Safety of intraoperative neuromonitoring

The identification of laryngeal nerves during thyroidectomy procedures is considered the safest method to prevent variations in the motility of the vocal cords; in fact, since 1938, when Lahey suggested the method of visualization and dissection of the inferior laryngeal nerve before the glandular dissection, this strategy has brought about a significant reduction in the percentage of recurring damages (1). Moreover, the only visualization of laryngeal nerves, in most situations, is not enough to ensure the result. In fact, anatomical wholeness does not always ensure the functional integrity (2). To respond to this need, in the last two decades, various devices have been used for intraoperative functional monitoring of the laryngeal nerves. These devices electrically stimulate the nerves, so as to conduct the signal up to the innervated muscles. The resulting muscle activity is then turned into acoustic and electromyographic signals; the information of neurophysiological signals can then be used for prognostic and medico legal purposes (3,4). Several techniques have been reported in the literature. Electromyographic signal recording (EMG) may include the use of needle electrodes inserted into the vocal cords endoscopically, the use of electrodes inserted through the cricothyroid ligament in the homolateral vocal muscle during surgical access or the use of surface electrodes endotracheal that can record the potential.

For several reasons, including non-invasiveness, safety, utility, ease of use and even the full market availability, systems with surface electrodes have found widespread and currently represent the most common format for monitoring equipment (5). The most recent acquisition is the continuous vagal monitoring, which requires the placement of electrodes even at the level of the vagus nerve, its continuous stimulation and recording of nerve signals, guaranteeing a “real-time” monitoring of the effects of manipulations during all phases of the surgery (6). Neuromonitoring techniques are presently believed to be safe methods; however, although infrequently, some complications and side effects related to the use of these methods have been reported. The complications described may occur from displaced electrodes, from the obstruction of the endotracheal tube, from the drugs used for anesthesia and from the undesirable effects of the stimulation on the nervous structures and at the systemic level.

Complications related to the electrodes

The direct and cruent placement of the needle endolaryngeal electrodes can be complex and requires experienced operators; in addition, the needle electrodes, in general, can be displaced during muscle contraction, producing an EMG signal unstable. For surface contact electrodes instead—integrated into dedicated endotracheal tubes or externally applied to standard tubes—the problems of functioning may depend on the migration of the endolaryngeal tube or accidental detachment, so as to reduce the sensitivity of the method (7,8). In order to check the correct positioning of the electrodes, the impedance measurement can be used (9).

As for the placement of the tube, two aspects can be noticed: first, it is important that anesthesiologist and surgeon both offer help in the final check of the endotracheal tube; secondly, it is advisable that those checks are done after the patient has been put in the final position, not in a neutral position. The best option available for checking the correct placement of the tube is laryngoscopy. The anesthesiologist or the surgeon can visualize the glottis, after positioning the patient, by direct or fiberoptical laryngoscopy. The repetition of laryngoscopy after the definitive positioning of the patient is the most accurate method for evaluating the correct position of the tube.

Some authors believe that the needle electrodes in comparison with the superficial ones, while offering more information, can cause tearing of the vocal cords, bruises, infections, rupture of the Needles or damage to the endotracheal tube cuff (7,10). In a multicentre study of 8,534 patients, 112 (1.3%) damage to the cuff was seen after inserting needle electrodes into vocal muscle. This complication, which did not compromise the surgery, was not associated with wound infections, postoperative bleeding or increased postoperative pulmonary morbidity. In addition, damage to the cuff can be avoided by positioning the endotracheal tube more distally. In this study, therefore, no major complications related to the method have been shown (11). However, although reusable and cost-effective, the needle electrodes are less commonly used, because they represent a more invasive and more complicated method than the method which involves the use of dedicated contact surface electrodes.

Complications from tube obstruction

In a recent paper, Oysu and Demir described two cases of obstruction of an endotracheal tube studied for intraoperative neuromonitoring: at the 35th and 40th minutes of general anesthesia there was an abrupt and complete arrest of the ventilation (12). Checking the presidium on an animal trachea, it was noticed that the hyperinsufflation made the cuff herniate, causing obstruction of the tip of the tube. A 25-mm displacement outward contributed to this cuff herniation. In this case the collaboration of the anesthesiologist is fundamental: the endotracheal tube must be inserted considering the variations that involves the repositioning of the neck for the intervention, from the neutral position to the complete extension (13). The authors concluded that to solve the problem it was sufficient to slightly deflate the cuff and that, generally, the latter should be inflated to the minimum volume required; obviously, the operating team must pay the utmost attention to the stability of the endotracheal tube.

