Dexmedetomidine Infusion and Postoperative Lung Aeration After Thoracic Surgery: A Randomized, Placebo-Controlled Pilot Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Lung aeration
研究概览
简要总结
This will be a randomized, placebo-controlled, double-blinded, pilot trial with two parallel groups (1:1 ratio) receiving either dexmedetomidine (initial bolus of 1 mcg/kg over 30 min after induction, followed by an infusion rate of 0.3 mcg/kg/hr that will be stopped 30-45 minutes before the end of the surgery or upon reaching maximum dose of 2mcg/kg, whichever comes first) or placebo (normal saline as a bolus followed by maintenance infusion at the same rate of the intervention group).
Dexmedetomidine is frequently administered in thoracic surgery. Using local data from the Brigham and Women's Hospital, dexmedetomidine was used in a third of the thoracic procedures performed over the past three years. However, there is no consensus as to the optimal protocol of administration, therefore clinical practice is highly heterogeneous (bolus versus continuous infusion) and mostly depends on the preferences of anesthesia providers. In our institution, the dose of dexmedetomidine is typically 0.5 mcg/kg but varies based on attending preferences and experience. Given the heterogenous practices in dexmedetomidine administration, one of the objectives is to assess the feasibility of adhering to a dexmedetomidine protocol using an initial loading dose of 1 mcg/kg over 30 minutes after induction followed by a continuous infusion of 0.3 mcg/kg/hr. The infusion will stop 30-45 minutes prior to the end of surgery or once a maximum dose of 2mcg/kg has been achieved, whichever comes first. The control group will receive normal saline (similar bolus followed by maintenance infusion at the same rate of the intervention group).
详细描述
Dexmedetomidine is an opioid-sparing anesthetic with minimal effect on adaptive physiologic processes such as respiratory drive and hypoxic pulmonary vasoconstriction (HPV). Recent translational research has demonstrated that dexmedetomidine is associated with less alveolar inflammation and better respiratory mechanics in thoracic surgery under one-lung ventilation (OLV). However, it is unclear whether such results translate into better postoperative lung aeration and superior pulmonary outcomes. Several biological mechanisms have been postulated to explain the lung protective effects of dexmedetomidine. Based on experimental models under OLV, dexmedetomidine has been shown to minimize mechanical ventilation-induced lung injury through the inhibition of inflammatory pathways, thus enhancing pulmonary function recovery, improving respiratory mechanics, and potentially preventing postoperative pulmonary complications (PPCs). There is also clinical evidence to suggest dexmedetomidine may improve respiratory mechanics as well as prevents non-cardiopulmonary complications such as acute kidney injury (AKI) in adult cardiac surgical patients, as well as delirium in both cardiac and non-cardiac patients.
The research group from the BWH anesthesia department recently conducted a meta-analysis about the current evidence on dexmedetomidine in thoracic surgery, demonstrating beneficial effects in atelectasis and hypoxemia with low to moderate certainty. Unfortunately, current trials on this topic have limited sample size, and do not provide accurate and standardized outcome measurements. Dexmedetomidine has been shown to have organ protection properties, but there is no conclusive evidence to support its use for pulmonary protection in thoracic surgery. This trial would be the first to demonstrate an effect of dexmedetomidine on the trajectory of postoperative lung aeration and diaphragmatic excursion measured by ultrasound. Furthermore, the feasibility of a large, randomized controlled trial on dexmedetomidine for the prevention of pulmonary complications in thoracic surgery will be assessed. It is important to note that all the trials conducted on this topic have been conducted in Asia (limiting its generalizability), are relatively small (sample size of 30-50 patients) and have studied mainly respiratory mechanics.
Postoperative pulmonary complications are relatively common among patients undergoing thoracic surgery. The development of PPCs raises hospital costs (5,000-10,000 USD), prolong length of hospital stay (2-3 days), and affects quality of recovery. Similarly, lung aeration loss is considered a subclinical characteristic of lung injury induced by OLV, which can persist for several days after thoracic surgery. Several protective ventilatory strategies have been proposed to prevent PPCs, such as low tidal volume (TV) (i.e., TV [< 6mL/kg] and alveolar recruitment), yet the literature shows conflicting results, and the incidence of pulmonary complications continues to occur. Therefore, it is imperative to study and implement novel, pharmacologic lung protective interventions in thoracic surgery for the prevention of lung aeration loss and subsequent pulmonary complications.
In this study protocol, dexmedetomidine is postulated as an adjunct with possible pulmonary clinical benefits. Previous evidence suggests a possible effect on atelectasis, hypoxemia, and pneumonia, but the certainty of the evidence is low to moderate. Undertaking a pilot trial on dexmedetomidine and lung aeration in thoracic surgery would be useful to assess the feasibility for a large, randomized trial.
2. Specific Aims and Objectives
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Dexmedetomidine or placebo infusion will be blinded (by pharmacist preparing the study drug) to the patient, treating physicians, and investigators
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients (Age >18 years until 80 years) undergoing lobectomy and/or segmentectomy.
排除标准
- •Urgent or emergency thoracic surgery.
- •Other concomitant non-pulmonary procedures (pleurectomy, diaphragmatic procedures, pericardiocentesis, esophageal procedures, thymectomy).
- •Prior lung resection surgery.
- •Epidural block for intraoperative or postoperative analgesia.
- •Preoperative arrhythmia (second degree AV block or pacemaker) or significant bradycardia (heart rate < 50).
- •Preoperative hypotension (mean arterial blood pressure < 65 mmHg).
- •Severe functional liver or kidney disease.
- •Non-English speakers
- •Consent withdrawal.
研究组 & 干预措施
Dexmedetomidine
Dexmedetomidine infusion arm
干预措施: Dexmedetomidine Hydrochloride (Drug)
Placebo
Normal saline infusion arm
干预措施: Placebo (Drug)
结局指标
主要结局
Lung aeration
时间窗: 2 days
Lung aeration score measured by ultrasound at the post-anesthesia care unit (PACU) as described by Monastesse et al. Serial assessments will be performed at postoperative days 1 and 2.
次要结局
- Reintubation(30 days)
- Postoperative atelectasis(30 days)
- Pneumonia(30 days)
- Acute Respiratory Distress Syndrome (ARDS)(30 days)
- Diaphragmatic dysfunction: defined as a diaphragmatic excursion < 1cm(2 days)
- Intraoperative hypoxemia (SpO2 < 90%)(1 day)
- Pulmonary edema(30 days)
研究者
Matthew B. Allen, MD
Staff Anesthesiologist
Brigham and Women's Hospital