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 Table of Contents  
ORIGINAL RESEARCH
Year : 2019  |  Volume : 11  |  Issue : 5  |  Page : 42-50  

Comparative analysis of intravenous midazolam with nasal spray for conscious sedation in minor oral and maxillofacial surgeries


1 Department of Oral and Maxillofacial Surgery, MNR Dental College and Hospital, Sangareddy, Hyderabad, Telangana, India
2 Department of Periodontology, MNR Dental College and Hospital, Sangareddy, Hyderabad, Telangana, India
3 Department of Oral and Maxillofacial Pathology, MNR Dental College and Hospital, Sangareddy, Hyderabad, Telangana, India
4 Department of Prosthodontics, MNR Dental College and Hospital, Sangareddy, Hyderabad, Telangana, India

Date of Web Publication7-Feb-2019

Correspondence Address:
Dr. Kranti Kiran Reddy Ealla
Department of Oral and Maxillofacial Pathology, MNR Dental College and Hospital, Sangareddy, Hyderabad, Telangana 502294
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JPBS.JPBS_199_18

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   Abstract 


Aim: The aim of the current study was to evaluate the efficacy of nasal spray midazolam by collating it with conventional intravenous midazolam for conscious sedation in minor oral surgeries. Materials and Methods: Sixty patients were selected randomly and divided into two groups: group A for intranasal midazolam atomized spray (n = 30) and group B for intravenous midazolam (n = 30). Physiological parameters, anxiety score, sedation rating, patient’s cooperation score, and retrograde and anterograde amnesia were recorded for each patient during preoperative, intraoperative, and postoperative period. Final evaluation of safety and efficacy in the nasal and intravenous routes of midazolam drug during minor oral surgery was compared. Results: In this study, both intranasal and intravenous groups showed decrease in systolic blood pressure and diastolic blood pressure intraoperatively but within physiological limits and increase in the average pulse rates in both the groups. The average oxygen saturation levels were maintained to normal range in both the groups. The average respiratory rate decreased in both intranasal and intravenous groups during surgical procedure. The preoperative to postoperative anxiety scores were decreased significantly in the both groups and there was no significant difference in pre- to postoperative anxiety scores between the groups. Conclusion: Both intravenous and intranasal administration of midazolam showed better patient cooperation, satisfaction, and clinical effectiveness. Intranasal midazolam spray is effective in the reduction of subjective stress, reliable anxiolysis while preserving protective reflexes.

Keywords: Anxiolysis, conscious sedation, midazolam, minor oral surgery


How to cite this article:
Kunusoth R, Tej G, Ealla KR, Kathuroju PK, Ayyagari A, Alwala AM. Comparative analysis of intravenous midazolam with nasal spray for conscious sedation in minor oral and maxillofacial surgeries. J Pharm Bioall Sci 2019;11, Suppl S1:42-50

How to cite this URL:
Kunusoth R, Tej G, Ealla KR, Kathuroju PK, Ayyagari A, Alwala AM. Comparative analysis of intravenous midazolam with nasal spray for conscious sedation in minor oral and maxillofacial surgeries. J Pharm Bioall Sci [serial online] 2019 [cited 2019 Feb 21];11, Suppl S1:42-50. Available from: http://www.jpbsonline.org/text.asp?2019/11/5/42/251804




   Introduction Top


Anxiety, defined as a state of apprehension and physical tension combined with activation of the autonomous nervous system, is a common emotional reaction to fear experienced by the patients before dental treatments or the application of local anesthetic. This emotional status is accompanied by a neuroendocrine response with hemodynamic disturbances and metabolic effects, which has been related to[1] the reduction of pain tolerance threshold,[2] an increase in the possibility that nonharmful stimulants may be interpreted as painful, and[3] occurrence of complications such as tachycardia, fluctuations in arterial pressure, or vasovagal responses. Control of anxiety before and during dental appointments is important to ensure safety of the procedure to promote overall patient and surgeon satisfaction. With that objective psychologic or pharmacologic techniques are frequently used in the dental office especially in patients undergoing oral surgery including dental implants. One of those technique is the use of sedation, which has emerged as a popular technique in the literature.[1] The use of benzodiazepines such as diazepam and midazolam has drawn a major development to avoid general anesthesia. In minor oral surgical procedures, Conscious sedation can be considered as a better option as it a simple procedure, it takes less time and can also be used on patients who are medically compromised. With patients who are likely to be less compliant because of fear of local anesthetic injections and anxiety toward surgical procedures under local anesthesia, conscious sedation can be useful. Midazolam is one of the available drugs for conscious sedation, commonly administered intravenously and also available as a nasal spray. Keeping all the aforementioned parameters in view, this study was carried out to compare conscious sedation with midazolam through intranasal spray and conventional intravenous (IV) routes.


