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andy55q   Wednesday, 05/12/21 06:44:38 AM
Re: None
Post # of 26706 
Case of the Week

Use of CytoSorb in a pediatric patient with combined drug intoxication and multisystem inflammatory syndrome in children (MIS-C)

Dr. Ekaterina Kabak, Dr. Thomas Wagner, Dr. Sandra Zentner-Gröbl, Dr. Christian Scheibenpflug Klinik Donaustadt, Children's Intensive Care Unit, Vienna, Austria
New!Other indicationsReduction in catecholaminesSafetyAnticoagulation CitrateCase of the weekCase reportCritical CareCRRT post filterInflammatory parametersIntoxication
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CoW 18/2021 – This case reports on a 10-year-old female (37 kg), who was admitted to the inpatient pediatric department with syncope with subsequent persistent somnolence and suspected intoxication.

Case presentation

Initial drug screening confirmed opiates in her urine and naloxone was administered
Admission to the pediatric ICU followed due to persistent somnolence, respiratory insufficiency and metabolic acidosis
Expanded toxicological analysis detected, apart from the opiates, triazolam, hydrocodeine, quetiapine in upper therapeutic range for adults; and hydrochlorothiazide, lisinopril and amlodipine in concentrations consistent with an overdose
Brain CT und MRI imaging showed no structural abnormalities; chest X-ray showed signs of acute respiratory distress syndrome (ARDS), presumably as the result of an aspiration
Upon admission to the ICU the inflammatory markers were increased (leukocytosis 17.3 Gpt/L with lymphopenia 0.4 Gpt/L; C-reactive protein CRP 214 mg/L; interleukin IL-6 1198 pg/mL – highest values on the next day after the ICU admission), and the patient had a persistent fever of ≥39°C
Further significant laboratory parameters included an elevated D-dimer of 2.76 mg/L, massively increased LDH 809 U/L; Ferritin 271 µg/L; and procalcitonin PCT 17.58 ng/mL
A septic focus could not be found: no active viral infection (including SARS-CoV-2 disease) could be detected in the expanded viral panel PCR, and bacteriological analysis remained negative with the exception of M. morganii isolated from the urine and the vaginal swab
Serological analysis was positive for antibodies reactive against SARS-CoV-2, suggesting a previous infection; no records of a prior SARS-CoV-2 disease were available
A combination of elevated markers of inflammation and shock prompted the initiation of empirical antibiotic and antiviral therapy
The condition of the patient continued to worsen, manifesting in a progressive decline of the level of consciousness with increasing hemodynamic instability and a deterioration of her respiratory function, which prompted initiation of high-frequency percussive ventilation (TwinStream)
The mean arterial pressure decreased to 40-50 mmHg with a very low system vascular resistance index (SVRI, ~300 dynes/sec/cm-5) despite administration of increasing doses of norepinephrine, which required the commencement of advanced vasoactive pharmacological therapy with epinephrine and vasopressin but also of hydrocortisone
Diffuse ischemic changes were detected on the electrocardiogram and cardiac enzymes were massively increased (NT-pro-BNP 29,344ng/L; CK 5028 U/L; CK-MB 235 U/L; Troponin I-hs >25,000ng/L)
Subsequent echocardiography showed septal dyskinesia with preserved left ventricular function; an initial scan showed no pathological changes to the coronary arteries
At this time of her ICU stay, the patient met the WHO criteria of MIS-C: (1) age below 20 years; (2) fever for three days or more; (3) minimum two signs of multisystem involvement, in her case, shock and coagulopathy; (4) elevated markers of inflammation; (5) no other identifiable inflammatory cause; and (6) evidence of recent or current SARS-CoV-2 infection
The patient did not display MIS-C mucocutaneous (rash, conjunctivitis, mucositis, swollen hands or feet) or gastrointestinal (vomiting, diarrhea, abdominal pain) manifestations
Because of the high clinical suspicion of MIS-C, an appropriate treatment regimen with cortisone, IV immunoglobulins and aspirin was initiated
After approximately one week of her ICU stay, the patient developed thrombocytopenia (lowest recorded platelet count 13 Gpt/L) and an associated multiple organ failure (TAMOF – Thrombocytopenia-Associated Multiple Organ Failure); thrombocyte transfusions and appropriate supportive therapy were administered
Taken into consideration the complex constellation of the clinical, laboratory and radiological findings, discrimination between combined drug intoxication and MIS-C was difficult; a concomitant diagnosis was possible and not unlikely
Due to the acute kidney failure (creatinine 2.9 mg/dL, BUN 39 mg/dL prior to the start of renal replacement) with oliguria and the septic/vasoplegic shock phenotype, combined continuous renal replacement therapy (CRRT) and CytoSorb hemadsorption were initiated

