Anesth Pain Med 2019;14:180-186 https://doi.org/10.17085/apm.2019.14.2.180 pissn 1975-5171 ㆍ eissn 2383-7977 임상연구 Benzydamine hydrochloride 분무가이중관기관지튜브삽관으로인한술후인후통에미치는영향 : 이중맹검, 무작위배정임상시험 박상희 1 ㆍ손석곤 1 ㆍ김상태 1,2 1 충북대학교병원마취통증의학과, 2 충북대학교의과대학마취통증의학교실 Received August 1, 2018 Revised 1st, September 5, 2018 2nd, October 15, 2018 3rd, October 22, 2018 4th, October 24, 2018 Accepted October 24, 2018 Effects of benzydamine hydrochloride spray on postoperative sore throat associated with doublelumen endobronchial intubation: a double-blind, randomized controlled clinical trial Sang Hi Park 1, Seok Gon Son 1, and Sang Tae Kim 1,2 1 Department of Anesthesiology and Pain Medicine, Chungbuk National University Hospital, 2 Department of Anesthesiology and Pain Medicine, Chungbuk National University College of Medicine, Cheongju, Korea Corresponding author Sang Tae Kim, M.D., Ph.D. Department of Anesthesiology and Pain Medicine, Chungbuk National University Hospital, Chungbuk National University College of Medicine, 776 1sunhwan-ro, Seowon-gu, Cheongju 28644, Korea Tel: 82-43-269-6237 Fax: 82-43-272-0264 E-mail: kimst@chungbuk.ac.kr ORCID https://orcid.org/0000-0001-9315-2107 Background: Postoperative sore throat is a common complication of endotracheal intubation; the thicker the endotracheal tube, the higher the frequency of postoperative sore throat. So, we evaluated the effect of benzydamine hydrochloride spray on postoperative sore throat, associated with double-lumen endobronchial intubation. Methods: Sixty patients undergoing thoracic surgery were scheduled and enrolled for intubation, with a double-lumen endobronchial tube. Of these patients, 30 were sprayed with benzydamine hydrochloride (group B), and 30 with normal saline (group N), 10 minutes before intubation was performed. Patients were randomly assigned to the two groups. Blood pressure and heart rate were recorded before, and after endotracheal intubation. Symptoms of sore throat, hoarseness, and dysphagia were examined one hour, as well as 24 hours, after surgery. Results: Incidence of sore throat was 73.3% and 23.3% (P < 0.001) in groups N and B, respectively, at one hour after surgery. In addition, incidence of sore throat at 24 hours after the operation, was also statistically significant (66.6% and 20.0%, P = 0.001). Frequency of dysphagia at one hour, and 24 hours after surgery, was lower in group B. There were no significant differences in heart rate, blood pressure, and hoarseness at 24 hours after surgery between the two groups. Conclusions: In cases wherein a double-lumen endobronchial tube was used, an oropharyngeal spray of benzydamine hydrochloride before tracheal intubation, reduced incidence of postoperative sore throat. Keywords: Benzydamine; Intubation, intratracheal; Pharyngitis; Postoperative period. