Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Critical Care
Published in: Critical Care 1/2019

Open Access 01-12-2019 | Metabolic Alkalosis | Research

Safety and efficacy of regional citrate anticoagulation for continuous renal replacement therapy in liver failure patients: a systematic review and meta-analysis

Authors: Wei Zhang, Ming Bai, Yan Yu, Lu Li, Lijuan Zhao, Shiren Sun, Xiangmei Chen

Published in: Critical Care | Issue 1/2019

Login to get access

Abstract

Background

Regional citrate anticoagulation (RCA) is a widely used strategy for continuous renal replacement therapy (CRRT). Most of the current guidelines recommend liver failure as one of the contraindications for citrate anticoagulation. However, some studies suggested that the use of citrate for CRRT in liver failure patients did not increase the risk of citrate-related complications. The purpose of this systematic review is to summarize the current evidences on the safety and efficacy of RCA for CRRT in liver failure patients.

Methods

We performed a comprehensive search on PubMed, Embase, and the Cochrane Library databases from the inception to March 1, 2018. Studies enrolled adult (age > 18 years) patients with various levels of liver dysfunction underwent RCA-CRRT were included in this systematic review.

Results

After the study screening, 10 observational studies with 1241 liver dysfunction patients were included in this systematic review. The pooled rate of citrate accumulation and bleeding was 12% [3%, 22%] and 5% [2%, 8%], respectively. Compared with the baseline data, the serum pH, bicarbonate, and base excess (BE), the rate of metabolic alkalosis, the serum ionized calcium (ionCa) and total calcium (totCa) level, and the ratio of total calcium/ionized calcium (totCa/ionCa) significantly increased at the end of observation. However, no significant increase was observed in serum citrate (MD − 65.82 [− 194.19, 62.55]), lactate (MD 0.49 [− 0.27, 1.26]) and total bilirubin concentration (MD 0.79 [− 0.70, 2.29]) at the end of CRRT. Compared with non-liver failure patients, the live failure patients showed no significant difference in the pH (MD − 0.04 [− 0.13, 0.05]), serum lactate level (MD 0.69 [− 0.26, 1.64]), and totCa/ionCa ratio (MD 0.03 [− 0.12, 0.18]) during CRRT. The median of mean filter lifespan was 55.9 h, with a range from 22.7 to 72 h.

