KSAP ------, 1 1 , Minkyung , Sehun Lim 1 1 Department of Pharmacology, Pharmacology, of Department 2 Clinical Research Clinical , Yongjae Han , Yongjae 1 , and Jeonghan Lee , and Jeonghan 3 , Soonho Cheong 1 , Kwanghee Kim 441 3 , Myoung-hun Kim , Myoung-hun 1 , Inwook Myoung 1 eISSN 2383-7977 • In patients who had undergone laparoscopic cholecystectomy, gargling with with gargling cholecystectomy, laparoscopic undergone had who In patients Postoperative sore throat (POST) is a complication that decreases patient sat patient decreases that is a complication (POST) throat sore Postoperative ; Endotracheal intubation; Laparoscopic cholecystectomy; Mouth Mouth cholecystectomy; Laparoscopic intubation; Endotracheal Dexamethasone; Study participants were 96 patients who had undergone laparoscopic cholecys laparoscopic undergone had who 96 patients participantsStudy were There were no significant differences in the total incidence of POST up to 24 post 24 to up POST of incidence total in the differences significant no were There , Yohan Park , Yohan 2 Department of Anesthesiology and Pain , Medicine, Pain and Anesthesiology of Department Department of Surgery, Inje University Busan Paik Hospital, Inje University College of Hospital, Inje University College of Busan Paik Department of Surgery, Inje University nous injection of 0.1 mg/kg dexamethasone. The incidence and severity of POST were not not were POST of severity and incidence The mg/kg dexamethasone. 0.1 of injection nous solu with 0.05% dexamethasone gargling of combination the between different significantly preven the of each use of and mg/kg dexamethasone 0.1 of injection intravenous and tion alone. methods tive Keywords: throat. Sore complication; Postoperative wash; I gargled with 0.9% normal saline and were infused intravenous 0.1 mg/kg dexamethasone; mg/kg dexamethasone; 0.1 infused intravenous were and saline with 0.9% normal I gargled 0.1 intravenous infused were and dexamethasone 0.05% with gargled GI group were cough hoarseness and POST, of severity and incidence The mg/kg dexamethasone. surgery. the h after 24 6, and 1, at recorded and evaluated Results: = incidence G Group = 0.367, (P GI Group I and Group G, Group among hours operative = 18.75%, I incidence Group 95% CI = 17.92–50.83], interval, 34.38%, [95% confidence other [95% CI = 12.55–43.70]). The = 28.13%, incidence GI Group [95% CI = 5.23–32.27], groups. the among comparable were outcomes Conclusions: as intrave effect prevention POST same the demonstrated solution 0.05% dexamethasone 3 Medicine, Busan, Korea Background: in to conducted was study present The complaints. postoperative increases and isfaction and injection dexamethasone intravenous dexamethasone, with gargling of effects vestigate POST. of severity and incidence the on two the of combination the Methods: dexamethasone with 0.05% G gargled Group groups. three into allocated randomly tectomy, group anesthesia; general before saline 0.9% normal infused intravenous were and solution Effect of dexamethasone gargle, intravenous intravenous gargle, of dexamethasone Effect on and their combination dexamethasone, sore throat: a randomized postoperative controlled trial Seunghee Ki Kwangrae Cho Oh 1 Anesth Pain Med 2020;15:441-450 Med Pain Anesth https://doi.org/10.17085/apm.20057 pISSN 1975-5171 October 5, 2020 October June 25, 2020 June

September 25, 2020 September 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 which (http://creativecommons.org/licenses/by-nc/4.0) License Non-Commercial Attribution Commons Creative the of terms the under Access article is an Open This distributed cited. is properly work original the provided in any medium, reproduction and distribution, use, non-commercial unrestricted 2020 Anesthesiologists, Society of Korean © the Copyright Tel: 82-51-890-6520 Tel: 82-51-898-4216 Fax: [email protected] E-mail: Pain Medicine, Inje University Busan University Inje Medicine, Pain College University Inje Hospital, Paik Busanjin-gu, 75 Bokji-ro, Medicine, of Korea Busan 47392, Corresponding author author Corresponding M.D., Ph.D Lee, Jeonghan and Anesthesiology of Department Received Accepted Revised Revised Anesth Pain Med Vol. 15 No. 4

