Title: Comparison of Intranasal Dexmedetomidine and Oral Midazolam for Premedication in Pediatric Anaesthesia - A Randomized Controlled Trial
Authors: Jamuna Rani J, Sheeila Rani Imanual, Unnikrishnan G
DOI: https://dx.doi.org/10.18535/jmscr/v5i2.119
Abstract
Introduction: Minimizing distress for children in the operating room (OR) environment and to facilitate a smooth induction of anaesthesia is one of the challenges for pediatric anesthesiologists. Midazolam is the most commonly used drug. Dexmedetomidine (22) is a newer α2-agonist with a more selective action on the α 2-adrenoceptor and a shorter half-life. Its bioavailability is 81.8% (72.6-92.1%) when administered via the buccal mucosa. Our aim of the study was primarily to compare the efficacy of intranasal dexmedetomidine and oral midazolam for preoperative anxiolysis and sedation in children before induction of anaesthesia and Secondary objective was to compare the hemodynamic changes-Systolic blood pressure and heart rate changes, wake-up behavior, time until ready for discharge from the PACU between the two groups.
Materials and Methods: Study was conducted at the Department of Pediatric Surgery and Department of Anesthesiology, SAT hospital Thiruvananthapuram during the period 2014 - 2015.Inclusion criteria : ASAI & 11, Children in the age group 4-12years, Duration of surgery < 2hrs, Elective surgery were included. Exclusion Criteria: Allergy or hypersensitive reaction to dexmedetomidine or midazolam, ASA III & IV, Age < 4years, Full stomach, Duration of surgery > 2hrs, Emergency surgery were excluded. Patients were divided into those receiving intranasal dexmedetomidine and those receiving oral midazolam. Children are randomly allocated to one of the two groups.
Observation and Results: Children premedicated with 1 µg /kg of intranasal dexmedetomidine attained more significant and satisfactory sedation at parental separation and at induction of anaesthesia than those patients who received oral midazolam.
Conclusion: In this study, we have shown that 1 ng/kg intranasal dexmedetomidine is another technique for producing sedation in children and it causes no discomfort during administration. Intranasal drug administration is relatively quick, simple, and may have benefits over transmucosal routes or rectal administration, which requires more patient cooperation.
References
1. 1. Kain ZN, Caldwell-Andrews AA, Krivutza DM, Weinberg ME, Wang S-M, Gaal D. Trends in the practice of parental presence during induction of anaesthesia and the use of preoperative sedative premedication in the United States, 1995-2002: results of a follow-up I national survey. Anesth Analg 2004;98:1252-9.
2. Kain ZN, Mayes L, Bell C, Weisman S, Hofstadter M, Rimar S. Premedication in the United States: a status report. Anesth Analg 1997;84:427-32.
3. Kain ZN, Mayes LC, Wang SM, Caramico LA, Hofstadter MB. Parental presence during induction of anaesthesia versus sedative premedication: which intervention is more effective? Anesthesiology 1998;89:1147-56.
4. Kain ZN, Hofstadter MB, Mayes LC, Krivutza DM, Alexander G, Waqjg SM, Reznick JS. Midazolam: effects on amnesia and anxiety in children. Anesthesiology 2000;93:676-84.
5. Cote CJ, Cohen IT, Suresh S, Rabb M, Rose JB, Weldon C, Davis PJ, Bikhazi GB, Karl HW, Hummer KA, Hannallah RS, Khoo KC, Collins P. A comparison of three doses of commercially prepared oral midazolam syrup in children. Anesth Analg 2002;94:37-43
6. Kogan A, Katz J, E-frat R, Eidelman LA. Premedication with midazolam in young children: a comparison of four routes of administration. Paediatr Anaesth 2002;12:685-9.
7. Splinter WM, MacNeill HB, Menard EA, Rhine EJ, Roberts DJ, Gould MH. Midaz-olam reduces vomiting after tonsillectomy in children. Can J Anaesth 1995;42:201-3.
