|Year : 2012 | Volume
| Issue : 2 | Page : 109-114
Comparison of oral midazolam with oral tramadol, triclofos and zolpidem in the sedation of pediatric dental patients: An in vivo study
S Bhatnagar1, UM Das2, G Bhatnagar3
1 Department of Pedodontics and Preventive Dentistry, Jodhpur Dental College General Hospital, Rajasthan, India
2 Department of Pedodontics and Preventive Dentistry, VS Dental College & Hospital, Bangalore, India
3 Department of Periodontics, Jodhpur Dental College General Hospital, Rajasthan, India
|Date of Web Publication||23-Aug-2012|
40 Hospital Road, C-Scheme, Jaipur, Rajasthan 302 001
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Objective: oral sedation is the simplest and most convenient sedation method for managing uncooperative child patients because it is easy to administer and there is no need for nasal hood or injection. Oral midazolam is the most commonly used preanesthetic medication for children. When given in amounts between 0.5 and 0.75 mg/kg of body weight, oral midazolam has been found to be an effective sedative agent for pediatric outpatients. Tramadol is a synthetic, centrally acting analgesic indicated for moderate to severe pain. Chloral hydrate is one of the sedatives most commonly used, has excellent absorption, fast induction, and exert minimal effects on respiration. zolpidem is the most commonly prescribed hypnotic due to its clinical efficacy, safety, and ability to be well tolerated with patients. Materials and Methods: 60 anxious and fearful children who reported to the department were treated under conscious sedation for the accomplishment of dental treatment. Patients were randomly assigned to four groups. Statistical analysis was done using Kruskal Wallis Test and decision criterion was to reject the null hypothesis if the P-value is less than 0.05. Results: it was observed that there is a statistically significant difference in median scores recorded for the level of sedation between the different groups (P < 0.001). Conclusion: this study concluded that midazolam is the best drug for producing conscious sedation followed by tramadol and triclofos. Zolpidem was not able to produce a sufficient level of sedation and it cannot be supported as a sedative agent at the present dosage.
Keywords: Conscious sedation, midazolam, tramadol, triclofos, zolpidem
|How to cite this article:|
Bhatnagar S, Das U M, Bhatnagar G. Comparison of oral midazolam with oral tramadol, triclofos and zolpidem in the sedation of pediatric dental patients: An in vivo study. J Indian Soc Pedod Prev Dent 2012;30:109-14
|How to cite this URL:|
Bhatnagar S, Das U M, Bhatnagar G. Comparison of oral midazolam with oral tramadol, triclofos and zolpidem in the sedation of pediatric dental patients: An in vivo study. J Indian Soc Pedod Prev Dent [serial online] 2012 [cited 2019 Jul 19];30:109-14. Available from: http://www.jisppd.com/text.asp?2012/30/2/109/99980
| Introduction|| |
The field of pediatric dentistry beholds the greatest challenge among the various other branches of dentistry in providing dental care without inflicting any adverse psychological impact upon the child.  Uncooperative children present a unique problem for practitioners. Wide variation seems to exist among practitioners with respect to personality and management styles. Perception of what constitutes the most appropriate modality for a given situation will vary from clinician to clinician and region to region. Some clinicians are more authoritarian in persona and demeanour. Such individuals hold high expectation for child cooperation, require minimal or no need for pharmacological agents, and report considerable success managing difficult and challenging child behaviors, even among preschoolers.  For most patients, acceptable behavior can be achieved by traditional nonpharmacological management techniques; however, for a small number, conscious sedation is used. The primary use of pharmacological sedation is to modify or eliminate negative behavior and allow the child to cooperate,  improve the patient's behavior, reduce apprehension, minimize the negative psychological response toward treatment by reducing anxiety, and maximize amnesia potential so as to control behavior during dental procedure.  Sedative drugs may be administered by oral, inhalation, rectal, submucosal, intramuscular, or intravenous routes. The selection of techniques is often made as a matter of clinical judgment. Oral sedation is regarded by many dentists to be the simplest and most convenient sedation method for managing un-cooperative child patient since it is easy to administer and there is no need for nasal hood or injection. 
