|Year : 2020 | Volume
| Issue : 2 | Page : 149-156
Intranasal premedication with dexmedetomidine versus midazolam for pediatric patients in ophthalmic surgery: a randomized controlled study
Ghada F Amer
Department of Anesthesia and Surgical Intensive Care, Faculty of Medicine, Mansoura University, Mansoura, Egypt
|Date of Submission||24-Jun-2019|
|Date of Acceptance||21-Aug-2019|
|Date of Web Publication||27-Jun-2020|
MD Ghada F Amer
Department of Anaesthesia, Faculty of Medicine, Mansoura University, 2 El-Gomhouria Street, Mansoura 35516
Source of Support: None, Conflict of Interest: None
Background Excessive anxiety has a bad implication on anesthetic practice in pediatric anesthesia; therefore, decreasing anxiety by premedication is an important issue. Intranasal administration of various drugs is an easy route with rapid onset of action allowing administration of variable drugs such as midazolam and dexmedetomidine used in pediatric preoperative sedation.
Patients and methods A total of 64 pediatric patients who were subjected to elective ophthalmic surgeries received either 0.5 mg/kg midazolam or 1 μg/kg dexmedetomidine intranasally. Basal heart and respiratory rate, blood pressure, sedation score, and oxygen saturation were recorded initially and every 5 min till the transfer to the operating room. Sedation score was also assessed at 30 min after drug administration. Postoperative monitoring was continued, and any postoperative complications were recorded.
Results Oxygen saturation, heart rate, systolic blood pressure, and respiratory rate values showed insignificant differences when both groups were compared together but showed significance differences when compared with the basal value in each group separately after 30 min. Sedation score was faster and child–parents separation score was higher in dexmedetomidine group when compared with midazolam group, and also both groups showed significant sedation score less than 3 when compared with the basal value at 15, 20, 25, and 30 min.
Conclusion Midazolam and dexmedetomidine were nearly equally effective as intranasal premedication for pediatric patients subjected to elective ophthalmic surgery with minimal adverse effects, and we recommend the use of midazolam owing to its safety, effectiveness, and lower cost.
Keywords: dexmedetomidine, intranasal route, midazolam, premedication, scoring, sedation, separation
|How to cite this article:|
Amer GF. Intranasal premedication with dexmedetomidine versus midazolam for pediatric patients in ophthalmic surgery: a randomized controlled study. Res Opin Anesth Intensive Care 2020;7:149-56
|How to cite this URL:|
Amer GF. Intranasal premedication with dexmedetomidine versus midazolam for pediatric patients in ophthalmic surgery: a randomized controlled study. Res Opin Anesth Intensive Care [serial online] 2020 [cited 2020 Sep 21];7:149-56. Available from: http://www.roaic.eg.net/text.asp?2020/7/2/149/287994
| Introduction|| |
Excessive anxiety has a bad implication on anesthetic induction and recovery in pediatric anesthesia and usually leads to functional and psychological disability after surgery . Premedication in pediatric patients has a great role in releasing anxiety and psychological trauma, which represent a great challenge in pediatric anesthesia .
Premedication of pediatric patients using intranasal route has been proved by multiple studies as an effective and safe way ,. Intranasal administration of various drugs is noninvasive easy route with high bioavailability and rapid onset of drug action owing to high blood supply of the upper airway mucosa and escaping from the first-pass metabolism .
Midazolam, which is a short-acting benzodiazepine, with short elimination half-life and anterograde amnesic effect, represents a widely used drug in preanesthetic and sedation . Like midazolam but with selective agonist action on α2 adrenoceptor, dexmedetomidine represents a new anesthetic premedication drug with a shorter duration of action ,.
This study aimed to compare the efficacy of dexmedetomidine versus midazolam as sedative premedication drugs given by intranasal route in pediatric patients undergoing elective surgical procedures.
| Patients and methods|| |
This double-blind comparative study was conducted in Mansoura Ophthalmology Centre over 6 months, after obtaining our Institutional Research Board approval and an informed written consent from all patients’ guardians.
The following were the inclusion criteria:
- Patients submitted for elective ophthalmic surgery.
- Age: 2–6 years.
- ASA status Ι and II.
The following were the exclusion criteria:
- Refusal by the parents.
- Congenital heart disease.
- History of allergy to any of the studied drugs.
- Nasal disorders such as repeated nasal bleeding or nasal tumors.
Mann–Whitey U-test was used for comparison of degree of sedation and setting α to 0.05. This study needed at least 29 cases in each group to detect the same difference with 80% power. So we increased the number of cases to 32 cases in each group to compensate for any possible dropouts. PS software Windows (William D. Dupont and Walton D.Plummer, NY, USA) was used for calculations.
