This case report is on a 13-year-old male patient who was referred from a peripheral hospital with the diagnosis of Dengue fever and multiple organ failure.
The CytoSorb therapy utilizes an extracorporeal blood purification method that has been demonstrated to significantly decrease elevated levels of inflammatory mediators. The purpose of this is to mitigate the excessive systemic inflammatory response that is linked to systemic hyper inflammation or septic shock. Therefore, it is possible to prevent the life-threatening effects of a cytokine storm and, most importantly, facilitate the stabilization of hemodynamics.1
CytoSorb Adsorber
The CytoSorb adsorber consists of porous polymer beads that are highly biocompatible and have many surface pores. Each bead, almost equivalent to the size of a salt grain, functions as a minuscule absorbent to extract chemicals from whole blood through the technique of adsorption. The adsorption surface is situated within the inside of the beads.
In the time of the COVID-19 pandemic, the US Food and Drug Administration (FDA) granted multiple Emergency Use Authorizations (EUAs) to accelerate the availability of innovative treatment methods. Extracorporeal hemoadsorption with CytoSorb (CytoSorbents Corporation, Princeton, NJ, USA) received FDA EUA in April 2020. This was due to its capability to remove various inflammatory mediators, such as cytokines, and alleviate hyper inflammation, which is a crucial factor in severe COVID-19 illness.
The reason for using hemoadsorption as an additional treatment in severely ill COVID-19 patients with respiratory failure that does not respond to traditional methods, such as extracorporeal membrane oxygenation (ECMO), is to facilitate the healing and rehabilitation of the lungs by decreasing excessive inflammation, while allowing the lungs to rest on ECMO. The concept of “enhanced lung rest” revolves around ECMO’s capacity to guarantee sufficient oxygenation and CO2 elimination while safeguarding against ventilator-induced lung injury (VILI). Additionally, hemoadsorption can effectively target the persistent hyper inflammation that potentially leads to endothelial tight junction impairment and capillary leak syndrome, thereby exacerbating lung and organ damage. The concurrent implementation of these therapies has the potential to mitigate the intensity of the sickness, expedite the recovery of organs, and potentially enhance the likelihood of survival.2
Composition of CytoSorb Adsorber
- The adsorption surface is around 45,000 square meters, which is quite large.
- Adsorption of hydrophobic compounds with a size limit of approximately 55 Kilo Daltons.
- Removal that is dependent on concentration, also known as ‘autoregulation’: Eliminates solely in high concentrations.1
Removal Spectrum
- Cytokines (e.g. IL-6, IL-8, TNF-alpha and more).
- Bilirubin, bile acid, ammonia.
- Myoglobin.
- Ticagrelor/Rivaroxaban during CPB.
- DAMPs (e.g. HMGB-1, cfDNA).
- PAMPs (e.g. bacterial toxins).
The CytoSorb adsorber has been shown to remove IL-1β, IL-6, IL-8, and TNF α in vivo, ex vivo and in vitro studies along with other inflammatory mediators. 3
Indications
Patient Selection
The existence of an imbalanced host response is frequently observed in critically sick patients, resulting from both viral and non-infectious causes. This dysregulation can lead to severe organ failure, which remains the leading cause of mortality in intensive care units globally. During its progression, excessive and uncontrolled amounts of inflammatory mediators are frequently released into the bloodstream, which is commonly known as a “cytokine storm”. Currently, there are no authorized treatments available to regulate the exaggerated immune response and restrict excessive inflammation, with the objective of averting organ failure and mortality. Extracorporeal blood purification therapies have gained attention in this setting. These therapies aim to modify the host inflammatory response by removing inflammatory mediators in a broad-spectrum and non-selective manner. A unique hemoadsorption device, known as CytoSorb, developed by CytoSorbents Inc. in Princeton, NJ, USA, has demonstrated encouraging outcomes in patients suffering from hyper inflammation of diverse aetiologies. Despite the existence of a substantial amount of literature, ongoing research is being conducted to tackle several crucial unresolved questions. These include determining the most suitable patient groups who would derive the greatest benefit, identifying the optimal timing for initiating therapy, establishing the ideal schedule for adsorber exchanges and therapy duration, and investigating the possibility of removing concomitant antibiotics and other medications. Some common problems that can be treated with CytoSorb therapy are:
- Refractory septic/vasoplegic shock.
- No response to standard therapy.
- High and increasing need for vasopressors.
- Biomarkers: IL-6 > 500 pg/ml, PCT > 3 µg/l, Ferritin > 1000 µg/l.
Timing
- < 24 hours after diagnosis/start of standard therapy.
- < 12 hours even better.
