连续血液滤过的柠檬酸盐剂量：对钙和镁平衡、甲状旁腺激素和维生素 D 状态的影响，一项随机对照试验。

Citrate dose for continuous hemofiltration: effect on calcium and magnesium balance, parathormone and vitamin D status, a randomized controlled trial.

机构信息

Department of Anesthesiology, Intensive Care Medicine, Emergency Medicine & Pain Medicine, Ziekenhuis Oost Limburg ZOL, Genk, Belgium.

I-BioStat, Data Science Institute, Hasselt University, Hasselt, Belgium.

出版信息

BMC Nephrol. 2021 Dec 11;22(1):409. doi: 10.1186/s12882-021-02598-2.

DOI:10.1186/s12882-021-02598-2

PMID:34895160

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8665615/

Abstract

BACKGROUND

Regional citrate anticoagulation may cause a negative calcium balance, systemic hypocalcemia and parathormone (PTH) activation but randomzed studies are not available. Aim was to determine the effect of citrate dose on calcium (Ca) and magnesium (Mg) balance, PTH and Vitamin D.

METHODS

Single center prospective randomized study. Patients, requiring continuous venovenous hemofiltration (CVVH) with citrate, randomized to low dose citrate (2.5 mmol/L) vs. high dose (4.5 mmol/L) for 24 h, targeting post-filter ionized calcium (pfiCa) of 0.325-0.4 mmol/L vs. 0.2-0.275 mmol/L, using the Prismaflex® algorithm with 100% postfilter calcium replacement. Extra physician-ordered Ca and Mg supplementation was performed aiming at systemic iCa > 1.0 mmol/L. Arterial blood, effluent and post-filter aliquots were taken for balance calculations (area under the curve), intact (i), oxidized (ox) and non-oxidized (nox) PTH, 25-hydroxy-Vitamin D (25D) and 1,25-dihydroxy-Vitamin D (1,25D).

RESULTS

35 patients were analyzed, 17 to high, 18 to low citrate. Mean 24-h Ca balance was - 9.72 mmol/d (standard error 1.70) in the high vs - 1.18 mmol/d (se 1.70)) (p = 0.002) in the low citrate group and 24-h Mg-balance was - 25.99 (se 2.10) mmol/d vs. -17.63 (se 2.10) mmol/d (p = 0.008) respectively. Physician-ordered Ca supplementation, higher in the high citrate group, resulted in a positive Ca-balance in both groups. iPTH, oxPTH or noxPTH were not different between groups. Over 24 h, median PTH decreased from 222 (25th-75th percentile 140-384) to 162 (111-265) pg/ml (p = 0.002); oxPTH from 192 (124-353) to 154 pg/ml (87-231), p = 0.002. NoxPTH did not change significantly. Mean 25 D (standard deviation), decreased from 36.5 (11.8) to 33.3 (11.2) nmol/l (p = 0.003), 1,25D rose from 40.9 pg/ml (30.7) to 43.2 (30.7) pg/ml (p = 0.046), without differences between groups.

CONCLUSIONS

A higher citrate dose caused a more negative CVVH Ca balance than a lower dose, due to a higher effluent Calcium loss. Physician-ordered Ca supplementation, targeting a systemic iCa > 1.0 mmol/L, higher in the high citrate group, resulted in a positive Ca-balance in both groups. iPTH and oxPTH declined, suggesting decreased oxidative stress, while noxPTH did not change. 25D decreased while 1,25-D rose. Mg balance was negative in both groups, more so in the high citrate group.

TRIAL REGISTRATION

ClinicalTrials.gov : NCT02194569. Registered 18 July 2014.

摘要

背景

局部枸橼酸抗凝可能导致负钙平衡、全身低钙血症和甲状旁腺激素（PTH）激活，但目前还没有随机研究。目的是确定枸橼酸盐剂量对钙（Ca）和镁（Mg）平衡、PTH 和维生素 D 的影响。

方法

单中心前瞻性随机研究。需要连续静脉-静脉血液滤过（CVVH）的患者，随机分为低剂量枸橼酸盐（2.5mmol/L）和高剂量（4.5mmol/L）24 小时，目标是滤后离子钙（pfiCa）为 0.325-0.4mmol/L 和 0.2-0.275mmol/L，使用 Prismaflex®算法，100%滤后钙替代。额外的医生开具的 Ca 和 Mg 补充剂旨在使系统 iCa＞1.0mmol/L。采集动脉血、流出液和滤后等分试样进行平衡计算（曲线下面积），测定 iPTH、oxPTH 和 noxPTH、25-羟维生素 D（25D）和 1,25-二羟维生素 D（1,25D）。

结果

分析了 35 名患者，17 名接受高剂量枸橼酸盐，18 名接受低剂量枸橼酸盐。高剂量枸橼酸盐组 24 小时 Ca 平衡平均为-9.72mmol/d（标准误差 1.70），而低剂量枸橼酸盐组为-1.18mmol/d（se 1.70）（p=0.002），24 小时 Mg 平衡分别为-25.99（se 2.10）mmol/d 和-17.63（se 2.10）mmol/d（p=0.008）。高剂量枸橼酸盐组需要更多的医生开具的 Ca 补充剂，导致两组均出现正 Ca 平衡。两组之间 iPTH、oxPTH 或 noxPTH 无差异。24 小时内，PTH 中位数从 222（25-75%分位数 140-384）降至 162（111-265）pg/ml（p=0.002）；oxPTH 从 192（124-353）降至 154pg/ml（87-231），p=0.002。noxPTH 无显著变化。25D（标准差）的平均水平从 36.5（11.8）降至 33.3（11.2）nmol/l（p=0.003），1,25D 从 40.9pg/ml（30.7）升至 43.2pg/ml（30.7），两组之间无差异。

结论

高剂量枸橼酸盐导致 CVVH Ca 平衡更负，原因是流出液钙丢失更多。高剂量枸橼酸盐组需要更多的医生开具的 Ca 补充剂，以达到系统 iCa＞1.0mmol/L，导致两组均出现正 Ca 平衡。iPTH 和 oxPTH 下降，表明氧化应激减少，而 noxPTH 没有变化。25D 下降，而 1,25-D 升高。两组均出现 Mg 负平衡，高剂量枸橼酸盐组更明显。