Hemoadsorption treatment with CytoSorb ® in patients with extracorporeal life support therapy: A case series

Abstract

Introduction:

Extracorporeal life support is an increasingly used technique for respiratory and cardiocirculatory support. Besides primary organ dysfunction, an excessive systemic hyperinflammatory response can be the underlying cause for acute organ failure necessitating extracorporeal life support therapy, or it may be associated with the extracorporeal life support itself. Controlling this overwhelming inflammatory response using CytoSorb^® hemoadsorption has been shown to be associated with improved hemodynamics and restored metabolic balance resulting in preserved organ functions.

Methods:

In this retrospective case series, we describe 23 patients undergoing extracorporeal life support therapy and CytoSorb hemoadsorption. Cytokine levels were monitored, hemodynamic and metabolic variables were recorded, and outcome measures such as duration of organ support, intensive care unit mortality, and hospital mortality were noted.

Results:

CytoSorb treatment was associated with a trend toward a reduction in plasma cytokine levels (first treatment median interleukin-6 pre 595 vs post 350 pg/mL (n.s.); second treatment median interleukin-6 317 vs 108 pg/mL, p < 0.05), a reduced vasoplegic response resulting in a reduction in vasopressor requirements (first treatment median norepinephrine pre 0.15 vs post 0.02 µg/kg/min (n.s.); second treatment median norepinephrine 0.1 vs 0.02 µg/kg/min, p < 0.05) as well as rebalancing of deranged metabolic parameters (first treatment median lactate pre-treatment 6 vs post-treatment median lactate 2 mmol/L, p < 0.05). The hemoperfusion treatment was well tolerated and safe, without the occurrence of any CytoSorb device-related adverse events.

Conclusion:

Hemoadsorption may offer a potentially promising therapeutic option for critically ill patients undergoing extracorporeal life support therapy, with cytokine reduction and a consecutively mitigated inflammatory response, decreased vasoplegia, and improved organ function as seen in our patients.

Keywords

Hemoadsorption CytoSorb cytokines extracorporeal life support outcome

Introduction

Extracorporeal membrane oxygenation (ECMO) is increasingly used for mechanical support of respiratory and cardiocirculatory failure of different origins, for example, various forms of shock, lung failure, and resuscitation. The two forms of ECMO application, either in veno-venous (VV) or in veno-arterial (VA) modality, are different in indications, complications, and underlying pathophysiology.¹ The latter is synonymously designated for extracorporeal life support (ECLS) and allows for cardiocirculatory assistance, blood decarboxylation, and oxygenation in patients with cardiac or combined cardiorespiratory failure, whereas VV ECMO primarily provides respiratory support.

While the development of dedicated ECMO systems has brought huge benefit to patients over the last decade, a considerable amount of patients develop a systemic hyperinflammatory response as a complication, with various mechanisms appearing to be responsible for activation of the inflammatory system.² This systemic inflammatory response is triggered by the underlying disease, which can be infectious or non-infectious in nature, as well as the ECMO support itself including shear forces from centrifugal pumps, hypothermia, and contact activation by the artificial surfaces of tubing, pumps, and oxygenator. This in turn leads to an inflammatory response with activation of the complement, coagulation, fibrinolytic, and kallikrein systems contributing to increased capillary permeability, accumulation of interstitial fluid, and tissue infiltration of neutrophils. Clinically, this may result in vasoplegia, acute kidney injury, intestinal ischemia, cognitive dysfunction, and multiple organ failure (MOF). Of note, these processes may be more pronounced in ECLS modality due to additional reperfusion injury and higher blood flow rates.

The clinical picture of a hyperinflammatory response caused by application of an extracorporeal pump-driven system (e.g. a cardiopulmonary bypass (CPB)) may clinically present as systemic inflammatory response syndrome (SIRS) sharing similar clinical features such as vasoplegia, organ dysfunction, and vascular leakage as seen in sepsis.