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright c the Korean Society of Anesthesiologists, 2019 180
Benzydamine Hcl 분무가술후인후통에미치는영향 서론 기관내삽관은술후인후통을야기할수있으며일반적으로단일관기관튜브 (single lumen endotracheal tube) 를삽관하였을때, 발생빈도는 14.4 73.9% 에달한다 [1 3]. 술후인후통은기관튜브의크기에연관이있으며 [2], 환자의만족도및수술후활동성에큰영향을미치게된다. 따라서이중관기관지튜브 (double lumen endobronchial tube) 를사용한환자에서술후인후통의발생빈도는더빈번하고, 통증의강도는심할것으로예상된다. 이중관기관지튜브는폐수술을받는환자에서수술의시야에중요한역할을하는필수적인장비이므로, 술후인후통의발생과강도를줄일수있는방법을고안하는것은환자의수술후관리에중요한일이다. Benzydamine hydrochloride (BH) 는구내염, 인두염, 후두염과같은인후통을야기하는염증에대해이비인후과영역에서흔히사용되는국소비스테로이드성소염진통제로진통, 해열, 항균효과를가지고있다 [4]. 단일관기관튜브로기관내삽관을하기전에예방적으로 BH를분무하여술후인후통을감소시킨다는연구는많이있으나 [5,6], 이중관기관지튜브를사용한환자에서의술후인후통감소효과의정도를보고한연구는드물다. 기관내발관직후한시간이내의술후인후통은전신마취시사용한진통제에의해감춰질수있으므로 [6], 본연구에서는이 중관기관지튜브삽관 10분전 BH 분무한군과생리식염수를분무한군으로나누어, 발관을시행한 1시간과 24시간후인후통을확인하여 BH 분무의영향을알아보자고하였다. 대상및방법 본원에서이중관기관지튜브삽관이예정되어있는미국마취과학회신체등급 (American Society of Anesthesiologists physical status classification) Ⅰ, Ⅱ에해당하는 20세이상의흉부외과환자를대상으로하였으며본원임상연구심의위원회의승인과환자의동의를얻은후진행되었다. 환자들은연구가시작된시점에 Research Randomizer TM (http:// www.randomizer.org) 를이용하여삽관 10분전 BH (Tantum Verde nebulizer, Angelini, Italy) 를분무한군 (group B) 과생리식염수를분무한군 (group N) 으로각각 30명씩두군으로무작위분배, 인쇄후제3자에의해보관되었으며, 수술실입구에서시술자에게전달되어군배정이이루어졌다 (Fig. 1). 구강내수술및갑상선혹은흉추수술을시행했던과거력이있거나 Mallampatti classification Ⅲ 이상의어려운기관내삽관이예상되는경우와 American Society of Anesthesiologists physical status classification Ⅲ 이상의환자는연구대상에서제외하였다. 전처치는시행하지않았으며수술실입구에서 BH KSCVA Fig. 1. Flow diagram of the patients. www.anesth-pain-med.org 181
Anesth Pain Med Vol. 14 No. 2 또는생리식염수를 4 5회 (1회분무량, 0.17 ml) 입인두강내에분무하였다. 수술실에입실하여비침습적혈압장치, 맥박산소계측기, 심전도를부착하였으며, 환자의활력징후를확인하여기저치로정한후마취유도를시작하였다. Propofol 1 2 mg/ kg을정주하고, remifentamil (Ultiva, GlaxSmithKline, UK) 을목표농도조절주입기 (Orchestra, Fresenius Vial, France) 를통하여 4 μg/ml의효과처농도로설정한후주입하였으며, 환자의의식이소실되었음을확인하고 vecuronium 0.15 mg/ kg을정주하여 3분간 100% 산소로마스크환기를하였다. 분무후 10분이되었을때곡형날후두경 3번을이용하여이중관기관지튜브 (Human broncho [DLT], Insung medical Co., Korea) 의삽관을시도하였다. 남성은 37 Fr, 여성은 35 Fr의이중관기관지튜브를숙련된한명의전공의가삽관하였으며한번의시도로삽관을성공하지못하였을경우연구대상에서제외하였다. 이중관기관지튜브는굴곡형기관지경으로편측기관지내삽관을유도하였으며, 흉부청진을통해일측폐환기를확인하였다. 기도평가를위하여 Mallampatti classification, Cormack and Lehane grade와 percentage of glottic opening (POGO) score를기록하였고, 시술자가후두경을잡은시점부터기관내삽관이성공할때까지시간을기관내삽관시간으로기록하였다. 