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Hemoadsorption treatment of patients with acute infective endocarditis during surgery with cardiopulmonary bypass - a case series

Hemoadsorption treatment of patients with acute infective endocarditis during surgery with cardiopulmonary bypass - a case series

Post author correction

Article Type: SHORT COMMUNICATION

DOI:10.5301/ijao.5000583

OPEN ACCESS ARTICLE

Authors

Karl Träger, Christian Skrabal, Guenther Fischer, Thomas Datzmann, Janpeter Schroeder, Daniel Fritzler, Jan Hartmann, Andreas Liebold, Helmut Reinelt

Abstract

Introduction

Infective endocarditis is a serious disease condition. Depending on the causative microorganism and clinical symptoms, cardiac surgery and valve replacement may be needed, posing additional risks to patients who may simultaneously suffer from septic shock. The combination of surgery bacterial spreadout and artificial cardiopulmonary bypass (CPB) surfaces results in a release of key inflammatory mediators leading to an overshooting systemic hyperinflammatory state frequently associated with compromised hemodynamic and organ function. Hemoadsorption might represent a potential approach to control the hyperinflammatory systemic reaction associated with the procedure itself and subsequent clinical conditions by reducing a broad range of immuno-regulatory mediators.

Methods

We describe 39 cardiac surgery patients with proven acute infective endocarditis obtaining valve replacement during CPB surgery in combination with intraoperative CytoSorb hemoadsorption. In comparison, we evaluated a historical group of 28 patients with infective endocarditis undergoing CPB surgery without intraoperative hemoadsorption.

Results

CytoSorb treatment was associated with a mitigated postoperative response of key cytokines and clinical metabolic parameters. Moreover, patients showed hemodynamic stability during and after the operation while the need for vasopressors was less pronounced within hours after completion of the procedure, which possibly could be attributed to the additional CytoSorb treatment. Intraoperative hemoperfusion treatment was well tolerated and safe without the occurrence of any CytoSorb device-related adverse event.

Conclusions

Thus, this interventional approach may open up potentially promising therapeutic options for critically-ill patients with acute infective endocarditis during and after cardiac surgery, with cytokine reduction, improved hemodynamic stability and organ function as seen in our patients.

Article History

Disclosures

Financial support: There was no financial support for this study.
Conflict of interest: KT and GF received honoraria for lectures from Cytosorbents. KT has an advisory contract with Cytosorbents. The other authors have no conflicts of interest associated with this report.

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Introduction

Infective endocarditis (IE) is a serious heart disease caused by microorganisms that enter the bloodstream and settle on the endocardium, heart valves or intracardiac devices. The cardiac effects of IE may include severe valve dysfunction and myocardial abscesses, which may finally lead to severe congestive heart failure. Therefore, depending on the causative microbes (e.g., staphylococci, enterococci, streptococci) and the clinical symptoms, valve replacement may be indicated for these patients (1, 2). Beside the described intracardiac effects, IE patients are at high risk for developing systemic inflammatory response and septic shock as a result of the bacterial spreadout from valve vegetations. Therefore, a surgical procedure (most often replacement of the affected valve) together with cardiopulmonary bypass (CPB) in a patient with an underlying IE disease represents an intervention with increased risks. The combination of surgical trauma, bacterial spreadout and artificial CPB surfaces results in a release of key inflammatory mediators such as IL-6 and IL-8. This may finally lead to an overshooting systemic hyperinflammatory state, frequently resulting in hemodynamic instability that in turn may induce organ dysfunction such as respiratory failure, acute kidney injury, intestinal ischemia and/or cognitive dysfunction (3). Of note, in case of prolonged CPB surgery, the risk of developing severe systemic inflammatory response syndrome (SIRS) postoperatively may increase even more. Postoperative therapeutic management of these patients includes an appropriate anti-infective therapy in combination with therapeutic approaches maintaining vital organ function.

Since inflammatory mediators are key triggers of inflammation and post-CPB SIRS, intra- or postoperative removal of such mediators from blood using blood purification with a cytokine adsorber has previously been described as an useful approach to control these hyperinflammatory processes, to restore immune homeostasis and potentially to prevent post-CPB SIRS and multiple organ dysfunction syndrome (MODS) (4, 5). Currently, the device most used as an adjunctive treatment to standard therapy in subjects suffering from SIRS, severe sepsis or septic shock to support the removal of cytokines as well as other inflammatory mediators via direct whole blood hemoadsorption is CytoSorb.

