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Prescription of CRRT: a pathway to optimize therapy

Abstract

Severe acute kidney injury (AKI), especially when caused or accompanied by sepsis, is associated with prolonged hospitalization, progression to chronic kidney disease (CKD), financial burden, and high mortality rate. Continuous renal replacement therapy (CRRT) is a predominant form of renal replacement therapy (RRT) in the intensive care unit (ICU) due to its accurate volume control, steady acid–base and electrolyte correction, and achievement of hemodynamic stability. This manuscript reviews the different aspects of CRRT prescription in critically ill patients with severe AKI, sepsis, and multiorgan failure in ICU. These include the choice of CRRT versus Intermittent and extended hemodialysis (HD), life of the filter/dialyzer including assessment of filtration fraction, anticoagulation including regional citrate anticoagulation (RCA), prescribed versus delivered CRRT dose, vascular access management, timing of initiation and termination of CRRT, and prescription in AKI/sepsis including adsorptive methods of removing endotoxins and cytokines.

Introduction

Continuous renal replacement therapy (CRRT) is a slow and smooth continuous extracorporeal blood purification, which is designed to replicate depurative function of the kidney [1, 2]. It is usually implemented over 24 h to several days with an aim of gentle correction of fluid overload and removal of excess uremic toxins. Untreated severe acute kidney injury (AKI) in critically ill patients is associated with high mortality rate. Renal replacement therapy (RRT) represents a better modality for the management of severe AKI. Though there is no clear evidence demonstrating the superiority of CRRT in survival rate to that of intermittent renal replacement therapy (IRRT), the CRRT superiority seems to find clear evidence when specific groups of patients are considered, and where a personalized treatment and modality is indicated. Furthermore, many observational studies considered CRRT as the predominant form of RRT in the intensive care unit (ICU) for critically ill patients with AKI and/or multiorgan failure (typically due to septic shock), along with acute brain injury or other causes of increased intracranial pressure or generalized brain edema. The effectiveness of CRRT is mainly due to its accurate volume control, steady acid–base and electrolyte correction, and achievement of hemodynamic stability in adults and pediatrics, where, in most cases, a clinical judgment has already been made that such patients cannot tolerate the relatively fast removal of fluids (and solutes) by conventional intermittent hemodialysis (HD) [3].

Continuous renal replacement therapy witnessed significant improvement since the technique was implemented by Peter Kramer of Göttingen (Germany) in 1977 [4]. The technique was established when Kramer was trying to introduce a catheter into the femoral vein for initiating HD. Although the catheter was inadvertently inserted into the femoral artery, Kramer realized that the patient’s mean arterial pressure could create a sufficient arteriovenous pressure difference in the extracorporeal circuit to drive blood flow. This fortuitous occurrence was the genesis of continuous arteriovenous hemofiltration (CAVH), which provided net convective solute removal (depuration) through the combination of ultrafiltration and plasma volume restitution with replacement solution. Later, in 1987, Peter Robert Uldall (Toronto, Canada) [5] introduced “continuous veno-venous hemofiltration (CVVH)” by incorporating a pump and replacing the dependence of blood flow rate on the patient’s mean arterial pressure. This technique avoided not only the potential risks and complications of puncturing a major artery (e.g., infection, distal thrombosis, and disconnection/bleeding), but also the unpredictability of extracorporeal blood flow rates due to changes in a patient’s hemodynamic status.

Prescription

The success of CRRT depends on the prescribed and achieved doses, which are a function of fluid replacement and/or dialysate administration rates, treatment duration, type of dialyzer and method, and dose of anticoagulation. Moreover, delivery and performance of CRRT require a well-established protocol (e.g., indications for initiation/cessation, catheter management) and well-trained medical and nursing staff [6].

CRRT versus intermittent and extended HD

Patients with severe AKI in the ICU usually require RRT in the form of intermittent HD (IHD), peritoneal dialysis (PD), extended HD (slow low-efficiency dialysis: SLED), or CRRT. The current evidence and KDIGO guideline support the implementation of CRRT in hemodynamically unstable patients and those with increased intracranial pressure [7]. Moreover, there is increasing evidence that CRRT is associated with a trend of short- and long-term dialysis independence [8,9,10,11]. However, there is no evidence demonstrating a mortality difference between all these modalities of RRT [8, 10]. The KDIGO guideline recommends the use of CRRT and IHD as complementary therapies in AKI patients [7].

Life of the filter/dialyzer

Premature (non-elective) termination of CRRT is usually due to clotting in the extracorporeal circuit, most commonly the filter. Filter clotting is associated with blood loss, inadequate dialysis due to treatment interruption, and increased costs related to set utilization. The major causes of short-lived circuits are inadequate anticoagulation, high filtration fraction (FF), and a compromised vascular access, which may result in stagnation of blood in the extracorporeal circuit while frequent machine alarms are managed.

Filtration fraction (FF) is the ratio of net plasma water removal rate to the plasma flow rate delivered to the filter. The official definition of FF is “the percentage ratio of ultrafiltration rate to plasma flow rate, where plasma flow rate equals blood flow rate X (1-hematocrit)”. Practically, FF should not exceed 20–25%—higher FFs correspond to higher post-filter hematocrit, which promotes clot formation and degradation of filter performance [12].

Anticoagulation

The aim of anticoagulation is to maintain patency of the extracorporeal circuit while minimizing patient complications. Appropriate anticoagulation is a subtle balance between clotting and bleeding. Strategies to prevent clotting include general measures, such as saline flushes and online pre-dilution, and different anticoagulants, such as unfractionated and low molecular weight heparin, heparin coated membranes (e.g., oXiris), and regional citrate anticoagulation (RCA).

Heparins are the most widely used anticoagulants in continuous renal replacement procedures. They are widely available and can be easily monitored but have some disadvantages. These include risks of hemorrhage, heparin resistance, and heparin-induced thrombocytopenia (HIT). The safety and efficacy of heparin therapy are based on monitoring the activated partial thromboplastin time (APTT), which is a good predictor of the risk for filter coagulation and patient hemorrhage. It is recommended to adjust the systemic APTT between 35 and 45 s [13].