After CPB, this specific phenomenon is described as post-CPB SIRS.³ As ECLS may be seen as prolonged exposure to CPB with surface contact, initiation of inflammatory pathways, and mechanical cell stress, the underlying pathophysiology resulting in pulmonary, cardiocirculatory, or combined disturbances may even be aggravated by the inflammatory overstimulation.

Cytokines are regarded as important mediators in the systemic inflammatory response to extracorporeal circuits (i.e. ECMO, CPB). Important pro-inflammatory cytokines in this context are interleukin (IL)-1, tumor necrosis factor (TNF), IL-6, and IL-8. A compensatory release of anti-inflammatory cytokines (e.g. IL-10) may be observed at the same time. Re-balancing the dysregulated inflammatory homeostasis with increased levels of pro-inflammatory and anti-inflammatory mediators is discussed to be important for maintenance of immune system equilibrium, and therefore, the therapeutic target of controlling hyperinflammation and its deleterious sequelae may be an attractive approach. The CytoSorb^® adsorber (CytoSorbents Corporation, Monmouth Junction, NJ, USA) has received increasing attention in recent years as an adjunctive treatment option for patients with elevated cytokine levels.^4–6 The device has also been approved for use in myoglobinemia and hyperbilirubinemia. Although several case reports and small case series have reported on the beneficial use of the device in ECMO patients, data in larger cohorts remain in short supply.^7,8 To study therapeutic effects in ECLS patients, we retrospectively collected and analyzed data from 23 patients who had undergone CytoSorb hemoadsorption during ECLS.

Patients and methods

This case series was conducted in the 12-bed adult cardiothoracic surgery ICU at the University Hospital Ulm, Germany. Informed consent for retrospective data evaluation was obtained from all patients or their relatives. From October 2013 until May 2018, we treated and monitored 23 consecutive patients undergoing combined ECLS (VA ECMO) and CytoSorb hemoadsorption therapy. Patient characteristics, diagnoses, and individual surgical procedure details are outlined in Table 1. A CytoSorb adsorber cartridge was integrated into the extracorporeal circuit of the renal replacement therapy (RRT) system (Multifiltrate, Fresenius Medical Care, Bad Homburg, Germany) in a pre-hemofilter position (Figure 1). Anticoagulation was achieved using heparin or argatroban as standard anticoagulant aiming at a partial thromboplastin time (PTT) range of 180–220 s. Blood flow rates through the adsorber were kept between 100 and 150 mL/h. As data acquisition did not follow a prespecified protocol, start of CytoSorb therapy was triggered in part by the decision of the treating intensivist and depended on the presence of an extracorporeal circuit for continuous RRT. Other trigger events were severe hyperinflammatory activation, severe reperfusion injury, extended CPB times with post-cardiotomy low cardiac output, and refractory vasoplegic response with rapid progressive organ dysfunction. Depending on the individual clinical course, patients could receive consecutive treatments. As there was no prespecified protocol, the decision to continue with hemoadsorption was up to the treating intensivist. Factors for continuing treatment were ongoing hyperinflammatory activation or other indications such as severe hemolysis and hyperbilirubinemia. Treatment durations are depicted in Table 1. Hemodynamic management with catecholamines and volume therapy was performed according to our standard of care protocol. Weaning was performed according to a standard ECLS weaning protocol with defined termination criteria.

Table 1.

Patient characteristics, treatment modalities, and clinically relevant outcome variables.

