Intravascular Hemolysis and AKI in Children Undergoing Extracorporeal Membrane Oxygenation.

Abstract

AKI is common in ECMO patients, with a variety of proposed mechanisms. We sought to describe the impact of laboratory evidence of ECMO-associated intravascular hemolysis on AKI and renal replacement therapy (RRT). This retrospective cohort study included patients treated with ECMO at a single center over ten years. The primary outcome was a composite of time to RRT or AKI (by creatinine based KDIGO criteria) after ECMO start. Serum creatinine closest to ECMO start time was considered the pre-ECMO baseline and used to determine abnormal kidney function at ECMO start. The patient's subsequent creatinine values were used to identify AKI on ECMO. Multivariable cause-specific cox proportional hazards models were used to assess the impact of separate markers of intravascular hemolysis on the time to the composite outcome after controlling for confounders. 501 children were evaluated with a median age 1.2 years, 56% male. Four separate multivariable models, each with a different marker of hemolysis (plasma free hemoglobin, LDH, minimum platelet count, minimum daily hemoglobin) were used to examine the impact on the composite outcome of AKI/RRT. An elevated plasma free hemoglobin, the most specific of these hemolysis markers, demonstrated an almost three-fold higher adjusted hazard for the composite outcome (HR 2.9, p-value <0.01, 95% CI 1.4-5.6). Elevated LDH was associated with an adjusted hazard ratio of 3.1 (p-value <0.01, 95% CI 1.7-5.5). Effect estimates were also pronounced in a composite outcome of only more severe AKI, stage 2+ AKI/RRT: HR 6.6 (p-value <0.01, 95% CI 3.3-13.2) for plasma free hemoglobin and 2.8 (p-value <0.01, 95% CI 1.5-5.6) for LDH. Laboratory findings consistent with intravascular hemolysis on ECMO were independently associated with a higher hazard of a composite outcome of AKI/RRT in children undergoing ECMO.