Systematic Use of Recurrent Laryngeal Nerve Neuromonitoring Changes the Operative Strategy in Planned Bilateral Thyroidectomy

Abstract

Background:

One of the worst complications in thyroid surgery is bilateral recurrent laryngeal nerve paralysis, which can lead to transient or definitive tracheotomy.

Methods:

We implemented a strict standard operative procedure beginning in January 2010 and modified our operative procedure. In all patients undergoing bilateral operation, we begin with the largest side or with the cancerous/suspicious side without dissecting the contralateral side. If the intraoperative neuromonitoring (IONM) signal is lost after stimulation of the vagus nerve at the end of the first side, we stop the procedure after the unilateral lobectomy, even if the recurrent nerve is anatomically intact and regardless of malignancy. If the IONM signal is lost, serial laryngoscopies are performed until recovery or definitive recurrent laryngeal nerve palsy is demonstrated. We report here our results in patients with loss of the IONM signal after lobectomy and discuss the medical implications for benign and malignant thyroid conditions.

Results:

Since January 2010, the operation has been stopped at the first side in 9 out of 220 planned bilateral thyroidectomies. There were five benign thyroid conditions and four thyroid cancers, including three papillary thyroid cancers and one bilateral medullary thyroid cancer in a patient with multiple endocrine neoplasia 2a. In two patients, it was a false-positive IONM loss. One of these two patients had the other lobe removed at day 3. In seven patients the laryngoscopy demonstrated total or partial laryngeal nerve palsy at day 1, but the recurrent nerve function recovered fully in all patients between 1 and 4 months postoperatively. All cancer patients were operated on the other side within 3 days to 3 months; one patient with a benign condition is being followed conservatively. One of the eight re-operated patients had transient recurrent nerve palsy postoperatively.

Conclusion:

In our opinion, the systematic use of IONM and the change in operative strategy will lead to an almost 0% rate of bilateral laryngeal nerve palsy, at least in benign thyroid conditions. A loss of signal after the first side should prompt a halt in the procedure, even in cases of malignancies.

Introduction

R ecurrent laryngeal nerve palsy (RLNP) is one of the most feared complications of thyroidectomy. Its rate has decreased over the past decades, likely secondary to routine identification of the recurrent laryngeal nerve (RLN) during thyroidectomy, which is now regarded as the standard of care in thyroid surgery since it reduces the incidence of definitive postoperative RLNP from over 5% to below 1% (1,2).

An impaired voice after unilateral RLNP can greatly affect quality of life and impacts daily and occupational functions. Fortunately it is mostly transitory, with a good voice recovery even when the recurrent nerve does not recover. This is not the case in bilateral RLNP, which can be life threatening due to airway obstruction requiring tracheotomy. Its incidence is between 0.2 and 0.5% (3,4), although it is probably underreported.

Intraoperative neuromonitoring of the RLN (IONM) during thyroidectomy has been described since 1970. There continues to be a debate regarding neuromonitoring and its role in reducing the risk of RLNP. In the current literature on the systematic use of IONM, there is no statistically proven reduction in the rate of RLNP when using neuromonitoring compared to nerve identification (5). This is possibly due to the low frequency of RLNP (2) and therefore to the difficulty to achieve statistical significance. Its utility, however, has been suggested in thyroid surgery of high-risk patients (re-operation, cancer, and Graves' disease), in which the prevalence of transient RLNP was 2.9% lower after surgery using IONM versus surgery using visualization alone (p=0.011) in one study (6).

IONM may help to identify patients with unilateral vocal cord paralysis after dissection of the first side, but there are many pitfalls and the rate of false pathologic findings in IONM is high, with a positive predictive value of only 35% (7,8). Even when no reason for nerve injury can be found, nerve visualization has been optimal, and the nerve is anatomically intact at the end of the dissection, nerve injuries are possible (9).

One of the utilities of IONM is the prevention of bilateral RLNP. When the signal is lost on the first side in planned bilateral thyroidectomy, the surgeon should evaluate the need to continue the surgery. If a strong signal on the vagus nerve is obtained at the end of dissection, there is a high chance of good vocal cord mobility postoperatively, with the risk of RLNP less than 0.1%–1% (2,6,10). If the nerve is anatomically intact during surgery, the chances of recovery are good, between 80% and 90% (2,10,11). According to Dionigi et al. (10), recovery of postoperative RLNP takes place in 87.5% of the cases during the first 6 months. The surgery can then be done without risk to the vocal cords in a two-stage operation.

We report here our results in patients with loss of the IONM signal after the first side in a thyroid lobectomy and their second operations. We also discuss the medical implications in cases of benign and malignant thyroid conditions.

