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PLOS One logoLink to PLOS One
. 2023 Sep 26;18(9):e0292036. doi: 10.1371/journal.pone.0292036

Effects of intraoperative neuromonitoring (IONM) technology on early recovery quality in patients after thyroid surgery: A randomized controlled trial

Haocong Chen 1, Zhijun Lu 2,*
Editor: Luigi La Via3
PMCID: PMC10522042  PMID: 37751457

Abstract

Background

Patient-focused evaluation of postoperative recover has been recognized as one of the most important concerns in postoperative medicine. Previous studies have shown that the Quality of Recovery-40 (QoR-40) Questionnaire can be used to accurately assess the quality of recovery from surgery. During thyroid surgery using intraoperative neuromonitoring (IONM) technology, the strategy of low dose of muscle relaxant, intubation of different endotracheal tubes and electrical stimulation on vocal cord are applied. Its still unknown if these performances would affect patients’ postoperative recovery in thyroid surgery patients.

Methods

82 patients were randomly assigned to the neuromonitoring group (NEURO Group) and the control group (CON Group). In the CON Group, rocuronium (0.6 mg / kg) was given for intubation and additional dose was injected if needed, while in the NEURO Group, only rocuronium (0.3 mg / kg) was given when induction. The primary outcome is the QoR-40 scores on postoperative day 1 (POD1) and postoperative day 3 (POD3). Other parameters, such as postoperative nausea or vomiting (PONV) and medical cost were also recorded.

Results

One subject in each group was excluded, leaving 80 for analysis. In the NEURO Group, the global QoR-40 score, emotional state, physical comfort, physical independence and pain were significantly lower both on POD1 and POD3 (P<0.05). Patients in the NEURO Group had a higher incidence of PONV (P<0.05) and medical expense (P<0.05).

Conclusions

After thyroidectomy, the patients using IONM suffer worse quality of recovery, more risk of PONV and increased medical expense.

Introduction

Postoperative recovery is a key concern for patients undergoing surgery. Delayed postoperative recovery may cause a patient discomfort, a longer hospital stay, a delayed return-to-work, and increased health care costs. Recent advances in anesthetic and surgical care mean that the quantitative analysis of fragmentary indicators of postoperative recovery, including morbidity or mortality rates, cannot accurately reflect patients’ recovery profiles. Rather, overall assessments of quality of life of patients who are undergoing surgery provide more appropriate measurements that facilitate investigations into the effects of anesthetic or surgical care on patients’ recovery and their satisfaction. The Quality of Recovery-40 (QoR-40) Questionnaire (S1 Table.) is a reliable multidimensional instrument to evaluate patients’ health status after surgery and anesthesia [1, 2]. Previous studies have shown that the QoR-40 can be used to accurately assess the quality of recovery from surgery [3, 4].

With the increasing pace of the modern life, the incidence of thyroid diseases in China has been increasing year by year [5]. According to the latest tally show, Chinese patients suffering from thyroid diseases increased significantly up to 36.9% [6]. One of the most severe complications of thyroid surgery is recurrent laryngeal nerve palsy (RLNP). In cases of bilateral cord involvement, RLNP can cause vocal fold paralysis as well as dysphonia, difficulty swallowing, and respiratory problems including aspiration symptoms and airway obstruction [7].

With the increasing use of artificial intelligence in anesthesia equipment, many use of monitoring with the bi-spectral index has shown benefits reducing time to extubation, orientation in time and place, and discharge from both the operating room [810]. Intraoperative neuromonitoring (IONM) technology was proposed as a means of verifying the functional integrity of the RLNP and it can rapidly locate the laryngeal nerve and protect the functional integrity of it, thereby minimizing the risk of recurrent laryngeal nerve palsy. The waveform, amplitude, threshold and time latency of electromyography (EMG) were analyzed to determine the integrity of nerve function [11]. Nevertheless, compared to traditional thyroid surgery, there are some differences during surgery with IONM. One of these is that a smaller dose of muscle relaxant should be used when IONM applied because the EMG amplitude is sensitive to neuromuscular blockade. Besides, the tracheal tube with larger outer diameter is used for intubation and the patient’s vocal cord is intermittently stimulated during the procedure with IONM. It is still unknown whether these changes will affect the early postoperative recovery quality in thyroid surgery patients.

This randomized controlled study aimed to evaluate the effects of IONM technology on early postoperative recovery quality by conducting the QoR-40 Questionnaire in thyroid surgery patients. We hypothesized that IONM technology would reduce the early recovery quality of thyroid surgery patients.

Materials and methods

Design and patients

This single-center, prospective randomized controlled research was conducted at Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from March 1st 2021 to September 30th 2021. Our research was approved by the Ethics Committee of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine [Ethics Committee Reference Number: (2020) Ethical Review Scientific Research No.173] and our research was prospectively registered in the Chinese Clinical Trial Registry on February 27, 2021 (registration number: ChiCTR2100043738). Each patient signed an informed consent form before to surgery. The Consolidated Standards of Reporting Trials (CONSORT) recommendations (CONSORT Checklist) are followed in our study; a CONSORT flow diagram is shown in Fig 1.

