Eur Arch Paediatr Dent DOI 10.1007/s40368-015-0187-7
ORIGINAL ARTICLE
A comparison of the sedative effect of oral versus nasal midazolam combined with nitrous oxide in uncooperative children I. E. Musani1 • N. V. Chandan1
Received: 3 February 2015 / Accepted: 26 March 2015 European Academy of Paediatric Dentistry 2015
Abstract Aim To compare a combination of oral midazolam (0.2 mg/kg body weight) and nitrous oxide–oxygen sedation with a combination of intranasal midazolam (0.1 mg/ kg body weight) and nitrous oxide–oxygen sedation for effectiveness, patient acceptability and safety profile in controlling the behaviour of uncooperative children. Methods Thirty children, 4–10 years of age, referred for dental treatment were included in the study with a crossover design. Each patient was sedated with a combination of either oral midazolam and nitrous oxide–oxygen sedation or intranasal midazolam and nitrous oxide–oxygen sedation at subsequent dental treatment visits. During the treatment procedure, the study recorded scales for drug acceptability, onset of sedation, acceptance of nasal mask, sedation, behavioural, safety, overall behaviour and alertness. Results The grade of acceptability of midazolam in both groups was consistently good. There was a significant difference (p \ 0.001) in the time of onset of sedation, which was significantly quicker with the intranasal administration of midazolam. The mean time of onset for oral midazolam was 20.1 (17–25) min and for intranasal midazolam 12.1 (8–18) min. The efficacy profile of the present study included: acceptance of nasal mask, sedation score, crying levels, motor movements and overall behaviour scores. The results did not show any statistically
& N. V. Chandan [email protected] 1
Department of Pediatric and Preventive Dentistry, M.A. Rangoonwala Dental College and Research Centre, Pune, 2390-B, K.B. Hidayatullah Road, Azam Campus, Camp, Pune 411001, Maharashtra, India
significant differences. All the parameters were highly satisfactory. The difference in alertness was statistically significant (p value \0.05), being higher in the intranasal group than the oral group and suggestive of faster recovery using intranasal midazolam. Conclusion The intranasal route of midazolam administration has a quick onset of action and a quick recovery of the patient from sedation as compared to the oral route of midazolam administration. Midazolam administered through the intranasal route is as effective as the oral route at a lower dosage. Therefore, it is an effective alternative to oral route for a paediatric dental situation. Keywords Intranasal midazolam Oral midazolam Nitrous oxide Local anaesthetic Uncooperative children Behaviour management
Introduction Behaviour management in children is the cornerstone that sets apart paediatric dentistry from the other dental specialities. The technical proficiency of a dentist alone is of little merit unless the child cooperates or at least passively accepts dental treatment. If psychological behaviour management techniques alone prove unproductive, pharmacological sedative agents should be considered as an effective option (Al-Zahrani et al. 2009). ‘‘The standard sedative technique’’ in paediatric dentistry at present is nitrous oxide–oxygen inhalation sedation (Council of European Dentists 2012). Its favourable properties include ease and rapidity of induction, quick recovery with no aftereffects, flexibility of dosage control and the absence of any systemic metabolism. However, it is a very technique-sensitive procedure and when used alone
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may prove insufficient in the treatment of very fearful children. Several studies have indicated that when other sedative agents are added to nitrous oxide, disruptive behaviours decrease. Nitrous oxide has been shown to potentiate the effect of benzodiazepines (Houpt et al. 1989, 1996; Hartgraves and Primosch 1994; Al-Zahrani et al. 2009). Midazolam, a newer-generation benzodiazepine, ‘‘potentially the ideal sedative agent’’, (Papineni et al. 2014) has a wide toxic/therapeutic ratio and safety margin (AlZahrani et al. 2009). The relatively short half-life of midazolam produces rapid onset and recovery and is well suited for ambulatory patients in dental practice (Wilson et al. 2002). However, its short duration of action makes its use limited (Nathan and Vargas 2002). Therefore, it would be a appropriate to combine the ‘‘standard technique’’ with the ‘‘potentially ideal sedative’’ to obtain the added benefits of both these agents. Midazolam can be administered through various routes. In a paediatric dental situation, oral and intranasal routes would be more suitable as they eliminate the need for painful injections that may increase anxiety in children. The question still remains as to which is the better route of administering midazolam as a sedative agent. Therefore, this study aimed to compare a combination of oral midazolam syrup (dosage 0.2 mg/kg body weight) and nitrous oxide inhalation sedation with a combination of intranasal midazolam spray (dosage 0.1 mg/kg body weight) and nitrous oxide inhalation sedation in terms of effectiveness, patient acceptability and safety profile.
Methods Study design The study was carried out in the Department of Paediatric and Preventive Dentistry at M.A. Rangoonwala Dental College and Research Centre, Pune (India). The study had a randomised crossover design where 30 paediatric patients aged 4–10 years, requiring dental treatment, were included. The children were divided randomly on the basis of odd and even numbers into two groups. Each child received two different routes of drug administration, that is, oral midazolam and intranasal midazolam in combination with nitrous oxide–oxygen sedation as follows at two subsequent dental visits. The two groups were as follows: Group O: 15 patients who received oral midazolam syrup and nitrous oxide inhalation sedation on their first visit, followed by intranasal midazolam and nitrous oxide inhalation sedation on their second visit. Group N: 15 patients who received intranasal midazolam spray and nitrous oxide on their first visit, followed by
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oral midazolam and nitrous oxide inhalation sedation on their second visit. The dental treatment was provided by the same operator (IM). Rating of behaviour, monitoring of the patient and recording of behaviour rating scores throughout the procedure were performed by the same observer (NC) during the two dental treatment visits. The study commenced only after due permission and clearance was obtained from the Institutional Review Board and Ethical Committee. Patients were selected as per the following inclusion and exclusion criteria. Inclusion criteria • • • •
Child within the age group of 4–10 years. Behaviour category: Frankl Behaviour Rating Scale negative and definitely negative. ASA 1 category (normal, healthy patient). Needing dental treatment in at least two quadrants with the use of local analgesia during the procedure. The dental treatment could include deep restorations, pulpectomy, pulpotomy or extractions.
Exclusion criteria • • •
•
Any respiratory condition that makes breathing through the nose difficult. Cognitive impairment Patients who have recently used medication such as erythromycin or anticonvulsants that might interfere with the pharmacokinetics of midazolam. Any history of any systemic disease.
