Neutrophil and cytokine activation with neonatal extracorporeal membrane oxygenation.
OBJECTIVE
To determine whether extracorporeal membrane oxygenation (ECMO), like cardiopulmonary bypass, produces systemic inflammatory responses that could potentiate organ injury in infants with respiratory failure.


METHODS
We evaluated the effects of neonatal ECMO on neutrophil surface adherence proteins, elastase release, and cytokine levels in blood samples from 15 patients before and during ECMO, and from banked blood and ECMO circuit blood before cannulation. Neutrophil elastase, tumor necrosis factor alpha, and interleukin types 1 beta, 6, and 8 were measured. Chest radiographs were evaluated by a radiologist using a lung injury score in blinded fashion.


RESULTS
Primed ECMO circuit blood, in comparison with patient pre-ECMO blood, demonstrated marked up-regulation of CD11b (mean fluorescence intensity 1660 +/- 109 vs 361 +/- 81; p < 0.001 (mean +/- SEM)), shedding of L-selectin (mean fluorescence intensity 10 +/- 2 vs 89 +/- 38; p < 0.01), and elevated elastase levels (349 +/- 76 vs 154 ng/ml +/- 38; p < 0.001), consistent with neutrophil activation. During ECMO, neutrophil CD11b levels increased but L-selectin was not significantly shed. Concentrations of circulating neutrophil elastase increase significantly during ECMO. Corrected circulating quantities of interleukin-8 also rose significantly, but the responses of tumor necrosis factor alpha and interleukin-1 beta were minimal. Radiographic lung injury scores worsened with the initiation of ECMO (median score: 6 before ECMO vs 11 in first hour of ECMO; p = 0.012), in conjunction with indicators of neutrophil activation.


CONCLUSIONS
Neonates with respiratory failure have activation of the inflammatory cascade. ECMO incites additional neutrophil and cytokine activation in association with early pulmonary deterioration. Routine leukodepletion of blood for circuit priming to remove activated neutrophils may be beneficial.
Fortenberry
J D
JD
Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Bhardwaj
V
V
Niemer
P
P
Cornish
J D
JD
Wright
J A
JA
Bland
L
L
D016207:Cytokines / Q000378:metabolism*; D015199:Extracorporeal Membrane Oxygenation; D006801:Humans; D007231:Infant, Newborn; D019272:Leukocyte Elastase / Q000097:blood; D008168:Lung / Q000000981:diagnostic imaging / Q000276:immunology*; D018375:Neutrophil Activation; D009504:Neutrophils / Q000201:enzymology; D010196:Pancreatic Elastase / Q000097:blood; D010547:Persistent Fetal Circulation Syndrome / Q000628:therapy; D011859:Radiography
D016207:Cytokines; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase