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Pediatr Crit Care Me · Oct 2013
Randomized Controlled Trial Multicenter StudyAltered Circulating Leukocytes and Their Chemokines in a Clinical Trial of Therapeutic Hypothermia for Neonatal Hypoxic Ischemic Encephalopathy*
- Dorothea D Jenkins, Timothy Lee, Cody Chiuzan, Jessica K Perkel, Laura Grace Rollins, Carol L Wagner, Lakshmi P Katikaneni, W Thomas Bass, David A Kaufman, Michael J Horgan, Sheela Laungani, Laurence M Givelichian, Koravangatta Sankaran, Jerome Y Yager, and Renee Martin.
- 1Department of Pediatrics, Medical University of South Carolina, Charleston, SC. 2Department of Pediatric Emergency Medicine, Akron Children's Hospital, Akron, OH. 3Department of Medicine, Division of Biostatistics and Epidemiology, Medical University of South Carolina, Charleston, SC. 4Department of Clinical Psychology, University of Massachusetts, Boston, MA. 5Department of Pediatrics, Eastern Virginia Medical School, Norfolk, VA. 6Department of Pediatrics, University of Virginia, Charlottesville, VA. 7Department of Pediatrics, Albany Medical Center, Albany, NY. 8Department of Pediatrics, Brooklyn Hospital Center, Brooklyn, NY. 9Department of Pediatrics, University of Saskatchewan, Saskatoon, SK, Canada. 10Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.
- Pediatr Crit Care Me. 2013 Oct 1;14(8):786-95.
ObjectivesTo determine systemic hypothermia's effect on circulating immune cells and their corresponding chemokines after hypoxic ischemic encephalopathy in neonates.DesignIn our randomized, controlled, multicenter trial of systemic hypothermia in neonatal hypoxic ischemic encephalopathy, we measured total and leukocyte subset and serum chemokine levels over time in both hypothermia and normothermia groups, as primary outcomes for safety.SettingNeonatal ICUs participating in a Neurological Disorders and Stroke sponsored clinical trial of therapeutic hypothermia.PatientsSixty-five neonates with moderate to severe hypoxic ischemic encephalopathy within 6 hours after birth.InterventionsPatients were randomized to normothermia of 37°C or systemic hypothermia of 33°C for 48 hours.Measurements And Main ResultsComplete and differential leukocyte counts and serum chemokines were measured every 12 hours for 72 hours. The hypothermia group had significantly lower median circulating total WBC and leukocyte subclasses than the normothermia group before rewarming, with a nadir at 36 hours. Only the absolute neutrophil count rebounded after rewarming in the hypothermia group. Chemokines, monocyte chemotactic protein-1 and interleukin-8, which mediate leukocyte chemotaxis as well as bone marrow suppression, were negatively correlated with their target leukocytes in the hypothermia group, suggesting active chemokine and leukocyte modulation by hypothermia. Relative leukopenia at 60-72 hours correlated with an adverse outcome in the hypothermia group.ConclusionsOur data are consistent with chemokine-associated systemic immunosuppression with hypothermia treatment. In hypothermic neonates, persistence of lower leukocyte counts after rewarming is observed in infants with more severe CNS injury.
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