Methods

Since January 2008, all thyroid surgeries in our unit have been performed with the use of IONM of the RLN. We implemented a strict standard operative procedure beginning in January 2010 that modified our operative procedure. In all patients undergoing bilateral operation, we begin with the larger side in cases of benign disease or with the cancerous/suspicious side in cases of malignant disease. If the IONM signal is lost after stimulation of the vagus nerve at the end of the first side, we stop the procedure after the unilateral lobectomy and after ensuring that there is no technical problem (e.g., displacement of the subcutaneous electrodes, malposition of the anesthesia tube, possibility that the patient is curarized). We then do not dissect the contralateral side. We stop the operation even if the recurrent nerve is anatomically intact and even in cases of malignancy. A loss of signal (LOS) with IONM is defined as an absence of acoustic response when the RLN is stimulated at a current between 1 and 2 mA or as a response below the threshold of 100 μV.

If the IONM signal is lost, we perform a laryngoscopy during the first 24 hours postoperatively to confirm the presence or absence of RLNP.

Preoperative laryngoscopy is performed selectively in our center for all patients with preoperative dysphonia and for all patients with previous neck operation. Postoperatively, a laryngoscopy is done in cases with IONM signal loss or postoperative voice modification.

According to the results of the first postoperative laryngoscopy, we perform serial examinations of the vocal cords until recovery or definitive RLNP is demonstrated. If the nerve recovers, we operate on the second side and complete the procedure as medically needed.

We report here nine planned bilateral thyroidectomy cases since January 2010 in which we had a LOS with IONM on the first side. It is a retrospective study of prospectively collected data in a consecutive series of cases, in which we analyzed our procedure with IONM and its final outcome using direct laryngoscopy. We present here our method of surgical care in benign and malignant cases.

Results

From January 2010 to March 2012, planned bilateral thyroidectomies were stopped after the first side in 9 of 220 patients (4.1%) because of LOS with IONM. The patient characteristics are shown in Table 1.

Table 1.

Characteristics and Operative Management of the Nine Cases

Case	Age/sex	Preoperative diagnosis	1st surgery: lobectomy with…	Pathology, 1st side	Laryngoscopy day 1	2nd laryngoscopy	Timing of 2nd surgery: completion thyroidectomy with…	Pathology, 2nd side
1	52/f	MNG	—	MNG, 71 g	uRLNP	M1: no uRLNP
2	60/m	Substernal MNG	—	MNG, 111 g	No uRLNP		D3	MNG, 65 g
3	50/f	MNG	—	MNG macrofollicular, 33 g	No uRLNP		M6	Nodular hyperplasia, 24 g
4	61/f	MNG+pHPT with osteoporosis	—	Adenoma, thyroid gland, 26 g, with FTC 1.2cm, pT1a	uRLNP	M1: no uRLNP	M6	MNG with micro PTC, 13 g
5	55/f	MNG	—	MNG, 27 g	uRLNP	D15: no uRLNP	M6	MNG, 35 g
6	45/m	PTC with N+	Central+lateral neck diss.	PTC 6 cm, pT3N1b (6/8), 17 g	uRLNP	D15: no uRLNP	M2: central+lateral neck diss.	PTC 0.8 cm, pN1b (2/10), 6 g
7	31/f	PTC with N+	Central+lateral neck diss.	PTC 3.2 cm, pT2N1b (7/14), 15 g	uRLNP	M1: no uRLNP	M3: central neck diss.	MNG+pN (1/4), 5 g
8	33/f	PTC with N+	Central+lateral neck diss.	PTC 1.1 cm, pT3N1 (10/26), 16 g	uRLNP		D3: RLN signal ok but uRLNP at postoperative laryngoscopy	PTC 1.2 cm, pN1 (1/4), 7 g
9	41/f	MEN2a, MTC bilateral with N+, HPT1	Central+lateral neck diss.	MTC infiltrative, 1 cm, pT3N1b (3/30 lat, 8/13 central), 4 g	uRLNP	M3: no uRLNP	M3: central+lateral neck diss.	MTC 2 cm, pT2N (1/21), 9 g

Tumor classification according to the TNM system of the American Joint Committee on Cancer (12).

D, day; diss., dissection; f, female; FTC, follicular thyroid cancer; pHPT, primary hyperparathyroidism; m, male; M, month; MEN, multiple endocrine neoplasia; MNG, multinodular goiter; MTC, medullary thyroid cancer; N+, positive lymph nodes; PTC, papillary thyroid cancer; RLN, recurrent laryngeal nerve; uRLNP, unilateral recurrent laryngeal nerve palsy.

There were five benign thyroid conditions and four thyroid cancers, including three papillary thyroid cancers and one bilateral medullary thyroid cancer in an index case of multiple endocrine neoplasia (MEN)2a.

