Alizadeh Zahra, Sahebnasagh Adeleh, Hadadzadegan Navid, Mohammadi Farhad, Saghafi Fatemeh
Pharmaceutical Sciences Research Center, School of Pharmacy, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran.
Clinical Research Center, Department of Internal Medicine, School of Medicine, North Khorasan University of Medical Science, Bojnurd, Iran.
Front Pharmacol. 2021 Dec 6;12:735594. doi: 10.3389/fphar.2021.735594. eCollection 2021.
Medroxyprogesterone and donepezil could be used as respiratory stimulants in ventilated patients. However, no randomized placebo-controlled trial is available to confirm this approach and compare these drugs. The aim of the current study was to evaluate the effects of donepezil or medroxyprogesterone compared to the placebo in improvement in respiratory status and weaning facilitation in critically ill adult patients receiving mechanical ventilation. This randomized, triple-blind trial was conducted on 78 ventilated patients in intensive care units (ICU). Patients who were intubated due to pulmonary disorders were ruled out. Patients were randomized in a 1:1:1 ratio to receive 5 mg donepezil (n = 23) or 5 mg medroxyprogesterone (n = 26), or placebo (n = 24) twice a day until weaning (maximum 10 days). The primary endpoints were weaning duration, and duration of invasive mechanical ventilation. Secondary endpoints included rate of successful weaning, changes in arterial blood gas (ABG) parameters, GCS and sequential organ failure assessment (SOFA) score, hemoglobin (Hgb), ICU-mortality, and duration of ICU stay, were measured before and after the intervention and if successful weaning was recorded. : Of 78 studied patients who were randomized, 59 weaned successfully. 87% patients in donepezil and 88.5% patients in medroxyprogesterone groups were successfully weaned compared to 66.7% patients in the placebo group. However, this difference was not statistically significant ( = 0.111). Changes in pH, mean duration of intubation, and weaning duration were statistically different in donepezil compared with the control group ( < 0.05). No significant difference in ABG, Hgb, GCS and SOFA score, and duration of intubation were seen in the medroxyprogesterone group, but weaning duration was significantly reduced to 1.429 days compared with the control group ( = 0.038). The results of this clinical trial have demonstrated that the administered dose of medroxyprogesterone and donepezil can expedite the weaning process by reducing the weaning duration compared to placebo. Furthermore, the total duration of invasive ventilation was significantly lower in the donepezil group compared to the control group. Future clinical trials with a larger sample size will determine the exact role of medroxyprogesterone and donepezil in mechanically ventilated patients. https://irct.ir/IRCT20190810044500N2 (April 1, 2020).
甲羟孕酮和多奈哌齐可作为机械通气患者的呼吸兴奋剂。然而，尚无随机安慰剂对照试验来证实这种方法并比较这些药物。本研究的目的是评估多奈哌齐或甲羟孕酮与安慰剂相比，对接受机械通气的成年危重症患者呼吸状态改善和撤机促进的效果。这项随机、三盲试验在重症监护病房（ICU）的78例机械通气患者中进行。因肺部疾病插管的患者被排除。患者按1:1:1的比例随机分组，每天两次接受5mg多奈哌齐（n = 23）或5mg甲羟孕酮（n = 26），或安慰剂（n = 24），直至撤机（最长10天）。主要终点是撤机持续时间和有创机械通气持续时间。次要终点包括撤机成功率、动脉血气（ABG）参数变化、格拉斯哥昏迷量表（GCS）和序贯器官衰竭评估（SOFA）评分、血红蛋白（Hgb）、ICU死亡率以及ICU住院时间，在干预前后进行测量，并记录是否成功撤机。在78例随机分组的研究患者中，59例成功撤机。多奈哌齐组87%的患者和甲羟孕酮组88.5%的患者成功撤机，而安慰剂组为66.7%。然而，这种差异无统计学意义（P = 0.111）。与对照组相比，多奈哌齐组的pH值变化、平均插管时间和撤机持续时间有统计学差异（P < 0.05）。甲羟孕酮组的ABG、Hgb、GCS和SOFA评分以及插管时间无显著差异，但与对照组相比，撤机持续时间显著缩短至1.429天（P = 0.038）。这项临床试验的结果表明，与安慰剂相比，给予甲羟孕酮和多奈哌齐的剂量可通过缩短撤机持续时间来加快撤机过程。此外，与对照组相比，多奈哌齐组的有创通气总持续时间显著更短。未来更大样本量的临床试验将确定甲羟孕酮和多奈哌齐在机械通气患者中的确切作用。https://irct.ir/IRCT20190810044500N2（2020年4月1日）
