van Meenen David M P, van der Hoeven Sophia M, Binnekade Jan M, de Borgie Corianne A J M, Merkus Maruschka P, Bosch Frank H, Endeman Henrik, Haringman Jasper J, van der Meer Nardo J M, Moeniralam Hazra S, Slabbekoorn Mathilde, Muller Marcella C A, Stilma Willemke, van Silfhout Bart, Neto Ary Serpa, Ter Haar Hans F M, Van Vliet Jan, Wijnhoven Jan Willem, Horn Janneke, Juffermans Nicole P, Pelosi Paolo, Gama de Abreu Marcelo, Schultz Marcus J, Paulus Frederique
Department of Intensive Care, Academic Medical Center, University of Amsterdam, the Netherlands.
Clinical Research Unit, Academic Medical Center, University of Amsterdam, the Netherlands.
JAMA. 2018 Mar 13;319(10):993-1001. doi: 10.1001/jama.2018.0949.
It remains uncertain whether nebulization of mucolytics with bronchodilators should be applied for clinical indication or preventively in intensive care unit (ICU) patients receiving invasive ventilation.
To determine if a strategy that uses nebulization for clinical indication (on-demand) is noninferior to one that uses preventive (routine) nebulization.
DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial enrolling adult patients expected to need invasive ventilation for more than 24 hours at 7 ICUs in the Netherlands.
On-demand nebulization of acetylcysteine or salbutamol (based on strict clinical indications, n = 471) or routine nebulization of acetylcysteine with salbutamol (every 6 hours until end of invasive ventilation, n = 473).
The primary outcome was the number of ventilator-free days at day 28, with a noninferiority margin for a difference between groups of -0.5 days. Secondary outcomes included length of stay, mortality rates, occurrence of pulmonary complications, and adverse events.
Nine hundred twenty-two patients (34% women; median age, 66 (interquartile range [IQR], 54-75 years) were enrolled and completed follow-up. At 28 days, patients in the on-demand group had a median 21 (IQR, 0-26) ventilator-free days, and patients in the routine group had a median 20 (IQR, 0-26) ventilator-free days (1-sided 95% CI, -0.00003 to ∞). There was no significant difference in length of stay or mortality, or in the proportion of patients developing pulmonary complications, between the 2 groups. Adverse events (13.8% vs 29.3%; difference, -15.5% [95% CI, -20.7% to -10.3%]; P < .001) were more frequent with routine nebulization and mainly related to tachyarrhythmia (12.5% vs 25.9%; difference, -13.4% [95% CI, -18.4% to -8.4%]; P < .001) and agitation (0.2% vs 4.3%; difference, -4.1% [95% CI, -5.9% to -2.2%]; P < .001).
Among ICU patients receiving invasive ventilation who were expected to not be extubated within 24 hours, on-demand compared with routine nebulization of acetylcysteine with salbutamol did not result in an inferior number of ventilator-free days. On-demand nebulization may be a reasonable alternative to routine nebulization.
clinicaltrials.gov Identifier: NCT02159196.
对于接受有创通气的重症监护病房（ICU）患者，黏液溶解剂与支气管扩张剂联合雾化吸入是用于临床指征还是预防性应用仍不确定。
确定按需进行雾化吸入（根据临床指征）的策略是否不劣于预防性（常规）雾化吸入策略。
设计、地点和参与者：一项随机临床试验，纳入荷兰7家ICU预计需要进行超过24小时有创通气的成年患者。
按需雾化吸入乙酰半胱氨酸或沙丁胺醇（基于严格的临床指征，n = 471）或常规雾化吸入乙酰半胱氨酸与沙丁胺醇（每6小时一次，直至有创通气结束，n = 473）。
主要结局是第28天时无呼吸机天数，两组差异的非劣效界值为-0.5天。次要结局包括住院时间、死亡率、肺部并发症的发生情况及不良事件。
922例患者（34%为女性；中位年龄66岁[四分位间距（IQR），54 - 75岁]）入组并完成随访。在第28天时，按需组患者的无呼吸机天数中位数为21天（IQR，0 - 26），常规组患者为20天（IQR，0 - 26）（单侧95%CI，-0.00003至∞）。两组在住院时间、死亡率或发生肺部并发症的患者比例方面无显著差异。常规雾化吸入的不良事件更频繁（13.8%对29.3%；差异，-15.5%[95%CI，-20.7%至-10.3%]；P <.001），主要与快速性心律失常（12.5%对25.9%；差异，-13.4%[95%CI，-18.4%至-8.4%]；P <.001）和躁动（0.2%对4.3%；差异，-4.1%[95%CI，-
