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Resuscitation in Paediatric Sepsis Using Metabolic Resuscitation–A Randomized Controlled Pilot Study in the Paediatric Intensive Care Unit (RESPOND PICU): Study Protocol and Analysis Plan

Introduction: Septic shock remains amongst the leading causes of childhood mortality. Therapeutic options to support children with septic shock refractory to initial resuscitation with fluids and inotropes are limited. Recently, the combination of intravenous hydrocortisone with high dose ascorbic a...

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Autores principales: Schlapbach, Luregn J., Gibbons, Kristen, Ridolfi, Roberta, Harley, Amanda, Cree, Michele, Long, Debbie, Buckley, David, Erickson, Simon, Festa, Marino, George, Shane, King, Megan, Singh, Puneet, Raman, Sainath, Bellomo, Rinaldo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142861/
https://www.ncbi.nlm.nih.gov/pubmed/34041208
http://dx.doi.org/10.3389/fped.2021.663435
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author Schlapbach, Luregn J.
Gibbons, Kristen
Ridolfi, Roberta
Harley, Amanda
Cree, Michele
Long, Debbie
Buckley, David
Erickson, Simon
Festa, Marino
George, Shane
King, Megan
Singh, Puneet
Raman, Sainath
Bellomo, Rinaldo
author_facet Schlapbach, Luregn J.
Gibbons, Kristen
Ridolfi, Roberta
Harley, Amanda
Cree, Michele
Long, Debbie
Buckley, David
Erickson, Simon
Festa, Marino
George, Shane
King, Megan
Singh, Puneet
Raman, Sainath
Bellomo, Rinaldo
author_sort Schlapbach, Luregn J.
collection PubMed
description Introduction: Septic shock remains amongst the leading causes of childhood mortality. Therapeutic options to support children with septic shock refractory to initial resuscitation with fluids and inotropes are limited. Recently, the combination of intravenous hydrocortisone with high dose ascorbic acid and thiamine (HAT therapy), postulated to reduce sepsis-related organ dysfunction, has been proposed as a safe approach with potential for mortality benefit, but randomized trials in paediatric patients are lacking. We hypothesize that protocolised early use of HAT therapy (“metabolic resuscitation”) in children with septic shock is feasible and will lead to earlier resolution of organ dysfunction. Here, we describe the protocol of the Resuscitation in Paediatric Sepsis Using Metabolic Resuscitation–A Randomized Controlled Pilot Study in the Paediatric Intensive Care Unit (RESPOND PICU). Methods and Analysis: The RESPOND PICU study is an open label randomized-controlled, two-sided multicentre pilot study conducted in paediatric intensive care units (PICUs) in Australia and New Zealand. Sixty children aged between 28 days and 18 years treated with inotropes for presumed septic shock will be randomized in a 1:1 ratio to either metabolic resuscitation (1 mg/kg hydrocortisone q6h, 30 mg/kg ascorbic acid q6h, 4 mg/kg thiamine q12h) or standard septic shock management. Main outcomes include feasibility of the study protocol and survival free of organ dysfunction censored at 28 days. The study cohort will be followed up at 28-days and 6-months post enrolment to assess neurodevelopment, quality of life and functional status. Biobanking will allow ancillary studies on sepsis biomarkers. Ethics and Dissemination: The study received ethical clearance from Children's Health Queensland Human Research Ethics Committee (HREC/18/QCHQ/49168) and commenced enrolment on June 12th, 2019. The primary study findings will be submitted for publication in a peer-reviewed journal. Trial Registration: Australian and New Zealand Clinical Trials Registry (ACTRN12619000829112). Protocol Version: V1.8 22/7/20.
