The Use of Dexamethasone in Total Thyroidectomy to Improve Voice Outcome and Hypocalcaemia

Study Overview
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Brief Summary
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Thyroidectomy is a standard procedure for benign and malignant pathologies of the thyroid gland. Each year, some 100 total thyroidectomies are performed in Kowloon East Cluster, Hospital Authority, Hong Kong. Total thyroidectomy is associated with voice dysfunction and temporary hypocalcaemia in up to 80% and 50%, respectively. Previous study from our institute showed a 3% rate of permanent vocal cord palsy and 16% of permanent hypoparathyroidism requiring calcium and/or vitamin D supplements. The use of dexamethasone has been studied in the past in total thyroidectomy patients and has been shown to be safe and effective in improving post-operative nausea and vomiting. No complications or drug related side effects were associated with a single dose of steroid. Recent studies have also shown that Dexamethasone is effective in improving voice outcome and hypocalcaemia in thyroidectomy patients. The investigators aim to study the effect of Dexamethasone in post-operative voice outcome and hypocalcaemia. Objective assessment of the vocal cords during phonation will be performed pre-operative and post-operatively. Serum Calcium level will be monitored.

Detailed Description
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This is a multi-specialty, double-blind, randomized, placebo-controlled trial involving the Departments of Surgery in United Christian Hospital, Tseung Kwan O Hospital and Department of Ear, Nose and Throat, United Christian Hospital and Tseung Kwan O Hospital, Kowloon East Cluster. The primary objective is to investigate the effect of Dexamethasone in post-operative voice outcome and hypocalcaemia in total thyroidectomy patients. The secondary outcome aims to investigate the mechanism of voice dysfunction in thyroidectomy patients using objective assessment tools. To streamline the practice among various departments and to minimize any potential confounders, the peri-operative anaesthetic and post-operative analgesic protocols are standardized. The surgical techniques are also standardized using capsular dissection with positive identification and preservation of the recurrent laryngeal nerve. Patient's voice and vocal cord mobility will be assessed pre-operatively and post-operatively. Objective assessment of the vocal cord will be carried out using video stroboscopy to document the mobility, waveform and vibration, symmetry and any arytenoid abnormality. Subjective and objective assessment of the voice outcome will be conducted by speech therapists using standardized voice assessment protocol. The trend of hypocalcaemia (Calcium level and parathyroid hormone level) will be monitored and correlated with the use of Dexamethasone. Possible side effect (e.g. wound infection) from the use of Dexamethasone will be analysed

Official Title
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The Use of Dexamethasone in Total Thyroidectomy to Improve Voice Outcome and Hypocalcaemia

Conditions
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Voice Change, Hypocalcemia

Intervention / Treatment
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* Drug: Dexamethasone
* Drug: Normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 or above Patients undergoing total thyroidectomy for benign pathologies MNG Toxic nodular goitre Graves' disease Exclusion Criteria: Non-communicable patients Patients contraindicated for steroid (DM, Hepatitis carrier, Tuberculosis, peptic ulcer disease) Patients contraindicated for analgesics including Panadol, Celebrex, Tramadol or Levobupivacaine Malignant thyroid disease Patients with previous thyroid surgery, or neck surgery Pre-existing hoarseness of voice of any cause or pre-existing vocal cord palsy Pregnancy / Lactating female patients Pre-existing renal disease / autoimmune disease on steroids Patients who require steroid cover during operation e.g. hydrocortisone perioperatively

