PMID- 33314078
OWN - NLM
STAT- MEDLINE
DCOM- 20210115
LR  - 20220928
IS  - 1469-493X (Electronic)
IS  - 1361-6137 (Linking)
VI  - 12
IP  - 12
DP  - 2020 Dec 14
TI  - Pharmacological interventions for preventing clotting of extracorporeal circuits 
      during continuous renal replacement therapy.
PG  - CD012467
LID - 10.1002/14651858.CD012467.pub3 [doi]
LID - CD012467
AB  - BACKGROUND: Acute kidney injury (AKI) is a major comorbidity in hospitalised 
      patients. Patients with severe AKI require continuous renal replacement therapy 
      (CRRT) when they are haemodynamically unstable. CRRT is prescribed assuming it is 
      delivered over 24 hours. However, it is interrupted when the extracorporeal 
      circuits clot and the replacement is required. The interruption may impair the 
      solute clearance as it causes under dosing of CRRT. To prevent the circuit 
      clotting, anticoagulation drugs are frequently used. OBJECTIVES: To assess the 
      benefits and harms of pharmacological interventions for preventing clotting in 
      the extracorporeal circuits during CRRT. SEARCH METHODS: We searched the Cochrane 
      Kidney and Transplant Register of Studies up to 12 September 2019 through contact 
      with the Information Specialist using search terms relevant to this review. 
      Studies in the Register are identified through searches of CENTRAL, MEDLINE, and 
      EMBASE, conference proceedings, the International Clinical Trials Register 
      (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We selected 
      randomised controlled trials (RCTs or cluster RCTs) and quasi-RCTs of 
      pharmacological interventions to prevent clotting of extracorporeal circuits 
      during CRRT. DATA COLLECTION AND ANALYSIS: Data were abstracted and assessed 
      independently by two authors. Dichotomous outcomes were calculated as risk ratio 
      (RR) with 95% confidence intervals (CI). The primary review outcomes were major 
      bleeding, successful prevention of clotting (no need of circuit change in the 
      first 24 hours for any reason), and death. Evidence certainty was determined 
      using the Grading of Recommendation Assessment, Development, and Evaluation 
      (GRADE) approach. MAIN RESULTS: A total of 34 completed studies (1960 
      participants) were included in this review. We identified seven ongoing studies 
      which we plan to assess in a future update of this review. No included studies 
      were free from risk of bias. We rated 30 studies for performance bias and 
      detection bias as high risk of bias. We rated 18 studies for random sequence 
      generation,AA AA six studies for the allocation concealment, three studies for 
      performance bias, three studies for detection bias,AA  nine studies for attrition 
      bias,AA 14 studies for selective reporting and nine studies for the other 
      potential source of bias, as having low risk of bias. We identified eight studies 
      (581 participants) that compared citrate with unfractionated heparin (UFH). 
      Compared to UFH, citrate probably reduces major bleeding (RR 0.22, 95% CI 0.08 to 
      0.62; moderate certainty evidence) and probably increases successful prevention 
      of clotting (RR 1.44, 95% CI 1.10 to 1.87; moderate certainty evidence). Citrate 
      may have little or no effect on death at 28 days (RR 1.06, 95% CI 0.86 to 1.30, 
      moderate certainty evidence). Citrate versus UFH may reduce the number of 
      participants who drop out of treatment due to adverse events (RR 0.47, 95% CI 
      0.15 to 1.49; low certainty evidence). Compared to UFH, citrate may make little 
      or no difference to the recovery of kidney function (RR 1.04, 95% CI 0.89 to 
      1.21; low certainty evidence). Compared to UFH, citrate may 
      reduceAA thrombocytopenia (RR 0.39, 95% CI 0.14 to 1.03; low certainty evidence). 
      It was uncertain whether citrate reduces a cost to health care services because 
      of inadequate data. For low molecular weight heparin (LMWH) versus UFH, six 
      studies (250 participants) were identified. Compared to LMWH, UFH may reduce 
      major bleeding (0.58, 95% CI 0.13 to 2.58; low certainty evidence). It is 
      uncertain whether UFH versus LMWH reduces death at 28 days or leads to successful 
      prevention of clotting. Compared to LMWH, UFH may reduce the number of patient 
      dropouts from adverse events (RR 0.29, 95% CI 0.02 to 3.53; low certainty 
      evidence). It was uncertain whether UFH versus LMWH leads to the recovery of 
      kidney function because no included studies reported this outcome. It was 
      uncertain whether UFH versus LMWH leads to thrombocytopenia. It was uncertain 
      whether UFH reduces a cost to health care services because of inadequate data. 
      For the comparison of UFH to no anticoagulation, one study (10 participants) was 
      identified. It is uncertain whether UFH compare to no anticoagulation leads to 
      more major bleeding. It is uncertain whether UFH improves successful prevention 
      of clotting in the first 24 hours, death at 28 days, the number of patient 
      dropouts due to adverse events, recovery of kidney function, thrombocytopenia, or 
      cost to health care services because no study reported these outcomes. For the 
      comparison ofAA citrate to no anticoagulation,AA no completed study was 
      identified. AUTHORS' CONCLUSIONS: Currently,AA available evidence does not 
      support the overall superiority of any anticoagulant to another. Compared to UFH, 
      citrate probably reduces major bleeding and prevents clotting and probably has 
      little or no effect on death at 28 days. For other pharmacological 
      anticoagulation methods, there is no available data showing overall superiority 
      to citrate or no pharmacological anticoagulation. Further studies are needed to 
      identify patient populations in which CRRT should commence with no 
      pharmacological anticoagulation or with citrate.
