Pharmacological Interventions for Post-operative Sore Throat (POST): A Network Meta-analysis

Background: To study the efficacy of current post-extubation pharmacologic treatments for postoperative sore throat (POST) prevention. Method: We searched nine databases for randomized controlled trials (RCTs) assessing the efficacy of post-extubation treatments in POST prevention. A network meta-analysis was used to pool the results. Results: Of the 124 records screened, we included 13 studies with 1820 patients. Ketorolac tromethamine was found to be the most effective with the lowest POST rates (P-score = 0.99), followed by ketamine (P-score = 0.68), amyl-m-cresol (P-score = 0.67), flurbiprofen (P-score = 0.66), benzydamine hydrochloride (P-score = 0.62), magnesium (P-score = 0.33), dexamethasone (P-score = 0.30), and lidocaine (P-score = 0.07). Moreover, the following treatments were found to be significantly effective in reducing POST in comparison to control/placebo treatment: ketorolac tromethamine (OR = 0.11; [95% CI=0.05 – 0.21]) followed by ketamine (OR = 0.32; [95% CI = 0.17 – 0.62]), amyl-m-cresol (OR = 0.32; [95% CI = 0.14 – 0.73]), flurbiprofen (OR = 0.33;[95% CI = 0.13 – 0.81]), and benzydamine hydrochloride (OR = 0.36; [95% CI = 0.24 –0.54]). Conclusion: Ketorolac tromethamine, ketamine, amyl-m-cresol, flurbiprofen, and benzydamine hydrochloride were found to be significantly effective in reducing POST. Moreover, ketorolac tromethamine was the most effective and significantly better than all other treatments in reducing POST rates.

Sore throat, Prevention, Systematic review

[1] Cardinale JP, Gillespie N, Germond L. Complications of General Anesthesia. Catastrophic Perioperative Complications and Management: A Comprehensive Textbook. Cham: Springer International Publishing. 2019. p. 95-103.

[2] Ahmed A, Abbasi S, Ghafoor HB, et al. Postoperative sore throat after elective surgical procedures. Journal of Ayub Medical College Abbottabad. 2007;19:12-14.

[3] Chinachoti T, Pojai S, Sooksri N, et al. Risk Factors of Post-operative Sore Throat and Hoarseness. J Med Assoc Thai. 2017;100:463-468.

[4] McHardy F, Chung F. Postoperative sore throat: cause, prevention and treatment. Anaesthesia. 1999;54:444-453.

[5] Scuderi PE. Postoperative Sore Throat: More Answers Than Questions. Anesthesia & Analgesia. 2010;111:831-832.

[6] Lehmann M, Monte K, Barach P, et al. Postoperative patient complaints: a prospective interview study of 12,276 patients. J Clin Anesth. 2010;22:13-21.

[7] Shahani J, Meena S. A randomized controlled study of reduction in severity of postoperative sorethroat using preoperative ketamine nebulization. International Journal of Scientific Research. 2019;8:1-2.

[8] Borazan H, Kececioglu A, Okesli S, et al. Oral Magnesium Lozenge Reduces Postoperative Sore ThroatA Randomized, Prospective, Placebo-controlled Study. Anesthesiology. 2012;117:512-518.

[9] Chang J-E, Min S-W, Kim C-S, et al. 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;62:1097-1103.

[10] Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS medicine. 2009;6:e1000100.

[11] Sterne JAC, Savović J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898.

[12] Nikolakopoulou A, Higgins JPT, Papakonstantinou T, et al. CINeMA: An approach for assessing confidence in the results of a network meta-analysis. PLOS Medicine. 2020;17:e1003082.

[13] Chapter 11: Undertaking network meta-analyses. accessable on: /handbook/current/chapter-11. https://training.cochrane.org/handbook/current/chapter-11.

[14] R Core Team. R: A language and environment for statistical computing. Vienna, Austria. 2013.

[15] Hashan MR, Ghozy S, El-Qushayri AE, et al. Association of dengue disease severity and blood group: A systematic review and meta-analysis. Rev Med Virol. 2020;e2147.

[16] Salanti G, Del Giovane C, Chaimani A, et al. Evaluating the Quality of Evidence from a Network Meta-Analysis. PLOS ONE. 2014;9:e99682.

[17] Rücker G, Schwarzer G. Ranking treatments in frequentist network meta-analysis works without resampling methods. BMC medical research methodology. 2015;15:58-58.

[18] Egger M, Smith GD, Schneider M, et al. Bias in meta-analysis detected by a simple, graphical test. Bmj. 1997;315:629-634.

[19] Begg CB, Mazumdar M. Operating Characteristics of a Rank Correlation Test for Publication Bias. Biometrics. 1994;50:1088-1101.

[20] Thompson SG, Sharp SJ. Explaining heterogeneity in meta-analysis: a comparison of methods. Stat Med. 1999;18:2693-2708.

[21] Aigbedia S, Tobi K, Amadasun F. A comparative study of ketamine gargle and lidocaine jelly application for the prevention of postoperative throat pain following general anaesthesia with endotracheal intubation. Nigerian journal of clinical practice. 2017;20:677-685.

