The Effect of Lidocaine Spray before Endotracheal Intubation on the Incidence of Cough and Hemodynamics during Emergence in Children

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1 대한마취과학회지 2007; 53: S 1~6 Korean J Anesthesiol Vol. 53, No. 3, September, 2007 영문논문 The Effect of Lidocaine Spray before Endotracheal Intubation on the Incidence of Cough and Hemodynamics during Emergence in Children Department of Anesthesiology and Pain Medicine, College of Medicine, Korea University, Seoul, Korea You Mi Ki, M.D., Nan Suk Kim, M.D., Sang Ho Lim, M.D., Myoung Hoon Kong, M.D., and Hee Zoo Kim, M.D. Background: Cough and hyperdynamic reaction cause considerable discomfort, and they may lead to postoperative surgical complication. To reduce coughing and hemodynamics during emergence, the efficacy of laryngotracheal spraying with lidocaine before intubation is not clear, particularly, in children. We investigated such effect during emergence from general anesthesia, in children. Methods: Children were studied in a double blind manner: 105 ASA physical status I-II, aged 2-16 yrs, undergoing tonsillectomy and adenoidectomy. Patients were randomly grouped into three (A, B, and C) by the lidocaine spray before endotracheal intubation: 4% lidocaine to the group A (n = 32), 10% lidocaine to the group B (n = 36), and normal saline to the group C (n = 37). The same dose (2 mg/kg) of lidocaine was applied. During emergence, patients were observed their cough and hemodynamics. Results: Lidocaine spray, irrespective of concentration, did not significantly diminish the cough and the hemodynamic reaction across the groups before and after the extubation as well as in the recovery room (P value = 0.44, 0.86, 0.17). Conclusions: These findings support that the laryngotracheal spraying with lidocaine (2 mg/kg of 4% and 10%) before endotracheal intubation does not reduce the cough and hemodynamic reactions during emergence from general anesthesia in children. (Korean J Anesthesiol 2007; 53: S 1~6) Key Words: child, cough, emergence, lidocaine. INTRODUCTION Cough and hemodynamic responses are common to general anesthesia. 1,2) Coughing causes patients' abrupt movement, dislodging the IV and bleeding on the operation site, bronchospasm, hypertension, and tachycardia, etc. 3,4) It is crucial to prevent children from coughing during such emergency situations as tonsillectomy and adenoidectomy. Various techniques and drugs have been proposed for the attenuation of cough and hemodynamic responses, but none have been proved successful. 5-7) Received:April 17, 2007 Comesponding to:nan Suk Kim, Department of Anesthesiology and Pain Medicine, College of Medicine, Korea University, 97, Guro-dong, Guro-gu, Seoul , Korea. Tel: , Fax: , nskim@korea.ac.kr It's a master's thesis. Coughing and hemodynamic responses result, at least in part, from the tracheal mucosa stimulated by the endotracheal tube (ETT). Application of local anesthetics to the laryngotracheal mucosa, which is on contact with the ETT, is theoretically appropriate to reduce coughing and hemodynamic responses during emergence from anesthesia. Various techniques have been tried in administering lidocaine to prevent the patients from cough and hemodynamics, only with controversial results. Endotracheal spraying with lidocaine has been widely accepted as a useful method for obtunding the pressor response to intubation. Prior studies focused mostly on the adults, applied lidocaine before extubation, and compared the effect at the time of emergence. Minogue et al. 8) studied the lidocaine spray effect on the adults before intubation and observed the effect at the time of emergence. It is unclear how effectively the lidocaine spray works when done before endotracheal intubation: especially, no research has S1

2 Korean J Anesthesiol:Vol. 53. No. 3, 2007 been done on children. Administering the varied concentrations maintaining the same volume, most researches assumed that 2 mg/kg of lidocaine was the effective dose to suppress cough. We observed whether lidocaine spray using 4% and 10% lidocaine (2 mg/kg) was also effective in suppressing cough and hemodynamic responses during emergence from general anesthesia in children. SUBJECTS AND METHODS This double blind study started with the randomly chosen patients of between 2-16 yrs: 105 ASA physical status I-II children, undergoing tonsillectomy and adenoidectomy. Following patients were excluded: anticipated difficulty in tracheal intubation; resistance during intubation; hepatic, cardiac or neuromuscular diseases; hypersensitivity reaction to lidocaine; asthma or respiratory diseases. For all the patients, we had interviews with their parents before operation, gave an exhaustive explanation about general anesthesia and the present research, and obtained their consent. We also excluded patients who had rejected this consent in this study. To calculate the sample size, we estimated the incidence of postoperative cough to be 75% on the basis of reported rates of 38-96%. 