Fig 1. CONSORT flow diagram.

Fig 1

The gender of the patients had no bearing on their selection, which was limited to patients aged 20–70 years with a BMI of 18–30 kg/m2 and American Society of Anesthesiologists (ASA) grades of I-II. These were the exclusion criteria: ASA physical status III or more; predicted difficult intubation; previous known vocal cord paralysis; significant heart, kidney or liver disease; psychiatric or neurological disorders; allergy to any anaesthetic drug and/or written informed consent denied.

Using a web-based response system (www.random.org) and a random sequence generator process, each eligible participant was randomly assigned to either the NEURO Group or the CON Group with a 1:1 allocation.

Anesthetic procedure

Before their surgeries, all of the participants regularly fasted and did not take any premeds. A variety of routine monitoring procedures were used, including electrocardiography (ECG), noninvasive blood pressure (NBP), peripheral pulse oximetry (SpO2), airway pressure monitoring, capnography, Narcotrend (MT MonitorTechnik GnbH & Co.KG, Narcotrend-Compact) and muscle relaxant monitor (GE Healthcare Finland Oy, SJC15300045HA). The heart rate (HR), systolic pressure (SBP), diastolic pressure (DBP) and mean arterial pressure (MAP) measured 10 minutes after the patients entered the room were taken as the base values. In both group, general anesthesia was induced using 0.04mg/kg midazolam, 1.5–2.5mg/kg propofol, 0.4ug/kg sufentanil and different dose of rocuronium.

Patients randomized to the CON Group received rocuronium 0.6mg/kg and traditional endotracheal tube. However, those in the NEURO group had rocuronium 0.3mg/kg, after that, The attending anesthesiologist used a video-laryngoscope to position the Never Integrity Monitor (NIM) endotracheal tube (Medtronic, USA) on the patient. The correct position of the NIM endotracheal tube was confirmed using both capnography and the IONM’s dedicated signal quality checking system.

Intravenous compound general anesthesia was used to treat the patients in both groups. During surgery, anesthesia was maintained with desflurane of a Minimal Alveolar Concentration (MAC) of 0.7–0.9 and with propofol through Target Controlled Infusion (TCI) at 1.0μg/ml. Level of sedation was monitored with Narcotrend and sedatives targeted to a Narcotrend value around 37–64. Intro-operative analgesia was guaranteed by continuous infusion of remifentanil at 0.05–0.1μg/(kg·min). No additional rocuronium was added to the patients in the NEURO Group during the operation, while in the CON Group, 1/3 induction dose of rocuronium was added when the TOF = 2.

If the mean arterial pressure (MAP) of the patient during anesthesia is less than 55 mmHg or its reduction exceeds the base value by more than 20%, intravenous injection of ephedrine 5 mg was given, and the infusion speed of remifentanil was slowed down or the concentration of desflurane was reduced as appropriate; If the mean arterial pressure (MAP) during anesthesia is higher than 110mmHg or exceeds the base value by more than 20%, 5μg sufentanil is injected intravenously; If the heart rate of the patient is less than 50 beats/minute, atropine 0.5mg shall be injected intravenously. 0.25mg palonosetron for participants to prevents postoperative nausea or vomiting (PONV) and 50mg flurbiprofen axetil was provided at the end of the surgery for postoperative analgesia.

Outcome measures

The QoR-40 Questionnaire is a valid and reliable tool that is extensively used to assess the quality of postoperative recovery [12, 13]. 40 items totaling five dimensions—emotional state, physical comfort, psychological support, physical independence, and pain—make up the QoR-40 Questionnaire. Each item is rated on a 5-point Likert scale (1 = none of the time, 2 = some of the time, 3 = usually, 4 = most of the time, 5 = all of the time) and the overall scores range from 40 to 200 [1416].

The primary outcome of the research was the global QoR-40 score on postoperative day 1 (POD1) and postoperative day 3 (POD3). On the day before surgery, POD1 and POD3, between 6 and 8 PM, a particular researcher who was not aware of the patient groups’ assignments visited each patient to conduct the QoR-40 survey. Patients filled out the survey in person while participating in a study and it was then checked to make sure all of the questions had been addressed.

The secondary outcomes included HR, SBP, DBP and MAP of immediately after intubation (T0), 1 minute after intubation (T1), 3 minutes after intubation (T2) and 5 minutes after intubation (T3); cumulative sufentanil, remifentanil and propofol consumption; the total cost of hospitalization and the adverse events on POD1.

Statistical analysis

The sample size was calculated using previous literature [17] and the global QoR-40 score. A clinically significant difference is defined as a change of 10 points or more on the QoR-40 Questionnaire. In our pilot study, we estimated an overall standard deviation of 13 points, and with an of 0.05, 37 patients would be needed in each group (assuming an 80% power). Since all patients were hospitalized and all studies were completed 24 hours after surgery, the dropout rate was low, estimated to be 10%. Therefore, we recruited 41 patients in each group for a total of 82 patients in this research.

For statistical analysis, SPSS version 20.0 software (SPSS Inc., Chicago, IL) was used. The mean, standard deviation, or median are used to express continuous variables (interquartile range). The t-test was used for inter group comparison if the data were normal, instead that, the non-parametric test was used to compare groups. P-values less than 0.05 were considered statistically significant.

Results

We assessed 82 patients for eligibility to participate in this research. One patient did not meet the inclusion criteria, one declined to participate and the remaining 80 patients consented to participate. The number of patients at each level of the investigation is depicted in the flowchart in Fig 1 and the Table 1 lists the characteristics of the study population. There was no difference between the groups in terms of gender, age, height, weight, BMI, ASA physical states I/II, preoperative QoR-40 score, operation time, anesthesia time or hospitalization time.

Table 1. Patient characteristics and surgical data.

NEURO Group CON Group P-Value
(N = 40) (N = 40)
Gender (Male/Female) 13 /27 15 /25 0.138
Age (year) 37.71 ± 11.41 40.91± 13.21 0.262
Height (cm) 164.11 ± 5.82 166.21 ± 7.69 0.177
Weight (kg) 63.31 ± 8.07 65.51 ± 11.91 0.123
BMI (kg/m 2 ) 24.21 ± 10.12 25.42 ± 10.81 0.634
ASA physical states I/II (n) 1/39 1/39 1
Preoperative QoR-40 score
Global QoR-40 score 182.72±1.79 183.63±1.36 0.196
Emotional state 38.40±3.20 38.85±2.19 0.555
Physical comfort 53.31±2.16 53.40±3.96 0.925
Psychological support 34.52±0.98 34.71±0.62 0.309
Physical independence 24.84±0.03 24.90±0.30 0.480
Pain 32.82±1.75 33.37±1.64 0.187
Operation time (h) 1.34 ± 0.51 1.30 ± 0.50 0.742
Anesthesia time (h) 1.84 ± 0.51 1.80 ± 0.62 0.785
Hospitalization time (day) 4.18±2.13 4.21 ± 2.39 0.941

Data are presented as mean ± standard or number of patients (%) where appropriate

Abbreviation: ASA American Society Anesthesiologists, BMI Body mass index

The distribution of the QoR-40 scores and sub-scores of each dimension on POD1 and POD3 are shown in Table 2. The NEURO Group had significantly lower global QoR-40 scores and sub-scale scores for emotional state, physical comfort, physical independence, and pain than the CON Group on POD1 and POD3 (P < 0.05). The scores of psychological support did not meet statistical significance compared with either NEURO Group or CON Group on POD1 and POD3 (P > 0.05).

Table 2. Dimensions of the QOR-40 questionnaire on POD1 and POD3.

NEURO Group (N = 40) CON Group (N = 40) P-Value
Global QoR-40 score
POD1 160.06 ± 4.68* 170.42 ± 5.16 <0.001
POD3 170.27 ± 4.51* 174.62 ± 4.00 0.006
QoR-40 Dimensions
Emotional state
  POD1 34.48 ± 2.61* 36.96 ± 2.89 0.002
  POD3 35.46 ± 2.41* 36.88 ± 2.10 0.026
Physical comfort
  POD1 45.11 ± 2.67* 52.00 ± 4.52 <0.001
  POD3 51.37 ± 2.94* 54.90 ± 3.60 <0.001
Psychological support
  POD1 33.55 ± 0.55 33.72 ± 0.94 0.365
  POD3 33.40 ± 0.55 33.48± 0.50 0.512
Physical independence
  POD1 22.37 ± 1.37* 24.26 ± 1.22 <0.001
  POD3 22.71 ± 1.21* 24.00 ± 0.87 <0.001
Pain
  POD1 26.28 ± 3.37* 29.80 ± 3.89 <0.001
  POD3 29.55 ± 2.93* 31.08 ± 3.09 0.034

Notes:

* P<0.05 (compared to the CON Group)

Data are presented as mean ± standard deviation

Abbreviation: POD Postoperative day, QoR-40 Quality of recovery-40 questionnaire.

There was no significant difference in HR, SBP and MAP between the two groups at each time point before and after intubation, but the DBP of the patients in the NEURO Group was lower immediately after intubation (T0), 1 minutes after intubation (T1), 3 minutes after intubation (T2) and 5 minutes after intubation (T3), and the difference was statistically significant (P < 0.05; Table 3).

Table 3. Comparison of hemodynamic changes before and after intubation.

