背景:甲羟孕酮和多奈哌齐可用作通气患者的呼吸兴奋剂。然而,目前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在改善接受机械通气的危重成年患者的呼吸状态和撤机促进方面的作用。材料和方法:随机,我们对重症监护病房(ICU)的78例通气患者进行了三盲试验.排除因肺部疾病而插管的患者。患者以1:1:1的比例随机接受5mg多奈哌齐(n=23)或5mg甲羟孕酮(n=26),或安慰剂(n=24),每天两次,直到断奶(最长10天)。主要终点是断奶时间,和有创机械通气的持续时间。次要终点包括成功断奶率,动脉血气(ABG)参数的变化,GCS和序贯器官衰竭评估(SOFA)评分,血红蛋白(Hgb),ICU-死亡率,和ICU住院时间,在干预前后进行测量,并记录是否成功断奶。结果:在78名随机分组的研究患者中,59断奶成功。与安慰剂组的66.7%的患者相比,多奈哌齐的87%的患者和甲羟孕酮组的88.5%的患者成功断奶。然而,这一差异无统计学意义(p值=0.111).pH值的变化,插管的平均持续时间,与对照组相比,多奈哌齐的断奶时间和断奶时间差异有统计学意义(p值<0.05)。ABG无显著差异,Hgb,GCS和SOFA评分,甲羟孕酮组的插管时间,但与对照组相比,断奶时间显著缩短至1.429天(p值=0.038)。结论:该临床试验的结果表明,与安慰剂相比,甲羟孕酮和多奈哌齐的给药剂量可以通过减少断奶时间来加快断奶过程。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较低.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。临床试验注册:https://irct。ir/IRCT20190810044500N2(2020年4月1日)。
Background: 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. Material and Methods: 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. Results: 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 (p-Value = 0.111). Changes in pH, mean duration of intubation, and weaning duration were statistically different in donepezil compared with the control group (p-Value < 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 (p-Value = 0.038). Conclusion: 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. Clinical
Trial Registration: https://irct.ir/IRCT20190810044500N2 (April 1, 2020).