Patients were allocated into two groups using closed envelope randomization method (32 each): intranasal midazolam group (M group), in which patients were given 0.5 mg/kg midazolam, and intranasal dexmedetomidine group (D group), in which patients received 1 μg/kg dexmedetomidine.
In the preoperative room, medications were given 30 min before anesthesia with attendance of one of the patient’s parents. Intranasal drugs were given into the infants nose using a 3-ml syringe in the recumbent position as nasal drops over 5 min. Basal HR and respiratory rate, blood pressure, and oxygen saturation were recorded initially and then every 5 min after giving the intranasal drug for 30 min till being transferred to the operating room. Assessment of sedation was carried out every 5 min for 30 min from giving the drug, using a four-point scale sedation level: agitated=4, awake=3, drowsy=2, and asleep=1 . Sedation score of 1 or 2 was considered satisfactory, and sedation score of 3 or more was considered unsatisfactory. Child patient response for separation from the guardian was assessed at 30 min using a four-point scale of separation score: patient unafraid, cooperative, sleep=1; fear, crying, quite with reassurance=2; moderate fear or crying but not quite with reassurance=3; and crying and need for restraint=4 .
On arrival to the operative room, monitoring equipment including electrocardiogram (ECG), NIBP, and SpO2 were connected to the patient. Sevoflurane 5% and oxygen 100% were used to induce anesthesia via a facemask, then an intravenous line was fixed in place, then patient airway was secured using an appropriate size of tube, and the patient was left to breath spontaneously after decreasing FiO2 to 50%. Sevoflurane concentration 2% was supplied to facilitate the surgical procedure and maintain stabilization of hemodynamics (bl pr, HR) at basal±20%. At the end of the surgical procedure, anesthesia was discontinued and 100% oxygen (4 l/min) was continued till removal of the tube when the patient gained consciousness. Postoperative monitoring was continued after transfer of the patient to the post anesthesia care unit (PACU) with recording of any postoperative complications.
Data were tested for normality by means of the Kolmogorov–Smirnov test. Normally distributed continuous data were analyzed using the Student t-test. Abnormal distributed continuous and ordinal data were analyzed using the Mann–Whitey U-test. Categorical data were analyzed by means of Fisher’s exact test as appropriate. The results were presented as mean (SD), median and range or number and percentage of patients as appropriate. P value less than 0.05 was considered statistically significant. Statistical analyses were performed using IPM SPSS for Windows, version 18 (IPM SPSS Inc., Chicago, Illinois, USA).
| Results|| |
Intranasal route was used for premedication of 64 patients, and their demographic data were comparable in both groups ([Table 1]).
Oxygen saturation values showed insignificant differences when both studied groups were compared together and when their values were compared with the basal one in each individual group ([Figure 1]). Although heart rate, systolic blood pressure, and respiratory rate values showed no significant statistical difference when both groups were put in comparison together, they showed significance differences when compared with the basal value in each group separately at 30-min interval ([Figure 2],[Figure 3],[Figure 4], respectively).
|Figure 1 Peripheral oxygen saturation of the studied groups. Data expressed as percent. *P<0.05, significant when compared with basal value.|
Click here to view
|Figure 2 Heart rate changes in the studied groups. Data expressed as mean±SD. *P<0.05, significant when compared with basal value.|
Click here to view
|Figure 3 Systolic blood pressure changes of the studied groups. Data expressed as mean±SD. *P<0.05 significant when compared with basal value.|
Click here to view
|Figure 4 Respiratory rate changes in the studied groups. Data expressed as mean±SD. *P<0.05, significant when compared with basal value.|
Click here to view
Patients who were premedicated with dexmedetomidine had achieved a significantly more rapid sedation score (lower than 3 after 10 min) than those of midazolam group, and after that, sedation score in both groups had comparable values. Moreover, both groups showed significant sedation score less than 3 when compared with the basal value at interval of 15, 20, 25, and 30 min ([Figure 5]).
|Figure 5 Sedation score of the studied groups, data are expressed as mean±SD. *P<0.05, significant when compared with basal value. †P<0.05, significant when compared with midazolam group.|
Click here to view
Children in dexmedetomidine group had achieved significant high child–parents separation score grade 1 in comparison with midazolam group ([Figure 6]). There was no significant incidence of nausea, vomiting, or bradycardia in the two groups.
| Discussion|| |
Children in operative theaters are often uncooperative and anxious; this may be attributed to pain anticipation, strange environment, parental separation, or a previous fearful experience . Perioperative anxiety is related to increased postoperative pain, stress hormones release with negative outcomes, postoperative maladaptive behaviors like eating problems, night mares, enuresis, and increased fear of doctors and hospitals .