수술실도착했을때, 기관내삽관전후, 삽관 1분, 3분및 5분후에심박수와수축기, 이완기, 평균동맥압의변화를측정하였다. 술후 1시간, 24시간의인후통, 애성, 연하곤란정도를조사하였다. 술후인후통의경중도는 Agarwal 등 [5] 이사용한 4-point scale (0 3) 를이용하였으며애성및연하곤란의경중도는사용한 4-point scale (0 3) 를변형하여분류하였다. 술후인후통은아무런증상이없는경우 (0점), 말할때만약간있는경우 (1점), 중등도인경우 (2점), 애성및목소리의변화와흉통을동반한술후인후통인경우 (3점) 로하였다. 애성은변화가없는경우 (0점), 약간의변화가있을때 (1점), 중등도인경우 (2점), 말할수없을정도로심한경우 (3점) 로나누었고, 연하곤란은없을경우 (0점), 경미한경우 (1점), 중등도인경우 (2점), 통증으로인하여삼킬수없을정도일때 (3점) 로분류하였다. 수술후환자의증상을조사한연구자는분무한군을알지못하도록하였다. 술후인후통은 1점이상인경우발생한것으로보았으며 BH 분무로인해발생가능한구강마비감, 작열감이나자상감이발생하였을경우, 부작용으로기록하였다. 통계분석이중관기관지튜브를사용한각각 30명의환자에서 lidocaine 과생리식염수를기관내삽관 10분전분무한본원의선행연구에서생리식염수를분무한군의술후 24시간인후통발생빈도는 85% 였다. 본연구의일차유효성평가변수 (primary endpoint) 는술후 24 시간의인후통발생빈도로선행연구를참고로 85% 에서 50% 로 35% 감소되는것을연구자들이임상적으로유 의하다고판정하였다. G* power (Ver. 3.1.9.2, Franz Faul, Germany) 를통하여표본수산정을한결과, 유의수준 α = 0.05, 80% power 에서각군당 27 명의대상환자수가필요하며, 10% 탈락률을고려하여각군당 30 명을목표표본수로결정하였다. 정규성검정은 Shapiro-Wilk test 를사용하였고, 통계처리는 SPSS (version 12.0, SPSS Inc., USA) 를사용하였다. 두군간의 성별비교, Mallampatti classification, Cormack and Lehane grade, POGO score, 인후통, 애성, 연하곤란정도는 chisquare test 또는 Fisher s exact test 를이용하였다. 두군간의 나이, 키, 체중, 기관내삽관시간, 마취시간및시간에따른혈압, 심박수변화의두군간비교는 Student s t-test 를사용하였으며, P 값이 0.05 미만일때유의한것으로판정하였다. 결 과 Group B 와 group N 의환자는각각 30 명으로성별, 연령, 키 와몸무게및 American Society of Anesthesiologists physical status classification 점수는통계적으로유의한차이가없 었다 (Table 1). Mallampatti classification, Cormack and Lehanne grade 및 POGO score 와같은기도평가항목들과기 관내삽관및마취시간도유의한차이가없었으며두군간의혈 역학적변화는기관내삽관직후와 1 분, 3 분, 5 분후에유의한차 이가없었다 (Fig. 2, Table 2). 술후인후통을 4-point scale 1 점이상일때발생하였다고계산하였고, 이에따른 group N 과 group B 의술후 1 시간, 24 시간인후통의발생빈도는 73.3% 와 23.3% (P < 0.001), 66.6% 와 20.0% (P = 0.001) 로유의한차이 를보였다. Group B 에서 BH 의분무에의한구강마비감, 작열감 이나자상감등의부작용들은발생하지않았다. Group B 의술 후 1 시간, 24 시간연하곤란은 group N 에비하여유의하게낮았 다 (13.3% vs. 56.7%, P = 0.001, 6.6% vs. 30.0%, P = 0.042). 술 후 1 시간의애성은두군간에유의한차이가있었으나, 술후 24 Table 1. Patient Characteristics Variable Group N Group B Sex (F/M) 18/12 22/8 Age (yr) 57 ± 19 52 ± 20 Height (cm) 161 ± 10 164 ± 9 Weight (kg) 61 ± 11 61 ± 12 ASA (I/II) 11/19 13/17 Values are presented as number of patients or mean ± SD. Group N: normal saline spray, Group B: benzydamine hydrochloride spray. ASA: American Society of Anesthesiologists physical status classification. There are no significant differences between two groups. 182 www.anesth-pain-med.org