Oral midazolam is the most commonly used preanaesthetic medication for children.  The pharmacological actions of midazolam are identical to those of other benzodiazepines including sleep induction, sedation, anxiolysis, and amnesia.  Midazolam is rapidly absorbed in the gastrointestinal tract and produces its peak effect in 30 min, and has a short half-life of 1.5 h. This makes it a desirable drug for short procedures.  Tramadol is a synthetic, centrally acting analgesic indicated for moderate to severe pain. It has two complementary mechanisms of action: it binds with low affinity to m-opioid receptors and inhibits reuptake of nor-epinephrine and serotonin.  Oral chloral hydrate or triclofos is easy to administer and has a low incidence of adverse effects.  The normal oral dose is 50 mg/kg of body weight with a suggested range of 40 to 60 mg/kg. Following oral administration the onset of action of chloral hydrate is rapid, drowsiness or a rousable sleep usually developing within 30 to 45 min. Duration of action is 2 to 5 h. 
Introduced into clinical practice in the United States in 1992, zolpidem is now the most commonly prescribed hypnotic due to its clinical efficacy, safety, and ability to be well tolerated with patients.  Following oral administration; zolpidem is rapidly absorbed from the GI tract, having an onset of action of 45 min and a peak effect seen in 1.5 h. It is metabolized in the liver, with an elimination half life of 2.5 h. Zolpidem is converted into inactive metabolites eliminated primarily through renal clearance. Zolpidem is one of a few CNS depressants that is recommended for administration during pregnancy. 
| Materials and Methods|| |
The study was conducted out on anxious and fearful children who reported to the Department of Pedodontics and Preventive Dentistry. The Institutional review board approval was obtained for the study. Informed consent was obtained from the parents before starting any treatment or administration of the drug. Patients with physical status ASA-I and aged between 3-9 years were selected for the study. A controlled clinical trial was done. Sixty patients were treated under conscious sedation for the accomplishment of dental treatment. Patients were randomly assigned to four groups.
GROUP I- Patients receiving Midazolam (0.5 mg/kg body weight) orally.
GROUP II- Patients receiving Tramadol (2 mg/kg body weight) orally.
GROUP III- Patients receiving Triclofos (70 mg/kg body weight) orally.
GROUP IV- Patients receiving Zolpidem (0.4 mg/kg body weight) orally.
- Patients between the age group of 3-9 years.
- Patients who exhibited fearful or refractory behavior at previous dental appointments, as documented by Frankl's behavior rating scale.
- Patients are in good health with physical status in accordance with ASA-I.
- Patients undergoing dental procedures like extraction, restoration, and endodontic treatment with or without anesthesia.
An anesthetist was always present during the procedure to monitor the vitals of the children. To mask their bitter taste and maintain uniformity the drugs were mixed with chilled fruit juice. The vehicle and quantity was kept same for each group in order to avoid any fallacy in observation. No additional drug was administered if the children had spat the drug out or vomited. The number of children who spat out the drug was not recorded. The time of drug administration was noted. After administration of the drug child was shifted to a calm room where he/she was kept under continuous observation. When sedative effect started to appear the time of onset was recorded and treatment was started. Two more readings were recorded of vital signs at the interval of 10 min intraoperatively.
- Patients who are allergic to drugs used for sedation.
- Patients with hepatic, respiratory, cardiac, endocrine, or metabolic impairment.
- Special children or patients with psychological needs, including mental retardation.
The operating and supervising dentists evaluated the overall level of sedation for each session based on a rating scale consisting of scale ranging from 1 to 8 [Table 1].
The ease of treatment completion was rated as 0 (excellent), 1 (satisfactory), 2 (unsatisfactory), and 3 (aborted).