INTRODUCTION differed following administration of the combination of gargling with 0.05% dexamethasone solution and intrave- Postoperative sore throat (POST) is a commonly postop- nous injection of 0.1 mg/kg dexamethasone and use of erative complication that occurs in 14.4% to 73.9% of pa- each of the preventive methods alone. Therefore, the aim tients who undergo general anesthesia with endotracheal of the present study was to investigate the effects of preop- intubation [1]. POST may cause patient dissatisfaction and erative 0.05% dexamethasone solution gargle, intravenous physical discomfort during recovery [2]. Causes of POST injection of 0.1 mg/kg dexamethasone, and combination of are known to be associated with inflammation and stimu- the two on the incidence and severity of POST, hoarseness lation by endotracheal intubation [3]. Various methods and cough in patients undergoing laparoscopic cholecys- have been found effective in reducing POST. The methods tectomy. that have been reported to be effective in reducing the inci- dence rate of POST include choice of a smaller endotrache- MATERIALS AND METHODS al tube, meticulous manipulation of the laryngoscope, in- tubation after complete muscle relaxation, minimization of The present study was conducted with patients undergo- cuff pressure inside the endotracheal tube, smooth suction ing elective laparoscopic cholecystectomy. Subjects were in the oropharynx, and complete contraction of the endo- 96 patients between the ages of 20–70, and with American tracheal tube cuff during the postoperative extubation [4]. Society of Anesthesiologists physical status classification I The pharmacological methods that have been found to or II. The duration of anesthesia was between 20 min and be effective in decreasing the incidence and severity of 120 min. Exclusion criteria were modified Mallampati POST include preoperative gargling with ketamine and score of 3 or higher; recent throat pain or upper respiratory magnesium solution [5], intravenous injection of dexa- infection; use of a device stimulating the oral cavity, phar- methasone [6], and gargling and tube soaking with dexa- ynx or larynx, such as Levin tube or endoscopic nasobiliary methasone [7]. drainage; previous experience of POST; contraindications Many recent studies have shown that dexamethasone to use of dexamethasone or allergic response to it. Addi- not only prevents postoperative nausea and vomiting but tionally, cases in which intubation was attempted three can also relieve pain or reduce general inflammatory re- times or more, in which endotracheal intubation was per- sponses [8]. The anti-inflammatory and immunosuppres- formed using a stylet, in which the Cormack-Lehane grade sant potency of orally administered dexamethasone is 26.6 was 3 or higher were excluded. times higher than that of cortisol, a natural hormone, and This study was approved by the Institutional Review Board 6.6 times higher than that of prednisone [9]. Dexametha- as a prospective, randomized, double-blind study (no. 19- sone is also used to decrease side effects during chemo- 0032), and registered with the Clinical Research Informa- therapy, treat Addison’s disease and adrenal insufficiency, tion Service (https://cris.nih.go.kr, no. KCT0004971). In the and facilitate fetal lung maturation in pregnant women at study, the patients were sufficiently informed and asked to high risk of preterm delivery [9]. sign a written consent prior to surgery. The patients were A previous meta-analysis showed that intravenous dexa- randomly allocated, using a computer-generated random methasone decreases the incidence and severity of POST number table, to three groups, Gargle group (Group G, n = at 1 h and 24 h after surgery [10]. Yang et al. [6] and Lee et 32), IV group (Group I, n = 32), and Gargle + IV group al. [11] also reported reduced incidence of POST through (Group GI, n = 32), at a ratio of 1:1:1. To blind the group al- intravenous injection of dexamethasone. location, the pharmacist was given a sealed envelope with In the dental field, dexamethasone gargle is used to re- a coding number written on it and asked to prepare syring- lieve the symptoms of burning mouth syndrome [12]. Lee es for and containers of the gargle solution. et al. [7] reported that gargling with 0.05% dexamethasone The syringes for drug injection contained either 0.9% nor- solution decreased the incidence of POST. mal saline solution 2 ml or mixed solution 2 ml (dexameth- No previous studies have been conducted to examine the asone 0.1 mg/kg + 0.9% normal saline). The containers of effect of the combination of dexamethasone gargle and in- the gargle solution contained either 0.9% normal saline 10 travenous dexamethasone injection on the incidence and ml or 0.05% dexamethasone solution 10 ml (dexametha- severity of POST. We thought that the incidence of POST sone 5 mg/ml + 0.9% normal saline 9 ml) prepared asepti-

442 www.anesth-pain-med.org KSAP ------443 Monitoring System, System, Monitoring ™ Group GI (n = 32) Analyzed (n = 32) Lost of follow-up (n = 0) , Organon Ltd., Ireland) count was 0 0 was count Ireland) Ltd., , Organon ® Intravenous injection with mixed solution 2 ml (dexamethasone 0.1 mg/kg + normal saline) Gargle with 0.05% dexamethasone, , Flexicare medical, USA) was used USA) was medical, for la , Flexicare ™ ). , Teleflex Medical, USA) for the male subjects and 7.0 subjects and 7.0 USA) the male for Medical, , Teleflex ® The patients were intramuscularly injected, as premedi intramuscularly were patients The Fig. 1 Fig. fully performed in two or fewer attempts in all of them. In In them. performed of all in fully two in feweror attempts # 3.5 men, Macintosh in intubation of tracheal the case (Briteblade pro ryngoscope not used. and # 3 in women, was and stylet The of the laryngoscope tube of the silicon inner diameter used 7.5 mm (Sheridan/ was intubation for the endotracheal CF airway Grip Endo (Ace An oral subjects. mm for the female 0.05% dexamethasone solution gargle for 30 s at 10 min be for 30 s at solution0.05% dexamethasone gargle back the head tilting sufficiently by anesthesia general fore dexa injection of 0.1 mg/kg intravenous followed by ward, with mixed solution saline 0.9% normal in a methasone, anesthesia general before of 2 ml, 5 min volume resulting ( 0.2 the surgery, with 30 min before glycopyrrolate cation lido and mg/kg) (2 Propofol mg. 20 famotidine and mg Ro used of anesthesia. for induction were (1 mg/kg) caine block used was as a neuromuscular (0.6 mg/kg) curonium performed was verifying after intubation Endotracheal er. VISTA index (BIS the bispectral that 60 and the train-of-four below USA) was Boulder, Covidien, SX (TOF-Watch TOF blocker. injection neuromuscular of the following (zero) included in the statistical of all patients grade Cormack The success was intubation endotracheal and 1, was analysis ------Analysis Follow-up Allocation Enrollment Group I (n = 32) Analyzed (n = 32) Randomized (n = 96) Lost of follow-up (n = 0) Agree to participate (n = 96) injection with mixed solution 2 ml (dexamethasone 0.1 mg/kg + normal saline) Gargle with normal saline, Intravenous Dexamethasone gargle and IV for POST for IV and gargle Dexamethasone , Bandgold Co., Korea), a filter a filter Korea), Co., , Bandgold ™ Group G (n = 32) Analyzed (n = 32) Lost of follow-up (n = 0) Intravenous injection with normal saline 2 ml Gargle with 0.05% dexamethasone, Flow diagram of study enrollment. study of diagram Flow A total of 96 patients were allocated to the three groups. groups. the three to allocated were of 96 patients A total www.anesth-pain-med.org Fig. 1.Fig. travenous injection group (Group GI) were treated with with treated were GI) (Group injection group travenous injection of 0.1 mg/kg dexamethasone, mixed with 0.9% with mixed 0.9% dexamethasone, injection of 0.1 mg/kg min 5 ml, 2 of volume solution saline resulting normal a in + in in the gargle patients The anesthesia. general before gargle for 30 s at 10 min before general anesthesia by suffi by anesthesia general 10 min before 30 s at for gargle intravenous by followed backward, the head tilting ciently of 0.9% normal saline solution 5 min before general anes general solutionof 0.9% normal saline 5 min before injection group in the intravenous patients The thesia. solution saline with normal 0.9% treated were I) (Group with 0.05% dexamethasone solution gargle for 30 s at 10 10 for 30 s at with solution 0.05% dexamethasone gargle the tilting sufficiently by anesthesia general min before injection of 2 ml intravenous by followed backward, head tion through an interview. tion through treated G) were (Group group the gargle in patients The one who performed for the surgery, the anesthesia visited examina the medical conduct to in the ward the patients according to the coding number, after which anesthetic in anesthetic which after number, the coding to according per were and extubation intubation duction, endotracheal formed.surgery,the the After not anesthesiologist, another system was used to prevent the inflow of tiny impurities impurities of tiny the inflow used was prevent to system of the unaware who was the body. An anesthesiologist into the drugs the patients to administered allocation, group cally and passed on to the anesthesiologist on the day of of on the day passed and the anesthesiologist on to cally use syringe a the of requiring procedures surgery. all In syringe filter (Bandgold Anesth Pain Med Vol. 15 No. 4

