Evolution of Intra-operative Nerve Monitoring as a revolution in Thyroid Surgery: A PRISMA compliant Systematic Review

Haleema Sadia; Hira Ashraf; Talat Waseem

Abstract

Introduction: Intra-operative nerve monitoring (IONM) has matured into a powerful risk minimisation tool in the past two decades. Meta-analysis and articles, most of which were limited by poor study designs, have failed to demonstrate superiority of IONM over visual identification of RLN during thyroidectomy in the absence of IONM. Continuous intra-operative nerve monitoring (C-IONM) is superior to intermittent intra-operative nerve monitoring (I-IONM) due to its real time electromyographic tracings during surgery and thus reducing the RLN palsy which in turn decreases vocal cord paralysis post-operatively. C-IONM urges surgeons to reverse the harmful surgical manoeuvres to avoid the permanent traction related nerve injury; it also forms an integral part in the surgical concept of staged thyroidectomy.

Objective: Objective of this review article is to shed some light on IONM technique, discuss its pros and cons and detailed review of its two types and how it is taking the neck surgery by storm, also how it’s equipping young surgeons with confidence by honing their surgical skills.

Methods: This review article is written according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Literature search was done through PubMed, Google scholar and ERIC. Search terms were: “intra-operative neuromonitoring” AND “continuous intro-operative nerve monitoring” or “intermittent intro-operative nerve monitoring” AND “recurrent laryngeal nerve” or “RLN” AND “thyroid gland” or “thyroidectomy”. 433 articles were identified out of which 41 were used for thematic analysis.

Results: In recent years, the volume of thyroid procedures are expanding, so did risk minimization measures protecting RLN, although the incidence of RLN palsy is low in experienced hands, it results in permanent post-operative compromise of voice quality that may diminish the patient’s quality of life and trigger litigation for malpractice for the surgeon. IONM especially C-IONM helps decreasing the incidence of imminent RLN palsy by providing the real-time neuromonitoring intra-operatively, it also helps in perfecting the surgical skills of young surgeons. Proper documentation of IONM helps in case of litigation as well.

Conclusion: This review article concludes that IONM could reduce the incidence of total, transient and permanent RLN injury compared with conventional visual identification of RLN. IONM has increased the precision in signaling impending nerve injury early on and in correctly predicting post-operative vocal cord palsy. This enables surgical teams to reflect on timely and improve their surgical skills.

Keywords: Intra-operative nerve monitoring (IONM), recurrent laryngeal nerve (RLN), recurrent laryngeal nerve palsy, thyroidectomy, continuous intro-operative nerve monitoring (c-IONM), intermittent intro-operative nerve monitoring (I-IONM).

Evolution of Intr a- operative NerveM onitoring as a R evolution in T hyroid S urgery

A PRISMA C ompliant Systematic Literature Review .

Authors:

Haleema Sadia MBBS (Department of Surgery, Shalamar Medical & Dental College, Lahore, Pakistan, haleemasadia707@gmail.com )

Hira Ashraf MBBS ( Department of Surgery, Shalamar Medical & Dental College, Lahore, Pakistan , hiraashraf_5@hotmail.com )

TalatWaseem FRCS Eng, FACS (Department of Surgery, Shalamar Medical & Dental College, Lahore, Pakistan, twaseem@gmail.com )

Corresponding Author:

Dr. TalatWaseem FRCS Eng, FACS

Consultant Surgeon

Shalamar Medical & Dental College, Lahore

( twaseem@gmail.com )

Discloser: All authors disclosed have no financial or personal relationships with individuals or organizations that could inappropriately influence (bias) their work.

Roles and Responsibilities:

Conceptualization: Haleema Sadia; Talat Waseem

Data curation: Haleema Sadia; Hira Ashraf; Talat Waseem

Formal analysis: Haleema Sadia; Talat Waseem

Funding acquisition: Haleema Sadia

Investigation, Methodology: Haleema Sadia; Talat Waseem

Project administration: Talat Waseem; Haleema Sadia

Resources, Software, Supervision: Haleema Sadia; Talat Waseem; Hira Ashraf

Roles/Writing - original draft; Writing - review & editing: Haleema Sadia; Hira Ashraf; Talat Waseem

Abstract :

Introduction: Intra-operative nerve monitoring (IONM) has evolved into a powerful risk minimisation tool in the past two decades. Most of the meta-analysis and articles were limited by poor study designs and have failed to demonstrate superiority of IONM over visual identification of RLN during thyroidectomy in the absence of IONM. Continuous intra-operative nerve monitoring (C-IONM) is superior to intermittent intra-operative nerve monitoring (I-IONM) due to its real time electromyographic tracings during surgery, thus reducing the RLN palsy whichin turn decreases vocal cord paralysis post-operatively. C-IONM urges surgeons to reverse the harmful surgical manoeuvres in order to avoid permanent traction related nerve injury. It also forms an integral part in the surgical concept of staged thyroidectomy.

