Case of the Week
The Sequential Use of Extracorporeal Cytokine Removal Devices in an Adolescent With COVID-19 Receiving Continuous Renal Replacement Therapy
Wun Fung Hui1, Renee Wan Yi Chan2,3,4,5 , Chun Kwok Wong6, Ka Hang Andy Kwok1, Wing Lum Cheung1, Fung Shan Chung1, Karen Ka Yan Leung1, Kam Lun Hon1, Shu Wing Ku1 1Department of Paediatrics and Adolescent Medicine, Hong Kong Children's Hospital, Hong Kong. 2Department of Paediatrics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong. 3Hong Kong Hub of Paediatric Excellence, The Chinese University of Hong Kong, Hong Kong. 4Laboratory for Paediatric Respiratory Research, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong. 5CUHK-UMCU Joint Research Laboratory of Respiratory Virus & Immunobiology, Department of Paediatrics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong. 6Department of Chemical Pathology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong. ASAIO J 2022; 68(12):e230-e234
12/21/2022
New!Peer Reviewed Published DataViral infectionCase of the Week / MonthCase reportCOVID-19Critical CareCRRT post filterInflammatory parameters
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Summary
CoW 43/2022 – This case reports on an a 14-year-boy (43 kg) without any respiratory symptoms, who was admitted to a regional hospital with a fever of one day associated with vomiting and breakthrough seizures.
Summary
A 14-year-old male (43kg) developed multisystem inflammatory syndrome in children (MIS-C) after acquiring the SARS-CoV-2 infection. He deteriorated rapidly requiring inotropic and ventilatory support as well as continuous renal replacement therapy (CRRT) due to rhabdomyolysis-associated acute kidney injury. CytoSorb was first incorporated into the post-CRRT filter circuit for myoglobin and cytokine removal (hour 18 – 40), which was followed by sequential use of Oxiris (hour 40 – 80), followed by another CytoSorb adsorber (hour 85 – 110), giving a total of 100 hours of extracorporeal blood purification [EBP] therapy. There were no major complications related to the EBP therapy including hemodynamic compromise. Cytokine profile revealed a marked reduction of levels of several cytokines including tumor necrosis factor-alpha (TNFa), interleukin (IL)-6, IL-8, and IL-10 after the EBP therapy. It was noted that both pro-inflammatory and anti-inflammatory cytokines were removed, and the removal efficacy varied between different devices. The authors note that the two devices appeared to complement each other’s adsorption capacity. His condition improved and the serum ferritin, C-reactive protein, and procalcitonin levels also dropped gradually, which correlated well with his clinical progress and the trend of cytokine levels. The authors conclude that this case demonstrates that extracorporeal cytokine removal can be safely applied in children with MIS-C and can be considered as adjunctive therapy in selected patients with critically ill conditions.
Case presentation
Known medical history included a de novo G-Protein Subunit Alpha O1 (GNAO1)-mutation with movement disorder, epilepsy, and severe intellectual disability receiving baclofen, tetrabenazine, carbamazepine, and clobazam
On admission, his temperature was 40.1°C, heart rate 150/min, blood pressure 90/50 mmHg, and desaturation requiring oxygen supplementation
He exhibited vigorous involuntary movements and developed a status dystonicus
Blood tests on admission showed a white blood cell count of 9.1×109/L (neutrophil and lymphocyte count of 7.7×109/L and 0.9 × 109/L, respectively), urea 2.9 mmol/L, creatinine 41 µmol/L (baseline creatinine level was 31 µmol/L) and creatine kinase (CK) level of 117575 IU/L. Moreover, he was also found to pass brownish-red (myoglobin-positive) urine
He went on to develop disseminated intravascular coagulation with thrombocytopenia with an abnormal clotting profile (INR 1.7, aPTT >120 s, D-dimer 5072.9 ng/ml and fibrinogen 2.24 g/L)
The nasopharyngeal swab proved positive for SARS-CoV-2
He was started on hyperhydration, empirical piperacillin/tazobactam and one dose of remdesivir
Oral chloral hydrate was used for sedation
Urine output was maintained at 2–3 ml/kg/hour but the persistent fever and tachycardia continued, as did the excessive movements
He later developed stage 2 acute kidney injury (AKI) with an estimated glomerular filtration rate (eGFR) of 75 ml/min/1.73 m2 and was therefore transferred to the pediatric intensive care unit (PICU) for further management
