Intraoperative recurrent laryngeal nerve monitoring in thyroid surgery: is it really useful?

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1 Neuromonitoring in thyroid surgery e193 Original article Clin Ter 2013; 164 (3):e doi: /CT Intraoperative recurrent laryngeal nerve monitoring in thyroid surgery: is it really useful? P.G. Calò 1, G. Pisano 1, F. Medas 1, A. Tatti 1, M.R. Pittau 2, R. Demontis 3, P. Favoriti 4, A. Nicolosi 1 Departments of 1 Surgical Sciences, and 2 School of Specialty in Forensic Medicine, and 3 Public Health, Clinical and Molecular Medicine, University of Cagliari; 4 Department of Surgical Sciences, Sapienza, University of Rome, Italy Abstract Aim. The aim of this study was to evaluate the ability of intraoperative recurrent laryngeal nerve monitoring to predict the postoperative functional outcome and the potential role of this technique in reducing the postoperative nerve palsy rate. Materials and Methods. Between June 2007 and December 2011, 1693 consecutive patients who underwent thyroidectomy by a single surgical team were evaluated. We compared patients who have had a neuromonitoring and patients who have undergone surgery with the only visualization. Patients in which NIM was not utilized (Group A) were 942 against the others 751 (group B). Results. In group A there were 28 recurrent laryngeal nerve injuries (2.97%) of which 21 were transients (2.22%) and 7 were permanents (0.74%). In group B there were 20 recurrent laryngeal nerve injuries (2.66%) of which 14 (1.86%) transients and 6 (0.8%) permanents. Differences between the two groups were not statistically significative. Conclusions. The technique of intraoperative neuromonitoring in thyroid surgery is safe and reliable in excluding postoperative recurrent laryngeal nerve palsy; it has high accuracy, specificity, sensitivity and negative predictive value. Neuromonitoring is useful to identify the recurrent laryngeal nerve and it can be a useful adjunctive technique for reassuring surgeons of the functional integrity of the nerve but it does not decrease the incidence of injuries compared with visualization alone. Its application can be particularly recommended for high-risk thyroidectomies. Clin Ter 2013; 164(3):e doi: / CT Key words: intraoperative neuromonitoring, recurrent laryngeal nerve, thyroid surgery Introduction Despite advances in surgical techniques during the last decades, the risk for recurrent laryngeal nerve injury during thyroid surgery has only declined, not disappeared (1). The incidence of recurrent laryngeal nerve palsy is different (1-20%), depending on the type of disease, the type of sur- gery, the extention of resection, the surgical technique and the surgeon s experience (2-5). Larger extent of resection and recurrent goiter are independent variables that increase the probability of recurrent laryngeal nerve injury; abnormal anatomy, bulky disease and surgeon inexperience are additional risk factors (1, 3, 4, 6, 7). Recurrent laryngeal nerve dysfunction commonly causes voice impairment, a disability that can diminish overall quality of life because of its attendant communication, social, psychological, and work-related problems (4, 8, 9). Intraoperative identification of the recurrent laryngeal nerve was proposed to be an integral part of thyroid surgery by Lahey in 1938 and has been demonstrated to decrease the incidence of postoperative nerve palsy (1, 2, 4, 8, 10). Since then, many prospective studies have confirmed this observation, advocating routine nerve identification as the gold standard in safe thyroid surgery (2, 4, 11, 12). But even in the most experienced hands recurrent laryngeal nerve palsy occurs occasionally, with permanent palsy rate of 1-2% and temporary palsy rate of up to 5-6%, owing to variability in nerve anatomy and difficulties in nerve identification (1, 2, 12-17). Many injuries are not recognized intraoperatively, although the possible causes of injury can result from transaction, clamping, stretching, electrothermal injury, ligature entrapment or ischemia. Several studies have reported that anatomical variations of the recurrent laryngeal nerve, such as extralaryngeal branches, distorted recurrent laryngeal nerve, intertwining between branches of the recurrent laryngeal nerve and inferior thyroid artery and non-recurrent laryngeal nerve, play an important role in the occurrence of nerve injury that can be caused by visual misidentification. Unrecognized transaction of the recurrent laryngeal nerve or its motor branch can be a cause of unexpected permanent palsy of these nerves (14). Despite the low rate of permanent recurrent laryngeal nerve injury, this complication continues to be problematic for patients and surgeons and frequent sources of medical Correspondence: Prof. Pietro Giorgio Calò. Via Gerolamo Fracastoro 33, Cagliari, Italia. Tel.: ; Fax: pgcalo@unica.it Copyright Società Editrice Universo (SEU) ISSN