Cytosorb (CytoSorbents Corporation) is a polymer bead-based cytokine hemoadsorption cartridge approved in Europe since 2011 that can be used in combination with conventional hemodialysis machines or with CPB systems. In general, with more than 17,000 single treatments performed worldwide to date, CytoSorb application can be considered a safe and biocompatible therapeutic intervention. In this paper we describe the intraoperative application of CytoSorb hemoadsorption in 39 patients during CPB surgery due to IE.

Patients and methods

This case series was conducted in the 12-bed adult cardiothoracic surgery Intensive Care Unit (ICU) at the University Hospital Ulm, Germany. Informed consent for retrospective data evaluation was obtained from all patients or their relatives. From September 2013 until August 2016 we treated and monitored 39 consecutive patients undergoing cardiac surgery with CPB due to acute infective endocarditis. Patient characteristics, diagnoses and individual surgical procedure details are outlined in Table I. Briefly, all patients underwent urgent or emergency cardiac surgery procedures with CPB application (Tab. I). A CytoSorb adsorber cartridge was integrated in a parallel circuit in post-hemofilter position within the extracorporeal CPB circuit. Anticoagulation was achieved using heparin as standard anticoagulant according to routine procedure. Blood flow rates through the adsorber were kept between 200 and 400 mL/min and patients consistently received only CytoSorb treatment during surgery for the entire CPB time and without exchange of the adsorber. Treatment durations are depicted in Table I. Hemodynamic management with catecholamines (i.e., epinephrine, norepinephrine) and volume therapy was performed according to the standard of care protocol. To assess the therapeutic impact of the hemoadsorption treatment we measured laboratory parameters of inflammation (i.e., IL-6 and IL-8) hemodynamics (vasopressor dose, MAP), metabolic variables (lactate, base excess) as well as the extent of postoperative organ support (mechanical ventilation, ECMO, CRRT). Furthermore, we evaluated severity of illness in all patients preoperatively using the European System for Cardiac Operative Risk Evaluation (EuroSCORE II) (6) and additionally assessed the postoperative and 24-hour postoperative Acute Physiology and Chronic Health Evaluation (APACHE II score). ICU length of stay as well as ICU and hospital survival were obtained as outcome parameters.

Patient characteristics, surgery details, treatment modalities and patient outcome (hemoadsorption group)