NEURO Group (N = 40) CON Group (N = 40) P-Value
HR(beats/min)
Basic values 79.91 ± 12.21 78.61 ± 14.21 0.650
Immediately after intubation (T0) 80.91 ± 14.82 81.91 ± 16.93 0.748
1 minute after intubation(T1) 71.81 ± 9.33 73.11 ± 16.82 0.687
3 minutes after intubation(T2) 70.92 ± 9.70 73.72 ± 16.22 0.352
5 minutes after intubation(T3) 69.92± 10.42 71.31 ± 12.02 0.592
SBP(mmHg)
Basic values 129.11 ± 20.32 132.12 ± 21.63 0.473
Immediately after intubation (T0) 108.21 ± 22.12 108.13 ± 19.71 1
1 minute after intubation(T1) 96.61 ± 20.91 96.62± 20.92 0.209
3 minutes after intubation(T2) 96.92 ± 18.31 95.63± 17.53 0.761
5 minutes after intubation(T3) 93.82 ± 11.91 96.32 ± 11.91 0.351
DBP(mmHg)
Basic values 80.11 ± 12.62 81.61 ± 16.22 0.877
Immediately after intubation (T0) 61.02 ± 15.61* 69.61 ± 18.22 0.026
1 minute after intubation(T1) 54.31 ± 15.41* 65.92 ± 14.32 <0.001
3 minutes after intubation(T2) 53.41 ± 13.72* 61.61 ± 11.82 0.005
5 minutes after intubation(T3) 59.22 ± 10.91* 61.12 ± 13.01 0.001
MAP(mmHg)
Basic values 94.71 ± 13.82 96.33 ± 18.11 0.663
Immediately after intubation (T0) 79.62 ± 15.92 77.91 ± 17.92 0.646
1 minute after intubation(T1) 71.52 ± 15.91 73.02 ± 15.61 0.666
3 minutes after intubation(T2) 71.12 ± 13.02 70.52 ± 11.71 0.822
5 minutes after intubation(T3) 70.01 ± 9.59 70.12 ± 11.42 0.975

Notes:

* P<0.05 (compared to the CON Group)

Data are presented as mean ± standard deviation

Abbreviation: HR Heart rate, SBP Systolic blood pressure, DBP Diastolic blood pressure, MAP Mean arterial pressure

There was no significant difference in the highest and lowest mean arterial pressures during anesthesia (P > 0.05; Table 4).

Table 4. Comparison of the highest and lowest MAP during anesthesia as well as the number of patients with the highest MAP exceed 20% of basic values and the lowest MAP less than 20% of basic values.

NEURO Group (N = 40) CON Group (N = 40) P-Value
The highest MAP(mmHg) 96.92 ± 14.91 98.20 ± 16.91 0.722
The lowest MAP(mmHg) 65.15 ± 7.60 66.43 ± 9.30 0.506
Number of patients with the highest MAP exceed 20% of basic values 1 (3%) 1 (3%) 1
Number of patients with the lowest MAP less than 20% of basic values 17 (43%) 23 (58%) 0.264

Data are presented as mean ± standard deviation or number (%)

Abbreviation: MAP Mean arterial pressure

There was no significant difference in the total dose of sufentanil and propofol in the two groups (P > 0.05). However, compared with the CON Group, the total dose of remifentanil and the total cost of hospitalization were significantly increased in the NEURO Group (P < 0.05; Table 5).

Table 5. Comparison of drug consumption in anesthesia and total hospitalization costs.

NEURO Group (N = 40) CON Group (N = 40) P-Value
Total dose of sufentanil(μg/kg) 0.56±0.11 0.52±0.11 0.152
Total dose of remifentanil(μg/kg) 9.24±4.23* 6.68±1.98 0.001
Total dose of propofol(mg/kg) 6.36±0.40 6.38±0.43 0.840
Total cost of hospitalization(10K CNY) 2.62 ± 1.25* 1.50± 0.28 <0.001

Notes:

* P<0.05 (compared to the CON Group)

Data are presented as mean ± standard deviation

There was no significant difference between the groups in terms of throat pain (VAS>3 point), hoarseness, drinking water cough, wound pain (VAS>3 point), wound bleeding (need surgery) and fatigue (P > 0.05). On the contrary, the incidence of PONV was significantly increased in the NEURO Group (P < 0.05; Table 6).

Table 6. Comparison of postoperative adverse reactions on POD1.

NEURO Group (N = 40) CON Group (N = 40) P-Value
Nausea and vomiting 13 (32%)* 4 (10%) 0.029
Throat pain(VAS>3 point) 34 (85%) 28 (70%) 0.181
Hoarseness (n, %) 24 (60%) 15 (38%) 0.074
Drinking water cough 9 (22%) 5 (12%) 0.377
Wound pain(VAS>3 point) 33 (82%) 29 (72%) 0.422
Wound bleeding(need surgery) 0 (0%) 0 (0%) 1
Fatigue 20 (50%) 18 (45%) 0.823

Notes:

* P<0.05 (compared to the CON Group)

Data are presented as number (%)

All patients in the NEURO Group were given nerve probe to stimulate the recurrent laryngeal nerve before the end of the operation and all patients had no RLNP during the operation. All patients in the CON Group had no adverse reactions such as hoarseness and drinking water cough before leave hospital, which indirectly proved that all patients in the CON Group had no RLNP during the operation.