1,2) An α value of 0.05 and a β value of 0.10 (power of 90%) necessitated a sample size of 31 in each group. On the morning of surgery, patients were administered with 2 mg/kg of 4% lidocaine and 10% lidocaine to Group A (n = 32) and Group B (n = 36), and normal saline to Group C (n = 37, 0.05 ml/kg, the same volume of 4% lidocaine). Patient allocation and double blinding were achieved as follows. The surface of syringe was wrapped in tapes. The names of three groups were written on the paper, distributed evenly by the groups, folded, put into a large envelope, and shuffled for the anesthesiologist to choose from for each and every patient. The patient's name was written on the sheet to record the group assignment. Finally, the sheet was sealed in another envelope. It was not opened again until the evaluation was finished. Neither the patients nor the interviewer was notified of the results of allocation. All the patients were premedicated with atropine one hour before induction of anesthesia. Standard monitoring techniques including electrocardiography, non-invasive blood pressure measurement and pulse oxymetry were applied in the operating room. Anesthesia was induced thiopental (5 mg/kg), fentanyl (0.5μg/ kg), and succinylcholine (1-1.5 mg/kg). After the epiglottis was lifted, the drug corresponding to each group was sprayed directly on the larynx using a mucous membrane sprayer (Mucosal Atomization Device, MAD, Wolfe Tory Medical Inc., USA). It was a disposable plastic sprayer, bent in C shape, one end connectable to an injector and the other to the multiple holes in case of speedier spraying (Fig. 1). The spray tip was inserted between the vocal cords, and the injector was pressed rapidly to produce a circumferential jet-like instillation, bathing the walls of the larynx and trachea with lidocaine. After laryngotracheal topicalization, endotracheal intubation was performed by an experienced anesthesiologist. Following the intubation, endotracheal cuff pressure was maintained at 25 ± 2 cm H 2O continuously with manometer. Vecuronium (0.05 mg/kg) was used for neuromuscular relaxation. Anesthesia was maintained with sevoflurane ( vol % end-tidal concentration) and 50% nitrous oxide (N 2O) and oxygen (O 2) using mechanical ventilation. Minute ventilation and respiratory rate were adjusted to maintain the end-expiratory carbon dioxide tension at mmhg and airway pressure at cm H 2O. With the surgery completed, the oropharynx was gently suctioned, sevoflurane and N 2O were discontinued, and manual ventilation was applied with 100% O 2. Pyridostigmine (0.2 mg/ kg) and glycopyrrolate (0.01 mg/kg) were given to reverse neuromuscular blockade. Extubation was done when the patient resumed regular spontaneous respiration and responded to Fig. 1. MAD R (Mucosal Atomization Device: Wolfe Tory Medical Inc., USA) for spraying topical anesthetics in the laryngotracheal region. S2

3 You Mi Ki, et al:the Effect of Lidocaine Spray before Endotracheal Intubation in Children Table 1. Three-Category Scale for Scoring Cough Severity Mild Moderate Severe Definition Single cough More than one episode of unsustained ( 5 sec) coughing Sustained (> 5s) bout (sec) of coughing If cough was present, it was graded using a three-category scale. 11) Table 2. Demographic Data Group A Group B Group C (n = 32) (n = 36) (n = 37) Age (yr) 7.5 ± ± ± 3.6 Body Mass Index (kg/m 2 ) 17.7 ± ± ± 6.9 Duration of anesthesia (min) 56.3 ± ± ± 17.6 Total Fentanyl dose (g) 15.9 ± ± ± 14.2 Values are mean SD. Group A: intralaryngotracheal spay of 2.0 mg/kg of 4% lidocaine, Group B: 2.0 mg/kg of 10% lidocaine, Group C: same volume of 4% lidocaine of normal saline. verbal order, which is called no touch extubation. 9) Hemodynamic variables were recorded just after entering the operating room, after endotracheal intubation, just before and after extubation and after arriving in the recovery room. A blinded observer recorded the presence or the absence of coughing during emergency, before and after extubation, and in the recovery room. The severity of coughing was graded using a three-category scale (Table 1). 