Effect of Bilateral Ultrasound-Guided Intermediate Cervical Plexus Block Combined With General Anesthesia on THE Stress Response in Patients Undergoing Anterior Cervical Spine Surgery. A Randomized Controlled Study
Phase: NA
Conditions: Stress
Sponsor: Cairo University

 
 
 
 
 
 
Effect of Bilateral Ultrasound-Guided 
intermediate cervical plexus Block combined with 
general anesthesia on THE stress response in 
patients undergoing anterior cervical spine 
surgery. A randomized controlled study 
 
 

Research Protocol Template                                                                                                          September 2023                          
 
1 
 
Table of Contents 
Title Page ........................................................................................................ Error! Bookmark not defined. 
Study Title .................................................................................................. Error! Bookmark not defined. 
Investigators .............................................................................................................................................. 2 
Introduction: ................................................................................................................................................. 4 
Aim of the work ............................................................................................................................................ 5 
Objectives: .................................................................................................................................................... 5 
Hypothesis..................................................................................................................................................... 6 
Ethical Considerations ................................................................................................................................... 6 
Methodology ................................................................................................................................................. 8 
I. 
Study design ...................................................................................................................................... 8 
II. 
Study setting and location ................................................................................................................ 8 
III. 
Study population ........................................................................................................................... 8 
IV. 
Eligibility Criteria ........................................................................................................................... 9 
1. 
Inclusion criteria ............................................................................................................................ 9 
2. 
Exclusion criteria ........................................................................................................................... 9 
V. 
Study Procedures ............................................................................................................................ 10 
1. 
Study Protocol ............................................................................................................................. 10 
2. 
Measurement tools ..................................................................................................................... 13 
VI. 
Study outcomes .......................................................................................................................... 13 
1. 
Primary outcome ........................................................................................................................ 13 
2. 
Secondary outcome(s) ................................................................... Error! Bookmark not defined. 
Statistical Analysis ....................................................................................................................................... 16 
I. 
Sample size ...................................................................................................................................... 16 
II. 
Statistical analysis ........................................................................................................................... 16 
References ..................................................................................................... Error! Bookmark not defined. 
 
 
 

Research Protocol Template                                                                                                          September 2023                          
 
2 
 
Effect of Bilateral Ultrasound-Guided intermediate cervical plexus 
Block combined with general anesthesia on THE stress response in 
patients undergoing anterior cervical spine surgery. A randomized 
controlled study. 
Investigators 
Candidate Details 
Name: Ahmed Raafat Taha Abdel Aziz 
Degree:M.sc. 
Affiliation: Faculty of medicine, Cairo University. 
Phone No: 01278996596 
Email: ahmedtaha840@hotmail.com 
Principle Investigator 
Name and Affiliation: prof. Dr/ Gomaa Zohry 
 
 
           Professor of anesthesia, surgical ICU & pain management. 
Phone No: 01122111165  
Email: Gomaaneel70@icloud.com 
Co-investigator (A): 
Name & Affiliation: Ass.Prof Dr/Safinaz Hassan Osman 
 
 
    Assistant Professor of anesthesia, surgical ICU & pain 
 Phone No: 01065007150 
Email: safinaz_hassan_osman@hotmail.com 
Co-investigator (B): 
Name & Affiliation: Dr/ Ahmed Ragab 
 
 
         Lecturer of anesthesia, surgical ICU & pain management. 
Phone No: 01272202204 
Email: Ahmedmaghrabi19782@gmail.com 
 

Research Protocol Template                                                                                                          September 2023                          
 
3 
 
   
 
 
INTRODUCTION 
 
 
 
 
 

Research Protocol Template                                                                                                          September 2023                          
 
4 
 
Introduction: 
 
 
Stress response is the name given to the hormonal and metabolic changes which follow 
injury or trauma.  It may lead to changes in the nervous, endocrine and immune systems, 
and alterations in metabolic processes and functions(1). The stress response can shift 
from an adaptive and protective role to a pathogenic occurrence, especially when it is 
strong and chronic. 
 
