24 January 2025: Articles
Dual Blood Purification with CytoSorb and oXiris in Managing Recurrent Septic Shock: A Case Report
Unusual clinical course, Unusual setting of medical care, Educational Purpose (only if useful for a systematic review or synthesis)
Bartłomiej Włochacz1ABCDEF*, Andrzej Rybak1AB, Agnieszka Próchnicka1B, Bartosz Rustecki


DOI: 10.12659/AJCR.945952
Am J Case Rep 2025; 26:e945952
Abstract
BACKGROUND: Extracorporeal blood purification strategies were recently developed as adjunctive treatments for sepsis. CytoSorb® is an approved medical device designed to reduce blood levels of inflammatory cytokines. The oXiris high-adsorption membrane filter is used in continuous hemofiltration adsorption. We describe the case of a 67-year-old man with recurrent septic shock, requiring treatment with antibiotics, vasopressors, inotropes, mechanical ventilation, continuous renal replacement therapy (CRRT), and adjunctive treatment with an oXiris filter and hemadsorption using the CytoSorb device.
CASE REPORT: A 67-year-old man was admitted to the Intensive Care Unit (ICU) with septic shock. He received antibiotics, fluids, vasopressors, and inotropes and was mechanically ventilated. Acute kidney failure was treated with CRRT. His condition improved, and he was transferred to the general ward. On day 3 in the ward, he developed a new episode of septic shock and was readmitted to ICU. Standard therapy with fluids, vasopressors, and empiric antibiotics was started. Despite treatment, his condition deteriorated dramatically. CRRT with an oXiris filter in combination with hemoadsorption using CytoSorb was started. After CRRT initiation and integration of the CytoSorb adsorber, rapid improvement in the patient’s condition was observed. Daily laboratory test results showed significant decreases in procalcitonin and CRP. The patient was discharged from ICU on day 5 after initiation of CytoSorb therapy.
CONCLUSIONS: Although no guidelines and large clinical trial data are yet available to support the use of CytoSorb and oXiris, this report supports the findings from previous reports and small studies, that they can be considered as adjunctive treatments for patients with sepsis.
Keywords: Critical Care, Endotoxins, Intensive Care Units, Sepsis, Shock, Septic
Introduction
The term “sepsis” is defined as a systemic inflammatory response syndrome with an identified infectious source. Septic shock, with a high mortality rate, can be considered the most severe complication of sepsis. In the presence of an infection, the body releases pro-inflammatory and anti-inflammatory agents. The capacity to strike a balance between pro-inflammatory responses aimed at eradicating the invading micro-organism and anti-inflammatory signals intended to regulate the overall inflammatory cascade ultimately determines the extent of morbidity [1]. As indicated by the World Health Organization, sepsis represents one of the most common causes of mortality on a global scale [2]. Data published in 2020 revealed that there were 48.9 million cases of sepsis and 11 million sepsis-related deaths worldwide, representing 20% of all global deaths [3]. It is estimated that for every 1000 patients admitted to the hospital, 15 will develop sepsis as a complication of receiving health care [4]. The signs and symptoms of sepsis can vary considerably, from fever and hypothermia, and tachycardia and tachypnea in the early stages, to oliguria or anuria, hypoxia, cyanosis, and hypotension in septic shock. Laboratory findings typically demonstrate leukocytosis, elevated C-reactive protein (CRP) and procalcitonin levels, coagulopathy, thrombocytopenia, and lactic acidosis. It is recommended that all patients undergo source culture sampling, including urine, tracheal secretions, and at least 2 sets of blood [1]. In accordance with the Surviving Sepsis Campaign Guidelines, all patients should be administered broad-spectrum antibiotics within 1 h of diagnosis, in conjunction with the removal of infected tissue, if feasible. The standard therapy and management of septic shock involves fluid management and the use of vasopressors, complemented by additional therapies, including renal replacement therapy, corticosteroids, and extracorporeal membrane oxygenation, which are indicated for specific patient groups [5].
Extracorporeal blood purification is an important clinical option in septic shock. This report describes the case of a 67-year-old man with recurrent septic shock who required treatment with antibiotics, vasopressors, inotropes, mechanical ventilation, continuous renal replacement therapy (CRRT), and adjunctive treatment with an oXiris filter and CytoSorb® device, for hemadsorption.
Case Report
A 67-year-old man was admitted from home to our Emergency Department (ED) by the emergency medical service. On arrival to the ED, the patient presented with a decreased level of consciousness (Glasgow coma scale of 11 points: E3M4V4) and tachypnea. To maintain a mean arterial pressure of greater than 65 mmHg, intravenous norepinephrine and dobutamine were started. Noninvasive ventilation with a face mask was used. A central venous catheter was placed into the right jugular vein, the placement of which was confirmed by chest X-ray, which also showed consolidations in the right middle and lower pulmonary lobes. Laboratory test results indicated normocytic anemia, with a hemoglobin level of 8 g/dL, and elevated levels of CRP (18.7 mg/dL), procalcitonin (1.2 ng/mL), creatinine (2.8 mg/dL), serum urea (147 mg/dL), and potassium (7.1 mmol/L). A computed tomography (CT) scan confirmed the presence of pulmonary consolidations and suggested aspiration pneumonia as a potential diagnosis.
