Effects of Intraoperative Intravenous Ketamine on Chronic Pain After Mastectomy
试验速览
- 阶段
- 4 期
- 状态
- 暂停
- 入组人数
- 135
- 试验地点
- 1
- 主要终点
- Severity of chronic pain
研究概览
简要总结
Preventive analgesia is when an administered analgesic drug provides reduction in pain beyond its duration of action. This can be used to reduce acute postoperative pain and prevent occurrence of chronic post-surgical pain.
According to the International Association for the Study of Pain (IASP), chronic pain can be defined as pain that persisted beyond the time of normal tissue healing (usually 3 months) and that was not related to other causes. Mastectomy is associated with a high incidence of chronic post-surgical pain. Breast cancer is the most common malignancy affecting females around the world. Many undergo mastectomy as part of curative treatment. However, a significant proportion of patients experience chronic post-surgical pain. This results in significant negative impact on physical, psychological and social wellbeing.
Ketamine is an intravenous anaesthetic drug with analgesic effects. It can be used to treat both acute and chronic pain. A recent meta-analysis of different surgeries showed that patients receiving ketamine had a modest but statistically significant reduction in incidence of chronic post-surgical pain. In a small sample single dose pilot study, patients given low dose intravenous ketamine intraoperatively had a statistically non-significant reduction in incidence of pain around the surgical scar at three months after radical mastectomy. Randomized control trials with larger sample sizes are needed to determine the effectiveness and optimal dosing regime of ketamine for reduction of chronic post-mastectomy pain. It is therefore hypothesized that intravenous ketamine given intraoperatively will reduce the incidence and severity of chronic pain after modified radical mastectomy. A double blind randomized controlled trial comparing placebo group with two different doses of ketamine is proposed.
The mechanism of action of ketamine in reducing pain is complex and multiple. How ketamine can prevent and reduce chronic pain is unknown. Ketamine has been shown to reduce immediate gene expression at site of mechanical injury. Transient Receptor Potential Vanilloid 1 (TRPV1) and Transient Receptor Ankyrin 1 (TRPA1) are receptors shown to mediate acute and chronic pain. Ketamine, shown to affect gene expression, may alter the expression of TRPV1 and TRPA1 via epigenetic mechanisms.
详细描述
Procedures Patients will be approached at the preadmission clinic or in the general ward before operation. The analgesic methods will be explained and s/he will be recruited into the study if s/he agrees. The patient will be randomized into one of three groups. The patients in the first group (C) will receive intraoperative morphine, local wound infiltration with local anaesthetic, cyclooxygenase-2 (COX-2) inhibitor post-operatively, and post operative Patient Controlled Analgesia (PCA) morphine. Patients in the second (K1) and third groups (K2) will receive different doses of intraoperative intravenous ketamine in addition to intraoperative morphine, local wound infiltration with local anaesthetic, COX-2 inhibitor, and PCA morphine.
Randomization and blinding Patients recruited for mastectomy will be stratified in randomization. To ensure equal distribution of patients between each type of operation (modified radical mastectomy with axillary dissection and mastectomy with sentinel lymph node without axillary dissection) block randomization will be used. There will be 9 blocks of 15 patients for each type of operation. The allocation order will be selected by a computer generated random sequence.
This is a double blind randomized control trial. Both the patients and the investigators will be blinded to the allocated analgesic modalities: ie the administration of ketamine. Ketamine or normal saline (placebo) will be prepared by clinical staff who will not participate in observation and data analysis.
Data collection
The following data will be collected during the perioperative period:
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)
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
- •the American Society of Anesthesiologists adopted physical status classification system (ASA) I-III
- •Age 18-80 years old
- •Scheduled for 1) modified radical mastectomy (including axillary lymph node dissection) and 2) mastectomy with sentinel lymph node (without axillary dissection). These are the common surgical treatments for breast cancer.
排除标准
- •Radical mastectomy, wide local excision or lumpectomy
- •Known allergy to opioids, local anaesthetic drugs, non-steroidal anti-inflammatory drugs (NSAIDS) including COX-2 inhibitors
- •History of chronic pain
- •Alcohol or drug abuse
- •Impaired renal function, defined as preoperative serum creatinine level over 120 micromol/L
- •Pre-existing neurological or muscular disorders
- •Psychiatric illness
- •Impaired or retarded mental state
- •Not self ambulatory before operation
- •Difficulties in using patient controlled analgesia (PCA)
- •Pregnancy
- •Local infection
- •Patient refusal
研究组 & 干预措施
Saline
A syringe of 50 ml 0.9% normal saline will be prepared as placebo for infusion and a syringe of 10ml 0.9% normal saline for bolus injection.
干预措施: Saline (Drug)
Ketamine 0.5mg/kg
A bolus injection of intravenous ketamine at a dose of 0.5mg/kg during anaesthetic induction before skin incision followed by 0.25mg/kg/hr intravenous ketamine infusion during the operation.
干预措施: Ketamine 0.5mg/kg (Drug)
Ketamine 0.75mg/kg
A bolus injection of intravenous ketamine at a dose of 0.75mg/kg during anaesthetic induction before skin incision followed by 0.5mg/kg/hr intravenous ketamine infusion during the operation.
干预措施: Ketamine 0.75mg/kg (Drug)
结局指标
主要结局
Severity of chronic pain
时间窗: At postoperative 3 months
Determine the severity using numerical rating scale
次要结局
- Incidence of neuropathic pain(At postoperative 3 months)
研究者
Wong Sau Ching Stanley
Clinical Assistant Professor
The University of Hong Kong