Patient number	Age	Gender	BMI	EuroSCORE II	APACHE II pre CytoSorb^®	SOFA pre CytoSorb	Diagnoses	Surgical procedures	Emergency surgery	Number of CytoSorb adsorbers	Treatment duration (h)	Hours on ECLS	Days on mechanical ventilation	Days on CRRT	ICU LOS (days)	Hospital LOS (days)	ICU survival	Hospital survival
1	37	M	31.6	10.1	28	17	Aortic dissection DeBakey A, LCOS	Aortic arch replacement, aortic valve replacement	Yes	1	40	70	4	2	4	4	No	No
2	46	M	26.1	53.0	19	7	Acute myocardial infarction, LCOS	CABG	Yes	3	∑116 (4; 44; 68)	212	39	42	51	51	Yes	Yes
3	76	M	28.3	3.8	28	12	CAD, postop. TRALI, pulmonary embolism	CABG, VA ECLS, pulmonary embolectomy	Yes	1	48	112	12	15	18	22	Yes	Yes
4	60	M	35.8	10.1	28	11	CAD, DCM, postop. TRALI, MV insufficiency	CABG, MV repair, ventriculoplasty, IABP	No	1	50	136	10	6	11	12	Yes	Yes
5	61	M	29.3	19.0	22	14	Acute myocardial infarction, CPR	CABG	Yes	3	∑78 (1; 42; 35)	291	14	12	13	14	No	No
6	53	M	22.5	2.9	19	13	Multitrauma, severe lung contusion	Laparotomy, pneumectomy	Yes	3	∑73 (23; 26; 24)	332	64	44	65	100	Yes	Yes
7	36	M	37.4	9.2	24	11	Aortic dissection DeBakey A, LCOS	Aortic arch replacement	Yes	3	∑119 (26; 50; 43)	429	21	14	21	21	No	No
8	62	M	27.7	83.3	10	8	MV prosthesis endocarditis, LCOS	MV prosthesis replacement	No	3	∑88 (3; 50; 35)	184	8	8	11	19	No	No
9	61	M	27.1	51.9	34	14	MV endocarditis, LCOS	MV replacement	Yes	2	∑41 (6; 35)	109	11	10	11	11	Yes	Yes
10	54	M	37.0	30.2	21	17	AV and MV endocarditis, septic shock	AV and MV replacement, ECLS implantation	Yes	3	∑56 (3; 30; 23)	64	3	2	2	2	No	No
11	53	M	45.7	46.0	21	15	Cardiogenic shock, LCOS	ECLS implantation	Yes	3	∑148 (60; 40; 48)	879	36	34	37	37	No	No
12	50	F	33.1	25.2	28	14	LCOS, CPR	ECLS implantation	Yes	2	∑66 (43; 23)	180	8	6	7	16	No	No
13	66	M	27.2	37.0	29	13	LCOS	Pericardial revision, ECLS implantation	Yes	1	38	40	4	3	2	4	No	No
14	63	F	33.1	2.6	26	11	AV insufficiency IV° post AV replacement, LCOS	Re AV replacement, CABG, ECLS implantation	No	1	42	132	6	5	6	6	No	No
15	70	M	34.6	25.9	34	10	Cardiogenic shock	CABG, IABP, ECLS implantation	No	3	∑84 (4; 34; 46)	127	6	5	6	6	No	No
16	57	M	24.2	10.8	23	12	ARDS, pneumonia	ECLS implantation	Yes	1	26	38	1	1	2	2	No	No
17	41	M	24.9	20.4	30	14	Acute respiratory failure, myocarditis	ECLS implantation	Yes	3	∑79 (25; 25; 29)	524	92	47	104	131	Yes	Yes
18	41	M	24.9	20.4	29	16	Aneurysm ascending aorta, LCOS	Bentall procedure, CABG	No	1	37	95	6	2	10	10	Yes	Yes
19	70	M	31.1	43.3	33	14	ACS, LCOS	CABG	Yes	1	34	110	5	5	5	5	No	No
20	53	M	29.2	21.5	32	13	Acute MV insufficiency, papillary muscle rupture, LCOS	MV replacement	Yes	1	13	144	17	8	19	40	Yes	Yes
21	54	M	27.2	5.5	31	13	CAD, MV insufficiency, LCOS	CABG, MV repair	No	1	29	213	11	10	22	25	Yes	Yes
22	36	F	24.2	19.0	26	12	Acute myocardial infarction, CPR, ARDS	ECLS implantation	No	2	∑48 (24; 24)	276	10	10	11	11	No	No
23	65	F	19.5	1.60	27	13	CAD	CABG	No	1	42	216	15	14	15	16	No	No

