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Year : 2008  |  Volume : 26  |  Issue : 3  |  Page : 97-101

Comparison of oral ketamine and oral midazolam as sedative agents in pediatric dentistry

1 Dept of Pediatric Dentistry, Post-Graduate Nair Hospital Dental College, Mumbai Central, Mumbai-400 008, Maharashtra, India
2 Nair Hospital Dental College, Mumbai Central, Mumbai-400 008, Maharashtra, India
3 Department of Anesthesiology Topiwala National Medical College, Dr. A. L. Nair Road, Mumbai Central, Mumbai-400 008, Maharashtra, India

Correspondence Address:
M Gandhi
B/8 New Purshotam Nagar, Jhari Mari Mandir Road, Bandra West, Mumbai-400 050
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0970-4388.43186

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The safe and effective treatment of uncooperative or combative preschool children with extensive dental needs is one of pediatric dentist's ongoing challenges. The traditional methods of behavior management are no longer acceptable to parents as they are not ready to spare more time for dental treatment of their children. Keeping this in mind, the present study was designed and carried out to evaluate the sedative effects of oral ketamine and oral midazolam prior to general anesthesia. Twenty uncooperative children in the age-group of 2-6 years were selected after thorough medical examination and investigations. Informed consent was obtained from the parent. This was a randomized double-blind study. An anesthesiologist administered either 0.5 mg/kg midazolam or 5 mg/kg ketamine orally. The heart rate, respiratory rate, and oxygen saturation were recorded at regular intervals. The sedation and anxiolysis scores were also recorded. The parents were asked to answer a questionnaire at the follow-up session the next day on the surgical experience of the parent and the child and side effects experienced, if any. When the data was subjected to statistical analysis, it was observed that both drugs resulted in adequate sedation at the end of 30 min, with oral midazolam providing significantly better anxiolysis. The heart rate and respiratory rate were marginally higher with oral ketamine. The questionnaire revealed a better response with oral midazolam; side effects were more prominent with oral ketamine.

Keywords: Oral ketamine, oral midazolam, sedative agents

How to cite this article:
Damle S G, Gandhi M, Laheri V. Comparison of oral ketamine and oral midazolam as sedative agents in pediatric dentistry. J Indian Soc Pedod Prev Dent 2008;26:97-101

How to cite this URL:
Damle S G, Gandhi M, Laheri V. Comparison of oral ketamine and oral midazolam as sedative agents in pediatric dentistry. J Indian Soc Pedod Prev Dent [serial online] 2008 [cited 2023 Feb 5];26:97-101. Available from: http://www.jisppd.com/text.asp?2008/26/3/97/43186

The safe and effective treatment of uncooperative or combative preschool children with extensive dental needs is one of pediatric dentistry's ongoing challenges. In today's world, parents are not comfortable with the traditional behavior management techniques such as intimidation, distraction, and voice control. Also, these techniques may cause traumatic memories in the child that may lead to lifelong dental phobias. A safe, fast, and nontraumatic dental treatment is needed and thus pharmacological management in the form of dental anesthesia comes into the picture. Earlier, parents were allowed to enter the dental operating theatre as the child was more apprehensive on separation from the parent, but entering the operatory made the parents anxious. [1],[2] This study was designed and carried out in the department of Pediatric and Preventive Dentistry, Nair Hospital Dental College, Mumbai. The aim was to study the overall behavior of the child during separation from the parent, IV line acceptance, and face mask acceptance, while continuously monitoring the heart rate, respiratory rate, and oxygen saturation. The recovery time was noted. The overall surgical experience of the child and the parents was assessed, along with side effects, if any.

The sedative drugs used as premedication for the study were oral ketamine 5 mg/kg and oral midazolam 0.5 mg/kg. The oral route was chosen as it is the most acceptable and familiar mode of drug administration. [3],[4],[5] Ketamine and midazolam are not available for oral administration in India and hence the syrup made was up of (levulose 40.5%, dextrose 34.02%, sucrose 1.9%, water 17.7%, and gum and dextrin) to bring volume to 10 ml; was mixed with honey this served to mask the bitter taste of the drug. [6]

Midazolam is an imidazobenzodiazepine that is given in the oral dose of 0.5-0.75 mg/kg. It has a short half-life of 1-2 h; high potency, i.e., twice that of diazepam; and a rapid onset of action (within 10-30 min). It has sedative and anxiolytic activities, provides antegrade amnesia, and also has anticonvulsant properties. [7],[8] Ketamine, on the other hand, is a 2-0-chlorophenyl 2-methylamine cyclohexine hydrochloride that is given in the oral dose of 3-10 mg/kg. The onset of action is rapid at 30 min. Ketamine provides well-documented anesthesia and analgesia. It has a wide margin of safety, as the protective reflexes are usually maintained. [9],[10]