Fix™, Ace Medical Co. Ltd., Korea) was fixed with an endo- [13]. POST was defined as discomfort at the larynx or phar- tracheal tube in all study patients. Anesthesia was main- ynx, while resting or swallowing the saliva after the surgery tained using sevoflurane 1.5 to 2.5 vol%, 50% O2 with air, [6]. The responses were categorized into cases of no sore and remifentanil 0.05–0.1 μg/kg/min. The nasopharyngeal throat (no sore throat, 0), cases in which throat pain could temperature, electrocardiogram, oxygen saturation, and be felt by the patient only when the patient was asked capnogram were monitored, and an airway without the about the presence of sore throat (minimal sore throat, 1), heating and humidifying functions was used. At the start cases in which the patient himself or herself complained and end of the surgery, a cuff pressure gauge (Mallinck- about sore throat (moderate sore throat, 2), and cases in rodt™ Hand Pressure Gauge, Covidien Deutschland GmbH, which the patient obviously felt discomfort due to sore Germany) was used to keep the pressure at 20 to 30 cm- throat (severe sore throat, 3). Hoarseness and cough were

H2O. Ten minutes before the end of the surgery, tramadol also evaluated using the same method [13]. Patients with 0.5 to 1 mg/kg and ramosetron 0.3 mg were intravenously minimal symptoms or more (1 point or more in four-point injected to prevent postoperative pain, nausea and vomit- scale) were included in incidence data estimates. Visual ing. After the end of the surgery, no endotracheal suction analog scale (VAS) scores of pain were recorded at was performed but oral suction was lightly performed. the same time points. Additionally, other side effects in ad- Sugammadex (2–4 mg/kg) was administered to reverse the dition to POST were identified and specifically recorded. neuromuscular blocker. Extubation was carried out gently To control postoperative abdominal pain, when the VAS after verifying that the TOF ratio was 0.9 or higher, moni- was 5 or higher in the PACU, ketorolac tromethamine 30 mg/ toring the patients’ recovery of consciousness, and follow- ml was administered and acetaminophen 1 g/100 ml was in- ing the anesthesiologist’s orders. travenously injected three times a day in the ward. When the An interview regarding POST was conducted with the VAS score of the pain at the surgical site was 5 or higher, in- patients within 24 h after the surgery, considering that an travenous injection of tramadol 0.5 mg/kg was additionally acute inflammatory response usually reaches its peak in performed to control the surgical pain. If the pain continued about 24 h and the incidence of POST is decreased within at a VAS score of 5 or higher despite the pain control, nalbu- 24 h when dexamethasone is used [11]. In each group, an phine 2.5 mg was intravenously injected. anesthesiologist who was unaware of the allocation of the The primary outcome measure was the incidence of POST. patients to the groups visited the ward at 1, 6, and 24 h after The secondary outcome measures were the incidence of the surgery to interview the patients about sore throat, hoarseness and cough, and the severity of POST, hoarseness hoarseness and cough. The severity of POST, hoarseness and cough. and cough was evaluated on a four-point scale (Table 1) Considering that the incidence of POST in the group that received prophylactic dexamethasone intravenous injec- Table 1. Scoring System for Sore Throat, Cough and Hoarseness [13] tion was 0.69 in the study by Park et al. [13], that the POST Severity score Description incidence in the dexamethasone gargle group was 0.33 in Sore throat Lee et al. [7], and that the POST incidence in the Gargle + 0 No sore throat IV Group would be lower than 0.33, the necessary number 1 Minimal sore throat of subjects in each group was calculated to be 29 with a sig- 2 Moderate sore throat nificance level of 0.05 and power of 80%. To adjust a fami- 3 Severe sore throat lywise error rate, we applied in sample size calculation. Cough Taking into consideration the 10% dropout rate, the num- 0 No cough 1 Minimal cough ber of subjects in each group was determined to be 32. 2 Moderate cough Data was presented as mean ± SD for continuous vari- 3 Severe cough ables, and count and percentage for categorical variables. Hoarseness Age, American Society of Anesthesiologists physical status 0 No hoarseness classification, height, weight, anesthesia time, initial time 1 Hoarseness at the time of interview, but noted only cuff pressure, end time cuff pressure, dose of drugs admin- by patient 2 Hoarseness that is readily apparent, but mild istered (remifentanil, tramadol, sugammadex, acetamino- 3 Hoarseness that is readily apparent and severe phen for postoperative wound pain) and wound pain VAS