His CK level rose sharply to the peak level of 449,100 IU/L with hypernatremia (sodium level of 155 mmol/L) and metabolic acidosis (pH 7.33, bicarbonate level of 13.8, and base excess of -11.8 mmol/L)
The lactate level was 2.3 mmol/L, troponin-T level was 170 ng/L and the eGFR reduced to 66 ml/min/1.73m2
He developed abnormal liver function tests with serum levels of alanine aminotransferase (ALAT) 1469 IU/L, aspartate aminotransferase (ASAT) 6577 IU/L, and ammonia 52 µmol/L
There were also elevated levels of inflammatory markers including ferritin 5842 pmol/L, procalcitonin 13.63 ng/ml, and C-reactive protein (CRP) 130 mg/L
The clinical diagnosis was multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 infection triggering status dystonicus and subsequent rhabdomyolysis-associated AKI
After his transfer to the PICU, his blood pressure dropped to 60/40mmHg and SpO2 was 90%
A bedside echocardiogram showed impaired septal motion and mildly impaired left ventricular contractility with fractional shortening of 25%
He subsequently required intubation for respiratory failure, and a norepinephrine infusion was started at 0.03 µg/kg/min for hemodynamic support
Multiple sedative medications were used for sedation and control of his dystonia and dyskinesia in addition to his usual medications
Remdesivir was not continued due to his impaired liver function. Tocilizumab was starter later
He was started on continuous renal replacement therapy (CRRT) due to rhabdomyolysis-associated AKI
Ten hours after CRRT initiation, a CytoSorb hemoadsorption column was integrated into the CRRT circuit to enhance myoglobin and cytokine removal
Treatment
CytoSorb was first incorporated into the CRRT circuit for myoglobin and cytokine removal (hour 18 – 40), which was followed by sequential use of Oxiris (hour 40 – 80), followed by another CytoSorb adsorber (hour 85 – 110), giving a total of 100 hours of extracorporeal blood purification [EBP] therapy
CytoSorb was used in conjunction with CRRT run in high-volume continuous veno-venous hemodiafiltration (HF CVVHDF) mode using the Prismaflex system
Position of the adsorber: post-CRRT filter
Measurements
Hemodynamics and catecholamine requirements
Inflammatory parameters
Creatine kinase
Results
Initially, he continued to deteriorate with persistent hypotension requiring escalation of inotropes. However, there were no major complications related to the EBP therapy including hemodynamic compromise
Cytokine profile revealed a marked reduction of levels of several cytokines including tumor necrosis factor-alpha (TNFa), interleukin (IL)-6, IL-8, and IL-10 after the EBP therapy. His condition improved under both EBP therapies and the serum ferritin, C-reactive protein, and procalcitonin levels also dropped gradually, which correlated well with his clinical progress and the trend of cytokine levels
The serum levels of CK gradually decreased
Patient Follow-Up
A dose of intravenous immunoglobulin (IVIG) and dexamethasone were added during therapy
It was possible to stop all inotropes 4 days after PICU admission
Extubation was possible on 8th day of PICU admission
The CRRT doses were gradually reduced, and it was possible to stop CRRT support 8 days after admission
The clinical course was complicated by secondary Pseudomonas aeruginosa pneumonia requiring an additional course of antibiotics for two weeks
The patient was finally discharged from the PICU to his original hospital one month after admission
Conclusions
In this case of an adolescent with MIS-C following SARS-CoV-2 infection as well as rhabdomyolysis-associated acute kidney injury, the application of extracorporeal blood purification therapy was associated with pronounced hemodynamic stabilization, as well as a marked reduction in levels of several cytokines and creatine kinase
It was noted that both pro-inflammatory and anti-inflammatory cytokines were removed, and the removal efficacy varied between different devices. However, the authors note that the two devices (CytoSorb + Oxiris) appeared to complement each other’s adsorption capacity
The authors conclude that this case demonstrates that extracorporeal cytokine removal can be safely applied in children with MIS-C and can be considered as adjunctive therapy in selected patients with critically ill conditions.
