Regional citrate versus systemic heparin for anticoagulation in critically ill patients on continuous venovenous haemofiltration: a prospective randomized multicentre trial

Hetzel, Gerd R.; Schmitz, Michael; Wissing, H.; Ries, W; Schott, G; Heering, Peter; Isgro, Frank; Kribben, Andreas; Himmele, Rainer; Grabensee, B; Rump, Lars Christian

doi:10.1093/ndt/gfq575

Cited by 205 publications

(223 citation statements)

References 19 publications

Supporting

Mentioning

189

Contrasting

Unclassified

Order By: Relevance

“…Citrate accumulation represents the most common complication of RCA, with a reported incidence of 0%-12% of patients depending on the RCA protocol used and the patient case mix (14,16,18,19,(44)(45)(46)(47)(48)(49)(50)(51). Because hepatic clearance represents the main metabolic fate of endogenous and exogenous citrate, citrate metabolism may be significantly slowed in clinical conditions where liver function is impaired, with a higher risk of citrate accumulation and consequent acid-base and electrolyte complications.…”

Section: Citrate Accumulation Risk and Rca Monitoringmentioning

confidence: 99%

“…In protocols using citrate-buffered replacement solutions, the buffer supply derives from citrate (predilution CVVH) or citrate and bicarbonate in various proportions (predilution and postdilution CVVH and CVVHDF) in relation to the composition and the combination of the solutions that are used (14,19,50,62,(64)(65)(66)(67). A simplification on the basis of the use of solutions with an appropriately low citrate concentration allows RCA CRRT as CVVH in the predilution-only modality (19,50). This approach has the advantage of allowing RCA despite the use of CRRT equipment without a dedicated citrate infusion pump, but the downside is that the CRRT dose is intimately linked to the citrate dose (50).…”

Section: Low-concentration Citrate Solutions (Isotonic In Sodium)mentioning

confidence: 99%

“…Several studies comparing citrate-based protocols with heparin-based protocols have reported better filter survival and/or fewer bleeding events during RCA (14)(15)(16)(17)(18)(19). Two separate meta-analyses, including six randomized trials comparing RCA with systemic anticoagulation with heparin, confirmed a significant decrease of bleeding events in the citrate arm (70,71); however, they provided slightly different results about filter survival.…”

Section: Safety and Efficacy Of Rcamentioning

confidence: 99%

“…To explain the survival benefit of RCA, the previously discussed interference of citrate with the activation of the inflammatory cascade was suggested (18). However, although RCA was associated with prolonged circuit patency and a marked reduction in bleeding complications, no survival benefit of citrate was shown in a subsequent multicenter randomized trial comparing unfractioned heparin with RCA in 170 patients undergoing CVVH (19).…”

Section: Safety and Efficacy Of Rcamentioning

confidence: 99%

“…A number of recent clinical studies has shown advantages of regional citrate anticoagulation (RCA) compared with heparin in terms of prolonged circuit life, reduced incidence of hemorrhagic complications, and lower transfusion needs (14)(15)(16)(17)(18)(19). On the basis of these data, the 2012 Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guidelines for Acute Kidney Injury recommend use of RCA as the preferred anticoagulation modality for continuous RRT (CRRT) in patients without contraindications for citrate, even in the absence of an increased bleeding risk or deranged coagulation (20).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Regional Citrate Anticoagulation for RRTs in Critically Ill Patients with AKI

Morabito

Pistolesi

Tritapepe

et al. 2014

Clinical Journal of the American Society of Nephrology

127

130

View full text Add to dashboard Cite

Hemorrhagic complications have been reported in up to 30% of critically ill patients with AKI undergoing RRT with systemic anticoagulation. Because bleeding is associated with significantly increased mortality risk, strategies aimed at reducing hemorrhagic complications while maintaining extracorporeal circulation should be implemented. Among the alternatives to systemic anticoagulation, regional citrate anticoagulation has been shown to prolong circuit life while reducing the incidence of hemorrhagic complications and lowering transfusion needs. For these reasons, the recently published Kidney Disease Improving Global Outcomes Clinical Practice Guidelines for Acute Kidney Injury have recommended regional citrate anticoagulation as the preferred anticoagulation modality for continuous RRT in critically ill patients in whom it is not contraindicated. However, the use of regional citrate anticoagulation is still limited because of concerns related to the risk of metabolic complications, the complexity of the proposed protocols, and the need for customized solutions. The introduction of simplified anticoagulation protocols based on citrate and the development of dialysis monitors with integrated infusion systems and dedicated software could lead to the wider use of regional citrate anticoagulation in upcoming years.

