Comparative Study Between Ultrasound Guided Mid-point Transverse Process to Pleura Block And Erector Spinae Plane Block For Perioperative Analgesia In Modified Radical Mastectomy In Breast Cancer Patients
Phase: NA
Conditions: Breast Cancer
Sponsor: National Cancer Institute, Egypt

 
 
Cover page 
COMPARITIVE STUDY BETWEEN ULTRASOUND GUIDED MID-
POINT TRANSVERSE PROCESS TO PLEURA BLOCK AND ERECTOR 
SPINAE PLANE BLOCK FOR PERIOPERATIVE ANALGESIA IN 
MODIFIED RADICAL MASTECTOMY IN BREAST CANCER 
PATIENTS. 
Candidate Name :     Mahmoud Saad Mahmoud Mohamed Mohamed 
Date of IRB approval  : 14  july 2024 
IRB APPROVAL  
The institutional review board of the national cancer institute (IRB-NCI) is constitute 
and operate according to ICH-GCP guidelines, institutional regulations and national 
regulation. All activities related to human subjects” research is guided by the ethical 
principles of the declaration Helsinki and Belmoni Report. IRB NCI is in charge with 
review and approval of all research involving human participants at NCI and other 
research sites. The Egyptian National Cancer Institute (NCI –Egypt) has a Federal –
wide Assurance (FWA) with the Office of Human Research Protection in the 
Department of Health and Human Services (USA) 
Organization No. IORG0003381 
IRB No. IRN00004025 
FWA No. FWA00029244 
MoHp No.:RHDIRB-NA-250224-01UC-GU- NO.0324 
Study ID :AP2407-201-014 
IRB Approval No. AP2407-201-014 

Background and Rationale: 
Breast cancer is the most commonly diagnosed malignancy and it is considered the leading cause 
of cancer-related mortality among women in more than 100 countries [1]. One of the main 
surgical treatments for breast cancer is Modified Radical Mastectomy (MRM) which accounts for 
31% of all breast surgeries [2].Erector Spinae Plane Block (ESPB) is a new regional anesthesia 
technique which provides regional anesthesia for breast surgeries. Breast surgeries are 
commonly associated with postoperative pain. Inadequate management of acute postoperative 
pain may lead to persistent postoperative pain, also known as chronic pain [3] Good 
postoperative analgesia plays a very important role in patient recovery. The thoracic 
paravertebral block (TPVB) is the gold standard regional analgesic technique for breast surgery. 
This block can reduce postoperative pain and opioid consumption [4]. However, the conventional 
TPVB can be technically difficult in identifying the thoracic paravertebral space (TPVS). This 
analgesic technique can cause complications, such as pleural puncture, epidural spread, 
accidental vascular injection of local anesthetic, intrathecal injection, and postural headache [5].  
Although recent ultrasound-guided TPVB studies results reported a low incidence rate (0.7%) of 
complications [6], it is not easy to localize the paravertebral space and the ventral transposition 
of the pleura cannot be visualized in some patients during injection of the local anesthetic or 
saline, resulting in  increasing the failure rate of Para thoracic nerve block and pleural puncture.In 
recent years, Erector Spinae Plane Block (ESPB) and mid-point transverse process to pleura (MTP) 
became new alternatives to thoracic paravertebral nerve block.[7] ESPB is defined as the injection 
of local anesthetic drugs between the erector spine muscle and the transverse process of 
vertebra while MTP is defined as injection point midway between the posterior border of the 
transverse process and the pleura.[8]  

Previous studies indicated that both blocks could be easy, safe, and effective analgesic techniques 
for breast surgery [8-9]. However, which block provides superior analgesia after MRM is still 
unclear due to lack of enough studies. This randomized study was designed to compare the intra 
operative and postoperative analgesic effects and adverse events associated with ultrasound-
guided ESPB and MTP after MRM. 
Hypothesis:  
We hypothesize that Ultrasound guided mid-point transverse process to pleura block is going to 
be as effective as ultrasound guided erector Spinae plane block in reducing post-operative 
morphine consumption in comparison to control group in cancer patients undergoing MRM. 
 
Objectives:  
Primary objectives: 
Assessment of post-operative opioid (morphine) consumption in the 1st 24 hours after 
using  
ultrasound guided mid-point transverse process to pleura block compared to ultrasound 
guided Erector Spinae Plane Block in patients undergoing modified radical mastectomy. 
 