Sedative premedications have a great role in pediatric anesthesia but still the route of administration represents great obstacle in pediatric anesthesia. Because of that anesthetists try to find an effective, easy, and applicable route for drug administration in pediatric patients. Drug injection by various routes is effective and reliable but very painful and leaves bad memories in children mind. Intranasal drug administration has been proved to be an effective convenient route for preoperative sedative drug administration in children. This may be attributed to its high bioavailability, simplicity of administration, and being noninvasive; however, cooperation is still required and some difficulty still presents in younger children . Moreover, increased vascularity of the subepithelium of the nose facilitates the intake of the drugs to the systemic circulation bypassing the first-pass metabolism in the liver .
Currently, the most commonly used sedative premedications include midazolam and dexmedetomidine. Midazolam has great efficacy when given intranasally, but it is associated with unpleasant burning sensation in the nasal cavity that may not favor its use in practice. However, other studies reported that intranasal administration of midazolam is better tolerated by infants and has higher plasma concentration in comparison with its oral administration ,.
Another widely used preanesthetic medication drug is dexmedetomidine which is an α2-adrenoreceptor agonist, which has sedative, analgesic, and anxiolytic effects via activation of central α2-adrenoreceptors in the locus coeruleus, approximately eight times that of clonidine . Intranasal administration of dexmedetomidine produced a clinical sedative effect lasting for more than 180 min studies have reported significant sedation when dexmedetomidine was administered intranasally to adult and pediatric patients undergoing minor surgery ,.
This study tried to compare the effects of both dexmedetomidine and midazolam given intranasally on satisfactory sedation and separation from parents in children aged between 2 and 6 years undergoing elective ophthalmic surgery, as this age is most suspected to separation anxiety and their understanding and cooperation is limited.
This study showed that patients’ oxygen saturation did not decrease with either intranasal midazolam or dexmedetomidine; this means that both drugs have no adverse implication on patient’s oxygenation.
Children who were premedicated with 1 μg/kg of dexmedetomidine had achieved a significantly faster and satisfactory sedation score (<3 after 10 min) than those premedicated with 0.5 mg/kg of midazolam, and after that, sedation score in both groups had comparable values. Children in dexmedetomidine group had achieved higher child–parents separation score grade 1 in comparison with midazolam group.
The minimal variation in the onset of sedation between midazolam and dexmedetomidine may be owing to the same mechanism of action of both drugs; both drugs act on the central nervous system (CNS) in locus coeruleus with EEG activity same to that occurred during natural sleep .
This result was similar to those proved by Wilton et al.  and McCormick et al. , who reported that 0.2 μg/kg midazolam intranasal premedication is a rapid and efficient method of pediatric sedation, and also Lejus et al. , who reported that midazolam through the nose is an effective route of premedication, although it is poorly accepted by some patients. Moreover, Cheung et al.  and Yuen et al.  in their studies showed that intranasal dexmedetomidine 1 μ/kg as premedication was effective as sedation for patients undergoing third molar surgery under local anesthesia with better postoperative pain relief and no delay in psychomotor recovery.
Mathai et al.  found that intranasal midazolam produced more rapid sedation (around 4.8 min), and time of peak sedation was only 12.7 min, which is not in agreement with the results of this study. This difference may be owing to age group of their study, which started from 6 month up to 6 years, and different dose used.
When comparing both drugs together regarding sedation, we found that dexmedetomidine produces more rapid onset of sedation but midazolam has more satisfactory sedative effects; this may match the results obtained by Akin et al.  that intranasal dexmedetomidine and midazolam are both effective in reducing anxiety during separation from parents; however, midazolam provides more satisfactory sedation during mask induction. However, this may be different from another study by Sundaram and Mathian  where pediatric patients premedicated with intranasal dexmedetomidine produced more satisfactory sedation than those patients who received midazolam intranasal. The sedation produced by dexmedetomidine differs from other drugs, as patients are easier to arouse and more cooperative.The results of this study found that there was a significant change in systolic blood pressure, heart rate, and respiratory rate in both groups after 30 min when compared with the basal values, with no difference between both the groups. This may be owing to increased level of sedation and reduction in sympathetic outflow and circulating level of catecholamines. This matches with previous studies by Remadev et al.  and Talke et al.  who reported that intranasal dexmedetomidine decreases the preoperative heart rate and systolic blood pressure.
| Conclusion|| |
Administration of 1 μg/kg intranasal dexmedetomidine produces convenient sedation in pediatric patients between 2 and 6 years of age. The children behavior during parental separation and during induction of anesthesia was comparable to the children premedicated with midazolam. This study concluded that both midazolam and dexmedetomidine are nearly equally effective as intranasal premedication for pediatric patients with minimal adverse effects. Dexmedetomidine produced 5 min earlier onset of sedation than midazolam through intranasal route; however, midazolam was equally effective after that with dexmedetomidine regarding sedation score and parent–child separation score. Considering the high cost of using dexmedetomidine as premedication, we recommend the use of midazolam owing to its safety and effectiveness as well as availability and lower cost compared with dexmedetomidine.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Sun GC, Hsu MC. Effects of age and gender on intravenous midazolam premedication: a randomized double-blind study. Br J Anaesth 2008 101:632–635.
