PaThERAS: ERAS Protocols in Thyroid & Parathyroid Surgery

Thyroid Diseases Clinical Trial

— PaThERAS  

Official title:

PaThERAS Study- Application Of Enhanced Recovery After Surgery Protocols in Thyroid and Parathyroid Surgery

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06274970
• Other study ID #: 2022-143-Mch-EXP-50
• Status: Recruiting
• Phase: N/A
• Start date: January 25, 2023
• Est. completion date: September 25, 2024

Study information

• Verified date: February 2024
• Source: Sanjay Gandhi Postgraduate Institute of Medical Sciences
• Contact: Gaurav Agarwal, MS
• Phone: 8004904646
• Email: gauravbsi[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Enhanced recovery after surgery protocols are evidence-based multidisciplinary programs implemented in the perioperative setting to improve postoperative recovery and attenuate the surgical stress response. They have been used with success after many different types of surgery to improve perioperative patient outcomes. However, evidence on their effectiveness in thyroid and parathyroid surgery remains sparse. Goal of PaThERAS study is to investigate the clinical benefits and cost-effectiveness of enhanced recovery protocols for the perioperative management in patients undergoing total thyroidectomy for large goiters/ cancers and parathyroidectomy for symptomatic hyperparathyroidism in non-day-care setting.

Description:

INTRODUCTION Enhanced recovery after surgery protocols are evidence-based multidisciplinary programs implemented in the perioperative setting to improve postoperative recovery and attenuate the surgical stress response. They have been used with success after many different types of surgery to improve perioperative patient outcomes. However, evidence on their effectiveness in thyroid and parathyroid surgery remains sparse. Therefore, our goal is to investigate the clinical benefits and cost effectiveness of enhanced recovery protocols for the perioperative management of thyroidectomy and parathyroidectomy.

AIMS AND OBJECTIVES

AIM: To evaluate if Enhanced recovery after surgery protocols; improves peri operative outcomes in patients undergoing thyroid and parathyroid surgery

OBJECTIVES:

Primary Objective: To compare the rate of hypocalcemia in patients undergoing thyroid and parathyroid surgery implementing Enhanced recovery after surgery protocols vs Conventional peri operative protocols Secondary Objective: To compare the following outcome measures in in patients undergoing thyroid and parathyroid surgery

• length of hospital stay- defined as length of hospital stay from the date of surgery to the date of discharge

• hospital costs

• readmission rate

• postoperative complication rates

MATERIALS AND METHODS

1. Study area: This study will be conducted in the Department of Endocrine and Breast Surgery of Sanjay Gandhi Post Graduate Institute, Lucknow, India

2. Study design: The present study will be an ambispective study

• Study group: Prospective cohort

• Control group: Retrospective and Prospective cohort

3. Study Population:

Study group (Group 1)

• Consecutive patients undergoing thyroid and parathyroid surgery in the Dept of Endocrine and Breast Surgery, SGPGI, consenting to participate in the study Control group (Group 2)

• Screening and review of clinical data from the HIS & patient files

• All age and sex matched patients who underwent similar procedures from Jan 2021-Sept 2024 4. Inclusion Criteria: Patients diagnosed to have ASA Grade 1 and Grade 2 patients with thyroid and/or parathyroid (1° and 2° hyperparathyroidism) disease undergoing the following procedures via open or endoscopic approach

• Total thyroidectomy/Focused parathyroidectomy/BNE with excision of enlarged glands +/- any additional procedure (Eg: Central compartment neck dissection, Lateral neck dissection, Cervical thymectomy etc) 5. Exclusion Criteria: Patients undergoing thyroid and/or parathyroid surgery who

• Undergo hemithyroidectomy

• Refuse to consent to participate in the study in the cohort group

• ASA Grade 3 and Grade 4*

*Comorbidities of severe nature which may independently impact perioperative hospital stay, complications and outcomes in the study and control group 6. Sample Size

• Primary objective -To compare the LOS in patients implementing enhanced recovery protocols versus conventional perioperative practices in thyroid and parathyroid surgery

• Considering the hospital stay to be 5 days in the control group and 3.5 days in the study group (expecting at least 30% reduction in hospital stay); the standard deviation (SD) being 2.5 days and 1.75 days respectively (assuming 50% SD of mean) at minimum two-sided Confidence interval and 95% Power of study- the study requires 55 patients each in the control group and the intervention group

• Sample size was calculated using software PASS 16 7. Study period: Jan 2023- to Sept 2024