8. Buffett-Jerrott SE, Stewart SH, Finley GA, Loughlan HL. Effects of benzodiazepines on explicit memory in a pediatric surgery setting. Psychopharmacology (Berl) 2003;168:377-86.
9. Marshall J, Rodarte A, Blumer J, Khoo KC, Akbari B, Kearns G. Pediatric pharmacodynamics of midazolam oral syrup. Pediatric Pharmacology Research Unit Network. J Clin Pharmacol 2000;40: 578-89.
10. Cox RG, Nemish U, Ewen A, Crowe M-J. Evidence-based clinical update: does premedication with oral midazolam lead to improved behavioral outcomes in children? Can J Anaesth 2006;53:1213-19.
11. Khalil S, Vije H, Kee S. A pediatric trial comparing midazolam/syrpalta mixture with premixed midazolam syrup (Roche). Paediatr Anaesth 2003;13:205-9
12. Lonnqvist PA, Habre W. Midazolam as premedication: is the emperor naked or just half-dressed? Paediatr Anaesth 2005;15: 263-5
13. Kanegaye JT, Favela JL, Acosta M, Bank DE. High-dose rectal midazolam for pediatric procedures: a randomized trial of sedative efficacy and agitation. Pediatr Emerg Care 2003;19:329-36.
14. McGraw T, Kendrick A. Oral midazolam premedication and I postoperative behavior in children. Paediatr Anaesth 1998;8:117—21.
15. Watson AT, Visram A. Children’s preoperative anxiety and postoperative behavior. Paediatr Anaesth 2003;13:188-204 16.
16. Bergendahl H, Lonnqvist P-A, Eksborg S. Clonidine in pediatric anaesthesia: a review of the literature and comparison with benzodiazepines for premedication. Acta Anaesthesiol Scand 2006;50:135-43
17. Schhiidt AP, Valinetti EA, Banderira D, Bertacchi MF, Simoes CM, JOSjE OTAVIO C Auler, JR. Effects of preane-sthetic administration of midazolam, clonidine, or dexmedetomidine on postoperative pain and anxiety in children. Paediatr Anaesth 2007; 17:667-74.
18. Mikawa K, Maekawa N, Nishina K, Takao Y, Yaku H, Obara H. Efficacy of oral clonidine premedication in children. Anesthesiology 1993;79:926-31
19. Ramesh VJ, Bhardwaj N, Batra YK. Comparative study of oral clonidine and diazepam as premedicants in children. Int J Clin Pharmacol Ther 1997;35:218-21.
20. Tazeroualti N, De Groote F, De Hert S, De Ville A, Dierick A, Van der Linden P. Oral clonidine vs midazolam in the prevention of sevoflurane-induced agitation in chil-dren. A prospective, randomized, contro-lled trial. Br J Anaesth 2007;98:667-71
21. Anttila M, Penttila J, Helminen A, Vuorilehto L, Scheinin H. Bioavailability of dexmedetomidine after extravascular doses in healthy subjects. Br J Clin Pharmacol 2003;56:691-3.
22. Yuen VM, Hui TW, Yuen MK, Irwin MG. A double blind crossover assessment of the sedative and analgesic effects of intranasal dexmedetomidine. Anesth Analg 2007;105:374-80
23. Weber F, Wulf H, el Saeidi G. Premedication with nasal s-ketamine and midazolam provides good conditions for induction of anaesthesia in p|eschool children. Can J Anaesth 2003;50:470-5
24. Alinkin JL, Fazi LM, Cuy RM, Chiavacci RM, Kurth CD, Shah UK, Jacobs IN, Watcha MF. Use of intranasal fentanyl in children undergoing myringotomy and tube placement during halothane and sevoflurane anaesthesia. Anesthesiology 2000;93: 1378-83
25. Almenrader N, Passariello M, Coccetti B, Haiberger R, Pietropaoli P. Steal-induction after clonidine premedication: a comparison of the oral and nasal route. Paediatr Anaesth 2007;17:230-4.
