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Effect of laryngotracheal topical anesthesia on recurrent laryngeal nerve monitoring during thyroid Surgery
Journal of Clinical Anesthesia (2016) 29, 10–13
Original contribution
Effect of laryngotracheal topical anesthesia on recurrent laryngeal nerve monitoring during thyroid Surgery Justin Pachuski MD a, Sonia Vaida MD a, Kathleen Donahue DO a, John Roberts MD b, Allen Kunselman MA c, Benjamin Oberman MD b, Hetal Patel MD b, David Goldenberg MD, FACS b,⁎ a
Department of Anesthesiology, Head and Neck Surgery, Penn State College of Medicine and Penn State Hershey Medical Center, Hershey, PA, USA b Department of Surgery, Division of Otolaryngology, Head and Neck Surgery, Penn State College of Medicine and Penn State Hershey Medical Center, Hershey, PA, USA c Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA Received 1 January 2015; accepted 16 September 2015
Keywords: Intraoperative neuromonitoring; Recurrent laryngeal nerve; Laryngotracheal topical anesthesia; Lidocaine; Thyroidectomy
Abstract Study Objective: Intraoperative neuromonitoring of the recurrent laryngeal nerve (RLN) is often used as an adjunct for RLN identification and preservation during thyroidectomies. Laryngotracheal anesthesia (LTA) with topical lidocaine reduces coughing upon emergence from anesthesia and in the immediate postoperative period; however, its use is prohibited with concerns that it could decrease the sensitivity of the intraoperative neuromonitoring. We hypothesize that there is no difference in measurements of nerve conduction made before and after LTA administration. Design: An observational study in which all patients were subjected to LTA administration was conducted. Recurrent laryngeal nerve threshold currents were measured before and after the intervention. Setting: Tertiary medical center operating room. Patients: Eighteen patients (total of 25 nerves at risk) with American Society of Anesthesiologists classes 1 to 3 undergoing thyroid surgery. Interventions: After the thyroid was removed and threshold currents at the RLN were obtained, LTA with endotracheal lidocaine was applied on the left and right side of the in situ endotracheal tube (2 cc of 4% lidocaine per side). Threshold currents were reassessed at 5 and 10 minutes after LTA administration. Measurements: Threshold currents (minimum stimulus current applied to the RLN required to generate a discernible electromyographic response at the vocal cords) were recorded along the RLN for a baseline at 5 and 10 mm from the insertion point of the RLN into the larynx. Threshold currents were reassessed at the same 2 positions on the RLN at 5 and 10 minutes after LTA administration. Differences in mean values, between threshold currents recorded at the 3 different times, at 2 positions on the RLN, were used to compare effects of LTA on nerve conduction.
⁎ Corresponding author at: Department of Surgery, Division of Otolaryngology–Head and Neck Surgery, Penn State Hershey Medical Center, 500 University Drive, Hershey, PA 17033, USA. Tel.: +1 717 531 8945. E-mail addresses: [email protected] (J. Pachuski), [email protected] (S. Vaida), [email protected] (K. Donahue), [email protected] (J. Roberts), [email protected] (A. Kunselman), [email protected] (B. Oberman), [email protected] (H. Patel), [email protected] (D. Goldenberg).
http://dx.doi.org/10.1016/j.jclinane.2015.09.003 0952-8180/© 2015 Elsevier Inc. All rights reserved.
11 Main Results: There were no statistically significant differences when comparing threshold currents before and after LTA administration. Conclusions: Laryngotracheal anesthesia had no significant effect on RLN nerve conduction in the period assessed. © 2015 Elsevier Inc. All rights reserved.
1. Introduction Recurrent laryngeal nerve (RLN) paralysis after thyroid surgery has a reported incidence of 0 to 11% [1], with an even higher incidence in cases presenting with large multinodular goiters, cancers, and revision surgery [2]. Intraoperative neuromonitoring (IONM) of the RLN has become a popular adjunct to aid the surgeon in locating and preserving the RLN during thyroid and other neck surgeries [3–5]. Another potential complication is postthyroidectomy hematoma resulting in airway compromise. Coughing upon emergence from anesthesia as well as in the postoperative period may be a contributing factor to the development of these hematomas [6]. Laryngotracheal anesthesia (LTA) with topical lidocaine applied to the trachea and glottis prior to intubation is used to decrease the incidence of coughing upon emergence from general anesthesia [7,8]. In light of the effects of lidocaine on nerve conduction and the proximity of the RLN to the trachea, concern has been expressed that LTA may decrease the ability to adequately monitor the function of the RLN. This concern is supported by previous work that demonstrated a reduction in percutaneous laryngeal electromyography (EMG) signal after transtracheal lidocaine administration in phonating patients [9]. On the basis of these concerns, 2 manufacturers of endotracheal tubes (ETTs) with embedded electrodes for sampling laryngeal EMG recommend avoiding endotracheal lidocaine [10,11]. This prohibition on topical local anesthetic has also been expressed in an article discussing anesthetic considerations for IONM of the RLN [12]. Our aim was to assess the effect of LTA on IONM of the RLN during thyroidectomy. We hypothesized that there is no difference in nerve conduction (as defined by the threshold current—minimum stimulus current applied to the RLN required to generate a discernible EMG response at the vocal cords) between measurements made before and after LTA.