   Materials and Methods Top

Twenty uncooperative children in the age-group of 2-6 years were selected from the outpatient department of Pediatrics and Preventive Dentistry, Nair Hospital Dental College. The procedure was explained to the parents and informed consent was obtained. The child was subjected to thorough medical and dental examinations and sent for chest x-ray and routine blood and urine investigations. The clinical examination was carried out by a pediatric dentist and an anesthesiologist. A randomized double-blind design was employed, with the anesthesiologist administering the sedative drug and the recording being done by the pediatric dentist, who was not aware of which drug was being administered.

The selection process followed strict inclusion criteria; these were as follows:

  1. Child in the age-group of 2-6 years
  2. Documentation of negative behavior: i.e., scored I and II on the Frankl's Behavior Rating Scale [Table 1]
  3. Categorized as ASA I and II [Table 2]
  4. No contraindication for the use of the medications to be administered
  5. Informed consent and accompanied by parents

Informed consent was taken from the parent after detailed explanation of the study protocol by the principal investigator. An opportunity to ask questions and address concerns was provided at the time of the explanation. The child was weighed and the parents were instructed to bring the child to the hospital an hour before the scheduled time; the parents were also instructed not to give the child anything to eat or drink 6 hrs prior to surgery. On the day of the treatment, the anesthesiologist prepared the drug as per the weight of the child and administered it. The examiner (pediatric dentist) was blinded regarding the drug administered. Ten randomly selected children (group A) were administered one drug and the other ten children (group B) were administered the second drug; both drugs were mixed in a syrup made up of levulose 40.5%, dextrose 34.02%, sucrose 1.9%, water 17.7%, and gum and dextrin. The baseline heart rate, respiratory rate, and oxygen saturation were recorded using a respiratory gas monitor, which includes a pulse oximeter, a capnograph, and ECG. The child was kept under observation in the waiting room. The sedative and anxiolysis scores were recorded at baseline and at 30 min. The child was also scored for separation anxiety and IV line and face mask acceptance [Table 3].

The anesthetic agents administered were standardized. [3] The child was induced with the required concentration of sevoflurane and nitrous oxide in oxygen via a face mask and Jackson-Reed circuit and maintained with the same drugs. The child was intubated with a nasoendotracheal tube of the required size after administering short-acting muscle relaxant (i.e., succinylcholine at a dose of 1 mg/kg) and an antisialagogue (i.e., glycopyrrolate at a dose of 4 µm/kg). Intravenous ataracurium 0.5 mg/kg and an antiemetic (Emeset) 0.1 mg/kg were also administered during the course of the treatment. The required dental treatment was completed, and at the end of the procedure the neuromuscular blockade was reversed with neostigmine (0.05 mg/kg), with atropine given to counter the side effects of neostigmine. The child was extubated and kept in the recovery room under observation till discharge was given by the anesthesiologist. The discharge time was noted and postprocedure instructions were given. The child was called for a checkup the following day, when the parents were asked to answer a questionnaire about the surgical experience of the parent and child and side effects experienced, if any [Table 4]. [11] The data was compiled and statistically analysed using the chi-square test; significance level was established at P < 0.05.

   Results Top

A total of 20 uncooperative preschool-age children were included in the study, with ten children in each group. Group A received 5 mg/kg of oral ketamine and group B received 0.5 mg/kg oral midazolam. The sedation score revealed that nine children (90%) in both groups were alert at baseline, nine children (90%) in group A and eight (80%) in group B were drowsy, and one (10%) asleep after 30 min [Figure 1]. The anxiolysis score showed a statistically significant result, with six (60%) children in group B being friendly as compared to none in group A [Figure 2]. Eight (80%) children in group B were calm at the time of separation from the parent as compared to only three (30%) in group A [Figure 3]. Acceptance of the IV line was better in group B, with four children (40 %) showing only minor resistance and three (30%) showing no resistance at all [Figure 4]. The face mask acceptance score also revealed fair results with group B as six (60%) children in group A showed poor results [Figure 5]. The heart rate and respiratory rate was marginally higher after administration of drug in group A [Figure 6]. Recovery was marginally faster in group B (mean value 3.10) [Figure 7]. The follow-up questionnaire revealed that 80% children and 70% parents of children in group B had a 'pleasant' experience, while 80% children and 70% parents of children in group A had an 'acceptable' experience. Side effects were fewer in group B; 90% of group B children had no side effects, whereas five (50%) children in group A complained of vomiting and one (10%) had behavioral change - hallucinations [Figure 8].

