Nosocomial infection and sepsis is a predominant contributor to morbidity and mortality in critically ill children. The B-cell, T- cell, and natural killer cell lymphocytes are important components of the host immune system which prevent and kill nosocomial infection. Lymphopenia (absolute lymphocte count < 1,000) is common in critically ill children and increases the risk of developing nosocomial sepsis 5.5 fold. Critical illness causes stress, and the stress hormone cortisol induces lymphocyte apoptosis. Prolactin is the counter-regulatory stress hormone which increase Bcl-2 expression and prevents cortisol-induced lymphocyte apoptosis. Although prolactin is increased after surgical stress, it is commonly decreased during critical illness, in part due to increased dopaminergic activity which inhibits prolactin release from the pituitary gland. Children with critical illness induced hypoprolactinemia have an 8-fold higher likelihood of prolonged lymphopenia and a 12 -fold higher likelihood of apoptosis-mediated lymphoid depletion. The objective of the proposed study is to determine if Metoclopramide, a gastrointestinal pro-kinetic and central dopamine-antagonist which maintains systemic prolactin levels in the high normal range, can prevent hypoprolactinemia, lymphopenia, and nosocomial sepsis when given as daily prophylaxis to critically ill children. The three specific aims of the proposed randomized double-blinded placebo-controlled trial are to determine if daily metoclopramide administration 1) maintains prolactin levels, 2) maintains absolute lymphocyte counts and lymphocyte subsets, and 3) reduces rates of nosocomial infection and sepsis. The secondary objective of the study is to determine if metoclopramide prophylaxis reduces duration of mechanical ventilation, organ dysfunction/failure scores, intensive care unit length of stay, and morbidity scores in these children. The long term goal of the project is to develop innovative strategies to improve immune function and reduce nosocomial infection and sepsis in critically ill children. ? ? ?

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 (04))
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Nicholson, Carol E
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University of Pittsburgh
Internal Medicine/Medicine
Schools of Medicine
United States
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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
Cashen, Katherine; Reeder, Ron W; Shanti, Christina et al. (2018) Is therapeutic hypothermia during neonatal extracorporeal membrane oxygenation associated with intracranial hemorrhage? Perfusion 33:354-362
Slomine, Beth S; Silverstein, Faye S; Christensen, James R et al. (2018) Neurobehavioural outcomes in children after In-Hospital cardiac arrest. Resuscitation 124:80-89
Davila, Sam; Halstead, E Scott; Hall, Mark W et al. (2018) Viral DNAemia and Immune Suppression in Pediatric Sepsis. Pediatr Crit Care Med 19:e14-e22
Meert, Kathleen; Slomine, Beth S; Christensen, James R et al. (2018) Burden of caregiving after a child's in-hospital cardiac arrest. Resuscitation 127:44-50
Muszynski, Jennifer A; Reeder, Ron W; Hall, Mark W et al. (2018) RBC Transfusion Practice in Pediatric Extracorporeal Membrane Oxygenation Support. Crit Care Med 46:e552-e559
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

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