|Year : 2006 | Volume
| Issue : 1 | Page : 7-14
Conscious sedation-An artist's science! An Indian experience with midazolam
ND Shashikiran, Subba V.V Reddy, CM Yavagal
Department of Paediatric Dentistry College of Dental Sciences, Davanagere, Rajiv Gandhi University of Health Sciences, Karnataka, Bangalore, India
N D Shashikiran
College of Dental Sciences Davanagere - 577 004, Karnataka
Source of Support: None, Conflict of Interest: None
The present study was undertaken to evaluate Midazolam as a Paediatric conscious sedative agent for a routine Indian dental setup and to compare its efficacy and safety when administered by intranasal and intramuscular routes, at a dosage of 0.2 mg/kg body weight. The present study was accomplished in two phases: Phase 1: Preliminary dose finding pilot study on 10 children. Phase 2: Single dose, randomized parallel clinical trial on 40 children between the ages of 2 and 5 years. These children were randomly assigned to two groups consisting of 20 subjects each. Group M, received Midazolam intramuscularly, while Group N received Midazolam intranasally. Both the intranasal and intramuscular groups showed highly significant decrease in crying levels, motor movements and sensory perception levels, post-sedation ( P < 0.001). Though both the routes almost matched each other in their efficacy and safety profiles, the intranasal route showed a significantly faster pharmacodynamic profile in terms of faster onset, peak and recovery times ( P <0.001). Midazolam could be safely and successfully employed by intranasal and intramuscular routes for Paediatric conscious sedation in a routine dental setup with basic facilities at a dosage of 0.2 mg/ kg body weight. Whenever the clinical situation warrants a faster action, peak and recovery, the intranasal route should be the obvious choice.
Keywords: Midazolam, Paediatric-Conscious Sedation
|How to cite this article:|
Shashikiran N D, Reddy SV, Yavagal C M. Conscious sedation-An artist's science! An Indian experience with midazolam. J Indian Soc Pedod Prev Dent 2006;24:7-14
|How to cite this URL:|
Shashikiran N D, Reddy SV, Yavagal C M. Conscious sedation-An artist's science! An Indian experience with midazolam. J Indian Soc Pedod Prev Dent [serial online] 2006 [cited 2020 Nov 26];24:7-14. Available from: https://www.jisppd.com/text.asp?2006/24/1/7/22830
Providing comprehensive oral care to young patients is a unique challenge because, a child's behavior can never become an alibi for a sub-standard work in the mouth., However, in spite of all its technical and materialistic advances, this science still seems to provide limited options for its uncooperative young clients because, for too long the guidance of children's behavior in dentistry has been limited to an art rather than a science. It is no wonder that today there are more dentists who are afraid of children than children who are afraid of dentists.,
Conscious sedation is a philosophy which has opened new vistas for managing uncooperative children in almost all the allied disciplines of healthcare and has rightly become popular with the busy modern day dentist in the developed countries.,,,
Midazolam has garnered a lot of attention in the recent years as a good paediatric sedative agent., ,, Hence, the present randomized clinical trial was undertaken to evaluate the efficacy and safety of Midazolam as a paediatric conscious sedative agent in a routine Indian dental setup and to compare its efficacy and safety when administered by intranasal and intramuscular routes, at a dosage of 0.2 mg/kg body weight.
| Materials and Methods|| |
The present study was accomplished in 2 distinct phases.
Phase I: Preliminary dose finding pilot study on 10 uncooperative children
Phase II: Single dose, randomised parallel clinical trial on 40 uncooperative children between the ages of 2 and 5 years, who attended the Paediatric dental clinics of College of Dental Sciences, Davanagere, India.
The research protocol for both the phases of the study was reviewed and approved by the ethical committee of the institution. The risks and possible discomforts, as well as the benefits of the procedure were explained to the parents and their informed consent was obtained before commencing the study.
During the first visit to the dental clinic, the child's behaviour was assessed by a senior paediatric dentist (professor who supervised the study) by employing the Frankl's behavioral rating scale. Children who were designated to have a negative or definitely negative behaviour and whose treatment necessitated the administration of a local analgesic injection, were recruited into the study. They were then randomly allocated to two groups of 20 subjects each. A comprehensive pre- anesthetic assessment (including tonsil and adenoid assessment, frequency of mouth breathing, snoring, speech hypo nasality, airway and chest examination by inspection & auscultation) was carried out and a paediatric physician's fitness certificate was obtained to ascertain the child's physiologic status for sedation. The weight of the child was noted as 1 kg less than the actual weight of the child fully clothed.