Stress hormones, the most prevalent of which is cortisol, have a circadian pattern in 
which they gradually climb after night sleep to reach a peak at early morning wake-up 
time, then gradually decline as the day progresses (2). 
This pattern, however, can be disrupted by any stressful situation, such as severe pain 
from surgery, which has been linked to a progressive rise in cortisol levels both 
intraoperatively and in the early postoperative period. 
 
Cytokines are group of low molecular weight proteins that modulate the systemic 
inflammatory response elicited by surgical intervention. Increased levels of 
proinflammatory cytokines, including interleukin‐6 (IL‐6) which is the main cytokine 
responsible for inducing the systemic changes, is an early features of acute injury. 
Interleukin‐6 could be a good marker for research purposes that reflects and compares 
postoperative stress levels. 
 
 
Spine surgeries are increasingly being performed as short-stay surgical procedures, and 
anterior cervical decompression and fusion is one such procedure (3).Postoperative 
incisional pain has been described as moderate in intensity, requiring opioid analgesics in 
most cases. Nonetheless, opioid-related side effects such as nausea, vomiting, and 
respiratory depression are undesirable in these patients who are at risk for airway 
problems due to surgical retraction or wound hematoma(4). 
 
Regional anesthesia inhibits the stress response to surgery and can also influence 
postoperative outcomes. . The endocrinal stress response to the surgical operation is 
reduced as a result of inhibiting afferent impulses from the surgical site. Furthermore, a 
reduction in this type of stress response is seen as a key indicator of a successful regional 
block. 
  
 
Intermediate cervical plexus block (CPB) is a safe and simple technique that has been 
shown to provide good pain relief through blocking all four cutaneous branches of the 

Research Protocol Template                                                                                                          September 2023                          
 
5 
 
cervical plexus, as well as sensory and motor branches (5).Not only Intermediate (CPB) is 
superior to superficial CPB in terms of effectiveness, but also is safer than deep (CPB) (6). 
 
There is a paucity of evidence for the effect of bilateral cervical plexus block for anterior 
cervical spine surgeries. Prior research had employed recovery questionnaire score, 24-h 
opioid usage and length of hospital stay in assessment of cervical plexus block 
effectiveness (7), however estimating the effect of Intermediate (CPB) on stress 
biomarkers as serum cortisol and interlukien-6 has not been discussed yet. 
Aim of the work 
 
The aim of the present study is to investigate the effect of Bilateral Ultrasound-Guided 
intermediate cervical plexus Block combined with general anesthesia on the stress and 
inflammatory response in patients undergoing anterior cervical spine surgery (ACSS). 
Objectives: 
 
 To compare between serum level of cortisol and interlukien-6 pre-operative and 
24 hours post-operative in both groups. 
 To identify Hemodynamics variables (mean arterial blood pressure and heart rate) 
peri-operatively. 
 To assess the pain score during 1st 24 hours postoperative according to numeric 
pain rating scale (NPRS). 
 To measure the incidence of complications within both groups. 

Research Protocol Template                                                                                                          September 2023                          
 
6 
 
 
 
Hypothesis: 
 
We hypothesize that intermediate cervical plexus block will offer a significant 
suppression of stress response and adequate post-operative analgesia in patients 
undergoing anterior cervical spine surgeries. 
Ethical Considerations: 
 
Our study will be conducted in Kasr El Aini Hospital, Cairo University after approval of the 
Research Ethics Committee. Full written informed consent will be obtained from the 
patients before inclusion in this study.  
 
 
 
 
 
 
 
 
 
 

Research Protocol Template                                                                                                          September 2023                          
 
7 
 
                             
 
 
 
 
 
 
 
Methodology 
 

Research Protocol Template                                                                                                          September 2023                          
 
8 
 
Methodology 
I. 
Study design: 
 
A randomized controlled study. 
II. 
Study setting and location: 
 
The study will be conducted in the Neurosurgery operating rooms at Cairo 
University hospital. 
III. 
Study population: 
 
        (66) Patients, aged from 18 to 65 years old, ASA physical status I-II, scheduled 
for anterior cervical spine surgery will be included in the study. Patients will be 
randomly allocated using concealed closed envelope method into one of two 
groups:  
 Group A (n=33): will include the patients who will undergo bilateral 
ultrasound guided intermediate cervical plexus block after general 
anesthesia. 
 Group B (control group) (n=33): will include the patients who will undergo 
general anesthesia with conventional analgesia. 

