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Systemic hyperinflammation in cardiac surgery patients

Approximately 1.5 million open heart surgeries are performed worldwide each year, including approximately 500,000 operations in Europe and a further 500,000 surgeries in the US [1]. In Germany alone, approximately 84,000 open heart interventions were performed in 2014 using cardiopulmonary bypass (CPB) [2].

Despite significant advances in perfusion technologies and the use of biocompatible materials used in CPB, patients undergoing complex procedures in cardiac surgery (e.g. repetitive procedures for coronary bypass – redo-coronary artery bypass grafts, multiple interventions, aortic surgery, valve replacement due to endocarditis or hypothermic cardiac arrest), still have a significantly high risk of complications, ranging from short-term organ dysfunction to multi-organ failure and death.

Factors such as the trauma of surgery, non-pulsatile blood flow, ischemic-reperfusion injury, and blood contact with air and the foreign surfaces of the CPB system may result in activation of the complement system and stimulation of inflammatory cytokine production. The concentration of these inflammatory mediators directly correlates with the complexity, length, and invasiveness of the procedure, and may result in postoperative systemic hyperinflammation with associated complications such as acute renal failure, respiratory and circulatory failure.

Furthermore, shear forces and cardiotomy suction can cause hemolysis, resulting in the release of free hemoglobin, an important risk factor for postoperative renal failure [3]. Once released, free hemoglobin is a potent scavenger of nitric oxide (NO), and may result in decreased renal blood flow, pulmonary hypertension, and increased systemic vascular resistance, thus exerting stress on the heart. In addition, the iron from free hemoglobin is also a potent generator of oxygen radicals that can damage cell membranes and cause additional damage to the kidney tubules.

Acute kidney injury (AKI) occurs in up to 30% of patients in on-pump cardiac surgery and is associated with mortality rates ranging from 7% to 38% [4]. Between one and five percent of these patients will develop dialysis-dependent renal failure with a significantly higher risk of dying from between 50% to 90% [4]. In addition to the increased mortality risk, post-operative AKI increases the direct costs of hospital care by up to 42%, notably through the cost of increased ICU utilization, as well as for medication, laboratory and radiology services [4].

Therefore, the reduction of inflammatory mediators such as cytokines and free hemoglobin by CytoSorb® represents an approach to reducing post-operative complications and costs. In vivo and in vitro data demonstrate the ability of CytoSorb® to remove a wide range of cytokines, C3a and C5a, as well as free hemoglobin. To date CytoSorb® has been safely used intra-operatively in heart-lung machines during more than 2,000 heart surgeries.

CytoSorb® has also been used several thousand times with standard dialysis machines to treat postoperative systemic hyperinflammation, occuring as a result of cardiac surgery.

This flexibility in the use of CytoSorb® allows the treatment of a wide variety of cardiac surgery patients who are either at high risk (intraoperative use) or who have already developed postoperative hyperinflammatory complications (postoperative use).

In summary, the following therapeutic objectives speak in favor of the perioperative application of CytoSorb® in cardiac surgery:

  • Effective reduction of excess cytokines and activated complement system
  • Reduction of free hemoglobin
  • Avoidance or reduction of capillary leak syndrome
  • Improvement in hemodynamics (macro- and micro-circulation) with reduced need for vasopressors and / or post-operative extracorporeal membrane oxygenation (ECMO)
  • Avoidance or reduction of cytokine and inflammatory mediator-induced organ damage
  • Other potential benefits include improved myocardial function, liver function, and decreased onset of cognitive dysfunction

Cardiac surgery patients with a high risk profile or patients who have to undergo long, complicated procedures can particularly benefit from the preemptive (intraoperative) application of CytoSorb®:

  • Endocarditis with operative valve replacement
  • Aortic dissection
  • Heart transplant
  • Complex combination and repeat interventions
  • Limited liver and / or kidney function

Intraoperative use of CytoSorb may also be beneficial in patients with a low primary risk, but who develop unexpected intraoperative complications (e.g. development of systemic hyperinflammation, prolongation of CPB time).

* Percentage refers to the total age distribution of cardiac surgery

** Percentage refers to the total number of open heart surgeries under extracorporeal circulation


[1] Importance of monitoring blood viscosity during cardiopulmonary bypass.

Holsworth RE Jr, Shecterle LM, St Cyr JA, Sloop GD.
Perfusion. 2013 Jan;28(1):91-2.

[2] Cardiac Surgery in Germany during 2014: A Report on Behalf of the German Society for Thoracic and Cardiovascular Surgery.

Beckmann A, Funkat AK, Lewandowski J, Frie M, Ernst M, Hekmat K, Schiller W, Gummert JF, Cremer JT
Thorac Cardiovasc Surg. 2015 Jun;63(4):258-69.

[3] Hemolysis during cardiac surgery is associated with increased intravascular nitric oxide consumption and perioperative kidney and intestinal tissue damage.

Vermeulen Windsant IC, de Wit NC, Sertorio JT, van Bijnen AA, Ganushchak YM, Heijmans JH, Tanus-Santos JE, Jacobs MJ, Maessen JG, Buurman WA
Front Physiol. 2014 Sep 8;5:340.

[4] Economic consequences of renal dysfunction among cardiopulmonary bypass surgery patients: a hospital-based perspective.

Callahan M, Battleman DS, Christos P, Efimba M, Whitelaw G
Value Health. 2003 Mar-Apr;6(2):137-43.