Intraoperative Nerve Monitoring Can Reduce Prevalence of Recurrent Laryngeal Nerve Injury in Thyroid Reoperations: Results of a Retrospective Cohort Study

IONM has gained widespread acceptance as an adjunct to the gold standard of visual nerve identification, and this technique can be used to identify the RLN and the external branch of the superior laryngeal nerve (EBSLN) in both primary thyroid surgery and thyroid reoperations [11, 14, 15, 18, 20‐23]. The nerve may be mapped out in the operative field before visual identification, and additional intermittent stimulation of adjacent non-neural tissue versus nerve can help in tracing the nerve and all its branches through the dissected field. In addition, electric nerve testing at the end of the operation can serve for postoperative prognostication of nerve function [14]. In a prospective, randomized study of 1,000 patients (1,000 NAR per arm) published in 2009 by Barczyński et al. [17] the prevalence of transient RLN paresis was significantly lower in the group of patients who had primary thyroid surgery with IONM (by 2.9 % in high-risk patients and by 0.9 % in low-risk patients). The rate of permanent nerve palsy tended to be lower in operations performed with versus without IONM (by 30 %), but the power of this study was not sufficient to validate this difference. A more recent study by the same authors published in 2012 showed that the use of IONM significantly improved the identification rate of the EBSLN during thyroidectomy, as well as reduced the risk of early phonation changes after thyroidectomy [22, 23].

A reoperation in the scar tissue of the central neck is more dangerous for the RLN (and also for the parathyroid glands) than a primary operation, and the utilization of IONM is believed to aid in redo dissection, which should minimize the risk of nerve injury. It is well known that the prevalence of RLN injury after thyroid reoperations is variable (details are shown in Table 5) and dependent on surgeons’ experience, and hence it is lower in high-volume centres [8, 24, 25]. Despite the fact that thyroid reoperations have become less common due to a wide acceptance of total thyroidectomy as a standard treatment for benign thyroid disease in tertiary referral centres, one-half of thyroid surgery worldwide is performed in low-volume centres, in which subtotal thyroidectomy is still a common procedure [25]. In recent years, the majority of patients undergoing thyroid reoperations in our unit were referred from outside low-volume institutions; n = 215 of 306 patients (70.3 %) undergoing surgery with IONM in 2004–2012. Referring physicians recognized both the experience with and the availability of the IONM system at our institution as a guarantee of redo thyroid surgery being performed as safely as possible. However, so far, this belief is not entirely evidence based. It is well known that experience and routine nerve exposure are crucial to minimization of RLN complications [1, 2, 24, 25]. However, the IONM-added value in reducing RLN-related morbidity in the reoperative setting remains unclear. Yarbrough et al. [20] employed IONM in 52 cervical re-exploration procedures and found that it could be performed safely, but did not decrease RLN morbidity. Alesina et al. [11] recently reported a retrospective series of 250 thyroid reoperations, including 91 operations performed with IONM, and 159 surgeries with direct nerve visualization but without IONM, and no significant differences were observed in this study in the prevalence of RLN injury between both groups. Nevertheless, the outcomes of these studies could be influenced by selection bias, as decision to use IONM was dependent on the availability of the equipment and individual surgeon’s preferences according to the planned extent of the surgical procedure (a more liberal use of IONM in more challenging dissections). On the other hand, these studies were based on relatively small groups of patients, and statistical validation of small differences in the prevalence of RLN injury requires much bigger study arms.

As indicated by the results of our power calculation, 492 NAR are required in each treatment arm to give the study a power of 80 % with p = 0.05 to reliably evaluate RLN injury reduction from 6 to 3 %. The present study is the largest comparative analysis of thyroid reoperations performed with versus without IONM. It is important to stress that the prevalence of transient RLN paresis was decreased by almost 60 % in operations with RLN visualization plus additional IONM than RLN visualization alone (2.5 vs. 6.3 %, respectively; p = 0.003). In addition, the prevalence of permanent RLN palsy was 40 % lower in reoperations with IONM than with RLN visualization alone, but this difference was statistically not significant (p = 0.202). Given the outcomes of this study, a sample size of 920 NAR per arm was calculated as required to reliably assess the difference in the prevalence of permanent RLN events.

