Due to enormous progress in surgical techniques, despite the increase in the scope of resection from subtotal resection to total extracapsular excision of the thyroid gland, it was possible to significantly reduce the number of intraoperative lesions of the recurrent laryngeal nerves, mainly due to their routine visualization. However, it is still not possible to completely eliminate this postoperative complication. In 1938, Lahey observed that careful preparation and visualization of the recurrent laryngeal nerves dramatically reduced the amount of damage1. In the following years, these findings were confirmed by several other scientists, including Riddell2. Despite the surgical technique described above, there are certain circumstances in which nerve damage may occur. Thomusch et al. showed that routine identification may be an independent, significant risk factor for damage of laryngeal nerve3. However, most researchers have demonstrated a significant reduction in the risk of injuries to the nerve structures after visualization4–6, hence the intraoperative visualization of the recurrent laryngeal nerves has become the gold standard in thyroid gland surgery. There are many risk factors for damage to the recurrent laryngeal nerves, such as the experience of the medical facility, being of female sex, a recurrent goiter, a retrosternal goiter and neoplastic diseases 7.
The mechanisms of nerve damage include partial or total transection, traction, compression, contusion, burn, clipping and ischemia8. Persistent palsy lasting more than 6–12 months is caused by cutting, ligation or cauterization of the nerve9.
In this study, the percentage of postoperative complications in the form of recurrent laryngeal nerve palsy was (4.9% vs 4,9%) for unilateral damage, as well as for bilateral damage (0.27% vs 0%) in the study and control groups, respectively. Most of the palsy incidents were persistent (3.9% vs. 4.9%). It should be emphasized that the study involved patients who had undergone total thyroidectomy due to a benign nodular goiter, hence the percentage of nerve damage is greater than in the case of less invasive surgeries, e.g. lobectomy or subtotal resection and lower than in the case of surgery due to recurrent, a retrosternal goiter or neoplastic diseases. In the literature, the frequency of transient recurrent laryngeal nerve palsy is 4.1% − 13.6%, whilst for persistent, 2.3% − 9% 10–12.
In unilateral tense palsy, the patient may experience only inspiratory dyspnea, and the patient's voice may remain voiced. In flaccid palsy, dyspnea is exercise-induced and the voice becomes aphonic. The most dangerous is bilateral palsy of the vocal folds, which may cause obstruction of the upper respiratory tract, requiring tracheostomy if the vocal folds are in the paramedian position. Occasionally, unilateral vocal fold palsy may be clinically silent and the only examination to determine the complication is indirect laryngoscopy. All patients operated on at the Clinic of General, Oncological and Endocrinological Surgery of Provincial Polyclinic Hospital in Kielce are routinely subjected to laryngoscopic examinations on the first or second day after surgery. In the event of a vocal fold palsy, it may remain in a paramedian, intermediary or lateral position.
In the studied group of patients, the palsy of the recurrent laryngeal nerve occurred in 10 patients (4.9%), including 9 patients (4.4%) unilaterally and 1 patient (0.5%) bilaterally. The right vocal fold was paralyzed in 6 cases (2.9%), and the left vocal fold in 5 cases (2.4%). All paralyzed vocal folds were in the intermediary position.
In the control group, the palsy of the recurrent laryngeal nerve occurred in 8 patients (4.9%) and it was unilateral in each case. The right vocal fold was paralyzed in 5 cases (3.1%), and the left vocal fold in 3 cases (1.9%). The paralyzed right vocal fold in 4 patients (2.5%) was in the intermediary position and in 1 patient (0.6%) in the lateral position. The paralyzed left vocal fold was in the intermediary position in each case.
A follow-up study performed 2 to 10 years after the surgery of total thyroidectomy included 153 patients from the study group (74.6%) and 122 (75.3%) patients from the control group. All patients who had vocal fold palsy in the postoperative examination reported for a follow-up examination.
