Clinical trial NCT02724033
Conditions: Anesthesia, Pediatrics, Surgery
Keywords: post operative nausea vomiting Inner ear surgery
Sponsor: Indiana University
Start date: 2014-05-01; Completion date: 2018-09-01
Enrollment: 37 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The investigators would like to compare the therapeutic and cost effectiveness of established therapies for postoperative nausea and vomiting to regional nerve blocks of the head and neck area an intervention known for analgesia but for which the antiemetic effects hasn't been entirely explored.

The rational is based on the knowledge of the anatomical innervation of the inner ear and the role of the parasympathetic nervous system in the emetic act. A lot of focus has been given on its counterpart the sympathetic nervous system and its role in painful conditions. The investigators believe that the nerve blockade of the parasympathetic innervation can have some beneficial effect in the post-surgical patient.

Detailed description:
The researchers hypothesize another potential antiemetic mechanism by the blockade of the auricular branch of the vagus nerve at the ear canal (commonly described as nerve of Arnold) in conjunction with a block of the greater auricular nerve and lesser occipital nerve at the superficial cervical plexus level. The block would cover both the sensory innervation and of the ear canal and the inner ear. A regional anesthetic block prior to the surgical intervention on the inner ear at the superficial cervical plexus block is performed. This latter is a branch of the vagus nerve at the superficial cervical plexus (erb's point). The block would inhibit the vagal afferent to area postrema through inhibition of afferent vagal input to the medullary center.

The emetic act (vomiting) is a highly integrated physiologic reflex involving both the somatic and autonomic nervous system. Researchers do not know how much of a relation there is between the vagal nerve branches involvement and incidence of nausea and vomiting effects are from the inner ear injury and or the inflammatory response type of response triggering the area postrema. The usual prophylactic treatment of PONV (post operative nausea and vomiting) has been limited to anti-emetics such as dexamethasone along with aggressive fluid therapy and adequate analgesia.

Investigators are proposing to conduct a comparative study of the therapeutic and cost effectiveness of regional anesthesia and antiemetic therapy in the prevention and treatment of PONV in children undergoing inner ear surgical procedures.

Arms: arm 1: Group A - regional nerve block arm 2: Group B - antiemetic arm 3: Group C - block and antiemetic
Interventions: intervention 1: regional nerve block intervention 2: Antiemetic
Intervention descriptions: intervention 1: regional nerve block intervention 2: Antiemetic

Protocol documents:
Prot_SAP_000.pdf: 
 
Page 1 of 12 
 
Comparative Study of Superficial Cervical Plexus 
Block and Nerve of Arnold Block with Intravenous 
antiemetic drugs Dexamethasone and Ondansetron 
and Incidence of Post-operative Nausea Vomiting for 
Inner Ear Surgery 
 
 
 
 
Indiana University School of Medicine 
Riley Hospital for Children 
 
 
 
Principal Investigator: Malik Nouri, MD 
      Co Investigator:    Charles Yates, MD  
 
 
Version 2.0 
Date: 01/27/2017 
 
 
 
 
 
 
 
 
 
 


 
Page 2 of 12 
 
 
Table of Contents: 
 
 
 
Study Schema 
 
1.0 
Background 
2.0 
Rationale and Specific Aims 
3.0 
Inclusion/Exclusion Criteria 
4.0 
Enrollment/Randomization 
5.0 
Study Procedures 
6.0 
Reporting of Adverse Events of Unanticipated Problems involving Risk to 
Participants or Others 
7.0 
Study Withdrawal/Discontinuation 
8.0 
Statistical Considerations 
9.0 
Privacy/Confidentiality Issues 
10.0 
Follow-up and Record Retention 
11.0 
Analysis of Results 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
Page 3 of 12 
 
 
 
1.0 
Background  
 
Patients that undergo inner ear surgery often complain of postoperative nausea and vomiting 
(PONV) despite prophylactic antiemetic regiments with 5HT3 antagonists, steroids and vigorous 
hydration. Patients still experience this unpleasant feeling that may prolong hospital stay and can 
lead to nutritional issues such as dehydration and huge patient and family dissatisfaction. We 
would like to explore the use of regional anesthesia and potential antiemetic proprieties and 
compare it’s efficacy to the existing therapy. 
 
