Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.
Intensive Care Med. 2019 Oct;45(10):1372-1381. doi: 10.1007/s00134-019-05767-y. Epub 2019 Oct 1.
Respiratory muscle weakness frequently develops in critically ill patients and is associated with adverse outcome, including difficult weaning from mechanical ventilation. Today, no drug is approved to improve respiratory muscle function in these patients. Previously, we have shown that the calcium sensitizer levosimendan improves calcium sensitivity of human diaphragm muscle fibers in vitro and contractile efficiency of the diaphragm in healthy subjects. The main purpose of this study is to investigate the effects of levosimendan on diaphragm contractile efficiency in mechanically ventilated patients.
In a double-blind randomized placebo-controlled trial, mechanically ventilated patients performed two 30-min continuous positive airway pressure (CPAP) trials with 5-h interval. After the first CPAP trial, study medication (levosimendan 0.2 µg/kg/min continuous infusion or placebo) was administered. During the CPAP trials, electrical activity of the diaphragm (EA), transdiaphragmatic pressure (P), and flow were measured. Neuromechanical efficiency (primary outcome parameter) was calculated.
Thirty-nine patients were included in the study. Neuromechanical efficiency was not different during the CPAP trial after levosimendan administration compared to the CPAP trial before study medication. Tidal volume and minute ventilation were higher after levosimendan administration (11 and 21%, respectively), whereas EA and P were higher in both groups in the CPAP trial after study medication compared to the CPAP trial before study medication.
Levosimendan does not improve diaphragm contractile efficiency.
危重病患者常出现呼吸肌无力，并与不良预后相关，包括难以从机械通气中撤机。目前，尚无药物被批准用于改善此类患者的呼吸肌功能。此前，我们已经证明钙增敏剂左西孟旦可改善体外人膈肌肌纤维的钙敏感性和健康受试者膈肌的收缩效率。本研究的主要目的是研究左西孟旦对机械通气患者膈肌收缩效率的影响。
在一项双盲、随机、安慰剂对照试验中，机械通气患者进行了两次 30 分钟的持续气道正压通气（CPAP）试验，间隔 5 小时。第一次 CPAP 试验后，给予研究药物（左西孟旦 0.2μg/kg/min 持续输注或安慰剂）。在 CPAP 试验期间，测量膈肌的电活动（EA）、跨膈压（P）和流量。神经肌肉效率（主要观察指标）。
39 例患者纳入研究。与研究药物前的 CPAP 试验相比，左西孟旦给药后 CPAP 试验中的神经肌肉效率没有差异。左西孟旦给药后潮气量和分钟通气量增加（分别为 11%和 21%），而与研究药物前的 CPAP 试验相比，给药后 CPAP 试验中两组的 EA 和 P 均升高。
左西孟旦不能改善膈肌收缩效率。