In the follow-up laryngoscopic examination in the study group, the symptoms of vocal fold paralysis were found in 2 patients (0.99%), including one with bilateral paralysis of the vocal folds. Thus, persistent paralysis occurred in 8 (3.9%) patients from the study group.
In the control group, in all 8 patients (4.9%), the palsy became persistent.
In this study, the high level of patients with postoperative hypocalcemia, statistically significantly higher in the study group (62.4% vs. 32.1%), also draws attention. The decreased level of parathyroid hormone (PTH < 15 pg / ml) in the postoperative period occurred in 25.6% of patients in the study group and 28.6% in the control group. There was no significant difference in this aspect. This percentage is similar to the results presented by other authors13,14. Low serum PTH levels are common after total thyroidectomy, but the vast majority of patients will experience recovery of parathyroid function within 2 months after surgery. Only some patients undergoing total thyroidectomy develop permanent hypoparathyroidism, determined by serum PTH levels < 10 pg / ml or the need to continue supplementation with calcium or calcitriol to prevent symptoms of hypocalcemia one year after surgery13. It should be emphasized that no histopathological specimens showed an accidental removal of parathyroid glands.
Injury to the recurrent laryngeal nerves is undoubtedly the most serious complication of thyroidectomy. It reduces the quality of life, but can also be a direct threat to it. Due to this threat, a way to avoid this complication has been sought for years. Feinstein first mentioned the use of electromyography in diagnosing disorders of the laryngeal nerves in 1946. At the end of the 1960s, Shedd and Durham made the first attempts to use an electric neurostimulator in humans to identify the recurrent laryngeal nerves. Therefore, in addition to the routine visualization of nerves and the appropriate knowledge of anatomy and surgical technique, for several decades we have had a new technique for intraoperative nerve monitoring. In recent years, this technique has been refined and the method has been standardized by the International Research Group on Neuromonitoring in Thyroid and Parathyroid Surgery15. Neuromonitoring has been used in the Clinic of General, Oncological and Endocrinological Surgery of Provincial Polyclinic Hospital in Kielce since 2011. Since 2017, all thyroid surgeries performed at this Clinic have been performed with the use of IONM.
This study compares the group of patients undergoing surgery of total thyroidectomy due to a nodular goiter with the use of intermittent intraoperative neuromonitoring, with the group of patients operated on for the same reason, only with macroscopic visualization of nerves, without the use of intraoperative neuromonitoring. Surgical procedures in all patients were performed by one very experienced surgeon with over 30 years of work experience, a specialist in general and oncological surgery. All patients were euthyroid, and did not have any disorders in the mobility of the vocal folds in the preoperative laryngoscopic examination.
There was no statistically significant difference p = 0.979 between the study group and the control group in the incidence of recurrent laryngeal nerve damage (4.9% [10/205] vs 4.9% [8/162]). It is worth noting that according to the research conducted by Dralle, neuromonitoring does not reduce the amount of damage to the laryngeal nerves in surgical procedures performed by an experienced surgeon, which is in accordance with the findings of this research study16.
The results of the research are consistent with the results presented in the literature. Higgins et al., in a meta-analysis evaluating 64,699 recurrent laryngeal nerves, showed no statistically significant difference in the frequency of vocal fold palsy after intraoperative neuromonitoring (3.52% [IONM] vs. 3.12%)17. Pisanu et al. analyzed 23,512 patients with a total of 35,513 recurrent laryngeal nerves, obtaining a score of 3.47% of recurrent laryngeal nerve injuries in the group with IONM, compared to 3.67% in the group with macroscopic visualization, which did not show a significant difference18. Zheng et al. analyzed 36,487 recurrent laryngeal nerves. In their study, the frequency of vocal fold palsy in patients operated with neuromonitoring was 3.37%, and in patients without IONM, it was 3.76% 19. Another meta-analysis conducted by Lombardi included 38,820 nerves, and the frequency of vocal fold palsy was 0.73% for the IONM group and 0.89% for the non-IONM20 group, respectively. Similar results, showing no statistically significant difference in the prevention of laryngeal nerve damage in the case of intraoperative neuromonitoring, were obtained in meta-analyzes by other authors, e.g. Sanabria and Malik21,22.
