The Efficacy of Neostigmine as an Adjuvant to Bupivacaine for Intrathecal Block in Reducing the Incidence and Severity of Post-Dural Puncture Headache for Parturients Scheduled for Elective Caesarean Section
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 240
- 试验地点
- 1
- 主要终点
- incidence of post-dural puncture headache
研究概览
简要总结
Neuraxial blocks continue to be the cornerstone of anesthesia and postoperative analgesia for normal vaginal delivery and elective caesarean section due to its approved safety and efficiency for decades. Post-dural puncture headache (PDPH) is still one of the most common complications of neuraxial anesthetic techniques. The headache could be severe and limit the activities of the new mother to care for her baby, prolong hospital stay.
PDPH is defined as a headache that develops within five days of dural puncture and can't be attributed to any other types of headache and mostly is postural in character.
Neostigmine methylsulfate is a synthetic carbamic acid ester which reversibly inhibits the enzyme Acetylcholine esterase (AChE) that makes more Acetylcholine molecules available at cholinergic receptors. Neostigmine is used in anesthesia mainly as a reversal for non-depolarizing neuromuscular agents.
Intrathecal (IT) neostigmine was tried as an adjuvant to local anesthetics in IT block for elective cesarean sections to decrease local anesthetic consumption and to prolong postoperative analgesia. Side effects of IT neostigmine are dose-dependent with doses more than 25 µg especially nausea and vomiting and could be decreased by increasing the baricities of the local anesthetic solutions and by early head up position after IT injection. However, its effect on PDPH was not investigated before in literature.
Parturients will be randomly assigned into one of two groups: the intervention group will receive 20 µg with IT Bupivacaine and the control group will receive an equivalent volume of dextrose 5% with the IT Bupivacaine.
The objective of the current study is to evaluate the efficacy and safety of IT neostigmine as an adjuvant to bupivacaine in reducing the incidence and severity of post-dural puncture headache in parturients scheduled for an elective cesarean section.
详细描述
The study will be performed from July 2018 to July 2019 at Fayoum University hospital after approval of the local institutional ethics committee and local institutional review board. The study design will be prospective, randomized, double-blind, parallel groups, placebo-controlled clinical trial. A detailed informed consent will be signed by the eligible participants before recruitment and randomization.
Randomization will be done by using computer-generated random numbers that will be placed in separate opaque envelopes that will be opened by study investigators just before IT block. Neither the participants, the study investigators, the attending clinicians, nor the data collectors will be aware of groups' allocation until the study end. The Consolidated Standards of Reporting Trials (CONSORT) recommendations for reporting randomized, controlled clinical trials will be followed.
Preoperative preparations and Premedication:
The study solutions will be prepared in a one milliliter syringe as following: For the intervention group (N), it will contain 20 µg of Neostigmine® (0.5 mg/ml ampules manufactured by Amriya for pharmaceutical industries in Alexandria, Egypt) neostigmine ampule will be diluted in 4 ml dextrose 5% to make a solution of 100 µg/ml, 0.2 ml of this solution will be used, while in the control group an equal volume (0.2 ml) of dextrose 5% will be prepared. The syringes used will be labeled as A and B per their content. The identical coded syringe will be prepared by trained anesthesia technicians who will not be included in the study.
All parturients will receive 150 mg Ranitidine oral tablet on the night before and on the morning of the operation as a premedication.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 20 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •American society association (ASA) physical status II parturients who will be scheduled for an elective caesarean section by IT anesthesia
排除标准
- •significant renal, hepatic, and cardiovascular diseases
- •pre-eclampsia
- •any contraindication to regional anesthesia such as local infection or bleeding disorders
- •allergy to neostigmine
- •long-term opioid use
- •a history of chronic pain, migraine, cluster headache
- •digestive problems with nausea or vomiting
- •cognitive or memory disorders
- •history of urinary retention; bronchial asthma
- •perioperative blood transfusion
研究组 & 干预措施
The Intervention Group (N)
Neostigmine Methylsulfate intervention : A one milliliter syringe will contain 20 µg of Neostigmine methyl sulfate. 0.5 mg ampule (1 ml) will be diluted in 4 ml dextrose 5% to make a solution of 100 µg/ml, 0.2 ml of this solution will be added to 2.5 ml of hyperbaric bupivacaine 0.5 % used for intrathecal injection.
干预措施: Neostigmine Methylsulfate (Drug)
The Intervention Group (N)
Neostigmine Methylsulfate intervention : A one milliliter syringe will contain 20 µg of Neostigmine methyl sulfate. 0.5 mg ampule (1 ml) will be diluted in 4 ml dextrose 5% to make a solution of 100 µg/ml, 0.2 ml of this solution will be added to 2.5 ml of hyperbaric bupivacaine 0.5 % used for intrathecal injection.
干预措施: Dextrose 5% in water (Drug)
The Control Group (P)
Dextrose 5% in water intervention : an equal volume (0.2 ml) of dextrose 5% will be added to 2.5 ml of hyperbaric bupivacaine 0.5 % used for intrathecal injection.
干预措施: Dextrose 5% in water (Drug)
结局指标
主要结局
incidence of post-dural puncture headache
时间窗: At day 5 from intrathecal block
any headache that develops within five days of dural puncture and can't be attributed to any other types of headache and mostly is postural in character
次要结局
- Percent of participants complained from postoperative nausea and vomiting(AT 48 hours after PDPH)
- incidence of memory and cognitive disorders(At 48 hours from intrathecal block)
- ephedrine requirements(From intrathecal block until discharge from PACU, assessed up to 24 hours)
- Age(6 hours before intervention)
- Weight(6 hours before intervention)
- Height(6 hours before intervention)
- Body mass index(6 hours before intervention)
- Headache onset(After intrathecal block for five days till appearance of PDPH)
- Duration of surgical procedures(After completion of surgical procedures, within about two hours of intervention)
- Percent of participants with neck stiffness(At 48 hours after headache onset)
- Visual analog score of post-dural puncture headache (PDPH) at presentation(At 24 hours after headache onset)
- Percent of participants in need for epidural blood patch(After 48 hours from onset of headache)
- atropine requirements(From intrathecal block until discharge from PACU, assessed up to 24 hours)
- incidence of shivering(From intrathecal block until discharge from PACU, assessed up to 24 hours)
- time to the first requirement of analgesic supplement(From intrathecal block until discharge from PACU, assessed up to 24 hours)
- total analgesic consumption(At 24 hour after intrathecal block)
- the assessment of duration of sensory blockade(From intrathecal block until the first appearance of pain at the T10 dermatome, assessed up to 24 hours)
- the assessment of duration of motor blockade(From intrathecal block until the modified Bromage score will be zero, assessed up to 24 hours)
- Visual analog score of post-dural puncture headache (PDPH) after medical treatment(At 48 hours after starting medical treatment)
- incidence of urine retention(At 48 hours from intrathecal block)
- incidence of hypotension(From intrathecal block until discharge from PACU, assessed up to 24 hours)
- highest Visual analog score of post-dural puncture headache(At 48 hours after starting medical treatment)
- Percent of participants complained from intraoperative nausea and vomiting(From intrathecal block until discharge from PACU, assessed up to 24 hours)
- incidence of desaturation(From intrathecal block until discharge from PACU, assessed up to 24 hours)
- incidence of respiratory depression(From intrathecal block until discharge from PACU, assessed up to 24 hours)
- incidence of bradycardia(From intrathecal block until discharge from PACU, assessed up to 24 hours)
研究者
Hany M Yassin, MD
Associate Professor of Anesthesiology
Fayoum University Hospital