Continuous venovenous haemofiltration with citrate-buffered replacement solution is safe and efficacious in patients with a bleeding tendency: a prospective observational study

BMC Nephrology

AB Johan Groeneveld²  Pieter M ter Wee¹  Gul Yldirim²  Marc G Vervloet¹  Borefore P Jallah²  Shaikh A Nurmohamed¹ 

[1]Departments of Nephrology, VU University Medical Centre, Amsterdam, The Netherlands

[2]Departments of Intensive Care, VU University Medical Centre, Amsterdam, The Netherlands

关键词: Safety;    Efficacy;    Replacement solution;    Citrate;    Continuous venovenous haemofiltration;   

Others  :  1082950
DOI  :  10.1186/1471-2369-14-89

 received in 2012-10-15, accepted in 2013-04-09,  发布年份 2013

【 摘 要 】

Background

There is ongoing controversy concerning optimum anticoagulation and buffering in continuous venovenous haemofiltration (CVVH). Regional anticoagulation with trisodium citrate also acting as a buffer in the replacement fluid has several advantages and disadvantages over prefilter citrate administration alone. We analysed a large cohort of patients with acute kidney injury (AKI) treated by the former method and hypothesized that it is safe and efficacious.

Methods

Patients admitted at the intensive care unit with AKI and a high bleeding risk, without exclusion of liver disease, treated by CVVH with citrate in a custom-made replacement solution were prospectively included. Patient and CVVH characteristics, including citrate accumulation, were evaluated in outcome groups. A standardized mortality rate (SMR) was calculated using the simplified acute physiology score II.

Results

Ninety-seven patients were included; metabolic control was adequate and did not differ between outcome groups, apart from lower pH/bicarbonate in non-survivors. Citrate accumulation was proven in 9% and was timely identified. These patients had about threefold higher plasma transaminases and higher CVVH dose and mortality. The hospital mortality was 60% with a SMR of 1.1 (95% confidence interval 0.90-1.40): age and hyperlactatemia, rather than CVVH-characteristics and citrate accumulation, predicted mortality in multivariable analysis.

Conclusion

In critically ill, patients with AKI at high risk of bleeding, CVVH with citrate-containing replacement solution is safe and efficacious. The risk for citrate accumulation is 9% and best predicted by levels of transaminases. It carries, when citrate is discontinued, no attributable mortality.

