Comparison of Ultrasound Guided Supraclavicular Brachial Plexus Block With and Without Peripheral Nerve Stimulation (PNS) Guidance: A Randomized Controlled Tria
Phase: NA
Conditions: Supraclavicular Plexus Block, Ultrasound, Anaesthesia
Sponsor: Aga Khan University

Protocol 
Title: Comparison of Ultrasound Guided Supraclavicular Brachial Plexus Block 
with and without Peripheral Nerve Stimulation (PNS) Guidance: A randomized 
controlled trial. 
Principle Investigator:  
Dr. Azhar Rehman, Assistant Professor, Department of Anaesthesiology, aga khan university 
hospital, Karachi. 
Co-investigator:  
Dr. Azhar Sharafat, Resident, Department of Anaesthesiology, aga khan university hospital, 
Karachi. 
 
Document Date: 01/June/2025 
Upload Date:       20/July/2025 
 
 
 
 

INTRODUCTION 
Peripheral Nerves Blockade (PNB) via local anaesthetics is a method of providing anesthesia 
and analgesia to the limbs and it was well established in the late 20th century. However, it did 
not come very well into practice because of unreliability, high rate of complications and 
failure due to lacking of accurate and reliable techniques of nerve localization at that point in 
time(1). It was only when newer nerve localization methods, such as Peripheral Nerve 
Stimulation (PNS) and Ultrasound (U/S) Imaging started becoming commercially available 
that the trend of Regional Anaesthesia started getting recognized among the physicians. PNB 
as a sole anaesthesia technique for limb surgery took further integration in practice and 
widespread acceptance among anaesthetist in the last decade, once ultrasound technology 
advanced to newer heights resulting in compact and more mobile units, higher resolution, 
needle recognition software etc.  
When compared to PNS guided regional anaesthesia (PGRA), ultrasound guided regional 
anaesthesia (UGRA) offers a number of important practical advantages such as direct real-
time visualization of the anatomy of interest, needle pathway and its passing through 
structures and spread of local anaesthetic, and the potential for instantaneous needle re-
adjustments as per need (2). All this allows for safer and more effective distribution of local 
anaesthetic in the region of desired peripheral nerve (3). This superiority of Ultrasound 
Guidance led to fade in the use of PNS guidance in the Regional Anaesthesia practice over the 
recent years.  
Regardless of the previously discussed superiority of U/S Guidance in Regional anaesthesia 
(RA), it has its own limitations. Such limitations include difficulty in visualization and 
identifying neural structures when they are lying far away from the skin either due to thick 
overlying subcutaneous adipose tissue in the obese patients or simply because of the presence 
of nerve bundle in the deeper tissue planes, and inability to confidently identify and exclude 
the placement of needle tip within the nerve, where if an injectate is injected will lead to nerve 
damage (4). 
Such limitations of U/S Guidance in RA can be circumvented by using PNS Guidance in its 
conjunction. PNS works by delivering a small pulse of electric current through the needle tip 
which when in close proximity to a neural structure will lead to its stimulation and its 
respective muscle contraction, thereby helping us in identifying the neural structure of 
interest. Current density (with pulse duration at 1ms and frequency 2Hz) of around 1 mA for 
superficial nerves and 1.5-2mA for deeper nerves is enough to elicit a desired motor 
response(5). Eliciting a motor response at an even higher current density can be discomforting 
to the patient as well as misleading to the operator as neural structures can get stimulated 
through tissues and fascial planes (6). Similarly, Current density can also be used to predict 
the intra-fascicular or intraneural needle placement. Bigeleisen et al showed that minimum 
stimulation (Median [interquartile range]) threshold outside was 0.60 mA [0.40-1.0] and 
inside 0.30 mA [0.20-0.40], where, the difference of 0.30 mA was statistically significant (7). 
Therefore, a lower limit for the current density can be used as a safety margin beyond which 
no muscle activity should be elicited by using PNS. 
So, considering the additional benefits of PNS Guidance that it can potentially concur in 
facilitating UGRA in achieving effective and safer PNB, we propose and design a randomized 

control trial by comparing the UGRA with and without PNS Guidance in achieving PNB and 
its outcomes.  
OBJECTIVES 
Primary Objective of this study is to compare the success rate of Ultrasound guided 
Supraclavicular brachial plexus block with and without PNS guidance. 
Secondary objectives are frequency of needle re-adjustments with US + PNS guidance 
depending upon the added information obtained via the PNS, duration of PNB procedure, rate 
of complications such as nerve damage between the two group, intra-op rescue analgesic 
requirement and conversion to General Anaesthesia. 
Primary Outcome:  
Time to onset of nerve blockade and rate of success of blockade between the study groups.  
Secondary Outcome:  
Needle re-adjustments, duration of PNB procedure, rate of complications, intra-op rescue 
analgesic requirement and conversion to General Anaesthesia between the study groups.  
 
