Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine / School of Public Health, Kyoto, Japan.
Department of Nephrology and Dialysis, Kyoritsu Hospital, Kawanishi, Japan.
Cochrane Database Syst Rev. 2021 Sep 14;9(9):CD013330. doi: 10.1002/14651858.CD013330.pub2.
Acute kidney injury (AKI) is a common complication amongst people who are critically ill, and it is associated with an increased risk of death. For people with severe AKI, continuous kidney replacement therapy (CKRT), which is delivered over 24 hours, is needed when they become haemodynamically unstable. When CKRT is interrupted due to clotting of the extracorporeal circuit, the delivered dose is decreased and thus leading to undertreatment.
This review assessed the efficacy of non-pharmacological measures to maintain circuit patency in CKRT.
We searched the Cochrane Kidney and Transplant Register of Studies up to 25 January 2021 which includes records identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov.
We included all randomised controlled trials (RCTs) (parallel-group and cross-over studies), cluster RCTs and quasi-RCTs that examined non-pharmacological interventions to prevent clotting of extracorporeal circuits during CKRT. DATA COLLECTION AND ANALYSIS: Three pairs of review authors independently extracted information including participants, interventions/comparators, outcomes, study methods, and risk of bias. The primary outcomes were circuit lifespan and death due to any cause at day 28. We used a random-effects model to perform quantitative synthesis (meta-analysis). We assessed risk of bias in included studies using the Cochrane Collaboration's tool for assessing risk of bias. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
A total of 20 studies involving 1143 randomised participants were included in the review. The methodological quality of the included studies was low, mainly due to the unclear randomisation process and blinding of the intervention. We found evidence on the following 11 comparisons: (i) continuous venovenous haemodialysis (CVVHD) versus continuous venovenous haemofiltration (CVVH) or continuous venovenous haemodiafiltration (CVVHDF); (ii) CVVHDF versus CVVH; (iii) higher blood flow (≥ 250 mL/minute) versus standard blood flow (< 250 mL/minute); (iv) AN69 membrane (AN69ST) versus other membranes; (v) pre-dilution versus post-dilution; (vi) a longer catheter (> 20 cm) placing the tip targeting the right atrium versus a shorter catheter (≤ 20 cm) placing the tip in the superior vena cava; (vii) surface-modified double-lumen catheter versus standard double-lumen catheter with identical geometry and flow design; (viii) single-site infusion anticoagulation versus double-site infusion anticoagulation; (ix) flat plate filter versus hollow fibre filter of the same membrane type; (x) a filter with a larger membrane surface area versus a smaller one; and (xi) a filter with more and shorter hollow fibre versus a standard filter of the same membrane type. Circuit lifespan was reported in 9 comparisons. Low certainty evidence indicated that CVVHDF (versus CVVH: MD 10.15 hours, 95% CI 5.15 to 15.15; 1 study, 62 circuits), pre-dilution haemofiltration (versus post-dilution haemofiltration: MD 9.34 hours, 95% CI -2.60 to 21.29; 2 studies, 47 circuits; I² = 13%), placing the tip of a longer catheter targeting the right atrium (versus placing a shorter catheter targeting the tip in the superior vena cava: MD 6.50 hours, 95% CI 1.48 to 11.52; 1 study, 420 circuits), and surface-modified double-lumen catheter (versus standard double-lumen catheter: MD 16.00 hours, 95% CI 13.49 to 18.51; 1 study, 262 circuits) may prolong circuit lifespan. However, higher blood flow may not increase circuit lifespan (versus standard blood flow: MD 0.64, 95% CI -3.37 to 4.64; 2 studies, 499 circuits; I² = 70%). More and shorter hollow fibre filters (versus standard filters: MD -5.87 hours, 95% CI -10.18 to -1.56; 1 study, 6 circuits) may reduce circuit lifespan. Death from any cause was reported in four comparisons We are uncertain whether CVVHDF versus CVVH, CVVHD versus CVVH or CVVHDF, longer versus a shorter catheter, or surface-modified double-lumen catheters versus standard double-lumen catheters reduced death due to any cause, in very low certainty evidence. Recovery of kidney function was reported in three comparisons. We are uncertain whether CVVHDF versus CVVH, CVVHDF versus CVVH, or surface-modified double-lumen catheters versus standard double-lumen catheters increased recovery of kidney function. Vascular access complications were reported in two comparisons. Low certainty evidence indicated using a longer catheter (versus a shorter catheter: RR 0.40, 95% CI 0.22 to 0.74) may reduce vascular access complications, however the use of surface-modified double lumen catheters versus standard double-lumen catheters may make little or no difference to vascular access complications.
AUTHORS' CONCLUSIONS: The use of CVVHDF as compared with CVVH, pre-dilution haemofiltration, a longer catheter, and surface-modified double-lumen catheter may be useful in prolonging the circuit lifespan, while higher blood flow and more and shorter hollow fibre filter may reduce circuit life. The Overall, the certainty of evidence was assessed to be low to very low due to the small sample size of the included studies. Data from future rigorous and transparent research are much needed in order to fully understand the effects of non-pharmacological interventions in preventing circuit coagulation amongst people with AKI receiving CKRT.