Benzydamine Hcl 분무가술후인후통에미치는영향 KSCVA Fig. 2. Comparison of cardiovascular changes. All values are expressed as mean ± SD. There were no significant differences between the two groups. Group N: normal saline spray, Group B: benzydamine hydrochloride spray. After intubation = just after the intubation; 1 minute = 1 minute after intubation; 3 minutes = 3 minutes after intubation; 5 minutes = 5 minutes after intubation. Table 2. Laryngeal View and Intubation Time Variable Group N Group B P value Mallampatti classification 26/4 24/6 0.731 (I/II) Cormack & Lehane grade 21/9 14/16 0.115 (I/II) POGO score (%) 84 ± 24 74 ± 31 0.169 Intubation time (s) 32 ± 18 29 ± 13 0.451 Anesthesia time (min) 151 ± 92 164 ± 92 0.582 Values are presented as number of patients or mean ± SD. Group N: normal saline spray, Group B: benzydamine hydrochloride spray. POGO: percentage of glottic opening. There are no significant differences between two groups. 시간애성은두군간에유의한차이가없었다 (Table 3). 4-point scale 점수에따른비교하였을때술후 1시간, 24시간의인후통과술후 1시간의연하곤란은유의한차이가있었으며, 애성및술후 24시간의연하곤란은차이가없었다 (Table 4). 고찰 술후인후통과애성은기관내삽관과연관되어흔히발생하는합병증이다 [7,8]. 환자의성별, 단일관기관튜브의크기, 커프형태, N 2 O의사용여부와같은요소들이연관있다는연구가있으며 [1,9 11], 특히흉부외과수술에서필요로하는이중관기관지튜브는단일관기관튜브에비하여굵기때문에이와같은합병증이발생할확률이증가하게된다 [2]. 일반적으로술후인후통은특별한치료가없어도시간이지나면자연히회복되는경 www.anesth-pain-med.org 183
Anesth Pain Med Vol. 14 No. 2 Table 3. Incidence of Postoperative Sore Throat, Hoarseness and Dysphagia 과를보이나, 환자에따라극심한술후인후통을호소하는경 우가있으므로술후인후통감소를위한여러연구가진행되어 졌다 [12 15]. 술후인후통은기관내삽관으로인한인두점막 (pharyngeal mucosa) 의염증에따른국소외상의결과이다 [16]. 이에따라즉각적인술후인후통은주로단일관기관튜브의삽 관이원인이며, 지연성인후통이기관점막외상에따른것으로 알려져왔다 [17]. 술후 1 시간의인후통은전신마취시사용한 진통제에의해감춰질수있으므로 [6], 본연구에서는술후 1 시 간과 24 시간인후통을모두비교하였다. 술후인후통을줄이기위하여사용되는약제중대표적으로 lidocaine 이있으며, 이는 aminoamide 국소마취제로기도반 사를저하시키고, 기도과민성을감소시키며진통, 항염증효과 로인하여기관내삽관시혈역학적변화를둔화시킨다고알려 져있다 [18]. Cho 등 [19] 은 dexamethasone 8 mg 과 lidocaine 1.5 mg/kg 을마취유도 5 분전에정주하여술후인후통과애성 을감소시키는효과를보았다. 그러나 lidocaine 의 hypoalgesic effect 가 15 분이내로영향을미치며수술이끝난후 ph 9.0 9.2 의알칼리성첨가제에의하여 lidocaine 을기도내분무할수 록기도자극이심해져술후인후통이증가한다는연구들도있 다 [20]. Variable Group N Group B P value Sore throat 1 h 22 (73.3) 7 (23.3) < 0.001 24 h 20 (66.6) 6 (20.0) 0.001 Hoarseness 1 h 26 (86.7) 18 (60.0) 0.039 24 h 26 (86.7) 20 (66.6) 0.125 Dysphagia 1 h 17 (56.7) 4 (13.3) 0.001 24 h 9 (30.0) 2 (6.6) 0.042 Values are presented as number (%). Group N: normal saline spray, Group B: benzydamine hydrochloride spray. 본연구에서사용된 BH 는국소비스테로이드성소염진통 제로염증부위에선택적으로 prostaglandin 합성을억제하 고국소마취작용을하여진통, 해열, 항균효과를가지고있다 [21]. Benzydamine 이특히 tumour necrosis factor-α, interleukin-1β 와같은 proinflammatory cytokines 생산의저해제 로작용한다는연구들에의해항염효과가설명이되고있으며 [22] BH 를국소적으로사용할경우, 흡수가완전하지않고, 느리 게진행되어목표로하는장기에높은농도로남게되므로전신 적인영향을줄이고치료효과를높일수있다 [21]. 