Research Protocol Template                                                                                                          September 2023                          
 
9 
 
IV. 
Eligibility Criteria  
1. Inclusion criteria: 
 
1. ASA I & ASA II patients. 
2. Age group: from 18 to 65 years old. 
3. Patients undergoing anterior cervical discectomy or fixation. 
4. Genders eligible for study: both sexes. 
 
2. Exclusion criteria: 
 
 Patient refusal. 
 Patient Undergoing posterior fixation in addition to anterior. 
 An allergy to local anaesthetics. 
 Infection at block puncture site. 
 Bleeding disorders (Coagulopathy: PTT > 40seconds, INR > 1.2, platelet 
count < 120 x 103 / L.). 
 Emergency surgeries & patients in sepsis.  
 
 
 
 
 
 

Research Protocol Template                                                                                                          September 2023                          
 
10 
 
V. 
Study Procedures 
 
 
 
1. Randomization: 
 
Patients will be randomly allocated by a computer-generated table into one of 
the study groups; the randomization sequence will be concealed in sealed 
opaque envelopes  
2. Study Protocol: 
Patients will be subjected to systematic preoperative assessment including 
history taking, physical examination and review of the results of routine 
investigations.  NPRS (numeric pain rating scale) will be explained to all 
candidates where zero corresponds to no pain, and 10 is indicative of the worst 
unbearable pain. Upon arrival to the preparation room: An18-gauge 
intravenous (IV) cannula will be inserted into a peripheral vein. Patients will 
be premedicated by intravenous 0.01 mg/kg midazolam and 10mg 
metoclopramide. Patients will be then transferred to the operating room where 
basic monitoring, Electrocardiography (ECG), Non-invasive Blood Pressure 
(NIBP) monitor and pulse oximetry will be attached.  
 
General anesthesia will be induced in a standardized way with intravenous 
propofol 2.5mg/kg, fentanyl 1 µ/kg and atracurium 0.5mg/kg. Anesthesia will be 
maintained 
by 
inhalational 
isoflurane 
and 
intravenous 
atracurium 
0.1mg/kg/20min. 
Group A: The patient will be placed in a supine or semi-sitting position, with 
the head turned slightly away from the side to be blocked to facilitate operator 
access.  The skin is disinfected and a linear-array ultrasound probe (Siemens 
ACUSON X300 Ultrasound   System) is placed on the lateral neck, overlying the 
sternocleidomastoid muscle at the level of its midpoint (approximately the level 

Research Protocol Template                                                                                                          September 2023                          
 
11 
 
of the cricoid cartilage), Once the SCM has been identified, the transducer is 
moved posteriorly until the tapering posterior edge is positioned in the middle of 
the screen. At this point, an attempt should be made to identify the brachial 
plexus and/or the interscalene groove between the anterior and middle scalene 
muscles. The cervical plexus is visible as a small collection of hypoechoic nodules 
(honeycomb appearance) immediately superficial to the prevertebral fascia that 
overlies the interscalene groove.  
Once the plexus has been identified, the needle is passed through the skin, 
platysma, and investing layer of the deep cervical fascia, and the tip is placed 
adjacent to the plexus. . Following negative aspiration, 1–2 mL of normal saline is 
injected to confirm the proper injection site. Then after confirmation of safe 
needle position and absence of vascular spread, bupivicaine 0.25% (5–15 mL) is 
administered to envelop the plexus, and the block is repeated with the same 
technique on the opposite side. 
 (Figure 1). 
 

