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502 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E

Research vignette
Bagshaw SM, Laupland KB, Boiteau PJ, Godinez-Luna T. Is regional data, along with details of the CRRT filter start and stop times, type
citrate superior to systemic heparin anticoagulation for continuous of anticoagulation and complications, were obtained. The study
renal replacement therapy? A prospective observational study in describes in detail the protocol for anticoagulation with both sys-
an adult regional critical care system. Journal of Critical Care 2005; temic heparin and regional citrate. This protocol had been imple-
20: 155–61. mented for approximately 3 years prior to the study, so the staff
involved have considerable experience using this protocol. All
Abstract patients received CRRT by the same CRRT machine. By protocol,
Purpose CVVH was the only modality used with systemic heparin, whereas
Continuous renal replacement therapy (CRRT) is commonly used for regional citrate the only modality was CVVHDf.
in the care of critically ill patients, although the optimal means of
anticoagulation is not well defined. We report on our regional CRRT The primary outcome measure was filter circuit lifespan (hours).
protocol that was developed using the principles of quality The difference in filter circuit lifespan between systemic heparin
improvement and compare the effect of regional citrate with sys- and regional citrate anticoagulation was analysed using the non-
temic heparin anticoagulation on filter lifespan. parametric Mann–Whitney U test, reported as median (interquar-
tile range) and Kaplan–Meier survival time. There were 212 filters
Materials and methods assessed in the citrate group and 97 in the heparin group. The
Prospective observational cohort study in a Canadian adult median time to failure was 40 hours and 20 hours for citrate and
regional critical care system. A standardised protocol for CRRT has heparin respectively. Further analysis considered the proportion of
been implemented at all adult intensive care units in the Calgary filter circuits reaching a lifespan >72 and <24 hours. The reasons
Health Region since August 1999. All patients with acute renal for filter circuit failure or discontinuation were also reported for
failure treated with CRRT during 1 October 2002 to 30 September 11,427 hours of CRRT. Several previous studies were reviewed and
2003, were identified and followed up prospectively until hospital compared with the findings of this study in a discussion highlight-
discharge or death. ing some very important points.

Results The evidence from this study favours the use of regional citrate as
Eighty-seven patients with acute renal failure requiring CRRT were the primary anticoagulant during CRRT; however, the authors
identified, 54 were initially treated with citrate, 29 with heparin, suggest that further study is warranted in the form of a randomised
and 4 with saline flushes. Citrate and heparin were used in 212 clinical trial. This study also suggests that the use of citrate may
(66%) and 97 (30%) of filters for 8776 and 2651 hours of CRRT, result in fewer bleeding episodes and the need for transfusions due
respectively. Overall median (interquartile range) filter lifespan to more reliable filter circuit lifespan, and a reduced time off CRRT.
with citrate was significantly greater than heparin (40 [14–72] vs 20 The implications for this are decreased nursing workload; however,
[5–44] hours, P < 0.001). Citrate anticoagulation resulted in greater the authors did not collect data specifically on these outcomes.
completion of scheduled filter life span (59% vs 10%, P < 0.001).
Citrate anticoagulation was well tolerated with no patient requir- While not a randomised comparison of systemic heparin and
ing elective discontinuation for hypernatraemia, metabolic alkalo- regional citrate anticoagulation, this study does have a few
sis, or hypocalcaemia. strengths. Specifically, it included patients from several centres in
which this protocol is used, and assessed a large total number of
Conclusions filter circuits. However, the study does have limitations. One pos-
Regional citrate anticoagulation was associated with prolonged sible weakness of an observational study is the inability to control
filter survival and increased completion of scheduled filter lifespan for ‘other’ confounding factors influencing filter lifespan, such as
compared with heparin. These data support small studies suggest- the CRRT modality or type and position of vascular access catheter
ing that citrate is a superior anticoagulant for CRRT and suggest where blood flow failure may have occurred. In addition, the study
the need for a future definitive randomised controlled trial. did not incorporate data on individual filter transmembrane pres-
sure (TMP) and selected patient-related factors (e.g. haematocrit,
Critique activated partial thromboplastin time). Finally, it did not integrate
This study was conducted in a single health region in Canada potentially important outcomes, such as clinically relevant throm-
(population ~1 million) where a standardised CRRT protocol for bocytopenia, bleeding episodes, need for blood product transfu-
management of ARF has been implemented. In a prospective sion or overall cost.
observational cohort design, patients were provided with either
systemic heparin or regional citrate anticoagulation during CRRT, Overall, this study is an important contribution to understanding
and filter circuit ‘lifespan’ was compared. Data were collected from methods for anticoagulation during CRRT, is useful reading and is
three adult multidisciplinary ICUs between October 2002 and very relevant to complement the information provided in this
September 2003. Patient demographic, clinical and laboratory chapter.