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Year : 2020  |  Volume : 4  |  Issue : 2  |  Page : 187-191

Safe total thyroidectomy by using intraoperative methylene blue spray

Department of ENT, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt

Date of Submission06-Mar-2020
Date of Decision10-Mar-2020
Date of Acceptance16-Mar-2020
Date of Web Publication29-Jun-2020

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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/sjamf.sjamf_34_20

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Background Intraoperative localization and preservation of recurrent laryngeal nerve (RLN) and parathyroid glands improve outcomes following thyroid surgery. This can be facilitated by methylene blue.
Aim the aim was to evaluate the value of spraying methylene blue dye during thyroidectomy for the help of the identification and dissection of RLN.
Patients and methods A total of 34 patients with benign goiter disorders were included in this prospective observational study. During the surgery, after ligation of the superior pole of the thyroid and before ligation of inferior pole, 1 ml (10 mg) of 1% methylene blue solution was sprayed over the thyroid bed and perithyroidal tissue. Identification and safe dissection of the thyroid gland from the RLN and parathyroid glands were done without injuring these structures.
Results RLN remained white, whereas thyroid and parathyroid glands were stained blue. The parathyroid glands washed out the stain within 5 min and were visible in its normal yellow color in all cases.
Conclusion Spraying of methylene blue dye during thyroidectomy is a safe and effective method for identification and avoiding injury to RLN and parathyroid glands during thyroid surgeries.

Keywords: intraoperative, methylene blue, recurrent laryngeal nerve, spraying, thyroidectomy

How to cite this article:
El-Hussieny F. Safe total thyroidectomy by using intraoperative methylene blue spray. Sci J Al-Azhar Med Fac Girls 2020;4:187-91

How to cite this URL:
El-Hussieny F. Safe total thyroidectomy by using intraoperative methylene blue spray. Sci J Al-Azhar Med Fac Girls [serial online] 2020 [cited 2020 Oct 26];4:187-91. Available from: http://www.sjamf.eg.net/text.asp?2020/4/2/187/288277

  Introduction Top

Disorders of the thyroid gland constitute the second most common endocrine disease following diabetes mellitus [1]. Thyroidectomy is one of the most frequent operations performed in iodine-deficient regions [2],[3]. When performed in specialized centers, the operation is safe with low morbidity and a virtually 0% mortality. Complications of thyroid surgery are directly correlated to the extent of resection and inversely proportional to the experience of the operating surgeon. Thus, the cornerstones of safe and effective thyroid surgery are adequate training, the understanding of the anatomy and pathology, as well as a meticulous dissection technique. The meticulous dissection technique is achieved by a proper exposure of all fine anatomic structures in a bloodless dry surgical field [4].

Several dissection devices have recently been propagated for thyroid surgery. The harmonic scalpel using ultrasonic frictional heating to seal vessels is widely used in laparoscopic and open abdominal surgery. It is documented to be safe and fast for cutting and coagulating tissue [5].

The main postoperative complications of thyroidectomy are recurrent laryngeal nerve (RLN) palsy and hypoparathyroidism [6]. Postoperative hypocalcemia after thyroidectomy leads to patient discomfort and prolonged hospital stay. The etiology appears to be multifactorial, that is, iatrogenic hypoparathyroidism, the extent of surgery, the number of functioning glands remaining, and the surgeon’s experience [7],[8].

Current guidelines for the prevention of parathyroid thyroid injury during thyroid surgery are anatomically locating the parathyroid gland. However, this gland is difficult to separate from the surrounding fat and lymph nodes, which is a reason that postoperative hypocalcemia still occurs. Other methods to identify the parathyroid gland during thyroidectomy include a partial biopsy of the gland for pathological examination [9], intravenous methylene blue injection [10], computerized tomography during thyroid surgery [11], parathyroid specific luminescence [12], and fine-needle aspiration for an analysis of parathyroid hormone levels [13].

Methylene blue, which is a medication and dye that has been used for more than a century, is safe and readily available. A previous case series found that methylene blue spray on the surgical field was absorbed by the parathyroid gland faster than in the surrounding perithyroidal area [14].

Although the overall incidence of RLN palsy is low when it does occur, nerve palsy is a devastating life-long handicap. Anatomic identification of the RLN has long been accepted as the safest way of reducing nerve injury rates.

Selective in-vivo staining of the parathyroid glands by intravenous and intra-arterial administration of toluidine blue was first described in dogs by Klopper and Moe [15]. The withdrawal of toluidine blue from general use because of its adverse effects led to a search for an alternative dyestuff.

In the present study, we aimed to investigate whether the methylene blue spraying technique during thyroidectomy allowed us to safely identify RLN and parathyroid glands.