Contradictory results, showing a significant benefit from the use of intraoperative neuromonitoring were presented by Wong et al. They analyzed only the surgical procedures of a recurrent goiter, retrosternal goiter and thyroid malignant neoplasms23. Yang and Bergenfelz, in independent studies, showed a statistically significant difference in the use of IONM to prevent transient vocal fold palsy. They did not observe similar results for persistent palsy24,25. Barczyński et al. demonstrated that the use of intraoperative neuromonitoring not only reduces the amount of damage to the recurrent laryngeal nerves, but also reduces the amount of residual gland tissue left, which is of particular importance in the case of neoplastic diseases26.
Currently, it is recommended to use intraoperative neuromonitoring in high-risk surgical procedures, including a recurrent goiter, toxic goiter, retrosternal goiter, malignant neoplasms, Hashimoto's disease and Graves' disease. In thyroid gland reoperations, the presence of scar tissue and altered anatomy make preparation and nerves identification difficult. The risk of palsy of the vocal folds in reoperation is even 4.6–10.4 times higher than in the case of primary surgery 27. In the case of surgeries of malignant thyroid neoplasms, nerve damage is more common during cervical lymphadenectomy28. In this case, the risk increases even 5 times27. Studies by some authors indicate a reduction in the number of RLN palsy after IONM application in high-risk surgical procedures29–31. Other authors have not shown such dependencies 32–34.
In this study, the use of intraoperative neuromonitoring (IONM) was carried out in accordance with the guidelines of the International Research Group on Neuromonitoring. The C2-Nerve Monitor by INOMED was used. The highest obtained peak-to-peak amplitude Vpp (mV) in a given stimulation was assessed. Intraoperative loss of neuromonitoring signal was defined as: no EMG signal after stimulation of the recurrent laryngeal nerve and vagus nerve, EMG signal amplitude below 100 µV after stimulation with 2.5 mA for the recurrent laryngeal nerve and 5 mA for the vagus nerve.
Intraoperative loss of neuromonitoring signal was found in 13 cases, out of which in 6 cases it was true and corresponded to paresis of the vocal fold, and in 7 cases it was false, as the mobility of the vocal fold was preserved. Among 192 cases of preserved neuromonitoring signal after thyroid lobe excision, in 188 cases the mobility of the vocal folds was normal, and in 4 cases paresis of the vocal fold was found. Hence, the negative predictive value of the neuromonitoring method was 97.9 and the positive 46.2. Thus, neuromonitoring was characterized by high specificity, but low sensitivity. This is consistent with the results of studies available in the literature16,32.
It is worth noting that the absent IONM signal did not always correlate with postoperative vocal fold paresis. This was the case in 7 cases (3.41%). In the case of a false positive, the problems with the device on both the stimulating and receiving sides, the lack of a dry operating site and the use of neuromuscular blocking agents should be considered. All situations related to the lack or loss of the signal were checked for the correct placement of the receiving electrode on the tracheal tube in relation to the vocal folds, the correct operation of the device and appropriate stimulation conditions in the operating site.
The most threatening situation is obtaining the correct signal from neuromonitoring with clinical palsy of the vocal folds in the postoperative period. Such false negative results were obtained in 4 cases (1.95%). This situation may occur in the case of stimulation distal from the site of the lesion of the recurrent laryngeal nerve, damage that occurs after the last stimulation, and delayed neuropraxia caused most often by edema 15.