All four thyroid cancer patients had macroscopically invaded lymph nodes in the central compartment.

All operations were performed by fully trained and experienced thyroid surgeons. All nine patients had a LOS at the first side, and thus ended the first operation with a hemithyroidectomy with a lateral and/or central neck dissection according to the preoperative diagnosis.

We describe here the results of our management according to the results of the observations made by direct laryngoscopy (Table 1).

In two patients (cases 2 and 3), there was a false-positive IONM loss (no RLNP at laryngoscopic examination on day 0 or 1). One of these patients (case 2) had the other lobe removed at day 3, and the second patient (case 3) had the other lobe removed at 6 months.

In seven patients, the laryngoscopic examination demonstrated a total or partial RLNP at day 1, but the recurrent nerve function recovered in all patients between 1 and 4 months postoperatively. In two of these patients (cases 1 and 8), the laryngoscopic examination demonstrated partial RLNP at day 1 without dysphonia, and one of the patients had the second operation performed on day 3 (case 8) and the patient with a benign condition is being followed conservatively (case 1). In the other five patients, unilateral RLNP was demonstrated at the first postoperative laryngoscopic examination. The recurrent nerve function fully recovered and thus prompted us to proceed with the completion thyroidectomy. As for patient number 9, whose follow-up postoperative laryngoscopies showed persistent unilateral RLNP at 1 month, the nerve function recovered 3 months after the first operation, and the voice normalized. This patient was informed of the risk of bilateral RLNP before the re-operation. In patients with thyroid cancer, our standard policy is to proceed with the completion thyroidectomy after 3 months.

In summary, all patients were re-operated on the contralateral side 3 days to 6 months after the first side, and one of the eight re-operated patients had transient RLNP after the second operation. This was a false-negative IONM signal at the completion surgery; case 8 had a normal IONM signal with a postoperative transient RLNP on the second side. The nerve recovered on both sides at 6 months after the completion surgery (third laryngoscopy).

All cancer patients were operated on the other side within 3 days to 3 months. The 3 patients (cases 6, 7, and 8) with papillary thyroid cancer were considered to be in remission after radioiodine treatment, with undetectable stimulated thyroglobulin levels on follow-up. The patient with MEN2a and bilateral medullary thyroid cancer with involvement of lymph nodes in the central and both lateral compartments still has measurable calcitonin levels around 400 ng/L, which have been stable for 2 years; she has no detectable pathologic cervical lymph nodes on ultrasound or magnetic resonance imaging (case 9).

Discussion

With the nine cases reported in this article, we illustrate an operative strategy that enables preventing bilateral RLNP, which is one of the worst complications of thyroid surgery. Specialized training, surgical experience, and a thorough dissection with visualization of the RLN in thyroid surgery help to prevent bilateral RLNP. With this strategy, the risk of bilateral RLNP can be reduced to almost 0% by interrupting the planned bilateral surgery after IONM signal loss at the first side, except in very rare cases in which the nerve has to be sacrificed because of cancer invasion.

Nerve recovery and the two-stage operation

Based on the current literature, with an intact nerve on dissection, the recovery of function is between 80% and 90% (2,10) and the contralateral surgery can then be done at a later time without risking both nerves at the same time (11). Goretzki et al. (11) showed no postoperative bilateral RLNP when the strategy was changed after the first side, compared to 3 out of 16 cases (19%) of bilateral RLNP when the surgeon did not modify his or her operative strategy after signal loss at the end of dissection of the first side (p<0.05). In our series, all cases of LOS after the first side were transient. One of the eight re-operated patients had transient RLNP on the contralateral side, which recovered at 6 months after completion surgery.

If the unilateral paralysis persists on postoperative laryngoscopic examinations, a referral to an experienced surgeon for the operation of the contralateral side is recommended because a signal loss can be very stressful for the surgeon and jeopardize the outcome of the completion surgery (11).

We have chosen to proceed with the treatment at 3 months after the first surgery in cases of thyroid cancer because it is acceptable from an oncological point of view and most transient RLNPs will have recovered in 3 months, as suggested by Dionigi et al. (10), who showed a full recovery of vocal cord function in 87.5% of cases at 6 months. In cases of cancer with a slow risk of progression, as is usually the case in well-differentiated thyroid cancer, the management can be done as mentioned, with a re-operation within 3 months. The situation is of course different in cases of invasive cancer or if there is invasion of the RLN and secondary RLNP presents before the first intervention. In those cases, the patients are at higher risk and have to be clearly informed about the risk of bilateral RLNP; these patients should be exclusively operated on by experienced thyroid surgeons.