  Patients and methods Top

Our Institutional Review Board approved this prospective observational study under the Helsinki Declaration.

A total of 34 patients with benign goiter disorders underwent total or near-total thyroidectomy. They provided written informed consent during a period from August 2018 to August 2019 and were admitted to the General Surgery Department at Al-Zahraa University Hospital, a teaching hospital attached to Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt.

All selected patients presented with goiter which was diagnosed by clinical examination, ultrasound scan, and confirmed by histopathological examination of the biopsy taken.

We include in this study all patients who presented with simple nodular goiter, solitary thyroid nodule, and controlled toxic goiter. Exclusion criteria were as follows: patients who refused to participate in the study, presence of preoperative cord dysfunction, giant goiter, Grave’s disease, retrosternal goiter, and patients unfit for general anesthesia.

All were subjected to the following:
  1. Personal data, risk factors, and history of present illness: swelling in the neck.
  2. General and local examination.
  3. Laboratory investigations (preoperative preparation and thyroid hormone levels).
  4. Radiology by ultrasound.
  5. Histopathological examination of biopsy.

Surgical technique

Operations were performed using general anesthesia. In each patient, the indirect laryngoscopic examination was performed to evaluate vocal cord motility both before and after surgery. The patients were placed in a supine position with the neck extended. A low-collar incision was made and carried down through the subcutaneous tissue and platysma muscle. Superior and inferior subplatysmal flaps were developed, and the strap muscles were separated vertically in the midline and retracted laterally. The thyroid lobe was bluntly dissected free from its investing fascia and rotated medially. The middle thyroid vein was ligated.

The superior pole was ligated and cut. At this point in the surgery, neither the parathyroid glands nor RLN can be easily identified. Before inferior pole ligation, the thyroid lobe was deviated medially to identify the RLN and parathyroid glands. A volume of 1 ml (10 mg) of 1% methylene blue solution was sprayed over the thyroid bed and perithyroidal tissue. All tissues were stained blue (thyroid and parathyroid glands) while RLN remained white (unstained). Three minutes after spraying, parathyroid glands had absorbed the blue stain and regained their original yellow color. Other tissues were still stained blue.

Statistical analysis

Data were collected, coded, revised, and entered the Statistical Package for the Social Sciences (IBM SPSS) version 20 (IBM Corp., Armonk, New York, USA). The data were presented as numbers and percentages for the qualitative data; mean, SD, and ranges for the quantitative data with parametric distribution; and median with interquartile range for the quantitative data with the nonparametric distribution.

The confidence interval was set to 95% and the margin of error accepted was set to 5%. So, the P value was considered significant as follows: P greater than 0.05: nonsignificant, P less than 0.05: significant, and P less than 0.01: highly significant.

  Result Top

A total of 34 patients participated in this study, comprising three (8.8%) males and 31 (91.2%) females, with age ranging from 25 to 62 years old ([Table 1]). Preoperative diagnoses were as follows: simple nodular goiter (82.4%, n=28), Diffuse goiter (2.9%, n=1), solitary thyroid nodule (8.8%, n=3), controlled toxic goiter (2.9%, n=1), and recurrent goiter (2.9%, n=1) ([Table 2]).
Table 1 Demographic data

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Table 2 Clinical diagnosis

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Overall, 28 patients underwent total thyroidectomy, one patient completion thyroidectomy, whereas five patients performed hemi-thyroidectomy ([Table 3]). Histopathology results of the thyroid nodules were as follows: follicular adenoma (17.6%, n=6), papillary thyroid carcinoma (8.8%, n=3), Hurthle cell adenoma (2.9%, n=1), diffuse thyroid hyperplasia (5.9%, n=2), colloid goiter (44.1%, n=15), and thyroiditis (20.6%, n=7) ([Table 4]). All patients in the study had mobile vocal cord by preoperative and postoperative vocal cord examination ([Table 5]).
Table 3 Operation

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Table 4 Final histopathology

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Table 5 Vocal cord examination

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Patients were discharged from the hospital with no major complications (no signs or symptoms of postoperative hypocalcemia, no postoperative vocal cord immobility, and no postoperative hematoma). None of the patients had allergic reactions to the methylene blue or methylene blue toxicity.

  Discussion Top

Morbidity and mortality from thyroidectomy occur rarely; however, possible serious postoperative complications could cause a devastating life-long handicap. The main postoperative complications of thyroidectomy are hypoparathyroidism and RLN injury. The extent of resection, reoperation for completion, and the surgeon’s inexperience are risk factors for the morbidity of thyroid surgery [16],[17].

Postoperative RLN palsy is a major concern that may lead to prolonged hospitalization and increased cost and results in significant impairment of the quality of life and negatively affects job performance [18].