2. Materials and methods Institutional review board approval was obtained. Adult patients with American Society of Anesthesiologists classes 1 to 3 undergoing total or hemi-thyroidectomy were included. In total, 18 patients were enrolled for a total of 25 nerves at risk: 11 hemi-thyroidectomies (1 nerve at risk) and 7 total thyroidectomies (2 nerves at risk). Patients with known difficult airway, suspected RLN invasion, preoperative
vocal cord paralysis, or anticipated RLN sacrifice due to gross disease were excluded from the study. The patients were intubated with a NuVasive NV JJB/M5 EMG ETT, Long Electrode (NuVasive, Inc, San Diego, CA), an ETT with embedded laryngeal surface electrodes. The neuromonitoring technique included placement of 2 surface electrodes at the wrist, overlying the ulnar nerve (train-of-four [TOF] stimulation), 2 needle electrodes in the muscle bellies of the abductor pollicus brevis and the abductor digiti minimi (monitoring TOF EMG), one needle in left deltoid (ground), and one needle placed in a midline cervical location (stimulus return). A sterilized Prass monopolar probe was used for RLN stimulation. After completion of thyroidectomy and hemostasis was achieved, a TOF ratio greater than 85% was confirmed by the neurophysiologist. The RLN was identified anatomically by the attending surgeon and stimulated at 2 points: 5 and 10 mm from the insertion of the RLN into the larynx. Resident surgeons in their postgraduate years 4 and 5 also participated under the supervision of the attending surgeon: however, all measurements were confirmed by the attending surgeon. The nerve was stimulated to the threshold current with each stimulus delivered for 100 μs at a frequency of 4 Hz. Stimuli start at 0 mA and increase by 0.05 mA until an EMG response was detected at the vocal cords. The current was then decreased by 0.1 mA and again increased by 0.05 mA until a response was detected. Threshold current was defined as the minimum stimulus current that produced a response detected via vocal cord EMG. All clinical neurophysiologists received Certification in Neurophysiologic Intraoperative Monitoring (CNIM) certified and the oversight reading neurologist performed real time Web-based guidance from an off-site location for all cases. After the baseline threshold value was obtained, the anesthesiologist performed laryngoscopy and visualized the larynx (direct laryngoscopy or indirect video laryngoscopy), suctioned any secretions, and then deflated the ETT cuff. The LTA device (“LTA 360 kit,” lidocaine hydrochloride topical solution, 4%; Hospira, Lake Forest, IL) was passed on each side of the ETT (inserted to appropriate depth to spray carina, with care taken not to touch the EMG electrodes taped onto the ETT), and lidocaine, a total of 4 mL of 4%, was administered bilaterally while withdrawing the LTA. The ETT cuff was then reinflated. Response thresholds were reassessed at 5 and 10 minutes after administration of topical lidocaine. Prior to study initiation, we assumed that a change in threshold current of 0.2 mA would be clinically meaningful and that the standard deviation would be 0.1 mA3 [3], with a
J. Pachuski et al.
within-nerve correlation of 0.7. Based on these assumptions, a sample size of 12 nerves was expected to provide greater than 90% power to detect a change in threshold current of 0.2 mA using a 2-sided test having a significance level of .05. A linear mixed-effects model [13] was used to compare the position on the nerve (5 or 10 mm), the time of data collection (0, 5, and 10 minutes), and their interaction with respect to the threshold current. The linear mixed-effects model is an extension of linear regression that accounts for the within-subject variability inherent in repeated-measures designs. Because there are 2 repeated factors in this study, that is, position and time, the Kronecker product of an unstructured and first-order autoregressive matrix was used in the mixed-effects model to specify the variance-covariance matrix [14]. Residual diagnostics were used to evaluate model fit. No adjustments for multiple testing were done. All hypotheses tests were 2 sided, and all analyses were performed using SAS software, version 9.3 (SAS Institute Inc, Cary, NC).
