Abbasi Saeed, Farsaei Shadi, Fazel Kamran, Golzari Samad Ej, Mahmoodpoor Ata
Anesthesiology and Critical Care Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
Department of Clinical Pharmacy and Pharmacy Practice, Isfahan University of Medical Sciences, Isfahan, Iran.
Daru. 2015 Mar 1;23(1):23. doi: 10.1186/s40199-015-0103-z.
Management of difficult to wean patients is a dilemma for health care system. Recently published studies demonstrated efficacy of donepezil to counteract respiratory depression in sleep apnea. However, to the best of our knowledge, pharmaceutical interventions with donepezil to facilitate weaning have not been tested so far. Therefore in the present study, we evaluated the efficacy of using donepezil on weaning course in difficult to wean patients.
In this non-randomized interventional clinical study, difficult to wean patients with prior inappropriately depressed respiratory responses were included from two referral intensive care units (ICU) in Iran. Patients with another potentially reasons of weaning failure were excluded from the study. Donepezil was started for eligible patients at dose of 10 mg daily for 2-4 weeks. For the primary outcomes, arterial blood gas (ABG) parameters were also measured before and after intervention to evaluate the possible effects of donepezil on them. In addition, weaning outcomes of patients were reported as final outcome in response to this intervention.
Twelve out of 16 studied patients experienced successful results to facilitate weaning with donepezil intervention. The mean duration of donepezil treatment until outcome measurement was 12 days. There were not any significant differences in ABG parameters among patients with successful and failed weaning trial on day of donepezil initiation. However after donepezil intervention, mean of PCO2 and HCO3 decreased in patients with successful weaning trial and mean of PCO2 increased in those with weaning failure.
Reduced central respiratory drive was infrequently reason of failed weaning attempts but it must be considered especially in patients with hypercapnia secondary to inefficient gas exchange and slow breathing. Our results in the clinical setting suggest that, the use of donepezil can expedite weaning presumably by stimulation of respiratory center and obviate the need to re-intubation in cases of respiratory drive problem in difficult to wean patients. We suggest decrease PCO2 and HCO3 during donepezil steady could be valuable predictors for positive response to donepezil intervention.
对于医疗系统而言，管理难以撤机的患者是一个难题。最近发表的研究表明，多奈哌齐可有效对抗睡眠呼吸暂停中的呼吸抑制。然而，据我们所知，迄今为止尚未对使用多奈哌齐促进撤机的药物干预进行过测试。因此，在本研究中，我们评估了多奈哌齐在难以撤机患者撤机过程中的疗效。
在这项非随机干预性临床研究中，从伊朗的两个转诊重症监护病房（ICU）纳入了先前呼吸反应异常抑制的难以撤机患者。排除有其他可能导致撤机失败原因的患者。符合条件的患者开始服用多奈哌齐，剂量为每日10毫克，持续2 - 4周。对于主要结局，在干预前后还测量了动脉血气（ABG）参数，以评估多奈哌齐对其可能产生的影响。此外，报告患者的撤机结局作为该干预的最终结局。
16例研究患者中有12例通过多奈哌齐干预成功实现撤机。直至进行结局测量时，多奈哌齐治疗的平均持续时间为12天。在开始使用多奈哌齐当天，撤机成功和失败的患者之间ABG参数没有任何显著差异。然而，在多奈哌齐干预后，撤机成功的患者PCO2和HCO3的平均值下降，而撤机失败的患者PCO2的平均值升高。
中枢呼吸驱动力降低很少是撤机尝试失败的原因，但必须予以考虑，尤其是在因气体交换效率低下和呼吸缓慢导致高碳酸血症的患者中。我们在临床环境中的结果表明，使用多奈哌齐可能通过刺激呼吸中枢加快撤机，并避免在难以撤机的患者出现呼吸驱动问题时重新插管的需要。我们建议，在多奈哌齐稳定期PCO2和HCO3的降低可能是对多奈哌齐干预产生阳性反应的有价值预测指标。
