Cell-Free Plasma Hemoglobin and Male Gender Are Risk Factors for Acute Kidney Injury in Low Risk Children Undergoing Cardiopulmonary Bypass

Abstract

Objective To determine the relationship between the production of cell-free plasma hemoglobin (PHb) and acute kidney injury (AKI) in infants and children undergoing cardiopulmonary bypass (CPB) for cardiac surgery. Design Prospective observational study Setting 12-bed cardiac ICU in a university-affiliated children’s hospital Patients Children were prospectively enrolled during their pre-operative outpatient appointment with the following criteria: >1month to <18 years old, procedures requiring CPB, no preexisting renal dysfunction. Interventions None Measurements and Main Results Plasma and urine were collected at baseline (in a subset), the beginning and end of CPB, and 2h and 24h after CPB in 60 subjects. Levels of PHb increased during CPB and were associated (p<0.01) with CPB duration (R2=0.22), depletion of Hp at end and 24h after CPB (R2=0.12 and 0.15, respectively), LDH levels at end CPB (R2=0.27), and change in creatinine (R2=0.12). 43% of patients developed AKI. There was an association between PHb level and change in creatinine that varied by age (overall [R2=0.12, p<0.01], in age >2yrs [R2=0.22, p<0.01], and in <2yrs [R2=0.03, p=0.42]). Change in PHb and male gender were found to be risk factors for AKI (OR 1.02 and OR 3.78, p<0.05). Conclusions Generation of PHb during CPB and male gender are associated with subsequent renal dysfunction in low risk pediatric patients, especially in those >2yrs of age. Further studies are needed to determine whether specific subgroups of pediatric patients undergoing CPB would benefit from potential treatments for hemolysis and PHb-associated renal dysfunction.

Association Between Early Postoperative Acetaminophen Exposure and Acute Kidney Injury in Pediatric Patients Undergoing Cardiac Surgery

“…30 This association was replicated in a cohort study of 60 children undergoing surgery requiring CPB, where those with AKI had greater increase in plasma hemoglobin concentration (53.9 vs. 38.3 mg/dL, p=0.03), and increase in plasma hemoglobin was an independent risk factor for AKI (OR 1.02 (95% CI 1.00–1.03) per mg/dL increase). 29 The mechanism whereby free hemoglobin leads to nephrotoxicity is postulated to be through lipid peroxidation, catalyzed by oxidized cell-free hemoglobin, a process that can be inhibited by acetaminophen. 32,40…”

“…27,28 Cell-free plasma hemoglobin has been associated with AKI after cardiac bypass in children. 29 Based on data from animal models and adults, it is hypothesized that free hemoglobin contributes to AKI through oxidation of the central iron of the heme moiety to the highly reactive and nephrotoxic ferryl (Fe 4+ ) form. 30–32 This pathogenic mechanism for AKI illuminates a potential therapeutic agent.…”

Redução de hemoglobina: risco para lesão renal aguda após revascularização do miocárdio

“…Os mecanismos relacionados ao desenvolvimento de LRA no pós-operatório de cirurgia cardíaca originam-se da redução de perfusão renal desencadeada pela circulação extracorpórea 7 . A redução de hemoglobina, como identificado no presente estudo se manifesta como vilã interferindo no adequado funcionamento do sistema renal ao aumentar o risco do paciente evoluir com LRA 12 .…”

The Effect of Optimized Ultrafiltration on Perioperative Pulmonary Function During Cardiopulmonary Bypass in Infants Under 10 kg

“…The amount of priming fluid used in cardiopulmonary bypass (CPB) is significantly higher (with respect to body surface area) in infants than in adults, especially in infants with body weight below 10 kg. Because of infants' low blood volume and the incomplete development of the immune system, vascular endothelial system, lung function, and kidney drainage function, changes in priming fluid composition and the interaction of related factors in the course of CPB have a significant influence on the internal environment of infants, and there is increased likelihood of acute kidney and lung injury (1)(2)(3). As such, mitigating these adverse factors for children with a body weight below 10 kg is very important.…”