444 www.anesth-pain-med.org KSAP , - - - 445 Table 3 Table ( 274 951 287 959 880 282 932 780 339 380 708 835 608 902 840 ...... ). 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 P value Table 2 Table ) 32 0 8 5 0 6 . . . . . ) ) ) 0 37 7 7 8 . . . . . ) ) ) ) 3 3 3 87 5 19 0 14 9 13 10 0 0 , , ,

62 38 56 2 2 2 44 ± ± ± ± ± ± ± ± ± ± ( ( ( ( ( ( (

3 3 3 5 9 8 0 4 3 8 0 4 ...... 14 18 20 12 63 , hoarseness group * time P * time group , hoarseness = . 2 47 27 65 52 28 45 162 199 190 Group GI (n GI Group = Table 4 Table ( ) 6 1 8 5 8 32 . . . . . ) ) ) 7 4 8 6 6 . . . . . ) ) ) 3 3 3 ) 4 23 0 13 7 11 13 0 0 77 , , ,

62 38 2 2 2 75 25 ± ± ± ± ± ± ± ± ± ± ( ( ( ( ( (

( 4 2 2 2 9 . 9 8 8 1 6 9 3 2 8 ...... 24 12 20 27 27 28 48 65 53 46 184 162 201 The sore throat incidence and severity over time did not not time did incidence and severity over throat sore The incidence and severity hoarseness a The did not show Group I (n Group = = [95% CI 46.88%, = GI incidence 29.58–64.17], group = 0.654, total hoarseness P incidence 0.654, total = G inci 0.415, group dence = 62.50%, [95% CI = I incidence 45.73–79.27], group CI [95% 50.00%, =and incidence cough The 67.32]). 32.68– time endotracheal tube cuff pressure and end time endo time end and pressure cuff tube endotracheal time doses total of drugs The ad pressure. cuff tube tracheal in and sugammadex tramadol, (remifentanil, ministered period,the perioperative for postoperative acetaminophen comparable were scores VAS and wound pain control) pain GI ( I, and Group Group G, Group among and I, Group G, Group among difference a significant show and swallowing 6 h and 24 h in resting 1 h, GI at Group * time P POST group resting = POST 0.558, swallowing * time P group = POST 0.751, total incidence P = 0.367, G incidence group = interval, 34.38%, [95% confidence 95% CI = I incidence 17.92–50.83], group = 18.75%, [95% CI = GI incidence 5.23–32.27], group = 28.13%, [95% CI = 12.55–43.70] ). 24 h 6 h and 1 h, at the groups among difference significant the surgeryafter ) - - - - 32 6 5 5 6 . . . . ) ) ) 2 4 3 6 8 . . . . . ) ) ) ) 3 3 3 0 12 8 10 10 0 0 63 4 18 , , ,

56 34 2 2 2 66 44 ± ± ± ± ± ± ± ± ± ± ( ( ( ( ( ( (

3 3 3 8 9 2 3 8 2 9 0 0 3 ...... 21 14 11 18 2 47 51 27 27 46 68 165 192 195 Group G (n Group = Dexamethasone gargle and IV for POST for IV and gargle Dexamethasone O) 2 O) 2 RESULTS RESULTS ) > 5.73) = 0.05/3 = macro 0.0167). SAS ] was performed to compare the scores scores the performed was ] compare to 10 2 Variable χ – 14 0 [ Patient Characteristics, Perioperative and Postoperative Data Postoperative and Perioperative Characteristics, Patient h h h 6 24 1 I II From September 2019 to April 2020, 96 patients were were 2020, 96 patients September April 2019 to From