【 授权许可】

   
2013 Nurmohamed et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】

• [1]Oudemans-van Straaten HM, Kellum JA, Bellomo R: Clinical review: anticoagulation for continuous renal replacement therapy – heparin or citrate? Crit Care 2011, 15:202.
• [2]Mehta RL, McDonald BR, Aguilar MM, Ward DM: Regional citrate anticoagulation for continuous arteriovenous hemodialysis in critically ill patients. Kidney Int 1990, 38:976-981.
• [3]Palsson R, Niles JL: Regional citrate anticoagulation in continuous venovenous hemofiltration in critically ill patients with a high risk of bleeding. Kidney Int 1999, 55:1991-1997.
• [4]Kutsogiannis DJ, Mayers I, Chin WDN, Gibney RTN: Regional citrate anticoagulation in continuous venovenous hemodiafiltration. Am J Kidney Dis 2000, 35:802-811.
• [5]Tolwani AJ, Campbell RC, Schenk MB, Allon M, Warnock DG: Simplified citrate anticoagulation for continuous renal replacement therapy. Kidney Int 2001, 60:370-374.
• [6]Hofmann RM, Maloney C, Ward DM, Becker BN: A novel method for regional citrate anticoagulation in continuous venovenous hemofiltration (CVVHF). Ren Fail 2002, 24:325-335.
• [7]Gabutti L, Marone C, Colucci G, Duchini F, Schonholzer C: Citrate anticoagulation in continuous venovenous hemodiafiltration: a metabolic challenge. Intensive Care Med 2002, 28:1419-1425.
• [8]Kramer L, Bauer E, Joukhadar C, Strobl W, Gendo A, Madl C, Gangl A: Citrate pharmacokinetics and metabolism in cirrhotic and noncirrhotic critically ill patients. Crit Care Med 2003, 31:2450-2455.
• [9]Mitchell A, Daul AE, Beiderlinden M, Schäfers RF, Heemann U, Kribben A, Peters J, Philipp T, Wenzel RR: A new system for regional citrate anticoagulation in continuous venovenous hemodialysis (CVVHD). Clin Nephrol 2003, 59:106-114.
• [10]Bihorac A, Ross EA: Continuous venovenous hemofiltration with citrate-based replacement fluid: efficacy, safety, and impact on nutrition. Am J Kidney Dis 2005, 46:908-918.
• [11]Naka T, Egi M, Bellomo R, Cole L, French C, Botha J, Wan L, Fealy N, Baldwin I: Low-dose citrate continuous veno-venous hemofiltration (CVVH) and acid–base balance. Int J Artif Organs 2005, 28:222-228.
• [12]Schmitz M, Taskaya G, Plum J, Hennersdorf M, Sucker C, Grabensee B, Hetzel GR: Continuous venovenous haemofiltration using a citrate buffered substitution fluid. Anaesth Intensive Care 2007, 35:529-535.
• [13]Durão MS, Monte JCM, Batista MC, Oliveira M, Iizuka IJ, Santos BF, Pereira VG, Cendoroglo M, Santos OFP: The use of regional citrate anticoagulation for continuous venovenous hemodiafiltration in acute kidney injury. Crit Care Med 2008, 36:3024-3029.
• [14]Morgera S, Schneider M, Slowinski T, Varrgas-Hein O, Zuckermann-Becker H, Peters H, Kindgen-Milles D, Neumayer H-H: A safe anticoagulation protocol with variable treatment efficacy and excellent control of acid–base status. Crit Care Med 2009, 37:2018-2024.
• [15]Oudemans-van Straaten HM, Bosman RJ, Koopmans M, van der Voort PH, Wester JP, van der Spoel JI, Dijksman LM, Zandstra DF: Citrate anticoagulation for continuous venovenous hemofiltration. Crit Care Med 2009, 37:545-552.
• [16]Hetzel GR, Schmitz M, Wissing H, Ries W, Schott G, Heering PJ, Isgro F, Kribben A, Himmele R, Grabensee B, Rump LC: Regional citrate versus systemic heparin for anticoagulation in critically ill patients on continuous venovenous haemofiltration: a prospective randomized multicentre trial. Nephrol Dial Transplant 2011, 26:232-239.
• [17]Link A, Klingele M, Speer T, Pöss J, Lerner-Gräber A, Fliser D: Total-to ionized calcium ratio predicts mortality in continuous renal replacement therapy with citrate anticoagulation in critically ill patients. Crit Care 2012, 16:R97. BioMed Central Full Text
• [18]Morabito S, Pistolesi V, Tritapepe L, Zeppilli L, Polistena F, Strampelli E, Pierucci A: Regional citrate anticoagulation in cardiac surgery patients at high risk of bleeding: a continuous veno-venous hemofiltration protocol with a low concentration citrate solution. Crit Care 2012, 27:R111.
• [19]Meier-Kriesche HU, Finkel KW, Gitomer JJ, DuBose TD: Unexpected severe hypocalcemia during continuous venovenous hemodialysis with regional citrate anticoagulation. Am J Kidney Dis 1999, 33:1-4.
• [20]Meier-Kriesche HU, Gitomer J, Finkel K, DuBose T: Increased total to ionized calcium ratio during continuous venovenous hemodialysis with regional citrate anticoagulation. Crit Care Med 2001, 29:748-752.
• [21]Ter Veldhuis SMJ, Wolthuis A, Bakker AJ, Van der Voort PHJ: Citrate, calcium, parathyroid hormone and anion gap in a patient with citrate intoxication during citrate based CVVH. Neth J Crit Care 2006, 10:74-76.
• [22]Kelleher SP, Schulman G: Severe metabolic alkalosis complicating regional citrate hemodialysis. Am J Kidney Dis 1987, IX:235-236.
• [23]Silverstein FJ, Oster JR, Perez GO, Materson BJ, Lopez RA, Al-Reshaid K: Metabolic alkalosis induced by regional citrate hemodialysis. ASAIO Trans 1989, 35:22-25.
• [24]Thoenen M, Schmid ER, Binswanger U, Schuepbach R, Aerne D, Schmidlin D: Regional citrate anticoagulation using a citrate-based substitution solution for continuous venovenous hemofiltration in cardiac surgery patients. Wien Klin Wochenschr 2002, 114:108-114.
• [25]Nurmohamed SA, Vervloet MG, Girbes AR, Ter Wee PM, Groeneveld AB: Continuous venovenous hemofiltration with or without predilution regional citrate anticoagulation: a prospective study. Blood Purif 2007, 25:316-323.
• [26]Aman J, Nurmohamed SA, Vervloet MG, Groeneveld AB: Metabolic effects of citrate- vs bicarbonate-based substitution fluid in continuous venovenous hemofiltration: a prospective sequential cohort study. J Crit Care 2010, 25:120-127.
• [27]Wu MY, Hsu YH, Bai CH, Lin YF, Wu CH, Tam KW: Regional citrate versus heparin anticoagulation for continuous renal replacement therapy: a meta-analysis of randomized controlled trials. Am J Kidney Dis 2012, 59:810-818.
• [28]Zhang Z, Hongying N: Efficacy and safety of regional citrate anticoagulation in critically ill patients undergoing continuous renal replacement therapy. Intensive Care Med 2012, 38:20-28.
• [29]Nurmohamed SA, Jallah BP, Vervloet MG, Beishuizen A, Groeneveld AB: Predilution versus postdilution continuous venovenous hemofiltration: no effect on filter life and azotemic control in critically ill patients on heparin. ASAIO J 2011, 57:48-52.