   Patients and Methods Top


A total of 60 patients were selected. Inclusion criteria for conscious sedations are patients between 10 and 50 years of age; patients who are ready for periodic review; patients having more stress, fear, and anxiety; patients who were uncooperative for surgery; and patients under American society of anesthesiologists grade I and II. Patients with a history of serious psychiatric illness, chronic use of central nervous system depressants or antidepressants, or alcohol abuse; morbidly obese patients (body mass index more than 30), who reported a history of anesthetic-related complications; and patients who were pregnant were excluded. The selected patients were randomly divided into two groups: In group A (test group), 30 patients in whom midazolam nasal spray (0.1mg/kg; Insed Atomizer) was used, with each metered dose of 100 µL of Insed Atomizer delivers 0.5mg midazolam, and in Group A patient with periapical cyst had enucleation done using intranasal midazolam spray. Patient had no pain throughout the procedure [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]. Group B patient with symphysis fracture had reduction done using IV midazolam and proper occlusion was attained [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12], [Figure 13]. Group B (control group), 30 patients in whom conventional IV midazolam (0.1mg/kg) was used. Physiological parameters, anxiety score, sedation rating, patient’s cooperation score, and retrograde and anterograde amnesia were recorded for each patient during preoperative, intraoperative, and postoperative period. Final evaluation of safety and efficacy in the nasal and IV routes of midazolam drug during minor oral surgery was compared [Table 4].
Figure 1: Midazolam nasal spray

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Figure 2: Intranasal midazolam administration

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Figure 3: Preoperative

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Figure 4: Cyst enucleation

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Figure 5: Bone defect after enucleation

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Figure 6: Closure

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Figure 7: Armamentarium used in intravenous route of midazolam administration

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Figure 8: Midazolam injection

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Figure 9: Administration of IV midazolam

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Figure 10: Preoperative

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Figure 11: Fracture line

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Figure 12: After plating

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Figure 13: Occlusion

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   Procedure Top


Preoperatively, on the day of surgery all the physiologic parameters such as heart rate, blood pressure, oxygen saturation, respiratory rate (RR), and anxiety scale were recorded. Prior to start of surgery, 0.1mg/kg midazolam was administered either intranasally or intravenously. Intraoperatively, all patients were monitored for every 5min till the end of procedure (15–60min) for the following parameters: blood pressure, RR, pulse, oxygen saturation, sedation ratings by Ramsay sedation scale[2] [Table 1], and patient’s cooperation score[3] [Table 2] were recorded [Table 6]. Patient verbal response was determined by talking to the patient intermittently.
Table 1: Ramsay sedation scale

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Table 2: Cooperation score during the procedure

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Table 3: Demographic data

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Table 4: Diagnosis

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Table 5: Parameters—systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse rate (PR), oxygen saturation, respiratory rate (RR)

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Table 6: Scores—cooperation score, sedation score

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Postoperatively, the following questions were asked after 30min of recovery to determine the postoperative sedation effects in each patient.

  1. Do you experience nausea/vomiting? Yes/No.
  2. Feeling sleepy? Yes/No.
  3. Had a headache: Yes/No.
  4. Feeling dizzy? Yes/No.
  5. Other aches/pain? Yes/No.
  6. Dreams? Yes/No.


After 1 hour of the procedure, patients were asked whether they were able to recollect the procedure to assess the retrograde and anterograde amnesia. Postoperative anxiety was assessed in all the patients using anxiety scale [Table 9]. Patients were discharged with an escort when they were able to walk steadily [Table 8].
Table 7: Anxiety score

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Table 8: Postoperative sedation

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Table 9: Amnesia

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Statistical analysis and correlations were performed using statistical package for social sciences statistics analyzing software.


   Results Top


The demographic data of the patients in group A are presented in [Table 3]. The average age was 26.5 years, of which 23 male and 7 female patients included under group A with a mean weight of 51.8kg. The demographic data of the patients in group B are presented in [Table 3]. The average age was 31.2 years, including 16 male and 14 female patients under group B with a mean weight of 54.5kg.