Secondary objectives: 
Assessment of: 
1 Post-operative Numeric Pain Rating Scale.  
2. Effect on hemodynamics: Mean arterial blood pressure and Heart rate.  
3. Intraoperative fentanyl consumption.  
4.Duration of analgesic effect.  
5.Block related complications. 
 

Study Design :  
This is randomized controlled trial. 
Population of study:  
Breast cancer patients who are candidates for MRM. 
Study location:  
National Cancer Institute Cairo University after approval by the institutional review board. 
Inclusion criteria: 
● Age starting from 18 to 60 years. 
● ASA I-II. 
● Undergoing modified radical mastectomy surgery. 
● Body mass index (BMI) from 18.5 to 30 kg/m2 
Exclusion criteria:  
● Patient refusal. 
● Known allergy to local anesthetics. 
● Bleeding disorders; platelets count <50,000 , prothrombin concentration < 60% or 
any coagulopathy disorder. 
● Use of any anti-coagulants. 
● Inability to provide informed consent. 
● ASA III-IV. 
● Neurological disorders.  
● Patient with psychiatric disorders. 
 

Methodology in details: 
Randomization:  
The patients will be randomly assigned into three equal comparable groups using 
computer-generated random numbers in opaque closed envelopes, each of which 
will include 30 patients. With allocation ratio 1:1 1
:  
 
Group M (mid-point transverse process to pleura block MTP) N=3o  
Patients will receive Ultrasound guided mid-point transverse process to pleura block 
preoperative with injection of 20 ml bupivacaine 0.25%.Then patients will be 
transferred to operating room.  
 
Group E (Erector Spinae Plane Block ESB) N=3o  
Patients will receive Ultrasound guided erector spinae plane block with injection of 
20 ml bupivacaine 0.25%. Patients will be transferred to operating room.  
 
Group C (control group) N=30 
Patients will not receive any block, as both blocks are not the gold standard to control 
post-operative analgesia. Induction will be performed by using a regimen of IV by 
fentanyl 1 μg/kg, Additional bolus doses of fentanyl 0.5 μg/kg will be given if the mean 
arterial blood pressure or heart rate rises above 20% of baseline levels. 
 
Randomization will be done by statistician and each group of the patient will revealed only 
when the included patient is transferred to preanesthetic room.  
 
Study Protocol:  
History, physical exam, laboratory and radiological investigations at preoperative 
assessment clinic National Cancer Institute Cairo University.  
Preoperative assessment at night of surgery.  
The patients will be instructed how to report pain by means of Numeric Pain Rating Scale, 
in which 0 = "no pain" and 10 = "worst possible pain".  
Informed consent will be obtained.  

Preoperative fasting; minimum of 6 hours for food and minimum of 2 hours for water and 
clear fluids.20G IV is inserted. All patients will be premedicated with IV midazolam 0.05-0.1 
mg\kg 30 minutes preoperatively.  
Both blocks will be done preoperative with the patients in the lateral position.  
The analgesic effect will be evaluated by the skin prick test 20 minutes after the block 
intervention, from the T3 to T7 nerve distribution segment. A successful ESPB or MTP block 
must contain at least T4, T5 and T6 segments; otherwise, the block will be considered 
unsuccessful and will be removed from the study.  
After allocation of patient to a study group patient of group M will receive mid-point 
transverse process to pleura block and patients of group E will receive erector spinae plane 
block.  
● ESPB 
Group E: The block will be performed preoperatively with full aseptic precautions. The 
ultrasound probe will be placed on the back in a vertical orientation on the lateral side of 
the posterior median line to identify the transverse process of the 5th thoracic vertebra 
and erector spine muscle. 
 A skin wheal using 3ml of 1% lidocaine will be made 2 to 3 cm superior to the superior 
aspect of the transducer. The puncture will be performed using the intra-plane needling 
technique after local anaesthesia infiltration. A 20-gauge Tuohy needle connected to a 
syringe containing the anesthetic mixture or saline will be advanced. When the puncture 
needle touch the transverse process, with no blood, gas, or cerebrospinal fluid observed 
on aspiration, 20 mL of 0.25% bupivacaine will be administered between the erector spine 
muscle and transverse process.  

