903 removal [28] Depending on the availability of resources and personnel expertise, as discussed earlier, the use of ELS, CRRT, and TPE should be adjudicated Regardless of the choice, con stant monit[.]
46 Extracorporeal Liver Support Therapies for Children 903 Table 46.3 Advantages and disadvantages of extracorporeal liver support systems Advantages Drawbacks MARS No exogenous protein delivery, no infectious and allergic risk Continuous administration feasible Good clinical tolerability Prometheus No exogenous protein delivery, no infectious and allergic risk Continuous administration feasible Good clinical tolerability SPAD No exogenous protein delivery, no infectious and allergic risk Good clinical tolerability Relatively easy to perform Bleeding risk, additional plasma substitution is associated with volume and nitrogen load High costs and workload (system exchange q 8–12 h) Bleeding risk, additional plasma substitution is associated with volume and nitrogen load High costs and workload (system exchange q 8–12 h) High extracorporeal volume Bleeding risk, additional plasma substitution is associated with volume and nitrogen load High amounts of albumin required for extended treatment and large children TPE/HD High detoxification capacity Efficient compensation of liver synthesis failure, reduces bleeding risk Volume and nitrogen neutral balance Cheaper Widely available Intermittent therapy (TPE) Infectious and allergic risks related to exogenous protein load MARS molecular adsorbent recirculating system, SPAD single-pass albumin dialysis, TPE/HD therapeutic plasma exchange combined with hemodialysis removal [28] Depending on the availability of resources and personnel expertise, as discussed earlier, the use of ELS, CRRT, and TPE should be adjudicated Regardless of the choice, constant monitoring of coagulation and pressure in a multi-modal system is mandatory to avoid adverse events [28] MARS and Prometheus therapies are usually performed for 6–8 h, but can be extended or may also be applied continuously in critical cases System exchanges are required two to three times a day to maintain good purification efficacy Of note, setup times are shorter and the material costs are usually lower (depending on patient size) with combined plasma exchange and hemodialysis than with MARS or Prometheus Of course, cost-efficacy considerations must also take center-specific reimbursement policies into account Several randomized prospective studies have compared MARS and Prometheus with standard medical therapy There does not appear to be any major differences in purification capacity with Prometheus and MARS, but one trial has suggested superior cardiovascular stability with MARS [36] SPAD is a technically simple liver support system, which is feasible in small children Several case reports including pediatric patients [37] suggest a dose- and time-dependent clearance efficacy of SPAD with respect to bilirubin, thyroxine, copper and, at least in vitro, of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) However, SPAD is associated with uncertain survival benefits as compared to standard medical treatment [38–42] Experimental and clinical comparisons of SPAD and MARS have yielded conflicting findings: both similar to slightly better [43, 44] and inferior efficacy of SPAD [45, 46], presumably mainly depending on the intensity of the treatments in terms of duration, flow rates, and albumin concentrations Neither MARS nor Prometheus or SPAD have been compared in prospective trials with combined hemodialysis and plasma exchange, the most readily available and least expensive extracorporeal liver support therapy Clinical observations in seven children, including an intraindividual comparison in five children, suggest better bilirubin removal and, not surprisingly, much better control of the coagulation status with combined TPE/HD as compared to B Schaefer et al 904 intermittent MARS therapy The MARSmini system appeared particularly limited in this comparison [22] Complications related to the constituents of ELS can add to the morbidity in these patients Although very little data have been published in this regard, anecdotal and observational data highlight the importance of understanding the potential negative effects of albumin and use of multiple extracorporeal devices in tandem Human serum albumin contains octanoate, a medium chain fatty acid, for stabilization during the manufacturing process An involvement of this compound in the pathogenesis of hepatogenic encephalopathy, both by direct neurotoxicity and by competitive displacement of albumin-bound toxins, has been suggested Markedly increased plasma octanoate levels have been described with MARS and even higher concentrations with SPAD [47] No such accumulation should be observed with plasmapheresis The relevance of octanoate accumulation on clinical outcomes is as yet unknown All extracorporeal devices cause mechanical platelet sequestration during blood passage through the filter and membrane-induced immune-mediated coagulation factor consumption, which has been associated with increased bleeding risk and major bleeding episodes [18, 19, 48] Consumptive coagulopathy induced by preexisting bleeding from predilection sites may further aggravate a coagulation deficiency Fresh frozen plasma and blood transfusions may insufficiently correct any coagulation failure and result in volume and protein overload; plasma exchange should be initiated in these children utcome of ELS in Patients O with Liver Failure The removal of an array of toxins with albumin dialysis has repeatedly been demonstrated to be followed by pruritus relief [12, 13], improved mean