   Discussion Top

Traditional behavior management techniques such as intimidation and voice control, along with adjuncts such as restraints, were once commonly used for carrying out dental treatment in uncooperative children. Nowadays, parents find these aversive management techniques unacceptable and hence newer methods have to be continuously sought to aid in successful treatment of dental problems in uncooperative children. [1],[2] There are various modes of drug administration, but oral premedication was chosen for this study as this route is more acceptable to children and, moreover, the absorption rate is documented to be rapid and adequate. [4],[12],[13],[14],[15] The drugs have a bitter taste hence honey was added to mask the taste. Honey is thick and sweet and children are willing to swallow it. The use of syrup honey as a vehicle has been tried for the first time and it may have altered the absorption rates.

Intraoperative opioids were avoided by the judicious use of local anesthetic blocks, thereby minimizing the impact of variables during assessment of recovery. The failure to have a placebo treatment group in the study can be defended by the fact that at least four studies showing the effectiveness of both midazolam and ketamine compared to placebo have been published; [3],[9],[16],[17],[18],[19],[20],[21],[22] also, scientifically and ethically it was not possible to justify the inclusion of a placebo where the null hypothesis was constructed to compare the effectiveness of two premedications.

The efficacy of oral midazolam as a sedative and anxiolytic in children in this study is consistent with previous reports. [17],[23] Two other studies have concluded that oral ketamine produces a uniform, predictable sedation within 20-25 min of administration and facilitates a calm separation and induction of anesthesia. [19],[20] Our findings differ from that of these studies and this could be attributed to the smaller dose of ketamine (5 mg/kg) used; the other studies used a higher dose (6 mg/kg) which, when multiplied by the weight of the child, would amount to a large difference. It is possible that with the lower dose that we used the maximum sedation may have not been achieved in 30 min.

Ketamine is a mild cardiopulmonary stimulant and this is consistent with the study results. [9] The recovery too was in accordance with previous results that suggests faster recovery after midazolam administration. [8],[18] The side effects-mainly vomiting-was more prominent in children administered oral ketamine, and this is consistent with the study carried out by Alfonzo-Echeverri et al. in 1993. They observed that 40% subjects complained of vomiting after the administration of ketamine [9] as compared to 5% of those administered meperidine and promethazine. A study carried out by Reinemer et al. in 1996 reported a 5.1% vomiting rate with ketamine administration, [23] but this low figure may be attributed to the small sample size. The response to the questionnaire was in accordance with the study carried out by Feld et al. in 1990.

The results of the present study reveal that:

  1. Adequate sedation is produced with both midazolam and ketamine at the time of separation. No statistically significant results were observed between the two drugs.
  2. Anxiolysis was significantly better with oral midazolam.
  3. IV line acceptance and face mask acceptance was similar in both groups.
  4. The heart rate and respiratory rate were marginally higher in children who were administered oral ketamine.
  5. Recovery was marginally faster in children given oral midazolam.
  6. The questionnaire revealed that the surgical experience was more pleasant in the oral midazolam group.
  7. Side effects, especially vomiting, were more prominent in the oral ketamine group.

To conclude, it can be seen that though the results were not statistically significant, oral midazolam was better tolerated and accepted by both the child and parents and was associated with negligible side effects. More research should be directed to finding an ideal sedative that can make dental treatment in uncooperative children a pleasant experience both for the child as well as the parent.