On the day of assessment, the treatment protocol and its advantages and disadvantages were explained. Verbal and written instructions were given to the parent/guardian. Fasting instructions were given emphasising no solid foods or nonclear liquids 4 h before the sedation procedure as per European Academy of Paediatric Dentistry Guidelines (2005). Informed consent for the treatment was obtained from the parent/guardian on the day of sedation. Each child had to undergo a physical examination by the anaesthetist on the day of sedation for medical clearance. The patient’s weight was taken with an electronic weighing scale. Baseline heart rate, oxygen saturation and blood pressure were recorded. Midazolam administration The dosage of oral midazolam was calculated for each child at 0.2 mg/kg body weight. Oral midazolam was administered in syrup form, i.e. midazolam hydrochloride syrup (Mezolam—manufactured by Neon Laboratories,
Eur Arch Paediatr Dent Table 1 Assessment of a patient’s acceptability of the drug
Table 3 Ellis Sedation Score
1—Good
Child accepts the drug without any refusal or resistance
Score 1
No uninvited limb movement. Total co-operation—no restlessness
2—Fair
Child accepts the drug administration with some verbal resistance
Score 2
Small amount of uninvited limb movement. Still total cooperation and no restlessness
3—Poor
Child accepts the drug with some physical resistance
4—Refused, crying
Child refuses administration of drug and it is possible only after much persuasion
Score 3
More uninvited limb movement. Small degree of restlessness and anxiety. Patient less co-operative. Still able to perform all dental procedures
Score 4
Considerable degree of limb movement. Perhaps, unhelpful head movements. Poor co-operation. Patient quite restless and anxious. Able to perform only basic dentistry. Advanced delicate work not possible
Score 5
Restless, anxious and limb movements severe. Impossible to perform any dentistry. Not determined = too uncooperative
Table 2 Level of co-operation during acceptance of the nasal mask Score 0
No co-operation at all—will not sit in the dental chair
Score 1
Patient sits in the chair but does not allow an intraoral examination with a mirror and does not accept the nasal mask
Score 2
Sits in the chair and allows an intraoral examination, but does not accept the nasal mask
Score 3
The patient sits in the chair, allows intraoral examination and accepts the nasal mask—very co-operative
Ltd.) Each millilitre of syrup contains 2 mg of midazolam. Oral midazolam was administered accurately using a 5 ml disposable syringe. Intranasal midazolam was administered in the form of a nasal spray (Midacip Nasal Spray manufactured by Cipla Ltd.) The dosage for intranasal midazolam was calculated at 0.1 mg/kg body weight. Each puff of the nasal spray delivered 0.5 mg of midazolam and was administered in both the nostrils. The dosage of intranasal midazolam was rounded off to the higher 0.5 dosage, as it was difficult to give a fraction of a spray. During the administration of the drug (oral/intranasal), the patient’s acceptability of the drug was evaluated using four code levels (Rakaf et al. 2001) (Table 1). Each child was made to wait in the waiting room with his/her parents until signs of onset of sedation were observed. This was defined as a relaxed appearance with slurring and slowing of speech. The time taken for onset of sedation was recorded. Prior to nitrous oxide inhalation sedation, each patient was then moved into the sedation room and seated on the dental chair. The nasal mask was fitted to the patient. The level of co-operation during acceptance of the nasal mask (Wood 2010) by the patient was evaluated using a fourpoint scale (Table 2). During nitrous oxide inhalation sedation, nitrous oxide/ oxygen sedation was administered using a Matrx Porter Digital relative analgesia machine. The nitrous oxide was titrated in 10 % increments to a final concentration of nitrous oxide 30 % and oxygen 70 %. A maximum concentration of nitrous oxide of 30 % was chosen during local
analgesia administration. Nitrous oxide at levels of 20–30 % provides adequate sedation, without the risk of oversedation (Wilson et al. 2003). Once nitrous oxide 30 % had been reached, injection of 2 % lidocaine (with adrenalin)—local analgesia—was administered to the patient. During the administration of local anaesthesia, Ellis Sedation Score was employed to record the level of sedation (Ellis 1996) (Table 3). The behaviour of the patient during treatment was observed for the each child’s crying and motor movements. This was graded using a modified version of the Houpt Behaviour Rating scale (Houpt et al. 1985; Al-Zahrani et al. 2009) (Table 4). A safety scale was used to record any adverse reaction such as deep/prolonged sedation, sneeze/cough/hiccough, vomiting, allergic reaction and respiratory depression that might occur during treatment (Shashikiran et al. 2006) (Table 5). Once the required dental treatment was completed, 100 % oxygen was administered to the patient for 3 min. The sensory perception levels (alertness) and overall behaviour of every child at the end of the dental procedure and sedation were evaluated using a modified version of the Houpt Behaviour Rating scale (Houpt et al. 1985; AlZahrani et al. 2009) (Table 4). On completion of treatment, each child was transferred to the recovery room. The patient was required to remain in the recovery area for 20–90 min, and then discharged after assessing the following (Smith et al. 1998): • • • • •
Vital signs within normal limits. Response to verbal stimulation. Absence of any signs and symptoms of compromised respiration. State of wakefulness without any adverse conditions. Able to walk unaided.
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Eur Arch Paediatr Dent Table 4 Houpt Behaviour Rating Scale
Table 5 Safety scale
Rating for movement during treatment
Vomiting score
1.
Violent movement interrupting treatment
2.
Continuous movement making treatment difficult
3.
Controllable movement that does not interfere with treatment
4.
No movement
Rating for crying during treatment
Score 0
Unsatisfactory: vomiting present
Score 1
Satisfactory: no vomiting
Allergic reaction Score 0
Unsatisfactory: allergic reaction present
Score 1
Satisfactory: no allergic reactions
1.
Hysterical crying that demands attention
2.
Continuous, persistent crying that makes treatment difficult
Score 0
0—Unsatisfactory: sneezing/coughing/hiccough present
3.
Intermittent, mild crying that does not interfere with treatment
Score 1
1—satisfactory: no sneezing/coughing/hiccough
4.
No crying
Rating for alertness 1.
Fully awake, alert
2.
Drowsy, disoriented
3.
Asleep
Rating for overall behaviour 1. Aborted, no treatment rendered 2.
Poor—treatment interrupted, only partial treatment completed
3.
Fair—treatment interrupted, but eventually all completed
4.
Good—difficult, but all treatment performed
5.
Very good—some limited crying or movement, or movement
6.
Excellent—no crying or movement
The next appointment for the patient was scheduled after 7 days when the same protocol was followed. Data analysis The collected data as per the above-mentioned protocol was entered in M.S. Excel and a master table was created. Further analysis was by using IBM-SPSS version 20. Statistical analysis used Chi square test to assess the scores obtained between the two groups. A p value of p \ 0.05 was considered for statistical significance.