In this study, the analysis of the intraoperative neuromonitoring signal was based on the values of the peak-to-peak amplitude. The mean value of this amplitude obtained after stimulation of the left vagus nerve before lobe resection (0.729 mV) was higher than after lobe resection (0.631 mV). For the left recurrent laryngeal nerve before the lobe resection, the mean values (1.059 mV) were higher than those obtained after the lobe resection (0.960 mV). On the right side, the mean value of the peak-to-peak amplitude of the vagus nerve before lobe resection was higher (0.709 mV) than that obtained after lobe resection (0.510 mV). For the right recurrent laryngeal nerve before the lobe resection, the mean value (1.027 mV) was higher than that obtained after the lobe resection (0.919 mV). The mean peak-to-peak amplitude values were higher for recurrent laryngeal nerves on both sides, and higher for the left vagus and laryngeal nerves. Other research results were presented by Lorenz et al. 35. They obtained higher peak-to-peak amplitude values for the vagus nerves and higher values for both the vagus and the reccurent laryngeal nerve on the right side35. Ozemir et al. obtained lower peak-to-peak amplitude values in diabetic patients, which may indicate the development of diabetic neuropathy in recurrent laryngeal nerves, similar to other peripheral nerves 36.
The differences in peak-to-peak amplitude values among patients may be due to contamination of the operating site, varying degrees of probe-nerve pressure, the presence of surrounding tissues, a different degree of adhesion of the receiving electrode to the vocal folds, or changes in the temperature of the surrounding of the nerve itself after fluid application.
In this study, the duration of the surgery with the use of neuromonitoring was significantly (p < 0.001) longer in the study group, and amounted to an average of 96.5 minutes, and 83.2 minutes in the control group. It was connected with the necessity to visualize the vagus nerve running in the sheath of the jugular vessels. Moreover, the time of the procedure was extended by the very use of neuromonitoring (nerve stimulation and the need to record it each time by using the appropriate buttons on the device). The record was taken by an OR nurse, who did not have contact with the patient and was not always in the operating room at that moment. Other authors similarly showed in their research a longer duration of surgery associated with the use of IONM. e. g. Gremillion.37. There were no significant differences (p = 0.771) in the total hospitalization time of the patients, which was 4.2 days on average. The use of IONM undoubtedly increases the costs of surgery 37,38.
In view of such ambiguous results of research on the improvement of the results of vocal fold palsy surgery with the use of intraoperative neuromonitoring, the study by Chan et al. seems interesting 39 . They noted that the main reason members of the American Society of Endocrine Surgeons use IONM was to protect themselves from legal liability 39 . 150,000 thyroid surgeries are performed annually in the United States of America. In the years 1995–2015, the number of court cases concerning thyroid gland surgery amounted to 128 cases. More than half of the lawsuits were related to a postoperative complication in the form of damage to the recurrent laryngeal nerve. The total cost of hearings and compensation payments amounted to over US $ 30 million. When analyzing the expert opinions, it should be emphasized that the consent obtained from the patient for the surgery must contain information about possible complications in the form of unilateral or bilateral damage to the recurrent laryngeal nerves. It is also necessary to include information on the visualization of the laryngeal nerves in the postoperative report. The issues of the lack of use of intraoperative neuromonitoring were raised, although in the United States of America, as in Poland, it is not a routine procedure used in thyroid surgery 40 .
Summarizing the results of the study, it should be stated that the use of intraoperative neuromonitoring did not reduce the frequency of recurrent laryngeal nerve injuries, compared to macroscopic visualization. For these reasons, it is understandable that IONM is not required to be included in standard medical care and that surgical departments are not required to be equipped with this device. The recent introduction of continuous neuromonitoring may be a significant step forward as it allows the surgeon to react before irreversible nerve damage occurs41, contrary to intermittent neuromonitoring, which informs us about impaired nerve function, usually after the damage 42. However, intermittent neuromonitoring, which has been in use for years, has made it possible for medical personnel to prepare for a new method of continuous monitoring of the recurrent laryngeal nerves.