Abstract
OBJECTIVE:: Continuous venovenous hemofiltration (CVVH) is applied in critically ill patients with acute renal failure for renal replacement. Heparins used to prevent circuit clotting may cause bleeding. Regional anticoagulation with citrate reduces bleeding, but has metabolic risks. The aim was to compare the safety and efficacy of the two. DESIGN:: Randomized, nonblinded, controlled single-center trial. SETTING:: General intensive care unit of a teaching hospital. PATIENTS:: Adult critically ill patients needing CVVH for acute renal failure and without an increased bleeding risk. INTERVENTIONS:: Regional anticoagulation with citrate or systemic anticoagulation with the low-molecular weight heparin nadroparin. MEASUREMENTS AND MAIN RESULTS:: End points were adverse events necessitating discontinuation of study anticoagulant, transfusion, metabolic and clinical outcomes, and circuit survival. Of the 215 randomized patients, 200 received CVVH per protocol (97 citrate and 103 nadroparin). Adverse events required discontinuation of citrate in two patients (accumulation and clotting) of nadroparin in 20 (bleeding and thrombocytopenia) (p < 0.001). Bleeding occurred in 6 vs. 16 patients (p = 0.08). The median number of red blood cell units transfused per CVVH day was 0.27 (interquartile range, 0.0-0.63) for citrate, 0.36 (interquartile range, 0-0.83) for nadroparin (p = 0.31). Citrate conferred less metabolic alkalosis (p = 0.001) and lower plasma calcium (p < 0.001). Circuit survival was similar. Three-month mortality on intention-to-treat was 48% (citrate) and 63% (nadroparin) (p = 0.03), per protocol 45% and 62% (p = 0.02). Citrate reduced mortality in surgical patients (p = 0.007), sepsis (p = 0.01), higher Sepsis-Related Organ Failure Assessment score (p = 0.006), and lower age (p = 0.009). CONCLUSIONS:: The efficacy of citrate and nadroparin anticoagulation for CVVH was similar, however, citrate was safer. Unexpectedly, citrate reduced mortality. Less bleeding could only partly explain this benefit, less clotting could not. Post hoc citrate appeared particularly beneficial after surgery, in sepsis and severe multiple organ failure, suggesting interference with inflammation.
| Original language | English |
|---|---|
| Pages (from-to) | 545-552 |
| Number of pages | 8 |
| Journal | Critical Care Medicine |
| Volume | 37 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 1 Jan 2009 |
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Citrate anticoagulation for continuous venovenous hemofiltration. / Oudemans-Van Straaten, Heleen M.; Bosman, Rob J.; Koopmans, Matty; Van Der Voort, Peter H.J.; Wester, Jos P.J.; Van Der Spoel, Johan I.; Dijksman, Lea M.; Zandstra, Durk F.
In: Critical Care Medicine, Vol. 37, No. 2, 01.01.2009, p. 545-552.Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Citrate anticoagulation for continuous venovenous hemofiltration
AU - Oudemans-Van Straaten, Heleen M.
AU - Bosman, Rob J.
AU - Koopmans, Matty
AU - Van Der Voort, Peter H.J.
AU - Wester, Jos P.J.
AU - Van Der Spoel, Johan I.
AU - Dijksman, Lea M.
AU - Zandstra, Durk F.
