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Table of Contents
CASE REPORT
Year : 2020  |  Volume : 14  |  Issue : 2  |  Page : 166-169

Experience of using an extracorporeal cytokine hemoadsorber (CytoSorb®) in systemic inflammatory response syndrome after heart transplantation


Advanced Heart Failure and Transplant Clinic, Max Super Specialty Hospital, New Delhi, India

Date of Submission12-Nov-2019
Date of Acceptance06-May-2020
Date of Web Publication06-Jul-2020

Correspondence Address:
Dr. Kewal Krishan
Advanced Heart Failure and Transplant Clinic, Max Super Specialty Hospital, East Block, 2, Press Enclave Road, Saket, New Delhi - 110 017
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijot.ijot_64_19

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  Abstract 


Heart transplantation is well-established and considered the most effective therapy for patients with end-stage heart failure. Systemic inflammatory response syndrome (SIRS) and renal dysfunction after heart transplantation are commonly experienced complications, which may significantly impact on overall survival. The extracorporeal cytokine hemoadsorber (CytoSorb®) is a novel nonpharmacologic hemocompatible adsorber, which has porous polymer beads capable of removing cytokines and other mid-molecular weight toxins from the blood. CytoSorb is a unique hemoadsorber, which has a huge surface area, a broad spectrum of adsorption, and is very easy to set up on any extracorporeal circuit. Here, we report our experience of using CytoSorb in the management of SIRS after heart transplantation in a 28-year-old male.

Keywords: Cytokines, CytoSorb, heart transplantation, hemoadsorption, systemic inflammatory response syndrome


How to cite this article:
Krishan K, Dutta R, Chand R, Malhotra R. Experience of using an extracorporeal cytokine hemoadsorber (CytoSorb®) in systemic inflammatory response syndrome after heart transplantation. Indian J Transplant 2020;14:166-9

How to cite this URL:
Krishan K, Dutta R, Chand R, Malhotra R. Experience of using an extracorporeal cytokine hemoadsorber (CytoSorb®) in systemic inflammatory response syndrome after heart transplantation. Indian J Transplant [serial online] 2020 [cited 2020 Aug 6];14:166-9. Available from: http://www.ijtonline.in/text.asp?2020/14/2/166/289050




  Introduction Top


Several modifications have been made heart transplantation for better outcomes. Immunosuppression is important in heart transplantation patients to prevent/treat cardiac allograft rejection and to reduce the risk of toxicities and improvements in immunosuppression may significantly improve outcomes.[1]

Systemic inflammatory response syndrome (SIRS) and renal dysfunction after heart transplantation are commonly experienced complications.[2],[3] SIRS induced by cardiopulmonary bypass (CPB) and the surgical procedure itself produces both pro-and anti-inflammatory cytokines.

The extracorporeal cytokine hemoadsorption device (CytoSorb®; Cytosorbents, Corporation, New Jersey, USA) is a unique hemoadsorber having porous polymer beads capable of removing cytokines and other mid-molecular weight toxins from the blood. CytoSorb is very easy to set up in any extracorporeal circuit (hemodialysis [HD], sustained low-efficiency dialysis [SLED], continuous renal replacement therapy [CRRT], heart-lung machines, and extracorporeal membrane oxygenation [ECMO]). CytoSorb is being widely used in patients with SIRS and sepsis.


  Case Report Top


A 28-year-old male was admitted to a tertiary care hospital with a history of breathlessness at rest and orthopnea and had a history of dilated cardiomyopathy with severe left ventricular dysfunction (left ventricular ejection fraction [LVEF] 20%–25%). Investigations confirmed end-stage heart failure and severe left ventricular dysfunction (LVEF 15%) with dilated cardiomyopathy. He underwent orthotopic heart transplantation using the bicaval technique on June 16, 2019, and was extubated on the postoperative day 1. Induction therapy used before the surgery (basiliximab 20 mg IV over 20 min and methylprednisolone 500 mg IV stat), just before removing the cross-clamp. No positive blood culture was reported. The patient was started with meropenem and teicoplanin, which was our routine antibiotics prophylaxis for all transplant patients (starting from intra-operative to postoperative till day 5). He was hemodynamically stable but had intermittent atrial fibrillation for which anti-arrhythmic medications were initiated. Immunosuppression (tacrolimus, mycophenolate mofetil, and prednisolone) was started.