PONV is an unpleasant complication following anesthesia, it is well known that patients 
undergoing certain surgical procedures such as those involving the inner ear, the 
tympanomastoid cells, and the cochlear organ may be more prone to PONV. This complication 
can be anticipated in those instances and prophylactically treated with antiemetics, Vigorous 
hydration and cautious selection of anesthetic technique and avoidance of drugs known to 
promote nausea1, 2, 3. Despite all the measures described above, vomiting still occurs often, 
leaving patients and their families wondering if more can be done4, 5. 
 
Regional anesthesia has a therapeutic and preventive role in the incidence of PONV by reducing 
post-operative pain and opioids consumption. 
  
2.0 
Rationale and Specific Aim   
 
We would like to compare the therapeutic and cost effectiveness of established therapies for 
postoperative nausea and vomiting to regional nerve blocks of the head and neck area an 
intervention known for analgesia but for which the antiemetic effects hasn’t been entirely 
explored. 
 
Our rational is based on the knowledge of the anatomical innervation of the inner ear and the role 
of the parasympathetic nervous system in the emetic act1. A lot of focus has been given on its 
counterpart the sympathetic nervous system and its role in painful conditions. We believe that 
the nerve blockade of the parasympathetic innervation can have some beneficial effect in the 
post-surgical patient.  
 
The role of the vagal nerve response in the act of vomiting has been extensively studied. 
Observation that the Vagus nerves are predominantly sensory nerves has been shown through 
direct electrophysiological recordings of this afferent traffic from the vagal distribution in the GI 
tract to the brain stem. Vagal afferent terminals stained with horseradish peroxidase (HRP) 
appear to project to the dorsal motor vagal nucleus (DMVN) and to the area postrema. This latter 
projection may provide a visceral input for vomiting1, 2, 3. In fact electrical stimulation of vagal 
afferent fibers readily evokes vomiting in experimental animals. Furthermore, stimulation of the 
concha of the ear which is innervated by the (sensory) auricular branch of the Vagus nerve 
produced activation of the solitary nucleus and its following projections: parabrachial nucleus, 
thalamus, amygdala, paracentral lobule, and insula shown during fMRI1, 2, 3 


 
Page 4 of 12 
 
This latter distribution is of interest to our study since it involves the area of surgery where the 
auricular branch of the vagus nerve should easily accessible for anesthetic blockade. 
 
There shouldn’t be a surprise that most of the anti-emetics in use today have a mechanism of 
action that involves the modulation of the vagal effect during the emetic act1, 2, 3. 
 
We hypothesize another potential antiemetic mechanism by the blockade of the auricular branch 
of the Vagus nerve at the ear canal (commonly described as nerve of Arnold) in conjunction with 
a block of the greater auricular nerve and lesser occipital nerve at the superficial cervical plexus 
level8, 9, 10. The block would cover both the sensory innervation and of the ear canal and the inner 
ear.  A regional anesthetic block prior to the surgical intervention on the inner ear at the 
superficial cervical plexus block is performed.  This latter is a branch of the vagus nerve at the 
superficial cervical plexus (erb's point).  The block would inhibit the vagal afferent to area 
postrema through inhibition of afferent vagal input to the medullary center. 
 
 The emetic act (vomiting) is a highly integrated physiologic reflex involving both the somatic 
and autonomic nervous system.  We do not know how much of a relation there is between the 
vagal nerve branches involvement and incidence of nausea and vomiting effects are from the 
inner ear injury and or the inflammatory response type of response triggering the area postrema. 
The usual prophylactic treatment of PONV has been limited to anti-emetics such 5-HT3 and 
dexamethasone6, 7, along with aggressive fluid therapy and adequate analgesia. 
 
We are proposing to conduct a comparative study of the therapeutic and cost effectiveness of 
regional anesthesia and antiemetic therapy in the prevention and treatment of PONV in children 
undergoing inner ear surgical procedures. 
 
3.0 
Inclusion/Exclusion 
  
 
Inclusion Criteria 
Patient Age 1-18 yo 
Scheduled to have cochlear implantation, tympanomastoidectomy, inner ear surgery  
Past history of PONV susceptibility  
 
Exclusion Criteria 
Patient/ Parents refusal  
Infection at the site of local anesthetic injection  
Known coagulopathy  
Existing VP shunt  
Severe mental disability 
Any known allergic to dexamethasone (Decadron) and/or ondansetron (Zofran)  
 
 
 
 
 


 
Page 5 of 12 
 
4.0 
 Enrollment/Randomization 
 
Subject will be approached by Dr. Yates, the surgeon at his office the day of the preoperative 
office visit appointment or by any member of the study team the day of the surgery in the 
preoperative area. 
 
After appropriate assent and consent is obtained subject will be given an identifier and will 
undergo randomization using a computer program. 
 
Subject will be assigned to either one of the three groups. 
 
Study will involve pediatric patients Age 1-18 years old who are scheduled to undergo inner ear 
surgery.  Subjects will be randomization into three different groups.  Each group will consist of 
20 patients; we intend to enroll 60 participants total.  
 
Group A   Nerve of Arnold block with superficial cervical plexus block (SCPB)     
Group B   IV dexamethasone (Decadron) + ondansetron ( Zofran)  
Group C   Block + IV  dexamethasone ( Decadron + ondansetron ( Zofran)  
 
5.0 
Study Procedures 
 
After proper informed consent and/or assent have been obtained, all patients will receive a 
general anesthesia using standard of care.  For all patients randomized to receive regional nerve 
block (Group A & C) a time out before regional anesthesia will be performed stating patient 
identification and proposed surgical procedure with location of the block to be performed and the 
medications to be injected.  
 
Patients randomized to receive regional anesthesia will be prepared following standard universal 
precautions with application of sterile cleaning solution of chlorhexidine (Chloraprep) or alcohol 
prior to injections.   
 
The site of local anesthetic injection will be identified according to the landmarks defined by 
their respective anatomical descriptions. The nerve of Arnold block is located at junction of the 
ear tragus and external 1/3 of ear canal which will be injected using a 30 G needle with 0.5 ml of 
Bupivacaine 0.25%.  na 
 
The Superficial Cervical Plexus located at Erb’s Point, posterior border of the 
sternocleidomastoid muscle and a bisecting horizontal line drawn from the cricoid cartilage at 
the level of the sixth vertebrae, which is slightly posterior to the external jugular vein, this site 
will be injected with 3-5ml of bupivacaine 0.25% with 1:200000 of epinephrine.  Surgical 
procedures lasting longer than 4hrs will require a repeat injection with 2.5-3 ml of bupivacaine 
0.25% with1:200000 epinephrine  at this latter location after  completion of the  surgical 
procedure prior emergence from anesthesia. 
  
Group A:  to receive a homolateral (same side) to surgical site or bilateral if surgery involves 
both ears regional block at the Erb’s point and Nerve of Arnold.  


 
Page 6 of 12 
 
The block will be performed prior to surgical incision and may be repeated at Erb’s point only 
with half the initial volume of local anesthetic (1.5 ml -2.5ml) at completion of surgery prior 
emergence from anesthesia, if the procedure lasted more than 4 hours after the initial block. 
  
Group B: will receive an anti-emetic drug regiment comprising of dexamethasone 150mcg/kg IV 
(max dose of 10 mg) and ondansetron 150mc/kg IV (max single dose of 4 mg) at any time after 
induction of anesthesia and as soon as an intravenous line is available.  If, at the 
anesthesiologist’s discretion, ondansetron is re-dose at the end of procedure, a max total dose of 
8 mg may be given. 
  
Group C: Will receive both a homolateral or bilateral if surgery involves both ears, a regional 
block at Erb’s point (superficial cervical plexus block) and will receive an anti-emetic drug 
regiment comprising of dexamethasone 150mcg/kg IV (max dose of 10 mg) and ondansetron 
150mc/kg IV (max single dose of 4 mg) at any time after induction of anesthesia and as soon as 
an intravenous line is available.  If, at the anesthesiologist’s discretion, ondansetron is re-dose at 
the end of procedure, a max total dose of 8 mg may be given. 
 