During thyroid surgery, the parathyroid glands and RLN can be protected by careful dissection. Various methods have been tried including capsular dissection, attention to the protection of the arterial branches to parathyroid, avoiding unnecessary manipulation in the area of RLN or its blood supply [19].

RLN function can be assessed by several methods like nerve stimulation and finger palpation of cricoarytenoid muscle, direct or fiberoptic laryngoscopy for observation of vocal cords, and the use of intramuscular vocal cord electrodes [20].

A multicenter study by Dralle et al. [21] observes that direct identification of RLN by sight is ideal and is considered the ‘gold standard’ of care.

Conventionally, surgeons identify the RLN by using judging its relationships with the inferior thyroid artery, tracheoesophageal groove, and ligament of Berry as anatomical landmarks. However, because of the numerous variations of this neurovascular relationship altered also by pathologic conditions of the gland, identification of the artery does not ensure accurate identification and preservation of the RLN.

We did not use an expensive device for identifying the important structures. The dye is inexpensive; it can be easily and safely applied. We sprayed the dye onto the perithyroidal area. Moreover, we aimed to identify not only parathyroid glands but also RLN and inferior thyroid artery.

After spraying the dye onto the perithyroidal area, however, a surgeon can easily identify the RLN, parathyroid glands, and inferior thyroid artery. Once found, the nerve with all the identified branches can be quickly and safely followed through its entire course until it enters the larynx. When all the parathyroid glands have been identified, special care can be easily taken to preserve their vascular pedicles.

The technique of using dyes in the identification of parathyroid glands and the prevention of hypoparathyroidism was first described by Klopper and Moe [15].

Initial studies were conducted using dyes like toluidine blue and trypan blue; however, these were replaced by methylene blue, as their teratogenic effects were discovered [22].

Methylene blue is certified by the US Food and Drug Administration. It can be used in a variety of medical treatments, including hereditary methemoglobinemia, acute acquired methemoglobinemia, prevention of urinary tract infection in the elderly, and localization of nerves and endocrine tissues. There are few adverse effects associated with methylene blue. However, toxicity can occur if more than 5 mg/kg is used. Symptoms of toxicity include dizziness, nausea, vomiting, headache, abdominal pain, and confusion [23],[24].

In the literature, all the studies related to thyroid surgery and parathyroid staining were performed by injecting the dye via intravenous or intra-arterial route. Dudley [25] used an intravenous infusion technique on 17 patients, and demonstration of one or more parathyroid was possible with this technique.

Elias et al. [26] used the same technique on 59 patients and was able to precisely localize the parathyroid glands in 87% cases.

With this technique, only the parathyroid glands can be visualized. This is because of the rich vascularity of the glands. The identification of the RLN is not possible with this method.

In 2012, Sari et al. [14] studied the effects of methylene blue spraying on the identification of RLN and performing safe thyroidectomy. They observed that dye did not stain the RLN and inferior thyroid arteries, whereas all other tissues stained blue. Furthermore, it was noted that although the parathyroid were stained, they washed out the color in three minutes and were visible in their original yellow color.

In this study, we observed that the wash-out time of parathyroid glands was 3 min but for thyroid glands was more than 15 min. Histologically, the lymphovascular structure of parathyroid glands is extremely dense. This peculiarity of the tissue is vital for immediate washout of methylene blue staining.Unstaining of the RLN during the procedure is not surprising, because like other peripheral nerves, it is covered by a Schwann sheath and has an avascular structure.

Guglielmo et al. [27] mentioned in their study that the only safeguard against RLN damage, when performing a thyroidectomy, is identifying rather than avoiding the nerve. It has been observed and widely agreed upon that the experience of the surgeon is also an important factor that accounts for the variation in the rate of occurrence of paralysis of vocal cords.

Lahey [28] reported his experience with deliberate exposure and identification of RLN over 10 000 thyroidectomies. The less than 1% RLN injury rate was significantly lower than any previously published series and led him to advocate the routine identification and dissection of the nerve during thyroid surgeries.

Steurer et al. [29] have concluded from their study that RLN preparation does not increase the overall number (temporary and permanent) of RLN palsies but effectively reduces the number of permanent RLN palsies. Whenever extracapsular thyroid or parathyroid surgery is performed, RLN preparation should be performed.

In this study, we have identified the RLN in all 34 cases and have avoided injury in all patients, as confirmed on postoperative indirect laryngoscopic examination.

  Conclusion Top

Safe thyroid surgery is based on visualization of the parathyroid glands, RLN, and thyroid arteries.

Methylene blue spraying technique ensures not only the identification of parathyroid glands within three minutes but also the identification of the RLN and thyroid arteries.

Moreover, it does not require intravenous or intra-arterial administration of methylene blue, and thus the potential complications of intravascular dye infusion can be avoided.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]


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