3. Results The threshold currents required to generate vocal cord EMG response as measured with stimulus delivered at 5 and 10 mm from the RLN insertion into the larynx are presented in Table 1 and Figure. Differences in means between threshold currents measured at different times (Table 2) and positions on the RLN (Table 3) were calculated with the associated 95% confidence interval and P value for each difference in means. No statistically significant differences were seen when comparing threshold currents before and after the administration of endotracheal lidocaine. No statistically significant differences were seen when comparing threshold currents with respect to stimulus position along the RLN.
4. Discussion Because of the nature of the mechanism of action of lidocaine and the proximity of the RLN to the site of administration of local anesthetic during LTA, there is a theoretical risk of causing an inhibitory effect on RLN Table 1 Mean and standard deviations of response threshold currents measured with stimulus delivered at 5 and 10 mm from the RLN insertion into the larynx Position
Time (min)
Mean (mA)
Standard deviation
5 mm
0 5 10 0 5 10
0.312 0.312 0.298 0.305 0.312 0.299
0.099 0.093 0.084 0.095 0.085 0.100
10 mm
Time zero is prior to endotracheal lidocaine administration, and times 5 and 10 minutes are the durations after administration of lidocaine. n = 25.
RLN threshold current (mA)
12
5 mm
10 mm
0.4
0.3
0.2
0.1
0 0
5
10
Time after LTA (min.)
Figure Mean and standard deviations of response threshold currents measured with stimulus delivered at 5 and 10 mm from the RLN insertion into the larynx. Time zero is prior to endotracheal lidocaine administration, and times 5 and 10 minutes are the durations after administration of lidocaine. n = 25.
conduction, which could diminish the efficacy of IONM of the RLN during thyroid surgery. To our knowledge, this was the first study investigating the effect of LTA on stimulation currents required to generate a discernable EMG response at the vocal cords. Our data suggest that LTA administration does not have an inhibitory effect on the conduction of the RLN in the setting of IONM for thyroid surgery. The outcome of this study differs from the results of previous work by Chitkara et al [9], which demonstrated a decrease in laryngeal EMG signal in phonating patients after administration of transtracheal lidocaine. Several variables differ between the 2 studies; Chitkara et al repeated EMG measurements only 60 seconds after lidocaine administration, whereas we measured at 5 and 10 minutes after LTA. In addition, the Chitkara study population was drawn from a neurolaryngology referral center with 39 of 43 subjects with diagnosed adductor spasmodic dysphonia. All subjects in this study had normal laryngeal function. Although this study attempted to reproduce conditions similar to the administration of endotracheal lidocaine prior to intubation, there were limitations in the timing of Table 2 Difference in means between the threshold currents measured at the same position on the RLN with respect to time Position Time
5 mm
Difference 95% Confidence in means interval for difference
0 min vs 5 min 0.000 0 min vs 10 min 0.014 5 min vs 10 min 0.014 10 mm 0 min vs 5 min − 0.008 0 min vs 10 min 0.006 5 min vs 10 min 0.013
P
(−0.0029 to 0.029) 1.00 (−0.023 to 0.052) .45 (−0.014 to 0.043) .32 (−0.033 to 0.018) .55 (−0.028 to 0.039) .74 (−0.012 to 0.039) .30
Position is measured as distance along the RLN with respect to the insertion point into the larynx. Time zero is prior to endotracheal lidocaine administration, and times 5 and 10 minutes are the durations after administration of lidocaine. n = 25.
13 Table 3 Difference in means between the threshold currents measured at the same time with respect to different positions on RLN Comparison
Difference 95% Confidence in means interval for difference
Position: 5 mm vs 10 mm 0.008 at time: 0 min Position: 5 mm vs 10 mm 0.000 at time: 5 min Position: 5 mm vs 10 mm 0.013 at time: 10 min
as well as Amy Feidt, supervisor neurophysiologist, for her help in coordinating data collection.
