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 #
5U10HD049983-10
Application #
8599783
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
2013-12-01
Budget End
2014-11-30
Support Year
10
Fiscal Year
2014
Total Cost
$240,333
Indirect Cost
$81,698
Name
University of Pittsburgh
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Dalton, Heidi J; Cashen, Katherine; Reeder, Ron W et al. (2018) Hemolysis During Pediatric Extracorporeal Membrane Oxygenation: Associations With Circuitry, Complications, and Mortality. Pediatr Crit Care Med 19:1067-1076
Berger, John T; Villalobos, Michele E; Clark, Amy E et al. (2018) Cognitive Development One Year After Infantile Critical Pertussis. Pediatr Crit Care Med 19:89-97
Basu, Sonali; Holubkov, Richard; Dean, J Michael et al. (2018) PICU Autopsies: Rates, Patient Characteristics, and the Role of the Medical Examiner. Pediatr Crit Care Med 19:1137-1145
Cornell, Timothy T; Selewski, David T; Alten, Jeffrey A et al. (2018) Acute kidney injury after out of hospital pediatric cardiac arrest. Resuscitation 131:63-68
Cashen, Katherine; Reeder, Ron; Dalton, Heidi J et al. (2018) Hyperoxia and Hypocapnia During Pediatric Extracorporeal Membrane Oxygenation: Associations With Complications, Mortality, and Functional Status Among Survivors. Pediatr Crit Care Med 19:245-253
Pollack, Murray M; Holubkov, Richard; Reeder, Ron et al. (2018) PICU Length of Stay: Factors Associated With Bed Utilization and Development of a Benchmarking Model. Pediatr Crit Care Med 19:196-203
Pollack, Murray M; Holubkov, Richard; Berg, Robert A et al. (2018) Predicting cardiac arrests in pediatric intensive care units. Resuscitation 133:25-32
Cashen, Katherine; Reeder, Ron; Dalton, Heidi J et al. (2018) Acquired infection during neonatal and pediatric extracorporeal membrane oxygenation. Perfusion 33:472-482
Berg, Robert A; Sutton, Robert M; Reeder, Ron W et al. (2018) Association Between Diastolic Blood Pressure During Pediatric In-Hospital Cardiopulmonary Resuscitation and Survival. Circulation 137:1784-1795
Meert, Kathleen; Telford, Russell; Holubkov, Richard et al. (2018) Paediatric in-hospital cardiac arrest: Factors associated with survival and neurobehavioural outcome one year later. Resuscitation 124:96-105

Showing the most recent 10 out of 73 publications