Regional citrate anticoagulation has been shown to be safe and effective for anticoagulation of CRRT in most ICU patients [14]. It is based on the ability of citrate to prevent coagulation in the extracorporeal circuit by binding and chelating free ionized calcium, which is a critical co-factor in both the intrinsic and extrinsic coagulation cascades. One molecule of citrate binds two calcium anions forming citrate–calcium complex. Based on the specific CRRT modality and other factors, including flow rates and membrane surface area, approximately 60% of this complex is lost in the CRRT effluent, due to its low molecular weight (298 D). Some complexes, however, are delivered by the venous blood line to the systemic circulation and are metabolized in the liver, where one citrate molecule is transformed into three bicarbonate molecules, and calcium is released into the circulation. However, because this amount of released calcium does not completely replace the calcium lost in the effluent, calcium is infused through a separate central blood line to maintain systemic (blood) ionized calcium in the normal range (1.1–1.3 mmol/L). Initially, circuit and patient ionized calcium levels are measured frequently, but once stable doses are documented they are measured every 6–8 h [15]. In the presence of severe liver failure, citrate accumulation may occur and is best detected by the total Ca++/iCa++ ratio. A ratio of > 2.5 indicates citrate accumulation syndrome and treatment must be stopped [16]. The dialysate and replacement solutions should be calcium-free to avoid interaction and reduction of the anticoagulation effect. RCA requires close monitoring, especially upon initiation of therapy, and management of RCA can prevent some possible side effects, such as metabolic alkalosis (1 mmol of citrate converted to 3 mmol of HCO3 in the liver), metabolic acidosis (citrate can accumulate if there is liver or skeletal muscle dysfunction), hypocalcemia and hypercalcemia (inadequate control of chelating calcium by citrate or excess infusion of calcium), hypernatremia (when hypertonic trisodium citrate is used), and hypomagnesaemia (from binding to citrate–Ca2+ complex). However, RCA has been associated with significantly less bleeding [17], less blood transfusion [18] and extended life of the extracorporeal circuit [19]. Generally, anticoagulation for CRRT should be adapted to the patient’s characteristics and institution’s experience. The KDIGO guidelines suggested using RCA rather than heparin in patients who do not have contraindications for citrate [7].

CRRT dose

CRRT dose may be represented by the volume of blood purified per unit of time and is quantified by effluent rate normalized to body weight (unit: mL/kg/h). In clinical practice, effluent comprises net ultrafiltrate (according to net fluid removal requirements) along with replacement fluid and/or dialysate, depending on the specific CRRT modality.

In a seminal 2000 publication, Ronco et al. [20] demonstrated that prescribed doses of 35 and 45 ml/kg/h in post-dilution hemofiltration were superior to 25 ml/kg/h with respect to survival, resulting in a 15–20% absolute increase and an approximately 40% relative increase among critically ill AKI patients. However, later studies of higher prescribed doses of 48 versus 20 ml/kg/h in post-dilution CVVH [21] and 35 versus 20 ml/kg/h in pre-dilution CVVHDF [22] showed no difference in survival rates. These studies were followed by three major multicenter randomized controlled trials: ATN-CVVHDF, 20 versus 35 ml/kg/h pre-dilution CVVHDF in USA [23]; RENAL-CVVHDF, 25 versus 40 ml/kg/h post-dilution CVVHDF in Australia and New Zealand [24]; and IVOIRE-CVVHF in France, Belgium and Netherlands, 35 versus 70 ml/kg/h combined pre/post-dilution hemofiltration [25], which confirmed that increasing dose intensity above 20–25 ml/kg/h does not improve survival in critically ill patients with severe AKI. Furthermore, two meta-analyses have evaluated CRRT dose effects in AKI. Van Wert et al. [26] assessed 12 studies with 3999 patients and showed no benefit of more intensive RRT with regard to survival or dialysis dependence among survivors. Clark et al. [24] evaluated high-volume hemofiltration (> 50 ml/kg/h) for septic AKI patients, and found no difference in mortality between high-dose and standard-volume hemofiltration, but significantly higher rates of hypophosphatemia and hypokalemia in high-volume hemofiltration-treated patients. Other studies have confirmed the higher rates of hypophosphatemia, hypokalemia, loss of amino acid or protein, vitamins, selenium, and folic acid—concern has been raised especially about inappropriately low concentrations of water-soluble antibiotics, especially in septic patients [27, 28]. In addition, the RENAL study found that higher dose post-dilution CVVHDF resulted in greater filters’ consumption, indicating more clotting events and frequent interruption occurred during therapy [25].

A common oversight in clinical practice is failure to differentiate between prescribed and delivered dose. Interruption of CRRT treatment, due to circuit clotting, machine alarms, change of replacement solutions, radiological investigations and/or surgical procedures, can have substantial impact on the actual delivered dose. The KDIGO clinical practice guideline recommends the following [7]:

  • In clinical practice, in order to achieve a delivered dose of 2025 ml/kg/h, it is generally necessary to prescribe in the range of 2530 ml/kg/h, and to minimize interruptions in CRRT”.

  • The dose should be frequently assessed, and prescription should be adjusted accordingly

Vascular access

A properly functioning vascular access is critical in delivering the prescribed dose of CRRT. An inadequate vascular access may not be able to provide sufficient blood flow to achieve treatment goals, especially in convective therapies. A very common occurrence is the development of high (negative) arterial and/or venous pressures when the blood pump attempts to deliver the prescribed blood flow rate to the circuit. If relatively simple interventions (i.e., repositioning the catheter or the patient) do not correct this problem fairly promptly, a prolonged period of blood stagnation in the circuit occurs, potentially leading to clotting, treatment interruption, and circuit loss. Proper nursing management of catheters is crucial, not only in avoiding these complications but also in ensuring that appropriate hygienic measures are taken to minimize infection risk.

The location of the vascular access should be dictated by blood flow rate requirements, the anticipated duration of use, and ease of placement according to patient-related attributes (e.g., obesity). As suggested previously, convective modalities (especially CVVH) require higher blood flow rates than CVVHD due to filtration fraction constraints in post-dilution and dilution-related efficiency impairment in pre-dilution. For doses currently recommended in clinical practice, blood flow rates of less than 200 mL/min are generally required in CVVH (irrespective of dilution mode), especially in larger patients. Parienti et al. [29] showed that, in a randomized controlled trial evaluating catheter dysfunction and dialysis performance according to vascular access among 736 critically ill adults, catheter survival is best with a right internal jugular vein location, followed by femoral vein and left internal jugular vein. The KDIGO AKI guideline [7] recommended the sites of catheter placement by order of preference: right internal jugular vein > > femoral vein > left internal jugular vein > subclavian vein (dominant side) > subclavian vein (non-dominant side).

Another consideration is catheter diameter, which is dependent on RRT modality. For example, in CVVHD modality, where blood flow rate ranges from 100 to 150 ml/min (though it is highly dependent on the rate of dialysate and the selected membrane), 11–12 French size is recommended. On the other hand, for CRRT performed in conjunction with extracorporeal CO2 removal (requiring a high blood flow rate of 400–500 ml/min), 14–16 French size is required [12].

Vascular access can be a major challenge in neonates and infants. Large-diameter catheter has been recommended in pediatric CRRT, as it has been associated with better functional survival of the CRRT circuit especially when the catheter is placed in the internal jugular vein versus the subclavian or femoral vein. Selection of catheter size (double- or triple-lumen) depends on patient’s body size, which varies from 7 to 12 French size for neonates of 3–6 kg to children of more than 30 kg body weight [30]. Unlike vascular access placement for long-term hemodialysis, the vascular access for pediatric CRRT is often placed percutaneously, without a cuff, and at the bedside [31]. When catheters are not in use, they are routinely locked with high-concentration heparin solutions, but not in small infants.

