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The successful application of hemoadsorption for extracorporeal liver support in a child with acute liver failure
Wun Fung Hui, Wing Lum Cheung, Fung Shan Chung, Karen Ka Yan Leung and Shu Wing Ku | Department of Paediatrics and Adolescent Medicine, Hong Kong Children’s Hospital, Kowloon, Hong Kong | Int J Artif Organs 2022; epub
08/17/2022
New!PediatricsPeer Reviewed Published DataSafetyBilirubinCase of the weekCase reportCritical CareCRRT (pre or post filter)Improv. hep. encephalopathy
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Summary
CoW 33/2022 – This case reports on a 6-year-old boy, who was admitted to the hospital due to prolonged dyskinetic movements resulting in rhabdomyolysis and acute kidney injury.
Summary
The following case report describes the use of CytoSorb in a pediatric patient for the reduction of hyperbilirubinemia and elevated serum bile acids in acute liver failure. A 6-year-old boy was admitted to hospital due to prolonged dyskinetic movements resulting in rhabdomyolysis and acute kidney injury. Over the following 10 days he was given multiple antibiotics for various infections and five days later developed acute liver failure with hepatic coma due to drug rash with eosinophilia and systemic symptoms (DRESS). He had hyperbilirubinemia, elevated serum bile acids and hyperammonemia as well as raised liver enzymes. Despite standard therapies his condition deteriorated, and he was admitted to the Pediatric Intensive Care Unit (PICU) for ongoing management. In addition to the use of systemic steroids and other supportive therapies, he was started on continuous renal replacement therapy (CRRT), into which a CytoSorb column was added as an extracorporeal liver support to try and reduce the bilirubin and bile acids. Three adsorbers were used for a total duration of 75 hrs (28, 22 and 25 hrs). Serum levels of total bilirubin reduced from 418 to 119 µmol/L, bile acids to from 174 to 58 µmol/L and ammonia reduced from 172 to 55 µmol/L. His conscious level gradually improved, as did his liver function. Except for mild, non-symptomatic thrombocytopenia and mild electrolyte disturbances, the therapy was well tolerated with no major complication encountered. He was finally able to be discharged from the PICU after 20 days. The authors state that hemoadsorption may have the merits of a faster initial rate of bilirubin removal and ease of set up compared to albumin dialysis. In summary this case demonstrates that hemoadsorption with CytoSorb can be safely employed as an adjunctive extracorporeal liver support modality in children with acute liver failure as it can efficiently remove bilirubin and bile acids. The potential role and technical concerns of applying such technique in pediatric patients requires further evaluation in future studies.
Case presentation
He was initially given ceftriaxone for potential central venous system infection. Later, his course was complicated by streptococcus mitis pneumonia resulting in the administration of vancomycin for 7 days. In the subsequent 10 days of hospitalization, he was given amoxicillin and clavulanic acid as well as piperacillin/tazobactam as empirical therapy for recurrence of fever, while all microbiological investigations showed no positive bacterial growth
Five days after stopping all antibiotics, he again developed low grade fever. He also had hepatomegaly, ascites and a generalized erythematous maculopapular rash associated with tender cervical lymphadenopathy
Blood tests revealed leukocytosis with white blood cell count 12.4×109/L, lymphocyte count 4.72×109/L, eosinophil count 0.37 × 109/L, and the presence of atypical lymphocytes
He also showed increased liver enzymes (serum levels of alanine aminotransferase [ALT] 1241 IU/L, alkaline phosphatase [ALP] 220 IU/L, aspartate aminotransferase [AST] 839 IU/L and gamma-glutamyl transferase [GGT] 160 IU/L), hypoalbuminemia (29 g/L), hyperbilirubinemia (25 µmol/L), and coagulopathy (international normalized ratio [INR] 1.49 and activated partial thromboplastin time [aPTT] 34.6 s). The ammonia level was <20 µmol/L
Ultrasound of the hepatobiliary system showed no focal hepatic lesions and no dilated biliary system