Haldar R, Srivastava D, Agrawal PM, Tiwari AK, Singh PK. Comparison between intranasal dexmedetomidine and intranasal ketamine as premedication for procedural sedation in children undergoing MRI: a double-blind, randomized, placebo-controlled trial. J Anesth 2014; 28:12–18.
Wang J, Bru G. Influence of intranasal medication on the structure of the nasal mucosa. China Med J (Engl) 2002; 115:617–619.
Abrams R, Morrison JE, Villassenor A. Safety and effectiveness of intranasal administration of sedative medications for urgent brief pediatric dental procedures. Anesth Prog 1993; 4:63–66.
Wilton NCT, Leigh J, Rosen DR, Pandit UA. Preanesthetic sedation in preschool children by using intranasal midazolam. Anesthesiology 1988; 69:972–975.
Dundee JW, Wilson DB. Amnesic action of midazolam. Anaesthesia 1980; 35:459–461.
Schmidt AP, Valinetti EA, Banderira D, Bertacchi MF, Simoes CM, Auler JO. Effects of preanesthetic administration of midazolam, clonidine, or dexmedetomidine on postoperative pain and anxiety in children. Pediatr Anesth 2007; 17:667–674.
Yuen VM, Irwin MG, Hui TW, Yuen MK, Lee LH. A double-blind,crossover assessment of the sedative and analgesic effects of intranasal dexmedetomidine. Anesth Analg 2007; 105:374–380.
Chhibber A, Fickling K, Lustik S. Pre-anesthetic midazolam: a randomized trial with three different routes of administration. J Anesth Clin Res 2011; 2:1.
Talgaonkar S, Mishra PR. Intranasal delivery: an approach to bypass the blood brain barrier. Indian J Pharmacol 2004; 36:140–147.
Turker S, Onur E, Ozer Y. Nasal route and drug delivery systems. Pharmacol World Sci 2004; 26:137–142.
Yildirim SV, Guc BU, Bozdogan N, Tokel K. Oral versus intranasal midazolam premedication for infants during echocardiographic study. Adv Ther 2006; 23:719–724.
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; 106:1715–1721.
Khan ZP, Ferguson CN, Jones RM. Alpha-2 and imidazoline receptor agonists. Anesthesia 1999; 54:146–165.
McCormick AS, Thomas VL, Berry D, Thomas PW. Plasma concentrations and sedation scores after nebulized andintranasal midazolam in healthy volunteers. Br J Anaesth 2008; 100:631–636.
Lejus C, Renaudin M, Testa S, Malinovsky JM, Vigier T, Sowon R. Midazolam for sedation in children nasal versus rectal administration. Eur J Anaethesiol 1977; 14:244–249.
Cheung WC, Ng GF, Yeun MY, Ho MH, Irwin MG. Analgesic and sedative effects of intranasal dexmedetomidine in third molar surgery under local anesthesia. Br J Anesth 2011; 107:430–437.
Mathai A, Nazareth M, Raju R. Preanesthetic sedation of preschool children: comparison of intranasal midazolam versus oral promethazine. Anesth Essays Res 2011 5:67–71.
Akin A, Bayram A, Esmaoglu A, Tosun Z, Aksu R, Altuntas R, Boyaci A. Dexmedetomidine versus midazolam for premedication of pediatric patients undergoing anesthesia. Pediatr Anesth 2012; 22:871–875.
Sundaram AL, Mathian VM. A comparative evaluation of intranasal dexmedetomidine and intranasal midazolam for premedication in children: a double blind randomised controlled trial. JIDA 2011; 5:777–784.
Remadev P, Chandrasekar L, Vasudevan A. Comparison of midazolam and ketamine as oral premedicants in pediatric patients. Int J Anesthesiol 2009; 2:2.
Talke P, Chen R, Thomas B, Aggarwall A, Gottlieb A, Thorborg P et al.
The hemodynamic and adrenergic effects of perioperative dexemdetomidine infusion after vascular surgery. Anesth Analg 2000; 90:834–839.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]