CRRT initiation and termination

The optimal time of initiation and termination of CRRT remains controversial. In this regard, a major problem is the lack of a definition of timing and what constitutes “early” versus “late” initiation. For example, should initiation be based on onset of symptoms, biomarkers thresholds, time measured relative to the onset of AKI or ICU admission, or AKI classification criteria? There are numerous perspectives but no broad consensus to guide clinicians. The KDIGO AKI guideline [7] recommends the following:

  • Initiate RRT emergently when life-threatening changes in fluid, electrolyte, and acidbase balance exist

  • Consider the broader clinical context, the presence of conditions that can be modified with RRT, and trends of laboratory tests, rather than single BUN and creatinine thresholds alone, when making the decision to start RRT”.

In 2016, two large prospective randomized controlled trials (RCTs) assessed the impact of different renal replacement therapy timing in severely ill ICU patients with AKI without potentially life-threatening complications. These are the Artificial Kidney Initiation in Kidney Injury (AKIKI) study, a multi-center trial performed in France, and the Early versus Late Initiation of Renal Replacement Therapy in Critically Ill Patients with AKI (ELAIN) trial, a single-center German study. The AKIKI trial, conducted in 620 ICU patients on mechanical ventilation and/or catecholamine infusion with KDIGO stage 3 AKI, showed no significant difference in 60-day mortality was found between early and delayed RRT [32]. However, a post-hoc analysis, in which patients who did not ultimately receive RRT were treated as a separate group, showed late start was associated with significantly higher mortality in comparison with the early group.

The ELAIN trial, conducted over a similar time period, screened 604 almost exclusively postsurgical and trauma patients to include 231 ICU patients with KDIGO stage 2 AKI with a plasma NGAL level > 150 ng/ml. An early initiation strategy resulted in lower 90-day mortality, more rapid recovery of renal function, and a significantly shorter duration of hospital stay [33]. Longer term (12 months) follow-up showed a persistent beneficial effect on survival rate in the group who received early versus late start CRRT. These findings require confirmation in larger, multicenter, RCTs involving different patient groups requiring RRT. Following these two studies, several meta-analysis studies comparing early and late CRRT initiation were published with conflicting results [34,35,36,37].

The most recent timing RCT involved either an early group who received RRT within 12 h after documentation of failure-stage AKI or a late group who received RRT after a delay of 48 h if renal recovery had not occurred [38]. This French study, which assessed the primary outcome as death at 90 days, showed no difference between early versus late start of CRRT. However, one major limitation of this trial was the reliance for timing decisions on the RIFLE classification system, which has been shown to be relatively insensitive for the purpose in comparison to other approaches. The second limitation is the choice of a delay period of only 48 h, which may not be sufficiently long to allow recovery of renal function or detect a difference between early and delayed RRT [38].

More recently, the Cochrane Database of Systematic Reviews studied the timing effect of RRT initiation for AKI on death (day 30 or after 30 days) and recovery of renal function according to modality of RRT (continuous RRT vs continuous and intermittent RRT), etiology of AKI (surgical vs non-surgical), clinical–biochemical criteria, length of stay in ICU, and adverse effects. This review, which included five randomized studies enrolling 1084 participants, concluded that early RRT may reduce the risk of death and may improve the recovery of kidney function in critically patients with AKI. However, there was an increased risk of adverse events with early RRT [11].

Finally, the acute disease quality initiative (ADQI) workgroup suggested that a more personalized approach can be developed based on the dynamic assessments of different clinical parameters that reflect the mismatch of demand and capacity [39]. While specific parameters quantifying demand and capacity have not been defined, this “precision” approach merits further assessment.

Discontinuation of CRRT, as defined by the KDIGO AKI guideline, is “when RRT is no longer required either because intrinsic kidney function has recovered to the point that it is adequate to meet patient needs, or because RRT is no longer consistent with the goals of care”. These guidelines also state that “using diuretics is not recommended to enhance kidney function recovery, or to reduce the duration or frequency of RRT” [7]. Recent studies showed that improvement in urine output and daily urinary creatinine evaluation remain reliable markers of renal recovery [40]. Clinical indicators, more specific to discontinuation of CRRT, include vasopressor cessation, increased urinary output ≥ 500 ml/24 h (without diuretics), hemodynamic stability, correction of fluid overload, and the possible need to shift to IHD due to imminent discharge from the ICU.

Prescription in sepsis

In 2016, The Sepsis Definitions Task Force of the Society of Critical Care Medicine/European Society of Intensive Care Medicine published a revised definition of sepsis in which sepsis was defined as life-threatening organ dysfunction caused by a dysregulated host response to infection [41]. Septic shock was defined as a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality.

Studies have reported that approximately 10% to 40% of ICU patients have sepsis [42,43,44], and approximately 25% to 30% of patients develop sepsis within 24 h of ICU admission [45,46,47]. The mortality of patients with sepsis in the ICU varies from 15 to 35% [48]. Furthermore, sepsis is the primary cause of AKI in the ICU and is associated with short- and long-term adverse outcomes along with increased risk of death. Renal dysfunction/failure has been reported to occur in 22% to 69% of patients with sepsis [49, 50]. In sepsis-associated AKI, 15–20% of patients develop severe stages of renal insufficiency and need RRT [51,52,53,54].

Untreated severe AKI in critically ill patients is associated with high mortality. RRT represents the cornerstone of the management of severe AKI, and CRRT has been considered as the predominant form of RRT in the ICU, especially in AKI with sepsis [55]. This is due to its ability to provide accurate volume control, slow correction of metabolic abnormalities, and hemodynamic stability [7, 56, 57]. In addition, CRRT has been shown to be associated with lower rate of dialysis dependence than intermittent hemodialysis [8,9,10,11].

Patients with sepsis typically have elevated blood levels of endotoxins [58] and cytokines [e.g., interleukin 6 (IL-6), IL-8, IL-10, and tumor necrosis factor alpha(TNF-α)] [59]. Increased plasma levels of endotoxin can be the result of either infection due to Gram-negative bacteria or the translocation of endotoxin from Gram-negative bacteria across the wall of the abnormally permeable gut [60, 61]. Levels of cytokines vary considerably by patient and cytokine, and by factors such as sepsis severity and time since diagnosis or ICU admission [62, 63]. A retrospective cohort study of the cytokine response to pneumonia found that levels of IL-6, IL-10, and TNF-α were significantly higher among those who developed severe sepsis (survivors and non-survivors) compared with those who did not [64]. Elevated levels of IL-6 are usually associated with an increased risk of mortality [65, 66] or post-discharge mortality [67, 68].

Removal of endotoxins and plasma cytokines by extracorporeal blood purification devices may control the associated dysregulation of the immune system (which is known to induce organ dysfunction) and is potentially associated with improved outcomes in patients with sepsis [69]. A meta-analysis of randomized controlled trials of patients with sepsis or septic shock found that when all types of extracorporeal blood purification were combined, the risk of hospital, 28-day, and overall mortality was reduced compared with no blood purification [70]. However, as mentioned previously, high-volume CVVH (IVOIRE, 70 ml/kg/h) did not improve clinical outcomes in septic AKI patients (vs a dose intensity of 35 ml/kg/h). Likewise, a systematic review/meta-analysis performed by Clark et al. [71] failed to find a clinical benefit for high-volume hemofiltration (> 50 ml/kg/h) in septic AKI patients. Removal of endotoxins and plasma cytokines by plasma exchange showed conflicting results in the reduction of mortality in patients with sepsis or septic shock [72, 73].

