A Prospective, Randomized, Control Trial of Ketorolac Versus Placebo on Opioid Analgesic Use, Estimated Blood Loss and Complications Following Cesarean Delivery With Epidural Morphine
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Estimated Blood Loss (EBL)
研究概览
简要总结
In this randomized, double-blind control trial to evaluate the effect of ketorolac given at the time of cord clamp has on estimated blood loss and postcesarean pain control. Patients will be randomized to either placebo or ketorolac prior to surgery. Those randomized to ketorolac will receive ketorolac at cord clamp and three additional doses every 6 hours (total 4 doses/24 hours). Those in the placebo group will receive normal saline during those time periods. Our primary outcome is to assess whether intra-operative ketorolac increases the estimated blood loss during Cesarean delivery.
详细描述
Background:
Opioid analgesics are among the most common medication employed for post-cesarean delivery pain management. However, opioid side-effects such as, nausea, vomiting, urinary retention, and sedation are problematic and can adversely impact post-operative recovery. Non-steroidal anti-inflammatory medications have analgesic as well as anti-inflammatory properties making them an ideal alternative for opioid analgesics. Ketorolac, which can be given by either oral and parenteral routes, is frequently employed as a post-surgical analgesic in a variety of procedures including gynecologic and obstetric, and has comparable analgesic properties to opioids without the aforementioned side-effects.(1)
Additionally, two studies have specifically evaluated administration of ketorolac in the treatment of post-cesarean section pain in patients receiving either patient controlled intravenous analgesia or patient controlled epidural analgesia.(2, 3) However, due to the known inhibition of prostaglandin synthesis, several retrospective and observational studies have suggested that ketorolac and other non-steroidal anti-inflammatory drugs (NSAIDs) may be associated with an increase in estimated blood loss (EBL) and uterine atony.(4,5) This research showed in vivo defects in platelet function, however a recent meta-analysis in a variety of different surgical procedures suggest there is no clinically significant difference in EBL attributed to the administration of ketorolac compared to placebo.(6)
Despite this, there still exists significant resistance to the intraoperative and post-operative use of ketorolac due to concerns of increasing EBL. This is particularly true with regard to cesarean sections, which, due to the nature of the procedure is associated with an EBL higher than found in many other surgeries and possibly leading to increased morbidity. To our knowledge there have only been three previous studies that specifically examined the use of ketorolac with cesarean delivery.
El-Tahan et al, administered ketorolac preoperatively and focused on the blunting of sympathetic response to intubation of healthy patients undergoing cesarean section under general anesthesia. This study evaluated only a single low dose followed by intraoperative infusion. Although they did look at intraoperative EBL, they did not give additional postoperative doses or assess postoperative bleeding.(7) Lowder et al and Pavy et al looked at postoperative use of ketorolac on pain control and EBL, but no intraoperative dose of ketorolac was given.(2,3)
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)
盲法说明
Placebo (normal saline) or ketorolac in syringe prepared by the investigational pharmacy with study kit number and blinding key maintained by investigational pharmacy until time of unblinding.
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Patients undergoing a scheduled or non-scheduled, non-urgent primary or repeat Cesarean delivery between 37-42 weeks gestational age,
- •Viable singleton intra-uterine pregnancy,
- •Patients undergoing a scheduled or unscheduled, non-emergent/non-urgent Cesarean delivery for placenta previa or vasa previa,
- •Neuraxial anesthesia with combined spinal-epidural placed for surgery,
- •Patients must be 18 years or older as well as willing and able to provide informed consent.
排除标准
- •Patients unable or unwilling to provide informed consent,
- •Urgent or emergent Cesarean delivery
- •Multiple fetal gestations (>1 intrauterine pregnancy),
- •Cesarean delivery for bleeding such as placental abruption or actively bleeding placenta previa or vasa previa,
- •Contraindication to NSAID use eg: allergy, chronic renal disease,
- •Patients with acute or chronic platelet dysfunction (e.g.: idiopathic thrombocytopenic purpura, HELLP syndrome),
- •Platelets <100k,
- •History of peptic ulcer disease,
- •Inherited or acquired coagulopathies or bleeding disorder, (disseminated intravascular coagulopathy, hemophilia),
- •Suspected or proven placenta accreta, increta or percreta,
- •Inability to receive epidural morphine,
- •Diagnosed chronic pain disorder on chronic adjunct or opioid analgesia,
- •Use of general anesthesia during procedure.
- •Intraoperative exclusion criteria:
- •EBL > 1000 ml prior to cord clamp
研究组 & 干预措施
Experimental
Patients in this arm will be given ketorolac at cord clamp with standard dose of 30 mg, then 3 additional 30 mg doses every 6 hours
干预措施: Ketorolac (Drug)
Control
Patients in this arm will be given a placebo medication at cord clamp, and then 3 additional doses of placebo every 6 hours.
干预措施: Placebo (Drug)
结局指标
主要结局
Estimated Blood Loss (EBL)
时间窗: Immediately post-op
Estimation of blood loss during surgery
次要结局
- Total Hydromorphone Dose(0 - 24 hours post-partum.)
- Anti-emetic Doses(0 - 24 hours post-partum)
- Hydromorphone Use(0 - 24 hours post-partum)
- Uterotonic Doses(0 - 24 hours post-partum)
- Units of Packed Reb Blood Cell Transfused(Intra-op until 24 hours post-partum.)
- Post-Partum Hemorrhage(0 - 24 hours post-partum)
- Corrected Change in Hct on POD1.(POD1)
- Pruritus Doses(0 - 24 hours post-partum)
- Percentile Change in Systolic Blood Pressure at 6,12, and 24 Hours(0 - 24 hours post-partum)
- Change in Pain Score Post-Cesarean Delivery(Up to 24 hours post-cesarean delivery)
- Percentile Change in Diastolic Blood Pressure (DBP) at 6,12, and 24 Hours(0 - 24 hours post-partum)
研究者
John J. Kowalczyk
Instructor of Anaesthesia - Beth Israel Deaconess Medical Center, Harvard Medical School / Harvard Medical School
University Hospitals Cleveland Medical Center