[22] Ebneshahidi A, Mohseni M. Strepsils® tablets reduce sore throat and hoarseness after tracheal intubation. Anesthesia & Analgesia. 2010;111:892-894.

[23] Huang Y-S, Hung N-K, Lee M-S, et al. The effectiveness of benzydamine hydrochloride spraying on the endotracheal tube cuff or oral mucosa for postoperative sore throat. Anesthesia & Analgesia. 2010;111:887-891.

[24] Mekhemar NA, El-agwany AS, Radi WK, et al. Estudo comparativo

entre cloridrato de benzidamina em gel, lidocaína a 5% em gel e lidocaína a 10% em spray no balonete do tubo endotraqueal em relação à dor de garganta pós-operatória. Revista Brasileira de Anestesiologia.2016;66:242-248.

[25] Muderris T, Tezcan G, Sancak M, et al. Oral flurbiprofen spray for post-operative sore throat and hoarseness: a prospective, randomized, double-blind, placebo-controlled study. Minerva anestesiologica. 2019;85:21-27.

[26] Park JH, Shim J-K, Song J-W, et al. A randomized, double-blind, non-inferiority trial of magnesium sulphate versus dexamethasone for prevention of postoperative sore throat after lumbar spinal surgery in the prone position. International journal of medical sciences. 2015;12:797.

[27] Thomas D, Bejoy R, Zabrin N, et al. Preoperative ketamine nebulization attenuates the incidence and severity of postoperative sore throat: A randomized controlled clinical trial. Saudi journal of anaesthesia. 2018;12:440.

[28] Mostafa RH, Saleh AN, Hussein MM. A Comparative Study of Three Nebulized Medications for the Prevention of Postoperative Sore Throat in the Pediatric Population. The Open Anesthesia Journal. 2018;12:85-93.

[29] Yang H, Liu F, Tsai S, et al. Ketorolac tromethamine spray prevents postendotracheal-intubation-induced sore throat after general anesthesia. Biomed Res Int. 2016;2016:4582439.

[30] Kim D, Jeong H, Kwon J, et al. The effect of benzydamine hydrochloride on preventing postoperative sore throat after total thyroidectomy: a randomized-controlled trial. Canadian Journal of Anesthesia/Journal canadien d’anesthésie. 2019;66:934-942.

[31] Puyo CA, Tricomi SM, Dahms TE. Early biochemical markers of in-flammation in a swine model of endotracheal intubation. Anesthesiology. 2008;109:88-94.

[32] McCarthy DT. Postoperative sore throat: a multifactorial problem. Br J Anaesth. 2012;108:1037-1038.

[33] Puyo CA, Earhart A, Staten N, et al. Endotracheal intubation results in acute tracheal damage induced by mtDNA/TLR9/NF-κB activity. Journal of Leukocyte Biology. 2019;105:577-587.

[34] Miller RD, Eriksson LI, Fleisher LA, et al. Anesthesia E-Book; Elsevier Health Sciences. 2009.

[35] Rooks WH, 2nd, Maloney PJ, Shott LD, et al. The analgesic and anti-inflammatory profile of ketorolac and its tromethamine salt. Drugs Exp Clin Res. 1985;11:479-492.

[36] Yang C, Jung SM, Bae YK, et al. The effect of ketorolac and dexamethasone on the incidence of sore throat in women after thyroidec-tomy: a prospective double-blinded randomized trial. Korean journal of anesthesiology. 2017;70:64-71.

[37] Ostrov CS, Sirkin SR, Deutsch WE, et al. Ketorolac, prednisolone, and dexamethasone for postoperative inflammation. Clin Ther. 1997;19:259-272.

[38] Paiva-Oliveira JG, Bastos PR, Cury Pontes ER, et al. Comparison of the anti-inflammatory effect of dexamethasone and ketorolac in the extractions of third molars. Oral Maxillofac Surg. 2016;20:123-133.

[39] Solomon KD, Cheetham JK, DeGryse R, et al. Topical ketorolac tromethamine 0.5% ophthalmic solution in ocular inflammation after cataract surgery. Ophthalmology. 2001;108:331-337.

[40] Yang HL, Liu FC, Tsai SC, et al. Ketorolac Tromethamine Spray Prevents Postendotracheal-Intubation-Induced Sore Throat after General Anesthe-sia. BioMed research international. 2016;2016:4582439-4582439.

[41] Yang HL, Liu FC, Tsai SC, et al. Ketorolac Tromethamine Spray Prevents Postendotracheal-Intubation-Induced Sore Throat after General Anesthesia. Biomed Res Int. 2016;2016: 4582439.

[42] Barkin RL. Topical Nonsteroidal Anti-Inflammatory Drugs: The Importance of Drug, Delivery, and Therapeutic Outcome. Am J Ther. 2015;22:388-407.

[43] Singla N, Singla S, Minkowitz HS, et al. Intranasal ketorolac for acute postoperative pain. Curr Med Res Opin. 2010;26:1915-1923.

[44] McCormack PL. Ketorolac 0.45% ophthalmic solution. Drugs Aging. 2011;28:583-589.