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Table 1 Characteristics of the included trials

From: 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

Source Setting Exclusion Patients (M/F)/circuits, number Mean age, years Severity Modality; dilution;
blood flow (ml/min)
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Stucker et al. [11] (2015; CH) ICU of the university hospitals Cirrhosis, severe coagulopathy, high risk of bleeding and sensitivity to heparin C: 54 (32/22)/NR C: 60 ± 14a C: 28 ± 9 (APACHE II)/63 ± 18 (SAPS)a CVVHDF; 2/3 pre-dilution and 1/3 post-dilution; 100–200 1.5 m2 High-flux membrane
H: 49 (32/17)/NR H: 65 ± 16a H: 29 ± 9 (APACHE II)/65 ± 18 (SAPS)a
Gattas et al. [12] (2015; AU) Seven different ICUs Liver failure, pregnant or breastfeeding, HIT, chronic dialysis C: 105 (74/31)/390 C: 66.4 ± 14.3a C: 25.6 ± 7.6 (APACHE II)a CVVHDF (61 %) CVVH (29 %); pre-dilution; 150 (52 %) 200 (23 %) Aquarius or Prismaflex
H: 107 (72/35)/467 H: 66.8 ± 14.9a H: 25.0 ± 6.9 (APACHE II)a
Schilder et al. [13] (2014; NL) Ten different ICUs High bleeding risk, other Therapeutic anticoagulation, HIT C: 66 (44/22)/NR C: 67 (36–87)b C: 23 (11–53) (APACHE II)/10 (2–19) (SOFA)b CVVH; pre-dilution; 180 NR
H: 73 (49/24)/NR H: 67 (23–85)b H: 25 (6–43) (APACHE II)/11 (3–18) (SOFA)b
Brain et al. [25] (2014; AU) A large metropolitan ICU Contraindication to citrate or heparin, pregnancy, or lactation C: 19 (12/7)/96
H: 11 (7/4)/125
C: 64 ± 13a
H: 51 ± 17a
C: 80 (58–99) (APACHE III)b
H: 61 (52.5–91.5) (APACHE III)b
CVVHDF; pre-dilution; mean 191 (citrate) and 217 (heparin) ST-100 (68.8 %); ST-150 (7.2 %); M100 (20.8 %); others (3.2 %)
Monchi et al. [27] (2004; BE) 32-Bed medical and surgical ICU Cirrhosis, severe coagulopathy, high risk of bleeding C: 8 (NR)/26 C: 67 (52–77)b C: 40 (31–53) (SAPS)b CVVH; post-dilution; 175 1.6 m2 Highly permeable PS membrane
H: 12 (/NR)/23 H: 64 (52–74)b H: 42 (33–55) (SAPS)b
Lin XM et al. [29] (2007; CN) Adult mixed ICU NR C: 27 (16/11)/NR C: 63 ± 21a C: 82.5 ± 22.4 (APACHE III)a CVVHDF; pre-dilution; 100–180 PRISMA M-100 AN69
H: 23 (14/9)/NR H: 64 ± 19a H: 75.6 ± 18.3 (APACHE III)a
Cui W et al. [30] (2011; CN) Adult mixed ICU NR C: 23 (12/11)/NR C: 46.9 ± 6.1a C: NR CVVH; NR; NR PRISMA
H: 23 (13/10)/NR H: 47.2 ± 5.9a H: NR
Yang ST et al. [31] (2014; CN) Adult mixed ICU severe coagulopathy, high risk of bleeding C: 25 (NR)/81 61.7 ± 8.6 C: NR CVVH; pre-dilution; 200–250 Aquarius, HF1200
H: 21 (NR)/53 H: NR
Oudemans-van Straaten et al. [28] (2009; NL) ICU of a teaching hospital Cirrhosis, bleeding, HIT, chronic dialysis, Contraindication to citrate or heparin C: 97 (66/31)/NR C: 73 (67–79)b C: 28 (27–30) (APACHE II)/59 (55–62) (SAPS)b CVVH; post-dilution; 220 1.9 m2 Cellulose triacetate hollow fibre membrane
N: 103 (70/33)/NR N: 73 (67–79)b N: 8 (27–29) (APACHE II)/61 (58–64) (SAPS)b
Betjes et al. [24] (2007; NL) Adult mixed ICU HIT, severe coagulopathy, high risk of bleeding, severe circulatory shock and liver failure C: 1 (15/6)/70 C: 57.8 ± 4.2a C: 51.4 ± 4.1 (SAPS)a CVVH;post-dilution; 150 High-flux triacetate
H: 27 (19/8)/72 H: 55.2 ± 2.8a H: 51.0 ± 2.6 (SAPS)a
Fealy et al. [26] (2007; AU) ICU of tertiary hospital Liver failure, hepatitis and contraindication to citrate or heparin C:10 (9/1)/10 71 (63.5–76.5)b SAPS: 41 (31–43) APACHE II:17 (15–21)b CVVH; pre-dilution; 150 APS650 PS hollow fibre membrane
H:10 (9/1)/10
Kutsogiannis et al. [34] (2005; CA) Tertiary and community hospital ICU Liver failure, Contraindication to citrate or heparin C: 16 (7/9)/36 C: 66.5 ± 14.5a C: 7.75 ± 3.53 (OD)a CVVHDF; pre-dilution; 125 Standard PRISMA M-100 AN69
H: 14 (8/6)/43 H: 63.9 ± 21.2a H: 9.42 ± 2.31 (OD)a
Tiranathanagul et al. [32] (2011; TH) Adult mixed ICU Severe hepatitis and cirrhosis, hypercalcaemia, Contraindication to citrate or heparin, other therapeutic anticoagulation C: 10 (5/5)/NR C: 69.5(32–78)b C: 21 (18–29) (APACHE II)b CVVH; pre-dilution; 120 1.5 m2 Polyethersulfone dialyzers
H: 10 (7/3)/NR H: 75.5 (18–87)b H: 22 (15–29) (APACHE II)b
Hetzel et al. [33] (2011; DE) Nine different ICUs Contraindication to citrate or heparin, metabolic, alkalosis, pregnancy or lactation, chronic dialysis, other therapeutic, anticoagulation, HIT C: 87 (57/30)/NR C: 62 ± 15.3a C: 21.8 ± 5.1 (APACHE II) CVVH; pre-dilution;
HF-solution flow 3:1
AV600S high-flux membrane
9.95 ± 2.9 (SOFA)a
H: 83 (59/24)/NR H: 65 ± 12.5a H: 22.04 ± 5.5 (APACHE II)
9.95 ± 2.6 (SOFA)a
  1. Abbreviations: M male, F female, APACHE Acute Physiology and Chronic Health Evaluation II, AU Australia, BE Belgium, C citrate, CA Canada, CH Switzerland, CN China, CRRT continuous renal replacement therapy, CVVH continuous venovenous haemofiltration, CVVHDF continuous venovenous haemodiafiltration, DE Germany, H heparin, HF haemofiltration, HIT heparin-induced thrombocytopenia, N nadroparin, NL the Netherlands, NR not reported, OD logistic organ dysfunction score, SAPS Simplified Acute Physiology II score, SOFA Sepsis-Related Organ Failure Assessment score. aMean ± standard error. bMedian (interquartile range)