He developed mild right ventricular dysfunction with increasing total leukocyte count followed by adjustment of antibiotic therapy; however, he remained acidotic and developed oliguria resulting in elective reintubation. Nephrology consultation diagnosed SIRS. His APACHE II score was 11 and SOFA score was 6 [Figure 1]. In addition, procalcitonin (PCT) was high (169 ng/dL) suggesting inflammatory pathology. [Table 1] and [Table 2] summarize clinical and laboratory parameters before and after the use of CytoSorb. The mean arterial pressure was > 65 mmHg under treatment with multiple vasopressors.
Figure 1: Improvement in APACHE II and SOFA scores when comparing pre and post CytoSorb therapy. APACHE II, acute physiology, age, chronic health evaluation II; SOFA, sequential organ failure assessment

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Table 1: Clinical parameters

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Table 2: Laboratory examination before and after Cytosorb treatment

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CytoSorb therapy was initiated in conjunction with SLED (Fresenius Medical Care) at a blood flow rate of 120 ml/min. He was given three cycles of CytoSorb therapy (run time: 6–12 h) and showed gradual improvement in urine output. The last SLED was performed 6 days postoperatively. As hemodynamics improved and his right ventricular dysfunction resolved the patient could be extubated and gradually started on a regular diet. He developed mild abdominal distension which resolved following advice from gastroenterology consultation. The tacrolimus levels were regularly monitored and no modifications were needed. He was eventually transferred to the ward, where the pacing wires were removed and a review echocardiogram showed good biventricular function. On day 3, post CytoSorb therapy, vasopressor was completely weaned, and PCT was reduced to 34 ng/dL. He was discharged 17 days after admission in a clinically stable condition. There was no impact of pre- and post-CytoSorb on immunosuppressive therapy. Due to CytoSorb therapy, there was no change in immunosuppressive therapy plan and it had no impact on rejection. The patient showed no signs of rejection observed in both biopsy and clinically.


  Discussion Top


Patients with advanced or end-stage heart failure have elevated levels of pro-inflammatory cytokines and chemokines including tumor necrosis factor α (TNF-α), interleukin (IL)-6, and IL-8.[4] In addition, heart transplantation compliments the cytokine activation and ischemia-reperfusion injury by graft tissue-induced response.[4]

In recent years, extracorporeal blood purification techniques have evolved significantly and are being used widely in acute conditions like sepsis.[5] Reducing inflammatory activation in high-risk patients with cardiopulmonary bypass and improve hemodynamic stability.

Several cytokines (TNF-α, transforming growth factor beta, IL-1 β, IL-4, IL-6, IL-8, IL-10, IL-13, and interferon-α), pathogen-associated molecular pattern molecules, damage-associated molecular pattern molecules, chemokines, and cell adhesion molecules contribute to the development of SIRS increasing the risk of morbidity and mortality.

The CytoSorb adsorber can be used as a stand-alone therapy or may be combined with extracorporeal circuits, both in pre-dialyzer and post-dialyzer mode, or incorporated into a CPB as well as ECMO. CytoSorb removes a broad spectrum of cytokines through concentration gradient dependent adsorption. The use of CytoSorb modulates the immune response, stabilizes hemodynamics, improves organ function, and reduces the risk of complications.[6] Several studies and case reports have demonstrated the usefulness of CytoSorb.[4],[7],[8] There is evidence of CytoSorb use among patients undergoing heart transplantation primarily to avoid the risk of posttransplant SIRS;[4] however, to the best of our knowledge, there is no report of its use in SIRS after heart transplantation.

Our patient developed SIRS during the posttransplant period with deranged renal function. A total of three CytoSorb adsorbers were used during the entire course of management. The initiation of CytoSorb is considered in patients with postoperative hemodynamic instability (norepinephrine > 0.3 μg/Kg/min, PCT > 3 μg/L, and increased serum lactate). Twenty-four hours postinitiation of CytoSorb in the presence of ongoing hemodynamic instability (decrease in norepinephrine dose by <20% in the past 12-hours post initiation) a second adsorber is initiated.[9] The patient is evaluated again after a period of 24 h and in the presence of insufficient stabilization (decrease of norepinephrine dose by <90% of baseline need and lactate 2 mmol/L) the third adsorber is initiated and the patient evaluated every 12–24 h.

After CytoSorb therapy, patient's clinical condition improved slowly including renal function. Several factors may contribute to renal dysfunction in heart transplant patients including vasopressor exposure, inotrope exposure and diuretic exposure, blood transfusion, anemia, hypovolemia, venous congestion, and cardiogenic shock.[10] In our case, the patient was receiving vasopressin, dobutamine, and norepinephrine. It has been shown that the use of cytokine adsorption reduces vasopressor demand and postoperative renal replacement therapy, leading to reduced length of ventilator support, hospital stay, and ICU stay. In our case, the dose of vasopressin was also reduced from 2 ml/h to 1.5 ml/h and dobutamine was completely weaned off.

