Intra-operative Steroid Irrigation for Reducing Recurrent Laryngeal Nerve Palsy Post-thyroidectomy
Phase: NA
Conditions: Nerve Condition
Sponsor: University of Malaya

 
1 
                                
RESEARCH PROPOSAL 
Version No:3  
Version Date: 4/7/2024 
Intra-operative Steroid Irrigation for Reducing Recurrent Laryngeal Nerve 
Palsy Post-thyroidectomy – A Pilot Study 
Study Duration: 1/11/2024 – 31/10/2026 
 
Kah Seng Khooa 
MBBS (UM) 
MRCS (Edinburgh) 
MSurg (UM) 
 
Joanne Aisha Mosiuna 
MBBS(UM) 
MRCS (Edinburgh) 
MSurg (UM) 
 
        Redzwan Shah Bin John Mohdb 
MBBS (UM), MSORLHNS 
(UM) 
 
Yoke Kiet Doona 
MD (MOSCOW)  
MSurg (UM) 
 
        Khoon Leong Nga 
MBBS (S’pore) 
FRCS (Glasg) FRCS (Ed) 
AM (Mal) 
 
Mee Hoong Seea 
MD (UPM)  
MSurg (UM) 
a Breast & Endocrine Surgery Unit, Department of Surgery, University of 
Malaya, Malaysia 
b Department of Otorhinolaryngology, University of Malaya, Malaysia 
*Corresponding author: Kah Seng Khoo, Tel: +6017-2489272, Email: 
kahseng901209@gmail.com 
 
 

 
2 
 
TABLE OF CONTENTS  
Title Page 
 
 
 
 
 
 
 
1 
Table of Contents 
 
 
 
 
 
 
2 
List of Abbreviations 
 
 
 
 
 
3 
Introduction   
 
 
 
 
 
 
4 
Literature Review  
 
 
 
 
 
 
5 
Objective and Hypothesis   
 
 
 
 
6 
Methodology:  
 
 
 
 
 
 
7-8 
Study Type and Design 
Inclusion Criteria   
Exclusion Criteria   
Withdrawal Criteria 
Study Duration and Timeline 
Data Collection Tools and Techniques 
Data Analysis   
Risk and Benefit to Study Participants 
Flow Chart 
 
 
 
 
 
 
 
9 
Ethics of Study 
 
 
 
 
 
 
9 
Informed Consent 
 
 
 
 
 
 
9 
Privacy and Confidentiality  
 
 
 
 
10 
Conflict of Interest 
 
 
 
 
 
 
10 
Gantt Chart 
 
 
 
 
 
 
 
11 
References   
 
 
 
 
 
 
12-13 
 
 
 
 

 
3 
List of Abbreviations 
Endocrine Surgery  - ECS 
GS – General Surgery 
Recurrent Laryngeal Nerve - RLN 
UMMC – University Malaya Medical Centre 
WHO – World Health Organization 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
4 
Introduction  
Recurrent laryngeal nerve palsy is a common and feared complication that can happened 
during thyroidectomy, with incidence reported varies between 1-30% being transient and 0.5-
5% being permanent injury1-2. Unilateral nerve palsy can lead to hoarness of voice, choking 
episodes whereas bilateral nerve palsy can lead to airway compromise and subsequently 
require tracheostomy. This complication has significant impact to quality of life of patient, 
health care expenditures and lastly, mental health of operating surgeon.  
Manipulation of nerve during thyroid surgery may lead to oedema of the neuron and 
subsequently dysfunction, ranging from neuropraxia to axonotmesis. Various studies 
supporting the fact that steroid administration may prevent or reduce neural oedema (facial 
nerve palsy/ recurrent laryngeal nerve palsy)3-5. Conflicting data in the past regarding benefit 
of intraoperative steroids in thyroid surgery in preventing nerve palsy, some proven beneficial6, 
whereas another prospective case controlled clinical trial proven not different in rate of nerve 
palsy7. A pilot study in dental surgery proven intra-operative hydrocortisone irrigation is a 
useful and low cost method to control oedema in inferior third molar removal8. 
Retrospective review of data from UMMC Endocrine Surgery Unit (ECS), the incidence rate 
of post thyroidectomy recurrent laryngeal nerve palsy were 10%, 7.2%, 5% in year 2021, 2022 
and 2023 respectively. Majority of the cases (80% in 2021, 100% in 2022, 67% in 2023) were 
intact nerve during surgery but dysfunction post-operatively (neuropraxia to axonotmesis).  
The main aim of this study is to elucidate whether the topical irrigation of steroid during thyroid 
surgery can reduce the rate of recurrent laryngeal nerve palsy as majority of nerve dysfunction 
was due to neuropraxia to axonotmesis.  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 