Dose of acetaminophen administered (g) administered acetaminophen Dose of ( pain VAS Wound Dose of tramadol administered (mg) administered tramadol Dose of (mg) administered sugammadex Dose of End time cuff pressure (cmH cuff pressure time End (μg) administered remifentanil Dose of Weight (kg) Weight (min) time Anesthesia (cmH cuff pressure time Initial (cm) Height F (yr) Age ASA Sex M Scale. injection with 0.9% normal saline 2 ml, Group I: gargle with 0.9% normal saline, intravenous injection with mixed solution 2 ml (dexamethasone 2 ml (dexamethasone solution with mixed injection intravenous saline, with 0.9% normal I: gargle Group 2 ml, saline with 0.9% normal injection 2 ml solution with mixed injection intravenous solution, with 0.05% dexamethasone gargle GI: Group saline), mg/kg + 0.9% normal 0.1 Analog Visual VAS: classification, status physical Anesthesiologists Society of American ASA: saline). mg/kg + 0.9% normal 0.1 (dexamethasone Data presented as number of patients, mean ± SD, or median (1Q, 3Q). Group G: gargle with 0.05% dexamethasone solution, intravenous intravenous solution, with 0.05% dexamethasone G: gargle (1Q, 3Q). Group median or ± SD, mean patients, of as number presented Data www.anesth-pain-med.org Table 2. Table age, anesthesia time, American Society of Anesthesiolo time, anesthesia age, initial weight, height, classification, status physical gists performed the inclusion who satisfied with the 96 patients with the study no drop completed criteria, and all patients in the sex found ratio, were differences significant No outs. screened and enrolled in the study. These patients were were These patients in the study. and enrolled screened was evaluation The groups. three to allocated randomly was conducted using SAS 9.4 (SAS Institute Inc., USA). A P Inc., Institute 9.4 (SAS SAS conducted using was significant. as statistically considered 0.05 was than less for nonparametric analysis of factorial longitudinal data in data of factorial longitudinal analysis for nonparametric Brunner al. et analysis Statistical measures. repeated groups, three from chi-square test. To adjust a type I error rate, we recalculat rate, a type I error adjust To test. chi-square the Bonferroni applying by of significance ed the level P ( method (i.e., were compared among treatment groups using analysis of of analysis using groups treatment among compared were inci The as appropriate. test variance or Kruskal–Wallis with analyzed were hoarseness and cough dence of pain, Anesth Pain Med Vol. 15 No. 4

Table 3. Incidence and Severity of Sore Throat among the Groups after Tracheal Extubation P value Post operation time (severity score) Group G (n = 32) Group I (n = 32) Group GI (n = 32) Group Time Group * time Resting 1 h (0/1/2/3) 26/6/0/0 29/3/0/0 29/3/0/0 0.258 0.006 0.558 6 h (0/1/2/3) 30/2/0/0 30/2/0/0 32/0/0/0 24 h (0/1/2/3) 31/1/0/0 32/0/0/0 32/0/0/0 Swallowing 1 h (0/1/2/3) 26/6/0/0 28/4/0/0 28/4/0/0 0.203 0.000 0.751 6 h (0/1/2/3) 23/9/0/0 24/8/0/0 28/4/0/0 24 h (0/1/2/3) 29/3/0/0 30/2/0/0 32/0/0/0 Total incidence (95% confidence inter- 34.38% (17.92–50.83) 18.75% (5.23–32.27) 28.13% (12.55–43.70) 0.367 val) Data are presented as number of patients. Severity of sore throat was assessed using 4 scoring system: 0, no sore throat; 1, mild sore throat; 2, moderate sore throat; 3, severe sore throat. The statistical significance was accepted with P values less than 0.05 for primary comparison among groups.

Table 4. Incidence and Severity of Hoarseness among the Groups after Tracheal Extubation P value Post operation time (severity score) Group G (n = 32) Group I (n = 32) Group GI (n = 32) Group Time Group * time 1 h (0/1/2/3) 15/17/0/0 20/12/0/0 24/8/0/0 0.062 0.000 0.654 6 h (0/1/2/3) 19/13/0/0 24/8/0/0 23/9/0/0 24 h (0/1/2/3) 26/6/0/0 31/1/0/0 30/2/0/0 Total incidence (95% confidence interval) 62.5% (45.73–79.27) 46.88% (29.58–64.17) 50% (32.68–67.32) 0.415 Data are presented as number of patients. Severity of hoarseness was assessed using 4 scoring system: 0, no hoarseness; 1, mild hoarseness; 2, moderate hoarseness; 3, severe hoarseness. The statistical significance was accepted with P values less than 0.05 for primary comparison among groups.

Table 5. Incidence and Severity of Cough among the Groups after Tracheal Extubation P value Post operation time (severity score) Group G (n = 32) Group I (n = 32) Group GI (n = 32) Group Time Group * time 1 h (0/1/2/3) 32/0/0/0 30/2/0/0 31/1/0/0 0.141 0.157 0.388 6 h (0/1/2/3) 32/0/0/0 31/1/0/0 31/1/0/0 24 h (0/1/2/3) 32/0/0/0 32/0/0/0 30/2/0/0 Total incidence (95% confidence interval) 0.00% 6.25% (0.00–14.64) 6.25% (0.00–14.64) 0.541 Data are presented as number of patients. Severity of cough was assessed using 4 scoring system: 0, no cough; 1, mild cough; 2, moderate cough; 3, severe cough. The statistical significance was accepted with P values less than 0.05 for primary comparison among groups. severity did not show a significant difference among the but our findings revealed no difference between the com- groups at 1 h, 6 h and 24 h after the surgery (Table 5, cough bined or single applications with respect to POST. group * time P = 0.388, total hoarseness incidence P = According to the experimental results of the present 0.541, group G incidence = 0.00%, group I incidence = study, the POST-preventing effect of gargling with 0.05% 6.25%, [95% CI = 0.00–14.64], group GI incidence = 6.25%, dexamethasone solution alone and that of intravenous in- [95% CI = 0.00–14.64]). jection of 0.1 mg/kg dexamethasone solution alone were No postoperative complication, except sore throat, cough equivalent to the effect of the combination of gargling with and hoarseness, was found in any of the patients in the 0.05% dexamethasone solution and subsequent intrave- three groups. nous injection of 0.1 mg/kg dexamethasone. The combined gargle and intravenous injection of dexa- DISCUSSION methasone did not demonstrate a better POST-preventing effect than the single use of each method, probably be- We predicted that combined gargle and intravenous in- cause the topical application of dexamethasone gargle did jection of dexamethasone would lead to a lower incidence not result in any increase in the plasma drug concentration of POST than use of each of the preventive methods alone, over that caused by the intravenous injection.