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spelling pubmed-81428612021-05-25 Resuscitation in Paediatric Sepsis Using Metabolic Resuscitation–A Randomized Controlled Pilot Study in the Paediatric Intensive Care Unit (RESPOND PICU): Study Protocol and Analysis Plan Schlapbach, Luregn J. Gibbons, Kristen Ridolfi, Roberta Harley, Amanda Cree, Michele Long, Debbie Buckley, David Erickson, Simon Festa, Marino George, Shane King, Megan Singh, Puneet Raman, Sainath Bellomo, Rinaldo Front Pediatr Pediatrics Introduction: Septic shock remains amongst the leading causes of childhood mortality. Therapeutic options to support children with septic shock refractory to initial resuscitation with fluids and inotropes are limited. Recently, the combination of intravenous hydrocortisone with high dose ascorbic acid and thiamine (HAT therapy), postulated to reduce sepsis-related organ dysfunction, has been proposed as a safe approach with potential for mortality benefit, but randomized trials in paediatric patients are lacking. We hypothesize that protocolised early use of HAT therapy (“metabolic resuscitation”) in children with septic shock is feasible and will lead to earlier resolution of organ dysfunction. Here, we describe the protocol of the Resuscitation in Paediatric Sepsis Using Metabolic Resuscitation–A Randomized Controlled Pilot Study in the Paediatric Intensive Care Unit (RESPOND PICU). Methods and Analysis: The RESPOND PICU study is an open label randomized-controlled, two-sided multicentre pilot study conducted in paediatric intensive care units (PICUs) in Australia and New Zealand. Sixty children aged between 28 days and 18 years treated with inotropes for presumed septic shock will be randomized in a 1:1 ratio to either metabolic resuscitation (1 mg/kg hydrocortisone q6h, 30 mg/kg ascorbic acid q6h, 4 mg/kg thiamine q12h) or standard septic shock management. Main outcomes include feasibility of the study protocol and survival free of organ dysfunction censored at 28 days. The study cohort will be followed up at 28-days and 6-months post enrolment to assess neurodevelopment, quality of life and functional status. Biobanking will allow ancillary studies on sepsis biomarkers. Ethics and Dissemination: The study received ethical clearance from Children's Health Queensland Human Research Ethics Committee (HREC/18/QCHQ/49168) and commenced enrolment on June 12th, 2019. The primary study findings will be submitted for publication in a peer-reviewed journal. Trial Registration: Australian and New Zealand Clinical Trials Registry (ACTRN12619000829112). Protocol Version: V1.8 22/7/20. Frontiers Media S.A. 2021-04-30 /pmc/articles/PMC8142861/ /pubmed/34041208 http://dx.doi.org/10.3389/fped.2021.663435 Text en Copyright © 2021 Schlapbach, Gibbons, Ridolfi, Harley, Cree, Long, Buckley, Erickson, Festa, George, King, Singh, Raman, Bellomo and the RESPOND PICU study investigators and the Australian New Zealand Intensive Care Society Paediatric Study Group (ANZICS PSG) https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pediatrics
Schlapbach, Luregn J.
Gibbons, Kristen
Ridolfi, Roberta
Harley, Amanda
Cree, Michele
Long, Debbie
Buckley, David
Erickson, Simon
Festa, Marino
George, Shane
King, Megan
Singh, Puneet
Raman, Sainath
Bellomo, Rinaldo
Resuscitation in Paediatric Sepsis Using Metabolic Resuscitation–A Randomized Controlled Pilot Study in the Paediatric Intensive Care Unit (RESPOND PICU): Study Protocol and Analysis Plan
title Resuscitation in Paediatric Sepsis Using Metabolic Resuscitation–A Randomized Controlled Pilot Study in the Paediatric Intensive Care Unit (RESPOND PICU): Study Protocol and Analysis Plan
title_full Resuscitation in Paediatric Sepsis Using Metabolic Resuscitation–A Randomized Controlled Pilot Study in the Paediatric Intensive Care Unit (RESPOND PICU): Study Protocol and Analysis Plan
title_fullStr Resuscitation in Paediatric Sepsis Using Metabolic Resuscitation–A Randomized Controlled Pilot Study in the Paediatric Intensive Care Unit (RESPOND PICU): Study Protocol and Analysis Plan
title_full_unstemmed Resuscitation in Paediatric Sepsis Using Metabolic Resuscitation–A Randomized Controlled Pilot Study in the Paediatric Intensive Care Unit (RESPOND PICU): Study Protocol and Analysis Plan
title_short Resuscitation in Paediatric Sepsis Using Metabolic Resuscitation–A Randomized Controlled Pilot Study in the Paediatric Intensive Care Unit (RESPOND PICU): Study Protocol and Analysis Plan
title_sort resuscitation in paediatric sepsis using metabolic resuscitation–a randomized controlled pilot study in the paediatric intensive care unit (respond picu): study protocol and analysis plan
topic Pediatrics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142861/
https://www.ncbi.nlm.nih.gov/pubmed/34041208
http://dx.doi.org/10.3389/fped.2021.663435
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