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multi-specialty, double-blind, randomized, placebo-controlled trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dexamethasone group<br>One dose of 8mg in 2ml Dexamethasone will be given | Drug: Dexamethasone<br>* Dexamethasone injection<br>|
| Placebo Comparator: Placebo group<br>One dose of 2ml 0.9% Normal saline will be given | Drug: Normal saline<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-operative calcium and parathyroid hormone level on POD1 | Serum calcium and parathyroid hormone level will be monitored | Post-op 1 day | 
| Post-operative calcium and parathyroid hormone level after 3 months post-op | Serum calcium and parathyroid hormone level will be monitored | Post-op 3 months | 
| Post-operative calcium and parathyroid hormone level after 6 months post-op | Serum calcium and parathyroid hormone level will be monitored | Post-op 6 months | 
| Voice Handicap Index (VHI-10) | Subjective voice assessment consisting of 10 questions. Each question 0-4 score | Post-op 1 week | 
| Voice Handicap Index (VHI-10) | Subjective voice assessment consisting of 10 questions. Each question 0-4 score | Post-op 3 months | 
| Voice Handicap Index (VHI-10) | Subjective voice assessment consisting of 10 questions. Each question 0-4 score | Post-op 6 months | 
| Perceptual Evaluation: Cantonese Perceptual Evaluation of Voice (CanPEV) | Objective voice assessment consisting of 10 questions. Each question 1-10 score. 1 being normal and 10 being the most severe voice dysfunction | Post-op 1 week | 
| Perceptual Evaluation: Cantonese Perceptual Evaluation of Voice (CanPEV) | Objective voice assessment consisting of 10 questions. Each question 1-10 score. 1 being normal and 10 being the most severe voice dysfunction | Post-op 3 months | 
| Perceptual Evaluation: Cantonese Perceptual Evaluation of Voice (CanPEV) | Objective voice assessment consisting of 10 questions. Each question 1-10 score. 1 being normal and 10 being the most severe voice dysfunction | Post-op 6 months | 
| Acoustic Evaluation | Instruct patient to sustain vowel /a/ and to read aloud the Hong Kong passage at a comfortable pitch and loudness level for about 3-5 seconds. Keep a distance of 15cm from the microphone for recording. Highlight the middle 3 seconds for analysis. To assess the fundamental frequency (Hz) and performance (dB) | Post-op 1 week | 
| Acoustic Evaluation | Instruct patient to sustain vowel /a/ and to read aloud the Hong Kong passage at a comfortable pitch and loudness level for about 3-5 seconds. Keep a distance of 15cm from the microphone for recording. Highlight the middle 3 seconds for analysis. To assess the fundamental frequency (Hz) and performance (dB) | Post-op 3 months | 
| Acoustic Evaluation | Instruct patient to sustain vowel /a/ and to read aloud the Hong Kong passage at a comfortable pitch and loudness level for about 3-5 seconds. Keep a distance of 15cm from the microphone for recording. Highlight the middle 3 seconds for analysis. To assess the fundamental frequency (Hz) and performance (dB) | Post-op 6 months | 
| Aerodynamic Evaluation (Maximum sustained phonation) | Instruct patient to sustain vowel /a/ at a comfortable pitch and loudness level for as long as possible after taking a deep breath. Recorded in seconds | Post-op 1 week | 
| Aerodynamic Evaluation (Maximum sustained phonation) | Instruct patient to sustain vowel /a/ at a comfortable pitch and loudness level for as long as possible after taking a deep breath. Recorded in seconds | Post-op 3 months | 
| Aerodynamic Evaluation (Maximum sustained phonation) | Instruct patient to sustain vowel /a/ at a comfortable pitch and loudness level for as long as possible after taking a deep breath. Recorded in seconds | Post-op 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Calcium and Rocaltrol requirement | The required dosage of Calcium Carbonate and Rocaltrol will be documented | Post-op 1 week | 