P
(−0.030 to 0.045)
References .68
(−0.041 to 0.041) 1.00 (−0.031 to 0.057)
.55
Position is measured as distance along the RLN with respect to the insertion point into the larynx. Time zero is prior to lidocaine administration, and times 5 and 10 minutes are the durations after administration of lidocaine. n = 25.
monitoring of the RLN after administration of lidocaine. Typically, the response to RLN stimulation is measured an hour after intubation; however, in this study, the RLN was interrogated only 5 and 10 minutes after lidocaine administration, in order to avoid unnecessary prolongation of the anesthetic time. Minogue et al [8] demonstrated the efficacy of endotracheal lidocaine for decreasing the incidence of coughing upon emergence from surgical procedures with an average duration of 85 minutes, significantly longer than would be expected based on the half-life of lidocaine alone. Previous work by Prengel et al [15] evaluated serum levels of lidocaine after endotracheal administration and demonstrated biphasic peak serum levels with peaks occurring immediately after administration, as well as a delayed peak ranging from 5 to 34 minutes after administration. This would suggest that there is delayed absorption of lidocaine by the respiratory mucosa. With this in mind, it is possible that in our study, the peak tissue concentrations along the RLN occurred after the RLN was interrogated for the final time (10 minutes after administration). Although this study suggests that LTA has no effect on RLN conduction, in order to overcome the above limitations, a prospective observational study in which patients are randomized to receive either endotracheal lidocaine or saline prior to intubation is proposed.
Acknowledgments The authors would like to acknowledge the help provided by Diane Mccloskey for her help in manuscript preparation
[1] Dralle H, Sekulla C, Lorenz K, Brauckhoff M, Machens A, German ISG. Intraoperative monitoring of the recurrent laryngeal nerve in thyroid surgery. World J Surg 2008;32:1358-66. [2] Goldenberg D, Randolph GW. The recurrent laryngeal nerve. In: Miccoli P, Terris DJ, Minuto MN, Seybt MW, editors. Thyroid Surgery: Preventing and Managing Complications. Wiley-Blackwell; 2013. p. 119-28. [3] Choby G, Hollenbeak CS, Johnson S, Goldenberg D. Surface electrode recurrent laryngeal nerve monitoring during thyroid surgery: normative values. J Clin Neurophysiol 2010;27:34-7. [4] Ho Y, Carr MM, Goldenberg D. Trends in intraoperative neural monitoring for thyroid and parathyroid surgery amongst otolaryngologists and general surgeons. Eur Arch Otorhinolaryngol 2013;270: 2525-30. [5] Johnson S, Goldenberg D. Intraoperative monitoring of the recurrent laryngeal nerve during revision thyroid surgery. Otolaryngol Clin N Am 2008;41:1147-54 [ix]. [6] Lee HS, Lee BJ, Kim SW, Cha YW, Choi YS, Park YH, et al. Patterns of post-thyroidectomy hemorrhage. Clin Exp Otorhinolaryngol 2009; 2:72-7. [7] D'Aragon F, Beaudet N, Gagnon V, Martin R, Sansoucy Y. The effects of lidocaine spray and intracuff alkalinized lidocaine on the occurrence of cough at extubation: a double-blind randomized controlled trial. Can J Anaesth 2013;60:370-6. [8] Minogue SC, Ralph J, Lampa MJ. Laryngotracheal topicalization with lidocaine before intubation decreases the incidence of coughing on emergence from general anesthesia. Anesth Analg 2004;99:1253-7. [9] Chitkara AMT, Cultrara A, Blitzer A. Dose response of topical anesthetic on laryngeal neuromuscular electrical transmission. Ann Otol Rhinol Laryngol 2005;114:819-21. [10] Medtronic. NIM® Standard Reinforced EMG Endotracheal Tube & NIM Contact® Reinforced EMG Endotracheal Tube: 68E4127 B. Medtronic; 2010 7[http://manuals.medtronic.com/wcm/groups/ mdtcom_sg/@emanuals/@era/@st/documents/documents/contrib_ 087079.pdf, Accessed 12.31.2014]. [11] NuVasive. NuVasive EMG Endotracheal Tube: 9500401 F. NuVasive Inc.; 2014 2 [https://nuvasive.app.box.com/s/h9wcds7vdbfktond4jja, Accessed 12.31.2014]. [12] Atlas GLM. The neural integrity monitor electromyogram tracheal tube: anesthetic considerations. J Anaesthesiol Clin Pharmacol 2013; 29:403-4. [13] Fitzmaurice GM, Laird NM, Ware JH. Applied longitudinal analysis. 2nd ed. Hoboken, New Jersey: John Wiley & Sons, Inc.; 2011. [14] Galecki AT. General class of covariance structures for two or more repeated factors in longitudinal data analysis. Commun Stat Theory Methods 1994;23:3105-19. [15] Prengel AW, Lindner KH, Hahnel JH, Georgieff M. Pharmacokinetics and technique of endotracheal and deep endobronchial lidocaine administration. Anesth Analg 1993;77:985-9.