2 e194 P.G. Calò et al. malpractice claims against surgeons, being the leading cause of medico-legal litigation after endocrine surgery (1, 10). Recurrent laryngeal nerve monitoring is an attempt to reduce the risk of nerve injury during thyroid surgery (1). Recent studies have shown that intraoperative neuromonitoring can aid recurrent laryngeal nerve identification (2). The reduction of frequency in recurrent laryngeal nerve injury and the value of predicting postoperative nerve function remain controversial (2, 4, 8). Many studies reported a high negative predictive value of % but a low and highly variable positive predictive value of 10-90% for intraoperative neuromonitoring (15). Recurrent laryngeal nerve monitoring is probably being used with increasing frequency in the United States during thyroidectomy, partly driven by the medico-legal system (18). However, the use of recurrent laryngeal nerve monitoring is associated with increased time of setup and increased cost of equipment (18). The aim of the present study was to evaluate the ability of this technique to predict the postoperative functional outcome and the potential role of intraoperative neuromonitoring in reducing the postoperative recurrent laryngeal nerve palsy rate by a comparison of the outcome of patients with intraoperative neuromonitoring with procedures that were performed by routine identification of recurrent laryngeal nerve only during thyroidectomy in a single endocrine surgical centre. Materials and Methods Between June 2007 and December 2011, 1693 consecutive patients underwent thyroidectomy by a single surgical team patients were submitted to total thyroidectomy, of which 201 with central lymphectomy, and 49 underwent completion total thyroidectomy were female and 345 male with a mean age of 52 years (range years). The final diagnosis were: 619 multinodular goiter (36.6%), 533 differentiated carcinoma (31.5%), 346 Hashimoto s thyroiditis (20.4%), 170 Graves disease (10.1%), 25 medullary carcinoma (1.4%). Histological diagnosis and surgical procedures are summarized in Table 1. In differentiated carcinoma, lymph node metastasis were found in 36 patients (6.75%) and micrometastasis in 12 (2.25%). Totally lymph node metastasis were observed in 48 patients (9.01%). All operations were performed by three experienced endocrine surgeons, with a standard Kocher s incision. All patients were submitted to preoperative and postoperative laryngoscopy. The recurrent laryngeal nerves were routinely identified by visualization and completely exposed. In 1540 of 1693 operations the relation between nerves and inferior thyroid artery and its branches was described. Recurrent laryngeal nerves were posterior to inferior thyroid artery in 85.44% of cases on the right side and 82.81% on the left side. Nerves were anterior in 5.4% of cases on the right and 5.01% of cases on the left. Nerves with extralaryngeal bifurcation were 2.38% on the right and 2.3% on the left, whilst course of the nerve between the branches of the artery was found in 5.78% on the right and 5.21% on the left. In 1% of cases a non recurrent nerve or a nerve with an extralaryngeal trifurcation was found. Intraoperative neuromonitoring was performed for 751 patients on the basis of the availability of the equipment. All these patients undergone general anesthesia and were intubated with Nerve Integrity Monitor Standard Reinforced Electromiography Endotracheal Tube (Medtronic Xomed ). The tube was placed with the middle of the blue-marked region (3 cm of the exposed electrodes) well in contact with the true vocal cords under direct laryngoscopy. When the monitor was well set up, we routinely checked the impedance of Table 1. Histological diagnosis and surgical procedures. Total Total Thyroidectomy Completion Thyroidectomy Total Thyroidectomy+ Lymphectomy Group A 942 (100%) 811 (86.09%) 40 (4.25%) 91 (9.66%) Multinodular goiter 358 (38%) 323 (34.29%) 20 (2.12%) 15 (1.59%) Differentiated carcinoma 278 (29.51%) 206 (21.87%) 7 (0.74%) 65 (6.9%) Hashimoto s thyroiditis 199 (21.13%) 182 (19.32%) 12 (1.27%) 5 (0.53%) Graves disease 93 (9.87%) 91 (9.66%) 1 (0.11%) 1 (0.11%) Medullary carcinoma 14 (1.49%) 9 (0.96%) 0 5 (0.53%) Group B 751 (100%) 632 (84.15%) 9 (1.2%) 110 (14.65%) Multinodular goiter 261 (34.75%) 236 (31.42%) 4 (0.53%) 21 (2.8%) Differentiated carcinoma 255 (33.95%) 172 (22.9%) 2 (0.27%) 81 (10.79%) Hashimoto s thyroiditis 147 (19.57%) 141 (18.77%) 2 (0.27%) 4 (0.53%) Graves disease 77 (10.25%) 76 (10.12%) 1 (0.13%) 0 Medullary carcinoma 11 (1.46%) 7 (0.93%) 0 4 (0.53%)