show abstract

Section: Citrate Accumulation Risk and Rca Monitoringmentioning

confidence: 99%

Section: Low-concentration Citrate Solutions (Isotonic In Sodium)mentioning

confidence: 99%

Section: Safety and Efficacy Of Rcamentioning

confidence: 99%

Section: Safety and Efficacy Of Rcamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Regional Citrate Anticoagulation for RRTs in Critically Ill Patients with AKI

Morabito

Pistolesi

Tritapepe

et al. 2014

Clinical Journal of the American Society of Nephrology

127

130

View full text Add to dashboard Cite

show abstract

Effect of Regional Citrate Anticoagulation vs Systemic Heparin Anticoagulation During Continuous Kidney Replacement Therapy on Dialysis Filter Life Span and Mortality Among Critically Ill Patients With Acute Kidney Injury

Zarbock

Küllmar

Kindgen‐Milles

et al. 2020

JAMA

193

174

View full text Add to dashboard Cite

IMPORTANCEAlthough current guidelines suggest the use of regional citrate anticoagulation (which involves the addition of a citrate solution to the blood before the filter of the extracorporeal dialysis circuit) as first-line treatment for continuous kidney replacement therapy in critically ill patients, the evidence for this recommendation is based on few clinical trials and meta-analyses.OBJECTIVE To determine the effect of regional citrate anticoagulation, compared with systemic heparin anticoagulation, on filter life span and mortality. DESIGN, SETTING, AND PARTICIPANTSA parallel-group, randomized multicenter clinical trial in 26 centers across Germany was conducted between March 2016 and December 2018 (final date of follow-up, January 21, 2020). The trial was terminated early after 596 critically ill patients with severe acute kidney injury or clinical indications for initiation of kidney replacement therapy had been enrolled. INTERVENTIONSPatients were randomized to receive either regional citrate anticoagulation (n = 300), which consisted of a target ionized calcium level of 1.0 to 1.40 mg/dL, or systemic heparin anticoagulation (n = 296), which consisted of a target activated partial thromboplastin time of 45 to 60 seconds, for continuous kidney replacement therapy. MAIN OUTCOMES AND MEASURESCoprimary outcomes were filter life span and 90-day mortality. Secondary end points included bleeding complications and new infections. RESULTS Among 638 patients randomized, 596 (93.4%) (mean age, 67.5 years; 183 [30.7%] women) completed the trial. In the regional citrate group vs systemic heparin group, median filter life span was 47 hours (interquartile range [IQR], 19-70 hours) vs 26 hours (IQR, 12-51 hours) (difference, 15 hours [95% CI, 11 to 20 hours]; P < .001). Ninety-day all-cause mortality occurred in 150 of 300 patients vs 156 of 296 patients (Kaplan-Meier estimator percentages, 51.2% vs 53.6%; unadjusted difference, -2.4% [95% CI, -10.5% to 5.8%]; unadjusted hazard ratio, 0.91 [95% CI, 0.72 to 1.13]; unadjusted P = .38; adjusted difference, -6.1% [95% CI, -12.6% to 0.4%]; primary adjusted hazard ratio, 0.79 [95% CI, 0.63 to 1.004]; primary adjusted P = .054). Of 38 prespecified secondary end points, 34 showed no significant difference. Compared with the systemic heparin group, the regional citrate group had significantly fewer bleeding complications (15/300 [5.1%] vs 49/296 [16.9%]; difference, -11.8% [95% CI, -16.8% to -6.8%]; P < .001) and significantly more new infections (204/300 [68.0%] vs 164/296 [55.4%]; difference, 12.6% [95% CI, 4.9% to 20.3%]; P = .002).CONCLUSIONS AND RELEVANCE Among critically ill patients with acute kidney injury receiving continuous kidney replacement therapy, anticoagulation with regional citrate, compared with systemic heparin anticoagulation, resulted in significantly longer filter life span. The trial was terminated early and was therefore underpowered to reach conclusions about the effect of anticoagulation strategy on mortality.

show abstract

Pharmacological interventions for preventing clotting of extracorporeal circuits during continuous renal replacement therapy

Tsujimoto

Nakata

et al. 2020

Cochrane Database of Systematic Reviews

View full text Add to dashboard Cite

Regional citrate versus systemic heparin for anticoagulation in critically ill patients on continuous venovenous haemofiltration: a prospective randomized multicentre trial

Cited by 205 publications

References 19 publications

Regional Citrate Anticoagulation for RRTs in Critically Ill Patients with AKI

Regional Citrate Anticoagulation for RRTs in Critically Ill Patients with AKI

Effect of Regional Citrate Anticoagulation vs Systemic Heparin Anticoagulation During Continuous Kidney Replacement Therapy on Dialysis Filter Life Span and Mortality Among Critically Ill Patients With Acute Kidney Injury

Pharmacological interventions for preventing clotting of extracorporeal circuits during continuous renal replacement therapy

Contact Info

Product

Resources

About