It may be said that cases of tube obstruction and tube misplacement are uncommon in this procedure and they can be managed with good medical practice by the anesthesiologist.

Complications related to anesthetic drugs

A fascinating aspect about complications of intraoperative neuromonitoring is that concerning the type of drugs to be used for the induction of anesthesia. In fact, the use of drugs that cause a neuromuscular block (neuromuscular blocking agents, NMBA), to make endotracheal intubation easier, can compromise the proper functioning of the method; for this reason, the usage of these drugs is not recommended during neuromonitoring. However, keeping in mind that the mechanical intubation and extubation procedures can themselves cause cord damage (14,15), some studies claim that the non-administration of NMBA, to make intubation easier, in adult patients is associated with a high number of local effects and laryngeal injuries (16). Nevertheless, in pediatric patients, intubation without the use of these drugs is common (17). In fact, by associating appropriate doses of propofol to an opioid, laryngeal relaxation and suppression of reflexes are sufficient to obtain a non-complicated intubation (18). In a recent retrospective study Birkholz et al. compared laryngeal morbidity after thyroid surgery, associated with neuromonitoring in intubated patients, with the use or non-use of NMBA, without statistically significant differences between the two patient groups (19). Therefore, anesthesia induction is recommended with the use of NMBA with a short half-life, able to perform well only in the initial stage of intubation and in order to be disposed during the central stage of the surgery, when neuromonitoring is used rather than.

Furthermore, the availability of new drugs (such as Sugammadex) and the development of an anesthesiological technique that is increasingly suited to these needs could guarantee a successful tube position with no complications.

Complications of electrical stimulation

Scholars are debate on the safety of direct electrical stimulation of the nerve and on what the optimal intensity, frequency and amplitude are. With the stimulation of the laryngeal or vagus nerves a biphasic wave is obtained; in normal language the amplitude of the wave ranges from 100 to 800 µV, but during the surgery, the amplitude may change due to the presence in the operating field of fluids or blood, of tissues that cover the nerve, due to inadequate probe-nerve contact, due to the temperature or to the position of the electrodes (20). The threshold indicates the minimum electrical stimulus capable of producing an EMG response. The vagus nerve and laryngeal nerve are activated roughly between 0.3 and 0.4 mA, when the nerve is dry and exposed. The maximum stimulation of all the fibers is gained at 0.8 mA; beyond this threshold, the greatest stimulation does not correspond to a greater response to the EMG. As a consequence, the stimulus threshold for evaluating nerve function is 1 mA in many cases, while 2 mA stimuli are used for area mapping, where this technique is used for recurring nerve research and recognition (10). In a recent study, Choby et al. wanted to find the minimum threshold of stimulation of the recurrent nerve before and after thyroidectomy, using contact surface electrodes for the neuromonitoring. The actual results show that the average minimum intensity needed to stimulate the recurrent laryngeal nerve was 0.50 mA before thyroidectomy, whereas it was 0.47 mA after, with an average difference of 0.03 mA. None of these values was significantly related to postoperative cord palsy (21). This contrast in stimulation thresholds (22), can be explained by the reduction of pressure on the nerve, which can be stimulated with lower intensity of the current. In this respect, Wu et al. performed a study on pigs whose vagus and laryngeal nerves were stimulated with currents of 0.1 to 1.0 mA (with increases of 0.1 mA) and subsequently with stimuli of 1.5, 2.0, 2.5 and 3.0 mA. The stimulus lasted 10 µs and was repeated 4 times/second (4 Hz) for 10 minutes, with an interval of 2 seconds every minute to record the EMG signal. After 10 minutes the amplitude of the EMG signal was not significantly lower than that recorded at the beginning and the maximum amplitude was obtained with stimuli <1 mA, both for the recurrent nerve and for the vagus nerve (23). Therefore, the authors concluded that minimum currents (about 1 mA) are sufficient to generate the maximum response to the EMG and can be used to reduce the risks of nerve damage and cardiopulmonary side effects. Systemic side effects of nerve stimulation have generated great interest, mostly since continuous vagal monitoring has been introduced. For many years, the stimulation of the vagus nerve has been used to treat depression and epilepsy refractory to drugs. While long-term stimulations (weeks or months) seem to elicit voice and cough abnormalities, short-term ones are not usually related to complications (24-26). Although vagal therapeutic stimulation is conventionally recognised as a safe treatment, there have been cases in which it has resulted in cardiac arrhythmias and severe haemodynamic changes (27,28). In a 2004 publication, Ali et al. have described 3 cases of cardiac arrest in patients with refractory epilepsy who underwent a vagal stimulation implant, in the perioperative time, during the initial device test. For 6–15 seconds, these patients had a atrioventricular block, completely self-resolving resolved and compatible with the stimulation of the left vagus nerve (29). It was assumed that the causes of this phenomenon may have been represented by the centrifugal direct activation of the parasympathetic system with an inhibitory effect on the atrioventricular node, or by the centripetal activation of afferent pathways of the left vagus nerve, with effect on other central systems that affect heart rhythm. To establish the safety of vagal stimulation during neuromonitoring, Friedrich et al. have recently completed a non-randomized prospective study. Changes in heart rhythm and immunomodulatory effects induced by vagal stimulation were analyzed in 22 patients (30). In this study, in spite of a significant increase in vagal tone, no haemodynamic abnormalities were observed and no decrease in plasma levels of cytokines was observed or TNF-α.