BMI: body mass index; EuroSCORE: European System for Cardiac Operative Risk Evaluation; APACHE: Acute Physiology and Chronic Health Evaluation; SOFA: sequential organ failure assessment; M: male; F: female; ECLS: extracorporeal life support; CRRT: continuous renal replacement therapy; ICU: intensive care unit; LOS: length of stay; LCOS: low cardiac output syndrome; CABG: coronary artery bypass graft; CAD: coronary artery disease; TRALI: transfusion-related acute lung injury; VA: veno-arterial; DCM: dilated cardiomyopathy; MV: mitral valve; IABP: intra-aortic balloon pump; CPR: cardiopulmonary resuscitation; AV: aortic valve; ARDS: acute respiratory distress syndrome; ACS: acute coronary syndrome.

The use of IV in the table stands for grade 4 (roman IV).

Figure 1.

The CytoSorb^® cartridge was integrated into the circuit of the renal replacement therapy system and was applied independently from the running ECLS system.

To assess the therapeutic impact of the hemoadsorption treatment, we measured laboratory parameters of inflammation and infection (IL-6, IL-8, procalcitonin (PCT)), for hemodynamics (epinephrine, norepinephrine, mean arterial pressure (MAP), ECLS flow rates), metabolic variables (lactate, pH, base excess) as well as the extent of postoperative organ support (days on mechanical ventilation and continuous renal replacement therapy (CRRT), and hours on ECLS). Furthermore, we evaluated the severity of illness in all patients using the Acute Physiology and Chronic Health Evaluation (APACHE II) and sequential organ failure assessment (SOFA) score directly before initiation of CytoSorb therapy. The European System for Cardiac Operative Risk Evaluation (EuroSCORE II) score was evaluated for cardiosurgical risk stratification according to the preoperative conditions and the surgical procedure. ICU length of stay as well as ICU and hospital survival was used as outcome parameters.

All sets of data were statistically analyzed and graphically presented by means of GraphPad Prism 5.01 software showing the median and interquartile ranges. IBM SPSS Statistics 25 (SPSS Inc. to IBM Company, Chicago, IL, USA) was used to perform the statistical analysis assuming a conventional 5% level of significance. The Wilcoxon matched pairs test was applied as a non-parametric statistical hypothesis test to compare pre- and post-treatment levels. Alpha adjustment for multiple testing was not applied; therefore, the results have a purely descriptive or exploratory character.

Results

Median age was 54 years (range: 36–76 years), body mass index (BMI) was 28.4, and the majority of patients were male (19 vs 4 females) (see Table 1). EuroSCORE II was 20.4 (median) for all patients. Severity of illness as represented by APACHE II and SOFA score before start of CytoSorb treatment was 28 and 13 (medians), respectively. All patients received up to three CytoSorb treatments (median two treatments) with total treatment durations ranging from 13 to 148 h (median 48 h) (Table 1). Treatment resulted in a decrease in cytokine and PCT plasma levels (Figure 2). Concerning hemodynamics, we observed a preserved ECLS flow (4.5 L/min before and after treatment, data not shown) and a maintained goal MAP (>65 mmHg) associated with a concomitant reduction in catecholamine requirements (epinephrine and norepinephrine) (Figure 3). Simultaneously, deranged metabolic parameters (i.e. lactate, pH, base excess) could be stabilized and normalized during and after the treatment period (Figure 4). On average, patients remained on ECLS support for 140 h (Table 1). Length of ICU stay ranged between 2 and 104 days (median 11). Of the 23 patients summarized in this case series, 14 patients died during their intensive care unit stay (all between ICU days 2 and 37, mortality 61%) (Table 1). While survivors had an average intensive care stay of 18 days, non-survivors spent 7 days in ICU before succumbing to their illness. Hospital mortality was equal to ICU mortality (39%) meaning that no patient died after leaving the ICU during his hospital stay at our center. Median days on mechanical ventilation were 12 days for survivors and 7 days for non-survivors. Surviving patients were on RRT for a median duration of 10 days (range: 2–47 days) and non-surviving patients had a median duration on RRT for 6 days (range: 1–34 days) (Table 1). One patient died from mesenteric ischemia with no option for surgical treatment, eight patients had therapy withdrawn in accordance with the patient’s advance directive, and five patients died of refractory MOF. Hemoadsorption treatment appeared to be well tolerated, without device-related adverse events during or after treatment (e.g. clotting of the adsorber, connection/deconnection issues). No technical problems with the implementation of CytoSorb as part of the CRRT circuit were observed.

