Effect of Continuous Renal Replacement Therapy on Outcome in Pediatric Acute Liver Failure: Is the Clearance Mechanism Appropriate for Detoxification?

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We congratulate Deep et al (1) on their study published in a recent issue of Critical Care Medicine that analyzed the effect of continuous renal replacement therapy CRRT) on outcome in pediatric acute liver failure (PALF). The authors have concluded that CRRT should be considered at an early stage to help prevent further deterioration and buy time for potential spontaneous recovery or bridge to liver transplantation.
However, there are certain aspects of the study which need more clarification for better understanding. The authors have mentioned that initiating CRRT in PALF serves a dual purpose: 1) for managing the acute kidney injury and fluid imbalances, which frequently complicate cases and 2) as a detoxification mechanism for the high ammonia, lactate, and metabolic disturbances which set in. We agree with the authors for the first purpose, but there is doubt regarding detoxification mechanism because the majority of toxins in liver failure is water insoluble and albumin-bound and is poorly cleared by conventional hemodialysis or hemofiltration systems. In vitro study by Sauer et al (2) has demonstrated that molecular adsorbent recirculation system and single-pass albumin dialysis are better than CRRT.
Hepatic encephalopathy is one of the inclusion criteria for the enrollment. In study methodology, it has been mentioned that patients with hepatic encephalopathy greater than grade 2 were enrolled, but Table 2 mentions that patients with grade 2 were also enrolled. There were only 27% patients who had hepatic encephalopathy grade 2 or more than 2. So the majority of patients had only grade 1 hepatic encephalopathy at enrollment. The severity of hepatic encephalopathy is directly linked to mortality in PALF (3). We would also like to know the survival according to the severity of hepatic encephalopathy.
There was no significant reduction in arterial ammonia level in nonsurvivors (Table 3) when compared with survivors. What were the factors considered responsible for no reduction in arterial ammonia level? In these cases, how was the CRRT therapy modified to improve clearance?
One more striking feature at baseline is that 93% patients were on vasoactive therapy. We would like to know the type of shock in these patients and Vasoactive-Inotrope Score in survivors and nonsurvivors. We also observed that patients who were on heparin had less filter life compared to the patients who were on prostacyclin. We would like to know author’s opinion to explain the mechanism for the same.

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