446 www.anesth-pain-med.org KSAP ------]. 7 ]. 447 21 [ ]. 23 [ ]. A wide spec 18 [ ]. In addition, corti ]. In ] and oral gargling [ gargling ] and oral 22 [ ]. There is no commer no is There ]. 24 25 [ ]. In the present study, the the study, the present ]. In 5 [ ]. ]. Gargling for prevention of postopera for prevention ]. Gargling ], or intravenously injecting dexametha ], or intravenously 7 ], and intraperitoneal administration of of administration ], and intraperitoneal [ 24 7 [ [ 20 [ -dependent phospholipids to inhibit phospholi to phospholipids -dependent 2+ ]. Intravenous injection showed of dexamethasone ]. Intravenous and decrease the synthesis of inflammatory media the synthesis and decrease 2 6 [ ], gargling with dexamethasone or soaking a endotra a soaking or with dexamethasone gargling ], Local use of dexamethasone for the reduction of postop Local use for the reduction of dexamethasone mucosa on the oral effective was Dexamethasone gargle Corticosteroid binds to annexin proteins and thus gener and thus annexin binds to proteins Corticosteroid ] that the total incidence within 24 h of dexamethasone incidence within the total 24 h of dexamethasone ] that 19 7 ing cellular integrity, and causes anti-inflammatory re anti-inflammatory integrity, and causes cellular ing of fibroblasts the growth inhibiting sponses by ultrasound-guided in addition its includes pain erative [ block plane abdominis transverse pletely removing the complication. Steroid has been often been often has Steroid complication. the removing pletely dexamethasone and systemic throat, sore used prevent to widelyis the most drug studied for POST be used the delivery for trum of methods may of steroid, with tube the endotracheal as soaking such [ in it tube cheal sone nausea of postoperative effect on the prevention significant and vomiting in decrease greater significantly a showed dexamethasone injection in comparison withnausea the intravenous Ca ates pase A leukotriene and , tor, of leukocytes the transport inflam to suppresses costeroid of cytokine maintain inhibits the release by matory sites, penetrate into the level of the basement membrane and re membrane of the basement level the into penetrate period for a longer effective main in comparison with in drug administration travenous in solution product gargle dexamethasone available cially of 0.01% to a concentration at However, Korea. mixing powder or dexamethasone by prepared 0.06% are and liquid with solution normal saline or distilled , In the patient undergoing unilateral inguinal hernia repair, repair, hernia inguinal unilateral undergoing the patient In during ultrasound-guided the addition of dexamethasone the numerical decreased block plane abdominis transverse levobu of administration the than more score scale rating alone pivacaine POST prevent to nociceptors local the on effect an showed throat sore tive effect a systemic than rather incidence of POSTtotal within 24 h of dexamethasone of Lee the findings to 34.4%, similar was et al. 0.05% gargle [ a thin horny has mucosa oral 33.3%. The was 0.05% gargle a of allowing and is capable vessels and many layer the to compared vessels, of drug reach to amount larger application through be administered can Drugsskin. that diseases they because mucosal can selected in oral are ] ------11 [ Dexamethasone gargle and IV for POST for IV and gargle Dexamethasone ]. As reported by Hung Hung by ]. As reported ]. 3 [ 16 [ ]; that change may have resulted resulted have may change ]; that 11 [ ] reported that the incidence and se the that ] reported ] reported that the intravenous injec the intravenous that ] reported 2 15 [ ]. 6 [ ], the incidence of POST was highest at 6 h postop at ], the incidence of POST highest was 3 [ ]. The intubation to the posterior to pharynx, intubation ]. The larynx and Various interventions have been attempted to reduce the the reduce to been attempted interventions have Various POST is caused by endotracheal intubation, which re which intubation, endotracheal POST by is caused In the present study, among the patients who received received who the patients among study, the present In The incidence of POST was investigated at 1 h, 6 h, and and 6 h, 1 h, at incidence of POSTThe investigated was De et al. Oliveira 17 www.anesth-pain-med.org mation mation of com incidence of POST capable was none of them but [ manipula and the direct airway, of the cuff, the expansion and inflam tion of the laryngoscope the stimulation cause sults in a mucosal injury or vocal cord injury injuryin the trachea cord in a mucosal sults vocal or the study by Lee by et al. the study and an pressure cuff tube in the endotracheal in a change location in the tube abnormality and 4% at 24 h after the surgery. The difference between between the surgery. 24 h after and 4% at difference The in the pa of the change be the result may the two studies surgery spine in lumbar the for required position tient`s intravenously injected with dexamethasone 0.1 mg/kg, the injected with 0.1 mg/kg, dexamethasone intravenously was pain of those of throat who complained proportion the surgery, 1 h after the surgery,40% at 6 h after 17% at the surgery, the surgery. 