890 pilot in Africa teaching bed side acute PD cathe ter insertion – often with “improvised” cathe ters – as well as the use of locally made dialysis fluid solutions PD catheters have ranged from any[.]
M I McCulloch and A Bagga 890 Table 45.1 Comparing different modalities of dialysis Modality Peritoneal dialysis (PD) Indications Most common form of dialysis in children Manual PD Infants 12 years old) PD 29.1% (14/48) HD 64.5% (31/48) CRRT 2% (1/48) SLED 2% (1/48) Availability of RRT’s PD 100% (48/48) HD 54.1% (26/48) CRRT 33.3% (16/48) SLED 25% (12/48) Indication for CRRT Fluid overload in critically ill child 12.5% (2/16) Hyperkalemia 81.2% (13/16) Persistent metabolic acidosis 31.2% (5/16) Hyperammonemia secondary to inborn errors 100% (16/16) and liver failure Preferred mode of CRRT CVVH 12.5% (2/16) CVVHD 43.7% (7/16) CVVHDF 12.5% (2/16) Depends on the clinical situation 25% (4/16) Change in dialysis modality choice in the past 41.6% (20/48) 10 years Plans to add CRRT/HD services in the next 10.4% (5/48) 10 years Access to newer dialysis machines 0% (0/48) (CARPEDIEM, Aquadex, NIDUS) Developed countries 100% (175/175) 91% (159/175) p 0.000 0.000 5.7% (10/175) 72% (126/175) 24% (42/175) 1.1% (2/175) 0.000 0.000 0.041 0.006 22.2% (39/175) 61.1% (107/175) 14.8% (26/175) 2.2% (4/175) 0.319 0.668 0.016 0.933 100% (175/175) 85.1% (149/175) 60% (105/175) 20% (35/175) 0.000 0.001 0.452 40% (42/105) 100% (105/105) 61.9% (65/105) 100% (105/105) 0.033 0.000 0.021 17.1% (18/105) 14.2% (15/105) 31.4% (33/105) 35.2% (37/105) 70.2% (123/175) 0.637 0.004 0.120 0.422 0.000 0% (0/175) 0.000 2.28% (4/175) 0.291 Open Access: Raina et al [18] rapid assessment of coagulation Citrate antico- and out-patient settings to determine the magniagulation is not widely available in less well- tude of the problem [22] Electronic detection resourced countries due to its cost algorithms may be useful in the future [23] Even basic forms of renal replacement therapy such as manual peritoneal dialysis may not Outcomes be available due to absence of dialysis fluid and peritoneal dialysis catheters This is a particular AKI in LLMIC remains a common yet treatable problem in infants and small children where condition if diagnosed and managed early and appropriately sized equipment may not be availappropriately However, many cases present late able at all centers; in addition, governments often and are unrecognized, resulting in poor out- not fund acute dialysis in children [24] comes Epidemiological studies in pediatric AKI In bigger children and adolescents, adult are needed at national levels in both in-patient hemodialysis units may provide short-term M I McCulloch and A Bagga 892 hemodialysis, but often families must pay for the dialysis, both the catheters as well as the dialysis sessions This is only possible in hemodynamically stable patients, as pediatric high care or intensive care facilities with cardiac monitors, inotropes, and continuous RRT are simply not available in many regions Ethical dilemmas are also related to the length of time for which children with AKI are dialyzed and what happens when this becomes chronic kidney failure with end-stage kidney disease (ESKD) Acute PD catheters inserted at the bedside would usually only be functional for 7–10 days before infection sets in, these devices become obstructed, or they become dislodged The difficult decision then remains as to whether to convert to chronic dialysis – if even possible and available – usually in the form of chronic HD. This may not be possible for smaller children and infants and in some cases may only be performed 1–2 times per week due to cost and availability of dialysis slots in many LLMIC An alternative is continuous ambulatory PD (CAPD) which does not require sophisticated equipment or infrastructure and should be an ideal form of RRT for those living in remote areas