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Hemoadsorption for severe MIS-C in critically ill children, should we consider it as a therapeutic opportunity?
Gabriella Bottari1, Flavia Severini2, Anna Hermine Markowich2, Giulia Lorenzetti2, Juan Carlos Ruiz Rodriguez3,4, Ricard Ferrer3,4, Paola Francalanci5, Antonio Ammirati6, Paolo Palma7 and Corrado Cecchetti1 |1 Pediatric Intensive Care Unit, Pediatric Emergency Department, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy | 2 Department of Pediatrics, University of Rome Tor Vergata, Residency School of Pediatrics, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy | 3 Intensive Care Department, Vall d’Hebron University Hospital, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain | 4 Shock, Organ Dysfunction and Resuscitation Research Group, Vall d’Hebron Research, Institute (VHIR), Barcelona, Spain | 5 Unit of Pathology, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy | 6 Pediatric Emergency Unit, Pediatric Emergency Department, Bambino Gesù Children’s Hospital, IRCSS, Rome, Italy Int J Artif Organs 2022; epub
08/10/2022
New!PediatricsPeer Reviewed Published DataReduction in catecholaminesReviewSafetyViral infectionCase of the weekCase reportCOVID-19Critical CareCRRT (pre or post filter)Inflammatory parameters
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Summary
CoW 32/2022 – This case reports on a 13 year old boy (weight 60 kg, height 160 cm) who presented with fever, rash, abdominal pain, and vomiting.
Summary
Multisystem inflammatory syndrome (MIS-C) is a new severe clinical condition that has emerged during the COVID-19 pandemic and affects children and the young usually after a mild or asymptomatic COVID-19 infection. Symptoms commonly include cardiovascular dysfunction for which support is required in the majority of cases. In the case report a 13 yr old boy with refractory shock secondary to left ventricular dysfunction (LVD) in the context of MIS-C, the use of hemoadsorption with CytoSorb is described. The therapeutic strategy resulted in hemodynamic and clinical stabilization (reduction then cessation of vasopressors) as well as control of the hyperinflammatory response (including C-Reactive Protein, interleukin – IL-6 and IL-10). The patient received in total 5 adsorbers over 72 hrs. with the first 2 adsorbers for 12 hours each, and a further 3 adsorbers for 24 hours each inserted into the continuous renal replacement circuit. Treatment appeared to be safe and feasible. The authors then compare this case with two more published cases where CytoSorb has been used as an adjuvant therapy in similarly critically ill children with severe forms of MIS-C. All three patients responded with a prompt improvement in their myocardial function (within the first 24 h) following the start of hemadsorption. The authors state that using this blood purification strategy could be a therapeutic opportunity in severe LVD due to MIS-C, sparing the need for extracorporeal membrane oxygenation (ECMO) and other mechanical cardiocirculatory supports, with the advantage of it being less invasive. They also state that CytoSorb does not appear to interfere with most common immunomodulatory therapies although further evidence is required.
Case presentation
Blood tests revealed elevated leukocytes with neutrophilia, high C-reactive protein (CRP) (29.31 mg/gL), procalcitonin (3.32 ng/mL), and hyperferritinemia (1529 ng/mL)
He had a positive history for SARS-CoV-2 infection 6 weeks previously with positive serology
Within 24 h he developed diarrhea, poor pallor, and hypotension
Cardiac markers were elevated, and 2D-echocardiogram showed left ventricular (LV) dysfunction (Ejection Fraction EF 35%)
Supportive care with milrinone and dopamine was started and, as multisystem inflammatory syndrome in children (MIS-C) was suspected, he received immunoglobulins and corticosteroids
The following day he deteriorated, with an 2D-echocardiogram showing a LVEF of 25%, therefore he was referred to the pediatric intensive care unit (PICU) requiring endotracheal intubation and invasive mechanical ventilation (IMV) due to cardiogenic shock
Given the increase in troponin I (high sensitivity troponin, hs-TnI) levels from 75 to 1200 pg/ml in 12 h, infectious myocarditis was suspected and an endomyocardial biopsy (EMB) was taken
Considering the clinical picture of hyperinflammation associated severe shock due to left ventricular dysfunction (LVD) and high lactate (7.9 mmol/l) with the need for high inotropic and vasopressor support (epinephrine 0.35 µ/kg/min, norepinephrine 0.06 µ/kg/min, and milrinone 0.5 µ/kg/min), hemoadsorption with CytoSorb was started in combination with continuous kidney replacement therapy (CKRT)
Of note, even though the patient fulfilled the diagnostic criteria of MIS-C, the authors could not completely rule out the development of fulminant myocarditis due to Parvovirus B19 (PVB19) positivity after suffering from COVID-19, which is why corticosteroids were withheld and immunoglobulins and anakinra were maintained
Treatment
The patient received in total 5 adsorbers over 72 hrs with the first 2 adsorbers for 12 hours each, and a further 3 adsorbers for 24 hours each inserted into the continuous renal replacement circuit
Anticoagulation protocol: citrate-calcium
Measurements
Hemodynamics and requirements for vasoactive substances
Inflammatory parameters
Left ventricular ejection fraction
Cardiac enzymes
Safety
Results
The therapeutic strategy resulted in hemodynamic stabilization with a rapid reduction followed by the cessation of vasopressors at the time of discontinuation of CytoSorb therapy
Treatment was also associated with control of the hyperinflammatory response as evidenced by a reduction in inflammatory parameters including CRP, interleukin – IL-6 and IL-10
After the first 24 h of combined hemoadsorption and CKRT therapy, an improvement in the LVEF to 50% was observed
Troponin I levels decreased from 1200 pg/ml to around 375 pg/ml within 12 hours of treatment with decreasing levels thereafter, reaching ~100 pg/ml by the end of blood purification therapy
No adverse events were noted
Patient Follow-up
CKRT was discontinued at the same time of hemoperfusion after 72 h (day 3)
He was weaned off invasive mechanical ventilation on day 6 and discharged from the PICU on day 8
After 2 weeks his cardiac function had completely restored and the patient was discharged from the hospital on day 20 requiring only the diuretic, spironolactone
Conclusion
In this adolescent with refractory shock secondary to LV dysfunction in the context of MIS-C, treatment with hemoadsorption in combination with immunomodulatory therapies resulted in hemodynamic and clinical stabilization as well as control of the hyperinflammatory response with the treatment appearing safe and feasible
The authors compare this case with two more published cases where CytoSorb has been used as an adjuvant therapy in similarly critically ill children with severe forms of MIS-C. All three patients responded with prompt improvements in their myocardial function (within the first 24 h) following the start of hemoadsorption
The authors state that using this blood purification strategy could be a therapeutic opportunity in severe LVD due to MIS-C, sparing the need for extracorporeal membrane oxygenation (ECMO) and other mechanical cardiocirculatory supports, with the advantage of it being less invasive. They also state that CytoSorb does not appear to interfere with most common immunomodulatory therapies although further evidence is required.
