the baseline model (16.5 deaths; standardized mortality rate 0.61, 95% CI 0.39-0.92). Multivariable analyses identified lower lactate, the absence of cardiac arrest prior to ECMO, and the central cannulation (OR 0.31, 95% CI 0.10-0.98, p = 0.046) as significant predictors of survival for those treated with VA-ECMO.ConclusionsThis binational study demonstrates that a rapidly available sepsis mortality prediction model can define thresholds for survival benefit in children with septic shock considered for ECMO. Survival on ECMO was associated with central cannulation. Our findings suggest that a fully powered RCT on ECMO in sepsis is unlikely to be feasible.
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