Certainly, a correct preoperative evaluation and proper intraoperative monitoring could prevent side effects and minimize the risk of dramatic events at the cardiovascular level.

In conclusion, intraoperative neuromonitoring of the superior and inferior laryngeal nerves, even with vagal stimulation, can be considered a safe method for the complications related to it.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the Guest Editors (Marcin Barczyński, Hui Sun and Xiaoli Liu) for the series “The Protection and Monitoring of Superior and Recurrent Laryngeal Nerve in Thyroid and Parathyroid Surgery” published in Annals of Thyroid. The article has undergone external peer review.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/aot.2019.04.01). The series “The Protection and Monitoring of Superior and Recurrent Laryngeal Nerve in Thyroid and Parathyroid Surgery” was commissioned by the editorial office without any funding or sponsorship. Gianlorenzo Dionigi serves as an unpaid editorial board member of Annals of Thyroid from Mar 2017 to June 2021. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the manuscript and ensure that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Lahey FH, Hoover WB. Injuries to the recurrent laryngeal nerve in thyroid operations: their management and avoidance. Ann Surg 1938;108:545-62. [Crossref] [PubMed]
2. Dralle H, Sekulla C, Haerting J, et al. Risk factors of paralysis and functional outcome after recurrent laryngeal nerve monitoring in thyroid surgery. Surgery 2004;136:1310-22. [Crossref] [PubMed]
3. Randolph GW, Dralle HInternational Intraoperative Monitoring Study Group, et al. Electrophysiologic recurrent laryngeal nerve monitoring during thyroid and parathyroid surgery: international standards guideline statement. Laryngoscope 2011;121:S1-16. [Crossref] [PubMed]
4. Dionigi G, Barczynski M, Chiang FY, et al. Why monitor the recurrent laryngeal nerve in thyroid surgery? J Endocrinol Invest 2010;33:819-22. [Crossref] [PubMed]
5. Dralle H, Sekulla C, Lorenz K, et al. Intraoperative monitoring of the recurrent laryngeal nerve in thyroid surgery. World J Surg 2008;32:1358-66. [Crossref] [PubMed]
6. Sanabria A, Silver CE, Suárez C, et al. Neuromonitoring of the laryngeal nerves in thyroid surgery: a critical appraisal of the literature. Eur Arch Otorhinolaryngol 2013;270:2383-95. [Crossref] [PubMed]
7. Johnson S, Goldenberg D. Intraoperative monitoring of the recurrent laryngeal nerve during revision thyroid surgery. Otolaryngol Clin North Am 2008;41:1147-54. [Crossref] [PubMed]
8. Hermann M. Hellebart, Freissmuth M. Neuromonitoring in thyroid surgery: prospective evaluation of intraoperative electrophysiological responses for the prediction of recurrent laryngeal nerve injury. Ann Surg 2004;240:9-17. [Crossref] [PubMed]
9. Chan WF, Lo CY. Pitfalls of intraoperative neuromonitoring for predicting postoperative recurrent laryngeal nerve function during thyroidectomy. World J Surg 2006;30:806-12. [Crossref] [PubMed]
10. Domosławski P, Lukieńczuk T, Kaliszewski K, et al. Safety and current achievements in thyroid surgery with neuromonitoring. Adv Clin Exp Med 2013;22:125-30. [PubMed]
11. Thomusch O, Sekulla C, Machens A, et al. Validity of intra-operative neuromonitoring signals in thyroid surgery. Langenbecks Arch Surg 2004;389:499-503. [Crossref] [PubMed]
12. Oysu C, Demir K. Life-threatening complication of recurrent laryngeal nerve monitoring with EMG reinforced silicone ETT. J Craniofac Surg 2011;22:2419-21. [Crossref] [PubMed]