Recent studies using different types of membrane adsorbers of endotoxin and cytokines have shown some promising results (Table 1). Some clinical improvement was reported in selected studies involving septic patients treated with hemoperfusion devices comprised polymyxin B-bound fibers designed to adsorb endotoxin [74,75,76,77,78,79]. However, other studies showed no difference in clinical endpoints between polymyxin B plus conventional therapy and conventional therapy alone [80,81,82,83]. Endotoxin removal by polymyxin B is thought to occur by a combination of ionic and hydrophobic interactions.

Table 1 Comparison between three different types of filters used in AKI/CRRT with sepsis

CytoSorb, a hemoperfusion device intended to remove cytokines by hydrophobic interactions, was employed recently in a small pilot study of patients with refractory septic shock. In this trial, a reduction in vasopressor dose compared to baseline in patients treated with the device was reported [84], although the results were difficult to interpret due to the lack of a control group. Moreover, an RCT [85] and a systematic review [86] found insufficient evidence to support a beneficial effect of CytoSorb on patient outcomes. Further, Schadler et al. did not find that CytoSorb achieved a significant reduction in plasma levels of IL-6 (vs conventional management), which may be necessary for improving patient outcomes. More recently, CytoSorb treatment in septic patients undergoing RRT showed a reduction in plasma levels of IL-8 but not of other cytokines. This study (of 24 h duration) showed an improvement of microcirculation despite no significant variation in macro-hemodynamics [87].

Clinical studies in patients with sepsis or septic shock using filters composed of the AN69 membrane, which is capable of adsorbing cytokines through ionic interactions due to its content of sulfonate groups, showed a reduction in vasopressor requirements [88], a decrease in lactate level after 3 h, and an increase in mean arterial pressure after 24 h of therapy [89]. These changes were accompanied by decreases in blood levels of TNF-α, IL-1β, IL-6, IL-8, IL-10, and HMGB1 after 72 h [89]. A registry study of CRRT in ICU patients (48% with sepsis) found that use of AN69 was associated with a reduction in mortality and ICU length of stay [90]. In later years, AN69 membrane was further developed and its surface was treated with polyethyleneimine (PEI) to produce AN69ST, which not only improved its biocompatibility but also offered the possibility to adsorb endotoxins through ionic interactions. The latest AN69-based generation of sets is oXiris, which has two unique features. One, enabled by the high concentration of PEI in the inner aspect of the membrane, is the increased potential to adsorb endotoxins from the blood. The other unique feature is grafted (immobilized) heparin, which imparts an anti-thrombogenic characteristic. Thus, in addition to its ability to perform CRRT treatment with an anti-thrombogenic membrane, oXiris has been shown to adsorb endotoxins and cytokines [55].

A retrospective case series of patients with septic AKI found that use of the oXiris set for CVVH was associated with a greater reduction in SOFA score after 48 h compared to historical controls. However, there was no difference between groups in vasopressor dose, ICU or hospital length of stay, or ICU or hospital mortality [91]. A recent Swedish clinical case report, in two patients with severe Gram-negative septic shock (KDIGO class 3 AKI) and verified endotoxemia, confirmed the ability of oXiris membrane to effectively adsorb endotoxins [92], thus corroborating earlier in vitro studies [93]. In another recent case report, a critically ill patient with severe sepsis secondary to a Gram-negative bacterial infection and sepsis-associated AKI was treated with CVVHDF using the oXiris set electively changed every 12 h for 3 consecutive days. The patient, who required high-dose vasopressor support and mechanical ventilation, showed reduction in the need for vasopressor support—by day 4, vasopressor requirements ceased and extubation occurred [94]. Similar findings were documented in a French study involving 31 septic patients receiving oXiris-based CRRT between 2014 and 2019. In this study, a lower hospital mortality than predicted (based on severity score) for the most critically ill patients was reported, although no improvement in the SOFA score over 48 h was observed. Nevertheless, there was an 88% relative decrease in norepinephrine infusion (with stabilization of hemodynamic status) and a significant improvement in lactatemia and pH over time. These improvements were most evident in patients with intra-abdominal sepsis and those with Gram-negative bacilli infection [95].

In a larger recent study, the medical records of 60 septic patients treated with CRRT using the oXiris set from April 2011 to December 2018 were reviewed—85% of patients had AKI. The results of this study, in which the use of oXiris was reported to be safe without adverse effects, showed improvement in cardio-renal and respiratory parameters, a decrease of the noradrenaline dosage, and a reduction in endotoxin activity assay, cytokines and procalcitonin [96].

Similar findings were recently documented in a prospective, randomized crossover, double-blind study of 16 patients, conducted between February 2016 and February 2018. These patients required CRRT for documented or suspected Gram-negative septic shock (blood endotoxin levels > 0.03 EU/mL) and KDIGO stage 3 AKI [97]. The patients received a total of 48 h of pre-dilution CVVHDF, 24 h each with the oXiris filter, and an AN69ST filter in random order. Endotoxin and cytokine levels were measured at baseline and at 1, 3, 8, 16, and 24 h after the start of each treatment period. Mean arterial pressure, norepinephrine infusion rate, and lactate levels were also recorded. Endotoxin level decreased more in the oXiris group than in the AN69ST group at 3, 8, and 16 h, which was accompanied with more substantial reduction in the cytokines TNF-α, IL-6, IL-8, and IFN-γ than in the standard filter group. oXiris treatment was associated with a favorable hemodynamic effect, as suggested by a more rapid decrease in blood lactate levels and lower doses of norepinephrine needed to maintain the mean arterial pressure.

Finally, a recent report included four sepsis-induced AKI patients who received CRRT with oXiris in ICUs of major Chinese hospitals. The aim of this study was to gain insights into the use of oXiris membrane for the stabilization of critically ill patients, which included start and end times, mode, dose, and additional anticoagulant. The authors concluded recommendations that oXiris should be considered for early treatment of septic AKI patients as an adjunctive therapy [98].

