Clinical Trials Unit, Intensive Care National Audit & Research Centre (ICNARC), London, UK.
Department of Health Services Research and Policy, London School of Hygiene & Tropical Medicine, London, UK.
Health Technol Assess. 2022 Feb;26(13):1-58. doi: 10.3310/ZXHI9396.
In the UK, 10% of admissions to intensive care units receive continuous renal replacement therapy with regional citrate anticoagulation replacing systemic heparin anticoagulation over the last decade. Regional citrate anticoagulation is now used in > 50% of intensive care units, despite little evidence of safety or effectiveness.
The aim of the Renal Replacement Anticoagulant Management study was to evaluate the clinical and health economic impacts of intensive care units moving from systemic heparin anticoagulation to regional citrate anticoagulation for continuous renal replacement therapy.
This was an observational comparative effectiveness study.
The setting was NHS adult general intensive care units in England and Wales.
Participants were adults receiving continuous renal replacement therapy in an intensive care unit participating in the Intensive Care National Audit & Research Centre Case Mix Programme national clinical audit between 1 April 2009 and 31 March 2017.
Exposure - continuous renal replacement therapy in an intensive care unit after completion of transition to regional citrate anticoagulation. Comparator - continuous renal replacement therapy in an intensive care unit before starting transition to regional citrate anticoagulation or had not transitioned.
Primary effectiveness - all-cause mortality at 90 days. Primary economic - incremental net monetary benefit at 1 year. Secondary outcomes - mortality at hospital discharge, 30 days and 1 year; days of renal, cardiovascular and advanced respiratory support in intensive care unit; length of stay in intensive care unit and hospital; bleeding and thromboembolic events; prevalence of end-stage renal disease at 1 year; and estimated lifetime incremental net monetary benefit.
Individual patient data from the Intensive Care National Audit & Research Centre Case Mix Programme were linked with the UK Renal Registry, Hospital Episode Statistics (for England), Patient Episodes Data for Wales and Civil Registrations (Deaths) data sets, and combined with identified periods of systemic heparin anticoagulation and regional citrate anticoagulation (survey of intensive care units). Staff time and consumables were obtained from micro-costing. Continuous renal replacement therapy system failures were estimated from the Post-Intensive Care Risk-adjusted Alerting and Monitoring data set. EuroQol-3 Dimensions, three-level version, health-related quality of life was obtained from the Intensive Care Outcomes Network study.
Out of the 188 (94.9%) units that responded to the survey, 182 (96.8%) use continuous renal replacement therapy. After linkage, data were available from 69,001 patients across 181 intensive care units (60,416 during periods of systemic heparin anticoagulation use and 8585 during regional citrate anticoagulation use). The change to regional citrate anticoagulation was not associated with a step change in 90-day mortality (odds ratio 0.98, 95% confidence interval 0.89 to 1.08). Secondary outcomes showed step increases in days of renal support (difference in means 0.53 days, 95% confidence interval 0.28 to 0.79 days), advanced cardiovascular support (difference in means 0.23 days, 95% confidence interval 0.09 to 0.38 days) and advanced respiratory support (difference in means, 0.53 days, 95% CI 0.03 to 1.03 days) with a trend toward fewer bleeding episodes (odds ratio 0.90, 95% confidence interval 0.76 to 1.06) with transition to regional citrate anticoagulation. The micro-costing study indicated that regional citrate anticoagulation was more expensive and was associated with an estimated incremental net monetary loss (step change) of -£2376 (95% confidence interval -£3841 to -£911). The estimated likelihood of cost-effectiveness at 1 year was less than 0.1%.
Lack of patient-level treatment data means that the results represent average effects of changing to regional citrate anticoagulation in intensive care units. Administrative data are subject to variation in data quality over time, which may contribute to observed trends.
The introduction of regional citrate anticoagulation has not improved outcomes for patients and is likely to have substantially increased costs. This study demonstrates the feasibility of evaluating effects of changes in practice using routinely collected data.
(1) Prioritise other changes in clinical practice for evaluation and (2) methodological research to understand potential implications of trends in data quality.
