Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05558748 |
| Other study ID # |
MREC#2919 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
December 6, 2022 |
| Est. completion date |
May 2024 |
Study information
| Verified date |
September 2022 |
| Source |
Sultan Qaboos University |
| Contact |
Jyoti Burad, MD, EDIC |
| Phone |
+96899578636 |
| Email |
jyotiburad[@]yahoo.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This study is designed to compare the analgesic effectiveness of caudal analgesia to
ilioinguinal regional analgesia techniques in children undergoing inguinal surgeries. Both
techniques will be done under ultrasound gaudiness, using the same local anesthesia. 128
patients will be included in this study, 64 for each technique. This study aims to know the
best regional analgesia technique in children undergoing inguinal surgeries, reduction in
rescue analgesia postoperatively, postoperative length of stay, and early resumption of
postoperative activity.
The patients will be followed up 30 minutes after the end of anesthesia in PACU,
postoperatively in Ward at 2 Hours, 3 hours, 6 hours from the end of anesthesia, and or at
the time of discharge from the ward & on days 2 and 7. Patient privacy and safety will be
respected at all times. An interim analysis will be done after recruiting 25% of cases (16
cases) in both arms. Once the sample size is reached, the data will be sent for statistical
analysis with coded patient identity.
Based on study findings, the practice will be optimized with the aim of improvement in pain
relief, reduction in opioid requirements, and enhanced recovery after surgery (ERAS),
reducing the bed occupancy time in the hospital.
Description:
Introduction Inguinal surgeries are commonly performed in children. Pain is a dreaded side
effect of any surgery and should be adequately assessed and treated. It has been shown that
even minor procedures can cause significant pain in children.
1. Assessment of adequate analgesia is complex in children. Inadequate analgesia can cause
neurological, metabolic, pulmonary, and other bodily effects.
2. Postoperative analgesia for inguinal surgeries can be provided with caudal and
ilioinguinal/iliohypogastric nerve blocks. These techniques are safe and reduce the
requirement for opioids postoperatively. This can help in early discharge from the
hospital and faster resumption of daily activities.
The caudal block involves an injection of local anesthetic agents into the caudal space.
The caudal space is the sacral portion of epidural space involving needle penetration of
sacrococcygeal ligament covering sacral hiatus. This block is commonly done to provide
analgesia for urogenital, rectal, and inguinal surgeries. This block was primarily
performed as a blind technique. The onset of action is typically in 8.8 minutes, as per
NYSORA guidelines. Fortunately, serious complications occur infrequently. Potential
complications include epidural abscess, meningitis, epidural hematoma, dural puncture,
post-dural puncture headache, subdural injection, pneumocephalus, air embolism, back
pain, and intracranial hypotension headache after uncomplicated caudal epidural
injection. Ilioinguinal/iliohypogastric nerve block is commonly performed for inguinal
surgeries. This nerve penetrates the transversus abdominis muscle above the iliac crest
and supplies the muscle, and provides cutaneous innervation to the skin of the scrotum
and adjacent thigh. This block is known to abolish pain following inguinal surgeries in
the pediatric population effectively.
The primary objective of the study is to find a better analgesia technique out of caudal
and ilioinguinal/iliohypogastric blocks. The secondary objective is to compare the
reduction in the use of rescue analgesics and find a technique that provides earlier
resumption of activities.
Methods:
Study type: Randomized Controlled Trial, with 2 parallel arms. Blinding: Double
blinding: The patient, as well as the postoperative assessor, will be blinded.
Crossover: Nil Study duration: Prospective for 6-12months depending on the case
recruitment rate.
Number of groups: 2 Sample size: 128 patients (64 patients for each technique ) Target
follow-up duration: Intraoperative period, at 30 minutes after arrival and before
discharge from PACU, postoperatively in Ward at 2 Hours, 3 hours, 6 hours, and or at
time of discharge from the ward and at home on day 2 and day 7.
