Comparison of Regional Citrate Anticoagulation (RCA) with Heparin (HA) or No (NA) anticoagulation strategy in paediatric intensive care patients receiving continuous renal replacement therapy: A 9-year single centre tertiary cohort study

Comparison of Regional Citrate Anticoagulation (RCA) with Heparin (HA) or No (NA) anticoagulation strategy in paediatric intensive care patients receiving continuous renal replacement therapy: A 9-year single centre tertiary cohort study | 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 Comparison of Regional Citrate Anticoagulation (RCA) with Heparin (HA) or No (NA) anticoagulation strategy in paediatric intensive care patients receiving continuous renal replacement therapy: A 9-year single centre tertiary cohort study Subodh Ganu, Georgia Letton This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7952360/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background & Objective: This is a single centre retrospective cohort study over period of 9 years of comparing regional citrate anticoagulation (RCA) vs heparin (HA) or no anticoagulation (NA) strategy in a paediatric intensive care patients using continuous renal replacement therapy. Results: A total of 107 CRRT circuits were used to deliver continuous renal replacement therapy to 42 children weighing at least 8 kg. Overall mortality was 14 out of 42 (33.3%); similar between the RCA (22.2%, 4/18) and HA (25%, 4/16) group. Sepsis or shock was the most common indication for CRRT followed by acute kidney injury in both the groups. A single circuit was sufficient to complete the required CRRT therapy with RCA in 8 out of 14 children (57.1%), compared to only 3 out of 12 children (25%) with HA. The median number of circuits required per patient was 2 in the RCA group and 3.3 in the HA group. The median circuit lifespan was highest in RCA circuits, 27 hours (SD ± 3 hours), followed by HA circuits at 20 hours (SD ± 3.2 hours) and shortest in NA circuits, 8.2 hours (SD ± 4.2 hours). Clots was commonest reason leading to circuit changes and occurred in 8 out of 36 (22.2%) RCA circuits, 14 out of 52 (26.9%) HA circuits, and 8 out of 18 (44.4%) NA circuits. Conclusions: In our study, RCA circuits had longer median lifespans, required fewer changes, and had lower rates of clotting and bleeding complications. However, due to small sample size results were not statistically significant. Paediatric Renal Replacement Therapy Regional Citrate Anticoagulation Heparin anticoagulation CRRT PRISMAX Introduction Acute kidney injury (AKI), a common complication among hospitalized neonates and children, is associated with high morbidity and mortality, especially when requiring renal replacement therapy (RRT) ( 1 ). In developed countries, continuous renal replacement therapy (CRRT) is the commonest form of renal replacement in the acute setting and has evolved to become a standard of care in paediatric intensive care over last 20 years ( 1 ). It is used in various indications, including severe sepsis with shock, acute kidney injury (AKI), severe electrolyte imbalance/metabolic acidosis, refractory or diuretic-resistant fluid overload, intoxications, acute liver failure and inborn errors of metabolism. The advantages of CRRT include the ability to promote both solute and fluid clearance in a slow continuous and controlled manner in haemodynamically unstable patients. Approximately 25% of children in PICU have some degree of acute kidney injury (AKI), however the need for CRRT varies, ranging from approximately 3 to 8% of the total admissions ( 2 ). Regional anticoagulation with citrate (RCA) is an alternative to heparin anticoagulation (HA) in continuous renal replacement therapies. In the past 15 years, the use of regional citrate anticoagulation (RCA) is increasing as compared to heparin or no anticoagulation therapy. RCA is postulated to prolong circuit lifetime and decrease haemorrhagic complications being a regional anticoagulation which is difficult to achieve with HA ( 3 ). We describe our experience in transition to regional citrate anticoagulation (RCA) as a preferred method of maintaining anticoagulation for CRRT at a mixed tertiary care referral paediatric centre over 9 years and its comparison to heparin-based anticoagulation (HA) and no anticoagulation in children weighing 8 Kg or more. Methods This was an analytical, observational, retrospective cohort study in all children who had CRRT at our tertiary care referral paediatric intensive care unit (PICU) after introduction of citrate-based anticoagulation system from January 2011 to December 2019. The Women’s and Children’s Hospital Human Research Ethics Committee approved this audit with waiver of consent and further extension over next 3 years, spanning 2011 to 2019 (Approval number 808A). The tertiary PICU admitted medical and surgical patients from newborn to 18 years of age but did not have immediate post-operative cardiac surgical admissions and patients on extra corporeal membrane oxygenation (ECMO) support. The children needing and eligible for liver transplant and renal transplant below 15 kg were not managed in this PICU and transferred interstate. Anticoagulation options available were heparin (HA), citrate (RCA), prostacyclin, or no anticoagulation (NA). The initiation of CRRT was clinician decision. Demographic data, diagnosis and outcome were obtained from institutional records maintained via Australia New Zealand Paediatric Intensive care (ANZPIC) registry and paper case notes. The details of CRRT therapy such as circuit size, vascular catheter details and flow settings, etc. were recorded from the PICU paper case notes review. CRRT was administered in Paediatric Intensive care Unit using PRISMAFLEX machines. The prescription and administration of CRRT was in adherence to the local protocol developed by the PICU multidisciplinary team of consultants, nurse educators and pharmacists. Brief synopsis of protocol and guidelines to prescribe CRRT using HA and RCA anticoagulation are attached in appendix 1. In children deemed not suitable for any anticoagulation HA protocol was used, replacing saline instead of heparin in the syringe, rest of protocol and prescriptions remaining same. CRRT had been performed in the unit using the same system (PRISMAFLEX; VANTIVE) for 5 years before the study began, using heparin anticoagulation and there was a successful induction/ongoing education program for the bedside nurses to upskill and maintain skills in administering CRRT. Dual or triple lumen vascular catheters ranging between 6.5 F and 14 F were used for central vascular access depending on the age and weight of the child, using the same criteria for any anticoagulation methods. Access was sited either in the femoral vein or the internal jugular or the subclavian vein. The size of CRRT filter/circuit was guided by the protocol and was dependent on the weight of the child from 1.0 m 2 (ST100; VANTIVE) in patients more than 30 Kg; 0.60m2 (ST60; VANTIVE) in 15 to 30 Kg and 0.20 m2 (HF-20; VANTIVE) in less than 15 kg patients. HA protocol had target ACT of 180 to 200 seconds and used HEMOSOL B0 or