본연구에서사용된 BH 는일정액이나오는분무형제제로이 비인후과영역에서인두염, 편도선염, 편도선수술및방사선치 Table 4. Severities of Postoperative Sore Throat, Hoarseness and Dysphagia Variable Group N Group B 료또는기관내삽관후점막염증이발생한경우와같이술후 인후통이있는경우또는잇몸, 발치전후의염증치료및진통 에흔히사용되는일반의약품이며, 같은효과를위해물에희 석, 양치하여사용하는 BH (Tantum solution Sam-A, Sama Pharm, Korea) 는전문의약품으로처방을통해사용하기도한 다. Tantum Verde nebulizer 는성인인경우 1 일 2 회에서 6 회 까지각횟수마다 4 8 번분무를하고, 6 세이상 12 세미만일경 우 4 번, 6 세미만인경우아이의몸무게 4 kg 당 1 번씩최대한도 4 번까지분무가가능하며 1 회분무량은 0.17 ml 이다. 여러연구를통해단일관기관튜브를사용한환자에서 BH 가 술후인후통을감소시킨다는결과를확인할수있었으며 [6], Chang 등 [23] 은이중관기관지튜브를사용한환자에서 BH 를입 인두강과튜브의 cuff 에동시에분무하여술후인후통이감소 되는의미있는결과를보았다. 저자들은 BH 의분무에의한술 후인후통감소효과정도를확인하기위하여본연구를진행하 였다. 결과적으로 group N 과 group B 의술후 1 시간, 24 시간 인후통을비교하였을때 BH 를전처치한환자들에서통계적으 로확연한차이 (P < 0.001) 를보이며술후인후통이감소하였다 (Table 4). 수술한당일의연하곤란역시감소하였으므로환자의 수술후만족도향상에도움이되는처치라고보여진다. P value Sore throat (0/1/2/3) 1 h 8/11/6/5 23/6/1/0 < 0.001 24 h 10/17/3/0 24/4/2/0 0.001 Hoarseness (0/1/2/3) 1 h 4/16/10/0 12/11/7/0 0.065 24 h 4/13/9/4 10/11/9/0 0.081 Dysphagia (0/1/2/3) 1 h 13/12/5/0 26/4/0/0 0.001 24 h 21/6/3/0 28/2/0/0 0.050 Values are presented as number of patients. Group N: normal saline spray, Group B: benzydamine hydrochloride spray. Sore throat was graded as 0, absent; 1, minimal; 2, moderate; 3, severe. Hoarseness was graded as 0, absent; 1, slight; 2, severe; 3, preventing speech. Dysphagia was graded as 0, absent; 1, slight; 2, moderate; 3, cannot swallow because of pain. 이전연구에서 lidocaine 분무가기침반사억제작용을하며 후두경조작및기관내삽관시나타나는순환계반응을약화시 키고중추신경억제작용의효과가있기때문에 lidocaine 을정 주하거나후두기관의살포, 기관내주사등을시행한연구에 서혈역학적변화를둔화시키는결과를보았다는연구가있다 [24,25]. 본연구에서 BH 는이러한연구결과들과는다르게기 관내삽관전후의혈역학적변화에는별다른차이를보이지않 184 www.anesth-pain-med.org
Benzydamine Hcl 분무가술후인후통에미치는영향 았다. 또한, BH의발생가능한부작용으로지적되는구강마비감 (local numbness), 작열감이나자상감 (burning or stinging sensation) 은본대상자들에게는발생하지않았으나 [5,26], group N의술후 1시간인후통이 73.3% 인것에반하여 group B의술후인후통이 23.3%, 술후 24시간인후통역시 66.6% 와 20.0% 로확연한차이를보이므로부작용에초점을맞춘후속연구를통해명확한빈도와정도를확인한다면이중관기관지튜브를사용하는환자들에대해임상적으로상용화될수있을것이라사료된다. 본연구의제한점으로는수술후사용된진통제에대한개별적조사가이루어지지않았으며, 환자의만족도를확인하지않은것이다. 인후통의유무및정도와연계하여환자의 BH 사용에대한만족도를조사하는것이상용화에필요하며, 진통제의사용이인후통에영향을줄수있으므로, 이에관한추가적인연구가시행되어야할것이다결론적으로이중관기관지튜브를사용할경우, 기관삽관전 BH를기관내분무하여술후인후통을감소시킬수있었다. CONFLICTS OF INTEREST No potential conflict of interest relevant to this article was reported. ORCID Sang Hi Park: https://orcid.org/0000-0003-1138-6028 Seok Gon Son: https://orcid.org/0000-0002-0165-2065 REFERENCES 1. Christensen AM, Willemoes-Larsen H, Lundby L, Jakobsen KB. Postoperative throat complaints after tracheal intubation. Br J Anaesth 1994; 73: 786-7. 