Research Protocol Template                                                                                                          September 2023                          
 
12 
 
 
 Figure 1. Cervical plexus (transverse view): desired distribution of local anesthetic (blue-
shaded area) to nerve block the cervical plexus. Needle path: 1. ASM, anterior scalene muscle; CA, 
carotid artery; CP, cervical plexus; MSM, middle scalene muscle; SCM, sternocleidomastoid muscle. 
Group B: Induction of general anesthesia as Group A, without performing 
intermediate cervical plexus block, intravenous morphine will be given in a dose of 0.1-
0.2mg/kg to maintain intraoperative analgesia. 
 
All operations will be performed in the morning, taking into consideration circadian 
rhythm of hormone release. In both groups, venous blood samples to measure serum 
cortisol and interlukien-6 level will be collected before surgery as a baseline, then 24 
hours post-operative.interlukien-6 is normally low and may be undetectable within 30-60 
min after start of surgery while reaching maximum level at 24 hours post-operative. 
 
      During the intraoperative period; heart rate and mean arterial blood pressure will be 
recorded every 15 minutes throughout the surgery. Intravenous fentanyl bolus doses (0.5 
μg/kg) will be adjusted to keep the HR and mean arterial blood pressure within 20% of 
the pre-induction values.  
 
At the end of surgery, atracurium will be stopped and neuromuscular blockade 
will be reversed with intravenous neostigmine 0.04 mg/kg and 0.01 mg/kg atropine and 
endotracheal tube will be removed. 
 
After operation, patients will be transferred to post anesthesia care unit (PACU) 
for complete recovery and monitoring. A standard postoperative analgesia regimen will 
be prescribed as intravenous paracetamol 1gm every 8 hours. Intravenous morphine 
0.05 mg/kg will be given as a rescue analgesic dose if numeric analogue score was ≥ 3. 
Metoclopramide 0.15 mg/kg IV will be prescribed for patients complaining of nausea or 
vomiting.  
 
        The maximum dose of morphine that will be given is 20 mg/24 hrs. 
The block will be considered a failed block if the patient required more than two 
doses of rescue analgesia in the first hour postoperatively. 

Research Protocol Template                                                                                                          September 2023                          
 
13 
 
 
Measurement tools 
 
 Demographic data: age, sex, body mass index (BMI). 
 Serum cortisol and interlukien-6 pre-operative and 24 hours post-operative. 
 Hemodynamics {heart rate, arterial blood pressure (systolic, diastolic and mean 
blood pressure)}will be recorded at the following intervals: baseline reading , 
Intraoperative 15 minutes post-intubation (pre-block), 15 minutes after the 
block/administration of morphine and then every 15 minutes throughout the 
surgery, and postoperative at 1 ,6,12 , 24  hours.. 
 NPRS score at 15, 30, and 60 min, 6, 12, 24   hours post-operatively. 
 Number of patients in each group who need intraoperative additional analgesic 
doses of fentanyl and total fentanyl dose for each patient. 
 Total postoperative analgesic requirements. 
 Failure rate of the block (the block will be considered a failed block if the patient 
required more than two doses of rescue analgesia in the first hour 
postoperatively. 
 
 
 
VI. 
Study outcomes 
 
1. Primary outcomes: 
 
 The serum cortisol level 24 hours postoperatively. 
 
 
 
 
 
 

Research Protocol Template                                                                                                          September 2023                          
 
14 
 
2. Secondary outcomes: 
 
 The serum interlukien-6 24 hours postoperatively. 
 Intraoperative hemodynamics {heart rate, arterial blood pressure (systolic, 
diastolic and mean blood pressure) 
 Intraoperative additional fentanyl requirements. 
 NPRS score postoperative during 1st 24 hours. 15, 30, and 60 min, 6, 12, 
and 24 hours after surgery. 
 Time to first postoperative analgesic request (duration of analgesia). 
 Block failure rate. 
 Incidence of complications. (Nerve injury, Hematoma formation, LA 
toxicity, intravascular injection. 
 Block failure: The block will be considered a failed block if the patient 
required more than two doses of rescue analgesia in the first hour 
postoperatively.  
 
