Risk of Overcorrection in Rapid Intermittent Bolus vs Slow Continuous Infusion Therapies of Hypertonic Saline for Patients With Symptomatic Hyponatremia The SALSA Randomized Clinical Trial
Risk of Overcorrection in Rapid Intermittent Bolus vs Slow Continuous Infusion Therapies of Hypertonic Saline for Patients With Symptomatic Hyponatremia The SALSA Randomized Clinical Trial
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DOI：
10.1001/jamainternmed.2020.5519
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发表时间：
2020-10-26
影响因子：
39
通讯作者：
Kim, Sejoong
中科院分区：
文献类型：
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作者：
Baek, Seon Ha;Jo, You Hwan;Kim, Sejoong
目的比较症状性低钠血症患者在慢速持续输注(SCI)和快速间歇输注(RIB)治疗中过度纠正的风险。设计、设置和参与者：这项前瞻性、研究者发起、多中心、开放标签、随机临床试验纳入178名年龄在18岁以上、中到重度低钠血症且经葡萄糖校正的血清钠(SNA)水平在125 mmol/L或以下的患者。从2016年8月24日到2019年8月21日，韩国3家综合医院的急诊科和病房进行了招募。根据临床症状的严重程度，干预24至48小时的高渗盐水肋骨或脊髓损伤，3%。主要结果和衡量标准是在任何给定的时间段过度矫正，定义为24或48小时内SNA水平分别上升超过12或18 mm ol/L。继发性和非治疗性结果包括治疗方法的有效性和安全性。结果将患者随机分为肋骨组(87例)和脊髓损伤组(91例)，其中男性80例(44.9%)，平均SNA浓度118.2[5.0]mmo1/L。肋骨组和脊髓损伤组87例患者中有15例(17.2%)和91例患者中有22例(24.2%)出现过度矫正(绝对风险差异，-6.9%[95%CI，-18.8%对4.9%]；P=.26)。肋骨组再降治疗的发生率低于脊髓损伤组(分别为41.4%和57.1%)，绝对风险差异为-15.8%[95%CI，-30.3%比-1.3%]；P=0.04；需要治疗的人数6.3)。两组在增加SNA浓度和改善症状方面的疗效没有差异，但与SCI相比，RIB在1小时内达到目标矫正率方面显示出更好的疗效(意向治疗分析：87例患者中28例(32.2%)对91例(17.6%)；绝对风险差异14.6%[95%CI，2%~27.2%]；P=0.02；需要治疗的数量，6.8；按方案分析：72例患者中21例(29.2%)对73例患者中的12例(16.4%)；绝对风险差异，12.7%[95%CI，-0.8%至26.2%]；P=0.07)。除了在1小时内达到目标矫正率外，所有结果的意向治疗和按方案分析的统计学意义相似。结论与相关性这项随机临床试验发现，肋骨疗法和SIC疗法治疗低钠血症都是有效和安全的，过度矫正风险没有差异。然而，肋骨具有较低的治疗性复压治疗的发生率，在1小时内达到SNA的效果往往好于SCI。建议将肋骨作为治疗症状性低钠血症的首选方法，这与目前的共识指南是一致的。
Importance Few high-quality studies have clarified whether hypertonic saline is best administered as slow continuous infusion (SCI) therapy or rapid intermittent bolus (RIB) therapy for symptomatic severe hyponatremia.Objective To compare the risk of overcorrection in RIB and SCI with hypertonic saline in patients with symptomatic hyponatremia.Design, Setting, and Participants This prospective, investigator-initiated, multicenter, open-label, randomized clinical trial enrolled 178 patients older than 18 years with moderately severe to severe hyponatremia and glucose-corrected serum sodium (sNa) levels of 125 mmol/L or less. Recruitment took place from August 24, 2016, until August 21, 2019, across emergency departments and wards of 3 general hospitals in the Republic of Korea.Interventions Either RIB or SCI of hypertonic saline, 3%, for 24 to 48 hours stratified by the severity of clinical symptoms.Main Outcome and Measures The primary outcome was overcorrection at any given period, defined as increase in the sNa level by greater than 12 or 18 mmol/L within 24 or 48 hours, respectively. Secondary and post hoc outcomes included efficacy and safety of the treatment approaches. The sNa concentrations were measured every 6 hours for 2 days.Results The 178 patients (mean [SD] age, 73.1 [12.2] years; 80 (44.9%) male; mean [SD] sNa concentrations, 118.2 [5.0] mmol/L) were randomly assigned to the RIB group (n = 87) or the SCI group (n = 91). Overcorrection occurred in 15 of 87 (17.2%) and 22 of 91 (24.2%) patients in the RIB and SCI groups, respectively (absolute risk difference, -6.9% [95% CI, -18.8% to 4.9%]; P = .26). The RIB group showed lower incidence of relowering treatment than the SCI group (36 of 87 [41.4%] vs 52 of 91 [57.1%] patients, respectively; absolute risk difference, -15.8% [95% CI, -30.3% to -1.3%]; P = .04; number needed to treat, 6.3). Groups did not differ in terms of efficacy in increasing sNa concentrations nor improving symptoms, but RIB, when compared with SCI, showed better efficacy in achieving target correction rate within 1 hour (intention-to-treat analysis: 28 of 87 (32.2%) vs 16 of 91 (17.6%) patients, respectively; absolute risk difference, 14.6% [95% CI, 2%-27.2%]; P = .02; number needed to treat, 6.8; per-protocol analysis: 21 of 72 (29.2%) vs 12 of 73 (16.4%) patients, respectively; absolute risk difference, 12.7% [95% CI, -0.8% to 26.2%]; P = .07). The statistical significance of the intention-to-treat and per-protocol analyses were similar for all outcomes except for achieving the target correction rate within 1 hour.Conclusions and Relevance This randomized clinical trial found that both RIB and SIC therapies of hypertonic saline for treating hyponatremia were effective and safe, with no difference in the overcorrection risk. However, RIB had a lower incidence of therapeutic relowering treatment and tended to have a better efficacy in achieving sNa within 1 hour than SCI. RIB could be suggested as the preferred treatment of symptomatic hyponatremia, which is consistent with the current consensus guidelines.