Conclusions

Severe AKI, especially when caused by or associated with sepsis, carries increased risk of progression to chronic kidney disease and end-stage renal failure. In addition, it is associated with prolonged hospitalization and increased mortality rate, along with being a significant public health burden from financial perspective. Critically ill patients with AKI and/or multiorgan failure in ICU require special modalities of therapies in an attempt to achieve hemodynamic stability, euvolemic status, and acid–base and electrolytes balance with an aim of speeding up renal recovery and avoiding deleterious consequences. The superiority of CRRT seems to find clear evidence when specific groups of patients are considered. This is exactly the reason why physicians should be aware of the possibility to prescribe a personalized treatment and modality. In comparison to conventional intermittent HD, CRRT provides slow and relatively gentle treatment, and is indicated in hemodynamically unstable and brain edema patients. The prescribed dose should be 20–25 ml/kg/h, but to deliver this dose, higher doses are required. To avoid degradation of filter performance due to hemoconcentration, filtration fraction should not exceed 20–25%. The recommended method of anticoagulation is RCA. The preferred location for catheters placement is the right internal jugular vein, followed by the femoral vein and left internal jugular vein. CRRT management also includes consideration of proper timing of initiation and termination—prospective trials have provided conflicting results. While early initiation may have better survival and renal recovery rates, it may be associated with more complications. Finally, although clinical data are relatively scant and also conflicting, removal of endotoxins and cytokines in different settings of sepsis (with or without AKI) may have a positive impact on clinical outcomes. The oXiris hemofilter has been shown to be effective in adsorbing endotoxins and cytokines in laboratory and clinical studies, in addition to its capability of performing CRRT with a membrane having anti-thrombogenic properties.

Availability of data and materials

Not applicable.

References

  1. 1.

    Bellomo R, Ronco C, Mehta RL. Nomenclature for continuous renal replacement therapies. Am J Kidney Dis. 1996;28(5):S2–7.

    Article  Google Scholar 

  2. 2.

    Ronco C, Ricci Z. Renal replacement therapies: physiological review. Intensive Care Med. 2008;34(12):2139–46.

    PubMed  Article  PubMed Central  Google Scholar 

  3. 3.

    Macedo E, Mehta RL. Continuous dialysis therapies: core curriculum 2016. Am J Kidney Dis. 2016;68(4):645–57.

    PubMed  Article  PubMed Central  Google Scholar 

  4. 4.

    Kramer P, Wigger W, Reiger J, et al. Arteriovenous haemofiltration: a new and simple method for treatment of overhydrated patients resistant to diuretics. Klin Wochenschr. 1977;55:1121–2 (in German).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  5. 5.

    deVeber GA. Peter Robert Uldall 1935–1995. Nephrol Dial Transplant 1996;11: 902–3. https://renal.org/about-the-renal-association/history/obituaries/peter-robert-uldall/.

  6. 6.

    Karkar A. Aspects in continuous renal replacement therapy. In: Karkar A, editor. INTECH CRRT Book. London: IntechOpen; 2019. https://doi.org/10.5772/intechopen.82503.

    Google Scholar 

  7. 7.

    Kidney Disease Improving Global Outcome KDIGO. Acute kidney injury work group: KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl. 2012;2:1–138.

    Article  Google Scholar 

  8. 8.

    Bell M, Granath F, et al. Continuous renal replacement therapy is associated with less chronic renal failure than intermittent haemodialysis after acute renal failure. Intensive Care Med. 2007;33:773–80.

    PubMed  Article  PubMed Central  Google Scholar 

  9. 9.

    Wald R, Shariff SZ, Adhikari NK, et al. The association between renal replacement therapy modality and long-term outcomes among critically ill adults with acute kidney injury a retrospective cohort study. Crit Care Med. 2014;42(4):868–77.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  10. 10.

    Wang AY, Bellomo R. Renal replacement therapy in the ICU intermittent hemodialysis, sustained low-efficiency dialysis or continuous renal replacement therapy? Curr Opin Crit Care. 2018;24(6):437–42.

    PubMed  Article  Google Scholar 

  11. 11.

    Fayad AI, Buamscha DG, Ciapponi A. Timing of renal replacement therapy initiation for acute kidney injury. Cochrane Syst Rev. 2018;12:10612.

    Google Scholar 

  12. 12.

    Joannidis M, Straaten HM. Clinical review: patency of the circuit in continuous renal replacement therapy. Crit Care. 2007;11:218. https://doi.org/10.1186/cc5937.

    Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    van de Wetering J, Westendorp RG, van der Hoeven JG, Stolk B, Feuth JD, Chang PC. Heparin use in continuous renal replacement procedures: the struggle between filter coagulation and patient hemorrhage. J Am Soc Nephrol. 1996;7(1):145–50.

    PubMed  Google Scholar 

  14. 14.

    Kindgen-Milles D, Brandenburger T, Dimski T. Regional citrate anticoagulation for continuous renal replacement therapy. Curr Opin Crit Care. 2018;24(6):450–4. https://doi.org/10.1097/MCC.0000000000000547.

    Article  PubMed  Google Scholar 

  15. 15.

    Brophy PD, Somers MJ, Baum MA, Symons JM, McAfee N, Fortenberry JD, Rogers K, Barnett J, Blowey D, Baker C, Bunchman TE, Goldstein SL. Multi-centre evaluation of anticoagulation in patients receiving continuous renal replacement therapy (CRRT). Nephrol Dial Transpl. 2005;20:1416–21.

    Article  Google Scholar 

  16. 16.

    Schneider AG, Journois D, Rimmelé T. Complications of regional citrate anticoagulation: accumulation or overload? Crit Care. 2017;21:281. https://doi.org/10.1186/s13054-017-1880-1.

    Article  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Bai M, Zhou M, He L, et al. Citrate versus heparin anticoagulation for continuous renal replacement therapy: an updated meta-analysis of RCTs. ICM. 2015;41(12):2098–110.

    CAS  Google Scholar 

  18. 18.

    Borg R, Ugboma D, Walker DM, Partridge R. Evaluating the safety and efficacy of regional citrate compared to systemic heparin as anticoagulation for continuous renal replacement therapy in critically ill patients: a service evaluation following a change in practice. J Intensive Care Soc. 2017;18(3):184–92.

    PubMed  PubMed Central  Article  Google Scholar 

  19. 19.

    Zhang Z, Hongying N. Efficacy and safety of regional citrate anticoagulation in critically ill patients undergoing continuous renal replacement therapy. ICM. 2012;38(1):20–8.

    Google Scholar 

  20. 20.

    Ronco C, Bellomo R, Homel P, et al. Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial. Lancet. 2000;356(9223):26–30.

    CAS  PubMed  Article  Google Scholar 

  21. 21.

    Bouman CS, Oudemans-Van Straaten HM, et al. Effects of early high-volume continuous venovenous hemofiltration on survival and recovery of renal function in intensive care patients with acute renal failure: a prospective, randomized trial. Crit Care Med. 2002;30(10):2205–11.

    PubMed  Article  Google Scholar 

  22. 22.

    Tolwani AJ, Campbell RC, Stofan BS, et al. Standard versus high-dose CVVHDF for ICU-related acute renal failure. J Am Soc Nephrol. 2008;19(6):1233–8.

    PubMed  PubMed Central  Article  Google Scholar 

  23. 23.

    Palevsky PM, Zhang JH, Connor TZ, Chertow GM, Crowley ST, Choudhury D, Finkel K, Kellum JA, Paganini E, Schein RM, Smith MW, Swanson KM, Thompson BT, Vijayan A, Watnick S, Star RA, Peduzzi P. VA/NIH Acute Renal Failure Trial Network: intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med. 2008;359(1):7–20.