   References Top

1.Lawrence SM, McTigue DJ, Wilson S, Odom JG, Waggoner WF, Fields HW Jr. Parental attitudes towards behaviour management techniques used in Pediatric dentistry. Pediatr Dent 1991;13:151-5.  Back to cited text no. 1  [PUBMED]  
2.Murphy MG, Fields HW Jr, Machen JB. Parental acceptance of pediatric dentistry behaviour management techniques. Pediatr Dent 1984;6:193-8.  Back to cited text no. 2  [PUBMED]  
3.Alderson, PJ, Lerman J. Oral Premedication for Pediatric ambulatory anaesthesia: A comparison of midazolam and ketamine. Can J Anaesth 1994;41:221-6.  Back to cited text no. 3    
4.Kogan A, Katz J, Efrat R, Eidelman LA. Premedication with midazolam in young children: A comparison of four routes of administration. Pediatr Anaesth 2002;12:685-9.  Back to cited text no. 4    
5.Sullivan DC, Webb MD, Wilson CFG. A comparison of two oral ketamine- diazepam regimens for sedation of anxious pediatric dental patients. Pediatr Dent 2001;23:233-7.  Back to cited text no. 5    
6.Vetter TR. A comparison of midazolam, diazepam and placebo as oral anesthetic premedicants in younger children. J Clin Anesth 1993;5:58-61.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]
7.Gerecke M. Clinical structure and properties of midazolam compared with other benzodiazepines. Br J Clin Pharmacol 1983;16:11-6.  Back to cited text no. 7    
8.Kupietzky A, Houpt MI. Midazolam: A review of it's uses for conscious sedation of children. Pediatric Dent 1993;15:237-41.  Back to cited text no. 8    
9.Alfonzo-Echeverri EC, Berg JH, Wild TW, Glass NL. Oral ketamine for pediatric outpatient dental surgery sedation. Pediatr Dent 1993;15:182-5.  Back to cited text no. 9  [PUBMED]  
10.Sekerci C, D φnmez A, Ate? Y, Okten F. Oral ketamine premedication in children (placebo controlled double-blind study) Eur J Anaesthesiol 1997;13:606-11.  Back to cited text no. 10    
11.Feld LH. Negus JB, White PF. Oral midazolam preanaesthetic medication in Pediatric outpatients. Anesthesiology 1990;73:831-4.  Back to cited text no. 11    
12.Weldon BC, Watcha MF, White PF. Oral midazolam in children: effect of time and adjunctive therapy. Anesth Analg 1992;75:51-5.  Back to cited text no. 12  [PUBMED]  [FULLTEXT]
13.Fuks AB, Kaufman E, Ram D, Hovav S, Shapira J. Assessment of two doses of intranasal midazolam for sedation of young Pediatric dental patients. Pediatr Dent 1994;16:301-5.  Back to cited text no. 13  [PUBMED]  
14.Roelofse JA, van der Bijl P, Stegmann DH, Hartshorne JE. Preanaesthetic medication with rectal midazolam in children undergoing dental extractions. J Oral Maxillofac Surg 1990;48:791-7.  Back to cited text no. 14  [PUBMED]  [FULLTEXT]
15.van der Bijl P, Roelofse JA, Stander IA. Rectal ketamine and midazolam for Premedication in Pediatric dentistry. J Oral Maxillofac Surg 1991;49:1050-4.  Back to cited text no. 15  [PUBMED]  [FULLTEXT]
16.Anderson BJ, Exarchos H, Lee K, Brown TC. Oral Premedication in children: a comparison of chloral hydrate, diazepam, alprazolam, midazolam and placebo for day surgery. Anaesth Intensive care 1990;18:185-93.  Back to cited text no. 16  [PUBMED]  
17.Warner DL, Cabaret J, Velling D. Ketamine plus midazolam a most effective pediatric oral Premedication. Pediatr Anaesth 1995;5:293-5.  Back to cited text no. 17    
18.Parnis SJ, Foate JA, van der Walt JH, Short T, Crowe CE. Oral Midazolam is an effective Premedication for children having day-stay anaesthesia. Anaesth Intensive Care 1992;20:9-14.  Back to cited text no. 18  [PUBMED]  
19.Humphries Y, Melson M, Gore D. Superiority of oral ketamine as an analgesic and sedative for wound care procedures in pediatric patients with burns. J Burn Care Rehabil 1997;18:34-6.  Back to cited text no. 19  [PUBMED]  
20.Gutstein HB, Johnson KL, Heard MB, Gregory GA. Oral ketamine preanaesthetic medication in children. Anesthesiology 1992;76:28-33.  Back to cited text no. 20  [PUBMED]  
21.Hackel, A Lin, Y.C. Moynihan, R.J. A comparison of oral midazolam, oral ketamine and oral midazolam combined with ketamine as preanaesthetic medication for pediatric outpatients. Anesthesiology 1993;77:1177.  Back to cited text no. 21    
22.McMillan CO, Spahr-Schopfer IA, Sikich N, Hartley E, Lerman J. Premedication of children with oral midazolam. Can J Anaesth 1992;39:545-50.  Back to cited text no. 22  [PUBMED]  [FULLTEXT]
23.Reinemer HC, Wilson CF, Webb MD. A comparison of two oral ketamine- diazepam regimens for sedating anxious pediatric dental patients. Pediatric Dent 1996;18:294-300.  Back to cited text no. 23    


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]

  [Table 1], [Table 2], [Table 3], [Table 4]

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