He was started on cefotaxime empirically, which was changed to meropenem 4 days later
Supportive treatment with vitamin K, albumin and fresh frozen plasma (FFP) was also commenced
However, serial investigations revealed evolving hepatic failure and he was subsequently transferred to the Pediatric Intensive Care Unit (PICU) for further management
Upon PICU admission, he was still arousable and his Glasgow Coma Scale (GCS) was 15, but he soon started to desaturate requiring high flow oxygen of 15 L/min
Multiple investigations were performed to try and determine the underlying cause of his acute hepatic failure. Finally, he was diagnosed with drug rash with eosinophilia and systemic symptoms (DRESS) syndrome (most probably due to previous exposure to multiple antibiotics, in particularly the beta-lactams) based on the RegiSCAR (Registry of Severe Cutaneous Adverse Reaction) criteria, with Wilson’s disease being an important differential diagnosis
Hence, all antibiotics were stopped after PICU admission
He was then given ursodeoxycholic acid and vitamin supplements for his cholestasis and lactulose to limit enteral ammonia absorption. His protein intake was limited to <1 g/kg/day
One dose of intravenous immunoglobulin was administered for potential Epstein-Barr virus infection
Methylprednisolone was also started 3 days after admission as a treatment for DRESS syndrome
Despite that, he continued to deteriorate with reduced conscious level (GCS dropped to 10) suggesting the development of grade three hepatic encephalopathy. Serum total bilirubin was 418 µmol/L, direct bilirubin 328 µmol/L, bile acids 174 µmol/L and ammonia levels had increased to 172 µmol/L, while INR increased to 3.12
There was also evolving bradycardia suggestive of bile acid-associated cardiac toxicity. The bedside echocardiogram showed normal contractility with a left ventricular fractional shortening of 37%
His highest Pediatric End-stage Liver Disease (PELD) score was 30 and he had a work up for potential liver transplant
Therefore, continuous renal replacement therapy (CRRT) was started for hyperammonemia 4 days after admission. In order to accelerate removal of bilirubin and bile acids, a CytoSorb hemoadsorption column was additionally integrated into the CRRT circuit
Treatment
Three adsorbers were used for a total duration of 75 hrs (28, 22 and 25 hrs)
Measurements
Bilirubin, bile acids, ammonia
Liver function
Level of consciousness
Coagulation profile
Platelets, electrolytes
Results
Under combined CRRT+CytoSorb treatment, serum levels of total bilirubin reduced from 418 to 119 µmol/L, bile acids to from 174 to 58 µmol/L and ammonia reduced from 172 to 55 µmol/L
His liver function showed gradual improvement following therapy initiation. Of note, one day after commencing combined CRRT+CytoSorb he was started on penicillamine based on the provisional diagnosis of Wilson’s Disease
His conscious level also improved and returned to his baseline level 2 days after CRRT+CytoSorb initiation
The coagulation profile improved and there was reduced requirement for FFP infusion
Except for mild, non-symptomatic thrombocytopenia and mild electrolyte disturbances, the therapy was well tolerated with no major complications encountered
Patient Follow-up
One dose of carglumic acid and regular sodium benzoate were started as a bridging therapy to prevent rebound of hyperammonemia upon CRRT termination
Sodium benzoate administration was stopped one week after CRRT termination
A drug challenge test was arranged and blood tests on day 20 of PICU admission showed serum levels of ammonia 37 µmol/L, total bilirubin 102 µmol/L, ALT 91 IU/L, ALP 170 IU/L, AST 43 IU/L, GGT 208 IU/L, INR was 0.95
He was finally discharged from the PICU 20 days after admission
Conclusion
In summary, this case demonstrates that hemoadsorption with CytoSorb can be safely employed as an adjunctive extracorporeal liver support modality in children with acute liver failure as it can efficiently remove bilirubin and bile acids
The authors state that hemoadsorption may have the advantages of a faster initial rate of bilirubin removal and ease of set up compared to albumin dialysis
The potential role of applying such technique in pediatric patients requires further evaluation in future studies.
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