Cirocchi Roberto, Arezzo Alberto, D'Andrea Vito, Abraha Iosief, Popivanov Georgi I, Avenia Nicola, Gerardi Chiara, Henry Brandon Michael, Randolph Justus, Barczyñski Marcin
Department of General Surgery, University of Perugia, Terni, Italy, 05100.
Cochrane Database Syst Rev. 2019 Jan 19;1(1):CD012483. doi: 10.1002/14651858.CD012483.pub2.
Injuries to the recurrent inferior laryngeal nerve (RILN) remain one of the major post-operative complications after thyroid and parathyroid surgery. Damage to this nerve can result in a temporary or permanent palsy, which is associated with vocal cord paresis or paralysis. Visual identification of the RILN is a common procedure to prevent nerve injury during thyroid and parathyroid surgery. Recently, intraoperative neuromonitoring (IONM) has been introduced in order to facilitate the localisation of the nerves and to prevent their injury during surgery. IONM permits nerve identification using an electrode, where, in order to measure the nerve response, the electric field is converted to an acoustic signal.
To assess the effects of IONM versus visual nerve identification for the prevention of RILN injury in adults undergoing thyroid surgery.
We searched CENTRAL, MEDLINE, Embase, ICTRP Search Portal and ClinicalTrials.gov. The date of the last search of all databases was 21 August 2018. We did not apply any language restrictions.
We included randomised controlled trials (RCTs) comparing IONM nerve identification plus visual nerve identification versus visual nerve identification alone for prevention of RILN injury in adults undergoing thyroid surgery DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts for relevance. One review author carried out screening for inclusion, data extraction and 'Risk of bias' assessment and a second review author checked them. For dichotomous outcomes, we calculated risk ratios (RRs) with 95% confidence intervals (CIs). For continuous outcomes, we calculated mean differences (MDs) with 95% CIs. We assessed trials for certainty of the evidence using the GRADE instrument.
Five RCTs with 1558 participants (781 participants were randomly assigned to IONM and 777 to visual nerve identification only) met the inclusion criteria; two trials were performed in Poland and one trial each was performed in China, Korea and Turkey. Inclusion and exclusion criteria differed among trials: previous thyroid or parathyroid surgery was an exclusion criterion in three trials. In contrast, this was a specific inclusion criterion in another trial. Three trials had central neck compartment dissection or lateral neck dissection and Graves' disease as exclusion criteria. The mean duration of follow-up ranged from 6 to 12 months. The mean age of participants ranged between 41.7 years and 51.9 years.There was no firm evidence of an advantage or disadvantage comparing IONM with visual nerve identification only for permanent RILN palsy (RR 0.77, 95% CI 0.33 to 1.77; P = 0.54; 4 trials; 2895 nerves at risk; very low-certainty evidence) or transient RILN palsy (RR 0.62, 95% CI 0.35 to 1.08; P = 0.09; 4 trials; 2895 nerves at risk; very low-certainty evidence). None of the trials reported health-related quality of life. Transient hypoparathyroidism as an adverse event was not substantially different between intervention and comparator groups (RR 1.25; 95% CI 0.45 to 3.47; P = 0.66; 2 trials; 286 participants; very low-certainty evidence). Operative time was comparable between IONM and visual nerve monitoring alone (MD 5.5 minutes, 95% CI -0.7 to 11.8; P = 0.08; 3 trials; 1251 participants; very low-certainty evidence). Three of five included trials provided data on all-cause mortality: no deaths were reported. None of the trials reported socioeconomic effects. The evidence reported in this review was mostly of very low certainty, particularly because of risk of bias, a high degree of imprecision due to wide confidence intervals and substantial between-study heterogeneity.
AUTHORS' CONCLUSIONS: Results from this systematic review and meta-analysis indicate that there is currently no conclusive evidence for the superiority or inferiority of IONM over visual nerve identification only on any of the outcomes measured. Well-designed, executed, analysed and reported RCTs with a larger number of participants and longer follow-up, employing the latest IONM technology and applying new surgical techniques are needed.
喉返神经（RILN）损伤仍然是甲状腺和甲状旁腺手术后主要的术后并发症之一。该神经损伤可导致暂时或永久性麻痹，进而引起声带轻瘫或麻痹。在甲状腺和甲状旁腺手术中，直视下识别RILN是预防神经损伤的常用方法。最近，术中神经监测（IONM）被引入，以促进神经定位并防止手术过程中神经损伤。IONM通过电极识别神经，为测量神经反应，电场会被转换为声信号。
评估IONM与直视下神经识别在预防成人甲状腺手术中RILN损伤方面的效果。
我们检索了Cochrane系统评价数据库、医学索引数据库、荷兰医学文摘数据库、国际临床试验注册平台检索入口和美国国立医学图书馆临床试验数据库。所有数据库的最后检索日期为2018年8月21日。我们未设任何语言限制。
我们纳入了比较IONM神经识别联合直视下神经识别与单纯直视下神经识别预防成人甲状腺手术中RILN损伤的随机对照试验（RCT）。数据收集与分析：两位综述作者独立筛选标题和摘要以确定相关性。一位综述作者进行纳入筛选、数据提取和“偏倚风险”评估，另一位综述作者进行核对。对于二分法结局，我们计算风险比（RR）及95%置信区间（CI）。对于连续性结局，我们计算平均差（MD）及95%CI。我们使用GRADE工具评估试验证据的确定性。
五项RCT（共1558名参与者，781名参与者被随机分配至IONM组，777名参与者仅被分配至直视下神经识别组）符合纳入标准；两项试验在波兰进行，一项试验分别在中国、韩国和土耳其进行。各试验的纳入和排除标准不同：三项试验将既往甲状腺或甲状旁腺手术作为排除标准。相反，在另一项试验中，这是一项特定的纳入标准。三项试验将中央颈部区域清扫术或侧颈部清扫术以及格雷夫斯病作为排除标准。平均随访时间为6至12个月。参与者的平均年龄在41.岁至51.9岁之间。对于永久性RILN麻痹（RR 0.77，95%CI 0.33至1.77；P = 0.54；4项试验；2895条神经有风险；极低确定性证据）或暂时性RILN麻痹（RR 0.62，95%CI 0.35至1.08；P = 0.09；4项试验；2895条神经有风险；极低确定性证据），比较IONM与单纯直视下神经识别，没有确凿证据表明存在优势或劣势。没有试验报告与健康相关的生活质量。干预组和对照组之间，作为不良事件的暂时性甲状旁腺功能减退没有显著差异（RR 1,25；95%CI 0.45至3.47；P = 0.66；2项试验；286名参与者；极低确定性证据）。IONM与单纯直视下神经监测的手术时间相当（MD 5.5分钟，95%CI -0.7至11.8；P = 0.08；3项试验；1251名参与者；极低确定性证据）。五项纳入试验中的三项提供了全因死亡率数据：未报告死亡病例。没有试验报告社会经济影响。本综述中报告的证据大多确定性极低，特别是由于存在偏倚风险、置信区间宽导致的高度不精确性以及研究间的显著异质性。
本系统评价和荟萃分析结果表明，目前没有确凿证据表明IONM在任何测量结局上优于或劣于单纯直视下神经识别。需要设计良好、执行、分析和报告的RCT，纳入更多参与者并进行更长时间的随访，采用最新的IONM技术并应用新的手术技术。
