Ultrasound-guided Intermediate Cervical Plexus Block for Carotid Endarterectomies
Phase: NA
Conditions: Internal Carotid Artery Stenosis
Sponsor: Helios Research Center

 
1 
 
Study Protocol 
 
 
 
Ronald Seidel, MD  
Katharina Zukowski, MD 
HELIOS Medical Center Schwerin 
Department for Anesthesiology and Intensive Care 
Wismarsche Strasse 393-7, DE-19055 Schwerin, Germany 
 
 
 
Title 
 
Ultrasound-guided intermediate cervical plexus block 
 
ID: A 2016-0027 
NCT: 02794974 
 
Final Version 
 
 
 
Date 22.01.2016 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Study protocol (Summary) 
 
Title 
 
Ultrasound-guided intermediate cervical plexus block 
 
Introduction 
 
For interventions on the carotid artery both general and regional anesthesia are 
established anesthetic procedures. The AWMF S3 guideline recommends that you 
make a selection based on the center-specific experience. Only for patients with 
contralateral carotid closure regional anesthesia is recommended as gold standard. 
 
Carotid surgery of the awake cooperative patient can be considered the gold 
standard of neuromonitoring. Critical changes in cerebral blood flow during the 
clamping phase can be detected immediately, an operative shunt can be applied as 
needed. Conservative treatment of carotid stenosis includes treatment with 
anticoagulants (usually aspirin). For this reason, a blockade of the cervical plexus 
should be performed under ultrasound control. Serious side effects such as an intra-
arterial injection of the local anesthetic can be avoided in this way. However, the 
increased safety of an ultrasound-guided approach is not yet proven in large studies. 
 
The innervation of the carotid triangle is complex and includes cranial nerves 
(innervation of the vessel wall and neck muscles) as well as portions of the cervical 
and brachial plexus. 
 
We investigate whether an ultrasound-assisted cervical plexus block in combination 
with additional subplatysmal application of local anesthetic to the superficial cervical 
ansa cervicalis (anastomosis between the cervical plexus and the facial branch of the 
facial nerve) results in hight  anesthetic quality. 
 
Study design 
 
single-center, prospective 
 
Study goal 
 
anesthetic quality 
 
Health economic goals 
 
We expect that the result will affect puncture technique in ultrasound-guided cervical 
plexus blocks for carotid surgery. 
 
 
 
 
 
 
 
 

 
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Interventions 
 
 
 
 
 
 
 
 
 
 
 
Intervention A 
20ml ropivacaine 0.75% (interfascial compartment at the level of 
 
 
 
the carotid bifurcation)  
 
Intervention B 
5ml prilocaine 1% (subplatysmal injection between the medial 
edge of the sternocleidomastoid muscle an the submandibular 
gland)  
 
Intervention C 
5ml prilocaine 1% (perivascular injection within the carotid  
 
 
 
sheath) 
 
Intervention D 
Supplementary local anesthetic infiltration by the surgeon 
(prilocaine 1%) 
 
Patient population 
 
Adult men and women undergoing open-surgical carotid desobliteration. 
 
Study center 
 
HELIOS Medical Center Schwerin, Germany 
 
Schedule 
 
12-18 months 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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1. Introduction 
 
For interventions on the carotid artery both general and regional anesthetics are 
established anesthetic procedures. Surgery of the awake patient can be considered 
the gold standard of neuromonitoring. 
 
2. Primary and secondary outcome parameters 
 
With this prospective study design of ultrasound-guided cervical plexus blocks in 
carotid surgery, we examine whether additional application of local anesthetic to the 
superficial cervical ansa (anastomosis between the cervical plexus and the cervical 
branch of the facial nerve) results in complete surgical anesthesia. 
The main objective is the quantity and location of the local anesthetic supplementary 
injected by the surgeon. Secondary outcome parameters are procedure-typical side 
effects. 
We further investigate the effect of perivascular injection inside the carotid sheath on 
side effects and anesthetic quality. 
 
3. Study design 
 
This is a single-center prospective study. 
 
4. Schedule 
 
The estimated recruitment schedule is approximately 12-18 months. 
 
5. Patient population 
5.1. Inclusion criteria 
 
The following inclusion criteria must be met : 
 
- Surgical carotid deobliteration in symptomatic or asymptomatic carotid stenosis 
- Age over 18 years 
- Written informed consent 
 
5.2. Exclusion criteria 
 
Patients who meet one or more of the following criteria should not be included in the 
study: 
 
- local as well as systemic signs of inflammation 
- comorbidities with the highest risk of anesthesia (ASA risk group V) 
- severe arrythmias in the absence of a pacemaker 
- pronounced anemia 
- decompensated heart failure 
- manifest shock 
- known allergy to local anesthetics used 
- manifest polyneuropathy 
- pregnancy, breastfeeding 
- participation in other studies 
- non-oriented or non-cooperative patients 

 
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- known persistent drug, drug or alcohol abuse 
 
5.3. Co-morbidities 
 
Preexisting co-morbidities are documented in the patient record.  
 
5.4. Co-medication 
 
All medications that are given in addition to the study medication are considered 
concomitant and are documented in the patient record (especially medications that 
have an inhibitory effect on the coagulation system). 
 
6. Study protocol 
6.1. Recruitment 
 
The patients are recruited in the context of anesthesiological preparation. Patients 
who have confirmed their participation in the exam by written informed consent will 
first be clinically evaluated. If the patient meets all inclusion and no exclusion criteria, 
the patient is enrolled in the study. 
 
6.2. Allocation of the study medication 
 
After admission to the study, each patient will receive a patient number, which will be 
noted on the Case Report Form (CRF). The decision on the intervention C (5 ml 
prilocaine 1% perivascular within the carotid sheath) is made by the investigator on 
the basis of the individual sonoanatomy. 
 
6.3. Monitoring and preoperative preparation 
 
Patients are initially treated in the context of a normal preoperative preparation. This 
includes the installation of a peripheral venous access with the connection of 1000 ml 
of electrolyte solution (Jonosteril®) by an anesthesia nurse in the induction room. 
Thereafter, the radial artery is cannulated on the non-operated side. The following 
parameters are monitored until complete postoperative recovery: 
 
- Non-invasive blood pressure 
- Invasive-arterial blood pressure  
- Electrocardiogram 
- Pulsoxymetry 
 
The parameters are documented in the anesthesia protocol.  
 
 
6.4. Interventions 
 
The ultrasound-guided regional anesthesia is performed by one of two experienced 
anesthesiologists. First, we perform a spray disinfection with octenidine. We use an 
ultrasound device from Sonosite (EDGE), Bothell, WA, United States, with a linear 
transducer (HFL38). The puncture is performed with a 24G cannula from Pajunk , 
Geisingen, Germany, in an in-plane technique. 
 
 
 
 
 
 
 
 
 

 
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Intervention A 
20ml ropivacaine 0.75% (interfascial compartment at the level of 
 
 
 
the carotid bifurcation)  
 
Intervention B 
5ml prilocaine 1% (subplatysmal injection between the medial 
edge of the sternocleidomastoid muscle an the submandibular 
gland)  
 
Intervention C 
5ml prilocaine 1% (perivascular injection within the carotid  
 
 
 
sheath) 
 
Intervention D 
Supplementary local anesthetic infiltration by the surgeon 
(prilocaine 1%) 
 
6.5. Follow-up 
 
Patients are initially cared for in the postoperative anesthesia care-unit (PACU). 
Depending on the clinical condition of the patients, further care is provided either at 
the normal ward or on an intensive care unit. For all study patients, a daily clinical 
visit is made until discharge. 
 
6.7. Health economic assessment 
 
We expect the study to have implications for the practice of ultrasound-guided 
cervical plexus blocks for carotid surgery. The fundamental goal is the optimization of 
this regional anesthesia technique. 
 
7. Adverse events 
7.1. Adverse events due to the local anesthetic 
 
Allergic reaction 
Allergic reactions are very rare in amide-type topical anesthetics and are mostly due 
to the methylparaben preservative contained in larger packs (e.g., 50ml bottles). 
 
Local Toxicity 
There are no major studies on local-toxic effects of prilocaine or ropivacaine. 
Possible would be a disturbance of the periaxonal milieu or the nervous blood supply 
(compartment effect of the local anesthetic depot). Neurological complications 
occurred after hyperbaric lidocaine was continuously administered intrathecally with 
7.5% glucose. Similar observations were not made for peripheral nerve blocks.  
 
Systemic Toxicity 
Systemic toxicity occurs at high plasma levels by intravascular injection or absolute 
or relative overdose with rapid resorption of the local anesthetic from the site of 
action. 
The cerebral tendency to seizure is increased by the local anesthetic effect on 
inhibitory cortical centers. With or without preconvulsive warning signs (numbness of 
the tongue and perioral, metal taste, slurred speech, ear blades, blurred vision, 
restlessness), generalized convulsions occur. With rising plasma levels, coma and 
respiratory paralysis can occur. 

