COMPARISON OF THE INCIDENCE OF RECURRENT LARYNGEAL INJURY FOLLOWING THE DISSECTİON OF THE NERVE BY CRANIO-CAUDAL AND LATERAL APPROACH BY USING INTROPERATIVE NERVE MONITORING
Phase: NA
Conditions: Recurrent Laryngeal Nerve Injuries
Sponsor: Istanbul University

Date: 1 March 2020 
 
Study Name: Comparıson Of The Incidence Of Recurrent Laryngeal Injury Following The 
Dissection Of The Nerve By Cranio-Caudal And Lateral Approach By Using Introperative 
Nerve Monitoring 
 
Study Design: This prospective study was approved by the institutional review board and 
ınformed consent was obtained from each patient . A total of 327 patients who were referred 
to undergo thyroid surgery between June 2018 and November 2019 were assessed  for the  
eligibility to  participate in the study. Of these, 233 were considered to be eligible for the 
study. Exclusion criteria included previous thyroid or parathyroid surgery, substernal goiter, 
preoperative VCP, evidence of lateral lymph node metastasis, intentional transection of the 
RLN due to tumor invasion, failure to assess RLN functioning due to equipment issues with 
the IONM setup, presurgical dissection amplitude of <500µV and patient’s refusal to 
participate in the study. Of 327 patients, 94 were excluded preoperatively due to previous 
neck surgery (n=47), evidence of lateral neck metastasis(n=24), patient’s  refusal (n=13) and 
presence of substernal goiter (n=10). The remaining 233 patients were randomized to have 
RLN’s identified by lateral (n=121) or cranio-caudal approach (n=112 (Figure 1).  Computer 
generated random numbers were generated and printed on cards. These cards were placed in 
sealed, opaque envelopes. On the morning of operation, one envelope was opened before the 
operation and, depending of the parity of the number, RLN’s of the patient were dissected 
either by cranio-caudal or lateral dissection during the operation.  The patients and the nerves 
at risk (NAR’s) in the lateral and cranio-caudal approach groups were classified as group 1 
and 2, respectively. In group 1 and 2, nine and twenty-six patients were further excluded, 
respectively, owing to  intraoperative  failure to assess RLN functioning due to equipment 
issues with the IONM setup or  presurgical dissection amplitude of <500µV. 
Thus, the data of 198 patients were analysed for primary and secondary outcome 
measures. The primary endpoint was RLN injury and the secondary endpoints included the 
effect of  clinicopathological features, anatomic variations and adverse EMG changes on the 
occurrence of RLN injury. Of 198 patients, 112 were in the lateral approach group (group 1) 
and 86 in the cranio-caudal approach group (group 2). Total thyroidectomy or lobectomy was 

performed in 158 (79.8%) and 40 (20.2%) patients, respectively. Sixteen (8%) patients 
underwent unilateral central lymph node dissection (CLND) additional to total thyroidectomy. 
Age, gender, body mass index (BMI), the indications for surgery, presence of  
hyperthyroidism, evidence of autoimmune thyroid disease (ATD) and thyroid lobe volume 
were recorded in all patients, preoperatively. Thyroid lobe volume was calculated by using the 
dimensions (lenght(L),width(W),thickness(T)) of each thyroid lobe measured by 
ultrasonography according to the following formula; π/6xLxWxT 18.   
All NAR’s were dissected by using CIONM including vagal response evaluation at the 
beginning and at the end of the operation (IONM = L1,V1, R1, R2,V2, L2) according to the 
recommendations  by the International Intraoperative Neural Monitoring Study Group 7. All 
patients underwent pre-, and postoperative laryngoscopic examination within 2 days after 
surgery, and repeated serially if abnormal (L1, L2). All operations were performed by 
experienced endocrine surgeons. Lenght of RLN dissection was defined as extended if it the 
nerve was dissected for 5 cm or greater. Duration of lobectomy for each site, period of time 
for initial identification of RLN after the mobilization of upper pole on each site, the 
relationship of the RLN to the ligament of Berry (LOB) and to the Tubercle of Zuckerkandl 
(TZ) (if present), extralaryngeal branching of the RLN, lenght of RLN dissection, presurgery 
and postsurgery amplitude and latency of the vagus and the RLN, occurrence of adverse EMG 
changes and recovery time or loss of signal (LOS) were recorded intraoperatively in all 
patients. Serum levels of calcium and parathormone on the first postoperative day were 
analyzed in all patients. The rates of post-thyroidectomy hypoparathyroidism and vocal cord 
palsy (VCP) were recorded. Final histopathological diagnosis was documented in all patients, 
postoperatively. 
Demographic data, BMI, the indications for surgery, clinicopathological features, 
thyroid volume, duration of the operation, period of time for RLN identification, anatomical 
variations, length of RLN dissection, presurgery and postsurgery amplitude and latency of the 
vagus and RLN, the rate of adverse EMG changes, LOS and morbidity (vocal cord palsy, 
hypoparathyroidism) were compared between group 1 and 2. The correlation between 
intraoperative adverse EMG changes and anatomic variations, lobe volume and type of 
thyroid disease was investigated as well.  
 