    CAS  PubMed  Article  Google Scholar 

  24. 24.

    Bellomo R, Cass A, Cole L, et al. RENAL Replacement Therapy Study Investigators, Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med. 2009;361(17):1627–38.

    PubMed  Article  Google Scholar 

  25. 25.

    Joannes-Boyau O, Honore PM, Perez P, et al. High-volume versus standard-volume haemofiltration for septic shock patients with acute kidney injury (IVOIRE study): a multicentre randomized controlled trial. Intensive Care Med. 2013;39:1535–46.

    PubMed  Article  Google Scholar 

  26. 26.

    Van Wert R, Friedrich JO, Scales DC, et al. High-dose renal replacement therapy for acute kidney injury: systematic review and meta-analysis. Crit Care Med. 2010;38(5):1360–9.

    PubMed  Article  Google Scholar 

  27. 27.

    Heintz BH, Matzke GR, Dager WE. Antimicrobial dosing concepts and recommendations for critically Ill adult patients receiving continuous renal replacement therapy or intermittent hemodialysis. Pharmacotherapy. 2009;29(5):562–77.

    CAS  PubMed  Article  Google Scholar 

  28. 28.

    Cano NJM, Aparicio M, Brunori G, Carrero JJ, Cianciaruso B, Fiaccadori E, Lindholm B, Teplan V, Fouque D, Guarnieri G. ESPEN guidelines on parenteral nutrition: adult renal failure. Clin Nutr. 2009;28:401–14.

    CAS  PubMed  Article  Google Scholar 

  29. 29.

    Parienti JJ, Mégarbane B, Fischer MO, Cathedia Study Group, et al. Catheter dysfunction and dialysis performance according to vascular access among 736 critically ill adults requiring renal replacement therapy: a randomized controlled study. Crit Care Med. 2010;38(4):1118–25.

    PubMed  Article  Google Scholar 

  30. 30.

    Bridgesa BC, Askenazib DJ, Smithb J, Goldstein SL. Pediatric renal replacement therapy in the intensive care unit. Blood Purif. 2012;34(2):138–48. https://doi.org/10.1159/000342129.

    CAS  Article  Google Scholar 

  31. 31.

    Hackbarth R, Bunchman TE, Chua AN, Somers MJ, Baum M, Symons JM, Brophy PD, Blowey D, Fortenberry JD, Chand D, Flores FX, Alexander SR, Mahan JD, McBryde KD, Benfield MR, Goldstein SL. The effect of vascular access location and size on circuit survival in pediatric continuous renal replacement therapy: a report from the PPCRRT registry. Int J Artif Organs. 2007;30(12):1116–21.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  32. 32.

    Gaudry S, Hajage D, Schortgen F, et al. Initiation strategies for renal-replacement therapy in the intensive care unit. N Engl J Med. 2016;375:122–33.

    PubMed  Article  PubMed Central  Google Scholar 

  33. 33.

    Zarbock A, Kellum JA, Schmidt C, et al. Effect of early vs delayed initiation of renal replacement therapy on mortality in critically Ill patients with acute kidney injury: the ELAIN randomized clinical trial. JAMA. 2016;315(20):2190–9.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  34. 34.

    Yang X, Tu W, Zheng JL, et al. A comparison of early versus late initiation of renal replacement therapy for acute kidney injury in critically ill patients: an updated systematic review and meta-analysis of randomized controlled trials. BMC Nephrol. 2017;18:264. https://doi.org/10.1186/s12882-017-0667-6.

    Article  PubMed  PubMed Central  Google Scholar 

  35. 35.

    Feng Y, Yang Y, Han X, et al. The effect of early versus late initiation of renal replacement therapy in patients with acute kidney injury: a meta-analysis with trial sequential analysis of randomized controlled trials. PLoS ONE. 2017;12(3):e0174158. https://doi.org/10.1371/journal.pone.0174158.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Lai T-S, Shiao C-C, Wang J-J, et al. Earlier versus later initiation of renal replacement therapy among critically ill patients with acute kidney injury: a systematic review and meta-analysis of randomized controlled trials. Ann Intensive Care. 2017;7:38. https://doi.org/10.1186/s13613-017-0265-6.

    Article  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Zou H, Hong Q, Gaosi XU. Early versus late initiation of renal replacement therapy impacts mortality in patients with acute kidney injury post cardiac surgery: a meta-analysis. Crit Care. 2017;21:150. https://doi.org/10.1186/s13054-017-1707-0.

    Article  PubMed  PubMed Central  Google Scholar 

  38. 38.

    Barbar SD, Clere-Jehl R, Bourredjem A, et al. for the IDEAL-ICU trial investigators and the CRICS TRIGGERSEP network. Timing of renal-replacement therapy in patients with acute kidney injury and sepsis. N Engl J Med. 2018;379:1431–42.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  39. 39.

    Ostermann M, Joannidis M, Pani A, et al. 17th acute disease quality initiative (ADQI) Consensus Group: patient selection and timing of continuous renal replacement therapy. Blood Purif. 2016;42:224–37.

    PubMed  Article  PubMed Central  Google Scholar 

  40. 40.

    Viallet N, Brunot V, Kuster N, et al. Daily urinary creatinine predicts the weaning of renal replacement therapy in ICU acute kidney injury patients. Ann Intensive Care. 2016;6:71. https://doi.org/10.1186/s13613-016-0176-y.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  41. 41.

    Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315:801–10.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  42. 42.

    Vincent JL, Sakr Y, Sprung CL, et al. Sepsis in European intensive care units: results of the SOAP study. Crit Care Med. 2006;34:344–53.

    PubMed  Article  Google Scholar 

  43. 43.

    Kaukonen KM, Bailey M, Suzuki S, et al. Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000–2012. JAMA. 2014;311:1308–16.

    CAS  PubMed  Article  Google Scholar 

  44. 44.

    van Vught LA, Klein Klouwenberg PM, Spitoni C, et al. Incidence, risk factors, and attributable mortality of secondary infections in the intensive care unit after admission for sepsis. JAMA. 2016;315:1469–79.

    Article  CAS  Google Scholar 

  45. 45.

    Padkin A, Goldfrad C, Brady AR, et al. Epidemiology of severe sepsis occurring in the first 24 h in intensive care units in England, Wales, and Northern Ireland. Crit Care Med. 2003;31:2332–8.

    PubMed  Article  Google Scholar 

  46. 46.

    van Gestel A, Bakker J, Veraart CPWM, van Hout BA. Prevalence and incidence of severe sepsis in Dutch intensive care units. Crit Care. 2004;8:R153–62.

    PubMed  PubMed Central  Article  Google Scholar 

  47. 47.

    Harrison DA, Welch CA, Eddleston JM. The epidemiology of severe sepsis in England, Wales and Northern Ireland, 1996 to 2004: secondary analysis of a high-quality clinical database, the ICNARC Case Mix Programme Database. Crit Care. 2006;10:R42. https://doi.org/10.1186/cc4854.