We decided to transfer the patient to the Intensive Care Unit (ICU) because of the above-mentioned status and the septic shock. An overdose of quetiapine, lamotrigine, and pregabalin was also considered, as the patient was on this medication for bipolar disorder. The patient was thereafter sedated, intubated, and mechanically ventilated, and vasopressors and inotropes were continued, along with fluids. An arterial blood pressure line was placed under ultrasound guidance for continuous hemodynamic monitoring. Empirical antibiotic therapy with piperacillin/tazobactam and vancomycin was started. Acute kidney failure was managed with the use of CRRT with regional citrate anticoagulation. The clinical condition of the patient improved, he was extubated after weaning on day 8, and CRRT was stopped on day 15. Rehabilitation was started. ICU delirium was treated with dexmedetomidine and low doses of quetiapine. Psychiatric evaluation revealed a low probability of suicidal attempt and no suicidal thoughts. The patient was fully alert, breathing on his own, and hemodynamically stable. On day 17, the patient was transferred to the general ward, where his condition remained stable for 2 days. The central venous catheter and arterial line were removed.
On the third day of the general ward stay, he developed fever, hypotension, and tachycardia, with an altered mental status; therefore, he was readmitted to the ICU. At this time, he was alert and responding to verbal commands, his blood pressure was 100/60 mmHg, and heart rate was 70/min. Laboratory test results showed elevated procalcitonin and CRP levels, leukocytosis, and increased creatinine and urea levels (Table 1). The patient received oxygen via a normal face mask. A central venous catheter and an arterial line were again placed, under ultrasound guidance. A low-dose norepinephrine infusion was commenced, and empiric antibiotic therapy with meropenem and linezolid was started.
During the first day of his second ICU stay, his condition deteriorated dramatically. He became comatose and required aggressive fluid resuscitation and further norepinephrine dose increases. On the second day of this ICU stay, the patient developed severe septic shock; therefore, argipressin was added.
The key biochemical parameters are presented in Table 1. It was decided to commence CRRT with an oXiris (Baxter, Deerfield, IL, USA) filter in combination with hemoadsorption with the CytoSorb device (CytoSorbents Inc, Princeton, NJ, USA). The setup is depicted in Figure 1. Additionally, a genetic blood sample was obtained, which showed the presence of
Following CRRT initiation and integration of the CytoSorb adsorber, rapid improvement of the patient’s condition was observed. CytoSorb therapy, which involved the use of a single adsorber, was terminated after 23 h. Norepinephrine and argipressin were reduced, and stopped after 44 h. The vasopressor doses are shown in Figure 2. CRRT was stopped after 70 h. Laboratory tests were conducted daily and demonstrated a notable decline in procalcitonin and CRP levels (Table 1). Blood cultures were positive for
Discussion
The aim of this case report is to present new options for combined extracorporeal blood purification therapies to optimize the treatment of septic shock. We discuss the etiology and course of septic shock, standard treatment, as well as extracorporeal blood purification therapies currently available and guidelines from scientific societies. In this case report, we present the successful use of the oXiris filter in combination with hemoadsorption by CytoSorb as an adjunct therapy for recurrent septic shock, namely the second episode of septic shock in the same patient, during one hospital stay. A number of techniques have been identified as potentially capable of enhancing the efficacy of CRRT in removing cytokines and endotoxins. These include hemadsorption, coupled plasma filtration adsorption, high-volume hemoperfusion, high-cutoff membranes, and combinations of these methods [6–9]. High-volume, high-efficiency filtration is defined as a continuous process of hemofiltration at a high rate, thereby facilitating the effective removal of inflammatory mediators from plasma via the convection method [9]. High-cutoff membranes are characterized by relatively large pore sizes, with a cut-off value that is typically close to the molecular weight of albumin, which leads to greater clearance of larger inflammatory mediators [10]. Hemoadsorption involves the passage of blood through sorbents that attract the solutes to adhere to them. In coupled plasma filtration adsorption, the blood plasma is first separated from the blood and then passed through an adsorber. Subsequently, the filtrate plasma is redirected and combined with the blood [9,11,12]. According to the third international consensus definition for sepsis and septic shock (sepsis-3), sepsis should now be defined as “a life-threatening organ dysfunction caused by a dysregulated host response to infection” [13]. This definition underlines the immune response, not only the pathogens, as being an important contributor to organ damage. This definition justifies the use of extrinsic toxin and cytokine removal as a potential therapeutic strategy in severe sepsis and septic shock. Several modalities have been proposed as extracorporeal modalities for blood purification, some that combine filtration with adsorption, and some that provide adsorption alone. Pure adsorption is achieved with polymyxin B columns (Toraymyxin; Toray, Tokyo, Japan), and the Alteco LPS adsorber (Alteco Medical AB; Lund, Sweden), invented to eliminate mostly gram-negative exotoxins, or the CytoSorb adsorber, designed to remove exotoxins and cytokines. Of note, the oX-iris filter also provides removal of bacterial toxins and cytokines with the use of adsorption, and, combined with filtration, oX-iris enables renal replacement therapy [14]. The first case report combining oXiris and CytoSorb was published by Ferraro et al in 2022, showing beneficial results by using this “double hemoadsorption” technique. In their case report, the authors present the case of a 70-year-old woman who was admitted to the ICU with a severe endotoxin septic shock due to