Objective: Objective of this review article is to shed some light on IONM technique, its pros and cons, its two types, how this technique is taking neck surgery by storm and how it is equipping young surgeons with confidence by honing their surgical skills.

Methods:This review article is written according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Literature search was done through PubMed, Google scholar and ERIC. Search terms used were: “intra-operative neuromonitoring” AND “continuous intra-operative nerve monitoring” OR “intermittent intra-operative nerve monitoring” AND “recurrent laryngeal nerve” OR “RLN” AND “thyroid gland” OR “thyroidectomy”.433 articles were identified through search process out of which 103 were used for full text review. Following thematic analysis 41 articles were included in this article. The article evidence was thoroughly evaluated and various themes were identified and discussed in table 1.

Results:In recent years, the volume of thyroid procedures has expanded and so did risk minimization measures that protectRLN. Although the incidence of RLN palsy is low in experienced hands, it results in permanentpost-operative compromise of voice quality that may diminish patient’s quality of life and trigger litigation formalpractice for the surgeon. IONM especially C-IONM helps in decreasing the incidence of imminent RLN palsy by providing the real-time neuromonitoring intra-operatively. It also helps in perfecting the surgical skills of young surgeons. Proper documentation of IONM helps in case of litigation as well.

Conclusion: This review article concludes that IONM could reduce the incidence of total, transient and permanent RLN injury compared with conventional visual identification of RLN. IONM has increased the precision in signaling impending nerve injury early on and in correctly predicting post-operative vocal cord palsy. This enables surgical teams to reflect on timely and improvetheir surgical skills.

Keywords: Intra-operative nerve monitoring (IONM), recurrent laryngeal nerve (RLN), recurrent laryngeal nerve palsy, thyroidectomy, continuous intra-operative nerve monitoring (c-IONM), intermittent intra-operative nerve monitoring (I-IONM).

Introduction :

A case of total thyroidectomy was planned in the Department of Surgery,HaydarpasaNumune Training and Research Hospital, Istanbul, Turkey, for papillary carcinoma of thyroid under the guidance of IONM. Surgeons first dissected right lobe containing the malignant solid nodule. Pre-dissection sound signals were obtained after stimulation ofvagus nerve and recurrent laryngeal nerve (RLN) from the device, while recording the wave amplitude. Upon dissection the right RLN was completely exposed and isolated. After dissection of the nodule, post-dissection stimulation of the anatomically intact RLN determined the loss of signal (LOS) without recordableamplitude. Post-dissection stimulation of vagus nerve confirmed the LOS, revealing the permanent or transient injury to the nerve. Further resection of left lobe was halted due to LOS after right hemi-thyroidectomy, electrophysiological monitoring of the right RLN showed a segmental (type1) injury. Postoperative laryngoscopy confirmedunilateral right vocal cord (VC) palsy. The pathological diagnosis was papillary thyroid cancer of the right lobe. The normal function of the right vocal cord was recovered in third post op month. After 4 months of the primary surgery, completion left lobectomy was performed under IONM as a delayed procedure. Postoperative laryngoscopy confirmed the normal function of both vocal cords.The delayed left lobectomy and timely identification of LOS of anatomically intact RLN with the use of IONM technique saved bilateral vocal cord palsy (VCP) in this papillary thyroid carcinoma patient.

Recurrent laryngeal nerve palsy (RLNP) is a very common and feared complication of thyroid and parathyroid surgery. However, its occurrence has markedly decreased due to routine visual identification of the RLN,. Unilateral RLNP causes hoarseness of voice and that in turn greatly affect the quality of life. Fortunately, this impairment is transitory in most cases, in contrast to bilateral RLNP which mostly causes permanent hoarseness. The gold standard has always been the visual identification of RLN before dissecting the thyroid gland.

One of the products of technology in surgical domain is intra-operative nerve monitoring in thyroid surgery (IONM). After its invention there is a continuous debate whether it significantly reduces the RLNP rates or not. Also, there is an open debate front regarding intermittent intra-operative nerve monitoring (I-IONM) and continuous intra-operative nerve monitoring (C-IONM). In recent literature,on the systematic use of I-IONM, there was no reduction in RLNP rates. But the advantage of I-IONM is the prevention of bilateral RLNP with the implementation of two staged thyroidectomy.

