Efficacy of Preoperative Pregabalin on the Post-caesarean Pain; a Dose-response Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 135
- 试验地点
- 2
- 主要终点
- cumulative patient controlled morphine consumptions
研究概览
简要总结
Post-cesarean pain management is essential for early mobilization of the mother so that she becomes able to care of her newborn. There choices for postoperative analgesia include spinal, systemic, or both opioids, non-steroidal anti-inflammatory drugs (NSAIDs), local anesthetic infiltrations of the wound, or transverse abdominis plane blocks, which are determined by drug availability, regional and individual preferences, resource limitations and financial considerations. The use of opioids is associated with adverse effects such as nausea, pruritus, sedation, and occasionally respiratory depression.
Pregabalin is an anticonvulsant drug structurally related to the inhibitory neurotransmitter gamma amino butyric acid, that exerts its action by binding to the α-2-δ subunit of the voltage-dependent calcium channel. It reduces the release of the excitatory neurotransmitters and inhibits the hyperalgesia and central sensitization.
A recent meta-analysis demonstrated that pregabalin reduce the postoperative 24 hours cumulative opioid consumption and opioid-related adverse effects namely, vomiting and visual disturbances after surgery. Compared with the use of pregabalin doses lower than 300 mg, the use of doses higher than 300 mg even reduced opioid consumption by 35%.
It is not known if pregabalin is excreted in human milk. There is a case report on the extensive excretion of pregabalin in breast milk, but with low measured concentrations in infant as a consequence of maternal exposure during breast feeding. Food and Drug Administration recommends to discontinue nursing or to discontinue pregabalin in nursing mothers. Pre-delivery single exposure to pregabalin is expected to be safe for the newborns.
Up to the authors' best knowledge, this is the first clinical study on the efficacy and safety of the administration of pregabalin before cesarean delivery.
We hypothesis that the preoperative administration of a single dose of pregabalin will improve the quality of postoperative analgesia after cesarean delivery.
This placebo-controlled study aims to compare the effects of preoperative administrations of single oral doses of pregabalin 150 mg and 300 mg on the postoperative pain scores, cumulative patient controlled morphine consumptions, neonatal Apgar and neurologic and adaptive capacity scores (NACS), and maternal and neonatal adverse effects in parturients scheduled to elective Cesarean delivery under spinal anesthesia.
详细描述
An independent investigator who will not be involved in the study will instruct the patients preoperatively about the use of patient controlled analgesia and visual analogue scale to assess the severity of postoperative pain (0 mm for no pain and100 mm for worst imaginable pain).
Anaesthetic management will be standardized. Oral ranitidine 150 mg and metoclopramide 10 mg will be given the night before and on the morning of surgery, with 0.3 mol/L sodium citrate 30 mL given 15 min before induction.
Ninety minutes before surgery, subjects will be allocated randomly into three groups by drawing sequentially numbered sealed opaque envelopes containing a software-generated randomization code to the placebo (n = 45), pregabalin 150 mg (n = 45) and the pregabalin 300 mg (n = 45) groups. The placebo and pregabalin capsules look identical and will be prepared by a local pharmacy. An anaesthesiologist not otherwise involved in the study and who will be blinded to treatment regimen will provide perioperative care. An independent investigator will collect perioperative data. All staff in the operating room will be unaware of patient allocation group.
Maternal monitoring will include electrocardiography, non-invasive blood pressure, and pulse oximetry. Left uterine displacement will be maintained.
Spinal anesthesia will be performed in all cases in sitting position at L3-L4 or L4-L5 spaces with hyperbaric bupivacaine 0.5% (12.5 mg) and fentanyl 20 µg. After the umbilical cord is clamped, a 10 IU infusion of oxytocin in 500 mL of lactated Ringer's solution will be infused.
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 38 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •spinal anesthesia
- •elective cesarean delivery
- •breech presentation
- •cephalopelvic disproportion
- •previous caesarean delivery
- •American Society of Anesthesiologists class I and II
排除标准
- •communication barriers
- •cardiovascular diseases
- •renal diseases
- •hepatic diseases
- •endocrinal diseases
- •neuropsychiatric diseases
- •morbid obesity
- •diabetes mellitus
- •bleeding disorders
- •prolonged P-R interval
- •hypersensitivity to pregabalin
- •receiving pregabalin
- •receiving anticonvulsants
- •receiving antidepressants
- •receiving antipsychotics
- •alcohol or drug abuse
- •Opiates abuse
- •benzodiazepines during the last week
- •pregnancy-induced hypertension
- •evidence of intrauterine growth restriction
- •fetal compromise
研究组 & 干预措施
Placebo
receive two identical placebo capsules
干预措施: Placebo (Drug)
Pregabalin 150 mg group
one capsule of pregabalin 150 mg
干预措施: Pregabalin 150 mg group (Drug)
Pregabalin 300 mg group
two capsules of pregabalin 150 mg
干预措施: Pregabalin 300 mg group (Drug)
结局指标
主要结局
cumulative patient controlled morphine consumptions
时间窗: 24 hours after delivery
cumulative patient controlled morphine consumptions 24 hours after delivery
次要结局
- neonatal Apgar scores(1 and 5 min aftr delivery)
- postoperative pain scores(1, 4, 6, 12, 24 and 48 hours after delivery)
- Neurologic and adaptive capacity scores(at 15 min, 2h, 24 and 48 h after delivery)
- Maternal sedation(every two hours after delivery, for 48 hours after delivery)
- Maternal nausea and vomiting(at 24 hours after delivery)
研究者
Mohamed R El Tahan
Associate Professor of Anesthesiology & SICU
Mansoura University