Once the treatment was completed patient was shifted in a quiet room free from disturbances for recovery. The time of recovery was noted. Patient was discharged after cardiovascular function was stable with patent airway and state of hydration adequate. Patient is well oriented to the surroundings, sit and stand unaided or with minimal assistance. Discharge of the children were done only after an anesthetist evaluation and time of discharge was noted.
| Results|| |
Statistical analysis was done using the Kruskal Wallis Test and decision criterion was to reject the null hypothesis if the P-value is less than 0.05. Otherwise we accept the null hypothesis. If there is a significant difference between the groups we carry out Mann- Whitney test to find out among which pair of groups there exists a significant difference.
Comparison of level of sedation
We observe that there is a statistically significant difference in median scores recorded for the level of sedation between the different groups (P < 0.001) [Table 2]. Higher mean and median score is recorded in Zolpidem group followed by Triclofos. Tramadol has a higher mean score compared to Midazolam but the median scores between the two are equal. The difference in median scores between the groups is found to be statistically significant [Figure 1].
It was observed that there is no significant difference between Midazolam and Tramadol with respect to the level of sedation (P > 0.05). The median score between them is equal.
Statistically significant difference is observed between Midazolam and Triclofos with respect to the level of sedation (P < 0.05). Triclofos has a higher median score compared to Midazolam and this difference is statistically significant.
Statistically significant difference is noticed between Midazolam and Zolpidem (P < 0.001). The median score for the level of sedation is found to be higher in Zolpidem compared to Midazolam and this difference is highly significant.
The difference in median score between Tramadol and Triclofos with respect to the level of sedation is found to be statistically significant (P < 0.001). The median score for the level of sedation was higher in Triclofos compared to Tramadol.
Higher median score for the level of sedation is noticed in Zolpidem compared to Tramadol and the difference in median scores between them is found to be statistically significant (P < 0.001).
The difference in median score with respect to level of sedation is found to be statistically significant between Ticlofos and Zolpidem (P < 0.01). Higher median score is recorded in Zolpidem compared to Triclofos.
Comparison of ease of treatment
We observe that there is a statistically significant difference in median scores recorded for the ease of treatment between the different groups (P < 0.01) [Table 3]. Higher mean and median score is recorded in Zolpidem group followed by Triclofos. Tramadol has a higher mean score compared to Midazolam but the median scores between the two are equal. The difference in median scores between the groups is found to be statistically significant [Figure 2].
Mann-Whitney test was carried out to found out the significant difference among the various groups.
No statistically significant difference is observed between Midazolam and Tramadol with respect to the ease of treatment (P > 0.05). The median score between them is equal.
No statistically significant difference is observed between Midazolam and Triclofos with respect to the ease of treatment (P > 0.05). The median score between them is equal.
Statistically significant difference is noticed between Midazolam and Zolpidem (P < 0.001). The median score for ease of treatment is found to be higher in Zolpidem compared to Midazolam and this difference is highly significant.
The difference in median score between Tramadol and Triclofos with respect to the level of sedation is not statistically significant (P > 0.05). The median score for the ease of treatment was equal in both Triclofos and Tramadol.
Higher median score for the ease of treatment is noticed in Zolpidem compared to Tramadol and the difference in median scores between them is found to be statistically significant (P < 0.001).
The difference in median score with respect to ease of treatment is found to be statistically significant between Ticlofos and Zolpidem (P < 0.01). Higher median score is recorded in Zolpidem compared to Triclofos.
| Discussion|| |
The oral route of administration is the most popular choice by pediatric dentists  for sedation. Haas  and colleagues compared the acceptance of oral chloral hydrate with oral midazolam for children 3 to 10 years of age, finding no difference in acceptance when both drugs were mixed with syrup and orange juice. The Chloral hydrate Midazolam Hydroxyzine oral regimen is a well-tolerated mixture, and they found that 91% of the children drank all their medicines from the cup at their first sedation visit. Keeping these facts in consideration we chose the oral route for administration of drug mixed in orange juice, since needle and nasal hood evoke anxiety and apprehension in majority of children. The level of sedation and the onset of action can be unpredictable at times because of the variability in absorption and metabolism.  considering this fact patients were monitored during the course of treatment. The success of sedation here was defined as achieving the restorative treatment planned even though there might have been some crying or movement. Everyone would not agree with this definition as it is argued that only if there is no crying or movement should the sedation be considered successful.