 
 

Research Protocol Template                                                                                                          September 2023                          
 
15 
 
 
 
 
Statistical Analysis 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Research Protocol Template                                                                                                          September 2023                          
 
16 
 
Statistical Analysis 
I. 
Sample size 
Our primary outcome is the serum cortisol level 24 hours postoperatively. In a 
previous study, the serum cortisol level after 24 hours was 21.8 ± 4.7 micrograms 
per deciliter (mcg (ref) after lumbar fixation surgeries. We calculated a sample 
size that could detect a mean difference of 20% between both study groups. 
MedCalc Software version 14 (MedCalc Software bvba, Ostend, Belgium) was 
used to calculate the sample size 60 patients (30 Patient per group) at least were 
estimated to have a study power of 95% and an alpha error of 0.05. This number 
will be increased to 66 patients (33 patients per group) to compensate for 
possible dropouts. 
Sample size calculation was performed guided by power of 95%, confidence level 
of 95 %.(8) 
II. 
Statistical analysis 
For data analysis, the Statistical Package for Social Science (SPSS) software, 
version 26 for Microsoft Windows (SPSS Inc., Chicago, IL, USA) will be used. The 
Chi squared test will be used to examine categorical data, which will be given as 
frequency (percent). The Shapiro-Wilk test will be used to verify for normality in 
continuous data, and the results will be provided as mean (standard deviation) or 
median (interquartile range) as appropriate. Depending on the data's normality, 
the unpaired t test or the Mann Whitney test will be used to assess it. Repeated 
measures will be examined using analysis of variance (ANOVA), with post-hoc 
pairwise comparisons using the Boneferroni tests. A P value less than 0.05 will be 
considered statistically significant.     
 
 
 

Research Protocol Template                                                                                                          September 2023                          
 
17 
 
 
 
 
 
References 
 
 
 

Research Protocol Template                                                                                                          September 2023                          
 
18 
 
References: 
 
1. Arfanis K, Fioratou E and Smith A: Safety culture in anaesthesiology: Basic 
concepts and practical application. Best Pract Res Clin Anaesthesiol 25: 
229-238, 2011. 
2. Katz FH, Romfh P, Smith JA. Diurnal variation of plasma aldosterone, 
cortisol and renin activity in supine man. J Clin Endocrinol Metab 
1975;40:125-34 
3. Garringer SM, Sasso RC. Safety of anterior cervical discectomy and fusion 
performed as outpatient surgery. J Spinal Discord Tech 2010; 23: 439-43. 
4. Sagi HC, Beutler W, Carroll E, Connolly PJ. Airway complications 
associated with surgery on the anterior cervical spine. Spine (Phila Pa 1976) 
2002; 27: 949-53. 
5. Kim JS, Lee J, Soh EY, Ahn H, Oh SE, Lee JD, et al. Analgesic effects of 
ultrasound-guided serratus-intercostal plane block and ultrasoundguided 
intermediate cervical plexus block after single-incision transaxillary robotic 
thyroidectomy: a prospective, randomized, controlled trial. Reg Anesth Pain 
Med 2016; 41: 584-8. 
6. Missaghi B. Sternocleidomastoid syndrome: a case study. J Can Chiropr 
Assoc 2004; 48: 201-5. 
7. Mulcahy M, Elalingam T, Jang K, D’Souza M, Tait M. Bilateral Cervical 
Plexus Block for Anterior Cervical Spine Surgery: Study Protocol for a 
Randomised Placebo-Controlled Trial. 2021; 
8. Ragheb, A. M. R., Abdul Rahman, A. E., Aldemrdash, A. M., & Arafa, S. K. 
H. (2020). Pressure Controlled Ventilation versus Volume-Controlled 
Ventilation Regarding Hemodynamics and Stress Response for Posterior 
Lumbar Spine Surgeries in The Prone Position. The Egyptian Journal of 
Hospital Medicine, 81(1), 1262-1268.‏