Abstract：
OBJECTIVE: Nonselective beta-blockers (NSBB) are the mainstay for treatment of portal hypertension (PH), but require caution in decompensated cirrhosis (DC) or acute-on-chronic liver failure (ACLF) with hypotension, hyponatremia, acute kidney injury (AKI) or type 2 hepatorenal syndrome (HRS). Midodrine is oral, rapidly acting, α1-adrenergic agonist. We evaluated acute effects of midodrine on hepatic venous pressure gradient (HVPG) in DC and ACLF with contraindications to NSBB.
METHODS: Patients of DC (n = 30) with grade III ascites and serum sodium (Na) <130/systolic blood pressure (SBP) <90/type II HRS (group I) and ACLF patients (n = 30) with Na <130/SBP <90/AKI (group II) were included. HVPG was done at baseline and repeated 3 h after 10 mg midodrine. Primary outcome was HVPG response (reduction by >20% or to <12 mmHg).
RESULTS: In group I, midodrine significantly reduced HVPG (19.2 ± 4.6 to 17.8 ± 4.2, p = .02) and heart rate (HR) (86.3 ± 11.6 to 77.9 ± 13.1, p < .01) and increased mean arterial pressure (MAP) (74.1 ± 6.9 to 81.9 ± 6.6 mmHg, p < .01). In group II also, midodrine reduced HVPG (19.1 ± 4.1 to 17.0 ± 4.2) and HR (92.4 ± 13.7 to 84.6 ± 14.1) and increased MAP (85.4 ± 7.3 to 91.2 ± 7.6 mmHg), p < .01 for all. HVPG response was achieved in 3/30 (10%) in group I and 8/30 (26.7%) in group II. On logistic regression analysis, prerenal AKI (OR 11.04, 95% CI 1.83-66.18, p < .01) and increase in MAP (OR 1.22, 95% CI 1.03-1.43, p = .02) were independent predictors of response. Increase in MAP by 8.5 mmHg with midodrine had best cut-off with AUROC of .76 for response.
CONCLUSIONS: In decompensated cirrhosis and ACLF patients with contraindications to NSBB, midodrine is useful in decreasing HVPG. Dose of midodrine should be titrated to increase MAP atleast by 8.5 mmHg.
METHODS: Patients of DC (n = 30) with grade III ascites and serum sodium (Na) <130/systolic blood pressure (SBP) <90/type II HRS (group I) and ACLF patients (n = 30) with Na <130/SBP <90/AKI (group II) were included. HVPG was done at baseline and repeated 3 h after 10 mg midodrine. Primary outcome was HVPG response (reduction by >20% or to <12 mmHg).
RESULTS: In group I, midodrine significantly reduced HVPG (19.2 ± 4.6 to 17.8 ± 4.2, p = .02) and heart rate (HR) (86.3 ± 11.6 to 77.9 ± 13.1, p < .01) and increased mean arterial pressure (MAP) (74.1 ± 6.9 to 81.9 ± 6.6 mmHg, p < .01). In group II also, midodrine reduced HVPG (19.1 ± 4.1 to 17.0 ± 4.2) and HR (92.4 ± 13.7 to 84.6 ± 14.1) and increased MAP (85.4 ± 7.3 to 91.2 ± 7.6 mmHg), p < .01 for all. HVPG response was achieved in 3/30 (10%) in group I and 8/30 (26.7%) in group II. On logistic regression analysis, prerenal AKI (OR 11.04, 95% CI 1.83-66.18, p < .01) and increase in MAP (OR 1.22, 95% CI 1.03-1.43, p = .02) were independent predictors of response. Increase in MAP by 8.5 mmHg with midodrine had best cut-off with AUROC of .76 for response.
CONCLUSIONS: In decompensated cirrhosis and ACLF patients with contraindications to NSBB, midodrine is useful in decreasing HVPG. Dose of midodrine should be titrated to increase MAP atleast by 8.5 mmHg.
摘要：
目的：非选择性β受体阻滞剂（NSBB）是治疗门静脉高压症（PH）的主要药物，但在失代偿期肝硬化（DC）或慢性急性肝衰竭（ACLF）伴有低血压时需要谨慎，低钠血症,急性肾损伤（AKI）或2型肝肾综合征（HRS）。米多君是口服的，行动迅速,α1-肾上腺素能激动剂。我们评估了米多君对DC和ACLF的肝静脉压力梯度（HVPG）的急性影响，并有NSBB禁忌症。
方法：纳入III级腹水和血清钠（Na）<130/收缩压（SBP）<90/II型HRS（I组）的DC患者（n=30）和Na<130/SBP<90/AKI（II组）的ACLF患者（n=30）。HVPG在基线时进行，并在10mg米多君后重复3小时。主要结果是HVPG反应（降低>20％或<12mmHg）。
结果：在第一组中，米多君显着降低HVPG（19.2±4.6至17.8±4.2，p=.02）和心率（HR）（86.3±11.6至77.9±13.1，p<.01），并升高平均动脉压（MAP）（74.1±6.9至81.9±6.6mmHg，p<.01)。在第二组中，米多君降低了HVPG（19.1±4.1至17.0±4.2）和HR（92.4±13.7至84.6±14.1），并增加了MAP（85.4±7.3至91.2±7.6mmHg），p<0.01为所有。HVPG反应在I组中达到3/30(10%),在II组中达到8/30(26.7%)。在逻辑回归分析中，肾前AKI(OR11.04,95%CI1.83-66.18,p<.01)和MAP升高(OR1.22,95%CI1.03-1.43,p=.02)是反应的独立预测因子。用米多君使MAP增加8.5mmHg具有最佳截止值，AUROC为0.76。
结论：在有NSBB禁忌症的失代偿期肝硬化和ACLF患者中，米多君可用于降低HVPG。米多君的剂量应滴定以使MAP至少增加8.5mmHg。
方法：纳入III级腹水和血清钠（Na）<130/收缩压（SBP）<90/II型HRS（I组）的DC患者（n=30）和Na<130/SBP<90/AKI（II组）的ACLF患者（n=30）。HVPG在基线时进行，并在10mg米多君后重复3小时。主要结果是HVPG反应（降低>20％或<12mmHg）。
结果：在第一组中，米多君显着降低HVPG（19.2±4.6至17.8±4.2，p=.02）和心率（HR）（86.3±11.6至77.9±13.1，p<.01），并升高平均动脉压（MAP）（74.1±6.9至81.9±6.6mmHg，p<.01)。在第二组中，米多君降低了HVPG（19.1±4.1至17.0±4.2）和HR（92.4±13.7至84.6±14.1），并增加了MAP（85.4±7.3至91.2±7.6mmHg），p<0.01为所有。HVPG反应在I组中达到3/30(10%),在II组中达到8/30(26.7%)。在逻辑回归分析中，肾前AKI(OR11.04,95%CI1.83-66.18,p<.01)和MAP升高(OR1.22,95%CI1.03-1.43,p=.02)是反应的独立预测因子。用米多君使MAP增加8.5mmHg具有最佳截止值，AUROC为0.76。
结论：在有NSBB禁忌症的失代偿期肝硬化和ACLF患者中，米多君可用于降低HVPG。米多君的剂量应滴定以使MAP至少增加8.5mmHg。