Study population Sample size The estimated sample size is 128 (64 in each group). The
estimation was based on the anticipated effect size (medium, Cohen's d= 0.5) for the
difference in the post-operative pain score between caudal and ilioinguinal block
methods. The power was set at 80%, and the alpha error was set at 5%. The allocation
ratio will be 1:1. The software used for the sample size calculation is G*Power version
3.1.9.7
Method:
An appropriate population posted for surgery will be approached as per eligibility
criteria, will be approached. An explanation of the study will be done in comprehensive
language. The patient's rights will be explained to the patient/relatives. Informed
consent will be taken on the consent form. The patient will then be randomized into 3
age-stratified groups (6 months up to 3 years, 3 years onwards to 6 years, and 6 years
onwards to 12 years). Each patient will be randomized to group A or B according to the
computer-generated stratified age group block randomization sequence. The randomization
sequence will be kept locked with a password-protected file. It will be accessed at the
time of randomization by the principal investigator only. A separate anesthetist will do
a pre-anesthetic checkup.
Premedication (Oral Midazolam 0.3 mg/kg) will be prescribed. On the day of surgery, the
patient will be premedicated; the intravenous cannula will be inserted inward. On
arrival of the patients to the operative theatre, ASA monitors will be attached ( ECG,
non-invasive blood pressure, and SPO2 ). Anesthesia will be induced with an intravenous
agent: Propofol: 2 mg/kg, inhalational anesthesia: sevoflurane, fentanyl 1 mic/kg,
glycopyrrolate 10 mics/kg and a supraglottic airway device (Laryngeal mask airway) will
be placed. Inhalational agent: Sevoflurane will be continued for the maintenance of
anesthesia. The patient will be positioned for the block, and the block will be given as
per randomization by one of the two expert pediatric anesthesia consultants following
the study protocol. The postoperative nausea and vomit prophylaxis will be given with
granisetron : 0.01 mg/kg & Dexamethasone 0.15mg/kg. For multimodal intraoperative
analgesia Paracetamol 7.5 mg/kg for < 10 kg weight and 15 mg/kg for > 10 kg weight will
be infused intravenously. At the end of the procedure, the anesthesia will be turned
off, and the child will be extubated after waking up as per the standard procedure. Then
the child will be shifted to PACU (Post-Anesthesia Care Unit).
For caudal block:
With the patient in the lateral position, the sacral cornua are identified by palpation
using the anatomic landmarks. Sterile skin preparation and draping of the entire region
are performed. A high-frequency ultrasound probe is placed in the transverse plane
across the two sacral cornua. The sacral cornua can be visualized as two symmetric
hyperechoic arches, with a hypoechoic shade underneath both lines, bridging these two
structures. An appropriately sized needle is inserted into the space between the two
cornua. A distinct "pop" is felt as the needle tip penetrates the sacrococcygeal
ligament. At this point, the probe's orientation is changed into the sagittal plane. The
caudal canal is identified as a hypoechoic canal tapering off caudally and bordered by
dorsal and ventral hyperechoic bands. The dorsal band is formed by the dorsal bony
aspect of the caudal canal cranially and the sacrococcygeal ligament caudally. The
ventral band is formed by the ventral bony surface of the caudal canal. The needle will
be advanced under ultrasound guidance, keeping the tip of the needle in view at all
times; the drug will be injected after placement of the needle tip in the caudal space.
Levobupivacaine 0.25%, 1 ml/kg will be injected into the space.
For Ilio-inguinal/iliohypogastric nerve block technique:
Position the patient supine. Prepare skin with antiseptic. Place the high-frequency
ultrasound probe on the anterior abdominal wall along the line joining the anterior
superior iliac spine (ASIS) and the umbilicus. The ilioinguinal and iliohypogastric
nerves are seen as hypoechoic structures with a hyperechoic border. They lie in the
plane between the internal oblique muscle and the transversus abdominis muscle close to
the ASIS. Insert the block needle in the plane from medial to lateral and ensure that
there is always a good image of the needle tip as the needle is advanced. The dose of
levobupivacaine will be 0.4 ml/kg of 0.25% concentration to be deposited slowly around
the nerves in the transversus abdominis plane.
Standard intraoperative ASA monitoring will be done and compared amongst the two groups.
PACU and Ward:
During the postoperative time, patients will be transferred to PACU and the ward when
they recover from anesthesia and will be observed by trained nurses. FLACC score will be
assessed & documented 30 minutes after the end of anesthesia and before discharge from
PACU, postoperatively in Ward at 2 Hours, 3 hours, 6 hours from the end of anesthesia,
and or at the time of discharge from the ward.
Follow up at Home:
The patients will be followed up on days 2 and 7 for pain with a Numeric rating scale
(NRS), consumption of analgesics, resumption of daily basic and routine preoperative
activities, and any untoward side effects.