The explanation of better outcomes achieved in thyroid reoperations with IONM versus RLN visual identification alone should include a few important issues. First, IONM provided improved recognition of the anatomical details in the scar tissues of the neck with the use of the nerve mapping technique (almost 20 % of the RLNs were identified with IONM before visual exposition of the nerve, and almost twofold more ramified nerves were identified in reoperations with IONM). In addition, the rare but particularly prone to injury non-RLN was almost fourfold more often identified in patients operated with versus without IONM (p = 0.02). A lack of the initial vagus response (V1) when stimulating below the inferior thyroid artery, but positivity when stimulating above the inferior thyroid artery in a patient with intact preoperative ipsilateral vocal cord mobility, and a latency of the response shorter than 3.5 ms may alert the surgeon to the occurrence of this rare variant of the nerve before any surgical dissection is undertaken. This technique is of paramount importance in avoiding inadvertent and in most cases unrecognized intraoperative injury to the non-RLN [26, 27]. Second, intermittent RLN stimulation during the operation allowed for functional testing of the nerve. In case of EMG amplitude decrease during the case amounting to a drop of more than 30–50 % from the baseline value, even if the RLN seemed to be anatomically intact, surgeons stopped the dissection for a while and continued it with reduced traction of the nerve, observing in most cases a spontaneous EMG signal recovery. Third, in case of a loss of signal on the dominant side of the neck, which was, as a rule, operated on first (defined as no EMG signal at all, or a weak EMG waveform amplitude of less than 100 μV after ipsilateral vagus stimulation), the contralateral thyroid reoperation was staged for both benign (n = 20) and malignant disease (n = 3). Contralateral thyroid surgery was undertaken afterwards when ipsilateral vocal fold mobility was restored (n = 11). Two patients refused to undergo completion thyroidectomy after staged procedure for loss of signal. Details are shown in Tables 2, 3 and 4. In general, contralateral thyroid surgery was avoided in patients with benign thyroid disease and the only functioning RLN (permanent palsy), but it was undertaken in selected patients with contralateral loco-regional recurrence of thyroid cancer. The concept of staged thyroidectomy was proven to be effective in preventing bilateral RLN injury [28, 29], which is particularly important in bilateral thyroid reoperations and has been accepted by many [18, 30], but not all, thyroid surgeons [31]. The opponents of staged thyroidectomy indicate that PPV of IONM is relatively low (varying from 50 to 75 % in the majority of reported series), which can result in unnecessary staging of operation in 25–50 % of patients who experience loss of signal on the first side, but have no ipsilateral RLN paresis [31]. In this study, PPV of IONM was within the upper limits of the reported values (see Table 4), and it was better for the systems based on EMG waveform analysis (90.9 %) than for simple nerve stimulators with acoustic signalling (66.7 %). Thus, further improvements in PPV can be expected with utilization of continuous IONM, based on automatic permanent stimulation of the vagus nerve and almost real-time monitoring of the EMG quantitative parameters during surgery [32]. It should be also recognized that a cost-effectiveness analysis of the routine utilization of IONM in thyroid reoperations has never been reported and was also out of scope for this study; this issue needs to be clarified in future.

In conclusion, in our hands, IONM decreased the incidence of transient RLN paresis in repeat thyroid operations as compared with nerve visualization alone. The prevalence of permanent RLN injury tended to be lower in reoperations with IONM. However, given the outcomes of this study, a sample size of 920 NAR per arm is required to reliably assess a difference in the prevalence of permanent RLN events. Experience and routine nerve exposure remain crucial to the minimization of RLN complications in thyroid reoperations, but the use of the lateral approach with mapping of the RLN low in the neck and tracing its path in the scar tissues towards the larynx may provide additional benefits: an improved recognition rate of the ramified or non-recurrent nerves, and functional RLN testing feedback alerting the surgeon to a possible stretching injury of the nerve, particularly in the region of the ligament of Berry [33].