13. Yap SJ, Morris RW, Pybus DA. Alterations in endotracheal tube position during general anesthesia. Anaesth Intensive Care 1994;22:586-8. [Crossref] [PubMed]
14. Paulsen FP, Rudert HH, Tillmann BN. New insights into the pathomechanism of postintubation arytenoid subluxation. Anesthesiology 1999;91:659-66. [Crossref] [PubMed]
15. Echternach M, Maurer CA, Mencke T, et al. Laryngeal complications after thyroidectomy: is it always the surgeon? Arch Surg 2009;144:149-53; discussion 153. Erratum in: Arch Surg 2009;144:595 Arch Surg 2009;144:412. Maurer, Christoph [corrected to Maurer, Christoph A]. [Crossref] [PubMed]
16. Sneyd JR, O’Sullivan E. Tracheal intubation without neuromuscular blocking agents: is there any point? Br J Anaesth 2010;104:535-7. [Crossref] [PubMed]
17. Shaikh SI, Bellagali VP. Tracheal intubation without neuromuscular block in children. Indian J Anaesth 2010;54:29-34. [Crossref] [PubMed]
18. Erhan E, Ugur G, Alper I, et al. Tracheal intubation without muscle relaxants: remifentanil or alfentanil in combination with propofol. Eur J Anaesthesiol 2003;20:37-43. [Crossref] [PubMed]
19. Birkholz T, Irouschek A, Saalfrank-Schardt C, et al. Laryngeal morbidity after intubation with or without neuromuscular block in thyroid surgery using recurrent laryngeal nerve monitoring. Auris Nasus Larynx 2012;39:288-93. [Crossref] [PubMed]
20. Wu CW, Dionigi G, Sun H, et al. Intraoperative neuromonitoring for the early detection and prevention of RLN traction injury in thyroid surgery: a porcine model. Surgery 2014;155:329-39. [Crossref] [PubMed]
21. Choby G, Hollenbeak CS, Johnson S, et al. Surface electrode recurrent laryngeal nerve monitoring during thyroid surgery: normative values. J Clin Neurophysiol 2010;27:34-7. [Crossref] [PubMed]
22. Marcus B, Edwards B, Yoo S, et al. Recurrent laryngeal nerve monitoring in thyroid and parathyroid surgery: the University of Michigan experience. Laryngoscope 2003;113:356-61. [Crossref] [PubMed]
23. Wu CW, Lu IC, Randolph GW, et al. Investigation of optimal intensity and safety of electrical nerve stimulation during intraoperative neuromonitoring of the recurrent laryngeal nerve: a prospective porcine model. Head Neck 2010;32:1295-301. [Crossref] [PubMed]
24. Wheless JW, Baumgartner J. Vagus nerve stimulation therapy. Drugs Today (Barc) 2004;40:501-15. [Crossref] [PubMed]
25. Schachter SC, Wheless JW. The evolving place of vagus nerve stimulation therapy. Neurology 2002;59:S1-2. [Crossref] [PubMed]
26. Rychlicki F, Zamponi N, Trignani R, et al. Vagus nerve stimulation: clinical experience in drug resistant pediatric epileptic patients. Seizure 2006;15:483-90. [Crossref] [PubMed]
27. Ben-Menachem E. Vagus nerve stimulation, side effects, and long-term safety. J Clin Neurophysiol 2001;18:415-8. [Crossref] [PubMed]
28. Annegers JF, Coan SP, Hauser WA, et al. Epilepsy, vagal nerve stimulation by the NCP system, all-cause mortality, and sudden, unexpected, unexplained death. Epilepsia 2000;41:549-53. [Crossref] [PubMed]
29. Ali II, Pirzada NA, Kanjwal Y, et al. Complete heart block with ventricular asystole during left vagus nerve stimulation for epilepsy. Epilepsy Behav 2004;5:768-71. [Crossref] [PubMed]
30. Friedrich C, Ulmer C, Rieber F, et al. Safety analysis of vagal nerve stimulation for continuous nerve monitoring during thyroid surgery. Laryngoscope 2012;122:1979-87. [Crossref] [PubMed]