Original contribution
Effect of laryngotracheal topical anesthesia on recurrent laryngeal nerve monitoring during thyroid Surgery Justin Pachuski MD a, Sonia Vaida MD a, Kathleen Donahue DO a, John Roberts MD b, Allen Kunselman MA c, Benjamin Oberman MD b, Hetal Patel MD b, David Goldenberg MD, FACS b,⁎ a
Department of Anesthesiology, Head and Neck Surgery, Penn State College of Medicine and Penn State Hershey Medical Center, Hershey, PA, USA b Department of Surgery, Division of Otolaryngology, Head and Neck Surgery, Penn State College of Medicine and Penn State Hershey Medical Center, Hershey, PA, USA c Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA Received 1 January 2015; accepted 16 September 2015
Keywords: Intraoperative neuromonitoring; Recurrent laryngeal nerve; Laryngotracheal topical anesthesia; Lidocaine; Thyroidectomy
Abstract Study Objective: Intraoperative neuromonitoring of the recurrent laryngeal nerve (RLN) is often used as an adjunct for RLN identification and preservation during thyroidectomies. Laryngotracheal anesthesia (LTA) with topical lidocaine reduces coughing upon emergence from anesthesia and in the immediate postoperative period; however, its use is prohibited with concerns that it could decrease the sensitivity of the intraoperative neuromonitoring. We hypothesize that there is no difference in measurements of nerve conduction made before and after LTA administration. Design: An observational study in which all patients were subjected to LTA administration was conducted. Recurrent laryngeal nerve threshold currents were measured before and after the intervention. Setting: Tertiary medical center operating room. Patients: Eighteen patients (total of 25 nerves at risk) with American Society of Anesthesiologists classes 1 to 3 undergoing thyroid surgery. Interventions: After the thyroid was removed and threshold currents at the RLN were obtained, LTA with endotracheal lidocaine was applied on the left and right side of the in situ endotracheal tube (2 cc of 4% lidocaine per side). Threshold currents were reassessed at 5 and 10 minutes after LTA administration. Measurements: Threshold currents (minimum stimulus current applied to the RLN required to generate a discernible electromyographic response at the vocal cords) were recorded along the RLN for a baseline at 5 and 10 mm from the insertion point of the RLN into the larynx. Threshold currents were reassessed at the same 2 positions on the RLN at 5 and 10 minutes after LTA administration. Differences in mean values, between threshold currents recorded at the 3 different times, at 2 positions on the RLN, were used to compare effects of LTA on nerve conduction.
⁎ Corresponding author at: Department of Surgery, Division of Otolaryngology–Head and Neck Surgery, Penn State Hershey Medical Center, 500 University Drive, Hershey, PA 17033, USA. Tel.: +1 717 531 8945. E-mail addresses: [email protected] (J. Pachuski), [email protected] (S. Vaida), [email protected] (K. Donahue), [email protected] (J. Roberts), [email protected] (A. Kunselman), [email protected] (B. Oberman), [email protected] (H. Patel), [email protected] (D. Goldenberg).
http://dx.doi.org/10.1016/j.jclinane.2015.09.003 0952-8180/© 2015 Elsevier Inc. All rights reserved.
11 Main Results: There were no statistically significant differences when comparing threshold currents before and after LTA administration. Conclusions: Laryngotracheal anesthesia had no significant effect on RLN nerve conduction in the period assessed. © 2015 Elsevier Inc. All rights reserved.
1. Introduction Recurrent laryngeal nerve (RLN) paralysis after thyroid surgery has a reported incidence of 0 to 11% [1], with an even higher incidence in cases presenting with large multinodular goiters, cancers, and revision surgery [2]. Intraoperative neuromonitoring (IONM) of the RLN has become a popular adjunct to aid the surgeon in locating and preserving the RLN during thyroid and other neck surgeries [3–5]. Another potential complication is postthyroidectomy hematoma resulting in airway compromise. Coughing upon emergence from anesthesia as well as in the postoperative period may be a contributing factor to the development of these hematomas [6]. Laryngotracheal anesthesia (LTA) with topical lidocaine applied to the trachea and glottis prior to intubation is used to decrease the incidence of coughing upon emergence from general anesthesia [7,8]. In light of the effects of lidocaine on nerve conduction and the proximity of the RLN to the trachea, concern has been expressed that LTA may decrease the ability to adequately monitor the function of the RLN. This concern is supported by previous work that demonstrated a reduction in percutaneous laryngeal electromyography (EMG) signal after transtracheal lidocaine administration in phonating patients [9]. On the basis of these concerns, 2 manufacturers of endotracheal tubes (ETTs) with embedded electrodes for sampling laryngeal EMG recommend avoiding endotracheal lidocaine [10,11]. This prohibition on topical local anesthetic has also been expressed in an article discussing anesthetic considerations for IONM of the RLN [12]. Our aim was to assess the effect of LTA on IONM of the RLN during thyroidectomy. We hypothesized that there is no difference in nerve conduction (as defined by the threshold current—minimum stimulus current applied to the RLN required to generate a discernible EMG response at the vocal cords) between measurements made before and after LTA.