Local anesthetic diffusion between the transverse process and erector spinae muscle is an 
indication of a successful puncture.  
● MTP 
Group M: The block will be performed preoperatively with full aseptic precautions. The 
ultrasound probe will be placed on the back in a vertical orientation on the lateral side of 
the posterior median line to identify the transverse processes of the 4th and 5th thoracic 
vertebrae and pleura.  
A skin wheal using 3ml of 1% lidocaine will be made 2 to 3 cm superior to the superior 
aspect of the transducer. Using the in plane needling technique in the space between the 
transverse processes of the 4th and 5th thoracic vertebrae, the puncture needle needle tip 
will be placed at the mid-point between the transverse process and pleura, with no blood, 
gas, or cerebrospinal fluid observed on aspiration, 20 mL of 0.25% bupivacaine will be 
administered. The local anesthetic spread will be noted in the area midway between the 
transverse process and pleura is an indication of a successful puncture.  
The transverse section and paramedian sagittal paravertebral space will be observed by 
ultrasound in both groups. All patients included will be anesthetized by the same 
anesthesiologist and operated on by the same surgeons.  
 
 
 
 
 

Anesthetic Management:  
Monitoring: 
all patients will be monitored continuously using electrocardiography, non-invasive blood 
pressure, peripheral oxygen saturation and end tidal carbon dioxide throughout the duration of 
the surgical procedure. 
Induction: 
Induction of general anaesthesia will be performed using a regimen of IV 2 μg/kg fentanyl and 
propofol IV 2 mg /kg. Tracheal intubation will be facilitated using 0.5 mg/kg IV of rocuronium. 
Maintenance: 
Anaesthesia will be maintained with inhaled sevoflurane 2-2.5% in oxygen enriched air 
(FiO2=0.5). Maintenance doses of rocuronium o.1 m\kg will be provided every 30 minutes. 
Paracetamol 1 gm and IV ketorolac 30mg will be provided as a part of multimodal anelgesia.  
Rescue analgesia of fentanyl 1 μg/kg will be given if the mean arterial blood pressure or heart 
rate rises above 20% of baseline levels. 
The patients will be mechanically ventilated at appropriate setting that keep end-tidal CO2 at 30- 
35 mmHg. 
1st reading of mean arterial pressure (MAP) and heart rate (HR) will be taken before induction of 
general anaesthesia to be defined as a baseline reading another reading will be taken 
immediately before surgical incision and at 5-minute intervals intraoperatively. 
Hypotension ((reduction of  more than 20% of baseline reading)) will be treated with 0.9% normal 
saline and/or 5mg ephedrine in incremental doses to maintain mean blood pressure above 70 
mmHg. 
The residual neuromuscular blockade will be reversed using neostigmine (0.05 mg/kg) and 
atropine (0.02 mg/kg), and extubation will be performed after complete recovery of the airway 
reflexes. 

The patients will be transferred to the post-anaesthesia care unit (PACU) where the, Numeric 
Pain Rating Scale score, MAP and heart rate will be noted immediately on arrival, where they will 
be observed for 2 hours then discharged to the ward.  
Lung ultrasound will be performed once again at PACU looking for signs of pneumothorax.  
If the patient indicates Numeric Pain Rating Scale ≥ 4, rescue analgesia will be provided in the 
form of increments of 3 mg morphine intravenously as needed with a maximum of 0.1 mg/kg in 
a period of 4 hours. The total amount of morphine given in 24 hours will be recorded for the two 
groups.  
Thereafter, the patients will be transported to their respective ward, Multimodal analgesia will 
be provided as the following: 
IV paracetamol 15 mg/kg /6 hours 
IV ketorolac 30mg/12 hours.  
 There, Numeric Pain Rating Scale score, MAP and heart rate will be noted at 4, 8, 12, 16, 20 and 
24 hours postoperatively 
Side effects such as nausea, vomiting, sedation, hallucination, respiratory depression (respiratory 
rate <10/minute) and nightmares will be recorded. Postoperative nausea and vomiting (PONV), 
as side effects of morphine, will be rated on a four-point verbal scale; (none =no nausea, mild 
=nausea but no vomiting, moderate=vomiting one attack, severe =vomiting >one attack). 0.1 
mg/kg of IV ondansetron will be given to patients with moderate or severe postoperative nausea 
and vomiting.  
Measurement tools: 
✔ Intraoperative fentanyl consumption.   
✔ Total amount of fentanyl used by the anaesthetic provider in the operating room will be 
recorded. 