METHODOLOGY This study will be undertaken after approval by the Institutional Ethics committee. This is a prospective study on all patients undergoing thyroid and/or parathyroid surgery who meet the inclusion criteria admitted in the Department of Endocrine Surgery ward, SGPGI, Lucknow. Each patient in the study will be identified using stickers on their file and OPD booklet/card as SGPGI Endocrine Surgery ERASP patients

Selection of subjects

Outcome measures: Those patients diagnosed as having either benign or malignant thyroid and/or parathyroid disease will be enrolled after taking an informed consent. In patients implementing enhanced recovery protocols versus conventional perioperative practices the following outcomes will be compared:

• The length hospital of stay- Date of surgery to date of discharge = Days of hospital stay

• Hospital costs- Absolute Billing Amount including hospital stay rental, investigations, medications & consumables, and surgical fees

• Postoperative complication rates:

• Hypocalcemia- defined as corrected S. Calcium levels <8.2mg/dl on Post operative day (POD) 1, POD2, POD7-10, 4-6 weeks after surgery, 3 months and 6 months after surgery

• Surgical site infection- Incisional infection within 30 days after surgery and at least one of the following-

• Purulent drainage, with/without lab confirmation from the superficial incision

• Organisms isolated from aseptically obtained culture fluid or tissue from the superficial incision

• At least one of the following signs or symptoms of infection pain or tenderness, localised swelling, erythema, heat and superficial incision is deliberately opened by the surgeon in a culture negative wound

• Seroma- Accumulation of clear fluid in a tissue or body cavity (will be assessed after drain removal)

• Pain- Measured on Numeric Pain Rating Scale daily until discharge and on 1st follow up at POD7-10 days

• Hematoma- Accumulation of blood in a tissue or body cavity (will be assessed daily until discharge)

• Readmission rate- Number of readmissions after discharge The steps followed in the Enhanced recovery protocol were based on adaptations from recommendations by the ERAS society guidelines on head and neck surgery with free flap reconstruction and literature including meta-analyses and systematic reviews as well as randomized controlled trials wherever possible.

In the absence of high level data, case series and nonrandomized studies, ATA statements in thyroid and parathyroid surgeries were considered. These recommendations were adapted and modified to make an Institutional Enhanced recovery protocol to cater to the Indian demographic. Critical team members include the OPD team, operating surgeon, OT team, anesthesiologist, and ward team and ward nursing staff.

Enhanced recovery Protocol Recommendation

Preoperative Considerations Preadmission education- All patients undergoing thyroid and parathyroid surgery will be counselled by a study team member and handed over the study patient information sheet for all information on what to expect before and after surgery

Perioperative nutritional care- All patients undergoing thyroid and parathyroid surgery should undergo preoperative nutritional assessment Grading of Nutritional Status of the patient (BMI) in kg/m2

Peri operative Calcium and Vitamin D supplementation-The role for perioperative vitamin D supplementation in preventing symptoms has been studied at length and shown to be beneficial. All Patients with preoperative Vitamin D levels <50ng/ml will be administered loading dose of Cholecalciferol 60k IU/gm for 5 days followed by once a month. Post operatively patients will be prophylactically started on 2g of oral Calcium carbonate tablets, Calcitriol supplementation +/- Parenteral Calcium supplementation only if symptomatic for hypocalcemia or Trousseaus sign positive

Preoperative fasting should be minimized Prior to anaesthesia -Clear fluids should be permitted for up to 2 hours and solids for up to 6 hours. Carbohydrate loading clear drink 200ml (250ml= 1glass) administered to the patient at 6:00 AM in the morning of surgery along with medicines as prescribed by the Anaesthesiologist Oral diet is the first choice for all patients tolerating it Nutrition interventions should be developed in consultation with the multidisciplinary team and individualized according to nutritional status and surgical procedure.

Antibiotic prophylaxis- Perioperative antibiotics are not indicated for short clean procedures.

Single dose preoperative Inj Amoxycillin 1g + Potassium Clavulanate 200mg (1.2gm) unless allergic (in which case appropriate substitute eg. Cefuroxime sodium 1.5gms ) iv will be given at the time of induction/ within 1 hour of incision. Dose will be repeated if operative time >4hrs

Postoperative nausea and vomiting prophylaxis- Patients undergoing thyroid and parathyroid surgery should receive preoperative medications to prevent postoperative nausea and/or vomiting.

Tab Pantoprazole 40mg HS and morning of surgery - All ASA Grade 1 and 2 patients are to take their premedication with 1 glass (250 ml) of Carbohydrate loading clear drink at 6:00 AM in the morning of surgery

Pre anaesthetic medications- Patients should receive short acting anxiolytics, given intravenously and titrated to required effect. Longer acting anxiolytics and opioids should be avoided.