2. Materials and methods Institutional review board approval was obtained. Adult patients with American Society of Anesthesiologists classes 1 to 3 undergoing total or hemi-thyroidectomy were included. In total, 18 patients were enrolled for a total of 25 nerves at risk: 11 hemi-thyroidectomies (1 nerve at risk) and 7 total thyroidectomies (2 nerves at risk). Patients with known difficult airway, suspected RLN invasion, preoperative
vocal cord paralysis, or anticipated RLN sacrifice due to gross disease were excluded from the study. The patients were intubated with a NuVasive NV JJB/M5 EMG ETT, Long Electrode (NuVasive, Inc, San Diego, CA), an ETT with embedded laryngeal surface electrodes. The neuromonitoring technique included placement of 2 surface electrodes at the wrist, overlying the ulnar nerve (train-of-four [TOF] stimulation), 2 needle electrodes in the muscle bellies of the abductor pollicus brevis and the abductor digiti minimi (monitoring TOF EMG), one needle in left deltoid (ground), and one needle placed in a midline cervical location (stimulus return). A sterilized Prass monopolar probe was used for RLN stimulation. After completion of thyroidectomy and hemostasis was achieved, a TOF ratio greater than 85% was confirmed by the neurophysiologist. The RLN was identified anatomically by the attending surgeon and stimulated at 2 points: 5 and 10 mm from the insertion of the RLN into the larynx. Resident surgeons in their postgraduate years 4 and 5 also participated under the supervision of the attending surgeon: however, all measurements were confirmed by the attending surgeon. The nerve was stimulated to the threshold current with each stimulus delivered for 100 μs at a frequency of 4 Hz. Stimuli start at 0 mA and increase by 0.05 mA until an EMG response was detected at the vocal cords. The current was then decreased by 0.1 mA and again increased by 0.05 mA until a response was detected. Threshold current was defined as the minimum stimulus current that produced a response detected via vocal cord EMG. All clinical neurophysiologists received Certification in Neurophysiologic Intraoperative Monitoring (CNIM) certified and the oversight reading neurologist performed real time Web-based guidance from an off-site location for all cases. After the baseline threshold value was obtained, the anesthesiologist performed laryngoscopy and visualized the larynx (direct laryngoscopy or indirect video laryngoscopy), suctioned any secretions, and then deflated the ETT cuff. The LTA device (“LTA 360 kit,” lidocaine hydrochloride topical solution, 4%; Hospira, Lake Forest, IL) was passed on each side of the ETT (inserted to appropriate depth to spray carina, with care taken not to touch the EMG electrodes taped onto the ETT), and lidocaine, a total of 4 mL of 4%, was administered bilaterally while withdrawing the LTA. The ETT cuff was then reinflated. Response thresholds were reassessed at 5 and 10 minutes after administration of topical lidocaine. Prior to study initiation, we assumed that a change in threshold current of 0.2 mA would be clinically meaningful and that the standard deviation would be 0.1 mA3 [3], with a
J. Pachuski et al.
within-nerve correlation of 0.7. Based on these assumptions, a sample size of 12 nerves was expected to provide greater than 90% power to detect a change in threshold current of 0.2 mA using a 2-sided test having a significance level of .05. A linear mixed-effects model [13] was used to compare the position on the nerve (5 or 10 mm), the time of data collection (0, 5, and 10 minutes), and their interaction with respect to the threshold current. The linear mixed-effects model is an extension of linear regression that accounts for the within-subject variability inherent in repeated-measures designs. Because there are 2 repeated factors in this study, that is, position and time, the Kronecker product of an unstructured and first-order autoregressive matrix was used in the mixed-effects model to specify the variance-covariance matrix [14]. Residual diagnostics were used to evaluate model fit. No adjustments for multiple testing were done. All hypotheses tests were 2 sided, and all analyses were performed using SAS software, version 9.3 (SAS Institute Inc, Cary, NC).
