Safety and sedative effect of intranasal dexmedetomidine in mandibular third molar surgery: a systematic review and meta-analysis

Shaopeng Liu, Ye Wang, Yong Zhu, Tingting Yu, Huaqiang Zhao, Shaopeng Liu, Ye Wang, Yong Zhu, Tingting Yu, Huaqiang Zhao

Abstract

Objective: The focus of this meta-analysis was to assess the sedative effect and safety of intranasal dexmedetomidine (Dex) in mandibular third molar surgery.

Methods: The PubMed/Medline, Web of Science, Cochrane Library, and China National Knowledge Infrastructure databases were searched for studies published until May 1, 2018. Eligible studies were restricted to randomized controlled trials (RCTs) and controlled clinical trials. The evaluation indicators mainly included the bispectral index, observer assessment of alertness/sedation scale, systolic blood pressure, and heart rate. Data for each period in the Dex and control groups were pooled to evaluate its sedative effect and safety.

Results: Five RCTs met the inclusion criteria. This study included 363 patients: 158 patients received intranasal inhalation of Dex before surgery, and 158 patients were negative controls. The pooled results showed a good sedative effect during tooth extraction when intranasal inhalation of Dex was performed 30 minutes before third molar extraction (assessment of alertness/sedation, Dex vs control SMD -1.20, 95% CI -1.73 to -0.67, I 2=0, P=0.95; bispectral index, Dex vs control SMD -11.68, 95% CI -19.49 to -3.87, I 2=89%; P=0.0001), and parameters returned to normal within 90 minutes after inhalation. During the operation, blood pressure and heart rate decreased to some extent, but the decreases did not exceed 20% of the baseline, and all patients returned to normal conditions within 90 minutes after inhalation.

Conclusion: Intranasal inhalation of Dex 30 minutes before third molar extraction can provide a good sedative effect, and large-sample multicenter RCTs are needed to evaluate the analgesic effect of Dex.

Keywords: intranasal dexmedetomidine; mandibular third molar; meta-analysis; sedation.

Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Study selection process. Abbreviation: CNKI, China National Knowledge Infrastructure.
Figure 2
Figure 2
Quality assessment of included studies.

References

    1. Breik O, Grubor D. The incidence of mandibular third molar impactions in different skeletal face types. Aust Dent J. 2008;53(4):320–324. doi: 10.1111/j.1834-7819.2008.00073.x.
    1. Slade GD, Foy SP, Shugars DA, Phillips C, White RP. The impact of third molar symptoms, pain, and swelling on oral health-related quality of life. J Oral Maxillofac Surg. 2004;62(9):1118–1124.
    1. Carter K, Worthington S. Predictors of third molar impaction: a systematic review and meta-analysis. J Dent Res. 2016;95(3):267–276. doi: 10.1177/0022034515615857.
    1. Tanidir AN, Atac MS, Karacelebi E. Information given by multimedia: influence on anxiety about extraction of impacted wisdom teeth. Br J Oral Maxillofac Surg. 2016;54(6):652–657. doi: 10.1016/j.bjoms.2016.03.026.
    1. Lenk M, Berth H, Joraschky P, Petrowski K, Weidner K, Hannig C. Fear of dental treatment – an underrecognized symptom in people with impaired mental health. Dtsch Arztebl Int. 2013;110(31–32):517–522. doi: 10.3238/arztebl.2013.0517.
    1. Astramskaitė I, Poškevičius L, Juodžbalys G. Factors determining tooth extraction anxiety and fear in adult dental patients: a systematic review. Int J Oral Max Surg. 2016;45(12):1630–1643. doi: 10.1016/j.ijom.2016.06.019.
    1. Brignardello-Petersen R. Previous bad experience, propensity to anxiety, and pain expectations may be associated with fear and anxiety when undergoing tooth extractions. J Am Dent Assoc. 2017;148(4):e4. doi: 10.1016/j.adaj.2016.11.015.
    1. Gerlach AT, Dasta JF. Dexmedetomidine: an updated review. Ann Pharmacother. 2007;41(2):245–252.
    1. Hoy SM, Keating GM. Dexmedetomidine: a review of its use for sedation in mechanically ventilated patients in an intensive care setting and for procedural sedation. Drugs. 2011;71(11):1481–1501. doi: 10.2165/11207190-000000000-00000.
    1. Davoudi A, Movahedian AB, Shadmehr E. Risks and benefits of pre-operative dexmedetomidine in oral and maxillofacial surgeries: a systematic review. Expert Opin Drug Saf. 2017;16(6):711–720. doi: 10.1080/14740338.2017.1323865.
    1. Chandanwale A, Langade D, Sonawane D, Gavai P. A randomized, clinical trial to evaluate efficacy and tolerability of trypsin: chymotrypsinas compared to serratiopeptidase and trypsin: bromelain:rutosidein wound management. Adv Ther. 2017;34(1):180–198. doi: 10.1007/s12325-016-0444-0.
    1. Bhagat S, Agarwal M, Roy V. Serratiopeptidase: a systematic review of the existing evidence. Int J Surg. 2013;11(3):209–217. doi: 10.1016/j.ijsu.2013.01.010.
    1. Rana M, Gellrich NC, Joos U, Piffkó J, Kater W. 3D evaluation of postoperative swelling using two different cooling methods following orthognathic surgery: a randomised observer blind prospective pilot study. Int J Oral Maxillofac Surg. 2011;40(7):690–696. doi: 10.1016/j.ijom.2011.02.015.
    1. Tachibana M, Mizukoshi O, Harada Y, Kawamoto K, Nakai Y. A multi-centre, double-blind study of serrapeptase versus placebo in post-antrotomy buccal swelling. Pharmatherapeutica. 1984;3(8):526–530.
    1. Cheung CW, Ng KF, Choi WS, Chiu WK, Ying CL, Irwin MG. Evaluation of the analgesic efficacy of local dexmedetomidine application. Clin J Pain. 2011;27(5):377–382. doi: 10.1097/AJP.0b013e318208c8c5.
    1. Jun JH, Kim KN, Kim JY, Song SM. The effects of intranasal dexmedetomidine premedication in children: a systematic review and meta-analysis. Can J Anaesth. 2017;64(9):947–961. doi: 10.1007/s12630-017-0917-x.
    1. Yuen VM, Hui TW, Irwin MG, Yuen MK. A comparison of intranasal dexmedetomidine and oral midazolam for premedication in pediatric anesthesia: a double-blinded randomized controlled trial. Anesth Analg. 2008;106(6):1715–1721. doi: 10.1213/ane.0b013e31816c8929.
    1. Higgins JP, Altman DG, Gøtzsche PC, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928. doi: 10.1136/bmj.d5928.
    1. Higgins JP, Green S. Cochrane handbook for systematic reviews of interventions 9.2.3 [updated March 2011] Cochrane Library. 2011
    1. Koletsi D, Fleming PS, Michelaki I, Pandis N. Heterogeneity in Cochrane and non-Cochrane meta-analyses in orthodontics. J Dent. 2018;74(undefined):90–94. doi: 10.1016/j.jdent.2018.05.003.
    1. van den Ende CH, Cornelia HM, Esther MJ, Steultjens EM, Lex M. Clinical heterogeneity was a common problem in Cochrane reviews of physiotherapy and occupational therapy. J Clin Epidemiol. 2006;59(9):914–919. doi: 10.1016/j.jclinepi.2005.12.014.
    1. Langan D, Higgins JP, Gregory W, Sutton AJ. Graphical augmentations to the funnel plot assess the impact of additional evidence on a meta-analysis. J Clin Epidemiol. 2012;65(5):511–519. doi: 10.1016/j.jclinepi.2011.10.009.