The parents then received comprehensive verbal as well as written instructions regarding the subsequent appointment scheduled under sedation. The parents were meticulously instructed to give the child a glass of milk or soft drink and one sandwich or small piece of cake atleast 2 hours before the commencement of the treatment under sedation. Based on the randomized group to which they belonged, children were either administered 0.2 mg/kg of Midazolam (Mezolam® - Neon Laboratories, Thane, India) intramuscularly with a super fine 0.30 x 8 mm needle insulin syringe (Dispovan® - Insulin syringe, Hindustan syringes and medical devices Ltd, Faridabad, India) or intanasally with a needle-less tuberculin syringe (Dispovan® - Tuberculin, Hindustan syringes and medical devices Ltd, Faridabad, India) [Figure - 1][Figure - 2]. After administration, the time taken for the initial onset of sedation, peak action and recovery times were noted. The clinical signs of onset of sedation included were initial drowsiness, calming, a glazed look or delayed eye movements, lack of muscle coordination, slurred speech or sleep like patterns.
After the initial onset of sedation, the operator who was blind to the route of administration, intermittently tried to inject the local analgesic solution until the child permitted to do so or offered little or no resistance. The time taken to accomplish the injection was noted as time to peak action. The child's crying, motor movements and sensory perception levels (alertness) were assessed at the base line (pre-sedation) and at 5 min intervals post - sedation, by using a modified version of the scale developed by Houpt et al [Table - 1]. The child's overall behavior for dental treatment was assessed at the baseline (pre-sedation) and at the end of the treatment (post - sedation) using a modified version of the scale developed by Fukuta et al [Table - 2]. The child's vital signs were recorded at the baseline and at every 5 min intervals, post sedation. 5 self-designed, dichotomised scales were used to record any adverse reactions such as Deep/Prolonged sedation, Sneeze/ Cough/ Hiccough, Vomiting, Allergic Reactions and Respiratory depression [Table - 3]. The validity of all the employed scales was checked before the start of the study.
Following the treatment, all patients were required to remain in the observatory area for at least 90mins. The return of the baseline sensory perception levels was noted as the recovery time. All children were discharged after ascertaining their response to verbal stimulation, absence of any signs or symptoms of compromised respiration and state of being fully awake without any adverse reactions. Verbal and written post sedation instructions were given to the parents along with emergency phone numbers of the clinic.
Interpretation and data analysis
All examinations and interventions were carried out by a single examiner who was calibrated before the study to ascertain the evidence of reliability (kappa value = 0.89). The Chi-square test was used to compare the intra-group pre and post sedation scores. For the inter-group comparison, the Mann-Whitney test was employed. Overall behaviour between the groups was assessed by Chi-square test. All the intra-group (pre and post) quantitative data were analysed by using the Student's paired 't' test while the unpaired 't' test was employed to compare quantitative data between the groups. For all the tests, a P -value of <0.05 was considered for statistical significance.
| Results|| |
Out of the 40 uncooperative young children selected for this study, there were 20 (11 boys, 9 girls) in Group M (intramuscular group) and 20 (08 boys, 12 girls) in Group N (intranasal group). None of the demographic variables showed any statistically significant difference between the two groups [Table - 4].
The efficacy profile of the present study included 4 major domains viz, crying, motor movements, sensory perception and overall behavior. Both the intramuscular and intranasal groups showed highly significant differences between the pre-sedation and post sedation scores ( P <0.001). A significant decrease in the crying levels, motor movements and sensory perception levels were observed and a highly significant improvement in the overall behaviour was seen ( P <0.001) [Figure - 3][Figure - 4][Figure - 5][Figure - 6][Figure - 7]. However, when the post-sedation outcomes and overall improvement in behaviour were compared between the two groups, the results did not show any statistical significant differences [Table - 5][Table - 6][Table - 7][Table - 8].
On the safety front, the cardio-respiratory profiles of both the groups showed good stability and the differences were statistically insignificant [Table - 9] [Figure - 8][Figure - 9]. Since there was not even a single incidence of vomiting or allergic reaction or respiratory depression in either group, all 40 patients got a 100% safety score with respect to these three adverse entities. 2 patients (10%) in the intramuscular group and 6 patients (30%) in the intranasal group showed instances of sneezing / coughing / hiccoughs after the administration of the sedative [Figure - 10]. The statistical differences between the two groups were again insignificant [Table - 10] Pharmacodynamically, the intranasal group consistently proved to be faster than the intramuscular group in terms of onset, peak and recovery times ( P <0.001), [Table - 11], [Figure - 11].