24 h after and 6% at Lee et al. who were in their study the patients among that reported dexamethasone 0.1 mg/kg intravenous injection,pro the intravenous 0.1 mg/kg dexamethasone during portion throat of those of sore complained who the surgery, 1 h after 6 h after 12% at was 25% at swallowing et al. erative. one hour after the surgery may be decreased by the analge by be the surgery decreased after one hour may anesthesia usedsic for the general no better effect on incidence of POST. effectno better of POST. on incidence within of pain the complaint because 24 h postoperatively gling with 0.05% dexamethasone solution and intravenous with solutiongling 0.05% dexamethasone and intravenous the not increase did dexamethasone injection of 0.1 mg/kg in in the blood, of dexamethasone resulting concentration gling with dexamethasone did not increase the effect, be the effect, withgling not increase did dexamethasone drug the plasma concen not increased have it may cause of gar the combination we that suspect Therefore, tration. centration was increased as the dose of dexamethasone as the dose of dexamethasone increased was centration Gar injection increased. was intravenous by administered ducing the incidence and severityducing of POST the intra than expla The injection 0.1 mg/kg. of dexamethasone venous drug con the plasma be that may for these findings nation dexamethasone 0.05 mg/kg was administered by the same same the by administered was mg/kg 0.05 dexamethasone et al. [ method. Park effective in re more was 0.2 mg/kg tion of dexamethasone verity of POST showed a decrease when dexamethasone dexamethasone when POST verityof decrease a showed when than intravenously administered was 0.1 mg/kg Anesth Pain Med Vol. 15 No. 4 used for patients in the departments of otolaryngology, administration method. This result may be due to a syner- dentistry, and hemato-oncology (burning mouth syn- gic effect caused by the anti-hyperalgesic effect of ketamine drome, oral lichen planus, intraoral ulcer) [26]. In the pres- and the anti-inflammatory effect of dexamethasone [28]. ent study, as in that reported by Lee et al. [7], dexametha- According to Cho et al. [29], the incidence of POST within sone 5 mg/ml was mixed with normal saline 9 ml to pre- 24 postoperative hours was lower in the group that re- pare a 0.05% solution, which was used for gargling for 30 s ceived dexamethasone 8 mg/kg intravenous injection in with the head sufficiently tilted backward. combination with lidocaine 1.5 mg/kg than in the group Dexamethasone gargle is considered to allow the drug to that received only dexamethasone 8 mg/kg intravenous in- function directly on the mucosa of the pharynx and larynx jection. In this case, a synergic effect might have been the where POST is caused. Gargling with dexamethasone has result of the suppression of the airway reflex, reduced advantages because it can be simply performed before a bronchial hyper-reactivity, and pain relief caused by lido- elective surgery and its effect is observed within several caine, and the anti-inflammatory effect of dexamethasone minutes [27]. According to Park et al. [26], patients who re- [29]. ceived dexamethasone gargle to treat oral manifestations Therefore, the use of drugs with different mechanisms of chronic graft versus host disease (cGVHD) had de- seems to be more effective than use of a single drug in the creased cGVHD severity and pain scores. prevention of POST. In the present study, the incidence of POST during swal- The present study has the following limitations. lowing in patients treated with the combination of 0.05% First, the plasma dexamethasone concentration was not dexamethasone solution gargle and intravenous injection measured in the cases of dexamethasone intravenous in- of dexamethasone 0.1 mg/kg was 13% at 1 h, 13% at 6 h, jection, dexamethasone gargle, and their combination. and 0% at 24 h postoperatively, indicating that the Even the use of a single dose of steroid has the risk of in- POST-preventing effect of the combination was not signifi- creasing postoperative infection, hemorrhage and inflam- cantly different from the use of either dexamethasone gar- mation [30]. Although such problems did not occur within gle or dexamethasone intravenous injection alone. This 24 postoperative hours in the present study, the possibility finding indicates that the topical application of dexameth- of systemic side effects thereafter was not predicted. Sec- asone gargle has an effect equivalent to that of dexametha- ond, the incidence and severity of POST were investigated sone intravenous injection, and suggests that the combina- in the present study by applying the dexamethasone ad- tion of the two administration methods does not provide a ministration methods only to patients undergoing laparo- superior outcome in the prevention of POST. scopic cholecystectomy, which requires a relatively short As mentioned at the beginning of the discussion, we surgical time. In comparison with laparotomy, the inci- think that the combined use of dexamethasone gargle and dence of POST may be higher in patients undergoing lapa- intravenous injection did not increase the concentration of roscopic surgery because the cuff pressure of the endotra- dexamethasone in the blood, resulting in no better effect cheal tube is higher owing to pneumoperitoneum and the on incidence of POST. Trendelenburg position. Since the duration of anesthesia In this experiment, using only dexamethasone did not for the laparoscopic cholecystectomy in the present study bring a better effect on incidence of POST, in contrast, the was about 50 min, further studies may need to be conduct- combination of dexamethasone with other drugs was ed to investigate the incidence and severity of POST in cas- found more effective in reducing POST than the use of a es in which the surgical duration is longer. Third, the dose single drug. Safavi et al. [28] reported that incidence of of dexamethasone for the intravenous injection was 0.1 POST at postoperative 0 h, 2 h, 4 h, 8 h and 24 h was lower mg/kg in the present study. The dose of the dexametha- in the group in which gargling with a 30 ml solution con- sone for the intravenous injection, tested with respect to taining 40 mg ketamine was used in combination with in- POST, was fixed or varied on the basis of the weight (0.1–0.2 travenous injection of dexamethasone 0.2 mg/kg than in mg/kg). Further studies may need to be conducted on the the other two groups in which only one of the two methods POST-preventing effect of dexamethasone depending on was used. The combination of intravenous injection of the dose [10,18]. Fourth, the evaluation of POST, hoarse- dexamethasone and ketamine gargle reduced the inci- ness and cough was performed in the present study based dence of POST in comparison with the single use of each on patient`s subjective responses obtained through inter-

