Transversus Abdominis Plane Block Combined With Rectus Sheath Block Versus Erector Spinae Plane Block for Postoperative Analgesia After Laparoscopic Liver Resection
Phase: NA
Conditions: Laparoscopic Hepatectomy, Nerve Block
Sponsor: Zhangyi

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Clinical Study Protocol
Program name: Comparison of the analgesic efficacy of the
combination of transversus abdominis plane block and rectus sheath
block in relation to erector spinae plane block after patients
undergoing laparoscopic liver resection surgery
NCT number:
Date of applicant: September 20, 2023

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1.Research background
According to the 2022
guidelines for perioperative
care for
liver surgery,
implementing Enhanced Recovery After Surgery(ERAS) in liver surgery may
improve postoperative outcomes. Compared with open hepatectomy, laparoscopic
hepatectomy has the advantages of less postoperative hospitalization time and lower
complication rates, which is recommended in well-trained teams and clinically
appropriate situations[1]. Postoperative pain after laparoscopic liver resection is
composed of multiple factors, including somatic and visceral pain,which is caused by
abdominal distension, laparoscopic port position and abdominal wall wounds[2]. The
peak pain of postlaparoscopic surgery mainly occurs in the first 24 hours[3], it is
particularly significant to find an appropriate way to relieve pain.
Epidural analgesia has been the gold standard for perioperative pain control, but it
is associated with longer hospitalization time and increased hospital costs and a higher
incidence of urinary tract infections. Additionally, its use is limited by an increasing
number of drugs that interfere with blood coagulation function[4,5]. Regional
anesthesia is an important component of multimodal analgesia, which can reduce the
dosage of opioids after surgery, thereby reducing the occurrence of adverse reactions
and it is helpful for postoperative recovery. Transversus abdominis plane block
(TAPB) and Rectus sheath blocks (RSB) are widely used in abdominal surgery. TAPB
blocks the sensory nerves of the anterolateral abdominal wall (T6-L1), and a
Meta-analysis has shown that it is effective as epidural analgesia while having fewer
episodes of hypotension[6]. Bilateral rectus sheath blocks (RSB) was originally
introduced to loosen the abdominal wall during surgery by blocking the terminal
branches of the 9th, 10th and 11th intercostal nerves between the internal oblique and
transversus abdominis muscles. It has now been shown to reduce opioid use and
alleviate postoperative pain[7], but if the needle tip too deep during RSB, it will has the
risk of puncture the abdominal organs. The limitation of both TAPB and RSB lied in
their ability to provide somatic analgesia only without visceral analgesia.
Some studies have applied Erector spinae plane block (ESPB) in abdominal surgery
where it can act on both the ventral and dorsal branches of spinal nerves, further
enhancing visceral analgesia by blocking sympathetic nerve. Altiparmak et al[8]
compared ultrasound-guided ESPB with oblique subcostal TAPB for postoperative
pain relief in patients undergoing laparoscopic cholecystectomy, and proved that
ESPB could reduce tramadol consumption and pain score more effectively. Kamel et

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al.
[9] concluded that bilateral ESPB provides longer duration of postoperative
analgesia and less morphine consumption than TAPB in patients undergoing open
abdominal total hysterectomy. In open hepatectomy, ESPB has been proved to have
better analgesic properties than oblique subcostal TAPB, specifically manifests in
lower postoperative pain scores, longer time to first need for morphine, and less
morphine consumption[10]. The analgesic effect of ESPB has been demonstrated after
abdominal surgery.
The analgesic and postoperative recovery effects of ESPB have not been compared
with TAPB combined with RSB in patients undergoing laparoscopic hepatectomy.
2. Study Purpose
Comparing the postoperative analgesic and recovery effect of TAPB combined with
RSB and ESPB in patients undergoing laparoscopic hepatectomy.
3. Study design
3.1 Study types
single-center, prospective, randomized, double-blind, controlled study
3.2 Random grouping
Patients were randomly divided into two groups according to computer generate
random number table: TAPB combined with RSB group (control group) and ESPB
group (experimental group). Group assignment information was stored in a sealed
opaque envelope and stored and distributed by a specific person.
3.3 Double-blind
All patients included in the study were required to sign informed consent. Before
anesthesia induction, the experimental group received ESPB while the control group
was given TAPB combined with RSB. The abdominal incision and puncture points
due to the block were covered with sterile dressings in both experimental and control
groups after surgery. The anesthesiologist who performed the nerve block carries out
the corresponding
nerve block
according to
the
groups in
the envelope.
Anesthesiologists responsible for anesthesia management, surgeons, and those
conducting postoperative follow-up visits were unaware of the group situations.
4. Selection and withdrawal of subjects