Figure 2.

Pre- and post-treatment levels of IL-6, IL-8, and PCT for patients receiving one, two, or three treatments, according to the number of treatments per patient as outlined in Table 1 (median with IQR). The data shown refer to the respective treatment number, that is, data for treatment 1 include all 23 patients, data for treatment 2 include 12 patients, and data for treatment 3 include 9 patients (11 patients with 1 treatment, 3 patients with 2 consecutive treatments, and 9 patients with 3 consecutive treatments). # indicates p < 0.05 between pre- and post-treatment levels. Please note that not all data were available from all patients.

Figure 3.

Pre- and post-treatment levels of mean arterial pressure (MAP) and required catecholamine doses (norepinephrine, epinephrine) for patients receiving one, two, or three treatments, according to the number of treatments per patient as outlined in Table 1 (median with IQR). The data shown refer to the respective treatment number, that is, data for treatment 1 include all 23 patients, data for treatment 2 include 12 patients, and data for treatment 3 include 9 patients (11 patients with 1 treatment, 3 patients with 2 consecutive treatments, 9 patients with 3 consecutive treatments). # indicates p < 0.05 between pre- and post-treatment levels. The dashed line in the MAP graph represents the 65 mmHg threshold. Please note that not all data were available from all patients.

Figure 4.

Pre- and post-treatment levels of metabolic parameters including lactate, pH, and base excess for patients receiving one, two, or three treatments, according to the number of treatments per patient as outlined in Table 1 (median with IQR). The data shown refer to the respective treatment number, that is, data for treatment 1 include all 23 patients, data for treatment 2 include 12 patients, and data for treatment 3 include 9 patients (11 patients with one treatment, 3 patients with two consecutive treatments, 9 patients with three consecutive treatments). # indicates p < 0.05 between pre- and post-treatment levels. Please note that not all data were available from all patients.

Discussion

In this case series, we report on 23 critically ill patients under ECLS therapy with concomitant CytoSorb hemoadsorption and RRT. Results suggest that the combined application of these measures together with standard therapy resulted in control of the hyperinflammatory response, consecutive weaning from catecholamine support, and restitution of deranged metabolic parameters, while combined treatment appeared to be feasible, well tolerated, and safe.

Critically, ill patients requiring ECLS support show comparable features to other hyperinflammatory states of infectious as well as non-infectious origins. Clinical consequences include peripheral vasoplegic shock, capillary leakage syndrome, metabolic acidosis, and many others, which are initially triggered by a dysregulated host response. In this respect, the release of inflammatory mediators (e.g. cytokines) in response to infectious or non-infectious stimuli initiates a self-perpetuating cascade of processes, that, if left uncontrolled, may aggravate multiple organ dysfunction and ultimately lead to death. A growing body of evidence provides reasonable proof that cytokine adsorption using the CytoSorb hemoadsorber results in the effective removal of cytokines, both in vitro^9,10 and in vivo.^6,11 In addition, the removal spectrum of CytoSorb also seems to encompass other inflammation-related trigger substances such as pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs), substances that can provoke and maintain a generalized inflammatory host response.¹²

In our set of patients, we observed a tendency toward a decrease not only in the two cytokines measured (i.e. IL-6 and IL-8) but also in PCT levels. The trend across all measurements (i.e. pre-treatment 1 to post-treatment 3) also showed long-term and sustained reductions in plasma cytokine concentrations.