3 Neuromonitoring in thyroid surgery e195 electrodes. A Prass monopolar stimulation probe (Medtronic Xomed ) was used for nerve stimulation during thyroidectomy. EMG activity was recorded on an NIM-response 2.0 or 3.0 monitor (Medtronic Xomed ). No muscle relaxants were used after the skin flaps were elevated. The NIM device is used in various phases of the operation: at the beginning to the level corresponding to the vagus nerve to ensure that the monitoring system is working; after to the structure believed to be attributable to the inferior laryngeal nerve; at the end to the level of both the vagus and the recurrent nerve after the removal of thyroid and the complete hemostasis of the surgical field and is used for predicting the postoperative outcome. We compared patients who have had a monitoring with the NIM and patients who have undergone surgery with nerve visualization alone without this method. Patients in which NIM was not utilized (Group A) were 942, 157 males and 785 females. 811(86.1%) were submitted to total thyroidectomy, 40 (4.2%) to completion total thyroidectomy and 91 (9.66%) to a total thyroidectomy associated to a central lymphadenectomy. In this group diagnosis was benign multinodular goiter in 358 (38%) patients, differentiated carcinoma in 278 (29.5%), Hashimoto s thyroiditis in 199 (21.1%), Graves disease in 93 (9.9%), medullary carcinoma in 14 (1.5%). Patients in which NIM was utilized (group B) were 751, 188 male and 563 female. 632 (84.2%) were submitted to a total thyroidectomy, 9 (1.2%) to a completion total thyroidectomy and 110 (14.6%) to a total thyroidectomy associated to a central lymphadenectomy. In this group diagnosis was benign multinodular goiter in 261 (34.8%) patients, differentiated carcinoma in 255 (34%), Hashimoto s thyroiditis in 147 (19.6%), Graves disease in 77 (10.3%), medullary carcinoma in 11 (1.5%). Groups were homogeneous for characteristics of patients, diagnosis and type of surgery. We define transient an injury in which the motility of the vocal cords was recovered within 12 months after surgery. Results In group A 26 unilateral recurrent laryngeal nerve paralysis were observed (2.76%) of which 20 cases (2.12%) transients and 6 permanents (0.63%). Bilateral palsy was observed in 2 cases (0.21%); in one patient a vocal cord recovered completely three months after surgery. The patient, which has had a completion thyroidectomy, had a nerve palsy by previous surgery. In the other case, the patient required a tracheostomy and the lesion was permanent. Totally in group A 28 recurrent laryngeal nerve injuries were observed (2.97%), 21 (2.22%) transient and 7 (0.74%) permanent. In group B 19 unilateral recurrent laryngeal nerve paralysis were observed (2.53%), 13 (1.73%) transients and 6 (0.8%) permanents. In this group of patients a bilateral recurrent laryngeal palsy was observed (0.13%) requiring a tracheostomy. Totally in group B 20 recurrent laryngeal nerve injuries were observed (2.66%), in 14 cases (1.86%) transient and in 6 (0.8%) permanent. Differences between the two groups were not statistically significative (Tab. 2). In the NIM group we had 18 true positives, 725 true negatives, 6 false positives and 2 false negatives. Accuracy of NIM was 98.9%, positive predictive value 75%, negative predictive value 99.7%. Sensitivity was 90% and specificity 99.1% (Tab. 3). Recurrent laryngeal nerve paralysis in the two groups in relation to type of surgery and histology are reported in Table 2. Differences were not statistically significant. Discussion The incidence of recurrent laryngeal nerve palsy varies from less than 1 per cent to as high as 20 per cent (17, 19). In view of the percentages of recurrent lesions, reported in the literature, it would be desirable to perform an accurate diagnosis, through elastography and biomolecular investigations, in lesions in uncertain behavior in order to avoid a surgical procedure potentially at risk (20-22). Several factors influence the likelihood of injury to the nerve, including the underlying disease, the extent of resection, and the experience of the surgeon (6, 17, 23). In substernal goiters the incidence of recurrent laryngeal nerve lesions is significantly higher (24). Even experienced surgeons report inadvertent injury to the nerve and persistent palsy in about 1-2% of patients (19, 23, 25). The lymphadenectomy of the central compartment