This trial is registered as ClinicalTrials.gov NCT03545750.
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 26, No. 13. See the NIHR Journals Library website for further project information.
在英国，过去十年中，10%的重症监护病房（ICU）患者接受连续肾脏替代治疗（CRRT），采用局部枸橼酸抗凝取代全身肝素抗凝。尽管局部枸橼酸抗凝的安全性和有效性证据有限，但目前在超过 50%的 ICU 中使用。
肾脏替代抗凝管理研究的目的是评估 ICU 从全身肝素抗凝转为局部枸橼酸抗凝用于 CRRT 的临床和健康经济影响。
这是一项观察性比较有效性研究。
英格兰和威尔士的 NHS 成人综合 ICU。
该研究纳入了在 ICU 中接受 CRRT 治疗的成年人，并参与了 Intensive Care National Audit & Research Centre Case Mix Programme 国家临床审计，时间为 2009 年 4 月 1 日至 2017 年 3 月 31 日。
暴露组 - ICU 中 CRRT 治疗完成后转为局部枸橼酸抗凝。对照组 - ICU 中 CRRT 治疗前开始或尚未开始过渡为局部枸橼酸抗凝。
90 天的全因死亡率。主要经济结局：1 年的增量净货币效益。次要结局：出院时、30 天和 1 年的死亡率；ICU 中肾脏、心血管和高级呼吸支持的天数；ICU 和医院的住院时间；出血和血栓栓塞事件；1 年时终末期肾病的患病率；以及估计的终生增量净货币效益。
个体患者数据来自 Intensive Care National Audit & Research Centre Case Mix Programme，与英国肾脏注册处、医院入院统计数据（英格兰）、患者入院数据（威尔士）和民事登记（死亡）数据集相结合，并结合全身肝素抗凝和局部枸橼酸抗凝（ICU 调查）的特定时期。工作人员时间和消耗品通过微成本核算获得。连续肾脏替代治疗系统故障从 Post-Intensive Care Risk-adjusted Alerting and Monitoring 数据集中估计。EuroQol-3 Dimensions，三级版本，健康相关生活质量从 Intensive Care Outcomes Network 研究中获得。
在 188 个（94.9%）回复调查的单位中，182 个（96.8%）使用 CRRT。在链接后，从 181 个 ICU 的 69001 名患者中获得了数据（60416 名患者在使用全身肝素抗凝期间，8585 名患者在使用局部枸橼酸抗凝期间）。改为局部枸橼酸抗凝并没有导致 90 天死亡率的显著变化（比值比 0.98，95%置信区间 0.89 至 1.08）。次要结局显示，肾脏支持天数（差值 0.53 天，95%置信区间 0.28 至 0.79 天）、高级心血管支持天数（差值 0.23 天，95%置信区间 0.09 至 0.38 天）和高级呼吸支持天数（差值 0.53 天，95%置信区间 0.03 至 1.03 天）均有显著增加，且有趋势表明出血事件减少（比值比 0.90，95%置信区间 0.76 至 1.06）。微成本研究表明，局部枸橼酸抗凝治疗更昂贵，且与估计的增量净货币损失（阶跃变化）为-£2376（95%置信区间-£3841 至-£911）相关。1 年时成本效益的估计可能性小于 0.1%。
缺乏患者层面的治疗数据意味着结果代表了 ICU 中转为局部枸橼酸抗凝的平均效果。行政数据随时间推移存在数据质量的变化，这可能导致观察到的趋势。
引入局部枸橼酸抗凝并未改善患者的预后，且可能大幅增加成本。本研究证明了使用常规收集的数据评估实践变化效果的可行性。
（1）优先评估其他临床实践变化，（2）进行方法学研究，以了解数据质量变化的潜在影响。
本试验在 ClinicalTrials.gov 注册，编号为 NCT03545750。
本项目由英国国家卫生研究院（NIHR）卫生技术评估计划资助，将在；第 26 卷，第 13 期全文发表。请访问 NIHR 期刊库网站了解更多项目信息。