 
5 
Literature Review 
According to the ‘Sixth National Audit Report 2021’ of The British Endocrine and Thyroid 
Surgeons (BAETS), the overall rate of recurrent laryngeal nerve (RLN) palsy following 
thyroidectomy was 6.7-7.8%9. Persistent RLN palsy was more common after total 
thyroidectomy (2.8%) than thyroid lobectomy (1.2%)9. Numerous research initiated by 
surgeons to find a way to reduce RLN palsy in thyroid surgery as this feared complication can 
impact greatly to the patient and the surgeon as well.  
The most common type of RLN palsy is due to manipulation of nerve during thyroid surgery, 
which lead to oedema of the neuron and subsequently dysfunction, ranging from neuropraxia 
to axonotmesis. This type of RLN palsy usually will recover overtime. Majority of the treatment 
of this group of palsy are speech therapies, steroids administration, injection laryngoplasty, 
thyroplasty and etc. Various studies supporting the fact that steroid administration may prevent 
or reduce neural oedema (facial nerve palsy/ recurrent laryngeal nerve palsy)3-5. A randomized 
double blind controlled study involving prednisolone administration to patient with idiopathic 
facial nerve paralysis (n=66), showed that patients received prednisolone have less 
denervation than placebo patients and also significant improvement in facial grade at recovery 
as well5. 
However, conflicting data in the past regarding benefit of intraoperative steroids in thyroid 
surgery in preventing nerve palsy, some proven beneficial6, whereas another prospective case 
controlled clinical trial proven not different in rate of nerve palsy7. A randomized clinical trial 
involving 64 patients were divided into two groups (preoperative dexamethasone and placebo) 
to study effect on voice change after thyroidectomy. There were no significant complication 
from the intervention group but the intervention group decrease voice change after 
thyroidectomy10. 
A cohort study published by Emre AU, et al, studied the efficacy of intraoperative single dose 
methylprednisolone on recurrence laryngeal nerve function after thyroidectomy. 438 nerves 
at risk was included and divided into intervention group and placebo group. They concluded 
single intraoperative dose of steroid does not seem to effect the rate and recovery period of 
RLN palsy in thyroid surgery11.  
With regards to the possible impact of perioperative intravenous dexamethasone side effects, 
a systematic review and meta-analysis performed by Waldron NH, et al. involving 45 studies 
(5796 patients) receiving a single dose of dexamethasone. It showed that patients received 
dexamethasone had significant analgesic benefits without increase in infection or delayed 
wound healing issue. However, blood glucose levels were higher at 24H in the 
dexamethasone group12. 
 
Lately, a pilot study conducted in dental surgery proven intra-operative hydrocortisone 
irrigation is a useful and low cost method to control oedema in inferior third molar removal 
which mimic the effect of intravenous steroid in reducing oedema and swelling of soft tissue 
and nerve8. By avoiding intravenous steroid administration, it could avoid the potential side 
effect of steroid such as wound complication and hyperglycaemia.  
 
 
 

 
6 
Research Question 
As majority of RLN palsy in thyroid surgery are due to neuropraxia and axonotmesis, and one 
of the modality of treatment involving steroid administration or perhaps given prophylactically 
to reduce the incidence of nerve palsy. With the evolving evidence that steroid irrigation proven 
to reduce oedema at the operative field, will steroid irrigation help to reduce oedema of the 
RLN and hence help in reduce the incidence of nerve palsy without its systemic side effect? 
Objectives  
Primary Objectives  
- 
To investigate whether intraoperative steroid irrigation post thyroidectomy 
reduces the rate of recurrent laryngeal nerve palsy compared to placebo 
Secondary Objectives  
- 
To investigate whether intraoperative steroid irrigation post thyroidectomy 
hasten the time interval for complete recovery of RLN palsy compared to 
placebo 
Hypothesis 
 
- 
Null hypothesis: Intraoperative steroid irrigation does not reduce the rate of recurrent 
laryngeal nerve palsy post thyroidectomy 
 
- 
Alternative hypothesis: Intraoperative steroid irrigation reduces the rate of recurrent 
laryngeal nerve palsy post thyroidectomy 
 
 
 
 
 
 
 
 
 
 
 
 

 
7 
Methodology 
Study Type and Design  
 
This is a single centre, double blinded and prospective randomized controlled trial which will 
be conducted in University Malaya Medical Centre (UMMC), Breast and Endocrine Surgery 
Unit. The duration of the study will be from November 2024 until October 2026 (2 years 
duration). 
 