   Discussion Top


Conscious sedation is a method of depression of the central nervous system, which allows the operator to perform a surgical procedure during which the patient retains protective reflexes. In combination with local anesthesia, it is a safe alternative to general anesthesia for the control of perioperative pain and anxiety in outpatient surgery.[4] It is useful in those patients whose anxiety levels are more and who are unlikely to cooperate during minor oral surgical procedures, and can be induced by various routes of administration such as inhalation, intranasal (IN) spray, IV, oral, and intramuscular routes.[5] In this study, patients were chosen for IN and IV routes of midazolam administration.

In this study, preoperative mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) were 129.6 and 82.7mm of Hg, respectively in patients of group A. There was a decrease in both SBP and DBP by 7mm of Hg and 3mm of Hg, respectively during intraoperative period from 5th to 60th minute. Preoperative mean SBP and DBP were 127.5 and 80.7mm of Hg, respectively in patients of group B and there was a decrease in both SBP and DBP of about 5mm of Hg and 2mm of Hg, respectively during intraoperative period from 5th to 60th minute [Table 5].

Gilchrist et al.[7] assessed the use of IN midazolam (0.25mg/kg) in pediatric dental patients requiring extractions or simple surgical procedures who may otherwise have required a general anesthetic and concluded that those physiological parameters remained stable. Gupta et al.[9] observed that higher dosage of midazolam (0.06mg/kg) produced better quality of anxiolysis and sedation with lesser rates of intraoperative recall without significantly affecting the heart rate, RR, and SBP as compared to a lower dose (0.02mg/kg). However, higher dose (0.06mg/kg) causes a significant fall in DBP and oxygen saturation in room air. Watanabe et al.[10] observed cardiovascular depression after midazolam administration, and the degree of depression depended on the plasma concentration. When used at higher doses (ranging from 0.2 to 0.3mg/kg) midazolam has been shown to decrease SBP and DBP, and mean arterial pressure.

Therefore, this study shows that the SBP and DBP decreased when midazolam was administrated either as IV or as an IN spray in all patients within the physiological limits.

In this study, in the IN group the average pulse rate preoperatively was 83 beats/min (bmp), and there was an increase in the average pulse from 5th minute (81.8 bpm) to 60th minute (84.94 bpm) intraoperatively. In IV group, the average pulse rate preoperatively was 83.5 bpm, and there was an increase in the average pulse rate from 5th minute (82.3 bpm) to 60th minute (83.16 bpm) intraoperatively.

In the literature review study by AlSarheed,[6] various IN sedatives used to achieve conscious sedation during dental procedures amongst children were compared and concluded that IN midazolam was effective for modifying behavior in mild to moderately anxious children; however, for more invasive or prolonged procedures, stronger sedatives are recommended. Similarly Shashikiran et al.[12] undertook a study to evaluate midazolam as a pediatric conscious sedative agent for a routine Indian dental setup and to compare its efficacy and safety when administered by IN and intramuscular routes, at a dosage of 0.2mg/kg body weight, and stated that there was slight increase in pulse rate in the IN group but that was not significant. Blumer et al.[13] in their study examined if changes in oxygen saturation and pulse rate of pediatric patients during conscious sedation with midazolam and nitrous oxide are associated with child’s behavior and concluded that poor behavior of pediatric patients does not affect oxygen saturation, but it increases the pulse rate of children under sedation with midazolam and nitrous oxide. Similarly, P. Van Der Bijl et al.[25] compared intravenously administered midazolam (0.1mg/kg) with placebo in a randomized study in 50 patients undergoing oral surgical procedures under local anesthesia and stated that there is no increase in pulse rate in both the groups. In this study, in both groups, all patients showed an increase in pulse rate irrespective of the route of administration of midazolam drug.

This study showed that in IN group, there was an average preoperative SPO2 of 98.45%. The SPO2 percentage at 5th minute was 99.1% and by 60th minute it was 98.56% intraoperatively. In IV group, there was an average preoperative SPO2 of 99.1%. The average SPO2 percentage at 5th minute was 99.65% and by 60th minute it was 97.9% intraoperatively. If midazolam is given rapidly, it may produce apnea. In doses used for induction (0.2mg/kg) of anesthesia, it causes respiratory depression, but in this study the dosage used was 0.1mg/kg, which is less than the dosage in induction anesthesia and none of the patients showed desaturation.[15]

Lloyd et al.[15] stated that there was no instance of oxygen desaturation below 94%. In a study by Rodrigo et al.,[8] it was stated that the mean oxygen saturation during both procedures was 98% and the range was 97%–100%. Rodrigo et al.[16] evaluated oxygen desaturation during third molar surgery under conscious sedation with midazolam and stated that there was no significant desaturation attributable to midazolam sedation. During the entire time up to the postoperative period, the oxygen saturation values were maintained and this observation is not different in both groups similar to the previous studies reported.