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4.1 Inclusion criteria
1)ASA grades I-II
2)age 18~70 years old
3)BMI 19～28 kg/m2
4)patients undergoing elective laparoscopic partial liver resection
4.2 Exclusive criteria:
1) The nerve block cannot be performed, such as skin infection at the puncture site
2) Daily using the opioid analgesics or have a history of opioid abuse
3) Allergy or a history of drug allergy to any of the drugs used in the study
4) Patients have cognitive impairment, mental or neurological diseases, motor or
sensory deficits
5) Coagulation disorders
6) Severe lung, heart, liver, or kidney dysfunction
7) Participating in other clinical trials within 3 months before being included in this
study
5. Sample estimation
The sample size was calculated based on previous literature[2], requiring 27 patients
per group to achieve a two-sided 0.05 significance level and 90% power of the test. A
sample size of 60 was required to set a dropout rate of 10%.
6. Research process
The experiment was carried out in Tongji Hospital, Tongji Medical College,
Huazhong University of Science and Technology. For patient who were going to
undergo laparoscopic partial hepatectomy, anesthesiologists went to the ward one day
before surgery for preoperative evaluation, signed the informed consent form, and
screened the subjects according to the inclusion and exclusion criteria. In according
with the random results, the patients were randomly divided into ESPB group
(experimental group) and TAPB&RSB group (control group). The patients were
instructed to use analgesic pump and visual analogue scale (VAS). (Visual analogue
scale (VAS): a 100 mm transverse line with 0mm at one end of the line indicates no
pain, 100mm at the other end indicates severe pain and the middle part shows
different levels of pain.)

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1) All patients were routinely fasted before surgery, and no preoperative
medication was given.
2) After entering the operation room, the patients in the experimental group and
the control group took the sitting position, and the VAS scores of the patients in the
resting state and the cough state were recorded. The subjects were scored
preoperatively using the QoR-15 patient questionnaire (see supplementary).
3) Electrocardiogram, blood pressure, pulse, and blood oxygen saturation were
monitored.
After
local
anesthesia,
ultrasound-guided
internal
jugular
vein
catheterization was performed, which could monitor central venous pressure(CVP)
and record preoperative CVP after connecting the transducer.
4) The experimental group received ultrasound-guided ESPB, and bilateral ESPB
was performed at T7 segment with 20ml 0.375% ropivacaine on each side.While the
control group receives ultrasound-guided TAPB combined with RSB, which was
performed under the costal margin with 10ml 0.375% ropivacaine for bilateral TAPB
and 10ml 0.375% ropivacaine for bilateral RSB.
5) Anesthesia was induced with methylprednisolone 5mg, dexamethasone 5mg,
penehyclidine hydrochloride 0.5 mg and palonosetron 0.25 mg, sufentanil 0.5μg·kg-1,
etomidate 0.15-0.20 mg·kg-1 and cisatracurium 0.20mg·kg-1.
6) Tracheal intubation was performed after 5 minutes of mask oxygen inhalation;
Ultrasound guided radial artery puncture catheterization was preformed to monitor
ambulatory blood pressure.
7)
Maintenance
of anesthesia
should
use
1-2%
sevoflurane
inhalation,
dexmedetomidine 0.5ug·kg-1min-1 and fentanyl 0.1 -0.2ug·kg -1·min - 1, and maintain
blood pressure at baseline values of plus or minus 20%. In volume controlled
ventilation mode, tidal volume was 6ml/kg, airway pressure was maintained within
25cmH2O, and end-tidal CO2 is maintained 35-45 mmHg. CVP values were recorded
at 5, 10, 15, and 30min after nerve block. ECG, HR, BP, SpO2, CVP, PetCO2, BIS
value, temperature, liquid intake and output are monitored during operation. Arterial
blood gas analysis was used to correct acid-base imbalance and electrolyte imbalance.
8) Analgesic coherence: 30 minutes before the end of surgery, sufentanil 5ug was
injected intravenously.
9) The patient was sent to PACU for observation for one hour after awake
extubation, and then connected to an analgesic pump: sufentanil 15ug, nojan 15mg,
palonosetron 0.3mg, 0.9% normal saline added to 150ml. The background infusion

