European Georges Pompidou Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
Nouvel Hôpital Civil, Medical Intensive Care Unit, Hôpitaux Universitaires de Strasbourg and EA 7293, Fédération de Médecine Translationnelle de Strasbourg, Strasbourg University, Strasbourg, France.
JAMA. 2016 Feb 2;315(5):480-8. doi: 10.1001/jama.2016.0019.
Acetazolamide has been used for decades as a respiratory stimulant for patients with chronic obstructive pulmonary disease (COPD) and metabolic alkalosis, but no large randomized placebo-controlled trial is available to confirm this approach.
To determine whether acetazolamide reduces mechanical ventilation duration in critically ill patients with COPD and metabolic alkalosis.
DESIGN, SETTING, AND PARTICIPANTS: The DIABOLO study, a randomized, double-blind, multicenter trial, was conducted from October 2011 through July 2014 in 15 intensive care units (ICUs) in France. A total of 382 patients with COPD who were expected to receive mechanical ventilation for more 24 hours were randomized to the acetazolamide or placebo group and 380 were included in an intention-to treat analysis.
Acetazolamide (500-1000 mg, twice daily) vs placebo administered intravenously in cases of pure or mixed metabolic alkalosis, initiated within 48 hours of ICU admission and continued during the ICU stay for a maximum of 28 days.
The primary outcome was the duration of invasive mechanical ventilation via endotracheal intubation or tracheotomy. Secondary outcomes included changes in arterial blood gas and respiratory parameters, weaning duration, adverse events, use of noninvasive ventilation after extubation, successful weaning, the duration of ICU stay, and in-ICU mortality.
Among 382 randomized patients, 380 (mean age, 69 years; 272 men [71.6%]; 379 [99.7%] with endotracheal intubation) completed the study. For the acetazolamide group (n = 187), compared with the placebo group (n = 193), no significant between-group differences were found for median duration of mechanical ventilation (-16.0 hours; 95% CI, -36.5 to 4.0 hours; P = .17), duration of weaning off mechanical ventilation (-0.9 hours; 95% CI, -4.3 to 1.3 hours; P = .36), daily changes of minute-ventilation (-0.0 L/min; 95% CI, -0.2 to 0.2 L/min; P = .72), or partial carbon-dioxide pressure in arterial blood (-0.3 mm Hg; 95% CI, -0.8 to 0.2 mm Hg; P = .25), although daily changes of serum bicarbonate (between-group difference, -0.8 mEq/L; 95% CI, -1.2 to -0.5 mEq/L; P < .001) and number of days with metabolic alkalosis (between-group difference, -1; 95% CI, -2 to -1 days; P < .001) decreased significantly more in the acetazolamide group. Other secondary outcomes also did not differ significantly between groups.
Among patients with COPD receiving invasive mechanical ventilation, the use of acetazolamide, compared with placebo, did not result in a statistically significant reduction in the duration of invasive mechanical ventilation. However, the magnitude of the difference was clinically important, and it is possible that the study was underpowered to establish statistical significance.
clinicaltrials.gov Identifier: NCT01627639.
乙酰唑胺作为一种呼吸兴奋剂，已被用于治疗慢性阻塞性肺疾病（COPD）和代谢性碱中毒患者数十年，但尚无大型随机安慰剂对照试验来证实这种方法。
确定乙酰唑胺是否可以减少 COPD 合并代谢性碱中毒的危重症患者机械通气的持续时间。
设计、地点和参与者：DIABOLO 研究是一项随机、双盲、多中心试验，于 2011 年 10 月至 2014 年 7 月在法国 15 个重症监护病房（ICU）进行。共有 382 例预计需要机械通气超过 24 小时的 COPD 患者被随机分为乙酰唑胺组或安慰剂组，380 例患者进行意向治疗分析。
乙酰唑胺（500-1000mg，每日两次）或安慰剂静脉给药，用于单纯或混合代谢性碱中毒，在 ICU 入院后 48 小时内开始，并在 ICU 期间持续使用，最长 28 天。
主要结局是通过气管内插管或气管切开进行有创机械通气的持续时间。次要结局包括动脉血气和呼吸参数的变化、脱机时间、不良事件、拔管后使用无创通气、成功脱机、ICU 住院时间和 ICU 内死亡率。
在 382 例随机患者中，380 例（平均年龄 69 岁；272 例男性[71.6%]；379 例[99.7%]经气管内插管）完成了研究。与安慰剂组（n=193）相比，乙酰唑胺组（n=187）机械通气时间中位数无显著差异（-16.0 小时；95%CI，-36.5 至 4.0 小时；P=0.17），脱机时间（-0.9 小时；95%CI，-4.3 至 1.3 小时；P=0.36），每分钟通气量的日变化（-0.0 L/min；95%CI，-0.2 至 0.2 L/min；P=0.72），或动脉血中二氧化碳分压的日变化（-0.3 mm Hg；95%CI，-0.8 至 0.2 mm Hg；P=0.25），尽管血清碳酸氢盐的日变化（组间差异，-0.8 mEq/L；95%CI，-1.2 至 -0.5 mEq/L；P<0.001）和代谢性碱中毒天数（组间差异，-1 天；95%CI，-2 至 -1 天；P<0.001）在乙酰唑胺组中显著减少。其他次要结局在两组间也无显著差异。
在接受有创机械通气的 COPD 患者中，与安慰剂相比，使用乙酰唑胺并未显著降低有创机械通气的持续时间。然而，差异的幅度具有临床意义，也可能是研究的效能不足以确定统计学意义。
clinicaltrials.gov 标识符：NCT01627639。