Sneezing/coughing/hiccough.
Respiratory depression Score 0
Unsatisfactory: too deep/too long sedation
Score 1
Satisfactory: easily arousable-optimum sedation
Prolonged/deep sedation Score 0
Unsatisfactory: prolonged/deep sedation present
Score 1
Satisfactory: no prolonged/deep sedation
midazolam ranged from 17 to 25 min (mean 20.1 min) and intranasal midazolam ranged from 8 to 18 min (mean 12.1 min). There was a significant difference (p \ 0.001) between the time of onset of sedation, with intranasal administration of midazolam being significantly quicker than oral administration of midazolam. The efficacy profile (Figs. 2, 3, 4, 5, 6) of the present study included level of cooperation for acceptance of nasal mask, sedation score, crying levels, motor movements and overall behaviour; the results did not show any statistical significant differences. As for the safety profile, all the parameters recorded for safety analysed either individually or together showed no adverse effects in either Group N or Group O. The difference in alertness (Fig. 5) was much higher in Group N than in Group O suggestive of faster recovery using intranasal midazolam. The difference between the two groups was statistically significant (p value \0.05).
Results Discussion Thirty children (19 males and 11 females) age 4–10 years were selected for the study as per inclusion and exclusion criteria. Patient’s drug acceptability All the 30 children accepted both oral midazolam syrup and intranasal midazolam atomised spray readily during subsequent dental treatment visits. The grade of acceptability in both the groups was consistently good (100 %) without any resistance. The time of onset of oral and intranasal midazolam sedation is shown in Fig. 1. The onset of action for oral
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Children requiring invasive procedures should be supported with appropriate anxiety management for effective dental treatment. It is widely accepted that conscious sedation is safer than general anaesthesia (Averley et al. 2004). Therefore, conscious sedation should be considered as an alternative to general anaesthesia wherever possible. The present study attempted to use a combination of nitrous oxide–oxygen inhalation sedation and midazolam to achieve conscious sedation in children aged 4–10 years as an adjunct to behaviour management. Most practitioners prefer the use of the oral route of drug administration due to its record of high safety, minimal
Eur Arch Paediatr Dent Fig. 1 Distribution of patients according to time of onset of midazolam sedation (oral midazolam and intranasal midazolam). Inference: Chi square: 56.4, p = 0.000 (p \ 0.05 is considered to be statistically significant). Thus, there was a significant difference in the time of onset of sedation, being significantly lower in the intranasal administration of midazolam. This indicates the better efficacy of this route. The mean time of onset was 12.1 min for intranasal and 20.1 min for oral sedation
Distribuon of Paents according to Time of Onset of Sedaon 70 60
53.33
60
INTRA NASAL
N=30 for each group Time of Onset 8 – 10 11 – 13 14 – 16 17 – 19 20 – 22 23 – 25
Intra nasal 7 16 6 1 0 0
Oral 0 0 0 10 18 2
ORAL
50 40 %
33.33 30 23.33
20
20
6.67
10
3.33 0
0
0 8-10
0 11-13
0 14-16
17-19
0
20-22
23-25
Time of Onset of Sedaon (min)
Fig. 2 Distribution of patients according to the level of cooperation recorded at the time of acceptance of the nasal mask. Inference: Chi square: 2.96, p = 0.085 (p \ 0.05 is considered to be statistically significant). Thus, there was no significant difference in the level of co-operation in the two groups
Distribuon of Paents according to Level of Co-operaon 120 INTRA NASAL 100
N=30 for each group Level Of Co-operaon 0 1 2 3
ORAL
80
Intra nasal Oral 0 0 0 0 5 1 25 29
96.67 83.33
% 60
40
16.67
20
3.33 0
0
0
0
0 0– will not sit in dental chair
1 –sits but disallows intraoral examinaon
2 –sits but does not accept the mask easily
3 – accepts everything, very co-operave
Level of Co-operaon
complications and its easy acceptance by children (Malamed and Quinn 1995). Midazolam has a disagreeable taste that is difficult to mask. Children may refuse to swallow the drug or may expectorate some of it resulting in abandoning of the sedation (Braham et al. 1993). The present study utilised a commercially available midazolam hydrochloride syrup formulation. The formulation contains a flavoured syrupy base that masked the bitter taste of midazolam and was readily accepted by the paediatric patients without any form of resistance. Intranasal midazolam was assessed as an alternative to oral midazolam in combination with nitrous oxide for invasive dental procedures in a paediatric dental setup. The use of nasal drops is associated with a burning sensation
that may require the need for administration of topical anaesthesia (Haas 1999) to eliminate the need for this intranasal midazolam was administered in the form of a nasal spray. It was observed that the nasal spray was well accepted by the patients without any form of resistance. When evaluating the two different modes of administration, it is important to take into account the time factor for the onset of sedation and time of recovery. Onset of action for oral midazolam ranged from 17 to 25 min (mean 20.13 min) and for intranasal midazolam from 8 to 18 min (mean 12.07 min).There was a statistically significant difference (p \ 0.001) between the time of onset of sedation, with intranasal administration of midazolam being significantly quicker than oral administration of midazolam.
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Eur Arch Paediatr Dent Fig. 3 Distribution of patients according to Ellis Sedation Score (rating movements) recorded at the time of administration of local anaesthetic. Inference: Chi square: 0.594, p = 0.743 (p \ 0.05 is considered to be statistically significant). Hence, there was no statistically significant difference in the Ellis Sedation Score between the two groups
Distribuon of Paents according to Ellis Sedaon Score(Rang Movements) 70 63.33 60
N=30 for each group Ellis Sedaon Score 1 2 3 4 5
60 50 40
Intra nasal Oral 7 8 18 19 5 3 0 0 0 0
% INTRA NASAL
26.67
30 23.33
ORAL 16.67
20
10 10
0
0
0
0
0 1 –Total co-operaon
2–small amount of limb movement, no restlessness
3 – more movement, some restlessness and anxiety
4 –considerable restlessness, anxious
5 –severe limb movements, too un co-operave
Ellis sedaon score
Distribuon of Childs Movements and Crying using Houpt behaviour Rang 60
Scale
53.33
INTRA NASAL 50
46.7
ORAL
46.7
40 40
%
Fig. 4 Distribution of child’s rating movement and crying category using Houpt Behaviour Rating Scale. Inference: Chi square: 0.287, p = 0.866 (p \ 0.05 is considered to be statistically significant). The difference between the two groups pertaining to movements and crying during treatment is not statistically significant
30
N=30 for each group Crying category 1 2 3 4
Intra nasal 0 3 12 16
Oral 0 2 14 14
20
10
6.67 0
6.67
0
0 1 – Violent movements and hysterical crying
2 – Connuous movements and 3 – Controllable movements and 4 – No movements and no crying persistent crying mild crying
Child's crying using Houpt behaviou rang scale
The difference in alertness (Fig. 5) was much higher in Group N than in Group O, suggestive of faster recovery using intranasal midazolam. The difference between two groups was statistically significant (p value \0.05). Nasal administration diffuses directly into the systemic circulation, owing to the rich vascularity of the nasal mucosa (Fukuta et al. 1993). There is rapid absorption of midazolam with no hepatic first-pass effect (Walbergh et al. 1991). However, oral route of midazolam administration is associated with delayed onset of drug action, unpredictable effect of the drug, variability in drug absorption across the gastrointestinal mucosa and hepatic first-pass effect (Braham et al. 1993).
