Randomised trial of software algorithm driven regional citrate anticoagulation versus heparin in continuous renal replacement therapy: the Filter Life in Renal Replacement Therapy pilot trial

Matthew Joseph Brain, Owen Roodenburg, Natalie Adams, Phoebe McCracken, Lisen Emma Hockings, Steven Musgrave, Warwick Butt, Carlos D Scheinkestel

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Abstract

The effectiveness of continuous renal replacement therapy (CRRT) increases when unplanned circuit failure is prevented. Adequate anticoagulation is an important component. Although heparin is the predominating anticoagulant, calcium chelation with citrate is an alternative, but systemic calcium monitoring and supplementation increase the complexity of CRRT. We assessed efficacy and safety of citrate delivery via integrated software algorithms against an established regional heparin protocol. Prospective computer randomisation allocated eligible patients to regional citrate or heparin between April and December 2012. Citrate fluids were Prismocitrate 18 mmol/L predilution and Prism0cal B22 dialysate. Hemosol B0 was the default fluid for heparin. The primary outcome was filter running time. Electively terminated circuits were censored. Intention-totreat (ITT) and per-protocol analyses were performed. Filter survival was compared by log-rank tests and hazard ratios were explored with a mixed-effects Cox model. 221 filters were analysed from 30 patients (of whom 19 were randomly allocated to citrate filters and 11 to heparin filters). Patients randomly allocated to citrate were older, sicker, with a higher male:female ratio, but of similar weight. Mortality was 37 in the citrate arm and 27 in the heparin arm. All deaths were attributed to underlying disease. Significant crossover occurred from the citrate arm to use of heparin. Median filter survival, by ITT, was not significantly different (citrate, 34 hours; heparin, 30.7 hours; P=0.58). Per-protocol survival favoured citrate (citrate, 42.1 hours; heparin, 24 hours; ?(2)=8.1; P=0.004). Considerable variation in filter life existed between patients, and between vascular access sites within patients. Safety end points were reached in one heparin and three citrate patients. Although the per-protocol results favoured citrate when it was actually delivered, the significant crossover between treatment arms hampered more definitive conclusions. Until further studies support improved patient outcomes, increased complexity and complications suggest that anticoagulation choice be made using patient-specific indications.
Original languageEnglish
Pages (from-to)131 - 137
Number of pages7
JournalCritical Care and Resuscitation
Volume16
Issue number2
Publication statusPublished - 2014

Cite this

@article{9e8ed8a80cbf4bc2afb5bfcc008be3c9,
title = "Randomised trial of software algorithm driven regional citrate anticoagulation versus heparin in continuous renal replacement therapy: the Filter Life in Renal Replacement Therapy pilot trial",
abstract = "The effectiveness of continuous renal replacement therapy (CRRT) increases when unplanned circuit failure is prevented. Adequate anticoagulation is an important component. Although heparin is the predominating anticoagulant, calcium chelation with citrate is an alternative, but systemic calcium monitoring and supplementation increase the complexity of CRRT. We assessed efficacy and safety of citrate delivery via integrated software algorithms against an established regional heparin protocol. Prospective computer randomisation allocated eligible patients to regional citrate or heparin between April and December 2012. Citrate fluids were Prismocitrate 18 mmol/L predilution and Prism0cal B22 dialysate. Hemosol B0 was the default fluid for heparin. The primary outcome was filter running time. Electively terminated circuits were censored. Intention-totreat (ITT) and per-protocol analyses were performed. Filter survival was compared by log-rank tests and hazard ratios were explored with a mixed-effects Cox model. 221 filters were analysed from 30 patients (of whom 19 were randomly allocated to citrate filters and 11 to heparin filters). Patients randomly allocated to citrate were older, sicker, with a higher male:female ratio, but of similar weight. Mortality was 37 in the citrate arm and 27 in the heparin arm. All deaths were attributed to underlying disease. Significant crossover occurred from the citrate arm to use of heparin. Median filter survival, by ITT, was not significantly different (citrate, 34 hours; heparin, 30.7 hours; P=0.58). Per-protocol survival favoured citrate (citrate, 42.1 hours; heparin, 24 hours; ?(2)=8.1; P=0.004). Considerable variation in filter life existed between patients, and between vascular access sites within patients. Safety end points were reached in one heparin and three citrate patients. Although the per-protocol results favoured citrate when it was actually delivered, the significant crossover between treatment arms hampered more definitive conclusions. Until further studies support improved patient outcomes, increased complexity and complications suggest that anticoagulation choice be made using patient-specific indications.",
author = "Brain, {Matthew Joseph} and Owen Roodenburg and Natalie Adams and Phoebe McCracken and Hockings, {Lisen Emma} and Steven Musgrave and Warwick Butt and Scheinkestel, {Carlos D}",
year = "2014",
language = "English",
volume = "16",
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journal = "Critical Care and Resuscitation",
issn = "1441-2772",
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Randomised trial of software algorithm driven regional citrate anticoagulation versus heparin in continuous renal replacement therapy: the Filter Life in Renal Replacement Therapy pilot trial. / Brain, Matthew Joseph; Roodenburg, Owen; Adams, Natalie; McCracken, Phoebe; Hockings, Lisen Emma; Musgrave, Steven; Butt, Warwick; Scheinkestel, Carlos D.

In: Critical Care and Resuscitation, Vol. 16, No. 2, 2014, p. 131 - 137.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Brain, Matthew Joseph

AU - Roodenburg, Owen

AU - Adams, Natalie

AU - McCracken, Phoebe

AU - Hockings, Lisen Emma

AU - Musgrave, Steven

AU - Butt, Warwick

AU - Scheinkestel, Carlos D

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