However, CAPD even in adults is scarcely available in many LLMICs due to high costs and unavailability of fluids, lack of expertise in catheter insertion, and management of complications combined with socio-economic complications [25] A large review of adults and children with ESKD in Sub-Saharan Africa showed that the majority of children (95%) who could not access dialysis died (or were presumed to have died) Among those with ESKD for which children were dialyzed, 36% died and 28% were lost to follow-up A large proportion (20%) of children left hospital against hospital advice [26] When government funding is not available and families are required to cover the cost of dialysis, this can result in families selling their homes and compromising the rest of the family for short-term dialysis with no foreseeable outcome if adequate long-term dialysis and renal transplantation with availability of drugs and monitoring are not available [27] Palliative or supportive care specifically in pediatric renal disease is an important component which has been unrecognized until recently both in well-resourced and possibly more importantly in LLMIC where failure of treatment or response to treatment of AKI frequently results in the demise of children and infants This is particularly relevant when the AKI becomes ESKD for which treatment is not available The priority is then to emphasize a good quality death rather than a lingering poor-quality life which results in death inevitably Most important is the role of advocacy by nephrologists and particularly pediatric nephrologists to urge authorities and governments to address preventative factors related to AKI – clean water, mosquito nets – as well as availability of treatment for AKI in children, with good training of both doctors and nurses at the local level [28] References Sutherland SM, Byrnes JJ, Kothari M, et al AKI in hospitalized children: comparing the pRIFLE, AKIN, and KDIGO definitions Clin J Am Soc Nephrol 2015;10(4):554–61 https://doi.org/10.2215/ CJN.01900214 Basu RK, Kaddourah A, Terrell T, et al Assessment of Worldwide Acute Kidney Injury, Renal Angina and Epidemiology in critically ill children (AWARE): study protocol for a prospective observational study BMC Nephrol 2015;16:24 Published 26 Feb 2015 https://doi.org/10.1186/s12882-015-0016-6 Selewski DT, Gist KM, Nathan AT, et al The impact of fluid balance on outcomes in premature neonates: a report from the AWAKEN study group Pediatr Res 2020;87(3):550–7 https://doi.org/10.1038/ s41390-019-0579-1 Madsen NL, et al Cardiac surgery in patients with congenital heart disease is associated with acute kidney injury and the risk of chronic kidney disease Kidney Int 2017;92(3):751–6 Aye KP, Thanachartwet V, Soe C, et al Clinical and laboratory parameters associated with acute kidney injury in patients with snakebite envenomation: a prospective observational study from Myanmar BMC Nephrol 2017;18(1):92 Published 16 Mar 2017 https://doi.org/10.1186/s12882-017-0510-0 Goldstein SL. Fluid management in acute kidney injury J Intensive Care Med 2014;29(4):183–9 Bhatt GC, Gogia P, Bitzan M, Das RR. Theophylline and aminophylline for prevention of acute kidney 45 Acute Kidney Injury in Less Well-Resourced Countries injury in neonates and children: a systematic review Arch Dis Child 2019;104(7):670–9 Jankowska M, et al Water soluble vitamins and peritoneal dialysis – state of the art Clin Nutr 2017;36(6):1483–9 Harshman LA, Lee-Son K, Jetton JG. Vitamin and trace element deficiencies in the pediatric dialysis patient Pediatr Nephrol 2018;33(7):1133–43 https:// doi.org/10.1007/s00467-017-3751-z 10 Goldstein SL, Somers MJ, Baum MA, Symons JM, Brophy PD, Blowey D, Bunchman TE, Baker C, Mottes T, McAfee N, Barnett J, Morrison G, Rogers K, Fortenberry JD. Pediatric patients with multi-organ dysfunction syndrome receiving continuous renal replacement