PHOXILIUM solutions (VANTIVE) using prefilter haemodilution as default. RCA protocol used the automated software version with calcium correction using automatically administered and delivered calcium gluconate via syringe driver on the PRISMAFLEX machine. We used PRISMOCITRATE 18/0 solution (VANTIVE) for anticoagulation, administered pre-filter and the flow rate was prescribed as citrate dose (mmol/L) guided by the patient’s ionized calcium level. PRISM0CAL B22 solution (VANTIVE) was used as dialysis fluid when indicated. Calcium gluconate was used to reverse the anticoagulant effect of citrate, ideally given through a separate central venous access or via the third lumen of the triple lumen vascular catheter, if available. Blood flow was prescribed based on actual or estimated weight, usually 3 to 4 ml/kg/min with minimal blood flow of 20 ml/min and highest of 200 ml/min. The actual prescription of CRRT flows and details such as ultrafiltration alone or in additional dialysis mode, was left to clinician discretion and patient clinical indication but were guided by a table published in the state-wide paediatric CRRT guidelines (appendix 1). The choice of anticoagulation and titration of anticoagulation was as per clinician’s discretion. RCA was the preferred default option throughout the study. Data Collection: A list of the children over 9 years, from Jan 2011 to Dec 2019, was obtained from institutional database which submits data to Australia New Zealand Paediatric Intensive care Registry database (ANZPICR). The data on patient demographics, PICU and hospital survival, primary diagnosis as well as comorbidities and length of stay as well as hospital discharge outcomes were obtained from this database. Paper records and case notes were scrutinized, and further data were recorded. All patients who were administered CRRT were included. We did not record if a circuit was prepared but was never connected to the patient either due to patient demise or CRRT was not indicated as per clinician by then. Detailed records of blood flows, circuit parameters and any problems or difficulties with the circuit documented in patient case notes were sought from the paper case notes and recorded. Data on urea and creatinine clearance were recorded for the first 24 hours on CRRT. Fluid balance in patients as well as circuit or machine fluid balance were also recorded. Post ICU utilisation of intermittent haemodialysis was recorded amongst the survivors. Ethics The study was approved by the local ethics and research governance committee. Statistical analyses: SPSS version 26 was used to analyse the data collected. Continuous variables are described via medians and standard deviation. Categorical variables are described in frequencies and percentages. Research Funding This was investigator-initiated study which was supported by funding from Baxter in 2016. The funding remunerated research nurse’s time spent for the data collection. Principal investigator did not receive any financial remuneration or salary from Baxter and has no conflict of interest to declare. Results A total of 107 CRRT circuits were used to deliver continuous renal replacement therapy to 42 children weighing 8 kg or more. The cohort included 20 boys and 22 girls. The median age was 54 months (range: 4 to 204 months), and the median weight was 20 kg (range: 8 to 70 kg). Citrate-based anticoagulation (RCA) was used in 18 children, delivered via 36 circuits. Heparin-based anticoagulation (HA) was used in 16 children, delivered via 53 circuits. No anticoagulation (NA) was used in 8 children, delivered via 18 circuits (Table 1). The circuit sizes and vascular catheter characteristics are provided in Table 2. Mortality and patient outcomes: Overall mortality was 14 out of 42 (33.3%). The mortality rates were similar between the RCA (22.2%, 4/18) and HA (25%, 4/16) groups. Mortality was the highest in children with NA circuits, with 6 out of 8 children dying (Table 1 and table 3). Among the survivors, 1 in the RCA group and 1 in the HA group were discharged from the ICU requiring intermittent haemodialysis. Table 3 summarizes the indications for CRRT and hospital mortality rates for patients receiving different types of anticoagulation: Citrate Anticoagulation (RCA), Heparin Anticoagulation (HA), and No Anticoagulation (NA). Sepsis and/or septic shock was the most common indication for CRRT, accounting for 19 patients. Among the patients with septic shock, both RCA and HA circuits were used in 8 patients each, with 4 deaths in each group (50% mortality). Severe acute kidney injury (AKI) or acute renal failure was the second most common indication, accounting for 15 patients with no deaths. Circuit Characteristics: (dup: abstract ?) Among survivors, a single circuit was sufficient to complete the indicated CRRT therapy with RCA in 8 out of 14 children (57.1%), compared to only 3 out of 12 children (25%) with HA. At least 3 or more circuits were necessary in 3 out of 14 children (21.4%) in the RCA group, while 7 out of 12 children (58.3%) in the HA group required multiple circuits. The median number of circuits required per patient was 2 in the RCA group and 3.3 in the HA group. In both RCA and HA circuits, difficulties in continuing therapy before the completion of the filter lifespan (72 hours) led to circuit changes in 13 out of 36 (36%) and 16 out of 53 (30%) circuits, respectively. NA circuits had the highest incidence of difficulties, with 8 out of 18 (44.4%) experiencing issues (Table 4). Clots leading to circuit changes occurred in 8 out of 36 (22.2%) RCA circuits, 14 out of 52 (26.9%) HA circuits, and 8 out of 18 (44.4%) NA circuits. Significant bleeding was rare, with no occurrences in the RCA group and 2 instances recorded in the HA group. The median circuit lifespan was the longest in RCA circuits at 27 hours (SD ± 3 hours), followed by HA circuits at 20 hours (SD ± 3.2 hours). NA circuits had the shortest median circuit lifespan at 8.2 hours (SD ± 4.2 hours). This difference did not reach statistical significance. Comparison of Clearance and other relevant parameters: Serum urea clearance was measured by comparing urea levels at initiation and after 12 hours. Data was available for 23 patients. Urea clearance was similar in both RCA and HA circuits, with a mean decline in urea levels of 6.8 mmol/L and 6.2 mmol/L over 12 hours, respectively. NA circuits, possibly due to factors such as clotting and interruptions, had a decline in urea of only 1.6 mmol/L over 12 hours. After starting CRRT, the median rise in serum bicarbonate after 12 hours was similar in RCA, HA, and NA circuits: 2.8, 3.1, and 2.2 mmol/L, respectively. There was no significant difference in creatinine clearance at 12 hours between RCA and HA circuits, with median clearances of 55.3 mmol/L and 42.4 mmol/L, respectively (p = 0.137). The fluid clearance or removal was calculated at 24 hours of circuit use, and the patients' estimated weight was used to calculate ml per kg per hour removal of fluid. There was a higher median fluid removal (ml/kg/hr) in RCA circuits (2.4 ml/kg/hr) compared to HA circuits (1.8 ml/kg/hr). However, this