Discussion

We evaluated and compared the effects of IONM technology on early postoperative recovery quality by means of the QoR-40 Questionnaire in patients after thyroid surgery on POD1 and POD3. Our results demonstrate that the global score of QoR-40 Questionnaire decreased significantly in the NEURO Group, mainly in the emotional state, physical comfort, physical independence and pain perception. In addition, the incidence of the PONV, the amount of remifentanil consumption and the total cost of hospitalization was significantly increased in the NEURO Group. The difference in these aspects between group NEURO and group CON meet statistical significance difference.

At present, there are few studies on evaluating the early recovery quality of thyroid surgery patients by QoR-40 Questionnaire. The results of Myoung’s research [17] show that the total score of QoR-40 after traditional thyroid surgery is 179.4, and our result is 173, which was similar to it. However, early recovery quality of patients after thyroid surgery with IONM technology has not been reported so far. This is the first research to observe the effects of IONM technology on early postoperative recovery quality of thyroid surgery patients undergoing by QoR-40 Questionnaire.

Our research found that the patients in the NEURO Group not only had a significant decrease in the global score of the QoR-40 Questionnaire on POD1 and POD3, but also had significantly lower scores in emotional state, physical comfort, physical independence and pain. When IONM applied on patients, the programs of anesthesia and surgery are different from traditional way. First, the patients in the NEURO Group only used 1*ED95 muscle relaxant during induction and no more muscle relaxant was allowed during whole procedure. This dose of muscle relaxant is less than half of that used in patients undergoing traditional thyroid surgery. As results, the clinical duration of muscle relaxant is shorter and recovery of neuromuscular block were faster in patients of NEURO group than those of CON group. Till now, there is no evidence about the postoperative recovery and the depth of neuromuscular block during operation in patients undergoing thyroid surgery. However, in laparoscopic surgery, Koo at all [18, 19] demonstrate that deep muscle relaxants can improve the postoperative satisfaction of patients. This hints that the lower dose of muscle relaxant may be one of the reasons why IONM decreases patients’ QoR40 scores after surgery. Next, the endotracheal tube used in IONM has a wider outer diameter and balloon inflation size than that used in traditional way. In our study, outer diameters of tubes are 8.8mm and 10.5mm for female and male patients respectively in NEURO group. In control group, the outer diameters of tubes are 8.7mm and 9.5mm for female and male patients. The wider tube probably bring more nociceptive stimulation in the procedure of intubation and extubation. In addition, the balloon inflation diameter is also larger in NURO group than that in CON group. For female patients, the balloon inflation diameter is 23mm in NEURO group and 19mm in the CON Group. For male patients, the balloon inflation diameter is 26mm in NEURO group and 22mm in the CON Group. Finally, the surgeon will use the probe to detect the nerve activities by intermittently stimulating patients’ vocal cords. If these stimulations deteriorate the patients’ satisfaction after surgery, there is still no evidence.

Our results also show that more events of PONV in the NEURO Group, compared with the CON Group. The patients in the NEURO Group induced only 1*ED95 muscle relaxant during induction and no muscle relaxant were added during the operation. In order to avoid unexpected movement, more opioids or sedatives would be used in these patients. In our research, the dosage of remifentanil in the NEURO Group patients increased significantly, and the thyroid surgery time was shorter, the accumulation of these opioids in patients will eventually leads to adverse reactions such as nausea and vomiting after surgery. Nonetheless, whether these factors will increase the incidence of PONV needs further research. In our research, the total hospitalization cost of the patients in the NEURO Group was higher than those of the CON Group, and we believe that it was the additional costs incurred by the NIM endotracheal tube and never probe that greatly increased the total hospitalization costs of these patients.

IONM technology can effectively prevent the RLNP, which make this technology gradually accepted by surgeon. However, our study confirmed that IONM technology does lead to a decrease in the early recovery quality. Although many new technologies will provide us with many conveniences at the beginning of their advent, at the same time they will also bring many new problems. This research proposed some adverse consequences of IONM technology from the perspective of anesthesia, and suggested that we need to explore a set of anesthesia programs to improve the early recovery quality of thyroid surgery patients.

Although our research demonstrates that IONM technology reduced early recovery quality of thyroid surgery, it did not negate this technology, but to improve this technology. It is necessary to optimize anesthesia protocol to improve early recovery quality, and it also put forward directions for future research. In order to cooperate with surgeons to improve this technology, it is particularly important to explore a set of anesthesia programs to improve the early recovery quality. Our future research will focus on explore how to improve the early recovery quality of thyroid surgery patients with IONM technology without affecting the operation of surgeon.