    1. Shetty SK, Aggarwal G. Efficacy of intranasal dexmedetomidine for conscious sedation in patients undergoing surgical removal of impacted third molar: a double-blind split mouth study. J Maxillofac Oral Surg. 2016;15(4):512–516. doi: 10.1007/s12663-016-0889-3.
    1. Ryu DS, Lee DW, Choi SC, Oh IH. Sedation protocol using dexmedetomidine for third molar extraction. J Oral Maxillofac Surg. 2016;74(5):921–926. doi: 10.1016/j.joms.2015.12.021.
    1. Nooh N, Sheta SA, Abdullah WA, Abdelhalim AA. Intranasal atomized dexmedetomidine for sedation during third molar extraction. Int J Oral Maxillofac Surg. 2013;42(7):857–862.
    1. Cheung CW, Ng KF, Liu J, Yuen MY, Ho MH, Irwin MG. Analgesic and sedative effects of intranasal dexmedetomidine in third molar surgery under local anaesthesia. Brit J Anaesth. 2011;107(3):430–437.
    1. Gu CM, Zhong YP, Huang LZ, Shi YH. Sedative and analgesic effects of intranasal dexmedetomidine in mandibular third molar extraction. J Oral Maxillofac Surg. 2014;24(3):220.
    1. March PA, Muir WW. Bispectral analysis of the electroencephalogram: a review of its development and use in anesthesia. Vet Anaesth Analg. 2005;32(5):241–255. doi: 10.1111/j.1467-2995.2005.00221.x.
    1. Li S, Yang Y, Yu C, et al. Dexmedetomidine analgesia effects in patients undergoing dental implant surgery and its impact on postoperative inflammatory and oxidative stress. Oxid Med Cell Longev. 2015:1–11. doi: 10.1155/2015/186736.
    1. Cheung CW, Ng KF, Choi WS, Chiu WK, Ying CL, Irwin MG. Evaluation of the analgesic efficacy of local dexmedetomidine application. Clin J Pain. 2011;5:377–382. doi: 10.1097/AJP.0b013e318208c8c5.
    1. Keating GM. Dexmedetomidine: a review of its use for sedation in the intensive care setting. Drugs. 2015;75(10):1119–1130. doi: 10.1007/s40265-015-0419-5.
    1. Sichrovsky TC, Mittal S, Steinberg JS. Dexmedetomidine sedation leading to refractory cardiogenic shock. Anesth Analg. 2008;106(6):1784–1786. doi: 10.1213/ane.0b013e318172fafc.
    1. Tobias JD, Gupta P, Naguib A, Yates AR. Dexmedetomidine: applications for the pediatric patient with congenital heart disease. Pediatr Cardiol. 2011;32(8):1075–1087. doi: 10.1007/s00246-011-0092-8.
    1. Weerink MA, Struys MM, Hannivoort LN, Barends CR, Absalom AR, Colin P. Clinical pharmacokinetics and pharmacodynamics of dexmedetomidine. Clin Pharmacokinet. 2017;56(8):893–913. doi: 10.1007/s40262-017-0507-7.
    1. Ouchi K, Sugiyama K. Dexmedetomidine dose dependently enhances the local anesthetic action of lidocaine in inferior alveolar nerve block: a randomized double-blind study. Reg Anesth Pain Med. 2016;41(3):348–355. doi: 10.1097/AAP.0000000000000380.
    1. Singh V, Thepra M, Kirti S, Kumar P, Priya K. Dexmedetomidine as an additive to local anesthesia: a step to development in dentistry. J Oral Maxillofac Surg. 2018;76(10):2091. doi: 10.1016/j.joms.2018.05.037.
    1. Cheung CW, Ying CL, Chiu WK, Wong GT, Ng KF. A comparison of dexmedetomidine and midazolam for sedation in third molar surgery. Anaesthesia. 2007;62(11):1132–1138. doi: 10.1111/j.1365-2044.2007.05230.x.
    1. Fawzy K, Eldeen AE, Said-Ahmed HA. A comparative study of dexmedetomidine and midazolam for third molar extraction under conscious sedation using bispectral index system. Acta Anaesthesiol Ital. 2007;58(2):164.
    1. Krauland AH, Leitner VM, Grabovac V, Bernkop-Schnürch A. In vivo evaluation of a nasal insulin delivery system based on thiolated chitosan. J Pharm Sci. 2006;95(11):2463–2472. doi: 10.1002/jps.20700.
    1. Sintov AC, Levy HV, Botner S. Systemic delivery of insulin via the nasal route using a new microemulsion system: in vitro and in vivo studies. J Control Release. 2010;148(2):168–176. doi: 10.1016/j.jconrel.2010.08.004.
    1. Deshmukh PV, Kulkarni SS, Parchandekar MK, Sikchi SP. Comparison of preanesthetic sedation in pediatric patients with oral and intranasal midazolam. J Anaesthesiol Clin Pharmacol. 2016;32(3):353–358. doi: 10.4103/0970-9185.168205.
    1. Knoester PD, Jonker DM, van der Hoeven RT, et al. Pharmacokinetics and pharmacodynamics of midazolam administered as a concentrated intranasal spray. A study in healthy volunteers. Brit J Clin Pharmacol. 2002;53(5):501–507. doi: 10.1046/j.1365-2125.2002.01588.x.
    1. Dale O, Nilsen T, Loftsson T, et al. Intranasal midazolam: a comparison of two delivery devices in human volunteers. J Pharm Pharmacol. 2006;58(10):1311–1318. doi: 10.1211/jpp.58.10.0003.
    1. Li A, Yuen VM, Goulay-Dufaÿ S, et al. Pharmacokinetic and pharmacodynamic study of intranasal and intravenous dexmedetomidine. Br J Anaesth. 2018;120(5):960–968. doi: 10.1016/j.bja.2017.11.100.

Source: PubMed

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