Continuous intra-operativenerve monitoring (C-IONM) is rather latest technique and it potentially enables the surgeonto react before irreversible damage to the RLNoccurs. In C-IONM electrode is applied on the vagus nerve during the entire operation in order to measure the electromyographic activity of the muscles which are innervated by the RLN. Commonly, lesions to the RLN occur by traction followed by clamping or thermal injury, as shown in a multi-centre study of 80% of 115 cases with loss of signal (LOS) caused by traction to RLN. The difference between each type of injury is critical when it comes to C-IONM because all of them cannot be prevented by IONM. If tension is released when detected early by IONM, traction injuries are reversible. This has been shown byPhelanand Schneider et al. that more than 73% and 82% of events, respectively, were reversible during surgery when prompt corrective measures were applied. It was concluded that C-IONM offers higher sensitivity for early post-operative detection of RLNP incidence upon comparing RLNP rates between the two techniques I-IONM and C-IONM . Furthermore, an analysis of 400 vagal nerve dissections, electrode positioning was reported to be safe during C-IONM . On the contrary, Terris et al. reports two cases of LOS, one due to hypotension and bradycardia after using the vagal electrode, and the other case was of trauma to the vagal nerve caused by electrode application with LOS resulting in temporary RNLP, concluding this to be a harmful and invasive technique. Another group, Katrin et al., studying high-risk neck surgeries reports one LOS which was caused by vagal electrode and multiple situations of EMG artefacts.To sum it all up,C-IONM is superior in effectivity over I-IONM in prevention of RLNP .C-IONM was introduced in Geneva in 2012 for selective use in complicated surgical cases for example invasive thyroid cancer, retrosternal goitre, Graves disease and re-intervention surgeries.

Material s and Methods:

This review article is written according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines with the objective to analysedata available for intra-operative nerve monitoring (IONM) in thyroid surgery.

Search Strategy and Data Extraction :

To review the literature, narrative approach was used in order to have comprehensive critical and objective analysis of the available data. A comprehensive literature search was done from the databases PubMed, ERIC, Google Scholar and Sci-Hub from 1996-2021. Relevant articles were added manually as well by reviewing the references. Search terms used for search were: “intra-operative nerve monitoring” AND “continuous intra-operative nerve monitoring” OR “intermittent intra-operative nerve monitoring” AND “recurrent laryngeal nerve” OR “RLN” AND “thyroid gland” OR “thyroidectomy”. Review of all search papers were conducted according to the selected search strategy. In addition,the reference search papers were also included for comprehensive literature review.

Selection C riteria and Quality Assessment:

433 articles were identified using thecomputerliteraturesearch of PubMed and Google scholar. Titles and abstracts of all the papers were reviewed using the inclusion and exclusion criteria. 32 articles were excluded for duplication, remaining 401 articles were viewed and 41 articles related to the topic were included in this literature review. 103 full-text articles were assessed for eligibility and 62 articles were excluded on the basis of exclusion criteria. No language, age or gender restrictions were applied. All papers from 1996 to 2021 were included. Exclusion criteria included duplicate articles, poster presentations, articles not related to the topic, articles on minimally invasive video thyroidectomy, articles on endoscopic thyroidectomy, papers on paediatricthyroidectomy and articles on robot assisted thyroidectomy. The article selection process is given in Diagram 1.

Data Extraction and Detailed Analysis:

Thematic analysis of each paper was done. Information about year of publication, name of the author, country of origin, methods of study and themes identified were collected and coded. The themes identified through analysis of the data are given in table 1.

Results:

433 articles were identified through comprehensive computer literature search. 41 articles were included after the screening process by removing duplicates, these articles were analysed thoroughly. The detailed analysis of the selected papers showed some recurrent themes which are described in Table1.

Diagram 1:

Table 1: Details of articles included in this literature review and themes extracted from them.