therapy Kidney Int 2005;67(2):653–8 11 Maitland K, Kiguli S, Opoka RO, Engoru C, Olupot- Olupot P, Akech SO, Nyeko R, Mtove G, Reyburn H, Lang T, Brent B, Evans JA, Tibenderana JK, Crawley J, Russell EC, Levin M, Babiker AG, Gibb DM, FEAST Trial Group Mortality after fluid bolus in African children with severe infection N Engl J Med 2011;364(26):2483–95 12 Levin M, Cunnington AJ, Wilson C, Nadel S, Lang HJ, Ninis N, McCulloch M, Argent A, Buys H, Moxon CA, Best A, Nijma RG, Hoggart CJ. Effects of saline or albumin fluid bolus in resuscitation: evidence from re-analysis of the FEAST trial Lancet Respir Med 2019;7(7):581–3 13 PRISM Investigators, Rowan KM, Angus DC, Bailey M, Barnato AE, Bellomo R, Canter RR, Coats TC, Delaney A, Gimbel E, Grieve RD, Harrison DA, Higgins AM, Howe B, Huang DT, Kellum JA, Mouncey PR, Music E, Peake SL, Pike F, Reade MC, Sadique MZ, Singer M, Yealy DM. Early goal-directed therapy for septic shock – a patient-level meta-analysis N Engl J Med 2017;376(23):2223–34 14 Montomoli J, Donati A, Ince C. Acute kidney injury and fluid resuscitation in septic patients: are we protecting the kidney? Nephron Clin Pract 2019;143(3):170–3 15 Raina R, Sethi SK, Nikita W, Vemuganti M, Krishnappa V, Bansal SB. Fluid overload in critically ill children Front Pediatr 2018;6:2296–360 16 Branco RG. Dopamine in sepsis-beginning of the end? Pediatr Crit Care Med 2016;17(11):1099–100 17 Sethi SK, Chakraborty R, Joshi H, Raina R. Renal replacement therapy in pediatric acute kidney injury Indian J Pediatr 2020 https://doi.org/10.1007/ s12098-019-03150-9 18 Raina R, Chauvin AM, Bunchman T, Askenazi D, Deep A, Ensley ME, Krishnappa V, Sethi SK. Treatment of AKI in developing and developed countries: an international survey of pediatric dialysis 893 modalities PLoS One 2017;12(5):e0178233 https:// doi.org/10.1371/journal.pone.0178233.t002 19 Abdou N, Antwi S, Koffi LA, Lalya F, Adabayeri VM, Nyah N, Palmer D, Brusselmans A, Cullis B, Feehally J, McCulloch M, Smoyer W, Finkelstein FO. Peritoneal dialysis to treat patients with acute kidney injury-The saving young lives experience in West Africa: proceedings saving young lives session, international conference of dialysis in West Africa, Dakar, Senegal Perit Dial Int 2017;37(2):155–8 20 Palmer D, Lawton WJ, Barrier C Jr, Fine BD Jr, Hemphill H, Nyah NN, Kinne V, Ringnwi NI, Yong G, Neufeldt AL, Mitterand Y, Finkelstein FO, Krahn TA. Peritoneal dialysis for AKI in Cameroon: commercial vs locally-made solutions Perit Dial Int 2018;38(4):246–50 21 Cullis B, Al-Hwiesh A, Kilonzo K, McCulloch M, Niang A, Nourse P, Parapiboon W, Ponce D, Finkelstein FO ISPD guidelines for peritoneal dialysis in acute kidney injury: 2020 update (adults) Perit Dial Int 2020 Dec 3:896860820970834 https://doi org/10.1177/0896860820970834 Epub ahead of print PMID: 33267747 22 Selby NM, Lennon R. Be on alert for pediatric AKI. Kidney Int 2017;92(2):286–8 23 Holmes J, Roberts G, Geen J, Dodd A, Selby NM, Lewington A, Scholey G, Williams JD, Phillips AO, Welsh AKI Steering Group Utility of electronic AKI alerts in intensive care: a national multicentre cohort study J Crit Care 2018;44:185–90 24 Lalji R, Francis A, Johnson DW, McCulloch MI. Health disparities in access to kidney replacement therapy amongst children and adolescents with end stage kidney disease in low- and lower-middle income countries Kidney Int 2020;97(3):463–5 25 Wearne N, Kilonzo K, Effa E, Davidson B, Nourse P, Ekrikpo U, Okpechi I. Continuous ambulatory peritoneal dialysis: perspectives on patient selection in lowto middle-income countries Int J Nephrol Renovasc Dis 2017;10:1–9 26 Ashuntantang G, Osafo C, Olowu WA, Arogundade F, Niang A, Porter J, Naicker S, Luyckx VA. Outcomes in adults and children with end-stage kidney disease requiring dialysis in sub-Saharan Africa: a systematic review Lancet Glob Health 2017;5(4):e408–17 27 Levy