Case Age Gender BMI Diagnosis Microbiological findings Operation procedure Emergency EuroSCORE II CPB time (min) X clamp time (min) CytoSorb treatment time (min) APACHE II postop APACHE II 24h postop Mechanical ventilation (days) ECMO (days) CRRT (days) Hydrocortisone ICU LOS (d) ICU survival Hospital survival
ARR = aortic root replacement; AVR = aortic valve replacement; MVR = mitral valve replacement; ARRec = aortic root reconstruction; TKR = tricuspid valve replacement.
1 43 M 20.7 AV Endocarditis Staph. aureus Re-Re ARR, Mechanoconduit No 18.96 253 151 253 1 2 No 12 Yes Yes
2 73 F 24.8 AV Endocarditis Streptococcus mitis/cristatis Re-AVR No 31.14 114 69 115 33 28 1 No 7 Yes Yes
3 75 F 20.8 AV Endocarditis Bio-Conduit ARR, CABG Yes 96.73 445 250 445 46 1 1 No 1 No No
4 67 M 21.3 AV Endocarditis Abiotropha defectiva AVR, abscess removal, CABG-RCA Yes 12.75 138 100 138 26 14 1 No 7 Yes Yes
5 75 M 28.7 AV Endocarditis Staph.aureus AVR Yes 4.96 71 49 72 1 No 9 Yes Yes
6 37 M 36.0 AV Endocarditis Staph. aureus, Stertococcus pyogenes AVR Yes 16.68 112 78 112 24 24 12 Yes 19 Yes Yes
7 52 M 26.5 MV + AV Endocarditis Streptococcus mitis MVR, AVR, ARRec, SCAE No 9.01 200 145 200 1 Yes 11 Yes Yes
8 69 F 49.5 MV Endocarditis Staph. aureus MVR Yes 64.18 115 70 115 32 26 No 32 No No
9 62 M 32.3 MV Endocarditis Streptococcus viridans MVR Yes 48.24 171 107 142 31 21 2 3 Yes 6 Yes Yes
10 75 M 25.1 MV + AV Endocarditis Streptococcus mitis AVR, MVR Yes 5.22 138 104 138 24 12 1 No 3 Yes Yes
11 75 F 22.8 AV Endocarditis AVR Yes 9.62 88 60 88 30 15 1 No 4 Yes Yes
12 64 M 26.9 MV Endocarditis Streptococcus agalactiae MVR Yes 2.21 117 90 116 28 20 2 No 4 Yes Yes
13 33 M 25.7 TK Endocarditis Staph. aureus, fungi MIC TKR No 4.43 101 61 102 31 17 1 No 5 Yes Yes
14 38 M 19.8 MV Endocarditis Streptococcus agalactiae MIC MVR Yes 6.2 109 75 91 33 20 1 No 4 Yes Yes
15 77 F 30.1 MV Endocarditis Streptococcus bovis MVR Yes 53.17 122 89 122 37 33 4 3 Yes 4 No No
16 60 M 30.0 AV Endocarditis AVR, MKR, TKR, RFA Yes 12.83 204 145 205 32 31 2 4 Yes 6 Yes Yes
17 58 M 28.4 MV Endocarditis Streptococcus dysgalactiae MVR, 2x CABG Yes 12.03 132 90 133 30 12 1 No 6 Yes Yes
18 79 F 26.8 MV Endocarditis Streptococcus mitis MVR No 3.99 66 45 64 28 18 3 No 4 Yes Yes
19 62 F 27.7 MV Endocarditis Staph. aureus MVR Yes 31.46 141 83 141 33 28 7 6 Yes 13 Yes Yes
20 73 M 23.5 AV Endocarditis Propionibacterium AVR No 4.15 101 67 102 32 11 1 No 4 Yes No
21 30 M 26.2 AV Endocarditis Staph. aureus Re-AVR, TKE, VA ECMO Yes 31.69 280 129 282 30 30 2 2 1 Yes 2 No No
22 76 F 29.3 MV Endocarditis Enterococcus faecalis MVR No 74.69 159 69 160 33 30 8 4 1 Yes 8 No No
23 57 M 27.1 MV Endocarditis Streptococcus agalactiae MVR Yes 33.1 128 95 128 27 2 3 Yes 11 Yes Yes
24 51 F 23.4 AV Endocarditis Streptococcus mitis AVR, SCAE Yes 4.49 224 161 224 25 14 1 No 3 Yes Yes
25 56 M 27.0 AV Endocarditis Staphylococcus aureus bio Bentall, CABG, SCAE No 9.62 340 257 340 22 10 8 No 8 Yes Yes
26 37 M 25.0 AV Endocarditis Streptokokken Bentall OP, SCAE, abscess removal No 9.01 180 132 180 2 No 5 Yes Yes
27 59 M 24.6 AV Endocarditis Staph aureus Re-AVR, RFA, LAA closure No 60.49 128 74 128 30 23 3 2 Yes 3 Yes No
28 48 M 23.4 AV Endocarditis Enterococcus faecalis mAVR, mMVR, SCAE Yes 11 148 126 148 30 16 1 No 4 Yes Yes
29 67 F 34.5 MV + AV Endocarditis RE AVR, MVR, ARR No 50.07 302 210 302 36 33 2 2 2 Yes 2 No No
30 60 F 44.5 AV Endocarditis Staph. aureus Re-AVR No 22.23 125 84 125 32 13 3 No 6 Yes Yes
31 77 M 23.7 AV Endocarditis Enterococcus faecalis AVR, TKR, RFA, VA ECMO Yes 78.23 208 114 208 39 36 7 2 7 Yes 7 No No
32 51 M 30.5 AV Endocarditis Streptococcus sanguinis AVR, SCAE Yes 16.17 117 94 116 32 29 1 No 5 Yes Yes
33 46 M 29.3 AV Endocarditis Staph. aureus AVR No 62.96 157 87 157 5 5 5 No 5 No No
34 56 M 22.6 AV Endocarditis Streptococcus agalactiae AVR No 2.15 90 61 90 26 10 1 No 3 Yes Yes
35 61 M 26.6 AV prothesis Endocarditis Re-AVR No 5.2 134 96 134 19 5 1 No 4 Yes Yes
36 68 M 39.2 AV Endocarditis AVR Yes 5.67 82 54 82 3 3 No 4 Yes Yes
37 70 M 33.8 AV Endocarditis Streptococcus mitis AVR Yes 28.3 110 73 110 1 3 No 10 Yes Yes
38 61 M 16.9 MV Endocarditis No microbiologiacal finding MVR, ACVB Yes 4.99 104 66 105 2 No 2 Yes Yes
39 75 F 39.7 MV Endocarditis Staphylococcus aureus MVR No 55.76 131 87 132 31 19 3 3 No 11 Yes Yes