RISKS AND BENEFITS OF STUDY: 
Benefits of the study are that we will be able to identify the most suitable modality for 
performing the PNB in terms of rate of success, time to onset of block and rate of 
complications, allowing patients to receive much effective and safe PNB. 
Risks of this study include infection, vascular puncture, hematoma, nerve damage, temporary 
phrenic nerve blockade, Horner’s syndrome, laryngeal nerve blockade and Local Anaesthetic 
Systemic Toxicity. 
OPERATIONAL DEFINITION 
Pain Score: Pain Scoring on a 0 to 10 numerical rating scale where 0 would be no pain and 10 
would be the worst possible pain experienced. 
Bradycardia: Heart Rate of less than 60bpm. 
Hypotension: Mean Arterial Pressure of less than 65mmHg. 
Significant rise in Blood Pressure: Sudden rise of more than 20% in systolic blood pressure 
from the baseline. 

Significant rise in Heart Rate: Sudden rise of more than 20% in Heart Rate from the base line. 
Successful Block: Patients showing complete sensory and motor blockade in the distribution 
of blocked nerves after 25mins of PNB.  
Partially Successful Block:  Patients showing in-complete or patchy sensory and motor 
blockade in the distribution of blocked nerves after 25mins of PNB.  
Failed Block: Patients showing absolutely no loss of sensory and motor blockade in the 
distribution of blocked nerves after 25mins of PNB.  
HYPOTHESIS 
‘Addition of PNS Guidance to UGRA will increase the success rate of PNB’. 
MATERIAL AND METHODS 
Study design:  
Single Blinded, Randomized Controlled Trial. 
Setting:  
The Aga Khan University Hospital, Karachi 
Duration of study:  
2 Years 
Sample size: 
An anticipated sample size of minimum 44 patients will need to be included in this study with 
99% confidence interval and 95% power, of which, 22 should receive receive PNB solely 
under the Ultrasound Guidance and 22 should receive PNB under the Ultrasound Guidance 
supplemented with PNS. Sample has been calculated by using OpenEpi software’s ‘Sample 
size for comparing two means’ function. Where, a mean (standard deviation) time (minutes) 
to onset of sensory blockade for patients who received PNB under US guidance was inserted 
as 10 (2.4506), while for patients who received received PNB under the Ultrasound plus PNS 
guidance was inserted as 7.5 (1.2253). The ratio of between both the groups was 1. These 
estimates were taken from the study conducted by Gökhan Demirelli et al, where they 
assessed ultrasound and ultrasound plus nerve stimulator guided Median Nerve Blockade as 
part of axillary plexus block (3). The study originally reported the onset of sensory blockade 
times in median (IQR), which were then converted to Mean (standard deviation) for the 
purpose of sample size calculation based upon the sample from Luo et al. (8) and Wan et al. 
(9). 

 
Sampling technique 
 Non-probability consecutive sampling with randomized group allocation. 
Sample selection 
 
Inclusion criteria: 
 Aged 18 years and older. 
 ASA 1 to IV 
 No contraindications to regional anaesthesia. 
 Operative site at mid to lower arm, elbow, forearm, wrist, and hand. 
 Ability to provide informed consent and reliably report symptoms to the research 
team for regional anesthesia. 
Exclusion criteria:  
 Patient’s refusal to participate. 
 Inability to provide first-party consent due to cognitive impairment. 
 Cognitive dysfunction which can lead to difficulties in communication and 
cooperation of patient. 
 Preexisting neuropathy. 
 Preexisting coagulopathy. 
 Patients who will be shifted to ICU due to post - operative ventilatory support. 
Randomization: 
Patients will be randomly divided by block randomization into two study groups at a ratio of 
1:1 using a computer-generated random number. 
Blinding: 
Study will be single blinded where only the patients will be unaware of the study group they 
will be made part of.   
Funding 
Investigators, after getting approval from ARC and ERC, will request for departmental grant 
for funding their research so study related interventions and consumables will not be charged 
to the patient. Insurance cover for the management of potential study related adverse events 
will be provided by research grant fund. 
Study groups 
Group US: Patients in this group will receive PNB solely under the Ultrasound 
Guidance. 