Lobb et al.[11] showed the characteristics of midazolam and fentanyl when each was administered first for moderate IV sedation in a dental clinic. When fentanyl was administered before midazolam, there was a significant reduction in sedative/hypnotic dosages. However, when midazolam was administered first, there may have been a reduction in administration time and procedural recollection by the patient. From these findings, practitioners may want to consider midazolam-first sedation when patients are experiencing high anxiety or high gag reflex, whereas the use of fentanyl-first sedation may be recommended when a strong stimulus or painful procedures are required. Moreover, when a lighter level of sedation is desired to provide comfort, a lower-dose fentanyl administration first may enable a (pharmacodynamic) reduction in the amount of midazolam required compared with a midazolam-only sedation.[14]

In this study, there was an average preoperative RR of 18.55 cycles/min in the IN group. The average RR at 5th minute was 19 cycles/min and at 60th minute was 15.17 cycles/min intraoperatively. Postoperatively average RR was 17.6 cycles/min. In IV group, the average RR preoperatively was 17.2 cycles/min. The average RR at 5th minute was 16.4 cycles/min and at 60th minute was 14 cycles/min intraoperatively. Postoperatively, the average RR reported was 15.5 cycles/min. Midazolam[17] produces some respiratory depression in healthy humans. Midazolam with a dose of 0.15mg/kg significantly reduces the ventilator response to CO2 and significantly reduces the mouth occlusion-pressure response to CO2, but in this study the dosage used was 0.1mg/kg, and there was no significant decrease in the respiration rate.[18]

Lloyd et al.[15] reported that there were no instances of respiratory depression. In the study by Shashikiran et al.,[12] slight decrease in the RR in IN group was stated, but that was not significant clinically. Different studies showed varying results corresponding to RR after administration of midazolam intravenously.

This study showed that in IN group the average preoperative anxiety score was 12.65 and postoperative anxiety score was 6.20. In the IV group, the average preoperative score was 11.70 and postoperative score was 6.95. Burstein et al.[18] evaluated midazolam following IN administration to adult dental surgery patients and ascertained the effect of midazolam on anxiety. Anxiety was evaluated using a 100-mm visual analogue scale and they stated that there was a reduction in anxiety score [Table 7]. Hollenhors et al.[19] evaluated the effectiveness of intranasally administered midazolam spray in preventing claustrophobic responses of patients undergoing magnetic resonance (MR) imaging and concluded that a sizeable reduction in MR imaging–related anxiety and improved MR image quality were seen with patients who received IN midazolam spray. Gilchrist et al.[7] assessed the use of IN midazolam (0.25mg/kg) and was found that it provided adequate anxiolysis for majority of the children. This study shows that there was significant decrease in anxiety score from preoperative to postoperative period in both the groups significantly in correlation with the previous studies.

The study showed complete anterograde amnesia in both the groups. Retrograde amnesia in IV group was seen in 15% and in intranasal group, it was seen in 10% of the patients. Luyk et al.[20] compared the amnesic properties and psychomotor recovery between a bolus injection of midazolam and a bolus injection followed by continuous infusion of midazolam in patients for third molar surgery and stated that the patients experienced significant amnesia to local anesthetic injection in both groups. Kupietzky et al.[21] compared anterograde amnesic effects of midazolam with hydroxyzine in children undergoing dental treatment with those drugs plus nitrous oxide, using a recall test and concluded that midazolam was more effective in creating amnesia than hydroxyzine.

This study shows that the patient cooperation was increased by midazolam in both routes of drug administration with patients who gave minimal movements during procedure, positioning of the patient remained appropriate, some verbalization, but it did not indicate pain or discomfort and occasional grimaces. Similarly Walbergh et al.[22] stated that most of the children were slightly drowsy when brought into the operatory and some of them were euphoric and smiling when midazolam was given intravenously. Lloyd et al.[15] used IN midazolam as an alternative to general anesthesia in the management of children with oral and maxillofacial trauma and stated that children were cooperative during the procedure. This study shows that there is an increase in patient’s cooperation levels after administrating the midazolam either intravenously or intranasally, in all the patients.