CS, Mudi A, Venter B, Geel J. Challenges facing children on chronic peritoneal dialysis in South Africa Perit Dial Int 2018;38(6):402–4 28 McCulloch M, Luyckx VA, Cullis B, Davies SJ, Finkelstein FO, Yap HK, Feehally J, Smoyer WE Challenges of access to kidney care for children in low-resource settings Nat Rev Nephrol 2021;17(1):33 45 https://doi.org/10.1038/s41581020-00338-7 Epub 2020 Oct PMID: 33005036 Extracorporeal Liver Support Therapies for Children 46 Betti Schaefer, Claus Peter Schmitt, and Rajit K. Basu Introduction ascites [5] Likewise, the majority of children with acute-on-chronic liver failure and those Acute liver failure (ALF) and acute-on-chronic with progressive chronic liver disease require liver failure are rare but life-threatening disor- liver transplantation Pediatric ALF accounts ders in children Disease pathophysiology often for approximately 10% of liver transplants perdepends on patient age Metabolic disorders and formed in the United States annually Since organ viral hepatitis are more frequent in infants with availability is limited and considerable bridging ALF, drug intoxication, and autoimmune dis- time may be required, extracorporeal liver supease in older children, while the etiology of ALF port therapies (ELS) are increasingly applied remains unexplained in 40–50% of cases [1] Therapies for ALF are targeted to two paraAge-specific algorithms may reduce the rate of digms of outcome The primary goal of therapy unexplained causes [1] In developing countries, is for the liver to recover back to normal health infectious etiologies predominate,while in adults For the most part, supportive care of other vital drug toxicity is the most common cause [2, 3] organs is required while liver function is supThe estimated frequency of ALF is unknown ported through supplemental restoration of synin children Many children in the developing thetic function products such as coagulation world are unaccounted for Across all age groups products (Factor VII) and albumin Meanwhile, in the United States, the estimated frequency is supportive care for the remainder of organs tar17 per 100,000 population per year While one- gets a return to primary health if the offending third of children recover with standard medical agent for the ALF abates In contrast, for patients care [4], the other two-thirds require emergency with acute-on-chronic liver failure, the primary liver transplantation Common features of pre- goal is to return to the pre-ALF morbidity level sentation for ALF include encephalopathy (presThe goal of ELS therapy is to bridge the ent in more than 50% of children), seizures, and patient until transplantation or recovery of liver function (Fig. 46.1) ELS options include both non-biological and biological systems The ideal system would be able to remove water, lipid, and B Schaefer (*) ∙ C P Schmitt protein-bound metabolites, correct coagulopathy, Center for Pediatric and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany and address ongoing immunologic deficits and e-mail: Betti.schaefer@med.uni-heidelberg.de perturbations The primary goal of ELS therapy is R K Basu to prevent or limit the severity of hepatic encephChildren’s Healthcare of Atlanta, Emory University, alopathy – along with important clinical manageDepartment of Pediatrics, Critical Care Medicine, ment adjuncts to limit other preventable causes Atlanta, GA, USA © Springer Nature Switzerland AG 2021 B A Warady et al (eds.), Pediatric Dialysis, https://doi.org/10.1007/978-3-030-66861-7_46 895 B Schaefer et al 896 Liver function Normal Recovery/LTx the potential for using a multi-modal approach, incorporating standard continuous renal replacement therapy (CRRT) with TPE concurrent with an ELS modality such as MARS – so-called – hybrid ELS – is possible and has demonstrated encouraging preliminary results [6] Bridging Lethal Time Fig 46.1 