 
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Inhibition of intracellular ATP production and blockade of sodium channels (vasal, 
cardiac, sympathetic) results in hypotension and variable cardiac arrhythmias 
(bradycardia to asystole, ventricular arrhythmias to ventricular fibrillation). 
In a large-scale prospective study by Auroy et al. (Anesthesiology 1997) in more than 
100,000 regional anesthesia, the risk of serious complications was stated as follows: 
cardiac arrest 3.1 / 10000, case of a convulsion 2.2 / 10000; Death 0.7 / 10000. 
 
7.2. Adverse events due to the peripheral nerve block 
 
Complications may be due to needle trauma (vascular or nerve lesion), local infection 
or as a result of improper storage on the operating table (pressure lesion). Long-term 
neurological damage was reported in 0.19% to 1.7% depending on the examination, 
with various possible causes (nerve block, surgery, storage) being subsumed here. 
In addition - usually not serious - complications may occur in connection with the 
unfamiliar stress situation of the surgical procedure: vagovasal syncope or anxiety 
with hypertensive circulatory regulation. 
 
7.3. Evaluation of adverse events 
 
Prilocaine and ropivacaine are drugs approved for peripheral nerve blocks that we 
use within the maximum permitted dose and indication. All occurring complications 
are documented and the likelihood of the causal relationship with the regional 
anesthesia procedure is stated. Since this is a standard regional anaesthesia 
procedure, it can not be expected that previously unknown complications will occur. 
 
7.4. Information to the ethics committee 
 
In accordance with the GCP Regulation, any severe adverse event (SAE) or 
unexpected (SUSAR) adverse event occurring during the trial that could affect the 
safety of the subjects or the conduct of the trial will be reported to the relevant local 
ethics committee. The report is issued by the head of the clinical trial. 
Non-serious adverse events are documented on the appropriate adverse events 
page in the Patient Documentation Sheet (CRF) and in the patient's medical record. 
 
8. Dropout of patients 
 
The non-therapy-related reasons for dropout from the study include in particular the 
revocation of consent by the patient. In addition, exclusion of the patient may result if 
the investigators subsequently become aware of exclusion criteria (e.g., pregnancy 
or participation in another clinical trial). 
 
Dropout reasons are documented as therapy-related if they make the surgical 
procedure impossible in connection with acute complications. These include e.g. 
severe cardiovascular complications (cardiac arrest, shock, threatening arrhythmias) 
due to the systemic toxicity of the local anesthetic. 
 
In case of incomplete nerve block, it is supplemented by the surgeon with prilocaine 
1%. Quantity and place of application are documented and the procedure is carried 
out as planned without excluding the patient from the study. Conversion of the 
anesthesia procedure (induction of general anesthesia) is also documented in the 
CRF. 

 
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9. Statistical Analysis 
 
The statistical test methods are described in the statistical analysis plan. The starting 
point is the assumption that the examined characteristics are not normally distributed. 
The evaluation is done in cooperation with a statistician (www.p-wert.de). 
 
10. Data management 
 
The investigator is responsible for the correct and complete input of patient data in 
the case report form (CRF). The CRF is deposited for at least 15 years together with 
a copy of the anesthesia protocol and surgical report. In the case of a data transfer 
(statistical analysis, publication of the data) only the patient number is forwarded, 
thus preserving the privacy of the patient. A later identification is possible by 
depositing the patient identification list in the examiner. 
The patient provide written informed consent on the evaluation and transfer of his 
data. The original of this protocol will be deposited in the examiner, a copy is given to 
the patient. 
 
11. Ethical, legal and administrative aspects 
 
The investigator ensures that the test is performed in accordance with existing laws 
and regulations (ICH and GCP Guidelines, AMG). The study protocol and patient 
information are submitted to the Ethics Committee of the University of Rostock. 
Before starting the study, each patient must give written consent to the investigator, 
having previously been fully informed in an understandable manner about the nature, 
significance and scope of the clinical trial. The content of this information is 
documented on the consent form. The patient will be given a copy of the signed 
consent form. The investigator copies the original of the consent form in the 
investigator folder. 
Carrying out a nerve blockade for carotid surgery is routine clinical practice. Thus, 
subjects and investigator are covered by the liability insurance of the HELIOS 
Medical Center Schwerin. The Liability Insurance Company was informed by the 
"Safety Department" about the planned study. 
 
12. Publication 
 
It is planned to present the results of the clinical trial in a scientific journal or at a 
congress. 
 
13. Sponsorship and conflict of interest 
 
The investigator hereby declares that there are no agreements for sponsorship with 
the industry for the conduct of the present trial. Thus, there is no conflict of interest 
for the physicians involved in the study. 
 