This study shows that the sedation score increased in both the groups after administration of midazolam from 5th minute to 60th minute. In both the groups, onset of action ranged between 5 and 10min and in IN group the onset of action was faster when compared to IV group, and the patients responded to verbal commands throughout the procedure. Rose et al.[23] evaluated 90 children sedated with IN midazolam and they were moderately drowsy but usually did not fall completely asleep. The average time to peak plasma concentrations and maximal effect is 10min. Walbergh et al.[22] stated that IN midazolam shows a rapid onset of 10–15min and a short duration of effect (40–60min). Bünz and Gossle[24] confirmed the bioavailability of midazolam via the nasal route in 38 children prior to ear, nose, and throat surgery. Their results revealed that by giving a dose of 0.2mg/kg intranasally, the level of premeditation was sufficient in 79% of the patients 5min after application. Within 10min, 95% of the children showed sufficient premedication. Lloyd et al.[15] used IN midazolam as an alternative to general anesthesia in the management of children with oral and maxillofacial trauma and stated that children were cooperative or with good to excellent sedation with a dose of 0.2mg/kg.

In this study, postoperatively all the patients in both groups were assessed for postoperative sedation effects and recovery. All the patients recovered from effects of sedation to full alertness and were able to walk steadily within 1h after the surgery. One patient in the IN group complained of hiccups in the recovery phase, which subsided within half an hour and one patient in IV group complained about drowsiness during recovery phase, which lasted for 45min. Overall recovery of patients was satisfactory in both groups irrespective of the route of administration.

Our study was a generalized study with a wide range of minor oral surgical procedures majorly in adults. The average duration of the procedure ranged between 20 and 60min, which cannot be compared with other studies as the other studies were either carried out only on a single surgical procedure in adults or in routine dental treatments in children.

Midazolam administered either intravenously or intranasally did not produce much difference in anxiety, patient cooperation, and sedation, and all the physiological parameters were maintained under normal range. The sedation and anxiolysis observed in patients with IN route of administration were better when compared to the IV route. Hence, the choice of administration of drug is based on the willingness of patient as the IV route demands needle puncture. In this study, it was proved that IN route of administration had better convenience and compliance of patient with the reduced chance of infection and over sedation caused through IV route, in addition to other advantages such as rapid onset of action and rapid absorption when given intranasally.


   Conclusion Top


It can be concluded that IN midazolam was not inferior to the conventional IV drug both in attaining conscious sedation and the recovery while maintaining the physiological parameters. It may also be said that IN spray has all the advantages of IV midazolam without the disadvantages of pain, fear, and infections associated with IV injections and also bypasses the portal circulation, increasing the bioavailability of drug absorbed through richly vascular nasal mucosa. More number of surgical procedures and large patients sample size are required for further research studies.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

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Bovaira M, Babiloni AH, Jovani M, Peñarrocha-Diago M, González-Lemonier S, Peñarrocha-Oltra D. Pre operative anxiety and its influence on patient and surgeon satisfaction in patients receiving dental implant surgery is performed under intravenous conscious sedation. Int J Oral Maxillofac Implants 2017;32:912-8.  Back to cited text no. 1
    
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Ramsay MA, Savege TM, Simpson BR, Goodwin R. Controlled sedation with alphaxalone-alphadolone. Br Med J 1974;2:656-9.  Back to cited text no. 2
    
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Parworth LP, Frost DE, Zuniga JR, Bennett T. Propofol and fentanyl compared with midazolam and fentanyl during third molar surgery. J Oral Maxillofac Surg 1998;56: 447-53.  Back to cited text no. 3
    
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Keerthy PH, Balakrishna R, Srungeri KM, Singhvi N, John J, Islam M. Comparative evaluation of propofol and midazolam as conscious sedatives in minor oral surgery. J Maxillofac Oral Surgery 2015;14:773-83.  Back to cited text no. 4
    
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Peerbhay F, Elsheikhomer AM. Intranasal midazolam sedation in a paediatric emergency dental clinic. Anesth Prog 2016;63:122-30.  Back to cited text no. 5
    
