Does a Single Intravenous Dose of Ketamine Reduce the Need for Supplemental Opioids in Post-Cesarean Section Patients?
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 188
- 试验地点
- 1
- 主要终点
- Number of Subjects Requiring Supplemental Analgesia in the First 24 Hours Following Cesarean Delivery
研究概览
简要总结
Pain control after cesarean delivery is associated with improved breastfeeding and infant rooming-in times. In addition, inadequate analgesia leads to elevated plasma catecholamine concentrations, which negatively affect every organ system. There is growing evidence that ketamine, N-methyl-D-aspartate receptor antagonist, is efficacious when used as an adjuvant in postoperative pain control. A 2006 Cochrane Collaboration systemic review and meta-analysis concluded, "Ketamine in subanesthetic doses....is effective in reducing morphine requirements in the first 24 hours after surgery."
Ketamine's prolonged analgesic effect, despite its short half-life and its use in low doses, is theorized to be due to blockade of spinal cord central sensitization. Central sensitization is a phenomenon whereby repeated painful stimulus leads to more severe pain perception over time despite no change in the intensity of the painful stimulus.Ketamine may also prevent the development of acute opioid tolerance. Ketamine's analgesic effects have also demonstrated in the obstetric population. Post-cesarean delivery morphine requirements in women who received ketamine as part of a general anesthesia technique were decreased. Similary, low-dose ketamine in conjunction with bupivacaine-only spinal anesthesia reduced postoperative analgesic requirements compared to bupivacaine-only spinal anesthesia and bupivacaine-fentanyl spinal anesthesia.
In the United States, healthy women scheduled for elective cesarean delivery commonly receive spinal anesthesia with bupivacaine-fentanyl-morphine. To our knowledge, IV ketamine has not been studied as an adjuvant to this regimen in the analgesic management in post-cesarean delivery patients. Multimodal therapy for postoperative pain control is widely practiced due to the advantage it provides in blocking multiple pain pathways while minimizing side effects of each individual pain medication. We hypothesize that low dose intravenous ketamine will improve multi-modal post-cesarean analgesia compared to placebo. The purpose of this study is to evaluate this hypothesis and study the possible side effects of this regimen in combination with bupivacaine-fentanyl-morphine spinal anesthesia.
详细描述
Eligible women for elective cesarean section admitted to the Labor and Delivery Unit of Prentice Women's Hospital will be approached for study participation immediately after the routine preanesthetic evaluation. This occurs shortly after admission to the Labor and Delivery Unit. Women who agree to participate will give written, informed consent at this time.
Subjects will be prepared preoperatively in the usual fashion with intravenous (IV) access, aspiration prophylaxis and intraoperative monitoring. Preincision antibiotics will be given and uterotonic medications will be used as per usual practice after delivery.
The anesthesiologist will perform a spinal anesthetic per routine with the subject in the sitting position using sterile technique at the L3-4 interspace (± one vertebral interspace). The spinal anesthetic will consist of 12 mg of hyperbaric bupivacaine + 15 μg fentanyl + 150 μg of morphine. The subject will be placed supine with left lateral tilt to alleviate aortocaval compression. Cesarean section will commence after adequate anesthesia is assured to a T4 sensory level to pinprick. Vasopressors and IV fluids will be administered at the anesthesiologist's discretion per usual practice.
At the time of delivery, subjects will be randomized to one of two groups using a computer generated random number table. Randomization will be blocked based on whether the cesarean procedure is a primary or a repeat procedure. Randomization assignments will be kept in sequentially numbered opaque envelopes. The envelope will be opened by a research nurse who will prepare a 20 mL syringe labeled "study drug". The syringe will be given to the anesthesiologist blinded to the treatment group who will subsequently administer the study drug. Subjects randomized to the treatment group will receive ketamine 10 mg (ketamine 10 mg/mL) diluted to 20 mL with 0.9% preservative free saline. Subjects randomized to the placebo group will receive 20 mL preservative free saline.
The study drug will be administered into the intravenous line via an infusion pump over 10 minutes. Five minutes after placebo or drug administration, the anesthesiologist will ask the subject if she has nausea, vomiting and pruritus. Nausea and pruritus will be graded as none, mild, moderate or severe; and vomiting as present or absent. Any spontaneous complaints of psychedelic effects will be noted at this time. Sedation will be assessed via the Richmond agitation-sedation scale (RASS [see Appendix 1]).
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 60 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Eligible women are at term (≥37 week gestation),
- •ASA class 1-2,
- •Scheduled for elective cesarean section whose anesthetic plan is for spinal anesthesia with intrathecal morphine and intravenous ketorolac analgesia for post operative analgesia
排除标准
- •Women with American Society of Anesthesiologists physical status >2,
- •Body mass index ≥40 kg/m2,
- •Known allergy to any of the study medications,
- •Contraindication to the spinal anesthesia,
- •History of substance abuse,
- •History of hallucinations,
- •Chronic opioid therapy,
- •Chronic pain.
研究组 & 干预措施
Ketamine
Subjects receive IV ketamine 10 mg 5 minutes after infant delivery.
干预措施: Ketamine (Drug)
Placebo
Subjects receive IV Saline 20 mL 5 minutes after infant delivery
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Subjects Requiring Supplemental Analgesia in the First 24 Hours Following Cesarean Delivery
时间窗: 24 hours
Request for oral hydrocodone/acetaminophen for pain not controlled by around the clock non-steroidal antiflammatory drugs in the first 24 hours following cesarean delivery.
次要结局
- Verbal Pain Scores (0 to 10) at First Analgesia Request(24 hours)
- Cumulative Hydrocodone/Acetaminophen for Supplemental Analgesia to Treat Breakthrough Pain(72 hours)
- Postoperative Nausea(24 hours)
- Postoperative Vomiting(24 hours)
- Postperative Pruritus(24 hours)
- Disturbing Dreams(72 hours)
研究者
Cynthia Wong
Professor of Anesthesiology
Northwestern University