did not reach statistical significance (p = 0.081). The data available for NA circuits were too small to compare. Discussion The results of this study provide valuable insights into the use of citrate-based anticoagulation (RCA), heparin-based anticoagulation (HA), and no anticoagulation (NA) in paediatric continuous renal replacement therapy (CRRT). Our findings indicate that, in our cohort of paediatric patients weighing more than 8 Kg, RCA circuits lasted longer and may be a technically safer, comparable and more effective option compared to HA and NA. There was no difference in mortality between RCA and HA circuits. Overall mortality rate in our study was 33.3%, which is consistent with previously reported mortality rates in paediatric CRRT patients. Symons et al. (2013) reported a mortality rate of 34.6% in a prospective registry of paediatric CRRT patients. Similarly, Bunchman et al. (2018) reported a mortality rate of 30.8% in a review of paediatric CRRT literature [2]. Interestingly, the mortality rates were significantly higher in the NA group. The patients in NA group were sicker and clinically deemed not suitable to be anticoagulated due to the level of multiorgan failure. This is more likely explanation to the increased mortality rather than survival due to the use of no anticoagulation per se. Circuit Characteristics: Our study found that RCA circuits had a longer median lifespan (27.2 hours) compared to HA (20 hours) and NA circuits (8.2 hours). This is consistent with previous studies demonstrating the efficacy and safety of RCA in CRRT. Brophy et al. (2018) reported a median circuit lifespan of 44.6 hours in paediatric CRRT patients receiving RCA [3]. Raymakers-Jansen et al, in a small single centre paediatric study of 20 patients (14 RCA and 6 HA circuits) report median circuit life span of 45.2 hours (IQR 37.5–52.8) with RCA as compared to 21 hours (IQR 14.5–27.5) with HA (p < 0.001) ( 4 ). In an adult randomized control trial in Australia, Gattas et al found significantly longer median circuits life span in RCA (39.2 hrs) versus in HA (22.8 hrs) ( 5 ).The reduced need for circuit changes and lower complication rates with RCA may be due to its ability to provide regional and better titratable anticoagulation, delivering better rheology of blood flow in the CRRT circuit and reducing the risk of systemic bleeding ( 6 ). Our results showed that RCA and HA circuits had similar urea clearance and creatinine clearance rates. However, RCA circuits had higher median fluid removal rates compared to HA circuits. This is possibly attributed to less interrupted, more stable and efficient nature of CA circuits, allowing for more effective fluid removal ( 7 ). Sutherland et al reported finding of prospective paediatric registry in 297 children across 13 PICUs in United States and found that that fluid overload more than 20% at initiation of CRRT was associated higher mortality (65.6%) as compared to children with 10–20% (43.1%) and less than 10% fluid overload (29.4%) ( 7 ). We would like to hypothesize that the ability of RCA circuits to provide more effective fluid removal may be an important factor in improving patient outcomes, potentially making them safer ( 8 ). Our study has several limitations. Firstly, the sample size was relatively small, which may limit the generalizability of our findings. Secondly, the study was retrospective in nature, which may introduce biases in data collection and analysis. The cohort of patients was from a single tertiary care centre with no post operative congenital heart surgery patients and non-liver transplant centre. This limits the external validity of the study to such as population. However, this study reflects that even in low volume centres, RCA is feasible and demonstrates valuable technical and patient related advantages as compared to HA. Finally, we did not collect data on long-term outcomes, including post ICU discharge utilization details of IHD which would be important to assess the sustainability of CRRT benefits. However, none of the patients required another run of CRRT after discharge from PICU. In conclusion, our study suggests that citrate-based anticoagulation (RCA) may be a safer and more effective option for paediatric CRRT compared to heparin-based anticoagulation (HA) and no anticoagulation (NA). RCA circuits had longer median lifespans, required fewer changes, and had lower rates of clotting and bleeding complications. Additionally, RCA circuits had higher median fluid removal rates. Further prospective studies are needed to confirm these findings and assess long-term outcomes. Declarations Financial Disclosure Research data manager GL received remuneration for her time paid through Baxter Investigator Initiated Research Program- Renal Acute with reference grant number GAUS7255 for USD $ 31000. References Khwaja A (2012) KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract 120(4):c179–c184 Epub 2012/08/15. doi: 10.1159/000339789. PubMed PMID: 22890468 Juncos LA, Chandrashekar K, Karakala N, Baldwin I (2021) Vascular access, membranes and circuit for CRRT. Semin Dial 34(6):406–415 Epub 2021/05/04. 10.1111/sdi Tobe SW, Aujla P, Walele AA, Oliver MJ, Naimark DM, Perkins NJ et al (2003) A novel regional citrate anticoagulation protocol for CRRT using only commercially available solutions. J Crit Care 18(2):121–129 Epub 2003/06/12. 10.1053/jcrc.2003.50006 Raymakers-Janssen P, Lilien M, van Kessel IA, Veldhoen ES, Wosten-van Asperen RM, van Gestel JPJ (2017) Citrate versus heparin anticoagulation in continuous renal replacement therapy in small children. Pediatr Nephrol 32(10):1971–1978 Epub 2017/06/05. 10.1007/s00467-017-3694-4 Gattas DJ, Rajbhandari D, Bradford C, Buhr H, Lo S, Bellomo R (2015) A Randomized Controlled Trial of Regional Citrate Versus Regional Heparin Anticoagulation for Continuous Renal Replacement Therapy in Critically Ill Adults. Crit Care Med 43(8):1622–1629 Epub 2015/04/09. doi: 10.1097/CCM.0000000000001004. PubMed PMID: 25853591 Zaoral T, Hladik M, Zapletalova J, Travnicek B, Gelnarova E (2016) Circuit Lifetime With Citrate Versus Heparin in Pediatric Continuous Venovenous Hemodialysis. Pediatr Crit Care Med 17(9):e399–405 Epub 2016/07/19. doi: 10.1097/PCC.0000000000000860. PubMed PMID: 27427878 Sutherland SM, Zappitelli M, Alexander SR, Chua AN, Brophy PD, Bunchman TE et al (2010) Fluid overload and mortality in children receiving continuous renal replacement therapy: the prospective pediatric continuous renal replacement therapy registry. Am J Kidney Dis 55(2):316–325 Epub 2010/01/01. 10.1053/j.ajkd.2009.10.048 Bunchman TE (2016) Anticoagulation in Continuous Renal Replacement Therapy: Citrate Appears to Be Superior to Heparin! Pediatr Crit Care Med 17(9):894–895 Epub 2016/09/02. 