Group US+PNS: Patients in this group will receive PNB under the Ultrasound 
Guidance supplemented with PNS. 
Data collection  
Patients’ enrollment in the study will begin after obtaining approval from the ERC and 
Clinical Trials unit. The trial will be conducted in compliance with Good Clinical Practice 
(GCP). Operating Room lists will be reviewed a day before and patients planed for surgeries 
involving regions of mid to lower arm, elbow, forearm, wrist, and hand will be considered for 
inclusion in study. These patients will then be interviewed in the ward or day care unit after 
they get admitted for surgery, where they will be assessed for participation in study based 
upon the inclusion and exclusion criteria. Patients fulfilling such criteria will be considered 
for participation and their primary surgeon will be informed of such. Patients, whose surgeon 
agrees for their participation, will be handed over the consent form after explaining them the 
whole procedure, advantages, and disadvantages of the procedure and their absolute free will 
to be part of the study. Patients who will consent to be part of our trial will be enrolled in our 
study. Study participants will then be taken to the OR where they will be applied with 
standard monitoring including Non-invasive Blood Pressure monitoring, Electrocardiography 
and Pulse Oximetry, and supplemental oxygen will be applied to the patients via nasal 
cannula at 4L/min. An intravenous access of 20 or 22 gauge will be established in 
contralateral arm for background fluid infusion and emergency intravenous access. 
Participants will then be positioned supine with slight head rotation to the contralateral side. 
PNB will be performed by a consultant anaesthetist proficient in performing supraclavicular 
block. In the US group, Ultrasound linear probe will be applied in the supraclavicular fossa in 
sterile manner and will be positioned to obtain short axis view of subclavian artery and first 
rib to achieve satisfactory image of elliptical hypoechoic trunks and divisions of brachial 
plexus at the supraclavicular fossa. 1–2 mL of 2% lignocaine will be injected subcutaneously 
into the skin 1 cm lateral to the transducer by using 27-gauge needle to decrease discomfort 
during block needle insertion The block needle will be introduced in lateral to medial 
direction under the US Guidance in-plane to the probe. Needle will then be directed towards 
the junction of first rib and subclavian artery, aiming for the neural cluster of brachial plexus. 
Once the operator feels satisfied with the needle tip placement, a negative aspiration will be 
attempted to rule out in-advert intravascular puncture and then 25ml of 0.5% Bupivacaine 
Local Anaesthetic (LA) will be injected all around the said neural cluster while observing for 
the hydro-dissection and spread of Bupivacaine all around the neural cluster. Needle will be 
redirected if desired spread of LA does not occur around the neural cluster until such is 
achieved with LA injection. In the US + PNS group, majority of the procedure similar to what 
was performed in the US group will be followed with differences that an insulated PNS 
compatible block needle will be used to perform the PNB and once the operator will be 
satisfied of their needle placement, a current of 1.0 mA will be delivered via block needle to 
achieve desired muscle response i.e., motor response in arm, forearm and/or hand. Failure to 
get such response will prompt the operator to re-adjust the block needle until such is achieved. 
Once desired muscle response will be achieved, current of PNS will be gradually decreased to 
up till 0.4 mA, where no muscle response should be elicited. Presence of muscle response at 
0.4 mA will suggest intraneural placement of block needle and operator will re-adjust the 
needle until such is abolished while preserving muscle response for the current window 
between 0.5-1.0 mA. 