Davies and Waters  showed that a dose of 0.5 mg/kg is safe and effective in producing anxiolysis and amnesia for a wide range of accident and emergency procedures. They also stated that children remained more anxious in procedures involving the face. The results obtained for midazolam in this study are same as compared to studies done earlier. Midazolam was able to produce sufficient amount of sedation in all the patients in which the drug was administered.
Liebig first introduced chloral hydrate into practice in 1832 and it is the oldest and best studied sedative - hypnotic used in pediatric dentistry. Its primary pharmacological effect is CNS depression. Singh et al. used triclofos (70 mg/kg) as a sedative agent and concluded that midazolam gave better results as compared to triclofos in producing sedation. This study showed that there is statistically significant difference observed between midazolam and triclofos with respect to the level of sedation (P < 0.05). Although no significant difference was observed regarding ease of treatment among the two groups. Two of the patients slept off during the treatment, their vitals were monitored and were kept under observation till the time they recovered completely.
Tramadol's mode of action is not completely understood, at least two complementary mechanisms contribute to its effect. Tramadol's opioid activity results from low affinity binding of the parent compound to opioid receptors and higher binding of the M1 (0-desmethylated) metabolite.  Tramadol is an effective opiod analgesic that binds with low affinity to m-opioid receptors.  The drug is most commonly used as an analgesic and less commonly as sedative agent. Koirala et al. used the drug as a sedative in combination with midazolam and zolpidem separately in their study. This study took tramadol (2 mg/kg) as a sedative agent. The results obtained were significantly different from previous studies. Earlier studies and literature state tramadol as an analgesic with lesser sedative potential. In this study the tramadol produced level of sedation as equivalent to midazolam and triclofos. Tramadol was as effective as midazolam in producing the same level of sedation. The ease of treatment was also as good as midazolam and triclofos. No statistically significant difference was observed among the vitals before and after the completion of the treatment. This kind of a result calls for further research and studies to evaluate and prove tramadol as an effective sedative agent.
Zolpidem 10 or 20 mg when used as an oral premedication was found to be superior to placebo in causing sedation and reducing the anesthetic dose.  It was used by Koirala et al. as a sedative alone and in a combination with tramadol in their study. In this study, zolpidem was taken alone as a sedative. The results obtained by us were similar to the study conducted by Koirala et al.  The children were not sedated up to the threshold where any treatment can be done on them. Children receiving zolpidem showed sedative effect in an hour's time which is significantly different from the results obtained by Langtry and Benfield.  They showed that effect of the drug takes place in 15 to 20 min. In this study, drowsiness in some patients were observed whereas some remain active throughout the stay in the clinic. Some of the patients after administration of drug started speaking irrelevant things to their parents or to the operating dentist. Two patients were excluded from the study as they vomited the drug out in 30 min time after administration.
| Conclusion|| |
In conclusion, within the limits of the present study it can be stated. Midazolam(0.5 mg/kg) is the most effective drug in producing sedation for the pediatric dental patients. Tramadol (2 mg/kg) has produced the sedation level equivalent to midazolam and further studies are required to clearly establish this result specifically for the use of conscious sedation in pediatric dental patients. Triclofos (70 mg/kg) has shown good results during the treatment but it has not shown the same level of sedation as midazolam. Zolpidem a strong hypnotic has not given satisfactory result as a conscious sedation agent. Further studies at higher dosage have to be done to support this drug as a sedative agent in pediatrics dental patients.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]