CytoSorb therapy was applied for a total of 3.5 days consisting of 4 treatment cycles approximately 24 hours each
CytoSorb was run in conjunction with CRRT (Prismaflex, Gambro) in continuous veno-venous hemodiafiltration (CVVHDF) mode
Blood flow rate: 110 ml/min
Regional citrate anticoagulation (RCA)
CytoSorb adsorber position: post-hemofilter

Hemodynamics and catecholamine requirements
Markers of systemic inflammation (leukocytes, CRP, IL-6)
Cardiac enzymes (Troponin I-hs, CK, CK-MB, NT-pro-BNP)
ECG findings
Renal function parameters (creatinine, BUN)

Hemodynamic situation showed prompt and continuous improvement under supportive care which included CytoSorb, and catecholamines could be discontinued 6 days after therapy start
Inflammatory markers showed a decreasing trend with leukocyte levels returning to the normal range on the second day after the start of therapy, and CRP and IL-6 returning to near-normal values towards the end of combined CRRT/hemadsorption treatment
Also cardiac enzymes showed a prompt and stable decrease
Pathological changes initially seen on the echocardiography showed improvement, at the end of the ICU stay only a slight desynchronization of the systolic function could be detected
Ischemia signs detected on the ECG in the LAD supply area improved continuously over the treatment time
Combined therapy with CVVHDF-RCA and CytoSorb resulted in the rapid restoration of renal function, with creatinine and BUN plasma levels returning to the values in the normal reference range on the second day after commencing hemodiafiltration/hemadsorption
Patient Follow-up

Hemodialysis could be discontinued after one week, with kidney function and diuresis returning to the normal range upon treatment discontinuation
Later in the course of her ICU stay, one day before extubation, S. epidermidis was isolated from the tracheal secretions; three days following extubation, the same pathogen was detected in the urine
Throughout the whole ICU stay, no septic focus could be identified
Cardiac MRI was performed several weeks following admission and showed no late enhancement or myocardial sequelae
Child and adolescent psychiatric assessment was carried out upon return of an adequate level of consciousness, and the child continued to receive psychiatric care on discharge to the normal ward and from the hospital
Transfer to the normal ward unit followed after 28 days of intensive care

In this pediatric patient with drug intoxication and/or MIS-C, the combined treatment of CVVHDF and CytoSorb hemoadsorption resulted in hemodynamic stabilization, control of the hyperinflammatory response, preservation of cardiac integrity as well as significant improvement in renal function
Differentiation between combined drug intoxication and MIS-C proved challenging because of an exceedingly complex presentation of this case; ultimately, these two disorders could occur independently of each other, with accompanying and/or subsequent coagulopathy, thrombocytopenia, TAMOF, ARDS, severe vasoplegia and cardiac dysfunction, within the same ICU stay
According to the medical team, CytoSorb allowed to dampen the extent of the inflammatory response and the associated complications, and helped prevent potentially grave long-term cardiac sequelae
CytoSorb was safe and easy to use in combination with CRRT in this pediatric patient.

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