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
Description:
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.
Intraoperative technique and management:
Upon arrival to the operating room standard monitors (Pulse oximeter, Noninvasive blood
pressure monitoring, and Electrocardiogram) will be applied and continued all over the
operation, an eighteen gauge (18G) peripheral intravenous (IV) cannula will be inserted, and
10 ml/kg of Ringer lactate solution warmed to 37°C will be infused over 15 minutes as a
preload.
IT block will be performed via a midline approach into the L4-5 interspaces in sitting
position with complete aseptic condition using a 25 gauge Quincke spinal needle after giving
3 ml of lidocaine 2% (60 mg) as a subcutaneous infiltration. After confirming free
cerebrospinal fluid (CSF) flow through the needle a 2.5 ml of hyperbaric bupivacaine 0.5 % in
addition to the content of the prepared study syringe will be slowly injected. Then, the
parturient will be immediately placed in the supine position with 15° left tilt, and an
oxygen mask will be applied at 2 l/min.
After ensuring sufficient anesthesia level, the surgical procedure will start with continuous
hemodynamics monitoring and recording. If the systolic blood pressure (SBP) decreased to 20%
below the baseline or less than 90 mmHg, ephedrine 5 mg will be administered intravenously.
Also, if heart rate (HR) will be less than 50 beats/min, atropine sulfate 0.5 mg will be
administered intravenously. Any intraoperative or postoperative nausea or vomiting will be
managed with 10 mg of metoclopramide Upon delivery of the fetus, ten units of oxytocin will
be given by IV infusion, and if the uterus is not well contracted, additional increments of 5
units will be added accordingly. One gm of Ceftriaxone will be also given after delivery of
the fetus by IV infusion.
Postoperative monitoring, Pain control and follow up:
At the end of surgery, Participant will be transferred to postoperative anesthesia care unit
(PACU) with standard monitoring applied. All Participants will receive 75 mg diclofenac
sodium intramuscular every 12 hours as a pain management per institution policy, 1,23 4 mg of
morphine will be given IV if rescue analgesia is needed postoperatively every 10 minutes with
a maximum of 20 mg in 6 hours or 32 mg in 24 hours. The participant will be transferred to
obstetrics ward after fulfilling the criteria of modified Aldrete scoring system. 24
Assessment for post-dural puncture headache and other associated symptoms will be done from
day 0 to day five postoperatively and if the participant will be discharged home, follow up
will be done by a phone call. If there will be a complaint of a headache, the participant
will be asked to come back to the hospital for proper assessment and management either on an
outpatient or inpatient bases per the headache severity.
The participants who will be diagnosed to have PDPH per the criteria of the International
Headache Society (HIS) will be treated by using oral medications Panadol extra™ (paracetamol
1gm + caffeine 130 mg) (Manufactured by: Alexandria company for pharmaceuticals & chemical
industries under license: GlaxoSmithKline Consumer Healthcare Ltd. Ireland) at 6-hour
interval in addition to hydration and bed rest. Severe Intractable headache (VAS ≥ 40)
persistent for more than 48 hours with no response to conservative measures will be managed
with an epidural blood patch after participant approval and consent signing.
Statistical analysis and sample size estimation:
Continuous variables will be tested for normal distribution by the Shapiro-Wilk test (P ≤
0.05). Parametric data will be expressed as mean and standard deviation (SD) and analyzed by
using the independent t-test. Data with kurtosis or skewness will be depicted as median and
interquartile range and compared for significant difference by implementation of Mann-Whitney
U test. Categorical variables will be presented as numbers and frequencies and the chi-square
test or Fisher exact test will be used to analyze the significant differences between the two
arms. A P value ≤ 0.05 will be considered statistically significant. Data will be analyzed
using SPSS (SPSS 16.0, SPSS Inc., Chicago, II, USA).
The sample size calculation based on that a 15 % reduction in the incidence of PDPH between
the two arms could be of clinically important relevance. The reported incidence of PDPH with
the use of 25 gauge Quincke needle is 25 %. Sample size of 100 participants per group were
found sufficient assuming (two tail) α = 0.05, β = 0.2 (80 % power), and 1:1 allocation
ratio. We will plan to recruit 120 participants per group to account for data loss or
protocol violation. The sample size calculation performed with G*Power software version
3.1.9.2 (Institute of Experimental Psychology, Heinrich Heine University, Dusseldorf,
Germany).
Condition:
Post-Dural Puncture Headache
Treatment:
Neostigmine Methylsulfate
Start Date:
August 4, 2018
Sponsor:
Fayoum University Hospital
For More Information:
https://clinicaltrials.gov/show/NCT03587441