Patient will be recruited from the endocrine surgery outpatient clinic who scheduled for elective 
thyroidectomy. There are several inclusion and exclusion criteria for recruitment into this 
study. After fulfilling the inclusion criteria, patients will be required to give consent and agree 
to participate in this study after explanation by the investigator in charge. Participants will be 
randomized into an intervention group (Group A) and a control group (Group B) with the ratio 
of 1:1 during admission for surgery by online computer system. The method of randomization 
utilised will be random randomization. Before and after thyroidectomy, vocal cord will be 
assessed by single otolaryngologist using indirect laryngoscopy who participate in this study. 
All surgery will be performed by 3 surgeons (Lectures) in Breast and Endocrine Surgery Unit 
(ECS). 
 
Intra-operatively, all participants recruited must have the recurrent laryngeal nerve identify and 
confirm with Intraoperative Nerve Monitoring (IONM) device. Participant will be excluded from 
the study if the nerve is being transected, unable to identify or no signal after stimulation with 
IONM. After removal of thyroid gland, 8mg of dexamethasone will be diluted in 100cc of 
irrigation water and irrigate the operative field for the intervention group. However for the 
placebo group, they will received water irrigation over the operative field only which is the 
current standard of practice at the moment. If there are objective vocal cord paresis during 
indirect laryngoscopy post thyroidectomy (within 24-48H), the participant will be labelled as 
nerve palsy. Recurrent laryngeal nerve palsy will then be classified into temporary (<6 months) 
or permanent (>6months) based on the duration of palsy and will be managed accordingly by 
otolaryngologist team.  
 
Both the assessor and patient are blinded throughout the whole study. Only the investigators 
and assistants of the surgery will be aware of the randomization of a patient.  
 
Inclusion Criteria 
 
• 
The target population are patients who scheduled for thyroidectomy (include both 
total or hemithyroidectomy) between November 2024 until October 2026 in UMMC. 
• 
Age between 18 years old till 80 years old 
 
Exclusion Criteria 
• 
Vocal cord paresis before surgery 
• 
No consent  
• 
Allergy towards dexamethasone 
Withdrawal Criteria 

 
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Subjects can choose to withdraw at any time during the study. 
 
Study Duration and Time-line (refer to Gannt Chart) 
 
The research period is from November 2024 till October 2026. After the proposal has been 
approved by the MREC, data collection will tentatively start from November 2024 till October 
2026. Data analysis will take 2 months and the report writing and submission to appropriate 
journal will take approximately 4 months. 
 
Data Collection Tools and Techniques 
 
As this is a prospective randomized controlled trial, relevant participants information and the 
outcomes will be recorded and documented in the Electronic Medical Record (EMR). These 
data will then be transcribed into SPSS for analysis. 
 
 
Data Analysis 
 
Data recorded will be analysed using SPSS Statistics Version 25. Continuous data will be 
expressed as Mean+/- standard deviation unless otherwise stated. Paired T- test was used 
for comparison of paired samples. The students’s T- test was used for comparison of 
continuous variables between different groups. Chi-square test will be used for categorical 
data analysis. A value of P<0.05 will be considered statistically significant. The data collected 
will be analysed using an intention to treat analysis. 
 
 
 
Risk and Benefits to Study Participants 
 
No risks will be imposed to the study participants as the dexamethasone is not administrated 
to the patient’s systemic circulation but instead of diluted irrigation over the operative field. In 
the other hand, this study does not present any direct benefit to the participants who involved 
in this study. However, information obtained from this study will help to formulate a better 
prophylactic measure  and treatment to reduce complication post thyroidectomy. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
9 
 
 
 
Flow Chart 
 
 
Eligible patients are identified in surgical clinic and formal written consent obtained 
 
 
Vocal cord assessment performed as out-patient by otolaryngologist 
 
 
Candidates will be randomized into control and intervention group in a 
ratio 1:1 during admission for thyroidectomy 
 
 
Intervention group will receive dexamethasone irrigation (8mg in 100cc of irrigation water) 
over the operative field after removal of thyroid gland 
 
 
Post thyroidectomy vocal cord assessment will be performed by otolaryngologist within 48H 
after surgery  
 
 
Participants with vocal cord palsy will be follow up till 12 months post thyroidectomy 
 
 
Relevant data will be documented and recorded in EMR 
 
 
Data collection and analysis using SPSS 
 
 
Writing report and submission of study to be published 
 
 
 
 
Ethics  
 
This study will be conducted in compliance with ethical principles outlined in the Declaration 
of Helsinki and Malaysian Good Clinical Practice Guideline. 
 