急性肾损伤（AKI）是重症患者中常见的并发症，与死亡风险增加有关。对于严重 AKI 患者，当血流动力学不稳定时，需要连续肾脏替代治疗（CKRT），这种治疗方式持续 24 小时。当由于体外回路凝结而中断 CKRT 时，输送的剂量会减少，从而导致治疗不足。
本综述评估了非药物措施在维持 CKRT 中回路通畅方面的疗效。
我们检索了截至 2021 年 1 月 25 日的 Cochrane 肾脏病和移植登记册中的研究，其中包括通过搜索 CENTRAL、MEDLINE 和 EMBASE、会议记录、国际临床试验注册中心（ICTRP）搜索门户和 ClinicalTrials.gov 确定的记录。
我们纳入了所有随机对照试验（RCT）（平行组和交叉研究）、集群 RCT 和准 RCT，这些研究检验了预防 CKRT 中外周体外回路凝结的非药物干预措施。
三对综述作者独立提取信息，包括参与者、干预措施/对照组、结局、研究方法和偏倚风险。主要结局是 28 天的回路寿命和任何原因导致的死亡。我们使用随机效应模型进行定量综合（荟萃分析）。我们使用 Cochrane 协作组评估偏倚风险的工具评估纳入研究的偏倚风险。使用随机效应模型获得效应的汇总估计值，并以风险比（RR）及其 95%置信区间（CI）表示二分类结局，以均数差（MD）及其 95%CI 表示连续结局。使用 Grading of Recommendations Assessment, Development and Evaluation（GRADE）方法评估证据的可信度。
综述共纳入 20 项研究，涉及 1143 名随机参与者。纳入研究的方法学质量较低，主要是由于干预措施的随机化过程和盲法不明确。我们发现了以下 11 种比较的证据：（i）连续静脉-静脉血液透析（CVVHD）与连续静脉-静脉血液滤过（CVVH）或连续静脉-静脉血液透析滤过（CVVHDF）；（ii）CVVHDF 与 CVVH；（iii）更高的血流（≥250mL/min）与标准血流（＜250mL/min）；（iv）AN69 膜（AN69ST）与其他膜；（v）前稀释与后稀释；（vi）导管尖端放置在右心房的较长导管（＞20cm）与导管尖端放置在上腔静脉的较短导管（≤20cm）；（vii）表面修饰的双腔导管与具有相同几何形状和流动设计的标准双腔导管；（viii）单点输注抗凝与双点输注抗凝；（ix）平板过滤器与相同膜类型的中空纤维过滤器；（x）具有更大膜表面积的过滤器与较小的过滤器；（xi）具有更多和更短中空纤维的过滤器与相同膜类型的标准过滤器。有 9 项比较报告了回路寿命。低确定性证据表明，CVVHDF（与 CVVH 相比：MD 10.15 小时，95%CI 5.15 至 15.15；1 项研究，62 个回路）、前稀释血液滤过（与后稀释血液滤过相比：MD 9.34 小时，95%CI-2.60 至 21.29；2 项研究，47 个回路；I²=13%）、将较长导管尖端放置在右心房（与将较短导管尖端放置在上腔静脉相比：MD 6.50 小时，95%CI 1.48 至 11.52；1 项研究，420 个回路）和表面修饰的双腔导管（与标准双腔导管相比：MD 16.00 小时，95%CI 13.49 至 18.51；1 项研究，262 个回路）可能延长回路寿命。然而，较高的血流可能不会增加回路寿命（与标准血流相比：MD 0.64，95%CI-3.37 至 4.64；2 项研究，499 个回路；I²=70%）。更多和更短的中空纤维过滤器（与标准过滤器相比：MD-5.87 小时，95%CI-10.18 至-1.56；1 项研究，6 个回路）可能会缩短回路寿命。有 4 项比较报告了任何原因导致的死亡。我们不确定 CVVHDF 与 CVVH、CVVHD 与 CVVH 或 CVVHDF、较长导管与较短导管或表面修饰的双腔导管与标准双腔导管是否能降低任何原因导致的死亡，证据确定性为极低。恢复肾功能的情况在 3 项比较中报告。我们不确定 CVVHDF 与 CVVH、CVVHDF 与 CVVH 或表面修饰的双腔导管与标准双腔导管是否能增加肾功能的恢复。血管通路并发症在 2 项比较中报告。低确定性证据表明，使用较长的导管（与较短的导管相比：RR 0.40，95%CI 0.22 至 0.74）可能会降低血管通路并发症的发生，但使用表面修饰的双腔导管与标准双腔导管可能对血管通路并发症没有影响或影响很小。
与 CVVH 相比，CVVHDF、前稀释血液滤过、较长导管和表面修饰的双腔导管可能有助于延长回路寿命，而较高的血流和更多和更短的中空纤维滤器可能会缩短回路寿命。总体而言，由于纳入研究的样本量较小，证据的确定性被评估为低至非常低。需要进行更多严格和透明的研究，以充分了解非药物干预措施在预防 AKI 患者接受 CKRT 时防止回路凝结的效果。