In addition we retrieved clinical parameters and outcome data from a historical control group (from the years 2013 and 2014) of patients with infective endocarditis who had surgery with CPB but without CytoSorb hemoadsorption intraoperatively. However, in this group perioperative cytokine levels were not routinely measured and are therefore not available. The data of this comparative historical group are given in Table II.

Patient characteristics, surgery details, treatment modalities and patient outcome (comparative historical group)

Case Age Gender BMI Diagnosis Microbiological findings Operation procedure Emergency Euro-SCORE II CPB time (min) X clamp time (min) Mechanical ventilation (days) ECMO (days) CRRT (days) Hydrocortisone ICU LOS (d) ICU survival Hospital survival
ARR = aortic root replacement; AVR = aortic valve replacement; MVR = mitral valve replacement; ARRec = aortic root reconstruction; TKR = tricuspid valve replacement.
Con01 57 m 31 MV endocarditis Staph. Aureus MVR Yes 3.3 100 59 3 No 21 Yes Yes
Con02 72 m 26 AV endocarditis Granulicatella adiacens aortic root conduit repair Yes 26.0 202 134 26 7 30 Yes 96 No No
Con03 79 m 27 AV endocarditis Enterococcus faecalis AVR No 23.0 190 86 3 10 No 9 Yes Yes
Con04 65 F 24 MV endocarditis Streptococcus pneumoniae MVR Yes 3.4 232 75 7 No 6 Yes Yes
Con05 75 m 23 MV endocarditis Streptococcus mitis MVR, TV repair No 14.9 127 84 7 Yes 9 Yes Yes
Con06 64 m 30 AV prothesis endocarditis none AVR Yes 25.9 138 96 1 4 No 10 Yes Yes
Con07 62 m 28 AV endocarditis Streptococcus gallolyticus AVR No 5.3 92 63 1 No 6 Yes Yes
Con08 59 m 23 MV endocarditis Staphylococcus aureus MV repair Yes 2.4 110 67 1 No 5 Yes Yes
Con09 56 m 26 AV and MV endocarditis Streptococcus mitis AV and MVR No 2.2 142 105 1 No 4 Yes Yes
Con10 76 m 31 AV prothesis endocarditis Enterococcus faecalis AVR No 8.6 115 86 6 2 No 14 Yes Yes
Con11 72 F 33 MV prothesis endocarditis, AV endocarditis Corynebacterium species MVR, AVR Yes 33.9 231 167 8 8 8 Yes 8 No No
Con12 85 F 35 AV prothesis endocarditis Aerococcus urinae AVR No 16.1 143 103 1 4 No 7 Yes Yes
Con13 80 m 23 MV endocarditis Citrobacter koseri MVR, AVR No 7.5 145 106 4 Yes 14 Yes Yes
Con14 79 F 28 MV endocarditis Staphylococcus aureus MVR No 24.6 164 106 2 7 Yes 8 Yes Yes
Con15 72 F 28 AV endocarditis Escherichia coli AVR No 4.0 39 27 1 No 9 Yes Yes
Con16 77 m 23 AV endocarditis Staphylococcus haemolyticus AVR No 10.9 116 81 1 No 3 Yes Yes
Con17 88 m 27 AV endocarditis Citrobacter koseri AVR No 12.0 105 66 1 No 5 Yes Yes
Con18 82 F 21 MV endocarditis Escherichia coli MVR No 15.6 125 90 2 5 Yes 12 Yes Yes
Con19 75 F 21 MV endocarditis Steptococcus mutans MVR No 11.8 120 80 1 3 No 4 Yes Yes
Con20 51 m 29 MV endocarditis Staphylococcus lugdunensis, Enterococcus faecalis MVR No 3.3 108 72 2 No 6 Yes Yes
Con21 37 m 26 TV endocarditis Staphylococcus aureus TVR No 1.3 78 54 5 No 10 Yes Yes
Con22 63 m 30 MV and Av endocarditis Enterococcus faecalis MV and AVR No 9.5 138 108 2 Yes 2 Yes Yes
Con23 41 m 20 MV endocarditis Streptococcus mitis MVR No 1.7 179 146 1 No 4 Yes Yes
Con24 76 F 32 MV endocarditis Streptococcus agalctiae MVR No 14.2 93 66 1 No 7 Yes Yes
Con25 82 m 21 AV prothesis endocarditis Enterococcus faecalis AVR No 13.2 182 82 2 No 10 Yes Yes
Con26 38 m 26 AV endocarditis none AVR No 2.2 73 51 1 No 3 Yes Yes
Con27 61 m 25 AV prothesis endocarditis Corynebacterium species AVR No 6.9 96 53 3 No 4 Yes Yes
Con28 36 m 28 TV endocarditis Staphylococcus aureus TVR Yes 19.2 122 58 41 46 Yes 57 Yes Yes