2. Xu YJ, Wang SL, Ren Y, Zhu Y, Tan ZM. A smaller endotracheal tube combined with intravenous lidocaine decreases post-operative sore throat - a randomized controlled trial. Acta Anaesthesiol Scand 2012; 56: 1314-20. 3. Canbay O, Celebi N, Sahin A, Celiker V, Ozgen S, Aypar U. Ketamine gargle for attenuating postoperative sore throat. Br J Anaesth 2008; 100: 490-3. 4. Turnbull RS. Benzydamine hydrochloride (tantum) in the management of oral inflammatory conditions. J Can Dent Assoc 1995; 61: 127-34. 5. Agarwal A, Nath SS, Goswami D, Gupta D, Dhiraaj S, Singh PK. An evaluation of the efficacy of aspirin and benzydamine hydrochloride gargle for attenuating postoperative sore throat: a prospective, randomized, single-blind study. Anesth Analg 2006; 103: 1001-3. 6. Hung NK, Wu CT, Chan SM, Lu CH, Huang YS, Yeh CC, et al. Effect on postoperative sore throat of spraying the endotracheal tube cuff with benzydamine hydrochloride, 10% lidocaine, and 2% lidocaine. Anesth Analg 2010; 111: 882-6. 7. Al-Qahtani AS, Messahel FM. Quality improvement in anesthetic practice--incidence of sore throat after using small tracheal tube. Middle East J Anaesthesiol 2005; 18: 179-83. 8. Biro P, Seifert B, Pasch T. Complaints of sore throat after tracheal intubation: a prospective evaluation. Eur J Anaesthesiol 2005; 22: 307-11. 9. Stout DM, Bishop MJ, Dwersteg JF, Cullen BF. Correlation of endotracheal tube size with sore throat and hoarseness following general anesthesia. Anesthesiology 1987; 67: 419-21. 10. Combes X, Schauvliege F, Peyrouset O, Motamed C, Kirov K, Dhonneur G, et al. Intracuff pressure and tracheal morbidity: influence of filling with saline during nitrous oxide anesthesia. Anesthesiology 2001; 95: 1120-4. 11. Loeser EA, Kaminsky A, Diaz A, Stanley TH, Pace NL. The influence of endotracheal tube cuff design and cuff lubrication on postoperative sore throat. Anesthesiology 1983; 58: 376-9. 12. Kalil DM, Silvestro LS, Austin PN. Novel preoperative pharmacologic methods of preventing postoperative sore throat due to tracheal intubation. AANA J 2014; 82: 188-97. 13. Ogata J, Minami K, Horishita T, Shiraishi M, Okamoto T, Terada T, et al. Gargling with sodium azulene sulfonate reduces the postoperative sore throat after intubation of the trachea. Anesth Analg 2005; 101: 290-3. 