Use of the Selective Cytopheretic Device to Support Critically Ill Children Requiring Continuous Renal Replacement Therapy: A Probable Benefit-Risk Assessment

Abstract

AbstractBackgroundCritically ill children with acute kidney injury (AKI) requiring continuous kidney replacement therapy (CRRT) are at increased risk of death. The selective cytopheretic device (SCD) promotes an immunomodulatory effect when circuit iCa2+is maintained at <0.40 mmol/L with regional citrate anticoagulation (RCA). In a randomized trial of adult patients on CRRT, those treated with the SCD maintaining an iCa2+<0.40 mmol/L had improved survival/dialysis independence. We have conducted two multicenter studies to evaluate safety and feasibility of the SCD in critically ill children with AKI receiving CRRT and multiorgan failure. We report the combined efficacy and safety data from these two studies for the first time.MethodsFour pediatric institutions enrolled children>10 kg in size with AKI and multiorgan dysfunction (MODS) receiving CRRT as part of standard of care to receive the SCD integrated post CRRT membrane. RCA was used to achieve a circuit iCa2+<0.40 mmol/L. We report serious adverse events, patient and CRRT-SCD related process and outcome variables and perform a Bayesian analysis to provide potential attributable benefit-risk assessment of SCD support in this critically ill population using a published matched cohort for the control population.ResultsTwenty-two patients (10 females) from the two studies comprise the combined population; 21 received mechanical ventilation, 14 received vasoactive medications, three received extracorporeal membrane oxygenation and 15 had sepsis at the time of CRRT-SCD initiation. Median SCD treatment duration was six days. Fifteen total serious adverse events were recorded, none of which were SCD related. All but one patient survived to the time of SCD discontinuation. Seventeen patients survived 60 days and 16 patients survived to the time ICU discharge. Fourteen patients surviving to ICU discharge had a normal eGFR and no patient was dialysis dependent at 60 days after CRRT-SCD initiation. Bayesian analyses revealed a 98-99% probable benefit of addition of SCD support.ConclusionThese data suggest SCD therapy is feasible, safe and demonstrates probably benefit for children who require CRRT for AKI in the setting of MODS.