should be reserved for those patients with risk factors of recurrence or metastases were demonstrated when at the level of lateral cervical compartment preoperatively, due to increased morbidity in terms of recurrent injury and hypoparathyroidism (26-28). Causes of nerve palsy include: damage to the nerve s anatomic integrity, thermal lesions, excessive nerve skeletization, axon damage caused by excessive strain, edema, hematoma, and difficult tracheal intubation, and neuritis caused by scar tissue and viral neuritis (29). In 1938 Lahey dissected the recurrent laryngeal nerve in virtually every case; careful dissection decreased the number of injuries to the recurrent laryngeal nerves. This approach is accepted by most endocrine surgeons (17). Nerve identification in certain types of operations may be very difficult, these difficult cases include reoperations, cancer excisions, anatomic distortion with large tumors, anatomic anomalies, and a history of irradiation or inflammation (6, 17). Nerve monitoring has been developed to facilitate identification of the recurrent laryngeal nerve during thyroid surgery (8, 13, 17, 30). Neuromonitoring may provide guidance for the surgeon in difficult situation; these include anatomic variants, reoperations and surgery for malignant disease (30). There are a wide variety of techniques for both nerve monitoring that can be either continuous, such as with endotracheal electrodes, or discontinuous with a nerve stimulator (16). Despite the increasing popularity of the adoption of this technology, the various roles on intraoperative neuromonitoring in thyroid operations, in particular its impact in the avoidance of nerve injury or the reduction of the incidence of postoperative nerve palsy, remain doubtful (13, 16).

4 e196 P.G. Calò et al. Table 2. Recurrent laryngeal nerve paralysis in the two groups in relation to type of surgery and histology. Group A (942 patients) Group B (751 patients) P-value Recurrent Nerve Palsy 28 (2.97%) 20 (2.66%) p>0.05 Unilateral 26 (2.76%) 19 (2.53%) p>0.05 Bilateral 2 (0.21%) 1 (0.13%) p>0.05 Transient Nerve Palsy 21 (2.23%) 14 (1.86%) p>0.05 Total Thyroidectomy 15 (1.59%) 9 (1.20%) p>0.05 Completion thyroidectomy 2** (0.21%) 2 (0.27%) p>0.05 Total thyroidectomy + lymphectomy 4 (0.42%) 3 (0.40%) p>0.05 Multinodular goiter 7 (0.74%) 7 (0.93%) p>0.05 Differentiated carcinoma 8** (0.85%) 4 (0.53%) p>0.05 Hashimoto s thyroiditis 4 (0.42%) 2 (0.27%) p>0.05 Graves disease 2 (0.21%) 1 (0.13%) p>0.05 Medullary carcinoma Permanent Nerve Palsy 7 (0.74%) 6 (0.80%) p>0.05 Total Thyroidectomy 5* (0.53%) 5* (0.67%) p>0.05 Completion thyroidectomy 1 (0.11%) p>0.05 Total thyroidectomy + lymphectomy 1 (0.11%) 1 (0.13%) p>0.05 Multinodular goiter 2* (0.21%) 3 (0.40%) p>0.05 Differentiated carcinoma 3 (0.32%) 2* (0.27%) p>0.05 Hashimoto s thyroiditis 1 (0.11%) 1 (0.13%) p>0.05 Graves disease 1 (0.11%) p>0.05 Medullary carcinoma *One patient had bilateral nerve palsy ** One patient with prior monolateral nerve palsy had controlateral nerve palsy in completion thyroidectomy Table 3. Correlation of neuromonitoring results with postoperative outcomes. True positives 18 True negatives 725 False positives 6 False negatives 2 Accuracy 98.9% Positive predictive value 75% Negative predictive value 99.7% Sensitivity 90% Specificity 99.1% Several non-randomised studies demonstrated that an improved intra-operative recurrent laryngeal nerve identification rate with intraoperative neuromonitoring resulted in lower palsy rates than in historical patient cohorts with identification without neuromonitoring (9). A large multicentre study of 4382 patients found a statistically significant reduction in rates of transient and permanent recurrent laryngeal nerve paralysis with the use of intraoperative nerve monitoring in surgery for benign goiter; subgroup analysis of the same study found higher rates of injury when intraoperative nerve monitoring was

5 Neuromonitoring in thyroid surgery e197 used for total thyroidectomy (9, 16). A large single-centre study of 1000 consecutive nerve at risk found that continuous nerve monitoring offered absolutely no benefit in reducing the risk of nerve injury compared with the adoption of routine nerve identification, with no difference in both the temporary and the permanent nerve injury rates in the neuromonitored and control groups (13, 16). In the study of Dralle (4) intraoperative nerve monitoring did not lower the risk of nerve injury although failure to visually identify the nerve was associated with a higher rate of injury; nerve injury rates were also higher for lowvolume hospitals and low-volume