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The recommended dosage of midazolam used orally is in the range of 0.2–1.0 mg/kg body weight (Singh et al. 2002). In the present study, as midazolam was used in combination with nitrous oxide, it was decided to select the lowest dosage of midazolam with the highest therapeutic index for the procedure. This was set at 0.2 mg/kg body weight. Since midazolam has a high hepatic clearance and the intranasal route avoids first-pass hepatic metabolism resulting in increased bioavailability (Davis et al. 1995), a lower dose of intranasal midazolam as compared to oral midazolam would be required. The dosage for intranasal midazolam was selected at 0.1 mg/kg body weight. Although there have been attempts to investigate the
Eur Arch Paediatr Dent Fig. 5 Distribution of patients according to rating for alertness using Houpt Behaviour Rating Scale recorded post-dental treatment and removal of nasal mask. Inference: Chi square: 9.02, p = 0.003 (p \ 0.05 is considered statistically significant). The difference in alertness was much higher in the intranasal midazolam group. The difference between two groups was statistically significant
Distribuon of Paents according to Rang for Alertness (Houpt behavior Rang Scale): 120 INTRA NASAL ORAL
96.67
100
80 N=30 for each group Rang sleeping 1 2 3
%
66.67 60
40
Intra nasal Oral 10 1 20 29 0 0
33.33
20 3.33
0
0
0 1 – Alert
Fig. 6 Distribution of patients according to overall behaviour recorded using Houpt Behaviour Rating Scale recorded at the end of each dental appointment. Inference: Chi square: 2.11, p = 0.348 (p \ 0.05 is considered to be statistically significant). Thus, the difference between the overall behaviour in the two groups is not statistically significant
3 - Asleep
Distribuon of Paents according to Overall Behavior
80 70
2 – Drowsy Rang for Alertness
73.33 INTRA NASAL ORAL 56.67
60 50 % 40 30
N=30 for each group Overall behavior 1 2 3 4 5 6
Intra nasal 0 0 0 2 17 11
Oral 0 0 0 2 22 6
36.67
20 20 6.67 6.67
10 0
0
0
0
0
0
0 1 - Aborted
2 - Poor
effects of oral and intranasal midazolam in paediatric dental patients (Hartgraves and Primosch 1994; Lee-Kim et al. 2004), to date there has been no randomised clinical trial to compare the effects of oral and intranasal midazolam at a dosage of 0.2 mg/kg body weight and 0.1 mg/kg body weight, respectively. The combination of midazolam and nitrous oxide proved to be an effective combination, resulting in good to excellent behaviour in uncooperative children. The operator was able to carry out the dental treatment
3 - Fair 4 - Good Overall behavior
5 – Very good
6 - Excellent
successfully at all the 60 appointments. No adverse reactions were reported and the vital parameters were within normal physiological limits. Although there was crying and movement reported at 12 appointments during treatment procedures, the potential amnesic effect of midazolam may have formed a positive carryover effect and the patient reported back at subsequent appointment with positive reinforcement of behaviour. Midazolam administered through the intranasal route was observed to be as effective as the oral route at a lower dosage.
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Conclusion The routes of midazolam administration: oral midazolam syrup and the intranasal midazolam spray are well accepted by children and are easy to administer by the dentists. The intranasal route of midazolam administration has a quick onset of action and a quick recovery of the patient from sedation as compared to the oral route of midazolam administration. Midazolam administered through the intranasal route is as effective as the oral route at a lower dosage. Therefore, it is an effective alternative to the oral route for a paediatric dental setup.
References Al-Zahrani AM, Wyne AH, Sheta SA. Comparison of oral midazolam with a combination of oral midazolam and nitrous oxide– oxygen inhalation in the effectiveness of dental sedation for young children. J Indian Soc Pedod Prev Dent. 2009;27(1):9–16. Averley PA, Lane I, Sykes J, et al. An RCT pilot study to test the effects of intravenous midazolam as a conscious sedation technique for anxious children requiring dental treatment—an alternative to general anaesthesia. Br Dent J. 2004;197(9):553–8 discussion 549. Braham RL, Bogetz MS, Kimura M. Pharmacologic patient management in pediatric dentistry: an update. ASDC J Dent Child. 1993;60(4–5):270–80. Council of European. Dentists: the use of nitrous oxide inhalation sedation in Dentistry. 2012. http://www.omd.pt/noticias/2012/ 06/201205cedsedacaoconsciente.pdf. Accessed 24 Sept 2014. Davis PJ, Tome JA, McGowan FX Jr, et al. Preanesthetic medication with intranasal midazolam for very brief pediatric surgical procedure: effect on recovery and hospital discharge time. Anesthesiology. 1995;82:2–5. EAPD Guidelines on Sedation in Paediatric Dentistry. 2005. http:// www.eapd.gr/dat/5CF03741/file.pdf. Accessed 24 Jan 2012. Ellis S. Response to intravenous midazolam sedation in general dental practice. Br Dent Jl. 1996;180:417–20. Fukuta O, Braham RL, Yanase H, Kurosu K. The sedative effects of intranasal midazolam administration in the dental treatment of pediatric patients. Part-1. J Clin Pediatr Dent. 1993;18:259–65. Haas DA. Oral and inhalation conscious sedation. Dent Clin North Am. 1999;43(2):341–59. Hartgraves PM, Primosch RE. An evaluation of oral and nasal midazolam for pediatric dental sedation. ASDC J Dent Child. 1994;61:175–81.