Of note, all sets of data were statistically analyzed and graphically presented by means of the GraphPad Prism 7.01 software showing the median and interquartile range.

Results

Preoperative EuroSCORE II values in the CytoSorb group were rather heterogeneous, ranging between 2.2 and 96.7 (median 11). In the CytoSorb group, the median EuroSCORE II values for ICU survivors (n = 31) and ICU non-survivors (n = 8) were 11 and 64, respectively. In the comparative historical control group, the median EuroSCORE II values for ICU survivors (n = 26) and ICU non-survivors (n = 2) were 9 and 30, respectively. CPB times and X clamp times are depicted in Table I. All patients in the CytoSorb group obtained CytoSorb treatments that ranged from 64 up to 445 minutes duration (median 132 minutes). All patients showed a marked intraoperative increase of inflammatory mediators IL-6 and IL-8 followed by peak levels measured directly after completion of the surgical procedure. This was followed by a clear decrease in levels of IL-6 and IL-8 on postoperative day 1 and a return to preoperative baseline levels on postoperative day 3 (Fig. 1). Metabolic variables (i.e., lactate and base excess) showed a comparable pattern with a most pronounced change postoperatively and a return to baseline levels on postoperative day 3 (Fig. 1). Corresponding courses of the same metabolic parameters of the comparative historical control group are depicted in Figure 1A. Moreover, we observed a stabilization of hemodynamic parameters, as demonstrated by a consistent and maintained increase in MAP postoperatively with a concomitant reduction of catecholamine need at the same time (epinephrine and norepinephrine) (Fig. 2). On postoperative day 3, 72% and 82% of the patients were free from norepinephrine and epinephrine support, respectively. On postoperative day 5, these percentages increased to 82% and 95% for norepinephrine and epinephrine, respectively (data not shown). Interestingly, 15 out of the 39 IE patients initially requiring vasopressor support in their postoperative phase did not require any further vasopressor support 18 hours post surgery (3 patients with high EuroSCORE II between 31-97; 2 patients with mid EuroSCORE II between 16-31; 10 patients with low EuroSCORE II between 0-16).

(A) CytoSorb group: Levels of IL-6 and IL-8 as well as metabolic parameters (lactate and base excess [median with IQR]), throughout the observation period. Values were assessed prior to treatment (baseline), during surgery, immediately after as well as on days 1 and 3 post treatment during CPB. (B) Historical control group: Metabolic parameters (lactate and base excess [median with IQR]), throughout the observation period. Values were assessed prior to treatment (baseline), during surgery, immediately after as well as on day 1 and 3 post CPB.