Year	Author	Country	Research Method	Themes Identified
1996	Lamade (Lamade et al., 1996)	Germany	Original Article	IONM system for RLN is reliable and easy to use, even the imminent injury to RLN can be demonstrated by signal changes.
1996	DavidW.Eisele(DW Eisele,1996)	USA	42 RLN were monitored in 31 patients by direct RLN stimulation with electrodes on ETT at the level of true vocal cords	NIM-2 EMG ETT is a safe, effective and simplified method for RLN monitoring during thyroidectomy or parathyroidectomy
2005	Dionigi (Dionigi et al., 2005)	Italy	Review article on the influence of new technology on thyroid surgery including IONM	RLN monitoring and stimulation may be a useful technique when identification of RLNis expected to be difficult (redo surgery) also specific training is required for this new device.
2007	Shindo (Shindo, Chheda, 2007)	USA	Retrospective study of 684 patients (1043 nerves at risk) who underwent thyroidectomy under GA	Monitoring of the RLN does not appear to reduce the incidence of post-operative vocal cord paralysis
2007	Lamadé (Lamadé et al., 2007)	Germany	Original article discusses c-IONM of RLN with a new vagal electrode	Continuous RLN monitoring by stimulation of the vagal nerve is feasible, safe, easy to handle andcompatible with all thyroid operations technique
2008	Dionigi (Dionigi et al., 2008)	Italy	A review article	Prevention of post-operative complications, such as laryngeal nerve paralysis with IONM
2009	Schneider (Schneider et al., 2009)	Germany & Austria	An original article about c-IONM of RLN by vagal nerve stimulation	The vagal anchor electrode is safe to use and allows c-IONM without any threats, this new technique will provide more security.
2010	Jonas (Jonas et al., 2010)	Germany	Original paper, in 100 patient’s thyroid resection was performed using vagus electrode for continuous stimulation	Parameters e.g.,signal amplitude, latency and stimulation threshold cannot be reliable warning criteria, LOS remains the most important criteria for the surgeon and this gives surgeon the possibility to react immediately.
2010	Dionigi (Dionigi et al., 2010)	Italy	Opinion paper on monitoring of RLN in thyroid surgery	New technologies have been applied in thyroid surgery; this is a transition period from the era of visualisation to era of neurophysiology of RLN
2011	Lee (Lee & Stack, 2011)	USA	Review article on intraoperativeneuromonitoring during thyroidectomy	IONM Still needs to improve, there is a strong argument for its use as a teaching and research tool, residents and less-experienced thyroid surgeons may benefit from its use.
2012	Angelos (Peter Angelos, 2012)	USA	Literature review of ethical and medicolegalissues in neuromonitoring during thyroid surgery	Neuromonitoringcan provide valuable information to surgeons about the functioning of RLN, but should not overestimate the benefits when discussing the technology with patients.
2012	Barczyński (Barczyński et al., 2012)	Poland	Randomized controlled trial of 210 patients for visual inspection vs neuromonitoring	Use of IONMsignificantly improved the identification rate of the nerve, as well as reduced the risk of post-operative phonation changes following thyroidectomy.
2012	Friedrich (Friedrich et al., 2012)	Germany	Prospective controlled study of 40 patients scheduled for thyroid or parathyroid surgery	C-IONM via vagal nerve stimulation appears to be safe and effective
2012	Refoyo (José Luis Pardal-Refoyo, 2012)	Spain	An original article of 259 RLNs at risk during thyroidectomy with neuromonitoring (group A: 129nerves) and without neuromonitoring (control group B: 130nerves)	Neuro-monitoringhelps to identify RLN and increases the security of the surgeon in the technique. It is advisable to perform neuro monitoring routinely in thyroid surgery.
2013	Schneider (Schneider et al., 2013)	Germany	Original article of 52 patients whounderwent C-IONM for thyroid surgery via vagus nerve stimulation	C-IONMReliably signaled impendingRLN injury, enabling immediate corrective action.
2013	Dionigi (Dionigi et al., 2013)	Italy	A PubMed indexed literature review of the limitations of I-IONM and commentary about C-IONM.	C-IONM by vagal nerve stimulation enhance the standardisation process, intra-operative information of RLN, documentation, protection, training and research in modern thyroid surgery.
2013	Sadowski ( Sadowski et al., 2013)	Switzerland	An original article discussing; bilateral thyroidectomy was delayed after LOS of unilateral lobectomy.	The systematic use of IONM and the change in operating strategy will lead to an almost 0% rate of bilateral recurrent laryngeal nerve palsy
2014	Barczyński (Barczyński et al., 2014)	Poland	A retrospective cohort study of 854 patients having re-operations of thyroid, now with IONM	IONM decreased the incidence of transient RLN paresis in repeat thyroid operations compared with nerve visualisation alone.
2014	Phelan (Phelan et al., 2014)	USA	Prospective multi-centertertiary study	C-IONM is safe and provides real-time RLN evaluation during surgical manoeuvres