According to a German study (13) on the use of IONM in bilateral thyroid surgery, 89% of the surgery departments have access to IONM, and 93.5% of the surgeons are willing to change their surgical strategy to prevent bilateral RLN palsy when unilateral LOS is present: 84.7% by discontinuing bilateral surgery and 8.8% by reducing the planned extent of surgery. This further supports the concept of a staged thyroidectomy.

Intraoperative problem-solving algorithm

According to Randolph et al. (14) in an international standards guideline statement based on a review of the literature, a LOS in IONM should prompt thorough troubleshooting of the equipment setup (determining causes of false positives, i.e., LOS with intact vocal cord mobility), followed by an identification of RLN with neural mapping and consideration of optimal contralateral surgery timing. Studies reviewed by Dralle et al. (9) showed high negative predictive values (absence of RLNP when the neuromonitoring signal is good) that varied between 92% to 100%, whereas the positive predictive values (presence of RLNP in case of LOS) were relatively low and variable, between 10% to 90% for IONM with a high number of false positives, thus limiting its utility for intraoperative RLN management. These variable positive predictive values can be considerably increased if a troubleshooting algorithm is used (PPV up to 75%) (14). In our study, we had two of nine cases with a LOS that showed a normal function of the RLN postoperatively (false-positive rate of 22%), which is a limitation of this procedure because it leads to stopping the operation when the RLN is in fact intact.

Standardization of laryngoscopic examination

Overall, the importance of laryngoscopic examination and its medico-legal implications are well known because nerve damage can be present without voice symptoms. Unilateral RLNP can be completely asymptomatic, as shown in the study by Dionigi et al. (10), in which more than 10% of the patients with postoperative RLNP at the laryngoscopic examination at day 2 had a normal voice. In our series, all RLN were anatomically intact after the dissection of the first side and the paralysis could not have been identified intraoperatively without IONM. Moreover, five of the seven patients with RLNP had a normal voice at the postoperative laryngoscopy, even if specifically asked about the presence of an impairment. This emphasizes the need to standardize the evaluation and reporting of RLN function postoperatively.

Proposed strategy for the use of IONM

We highlight here our operative strategy with IONM in planned bilateral thyroidectomy in order to limit the number of false positives (i.e., LOS with intact vocal cord mobility) and to prevent bilateral RLNP:

1. Communication with anesthesiologist: No use of long-acting curare for intubation. No grease on the tube around the electrodes. Good positioning of the tubes with the electrodes between the vocal cords using laryngoscopy during intubation.

2. Check all the electrodes and the installation of the IONM before starting surgery.

3. Start the surgery on the larger side or the suspicious/malignant side (according to preoperative fine needle aspiration cytology).

4. Before accessing the thyroid bed, test the correct function of the IONM system using stimulation of the vagus nerve.

5. Systematic dissection and visualization of the RLN. Stimulation with the IONM system is done during dissection.

6. At the end of dissection of the first side, when hemostasis is finished, the vagus nerve is stimulated.

7. If a good signal follows the vagus stimulation, surgery can be continued as planned on the contralateral side.

8. If no signal is obtained from the vagus stimulation, after excluding technical problems and even if the RLN is anatomically intact, we stop the surgery at the first side and a laryngoscopy is done postoperatively.

9. In case of a good mobility of both vocal cords on postoperative laryngoscopy, the second surgery can be scheduled without delay and according to the patient's wishes.

10. In case of postoperative RLNP on laryngoscopy, we recommend waiting 3, 6, or 12 months depending on the recovery and then proceeding with the surgical management. If the paralysis is definitive (generally considered after 12 months, but according to the literature, the recovery chances are low after 6 months [10]), we recommend reevaluating the necessity for a completion surgery and most importantly, in case of surgery, informing the patients of the risk of bilateral RLNP. In case of malignancy, we proceed after 3 months.

Conclusion

The systematic use of IONM changes the operative strategy and may lead to a rate of almost 0% for bilateral laryngeal nerve palsy, at least in benign thyroid conditions. In our opinion, a LOS after the first side of a planned bilateral thyroidectomy should prompt a halt in the procedure to prevent bilateral RLNP. Whether this should also be the case in malignant conditions is debatable, but we strictly adhere to this rule. As shown in our malignant cases, the oncologic management can be done without much delay. Furthermore, in our small series, all laryngeal nerve palsies were transient and could thus be managed as illustrated.

Footnotes

Author Disclosure Statement

All aspects of the design, conduct, and analysis were under the sole authority of the authors, without any restriction on publication. All co-authors have had full access to the data and take responsibility for the accuracy of the data analysis. The authors declare no conflict of interest. The results presented in this paper have not been published previously in whole or part, except in abstract form.

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