| Calcium and Rocaltrol requirement | The required dosage of Calcium Carbonate and Rocaltrol will be documented | Post-op 3 months | 
| Calcium and Rocaltrol requirement | The required dosage of Calcium Carbonate and Rocaltrol will be documented | Post-op 6 months | 
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | Number of participants experiencing side effects from Dexamethasone will be documented | Post-op 1 week | 
| Stroboscopic Assessment (Vocal Fold Edge) | Score 1-5 (1 - Smooth and straight; 5 - Rough and irregular) | Post-op 1 week | 
| Stroboscopic Assessment (Vocal Fold Edge) | Score 1-5 (1 - Smooth and straight; 5 - Rough and irregular) | Post-op 3 months | 
| Stroboscopic Assessment (Vocal Fold Edge) | Score 1-5 (1 - Smooth and straight; 5 - Rough and irregular) | Post-op 6 months | 
| Stroboscopic Assessment (Glottic Closure) | Grading 1-7 (1. Complete 2. Anterior chink 3. Irregular 4. Bowing 5.Posterior chink 6. Hourglass 7 Incomplete) | Post-op 1 week | 
| Stroboscopic Assessment (Glottic Closure) | Grading 1-7 (1. Complete 2. Anterior chink 3. Irregular 4. Bowing 5.Posterior chink 6. Hourglass 7 Incomplete) | Post-op 3 months | 
| Stroboscopic Assessment (Glottic Closure) | Grading 1-7 (1. Complete 2. Anterior chink 3. Irregular 4. Bowing 5.Posterior chink 6. Hourglass 7 Incomplete) | Post-op 6 months | 
| Stroboscopic Assessment (Vertical Level of Approximation) | 1 - Equal 2 - Right lower 3 - Left lower 4 - Questionable | Post-op 1 week | 
| Stroboscopic Assessment (Vertical Level of Approximation) | 1 - Equal 2 - Right lower 3 - Left lower 4 - Questionable | Post-op 3 months | 
| Stroboscopic Assessment (Vertical Level of Approximation) | 1 - Equal 2 - Right lower 3 - Left lower 4 - Questionable | Post-op 6 months | 
| Stroboscopic Assessment (Amplitude) | 1 - Normal 2 - Slightly decreased 3 - Moderately decreased 4 - Severely decreased 5 - No visible movement | Post-op 1 week | 
| Stroboscopic Assessment (Amplitude) | 1 - Normal 2 - Slightly decreased 3 - Moderately decreased 4 - Severely decreased 5 - No visible movement | Post-op 3 months | 
| Stroboscopic Assessment (Amplitude) | 1 - Normal 2 - Slightly decreased 3 - Moderately decreased 4 - Severely decreased 5 - No visible movement | Post-op 6 months | 
| Stroboscopic Assessment (Mucosal wave) | 1 - Normal 2 - Slightly decreased 3 - Moderately decreased 4 - Severely decreased 5 - Absent | Post-op 1 week | 
| Stroboscopic Assessment (Mucosal wave) | 1 - Normal 2 - Slightly decreased 3 - Moderately decreased 4 - Severely decreased 5 - Absent | Post-op 3 months | 
| Stroboscopic Assessment (Mucosal wave) | 1 - Normal 2 - Slightly decreased 3 - Moderately decreased 4 - Severely decreased 5 - Absent | Post-op 6 months | 
| Stroboscopic Assessment (Regularity) | 1 - Regular 2 - Sometimes irregular 3 - Most irregular 4 - Always irregular | Post-op 1 week | 
| Stroboscopic Assessment (Regularity) | 1 - Regular 2 - Sometimes irregular 3 - Most irregular 4 - Always irregular | Post-op 3 months | 
| Stroboscopic Assessment (Regularity) | 1 - Regular 2 - Sometimes irregular 3 - Most irregular 4 - Always irregular | Post-op 6 months | 
| Stroboscopic Assessment (Ventricular folds) | Movement - 1.Normal 2.Slight compress 3.Moderate compress 4.Full compress | Post-op 1 week | 
| Stroboscopic Assessment (Ventricular folds) | Movement - 1.Normal 2.Slight compress 3.Moderate compress 4.Full compress | Post-op 3 months | 
| Stroboscopic Assessment (Ventricular folds) | Movement - 1.Normal 2.Slight compress 3.Moderate compress 4.Full compress | Post-op 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Voice dysfunction, Hoarseness of Voice, Vocal cord palsy, Hypocalcemia, Hypoparathyroidism, Thyroidectomy, Dexamethasone, Steroid