There are some limitations in this research. First, we didn’t measure the train-of-four ratio and balloon pressure in this study, so we haven’t direct evidences to say that the lower QoR40 score is associated with the smaller dose of muscle relaxant and larger size of inflation balloon used in patients undergoing thyroid surgery with IONM. This study was not designed to identify the factors involved in quality of recovery and IONM used in surgery. Our objective is to observe the effects of IONM technology on recovery quality in patients after thyroid surgery. So, we believe our results are reliable for our conclusion. We need further clinical trials to study why patients undergoing thyroid surgery with IONM suffer the worse postoperative recovery. Second, this research was not a blinded study. This is because the surgical method must be informed to the patients in detail before surgery, which cannot be concealed, and the NEURO Group also needs NIM endotracheal tube and never probe, so the anesthesiologist must also know it. Furthermore, our research did not distinguish between male and female genders. The recovery quality of male and female patients after thyroid surgery may be different. Although this does not affect the results of this study, future research should further compare the early recovery quality between different genders after the use of IONM technology. Lastly, our research concluded that the patients in the NEURO Group were less cost-effective. This is because the primary outcome of the study was the QoR-40 score, after sample evaluation according to this indicator, only 40 patients were included in each group, and all 80 patients did not suffer from RLNP eventually. With the increase of the risk of RLNP, the potential cost benefits of IONM technology will also increase. If the recurrent laryngeal nerve is injured due to the absence of IONM technology, the cost of NIM endotracheal tube and nerve probe is insignificant compared with the follow-up cost of treating RLNP and other complications.

Conclusion

After thyroidectomy, the patients using IONM suffer worse quality of recovery, more risk of PONV and increased medical expense.

Supporting information

S1 Table. The quality of recovery-40 (QoR-40) questionnaire.

(PDF)

S1 File. Protocol for publication (Chinese version).

(PDF)

S2 File. Protocol for publication (English version).

(PDF)

S3 File. CONSORT 2010 checklist of information to include when reporting a randomised trial.

(PDF)

Data Availability

All relevant data are within the paper and its Supporting information files.

Funding Statement

The author(s) received no specific funding for this work.

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Decision Letter 0

Luigi La Via

11 Jul 2023

PONE-D-23-11841Effects of intraoperative neuromonitoring (IONM) technology on early recovery quality in patients after thyroid surgery: a randomized controlled trialPLOS ONE

Dear Dr. LU,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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PLOS ONE

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[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: No

Reviewer #2: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

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Reviewer #1: No

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors conducted a randomized controlled study comparing the recovery of the patients after receiving a regular dose versus a low dose of rocuronium during the IONM in thyroid surgery. There are several concerns. First, it is unclear whether the authors wanted to investigate the effect of the low-dose rocuronium or the impact of IONM on the recovery.

Major

1. Figure 2 should be re-drawn to have the y-axis scale from 0. If it is drawn as it is now (e.g., QoR score begins from 150), the difference between the two groups looks exaggerated.

2. The results section is very painful to read. Lines 224 – 233 have too many numbers, and it isn't easy to understand the significance. Please focus on the positive findings with p values.

3. Patients in the two groups had different doses of rocuronium, and only the NEURO group underwent IONM. The difference in the results is from the difference in the dose of rocuronium or the use of IONM?

4. The authors suggest that the low dose of rocuronium is the cause of the low questionnaire scores in the IONM group. Despite the references the authors suggested, the assertion is not well backed by solid evidence. The reference paper by Koo was about laparoscopic abdominal surgery, which is quite different from thyroid surgery in terms that abdominal surgery requires deeper relaxation. Furthermore, the hemodynamics in the two groups in the current study are not different, suggesting a different dose of rocuronium was not critical to the participants.

5. The results of ToFr measurement should be demonstrated to assert that the dose of rocuronium made a difference in the questionnaire scores of the two groups.

6. The authors claim that the quality of life of the NEURO group is worse than the control group because the QoR score in the NEURO group is lower than the control group. Although the scores were statistically different, the difference in the absolute number was not so impressive (e.g., 160 vs 170 on POD1, 170 vs 174 on POD3). Does this difference is significant enough to conclude so?

7. Does the balloon size matter or balloon pressure matter? If the balloon pressure was controlled well, balloon size might not affect the tracheal symptoms. If the balloon size mattered, the dose of rocuronium is not important, and what mattered was just a tube.

Minor

1. English editing is mandatory.

2. Questionnaires should be given for the readers can understand the results better.

3. Detailed descriptions of the questionnaires should be moved from introduction to Methods.

4. Line 156-163 is unnecessary.

5. Line 335. "cost of the patients in the NEURO Group was less." It looks like a mistake because Table 5 shows that the cost in the NEURO group was higher.

