The Comparison of Circuit Lifespan between Integration and Separation Approach in Extracorporeal Membrane Oxygenation Patient Requiring Continuous Renal Replacement Therapy Support, A Randomized Controlled Trial (E-CRRT Trial)

The Comparison of Circuit Lifespan between Integration and Separation Approach in Extracorporeal Membrane Oxygenation Patient Requiring Continuous Renal Replacement Therapy Support, A Randomized Controlled Trial (E-CRRT Trial) | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The Comparison of Circuit Lifespan between Integration and Separation Approach in Extracorporeal Membrane Oxygenation Patient Requiring Continuous Renal Replacement Therapy Support, A Randomized Controlled Trial (E-CRRT Trial) Prasittiporn Tangjitaree, Peerapat Thanapongsatorn, Tanyapim Sinjira, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8049207/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 05 Feb, 2026 Read the published version in Intensive Care Medicine → Version 1 posted 4 You are reading this latest preprint version Abstract Background The estimated incidence of acute kidney injury requiring renal replacement therapy (RRT), mainly continuous RRT (CRRT), in patients necessitating extracorporeal membrane oxygenation (ECMO) is approximately 50%. Currently, two well-known techniques, integration and separation are utilized for combining CRRT and ECMO circuits, neither of which is considered a standard treatment. Purpose This study aimed to compare circuit lifespan of CRRT between these two techniques during ECMO support. Methods A multicentered randomized controlled trial was conducted from May 2021 to March 2025. ECMO patients who required CRRT support were enrolled. Primary outcome was CRRT circuit lifespan. Results Eighty patients were recruited, with 40 allocated to the integration group and 40 to the separation group. Median circuit lifespan did not significantly differ between the groups (72 hours [IQR 45–96.5] vs. 71 hours [IQR 45–84]; p = 0.52). Twenty-eight-day mortality rates were also comparable (32.5% vs. 35%; p = 0.81). No significant differences were observed in the incidence of serious adverse events, including air embolism. Transmembrane pressure and CRRT machine alarm frequencies were similar between groups. Conclusion Among critically ill ECMO patients with CRRT support, integrated CRRT circuit into ECMO circuit shows no significant difference in efficacy and serious adverse events when compared to separation technique. Trial registration NCT05036616 CRRT ECMO circuit combination integration Figures Figure 1 Figure 2 Figure 3 Figure 4 TAKE HOME MESSAGE In this study which compare two configurations of CRRT support during ECMO treatment, there is no significant CRRT circuit lifespan between the integration and separation techniques. Both approaches were shown feasible and safe, with comparable 28-day mortality. INTRODUCTION In contemporary critical care, extracorporeal membrane oxygenation (ECMO) has emerged as a pivotal life-saving intervention for critically ill patients. The severity of patients necessitating ECMO is often accompanied by multifactorial factors leading to acute kidney injury (AKI), including nosocomial infections, exposure to nephrotoxic drugs, hypotensive states, and systemic inflammatory conditions [ 1 – 5 ]. The incidence of AKI in critically ill patients can be as high as 80%, with up to 50% requiring renal replacement therapy (RRT) within the first week [ 6 – 8 ]. Due to the state of hemodynamic instability, continuous renal replacement therapy (CRRT) is preferred. The CRRT methods combined with ECMO have three main ways consisting of 1. In-line technique, 2. Separation technique, and 3. Integration technique [ 1 , 9 , 10 ]. Currently, separation and integration are more popular methods as shown in Fig. 1 , The separation technique offers advantages such as an independent circuit and easy circuit modifications [ 11 ]. However, it is associated with the risk of additional vascular access and catheter-related bloodstream infections (CRBSI). On the other hand, the integration technique eliminates the need for additional vascular access for renal replacement therapy. Yet, concerns include the potential for air emboli, difficulties in managing pressure circuit issues, and limitations in certain CRRT machines that do not support integration techniques with pressure limitations [ 12 ]. Despite the absence of conclusive evidence supporting the superiority of either technique [ 13 ], a questionnaire study by Michael Thy, and et al. [ 14 ] revealed that method selection is often based on physician’s experience. This study aims to address this gap by comparing the CRRT circuit lifespan, along with assessments of pressure at various points, CRRT machine alarms, serious adverse events during CRRT and 28-day mortality when combined with ECMO for each technique. MATERIALS AND METHODS Population This multicenter, open-label randomized controlled trial was conducted in the surgical and medical intensive care units of two tertiary referral centers in Thailand: King Chulalongkorn Memorial Hospital (KCMH) and the Central Chest Institute of Thailand (CCIT). The primary objective was to compare CRRT circuit lifespan between the integration and separation groups. Secondary objectives included comparisons of serious adverse events, 28-day mortality, pressures at various points in the CRRT circuit, and CRRT machine alarms. Eligible participants were adults (≥ 18 years) admitted to the ICU, requiring ECMO, and diagnosed with AKI necessitating CRRT. Exclusion criteria included pregnancy, contraindication to heparin, and AKI due to bilateral renal artery thrombosis, vasculitis, glomerulonephritis, or post-obstructive causes. ECMO indications included cardiogenic shock, post-cardiotomy support, primary graft failure after transplantation, procedural support, bridging to transplant, and severe pulmonary conditions such as acute respiratory distress syndrome (ARDS), lung hyperinflation, hemorrhage, or post-transplant management. CRRT was initiated for severe metabolic acidosis (arterial pH < 7.2 or bicarbonate 6.2 mEq/L or ECG abnormalities), oliguria or anuria (urine output of less than 0.5 mL/kg/h for at least 6 hours), azotemia (Blood Urea Nitrogen more than 100 mg/dL), uremia, or increased intracranial pressure. The trial was registered at ClinicalTrial.gov (NCT05036616) on April 1, 2021 and approved by the Institutional Review Board of King Chulalongkorn Memorial Hospital (COA No. 0607/2023). The study was conducted in accordance with the Declaration of Helsinki and all applicable regulations. Written informed consent was obtained from the patients or their legally authorized representatives. Randomization Patients meeting eligibility criteria are pre-stratified by ECMO type (VV-ECMO or VA-ECMO) to address potential pressure-related influences on CRRT circuit longevity. Randomization, occurring in blocks of four within each ECMO type, establishes the integration and separation groups. This pre-stratification ensures balanced representation of ECMO types across both groups (Supplementary Fig. 6). In the separation technique group, a nephrologist or intensivist inserts the dialysis catheter, proceeding with separate CRRT and ECMO. In the integration technique, perfusionist integrates CRRT into the ECMO circuit. The case record form captures data throughout the CRRT circuit's lifespan, documenting reasons for ECMO or CRRT discontinuation, vital signs, daily laboratory results, anticoagulant and citrate use, vasopressor/inotrope doses, access and return CRRT cannula pressures, alarms, and ECMO-related complications like bleeding, hemolysis, or embolic events. Follow-up extends until the end of the first CRRT circuit, with mortality at 28-day post-randomization recorded. Both groups receive standardized care throughout data collection. ECMO Circuit Configuration The Maquet Rotaflow I or II ECMO System (Getinge, Sweden) was used as the primary apparatus. ECMO cannula insertion was performed by cardiovascular thoracic or vascular surgeons. Return cannulas ranged from 15–17 French for VA ECMO and 15–19 French for VV ECMO, with drainage cannulas standardized at 25–27 French. Patient integration into the ECMO circuit was done by experienced perfusionists. ECMO initiation began with a flow rate of 3–5 LPM, overseen by cardiologists, cardiovascular thoracic surgeons, or intensivists. Systemic heparin was administered, serving as the anticoagulant to prevent circuit clotting. The heparin dose is adjusted in unit per hour to maintain an activated clotting time (ACT) of 180–220 seconds every 2 hours, and an activated partial thromboplastin time (aPTT) 1.5–2.5 times the normal value, measured every 6–12 hours [ 15 ]. CRRT prescription and circuit set up CRRT procedures utilized the Prismaflex system from Baxter (Lund, Sweden) employing CVVHDF mode with a prescribed dose of 25–30 mL/kg/hour. The blood flow rate was set at a minimum of 100 mL/min, and and regional citrate may be employed as the anticoagulant for the CRRT circuit in case of delayed heparin use in the ECMO circuit, the decision to use regional citrate depends on primary doctor judement, except in cases of hyperlactatemia (arterial lactate > 8 mmol/L), advanced cirrhosis or acute liver failure [ 16 ]. However, there is no specific guideline for CRRT with ECMO. Double lumen catheters for CRRT ranged from 12.5 to 13.5 French, with specific insertion depths depending on vein placement: 16 cm in the right internal jugular vein, 19 cm in the left internal jugular vein, and 25 cm in the femoral vein. In the integration group, pigtails integrating the CRRT-ECMO circuit measured 1.52 cm in diameter and were connected seamlessly via a three-way stopcock in the P2 segment. The CRRT machine operates with an access pressure range of -250 to + 450 mmHg, triggering a high pressure alarm at + 300 mmHg or higher, and a low pressure alarm at -250 mmHg or lower. Return pressure ranges from − 50 to + 350 mmHg, with a high pressure alarm set at + 350 mmHg or higher. Transmembrane pressure (TMP) and pressure drop serve as indicators for filter clogging and clotting. A high TMP alarm is set at 300 mmHg or higher, and a high pressure drop alarm is set at 100 mmHg or higher. Blood leakage is detected using an infrared blood leak detector in the effluent line, while a bubble detection system utilizes ultrasonic technology to detect bubbles in the effluent line [ 17 ]. Operative Definitions AKI definition was defined by KDIGO 2012 guideline [ 18 ] as the serum creatinine increase at least 0.3 mg/dL from baseline within 48 hours or increased 1.5 times from baseline within 7 days or urine output less than 0.5 mL/kg/hour for 6 hours. The decision to initiate CRRT is made by intensivists or nephrologists. The primary outcome, CRRT circuit lifespan, measures the duration from blood flow initiation to circuit completion lasting up to 72 hours, extendable to 120 hours if circuit function remained satisfactory (maximum 72 hours as per manufacturer’s suggestion [ 19 ]), or its premature clotting, meaning the circuit lifespan is less than 72 hours, with the occurrence of circuit clotting, including visible clotting or a pressure drop > 100 mmHg, or clogging where TMP > 300 mmHg, events reported by trained nurses familiar with renal replacement therapy, or until specific criteria for renal function improvement are met, characterized by urine output surpassing 1000 mL without diuretics or exceeding 2000 mL with diuretic use [ 20 , 21 ], or events affecting termination include ECMO discontinuation, extended circuit downtime, and participant mortality. Crossover between 2 techniques is accounted for, and nurse-recorded parameters such as pressures and machine alarms are monitored hourly, with daily averages computed. Additionally, 28-day mortality status is assessed from the day of randomization. Serious Adverse Events Serious adverse events recorded during the data collection period for circuit lifespan include bleeding at the ECMO cannula or vascular access exit site, new onset of hemolysis during ECMO combined with CRRT treatment, systemic or major bleeding, new positive blood cultures with clinical correlation of infection (≥ 1 blood bottle), and air embolic event. SAMPLE SIZE ESTIMATION This study was designed as a superiority trial. A total of 80 patients were required, with 40 participants in each group. The sample size calculation was based on published data from Michael Thy et al. [ 12 ], under the assumption that the integration strategy would prolong circuit lifespan by a mean of 28 hours compared with the separation approach. With an allocation ratio of 1:1, the study was powered at 80% to detect this difference at a two-sided significance level of 0.05, accounting for a 5% dropout rate [ 22 ]. STISTICAL ANALYSIS Statistical analysis was performed using STATA version 18. Categorical variables were presented as frequencies and percentages, and comparisons were made using the Chi-square test or Fisher’s exact test, as appropriate. Continuous variables were expressed as means or medians, and differences were assessed using either the unpaired t -test or the Mann–Whitney U test, depending on the distribution of the data. The primary analysis was conducted using the intention-to-treat (ITT) approach, with a significance level set at p < 0.05. A per-protocol analysis or as-treated was also performed to support the noninferiority findings of the trial. Sensitivity analyses of the primary outcome were conducted, considering anticipated clinical events such as renal recovery, ECMO discontinuation, or death during CRRT that could potentially influence the true effect. Additionally, Kaplan–Meier analysis was used to assess cumulative survival of circuit lifespan. RESULTS Between May 1, 2021, and March 10, 2025, a total of 80 eligible and consenting patients were recruited from the intensive care units of KCMH and CCIT. Forty patients were randomized to the integration group and 40 to the separation group. Baseline characteristics, including age, sex, comorbidities, severity scores [ 23 , 24 ], ECMO indications, and causes of AKI, were comparable