Tab. Alprazolam 0.25mg will be given HS and on the morning of surgery

Skin preparation Chlorhexidine bath on the night prior to and morning of surgery On table part preparation with Chlorhexidine 4% solution/ Povidone-Iodine 10% solution. Prep must be allowed to air dry (minimum 3 minutes) before draping and incision Operative Considerations Preventing hypothermia Normothermia should be maintained intraoperatively. Temperature monitoring is necessary to ensure normothermia is maintained.

Patient adequately covered after placement of ECG leads (use cotton/blanket/warmer) Warmer used Warm Fluids used at ALL time Head adequately covered (especially in children) Hot line used wherever appropriate Always aim for >36 degrees C temperature

Perioperative fluid management- Fluids should be managed in a goal-directed manner, avoiding over and under hydration. No fluids should be administered in preop room. Discontinue IV fluids once patient can tolerate orally >500ml or 4-6 hours post extubation

Intra operative Nerve monitoring (IONM)- Laryngeal nerve monitoring can prevent nerve injuries, will be used as operating surgeon discretion. Long-acting neuro muscular blockade should be avoided if IONM is being used

Dressings and drain use- Pressure dressings do not prevent postoperative hematoma, and may obscure visualization of a hematoma. Several randomized prospective studies have shown that the use of a drain after uncomplicated total thyroidectomy, lobectomy, and subtotal thyroidectomy likewise does not reduce the rate of postoperative bleeding Patient will be discharged with drain once there are no signs of bleeding in the drain or after drain removal if drain out put <20ml/day

Post operative Considerations Pain management Opioid-sparing, multimodal analgesia, utilizing NSAIDs and paracetamol, are preferred Pain will be assessed using Numeric Pain Rating Scale Inj Paracetamol 1gm iv TDS will be administered until the patient is able to tolerate orallyOnce the patient is orally allowed -Tab Paracetamol 650mg po TDS will be administered if pain 0-3-mild on Numeric Pain Rating Scale. If Pain on Numeric Pain Rating Scale >/= 4 SOS NSAIDS will be added

Postoperative mobilization- Early mobilization, within the first 24 hours of surgery is recommended

Urinary catheterization- Urinary catheters should be removed as soon as the patient is able to void, ideally less than24 hours after completion of surgery

Postoperative pulmonary physical therapy-Pulmonary physical therapy should be initiated as early as possible after surgery to avoid pulmonary complications.

Head of bed elevation to 30 degrees Steam Inhalation 5 mins thrice daily Incentive spirometry 15 repetitions every 2 hours when the patient is awake Chest Physiotherapy - Attendant/nurse/doctor using cupped hands, Thumping/percussion of posterior lung fields for 5 mins thrice daily

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 110
• Est. completion date: September 25, 2024
• Est. primary completion date: September 25, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients diagnosed to have ASA Grade 1 and Grade 2 patients with thyroid and/or parathyroid (1° and 2° hyperparathyroidism) disease undergoing the following procedures via open or endoscopic approach • Total thyroidectomy/Focused parathyroidectomy/BNE with excision of enlarged glands +/- any additional procedure (Eg: Central compartment neck dissection, Lateral neck dissection, Cervical thymectomy etc)

Exclusion Criteria:

• Patients undergoing thyroid and/or parathyroid surgery who

• Undergo hemithyroidectomy

• Refuse to consent to participate in the study in the cohort group

• ASA Grade 3 and Grade 4* *Comorbidities of severe nature which may independently impact perioperative hospital stay, complications and outcomes in the study and control group

Related Conditions & MeSH terms

• ERAS
• Parathyroid Diseases
• Thyroid Diseases

Intervention

Other:
• Enhanced recovery protocols
Enhanced recovery Protocol with Recommendations Preoperative Consideration-Preadmission education, nutritional assessment, Peri operative Calcium and Vitamin D supplementation, Reduce preoperative fasting Preoperative fasting, Precarb drink (250ml= 1glass) administered to the patient at 6:00 AM, Nutrition interventions individualized, Antibiotic prophylaxis, Postoperative nausea and vomiting prophylaxis, Patients should receive short acting anxiolytics Operative Considerations-Hypothermia prevention, Goal-directed fluid management,Nerve monitoring can prevent nerve injuries, may be useful Dressings and drain use -individualized Postoperative Considerations- No post operative antibiotics in clean surgery, Pain management Opioid-sparing, multimodal analgesia, Postoperative Early mobilization, Urinary catheters should be removed less than 24 hours after completion of surgery Perioperative pulmonary physical therapy Steam Inhalation Incentive spirometry Chest Physiotherapy
• Conventional Protocols
Preoperative- Antibiotic prophylaxis, short or long-acting anxiolytics, no post operative nausea and vomiting, no Serum vitamin D correction Operative-Hypothermia prevention, Postoperative- Routine use of post operative prophylactic antibiotics, pain management multimodal analgesia, urinary catheters maybe be removed less than 24 hours after completion of surgery, Perioperative pulmonary physical therapy Steam Inhalation Incentive spirometry Chest Physiotherapy

