Main question1What are the performance characteristics of currently used scoring tools andor clinical guidelines for single and multiple organ dysfunction syndrome MODS in critically ill children Other questions of interest2What are the comparative risks and benefits of therapies currently used for MODS in critically ill children3What are the critical data elements minimal data set that should routinely be collected in future investigations examining pediatric MODS4Does cumulative existing published data suggest an underlying unifying pathophysiology for pediatric MODS that might be pharmacologically addressedPatientsThe focus of this proposal is the critically ill child admitted to the Pediatric Intensive Care Unit PICU with MODS or who develops MODS during the hospital stay where MODS is defined as the simultaneous dysfunction of two or more organ systems.1

There are 250000 admissions per year to 300 PICUs in the U.S.2 MODS is a poorly understood entity that accounts for 18 of PICU admission diagnoses1 and is present in the vast majority of children who die in the PICU.34 There are multiple pediatric severity of illness scores that consider MODS when estimating risk of mortality.510 In particular the Pediatric Logistic Organ Dysfunction PELOD25 score has been shown to predict mortality in the setting of MODS.51112 The criteria used to define organ dysfunction though vary significantly between scoring tools. Scoring tools for pediatrics MODS have evolved over the last 20 years but their performance characteristics are not well described andor compared. Scoring tools for pediatric MODS rely on estimating the number of organ systems with dysfunction using a combination of physiologic data e.g. vital sign abnormalities laboratory data e.g. blood gas abnormalities or therapeutic intervention e.g. vasoactiveinotropic score. The definition for each single organ dysfunction varies from one tool to another e.g. different cutoffs exist for abnormal vital signs such as heart rate or respiratory rate. We therefore propose a systematic review of the literature to evaluate the evidence base supporting the use of scoring tools for pediatric organ dysfunction for1MODS as an entity and2Dysfunction of individual organ systems for exampleoNeurologic e.g. Glasgow Coma Score pupillary reactionoRespiratory e.g. respiratory rate blood pH partial pressure of arterial oxygen PaO2 PaO2 to fraction of inspired oxygen PaO2FiO2 ratio partial pressure of carbon dioxide PCO2 oxygenation index mean airway pressure x fraction of inspired oxygen x 100PaO213 oxygen saturation index mean airway pressure x fraction of inspired oxygen x 100oximetry saturation13 dead space fraction need for mechanical ventilationoCardiovascular e.g. heart rate systolic andor diastolic blood pressure vasoactiveinotropic score1415 vascular endothelial abnormalitiesoGastrointestinalHepatic blood concentration of potassium aspartate transaminase AST bilirubin prothrombin time PT international normalized ratio INRoRenal e.g. hourly urine output blood concentration of blood urea nitrogen BUN creatinine creatinine clearance need for renal replacement therapy novel renal biomarkersoHematologic e.g. white blood cell count platelet count coagulation abnormalitiesoEndocrine e.g. blood concentration of glucose cortisol thyroxin.We further propose to determine the validity and performance characteristics of such tools. This systematic review is a crucial first step needed to further our understanding of pediatric MODS how to define and quantify it using existing evidence and rigorous consensus in the absence of evidence and how to study it in the future minimal data sets so that critically ill children can benefit from better and earlier detection of organ dysfunction and eventually from better and earlier treatments.

The NIH NICHD Pediatric Trauma and Critical Care Branch convened a workshop to discuss pediatric MODS on March 2627 2015. A group of pediatric critical care medicine experts was formed following the workshop the Pediatric Organ Dysfunction Information Update Mandate PODIUM.The answer to the research questions will help inform experts that compose the PODIUM group on the evidence behind scoring tools for pediatric MODS. This synthesis of existing published data will support the development of consensus statements in the area of pediatric MODS for clinical guidance and future research efforts. Specifically the aims of our group are to develop 1 a contemporary definition for pediatric MODS as a unifying concept and at the organ system level and 2 a set of common data elements for pediatric MODS research that will facilitate data sharing among researchers and will improve the evidence base for development of future therapies. In order to achieve our aims we plan to use methodology similar to that employed in the development of the Surviving Sepsis Campaign guidelines16 and the Pediatric Acute Lung Injury Consensus Conference1317 for Aim 1 and similar to the process employed for pediatric traumatic brain injury18 for Aim 2. PODIUM members have played an active role in all the above initiatives and have experience in the consensus development process.

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The nominators have partnered in submitting this topic nomination on behalf of PODIUM. The nominators are specialists in Pediatrics as well as Pediatric Critical Care Medicine and will provide content and methodology guidance respectively to the PODIUM group members.

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