Conclusions

Regional citrate anticoagulation seems to be a safe anticoagulation method in liver failure patients underwent CRRT and could yield a favorable filter lifespan. Closely monitoring the acid base status and electrolyte balance may be more necessary during RCA-CRRT in patients with liver failure.
Appendix
Available only for authorised users
Literature
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.PubMedPubMedCentralCrossRef
2.
Liu C, Mao Z, Kang H, Hu J, Zhou F. Regional citrate versus heparin anticoagulation for continuous renal replacement therapy in critically ill patients: a meta-analysis with trial sequential analysis of randomized controlled trials. Crit Care. 2016;20:144.PubMedPubMedCentralCrossRef
3.
Apsner R, Schwarzenhofer M, Derfler K, Zauner C, Ratheiser K, Kranz A. Impairment of citrate metabolism in acute hepatic failure. Wien Klin Wochenschr. 1997;109:123–7.PubMed
4.
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;29:748–52.PubMedCrossRef
5.
Kramer L, Bauer E, Joukhadar C, Strobl W, Gendo A, Madl C, et al. Citrate pharmacokinetics and metabolism in cirrhotic and noncirrhotic critically ill patients. Crit Care Med. 2003;31:2450–5.PubMedCrossRef
6.
Kidney Disease. Improving global outcomes (KDIGO) acute kidney injury work group. KDIGO clinical practice guidelines for acute kidney injury. Kidney Int Suppl. 2012;2:1–138.CrossRef
7.
Chen X. Anticoagulation in blood purification: contraindications. In: Sun X, Ding X, Liu F, Liu Z, Chen J, Mei C, editors. Blood purification standard operating procedure (SOP). Beijing: PEOPLE'S MILITARY MEDICAL PRESS; 2010. p. 45.
8.
Link A, Klingele M, Speer T, Rbah R, Poss J, Lerner-Graber A, et al. Total-to-ionized calcium ratio predicts mortality in continuous renal replacement therapy with citrate anticoagulation in critically ill patients. Crit Care. 2012;16:R97.PubMedPubMedCentralCrossRef
9.
Schultheiss C, Saugel B, Phillip V, Thies P, Noe S, Mayr U, et al. Continuous venovenous hemodialysis with regional citrate anticoagulation in patients with liver failure: a prospective observational study. Crit Care. 2012;16:R162.PubMedPubMedCentralCrossRef
10.
Lahmer T, Messer M, Rasch S, Beitz A, Schnappauf C, Schmid RM, et al. Sustained low-efficiency dialysis with regional citrate anticoagulation in medical intensive care unit patients with liver failure: a prospective study. J Crit Care. 2015;30:1096–100.PubMedCrossRef
11.
Slowinski T, Morgera S, Joannidis M, Henneberg T, Stocker R, Helset E, et al. Safety and efficacy of regional citrate anticoagulation in continuous venovenous hemodialysis in the presence of liver failure: the Liver Citrate Anticoagulation Threshold (L-CAT) observational study. Crit Care. 2015;19:349.PubMedPubMedCentralCrossRef
12.
13.
Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014;14:135.PubMedPubMedCentralCrossRef
14.
15.
16.
Wonnacott R, Josephs B, Jamieson J. CRRT regional anticoagulation using citrate in the liver failure and liver transplant population. Crit Care Nurs Q. 2016;39:241–51.PubMedCrossRef
17.
Pertica N, Cicciarella L, Carraro A, Montin U, Violi P, Lupo A, et al. Safety and efficacy of citrate anticoagulation for continuous renal replacement therapy for acute kidney injury after liver transplantation: a single-center experience. Transplant Proc. 2017;49:674–6.PubMedCrossRef
18.
Sponholz C, Settmacher U, Bauer M, Kortgen A. Regional citrate anticoagulation for continuous renal replacement therapy in the perioperative care of liver transplant recipients: a single center experience. Ther Apher Dial. 2015;19:8–15.PubMedCrossRef
19.
Durao MS, Monte JC, Batista MC, Oliveira M, Iizuka IJ, Santos BF, et al. The use of regional citrate anticoagulation for continuous venovenous hemodiafiltration in acute kidney injury. Crit Care Med. 2008;36:3024–9.PubMedCrossRef
20.
De Vico P, Messino V, Tartaglione A, Beccaris C, Buonomo C, Talarico D, et al. Safety and efficacy of citrate anti-coagulation continuous renal replacement therapies in post-cardiac surgery patients with liver dysfunction. Ther Apher Dial. 2015;19:272–8.PubMedCrossRef
21.
Saner FH, Treckmann JW, Geis A, Losch C, Witzke O, Canbay A, et al. Efficacy and safety of regional citrate anticoagulation in liver transplant patients requiring post-operative renal replacement therapy. Nephrol Dial Transplant. 2012;27:1651–7.PubMedCrossRef
22.
Balogun RA, Turgut F, Caldwell S, Abdel-Rahman EM. Regional citrate anticoagulation in critically ill patients with liver and kidney failure. J Nephrol. 2012;25:113–9.PubMedCrossRef
23.
Klingele M, Stadler T, Fliser D, Speer T, Groesdonk HV, Raddatz A. Long-term continuous renal replacement therapy and anticoagulation with citrate in critically ill patients with severe liver dysfunction. Crit Care. 2017;21:294.PubMedPubMedCentralCrossRef
24.
Yu Y, Peng S, Cen Z, Cai J, Wang W, Tang Y, et al. Applying regional citrate anticoagulation in continuous renal replacement therapy for acute kidney injury patients with acute liver dysfunction: a retrospective observational study. Kidney Blood Press Res. 2018;43:1065–74.PubMedCrossRef
25.
Amitrano L, Guardascione MA, Brancaccio V, Balzano A. Coagulation disorders in liver disease. Semin Liver Dis. 2002;22(1):83–96.PubMedCrossRef
26.
Tripodi A, Primignani M, Chantarangkul V, Dell'Era A, Clerici M, de Franchis R, et al. An imbalance of pro- vs anti-coagulation factors in plasma from patients with cirrhosis. Gastroenterology. 2009;137:2105–11.PubMedCrossRef
