Intraoperative Methylene Blue Spray for the Identification and Preservation of Vital Structures in Thyroidectomy

Intraoperative Methylene Blue Spray for the Identification and Preservation of Vital Structures in Thyroidectomy: A Randomized Controlled Trial

This randomized controlled trial aims to evaluate the efficacy of intraoperative methylene blue (MB) spray in improving the identification and preservation of the recurrent laryngeal nerve (RLN) and parathyroid glands (PGs) during thyroidectomy. The study compares outcomes between patients receiving topical MB spray and those undergoing conventional visual dissection alone. Primary outcomes include the incidence of RLN injury and postoperative serum calcium levels.

Study Overview

• Status: Completed
• Conditions: Hypoparathyroidism; Thyroidectomy; Recurrent Laryngeal Nerve Injury; Benign Multinodular Goiter
• Intervention / Treatment: Procedure: Intraoperative topical methylene blue spray; Procedure: Conventional Dissection

Detailed Description

Thyroidectomy is associated with risks of iatrogenic injury to the RLN and PGs, leading to vocal cord paralysis and hypocalcemia. This study investigates whether topical application of methylene blue spray can enhance intraoperative visualization and preservation of these structures. A total of 136 patients with benign multinodular goiter were randomized into two groups: an experimental group receiving MB spray and a control group receiving conventional dissection. RLN injury was assessed via postoperative laryngoscopy, and serum calcium levels were measured at 72 hours postoperatively.

• Study Type: Interventional
• Enrollment (Actual): 136
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Pakistan
  • Punjab Province
    • Lahore, Punjab Province, Pakistan, 54000
      • Services Institute of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• benign multinodular goiter scheduled for thyroidectomy.

Exclusion Criteria:

• Recurrent/metastatic disease
• Preoperative vocal cord dysfunction
• Coagulopathy
• Methylene blue allergy
• Hepatic/renal impairment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Methylene Blue labelling	Procedure: Intraoperative topical methylene blue spray; Intraoperative topical spray of 0.5 mL methylene blue applied to the thyroid lobe and surrounding tissue after mobilization.
Active Comparator: Conventional Dissection	Procedure: Conventional Dissection; Conventional visual identification and dissection without dye.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of recurrent laryngeal nerve injury	Incidence of recurrent laryngeal nerve injury (assessed by indirect laryngoscopy	2 hours (at extubation)
Postoperative serum calcium levels	Postoperative serum calcium levels	At 72 hours

Collaborators and Investigators

• Sponsor: Services Hospital, Lahore
• Investigators: Principal Investigator: Awais Amjad Malik, MBBS, FCPS, Services Institute of Medical Sciences

Publications and helpful links

General Publications

• 6. Farghaly AEA, Ahmed MT, Kotb MB, Ibrahim IA. Conventional surgical techniques versus intraoperative methylene blue spraying for safe total thyroidectomy. J Curr Med Res Pract. 2019;4(1):67-71.
• 7. Sebaey AE, Khalil AM, Elkilany MM, Ali RM. Recurrent laryngeal nerve identification in thyroidectomy by intraoperative staining with methylene blue. Eur J Mol Clin Med. 2021;8(2):644-9.
• 8. Piromchai P, Juengtrakool T, Laohasiriwong S, Kasemsiri P, Ungarereevittaya P. The sensitivity and specificity of methylene blue spray to identify the parathyroid gland during thyroidectomy. PeerJ. 2019;7:e6376.
• 1. Eldeen Abdulrahman ZN, Rajab WQ, Jameel Ali Z. Identification of recurrent laryngeal nerve and parathyroid glands intraoperatively by methylene blue spraying technique. Indian J Forensic Med Toxicol. 2020;14(1):1355-60.

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2022
• Primary Completion (Actual): December 31, 2025
• Study Completion (Actual): January 20, 2026

Study Registration Dates

• First Submitted: February 1, 2026
• First Submitted That Met QC Criteria: February 1, 2026
• First Posted (Actual): February 9, 2026

Study Record Updates

• Last Update Posted (Actual): February 9, 2026
• Last Update Submitted That Met QC Criteria: February 1, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Thyroidectomy; Hypocalcemia; Methylene Blue; Recurrent Laryngeal Nerve Injury; Nerve Preservation
• Additional Relevant MeSH Terms: Endocrine System Diseases; Nervous System Diseases; Wounds and Injuries; Metabolic Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Water-Electrolyte Imbalance; Parathyroid Diseases; Craniocerebral Trauma; Trauma, Nervous System; Cranial Nerve Diseases; Laryngeal Diseases; Calcium Metabolism Disorders; Cranial Nerve Injuries; Vagus Nerve Injuries; Nutritional and Metabolic Diseases; Laryngeal Nerve Injuries; Hypoparathyroidism; Hypocalcemia; Recurrent Laryngeal Nerve Injuries
• Other Study ID Numbers: RCT22SIMS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No