Comparisons of anticoagulatory and therapeutic effects of low-molecular-weight heparin sodium versus sodium citrate in patients with severe acute kidney injury on continuous renal replacement therapy
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摘要: 目的 探讨局部枸橼酸钠抗凝对连续性肾脏替代治疗（continuous renal replacement therapy，CRRT）的重症急性肾损伤（acute kidney injury，AKI）患者炎症状态的影响。方法 随机抽取我院重症监护病房（intensive care unit，ICU）2018年1月至2019年12月行CRRT治疗的AKI患者枸橼酸钠组（有出血倾向或外科围手术期）和低分子肝素组（无出血倾向）各50例。枸橼酸钠组给予枸橼酸钠抗凝。低分子肝素组给予低分子肝素抗凝。比较两组治疗前后肿瘤坏死因子（tumor necrosis factor-α，TNF-α）、白细胞介素6（interleukin 6，IL-6）、降钙素原（procalcitonin，PCT）、C反应蛋白（C-reactive protein，CRP）、白细胞计数（white blood cell，WBC）、中性粒细胞与淋巴细胞比值（neutrophils lymphocytes ratio，NLR）、活化部分凝血活酶时间（activated partial thromboplastin time，APTT）、凝血酶原时间（prothrombin time，PT）、凝血酶时间（thrombin time，TT）、血清总钙、血镁、血磷、临床疗效。结果 共100例/207台次纳入本研究，枸橼酸钠组50例/103台次，低分子肝素钠组50例/104台次。治疗后，枸橼酸钠组患者TNF-a、IL-6、PCT下降幅度显著高于低分子肝素组，差异均有统计学意义（P<0.05），且治疗时间越长，下降幅度越大；透析时长>24 h时枸橼酸钠组患者NLR下降幅度显著高于低分子肝素组，差异有统计学意义（P<0.05）。针对明确合并重症感染AKI的这部分患者进一步进行亚组分析，与低分子肝素组相比，枸橼酸钠组在透析6 h、12 h、24 h后，TNF-a、IL-6、PCT明显下降，且治疗时长越长，下降幅度越大，差异均有统计学意义（P<0.05）。透析24 h后WBC下降幅度和12 h、24 h后NLR下降幅度两组差异均有统计学意义（P<0.05），且枸橼酸钠组下降幅度比低分子肝素组大；透析时长>24 h时血磷、血镁、血清总钙下降幅度两组差异有统计学意义（P<0.05），血磷与血镁在枸橼酸钠组下降幅度较大，而血清总钙在低分子肝素组下降幅度较大。透析时长6~12 h时，枸橼酸钠组患者APTT、TT延长幅度比低分子肝素组小，差异有统计学意义（P<0.05）。两组治疗后，死亡患者比例、肾功能恢复比例、肾功能未恢复比例、持续透析患者比例差异均无统计学意义（P>0.05）。结论 对行连续性肾脏替代治疗的重症AKI患者采用局部枸橼酸钠抗凝不仅安全，而且可以减轻患者体内炎症状态。Abstract: Objective To explore the effects of sodium citrate anticoagulation on inflammatory state in patients with severe acute renal injury(AKI)on continuous renal replacement therapy(CRRT).Methods From January 2018 to December 2019,50 AKI patients on CRRT in intensive care unit(ICU)were randomly assigned into two groups of sodium citrate(with bleeding tendency or surgical perioperative period)and low-molecular-weight heparin(without bleeding tendency).The levels of tumor necrosis factor(TNF-a),interleukin-6(IL-6),procalcitonin(PCT),C-reactive protein(CRP),white blood cell count(WBC),neutrophil to lymphocyte ratio(NLR),activated partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),serum total calcium,serum magnesium,blood phosphorus and clinical curative effect were compared between two groups before and after treatment.Results A total of 100 cases/207 times were recruited,including 50 cases/103 times in sodium citrate group and 50 cases/104 times in low-molecular-weight heparin group.After treatment,the declines of TNF-a,IL-6 and PCT was significantly greater in sodium citrate group than those in low-molecular-weight heparin group.And the differences were statistically significant(P<0.05).The longer treatment duration,the greater reduction.When dialysis duration was >24 h,the decline in NLR was significantly higher in regional citrate group than that in low-molecular-weight heparin group.And the difference was statistically significant(P<0.05);Further subgroup analysis was carried out for these patients with AKI patients complicated by severe infection.Compared with low-molecular-weight heparin group,the levels of TNF-a,IL-6 and PCT decreased markedly in sodium citrate group at 6/12/24 h post-dialysis.The longer treatment duration,the greater reduction.And the difference was statistically significant(P<0.05).Significant inter-group differences existed in the declines of WBC at 6/12/24 hours.And the declines of serum levels of phosphorus,magnesium and total calcium were significantly higher in sodium citrate group than those in low-molecular-weight heparin group(P<0.05).Serum levels of phosphorus and magnesium dropped markedly in sodium citrate group while serum total calcium decreased obviously in low-molecular-weight heparin group.When the duration of dialysis was 6-12 hours,the prolongation of APTT/TT was significantly lower in sodium citrate group than that in low-molecular-weight heparin group.After treatment,no significant inter-group difference existed in the proportion of deceased patients,the recovery of renal function,the proportion of non-recovery of renal function or the proportion of patients with continuous dialysis(P>0.05).Conclusion Regional use of sodium citrate anticoagulation is not only safe,but also it lowers the inflammatory state in AKI patients in ICU on CRRT.
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