6. Line 239-242 is too lengthy. The difference in MAP was already explained in Methods.

7. Line 267-287 is just a repetition of Introduction.

Reviewer #2: Thank you for the opportunity to read this manuscript on the effects of intraoperative neuromonitoring technology on early recovery quality in patients after thyroid surgery. The paper is interesting and sound. However, I have some comments to make:

- Line 75. Before introducing neuromonitoring, authors should report the increasing development of intraoperative monitoring in anesthesia with the use of artificial intelligence (doi: 10.1097/ALN.0000000000002960 - doi: 10.1016/j.bjane.2015.09.001 - doi: 10.3390/jcm11020392). Please briefly discuss and add these 3 references.

- Why did authors include only patient aged between 20 and 70 years? Please explain.

- Line 135. Who was aware of the group allocation?

- Line 174-175. Please replace "is" with "was".

- Line 212. Please replace decline with declined.

**********

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Reviewer #1: No

Reviewer #2: No

**********

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PLoS One. 2023 Sep 26;18(9):e0292036. doi: 10.1371/journal.pone.0292036.r002

Author response to Decision Letter 0


19 Aug 2023

Dear editors and reviewers,

Thank you very much for your comments and professional advice. These opinions help to improve academic rigor of our article. Based on your suggestion and request, we have made corrected modifications on the revised manuscript. Besides, our study’s original protocol and supporting information were uploaded to the editors when we submitting our revised manuscript. Furthermore, we would like to show the details as follows:

Reviewer 1#

Major

1.Figure 2 should be re-drawn to have the y-axis scale from 0. If it is drawn as it is now (e.g., QoR score begins from 150), the difference between the two groups looks exaggerated.

The author’s answer: We agree your opinion. All database have been shown in Table 2, so we think Figure 2 maybe a little bit repetition. So we deleted the Figure 2 .

2.The results section is very painful to read. Lines 224 – 233 have too many numbers, and it isn't easy to understand the significance. Please focus on the positive findings with p values.

The author’s answer: We agree that too many numbers isn't easy to understand the significance. Thank you for your reminder. We have deleted it.

3.Patients in the two groups had different doses of rocuronium, and only the NEURO group underwent IONM. The difference in the results is from the difference in the dose of rocuronium or the use of IONM?

The author’s answer: We have no evidence to conform that the lower dose of rocuronium leads to worse quality of recovery. This study is to compare the different qualities of recovery between thyroid surgery in traditional way and with IONM. Compared to traditional way, procedure with IONM have some different points, including A smaller dose of muscle relaxant, intubation of endotracheal tube with bigger outer diameter and intermittent stimulation on vocal cord. All of these are possible involved in decreased QoR40 scores in NRURO group. We have modified words expression in some paragraphs of introduction and discussion.

4.The authors suggest that the low dose of rocuronium is the cause of the low questionnaire scores in the IONM group. Despite the references the authors suggested, the assertion is not well backed by solid evidence. The reference paper by Koo was about laparoscopic abdominal surgery, which is quite different from thyroid surgery in terms that abdominal surgery requires deeper relaxation. Furthermore, the hemodynamics in the two groups in the current study are not different, suggesting a different dose of rocuronium was not critical to the participants.

The author’s answer: We agree with your opinion that, till now, there have been no solid evidence in relationship between neuromuscular block and quality of recovery in thyroid surgery. We didn’t monitored neuromuscular block for the whole surgical procedure. So we cannot provide direct evidence in this study. This is one of our limitation. In revision, we’ve written this limitation in the part of discussion. Our objective is not to study the quality of recovery and the depth of neuromuscular block. In NEURO group, the patients received no more than half dose of rocuronium, compared to those in control group. So, in theory, the clinical duration of rocuronium is shorter and recovery of neuromuscular block is faster in patients of NEURO group. According to the paper by Koo, we think this is a possible cause. Besides, the harder endotracheal tube enwrapped by electrode with wider outer diameter and intermittent stimulation on cocal cord during surgery also probably lead to a lower QoR40 score. These need further researches. We’ve revised several paragraphs in manuscript to express more correctly.

5.The results of ToFr measurement should be demonstrated to assert that the dose of rocuronium made a difference in the questionnaire scores of the two groups.

The author’s answer: We just measured the TOFR at the beginning and end of the anesthesia, so we can estimate the timing of intubation and extubation. This is one of our limitations. We’ve written this in the part of discussion in revision. Our objective is to observe the effects of thyroid surgery with IONM on patients’ postoperative recovery. This clinical trial is not designed to study the relationship between the depth of neuromuscular block and quality of recovery. So we didn’t measure TOFR for whole surgery. We’ve revised several paragraphs in manuscript to express more correctly.

6.The authors claim that the quality of life of the NEURO group is worse than the control group because the QoR score in the NEURO group is lower than the control group. Although the scores were statistically different, the difference in the absolute number was not so impressive (e.g., 160 vs 170 on POD1, 170 vs 174 on POD3). Does this difference is significant enough to conclude so?