Scheme illustrating the principle of extracorporeal liver support in the course of liver failure Ltx liver transplantation (Modified from Schaefer and Schmitt [56]) of increased intracranial pressure (e.g., pain, agitation, excessive cerebral blood flow), limitation of protein delivery, and elimination of ammoniabased waste products The non-biological systems include hemofiltration, hemoperfusion, plasma exchange, and albumin dialysis To perform these actions, there are currently several options for mechanical, or extracorporeal liver support systems: the molecular adsorbent recirculating system (MARS), Prometheus dialysis, therapeutic plasma exchange combined with hemodialysis (TPE/HD), and single-pass albumin dialysis (SPAD) Smaller reports are published on ELS systems such as open albumin dialysis (OPAL) and ADVanced Organ Support (ADVOS) The biological systems include extracorporeal whole liver perfusion, cross-circulation, and hybrid bioartificial liver support systems This chapter focuses on the non-biological systems, which are increasingly applied in children with liver failure The four main ELS modalities are based on different technical approaches to remove protein- bound toxins These consist of hemodialysis against a closed albumin circuit with additional toxin adsorbers (MARS), plasma separation followed by plasma purification and reinfusion (Prometheus), plasma separation in combination with hemodialysis, and single-pass albumin dialysis (SPAD) Knowledge about the specific advantages and shortcomings of each technology is vital in order to select the most appropriate liver support system available in a given critical care unit setting Additionally, understanding I ndications for Extracorporeal Liver Support Therapy cute and Acute-on-Chronic Liver A Failure The liver plays a key role in a variety of bodily functions: maintains metabolic balance, the endocrine milieu, and acid–base status; synthesizes binding proteins, complement, and coagulation factors; metabolizes water soluble and albuminbound endogenous and exogenous toxins; and neutralizes intestinal bacterial fragments In patients with liver failure, all of these functions require careful consideration and appropriate therapeutic measures Extracorporeal liver dialysis should be started in patients with ALF and in those with acute-on-chronic liver failure if a curative therapy, i.e., usually liver transplantation, or significant recovery of liver function can be expected (Tables 46.1 and 46.2) Of note, one-third of children with acute liver failure may recover [4], possibly in cases of intoxications, metabolic diseases, and autoimmune hepatitis, Table 46.1 Potential clinical setting for liver replacement therapy Acute liver failure Bridging to LTX Post LTX in case of primary organ dysfunction Liver dysfunction after hepatobiliary surgery Acute intoxication Acute/chronic hepatitis (viral, autoimmune) Secondary liver dysfunction (due to sepsis, systemic inflammatory response syndrome, multiorgan dysfunction syndrome) Acute-on-chronic liver failure (biliary atresia, PFIC) Cholestatic pruritus (biliary atresia, PFIC, ARPKD) Legend: LTX liver transplantation, PFIC progressive familial intrahepatic cholestasis, ARPKD autosomal recessive polycystic kidney disease ... simply not available in many regions Ethical dilemmas are also related to the length of time for which children with AKI are dialyzed and what happens when this becomes chronic kidney failure with... to primary health if the offending third of children recover with standard medical agent for the ALF abates In contrast, for patients care [4], the other two-thirds require emergency with acute-on-chronic... may not Outcomes be available due to absence of dialysis fluid and peritoneal dialysis catheters This is a particular AKI in LLMIC remains a common yet treatable problem in infants and small children