PY - 2009/1/1
Y1 - 2009/1/1
N2 - OBJECTIVE:: Continuous venovenous hemofiltration (CVVH) is applied in critically ill patients with acute renal failure for renal replacement. Heparins used to prevent circuit clotting may cause bleeding. Regional anticoagulation with citrate reduces bleeding, but has metabolic risks. The aim was to compare the safety and efficacy of the two. DESIGN:: Randomized, nonblinded, controlled single-center trial. SETTING:: General intensive care unit of a teaching hospital. PATIENTS:: Adult critically ill patients needing CVVH for acute renal failure and without an increased bleeding risk. INTERVENTIONS:: Regional anticoagulation with citrate or systemic anticoagulation with the low-molecular weight heparin nadroparin. MEASUREMENTS AND MAIN RESULTS:: End points were adverse events necessitating discontinuation of study anticoagulant, transfusion, metabolic and clinical outcomes, and circuit survival. Of the 215 randomized patients, 200 received CVVH per protocol (97 citrate and 103 nadroparin). Adverse events required discontinuation of citrate in two patients (accumulation and clotting) of nadroparin in 20 (bleeding and thrombocytopenia) (p < 0.001). Bleeding occurred in 6 vs. 16 patients (p = 0.08). The median number of red blood cell units transfused per CVVH day was 0.27 (interquartile range, 0.0-0.63) for citrate, 0.36 (interquartile range, 0-0.83) for nadroparin (p = 0.31). Citrate conferred less metabolic alkalosis (p = 0.001) and lower plasma calcium (p < 0.001). Circuit survival was similar. Three-month mortality on intention-to-treat was 48% (citrate) and 63% (nadroparin) (p = 0.03), per protocol 45% and 62% (p = 0.02). Citrate reduced mortality in surgical patients (p = 0.007), sepsis (p = 0.01), higher Sepsis-Related Organ Failure Assessment score (p = 0.006), and lower age (p = 0.009). CONCLUSIONS:: The efficacy of citrate and nadroparin anticoagulation for CVVH was similar, however, citrate was safer. Unexpectedly, citrate reduced mortality. Less bleeding could only partly explain this benefit, less clotting could not. Post hoc citrate appeared particularly beneficial after surgery, in sepsis and severe multiple organ failure, suggesting interference with inflammation.
AB - OBJECTIVE:: Continuous venovenous hemofiltration (CVVH) is applied in critically ill patients with acute renal failure for renal replacement. Heparins used to prevent circuit clotting may cause bleeding. Regional anticoagulation with citrate reduces bleeding, but has metabolic risks. The aim was to compare the safety and efficacy of the two. DESIGN:: Randomized, nonblinded, controlled single-center trial. SETTING:: General intensive care unit of a teaching hospital. PATIENTS:: Adult critically ill patients needing CVVH for acute renal failure and without an increased bleeding risk. INTERVENTIONS:: Regional anticoagulation with citrate or systemic anticoagulation with the low-molecular weight heparin nadroparin. MEASUREMENTS AND MAIN RESULTS:: End points were adverse events necessitating discontinuation of study anticoagulant, transfusion, metabolic and clinical outcomes, and circuit survival. Of the 215 randomized patients, 200 received CVVH per protocol (97 citrate and 103 nadroparin). Adverse events required discontinuation of citrate in two patients (accumulation and clotting) of nadroparin in 20 (bleeding and thrombocytopenia) (p < 0.001). Bleeding occurred in 6 vs. 16 patients (p = 0.08). The median number of red blood cell units transfused per CVVH day was 0.27 (interquartile range, 0.0-0.63) for citrate, 0.36 (interquartile range, 0-0.83) for nadroparin (p = 0.31). Citrate conferred less metabolic alkalosis (p = 0.001) and lower plasma calcium (p < 0.001). Circuit survival was similar. Three-month mortality on intention-to-treat was 48% (citrate) and 63% (nadroparin) (p = 0.03), per protocol 45% and 62% (p = 0.02). Citrate reduced mortality in surgical patients (p = 0.007), sepsis (p = 0.01), higher Sepsis-Related Organ Failure Assessment score (p = 0.006), and lower age (p = 0.009). CONCLUSIONS:: The efficacy of citrate and nadroparin anticoagulation for CVVH was similar, however, citrate was safer. Unexpectedly, citrate reduced mortality. Less bleeding could only partly explain this benefit, less clotting could not. Post hoc citrate appeared particularly beneficial after surgery, in sepsis and severe multiple organ failure, suggesting interference with inflammation.
KW - Acute renal failure
KW - Anticoagulation
KW - Citrate
KW - Hemofiltration
KW - Heparin
KW - Nadroparin
KW - Sepsi
UR - http://www.scopus.com/inward/record.url?scp=67649904300&partnerID=8YFLogxK
U2 - 10.1097/CCM.0b013e3181953c5e
DO - 10.1097/CCM.0b013e3181953c5e
M3 - Article
VL - 37
SP - 545
EP - 552
JO - Critical Care Medicine
JF - Critical Care Medicine
SN - 0090-3493
IS - 2
ER -