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REFERENCES , Lee W, Ki S, Kim MH, Cho K, MH, Cho Kim of et al. Effects , Lee S, W, Ki xamethasone decreases the incidence of sore throat and throat incidence of sore the decreases xamethasone

Al-Qahtani AS, Messahel FM. Quality improvement in anes improvement FM. Quality Messahel AS, Al-Qahtani Teymourian H, Mohajerani SA, Farahbod A. Magnesium and A. and Magnesium SA, Farahbod H, Mohajerani Teymourian Hung NK, Wu CT, Chan SM, Lu CH, Huang YS, Yeh CC, et al. Yeh YS, CH, Huang Lu SM, Chan NK, CT, Wu Hung Lee SB Kim JH, Yang C, Jung SM, Bae YK, Park SJ. The effect of ketorolac and and effect of ketorolac The SJ. YK, Bae SM, Park C, Jung Yang Moon YE. Postoperative nausea and vomiting. Korean J Anes Korean and vomiting. nausea YE. Postoperative Moon phylactic effect of dexamethasone on postoperative sore throat throat sore effect on postoperative of dexamethasone phylactic 2016; 69: 255- J Anesthesiol position surgery.in prone Korean 61. of characteristics and clinical treatment gargle of steroid sults J Otolaryn Korean syndrome. mouth with burning patients and 2% lidocaine. Anesth Analg 2010; 111: 882-6. 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Analg Anesth tube. dobronchial thr sore on postoperative Effect 10% lidocaine, with cuff al tube benzydamine hydrochloride, Xu YJ, Wang SL, Y Ren Wang YJ, Xu Park SH, Han SH, Do SH, Kim JW, Rhee KY, Kim JH. Prophylac JH. Kim JW, Do SH, Kim Rhee SH, KY, Han SH, Park Lee Lee SH, Lee YC, SR, Choi JH, Lee SC, Lee pro et al. The JH, Zhao X, Cao X, Li Q. Dexamethasone for the prevention of post of Dexamethasoneprevention the for LiX, Q. ZhaoCao X, . 4 5. 6. 7. 8. in reducing of dexamethasone role The BT. Al-Ali HS, 9. Haider 1. 2. 3. 11. re Preliminary SO. Kang CH, Lee Kim J, MJ, YH, Cho 12. Choung 10. Yohan Park, https://orcid.org/0000-0002-2242-0968 https://orcid.org/0000-0002-2242-0968 Park, Yohan https://orcid.org/0000-0003-2013-0788 Kim, Kwanghee https://orcid.org/0000-0002-4616-0355 Lee, Jeonghan ------Dexamethasone gargle and IV for POST for IV and gargle Dexamethasone ORCID CONFLICTS OF INTEREST CONFLICTS AUTHOR CONTRIBUTIONS Conceptualization: Seunghee Ki, Jeonghan Lee. Data cu Data Lee. Jeonghan Seunghee Ki, Conceptualization: No potential conflict of interest relevant to this article this article to relevant conflict of interest potential No In conclusion, in the patients who had undergone lapa undergone had who the patients in conclusion, In www.anesth-pain-med.org Myoung-hun Kim, https://orcid.org/0000-0002-4350-0078 https://orcid.org/0000-0002-4350-0078 Kim, Myoung-hun https://orcid.org/0000-0001-7321-1376 Han, Yongjae https://orcid.org/0000-0001-7584-5436 Oh, Minkyung Soonho https://orcid.org/0000-0002-9368-6026 Cheong, https://orcid.org/0000-0001-8450-0595 Lim, Sehun https://orcid.org/0000-0002-9805-9582 Cho, Kwangrae Seunghee Ki, https://orcid.org/0000-0002-1792-3771 Seunghee Ki, https://orcid.org/0000-0003-0001-3306 Myoung, Inwook Myoung-hun Kim, Minkyung Oh. Supervision: Seunghee Oh. Ki, Minkyung Kim, Myoung-hun Soonho Cheong, Validation: Lim. Soonho Sehun Cheong, Oh. Minkyung Lim, Sehun Kim, Minkyung Oh, Yohan Park. Resources: Inwook Resources: Inwook Park. Yohan Oh, Minkyung Kim, Han, Yongjae Kim, Myoung-hun Cho, Kwangrae Myoung, Software: Kim. Kwanghee Park, Yohan Oh, Minkyung view & editing: Seunghee Ki, Soonho Cheong, Jeonghan Lee. Lee. Jeonghan Soonho Seunghee & editing: view Cheong, Ki, Myoung-hun Cho, Kwangrae Myoung, Inwook Investigation: Cho, Yohan Park, Kwanghee Kim. Visualization: Myoung- Visualization: Kim. Kwanghee Park, Yohan Cho, draft: Writing - original Han. Seunghee Ki, Yongjae Kim, hun Lee. Writing - re Jeonghan Han, Yongjae Myoung, Inwook Sehun Lim, Kwangrae Cho, Yongjae Han, Minkyung Oh, Yo Oh, Minkyung Han, Yongjae Cho, Kwangrae Lim, Sehun Yohan Lim, Sehun Seunghee Ki, Methodology: Park. han Soonho Kwangrae Cheong, administration: Project Park. ration: Inwook Myoung, Kwanghee Kim. Formal analysis: Formal Kim. Kwanghee Myoung, Inwook ration: was reported. reported. was methods alone. methods alone. sone solution gargle and 0.1 mg/kg dexamethasone intra dexamethasone mg/kg and 0.1 sone solution gargle injection and the use of the twovenous of each preventive the intravenous injection of 0.1 mg/kg dexamethasone. dexamethasone. injectionmg/kg of 0.1 the intravenous incidence and severity The not significantly of POST were dexametha 0.05% of between combination the different roscopic cholecystectomy, gargling with dexametha 0.05% cholecystectomy, gargling roscopic as effect POST-preventing same the sone showed solution view. Therefore, the individual patients might have ex have might the individual patients view. Therefore, on their ex depending differently symptoms their pressed state. periences and psychological Anesth Pain Med Vol. 15 No. 4

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