Although, our patient appeared to be similar to bacterial infection in many cases, patients with orthotopic heart transplant may present with SIRS mimicking bacterial infection. In our case, leukocytes, PCT level, and liver parameters (Serum glutamic-oxaloacetic transaminase SGOT and Serum glutamic-pyruvic transaminase SGPT) were higher before starting CytoSorb and were found to be normal after CytoSorb therapy. PCT is the precursor protein of calcitonin and is used as a diagnostic marker for various inflammatory processes. In healthy individuals, PCT plasma concentrations are normally very low.


  Conclusion Top


SIRS and renal dysfunction after heart transplantation are commonly experienced complications, which may significantly impact on overall survival. Extracorporeal blood purification techniques have evolved significantly and they have been in high-risk patients with cardiopulmonary bypass to bring about hemodynamic stability. This case has demonstrated the successful utilization of CytoSorb in managing SIRS after heart transplantation. CytoSorb prevented clinical deterioration and helped in regaining control over the hyperinflammatory condition in this patient. The use of CytoSorb resulted in a relatively short hospital and ICU stay reducing the financial burden. The effectiveness of CytoSorb to adsorb cytokines and other harmful metabolites (bilirubin, ammonia, and bile acid) demonstrates its usefulness in various other conditions with a similar pathogenesis. No adverse events were recorded during the entire course of the utilization of this device.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Acknowledgment

The authors would like to acknowledge Ms. Babita Kumari and Mr. Shishir Agarwal for end to end coordination to conclude this case study under the leadership guidance of Mr. Pradeep Yanamala and Point Blank Advertising Pvt Ltd, India for medical writing assistance.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Söderlund C, Rådegran G. Immunosuppressive therapies after heart transplantation—The balance between under-and over-immunosuppression. Transplant Rev (Orlando) 2015;29:181-9.  Back to cited text no. 1
    
2.
Gude E, Andreassen AK, Arora S, Gullestad L, Grov I, Hartmann A, et al. Acute renal failure early after heart transplantation: Risk factors and clinical consequences. Clin Transplant 2010;24:E207-13.  Back to cited text no. 2
    
3.
Laffey JG, Boylan JF, Cheng DC. The systemic inflammatory response to cardiac surgery: Implications for the anesthesiologist. Anesthesiology 2002;97:215-52.  Back to cited text no. 3
    
4.
Nemeth E, Kovacs E, Racz K, Soltesz A, Szigeti S, Kiss N, et al. Impact of intraoperative cytokine adsorption on outcome of patients undergoing orthotopic heart transplantation-an observational study. Clin Transplant 2018;32:e13211.  Back to cited text no. 4
    
5.
Ankawi G, Xie Y, Yang B, Xie Y, Xie P, Ronco C. What have we learned about the use of Cytosorb adsorption columns? Blood Purif 2019;48:196-202.  Back to cited text no. 5
    
6.
Clark WR, Ferrari F, La Manna G, Ronco C. Extracorporeal sorbent technologies: Basic concepts and clinical application. Contrib Nephrol 2017;190:43-57.  Back to cited text no. 6
    
7.
Tomescu DR, Olimpia Dima S, Ungureanu D, Popescu M, Tulbure D, Popescu I. First report of cytokine removal using CytoSorb® in severe noninfectious inflammatory syndrome after liver transplantation. Int J Artif Organs 2016;39:136-40.  Back to cited text no. 7
    
8.
Gleason TG, Argenziano M, Bavaria JE, Kane LC, Coselli JS, Engelman RM, et al. Hemoadsorption to reduce plasma-free hemoglobin during cardiac surgery: Results of REFRESH I pilot study. Semin Thorac Cardiovasc Surg 2019;31:783-93.  Back to cited text no. 8
    
9.
CytoSorb Therapy. Decision support in cardiac surgery use. Available from: https://cytosorb-therapie.de/wp-conten t/uploads/2019/06/Decision_Support_Ca rdio_English_B1082R02EN2019_l r. pdf. [Last accessed on 2019 Nov 07].  Back to cited text no. 9
    
10.
O'Neal JB, Shaw AD, Billings FT 4th. Acute kidney injury following cardiac surgery: Current understanding and future directions. Crit Care 2016;20:187.  Back to cited text no. 10
    


    Figures

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    Tables

  [Table 1], [Table 2]



 

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