The author’s answer: The differences of QoR40 scores between Neuro group and Control groupare minor on POD1 and POD2, but these differences are really significant in statistic. The QoR40 questionnaire has been demonstrated as a reliable muti-dimensional assessment tool, which can evaluate patient’s health status after surgery and anesthsia. Our conclusion is drawn according to the statistical difference in QoR40 scorces.

7.Does the balloon size matter or balloon pressure matter? If the balloon pressure was controlled well, balloon size might not affect the tracheal symptoms. If the balloon size mattered, the dose of rocuronium is not important, and what mattered was just a tube.

The author’s answer: We agree with your opinion the balloon pressure is very impertant. In this study, we didn’t measure the balloon pressure. This is one of limitations of this study. In revision, we’ve written this limitation in part of discussion. Not only balloon size but also the tube outer diameter of IONM tube is larger than traditional one. The endotracheal tube with larger outer diameter is another possible facor to bring nociceptive stimulation during intubation and extubation. We think these factors probably affect patient’s satisfaction after surgery and we need more studies to demonstrate.

Minor

1.English editing is mandatory.

The author’s answer: We have edited English of this article.

2.Questionnaires should be given for the readers can understand the results better.

The author’s answer: We have put the QoR-40 Questionnaires as supporting information at the end of the manuscript.

3.Detailed descriptions of the questionnaires should be moved from introduction to Methods.

The author’s answer: We have moved detailed descriptions of the questionnairesfrom introduction to Methods.

4.Line 156-163 is unnecessary.

The author’s answer: We agree that this is unnecessary of the study. We have deleted it.

5.Line 335. "cost of the patients in the NEURO Group was less." It looks like a mistake because Table 5 shows that the cost in the NEURO group was higher.

The author’s answer: We were really sorry for our careless mistakes. Thank you for your reminder. We have replaced“less” to “higher”.

6.Line 239-242 is too lengthy. The difference in MAP was already explained in Methods.

The author’s answer:We agree that this is repetition of the explanation of MAP. Thank you for your reminder. We have deleted it.

7.Line 267-287 is just a repetition of Introduction.

The author’s answer: We agree that this is repetition of Introduction. Thank you for your reminder. We have deleted it.

Reviewer 2#

1.Line 75. Before introducing neuromonitoring, authors should report the increasing development of intraoperative monitoring in anesthesia with the use of artificial intelligence (doi: 10.1097/ALN.0000000000002960 - doi: 10.1016/j.bjane.2015.09.001 - doi: 10.3390/jcm11020392). Please briefly discuss and add these 3 references.

The author’s answer: We sincerely appreciate the valuable comments. We report the increasing development of intraoperative monitoring in anesthesia with the use of artificial intelligence and we also have added more references (doi: 10.1097/ALN.0000000000002960 - doi: 10.1016/j.bjane.2015.09.001 - doi: 10.3390/jcm11020392) before introducing neuromonitoring in the revised manuscript. Please see line 93-96.

2.Why did authors include only patient aged between 20 and 70 years? Please explain.

The author’s answer: Our research in the first research, so we choose the adults, and the elderly and minors may have organ function degeneration or immaturity. We will study different ages of people in the follow-up research.

3.Line 135. Who was aware of the group allocation?

The author’s answer: Surgeon and anesthesiologist aware of the group allocation. This research was not a blinded study. This is because the surgical method must be informed to the patients in detail before surgery, which cannot be concealed, and the NEURO Group also needs NIM endotracheal tube and never probe, so the anesthesiologist must also know it.

4.Line 174-175. Please replace "is" with "was".

The author’s answer: We have changed “is” to “was”. Please see line 167-168

5.Line 212. Please replace decline with declined.

The author’s answer: We have changed “decline” to “declined”. Please see line 211

Thank you very much for your attention and time. Look forward to hearing from you.

Yours sincerely,

Lu Zhijun

August 20, 2023

Attachment

Submitted filename: 20230820 Response to reviewers.docx

Decision Letter 1

Luigi La Via

11 Sep 2023

Effects of intraoperative neuromonitoring (IONM) technology on early recovery quality in patients after thyroid surgery: a randomized controlled trial

PONE-D-23-11841R1

Dear Dr. LU,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Luigi La Via

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Authors replied all the questions and revised the manuscript properly. No further questions or comments.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

**********

Acceptance letter

Luigi La Via

18 Sep 2023

PONE-D-23-11841R1

Effects of intraoperative neuromonitoring (IONM) technology on early recovery quality in patients after thyroid surgery: a randomized controlled trial

Dear Dr. Lu:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Luigi La Via

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Table. The quality of recovery-40 (QoR-40) questionnaire.

    (PDF)

    S1 File. Protocol for publication (Chinese version).

    (PDF)

    S2 File. Protocol for publication (English version).

    (PDF)

    S3 File. CONSORT 2010 checklist of information to include when reporting a randomised trial.

    (PDF)

    Attachment

    Submitted filename: 20230820 Response to reviewers.docx

    Data Availability Statement

    All relevant data are within the paper and its Supporting information files.


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