14. Amendments 
 
Any change to the study protocol will be substantiated and documented. The 
changes are considered part of the study protocol. 
 
 

 
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15. Literature 
 
1. 
Auroy Y, Narchi P, Messiah A, Litt L, Rouvier B, Samii K. (1997) Serious 
complictions related to regional anesthesia. Anesthesiology 87:479-86 
 
 
2. 
Barone M, Diemunsch P, Baldassarre E et al. (2010) Carotid endarterectomy 
with intermediate cervical plexus block. Tex Heart Inst J 37: 297-300 
 
3. 
Berg AP, Rosenquist RW (2007) Complications of peripheral nerve blocks. 
Techniques in Regional Anesthesia and Pain Management 11: 133-40 
 
4.  
Choquet O, Dadure C, Cabdevila X (2010) Ultrasound-guided deep or 
intermediate cervical plexus block: the target should bet he posterior cervical 
space. Anesth Analg 111: 1563-4 
 
5. 
GALA Trial Collaborative group (2008) General anaesthesia versus local 
anaesthesia for carotid surgery. Lancet 372: 2213-2142 
 
6.  
Herring AA, Stone MB, Frenkel O et al. (2012) The ultrasound-guided 
superficial cervical plexus block for anesthesia and analgesia in emergency 
case settings. Am J Emerg Med 30: 1263-7 
 
7.  
Kefalianakis K, Koeppel T, Geldner G et al. (2005) Carotid-surgery in 
ultrasound-guided anesthesia of the regio colli lateralis. Anasthesiol 
Intensivmed Notfallmed Schmerzther 40: 576-81 
 
8.  
Martusevicius R, Swiatek F, Joergensen LG et al. (2012) Ultrasound-guided 
locoregional anaesthesia for carotid endarterectomy: a prospective 
observational study. Eur J Vasc Endovasc Surg 44: 27-30 
 
9. 
Niesel HC, van Aken H (Hrsg.). Lokalanästhesie, Regionalanästhesie, 
regionale Schmerztherapie. Thieme, Stuttgart. 2.Auflage 2002 
 
10.  
Pandit JJ, Dutta D, Morris JF (2003): Spread of injectate with superficial 
cervical plexus block in humans: an anatomical study. Br J Anaesth 91: 733-5 

 
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11. 
Pandit JJ et al.. Superficial or deep cervical plexus block for carotid 
endarterectomy (2007): a systematic review of complications. British J 
Anaesthesia 99: 159-69 
 
12.  
Ramachandran SK, Picton P, Shanks A et al. (2011) Comparison of 
intermediate vs subcutaneous cervical plexus block for carotid 
endarterectomy. Br J Anaesth 107: 157-63 
 
13.  
Rössel T, Kersting S, Heller AR, Koch T (2013) Combination of high-resolution 
ultrasound-guided perivascular regional anesthesia of the internal carotid 
artery and intermediate cervical plexus block for carotid surgery. Ultrasound 
Med Biol 39: 981-6 
 
14.  
Shoja MM, Oyesiku NM, Shokouhi G et al. (2014) Anastomoses between 
lower cranial and upper cervical nerves: a comprehensive review with potential 
significance during skull base and neck operations, part I: trigeminal, facial and 
vestibulocochlear nerves. Clinical Anatomy 27: 118-30 
 
15.  
Shoja MM, Oyesiku NM, Shokouhi G et al. (2014) Anastomoses between 
lower cranial and upper cervical nerves: a comprehensive review with potential 
significance during skull base and neck operations, part II: glossopharyngeal, 
vagus, accessory, hypoglossal and cervical spinal nerves 1-4. Clinical 
Anatomy 27: 131-44 
 
16. 
Sindjelic RP, Vlajkovic GP, Davidovic LB et al. (2010) The addition of fentanyl 
to local anesthetics affects the quality and duration of cervical plexus block: a 
randomized, controlled trial. Anesth Analg 111: 234-7 
 
17.  
Usui J, Kobayashi T, Kakinuma H et al. (2010) An anatomical basis for 
blocking of the deep cervical plexus and cervical sympathetic tract using an 
ultrasound-guided technique. Anesth Analg 110: 964-8 
 
 

 
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16. Responsibilities 
 
Ronald Seidel, MD  
Principal investigator 
 
Katharina Zukowski, MD Investigator 
 
 
17. Attachements 
 
 
Attachement 1 
 
Informed Consent Form 
 
Attachement 2 
 
Case Report Form