Neutrophil Phenotype Correlates With Postoperative Inflammatory Outcomes in Infants Undergoing Cardiopulmonary Bypass

Objectives: Infants with congenital heart disease frequently require cardiopulmonary bypass, which causes systemic inflammation. The goal of this study was to determine if neutrophil phenotype and activation status predicts the development of inflammatory complications following cardiopulmonary bypass. Design: Prospective cohort study. Setting: Tertiary care PICU with postoperative cardiac care. Patients: Thirty-seven patients 5 days to 10 months old with congenital heart disease requiring cardiopulmonary bypass. Interventions: None. Measurements and Main Results: Laboratory and clinical data collected included length of mechanical ventilation, acute kidney injury, and fluid overload. Neutrophils were isolated from whole blood at three time points surrounding cardiopulmonary bypass. Functional analyses included measurement of cell surface protein expression and nicotinamide adenine dinucleotide phosphate oxidase activity. Of all patients studied, 40.5% displayed priming of nicotinamide adenine dinucleotide phosphate oxidase activity in response to N-formyl-Met-Leu-Phe stimulation 24 hours post cardiopulmonary bypass as compared to pre bypass. Neonates who received steroids prior to bypass demonstrated enhanced priming of nicotinamide adenine dinucleotide phosphate oxidase activity at 48 hours. Patients who displayed priming post cardiopulmonary bypass were 8.8 times more likely to develop severe acute kidney injury as compared to nonprimers. Up-regulation of neutrophil surface CD11b levels pre- to postbypass occurred in 51.4% of patients, but this measure of neutrophil priming was not associated with acute kidney injury. Subsequent analyses of the basal neutrophil phenotype revealed that those with higher basal CD11b expression were significantly less likely to develop acute kidney injury. Conclusions: Neutrophil priming occurs in a subset of infants undergoing cardiopulmonary bypass. Acute kidney injury was more frequent in those patients who displayed priming of nicotinamide adenine dinucleotide phosphate oxidase activity after cardiopulmonary bypass. This pilot study suggests that neutrophil phenotypic signature could be used to predict inflammatory organ dysfunction. † Deceased. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://ift.tt/2gIrZ5Y). Supported, in part, by the University of Iowa Children’s Miracle Network Training Grant (Number 2218) and the University of Iowa Infectious Disease T32 Training Grant (Number 5-T32-AI 07343-20) Dr. Huber received funding from University of Iowa Children’s Miracle Network Grant. Dr. Brophy disclosed other funding from the American Board of Pediatrics, the American Society of Pediatric Nephrology, and UpToDate. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: Jessica.Moreland@UTSouthwestern.edu ©2017The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

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