between groups. Among the indications for initiating CRRT in ECMO patients, fluid overload was the most common (46.3%), followed by refractory metabolic acidosis (25%) (Table 1 ). Table 1 Baseline characteristic, ECMO and CRRT indication Characteristics Total (N = 80) Integration (n = 40) Separation (n = 40) Male, n (%) 50 (62.5) 27 (67.5) 23 (57.5) Age (year), median (IQR) 58 (47.5–67) 54.5 (46- 66.5) 58 (49- 68.5) Ideal body weight (kg), median (IQR) 59.5 (52–66) 61 (55.5–67.5) 57 (52–62) Underlying, n (%) - Diabetes Mellitus 25 (31.3) 12 (30) 13 (32.5) - Chronic kidney disease 24 (30) 9 (22.5) 15 (37.5) - Ischemic heart disease 29 (36.3) 13 (32.5) 16 (40) - Cirrhosis 37 (46.3) 17 (42.5) 20 (50) - Malignancy 4 (5) 2 (5) 2 (5) - Nephrotoxic agent use 16 (20) 10 (25) 6 (15) APACHE II score, median (IQR) 30 (26–35) 31.5 (27–35.5) 30 (25–34.5) SOFA score, median (IQR) 16 (14–19) 16.5 (14–19) 15 (13–19) ECMO type , n (%) - VV ECMO 13 (16.3) 8 (20) 5 (12.5) - VA ECMO 67 (83.7) 32 (80) 35 (87.5) ECMO indication - Cardiogenic shock 23 (28.8) 13 (32.5) 10 (25) - ECPR 7 (8.8) 5 (12.5) 2 (5) - Post heart transplant 8 (10) 4 (10) 4 (10) - Postcardiotomy 23 (28.8) 9 (22.5) 14 (35) - ARDS 10 (12.5) 5 (12.5) 5 (12.5) Initial ECMO setting Blood flow rate, LPM 3.8 (3–4.3) 4 (3–4.4) 3.7 (3–4.2) Pump speed, RPM 3202.5 (2922.5-3529.5) 3177.5 (2840-3475.5) 3260 (3040–3600) Laboratory Hemoglobin (g/dL), median (IQR) 9.4 (8.4–10.8) 9.5 (8.5–11.1) 9.3 (8.1–10.2) Platelet (/µL), median (IQR) 96000 (63500–164500) 96000 (60000–201500) 97500 (65500–133500) INR, median (IQR) 1.8 (1.4–2.4) 1.6 (1.3–1.8) 2 (1.5–3.2) aPTT (sec), median (IQR) 42.8 (33.2–56.8) 39.9 (30.9–52.4) 44 (34.5–59.7) Blood urea nitrogen (mg/dL), median (IQR) 46 (27.3–70.9) 49 (24–74) 44 (28.5–68.9) Creatinine (mg/dL), median (IQR) 2.32 (1.52–4.16) 2.29 (1.45–4.19) 2.40 (1.75–4.09) Potassium (mmol/L), median (IQR) 5.1 (3.5–6.9) 5 (3.5–6.9) 5.3 (3.3–7.3) HCO 3 (mEq/L), median (IQR) 22 (17–25) 22 (17–25) 22 (18–25) Albumin (mg/L), median (IQR) 3 (2.6–3.4) 3 (2.6–3.2) 3 (2.6–3.4) Arterial pH, median (IQR) 7.41 (7.32–7.46) 7.40 (7.31–7.46) 7.41 (7.32–7.46) Arterial lactate (mmol/L), median (IQR) 3.9 (2.4–10.4) 3.1 (2.4–8.4) 4.4 (2.2–11.8) Cause of AKI , n(%) Cardiorenal syndrome 44 (55) 23 (57.5) 21 (52.5) Prerenal cause 5 (6.3) 2 (5) 3 (7.5) Sepsis 8 (10) 5 (12.5) 3 (7.5) Multifactorial cause 8 (10) 5 (12.5) 3 (7.5) CRRT indication , n(%) Anuria or oliguria 16 (20) 9 (22.5) 7 (17.5) High blood urea nitrogen 10 (12.5) 5 (12.5) 5 (12.5) Refractory acidosis 20 (25) 9 (22.5) 11 (27.5) Refractory hyperkalemia 3 (3.8) 1 (2.5) 2 (5) Refractory volume overload 37 (46.3) 19 (47.5) 18 (45) CRRT setting Prescribe dose (mL/kg/hour), median (IQR) 30 (30–32) 30 (30–32) 30 (30–32) Blood flow rate (mL/min), median (IQR) 150 (100–150) 150 (100–175) 150 (100–150) Reginal citrate anticoagulation, n(%) 24 (30) 13 (32.5) 11 (27.5) Data are presented as mean (SD) or median (IQR1-IQR3) for continuous measures, and n (%) for categorical measures APACHE II = Acute physiology and chronic health evaluation II [ 23 ], aPTT = Activated partial thromboplastin time, ECPR = Extra-corporeal cardiopulmonary resuscitation, LPM = liter per minute, RPM = revolution per minute, SOFA score = Sequential Organ Failure Assessment Score [ 24 ] Crossover between treatment arms occurred during the study. One patient in the integration group developed excessively high access pressures during CRRT and required a switch to the separation technique. Conversely, nine patients in the separation group could not undergo catheter insertion for RRT and were subsequently switched to the integration group (Fig. 2 ). Primary outcome There was no significant difference in the median total CRRT circuit lifespan between the integration and separation groups: 72 hours (IQR 45–96.5) vs. 71 hours (IQR 45–84), respectively ( p = 0.52) (Table 2 ). A sensitivity analysis accounting for clinical events that could prematurely influence circuit termination—such as renal recovery, ECMO discontinuation, or death during CRRT—also showed no significant median difference: 72 hours (IQR 43–92) vs. 72 hours (IQR 60–88); p = 0.65. Similarly, when circuit lifespan was limited to a maximum of 72 hours per the manufacturer's recommendation, no significant difference was observed (Supplementary Table 5). Kaplan–Meier survival analysis revealed no overall difference in circuit lifespan between the two groups. However, circuit survival was significantly better in the integration group during the first 42 hours ( p = 0.003, log-rank test) (Figs. 3 , 4 ). Table 2 Comparison of median CRRT circuit lifespan between integration and separation techniques Primary outcome Integration Separation p-value Intention-to-treat n = 40 n = 40 Total circuit lifespan (h), Median (IQR) 72 (45-96.5) 71 (45–84) 0.52 n = 29 n = 31 Total circuit lifespan* (h), Median (IQR) 72 (43–92) 72 (60–88) 0.65 As-treated n = 48 n = 32 Total circuit lifespan (h), Median (IQR) 70 (48–97) 70 (44–83) 0.39 n = 38 n = 22 Total circuit lifespan* (h), Median (IQR) 72 (47–100) 72 (49–81) 0.89 *Patients who experienced death before the first circuit reached 72 hours, renal recovery leading to CRRT termination, or ECMO discontinuation were excluded. h = hour Table 3 Secondary outcomes Outcome Integration (n = 40) Separation (n = 40) p-value Serious adverse events, n (%) Exit site bleeding 6 (15) 9 (22.5) 0.39 Systemic bleeding 6 (15) 10 (25) 0.26 Hemolysis 4 (10) 2 (5) 0.40 Blood transfusion need 24 (60) 27 (67.5) 0.48 New-positive blood culture infection 0 0 Air embolism 0 0 28-day mortality, n (%) 13 (32.5) 14 (35) 0.81 Number of CRRT machine alarm, n (%) 0.81 0 26 (65) 27 (67.5) 1–5 14 (35) 13 (32.5) Number of high access pressure alarm, n (%) 0.56 0 38 (95) 39 (97.5) 1 2 (5) 1 (2.5) Number of low access pressure alarm, n (%) 0.31 0 37 (92.5) 33 (82.5) 1–5 3 (7.5) 7 (17.5) Number of high return pressure alarm, n (%) 0.49 0 38 (95) 40 (100) 1–2 2 (5) 0 (0) Number of low return pressure alarm, n (%) 0.31 0 39 (97.5) 40 (100) 1 1 (2.5) 0 (0) Number of high TMP alarm, n (%) 0.56 0 32 (80) 34 (85) 1–2 8 (20) 6 (15) Blood leak alarm, n 0 0 Air detect alarm, n 0 0 TMP = transmembrane pressure Subgroup analyses were performed to evaluate the impact of regional citrate anticoagulation, ECMO type, and study site. Among patients receiving regional citrate anticoagulation, no significant differences were observed in circuit lifespan compared to non-citrate users. CRRT circuit lifespan also remained comparable across ECMO types and between study centers (Supplementary Table 6). Secondary outcome CRRT circuit pressures were significantly higher in the integration group compared with the separation group, specifically in the access and return pressures, and these differences persisted throughout the treatment period. However, TMP and pressure drop were not significantly different between the groups (Table 4 , Supplementary Fig. 9). Despite these variations in CRRT circuit pressures, The frequency of CRRT machine alarms did not differ significantly between groups. Table 4 Median of various pressure points were monitored in the CRRT machine and circuit during each day of CRRT treatment. CRRT Pressure Median (IQR) Remaining participants Integration Separation p-value Integration Separation Access pressure , mmHg Day 1 132 (103–188) -54 (-67-140) < 0.001 36 35 Day 2 149 (96–190) -69 (-90-111) < 0.001 38 39 Day 3 126 (87–157) -50 (-91-95) < 0.001 29 33 Day 4 139 (108–167) -55.5 (-86-160) 0.007 21 24 Day 5 129 (97–175) 51 (-60-167) 0.26 14 9 Return pressure , mmHg Day 1 178 (124-226.5) 46 (28–180) < 0.001 36 35 Day 2 186.5 (148–231) 60 (38–156) < 0.001 38 39 Day 3 178 (141–226) 57 (33–131) < 0.001 29 33 Day 4 152 (124–184) 65.5 (32–164) 0.005 21 24 Day 5 165.5 (116–188) 49 (20–180) 0.12 14 9 TMP , mmHg Day 1 38.5 (21-63.5) 42 (30–65) 0.26 36 35 Day 2 55.5 (34–71) 54 (40–80) 0.52 38 39 Day 3 57 (40–83) 70 (54–128) 0.17 29 33 Day 4 62 (41.5–78.5) 78 (58-115.5) 0.10 21 24 Day 5 63 (49–84) 55 (50–78) 0.96 14 9 Pressure drop , mmHg Day 1 24.5 (16-38.5) 23.5 (12–38) 0.63 36 35 Day 2 34 (14–70) 31.5 (23.5–50.5) 0.46 38 39 Day 3 36 (20–70) 34.5 (20–64) 0.65 29 33 Day 4 35 (15–57) 43 (30–63) 0.16 21 24 Day 5 37 (10–60) 30 (20–45) 0.68 14 9 mmHg = Millimeter of Mercury Serious adverse events The incidence of serious adverse events was also similar between groups. No significant differences were observed in hemolysis, bleeding events, transfusion requirements, and new positive blood-culture infections. Notably, no cases of air embolism were reported in either group (Table 4 ). Furthermore, 28-day mortality was comparable between the integration and separation groups (32.5% vs. 35%; p = 0.81). DISCUSSIONS Currently, there are no standardized guidelines for performing CRRT in conjunction with ECMO. Two commonly used techniques—circuit integration and separation—are employed in clinical practice, but their comparative effectiveness remains unclear. In the E-CRRT multicenter randomized controlled trial, no significant difference in median CRRT circuit lifespan was observed between the integration and separation techniques in ECMO patients. Although the integration group exhibited higher CRRT circuit access and return pressures (positive pressures exceeding 100 mmHg), this was not associated with increased alarm frequencies. Importantly, Both strategies showed comparable rates of serious adverse events and 28-day mortality. It is well established that CRRT circuit lifespan is primarily determined by factors that minimize clotting and maintain stable blood flow. These include appropriate anticoagulation, adequate blood flow rates to prevent stasis, avoidance of hemoc oncentration, and minimizing downtime or therapy interruptions [ 16 , 25 – 30 ]. In the E-CRRT trial, the integration technique was designed with CRRT access and return lines connected at the P2 segment of the ECMO circuit, located between the centrifugal pump and the membrane oxygenator. This configuration exposes the CRRT circuit to positive pressures generated by the post-pump flow. Theoretically, this positive pressure may help maintain stable blood flow through the CRRT circuit and potentially prolong filter lifespan. However, prior evidence regarding the impact of ECMO-CRRT integration on circuit survival remains controversial. Wu et al. [ 31 ] reported longer filter lifespans and fewer bleeding events with integration, while Raja et al. [ 32 ] observed higher rates of complete 72-hour circuit use without an increase in adverse events. In contrast, Kouch et al. [ 33 ] found no significant difference between the two strategies. These discrepancies across studies may reflect heterogeneity in anticoagulation regimens (systemic heparin versus regional citrate), circuit connection sites, CRRT machine types, dialysis catheter characteristics in the separation method, patient hypercoagulability, and variations in ECMO flow management. In our study, CRRT circuit lifespan may be influenced more by advances in circuit management and modern CRRT practices than by circuit pressure differences alone. Factors such as optimized anticoagulation, consistent use of CVVHDF, reduced downtime, and standardized nursing and perfusionist care possibly contributed to the prolonged filter survival observed. These contemporary practices may explain why both groups achieved longer circuit lifespans than those reported in previous studies [ 12 , 31 , 33 ] with more than 30% of participants maintaining circuit function beyond 72 hours. Our trial also highlighted a real-world challenge in pressure management. Most integrated circuits tolerated ECMO pump pressures without adverse events or technical issues. Only one patient required conversion from integration to separation when access pressures exceeded + 300 mmHg, despite a reduction in CRRT blood-flow rate. This finding suggests that integration at the P2 connection site (post-pump, Fig. 1 ) may be limited under certain high-pressure conditions, particularly when the ECMO blood flow rate is high. Alternative configurations—such as connecting CRRT to the P1 (pre-pump) or P3 (post-oxygenator) sites, employing pressure-regulating devices [ 34 ], or utilizing next-generation CRRT systems specifically designed for ECMO integration—may mitigate these issues and improve circuit safety. Bleeding events in this study were less frequent than previously reported. Juan Wu et al. [ 31 ] observed a 93.3% incidence of local bleeding in the separation group, compared to only 18.75% in our cohort. This difference may be attributed to variations in catheter insertion techniques and circuit care practices. Additionally, most patients in our study maintained platelet counts above 60,000/µL, which may have contributed to a lower risk of bleeding. Importantly, no cases of air embolism or air circuit obstruction occurred in either group. This may be due to precise circuit management. In the integration group, the CRRT line was connected at the P2 segment, located near the membrane oxygenator, which may help trap air emboli [ 1 ]. This setup, combined with the support of experienced perfusionists and well-trained nursing staff, likely contributed to the safe circuit performance. No catheter-related infections were reported, possibly due to the short duration of observation. The observed 28-day mortality rate in this study was 33.75%, which is substantially lower than rates reported in earlier literature. For example, a systematic review by Saikat Mitra et al. [ 35 ] reported a pooled mortality of 63%, while regional data from Asia showed mortality rates as high as 65.7%, with some retrospective studies suggesting improvement over time. In Germany, Kielstein et al. [ 7 ] reported a 90-day survival rate of only 17% among ECMO patients, 50% of whom received CRRT. The lower mortality in the current trial may be attributed to improved patient selection and enhanced ECMO management, reflecting a trend of declining mortality in ECMO-CRRT patients since 2016. At present, no formal recommendations exist regarding the use of regional citrate anticoagulation for CRRT in patients receiving ECMO, with systemic heparin remaining the mainstay. In this