surgeons and this fact was confirmed by others (2, 13, 17, 18). Other studies claim that the nerve monitoring is really only of value with high-risk surgery or in re-operative cases or recurrent goiters (16, 18), but an impractically large number of patients would be needed because of the rarity of nerve injury that is achieved in specialized centers (13). In our experience NIM did not lower the incidence of recurrent laryngeal nerve injuries. Our opinion is that NIM can improve results in difficult situation such as reoperative surgery or anatomic variations but the small number of cases does not allow a statistically significant evaluation. On the other hand difficult situation are not always predictable preoperatively. However NIM can be used to quickly facilitate initial localization of the nerve (18), particularly in difficult situation. It has been observed that an anatomically intact nerve does not always correlate with normal vocal fold function and that the absence of signal does not necessarily imply nerve dysfunction (18). In the study of Thomusch (9) a normal intraoperative neuromonitoring signal certainly excluded postoperative vocal cord dysfunction. Indirect neurostimulation of the recurrent laryngeal nerve via the vagus nerve was a significantly better predictor of postoperative dysfunction than direct stimulation and should be always performed to monitor the axonal excitability and mechanical intactness of the nerve. Direct stimulation of the nerve is exclusively recommended to detect the recurrent laryngeal nerve anatomy. After indirect stimulation of the nerve and a normal intraoperative neuromonitoring signal, the surgeon can extend the operation to the contralateral side, being reassured that the nerve on the resected side has a 99.6% chance of being intact (9). Our experience confirm the high accuracy (98.9%), sensitivity (90%) and specificity (99.1%) of this method; positive predictive value was 75% and negative predictive value 99.7% confirming the data reported in the literature. In some cases an absent or abnormal intraoperative neuromonitoring signal failed to predict reliably a postoperative palsy. This failure may be due to problems with the technical device, wrong application by the performing surgeon or continuous relaxation during the operation with paralysed vocal musculature, resulting in an absent signal. An absent or abnormal signal was a rare phenomenon, with an incidence of 2.7% after indirect recurrent laryngeal nerve stimulation. In cases of this rare event, % of the patients had postoperative vocal cord dysfunction (9). The use of these devices in thyroid surgery seems to be more expensive than the conventional technique. This is probably the major disadvantage of these devices (17) and particularly for this reason routine nerve monitoring is no cost-effective (16). The proponents of routine nerve monitoring claim that its use can still be justified for bilateral surgery stating that if nerve monitoring is undertaken after completion of one side of the procedure and there is evidence of impaired function, then the procedure should be abandoned to avoid the risk of bilateral damage and tracheostomy (2, 8, 9, 16, 30). Neuromonitoring provides comfort during thyroidectomy for identification, dissection, and control of recurrent laryngeal nerves; it can reduce the stress associated with nerve dissection when a surgeon operates on a patient with a challenging anatomy or in cases of extensive surgery (10). The main benefit of neuromonitoring is its ability to guide the surgeon in situations where the anatomic situation diverges from the normal situs (30). In our experience, the use of this technique has decreased the stress of the surgeon, facilitated the identification of the nerve and given greater safety in the prosecution of the most difficult operations. These effects, however, are difficult to quantify. However, recurrent laryngeal nerve paresis occurrence diminishes the quality of life for a few weeks to months after thyroid surgery; so any improvement in this field is welcome (2). Recurrent laryngeal nerve monitoring also allows for nerve function documentation before and after thyroid resection (by printing the electromyographic signal of evoked potentials), which is of great importance in an increasing number of litigation (2). In conclusion, the technique of intraoperative neuromonitoring in thyroid surgery is safe and reliable in excluding postoperative recurrent laryngeal nerve palsy; it has an high accuracy, specificity, sensitivity and negative predictive value. 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