Rescue analgesia:
Intraoperative rescue analgesia: For inadequate analgesia due to block, rescue analgesia
will be provided with morphine 50 mics/kg aliquots.
Postoperative rescue analgesia:
PACU: The pain will be assessed by PACU staff and nurses in the ward using the FLACC
scale, and rescue analgesia will be given with Morphine 50 mics/kg aliquots (highest 200
mic/kg).
Ward: In the ward rescue will be with Paracetamol 7.5-10 mg/kg for children< 10 kg and
15 mg/kg for children > 10 kg. The number of times the rescue is given will be recorded.
Home: Syrup Paracetamol 10 mg/kg sos (when needed) or every 8 hours will be prescribed.
Complications:
- Local anesthetic systematic toxicity (LAST)
- Hemodynamic changes
- Infection
- Injury to the nerve roots
- Subdural injection & Hematoma formation
- Urinary retention
- Bleeding
Troubleshooting:
Inadequate block or Failed block:
The depth of the sacral canal at the apex of the sacral hiatus and the length of the
sacrococcygeal ligament between the apex of the sacral hiatus and the sacral base is
associated with difficulty in performing CEB. In case of failed or inadequate block
patient, rescue analgesia will be provided with morphine 50 mics/kg. The pain will be
assessed by PACU staff and nurses in the ward using the FLACC scale. In the ward, rescue
will be with Paracetamol 15 mg/kg orally.
Hemodynamic changes:
Mainly hemodynamic changes are observed immediately after the block, and they are mild.
The patients will be continuously monitored during the perioperative period. And any
hemodynamic instability will be immediately treated with intravenous fluids and
vasopressors if it is significant.
Bleeding:
It is rarely encountered. Bleeding can be controlled by putting pressure on the area of
direct needle trauma with hematoma formation. The management includes conservative
treatment and surgical exploration. Especially if a hematoma forms, it should be removed
promptly. Comprehensive knowledge of anatomy and adept skills are crucial to avoid nerve
injuries, and that's why experts in this study will perform the blocks.
LAST:
It is rare as the blocks are usually ultrasound-guided, and drugs are given in smaller
amounts than the toxic levels. They are given with frequent aspirations to prevent
injecting into blood vessels. In pediatric practice, early warning signs and symptoms of
toxicity may be masked by the concurrent administration of general anesthesia. This
means the first sign may be arrhythmia or cardiovascular collapse. Consider the
following when managing local anesthetic toxicity:
- Stop the local anesthetic injection.
- Institute essential life support and call for assistance.
- Secure the airway, ventilate with 100% oxygen, and gain intravenous access.
- Seizures can be managed with a benzodiazepine or anesthetic induction agent.
- If a cardiac arrest has occurred, commence advanced life support.
- Note that arrhythmias are often refractory, and resuscitation should therefore be
prolonged.
- Treatment with IntraLipid: An initial dose of 20% lipid emulsion at 1.5 ml/kg or a
100 ml bolus can be administered over a few minutes. This can be repeated after 5
minutes for 2 or more times for persistent hemodynamic instability. The bolus(es)
should immediately be followed by a continuous infusion at 0.25-0.5 ml/kg/min.[3]
The infusion should run for a minimum of 10 minutes after the return of hemodynamic
stability. However, there are documented reports of recurrent systemic toxicity
even after this. For this reason, patients should be admitted for at least 12 hours
for observation and additional doses of intralipid as needed for rebound symptoms
or hemodynamic compromise.12
Infection:
It is a rare complication, might be seen after a few days postoperatively, and it will
be treated with appropriate antibiotics after postoperative surveillance during the
follow-up.
Injury to nerve roots:
This is a rare complication, especially so when a block is guided by ultrasound. But in
case of a very rare event, it still happens; it usually recovers within a few weeks, and
follow-up is required if the recovery is not observed, then the patient will be managed
by neurology consultation.
Subdural injection These complications are rare as the subdural sac is away from caudal
space in children. And the blocks in this study will be done with ultrasound guidance.
Still, if it occurs, the chance of hemodynamic instability is low as the volume and
concentration of local anesthetics will be low (0.25%) for analgesia.
Urinary retention:
It is usually transient and improves with regression in the block.
Roles:
A statistician will send an age-stratified-computer-generated block randomization
sequence to the Principal investigator, who will keep it under lock. The Principal
Investigator will allocate the cases according to the computerized randomization
sequence received.