8) All the measurements were mean value ± standard deviation. Patient age, body mass index, duration of anesthesia, and total fentanyl dose were compared between the groups, and tested statistically by the analysis of variance (one way and repeated Measures ANOVA). Coughing score was analyzed by the Fisher's exact test. P values less than 0.05 were considered significant. RESULTS No statistically significant difference was observed among the groups in age, body mass index, duration of anesthesia, and the distribution of the total dose of fentanyl (Table 2). No statistically significant difference was observed among the Fig. 2. Bar chart showing distribution of patients with coughing on emergence from general anesthesia and in PACU. The vertical axis indicated an incidence of cough on each group, and it was graded using a three-category scale. groups in the incidence and severity of coughing before and after extubation, and in the recovery room (Fig. 2). No significance was noteworthy in the heart rate and blood pressure before and after intubation, before and after extubation and in the recovery room (Table 3). DISCUSSION Coughing during emergence from general anesthesia causes considerable discomfort on the patient, and the coughing in certain surgical procedures may lead to postoperative surgical complication. Coughing reflex is affected by the inhalation agents, intravenous anesthetics, local anesthetics, opioid and end-expiratory carbon dioxide concentration, etc. Ishikawa et al. 10) reported that sevoflurane inhibits coughs in the deep anesthesia, but it's effect falls in the light anesthesia. Our study observed that the end-expiratory sevoflurane concentration during emergence was vol %, which is presumed too weak to suppress airway reflex. A report tells that the increase in the endexpiratory carbon dioxide concentration increases ventilation but it reduces the degree and length of reflective reaction to irritation on airway mucous membrane. 11) Therefore, we performed controlled ventilation in order to keep the end- expiratory carbon dioxide tension constant in all the patients. Opioid is also effective in suppressing airway reflex, but dose of fentanyl for inhibiting airway reflect is reported to be 5μg/kg. 12) S3

4 Korean J Anesthesiol:Vol. 53. No. 3, 2007 Table 3. Changes in Heart Rate (beat/minute) and Mean Blood Pressure (mmhg) Group A (n = 32) Group B (n = 36) Group C (n = 37) HR BP HR BP HR BP Baseline 115 ± ± ± Post I 123 ± ± ± Pre E 137 ± ± ± Post E 138 ± ± ± PACU 114 ± ± ± Values are mean ± SD. Group A: intralaryngotracheal spay of 2.0 mg/kg of 4% lidocaine, Group B: 2.0 mg/kg of 10% lidocaine, Group C: 0.05 ml/kg of normal saline, Baseline: preinduction, Post I: immediately after intubation, Pre E: immediately before extubation, Post E: immediately after extubation, PACU: in PACU. Conflicting with this, Hong et al. 13) reported fentanyl cough response (FCR, ED 50 = 4.25μg/kg): coughing was induced by a small amount of fentanyl administered for the purpose of mitigating hemodynamic responses to endotracheal intubation before anesthesia induction. However, the average interval between their intravenous injection of fentanyl and the cough was 12.5 seconds. The time lapse of this study being over 56 minutes on the average, no significant effect on the incidence of coughing is presumed during emergence. In the research by Tsui et al. 9) with patients receiving tonsillectomy and adenoidectomy, no touch extubation was done and the epiglottic spasm decreased. No touch extubation seems more effective to reduce cough reflex and epiglottic spasm for the children patients than administering the drug like lidocaine. We performed no touch extubation, and the factors influencing the cough reflex were eliminated, mostly. The precise mechanism of hemodynamic variables after endotracheal intubation and during tracheal extubation remains to be elucidated, but the effect is presumed to come from stimulating the sympathetics or increased serum catecholamine following mechanical stimulation, wound pain, emergence from anesthesia, and tracheal irritation. 14) Tracheal extubation causes transient increases in BP and HR, lasting 5-15 minutes. 15) Although the mechanisms responsible for coughing and hemodynamic responses during emergence are not exactly known, a possible factor may be tracheal irritation. 