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Cardiopulmonary Bypass Is Associated With Hemolysis and Acute Kidney Injury in Neonates, Infants, and Children*

Mamikonian, Lara S. MD1; Mamo, Lisa B. MS1; Smith, P. Brian MD, MPH, MHS1,2; Koo, Jeannie RN, CPNP-AC1; Lodge, Andrew J. MD3; Turi, Jennifer L. MD1

Pediatric Critical Care Medicine: March 2014 - Volume 15 - Issue 3 - p e111–e119
doi: 10.1097/PCC.0000000000000047
Online Clinical Investigations

Objectives: This pilot study assesses the degree of hemolysis induced by cardiopulmonary bypass and determines its association with acute kidney injury in pediatric patients. Further, it evaluates the degree to which the use of urinary biomarkers neutrophil gelatinase–associated lipocalin and cystatin C correlate with the presence of acute kidney injury and hemolysis following cardiopulmonary bypass.

Design: Prospective observational study.

Setting: A 13-bed pediatric cardiac ICU in a university hospital.

Patients: Children undergoing cardiac surgery with the use of cardiopulmonary bypass.

Interventions: None.

Measurements and Main Results: Blood and urine samples were obtained at multiple time points before and after cardiopulmonary bypass. Hemolysis was assessed by measuring levels of plasma hemoglobin and haptoglobin. Acute kidney injury was defined as a doubling in serum creatinine from preoperative baseline and by using the pediatric-modified RIFLE criteria. Urinary neutrophil gelatinase–associated lipocalin and cystatin C levels were measured. A total of 40 patients (range, 3 d to 4.8 yr) were enrolled. Plasma hemoglobin levels increased markedly on separation from cardiopulmonary bypass with a concurrent decrease in haptoglobin. This was associated with an increase in protein oxidation in the plasma. Hemolysis was more evident in younger patients with a longer duration of bypass and in those requiring a blood-primed circuit. Forty percent of patients had a doubling in serum creatinine and acute kidney injury was developed in 88% of patients when defined by the pediatric-modified RIFLE criteria. Controlling for cardiopulmonary bypass time, persistently elevated levels of plasma hemoglobin were associated with a five-fold increase in acute kidney injury. Further, urinary neutrophil gelatinase–associated lipocalin measured 2 hours after separation from cardiopulmonary bypass was associated with acute kidney injury and with elevations in plasma hemoglobin.

Conclusions: Cardiopulmonary bypass in pediatric patients results in significant hemolysis, which is associated with the development of acute kidney injury. The biomarker neutrophil gelatinase–associated lipocalin correlates with both acute kidney injury and hemolysis in this population.

1Department of Pediatrics, Duke University, Durham, NC.

2Duke Clinical Research Institute, Durham, NC.

3Department of Surgery, Duke University, Durham, NC.

Dr. Mamikonian and Dr. Lodge were supported by grants from Children’s Miracle Network. Dr. Smith received salary support for research from the National Institutes of Health and the U.S. Department of Health and Human Services (NICHD 1K23HD060040-01 and DHHS-1R18AE000028-01). The remaining authors have disclosed that they do not have any potential conflicts of interest.

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©2014The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies