A Comparative Study Between Dexmedetomidine, Ozone and Dexamethasone Local Injection in Carpal Tunnel Syndrome for Long- Term Pain Relief
Phase: NA
Conditions: Carpal Tunnel, Dexmedetomidine, Ozone, Dexamethasone
Sponsor: Tanta University

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A comparative study between Dexmedetomidine 
,Ozone and Dexamethasone local injection in 
carpal tunnel syndrome for long-term pain relief 
 
 
 
A Protocol of Thesis 
Submitted to 
Faculty of Medicine 
Tanta University 
 
In the Partial Fulfillment of 
Requirements of  
MD degree in 
Anesthesia, Surgical Intensive Care 
and Pain Medicine 
 
Submitted by  
Mahmoud Talat Elgebaly 
Assistant Lecturer of Anesthesia,  
Surgical Intensive Care  
and Pain Medicine 
 
Master degree of Anesthesia, Intensive 
Care and Pain Medicine 
Tanta University 2022 

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Supervisors 
Prof.  
Ayman Abd Elmaksoud yousef 
Professor of Anesthesia, Surgical 
Intensive Care and Pain Medicine 
Faculty of Medicine 
Tanta University 
 
 
Prof.  
Ashraf Ali Abo Elfotouh  Abo Elsafa 
Professor of Neuropsychiatry 
Faculty of Medicine 
Tanta University 
 
 
Prof.  
Ahmed Esam-Eldein Ali Salim 
Professor of  Anesthesia , Surgical 
Intensive Care and Pain Medicine 
Faculty of Medicine 
Tanta University  
 
Dr. 
Wafaa  Madhy  Attia 
Lecturer of Anesthesia, Surgical 
Intensive Care and Pain Medicine  
Faculty of Medicine 
 Tanta University 
 
 
 
 
 
 
 

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Introduction 
 
Carpal tunnel syndrome (CTS) is a collection of symptoms and 
signs associated with median neuropathy at the carpal tunnel. Most CTS 
is related to idiopathic compression of the median nerve as it travels 
through the wrist at the carpal tunnel.[1] 
Carpal tunnel syndrome (CTS) is the most common entrapment 
neuropathy in the upper limb which is caused by compression of the 
median nerve as it travels through the carpal tunnel within the flexor 
retinaculum of the wrist.[2,3 ]  
The incidence of CTS has been reported to be 1–3 per 100 people 
per year. Surgical release of the retinaculum in advanced cases has been 
proposed as the method of choice.[4] 
The most commonly suggested explaining  mechanism is  that 
increased mechanical pressure in the carpal tunnel can lead to 
compression, inflammation and decreased blood supply to the nerve 
which all-together can lead to nerve lesion; thereby producing typical 
symptoms such as pain, numbness, weakness in grip and tingling usually 
in the thumb, index and middle fingers.[3,4]  
Surgery resolves CTS in 70% of cases with clinical remission 
lasting up to 30 months. Sometimes severe complications may occur such 
as nerve injury and infection. Considering the burden and possible 
complications of surgery, many patients with mild to moderate grades 
might prefer to select one of the conservative treatments including: oral 
non-steroidal anti-inflammatory drugs (NSAIDs), diuretics, pyridoxine, 
wrist splinting, physical agent modalities like LASER, ultrasound 
(US),[5,6] and the most recent method, i.e., local injections of 

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corticosteroid, ozone ,progesterone and platelet-rich plasma (PRP) 
etc.[7,8] 
Corticosteroid injection is an extensively used and accepted 
treatment in mild to moderate CTS according to the guidelines of the 
American Academy of Orthopedic Surgeons [9] as corticosteroids reduce 
the inflammation and edema associated with CTS. However, there is no 
guideline as to which corticosteroid has to be used as the standard 
treatment in CTS.  
Triamcinolone acetonide, a commonly used steroid for this 
indication, is a particulate steroid, which can cause permanent nerve 
injury if accidentally injected into the nerve [10]. Dexamethasone sodium 
phosphate is another steroid with a better safety profile that has also been 
shown to be effective in CTS. It is a non particulate steroid that would not 
cause permanent nerve damage even if it is accidentally injected into the 
nerve. [10] 
Local ozone injection as a therapeutic option in some 
musculoskeletal conditions; ozone (O3) gas is a molecule consisting of 
three oxygen atoms in a dynamically unstable structure. Ozone therapy 
has been utilized and studied for more than a century. Ozone is a re-
emerging substance that has many biological effects such as bactericidal, 
immune-modulatory, analgesic, anti-inflammatory, anti-oxidative, as well 
as enhancing the blood circulation. [11] 
The most established therapeutic mechanisms are:  
A) Indirect mechanical decompression in the site of nerve 
entrapment by increasing tissue oxygenation with reduced venous 
or lymphatic stasis.  