2015	Schneider (Schneider et al., 2015)	Germany	An original article comparing C-IONM and I-IONM	Operation with C-IONM resulted in fewer permanent vocal fold palsies compared with I-IONM after thyroid surgery in patients with benign disease
2015	Deniwar(Deniwar, Kandil& Randolph, 2015)	USA	A literature review	C-IONM prevent nerve injury by detecting EMG waveform change indicating impending nerve injury.
2015	Angeletti (Angeletti, B. Musholt, J. Musholt, 2015)	Germany	An original article discussing c-IONM	C-IONM potentially enables the surgeon to react before irreversible damage to the RLN occurs.
2016	Schneider (Schneider et al., 2016)	Germany	A review article	C-IONM facilitate for early corrective action before permanent damage to the RLN has been done.
2016	Refoyo (Refoyo&Sangrador, 2016)	Spain	Systematic review of 40 articles and 54 case studies (without NM, 25; with NM, 29) with 30,922 patients	The risk of bilateral paralysis is lower in studies withneuromonitoring
2016	Schneider ( Schneider et al., 2016)	Germany &USA	An original article	C-IONM can prompt corrective actions before LOS occurs, C-IONM provide better nerve protection than I-IONM, permanent RLN palsy rates are 0% with c-IONM vs. 0.4% with I-IONM
2017	Schneider (Schneider et al. 2017)	Germany	Review article	Review summarises the current key achievements of IONM; outlines opportunities for improvement regarding clinical implementation and suggests areas of future researchin this rapidly evolving field.
2017	Qurayshi (Qurayshi, Kandil& Randolph, 2017)	USA	A Markov chain model was constructed based on IONM use	Use of IONM is cost effective in patients undergoing bilateral thyroid surgery
2017	Randolph (Randolph &Kamani)	USA	Retrospective study of electrophysiologic response of 1381 RLNs	IONM of the RLN can aid in the nerve mapping, nerve identification and prognostication of post-operative vocal cord function, which can influence the surgeon’s decision to proceed to bilateral surgery
2017	Christoforides (Christoforides et al., 2017)	Greece	A retrospective cohort study	Staged thyroidectomy seems very promising procedure for both patient and surgeon since it nearly eliminates one of the most fearful complications in thyroid surgery, RLN palsy
2017	Mannelli (Mannelli et al., 2017)	UK	Research article	IONM withautomated periodic stimulation (APS) technical and practical steps, encourage surgeons to widen their skills and gain knowledge about its potential use
2018	Bai (Bai & Chen, 2018)	China	Literature review article	Literature search indicated that IONM could reduce the incidence of total, transient and permanent RLN injury compared with conventional visual identification
2018	Arteaga (Arteaga et al., 2018)	Switzerland	Retrospective study	C-IONM provides real-time evaluation of the RLN function, allowing for adaptation of surgical maneuvers to prevent RLNP
2018	Basarrate (Basarrate et al., 2018)	Spain	A prospective cohort study,248 consecutive thyroidectomies were included	Continuous vagal nerve monitoring is safe and allows us to assess nerve function intraoperatively
2018	Singer (Michael C. Singer, 2018)	USA	50 patients scheduled to undergo thyroidectomy were enrolled, a lead designed for CIONM was placed on the nerve	This study demonstrates the apparent safety and viability of a CIONM technique using a lead placed directly on the RLN, widespread adoption of CIONM during thyroidectomy may reduce RLN injuries.
2019	Yu (Yu et al., 2019)	China	A total of 344 patients who underwent high-risk thyroid surgery, with 238 patients operated with I-IONM and 106 patientsoperated with C-IONM.	Both I-IONM and C-IONM are equally safe and effective in high-risk thyroid surgery. C-IONM can help predict impending recurrent laryngeal nerve injury in real time, thereby minimizing critical maneuvers in high-risk thyroid surgery.
2019	Gürleyik (EminGürleyik, GünayGürleyik, 2019)	Turkey	Case study	IONM establishes the outcome of the neural palsy, affects the surgical decision-making, and prevents the risk of bilateral palsy.
2020	Schneider (Schneider et al., 2020)	Germany	Literature review	Review summarizes the advances of continuous IONM technology that caused a quantum leap in risk minimization for thyroid surgery, shifting current paradigms.
2020	Kim (Kim et al., 2020)	USA	An original article	Nationally, IONM is used in nearly two thirds of thyroid surgeries. IONM is associated with a lower risk of RLN palsy.
2020	Kartal (Kartal et al., 2020)	Turkey	Clinical study	Intraoperativeneuromonitoring may decrease the incidence of total VCP and prevent the development of bilateral VCP, which has unfavorable results for both patients and health-care professionals.
2021	Sinclair (Sinclair et al., 2021)	USA	Observational case-control study	CIONM significantly decreased rates of postoperative transient VF paralysis and paresis over intermittent IONM alone.
2021	Abdelhamid (Abdelhamid, Aspinall, 2021)	UK	An original article	Use of IONM is associated with a decreased risk of RLN injury in thyroidectomy.