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Houpt MI, Weiss NJ, Koenigsberg SR, Desjardins PJ. Comparison of chloral hydrate with and without promethazine in the sedation of young children. Pediatr Dent. 1985;7:41–6. Houpt M, Manetas C, Joshi A, Desjardins P. Effects of chloral hydrate on nitrous oxide sedation of children. Pediatr Dent. 1989;11:26–9. Houpt MI, Kupietzky A, Tofsky NS, Koenigsberg SR. Effects of nitrous oxide on diazepam sedation of young children. Pediatr Dent. 1996;18:236–41. Lee-Kim SJ, Fadavi S, Punwani I, Koerber A. Nasal versus oral midazolam sedation for pediatric dental patients. J Dent Child (Chic). 2004;71(2):126–30. Malamed SF, Quinn CL. Sedation: a guide to patient management. 3rd ed. St. Louis: Mosby Year Book; 1995. p. 99–137. Nathan JE, Vargas KG. Oral midazolam with and without meperidine for management of the difficult young pediatric dental patient: a retrospective study. Pediatr Dent. 2002;24:129–38. Papineni A, Lourenc¸o-Matharu L, Ashley PF. Safety of oral midazolam sedation use in paediatric dentistry: a review. Int J Pediatr Dent. 2014;24(1):2–13. Rakaf HA, Bello LL, Turkustani A, Adenubi JO. Intra-nasal midazolam in conscious sedation of young pediatric dental patients. Int J Pediatr Dent. 2001;11:33–40. 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(1):7–14. Singh N, Pandey RK, Saksena AK, Jaiswal IN. A comparative evaluation of oral midazolam with other sedatives as premedication in pediatric dentistry. J Clin Pediatr Dent. 2002;26(2):161–4. Smith BM, Cutilli BJ, Saunders W. Oral midazolam: Pediatric conscious sedation. Compend Contin Educ Dent 1998;19:586–88, 590, 592. Walbergh EJ, Wills RJ, Eckhert J. Plasma concentrations of midazolam in children following intranasal administration. Anesthesiology. 1991;74(2):233–5. Wilson KE, Welbury RR, Girdler NM. A randomised, control crossover trial of oral midazolam and nitrous oxide for paediatric dental sedation. Anaesthesia. 2002;57(9):860–7. Wilson KE, Girdler NM, Welbury RR. Randomized, controlled, cross-over clinical trial comparing intravenous midazolam sedation with nitrous oxide sedation in children undergoing dental extractions. Br J Anaesth. 2003;91:850–6. Wood M. The safety and efficacy of intranasal midazolam sedation combined with inhalation sedation with nitrous oxide and oxygen in paediatric dental patients as an alternative to general anaesthesia. SAAD Dig. 2010;26:12–22.
ORIGINAL ARTICLE
A comparison of the sedative effect of oral versus nasal midazolam combined with nitrous oxide in uncooperative children I. E. Musani1 • N. V. Chandan1
Received: 3 February 2015 / Accepted: 26 March 2015 European Academy of Paediatric Dentistry 2015
Abstract Aim To compare a combination of oral midazolam (0.2 mg/kg body weight) and nitrous oxide–oxygen sedation with a combination of intranasal midazolam (0.1 mg/ kg body weight) and nitrous oxide–oxygen sedation for effectiveness, patient acceptability and safety profile in controlling the behaviour of uncooperative children. Methods Thirty children, 4–10 years of age, referred for dental treatment were included in the study with a crossover design. Each patient was sedated with a combination of either oral midazolam and nitrous oxide–oxygen sedation or intranasal midazolam and nitrous oxide–oxygen sedation at subsequent dental treatment visits. During the treatment procedure, the study recorded scales for drug acceptability, onset of sedation, acceptance of nasal mask, sedation, behavioural, safety, overall behaviour and alertness. Results The grade of acceptability of midazolam in both groups was consistently good. There was a significant difference (p \ 0.001) in the time of onset of sedation, which was significantly quicker with the intranasal administration of midazolam. The mean time of onset for oral midazolam was 20.1 (17–25) min and for intranasal midazolam 12.1 (8–18) min. The efficacy profile of the present study included: acceptance of nasal mask, sedation score, crying levels, motor movements and overall behaviour scores. The results did not show any statistically
& N. V. Chandan [email protected] 1
Department of Pediatric and Preventive Dentistry, M.A. Rangoonwala Dental College and Research Centre, Pune, 2390-B, K.B. Hidayatullah Road, Azam Campus, Camp, Pune 411001, Maharashtra, India
significant differences. All the parameters were highly satisfactory. The difference in alertness was statistically significant (p value \0.05), being higher in the intranasal group than the oral group and suggestive of faster recovery using intranasal midazolam. Conclusion The intranasal route of midazolam administration has a quick onset of action and a quick recovery of the patient from sedation as compared to the oral route of midazolam administration. Midazolam administered through the intranasal route is as effective as the oral route at a lower dosage. Therefore, it is an effective alternative to oral route for a paediatric dental situation. Keywords Intranasal midazolam Oral midazolam Nitrous oxide Local anaesthetic Uncooperative children Behaviour management
Introduction Behaviour management in children is the cornerstone that sets apart paediatric dentistry from the other dental specialities. The technical proficiency of a dentist alone is of little merit unless the child cooperates or at least passively accepts dental treatment. If psychological behaviour management techniques alone prove unproductive, pharmacological sedative agents should be considered as an effective option (Al-Zahrani et al. 2009). ‘‘The standard sedative technique’’ in paediatric dentistry at present is nitrous oxide–oxygen inhalation sedation (Council of European Dentists 2012). Its favourable properties include ease and rapidity of induction, quick recovery with no aftereffects, flexibility of dosage control and the absence of any systemic metabolism. However, it is a very technique-sensitive procedure and when used alone
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may prove insufficient in the treatment of very fearful children. Several studies have indicated that when other sedative agents are added to nitrous oxide, disruptive behaviours decrease. Nitrous oxide has been shown to potentiate the effect of benzodiazepines (Houpt et al. 1989, 1996; Hartgraves and Primosch 1994; Al-Zahrani et al. 2009). Midazolam, a newer-generation benzodiazepine, ‘‘potentially the ideal sedative agent’’, (Papineni et al. 2014) has a wide toxic/therapeutic ratio and safety margin (AlZahrani et al. 2009). The relatively short half-life of midazolam produces rapid onset and recovery and is well suited for ambulatory patients in dental practice (Wilson et al. 2002). However, its short duration of action makes its use limited (Nathan and Vargas 2002). Therefore, it would be a appropriate to combine the ‘‘standard technique’’ with the ‘‘potentially ideal sedative’’ to obtain the added benefits of both these agents. Midazolam can be administered through various routes. In a paediatric dental situation, oral and intranasal routes would be more suitable as they eliminate the need for painful injections that may increase anxiety in children. The question still remains as to which is the better route of administering midazolam as a sedative agent. Therefore, this study aimed to compare a combination of oral midazolam syrup (dosage 0.2 mg/kg body weight) and nitrous oxide inhalation sedation with a combination of intranasal midazolam spray (dosage 0.1 mg/kg body weight) and nitrous oxide inhalation sedation in terms of effectiveness, patient acceptability and safety profile.