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B) Suppression of the cell-mediated immune response by inhibiting 
macrophages from the release of proteinase, and also by induction 
of inhibitory mediators such as interleukin-10 and tissue growth 
factor beta (TGF-β). 
C)Suppression of the humoral immune system, by decreasing the 
prostaglandins release and pro-inflammatory bradykinins.[12] 
Dexmedetomidine is a super-selective α2-adrenergic agonist with 
considerable sedative and analgesic actions. The mechanism of its intra-
articular analgesic action is not yet fully elucidated, but it is similar to 
clonidine. Clonidine acts on presynaptic receptors, inhibiting the release 
of nor epinephrine in peripheral afferent receptors, and exhibits local 
anesthetic action via inhibition of stimuli conduction through C and A-
delta fibers. [13] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Aim of the work 
 
The aim of the present study is to compare the analgesic efficacy of 
Dexmedetomidine, Ozone and Dexamethasone  regional injection in 
carpal tunnel syndrome. 
- primary outcome: is to evaluate the  analgesic efficacy and 
functional status improvement of Dexmedetomidine, Ozone and 
Dexamethasone  regional injection in carpal tunnel syndrome via 
assessment of Visual Analogue Scale (VAS) before and after 
injection. 
- Secondary outcome: is to evaluate : 
1) Median motor and sensory nerve conduction study(NCS) 
evaluation before and after injection. 
2) Analgesic requirement ( dose and frequency of oral acetaminophen 
intake in first 48 hours) for post injection . 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Patients and Methods 
This prospective randomized study will be carried out in Tanta 
University Hospitals for a period of nearly one year from February 2023 
to February 2024, after approval from institutional ethical committee. 
Informed written consent will be obtained from every patient after 
receiving an explanation of the purpose of the study and every patient 
will have a secret code number. All data of the patients will be 
confidential with secret codes and private file for every patient. All given 
data will be used for the current medical research only. 
Any unexpected risks appeared during the course of the research 
will be cleared to the participants and ethical committee on time. 
Inclusion Criteria: 
One hundred and thirty five  patients aged 20-60 years who are 
presented  to Tanta university  outpatient pain clinic at a period from 
February 2023 to February 2024 with clinical, electro physiologic, and 
ultrasonographic evidence of mild-to-moderate CTS will be included in 
this study.  
Inclusion criteria will include numbness and  pain in the median nerve 
(MN) distribution persisting for minimum of 3 months , nerve conduction 
studies (NCS) consistent with carpal tunnel syndrome  (CTS)  as per the 
American Association of  Neuromuscular and Electro diagnostic 
Medicine (AANEM) guidelines, and an median nerve (MN) cross-
sectional area (CSA)at the wrist >12 mm2 suggesting mild-to-moderate 
CTS forms. [14] 
 
 
 

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CTS grade                                 
-Minimal 
 -Mild  
-Moderate  
-Severe  
-Extreme  
NCS finding 
-Abnormal segmental or comparative tests only 
-Abnormal SNCV only with normal DML 
-Abnormal SNCV and abnormal DML 
-Absent sensory response and abnormal DML 
-Absence of motor and sensory responses 
 
 
AANEM grading of CTS based on NCS findings 
AANEM: American Association of Neuromuscular and Electro diagnostic Medicine 
CTS: carpal tunnel syndrome 
NCS: nerve conduction study 
SNCV: sensory nerve conduction velocity 
DML: distal motor latency 
In the case of bilateral involvement, only the side with more severity 
was included. 
Exclusion Criteria: 
 Patient refusal. 
 Patients with severe symptoms  and signs of CTS as identified per 
the American Association of  Neuromuscular and Electro 
diagnostic Medicine (AANEM) guidelines,[14] as this is an 
indication for surgery, 
 Patients who show improvement on medical treatment, 
 previous surgical or injectional CTS treatment, 
 Pregnancy ,co existence  of brachial plexopathy, or thoracic outlet 
syndrome, polyneuropathy, radiculopathy and peripheral nerve 
lesion in upper limb. 
 Severe cardiovascular disease 
 Morbid obese patients (body mass index (BMI) of >35 kg/m2) 
 Infection at site of injection. 
 Bleeding diathesis 