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AlSarheed MA. Intranasal sedatives in pediatric dentistry. Saudi Med J 2016;37:948-56.  Back to cited text no. 6
    
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Gilchrist F, Cairns AM, Leitch JA. The use of intranasal midazolam in the treatment of paediatric dental patients. Anaesthesia 2007;62:1262-5.  Back to cited text no. 7
    
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Rodrigo C, Chow KC. A comparison of 1- and 3-minute lockout periods during patient-controlled sedation with midazolam. J Oral Maxillofac Surg 1995;53:406-10.  Back to cited text no. 8
    
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Gupta R, Santha N, Upadya M, Manissery JJ. Effect of different dosages of intravenous midazolam premedication on patients undergoing head and neck surgeries double blinded randomised controlled study. J Clin Diagn Res 2017;11:UC01-4.  Back to cited text no. 9
    
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Watanabea Y, Higuchia H, Ishii-Maruhamab M, Hondaa, Y, Yabuki-Kawasec, A, Yamane-Hiranoa, A et al. Effect of a low dose of midazolam on high blood pressure in dental patients: a randomised, double-blind, placebo-controlled, two-centre study. Br J Oral Maxillofac Surg 2016;54:443-8.  Back to cited text no. 10
    
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Lobb D, Clarke A, Lai H. Administration order of midazolam/fentanyl for moderate dental sedation. J Dent Anesth Pain Med 2018;18:47-56.  Back to cited text no. 11
    
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Shashikiran ND, Reddy SV, Yavagal CM. Conscious sedation—an artist’s science! An Indian experience with Midazolam. J Indian Soc Pedod Prev Dent 2006;24:7-14.  Back to cited text no. 12
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Blumer S, Iraqi R, Bercovich R, Peretz B. Oxygen saturation and pulse rate change in children during sedation with oral midazolam and nitrous oxide. J Clin Pediatr Dent 2018;42:461-4.  Back to cited text no. 13
    
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Reves JG, Fragen RJ, Vinik HR, Greenblatt DJ. Midazolam: pharmacology and uses. Anesthesiology 1985;62:310–24.  Back to cited text no. 14
    
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Lloyd CJ, Alredy T, Lowry JC. Intranasal midazolam as an alternative to general anaesthesia in the management of children with oral and maxillofacial trauma. Br J Oral Maxillofac Surg 2000;38:593–5.  Back to cited text no. 15
    
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Rodrigo MR, Rosenquist JB. Effect of conscious sedation with midazolam on oxygen saturation. J Oral Maxillofac Surg 1988;46:746-50.  Back to cited text no. 16
    
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Forster A, Gardaz JP, Suter PM, Gemperle M. Respiratory depression by midazolam and diazepam. Anesthesiology 1980;53:494–7.  Back to cited text no. 17
    
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Burstein AH, Modica R, Hatton M, Gengo FM. Intranasal midazolam plasma concentration profile and its effect on anxiety associated with dental procedures. Anesth Prog 1996;43:52-7.  Back to cited text no. 18
    
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Hollenhorst J, Münte S, Friedrich L, Heine J, Leuwer M, Becker H et al. Using intranasal midazolam spray to prevent claustrophobia induced by MR imaging. AJR Am J Roentgenol 2001;176:865-8.  Back to cited text no. 19
    
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Luyk NH, Zacharias S, Wanwimolaruk S. Bolus dose with continuous infusion of midazolam as sedation for outpatient surgery. Int J Oral Maxillofac Surg 1992;21:172-5.  Back to cited text no. 20
    
21.
Kupietzky A, Holan G, Shapira J. Intranasal midazolam better at effecting amnesia after sedation than oral hydroxyzine: a pilot study. Pediatr Dent 1996;18:32-4.  Back to cited text no. 21
    
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Walbergh EJ, Wills RJ, Eckhert J. Plasma concentrations of midazolam in children following intranasal administration. Anesthesiology 1991;74:233-5.  Back to cited text no. 22
    
23.
Rose E, Simon D, Haberer JP. [Premedication with intranasal midazolam in pediatric anesthesia]. Ann Fr Anesth Reanim 1990;9:326-30.  Back to cited text no. 23
    
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Bünz R, Gossler M. [Intranasal premedication of young children using midazolam (dormicum). Clinical experience]. Anasthesiol Intensivmed Notfallmed Schmerzther 1991;26:76-8.  Back to cited text no. 24
    
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12], [Figure 13]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9]



 

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