 
All three groups will receive a standardized general anesthetic regiment, prior to induction the 
patient might require an oral dose of versed 0.5mg/kg as premedication for separation anxiety.   
Patients will also receive induction of anesthesia either inhalational oxygen in sevoflurane or 
intravenous induction if subject patient has an IV access, muscle relaxants will be avoided to 
preserve facial nerve monitoring as required by the surgical approach. Anesthesia will be 
maintained with oxygen in sevoflurane or desflurane.  Prior to emergence of anesthesia and at 
any point during the procedure, patients may receive IV analgesics (acetaminophen, morphine, 
fentanyl, ketamine) for postoperative analgesia according to the standard recommended pediatric 
dosing regiments commonly used at Riley Hospital. 
 
All three groups will receive the standard PACU protocol for pain management and anti-nausea 
and vomiting intervention. Following patient’s recovery starting upon emergence (t0), all 
symptoms indicating nausea and/or vomiting and pain will be recorded and every 15min (t15) 
thereafter in PACU than every 4-6 hrs. while on the inpatient unit for 24 hrs and will be treated 
as deemed necessary. For pain assessment a FLACC scale and Visual Analogue Scale (VAS) 
will be used. Complaints of, or signs or symptoms of, nausea, retching and/or vomiting will be 
documented in the PACU or floor for 24 hours post-operatively.  For patients discharged to 
home prior to the 24 hours, follow up will be done by phone call using the Rhodes INRV to 
report post-operative nausea and vomiting.  
We will also review patients chart for requests or demands for any pain medications and anti-
emetics, documentation of their usage as well as times of discharge from the recovery room to 
the floor and their discharge from the hospital. For cost comparison and analysis we will look at 
itemized billing for medical services related to anesthesia, pharmacy use and IV fluid use, 
antiemetic interventions, medication for pain throughout hospital stay from recovery room to 
time of discharge from the hospital.  For patients that are discharged the same day of their 
surgery they will be given The Rhodes INRV survey to fill out at home and will be called by 
phone the following day to collect that information. 
 


 
Page 7 of 12 
 
A cost analysis between the three study groups taking into account all the items above will be 
done to compare overall cost of care between the three study groups.   
 
6.0 
Reporting of Adverse Events or Unanticipated Problems Involving Risk 
to Participants or Others  
 
Risk related to the Blocks 
Bleeding  
Infection at the site  
Intravascular local anesthetic injection  
Anaphylactic/allergic reaction  
Rare spread of local to deeper structures, inadvertent Phrenic nerve blockade (the injection are 
superficial, subcutaneous with specific landmarks) 
Failure of the block to produce pain relief or to prevent nausea and vomiting 
Complications related to the surgical procedure including but not limited to: 
Facial nerve blockade  
 
Risk of General Anesthesia  
 
All precautions will be taken care of to avoid the above complications by adhering to standard  
of practice with strict adherence to standard ASA monitoring will be used at all time, observance 
of the time out procedure and surgical site marking, using universal precautions for sterility and 
observance of safe injection technique for the regional blocks with intermittent aspiration and 
injection to avoid intravascular injection and use of  live imaging with ultrasound guidance if 
necessary.  
 
7.0 
Study Withdrawal/Discontinuation 
 
Subject patient can withdraw from study at their own will and they can do so by letting know the 
principal investigator or members of the study team.  Failure to comply with study protocol may 
result in withdrawal of patient subject from the study.  Should any unanticipated adverse events 
known to have a direct relation to the procedure occur, the study will be discontinued and IRB 
will be notified.  
 
8.0 
Statistical Considerations 
 
A sample size of 20 subjects per group was selected to provide 80% power for finding a 
difference between all three groups with nausea/vomiting of 90% vs. 50%, assuming two-sided 
chi-square tests conducted at a 5% significance level. At completion of study we will submit our 
data to statistical analysis.  
 
9.0 
Privacy/Confidentiality Issues 
 
Adequate provisions to protect the privacy interests of research subjects and the confidentiality 
of research data will be taken in accordance of IUSM research policy. All patient information 


 
Page 8 of 12 
 
will be kept confidential and all data will be carefully processed and stored in accord with federal 
and institutional regulatory policies.  Paper collected study information will be stored in the 
locked anesthesia offices.  Data may also be entered and stored into a secure electronic database 
(example REDCap). 
 