Afterwards, progression of sensory blockade will be assessed by evaluating for absence of 
sensation to cold using an ice pack in musculocutaneous, median, ulnar, and radial nerve 
distribution and comparing it with contralateral arm. This assessment will be done every 1 
minute after completion of injection until complete sensory blockade in each of the four major 
nerve territories. Time to onset of sensory blockade will be defined as the time duration from 
injection completion to sensory blockade in any of the four nerve territories. Whereas time to 
complete sensory blockade will be defined as the time duration from injection completion to 
sensory blockade in all the four nerve territories. Progression of motor blockade will be 
assessed by asking the patient to move their elbow, wrist and fingers and observing for 
absence of movement (plegia). This assessment will be done every 2 minutes after completion 
of injection until complete motor blockade is achieved. Time to onset of motor blockade will 
be defined as the time duration from injection completion to plegia at either elbow, wrist, or 
fingers. Whereas time to complete motor blockade will be defined as the time duration from 
injection completion to plegia at elbow, wrist, and fingers. Once complete motor and sensory 
blockade will be achieved, surgeon will be given go-ahead to proceed with surgery. Any 
intra-op analgesic requirement will be documented. After completion of surgery, patients will 
be shifted to PACU where their surgical pain will be assessed. Patients will be followed for 
any PNB related complication. 
 
ETHICAL CONSIDERATION: 
The information provided will remain confidential. Nobody except the principal investigator 
will have access to it. Name and identity will also not be recorded at any time and all the 
important details by which identity can be revealed will not be mentioned on the Proforma. 
However, the data may be seen by Ethical Review Committee and may be published in 
Journals and somewhere. 
DATA ANALYSIS  
 The data of the study will be encoded and analyzed through SPSS. The overall quantitative 
variables such age, weight, height, duration of PNB, duration of onset of nerve blockade, etc. 
will be conveyed as mean ± SD or median (IQR) depending upon their distribution. While, for 
the qualitative variables such as gender, co-morbidities, needle re-adjustment, success of 
block etc., frequency and percentages will be used. Stratification analysis will be done with 
respect to US guided and US + PNS guided PNB groups to fulfill primary and secondary 
outcomes such as time to onset of nerve blockade, success of block, needle re-adjustments, 
duration of PNB procedure, rate of complications, intra-op rescue analgesic requirement and 
conversion to general anaesthesia. Furthermore, the association between US guided and US + 
PNS guided PNB groups with respect to outcome variables will be evaluated by independent 
t-test or Mann Whitteny U test and Chi-square test of association. p value of < 0.05 will be 
considered as statistically significant. 
DATA HANDLING 
The primary investigator will be responsible for data handling. The primary investigator will 
be responsible for monitoring the study for protocol compliance, ethical standards, regulatory 

compliance and data quality. The confidentiality of the participants will be maintained by 
assigning each patients a number. All Hardcopies of the data will be stored under lock and 
key, While, all soft copies will be password protected. A per regulatory requirements this data 
will be encrypted and stored for 15 years.  
 
ADVERSE EVENTS 
Adverse Events are defined as ‘Any untoward medical occurrence in a trial patient to whom a 
research treatment or procedure has been administered, including occurrences which are not 
necessarily caused by or related to that treatment or procedure. 
Such events include, infection, vascular puncture, hematoma, nerve damage, temporary 
phrenic nerve blockade, Horner’s syndrome, and laryngeal nerve blockade. 
Patient will be followed and monitored till the resolution of symptoms and discharge. all AEs 
will be reported to the ERC in the progress report. 
SERIOUS ADVERSE EVENTS 
Serious Adverse Events are defined as an untoward event that: Results in death; Is life-
threatening; Requires hospitalization or prolongation of existing hospitalization; Results in 
persistent or significant disability or incapacity; Or is otherwise considered medically 
significant by the Investigator. 
The term “life-threatening” refers to an event in which the patient was at risk of death at the 
time of the event; it does not refer to an event which hypothetically might have caused death 
if it were more severe. Patients must be formally admitted – waiting in out-patients or A&E 
does not constitute an SAE (even though this can sometimes be overnight). Similarly, planned 
hospitalizations that clearly are not related to the condition under investigation or 
hospitalizations/prolongation of hospitalization due to social reasons should not be considered 
as SAEs. Such serious adverse events can include pneumothorax, intravascular injection of 
local anaesthetic and local anaesthetic systemic toxicity. 
 All SAEs will be reported within 24 hours to the sponsor, ERC, and hospital management 
through online incident report. 
Insurance cover for the management of potential adverse events associated with the 
intervention will be taken before initiating the study.  
 
 

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