Methods Study design The study was carried out in the Department of Paediatric and Preventive Dentistry at M.A. Rangoonwala Dental College and Research Centre, Pune (India). The study had a randomised crossover design where 30 paediatric patients aged 4–10 years, requiring dental treatment, were included. The children were divided randomly on the basis of odd and even numbers into two groups. Each child received two different routes of drug administration, that is, oral midazolam and intranasal midazolam in combination with nitrous oxide–oxygen sedation as follows at two subsequent dental visits. The two groups were as follows: Group O: 15 patients who received oral midazolam syrup and nitrous oxide inhalation sedation on their first visit, followed by intranasal midazolam and nitrous oxide inhalation sedation on their second visit. Group N: 15 patients who received intranasal midazolam spray and nitrous oxide on their first visit, followed by
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oral midazolam and nitrous oxide inhalation sedation on their second visit. The dental treatment was provided by the same operator (IM). Rating of behaviour, monitoring of the patient and recording of behaviour rating scores throughout the procedure were performed by the same observer (NC) during the two dental treatment visits. The study commenced only after due permission and clearance was obtained from the Institutional Review Board and Ethical Committee. Patients were selected as per the following inclusion and exclusion criteria. Inclusion criteria • • • •
Child within the age group of 4–10 years. Behaviour category: Frankl Behaviour Rating Scale negative and definitely negative. ASA 1 category (normal, healthy patient). Needing dental treatment in at least two quadrants with the use of local analgesia during the procedure. The dental treatment could include deep restorations, pulpectomy, pulpotomy or extractions.
Exclusion criteria • • •
•
Any respiratory condition that makes breathing through the nose difficult. Cognitive impairment Patients who have recently used medication such as erythromycin or anticonvulsants that might interfere with the pharmacokinetics of midazolam. Any history of any systemic disease.
On the day of assessment, the treatment protocol and its advantages and disadvantages were explained. Verbal and written instructions were given to the parent/guardian. Fasting instructions were given emphasising no solid foods or nonclear liquids 4 h before the sedation procedure as per European Academy of Paediatric Dentistry Guidelines (2005). Informed consent for the treatment was obtained from the parent/guardian on the day of sedation. Each child had to undergo a physical examination by the anaesthetist on the day of sedation for medical clearance. The patient’s weight was taken with an electronic weighing scale. Baseline heart rate, oxygen saturation and blood pressure were recorded. Midazolam administration The dosage of oral midazolam was calculated for each child at 0.2 mg/kg body weight. Oral midazolam was administered in syrup form, i.e. midazolam hydrochloride syrup (Mezolam—manufactured by Neon Laboratories,
Eur Arch Paediatr Dent Table 1 Assessment of a patient’s acceptability of the drug
Table 3 Ellis Sedation Score
1—Good
Child accepts the drug without any refusal or resistance
Score 1
No uninvited limb movement. Total co-operation—no restlessness
2—Fair
Child accepts the drug administration with some verbal resistance
Score 2
Small amount of uninvited limb movement. Still total cooperation and no restlessness
3—Poor
Child accepts the drug with some physical resistance
4—Refused, crying
Child refuses administration of drug and it is possible only after much persuasion
Score 3
More uninvited limb movement. Small degree of restlessness and anxiety. Patient less co-operative. Still able to perform all dental procedures
Score 4
Considerable degree of limb movement. Perhaps, unhelpful head movements. Poor co-operation. Patient quite restless and anxious. Able to perform only basic dentistry. Advanced delicate work not possible
Score 5
Restless, anxious and limb movements severe. Impossible to perform any dentistry. Not determined = too uncooperative
Table 2 Level of co-operation during acceptance of the nasal mask Score 0
No co-operation at all—will not sit in the dental chair
Score 1
Patient sits in the chair but does not allow an intraoral examination with a mirror and does not accept the nasal mask
Score 2
Sits in the chair and allows an intraoral examination, but does not accept the nasal mask
Score 3
The patient sits in the chair, allows intraoral examination and accepts the nasal mask—very co-operative
Ltd.) Each millilitre of syrup contains 2 mg of midazolam. Oral midazolam was administered accurately using a 5 ml disposable syringe. Intranasal midazolam was administered in the form of a nasal spray (Midacip Nasal Spray manufactured by Cipla Ltd.) The dosage for intranasal midazolam was calculated at 0.1 mg/kg body weight. Each puff of the nasal spray delivered 0.5 mg of midazolam and was administered in both the nostrils. The dosage of intranasal midazolam was rounded off to the higher 0.5 dosage, as it was difficult to give a fraction of a spray. During the administration of the drug (oral/intranasal), the patient’s acceptability of the drug was evaluated using four code levels (Rakaf et al. 2001) (Table 1). Each child was made to wait in the waiting room with his/her parents until signs of onset of sedation were observed. This was defined as a relaxed appearance with slurring and slowing of speech. The time taken for onset of sedation was recorded. Prior to nitrous oxide inhalation sedation, each patient was then moved into the sedation room and seated on the dental chair. The nasal mask was fitted to the patient. The level of co-operation during acceptance of the nasal mask (Wood 2010) by the patient was evaluated using a fourpoint scale (Table 2). During nitrous oxide inhalation sedation, nitrous oxide/ oxygen sedation was administered using a Matrx Porter Digital relative analgesia machine. The nitrous oxide was titrated in 10 % increments to a final concentration of nitrous oxide 30 % and oxygen 70 %. A maximum concentration of nitrous oxide of 30 % was chosen during local
analgesia administration. Nitrous oxide at levels of 20–30 % provides adequate sedation, without the risk of oversedation (Wilson et al. 2003). Once nitrous oxide 30 % had been reached, injection of 2 % lidocaine (with adrenalin)—local analgesia—was administered to the patient. During the administration of local anaesthesia, Ellis Sedation Score was employed to record the level of sedation (Ellis 1996) (Table 3). The behaviour of the patient during treatment was observed for the each child’s crying and motor movements. This was graded using a modified version of the Houpt Behaviour Rating scale (Houpt et al. 1985; Al-Zahrani et al. 2009) (Table 4). A safety scale was used to record any adverse reaction such as deep/prolonged sedation, sneeze/cough/hiccough, vomiting, allergic reaction and respiratory depression that might occur during treatment (Shashikiran et al. 2006) (Table 5). Once the required dental treatment was completed, 100 % oxygen was administered to the patient for 3 min. The sensory perception levels (alertness) and overall behaviour of every child at the end of the dental procedure and sedation were evaluated using a modified version of the Houpt Behaviour Rating scale (Houpt et al. 1985; AlZahrani et al. 2009) (Table 4). On completion of treatment, each child was transferred to the recovery room. The patient was required to remain in the recovery area for 20–90 min, and then discharged after assessing the following (Smith et al. 1998): • • • • •
Vital signs within normal limits. Response to verbal stimulation. Absence of any signs and symptoms of compromised respiration. State of wakefulness without any adverse conditions. Able to walk unaided.