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rate was set according to the weight <50 kg at 1ml/h, 1.5ml/h for 50-60 kg and >70 kg
at 2ml/h with a single compression dose of 2ml and a lockout time of 10min.
According to the needs of patients, the analgesic pump could be pressed by
themselves for analgesia. If pain cannot relieve (VAS&gt>4 at rest), the remedial
analgesia with a single dose of 2mg oxycodone can be used. At 1 hour after the end of
surgery, recording the VAS scores of patients in resting and coughing states and the
dose of analgesic pump. Asking patients if they had any adverse reactions, such as
nausea, vomiting, pruritus, dizziness, headache, respiratory depression, etc.
10) After returning to the ward, patients could press the analgesic pump by
themselves for additional analgesia. Lack of pain relief (VAS&gt at rest; 4 points) or,
at the patient's request, rescue analgesia with a single dose of diclofenac sodium
suppository. The dosage of analgesic pump, times of rescue analgesia, VAS scores in
the resting and coughing and adverse reactions were recorded at 2h, 4h, 8h and 24h
after operation. The QoR-15 patient questionnaire was used to evaluate the
postoperative recovery at 24 hours after surgery.
7. Possible risks and preventive measures
7.1 Adverse event
The investigators should faithfully fill in the adverse event recording form, record the
time, severity, duration, measures taken and outcomes of adverse events. Explaining
the criteria for the severity of adverse events, judging the relationship between
adverse events and the trial drug was the 5-level classification standard (definitely
related, possibly related, possibly unrelated, unrelated, and could not be determined).
All adverse events should be traced until resolved properly or the patient's condition is
stable.
Precautions for adverse events:
①Ultrasound-guided nerve block can visualize the puncture needle tips,
effectively and greatly reduce the risk of local anesthetic poisoning and puncture
injury.
②Local anesthetic poisoning: strict control the dose of drug, strict intraoperative
monitoring. Once local anesthetic poisoning presents, it should be treated immediately
according to the treatment procedure of local anesthetic poisoning, such as
electrocardiogram monitoring, respiratory tract management, volume control, sedation
and anticonvulsion, and the use of corresponding vasoactive drugs.

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③Puncture injury: Performing carefully and discreetly under visualization of
ultrasound to ensure that tissue damage is minimized. Once present, surgery may
intervene depending on severity.
Doctor will closely monitor your condition to ensure your health, and will
truthfully tell you any changes in the course of the study and any newly identified
adverse effects.
If you are harmed or have anything unexpected circumstances because of
participating in this study, whether it is related to the intervention or not, your doctor
will make a judgment and take medical action.
Physicians will try their best to prevent and treat possible harm as a result of this
study. If an adverse event occurs during a clinical trial, a committee of medical
experts will determine whether it is related to the intervention. Finally, according to
the provisions of "Good Clinical Practice" in China, the sponsor will provide the cost
of treatment and corresponding economic compensation for trial-related injuries.
7.2 Serious adverse event
Serious adverse events are defined as an adverse event leading to one of the following
consequences: death, extension of hospitalization time, disability, fatal reaction or
teratogenicity. Any serious adverse events occurring during the clinical trials must be
reported within 24 hours to the principal investigator of the Department of
Anesthesiology of Tongji Hospital and the Ethics Committee of the Drug Clinical
Research Base of Tongji Hospital.
7.3 Safety monitoring
The data and safety management committee consists of anesthesiologists. The
committee will conduct the interim analysis when half of the patients have been
enrolled. If the interim analysis shows an extremely higher rate of death or
significantly more complications in the trial group, the trial will stop.
8.Data collection and statistical analysis
8.1 Data collection
Main observation indicator: consumption of morphine within 24 hours after surgery
Secondary observation indicators
1) Morphine consumption at 1h, 2h, 4h and 8h after surgery

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2) Number of rescue analgesia at 1h, 2h, 4h, 8h and 24 hours after surgery
3) VAS scores in resting and coughing at 1h, 2h, 4h, 8h and 24h after surgery
4) CVP values at 5, 10, 15 and 30min after nerve block
5) QoR-15 patient questionnaire scores before and 24h after surgery
6) Postoperative liver function (the percentage increase of AST and ALT compare
with preoperative), postoperative complications and discharge time
8.2 Statistical analysis
The Shapiroe Wilk test was used to determine the normality of data distribution for
measurement data. Measurement data with normal distribution were expressed as
mean ± standard deviation, and measurement data with non-normal distribution were
expressed as median (interquartile range, IQR). Measurement data were compared
between groups by t test or Mann-Whitney U test according to whether the data were
normal distribution, and VAS scores were compared by repeated measures analysis of
variance. Count data were expressed as frequency (%), and compared between groups
by using chi-square test or Fisher exact test.The value of P less than 0.05 was
considered statistical significance.

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References
Uncategorized References
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