    Article  PubMed  PubMed Central  Google Scholar 

  48. 48.

    SepNet Critical Care Trials Group. Incidence of severe sepsis and septic shock in German intensive care units: the prospective, multicentre INSEP study. Intensive Care Med. 2016;42:1980–9. https://doi.org/10.1007/s00134-016-4504-3.

    Article  Google Scholar 

  49. 49.

    Mayr FB, Yende S, Linde-Zwirble WT, et al. Infection rate and acute organ dysfunction risk as explanations for racial differences in severe sepsis. JAMA. 2010;303(24):2495–503.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  50. 50.

    Yébenes JC, Ruiz-Rodriguez JC, Ferrer R, et al. Epidemiology of sepsis in catalonia: analysis of incidence and outcomes in a European setting. Ann Intensive Care. 2017;7:19. https://doi.org/10.1186/s13613-017-0241-1.

    Article  PubMed  PubMed Central  Google Scholar 

  51. 51.

    Uchino S, Kellum JA, Bellomo R, et al. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005;294:813–8.

    CAS  PubMed  Article  Google Scholar 

  52. 52.

    Bagshaw SM, George C, Bellomo R, the ANZICS Database Management Committee. Early acute kidney injury and sepsis: a multicentre evaluation. Crit Care. 2008;12:R47.

    PubMed  PubMed Central  Article  Google Scholar 

  53. 53.

    Mehta RL, Bouchard J, Soroko SB, et al. Sepsis as a cause and consequence of acute kidney injury: program to improve care in acute renal disease. Intensive Care Med. 2011;37:241–8.

    PubMed  Article  Google Scholar 

  54. 54.

    Nagata I, Uchino S, Tokuhira N, et al. Sepsis may not be a risk factor for mortality in patients with acute kidney injury treated with continuous renal replacement therapy. J Crit Care. 2015;30:998–1002.

    PubMed  Article  Google Scholar 

  55. 55.

    Monard C, Rimmele T, Ronco C. Extracorporeal therapies for sepsis. Blood Purif. 2019;47(suppl 3):2–15.

    CAS  Google Scholar 

  56. 56.

    Bellomoa R, Ramanb J, Ronco C. Intensive care unit management of the critically ill patient with fluid overload after open heart surgery. Cardiology. 2001;96:169–76.

    Article  Google Scholar 

  57. 57.

    Ronco C. Evolution of technology for continuous renal replacement therapy: forty years of continuous renal replacement therapy. In: Bellomo R, Kellum JA, La Manna G, Ronco C, editors. 40 years of continuous renal replacement therapy, vol. 194. Basel: Karger; 2018. p. 1–14. https://doi.org/10.1159/000485596.

    Google Scholar 

  58. 58.

    Opal SM, Scannon PJ, Vincent JL, et al. Relationship between plasma levels of lipopolysaccharide (LPS) and LPS-binding protein in patients with severe sepsis and septic shock. J Infect Dis. 1999;180:1584–9.

    CAS  PubMed  Article  Google Scholar 

  59. 59.

    Pinsky MR, Vincent JL, Deviere J, et al. Serum cytokine levels in human septic shock. Relation to multiple-system organ failure and mortality. Chest. 1993;103:565–75.

    CAS  PubMed  Article  Google Scholar 

  60. 60.

    Marshall JC. Endotoxin in the pathogenesis of sepsis. Contrib Nephrol. 2010;167:1–13.

    CAS  PubMed  Article  Google Scholar 

  61. 61.

    Deitch EA. Gut-origin sepsis: evolution of a concept. Surgeon. 2012;10:350–6.

    PubMed  PubMed Central  Article  Google Scholar 

  62. 62.

    Gogos CA, Drosou E, Bassaris HP, Skoutelis A. Pro- versus anti-inflammatory cytokine profile in patients with severe sepsis: a marker for prognosis and future therapeutic options. J Infect Dis. 2000;181:176–80.

    CAS  PubMed  Article  Google Scholar 

  63. 63.

    Mera S, Tatulescu D, Cismaru C, et al. Multiplex cytokine profiling in patients with sepsis. APMIS. 2011;119:155–63.

    CAS  PubMed  Article  Google Scholar 

  64. 64.

    Kellum JA, Kong L, Fink MP, et al. Understanding the inflammatory cytokine response in pneumonia and sepsis: results of the genetic and inflammatory markers of sepsis (GenIMS) study. Arch Intern Med. 2007;167:1655–63.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  65. 65.

    Andaluz-Ojeda D, Bobillo F, Iglesias V, et al. A combined score of pro- and anti-inflammatory interleukins improves mortality prediction in severe sepsis. Cytokine. 2012;57:332–6.

    CAS  PubMed  Article  Google Scholar 

  66. 66.

    Mat-Nor MB, Md RA, Abdulah NZ, Pickering JW. The diagnostic ability of procalcitonin and interleukin-6 to differentiate infectious from noninfectious systemic inflammatory response syndrome and to predict mortality. J Crit Care. 2016;33:245–51.

    CAS  PubMed  Article  Google Scholar 

  67. 67.

    Frencken JF, van Vught LA, Peelen LM, et al. An unbalanced inflammatory cytokine response is not associated with mortality following sepsis: a prospective cohort study. Crit Care Med. 2017;45:e493–9.

    CAS  PubMed  Article  Google Scholar 

  68. 68.

    Oberholzer A, Souza SM, Tschoeke SK, et al. Plasma cytokine measurements augment prognostic scores as indicators of outcome in patients with severe sepsis. Shock. 2005;23:488–93.

    CAS  PubMed  Google Scholar 

  69. 69.

    Ronco C, Tetta C, Mariano F, et al. Interpreting the mechanisms of continuous renal replacement therapy in sepsis: the peak concentration hypothesis. Artif Organs. 2003;27(9):792–801.

    PubMed  Article  Google Scholar 

  70. 70.

    Zhou F, Peng Z, Murugan R, Kellum JA. Blood purification and mortality in sepsis: a meta-analysis of randomized trials. Crit Care Med. 2013;41:2209–20.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  71. 71.

    Clark E, Molnar AO, Joannes-Boyau O, et al. High-volume hemofiltration for septic acute kidney injury: a systematic review and meta-analysis. Crit Care. 2007;11:218. https://doi.org/10.1186/cc5937.

    Article  Google Scholar 

  72. 72.

    Rimmer E, Houston BL, Kumar A, et al. The efficacy and safety of plasma exchange in patients with sepsis and septic shock: a systematic review and meta-analysis. Crit Care. 2014;18:699.

    PubMed  PubMed Central  Article  Google Scholar 

  73. 73.

    Busund R, Koukline V, Utrobin U, Nedashkovsky E. Plasmapheresis in severe sepsis and septic shock: a prospective, randomised, controlled trial. Intensive Care Med. 2002;28:1434–9.

    PubMed  Article  PubMed Central  Google Scholar 

  74. 74.

    Lee CT, Tu YK, Yeh YC, et al. Effects of polymyxin B hemoperfusion on hemodynamics and prognosis in septic shock patients. J Crit Care. 2018;43:202–6.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  75. 75.