26. Khan ZP, Ferguson CN, Jones RM. alpha-2 and imidazoline receptor agonists. Their pharmacology and therapeutic role. Anaesthesia 1999;54:146-65.
27. 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
28. Darlong V, Shende D, Subramanyam MS, Sunder R, Naik A. Oral ketamine or midazolam or low dose combination for premedication in children. Anaesth Intensive Care 2004;32:246-9.
29. Horiuchi T, Kawaguchi M, Kurehara K, Kawaraguchi Y, Sasaoka N, Furuya H. Evaluation of relatively low dose of oral transmucosal ketalnine premedication in children: a comparison with oral mi-d|zolam. Paediatr Anaesth 2005;15:643-7.
30. McMillan CO, Spahr-Schopfer IA, Sikich N, Hartley E, Lerman J. Premedication of children with oral midazolam. Can J Anaesth 1992;39:545-50.
31. Feld LH, Negus JB, White PF. Oral midazolam preanesthetic medication in pediatric outpatients. Anesthesiology 1990;73:831-4. Samarkandi A, Naguib M, Riad W, Thalaj A, Alotibi W, Aldammas F, Albassam A. Melatonin vs. midazolam premedication in children: a double-blind, placebo-controlled study. Eur J Anaesthesiol 2005;22:189-96.
32. Kain ZN, Mayes LC, Cicchetti DV, Bagnall AL, Finley JD, Hofstadter MB. The Yale Preoperative Anxiety Scale: how does it compare with a “gold standard”? Anesth Analg 1997;85:783-8.
33. Bloor B, Ward D, Belleville J, Maze M. Effects of intravenous dexmedetomidine in humans. II. Hemodynamic changes. Anesthesiology 1992;77:1134-42.
34. Petroz GC, Sikich N, James M, van Dyk H, Shafer SL, Schily M, Lerman J. A phase I, two-center study of the pharmacokinetics and of dexmedetomidine in children. Anesthesiology
35. Munro HM, Tirotta CF, Felix DE, Lagueruela RG, Madril DR, Zahn EM, Nykanen DG. Initial experience with dexmedetomidine for diagnostic and interventional cardiac catheterization in children. Paediatr Anaesth 2007; 17:109-12.
36. Finley GA, Stewart SH, Buffett-Jerrott S, Wright KD, Millington D. High levels of impulsivity may contraindicate midazolam premedication in children. Can J Anaesth 2006;53:73-8
37. Peeters MY, Prins SA, Knibbe CA, DeJongh J, van Schaik RH, van Dijk M, et al. Propofol pharmacokinetics and pharmacodynamics for depth of sedation in nonventilated infants after major craniofacial surgery. Anesthesiology. 2006;104(3):466-74.
38. Civantos Calzada B, Aleixandre de Artinano A. Alpha-adrenoceptor subtypes. Pharmacological Research. 2001;44(3): 195-208.
39. Ahlquist RP. A study of the adrenotropic receptors. Am J Physiol. 1948;153(3):586- 600.
40. Laner SZ. Presynaptic regulation of cathecolamine release. Biochemical Pharmacology. 1974;23:1793-800.
41. Schimmel RJ. Roles of alpha and beta adrenergic receptors in control of glucose oxidation in hamster epididymal adipocytes. Biochimica et If Biophysical Acta. 1976;428(2):379-87.\
42. Berthelsen S, Pettinger WA. A functional basis for classification of alpha-adrenergic receptors. Life Sciences. 1977;21(5):595-606.
43. Drew GM, Whiting SB. Evidence for two distinct types of postsynaptic alphaadreno-ceptor in vascular smooth muscle in vivo. Br J Pharmacol. 1979;67(2):207-15.
44. Bylund DB. Heterogeneity of alpha-2 adrenergic receptors. Pharmacology, Biochemistry & Behavior. 1985;22(5): 835-43.