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Original Research

Open Access

Premedication with midazolam is equally effective via the sublingual and intravenous route of administration


1,Department of Anesthesiology Resuscitation and Intensive care unit University Hospital Osijek

2Department of Anesthesiology, Resuscitation and Intensive care unit Clinical Hospital Centre Osijek Medical Faculty, University Josip Juraj Stross-mayer Osijek

3,Institute of Public Health for Osijek-Baranya

DOI: 10.22514/SV92.112014.5 Vol.9,Issue 2,November 2014 pp.32-36

Published: 03 November 2014

*Corresponding Author(s): TOMISLAV RUŽMAN E-mail:


Background. The aim of this study was to investigate the clinical efficacy and potential side effects of sublingual midazolam, used for premedication, in comparison with intravenous midazolam. The second aim was to explore cost-effectiveness of sublingual midazolam administration.

Methods. A prospective, randomized, controlled, single-blinded trial was conducted at the Clinical Hospital Centre Osijek, Croatia, during the period 1st of May till 31st of October, 2012. We enrolled 140 patients (American Society of Anesthesio-logists (ASA) physical status I-II, age≥18 years) scheduled for some kind of elective surgical procedure. Exclusion criteria were ASA III or higher, psychiatric disorders, allergy to midazolam and use of psychotropic drugs. Patients were randomi-zed into one of two groups. One group received 2.5 mg of midazolam intravenously and the other group received 1/4 of a midazolam tablet (approximately 3.75 mg) sublingually. Sedation was clinically evaluated using the Ramsey sedation scale at 0, 10, 20 and 30 minutes after drug administration. We also noted side effects and degree of amnesia.

Results. Ten minutes after administration of premedication, a significantly higher number of patients in the intravenous group had a Ramsey score of 2 (p=0.000). Ten and twenty minutes after drug administration, most of the patients in the sublingual group had a Ramsey score 1-2, and after 30 minutes most of them had a Ramsey score 2-3, which is comparable with the intravenous (p=0.642) group. 

Conclusion. Sublingual application of midazolam has an equivalent sedative effect as intravenous midazolam 20 minutes after administration but is associated with a bitter taste and weaker amnestic effect.


premedication, midazo-lam, sublingual, intravenous

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TOMISLAV RUŽMAN,MARINA KREŠIĆ,DUBRAVKA IVIĆ,DANIJELA GULAM,NATAŠA RUŽMAN,JELENA BURAZIN. Premedication with midazolam is equally effective via the sublingual and intravenous route of administration. Signa Vitae. 2014. 9(2);32-36.


9. Kumar N, Sharma R, Sharma M, Verma I, Sharma M. Midazolam Pre-medication in Paediatrics: Comparison of the Intranasal and Sublin-gual Routes by Using an Atomizer Spray. JCDR 2012;6:65-8.

10. Bergendahl H, Lonnqvist PA, Eksborg S. Clonidine in paediatric anaesthesia: A review of the literature and comparison with benzodiaze-pines for premedication. Acta Anaesthesiol Scand 2000;50:135-43.

11. Ghai B, Grandhe RP, Kumar A, Chari P. Comparative evaluation of midazolam and ketamine with midazolam alone as oral premedication. Paediatr Anaesth 2005;15:554-9.

12. Schmidt AP, Valinetti EA, Banderira D, Bertacchi MF, Simoes CM, Auler JR. Effects of preanesthetic administration of midazolam, clonidine, or dexmedetomidine on postoperative pain and anxiety in children. Paediatr Anaesth 2007;17:667-74.

13. Dundee JW, Wilson DB. Amnesic action of midazolam. Anaesthesia 1980;35:459-61.

14. Marshall J, Rodarte A, Blumer J, Khoo KC, Akbari B, Kearns G. Pediatric pharmacodynamics of midazolam oral syrup. Pediatric Pharma-cology Research Unit Network. J Clin Pharmacol 2000;40:578-89.

15. Karl HW, Rosenberger JL, Larach MG, Ruffle JM. Transmucosal administration of midazolam for premedication of pediatric patients. Comparison of the nasal and sublingual routes. Anaesthesiology 1993;78:885-91.

16. Lim TW, Thomas E, Choo SM. Premedication with midazolam is more effective by the sublingual than oral route. CJA July 1997;44:723-6.

17. Kogan A, Katz J, Efrat R, Eidelman LA. Premedication with midazolam in young children: A comparison of four routes of administration. Paediatr Anaesth 2002;12:685-92.

18. Wilton NC, Leigh J, Rosen DR, Pandit UA. Preanaesthetic sedation of pre schoolchildren using intranasal midazolam. Anesthesiology 1988;69:972-5.

19. Coté CJ, Cohen IT, Suresh S, Rabb M, Rose JB, Weldon BC et al. A comparison of three doses of commercially prepared oral midazolam syrup in children. Anaesth Analg 2002;94:37-43.

20. Naqash I, Waqar-ul N, Zargar J. Midazolam premedication in children: Comparision of nasal and sublingual routes. Anaesth Clin Pharmacol 2004;20:141-5.

21. Saint-Maurice C, Meistleman C, Rey E. Pharmacokinetics of rectal midazolam for Pre-medication. Anesthesiology 1986;65:536-8.

22. Fujii J, Intosume N, Nakano M. Relative bioavailabiliy of midazolam following sublingual versus oral administration in healthy volunteers. J Pharmacobio Dyn 1988;11:206-9.

23. Gupta S, Gadani H, Kedia S. Is premedication with midazolam more effective by the sublingual than the oral route? Anesth Essays Res 2011;5:43-7.

24. Odou P, Barthélémy C, Chatelier D, Luyckx M, Brunet C, Dine T et al. Pharmacokinetics of midazolam: comparison of sublingual and intravenous routes in rabbit: Eur J Drug Metab Pharmacokinet 1999;24:1-7.

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