study, subgroup analysis showed no statistically significant differences in circuit lifespan between citrate users and non-users. However, a trend toward longer lifespans was noted among citrate users. Given that only 30% of participants received citrate, further research is warranted to clarify its role and safety profile in ECMO-CRRT patients. This study offers several strengths. It represents one of the first randomized controlled trials to compare CRRT circuit lifespan between integrated and separated techniques in ECMO patients. The multicenter design, involving high-acuity tertiary care centers with cardiovascular thoracic surgical and perfusionist support, enhances generalizability. However, several limitations must be acknowledged. The single-blinded design, in which only the statistician was blinded to treatment allocation, introduces potential bias in outcome assessment. Additionally, a higher-than-expected crossover rate from the separation to the integration group could have influenced results. Nevertheless, this reflects real-world challenges in dialysis access among ECMO patients, where multiple central venous access attempts are often limited by anatomical or clinical constraints. The as-treated analysis confirmed no significant difference in circuit lifespan, supporting the consistency of the findings. It is also important to consider potential confounding factors—such as real-time variation in heparin dosing and ECMO blood flow pressures—which may have affected circuit lifespan independently of the combination technique used. These findings support the feasibility of both integration and separation techniques in clinical practice. The separation technique is appropriate for patients with pre-existing or easily accessible dialysis catheters, while the integration technique may be advantageous when additional vascular access is difficult. However, the choice of technique should also account for CRRT machine compatibility with ECMO circuit pressures and the expertise of the multidisciplinary team in managing circuit-related complications. CONCLUSIONS Among critically ill ECMO patients with CRRT support integrated CRRT circuit into ECMO circuit shows no significant difference in CRRT circuit lifespan and serious adverse events when compared to separation technique. Declarations Conflicts of Interest The authors declare that they have no financial or non-financial conflicts of interest relevant to this study. No author has received any personal fees, honoraria, or research funding from companies related to extracorporeal or renal replacement technologies during the conduct of this trial. Ethical Considerations The E-CRRT trial was conducted in accordance with the ethical standards of the institutional and national research committees and with the principles of the Declaration of Helsinki. The study received ethical approval from the Institutional Review Board of the Faculty of Medicine, Chulalongkorn University (No. 0151/64) and the Research Ethics Committee of the Central Chest Institute of Thailand (REC 003/2022). The trial was also registered with the U.S. Clinical Trials Registry (ClinicalTrials.gov Identifier: NCT05036616). Given the observational and non-interventional nature of the study, the requirement for written informed consent was waived. All data were anonymized prior to analysis to ensure participant confidentiality. SOURCE OF SUPPORT AND FUNDING The research project has received funding from the Critical Care Nephrology Excellence Center at King Chulalongkorn Memorial Hospital, Bangkok, Thailand. AUTHORS’ CONTRIBUTIONS (I) Conceptualization: Prasittiporn Tangjitaree; (II) Data curation: Prasittiporn Tangjitaree ,Ekkapong Surinrat; (III) Formal analysis: Prasittiporn Tangjitaree, Pompon Suttiruk; (IV) Funding acquisition: Prasittiporn Tangjitaree, Nattachai Srisawat; (V) Methodology: Prasittiporn Tangjitaree, Tanyapim Sinjira; (VI) Project administration: Prasittiporn Tangjitaree, Peerapat Thanapongsatorn; (VII) Visualization: Prasittiporn Tangjitaree; (VIII) Writing – original draft: Prasittiporn Tangjitaree; [36] Writing – review & editing: Prasittiporn Tangjitaree, Peerapat Thanapongsatorn, Nattachai Srisawat. ACKNOWLEDGEMENT The authors express gratitude to all the patients and their families who participated in this project. Additionally, we extend our appreciation to the staffs and nurses of the surgical and medical intensive care units at King Chulalongkorn Memorial Hospital and the Central Chest Institute of Thailand for their excellent patient care and collaborative efforts throughout this study. References Ostermann M, Lumlertgul N (2021) Acute kidney injury in ECMO patients. Crit Care 25(1):313 Zhou XL, Chen YH, Wang QY (2017) A new approach combining venoarterial extracorporeal membrane oxygenation and CRRT for adults: a retrospective study. Int J Artif Organs 40(7):345–349 Srisawat N et al (2010) Cost of acute renal replacement therapy in the intensive care unit: results from The Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) study. Crit Care 14(2):R46 Yan X et al (2010) Acute kidney injury in adult postcardiotomy patients with extracorporeal membrane oxygenation: evaluation of the RIFLE classification and the Acute Kidney Injury Network criteria. Eur J Cardiothorac Surg 37(2):334–338 Smith AH et al (2009) Acute renal failure during extracorporeal support in the pediatric cardiac patient. ASAIO J 55(4):412–416 Van Dyk M (2018) The use of CRRT in ECMO patients. Egypt J Crit Care Med 6(3):95–100 Kielstein JT et al (2013) Renal function and survival in 200 patients undergoing ECMO therapy. Nephrol Dial Transpl 28(1):86–90 Aubron C et al (2013) Factors associated with outcomes of patients on extracorporeal membrane oxygenation support: a 5-year cohort study. Crit Care 17(2):R73 Ostermann M, Connor M Jr., Kashani K (2018) Continuous renal replacement therapy during extracorporeal membrane oxygenation: why, when and how? Curr Opin Crit Care 24(6):493–503 Seczynska B et al (2014) Continuous renal replacement therapy during extracorporeal membrane oxygenation in patients treated in medical intensive care unit: technical considerations. Ther Apher Dial 18(6):523–534 Austin D, McCanny P, Aneman A (2020) Post-operative renal failure management in mechanical circulatory support patients. Ann Transl Med 8(13):833 de Tymowski C et al (2018) Impact of connecting continuous renal replacement therapy to the extracorporeal membrane oxygenation circuit. Anaesth Crit Care Pain Med 37(6):557–564 Suga N et al (2017) A safe procedure for connecting a continuous renal replacement therapy device into an extracorporeal membrane oxygenation circuit. J Artif Organs 20(2):125–131 Thy M et al (2022) Renal Replacement Therapy for Patients Requiring Extracorporeal Membrane Oxygenation: A Multicenter International Survey. Blood Purif 51(11):899–906 McMichael ABV et al (2022) 2021 ELSO Adult and Pediatric Anticoagulation Guidelines. Asaio j 68(3):303–310 Zarbock A et al (2020) Effect of Regional Citrate Anticoagulation vs Systemic Heparin Anticoagulation During Continuous Kidney Replacement Therapy on Dialysis Filter Life Span and Mortality Among Critically Ill Patients With Acute Kidney Injury: A Randomized Clinical Trial. JAMA 324(16):1629–1639 Baxter (2015) Prismaflex® Addendum to Operator’s Manual Khwaja A (2012) KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract 120(4):c179–c184 Baxter India Pvt L (2020) Instructions for Use: PRISMAFLEX M60/M100/M150 Set (Part No. 1000014921). Baxter India Pvt. Ltd., Gurgaon, India Gaudry S et al (2015) Comparison of two strategies for initiating renal replacement therapy in the intensive care unit: study protocol for a randomized controlled trial (AKIKI). Trials 16:170 Barbar SD et al (2018) Timing of Renal-Replacement Therapy in Patients with Acute Kidney Injury and Sepsis. N Engl J Med 379(15):1431–1442 Ngamjarus C, Chongsuvivatwong V, McNeil E (2016) n4Studies: Sample Size Calculation for an Epidemiological Study on a Smart Device. Siriraj Medical Journal, 68: pp. 160–170 Knaus WA et al (1985) APACHE II: a severity of disease classification system. Crit Care Med 13(10):818–829 Vincent JL et al (1998) Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on sepsis-related problems of the European Society of Intensive Care Medicine. Crit Care Med 26(11):1793–1800 Holt AW et al (1996) Continuous renal replacement therapy in critically ill patients: monitoring circuit function. Anaesth Intensive Care 24(4):423–429 Baldwin I, Bellomo R, Koch B (2004) Blood flow reductions during continuous renal replacement therapy and circuit life. Intensive Care Med 30(11):2074–2079 Dunn WJ, Sriram S (2014) Filter lifespan in critically ill adults receiving continuous renal replacement therapy: the effect of patient and treatment-related variables. Crit Care Resusc 16(3):225–231 Oudemans-van Straaten HM (2010) Citrate anticoagulation for continuous renal replacement therapy in the critically ill. Blood Purif 29(2):191–196 Tsujimoto Y, Fujii T (2022) How to Prolong Filter Life During Continuous Renal Replacement Therapy? Crit Care 26(1):62 Zhao ZH et al (2025) Interruptions and downtime of continuous renal replacement therapy in critically ill adults: A retrospective observational study. Nurs Crit Care 30(2):e13265 Wu J et al (2023) Impact of connecting methods of continuous renal replacement therapy device on patients underwent extracorporeal membrane oxygenation: A retrospectively observational study. Aust Crit Care 36(5):695–701 Raja M, Leal R, Doyle J (2023) Continuous renal replacement therapy in patients receiving extracorporeal membrane oxygenation therapy. J Intensive Care Soc 24(2):227–229 Kouch M et al (2022) A Comparison of Separate Access versus In-Line Configuration for Continuous Renal Replacement Therapy in VV ECMO. medRxiv, : p. 2022.11.16.22282382 Huang X et al (2024) Optimizing the connection of CRRT and ECMO lines with additional pressure regulator on the therapeutic effect, filter life, and incidence of complications. Med (Baltim) 103(25):e38580 Mitra S et al (2021) Concurrent Use of Renal Replacement Therapy during Extracorporeal Membrane Oxygenation Support: A Systematic Review and Meta-Analysis. J Clin Med, 10(2) Li P et al (2021) Effect of Dynamic Circuit Pressures Monitoring on the Lifespan of Extracorporeal Circuit and the Efficiency of Solute Removal During Continuous Renal Replacement Therapy. Frontiers in Medicine, p 8 Supplementary Files CONSORT2025editablechecklistofECRRT.docx Supplementary.docx Cite Share Download PDF Status: Published Journal Publication published 05 Feb, 2026 Read the published version in Intensive Care Medicine → Version 1 posted Reviewers agreed at journal 10 Nov, 2025 Reviewers invited by journal 10 Nov, 2025 Editor assigned by journal 10 Nov, 2025 First submitted to journal 06 Nov, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8049207","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":542594424,"identity":"49117365-f189-4630-b46f-f7035be0cb4a","order_by":0,"name":"Prasittiporn Tangjitaree","email":"","orcid":"","institution":"Chulalongkorn University Faculty of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Prasittiporn","middleName":"","lastName":"Tangjitaree","suffix":""},{"id":542594425,"identity":"84e8a47c-5c48-4e19-b52a-e97229b34363","order_by":1,"name":"Peerapat Thanapongsatorn","email":"","orcid":"","institution":"Thammasat University","correspondingAuthor":false,"prefix":"","firstName":"Peerapat","middleName":"","lastName":"Thanapongsatorn","suffix":""},{"id":542594426,"identity":"439ad501-3274-4411-afbe-60f80680de5f","order_by":2,"name":"Tanyapim Sinjira","email":"","orcid":"","institution":"Chulalongkorn University Faculty of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Tanyapim","middleName":"","lastName":"Sinjira","suffix":""},{"id":542594427,"identity":"89fba436-e0df-4379-9cf2-e9291954da7c","order_by":3,"name":"Ekkapong Surinrat","email":"","orcid":"","institution":"Central Chest Institute of Thailand","correspondingAuthor":false,"prefix":"","firstName":"Ekkapong","middleName":"","lastName":"Surinrat","suffix":""},{"id":542594428,"identity":"70f2bd93-cf2c-4d78-8462-9a3d6adc0194","order_by":4,"name":"Pompon Suttiruk","email":"","orcid":"","institution":"Chulalongkorn University Faculty of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Pompon","middleName":"","lastName":"Suttiruk","suffix":""},{"id":542594429,"identity":"50519e09-686c-4a98-bfcb-a55fbe2c8a82","order_by":5,"name":"Nattachai Srisawat","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3UlEQVRIiWNgGAWjYDCCA1DagIGx8QGCS0jLgQSwlmYDUrUwsEkQpYXv9tmDnz/+sJM3Zz/cVs1Tc0eOn4H54aMbeLRInstLljiQkGy4syex7TbPsWfGkg1sxsY5eLQYnOExAGphTjA4ANLCdjhxwwEeNmkCWox/HEioTzA4/7CtmOcfcVrMgLYcTjC4kdjGzNtGhBZJoBaLM2nHDTfceNgsObfvsLFkMwG/8AEddqPCplre4Hz6ww9vvh2W42dvfvgYnxYUwMQDIpmJVQ4CjD9IUT0KRsEoGAUjBgAAn4RTzdfH2hMAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-8544-8132","institution":"Chulalongkorn University Faculty of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Nattachai","middleName":"","lastName":"Srisawat","suffix":""}],"badges":[],"createdAt":"2025-11-06 14:39:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8049207/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8049207/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00134-026-08302-y","type":"published","date":"2026-02-05T15:59:54+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":96287034,"identity":"72a7b30e-39ec-4fa0-94bc-1b2e3ebed808","added_by":"auto","created_at":"2025-11-19 12:07:22","extension":"xml","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":9538,"visible":true,"origin":"","legend":"","description":"","filename":"icmeICMED2502069.xml","url":"https://assets-eu.researchsquare.com/files/rs-8049207/v1/1c9f254d8fb539871f3b8a9a.xml"},{"id":96287038,"identity":"3585b799-00a3-4b37-875c-75585dbf07d3","added_by":"auto","created_at":"2025-11-19 12:07:23","extension":"xml","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1040,"visible":true,"origin":"","legend":"","description":"","filename":"ICMED250206929950.go.xml","url":"https://assets-eu.researchsquare.com/files/rs-8049207/v1/138f0256d568e1350dd4486a.xml"},{"id":96287036,"identity":"89120395-a049-43e7-a29e-570c529dd424","added_by":"auto","created_at":"2025-11-19 12:07:23","extension":"xml","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":916,"visible":true,"origin":"","legend":"","description":"","filename":"ICMED2502069Import.xml","url":"https://assets-eu.researchsquare.com/files/rs-8049207/v1/c01eb77b87b8d710d0eaf080.xml"},{"id":96287039,"identity":"160fe638-559c-4ef1-a205-24bd9b9de073","added_by":"auto","created_at":"2025-11-19 12:07:23","extension":"xml","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":124352,"visible":true,"origin":"","legend":"","description":"","filename":"ICMED25020690enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-8049207/v1/80e66d052238482ecf97a49b.xml"},{"id":96287044,"identity":"fdbfbb50-4c4d-47ad-9875-e5a340a8a4ef","added_by":"auto","created_at":"2025-11-19 12:07:23","extension":"png","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":48195,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8049207/v1/b9662a66ab6c4cc3c0e2d84c.png"},{"id":96287046,"identity":"2d845fc7-9091-41fd-9cef-92968e54fdfc","added_by":"auto","created_at":"2025-11-19 12:07:23","extension":"png","order_by":12,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":38406,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8049207/v1/dd50e723568ae27c26171245.png"},{"id":96365177,"identity":"12d41c1d-fc83-473d-bd47-fa5a7de43b60","added_by":"auto","created_at":"2025-11-20 10:10:04","extension":"png","order_by":13,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":24823,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8049207/v1/f9e427e692fe1f7da336aaa0.png"},{"id":96287047,"identity":"aac29fb4-5e5d-4cb6-9c40-03dde0e83cc5","added_by":"auto","created_at":"2025-11-19 12:07:23","extension":"png","order_by":14,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":23795,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-8049207/v1/b7d000cbbe6439b1baf7a029.png"},{"id":96287050,"identity":"f402339b-c462-4e06-8644-38b4e22133e4","added_by":"auto","created_at":"2025-11-19 12:07:23","extension":"xml","order_by":15,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":120371,"visible":true,"origin":"","legend":"","description":"","filename":"ICMED25020690structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8049207/v1/01d88b3f6c2645bd91768078.xml"},{"id":96365224,"identity":"f8e820d6-7cea-41e5-90f3-f96c5883672f","added_by":"auto","created_at":"2025-11-20 10:10:06","extension":"html","order_by":16,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":132588,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8049207/v1/de12959e5ea135ab5a883344.html"},{"id":96364026,"identity":"49b5b663-5a65-4468-a490-15ffe3f120e9","added_by":"auto","created_at":"2025-11-20 10:08:47","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":905376,"visible":true,"origin":"","legend":"\u003cp\u003eon the left shows the separation technique and the right is the integration technique.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8049207/v1/abdc04729aed9dd63df45cae.png"},{"id":96364047,"identity":"8f0e3001-ee15-4e01-acad-1dd4d2735029","added_by":"auto","created_at":"2025-11-20 10:08:48","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":173823,"visible":true,"origin":"","legend":"\u003cp\u003eThe number of participants who meet the eligibility criteria, are excluded after screening, and are randomized into the study groups.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8049207/v1/611e9105f14943050e080bc2.png"},{"id":96287041,"identity":"79a64d0c-6807-432a-bd43-8e4afbc15fb1","added_by":"auto","created_at":"2025-11-19 12:07:23","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":89240,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier curves comparing CRRT circuit lifespan between the integration and separation techniques, using a 72-hour cut-off point.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8049207/v1/ef3e9c14c1db6efdc2717b9c.png"},{"id":96364749,"identity":"ff83fa5e-67fb-40d1-ace5-96d64ac70e4d","added_by":"auto","created_at":"2025-11-20 10:09:36","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":88502,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier curves comparing CRRT circuit lifespan between the integration and separation techniques, using a 42-hour cut-off point.\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-8049207/v1/865ad539d7088b3363a688d7.png"},{"id":102234274,"identity":"56dc0059-eddd-4182-937d-a506e8fce42c","added_by":"auto","created_at":"2026-02-09 16:08:56","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2067391,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8049207/v1/81031233-8908-49bf-97f0-363d8e7206a1.pdf"},{"id":96287043,"identity":"f3f1da7f-c8da-46a2-9589-f9639042056b","added_by":"auto","created_at":"2025-11-19 12:07:23","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":33381,"visible":true,"origin":"","legend":"","description":"","filename":"CONSORT2025editablechecklistofECRRT.docx","url":"https://assets-eu.researchsquare.com/files/rs-8049207/v1/6a525085a3b384f591811065.docx"},{"id":96364475,"identity":"7a3adfc3-894b-41d2-845a-7a6e6d6d564b","added_by":"auto","created_at":"2025-11-20 10:09:20","extension":"docx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":1604911,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementary.docx","url":"https://assets-eu.researchsquare.com/files/rs-8049207/v1/e245dbc8c2b59f6c5fbb5d20.docx"}],"financialInterests":"","formattedTitle":"The Comparison of Circuit Lifespan between Integration and Separation Approach in Extracorporeal Membrane Oxygenation Patient Requiring Continuous Renal Replacement Therapy Support, A Randomized Controlled Trial (E-CRRT Trial)","fulltext":[{"header":"TAKE HOME MESSAGE","content":"\u003cp\u003eIn this study which compare two configurations of CRRT support during ECMO treatment, there is no significant CRRT circuit lifespan between the integration and separation techniques. Both approaches were shown feasible and safe, with comparable 28-day mortality.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"INTRODUCTION","content":"\u003cp\u003eIn contemporary critical care, extracorporeal membrane oxygenation (ECMO) has emerged as a pivotal life-saving intervention for critically ill patients. The severity of patients necessitating ECMO is often accompanied by multifactorial factors leading to acute kidney injury (AKI), including nosocomial infections, exposure to nephrotoxic drugs, hypotensive states, and systemic inflammatory conditions [\u003cspan additionalcitationids=\"CR2 CR3 CR4\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The incidence of AKI in critically ill patients can be as high as 80%, with up to 50% requiring renal replacement therapy (RRT) within the first week [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Due to the state of hemodynamic instability, continuous renal replacement therapy (CRRT) is preferred.\u003c/p\u003e\u003cp\u003eThe CRRT methods combined with ECMO have three main ways consisting of 1. In-line technique, 2. Separation technique, and 3. Integration technique [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Currently, separation and integration are more popular methods as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, The separation technique offers advantages such as an independent circuit and easy circuit modifications [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. However, it is associated with the risk of additional vascular access and catheter-related bloodstream infections (CRBSI). On the other hand, the integration technique eliminates the need for additional vascular access for renal replacement therapy. Yet, concerns include the potential for air emboli, difficulties in managing pressure circuit issues, and limitations in certain CRRT machines that do not support integration techniques with pressure limitations [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eDespite the absence of conclusive evidence supporting the superiority of either technique [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], a questionnaire study by Michael Thy, and et al. [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] revealed that method selection is often based on physician\u0026rsquo;s experience. This study aims to address this gap by comparing the CRRT circuit lifespan, along with assessments of pressure at various points, CRRT machine alarms, serious adverse events during CRRT and 28-day mortality when combined with ECMO for each technique.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003ePopulation\u003c/h2\u003e\u003cp\u003e This multicenter, open-label randomized controlled trial was conducted in the surgical and medical intensive care units of two tertiary referral centers in Thailand: King Chulalongkorn Memorial Hospital (KCMH) and the Central Chest Institute of Thailand (CCIT). The primary objective was to compare CRRT circuit lifespan between the integration and separation groups. Secondary objectives included comparisons of serious adverse events, 28-day mortality, pressures at various points in the CRRT circuit, and CRRT machine alarms. Eligible participants were adults (\u0026ge;\u0026thinsp;18 years) admitted to the ICU, requiring ECMO, and diagnosed with AKI necessitating CRRT. Exclusion criteria included pregnancy, contraindication to heparin, and AKI due to bilateral renal artery thrombosis, vasculitis, glomerulonephritis, or post-obstructive causes. ECMO indications included cardiogenic shock, post-cardiotomy support, primary graft failure after transplantation, procedural support, bridging to transplant, and severe pulmonary conditions such as acute respiratory distress syndrome (ARDS), lung hyperinflation, hemorrhage, or post-transplant management. CRRT was initiated for severe metabolic acidosis (arterial pH\u0026thinsp;\u0026lt;\u0026thinsp;7.2 or bicarbonate\u0026thinsp;\u0026lt;\u0026thinsp;15 mEq/L), refractory volume overload, persistent hyperkalemia (\u0026gt;\u0026thinsp;6.2 mEq/L or ECG abnormalities), oliguria or anuria (urine output of less than 0.5 mL/kg/h for at least 6 hours), azotemia (Blood Urea Nitrogen more than 100 mg/dL), uremia, or increased intracranial pressure. The trial was registered at ClinicalTrial.gov (NCT05036616) on April 1, 2021 and approved by the Institutional Review Board of King Chulalongkorn Memorial Hospital (COA No. 0607/2023). The study was conducted in accordance with the Declaration of Helsinki and all applicable regulations. Written informed consent was obtained from the patients or their legally authorized representatives.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eRandomization\u003c/h3\u003e\n\u003cp\u003ePatients meeting eligibility criteria are pre-stratified by ECMO type (VV-ECMO or VA-ECMO) to address potential pressure-related influences on CRRT circuit longevity. Randomization, occurring in blocks of four within each ECMO type, establishes the integration and separation groups. This pre-stratification ensures balanced representation of ECMO types across both groups (Supplementary Fig.\u0026nbsp;6).\u003c/p\u003e\u003cp\u003eIn the separation technique group, a nephrologist or intensivist inserts the dialysis catheter, proceeding with separate CRRT and ECMO. In the integration technique, perfusionist integrates CRRT into the ECMO circuit.\u003c/p\u003e\u003cp\u003eThe case record form captures data throughout the CRRT circuit's lifespan, documenting reasons for ECMO or CRRT discontinuation, vital signs, daily laboratory results, anticoagulant and citrate use, vasopressor/inotrope doses, access and return CRRT cannula pressures, alarms, and ECMO-related complications like bleeding, hemolysis, or embolic events. Follow-up extends until the end of the first CRRT circuit, with mortality at 28-day post-randomization recorded. Both groups receive standardized care throughout data collection.\u003c/p\u003e\n\u003ch3\u003eECMO Circuit Configuration\u003c/h3\u003e\n\u003cp\u003eThe Maquet Rotaflow I or II ECMO System (Getinge, Sweden) was used as the primary apparatus. ECMO cannula insertion was performed by cardiovascular thoracic or vascular surgeons. Return cannulas ranged from 15\u0026ndash;17 French for VA ECMO and 15\u0026ndash;19 French for VV ECMO, with drainage cannulas standardized at 25\u0026ndash;27 French. Patient integration into the ECMO circuit was done by experienced perfusionists. ECMO initiation began with a flow rate of 3\u0026ndash;5 LPM, overseen by cardiologists, cardiovascular thoracic surgeons, or intensivists. Systemic heparin was administered, serving as the anticoagulant to prevent circuit clotting. The heparin dose is adjusted in unit per hour to maintain an activated clotting time (ACT) of 180\u0026ndash;220 seconds every 2 hours, and an activated partial thromboplastin time (aPTT) 1.5\u0026ndash;2.5 times the normal value, measured every 6\u0026ndash;12 hours [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eCRRT prescription and circuit set up\u003c/h3\u003e\n\u003cp\u003eCRRT procedures utilized the Prismaflex system from Baxter (Lund, Sweden) employing CVVHDF mode with a prescribed dose of 25\u0026ndash;30 mL/kg/hour. The blood flow rate was set at a minimum of 100 mL/min, and and regional citrate may be employed as the anticoagulant for the CRRT circuit in case of delayed heparin use in the ECMO circuit, the decision to use regional citrate depends on primary doctor judement, except in cases of hyperlactatemia (arterial lactate\u0026thinsp;\u0026gt;\u0026thinsp;8 mmol/L), advanced cirrhosis or acute liver failure [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. However, there is no specific guideline for CRRT with ECMO. Double lumen catheters for CRRT ranged from 12.5 to 13.5 French, with specific insertion depths depending on vein placement: 16 cm in the right internal jugular vein, 19 cm in the left internal jugular vein, and 25 cm in the femoral vein. In the integration group, pigtails integrating the CRRT-ECMO circuit measured 1.52 cm in diameter and were connected seamlessly via a three-way stopcock in the P2 segment.\u003c/p\u003e\u003cp\u003eThe CRRT machine operates with an access pressure range of -250 to +\u0026thinsp;450 mmHg, triggering a high pressure alarm at +\u0026thinsp;300 mmHg or higher, and a low pressure alarm at -250 mmHg or lower. Return pressure ranges from \u0026minus;\u0026thinsp;50 to +\u0026thinsp;350 mmHg, with a high pressure alarm set at +\u0026thinsp;350 mmHg or higher. Transmembrane pressure (TMP) and pressure drop serve as indicators for filter clogging and clotting. A high TMP alarm is set at 300 mmHg or higher, and a high pressure drop alarm is set at 100 mmHg or higher. Blood leakage is detected using an infrared blood leak detector in the effluent line, while a bubble detection system utilizes ultrasonic technology to detect bubbles in the effluent line [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eOperative Definitions\u003c/h3\u003e\n\u003cp\u003eAKI definition was defined by KDIGO 2012 guideline [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] as the serum creatinine increase at least 0.3 mg/dL from baseline within 48 hours or increased 1.5 times from baseline within 7 days or urine output less than 0.5 mL/kg/hour for 6 hours. The decision to initiate CRRT is made by intensivists or nephrologists.\u003c/p\u003e\u003cp\u003eThe primary outcome, CRRT circuit lifespan, measures the duration from blood flow initiation to circuit completion lasting up to 72 hours, extendable to 120 hours if circuit function remained satisfactory (maximum 72 hours as per manufacturer\u0026rsquo;s suggestion [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]), or its premature clotting, meaning the circuit lifespan is less than 72 hours, with the occurrence of circuit clotting, including visible clotting or a pressure drop\u0026thinsp;\u0026gt;\u0026thinsp;100 mmHg, or clogging where TMP\u0026thinsp;\u0026gt;\u0026thinsp;300 mmHg, events reported by trained nurses familiar with renal replacement therapy, or until specific criteria for renal function improvement are met, characterized by urine output surpassing 1000 mL without diuretics or exceeding 2000 mL with diuretic use [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], or events affecting termination include ECMO discontinuation, extended circuit downtime, and participant mortality. Crossover between 2 techniques is accounted for, and nurse-recorded parameters such as pressures and machine alarms are monitored hourly, with daily averages computed. Additionally, 28-day mortality status is assessed from the day of randomization.\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eSerious Adverse Events\u003c/h2\u003e\u003cp\u003eSerious adverse events recorded during the data collection period for circuit lifespan include bleeding at the ECMO cannula or vascular access exit site, new onset of hemolysis during ECMO combined with CRRT treatment, systemic or major bleeding, new positive blood cultures with clinical correlation of infection (\u0026ge;\u0026thinsp;1 blood bottle), and air embolic event.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eSAMPLE SIZE ESTIMATION\u003c/h3\u003e\n\u003cp\u003eThis study was designed as a superiority trial. A total of 80 patients were required, with 40 participants in each group. The sample size calculation was based on published data from Michael Thy \u003cem\u003eet al.\u003c/em\u003e [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], under the assumption that the integration strategy would prolong circuit lifespan by a mean of 28 hours compared with the separation approach. With an allocation ratio of 1:1, the study was powered at 80% to detect this difference at a two-sided significance level of 0.05, accounting for a 5% dropout rate [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eSTISTICAL ANALYSIS\u003c/h3\u003e\n\u003cp\u003eStatistical analysis was performed using STATA version 18. Categorical variables were presented as frequencies and percentages, and comparisons were made using the Chi-square test or Fisher\u0026rsquo;s exact test, as appropriate. Continuous variables were expressed as means or medians, and differences were assessed using either the unpaired \u003cem\u003et\u003c/em\u003e-test or the Mann\u0026ndash;Whitney \u003cem\u003eU\u003c/em\u003e test, depending on the distribution of the data.\u003c/p\u003e\u003cp\u003eThe primary analysis was conducted using the intention-to-treat (ITT) approach, with a significance level set at \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05. A per-protocol analysis or as-treated was also performed to support the noninferiority findings of the trial. Sensitivity analyses of the primary outcome were conducted, considering anticipated clinical events such as renal recovery, ECMO discontinuation, or death during CRRT that could potentially influence the true effect. Additionally, Kaplan\u0026ndash;Meier analysis was used to assess cumulative survival of circuit lifespan.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eBetween May 1, 2021, and March 10, 2025, a total of 80 eligible and consenting patients were recruited from the intensive care units of KCMH and CCIT. Forty patients were randomized to the integration group and 40 to the separation group. Baseline characteristics, including age, sex, comorbidities, severity scores [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], ECMO indications, and causes of AKI, were comparable between groups. Among the indications for initiating CRRT in ECMO patients, fluid overload was the most common (46.3%), followed by refractory metabolic acidosis (25%) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline characteristic, ECMO and CRRT indication\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharacteristics\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;80)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eIntegration\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;40)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eSeparation\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;40)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e50 (62.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27 (67.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e23 (57.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (year), median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e58 (47.5\u0026ndash;67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e54.5 (46- 66.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e58 (49- 68.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIdeal body weight (kg), median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e59.5 (52\u0026ndash;66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e61 (55.5\u0026ndash;67.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e57 (52\u0026ndash;62)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUnderlying, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Diabetes Mellitus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e25 (31.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13 (32.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Chronic kidney disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24 (30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (22.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15 (37.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Ischemic heart disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e29 (36.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13 (32.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16 (40)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Cirrhosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e37 (46.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e17 (42.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e20 (50)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Malignancy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Nephrotoxic agent use\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16 (20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10 (25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 (15)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAPACHE II score, median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e30 (26\u0026ndash;35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e31.5 (27\u0026ndash;35.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e30 (25\u0026ndash;34.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSOFA score, median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16 (14\u0026ndash;19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16.5 (14\u0026ndash;19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15 (13\u0026ndash;19)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eECMO type\u003c/b\u003e, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- VV ECMO\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (16.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5 (12.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- VA ECMO\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e67 (83.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e32 (80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e35 (87.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eECMO indication\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Cardiogenic shock\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23 (28.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13 (32.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10 (25)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- ECPR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (8.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (12.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Post heart transplant\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4 (10)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Postcardiotomy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23 (28.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (22.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14 (35)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- ARDS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10 (12.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (12.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5 (12.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eInitial ECMO setting\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlood flow rate, LPM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.8 (3\u0026ndash;4.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (3\u0026ndash;4.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3.7 (3\u0026ndash;4.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePump speed, RPM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3202.5 (2922.5-3529.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3177.5 (2840-3475.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3260 (3040\u0026ndash;3600)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLaboratory\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHemoglobin (g/dL), median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9.4 (8.4\u0026ndash;10.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9.5 (8.5\u0026ndash;11.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9.3 (8.1\u0026ndash;10.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlatelet (/\u0026micro;L), median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e96000 (63500\u0026ndash;164500)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e96000 (60000\u0026ndash;201500)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e97500 (65500\u0026ndash;133500)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eINR, median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.8 (1.4\u0026ndash;2.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.6 (1.3\u0026ndash;1.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (1.5\u0026ndash;3.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eaPTT (sec), median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e42.8 (33.2\u0026ndash;56.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e39.9 (30.9\u0026ndash;52.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e44 (34.5\u0026ndash;59.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlood urea nitrogen (mg/dL), median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e46 (27.3\u0026ndash;70.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e49 (24\u0026ndash;74)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e44 (28.5\u0026ndash;68.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCreatinine (mg/dL), median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.32 (1.52\u0026ndash;4.16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.29 (1.45\u0026ndash;4.19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.40 (1.75\u0026ndash;4.09)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePotassium (mmol/L), median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5.1 (3.5\u0026ndash;6.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (3.5\u0026ndash;6.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.3 (3.3\u0026ndash;7.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHCO\u003csub\u003e3\u003c/sub\u003e (mEq/L), median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22 (17\u0026ndash;25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22 (17\u0026ndash;25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e22 (18\u0026ndash;25)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlbumin (mg/L), median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (2.6\u0026ndash;3.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (2.6\u0026ndash;3.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (2.6\u0026ndash;3.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eArterial pH, median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7.41 (7.32\u0026ndash;7.46)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.40 (7.31\u0026ndash;7.46)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7.41 (7.32\u0026ndash;7.46)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eArterial lactate (mmol/L), median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.9 (2.4\u0026ndash;10.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.1 (2.4\u0026ndash;8.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.4 (2.2\u0026ndash;11.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCause of AKI\u003c/b\u003e, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCardiorenal syndrome\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e44 (55)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23 (57.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e21 (52.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePrerenal cause\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (6.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (7.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSepsis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (12.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (7.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMultifactorial cause\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (12.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (7.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCRRT indication\u003c/b\u003e, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnuria or oliguria\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16 (20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (22.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7 (17.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHigh blood urea nitrogen\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10 (12.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (12.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5 (12.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRefractory acidosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20 (25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (22.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11 (27.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRefractory hyperkalemia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (3.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (2.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRefractory volume overload\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e37 (46.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19 (47.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e18 (45)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCRRT setting\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePrescribe dose (mL/kg/hour), median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e30 (30\u0026ndash;32)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e30 (30\u0026ndash;32)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e30 (30\u0026ndash;32)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlood flow rate (mL/min), median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e150 (100\u0026ndash;150)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e150 (100\u0026ndash;175)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e150 (100\u0026ndash;150)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eReginal citrate anticoagulation, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24 (30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13 (32.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11 (27.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are presented as mean (SD) or median (IQR1-IQR3) for continuous measures, and n (%) for categorical measures\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eAPACHE II\u0026thinsp;=\u0026thinsp;Acute physiology and chronic health evaluation II [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], aPTT\u0026thinsp;=\u0026thinsp;Activated partial thromboplastin time, ECPR\u0026thinsp;=\u0026thinsp;Extra-corporeal cardiopulmonary resuscitation, LPM\u0026thinsp;=\u0026thinsp;liter per minute, RPM\u0026thinsp;=\u0026thinsp;revolution per minute, SOFA score\u0026thinsp;=\u0026thinsp;Sequential Organ Failure Assessment Score [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eCrossover between treatment arms occurred during the study. One patient in the integration group developed excessively high access pressures during CRRT and required a switch to the separation technique. Conversely, nine patients in the separation group could not undergo catheter insertion for RRT and were subsequently switched to the integration group (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003ePrimary outcome\u003c/h2\u003e\u003cp\u003eThere was no significant difference in the median total CRRT circuit lifespan between the integration and separation groups: 72 hours (IQR 45\u0026ndash;96.5) vs. 71 hours (IQR 45\u0026ndash;84), respectively (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.52) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). A sensitivity analysis accounting for clinical events that could prematurely influence circuit termination\u0026mdash;such as renal recovery, ECMO discontinuation, or death during CRRT\u0026mdash;also showed no significant median difference: 72 hours (IQR 43\u0026ndash;92) vs. 72 hours (IQR 60\u0026ndash;88); \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.65. Similarly, when circuit lifespan was limited to a maximum of 72 hours per the manufacturer's recommendation, no significant difference was observed (Supplementary Table\u0026nbsp;5). Kaplan\u0026ndash;Meier survival analysis revealed no overall difference in circuit lifespan between the two groups. However, circuit survival was significantly better in the integration group during the first 42 hours (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003, log-rank test) (Figs.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of median CRRT circuit lifespan between integration and separation techniques\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePrimary outcome\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIntegration\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSeparation\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eIntention-to-treat\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal circuit lifespan (h), Median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e72 (45-96.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e71 (45\u0026ndash;84)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.52\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal circuit lifespan* (h), Median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e72 (43\u0026ndash;92)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e72 (60\u0026ndash;88)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.65\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAs-treated\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;48\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal circuit lifespan (h), Median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e70 (48\u0026ndash;97)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e70 (44\u0026ndash;83)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.39\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal circuit lifespan* (h), Median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e72 (47\u0026ndash;100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e72 (49\u0026ndash;81)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.89\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e*Patients who experienced death before the first circuit reached 72 hours, renal recovery leading to CRRT termination, or ECMO discontinuation were excluded. h\u0026thinsp;=\u0026thinsp;hour\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSecondary outcomes\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOutcome\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIntegration\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;40)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSeparation\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;40)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSerious adverse events, n (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eExit site bleeding\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (22.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.39\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSystemic bleeding\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10 (25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.26\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHemolysis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.40\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlood transfusion need\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24 (60)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27 (67.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.48\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNew-positive blood culture infection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAir embolism\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e28-day mortality, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (32.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14 (35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.81\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e\u003cp\u003eNumber of CRRT machine alarm, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.81\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26 (65)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27 (67.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u0026ndash;5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14 (35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13 (32.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eNumber of high access pressure alarm, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.56\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e38 (95)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e39 (97.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (2.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eNumber of low access pressure alarm, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.31\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e37 (92.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e33 (82.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u0026ndash;5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (7.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (17.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eNumber of high return pressure alarm, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.49\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e38 (95)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e40 (100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u0026ndash;2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eNumber of low return pressure alarm, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.31\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e39 (97.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e40 (100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (2.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e\u003cp\u003eNumber of high TMP alarm, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.56\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e32 (80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e34 (85)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u0026ndash;2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlood leak alarm, n\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAir detect alarm, n\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eTMP\u0026thinsp;=\u0026thinsp;transmembrane pressure\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eSubgroup analyses were performed to evaluate the impact of regional citrate anticoagulation, ECMO type, and study site. Among patients receiving regional citrate anticoagulation, no significant differences were observed in circuit lifespan compared to non-citrate users. CRRT circuit lifespan also remained comparable across ECMO types and between study centers (Supplementary Table\u0026nbsp;6).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eSecondary outcome\u003c/h2\u003e\u003cp\u003eCRRT circuit pressures were significantly higher in the integration group compared with the separation group, specifically in the access and return pressures, and these differences persisted throughout the treatment period. However, TMP and pressure drop were not significantly different between the groups (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, Supplementary Fig.\u0026nbsp;9). Despite these variations in CRRT circuit pressures, The frequency of CRRT machine alarms did not differ significantly between groups.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMedian of various pressure points were monitored in the CRRT machine and circuit during each day of CRRT treatment.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eCRRT Pressure\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003eMedian (IQR)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003eRemaining participants\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIntegration\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSeparation\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eIntegration\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eSeparation\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAccess pressure\u003c/b\u003e, mmHg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e132 (103\u0026ndash;188)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-54 (-67-140)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e35\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e149 (96\u0026ndash;190)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-69 (-90-111)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e39\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e126 (87\u0026ndash;157)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-50 (-91-95)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e33\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e139 (108\u0026ndash;167)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-55.5 (-86-160)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.007\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e24\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e129 (97\u0026ndash;175)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e51 (-60-167)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eReturn pressure\u003c/b\u003e, mmHg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e178 (124-226.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e46 (28\u0026ndash;180)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e35\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e186.5 (148\u0026ndash;231)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e60 (38\u0026ndash;156)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e39\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e178 (141\u0026ndash;226)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e57 (33\u0026ndash;131)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e33\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e152 (124\u0026ndash;184)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e65.5 (32\u0026ndash;164)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.005\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e24\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e165.5 (116\u0026ndash;188)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e49 (20\u0026ndash;180)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTMP\u003c/b\u003e, mmHg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e38.5 (21-63.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e42 (30\u0026ndash;65)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e35\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e55.5 (34\u0026ndash;71)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e54 (40\u0026ndash;80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.52\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e39\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e57 (40\u0026ndash;83)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e70 (54\u0026ndash;128)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e33\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e62 (41.5\u0026ndash;78.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e78 (58-115.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e24\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e63 (49\u0026ndash;84)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e55 (50\u0026ndash;78)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.96\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePressure drop\u003c/b\u003e, mmHg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24.5 (16-38.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23.5 (12\u0026ndash;38)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.63\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e35\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e34 (14\u0026ndash;70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e31.5 (23.5\u0026ndash;50.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e39\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e36 (20\u0026ndash;70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e34.5 (20\u0026ndash;64)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.65\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e33\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e35 (15\u0026ndash;57)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e43 (30\u0026ndash;63)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e24\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDay 5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e37 (10\u0026ndash;60)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e30 (20\u0026ndash;45)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003emmHg\u0026thinsp;=\u0026thinsp;Millimeter of Mercury\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003eSerious adverse events\u003c/h2\u003e\u003cp\u003eThe incidence of serious adverse events was also similar between groups. No significant differences were observed in hemolysis, bleeding events, transfusion requirements, and new positive blood-culture infections. Notably, no cases of air embolism were reported in either group (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Furthermore, 28-day mortality was comparable between the integration and separation groups (32.5% vs. 35%; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.81).\u003c/p\u003e\u003c/div\u003e"},{"header":"DISCUSSIONS","content":"\u003cp\u003e Currently, there are no standardized guidelines for performing CRRT in conjunction with ECMO. Two commonly used techniques\u0026mdash;circuit integration and separation\u0026mdash;are employed in clinical practice, but their comparative effectiveness remains unclear. In the E-CRRT multicenter randomized controlled trial, no significant difference in median CRRT circuit lifespan was observed between the integration and separation techniques in ECMO patients. Although the integration group exhibited higher CRRT circuit access and return pressures (positive pressures exceeding 100 mmHg), this was not associated with increased alarm frequencies. Importantly, Both strategies showed comparable rates of serious adverse events and 28-day mortality.\u003c/p\u003e\u003cp\u003eIt is well established that CRRT circuit lifespan is primarily determined by factors that minimize clotting and maintain stable blood flow. These include appropriate anticoagulation, adequate blood flow rates to prevent stasis, avoidance of hemoc oncentration, and minimizing downtime or therapy interruptions [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan additionalcitationids=\"CR26 CR27 CR28 CR29\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. In the E-CRRT trial, the integration technique was designed with CRRT access and return lines connected at the P2 segment of the ECMO circuit, located between the centrifugal pump and the membrane oxygenator. This configuration exposes the CRRT circuit to positive pressures generated by the post-pump flow. Theoretically, this positive pressure may help maintain stable blood flow through the CRRT circuit and potentially prolong filter lifespan. However, prior evidence regarding the impact of ECMO-CRRT integration on circuit survival remains controversial. \u003cem\u003eWu et al.\u003c/em\u003e [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] reported longer filter lifespans and fewer bleeding events with integration, while \u003cem\u003eRaja et al.\u003c/em\u003e [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] observed higher rates of complete 72-hour circuit use without an increase in adverse events. In contrast, \u003cem\u003eKouch et al.\u003c/em\u003e [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] found no significant difference between the two strategies. These discrepancies across studies may reflect heterogeneity in anticoagulation regimens (systemic heparin versus regional citrate), circuit connection sites, CRRT machine types, dialysis catheter characteristics in the separation method, patient hypercoagulability, and variations in ECMO flow management.\u003c/p\u003e\u003cp\u003eIn our study, CRRT circuit lifespan may be influenced more by advances in circuit management and modern CRRT practices than by circuit pressure differences alone. Factors such as optimized anticoagulation, consistent use of CVVHDF, reduced downtime, and standardized nursing and perfusionist care possibly contributed to the prolonged filter survival observed. These contemporary practices may explain why both groups achieved longer circuit lifespans than those reported in previous studies [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] with more than 30% of participants maintaining circuit function beyond 72 hours.\u003c/p\u003e\u003cp\u003eOur trial also highlighted a real-world challenge in pressure management. Most integrated circuits tolerated ECMO pump pressures without adverse events or technical issues. Only one patient required conversion from integration to separation when access pressures exceeded\u0026thinsp;+\u0026thinsp;300 mmHg, despite a reduction in CRRT blood-flow rate. This finding suggests that integration at the P2 connection site (post-pump, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) may be limited under certain high-pressure conditions, particularly when the ECMO blood flow rate is high. Alternative configurations\u0026mdash;such as connecting CRRT to the P1 (pre-pump) or P3 (post-oxygenator) sites, employing pressure-regulating devices [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e], or utilizing next-generation CRRT systems specifically designed for ECMO integration\u0026mdash;may mitigate these issues and improve circuit safety.\u003c/p\u003e\u003cp\u003eBleeding events in this study were less frequent than previously reported. Juan Wu et al. [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] observed a 93.3% incidence of local bleeding in the separation group, compared to only 18.75% in our cohort. This difference may be attributed to variations in catheter insertion techniques and circuit care practices. Additionally, most patients in our study maintained platelet counts above 60,000/\u0026micro;L, which may have contributed to a lower risk of bleeding. Importantly, no cases of air embolism or air circuit obstruction occurred in either group. This may be due to precise circuit management. In the integration group, the CRRT line was connected at the P2 segment, located near the membrane oxygenator, which may help trap air emboli [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. This setup, combined with the support of experienced perfusionists and well-trained nursing staff, likely contributed to the safe circuit performance. No catheter-related infections were reported, possibly due to the short duration of observation.\u003c/p\u003e\u003cp\u003eThe observed 28-day mortality rate in this study was 33.75%, which is substantially lower than rates reported in earlier literature. For example, a systematic review by Saikat Mitra et al. [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e] reported a pooled mortality of 63%, while regional data from Asia showed mortality rates as high as 65.7%, with some retrospective studies suggesting improvement over time. In Germany, Kielstein et al. [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] reported a 90-day survival rate of only 17% among ECMO patients, 50% of whom received CRRT. The lower mortality in the current trial may be attributed to improved patient selection and enhanced ECMO management, reflecting a trend of declining mortality in ECMO-CRRT patients since 2016.\u003c/p\u003e\u003cp\u003eAt present, no formal recommendations exist regarding the use of regional citrate anticoagulation for CRRT in patients receiving ECMO, with systemic heparin remaining the mainstay. In this study, subgroup analysis showed no statistically significant differences in circuit lifespan between citrate users and non-users. However, a trend toward longer lifespans was noted among citrate users. Given that only 30% of participants received citrate, further research is warranted to clarify its role and safety profile in ECMO-CRRT patients.\u003c/p\u003e\u003cp\u003eThis study offers several strengths. It represents one of the first randomized controlled trials to compare CRRT circuit lifespan between integrated and separated techniques in ECMO patients. The multicenter design, involving high-acuity tertiary care centers with cardiovascular thoracic surgical and perfusionist support, enhances generalizability. However, several limitations must be acknowledged. The single-blinded design, in which only the statistician was blinded to treatment allocation, introduces potential bias in outcome assessment. Additionally, a higher-than-expected crossover rate from the separation to the integration group could have influenced results. Nevertheless, this reflects real-world challenges in dialysis access among ECMO patients, where multiple central venous access attempts are often limited by anatomical or clinical constraints. The as-treated analysis confirmed no significant difference in circuit lifespan, supporting the consistency of the findings. It is also important to consider potential confounding factors\u0026mdash;such as real-time variation in heparin dosing and ECMO blood flow pressures\u0026mdash;which may have affected circuit lifespan independently of the combination technique used.\u003c/p\u003e\u003cp\u003eThese findings support the feasibility of both integration and separation techniques in clinical practice. The separation technique is appropriate for patients with pre-existing or easily accessible dialysis catheters, while the integration technique may be advantageous when additional vascular access is difficult. However, the choice of technique should also account for CRRT machine compatibility with ECMO circuit pressures and the expertise of the multidisciplinary team in managing circuit-related complications.\u003c/p\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003eAmong critically ill ECMO patients with CRRT support integrated CRRT circuit into ECMO circuit shows no significant difference in CRRT circuit lifespan and serious adverse events when compared to separation technique.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003ch2\u003eConflicts of Interest\u003c/h2\u003e\u003cp\u003eThe authors declare that they have no financial or non-financial conflicts of interest relevant to this study. No author has received any personal fees, honoraria, or research funding from companies related to extracorporeal or renal replacement technologies during the conduct of this trial.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003ch2\u003eEthical Considerations\u003c/h2\u003e\u003cp\u003e The E-CRRT trial was conducted in accordance with the ethical standards of the institutional and national research committees and with the principles of the Declaration of Helsinki. The study received ethical approval from the Institutional Review Board of the Faculty of Medicine, Chulalongkorn University (No. 0151/64) and the Research Ethics Committee of the Central Chest Institute of Thailand (REC 003/2022). The trial was also registered with the U.S. Clinical Trials Registry (ClinicalTrials.gov Identifier: NCT05036616). Given the observational and non-interventional nature of the study, the requirement for written informed consent was waived. All data were anonymized prior to analysis to ensure participant confidentiality.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eSOURCE OF SUPPORT AND FUNDING\u003c/strong\u003e\u003cp\u003e The research project has received funding from the Critical Care Nephrology Excellence Center at King Chulalongkorn Memorial Hospital, Bangkok, Thailand.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eAUTHORS\u0026rsquo; CONTRIBUTIONS\u003c/h2\u003e\u003cp\u003e(I) Conceptualization: Prasittiporn Tangjitaree; (II) Data curation: Prasittiporn Tangjitaree ,Ekkapong Surinrat; (III) Formal analysis: Prasittiporn Tangjitaree, Pompon Suttiruk; (IV) Funding acquisition: Prasittiporn Tangjitaree, Nattachai Srisawat; (V) Methodology: Prasittiporn Tangjitaree, Tanyapim Sinjira; (VI) Project administration: Prasittiporn Tangjitaree, Peerapat Thanapongsatorn; (VII) Visualization: Prasittiporn Tangjitaree; (VIII) Writing \u0026ndash; original draft: Prasittiporn Tangjitaree; [36] Writing \u0026ndash; review \u0026amp; editing: Prasittiporn Tangjitaree, Peerapat Thanapongsatorn, Nattachai Srisawat.\u003c/p\u003e\u003ch2\u003eACKNOWLEDGEMENT\u003c/h2\u003e\u003cp\u003eThe authors express gratitude to all the patients and their families who participated in this project. Additionally, we extend our appreciation to the staffs and nurses of the surgical and medical intensive care units at King Chulalongkorn Memorial Hospital and the Central Chest Institute of Thailand for their excellent patient care and collaborative efforts throughout this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eOstermann M, Lumlertgul N (2021) Acute kidney injury in ECMO patients. Crit Care 25(1):313\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhou XL, Chen YH, Wang QY (2017) A new approach combining venoarterial extracorporeal membrane oxygenation and CRRT for adults: a retrospective study. Int J Artif Organs 40(7):345\u0026ndash;349\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSrisawat N et al (2010) Cost of acute renal replacement therapy in the intensive care unit: results from The Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) study. Crit Care 14(2):R46\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYan X et al (2010) Acute kidney injury in adult postcardiotomy patients with extracorporeal membrane oxygenation: evaluation of the RIFLE classification and the Acute Kidney Injury Network criteria. Eur J Cardiothorac Surg 37(2):334\u0026ndash;338\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSmith AH et al (2009) Acute renal failure during extracorporeal support in the pediatric cardiac patient. ASAIO J 55(4):412\u0026ndash;416\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eVan Dyk M (2018) The use of CRRT in ECMO patients. Egypt J Crit Care Med 6(3):95\u0026ndash;100\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKielstein JT et al (2013) Renal function and survival in 200 patients undergoing ECMO therapy. Nephrol Dial Transpl 28(1):86\u0026ndash;90\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAubron C et al (2013) Factors associated with outcomes of patients on extracorporeal membrane oxygenation support: a 5-year cohort study. Crit Care 17(2):R73\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOstermann M, Connor M Jr., Kashani K (2018) Continuous renal replacement therapy during extracorporeal membrane oxygenation: why, when and how? Curr Opin Crit Care 24(6):493\u0026ndash;503\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSeczynska B et al (2014) Continuous renal replacement therapy during extracorporeal membrane oxygenation in patients treated in medical intensive care unit: technical considerations. Ther Apher Dial 18(6):523\u0026ndash;534\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAustin D, McCanny P, Aneman A (2020) Post-operative renal failure management in mechanical circulatory support patients. Ann Transl Med 8(13):833\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ede Tymowski C et al (2018) Impact of connecting continuous renal replacement therapy to the extracorporeal membrane oxygenation circuit. Anaesth Crit Care Pain Med 37(6):557\u0026ndash;564\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSuga N et al (2017) A safe procedure for connecting a continuous renal replacement therapy device into an extracorporeal membrane oxygenation circuit. J Artif Organs 20(2):125\u0026ndash;131\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eThy M et al (2022) Renal Replacement Therapy for Patients Requiring Extracorporeal Membrane Oxygenation: A Multicenter International Survey. Blood Purif 51(11):899\u0026ndash;906\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMcMichael ABV et al (2022) 2021 ELSO Adult and Pediatric Anticoagulation Guidelines. Asaio j 68(3):303\u0026ndash;310\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZarbock A et al (2020) Effect of Regional Citrate Anticoagulation vs Systemic Heparin Anticoagulation During Continuous Kidney Replacement Therapy on Dialysis Filter Life Span and Mortality Among Critically Ill Patients With Acute Kidney Injury: A Randomized Clinical Trial. JAMA 324(16):1629\u0026ndash;1639\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBaxter (2015) \u003cem\u003ePrismaflex\u0026reg; Addendum to Operator\u0026rsquo;s Manual\u003c/em\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKhwaja A (2012) KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract 120(4):c179\u0026ndash;c184\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBaxter India Pvt L (2020) Instructions for Use: PRISMAFLEX M60/M100/M150 Set (Part No. 1000014921). Baxter India Pvt. Ltd., Gurgaon, India\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGaudry S et al (2015) Comparison of two strategies for initiating renal replacement therapy in the intensive care unit: study protocol for a randomized controlled trial (AKIKI). Trials 16:170\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBarbar SD et al (2018) Timing of Renal-Replacement Therapy in Patients with Acute Kidney Injury and Sepsis. N Engl J Med 379(15):1431\u0026ndash;1442\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNgamjarus C, Chongsuvivatwong V, McNeil E (2016) \u003cem\u003en4Studies: Sample Size Calculation for an Epidemiological Study on a Smart Device.\u003c/em\u003e Siriraj Medical Journal, 68: pp. 160\u0026ndash;170\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKnaus WA et al (1985) APACHE II: a severity of disease classification system. Crit Care Med 13(10):818\u0026ndash;829\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eVincent JL et al (1998) Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on sepsis-related problems of the European Society of Intensive Care Medicine. Crit Care Med 26(11):1793\u0026ndash;1800\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHolt AW et al (1996) Continuous renal replacement therapy in critically ill patients: monitoring circuit function. Anaesth Intensive Care 24(4):423\u0026ndash;429\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBaldwin I, Bellomo R, Koch B (2004) Blood flow reductions during continuous renal replacement therapy and circuit life. Intensive Care Med 30(11):2074\u0026ndash;2079\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDunn WJ, Sriram S (2014) Filter lifespan in critically ill adults receiving continuous renal replacement therapy: the effect of patient and treatment-related variables. Crit Care Resusc 16(3):225\u0026ndash;231\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOudemans-van Straaten HM (2010) Citrate anticoagulation for continuous renal replacement therapy in the critically ill. Blood Purif 29(2):191\u0026ndash;196\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTsujimoto Y, Fujii T (2022) How to Prolong Filter Life During Continuous Renal Replacement Therapy? Crit Care 26(1):62\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhao ZH et al (2025) Interruptions and downtime of continuous renal replacement therapy in critically ill adults: A retrospective observational study. Nurs Crit Care 30(2):e13265\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWu J et al (2023) Impact of connecting methods of continuous renal replacement therapy device on patients underwent extracorporeal membrane oxygenation: A retrospectively observational study. Aust Crit Care 36(5):695\u0026ndash;701\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRaja M, Leal R, Doyle J (2023) Continuous renal replacement therapy in patients receiving extracorporeal membrane oxygenation therapy. J Intensive Care Soc 24(2):227\u0026ndash;229\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKouch M et al (2022) \u003cem\u003eA Comparison of Separate Access versus In-Line Configuration for Continuous Renal Replacement Therapy in VV ECMO.\u003c/em\u003e medRxiv, : p. 2022.11.16.22282382\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHuang X et al (2024) Optimizing the connection of CRRT and ECMO lines with additional pressure regulator on the therapeutic effect, filter life, and incidence of complications. Med (Baltim) 103(25):e38580\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMitra S et al (2021) Concurrent Use of Renal Replacement Therapy during Extracorporeal Membrane Oxygenation Support: A Systematic Review and Meta-Analysis. J Clin Med, 10(2)\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLi P et al (2021) Effect of Dynamic Circuit Pressures Monitoring on the Lifespan of Extracorporeal Circuit and the Efficiency of Solute Removal During Continuous Renal Replacement Therapy. Frontiers in Medicine, p 8\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"intensive-care-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"icme","sideBox":"Learn more about [Intensive Care Medicine](http://link.springer.com/journal/134)","snPcode":"134","submissionUrl":"https://www.editorialmanager.com/icme/default2.aspx","title":"Intensive Care Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"CRRT, ECMO, circuit, combination, integration","lastPublishedDoi":"10.21203/rs.3.rs-8049207/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8049207/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eThe estimated incidence of acute kidney injury requiring renal replacement therapy (RRT), mainly continuous RRT (CRRT), in patients necessitating extracorporeal membrane oxygenation (ECMO) is approximately 50%. Currently, two well-known techniques, integration and separation are utilized for combining CRRT and ECMO circuits, neither of which is considered a standard treatment.\u003c/p\u003e\u003ch2\u003ePurpose\u003c/h2\u003e\u003cp\u003eThis study aimed to compare circuit lifespan of CRRT between these two techniques during ECMO support.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eA multicentered randomized controlled trial was conducted from May 2021 to March 2025. ECMO patients who required CRRT support were enrolled. Primary outcome was CRRT circuit lifespan.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eEighty patients were recruited, with 40 allocated to the integration group and 40 to the separation group. Median circuit lifespan did not significantly differ between the groups (72 hours [IQR 45\u0026ndash;96.5] vs. 71 hours [IQR 45\u0026ndash;84]; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.52). Twenty-eight-day mortality rates were also comparable (32.5% vs. 35%; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.81). No significant differences were observed in the incidence of serious adverse events, including air embolism. Transmembrane pressure and CRRT machine alarm frequencies were similar between groups.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eAmong critically ill ECMO patients with CRRT support, integrated CRRT circuit into ECMO circuit shows no significant difference in efficacy and serious adverse events when compared to separation technique.\u003c/p\u003e\u003ch2\u003eTrial registration\u003c/h2\u003e\u003cp\u003eNCT05036616\u003c/p\u003e","manuscriptTitle":"The Comparison of Circuit Lifespan between Integration and Separation Approach in Extracorporeal Membrane Oxygenation Patient Requiring Continuous Renal Replacement Therapy Support, A Randomized Controlled Trial (E-CRRT Trial)","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-19 12:07:18","doi":"10.21203/rs.3.rs-8049207/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2025-11-10T11:49:40+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-10T10:31:15+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-10T06:13:35+00:00","index":"","fulltext":""},{"type":"submitted","content":"Intensive Care Medicine","date":"2025-11-06T09:38:06+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"intensive-care-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"icme","sideBox":"Learn more about [Intensive Care Medicine](http://link.springer.com/journal/134)","snPcode":"134","submissionUrl":"https://www.editorialmanager.com/icme/default2.aspx","title":"Intensive Care Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"93326820-e419-444f-a245-f32268450cdf","owner":[],"postedDate":"November 19th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-02-09T16:05:30+00:00","versionOfRecord":{"articleIdentity":"rs-8049207","link":"https://doi.org/10.1007/s00134-026-08302-y","journal":{"identity":"intensive-care-medicine","isVorOnly":false,"title":"Intensive Care Medicine"},"publishedOn":"2026-02-05 15:59:54","publishedOnDateReadable":"February 5th, 2026"},"versionCreatedAt":"2025-11-19 12:07:18","video":"","vorDoi":"10.1007/s00134-026-08302-y","vorDoiUrl":"https://doi.org/10.1007/s00134-026-08302-y","workflowStages":[]},"version":"v1","identity":"rs-8049207","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8049207","identity":"rs-8049207","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}