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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)

Filter material

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)