3. Results The threshold currents required to generate vocal cord EMG response as measured with stimulus delivered at 5 and 10 mm from the RLN insertion into the larynx are presented in Table 1 and Figure. Differences in means between threshold currents measured at different times (Table 2) and positions on the RLN (Table 3) were calculated with the associated 95% confidence interval and P value for each difference in means. No statistically significant differences were seen when comparing threshold currents before and after the administration of endotracheal lidocaine. No statistically significant differences were seen when comparing threshold currents with respect to stimulus position along the RLN.
4. Discussion Because of the nature of the mechanism of action of lidocaine and the proximity of the RLN to the site of administration of local anesthetic during LTA, there is a theoretical risk of causing an inhibitory effect on RLN Table 1 Mean and standard deviations of response threshold currents measured with stimulus delivered at 5 and 10 mm from the RLN insertion into the larynx Position
Time (min)
Mean (mA)
Standard deviation
5 mm
0 5 10 0 5 10
0.312 0.312 0.298 0.305 0.312 0.299
0.099 0.093 0.084 0.095 0.085 0.100
10 mm
Time zero is prior to endotracheal lidocaine administration, and times 5 and 10 minutes are the durations after administration of lidocaine. n = 25.
RLN threshold current (mA)
12
5 mm
10 mm
0.4
0.3
0.2
0.1
0 0
5
10
Time after LTA (min.)
Figure Mean and standard deviations of response threshold currents measured with stimulus delivered at 5 and 10 mm from the RLN insertion into the larynx. Time zero is prior to endotracheal lidocaine administration, and times 5 and 10 minutes are the durations after administration of lidocaine. n = 25.
conduction, which could diminish the efficacy of IONM of the RLN during thyroid surgery. To our knowledge, this was the first study investigating the effect of LTA on stimulation currents required to generate a discernable EMG response at the vocal cords. Our data suggest that LTA administration does not have an inhibitory effect on the conduction of the RLN in the setting of IONM for thyroid surgery. The outcome of this study differs from the results of previous work by Chitkara et al [9], which demonstrated a decrease in laryngeal EMG signal in phonating patients after administration of transtracheal lidocaine. Several variables differ between the 2 studies; Chitkara et al repeated EMG measurements only 60 seconds after lidocaine administration, whereas we measured at 5 and 10 minutes after LTA. In addition, the Chitkara study population was drawn from a neurolaryngology referral center with 39 of 43 subjects with diagnosed adductor spasmodic dysphonia. All subjects in this study had normal laryngeal function. Although this study attempted to reproduce conditions similar to the administration of endotracheal lidocaine prior to intubation, there were limitations in the timing of Table 2 Difference in means between the threshold currents measured at the same position on the RLN with respect to time Position Time
5 mm
Difference 95% Confidence in means interval for difference
0 min vs 5 min 0.000 0 min vs 10 min 0.014 5 min vs 10 min 0.014 10 mm 0 min vs 5 min − 0.008 0 min vs 10 min 0.006 5 min vs 10 min 0.013
P
(−0.0029 to 0.029) 1.00 (−0.023 to 0.052) .45 (−0.014 to 0.043) .32 (−0.033 to 0.018) .55 (−0.028 to 0.039) .74 (−0.012 to 0.039) .30
Position is measured as distance along the RLN with respect to the insertion point into the larynx. Time zero is prior to endotracheal lidocaine administration, and times 5 and 10 minutes are the durations after administration of lidocaine. n = 25.
13 Table 3 Difference in means between the threshold currents measured at the same time with respect to different positions on RLN Comparison
Difference 95% Confidence in means interval for difference
Position: 5 mm vs 10 mm 0.008 at time: 0 min Position: 5 mm vs 10 mm 0.000 at time: 5 min Position: 5 mm vs 10 mm 0.013 at time: 10 min
as well as Amy Feidt, supervisor neurophysiologist, for her help in coordinating data collection.