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 History of thyroid deficiency, uncontrolled diabetes mellitus , 
rheumatoid arthritis and  history of glucose-6-phosphate 
dehydrogenase (G6PD) deficiency 
 History of Ozone or Dexmedetomidine allergy. 
 End stage renal and hepatic disease. 
 History of inflammatory joint , connective tissue disorders, , burns, 
any local tissue contractures and history of wrist trauma. 
 Patients who will not consent to completing The visual analogue 
scale (VAS) for pain or nerve conduction study before and after 
injection. 
Methods: 
The patients will be randomly classified into three equal groups (45 
patients each). Group allocation will be done by computer generated 
random numbers and closed opaque envelopes: 
Group A (n=45): the participants will receive a single local injection 
of 4 ml ozone (10 micrograms/dl) plus to 1 ml lidocaine (1%) using a 25 
G needle.  
Needle insertion using ultrasonography will be on the volar side 
(conventional midline approach), one finger-breadth proximal to distal 
wrist crease (between the tendons of flexor Carpi radialis and Palmaris 
longus) with a 45-degree angle between needle and skin. US-guided 
intracarpal 
injection 
using 
ultrasonography 
(SonoScape 
E1Exp; 
Shenzhen, China) with a 10–18 MHz linear array transducer will be 
performed by the same physician who will not be  aware of study groups, 
3 mL of solution will be injected through the in-plane ulnar approach, to 
detach the MN from the transverse carpal ligament, and an additional 2 
mL will be injected to separate the MN from the underlying flexor 
tendons. 

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Group B (n=45): patients will receive a single local injection of  5 
mL (3 mL lidocaine (1%)  and 2 mL [8 mg] dexamethasone) via the same 
technique. 
Group C (n=45): patients will receive injection of 1 microgram/kg 
dexmedetomidine average (70-100-microgram) (0.7-1ml) plus 4ml 
lidocaine  injection nearby median nerve via the same technique. 
During the preoperative assessment, all enrolled  patients will be  
informed about the study objectives and  protocol. 
Full history, clinical examination, complete blood count, 
coagulation profile, blood sugar, renal and hepatic profile, ECG, and 
echocardiography will be  performed in all patients . 
After establishing an intravenous access (20 G), Patients will be  
monitored for noninvasive blood pressure, ECG, and peripheral oxygen 
saturation. 
All blocks will be performed by one pain physician who will 
neither be aware of study groups  nor participate in data collection or 
analysis. 
All patients will be  observed for 30-min post injection for possible 
side effects before discharge. 
All patients will be  allowed to use acetaminophen in the case of 
possible post injection pain during the first 48 hrs.  
 -  Sample size Justification : 
The sample size and power analysis was calculated using Epi-Info 
software statistical package created by World Health organization and 
center for Disease Control and Prevention, Atlanta, Georgia, USA version 
2002. 
 

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The criteria used for sample size calculation were as follows: 
- 95% confidence limit 
- 80% power of the study 
- Expected long term pain relief among 90% in best treatment groups 
as compared to 65% in least favorable treatment groups. 
The sample size based on the previously mentioned criteria was 
found at N=44 in each group. The researcher will increase the sample size 
to 45 cases to compensate for incomplete results. 
Measurements: 
All measurement will be recorded by an investigator who will not be 
aware about the study design or intervention. 
1) Age, gender, and BMI of the patients will be recorded. 
2) Visual Analogue Scale (VAS) used as an effective tool to detect 
intensity of pain will be recorded; 
- "0" represents no pain ,"10" worst pain, "1-3" mild pain,"4-6 " moderate 
pain and" 7-10 " severe pain. [15]   
Each patient will be assessed at the baseline (before injection) , at 1week, 
1month, 3month, and 6month intervals after injection. 
3) Median motor and sensory nerve conduction study(NCS): the grade of 
CTS, determined via electrophysiological study, will be classified as 
mentioned before at the American Association of  Neuromuscular and 
Electro diagnostic Medicine (AANEM) guidelines. [14]  
Only participants with mild to moderate CTS will be  included in the 
study. Each patient will be assessed regarding electrophysiological 

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changes sensory nerve conduction velocity in millimeter/seconds and dis-
tal motor latency in milliseconds at the baseline (before injection) 
, at 1week, 1month, 3month, and 6month intervals after injection. 
4) Analgesic requirement ( Dose and frequency of oral acetaminophen 
intake in first 48 hours) for post injection . 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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