16,17) Topical application of local anesthetics is a reliable technique to decrease irritation of the respiratory mucosa by the ETT. Lidocaine has been used with apparently good effect to suppress not only the ETT-associated coughing but also the hemodynamic response to extubation. 4) However, the mechanism in which lidocaine works remains unclear. Lidocaine spray may provoke local anesthesia to some part of the tracheal mucosa which is in contact with the tube and cuff. Prengel et al. 16) administered 2 mg/kg of lidocaine through the ETT. According to their report, the mean blood concentration after 20 and 120 minutes were 1.4 and 0.47 ug/ml. Diachun et al. 17) observed cough inhibition during emergence after administration 2 mg/kg of 4% lidocaine through laryngotracheal instillation of topical anesthesia (LITA TM ) before tracheal extubation with mean serum level 0.43 ug/ml. They suggested that a local effect of lidocaine on the laryngotrachea by spraying mucosa would not be dependent on serum concentrations nor would they reflect efficacy. Lin et al. 18) and Wu et al. 19) have obtained 77 to 100% cough suppression using topical lidocaine administered via the LITA TM tube 15 to 60 minutes before extubation. Minogue et al. 8) reported that coughing from general anesthesia decreased significantly after spraying 4 ml of 4% lidocaine on the subglottic larynx before endotracheal intubation in adults. Anesthesia duration is between 30 and 120 min (mean case duration, 85 minutes). They enabled the efficacy for up to 2 hours after endotracheal administration of lidocaine. In the present study, average duration of the case is 56 minutes. Greater volume or concentration of topical lidocaine might have proven even more effective. In the most of studies, varied concentrations with the same volume were administered. Many previous studies assume that 2 mg/kg lidocaine is an effective endotracheal dose in attenuating the cough, on which we wanted to know the same effect was achievable with different concentration but with the same dose (2 mg/kg). Mikawa et al. 20) reported that IV lidocaine two minutes before tracheal extubation attenuated increase in BP and the cough reflex, whereas others did not. 21) S4

5 You Mi Ki, et al:the Effect of Lidocaine Spray before Endotracheal Intubation in Children Bidwai 22) reported that lidocaine sprayed down the ETT before and during extubation prevents BP and HR from going up. Like Bidwai, 22) Wu et al. 19) showed significant improvement in hemodynamic stability with topical lidocaine administration and in the associated prevention of cough. In the present study, the cough and hemodynamic responses were not suppressed significantly. This result is different from that of Minogue's where adults were subjected to the same technique. Since the effect of age on ETT-induced coughing is not known, it is unknown whether these differences bear any clinical significance. Schreiner et al. 23) reported that laryngospasm may occur more frequently in children. In research by Koc et al. 24) the mean lidocaine concentration in plasma 5 minutes after intravenous injection of 1 mg/kg of lidocaine was 3.4μg/kg, at which a cough reflex inhibition effect is observed. In the research by Chang et al., 25) however, lidocaine was administered 5 minutes before extubation in children receiving strabismus surgery, its blood concentration became over 3μg/kg, but cough reflex was not inhibited. This shows differences between adults and children. We did not measure the blood concentration of lidocaine at the time of tracheal extubation. The blood concentration of the children patients, unlike adult patients, may not retain enough lidocaine till the time of emergence to inhibit the coughing reflex, as it was sprayed before endotracheal intubation. It may also be possible that other mechanisms are responsible for the cough and hemodynamic response. Further researches, with more cases of pediatric patients sprayed with lidocaine before endotracheal intubation, may help find out whether coughing of the patients has a correlation with the serum lidocaine concentration that suppresses coughing, or whether other factors induce coughing regardless of the topical anesthesia of respiratory mucosa. In conclusion, 4% and 10% lidocaine (2 mg/kg) sprayed directly on the subglottic larynx before endotracheal intubation does not significantly mitigate the