arterial pressure, systemic vascular resistance, cardiac output, cerebral flow [49], intracranial pressure [50], kidney function, and hepatic encephalopathy [21, 49–54] Several pediatric observational studies also suggest good clinical tolerability and efficacy of ELS in terms of biochemical correction of liver failure and improvement of hepatic encephalopathy [6, 22, 23, 33] In addition to these early studies, seven RCTs in adults with different ELS modalities and different indications have been performed with varying doses of ELS. These were included in a recent meta-analysis together with 18 small-size prospective trials in adults with liver failure, altogether comprising a total of 1796 patients [55] This analysis has suggested with moderate certainty an improved overall survival (RR 0.84; 95% CI 0.74, 0.96) and reduced hepatic encephalopathy (RR 0.71; 95% CI 0.60, 0.84, low certainty) with ELS. The risk of bleeding, hypotension, and thrombocytopenia was increased with ELS, but the quality of the studies precludes firm conclusions regarding these potential complications Conclusion Taken together, there is increasing evidence that ELS improves hepatic encephalopathy and survival in patients with liver failure waiting for liver transplantation or recovery of liver function, which may be expected in one-third of patients depending on the underlying disease In terms of the various devices available for ELS, plasma exchange together with hemodialysis/hemodiafiltration is easy to perform, widely available in pediatric dialysis centers, and cost-effective Limited observational comparisons suggest comparable efficiency to MARS, while comparisons with other albumin-based ELS systems have not yet been performed Children with otherwise refractory, unbearable cholestatic pruritus, can efficiently be treated with albumin dialysis without exposure to large amounts of foreign protein References Narkewicz MR, Horslen S, Hardison RM, Shneider BL, Rodriguez-Baez N, Alonso EM, Ng VL, Leonis MA, Loomes KM, Rudnick DA, Rosenthal P, Romero R, Subbarao GC, Li R, Belle SH, Squires 46 Extracorporeal Liver Support Therapies for Children RH. 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The role of molecular adsorbent recirculating system dialysis for extracorporeal liver support in children Pediatr Nephrol 2013;28(9):1763–9 Dialytic Therapy of Inborn Errors of Metabolism in Case of Acute Decompensation 47 Lucile Barcat, Patricia Monnier, Franz Schaefer, and Philippe Jouvet Introduction Some inborn errors of metabolism involve enzyme defects in the catabolic pathway of amino acids that induce a metabolic encephalopathy by accumulation of neurotoxic metabolites (endogenous intoxication) In these diseases, intermediate products of amino acid catabolism are not detoxified by the liver, accumulate, and contribute to neurologic symptoms (Fig. 47.1) Cerebral edema is frequently associated with these disorders and is mainly due to cytotoxic mechanisms [1, 2] Since the encephalopathy is related to the accumulation of toxic metabolites, specific therapeutic strategies are required to decrease this accumulation and restore brain function, including dialysis Rapid elimination of these metabolites is crucial in order to prevent irreversible neuronal damage since long- L Barcat · P Jouvet (*) Sainte-Justine Hospital, Department of Pediatrics, Montreal, QC, Canada e-mail: philippe.jouvet@umontreal.ca P Monnier Department of Obstetrics Gynecology, Royal Victoria Hospital, Montreal, QC, Canada F Schaefer Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany term outcome is correlated with the duration of the metabolic crisis Metabolic crises are challenging indications for dialysis in several ways: the initial treatment is the institution of protein anabolism to suppress further neurotoxic metabolite production It is important not to miss the time point when dialysis becomes necessary to prevent irreversible brain damage Small infants and neonates, who usually have the most rapid and severe course of disease and the greatest need for efficient detoxification, are particularly challenging with respect to vascular access and methodological efficacy and accuracy This chapter reviews the principles of anabolic treatment and management by dialysis of neonatal and pediatric metabolic emergencies Clinical Manifestations and Laboratory Investigations In some circumstances, the patient’s diagnosis is clear at the time of admission and clinical management can focus on specific treatment This is the case in one-third of the neonates and two- thirds of the children with inborn errors of metabolism (IEM) who are admitted to the Pediatric Intensive Care Unit (PICU), in our experience [3] Unfortunately, there is almost no exact report on the incidence of IEM in Neonatal Intensive Care Units [4] Indeed, the first challenge is to quickly diagnose treatable disorders so as to ensure prompt treatment and recovery © Springer Nature Switzerland AG 2021 B A Warady et al (eds.), Pediatric Dialysis, https://doi.org/10.1007/978-3-030-66861-7_47 909 ... of admission and clinical management can focus on specific treatment This is the case in one-third of the neonates and two- thirds of the children with inborn errors of metabolism (IEM) who are... particularly limited in this comparison [22] Complications related to the constituents of ELS can add to the morbidity in these patients Although very little data have been published in this regard, anecdotal... prospective trials in adults with liver failure, altogether comprising a total of 1796 patients [55] This analysis has suggested with moderate certainty an improved overall survival (RR 0.84; 95% CI