Thyroid surgery and CIONM technique 

All operations were performed under general anesthesia by using a small dose (0.3 
mg/kg) of  non-depolarizing muscle relaxant  (Esmeron; MSD Sharp &Dohme GmbH, Haar, 
Germany)  at intubation.  The endotracheal tube was properly inserted to ensure that the 
recording surface electrode was placed at the level of the vocal cords. Prior to lobectomy, the  
carotid sheath was carefully dissected and the vagus nerve was identified using a hand held 
stimulation probe. The vagus nerve was dissected over a distance of ≤ 1 cm to place the vagus 
electrode.  (automated periodic stimulation (APS) (Medtronic Xomed, Jacksonville,FL) or 
saxaphone probe (vagus electrode)  (Dr.Langer Medical GmbH, Avalanche SI, Germany). 
The baselines for latency and amplitude were automatically calibrated after the 
connection of the vagus electrode with the neuromonitoring system. CIONM had been carried 
out with one of the two following commercially available neuromonitoring devices: (1)NIM 
3.0 Nerve Monitoring Systems; Medtronic Xomed, Jacksonville,FL; or (2) Dr. Langer 
Medical GmbH, Avalanche SI, Germany. Achievement of initial presurgical dissection 
amplitude of ≥500µV was aimed in all patients.  During the operations, adverse EMG 
parameters were defined as amplitude decrease of  50% or more of baseline value and,or 
latency increase of 10% or more 11.A combined event (CE) was defined as concordant 
amplitude decrease of  more than 50% and latency increase of  more than 10%, regarding to 
baseline values 11. The surgical maneuver was immediately altered and the traction released if 
adverse EMG changes were noted during surgery and waited to achieve the recovery of EMG 
changes. Recovery was defined as amplitude recovery to >50% of the initial baseline 
amplitude. Loss of signal (LOS) was defined as amplitude <100µV 19. In case of LOS during 
the surgery of initial site, contralateral surgery was aborted if the amplitude did not recover to 
greater than 50% of the initial baseline amplitude within 20 minutes of the initial decline. 
During surgery, isthmus was divided first in both group of patients. Then the upper lobe of the 
gland was dissected through the avascular zone between the upper lobe and the cricothyroid 
muscle. The external branch of the superior laryngeal nerve was identified visually and, or by 
using neuro-monitoring hand probe prior to dissection of the upper pole vessels, and then the 
branches of upper pole vessels were ligated individually. Identification and preservation of all 
parathyroid glands and their vascular supply was tried in all cases. In case of incidental 
parathyroidectomy or totally compromised vascularity of the parathyroid glands, 
autotransplantation in to sternocleidomastoid muscle was performed.  
RLN identification  

Lateral approach:  Following the ligation of upper pole vessels, the thyroid lobe was 
pulled anteromedially and the RLN was seeked within the carotid triangle at the level of 
inferior thyroid artery (ITA). The tissue between the carotid artery and the trachea was 
dissected gently parallel to the direction of the nerve until the nerve is identified visually and 
by hand held stimulation probe.  After the identification of RLN, the vessels of inferior 
thyroid lobe was ligated. The nerve was dissected along its course to the entry point, and then 
the thyroid lobe was totally dissected from the trachea and the lobectomy was completed. If 
adverse EMG changes were encountered during lateral approach, traction was released 
immediately and waited for recovery. If the adverse EMG changes recovered, RLN dissection 
was proceeded by lateral approach again. If the adverse EMG changes did not recover after 
traction release or in case of repeated adverse EMG changes, lateral approach was abandoned. 
The thyroid lobe was retracted laterally and medial aspect of the lobe was dissected from the 
trachea. The RLN dissection was continued by medial approach in such cases. 
Cranio-caudal approach: Following the ligation of upper pole vesels, the upper pole 
was  retracted antero-medially to expose crico-pharyngeal muscle. The RLN was identified at 
the point of entry both visually and with hand held stimulation probe. The RLN dissection 
was proceeded craniocaudally by the division of the suspensory ligaments of the LOB through 
the level of ITA. After the identification and visualization of the RLN through its whole 
course, the medial and inferior vessels of the thyroid gland were dissected and ligated. Then, 
the lobe was dissected from the trachea and lobectomy was completed.  If adverse EMG 
changes were encountered during cranio-caudal approach, traction was released immediately 
and waited for recovery. The RLN dissection was proceeded by cranio-caudal fashion again if 
the EMG changes recovered. If the EMG changes did not recover or in case of repeated 
adverse EMG changes, cranio-caudal approach was abandoned and RLN was dissected by 
lateral approach. If repeated adverse EMG changes were encountered despite conversion from 
cranio-caudal to lateral approach, then the lobe was retracted laterally and medial aspect of 
the lobe was dissected from the trachea. The RLN was dissected by medial approach in such 
cases with repeated adverse EMG changes.