CI  - Copyright (c) 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
FAU - Tsujimoto, Hiraku
AU  - Tsujimoto H
AD  - Hospital Care Research Unit, Hyogo Prefectural Amagasaki General Medical Center, 
      Hyogo, Japan.
FAU - Tsujimoto, Yasushi
AU  - Tsujimoto Y
AD  - Department of Healthcare Epidemiology, School of Public Health in the Graduate 
      School of Medicine, Kyoto University, Kyoto, Japan.
FAU - Nakata, Yukihiko
AU  - Nakata Y
AD  - Department of Mathematics, Shimane University, Matsue, Japan.
FAU - Fujii, Tomoko
AU  - Fujii T
AD  - Australian and New Zealand Intensive Care Research Centre, Department of 
      Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
FAU - Takahashi, Sei
AU  - Takahashi S
AD  - Department of Healthcare Epidemiology, School of Public Health in the Graduate 
      School of Medicine, Kyoto University, Kyoto, Japan.
AD  - Center for Innovative Research for Communities and Clinical Excellence (CiRC2LE), 
      Fukushima Medical University, Fukushima, Japan.
FAU - Akazawa, Mai
AU  - Akazawa M
AD  - Department of Anesthesia, Shiga University of Medical Science Hospital, Otsu, 
      Japan.
FAU - Kataoka, Yuki
AU  - Kataoka Y
AD  - Department of Respiratory Medicine, Hyogo Prefectural Amagasaki General Medical 
      Center, Hyogo, Japan.
LA  - eng
SI  - ClinicalTrials.gov/NCT00890214
SI  - ClinicalTrials.gov/NCT00209378
SI  - ClinicalTrials.gov/NCT02478242
SI  - ClinicalTrials.gov/NCT01761994
SI  - ClinicalTrials.gov/NCT00286273
SI  - ClinicalTrials.gov/NCT01269112
SI  - ClinicalTrials.gov/NCT00798525
SI  - ClinicalTrials.gov/NCT01228292
SI  - ClinicalTrials.gov/NCT01318811
SI  - ClinicalTrials.gov/NCT02194569
SI  - ClinicalTrials.gov/NCT00965328
SI  - ClinicalTrials.gov/NCT01962116
SI  - ClinicalTrials.gov/NCT02423642
SI  - ClinicalTrials.gov/NCT01486485
SI  - ClinicalTrials.gov/NCT01839578
SI  - ClinicalTrials.gov/NCT02669589
SI  - ClinicalTrials.gov/NCT02860130
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
PT  - Systematic Review
DEP - 20201214
PL  - England
TA  - Cochrane Database Syst Rev
JT  - The Cochrane database of systematic reviews
JID - 100909747
RN  - 0 (Anticoagulants)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 2968PHW8QP (Citric Acid)
RN  - 9005-49-6 (Heparin)
SB  - IM
UOF - Cochrane Database Syst Rev. 2020 Mar 13;3:CD012467. PMID: 32164041
MH  - Acute Kidney Injury/mortality/*therapy
MH  - Anticoagulants/*administration & dosage/adverse effects
MH  - Bias
MH  - Blood Coagulation/*drug effects
MH  - *Catheter Obstruction/etiology
MH  - Citric Acid/administration & dosage/adverse effects
MH  - Continuous Renal Replacement Therapy/adverse effects/*instrumentation/mortality
MH  - Filtration/instrumentation
MH  - Hemorrhage/chemically induced/prevention & control
MH  - Heparin/administration & dosage/adverse effects
MH  - Heparin, Low-Molecular-Weight/administration & dosage/adverse effects
MH  - Humans
MH  - Kidney/physiology
MH  - Patient Dropouts
MH  - Randomized Controlled Trials as Topic
MH  - Recovery of Function/drug effects
MH  - Thrombocytopenia/prevention & control
PMC - PMC8812343
COIS- Hiraku Tsujimoto: none known. Yasushi Tsujimoto: none known. Yukihiko Nakata: 
      none known. Tomoko Fujii: none known. Sei Takahashi: none known. Mai Akazawa: 
      none known. Yuki Kataoka: none known.
EDAT- 2020/12/15 06:00
MHDA- 2021/01/16 06:00
PMCR- 2021/12/14
CRDT- 2020/12/14 11:05
PHST- 2020/12/14 11:05 [entrez]
PHST- 2020/12/15 06:00 [pubmed]
PHST- 2021/01/16 06:00 [medline]
PHST- 2021/12/14 00:00 [pmc-release]
AID - CD012467.pub3 [pii]
AID - 10.1002/14651858.CD012467.pub3 [doi]
PST - epublish
SO  - Cochrane Database Syst Rev. 2020 Dec 14;12(12):CD012467. doi: 
      10.1002/14651858.CD012467.pub3.