(A) CytoSorb group: Mean arterial pressure (MAP), catecholamine doses (norepinephrine and epinephrine) throughout the observation period (median with IQR). Values were assessed prior to treatment (baseline), at end of surgery, at 6, 12, 18 and 36 hours as well as on day 1, 2 and 3 postoperatively. Please note that data sets were not completed for every patient. (B) Historical control group: Mean arterial pressure (MAP), catecholamine doses (norepinephrine and epinephrine) throughout the observation period (median with IQR). Values were assessed prior to treatment (baseline), at end of surgery, at 6, 12, 18 and 36 hours as well as on day 1, 2 and 3 postoperatively.

The severity of illness in the short-term postoperative period using the APACHE II also showed a trend to improvement from a median of 31 directly post operation to a median of 20 on day 1 post-surgery (Tab. I). A total of 18 patients were able to be weaned from mechanical ventilation within 24 hours after surgery, whereas 21 patients had a prolonged ventilation ranging from 1 to 12 days. Extracorporeal membrane oxygenation (ECMO) was mandatory in 5 patients for up to 5 days. High grade AKI necessitating CRRT was applied in 16 patients for up to 4 days (Tab. I).

In the comparative historical control group, 12 patients were able to be weaned from mechanical ventilation within 24 hours after surgery, whereas 16 patients had a prolonged ventilation ranging from 2 to 41 days. Extracorporeal membrane oxygenation (ECMO) was mandatory in 2 patients for up to 8 days. High grade AKI necessitating CRRT was applied in 10 patients for up to 46 days (Tab. II).

Length of ICU stay in the CytoSorb group ranged between 1 and 32 days (median 5). Of the 39 patient treatments summarized in this case series, 8 patients died during their ICU stay (7 between ICU days 1 and 8, 1 patient on ICU day 32) and 2 patients later died during their hospitalization period (Tab. I). Of note, the death of these patients could not be attributed to any specific treatment. One patient died from mesenteric ischemia with no option for surgical treatment, 1 patient had therapy withdrawn in accordance with the patient’s advance directive, 5 patients died of refractory multiple organ failure, and 1 patient with refractory cardiac failure.

The length of ICU stay in the comparative historical control group ranged between 2 and 96 days (median 7.5 days). Of the 28 patient evaluated as a historical control group, 2 patients died during ICU stay (days 8 and 96) (Tab. II)

Intraoperative hemoadsorption treatment appeared to be well-tolerated, without device-related adverse events during or after treatment. No technical problems with the implementation of CytoSorb as part of the CPB circuit were observed.

Discussion

This retrospective case series reports on the application of the hemoadsorption cartridge CytoSorb during the intraoperative treatment of 39 patients with IE undergoing cardiac surgery with CPB. The clinical and laboratory parameters measured along this case series revealed (i) a consistent balanced control of the inflammatory response postoperatively, shown by a marked reduction of IL-6 and IL-8 plasma levels, (ii) the rapid adjustment of metabolic processes indicated by a normalization of lactate and base excess back to preoperative baseline levels within 3 days and (iii) hemodynamic stability before, during, and after the operation accompanied by a rapid decrease in need for vasopressors.

As circulating proinflammatory mediators like IL-6 and IL-8 play a central role in the development of SIRS and sepsis, the application of hemoadsorption devices represents a potential interesting interventional tool to avoid detrimental cross-talk between mediators, DAMPS and PAMPS with the immune system. CytoSorb has been shown to effectively remove hydrophobic molecules from 5 kDa up to approximately 55 kDa such as cytokines, chemokines, myoglobin and various other substances (7, 8). Moreover, cytokine reduction by means of CytoSorb application was reported for critically ill and cardiac surgery patients, as supported by a number of published preclinical and clinical data (4, 9, 10). After an initial intraoperative increase of cytokine levels, the application of CytoSorb hemoadsorption in this set of patients was associated with a decrease in the postoperative course. Of note, we are aware of the fact that the standard treatment regimen of these critically ill patients including hydrocortisone and CRRT could also have resulted in an additional decrease of these inflammatory parameters. Despite the exclusively intraoperative use of the cytokine adsorber, a reduction of cytokine levels was observable on postoperative day 1, returning back to preoperative levels on day 3, an effect that could possibly have been supported by the CytoSorb treatment. This long-term effect of even 1 CytoSorb treatment might be explained by the fact that hemoadsorption using CytoSorb might function at the level of the circulating immune effector cells, resulting in decreased activation of NfκB (in neutrophils and Kupffer cells) by a diminished cytokine load in the circulation and a subsequent decrease in cytokine production (11).