14. Park SY, Kim SH, Lee AR, Cho SH, Chae WS, Jin HC, et al. Prophylactic effect of dexamethasone in reducing postoperative sore throat. Korean J Anesthesiol 2010; 58: 15-9. 15. Kang HY, Seo DY, Choi JH, Park SW, Kang WJ. Preventive effect of ketamine gargling for postoperative sore throat after endotracheal intubation. Anesth Pain Med 2015; 10: 257-60. 16. McHardy FE, Chung F. Postoperative sore throat: cause, prevention and treatment. Anaesthesia 1999; 54: 444-53. 17. Keane WM, Denneny JC, Rowe LD, Atkins JP Jr. Complications of intubation. Ann Otol Rhinol Laryngol 1982; 91: 584-7. 18. Solway J, Leff AR. Sensory neuropeptides and airway function. J Appl Physiol (1985) 1991; 71: 2077-87. 19. Cho CK, Kim JE, Yang HJ, Sung TY, Kwon HU, Kang PS. The effect of combining lidocaine with dexamethasone for attenuating postoperative sore throat, cough, and hoarseness. Anesth Pain Med 2016; 11: 42-8. 20. Maruyama K, Sakai H, Miyazawa H, Iijima K, Toda N, Kawahara S, et al. Laryngotracheal application of lidocaine spray increases KSCVA www.anesth-pain-med.org 185
Anesth Pain Med Vol. 14 No. 2 the incidence of postoperative sore throat after total intravenous anesthesia. J Anesth 2004; 18: 237-40. 21. Baldock GA, Brodie RR, Chasseaud LF, Taylor T, Walmsley LM, Catanese B. Pharmacokinetics of benzydamine after intravenous, oral, and topical doses to human subjects. Biopharm Drug Dispos 1991; 12: 481-92. 22. Riboldi E, Frascaroli G, Transidico P, Luini W, Bernasconi S, Mancini F, et al. Benzydamine inhibits monocyte migration and MAPK activation induced by chemotactic agonists. Br J Pharmacol 2003; 140: 377-83. 23. Chang JE, Min SW, Kim CS, Han SH, Kwon YS, Hwang JY. Effect of prophylactic benzydamine hydrochloride on postoperative sore throat and hoarseness after tracheal intubation using a double-lumen endobronchial tube: a randomized controlled trial. Can J Anaesth 2015; 62: 1097-103. 24. Yu BS. A comparison of the cardiovascular response with various administration method of lidocaine during tracheal intubation. Korean J Anesthesiol 1991; 24: 722-30. 25. Honma K, Kamachi M, Akamatsu Y, Yoshioka M, Yamashita N. Lidocaine spray 10 min prior to intubation: effects on postoperative sore throat. J Anesth 2010; 24: 962-5. 26. Mazzarella B, Macarone Palmieri A, Mastronardi P, Spatola R, Lamarca S, De Rosa G, et al. Benzydamine for the prevention of pharyngo-laryngeal pathology following tracheal intubation. Int J Tissue React 1987; 9: 121-9. 186 www.anesth-pain-med.org