P
(−0.030 to 0.045)
References .68
(−0.041 to 0.041) 1.00 (−0.031 to 0.057)
.55
Position is measured as distance along the RLN with respect to the insertion point into the larynx. Time zero is prior to lidocaine administration, and times 5 and 10 minutes are the durations after administration of lidocaine. n = 25.
monitoring of the RLN after administration of lidocaine. Typically, the response to RLN stimulation is measured an hour after intubation; however, in this study, the RLN was interrogated only 5 and 10 minutes after lidocaine administration, in order to avoid unnecessary prolongation of the anesthetic time. Minogue et al [8] demonstrated the efficacy of endotracheal lidocaine for decreasing the incidence of coughing upon emergence from surgical procedures with an average duration of 85 minutes, significantly longer than would be expected based on the half-life of lidocaine alone. Previous work by Prengel et al [15] evaluated serum levels of lidocaine after endotracheal administration and demonstrated biphasic peak serum levels with peaks occurring immediately after administration, as well as a delayed peak ranging from 5 to 34 minutes after administration. This would suggest that there is delayed absorption of lidocaine by the respiratory mucosa. With this in mind, it is possible that in our study, the peak tissue concentrations along the RLN occurred after the RLN was interrogated for the final time (10 minutes after administration). Although this study suggests that LTA has no effect on RLN conduction, in order to overcome the above limitations, a prospective observational study in which patients are randomized to receive either endotracheal lidocaine or saline prior to intubation is proposed.
Acknowledgments The authors would like to acknowledge the help provided by Diane Mccloskey for her help in manuscript preparation
[1] Dralle H, Sekulla C, Lorenz K, Brauckhoff M, Machens A, German ISG. Intraoperative monitoring of the recurrent laryngeal nerve in thyroid surgery. World J Surg 2008;32:1358-66. [2] Goldenberg D, Randolph GW. The recurrent laryngeal nerve. In: Miccoli P, Terris DJ, Minuto MN, Seybt MW, editors. Thyroid Surgery: Preventing and Managing Complications. Wiley-Blackwell; 2013. p. 119-28. [3] Choby G, Hollenbeak CS, Johnson S, Goldenberg D. Surface electrode recurrent laryngeal nerve monitoring during thyroid surgery: normative values. J Clin Neurophysiol 2010;27:34-7. [4] Ho Y, Carr MM, Goldenberg D. Trends in intraoperative neural monitoring for thyroid and parathyroid surgery amongst otolaryngologists and general surgeons. Eur Arch Otorhinolaryngol 2013;270: 2525-30. [5] Johnson S, Goldenberg D. Intraoperative monitoring of the recurrent laryngeal nerve during revision thyroid surgery. Otolaryngol Clin N Am 2008;41:1147-54 [ix]. [6] Lee HS, Lee BJ, Kim SW, Cha YW, Choi YS, Park YH, et al. Patterns of post-thyroidectomy hemorrhage. Clin Exp Otorhinolaryngol 2009; 2:72-7. [7] D'Aragon F, Beaudet N, Gagnon V, Martin R, Sansoucy Y. The effects of lidocaine spray and intracuff alkalinized lidocaine on the occurrence of cough at extubation: a double-blind randomized controlled trial. Can J Anaesth 2013;60:370-6. [8] Minogue SC, Ralph J, Lampa MJ. Laryngotracheal topicalization with lidocaine before intubation decreases the incidence of coughing on emergence from general anesthesia. Anesth Analg 2004;99:1253-7. [9] Chitkara AMT, Cultrara A, Blitzer A. Dose response of topical anesthetic on laryngeal neuromuscular electrical transmission. Ann Otol Rhinol Laryngol 2005;114:819-21. [10] Medtronic. NIM® Standard Reinforced EMG Endotracheal Tube & NIM Contact® Reinforced EMG Endotracheal Tube: 68E4127 B. Medtronic; 2010 7[http://manuals.medtronic.com/wcm/groups/ mdtcom_sg/@emanuals/@era/@st/documents/documents/contrib_ 087079.pdf, Accessed 12.31.2014]. [11] NuVasive. NuVasive EMG Endotracheal Tube: 9500401 F. NuVasive Inc.; 2014 2 [https://nuvasive.app.box.com/s/h9wcds7vdbfktond4jja, Accessed 12.31.2014]. [12] Atlas GLM. The neural integrity monitor electromyogram tracheal tube: anesthetic considerations. J Anaesthesiol Clin Pharmacol 2013; 29:403-4. [13] Fitzmaurice GM, Laird NM, Ware JH. Applied longitudinal analysis. 2nd ed. Hoboken, New Jersey: John Wiley & Sons, Inc.; 2011. [14] Galecki AT. General class of covariance structures for two or more repeated factors in longitudinal data analysis. Commun Stat Theory Methods 1994;23:3105-19. [15] Prengel AW, Lindner KH, Hahnel JH, Georgieff M. Pharmacokinetics and technique of endotracheal and deep endobronchial lidocaine administration. Anesth Analg 1993;77:985-9.