    Cruz DN, Antonelli M, Fumagalli R, et al. Early use of polymyxin B hemoperfusion in abdominal septic shock: the EUPHAS randomized controlled trial. JAMA. 2009;301:2445–52.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  76. 76.

    Nakamura Y, Kitamura T, Kiyomi F, et al. Potential survival benefit of polymyxin B hemoperfusion in patients with septic shock: a propensity-matched cohort study. Crit Care. 2017;21:134.

    PubMed  PubMed Central  Article  Google Scholar 

  77. 77.

    Iwagami M, Yasunaga H, Noiri E, et al. Potential survival benefit of polymyxin B hemoperfusion in septic shock patients on continuous renal replacement therapy: a propensity-matched analysis. Blood Purif. 2016;42:9–17.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  78. 78.

    Klein DJ, Foster D, Walker PM, et al. Polymyxin B hemoperfusion in endotoxemic septic shock patients without extreme endotoxemia: a post hoc analysis of the EUPHRATES trial. Intensive Care Med. 2018;44:2205–12.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  79. 79.

    Vincent JL, Laterre PF, Cohen J, et al. A pilot-controlled study of a polymyxin B-immobilized hemoperfusion cartridge in patients with severe sepsis secondary to intra-abdominal infection. Shock. 2005;23:400–5.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  80. 80.

    Dellinger RP, Bagshaw SM, et al. Effect of targeted polymyxin B hemoperfusion on 28-day mortality in patients with septic shock and elevated endotoxin level: the EUPHRATES Randomized Clinical Trial. JAMA. 2018;320:1455–63.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  81. 81.

    Fujii T, Ganeko R, Kataoka Y, et al. Polymyxin B-immobilized hemoperfusion and mortality in critically ill adult patients with sepsis/septic shock: a systematic review with meta-analysis and trial sequential analysis. Intensive Care Med. 2018;44:167–78.

    CAS  PubMed  Article  Google Scholar 

  82. 82.

    Payen DM, Guilhot J, Launey Y, et al. Early use of polymyxin B hemoperfusion in patients with septic shock due to peritonitis: a multicenter randomized control trial. Intensive Care Med. 2015;41:975–84.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  83. 83.

    Iwagami M, Yasunaga H, Doi K, et al. Postoperative polymyxin B hemoperfusion and mortality in patients with abdominal septic shock: a propensity-matched analysis. Crit Care Med. 2014;42:1187–93.

    CAS  PubMed  Article  Google Scholar 

  84. 84.

    Friesecke S, Stecher SS, Gross S, et al. Extracorporeal cytokine elimination as rescue therapy in refractory septic shock: a prospective single-center study. J Artif Organs. 2017;20:252–9.

    CAS  PubMed  Article  Google Scholar 

  85. 85.

    Schadler D, Pausch C, Heise D, et al. The effect of a novel extracorporeal cytokine hemoadsorption device on IL-6 elimination in septic patients: a randomized controlled trial. PLoS ONE. 2017;12:e0187015.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  86. 86.

    Hawlik K, Wild C. Extracorporeal cytokine haemadsorption therapy in patients with sepsis or SIRS. In: Decision support document No. 106. Vienna: Ludwig Boltzmann Institute for Health Technology Assessment; 2017.

  87. 87.

    Zuccari S, Damiani E, Domizi R, et al. Changes in cytokines, haemodynamics and microcirculation in patients with sepsis/septic shock undergoing continuous renal replacement therapy and blood purification with CytoSorb. Blood Purif. 2019. https://doi.org/10.1159/000502540.

    Article  PubMed  Google Scholar 

  88. 88.

    Haase M, Silvester W, Uchino S, et al. A pilot study of high-adsorption hemofiltration in human septic shock. Int J Artif Organs. 2007;30:108–17.

    CAS  PubMed  Article  Google Scholar 

  89. 89.

    Shiga H, Hirasawa H, Nishida O, et al. Continuous hemodiafiltration with a cytokine-adsorbing hemofilter in patients with septic shock: a preliminary report. Blood Purif. 2014;38:211–8.

    CAS  PubMed  Article  Google Scholar 

  90. 90.

    Doi K, Iwagami M, Yoshida E, Marshall MR. Associations of polyethylenimine-coated AN69ST membrane in continuous renal replacement therapy with the intensive care outcomes: observations from a claims database from Japan. Blood Purif. 2017;44:184–92.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  91. 91.

    Shum HP, Chan KC, Kwan MC, Yan WW. Application of endotoxin and cytokine adsorption haemofilter in septic acute kidney injury due to Gram-negative bacterial infection. Hong Kong Med J. 2013;19:491–7.

    CAS  PubMed  Google Scholar 

  92. 92.

    Broman ME, Bodelsson M. Analysis of endotoxin adsorption in two swedish patients with septic shock. Blood Purif. 2019;47(suppl 3):51–3.

    CAS  Google Scholar 

  93. 93.

    Malard B, Lambert C, Kellum JA. In vitro comparison of the adsorption of inflammatory mediators by blood purification devices. Intensive Care Med Exp. 2018;6(1):12. https://doi.org/10.1186/s40635-018-0177-2.

    Article  PubMed  PubMed Central  Google Scholar 

  94. 94.

    Tan HK, Kaushik M, Tan CW. Augmented adsorptive blood purification during continuous veno-venous hemodiafiltration in a severe septic, acute kidney injury patient: use of oXiris: a single center case report. Blood Purif. 2019;47(suppl 3):59–64.

    Google Scholar 

  95. 95.

    Schwindenhammer V, Girardot T, Chaulier K, Gregoire A, Monard C, Huriaux L, Illinger J, Leray V, Uberti T, Crozon-Clauzel J, Rimmele T. oXiris use in septic shock: experience of two french centers. Blood Purif. 2019;47(suppl 3):29–35.

    Google Scholar 

  96. 96.

    Turani F, Barchetta R, Falco M, et al. Continuous renal replacement therapy with the adsorbing filter oXiris in septic patients: a case series. Blood Purif. 2019;47(suppl 3):54–8.

    Google Scholar 

  97. 97.

    Broman ME, Hansson F, Vincent J-L, Bodelsson M. Endotoxin and cytokine reducing properties of the oXiris membrane in patients with septic shock: a randomized crossover double-blind study. PLoS ONE. 2019;14(8):e0220444. https://doi.org/10.1371/journal.pone.0220444.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  98. 98.

    Zhang L, Tang GKY, Liu S, et al. Hemofilter with adsorptive capabilities: case report series. Blood Purif. 2019;47(suppl 3):45–50.

    Google Scholar 

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Karkar, A., Ronco, C. Prescription of CRRT: a pathway to optimize therapy. Ann. Intensive Care 10, 32 (2020). https://doi.org/10.1186/s13613-020-0648-y

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Keywords

  • Acute kidney injury
  • Sepsis
  • oXiris
  • Adsorption
  • Continuous renal replacement therapy
  • Anticoagulation
  • Vascular access