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Eur Arch Paediatr Dent Table 4 Houpt Behaviour Rating Scale
Table 5 Safety scale
Rating for movement during treatment
Vomiting score
1.
Violent movement interrupting treatment
2.
Continuous movement making treatment difficult
3.
Controllable movement that does not interfere with treatment
4.
No movement
Rating for crying during treatment
Score 0
Unsatisfactory: vomiting present
Score 1
Satisfactory: no vomiting
Allergic reaction Score 0
Unsatisfactory: allergic reaction present
Score 1
Satisfactory: no allergic reactions
1.
Hysterical crying that demands attention
2.
Continuous, persistent crying that makes treatment difficult
Score 0
0—Unsatisfactory: sneezing/coughing/hiccough present
3.
Intermittent, mild crying that does not interfere with treatment
Score 1
1—satisfactory: no sneezing/coughing/hiccough
4.
No crying
Rating for alertness 1.
Fully awake, alert
2.
Drowsy, disoriented
3.
Asleep
Rating for overall behaviour 1. Aborted, no treatment rendered 2.
Poor—treatment interrupted, only partial treatment completed
3.
Fair—treatment interrupted, but eventually all completed
4.
Good—difficult, but all treatment performed
5.
Very good—some limited crying or movement, or movement
6.
Excellent—no crying or movement
The next appointment for the patient was scheduled after 7 days when the same protocol was followed. Data analysis The collected data as per the above-mentioned protocol was entered in M.S. Excel and a master table was created. Further analysis was by using IBM-SPSS version 20. Statistical analysis used Chi square test to assess the scores obtained between the two groups. A p value of p \ 0.05 was considered for statistical significance.
Sneezing/coughing/hiccough.
Respiratory depression Score 0
Unsatisfactory: too deep/too long sedation
Score 1
Satisfactory: easily arousable-optimum sedation
Prolonged/deep sedation Score 0
Unsatisfactory: prolonged/deep sedation present
Score 1
Satisfactory: no prolonged/deep sedation
midazolam ranged from 17 to 25 min (mean 20.1 min) and intranasal midazolam ranged from 8 to 18 min (mean 12.1 min). There was a significant difference (p \ 0.001) between the time of onset of sedation, with intranasal administration of midazolam being significantly quicker than oral administration of midazolam. The efficacy profile (Figs. 2, 3, 4, 5, 6) of the present study included level of cooperation for acceptance of nasal mask, sedation score, crying levels, motor movements and overall behaviour; the results did not show any statistical significant differences. As for the safety profile, all the parameters recorded for safety analysed either individually or together showed no adverse effects in either Group N or Group O. The difference in alertness (Fig. 5) was much higher in Group N than in Group O suggestive of faster recovery using intranasal midazolam. The difference between the two groups was statistically significant (p value \0.05).
Results Discussion Thirty children (19 males and 11 females) age 4–10 years were selected for the study as per inclusion and exclusion criteria. Patient’s drug acceptability All the 30 children accepted both oral midazolam syrup and intranasal midazolam atomised spray readily during subsequent dental treatment visits. The grade of acceptability in both the groups was consistently good (100 %) without any resistance. The time of onset of oral and intranasal midazolam sedation is shown in Fig. 1. The onset of action for oral
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Children requiring invasive procedures should be supported with appropriate anxiety management for effective dental treatment. It is widely accepted that conscious sedation is safer than general anaesthesia (Averley et al. 2004). Therefore, conscious sedation should be considered as an alternative to general anaesthesia wherever possible. The present study attempted to use a combination of nitrous oxide–oxygen inhalation sedation and midazolam to achieve conscious sedation in children aged 4–10 years as an adjunct to behaviour management. Most practitioners prefer the use of the oral route of drug administration due to its record of high safety, minimal
Eur Arch Paediatr Dent Fig. 1 Distribution of patients according to time of onset of midazolam sedation (oral midazolam and intranasal midazolam). Inference: Chi square: 56.4, p = 0.000 (p \ 0.05 is considered to be statistically significant). Thus, there was a significant difference in the time of onset of sedation, being significantly lower in the intranasal administration of midazolam. This indicates the better efficacy of this route. The mean time of onset was 12.1 min for intranasal and 20.1 min for oral sedation
Distribuon of Paents according to Time of Onset of Sedaon 70 60
53.33
60
INTRA NASAL
N=30 for each group Time of Onset 8 – 10 11 – 13 14 – 16 17 – 19 20 – 22 23 – 25
Intra nasal 7 16 6 1 0 0
Oral 0 0 0 10 18 2
ORAL
50 40 %
33.33 30 23.33
20
20
6.67
10
3.33 0
0
0 8-10
0 11-13
0 14-16
17-19
0
20-22
23-25
Time of Onset of Sedaon (min)
Fig. 2 Distribution of patients according to the level of cooperation recorded at the time of acceptance of the nasal mask. Inference: Chi square: 2.96, p = 0.085 (p \ 0.05 is considered to be statistically significant). Thus, there was no significant difference in the level of co-operation in the two groups
Distribuon of Paents according to Level of Co-operaon 120 INTRA NASAL 100
N=30 for each group Level Of Co-operaon 0 1 2 3
ORAL
80
Intra nasal Oral 0 0 0 0 5 1 25 29
96.67 83.33
% 60
40
16.67
20
3.33 0
0
0
0
0 0– will not sit in dental chair
1 –sits but disallows intraoral examinaon
2 –sits but does not accept the mask easily
3 – accepts everything, very co-operave
Level of Co-operaon
complications and its easy acceptance by children (Malamed and Quinn 1995). Midazolam has a disagreeable taste that is difficult to mask. Children may refuse to swallow the drug or may expectorate some of it resulting in abandoning of the sedation (Braham et al. 1993). The present study utilised a commercially available midazolam hydrochloride syrup formulation. The formulation contains a flavoured syrupy base that masked the bitter taste of midazolam and was readily accepted by the paediatric patients without any form of resistance. Intranasal midazolam was assessed as an alternative to oral midazolam in combination with nitrous oxide for invasive dental procedures in a paediatric dental setup. The use of nasal drops is associated with a burning sensation
that may require the need for administration of topical anaesthesia (Haas 1999) to eliminate the need for this intranasal midazolam was administered in the form of a nasal spray. It was observed that the nasal spray was well accepted by the patients without any form of resistance. When evaluating the two different modes of administration, it is important to take into account the time factor for the onset of sedation and time of recovery. Onset of action for oral midazolam ranged from 17 to 25 min (mean 20.13 min) and for intranasal midazolam from 8 to 18 min (mean 12.07 min).There was a statistically significant difference (p \ 0.001) between the time of onset of sedation, with intranasal administration of midazolam being significantly quicker than oral administration of midazolam.
