Prospective Evaluation of the Effects of IV Ketorolac on Platelet Function Post-Cesarean Delivery
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Platelet Aggregometry
研究概览
简要总结
Cesarean delivery has become the most common surgical procedure in the US. Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to improve the quality of post-cesarean analgesia and markedly reduce opioid consumption. The effect of NSAIDs on healthy volunteers results in inhibition of platelet aggregation and prolonged bleeding time. However, in the obstetric population, the presence and degree of platelet inhibition after NSAID exposure is less clear. The investigators plan to use Platelet Aggregometry and Thromboelastography (TEG) to evaluate the effect of ketorolac on platelets.
详细描述
Cesarean delivery has become the most common surgical procedure in the US, with over 1.2 million cesarean deliveries performed each year. The addition of non-steroidal anti-inflammatory drugs (NSAIDs) to a post-cesarean analgesic regimen has been shown to improve the quality of post-cesarean analgesia and markedly reduce opioid consumption. As a result, fewer patients incur opioid related side-effects such as nausea and vomiting, respiratory compromise, sedation, and impaired breast-feeding.
The effect of NSAIDs on healthy volunteers is relatively well-described. Most commonly, NSAIDs inhibit membrane-bound cyclooxygenase 1 (COX-1), the enzyme responsible for the production of the platelet agonist thromboxane A2. This ultimately results in inhibition of platelet aggregation and prolonged bleeding time. However, in the obstetric population, the presence and degree of platelet inhibition after NSAID exposure is less clear. This has limited the incorporation of NSAIDs into protocols for postpartum analgesia following cesarean delivery.
Platelet Function Assessment 100 (PFA) assays, with collagen/epinephrine and collagen/ADP (adenosine diphosphate) as agonists, can reliably test for platelet inhibition. PFA has been utilized to examine the anti-platelet effects of platelet inhibitors including NSAIDs in studies involving non-obstetric patients. Similarly, platelet aggregometry has been used to evaluate the platelet inhibitory effects of NSAIDs. Thromboelastography (TEG) has been shown in numerous studies to represent in-vivo clot strength and function.
Research in this field is needed as physiologic changes of pregnancy combined with significant surgical blood loss and hemodilution at cesarean delivery may alter the effect on maternal platelet function. This has become more pressing as postpartum thromboprophylaxis is likely to be more commonly considered for patients after cesarean delivery. In their most recent unofficial guidelines, the American Society of Regional Anesthesia state that NSAIDs should not be used with thromboprophylaxis after patients received neuraxial blockade (ASRA App). However, to the best of our knowledge, there is limited data, only utilizing bleeding time,5 examining the potential platelet inhibitory effect of NSAIDs in a low-risk healthy cohort undergoing cesarean delivery.
Protocol:
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 patient 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
- •Undergoing routine, scheduled cesarean section
- •Gestation >37 weeks
- •Singleton gestation
- •Intraoperative anesthesia - 1.5 ml of intrathecal bupivicaine 0.75%, 25mcg of intrathecal fentanyl and 250 mcg of intrathecal morphine via Spinal or Combined Spinal Epidural
排除标准
- •Pre-eclampsia with severe features or HELLP
- •Allergy to NSAIDs
- •Pre-existing bleeding disorder
- •Other major risk factor for postpartum hemorrhage (placenta accreta, large uterine fibroid)
- •Chronic kidney disease
- •Plt count less than 100k
- •Gastric ulcer or gastric bleeding
- •Pre-existing uterine bleeding or disseminated intravascular coagulation
- •Patient or Obstetrician refusal
- •Intraoperative exclusion criteria - Postpartum hemorrhage (EBL >1000 ml) or unplanned intraoperative extension of surgery
研究组 & 干预措施
Placebo
1 ml of normal saline
干预措施: Placebos (Drug)
Ketorolac
30 mg of ketorolac in 1 ml
干预措施: Ketorolac Tromethamine 30 MG/ML (Drug)
结局指标
主要结局
Platelet Aggregometry
时间窗: 15 minutes after dosing of placebo or ketorolac
Platelet Aggregometry measures the percent change in light transmission as a marker of platelet aggregation. The outcome is determined by the percentage of inhibition of platelet aggregation comparing the pre-drug values and the post-drug values. Higher number of inhibition indicates greater inhibition, meaning greater drug effect on platelet function.
次要结局
- Thromboelastogram Parameters Including Reaction Time (R)(15 minutes after dosing of placebo or ketorolac)
- Thromboelastogram Parameters Including Kinetics (K-time)(15 minutes after dosing of placebo or ketorolac)
- Thromboelastogram Parameters Including Angle (Alpha)(15 minutes after dosing of placebo or ketorolac)
- Thromboelastogram Parameters Including Maximum Amplitude (MA)(15 minutes after dosing of placebo or ketorolac)
研究者
Phillip Hess
Associate Professor of Anaesthesia
Beth Israel Deaconess Medical Center