Arginine Therapy and Cardiopulmonary Hemodynamics in Hospitalized Children with Sickle Cell Anemia: A Prospective, Double-blinded, Randomized Placebo-controlled Clinical Trial.
Arginine Therapy and Cardiopulmonary Hemodynamics in Hospitalized Children with Sickle Cell Anemia: A Prospective, Double-blinded, Randomized Placebo-controlled Clinical Trial.
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镰状细胞性贫血住院儿童的精氨酸治疗和心肺血流动力学：一项前瞻性、双盲、随机安慰剂对照临床试验。
DOI：
10.1164/rccm.202108-1930oc
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发表时间：
2022
影响因子：
24.7
通讯作者：
Morris,ClaudiaR
中科院分区：
文献类型：
--
作者：
Onalo,Richard;Cilliers,Antoinette;Cooper,Peter;Morris,ClaudiaR
原理：在镰状细胞性血管闭塞性疼痛和急性胸部综合征（ACS）期间，经常会遇到心肺血流动力学的急性变化，包括多普勒超声心动图测量的三尖瓣返流速度（TRV）升高。精氨酸和一氧化氮耗竭发生在有这些并发症的患者中。精氨酸管理，因此可能会提高一氧化氮的生物利用度和增强肺血管dilatation. Objective. To评估影响ofl-精氨酸补充剂对多普勒指数的心肺血流动力学在儿童镰状细胞贫血经历pain.Methods：这是一个前瞻性的，双盲，随机安慰剂对照试验口服精氨酸在儿童镰状细胞贫血年龄5-17岁住院的严重疼痛和/或ACS. Measures和主要结果：血液生物标志物和多普勒超声心动图指数的心肺血流动力学进行了测量之前和之后补充。TRV、肺动脉收缩压、平均肺动脉压和其他心肺血流动力学指标的平均变化采用配对Student检验，并采用Pearson相关性与精氨酸生物利用度标志物相关。66名儿童被随机分为精氨酸组和安慰剂组。在40例（61%）患者中观察到TRV升高≥ 2.5 m/s。对47例住院患者进行了第5天多普勒超声心动图检查。精氨酸组TRV中位数的下降幅度大于安慰剂组（22.2%，n = 22 vs.3.8%，n = 25;p< 0.01）。补充5天后，总体精氨酸生物利用度的较大百分比增加与较低的TRV相关（r=-0.533;P= 0.001）。精氨酸治疗后，心肺血流动力学和平均N-末端B型脑钠肽前体的多个指标也有显著差异。结论：口服精氨酸补充剂可改善镰状细胞病血管闭塞性疼痛和ACS期间的心肺血流动力学。临床试验在泛非临床试验注册中心注册https://pactr.samrc.ac.za/Search.aspx（PACTR 201611001864290）。
Rationale:Acute changes in cardiopulmonary hemodynamics that include tricuspid regurgitant jet velocity (TRV) elevation measured by Doppler echocardiography are often encountered during sickle cell vasoocclusive pain and acute chest syndrome (ACS). Arginine and nitric oxide depletion develop in patients with these complications. Arginine administration may therefore improve nitric oxide bioavailability and potentiate pulmonary vasodilatation.Objectives:To evaluate effects ofl-arginine supplementation on Doppler indices of cardiopulmonary hemodynamics in children with sickle cell anemia experiencing pain.Methods:This was a prospective, double-blinded, randomized placebo-controlled trial of oral arginine in children with sickle cell anemia age 5–17 years hospitalized with severe pain and/or ACS.Measurements and Main Results:Blood biomarkers and Doppler echocardiographic indices of cardiopulmonary hemodynamics were measured before and after supplementation. The mean change in TRV, pulmonary artery systolic pressure, mean pulmonary artery pressure, and other indices of cardiopulmonary hemodynamics were tested with paired Student’sttest and correlated with markers of arginine bioavailability using Pearson correlation. Sixty-six children were randomized into arginine versus placebo groups. An elevated TRV ⩾ 2.5 m/s was seen in 40 (61%) patients. A Day 5 Doppler echocardiogram was performed in 47 patients who remained hospitalized. A greater reduction in median TRV occurred in the arginine group than placebo (22.2%,n= 22 vs. 3.8%,n= 25;p< 0.01). A larger percentage increase in global arginine bioavailability was associated with a lower TRV after 5 days of supplementation (r= −0.533;P= 0.001). Significant differences in multiple indices of cardiopulmonary hemodynamics and mean N-terminal pro B-type brain natriuretic peptide were also noted after arginine therapy.Conclusions:Oral arginine supplementation improves cardiopulmonary hemodynamics during sickle cell disease vasoocclusive pain and ACS.Clinical trial registered with Pan African Clinical Trial Registry https://pactr.samrc.ac.za/Search.aspx (PACTR201611001864290).