A Prospective, Open-Label Pilot Clinical Trial of Oral Ketamine for Acute Pain Management After Amputation Surgery
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Incidence of Adverse Events
研究概览
简要总结
The purpose of this pilot study is to test the safety of oral ketamine to treat acute pain after amputation surgery. The objective of the proposed research is to conclusively determine if oral ketamine is a safe alternative analgesic to opioid for acute pain in subjects undergoing elective amputation of the lower extremity. All participants will receive oral ketamine.
详细描述
A prospective open-label clinical trial to decrease the incidence of expected side effects of oral ketamine dose administered presurgery and postsurgery, in 10 subjects undergoing elective amputation of the lower extremity. The primary outcome measure is the incidence of adverse events. Secondary outcome measures are decreased acute pain levels and decreased incidence of stump and phantom limb pain at 6 months. Enrollment of participants will occur at Rush University Medical Center (Rush), Chicago, Illinois. Consented participants will be included in the study undergoing elective amputation of the lower extremity from all causes.
Rationale for using oral ketamine for acute pain after amputation surgery:
The common analgesic, morphine, has a narrow therapeutic window and numerous side effects.1 Ketamine, is a chemically stable compound, non-opioid with analgesic properties at low doses. In addition, ketamine stimulates the cardio-respiratory system which is of great benefit in injured patients.2-4 Ketamine is generally administered by the intravenous (IV) route and provides analgesia via antagonism of the N-Methyl-D-Asparate (NMDA) receptor. Ketamine has the added benefit of a wide therapeutic safety index. IV ketamine has been shown to provide postoperative analgesia in many clinical trials; in particular to reduce opioid consumption.5 Severe acute pain has been shown to progress to chronic pain due to central sensitization.6 Perioperative IV ketamine has been shown in limited studies to decrease the incidence of chronic pain after surgery. However, the IV route of administration of ketamine has limitations due to difficulties with IV placement in certain tactical situations. Therefore, the use of oral ketamine (non-opioid) for the purpose of acute pain management after trauma or surgery is highly desirable.
Pharmacokinetic studies: Oral ketamine may seem disadvantageous because of 17% bioavailability, mainly due to first-pass drug metabolism in the liver. However, there is not a wide variability in bioavailability from patient-to-patient (mean 16.6%, Standard Error (SE) = 2.8%) and hence a predictable oral dosing can be achieved. Although investigators have tested formulations with sublingual or buccal transmucosal administration of ketamine, in practice they fail to increase the ketamine bioavailability versus oral ketamine. Ketamine as nasal spray is problematic for acute use, since the amount of drug is difficult to control using an atomizer.
Day 1 (day of surgery) Before Surgery: An analgesic dose of the oral ketamine (1.0 mg/kg) will be administered one hour before surgery in the preoperative holding area.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Adults of at least 18 years of age, but not older than 80 years
- •Due to undergo elective major amputation of the lower extremity (above the knee amputation (AKA), below the knee amputation (BKA), total knee amputation (TKA), transmetatarsal amputation (TMA), toe amputation) from all causes.
排除标准
- •Increased intracranial pressure or intraocular pressure
- •Allergy to ketamine
- •Morbid obesity (BMI > 40 kg/m2)
- •Significant comorbidity (ASA physical status classification > 3)
- •Inability to communicate with the investigators
- •Any history of known or suspected drug or alcohol abuse
- •History of impaired liver function
- •Significant history of hallucinations, delusions or other psychiatric medical condition the investigator feels will prevent assessment of adverse events of study drug.
- •Significant psychiatric history; a diagnosis of schizophrenia, bipolar disorder, or severe depression.
- •Exposure to cytochrome P450 3A4 inhibitors or inducers (including grapefruit products) within 2 weeks before enrollment; the inability to avoid these products during ketamine administration.
- •Poorly-controlled hypertension
研究组 & 干预措施
Oral Ketamine
Subjects will receive Oral Ketamine (1.0 mg/kg) ) presurgery and 3 days postsurgery (including surgery day).
干预措施: Oral Ketamine (Drug)
结局指标
主要结局
Incidence of Adverse Events
时间窗: up to 72 hours post-surgery or until discharge
Incidence of adverse events with oral ketamine
次要结局
- Acute Postoperative Pain (NRS (numerical rating scale, 0=no pain, 10=worst imaginable pain) score)(0 to 72 hours post-surgery)
- Chronic Postoperative Pain (SF-MPQ scale for phantom limb and stump pain;Defense and Veterans Pain Rating Scale (DVPRS)(1, 3, 6 months post-surgery)
- Pharmacokinetics of Plasma Ketamine and Norketamine Levels (ng/mL)(Post-operative day 1 and 1 and hours after the first morning study drug dose)
- Liver Function Test(1 month after surgery and every month until liver function levels return to normal)
研究者
Asokumar Buvanendran
Professor, Department of Anesthesiology
Rush University Medical Center