Anesthetist doctor 1 will assess the patient and give anesthesia, perform the block and
fill proforma 1 and give the patient a code on proforma 2. There will be 2 anesthetists,
well-trained in the block and pediatric anesthesia techniques, will be performing the
blocks and giving anesthesia. Anesthetist doctor 2 will do the same procedure next time.
Assessor 1 will assess the patient in PACU using the FLACC scale 30 minutes after the
end of anesthesia and before discharge from PACU. He/She will fill the proforma 2 with
the patient code and not the identity.
Assessor 2 will assess the patient in the ward at 2, 3, and 6 hours and or at discharge
from the ward.
Assessors 1 or 2 will follow up with the patient telephonically at home on days 2 and 7.
The data entry with patient code on the master chart by the Principal investigator
without knowing the patient's identity.
Data collection:
The following data will be collected:
Demographic Data: Age, gender, ASA grading, comorbidities, surgery Lab Data: Routine
blood investigations like complete blood count and coagulation profile.
Anesthesia and block details: Type of airway device, hemodynamic, block details: block
name, normal/abnormal anatomy, local anesthetics injected; rescue analgesics needed,
FLACC score at 30 minutes after arrival and before discharge from PACU, postoperatively
in Ward at 2 Hours, 3 hours, 6 hours and or at time of discharge from the ward and at
home on day 2 and day 7.
The recorded patient data with code and no name will be entered by one of the assigned
co-investigators into the password-protected master chart.
Pain assessment: FLACC score will be assessed & documented 30 minutes after arrival and
before discharge from PACU, postoperatively in Ward at 2 Hours, 3 hours, 6 hours, and or
at the time of discharge. Our target FLACC score is 1-3. Whereas pain assessment at home
will be done with a numeric rating scale (NRS).
Justification of the current study:
This study will help to identify a more effective analgesia technique for common
pediatric inguinal surgeries. These nerve block techniques are safe and have been in use
already but not evaluated. Hence, this will be a valuable study to evaluate analgesia
efficacy as well as a reduction in the use of rescue analgesics, thereby avoiding the
side effects of rescue analgesics. Not only effectiveness, but we will also study the
time of discharge and resumption of independent activities. The better-found technique
may help enhance recovery after surgery (ERAS) for this patient population.
ETHICAL REVIEW:
After getting ethical approval and a Clinicaltrials registry, an appropriate population
of patients will be approached. A proper explanation will be done with the help of a
patient information sheet in the local and English languages. Informed consent will be
obtained before randomization from parents. Patient confidentiality will be maintained
strictly. All Proforma and Consent forms will be kept under lock and key. The master
chart will not carry patient names, and even MRN will not be accessible to anyone except
the principal investigator. In the end, the study subjects will be given code numbers in
the final master chart, and their ID will not be revealed to the statistician. An
interim analysis will be done to assess the results then continuation with the study
will be decided after 25% of the cases on each arm.
Data Management and Analyses:
Statistical Method The null hypothesis for the primary endpoint is that the analgesic
effect between the two blocks is not different. The alternative hypothesis is that the
block has different analgesic efficacy, measured in terms of pain score (FLACC and NRS).
The hypothesis will be two-sided and tested at the 5% significance level.
Demographics and baseline characteristics will be summarized. Summary of continuous
variables will be presented using N, Mean, Standard Error of mean (SE), Standard
Deviation (SD), Median and Range (Minimum and Maximum), and interquartile ranges (IQR).
The categorical variables will be presented using numbers and percentages. A Student's
t-test will be applied for primary and secondary endpoints of continuous variables to
test the mean difference between the groups. The t-test will be tested as two-sided
hypotheses at a 5% significance level. Treatment differences will be confirmed and
considered significant if the p-value reported is < 0.05. The presentation of results
from a statistical analysis using a t-test will include the estimated mean difference
between the groups for endpoint values. Continuous variables with non-normal
distribution will also be analyzed using the Mann-Whitney test. The Hodges-Lehmann
estimate and 95% confidence interval for the median difference will be presented along
with p-values using the Mann-Whitney test. Dichotomous or nominal categorical variables
were analyzed by either the Pearson Chi-square or Fisher's exact test. Disposition of
patients (subject screened, randomized, and disposition at the end of study along with
reasons for withdrawals) in the study will be summarized as the number of subjects and
percentage.