Results:

In recent years, the volume of thyroid procedures has expanded and so did risk minimization measures to protectRLN.Although the incidence of RLN palsy is low in experienced hands, it results in permanent post-operative compromise of voice quality that may diminish patient’s quality of life and trigger litigation for malpractice for the surgeon. IONM contains three interdependent steps of nerve monitoring: preoperative, intra-operative and post-operative monitoring of RLN function.These three levels of monitoring add another dimension to thyroid surgery. The prerequisites are advanced surgical skills, dissection and isolation of the RLNfollowing its visual identification.

Stages in the evolution of IONM:

Intermittent intra-operative nerve monitoring done with handheld mono-polar probes stimulating the RLN and needle electrodes inserted through the cricothyroid membrane into the vocal muscle, recording the electrophysiological response signal.
Intermittent intra-operative nerve monitoring with handheld mono-polar probes stimulating the RLN and surface electrodes fixed to the endotracheal tube, recording the electrophysiological response signal.
Continuous intra-operative nerve monitoring with a clip electrode mounted on vagus nerve and surface electrodes fixed to the endotracheal tube, recording the electrophysiological response signal.

The advances in continuous IONM have caused a quantum leap in risk minimization of thyroid surgery. IONM has gained popularity and is considered a standard of care in some countries, the cost effectiveness of this technology remains controversial in resource-conscious environments.

Meta-analysis and systematic reviews on IONM:

There are multiple published systematic reviews and meta-analysis of studies comparing IONM againstvisual nerve identification in the absence of IONM. Astonishingly, many of these reviews arrived at opposing conclusions.There was evidence to suggest that IONM decreases both permanent and transient RLN injury rate, only transient RLN injury rate, or only permanent RLN injury rate . On the contrary, other researchers found no substantial reduction of permanent RLN injury rate or no substantial reduction of both transient and permanent RLN injuries. These contradictory results are best explained by the stepwise evolution of IONM technology and gradual recognition of the importance of standardisation based on the principles laid down by the International Neural Monitoring Study Group. According to Schneider et al. IONM especiallyC-IONM is shiftingcurrent paradigms.

Use of intermittent and continuous IONM among surgeons:

A survey by German Society of EndocrineSurgeons (GAEK) based on 12,888 patients with benign goitre and 18,793 nerves at risk, found that IONM was used in 98.4% of patients and I-IONM (82.6%) was used more often than C-IONM (17.4%). A 2012 questionnaire survey of German surgical centres showed that IONM was employed in 91% of thyroidectomies.

In 2016 survey ofSurgeonsof theAmerican Head and Neck Society, 95% of respondents said that they either used IONM routinely (60%) or selectively (35%). The most common reason for using IONM was increased surgeon confidence (55%) and improved safety (54%). A survey conducted in 2019 among 1015 surgeons, reported greater adoption of IONM for thyroid and parathyroid surgery in the past decade, with 83% of surgeons employingIONM for some or all of their operations. Uptake of IONMis greater among younger surgeons but is unrelated to surgical volume, type of practice or fellowship training.

Honing surgical skills with the help of IONM by constant feedback on nerve function:

Continuous electrophysiological feedback on the functional state of a nerve makes the surgical team to reflect on and hone their surgical skills. This reassurance is likely to reduce stress of the surgical team . Introducing IONM routinely in thyroid surgery also help less experienced surgeons to perform operations more safely and comfortably, with complication rates comparable to an experienced surgeon.

Documentation of and informed consent for IONM in case of L itigation:

Use of reasonable risk minimization strategies is demand of ethical considerations, even if the expected benefits have not been clearly established. In the event of litigation, informed consent detailing the strengths and weaknesses of IONM and the need to change plans in the event of LOS may serve as a line of defence.

A 2012 study by Dralle et al. shows 75 lawsuits in a 15-year period for Germany, 60% involved RLN palsies, half of which are bilateral.Gartlandet al. supported these findings and found that bilateral RLN injury was predictive of plaintiff verdicts (OR 3.58, P=0.03), accounting for up to 18% of 128 malpractice suits in the US.These verdicts highlight the importance of properly documenting and implementing the use of risk minimisation strategies. Normal vagus and RLN electrophysiology documentation before and after dissection provides a strong line of defence.

IONM superiority in thyroid surgery:

There are two types of loss of signal (LOS), type 1 (segmented LOS)and type 2(diffuse LOS).Both intermittent and continuous IONM are able to differentiate between the two types. Whereascontinuous IONM offers added benefitinminimisation of traction induced RLN injury, avoidance of thermal RLN injury, real-time functional monitoring over the entire RLN and detailed EMG documentation.Both IONM types suggest informed surgical treatment plan and provide strategic direction regarding the need for staged thyroidectomy after definitive LOS on the first side of operation. According to Australian College of Surgeons and the German Association of Endocrine Surgeons IONM has become standard of care in some countries. C-IONM provideintra-operative registration of nerve signals virtually in real time.It has been demonstrated that instant release of a distressed nerve minimizes RLNinjury.