In addition, removal of substances is concentration-dependent. While low cytokine plasma concentrations are not affected, high cytokine plasma levels are reduced effectively. Supporting this line of argumentation, a recent blinded, randomized controlled trial in cardiosurgical patients with CPB compared (i) the CytoSorb application during CPB with (ii) a control group without hemoadsorption during CPB (12). Therefore, for instance, the IL-6 level monitored in the plasma of CPB patients did not exceed 254 pg/mL throughout the measurement duration. It is important to note that these were patients (and procedures) with only moderately increased risk who did not suffer from IE at the time of CPB surgery. In contrast, IE patients in our study undergoing CPB had a much more pronounced IL-6 cytokine release level of up to 5,000 pg/mL post treatment. This relevant difference shows that cytokine adsorption might preferably be effective in patients who are in a state of hyperinflammation (e.g., in infective endocarditis). This notion should be even more underlined as Bernardi et al stated that the authors did not find any differences for IL-6 in patients with or without CytoSorb treatment during CPB (12).

The decrease in cytokine levels in our case series was paralleled by a stabilization of hemodynamic parameters, during, and after the operation, as demonstrated by reduced catecholamine support (epinephrine and norepinephrine) and an increase in MAP. This effect has been observed in pre-clinical studies as well as in case report and series (4, 5, 9, 13).

Of note, it should be considered that the historical control group in our study showed a markedly lower risk profile as compared to the CytoSorb group as evidenced by the EuroSCORE II. This important limitation of historical case control analyses needs to be taken into account when comparing outcome data of both groups.

An important point to justify such a preventive treatment approach is the proof of potential outcome benefits despite the additional costs associated with Cytosorb treatment. From our perspective, such treatment might result in a mitigated inflammatory response postoperatively and hence preserve organ function and result in faster recovery during the postoperative course. While systematic data on these cost/benefit questions are still lacking, there is preliminary evidence available on improved organ function after CytoSorb use. Next to descriptions of unexpectedly fast hemodynamic stabilization (5, 14, 15), there is also a recent report indicating (16) a protected vascular barrier function after CytoSorb treatment, which might play an important role in earlier recovery of organ function in systemic hyperinflammation.

Since the question of whether there is a reproducible positive benefit/cost ratio to generally justify preventive CytoSorb treatment in patients with infective endocarditis undergoing cardiac surgery cannot definitely be answered from our case series, it will have to be established in future prospective studies.

Conclusions

With these clinical data and outcomes from 39 patients suffering from IE and undergoing cardiac surgery with CPB in combination with a CytoSorb adsorption device we were able to confirm and extend the results published earlier (5). Treatment with the CytoSorb device was safe and well-tolerated with no device- related adverse events during or after the treatment sessions. Even though clinical experience from this case series looks interesting, it is hard to draw any definite conclusions from this uncontrolled, retrospective, observational trial as to whether the effects seen in these patients were a primary therapy effect of CytoSorb or the consequence of a combination of all conducted treatments. With the insight of this recent case series, randomized controlled trials are warranted to further stress the potential benefits of this new treatment option for IE patients receiving cardiac surgery with CPB.

Disclosures

Financial support: There was no financial support for this study.
Conflict of interest: KT and GF received honoraria for lectures from Cytosorbents. KT has an advisory contract with Cytosorbents. The other authors have no conflicts of interest associated with this report.
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Authors

Affiliations

  • Department of Cardiac Anesthesiology, University Hospital Ulm, Ulm - Germany
  • Clinic of Cardiothoracic and Vascular Surgery, University Hospital Ulm, Ulm - Germany

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