coughing and hemodynamic responses during emergence in children. REFERENCES 1. Asai T, Koga K, Vaughan RS: Respiratory complications associated with tracheal intubation and extubation. Br J Anaesth 1998; 80: Koga K, Asai T, Vaughan RS, Latto IP: Respiratory complications associated with tracheal extubation. Timing of tracheal extubation and use of the laryngeal mask during emergence from anaesthesia. Anaesthesia 1998; 53: Gonzalez RM, Bjerke RJ, Drobycki T, Stapelfeldt WH, Green JM, Janowitz MJ, et al: Prevention of endotracheal tube-induced coughing during emergence from general anesthesia. Anesth Analg 1994; 79: Bidwai AV, Bidwai VA, Rogers CR, Stanley TH: Blood pressure and pulse-rate responses to endotracheal extubation with and without prior injection of lidocaine. Anesthesiology 1979; 51: Cahraemmer-Jorgensen B, Hoilund-Carlsen PF, Marving J, Christensen V: Lack of effect of intravenous lidocaine on hemodynamic responses to rapid sequence induction of general anesthesia: a double-blind controlled clinical trial. Anesth Analg. 1986; 65: Derbyshire DR, Smith G, Achola KJ: Effect of topical lignocaine on the sympathoadrenal responses to tracheal intubation. Br J Anaesth 1987; 59: Denlinger JK, Ellison N, Ominsky AJ: Effects of intratracheal lidocaine on circulatory responses to tracheal intubation. Anesthesiology 1974; 41: 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: Tsui BC, Wagner A, Cave D, Elliott C, El-Hakim H, Malherbe S: The incidence of laryngospasm with a no touch extubation technique after tonsillectomy and adenoidectomy. Anesth Analg 2004; 98: Ishikawa T, Isono S, Tanaka A, Tagaito Y, Nishino T: Airway protective reflexes evoked by laryngeal instillation of distilled water under sevoflurane general anesthesia in children. Anesth Analg 2005; 101: Nishino T, Hiraga K, Honda Y: Inhibitory effects of CO 2 on airway defensive reflexes in enflurane-anesthetized humans. J Appl Physiol 1989; 66: Dahlgren N, Messeter K: Treatment of stress response to laryngoscopy and intubation with fentanyl. Anaesthesia 1981; 36: Hong JY, Kim WO, Kil HK, Kim JH, Lee SL: Dose response of fentanyl cough reflex through peripheral venous catheter. Korean J Anesthesiol 1997; 33: Miller KA, Harkin CP, Bailey PL: Postoperative tracheal extubation. Anesth Analg 1995; 80: Fuhrman TM, Ewell CL, Pippin WD, Weaver JM: Comparison of the efficacy of esmolol and alfentanil to attenuate the hemodynamic responses to emergence and extubation. J Clin Anesth 1992; 4: Prengel AW, Lindner KH, Hahnel JH, Georgieff M: Pharmacokinetics and technique of endotracheal and deep endobronchial lidocaine adminstration. Anesth Analg 1993; 77: Diachun CA, Tunink BP, Brock-Utne JG: Suppression of cough during emergence from general anesthesia: laryngotracheal lido- S5

6 Korean J Anesthesiol:Vol. 53. No. 3, 2007 caine through a modified endotrachal tube. J Clin Anesth 2001; 13: Lin SY, Wu TJ, Lun KC, Hwang CL, Cheng YJ, Lin YS, et al: A new approach to suppress bucking before extubation-lidocaine through modified endotracheal tube. Ma Zui Xue Za Zhi 1990; 28: Wu TJ, Liu CC, Lin SY, Jiang CJ, Chen CL, Hou WY, et al: Comparison of lower concentrations of lidocaine to suppress bucking before extubation during recovery of general anesthesia. Ma Zui Xue Za Zhi 1990; 28: Mikawa K, Nishina K, Takao Y, Shiga M, Maekawa N, Obara H: Attenuation of cardiovascular responses to tracheal extubaton: comparison of verapamil, lidocaine, and verapamil-lidocaine combination. Anesth Analg 1997; 85: Wilson IG, Meiklejohn BH, Smith G: Intravenous lignocaine and sympathoadrenal responses to laryngoscopy and intubation: the effect of varying time of injection. Anaesthesia 1991; 46: Bidwai AV, Stanley TH, Bidwai VA: Blood pressure and pulse rate response to extubation with and without priortopical tracheal anesthesia. Can Anaesth Soc J 1978; 25: Schreiner MS, O'Hara I, Markakis DA, Politis GD: Do children who experience laryngospasm have an increased risk of upper respiratory tract infection? Anesthesiology 1996; 85: Koç C, Kocaman F, Aygenç E, Özdem C, Çekiç A: The use of preoperative lidocaine to prevent stridor and laryngospasm after tonsillectomy and adenoidectomy. Otolaryngol Head Neck Surg 1998; 118: Chang SH, Kim DH, Park JY, Kang PS, Lee HW, Lim HJ, et al: The effect of lidocaine injection just before extubation on laryngospasm or stridor in pediatric strabismus surgery. Korean J Anesthesiol 2003; 44: S6

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