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Eur Arch Paediatr Dent Fig. 3 Distribution of patients according to Ellis Sedation Score (rating movements) recorded at the time of administration of local anaesthetic. Inference: Chi square: 0.594, p = 0.743 (p \ 0.05 is considered to be statistically significant). Hence, there was no statistically significant difference in the Ellis Sedation Score between the two groups
Distribuon of Paents according to Ellis Sedaon Score(Rang Movements) 70 63.33 60
N=30 for each group Ellis Sedaon Score 1 2 3 4 5
60 50 40
Intra nasal Oral 7 8 18 19 5 3 0 0 0 0
% INTRA NASAL
26.67
30 23.33
ORAL 16.67
20
10 10
0
0
0
0
0 1 –Total co-operaon
2–small amount of limb movement, no restlessness
3 – more movement, some restlessness and anxiety
4 –considerable restlessness, anxious
5 –severe limb movements, too un co-operave
Ellis sedaon score
Distribuon of Childs Movements and Crying using Houpt behaviour Rang 60
Scale
53.33
INTRA NASAL 50
46.7
ORAL
46.7
40 40
%
Fig. 4 Distribution of child’s rating movement and crying category using Houpt Behaviour Rating Scale. Inference: Chi square: 0.287, p = 0.866 (p \ 0.05 is considered to be statistically significant). The difference between the two groups pertaining to movements and crying during treatment is not statistically significant
30
N=30 for each group Crying category 1 2 3 4
Intra nasal 0 3 12 16
Oral 0 2 14 14
20
10
6.67 0
6.67
0
0 1 – Violent movements and hysterical crying
2 – Connuous movements and 3 – Controllable movements and 4 – No movements and no crying persistent crying mild crying
Child's crying using Houpt behaviou rang scale
The difference in alertness (Fig. 5) was much higher in Group N than in Group O, suggestive of faster recovery using intranasal midazolam. The difference between two groups was statistically significant (p value \0.05). Nasal administration diffuses directly into the systemic circulation, owing to the rich vascularity of the nasal mucosa (Fukuta et al. 1993). There is rapid absorption of midazolam with no hepatic first-pass effect (Walbergh et al. 1991). However, oral route of midazolam administration is associated with delayed onset of drug action, unpredictable effect of the drug, variability in drug absorption across the gastrointestinal mucosa and hepatic first-pass effect (Braham et al. 1993).
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The recommended dosage of midazolam used orally is in the range of 0.2–1.0 mg/kg body weight (Singh et al. 2002). In the present study, as midazolam was used in combination with nitrous oxide, it was decided to select the lowest dosage of midazolam with the highest therapeutic index for the procedure. This was set at 0.2 mg/kg body weight. Since midazolam has a high hepatic clearance and the intranasal route avoids first-pass hepatic metabolism resulting in increased bioavailability (Davis et al. 1995), a lower dose of intranasal midazolam as compared to oral midazolam would be required. The dosage for intranasal midazolam was selected at 0.1 mg/kg body weight. Although there have been attempts to investigate the
Eur Arch Paediatr Dent Fig. 5 Distribution of patients according to rating for alertness using Houpt Behaviour Rating Scale recorded post-dental treatment and removal of nasal mask. Inference: Chi square: 9.02, p = 0.003 (p \ 0.05 is considered statistically significant). The difference in alertness was much higher in the intranasal midazolam group. The difference between two groups was statistically significant
Distribuon of Paents according to Rang for Alertness (Houpt behavior Rang Scale): 120 INTRA NASAL ORAL
96.67
100
80 N=30 for each group Rang sleeping 1 2 3
%
66.67 60
40
Intra nasal Oral 10 1 20 29 0 0
33.33
20 3.33
0
0
0 1 – Alert
Fig. 6 Distribution of patients according to overall behaviour recorded using Houpt Behaviour Rating Scale recorded at the end of each dental appointment. Inference: Chi square: 2.11, p = 0.348 (p \ 0.05 is considered to be statistically significant). Thus, the difference between the overall behaviour in the two groups is not statistically significant
3 - Asleep
Distribuon of Paents according to Overall Behavior
80 70
2 – Drowsy Rang for Alertness
73.33 INTRA NASAL ORAL 56.67
60 50 % 40 30
N=30 for each group Overall behavior 1 2 3 4 5 6
Intra nasal 0 0 0 2 17 11
Oral 0 0 0 2 22 6
36.67
20 20 6.67 6.67
10 0
0
0
0
0
0
0 1 - Aborted
2 - Poor
effects of oral and intranasal midazolam in paediatric dental patients (Hartgraves and Primosch 1994; Lee-Kim et al. 2004), to date there has been no randomised clinical trial to compare the effects of oral and intranasal midazolam at a dosage of 0.2 mg/kg body weight and 0.1 mg/kg body weight, respectively. The combination of midazolam and nitrous oxide proved to be an effective combination, resulting in good to excellent behaviour in uncooperative children. The operator was able to carry out the dental treatment
3 - Fair 4 - Good Overall behavior
5 – Very good
6 - Excellent
successfully at all the 60 appointments. No adverse reactions were reported and the vital parameters were within normal physiological limits. Although there was crying and movement reported at 12 appointments during treatment procedures, the potential amnesic effect of midazolam may have formed a positive carryover effect and the patient reported back at subsequent appointment with positive reinforcement of behaviour. Midazolam administered through the intranasal route was observed to be as effective as the oral route at a lower dosage.
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Conclusion The routes of midazolam administration: oral midazolam syrup and the intranasal midazolam spray are well accepted by children and are easy to administer by the dentists. The intranasal route of midazolam administration has a quick onset of action and a quick recovery of the patient from sedation as compared to the oral route of midazolam administration. Midazolam administered through the intranasal route is as effective as the oral route at a lower dosage. Therefore, it is an effective alternative to the oral route for a paediatric dental setup.
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