Locations

Country	Name	City	State
India	Sanjay Gandhi Post Graduate Institute of Medical Sciences	Lucknow	Uttar Pradesh

Sponsors (1)

Lead Sponsor	Collaborator
Sanjay Gandhi Postgraduate Institute of Medical Sciences

Country where clinical trial is conducted

India, 

References & Publications (6)

Chorath K, Luu N, Go BC, Moreira A, Rajasekaran K. ERAS Protocols for Thyroid and Parathyroid Surgery: A Systematic Review and Meta-analysis. Otolaryngol Head Neck Surg. 2022 Mar;166(3):425-433. doi: 10.1177/01945998211019671. Epub 2021 Jun 15. — View Citation

Dort JC, Farwell DG, Findlay M, Huber GF, Kerr P, Shea-Budgell MA, Simon C, Uppington J, Zygun D, Ljungqvist O, Harris J. Optimal Perioperative Care in Major Head and Neck Cancer Surgery With Free Flap Reconstruction: A Consensus Review and Recommendations From the Enhanced Recovery After Surgery Society. JAMA Otolaryngol Head Neck Surg. 2017 Mar 1;143(3):292-303. doi: 10.1001/jamaoto.2016.2981. — View Citation

Khatiwada AS, Harris AS. Use of pre-operative calcium and vitamin D supplementation to prevent post-operative hypocalcaemia in patients undergoing thyroidectomy: a systematic review. J Laryngol Otol. 2021 Jul;135(7):568-573. doi: 10.1017/S0022215121001523. Epub 2021 Jun 14. — View Citation

Smith TW Jr, Wang X, Singer MA, Godellas CV, Vaince FT. Enhanced recovery after surgery: A clinical review of implementation across multiple surgical subspecialties. Am J Surg. 2020 Mar;219(3):530-534. doi: 10.1016/j.amjsurg.2019.11.009. Epub 2019 Nov 16. — View Citation

Terris DJ, Snyder S, Carneiro-Pla D, Inabnet WB 3rd, Kandil E, Orloff L, Shindo M, Tufano RP, Tuttle RM, Urken M, Yeh MW; American Thyroid Association Surgical Affairs Committee Writing Task Force. American Thyroid Association statement on outpatient thyroidectomy. Thyroid. 2013 Oct;23(10):1193-202. doi: 10.1089/thy.2013.0049. Epub 2013 Sep 14. — View Citation

Xing T, Hu Y, Wang B, Zhu J. Role of oral calcium supplementation alone or with vitamin D in preventing post-thyroidectomy hypocalcaemia: A meta-analysis. Medicine (Baltimore). 2019 Feb;98(8):e14455. doi: 10.1097/MD.0000000000014455. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To compare the rate of hypocalcemia in patients undergoing thyroid and parathyroid surgery implementing Enhanced recovery after surgery protocols vs Conventional peri operative protocols	S. Calcium levels will be measured. Levels >8mg/dl were considered normal	Post operative day 1, 2 & 7, 1 month post surgery, 3 month post surgery, 6 months post surgery
Secondary	To compare length of hospital stay in patients undergoing thyroid and parathyroid surgery in days	length of hospital stay defined as length of hospital stay in days from the date of surgery to the date of discharge	from date of surgery till Post operative Day 7
Secondary	To compare hospital costs in patients undergoing thyroid and parathyroid surgery implementing Enhanced recovery after surgery protocols vs Conventional peri operative protocols	In hospital costs will be compared from date of surgery till date of discharge	from date of surgery till Post operative Day 7
Secondary	To compare postoperative complication rates in patients undergoing thyroid and parathyroid surgery implementing Enhanced recovery after surgery protocols vs Conventional peri operative protocols	Occurrence of Hematoma, seroma, Surgical site infection	from date of surgery till 6 months post surgery
Secondary	To compare readmission rate	Readmissions for any complications related to surgery	from date of surgery till 6 months post surgery