✔ Intraoperative hemodynamics heart rate and mean arterial blood pressure every 30 
minutes.  
✔ The total amount of morphine consumption postoperatively.  
✔ Postoperative hemodynamics heart rate and mean arterial blood pressure taken at 
0,4,8.12,16,20 and 24  
✔ Pain using Numerical rating scale (NRS), both at rest and during movement:   
✔ Pain scores using NRS will be recorded in the PACU, and for the next 24 hours 
postoperatively.   
✔ Presence of side effects such as Nausea, vomiting and local anesthetic toxicity. 
✔ Time of first rescue analgesia. 
✔ Presence of side effects of block such as pneumothorax (US check postoperative). 
Study outcomes:  
Primary outcomes: 
post-operative opioid (morphine) consumption in the 1st 24 hours  
Secondary outcome parameters:  
● Time to first rescue analgesia, starting after extubation. 
● Total dose of fentanyl required intraoperative (including induction dose) 
● Pain score at 15, 30, 45 and 60 min., 3,6,12 and 24 h after surgery. 
● Block failure rate which can be defined by persistence of pain sensation by 
skin prick test 20 minutes after each block. 
● The incidence of side effects. 
● Change in heart rate and mean arterial blood pressure intraoperatively at 30 
minutes interval in comparison to baseline reading.  
● Heart rate, mean arterial blood pressure at 0, 4, 8, 12, 16, 20 and 24 
hours postoperatively  

Risks: 
1. Local anesthetic toxicity. 
2. Failure of block.  
Sample Size: 
A randomized Controlled trial aiming to assess postoperative 24 hours morphine consumption 
after using ultrasound guided mid-point transverse process to pleura block (Group 1) compared 
to ultrasound guided Erector Spinae Plane Block  (Group 2) and control group receiving IV  
morphine (Group 3) in patients undergoing modified radical mastectomy. Comparing the 
previously mentioned block with ratio 1:1:1, based on (Mohammed HA et al, 2023)(10) & (Singh 
S et al., 2019) (11) the average total morphine consumption in the first 24 h is (0, 1.95 and 9.3, in 
group 1,2 & 3 respectively) with standard deviation (3, 2.01 &2.36 for the three mentioned 
groups respectively), so we will need to study 24 participant, it will be compensated by 15% due 
to the use of nonparametric tests,  so the final sample size will be 90 subjects (30 per group) to 
be able to reject the null hypothesis that the population means of opioid consumption in the 
three groups are equal with probability (power) 0.9999. The Type I error probability associated 
with test of this null hypothesis is 0.05. Sample size was calculated using G power program (12). 
 
 
Statistical analysis: 
Data will be analyzed using IBM SPSS advanced statistics (Statistical Package for Social Sciences), 
version 27 (SPSS Inc., Chicago, IL). Numerical data will be described as mean and standard 
deviation or median and range, as appropriate. Categorical data will be summarized as numbers 
and percentages. Data will be explored for normality using Kolmogrov-Smirnov test and Shapiro-

Wilk test. Comparisons between the 2 groups for normally distributed numeric variables will be 
done using the Student t-test while for non-normally distributed numeric variables will be done 
by Mann-Whitney test. Comparisons between more than 2 groups will be performed by the one 
analysis of variance (ANOVA) for normally distributed variables (Post Hoc comparison will be 
done and P value will be adjusted using Bonferroni adjustment) and Kruskal-Wallis for non-
normally distributed variables. Comparison between multiple related groups of normally 
distributed numerical data will be done using Repeated measures ANOVA. Comparison between 
multiple related groups of non-normally distributed numeric variables will be done using 
Friedman test. Chi square or Fisher’s tests will be used to compare between the groups with 
respect to categorical data. A p-value less than or equal to 0.05 will be considered statistically 
significant. All tests will be two tailed. 
Sources of funding:  
National Cancer Institute Cairo University. 
Time plan: 
The study will start after the approval of the Ethical Committee. 
Ethical committee approval: 
● This study will be started after approval of Institutional Review Board and Ethical Research 
Committee.  
● The study protocol will be presented to the Scientific Ethics Committee of the Anaesthesia, 
Pain Relief, and ICU Department at the National Cancer Institute – Cairo University. 
●  Patients’ data will be presented anonymously with protection of privacy and confidentiality.  
● The aim and nature of the study will be explained to each patient before their inclusion in 
the study. An informed written consent will be obtained from each patient, or a first degree 
relative before enrolment.  
 

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