Of note, clinical data suggest an inter-relationship of cytokine response and associated clinical course.¹³ A cohort study analyzing 1886 patients with sepsis following community-acquired pneumonia with special attention on their IL-6 and IL-10 levels found that the highest risk of death was with combined high levels of the pro-inflammatory IL-6 and anti-inflammatory IL-10 cytokine activity with a hazard ratio of 20.5. Certainly, as we are lacking a control group and are applying a multimodal concept, we cannot rule out that cytokine levels and therefore the inflammatory situation could have also stabilized independent from the use of CytoSorb, due to the combined intensive care measures such as the ECLS itself, appropriate antibiotic therapy, or hydrocortisone administration. This, however, was beyond the scope of this article and should be considered in future controlled trials.

Many publications on CytoSorb to date consistently report on the almost immediate effect of this treatment on the patients’ hemodynamic situation.^3,4–6 Importantly, hemodynamics in ECLS patients are determined to a large extent by machine settings which therefore only allows for limited conclusions on the underlying cardiocirculatory state of the patients. However, vasopressor requirements, even under total artificial cardiopulmonary support to generate appropriate perfusion pressures, point toward ongoing peripheral vasoplegia and capillary leakage together with their well-known association with poor clinical outcomes.^14,15 Any therapeutic option that is able to support more rapid weaning from vasopressors (decatecholaminization) is therefore appreciated and might result in better recovery and outcome. Prolonged catecholamine administration has been shown to reduce peripheral (extremities and phalanges), renal, and hepato-splanchnic blood flow, contribute to late-phase immunosuppression, increase apoptotic and anti-inflammatory responses, and to stimulate bacterial growth.¹⁶

The improvement in the hemodynamic situation, paralleled by stabilization in metabolic parameters such as lactate, base excess, and pH has been already shown by our group in patients with SIRS post-CPB and with endocarditis.^3,17 We suppose this effect is potentially due to a restoration of hyperinflammation-associated microcirculatory disturbances. If the observed metabolic stabilization during the treatment course, as shown in the tendency to normalize deranged lactate, pH, and base excess, is exclusively linked to initiation of ECLS, the consecutive restoration of tissue perfusion and oxygen supply¹⁸ may be discussed. A contribution of hemoadsorption to this stabilization is potentially conceivable; however, this cannot be proven from our data.

Importantly, CytoSorb might have also played a role in the attenuation of the resulting ischemia–reperfusion injury to tissues and organs that were initially deprived of blood flow, as involved processes share similarities with inflammation. The question remains, however, whether this effect would have also occurred without CytoSorb application, and, if yes, whether the observed stabilization would have happened more rapidly or more slowly than with CytoSorb. Several case reports have reported on the successful use of the CytoSorb adsorber in combination with ECLS therapy. Lees et al. described a case of a 33-year-old patient who developed acute cardiovascular collapse and acute respiratory distress syndrome (ARDS) secondary to superinfection of Panton–Valentine leukocidin-positive Staphylococcus aureus and H1N1 pneumonia. The use of the CytoSorb appeared to result in the rapid resolution of neutropenia, reversal of toxic shock, and rapid weaning from high-dose vasopressors.¹⁹ Another case by Bruenger and colleagues in a 39-year-old patient with fulminant ARDS and cardiogenic septic shock with subsequent implantation of ECLS for circulatory support plus CRRT and left ventricular assist device (LVAD), the additional implementation of a CytoSorb adsorber resulted in a decrease in IL-6, PCT, and C-reactive protein levels as well as significantly reduced vasopressor support.²⁰ Both cases stated that the combination with all other extracorporeal techniques was practical, technically feasible, and beneficial for the patient. In a recent retrospective case series study in 40 critically ill cardiac surgery patients with MOF, the use of CytoSorb therapy combined with ECLS showed that CytoSorb treatment was associated with a significant decrease in total bilirubin, lactate, creatinine phosphokinase (CPK), and lactate dehydrogenase (LDH) levels, as well as a reduction in the vasoactive–inotropic score. Thirty-day mortality was 55% and ICU mortality was 52.5% with expected ICU mortality of 80% according to the sepsis-related organ failure assessment (SOFA) score.⁷