The oXiris filter (Baxter, Meyzieu, France) exhibits a multifaceted functionality. It has been designed to combine the removal of cytokines and endotoxins with renal replacement capabilities and antithrombotic properties [14]. The structure of the device includes an AN69 membrane that has been modified with a polyimine ethylene layer, which is capable of adsorbing endotoxins. Furthermore, the heparin grafting reduces local thrombogenicity [19]. The ability to provide renal support and remove cytokines and endotoxins makes this an effective treatment option in many clinical scenarios [20]. The oXiris Set is indicated for use only with the Prismaflex and PrisMax control units. At the time of writing this article, oXiris is approved for use in the European Union and authorized by the U.S. Food and Drug Administration for emergency treatment of COVID-19 (emergency use authorization) [21].
CytoSorb is an extracorporeal cytokine adsorber that has been widely used around the world [22]. It is composed of porous polymer beads that facilitate the binding of molecules through the combined action of hydrophobic interactions, van der Waals forces, and charge-induced interactions [23]. It is capable of removing hydrophobic substances with a molecular weight of up to 60 kDa, including cytokines [24], bilirubin [25], myoglobin [26] and pharmacologic substances (eg, anticoagulants such as ticagrelor or rivaroxaban [27–29]). The instructions for use include severe inflammation (eg, sepsis shock, acute respiratory distress syndrome, and extensive surgery), rhabdomyolysis, liver failure, and life-threatening bleeding under direct oral anticoagulants [23]. It can be used in combination with CRRT but also with extracorporeal membrane oxygenation [30]. Currently, CytoSorb is approved for use in the European Union and authorized by the U.S. Food and Drug Administration for emergency treatment of COVID-19 (emergency use authorization).
A recent meta-analysis of CytoSorb use by Becker et al, comprised of 34 studies with 1297 individuals treated with CytoSorb and 1314 patients serving as controls, showed no improved overall survival, but also included subgroups of patients with sepsis, patients after cardiac surgery with cardiopulmonary bypass, and patients with COVID-19 [31]. The only subgroup in which CytoSorb reduced mortality was the subset of patients after cardiac arrest, with an odds ratio of 1.22 (95% CI 1.02–1.46) [31]. Several reasons for the inconclusive results of this meta-analysis should be highlighted, including the fact that no explicit recommendations exist regarding which septic patient should be considered as a potential candidate for extracorporeal hemoadsorption therapy. Common sense suggests that an ideal patient should neither be “too healthy” nor “too sick”. Such an approach is advocated by Klinkmann et al [32], who proposed the initiation of blood purification for patients with high scores in severity scales, with procalcitonin >3 ng/mL and/or serum interleukin 6 >500 pg/mL. Another approach is that described by Kogelmann et al, in which a dynamic scoring system was evaluated in a large patient cohort [33]. Proposed recommendations against commencing CytoSorb therapy are serum lactate ³6 mmol/L or platelets <100 nL. CytoSorb therapy should be started early, within 12 to 24 h after onset of septic shock, with intense treatment (>6 L of blood/kg body weight) and frequent change of the adsorber (eg, every 12 h), following the well-known concept of anti-infective treatment – “hit hard and early”. These recommendations are based on linking survival to CytoSorb use in patients and need further confirmation with randomized controlled trials, using the same or equivalent criteria for patient enrollment [18]. Further clinical trials are needed to substantiate the efficacy of extracorporeal blood purification techniques before they can be recommended in clinical guidelines.
Conclusions
Septic shock is a severe and life-threatening condition, especially when associated with hyper-inflammation and multi-organ failure. Standard therapy consists of timely administration of antibiotics, fluid management, and vasopressors. This case report demonstrates that the combination of 2 extracorporeal blood purification methods was well tolerated and led to rapid improvements in the patient’s condition. Moreover, the therapy was safe, and the CytoSorb adsorber could be easily integrated into the CRRT system. Despite the absence of clinical trial data to substantiate the use of CytoSorb and oXiris, this report corroborates the conclusions of preceding reports, indicating that CytoSorb and oXiris can be regarded as supplementary treatments for patients with sepsis. Further studies evaluating the effectiveness of combinations of extracorporeal blood purification methods should be conducted.
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