27.
Tripodi A, Primignani M, Lemma L, Chantarangkul V, Dell'Era A, Iannuzzi F, et al. Detection of the imbalance of procoagulant versus anticoagulant factors in cirrhosis by a simple laboratory method. Hepatology. 2010;52:249–55.PubMedCrossRef
28.
Agarwal B, Shaw S, Shankar Hari M, Burroughs AK, Davenport A. Continuous renal replacement therapy (CRRT) in patients with liver disease: is circuit life different? J Hepatol. 2009;51:504–9.PubMedCrossRef
29.
Chua HR, Baldwin I, Bailey M, Subramaniam A, Bellomo R. Circuit lifespan during continuous renal replacement therapy for combined liver and kidney failure. J Crit Care. 2012;27:744.e747–15.
30.
Mehta RL, McDonald BR, Aguilar MM, Ward DM. Regional citrate anticoagulation for continuous arteriovenous hemodialysis in critically ill patients. Kidney Int. 1990;38:976–81.PubMedCrossRef
31.
Palsson R, Niles JL. Regional citrate anticoagulation in continuous venovenous hemofiltration in critically ill patients with a high risk of bleeding. Kidney Int. 1999;55:1991–7.PubMedCrossRef
32.
Kutsogiannis DJ, Mayers I, Chin WD, Gibney RT. Regional citrate anticoagulation in continuous venovenous hemodiafiltration. Am J Kidney Dis. 2000;35:802–11.PubMedCrossRef
33.
Gabutti L, Marone C, Colucci G, Duchini F, Schonholzer C. Citrate anticoagulation in continuous venovenous hemodiafiltration: a metabolic challenge. Intensive Care Med. 2002;28:1419–25.PubMedCrossRef
34.
Monchi M, Berghmans D, Ledoux D, Canivet JL, Dubois B, Damas P. Citrate vs. heparin for anticoagulation in continuous venovenous hemofiltration: a prospective randomized study. Intensive Care Med. 2004;30:260–5.PubMedCrossRef
35.
Stucker F, Ponte B, Tataw J, Martin PY, Wozniak H, Pugin J, et al. Efficacy and safety of citrate-based anticoagulation compared to heparin in patients with acute kidney injury requiring continuous renal replacement therapy: a randomized controlled trial. Crit Care. 2015;19:91.PubMedPubMedCentralCrossRef
36.
Simpson DP. Citrate excretion: a window on renal metabolism. Am J Phys. 1983;244:F223–34.
37.
Mariano F, Morselli M, Bergamo D, Hollo Z, Scella S, Maio M, et al. Blood and ultrafiltrate dosage of citrate as a useful and routine tool during continuous venovenous haemodiafiltration in septic shock patients. Nephrol Dial Transplant. 2011;26:3882–8.PubMedCrossRef
38.
Khadzhynov D, Schelter C, Lieker I, Mika A, Staeck O, Neumayer HH, et al. Incidence and outcome of metabolic disarrangements consistent with citrate accumulation in critically ill patients undergoing continuous venovenous hemodialysis with regional citrate anticoagulation. J Crit Care. 2014;29:265–71.PubMedCrossRef
39.
Zheng Y, Xu Z, Zhu Q, Liu J, Qian J, You H, et al. Citrate pharmacokinetics in critically ill patients with acute kidney injury. PLoS One. 2013;8:e65992.PubMedPubMedCentralCrossRef
40.
41.
Mehta RL, McDonald BR, Ward DM. Regional citrate anticoagulation for continuous arteriovenous hemodialysis. An update after 12 month. Contrib Nephrol. 1991;93:210–4.PubMedCrossRef
42.
Morgera S, Scholle C, Voss G, Haase M, Vargas-Hein O, Krausch D, et al. Metabolic complications during regional citrate anticoagulation in continuous venovenous hemodialysis: single-center experience. Nephron Clin Pract. 2004;97:c131–6.PubMedCrossRef
43.
Diaz J, Acosta F, Parrilla P, Sansano T, Contreras RF, Bueno FS, et al. Correlation among ionized calcium, citrate, and total calcium levels during hepatic transplantation. Clin Biochem. 1995;28:315–7.PubMedCrossRef
44.
Llach F, Weidmann P, Reinhart R, Maxwell MH, Coburn JW, Massry SG. Effect of acute and long-standing hypocalcemia on blood pressure and plasma renin activity in man. J Clin Endocrinol Metab. 1974;38:841–7.PubMedCrossRef
45.
46.
47.
Sterne JA, Sutton AJ, Ioannidis JP, Terrin N, Jones DR, Lau J, et al. Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BMJ. 2011;343:d4002.PubMedCrossRef
48.
Morimatsu H, Uchino S, Bellomo R, Ronco C. Continuous renal replacement therapy: does technique influence electrolyte and bicarbonate control? Int J Artif Organs. 2003;26:289–96.PubMedCrossRef
Metadata
Title
Safety and efficacy of regional citrate anticoagulation for continuous renal replacement therapy in liver failure patients: a systematic review and meta-analysis
Authors
Wei Zhang
Ming Bai
Yan Yu
Lu Li
Lijuan Zhao
Shiren Sun
Xiangmei Chen
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2019
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-019-2317-9

Other articles of this Issue 1/2019

Critical Care 1/2019 Go to the issue

Letter

Impact of acute renal failure on plasmatic levels of cleaved endocan

Research

Association between hydroxocobalamin administration and acute kidney injury after smoke inhalation: a multicenter retrospective study

Letter

Candida bloodstream infection under veno-arterial ECMO therapy

Letter

Matrix metalloproteinase-8: a useful biomarker to refine the diagnosis of community-acquired pneumonia upon intensive care unit admission?

Letter

How to understand real net ultrafiltration and its association with low blood pressure in critically ill patients with renal replacement therapy

Research

Impact of nutrition route on microaspiration in critically ill patients with shock: a planned ancillary study of the NUTRIREA-2 trial