- Don’t wait until lactate is > 6.5/7 mmol/L.
Dosing
- Continue until sufficient hemodynamic stabilization is achieved.
- Change after 12 hours if instability persists.4
With the recent increase of dengue fever incidence and its associated complications, including respiratory failure, the use of CytoSorb has significant lifesaving potential. Such a case has been described below.
Case presentation
- The patient had a history of fever for nine days associated with headache and vomiting.
- He had abdominal distension and subconjunctival hemorrhage at the time of admission.
- Generalized edema was present and he was dehydrated.
- He was hemodynamically stable with inotrope support.
- HR 130 BPM, RR 60 BRPM, SPO2 94% with NRB mask, BP 110/80 MM HG, Temp 101 F.
- He also developed respiratory distress and was on HFNC.
- He was maintaining SPO2 with oxygen inhalation 10L/M through NRB mask.
- Examination showed poor air entry on lower zone of both lungs with bilateral spasm.
- Within an hour of admission, the patient developed tachypnea and severe respiratory distress.
- Chest X-ray was suggestive of bilateral infiltration and progressive development of respiratory distress necessitating intubation and ventilation.
- The patient was immediately transferred to the intensive care unit (ICU).
- The patient was on mechanical ventilator support from 20/07/23 to 25/07/23 then was on BIPAP.
- Platelet count was 70,000/µl and due to persistent thrombocytopenia received blood products (PRBC, FFP and Platelet apheresis) for several times.
- The lactate level was elevated to 3.8 mmol/L.
- Fluid resuscitation commenced, and antibiotic therapy started with Meropenem, Linezolid, Colistin and Levofloxacin.
- Patient developed septic shock, hemodynamic instability, and lactic acidosis.
- As the patient did not respond to the applied standard therapeutic measures and to stabilize the rapid clinical deterioration, the decision was made to initiate sustained low efficiency dialysis (SLED) supplemented by integration of a CytoSorb hemoadsorption cartridge into the circuit.
Treatment
- The patient was treated with CytoSorb hemoadsorption on days 1 and 3 after ICU admission.
- CytoSorb was integrated directly into the SLED circuit.
- Anticoagulation: unfractionated Heparin
- CytoSorb adsorber position: stand alone.
- Blood flow rate: 120 ml/min
- Duration:
- 1st session: 08 hours
- 2nd session: 12 hours
Measurements
- Inflammatory markers
- Lactate
- Renal function
- Liver function
Results
- Normalization of inflammatory markers.
- Serum lactate decreased from 3.8 mmol/L to 1.7 mmol/L during the course of treatment.
- T1 Respiratory failure corrected.
- Reduced bilateral infiltrates; extubated 2 days after the last CytoSorb treatment.
Patient follow-up
The patient was transferred from the ICU to the normal ward after 7 days in a stable condition and was finally discharged from the hospital 13 days post admission.
Conclusion
- In this patient with Dengue Shock Syndrome with multiple organ failure (DSS with MODS) including type one respiratory failure, combined treatment with SLED and CytoSorb resulted in control of the hyper inflammatory response, reduction of bilateral infiltrates, and resolution of lactic acidosis.
- According to the authors, CytoSorb contributed to a faster recovery and discharge of the patient than expected.
- Applying CytoSorb in conjunction with SLED proved safe and easy.
Authors of this article
- Dr. Mohammad Jhahidul Alam Zico, Senior specialist & Head of Accident and Emergency, Critical Care Medicine, Apollo Imperial Hospital, Chattogram.
- Dr. Showkat Azaz, Consultant, Nephrology, MBBS, MD (Nephrology), FASN (USA), FISN, MACP (USA) (Special Training on Interventional Nephrology, and Renal Transplantation)
References:
- The Therapy – CytoSorbents Europe GmbH. Accessed February 27, 2024. https://cytosorb-therapy.com/en/the-therapy/
- Extracorporeal hemoadsorption in critically ill COVID-19 patients on VV ECMO: the CytoSorb therapy in COVID-19 (CTC) registry | Critical Care | Full Text. Accessed February 27, 2024. https://ccforum.biomedcentral.com/articles/10.1186/s13054-023-04517-3
- Becker S, Lang H, Vollmer Barbosa C, Tian Z, Melk A, Schmidt BMW. Efficacy of CytoSorb®: a systematic review and meta-analysis. Crit Care. 2023;27(1):215. doi:10.1186/s13054-023-04492-9
- JCM | Free Full-Text | Adjunctive Hemoadsorption Therapy with CytoSorb in Patients with Septic/Vasoplegic Shock: A Best Practice Consensus Statement. Accessed February 27, 2024. https://www.mdpi.com/2077-0383/12/23/7199