Informed Consent 
 
Eligible patients will be identified during clinic visits. Information regarding the study will be 
given and explained to them during clinic visit. They will be allowed to take the patient 
information sheet home and consult with their family members. Informed consent will be 
obtained during clinic visits. 
 
Privacy and Confidentiality 
 
Subject’s names will be kept private and an identification number instead of patient identifiers 
will be used on subject data sheets.  Strict confidentiality will be maintained. All identification 
labels will be anonymised in any future presentations or publications. All data will be entered 

 
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into a computer that is password protected. On completion of study, data in the computer will 
be copied to a thumb-drive/USB drive and the data in the computer erased. Thumb-drive/USB 
drive and any hardcopy data will be stored in a locked office of the investigator in the 
Department of Surgery and securely disposed after 7 years on conclusion of the study.  
 
Conflict of Interest 
 
The investigators declare that they have no conflict of interest.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Gannt Chart 
 
 
Apr-May 
2024 
Jun-Aug 
2024 
Nov 2024-
Oct 2026 
Nov-Dec 
2026 
Jan-Oct 
2027 
Literature review & 
research proposal 
 
 
 
 
 
Ethnics approval  
 
 
 
 
 
Data collection 
 
 
 
 
 
Data analysis 
 
 
 
 
 
Report writing and 
journal submission 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
12
 
 
References 
 
1. Uruno T, et al. A prophylactic infusion of calcium solution reduces the risk of 
symptomatic hypocalcemia in patients after total thyroidectomy. World J Surg, 2006. 
30(3): p. 304-8. 
2. Joliat GR, Guarnero V, Demartines N, et al. Recurrent laryngeal nerve injury after 
thyroid and parathyroid surgery. Medicine, 2017 96:17. 
3. Bansberg SF, McCaffrey TV. The effect of systemic triamcinolone acetonide on nerve 
repair. Otolaryngol Head Neck Surg, 1987; 96(2): 158-164.  
4. Stankiewicz JA. A review of the published data on steroids and idiopathic facial 
paralysis. Otolaryngol Head Neck Surg, 1987; 97(5):481-486. 
5. Austin JR, Peskind SP, Austin SG, et al. Idiopathic facial nerve paralysis: a 
randomized double blind controlled study of placebo versus prednisone. 
Larynoscope, 1993; 103(12): 1326-1333. 
6. Lore JM Jr, Farrell M, Castillo NB. Endocrine surgery. In: Lore JM Jr, Medina JE 
(eds). An atlas of Head and Neck Surgery, 4th edn. Elsevier, Philadephia, 2005:963-
965.  
7. Wang LF, Lee KW, Kuo WR, Wu CW, Lu SP, et al. The efficacy of intraoperative 
corticosteroids in recurrent laryngeal nerve palsy after thyroid surgery. World Journal 
of Surgery, 2006 (30):299-303. 
8. Rodrigues VP, Deboni MCZ, Cecchetti MM, Ocana RP, Frare JG, et al. 
Hydrocortisone irrigation for postoperative control of oedema in inferior third molar 
removal-A pilot study. Journal of Oral and Maxillofacial Surgery, Medicine, and 
Pathology, 2020 (32)5: 351-355. 
 
9. Aspinall S, Mihai R, Kinsman R, Walton P.  The British Association of Endocrine and 
Thyroid Surgeon Sixth National Audit. 2021. 
 
10. Nasiri S, Shafaq S, Hedayat A, Khorgami Z, Sodagari N, et al. Does corticosteroid 
have any beneficial effect on voice change after thyroidectomy? The American 
Surgeon, 2013;79 (12):1258-1262.  
 
11. Emre A, Cakmak GK, Arpaci DK, Ilikhan SU, Damar M. The efficacy of intraoperative 
single dose methylprednisolone on recurrent laryngeal nerve function after 
thyroidectomy. International Surgery, 2016, 101 (3-4):116-120.  

 
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12. Waldron NH, Jones CA, Gan TJ, Allen TK, Habib AS. Impact of perioperative 
dexamethasone on postoperative analgesia and side-effects: systematic review and 
meta-analysis. British Journal of Anasthesia, 2013, 110 (2): 191-200.