Preoperative Ketamine as a Strategy to Decrease Perioperative Depression During the Perioperative Period: a Randomized Active Controlled Pilot Study
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 主要终点
- Change in depressive symptoms in the perioperative period.
研究概览
简要总结
Depressive symptoms, in patients with a life history of major depressive disorder (MDD), are very common in the general population, and are especially so in elderly adults undergoing surgery.Symptoms of depression at the time of surgery is associated with risk for postoperative complications.Attenuating depressive symptoms in patients undergoing surgery is thus a plausible but not adequately tested strategy for improving patient postoperative outcomes. Conventional treatment of depression takes weeks and, therefore, is not always a realistic option, particularly when surgery is urgent. Importantly, there are currently no guidelines for diagnosing and managing MDD in surgical patients. Given its association with complications including perioperative cognitive disorders such as delirium, and over longer periods of time with dementing disorders, the feasibility and efficacy of quick-acting treatments for depressive symptoms in surgical patients are direly needed. This need is particularly acute given the rising number of elderly patients undergoing surgery who are prone to depression and surgical complications.
Aim 1: To assess the feasibility of enrolling patients in a clinical trial where a sub-anesthetic dose of ketamine (0.5 mg/kg over 40 min) or midazolam (0.045 mg/kg) is given 1 to 3 days before surgery in the preoperative clinic as a strategy to improve depressive symptoms during the perioperative period.
Aim 2: To obtain estimates of the variability in improvements of depressive symptoms (increase from baseline in MADRS score ≥ 2)1 day after surgery for patients given a sub-anesthetic dose of ketamine (0.5 mg/kg over 40 min) 1 to 3 days before surgery compared with midazolam 0.045 mg/kg.
Aim 3: To assess for the safety and tolerability of administration of a sub-anesthetic dose of ketamine (0.5 mg/kg over 40 min) given 1 to 3 days before surgery in the preoperative clinic (as an outpatient) by assessment of dysphoric symptoms or other complications including the need for hospitalization.
Hypothesis:
Aim 1: Hypothesis: Patients with preoperative depressive symptoms can be identified before surgery and successfully enrolled in a clinical trial comparing a sub-anesthetic dose of ketamine versus midazolam for improving perioperative depressive symptoms.
Aim 2: Hypothesis: Compared with midazolam, a sub-anesthetic dose of ketamine given preoperatively leads to an improvement in MADRS score ≥ 2 on day 1 after surgery.
Aim 3: Hypothesis: Compared with midazolam, a sub-anesthetic dose of ketamine is not associated with dysphoria or other complications.
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
- Double (Participant, Care Provider)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients age ≥ 65 years
- •Planned lumbar surgery for degenerative disc disease or spinal stenosis involving 2 or more levels
- •A life history of MDD (DSM-5 criteria) and a MADRS score ≥20
- •Mini-Mental State Examination (MMSE) score ≥ 15
- •MMSE is between15-26
- •Ability to understand English.
排除标准
- •MMSE < 15
- •History of psychosis
- •Poorly controlled hypertension
- •Pre-existing aneurysmal vascular disorders
- •Cocaine or other illicit drug use.
研究组 & 干预措施
Ketamine Group
Ketamine 0.5 mg/kg over 40 min via intravenous catheter.
干预措施: Ketamine Group (Drug)
MIdazolam Group
Midazolam 0.045 mg/kg administered via intravenous catheter.
干预措施: Midazolam injection (Drug)
结局指标
主要结局
Change in depressive symptoms in the perioperative period.
时间窗: 3 Days before surgery to 30 days after the surgical procedure
Ketamine administration changes depressive symptoms perioperatively. Measured using Depression will be measured with the Montgomery-Asberg Depression Scale (MADRS) scale. Scale ranges from 0 no depresson- 60 severe depression.
次要结局
- Change in depressive symptoms 1 day after surgery(24 hours after surgical procedure)
- Safety analsysis of administration of a sub-anesthetic dose of ketamine: CADSS(65 minutes after study drug has been infused.)
研究者
Charles W Hogue
Chair, Department of Anesthesiology
Northwestern University