The principal investigators and all research study team members are properly trained and will 
ensure these provisions exist and are followed.  
 
Pediatric patients will be approached in the presence of their parents for enrollment either in the 
privacy of ENT office or their private cubicle in the day surgery area at Riley Hospital. A proper 
consent and assent for children of age 7 or older will be obtained by members of the research 
team this will be done by either principal investigators Dr. Nouri and Dr. Yates or anesthesia 
nurse research coordinator.  
 
10.0  Follow-up and Record Retention 
 
Records will be retained for 7 years after the study is completed in order to properly analyze the 
results.  All paperwork, data collection sheets will be physically shredded after being scanned 
and stored electronically in a password protected database for an indefinite duration. 
 
11.0    Analysis of Results  
 
At completion of study we will submit our data for expert statistical analysis. 
 
 
References 
1. AL Kovac., (2000). Prevention and treatment of postoperative nausea and vomiting. 
Drugs, 59 (2):213-43. 
2. E Frangos, J Ellrich, et al., (2007). Activation of Human Vagus Nerve Afferent 
Projections Via Electrical Stimulation of External Ear. British Journal of Anesthesia, Oct; 
99(4):561-6. Epub 2007 Aug6. 
3. PLR Andrews, J Hawthorn, (1988), The Neurophysiology of vomiting, Baillere’s 
Clinical Gastroenterology, Jan; 2(1): 141-168. 
4. FJ Overdyk, SC Harvey, D Baldwin, P Rust, M Multani, J Marcell, (1999), Individual 
outcome feedback produces voluntary antiemetic prescribing practice changes. Journal of 


 
Page 9 of 12 
 
Clinical Anesthesia, Feb;11(1):17-23. Drug Class Review: Newer Antiemetics: Final 
Report 
5. K Peterson, M McDonagh, S Carson, S Thakurta, (2009). Drug Class Review: Newer 
Antemetics: Final Report Update 1. Portland (OR): Organ Health & Science University, 
Jan 2009. Drug Class Reviews.  
6. I Tarantino, U Beutner, W. Kolb, S Muller, C Luthi, A Luthi, B Schmied, T Clerci, R 
Warschkow, (2013), Study protocol for a randomized, double-blind, placebo controlled 
trial of single preoperative steroid dose to prevent nausea and vomiting after 
thyroidectomy: the tPONV study. BMC Anesthesia, Sep9;13(1):19. 
7. C Chen, F Siddiqui, E Chin, K Tam, (2012), Dexamethasone for prevention of 
postoperative nausea and vomiting in patients undergoing thyroidectomy: meta-analysis 
controlled trials. World journal of Surgery, Jan;36(1):61-8.  
8. V Karthikeyan, S Sistla, et al. (2012), Randomized controlled trial on the efficacy of 
bilateral superficial cervical plexus block in thyroidectomy. Pain Practice: World 
Institute of Pain, 13(7):539-546. 
9. G Andrieu, H Amrouni, E Robin, et. al., (2007), Analgesic efficacy of bilateral 
superficial cervical plexus block administered before thyroid surgery under general 
anesthesia, British Journal of Anesthesia, OCT;99(4):561-6. Epub 2007 Aug 6. 
10.  HD Cai, CZ Lin, CX Yu, XZ Lin, (2012), Bilateral superficial cervical plexus block 
reduces postoperative nausea and vomiting and early postoperative pain after 
thyroidectomy. The Journal of International Medical Research, 40:1390-1398. 
11. V Rhodes, W Roxanne, W McDaniel, (2001), Nausea, Vomitin, and Retching: Complex 
Problems in Palliative Care, CA A Cancer Journal for Clinicians, 51(4):232-248. 


 
Page 10 of 12 
 
 
 
Ear Innervation  
 
 
Superficial Cervical Plexus Anatomical Relations and Injection Site  
 
 
 
 
 
 
 
  
 
                         


 
Page 11 of 12 
 
RHODES INDEX OF NAUSEA, VOMITING AND RETCHING 
 
 


 
Page 12 of 12 
 
              
                     
                                                                
                                  
 
 
Superficial cervical Plexus infiltration   
         Nerve of Arnold Injection