Predictionof Post-operative vocal cord functions Intra-operatively:

The prediction ofpost-operative vocal cord palsy with the help of IONM is characterised by two scales:

Sensitivity; 63.0-91.3% for intermittent and 90.9-100% for continuous IONM
Specificity; 97.1-99.5% for intermittent and 90.2-99.7% for continuous IONM

In case of laryngeal nerve palsy the positive predictive value (PPV) is bound to be lower than the negative predictive value (NPV):

PPV; 37.8-80.5% for I-IONM and 47.6-88.2% for c-IONM
NPV; 97.3-99.8% for I-IONM and 99.8-100% for c-IONM

Rates of post-operative vocal cord palsy are significantly lower with this technique

Early palsy; 0.8-10.5% for I-IONM and 2.6-2.9% for c-IONM
Permanent palsy; 0.2-1.5% for I-IONM and 0-1.5% for c-IONM.

The main difference between continuous IONM and intermittent IONM is seamless monitoring of functional integrity by C-IONM along the entire vagus-RLN axis in real time for detection and timely prevention of traction related RLN injury. In experienced hands C-I0NM can diminish permanent vocal cord palsy rate to 0% comparing against 0.4% with I-IONM. For optimal results it is important to get nerve amplitudes of greater than or equal to 500microvolts at baseline with stimulation current of 1mA.

Mobilisation and resection of thyroid with greater flexibility :

C-IONM is a powerful technique enabling immediate recognition of RLN injury. A multi-centre study with LOS for 115 nerves showed that traction produced 83% of RLN injuries, 60% of which took place near or at the ligament of Berry. These findings highlight the importance of IONM-guided thyroid mobilisation and resection. Traction related injuries are preceded by “combined events”, changes in amplitude and latency relative to baseline. If no action is taken injury to the nerves may progress to LOS, which can be a serious and less reversible condition. When these changes happen, it is crucial to release the nerve immediately by relaxing hold on the thyroid gland until the nerve amplitude has regained its baseline. If these events occur more than once it may be more prudent to take a median route to thyroid hilum than continuing a risky dissection.

C-I0NM can show its true importance when the operatingfield is scarred and surgical layers are obliterated such as during mobilisation of thyroid, dissection of thyroid capsule, or digital mobilisation of retrosternal thyroid.In these situations, it is often impossible to identify and map the nerves. A stimulating electrode mounted on the vagus nerve is activated and the operative team is constantly alerted of impending injury to a nerve that remains invisible.

I ntr a- operative a mplitude recovery for restoring post-operative vocal cord function:

After LOS, segmental type 1 injury typically resolves within 6.9 to 8 minutes and global type 2 injury resolves in 13 to 15.6 minutes. This observation illustrates the futility of waiting longer than 20 minutes for the nerve to re-gain 50% of its baseline amplitude . Amplitude recovery of almost 50%accurately predicts normal post-operative vocal cord function in all patients after segmental type 1 or global Type 2 injury.Early vocal cord function is impaired in 25% of patients with a temporary global Type 2injury and 64% of patients with temporary segmental type 1 injury

Staged Thyroidectomy vs same-session thyroidectomy:

When LOSis detected onfirst side of resection and traction on the nerve is stopped immediately, standard procedure is to give nerve around 20 minutes to regain 50% of its preoperative baseline.If the nerve fails to do so within 20 minutes, there is 85% risk of early post-operative VCP. In such cases it is absolute necessity to postpone completion thyroidectomy of the other side for at least three months until vocal cord function has fully recovered. Contralateral surgery should only be pursued under exceptional circumstances such as advanced cancerand only at surgical centres experienced in complex neck surgery.

Cost effectiveness of IONM:

Practice and adoption of IONM technique varies by country and geographic region, cost also varies from $5000-$40,000 for the IONM equipment and from $72-$5000 for disposables per application (vagus electrodes and recording surface tubes). In addition, indirect costs includeGlidescope video laryngoscope required to ensure correct positioning of the recording tube electrodes, or ancillary staff in the operating theatre to aid in monitoring RLN function. The utilisation of IONM may amount to 5 to 7% of the total inpatient expense charged for thyroidectomy.

D i scussion :

RLN injury resulting in RLN palsy is a major complication of thyroid surgery. It greatly affects patient’s quality of life post-operatively. RLNinjury rate is reported to range from 0.5% to 10% . Most surgeons believe that routine exposureof RLNcan protect anatomical integrity of the nerveand reduce its rate of injury. Development of IONM has contributed in exposure and localization of RLN during thyroidectomy.Furthermore, it has been employed to decrease the rate of RLN injuries.

Visually intact nerve does not reflect that it is functionally intact. Even if the anatomical integrity of RLN is ensured during surgery complete avoidance of injury to the nerve cannot be guaranteed following operation.Technique of IONM has enabled recognition of temporary injury to RLN during the surgery and provide early warning signs for surgeons to manoeuvre themselves to decrease or eliminate damage caused to the nerve. IONM can indicate non-dissociative damage such as damage from clamping, traction, suction and electric cautery.

