Sepsis-induced multiple organ failure (MOF) remains an important cause of child morbidity and death. In over ten years of mechanistic investigation we have reported that organ failure is associated with increased inflammation and coagulation, and reduced immune function. We have characterized three pediatric sepsis- induced MOF syndrome phenotypes;1) the virus / lymphoproliferative disease associated Sequential Multiple Organ Failure Syndrome, 2) the Compensatory Anti-inflammatory Response / Prolonged Lymphopenia / Immuneparalysis Syndrome, and 3) the microvascular thrombosis related Thrombocytopenia Associated Multiple Organ Failure Syndrome. In our single center, these patients can have a 92% survival when phenotype specific therapeutic strategies are directed to restoring immune and coagulation system function respectively, compared to only a 63% survival when these specific therapies are not used. Because diagnosis of these phenotypes requires specialized diagnostic tests, the characterization of these MOF phenotypes and the use of specific therapies have not been systematically investigated in Pediatric Intensive Care Units, other than our own. The purpose of our proposal is to determine the incidence and outcome of these sepsis induced MOF phenotypes in the Collaborative Pediatric Critical Care Research Network (CPCCRN) population. This proposal will establish the incidence and outcome of these phenotypes, already observed in our Northeastern and predominantly Caucasian population, across the ethnically and geographically diverse CPCCRN population. This knowledge will allow us to determine the feasibility of future trials of phenotype specific therapeutic strategies for pediatric sepsis induced MOF in the CPCCRN. For the past four years we have been one of 6 sites privileged to participate in the CPPCRN. Our principal study during this time was the Critical Illness Stress Induced Immune Suppression Trial which tests the ability of a prophylaxis strategy to prevent stress induced lymphocyte apoptosis and consequent nosocomial infection / sepsis. Our present proposal represents the next step in investigation into the role of immune depression in the ongoing epidemic of nosocomial sepsis and sepsis induced morbidity and mortality

Public Health Relevance

Noscomial and resistant organism sepsis is a signifcant public health problem. Our present proposal aims to phenotype patients with sepsis to determine the feasibility of designing novel phenotype specific prophylaxis and treatment trials which can potentially decrease the national and global burden of nosocomial and drug resistant organism sepsis in chidlren.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Cooperative Clinical Research--Cooperative Agreements (U10)
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Special Emphasis Panel (ZHD1-DSR-A (25))
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Maholmes, Valerie
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University of Pittsburgh
Internal Medicine/Medicine
Schools of Medicine
United States
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Carcillo, Joseph A; Dean, J Michael; Holubkov, Richard et al. (2016) Inherent Risk Factors for Nosocomial Infection in the Long Stay Critically Ill Child Without Known Baseline Immunocompromise: A Post Hoc Analysis of the CRISIS Trial. Pediatr Infect Dis J 35:1182-1186
Silverstein, Faye S; Slomine, Beth S; Christensen, James et al. (2016) Functional Outcome Trajectories After Out-of-Hospital Pediatric Cardiac Arrest. Crit Care Med 44:e1165-e1174
Meert, Kathleen L; Telford, Russell; Holubkov, Richard et al. (2016) Pediatric Out-of-Hospital Cardiac Arrest Characteristics and Their Association With Survival and Neurobehavioral Outcome. Pediatr Crit Care Med 17:e543-e550
Carcillo, Joseph A; Sward, Katherine; Halstead, E Scott et al. (2016) A Systemic Inflammation Mortality Risk Assessment Contingency Table for Severe Sepsis. Pediatr Crit Care Med :
Keele, Linda; Meert, Kathleen L; Berg, Robert A et al. (2016) Limiting and Withdrawing Life Support in the PICU: For Whom Are These Options Discussed? Pediatr Crit Care Med 17:110-20
Meert, Kathleen; Telford, Russell; Holubkov, Richard et al. (2016) Exploring the safety and efficacy of targeted temperature management amongst infants with out-of-hospital cardiac arrest due to apparent life threatening events. Resuscitation 109:40-48
Meert, Kathleen L; Slomine, Beth S; Christensen, James R et al. (2016) Family Burden After Out-of-Hospital Cardiac Arrest in Children. Pediatr Crit Care Med 17:498-507
Moler, Frank W; Hutchison, Jamie S; Nadkarni, Vinay M et al. (2016) Targeted Temperature Management After Pediatric Cardiac Arrest Due To Drowning: Outcomes and Complications. Pediatr Crit Care Med 17:712-20
Sward, Katherine A; Rubin, Sarah; Jenkins, Tammara L et al. (2016) Case Study: Semantic Annotation of a Pediatric Critical Care Research Study. Comput Inform Nurs 34:101-4
Willson, Douglas F; Webster, Angela; Heidemann, Sabrina et al. (2016) Diagnosis and Treatment of Ventilator-Associated Infection: Review of the Critical Illness Stress-Induced Immune Suppression Prevention Trial Data. Pediatr Crit Care Med 17:287-93

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