Siegel D, Hulley S B, Black D M, Cheitlin M D, Sebastian A, Seeley D G, Hearst N, Fine R
Department of Epidemiology and Biostatistics, University of California, San Francisco.
JAMA. 1992 Feb 26;267(8):1083-9.
To investigate the patterns of electrolyte abnormalities resulting from thiazide administration and whether they cause ventricular arrhythmias, and to help resolve the controversy over whether clinicians should routinely prescribe potassium-conserving therapy to all patients treated with thiazides.
Double-blind, randomized controlled trial.
A total of 233 hypertensive men aged 35 to 70 years.
Participants were withdrawn from prior diuretic treatment and were replenished with oral potassium chloride and magnesium oxide. They were then randomized to 2 months of treatment with (1) hydrochlorothiazide; (2) hydrochlorothiazide with oral potassium; (3) hydrochlorothiazide with oral potassium and magnesium; (4) hydrochlorothiazide and triamterene; (5) chlorthalidone; or (6) placebo.
Ventricular arrhythmias on 24-hour Holter monitoring and serum and intracellular potassium and magnesium levels.
Of the 233 participants, 212 (91%) completed the study. Serum potassium levels were 0.4 mmol/L lower in the hydrochlorothiazide group than in the placebo group (P less than 0.01), and this mean difference was not affected by supplementation with potassium, with potassium and magnesium, or with triamterene. However, the supplements did prevent the occasional occurrence of marked hypokalemia; all 12 of the men who developed serum potassium levels of 3.0 mmol/L or less were among the 90 who received diuretics without supplementation (P less than 0.01). Similarly, the overall proportion of men with ventricular arrhythmias was not affected by randomized treatment, but there was a twofold increase in the proportion with arrhythmias among the 12 men with serum potassium levels of 3.0 mmol/L or less (P = .02). Serum magnesium and intracellular potassium and magnesium levels were not reduced by hydrochlorothiazide, nor were they related to ventricular arrhythmias.
In the majority of hypertensive patients, treatment with 50 mg/d of hydrochlorothiazide does not cause marked hypokalemia or ventricular arrhythmias. However, because some individuals will develop hypokalemia after starting diuretic therapy, serum potassium levels should be monitored and potassium-sparing strategies should be used when indicated.
研究噻嗪类药物导致的电解质异常模式以及它们是否会引起室性心律失常，并帮助解决临床医生是否应对所有接受噻嗪类药物治疗的患者常规开具保钾治疗药物这一争议。
双盲、随机对照试验。
共233名年龄在35至70岁之间的男性高血压患者。
参与者停止先前的利尿剂治疗，并补充口服氯化钾和氧化镁。然后将他们随机分为接受以下治疗2个月的组：（1）氢氯噻嗪；（2）氢氯噻嗪加口服钾；（3）氢氯噻嗪加口服钾和镁；（4）氢氯噻嗪和氨苯蝶啶；（5）氯噻酮；或（6）安慰剂。
24小时动态心电图监测的室性心律失常以及血清和细胞内钾、镁水平。
233名参与者中，212名（91%）完成了研究。氢氯噻嗪组的血清钾水平比安慰剂组低0.4 mmol/L（P<0.01），且这种平均差异不受补充钾、钾和镁或氨苯蝶啶的影响。然而，这些补充剂确实预防了偶尔出现的明显低钾血症；血清钾水平降至3.0 mmol/L或更低的12名男性均在未补充药物的90名接受利尿剂治疗的男性之中（P<0.01）。同样，随机治疗对有室性心律失常男性的总体比例没有影响，但在血清钾水平为3.0 mmol/L或更低的12名男性中，心律失常的比例增加了两倍（P = 0.02）。氢氯噻嗪未降低血清镁以及细胞内钾和镁水平，它们也与室性心律失常无关。
在大多数高血压患者中，每日50 mg氢氯噻嗪治疗不会导致明显的低钾血症或室性心律失常。然而，由于一些个体在开始利尿剂治疗后会出现低钾血症，应监测血清钾水平，并在有指征时采用保钾策略。