IONM technique uses the principles of electrophysiology. Severity of injury to RLN is determined by analyzing the waveform, amplitude and latency of the vocal cord EMG signal. Scott et al. showed that decreased amplitude and increased latency is indication of nerve injury and the signal returns to normal if function of nerve is restored . Tian et al. found significant relationship between temporary injury of RLN and extent of resection.The risk of temporary injury to RLN during total thyroidectomy was three times greater than during right lobectomy. Dralle et al. concluded that risk of permanent RLN paralysis was significantly higher in lobectomy (1.34%) than in subtotal resection (0.68%). These results suggest that surgeons should consider benefits and complications while deciding extent of surgery. American Thyroid Association guidelines of 2015 state that hemi-thyroidectomy may be sufficient for patients without clinically or radiologicallyinvolved cervical lymph node metastasis orextra-thyroidal extension.

The anatomy of right and left RLNis different.Left RLN winds around aortic arch and travels almost vertically up to the trachea while rightRLN winds around subclavian artery and travels obliquely towards the larynx. A few studies have examined differences between left and right RLN injury. Tian et al. study showed that the left recurrent laryngeal nerve was more susceptible to surgical manipulation than the right RLN.

Normal quantitative parameters of IONM were analysed by a multi-centre study involving six centres, itconcluded that the right vagus nerve showed a significantly larger median amplitude (P<0.001) and a significantly shorter latency (P<0.001) compared with the left vagus nerve.Phelanet al.concluded that right and left RLN latencies were similar. Latency of right vagus nerve was less than left vagus nerve but the difference was not significant. Latency of RLN was significantly shorter than vagusnerve. Amplitude of left vagusnerve was significantly less than right vagus nerve. However, there was no difference in the amplitude of either the RLNor thevagus nerve between men and women. Another study found that the main latency of left vagus nerve was significantly longer than right vagus nerve.

Among the two major categories of IONM,C-IONM is considered superior and more effective in preventing damage to RLN as compared toI-IONM.Study by Andres et al.on101 cases, performed with C-IONM in neck surgeries,13 patients showed temporary loss of signal.After a change in surgical approach LOS was prevented and recovered.In three cases LOS occurred due to electrode placement on vagus nerve (3/101).In one case LRN palsy persisted even after six months due to an accidental section of the anterior branch of RLN (1/101 =1%).Vagus nerve was intact in all three cases, exact reason for this trauma is unclear but might be due to peri neural bleeding or traction by surgical instruments while exposing the nerve. A study by Brauckhoff et al. cites two cases of loss of signal by the electrode in high-risk surgery, one at placement due to perineural bleeding, and the other caused by an undetected torsion of the electrode. Mangano et al. report an increase in vagal nerve size after electrode placement of 0.82 mm and an electrode dislocation rate of 11% per procedure. Thus, highlighting the importance of selecting suitable electrode size and using careful standardised technique for electrode placement. The studies led us to believe that LOS might be caused by the upward traction of the right-angel dissector used for 360° nerve dissection necessary for electrode placement.In order to verify that it is mandatory to check signal on vagus nerve above the site of electrode placement (proximal) at the end of surgery in addition to C-IONM signal from the electrode.Furthermore, it can be assumed that some of the traction injuries during I-IONM cases could have been avoided if C-IONM had been used. This assumption is based on the findings from otherstudies reporting events to be reversible when prompt corrective measures were applied during surgery .

Conclusion :

IONM can reduce the incidence of total, transient and permanent RLN.IONM is recommended in bilateral operations and malignancy cases. The benefit of this technique in the re-operation cases needs to be further explored.Among the two types of IONM, C-IONM is superior as it provides a real-time evaluation of the RLN function, allowing for adaptation of surgical manoeuvres to prevent RLNP intra-operatively. The risk benefit ratio of C-IONM should be further evaluatedas it implies a risk at electrode placement. It is particularly useful in situations where the RLN is difficult to identify by the standard lateral approach such as redo surgery, posterior nodules, large and/or retrosternal goiter or in rare instance when RLN is invaded by a tumor.

In large or retrosternal goitre superior approach to reach RLN is favoured. When using C-IONM, vagal stimulation above the site of electrode placement should be performed at the end of the resection to ensure integrity of the vagal nerve and RLN and to avoid false negative IONM result.IONM has augmented the precision in signaling the impending nerve injury early on and in correctly predicting post-operative vocal cord palsy. This enables surgical teams to reflect on and hone their surgical skills. IONMhas developed into a powerful risk minimisation instrument used in thyroid surgeries since 2010s. IONM technology needs to keep pace with the endoscopic and robotic surgery which is gaining momentum in the Western Hemisphere.

References :

Evolution of Intra-operative Nerve Monitoring as a revolution in Thyroid Surgery: A PRISMA compliant Systematic Review

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