Nemeth and colleagues described the case of a 46-year-old male patient undergoing emergency cardiac surgery due to infective endocarditis (IE). The development of post-cardiotomy cardiogenic shock associated with the cardiac surgery required the implantation of ECLS. Three days later, CytoSorb was installed into the ECLS due to the development of a secondary septic shock with rapidly increasing vasopressor requirements, resulting in a significant and rapid improvement in the patients’ hemodynamic and metabolic parameters after only 24 h of treatment. Despite the fact that the patient died from a new onset of fulminant septic shock 2 months after his initial cardiac surgery, this case highlights the feasibility and effectiveness of CytoSorb in such patients with simultaneous post-cardiotomy cardiogenic shock and septic shock.²¹

In our patients suffering from critical illness, a multifaceted therapeutic approach, including a broad bundle of life-sustaining therapeutic measures, was applied simultaneously. Therefore, it may be debated as to how much single interventions, per se, contributed to the observed clinical course and finally led to an impact on the observed cardiovascular and clinical parameters. Although there are data that ECMO/ECLS may trigger an inflammatory response,² there are also data that demonstrate a mitigated inflammatory response after initiation of VV ECMO in patients with acute respiratory failure.²² These effects are supposedly mainly due to the reduced invasiveness of mechanical ventilation, restored oxygenation, and consecutively mitigated inflammatory triggers as a consequence of VV ECMO installation. However, whether this response would hold true for patients with ECLS (VA ECMO) is speculative. In fact, identifying which components influenced the different treatment approaches is not possible. As one may assume that the time and the degree of a harmful trigger may have an impact on the ongoing course of an illness. Treatment approaches that help to deal with these triggers may have a rationale in the general therapeutic milieu. However, further studies will still be necessary to prove the potential of hemoadsorption in these complex cases. Overall, the assessed clinically relevant outcome variables appear very inhomogeneous. For example, some patients developed complications such as sternal wound infection, which consequently results in a longer ICU length of stay, irrespective of the initial pathophysiology requiring ECLS therapy. Likewise, reasons/indications for the installation of ECLS were multifactorial.

The results of the present study must be interpreted with some caution due to the retrospective design and consecutively some missing data, the heterogeneous patient population with different ECLS indications, and finally other unknown confounders due to a complex disease state of the patients. This prevents us from making any definite conclusions concerning clinically relevant outcome variables. To overcome these shortcomings, studies with more specified target parameters as well as better stratified patients are recommended.

Conclusion

To our knowledge, this is the first case series reporting on the use of CytoSorb therapy specifically in VA ECMO patients. Treatment of such patients with CytoSorb in conjunction with continuous veno-venous hemodialysis (CVVHD) was associated with decreases in inflammatory cytokines, as well as stabilization in hemodynamic and metabolic variables. Due to a modulation of the cytokine response, CytoSorb may offer a potentially promising new treatment option for severe ECLS-related hyperinflammation that presents with hemodynamic instability and requires high doses of vasopressors. Treatment with the CytoSorb device was safe and well tolerated with no device-related adverse events during or after the treatment sessions and was easy to implement as part of the CRRT circuit. Given the positive clinical experience of this case series, randomized controlled trials are warranted to further delineate the potential benefits of this new treatment option.

Footnotes

Declaration of conflicting interests

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: K.T. and G.F. have received honoraria for lectures from CytoSorbents. The other authors have no conflicts of interest associated with this report. This article describes original research has not been published previously, has been approved by all authors, and is not currently being assessed for publication by any journal other than the International Journal of Artificial Organs. The authors have declared that this study was performed in accordance with the research ethical guidelines.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Karl Träger

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, et al. Continuous cytokine haemoadsorption incorporated into a venoarterial ECMO circuit for the management of postcardiotomy cardiogenic and septic shock—a case report. Perfusion 2018; 33(7): 593–596.

22.

Burrell

AJC

Lubnow

Enger

, et al. The impact of venovenous extracorporeal membrane oxygenation on cytokine levels in patients with severe acute respiratory distress syndrome: a prospective, observational study. Crit Care Resusc 2017; 19(Suppl. 1): 37–44.