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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Cooperative Clinical Research--Cooperative Agreements (U10)
Project #
5U10HD049983-09
Application #
8401900
Study Section
Special Emphasis Panel (ZHD1-DSR-A (25))
Program Officer
Maholmes, Valerie
Project Start
2005-05-01
Project End
2014-11-30
Budget Start
2012-12-01
Budget End
2013-11-30
Support Year
9
Fiscal Year
2013
Total Cost
$253,514
Indirect Cost
$86,178
Name
University of Pittsburgh
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Pollack, Murray M; Holubkov, Richard; Funai, Tomohiko et al. (2014) Relationship between the functional status scale and the pediatric overall performance category and pediatric cerebral performance category scales. JAMA Pediatr 168:671-6
Jardine, David; Emond, Mary; Meert, Kathleen L et al. (2014) A single nucleotide polymorphism in the corticotropin receptor gene is associated with a blunted cortisol response during pediatric critical illness. Pediatr Crit Care Med 15:698-705
Berg, Robert A; Sutton, Robert M; Holubkov, Richard et al. (2013) Ratio of PICU versus ward cardiopulmonary resuscitation events is increasing. Crit Care Med 41:2292-7
Moler, Frank W; Silverstein, Faye S; Meert, Kathleen L et al. (2013) Rationale, timeline, study design, and protocol overview of the therapeutic hypothermia after pediatric cardiac arrest trials. Pediatr Crit Care Med 14:e304-15
Heidemann, Sabrina M; Holubkov, Richard; Meert, Kathleen L et al. (2013) Baseline serum concentrations of zinc, selenium, and prolactin in critically ill children. Pediatr Crit Care Med 14:e202-6
Berger, John T; Carcillo, Joseph A; Shanley, Thomas P et al. (2013) Critical pertussis illness in children: a multicenter prospective cohort study. Pediatr Crit Care Med 14:356-65
Anand, Kanwaljeet J S; Clark, Amy E; Willson, Douglas F et al. (2013) Opioid analgesia in mechanically ventilated children: results from the multicenter Measuring Opioid Tolerance Induced by Fentanyl study. Pediatr Crit Care Med 14:27-36
Eggly, Susan; Meert, Kathleen L; Berger, John et al. (2013) Physicians' conceptualization of "closure" as a benefit of physician-parent follow-up meetings after a child's death in the pediatric intensive care unit. J Palliat Care 29:69-75
Carcillo, Joseph A; Dean, J Michael; Holubkov, Richard et al. (2012) The randomized comparative pediatric critical illness stress-induced immune suppression (CRISIS) prevention trial. Pediatr Crit Care Med 13:165-73
Meert, Kathleen L; Eggly, Susan; Berger, John et al. (2011) Physicians' experiences and perspectives regarding follow-up meetings with parents after a child's death in the pediatric intensive care unit. Pediatr Crit Care Med 12:e64-8

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