10.1097 Tables Table 1 Demographics of patients RCA HA NA All n (%) 18 16 8 42 Median age (months) 42 48 13 54 Median baseline weight (kg) 20 16.5 14.5 20 Male/Female 10/8 8/8 2/6 20/22 Total circuits used (Median circuits per patient) 36 ( 2 ) 53* (3.31) 18 107 PIM 2 score, mean (SD) 5.93 (6.3) 7.32 (13.0) 16.0 (13.1) 8.32 (11.7) PIM 3 score, mean (SD) 4.91 (4.8) 7.86 (13.9) 20.8 (13.7) 8.91 (12.8) Individual Circuit median time, hrs (n) (SE Mean) 27 (36) (3.18) 18 (53) (3.06) 21.5 (18) (5.88) 22 (107) (2.15) Total CRRT time, median (hrs) 68.04 64.17 19.2 PICU LOS, median (hrs) TBC TBC TBC TBC Deaths (%) 4 (22.2%) 4 (25%) 6 (75%) 14/42 (33%) RCA = Regional Citrate Anticoagulation; HA = Heparin based Anticoagulation ; NA = No Anticoagulation; IQR = Inter Quartile Range; PICU LOS = Paediatric ICU Length of Stay; HOS LOS = Hospital Length of Stay; * = 2 circuits had heparin anticoagulation along with protamine reversal’ some data available in 52 circuits TBC: To be Confirmed with data manager Table 2 CRRT circuits and vascular Catheter characteristics Type of Anticoagulation RCA (18) HA (16) NA ( 8 ) All Circuit sizes HF 20 5 6 6 17 ST 60 9 6 2 17 ST 100 4 4 0 8 Vascular catheter Size 6.5 F double lumen 4 3 2 5 8 F double lumen 2 6 1 9 11 F double lumen 2 3 2 7 12 F triple lumen 6 1 1 8 13 F triple lumen 3 1 2 3 14 F triple lumen 1 2 0 2 RCA = Regional Citrate Anticoagulation; HA = Heparin based Anticoagulation; NA = No Anticoagulation Table 3 Indications for CRRT and mortality Indications for CRRT RCA (deaths) HA (deaths) NA (deaths) Total (deaths) Sepsis or Shock 8 ( 4 ) 8 ( 4 ) 3 ( 2 ) 19 (10) Acute Renal Failure 8 (0) 6 (0) 1 (0) 15 (0) Acute Liver Failure 0 0 2 ( 2 ) 2 ( 2 ) Intoxication or poisoning 2 (0) 2 (0) 0 4 (0) Miscellaneous other 0 0 2 ( 2 ) 2 ( 2 ) Hospital Mortality, n (%) 4/18 (22.2%) 4/16 (25%) 6/8 (75%) 14/42 (33.3%) RCA = Regional Citrate Anticoagulation; HA = Heparin based Anticoagulation; NA = No Anticoagulation Table 4 Reasons for therapy requiring circuit change before completion of 72 hours Complications of Therapy RCA HA NA Clotting of circuit 8/36 14/52 14/18 Significant Bleeding 0 2 5/18 Vascular catheter replacement required 2 4 0 Calcium instability 1 - - Metabolic alkalosis 2 0 0 Total 13 20 19 RCA = Regional Citrate Anticoagulation; HA = Heparin based Anticoagulation; NA = No Anticoagulation Supplementary Files Appendix1CRRTprotocols.docx Cite Share Download PDF Status: Posted Version 1 posted 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. 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11:31:15","extension":"docx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":5924506,"visible":true,"origin":"","legend":"","description":"","filename":"Appendix1CRRTprotocols.docx","url":"https://assets-eu.researchsquare.com/files/rs-7952360/v1/301b3b406e0742f14921a506.docx"}],"financialInterests":"","formattedTitle":"Comparison of Regional Citrate Anticoagulation (RCA) with Heparin (HA) or No (NA) anticoagulation strategy in paediatric intensive care patients receiving continuous renal replacement therapy: A 9-year single centre tertiary cohort study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAcute kidney injury (AKI), a common complication among hospitalized neonates and children, is associated with high morbidity and mortality, especially when requiring renal replacement therapy (RRT) (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). In developed countries, continuous renal replacement therapy (CRRT) is the commonest form of renal replacement in the acute setting and has evolved to become a standard of care in paediatric intensive care over last 20 years (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). It is used in various indications, including severe sepsis with shock, acute kidney injury (AKI), severe electrolyte imbalance/metabolic acidosis, refractory or diuretic-resistant fluid overload, intoxications, acute liver failure and inborn errors of metabolism. The advantages of CRRT include the ability to promote both solute and fluid clearance in a slow continuous and controlled manner in haemodynamically unstable patients. Approximately 25% of children in PICU have some degree of acute kidney injury (AKI), however the need for CRRT varies, ranging from approximately 3 to 8% of the total admissions (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eRegional anticoagulation with citrate (RCA) is an alternative to heparin anticoagulation (HA) in continuous renal replacement therapies. In the past 15 years, the use of regional citrate anticoagulation (RCA) is increasing as compared to heparin or no anticoagulation therapy. RCA is postulated to prolong circuit lifetime and decrease haemorrhagic complications being a regional anticoagulation which is difficult to achieve with HA (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). We describe our experience in transition to regional citrate anticoagulation (RCA) as a preferred method of maintaining anticoagulation for CRRT at a mixed tertiary care referral paediatric centre over 9 years and its comparison to heparin-based anticoagulation (HA) and no anticoagulation in children weighing 8 Kg or more.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e This was an analytical, observational, retrospective cohort study in all children who had CRRT at our tertiary care referral paediatric intensive care unit (PICU) after introduction of citrate-based anticoagulation system from January 2011 to December 2019. The Women\u0026rsquo;s and Children\u0026rsquo;s Hospital Human Research Ethics Committee approved this audit with waiver of consent and further extension over next 3 years, spanning 2011 to 2019 (Approval number 808A). The tertiary PICU admitted medical and surgical patients from newborn to 18 years of age but did not have immediate post-operative cardiac surgical admissions and patients on extra corporeal membrane oxygenation (ECMO) support. The children needing and eligible for liver transplant and renal transplant below 15 kg were not managed in this PICU and transferred interstate. Anticoagulation options available were heparin (HA), citrate (RCA), prostacyclin, or no anticoagulation (NA). The initiation of CRRT was clinician decision. Demographic data, diagnosis and outcome were obtained from institutional records maintained via Australia New Zealand Paediatric Intensive care (ANZPIC) registry and paper case notes. The details of CRRT therapy such as circuit size, vascular catheter details and flow settings, etc. were recorded from the PICU paper case notes review.\u003c/p\u003e\u003cp\u003eCRRT was administered in Paediatric Intensive care Unit using PRISMAFLEX machines. The prescription and administration of CRRT was in adherence to the local protocol developed by the PICU multidisciplinary team of consultants, nurse educators and pharmacists. Brief synopsis of protocol and guidelines to prescribe CRRT using HA and RCA anticoagulation are attached in appendix 1. In children deemed not suitable for any anticoagulation HA protocol was used, replacing saline instead of heparin in the syringe, rest of protocol and prescriptions remaining same. CRRT had been performed in the unit using the same system (PRISMAFLEX; VANTIVE) for 5 years before the study began, using heparin anticoagulation and there was a successful induction/ongoing education program for the bedside nurses to upskill and maintain skills in administering CRRT. Dual or triple lumen vascular catheters ranging between 6.5 F and 14 F were used for central vascular access depending on the age and weight of the child, using the same criteria for any anticoagulation methods. Access was sited either in the femoral vein or the internal jugular or the subclavian vein. The size of CRRT filter/circuit was guided by the protocol and was dependent on the weight of the child from 1.0 m\u003csup\u003e2\u003c/sup\u003e (ST100; VANTIVE) in patients more than 30 Kg; 0.60m2 (ST60; VANTIVE) in 15 to 30 Kg and 0.20 m2 (HF-20; VANTIVE) in less than 15 kg patients. HA protocol had target ACT of 180 to 200 seconds and used HEMOSOL B0 or PHOXILIUM solutions (VANTIVE) using prefilter haemodilution as default. RCA protocol used the automated software version with calcium correction using automatically administered and delivered calcium gluconate via syringe driver on the PRISMAFLEX machine. We used PRISMOCITRATE 18/0 solution (VANTIVE) for anticoagulation, administered pre-filter and the flow rate was prescribed as citrate dose (mmol/L) guided by the patient\u0026rsquo;s ionized calcium level. PRISM0CAL B22 solution (VANTIVE) was used as dialysis fluid when indicated. Calcium gluconate was used to reverse the anticoagulant effect of citrate, ideally given through a separate central venous access or via the third lumen of the triple lumen vascular catheter, if available. Blood flow was prescribed based on actual or estimated weight, usually 3 to 4 ml/kg/min with minimal blood flow of 20 ml/min and highest of 200 ml/min. The actual prescription of CRRT flows and details such as ultrafiltration alone or in additional dialysis mode, was left to clinician discretion and patient clinical indication but were guided by a table published in the state-wide paediatric CRRT guidelines (appendix 1). The choice of anticoagulation and titration of anticoagulation was as per clinician\u0026rsquo;s discretion. RCA was the preferred default option throughout the study.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eData Collection:\u003c/h2\u003e\u003cp\u003eA list of the children over 9 years, from Jan 2011 to Dec 2019, was obtained from institutional database which submits data to Australia New Zealand Paediatric Intensive care Registry database (ANZPICR). The data on patient demographics, PICU and hospital survival, primary diagnosis as well as comorbidities and length of stay as well as hospital discharge outcomes were obtained from this database. Paper records and case notes were scrutinized, and further data were recorded. All patients who were administered CRRT were included. We did not record if a circuit was prepared but was never connected to the patient either due to patient demise or CRRT was not indicated as per clinician by then. Detailed records of blood flows, circuit parameters and any problems or difficulties with the circuit documented in patient case notes were sought from the paper case notes and recorded. Data on urea and creatinine clearance were recorded for the first 24 hours on CRRT. Fluid balance in patients as well as circuit or machine fluid balance were also recorded. Post ICU utilisation of intermittent haemodialysis was recorded amongst the survivors.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eEthics\u003c/strong\u003e\u003cp\u003e The study was approved by the local ethics and research governance committee.\u003c/p\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eStatistical analyses:\u003c/h3\u003e\n\u003cp\u003eSPSS version 26 was used to analyse the data collected. Continuous variables are described via medians and standard deviation. Categorical variables are described in frequencies and percentages.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResearch Funding\u003c/strong\u003e\u003cp\u003eThis was investigator-initiated study which was supported by funding from Baxter in 2016. The funding remunerated research nurse\u0026rsquo;s time spent for the data collection. Principal investigator did not receive any financial remuneration or salary from Baxter and has no conflict of interest to declare.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 107 CRRT circuits were used to deliver continuous renal replacement therapy to 42 children weighing 8 kg or more. The cohort included 20 boys and 22 girls. The median age was 54 months (range: 4 to 204 months), and the median weight was 20 kg (range: 8 to 70 kg). Citrate-based anticoagulation (RCA) was used in 18 children, delivered via 36 circuits. Heparin-based anticoagulation (HA) was used in 16 children, delivered via 53 circuits. No anticoagulation (NA) was used in 8 children, delivered via 18 circuits (Table\u0026nbsp;1). The circuit sizes and vascular catheter characteristics are provided in Table\u0026nbsp;2.\u003c/p\u003e\n\u003ch3\u003eMortality and patient outcomes:\u003c/h3\u003e\n\u003cp\u003eOverall mortality was 14 out of 42 (33.3%). The mortality rates were similar between the RCA (22.2%, 4/18) and HA (25%, 4/16) groups. Mortality was the highest in children with NA circuits, with 6 out of 8 children dying (Table\u0026nbsp;1 and table 3).\u003c/p\u003e\u003cp\u003eAmong the survivors, 1 in the RCA group and 1 in the HA group were discharged from the ICU requiring intermittent haemodialysis.\u003c/p\u003e\u003cp\u003eTable\u0026nbsp;3 summarizes the indications for CRRT and hospital mortality rates for patients receiving different types of anticoagulation: Citrate Anticoagulation (RCA), Heparin Anticoagulation (HA), and No Anticoagulation (NA).\u003c/p\u003e\u003cp\u003eSepsis and/or septic shock was the most common indication for CRRT, accounting for 19 patients. Among the patients with septic shock, both RCA and HA circuits were used in 8 patients each, with 4 deaths in each group (50% mortality). Severe acute kidney injury (AKI) or acute renal failure was the second most common indication, accounting for 15 patients with no deaths.\u003c/p\u003e\n\u003ch3\u003eCircuit Characteristics: (dup: abstract ?)\u003c/h3\u003e\n\u003cp\u003eAmong survivors, a single circuit was sufficient to complete the indicated CRRT therapy with RCA in 8 out of 14 children (57.1%), compared to only 3 out of 12 children (25%) with HA. At least 3 or more circuits were necessary in 3 out of 14 children (21.4%) in the RCA group, while 7 out of 12 children (58.3%) in the HA group required multiple circuits. The median number of circuits required per patient was 2 in the RCA group and 3.3 in the HA group.\u003c/p\u003e\u003cp\u003eIn both RCA and HA circuits, difficulties in continuing therapy before the completion of the filter lifespan (72 hours) led to circuit changes in 13 out of 36 (36%) and 16 out of 53 (30%) circuits, respectively. NA circuits had the highest incidence of difficulties, with 8 out of 18 (44.4%) experiencing issues (Table\u0026nbsp;4). Clots leading to circuit changes occurred in 8 out of 36 (22.2%) RCA circuits, 14 out of 52 (26.9%) HA circuits, and 8 out of 18 (44.4%) NA circuits.\u003c/p\u003e\u003cp\u003eSignificant bleeding was rare, with no occurrences in the RCA group and 2 instances recorded in the HA group. The median circuit lifespan was the longest in RCA circuits at 27 hours (SD\u0026thinsp;\u0026plusmn;\u0026thinsp;3 hours), followed by HA circuits at 20 hours (SD\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2 hours). NA circuits had the shortest median circuit lifespan at 8.2 hours (SD\u0026thinsp;\u0026plusmn;\u0026thinsp;4.2 hours).\u003c/p\u003e\u003cp\u003eThis difference did not reach statistical significance.\u003c/p\u003e\n\u003ch3\u003eComparison of Clearance and other relevant parameters:\u003c/h3\u003e\n\u003cp\u003e Serum urea clearance was measured by comparing urea levels at initiation and after 12 hours. Data was available for 23 patients. Urea clearance was similar in both RCA and HA circuits, with a mean decline in urea levels of 6.8 mmol/L and 6.2 mmol/L over 12 hours, respectively. NA circuits, possibly due to factors such as clotting and interruptions, had a decline in urea of only 1.6 mmol/L over 12 hours.\u003c/p\u003e\u003cp\u003eAfter starting CRRT, the median rise in serum bicarbonate after 12 hours was similar in RCA, HA, and NA circuits: 2.8, 3.1, and 2.2 mmol/L, respectively. There was no significant difference in creatinine clearance at 12 hours between RCA and HA circuits, with median clearances of 55.3 mmol/L and 42.4 mmol/L, respectively (p\u0026thinsp;=\u0026thinsp;0.137).\u003c/p\u003e\u003cp\u003eThe fluid clearance or removal was calculated at 24 hours of circuit use, and the patients' estimated weight was used to calculate ml per kg per hour removal of fluid. There was a higher median fluid removal (ml/kg/hr) in RCA circuits (2.4 ml/kg/hr) compared to HA circuits (1.8 ml/kg/hr). However, this did not reach statistical significance (p\u0026thinsp;=\u0026thinsp;0.081). The data available for NA circuits were too small to compare.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe results of this study provide valuable insights into the use of citrate-based anticoagulation (RCA), heparin-based anticoagulation (HA), and no anticoagulation (NA) in paediatric continuous renal replacement therapy (CRRT). Our findings indicate that, in our cohort of paediatric patients weighing more than 8 Kg, RCA circuits lasted longer and may be a technically safer, comparable and more effective option compared to HA and NA.\u003c/p\u003e\u003cp\u003eThere was no difference in mortality between RCA and HA circuits. Overall mortality rate in our study was 33.3%, which is consistent with previously reported mortality rates in paediatric CRRT patients. Symons et al. (2013) reported a mortality rate of 34.6% in a prospective registry of paediatric CRRT patients. Similarly, Bunchman et al. (2018) reported a mortality rate of 30.8% in a review of paediatric CRRT literature [2]. Interestingly, the mortality rates were significantly higher in the NA group. The patients in NA group were sicker and clinically deemed not suitable to be anticoagulated due to the level of multiorgan failure. This is more likely explanation to the increased mortality rather than survival due to the use of no anticoagulation per se.\u003c/p\u003e\n\u003ch3\u003eCircuit Characteristics:\u003c/h3\u003e\n\u003cp\u003eOur study found that RCA circuits had a longer median lifespan (27.2 hours) compared to HA (20 hours) and NA circuits (8.2 hours). This is consistent with previous studies demonstrating the efficacy and safety of RCA in CRRT. Brophy et al. (2018) reported a median circuit lifespan of 44.6 hours in paediatric CRRT patients receiving RCA [3]. Raymakers-Jansen et al, in a small single centre paediatric study of 20 patients (14 RCA and 6 HA circuits) report median circuit life span of 45.2 hours (IQR 37.5\u0026ndash;52.8) with RCA as compared to 21 hours (IQR 14.5\u0026ndash;27.5) with HA (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). In an adult randomized control trial in Australia, Gattas et al found significantly longer median circuits life span in RCA (39.2 hrs) versus in HA (22.8 hrs) (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).The reduced need for circuit changes and lower complication rates with RCA may be due to its ability to provide regional and better titratable anticoagulation, delivering better rheology of blood flow in the CRRT circuit and reducing the risk of systemic bleeding (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eOur results showed that RCA and HA circuits had similar urea clearance and creatinine clearance rates. However, RCA circuits had higher median fluid removal rates compared to HA circuits. This is possibly attributed to less interrupted, more stable and efficient nature of CA circuits, allowing for more effective fluid removal (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Sutherland et al reported finding of prospective paediatric registry in 297 children across 13 PICUs in United States and found that that fluid overload more than 20% at initiation of CRRT was associated higher mortality (65.6%) as compared to children with 10\u0026ndash;20% (43.1%) and less than 10% fluid overload (29.4%) (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). We would like to hypothesize that the ability of RCA circuits to provide more effective fluid removal may be an important factor in improving patient outcomes, potentially making them safer (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eOur study has several limitations. Firstly, the sample size was relatively small, which may limit the generalizability of our findings. Secondly, the study was retrospective in nature, which may introduce biases in data collection and analysis. The cohort of patients was from a single tertiary care centre with no post operative congenital heart surgery patients and non-liver transplant centre. This limits the external validity of the study to such as population. However, this study reflects that even in low volume centres, RCA is feasible and demonstrates valuable technical and patient related advantages as compared to HA. Finally, we did not collect data on long-term outcomes, including post ICU discharge utilization details of IHD which would be important to assess the sustainability of CRRT benefits. However, none of the patients required another run of CRRT after discharge from PICU.\u003c/p\u003e\u003cp\u003eIn conclusion, our study suggests that citrate-based anticoagulation (RCA) may be a safer and more effective option for paediatric CRRT compared to heparin-based anticoagulation (HA) and no anticoagulation (NA). RCA circuits had longer median lifespans, required fewer changes, and had lower rates of clotting and bleeding complications. Additionally, RCA circuits had higher median fluid removal rates. Further prospective studies are needed to confirm these findings and assess long-term outcomes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFinancial Disclosure\u003c/h2\u003e\u003cp\u003eResearch data manager GL received remuneration for her time paid through Baxter Investigator Initiated Research Program- Renal Acute with reference grant number GAUS7255 for USD\u003cspan\u003e$\u003c/span\u003e31000.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKhwaja A (2012) KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract 120(4):c179\u0026ndash;c184 Epub 2012/08/15. doi: 10.1159/000339789. PubMed PMID: 22890468\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJuncos LA, Chandrashekar K, Karakala N, Baldwin I (2021) Vascular access, membranes and circuit for CRRT. Semin Dial 34(6):406\u0026ndash;415 Epub 2021/05/04. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/sdi\u003c/span\u003e\u003cspan address=\"10.1111/sdi\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTobe SW, Aujla P, Walele AA, Oliver MJ, Naimark DM, Perkins NJ et al (2003) A novel regional citrate anticoagulation protocol for CRRT using only commercially available solutions. J Crit Care 18(2):121\u0026ndash;129 Epub 2003/06/12. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1053/jcrc.2003.50006\u003c/span\u003e\u003cspan address=\"10.1053/jcrc.2003.50006\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRaymakers-Janssen P, Lilien M, van Kessel IA, Veldhoen ES, Wosten-van Asperen RM, van Gestel JPJ (2017) Citrate versus heparin anticoagulation in continuous renal replacement therapy in small children. Pediatr Nephrol 32(10):1971\u0026ndash;1978 Epub 2017/06/05. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00467-017-3694-4\u003c/span\u003e\u003cspan address=\"10.1007/s00467-017-3694-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGattas DJ, Rajbhandari D, Bradford C, Buhr H, Lo S, Bellomo R (2015) A Randomized Controlled Trial of Regional Citrate Versus Regional Heparin Anticoagulation for Continuous Renal Replacement Therapy in Critically Ill Adults. Crit Care Med 43(8):1622\u0026ndash;1629 Epub 2015/04/09. doi: 10.1097/CCM.0000000000001004. PubMed PMID: 25853591\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZaoral T, Hladik M, Zapletalova J, Travnicek B, Gelnarova E (2016) Circuit Lifetime With Citrate Versus Heparin in Pediatric Continuous Venovenous Hemodialysis. Pediatr Crit Care Med 17(9):e399\u0026ndash;405 Epub 2016/07/19. doi: 10.1097/PCC.0000000000000860. PubMed PMID: 27427878\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSutherland SM, Zappitelli M, Alexander SR, Chua AN, Brophy PD, Bunchman TE et al (2010) Fluid overload and mortality in children receiving continuous renal replacement therapy: the prospective pediatric continuous renal replacement therapy registry. Am J Kidney Dis 55(2):316\u0026ndash;325 Epub 2010/01/01. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1053/j.ajkd.2009.10.048\u003c/span\u003e\u003cspan address=\"10.1053/j.ajkd.2009.10.048\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBunchman TE (2016) Anticoagulation in Continuous Renal Replacement Therapy: Citrate Appears to Be Superior to Heparin! Pediatr Crit Care Med 17(9):894\u0026ndash;895 Epub 2016/09/02. 10.1097\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\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\u003eDemographics of patients\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\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\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRCA\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eHA\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eAll\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003en (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e42\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMedian age (months)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e48\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e54\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMedian baseline weight (kg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale/Female\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10/8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8/8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2/6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e20/22\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal circuits used (Median circuits per patient)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e36 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e53* (3.31)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e107\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePIM 2 score, mean (SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5.93 (6.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.32 (13.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16.0 (13.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e8.32 (11.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePIM 3 score, mean (SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.91 (4.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.86 (13.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e20.8 (13.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e8.91 (12.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIndividual Circuit median time, hrs (n) (SE Mean)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e27 (36) (3.18)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18 (53) (3.06)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e21.5 (18) (5.88)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e22 (107) (2.15)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal CRRT time, median (hrs)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e68.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e64.17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e19.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePICU LOS, median (hrs)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTBC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTBC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTBC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTBC\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDeaths (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (22.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (25%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 (75%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e14/42 (33%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eRCA\u0026thinsp;=\u0026thinsp;Regional Citrate Anticoagulation; HA\u0026thinsp;=\u0026thinsp;Heparin based Anticoagulation ; NA\u0026thinsp;=\u0026thinsp;No Anticoagulation; IQR\u0026thinsp;=\u0026thinsp;Inter Quartile Range; PICU LOS\u0026thinsp;=\u0026thinsp;Paediatric ICU Length of Stay; HOS LOS\u0026thinsp;=\u0026thinsp;Hospital Length of Stay; * = 2 circuits had heparin anticoagulation along with protamine reversal\u0026rsquo; some data available in 52 circuits\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eTBC: To be Confirmed with data manager\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\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\u003e\u003cb\u003eCRRT circuits and vascular Catheter characteristics\u003c/b\u003e\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eType of Anticoagulation\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRCA (18)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eHA (16)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNA (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eAll\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCircuit sizes\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\u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHF 20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e17\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eST 60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e17\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eST 100\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eVascular catheter Size\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\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e6.5 F double lumen\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e8 F double lumen\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e11 F double lumen\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e12 F triple lumen\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e13 F triple lumen\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e14 F triple lumen\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eRCA\u0026thinsp;=\u0026thinsp;Regional Citrate Anticoagulation; HA\u0026thinsp;=\u0026thinsp;Heparin based Anticoagulation; NA\u0026thinsp;=\u0026thinsp;No Anticoagulation\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\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\u003eIndications for CRRT and mortality\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\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\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIndications for CRRT\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRCA (deaths)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eHA (deaths)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNA (deaths)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTotal (deaths)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSepsis or Shock\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e19 (10)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAcute Renal Failure\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e15 (0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAcute Liver Failure\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\u003cp\u003e2 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIntoxication or poisoning\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4 (0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMiscellaneous other\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\u003cp\u003e2 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHospital Mortality, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4/18 (22.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4/16 (25%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6/8 (75%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e14/42 (33.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eRCA\u0026thinsp;=\u0026thinsp;Regional Citrate Anticoagulation; HA\u0026thinsp;=\u0026thinsp;Heparin based Anticoagulation; NA\u0026thinsp;=\u0026thinsp;No Anticoagulation\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\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\u003eReasons for therapy requiring circuit change before completion of 72 hours\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\u003eComplications of Therapy\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRCA\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eHA\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eClotting of circuit\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8/36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14/52\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14/18\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSignificant Bleeding\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\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5/18\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVascular catheter replacement required\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCalcium instability\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMetabolic alkalosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\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\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTotal\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eRCA\u0026thinsp;=\u0026thinsp;Regional Citrate Anticoagulation; HA\u0026thinsp;=\u0026thinsp;Heparin based Anticoagulation; NA\u0026thinsp;=\u0026thinsp;No Anticoagulation\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Paediatric Renal Replacement Therapy, Regional Citrate Anticoagulation, Heparin anticoagulation, CRRT, PRISMAX","lastPublishedDoi":"10.21203/rs.3.rs-7952360/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7952360/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground \u0026amp; Objective: \u003c/strong\u003eThis is a single centre retrospective cohort study over period of 9 years of comparing regional citrate anticoagulation (RCA) vs heparin (HA) or no anticoagulation (NA) strategy in a paediatric intensive care patients using continuous renal replacement therapy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eA total of 107 CRRT circuits were used to deliver continuous renal replacement therapy to 42 children weighing at least 8 kg. Overall mortality was 14 out of 42 (33.3%); similar between the RCA (22.2%, 4/18) and HA (25%, 4/16) group. Sepsis or shock was the most common indication for CRRT followed by acute kidney injury in both the groups. A single circuit was sufficient to complete the required CRRT therapy with RCA in 8 out of 14 children (57.1%), compared to only 3 out of 12 children (25%) with HA. The median number of circuits required per patient was 2 in the RCA group and 3.3 in the HA group. The median circuit lifespan was highest in RCA circuits, 27 hours (SD ± 3 hours), followed by HA circuits at 20 hours (SD ± 3.2 hours) and shortest in NA circuits, 8.2 hours (SD ± 4.2 hours). Clots was commonest reason leading to circuit changes and occurred in 8 out of 36 (22.2%) RCA circuits, 14 out of 52 (26.9%) HA circuits, and 8 out of 18 (44.4%) NA circuits.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eIn our study, RCA circuits had longer median lifespans, required fewer changes, and had lower rates of clotting and bleeding complications. However, due to small sample size results were not statistically significant.\u003c/p\u003e","manuscriptTitle":"Comparison of Regional Citrate Anticoagulation (RCA) with Heparin (HA) or No (NA) anticoagulation strategy in paediatric intensive care patients receiving continuous renal replacement therapy: A 9-year single centre tertiary cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-14 11:31:11","doi":"10.21203/rs.3.rs-7952360/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2d9f6336-9017-4535-8d35-472766b35d47","owner":[],"postedDate":"November 14th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-26T17:26:55+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-14 11:31:11","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7952360","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7952360","identity":"rs-7952360","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}