| Discussion|| |
Gone are the days when voice control and H.O.M.E. were liberally employed to manage an uncooperative child. Modern day Paediatric dentistry is expected to portray itself as something very pleasurable, refined and tech-savvy. Midazolam hydrochloride is a widely accepted and most widely employed benzodiazepine for conscious sedation in children.,,,,,
In the present study, a single- dose, parallel, randomized clinical design was employed to assess the safety and efficacy of Midazolam in typical Indian settings. In previous studies involving a comparison between 2 drugs or routes, a cross- over design was employed. We decided against a cross- over design as it has been suggested previously, that the psychological implications of the first appointment could have a bearing on the second. The absence of a placebo control group reflects the conviction of the investigators on the basis of published literature and personal experience in this institution that, withholding a needed drug for the sake of a study would not be justified in children. Hence, in the present study the behavior during the resting period (pre-sedation) was designated as the control behavior. We employed the intramuscular and intranasal routes as these are the most practical modes which can be incorporated in an Indian setup (Oral Midazolam is not available in India and most dentists are not comfortable with the Intravenous route and its aggressive monitoring requirements).
Almost all the previous studies on Midazolam sedation have insisted on the nil-per-oral doctrine, at least 2-3 hours preceding the sedation appointment.,,, This is the first study which has compared two routes of Midazolam administration without insistence on the nil per oral regimen so as to ascertain its practical outcomes and possible benefits for children.
In the present study, children in both the groups showed statistically significant improvement in their cooperation levels, with respect to crying, motor movement and sensory perceptions which are corroborative to previous studies.,,
Similarly, in both the groups, the overall behavior for dental treatment showed statistically significant improvement after sedation. These results are again in positive accordance to the results of the previous studies., Since our objective was to test Midazolam under normal Indian conditions, we employed routine tuberculin and insulin syringes for intranasal and intramuscular administrations respectively. The use of a nasal atomizer for intranasal or the use of bioject for intramuscular administration could have further boosted the results because of enhanced drug absorption from the respective sites.,, Since both the routes were equally successful, the intramuscular and intranasal groups did not show statistical differences in their respective efficacy profiles, which is in positive accordance to previous reports.
The safety aspects of Midazolam sedation in Children have been reiterated again by the present study. A relatively low dosage of Midazolam (0.2 mg/kg) which was selected through the initial pilot study (phase-I) could be attributable for this observed cardio-respiratory stability. The absence of nausea, vomiting and respiratory depression in 40 children who had a light snack/juice/cake before the sedation appointment, appears to be a good enough indicator to suggest that it may not be absolutely imperative to subject tiny children to the discipline of fasting 4-6 hours before sedation. This finding could open new vistas for conscious sedation of young uncooperative children who are not on empty stomach but have to be intervened on an emergency basis such as paediatric oral-maxillofacial trauma cases, endodontic emergencies etc.
Pharmacodynamic profile of this study indicates a mean onset time of 15.7± 2.0 mins and 10.8± 2.0 mins for intramuscular and intranasal routes respectively. These numbers are corroborative of earlier reports.,, The previous studies reporting a faster peak action of both intramuscular and intranasal Midazolam have mostly employed the agent as a premedicant before anesthesia.,,, However in dentistry the reaction of children to local analgesic injection seems a more objective measure of the adequacy of sedation rather than appreciation of the quality of the pre-medicated/sedated state. Hence in the present study the point at which L.A. injection was successfully accomplished was designated as the point of peak sedation, which explains why our values tend to be on the higher side of the time spectrum. It has also been suggested that the nasally administered drugs achieve a very rapid entry into the central nervous system by passing through the cribriform plate. This again explains why the intranasal group has shown a faster clinical pharmacodynamic activity when compared to the intramuscular group in the present study.
It is evident from the present study that Midazolam could be safely and successfully employed for conscious sedation in a routine Indian dental setup when used at a dosage of 0.2 mg/kg body weight. Nonetheless, it stills requires the operator to be adequately trained for the procedure. The study has also revealed that though the intramuscular and intranasal routes almost match each other in their efficacy & safety profiles, they show statistically significant differences pharmacodynamically, with regards to the onset of sedation, peak action and recovery periods, which are seen to be faster by the intranasal route. Hence, the potential of Midazolam as an ideal paediatric conscious sedative agent must be harnessed by meticulous planning and diligent utilization based on the needs of the individual children as well as demands of the prevailing clinical scenario.
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[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6], [Figure - 7], [Figure - 8], [Figure - 9], [Figure - 10], [Figure - 11]
[Table - 1], [Table - 2], [Table - 3], [Table - 4], [Table - 5], [Table - 6], [Table - 7], [Table - 8], [Table - 9], [Table - 10], [Table - 11]
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