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| ORIGINAL ARTICLE |
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| Year : 2020 | Volume
: 21
| Issue : 2 | Page : 104-108 |
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Comparison of intranasal midazolam versus intranasal ketamine for preoperative anesthetic sedation in pediatric patients
Nandini Chouhan1, Janhavi Thatte1, Deepak Phalgune2, Charushila Patkar1
1 Department of Anaesthesiology, Poona Hospital and Research Centre, Pune, Maharashtra, India
2 Department of Research, Poona Hospital and Research Centre, Pune, Maharashtra, India
| Date of Submission | 07-Jan-2020 |
| Date of Acceptance | 26-Feb-2020 |
| Date of Web Publication | 19-Sep-2020 |
Correspondence Address:
Dr. Deepak Phalgune
18/27, Bharat Kunj-1, Erandawane, Pune - 411 038, Maharashtra
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/TheIAForum.TheIAForum_3_20
Introduction: During induction of anesthesia anxiety of children may be reduced more effectively by sedative medication than parental presence. Keeping in view, the necessity of reducing preoperative anxiety and postoperative psychological problem in pediatric patients, this study was conducted to compare the efficacy and safety of intranasal midazolam versus intranasal ketamine for preanesthetic sedation in pediatric patients.
Methods: Ninety patients scheduled for the surgery lasting between 30 min and 120 min under general anesthesia were randomly divided into two groups: Group A patients received intranasal midazolam 0.2 mg/kg as premedication (5 mg/mL ampoule), whereas Group B patients received intranasal ketamine 5 mg/kg as premedication (50 mg/mL vial). The primary outcome measures were the comparison of degree of sedation of intranasal midazolam versus intranasal ketamine for preanesthetic sedation in pediatric patients by accessing parental separation, acceptance of face mask, venipuncture score, and postoperative sedation, whereas the secondary outcome measures were the comparison of side effects. The comparison of quantitative and qualitative variables between the groups was done using the unpaired student's “t”-test and Chi-square test or Fisher's exact test, respectively.
Results: The percentage of patients in the ketamine group with parental separation score more than 2 was significantly higher as compared to the midazolam group. Acceptance of face mask, response to venipuncture, postoperative sedation, and postoperative side effects were comparable between the two groups. Both groups have minimal side effects.
Conclusions: Both midazolam and ketamine nasally are an effective pediatric premedication for sedation with minimal side effects. Parental separation was better in the ketamine group as compared to the midazolam group.
Keywords: Intranasal, ketamine, midazolam, sedation
How to cite this article:
Chouhan N, Thatte J, Phalgune D, Patkar C. Comparison of intranasal midazolam versus intranasal ketamine for preoperative anesthetic sedation in pediatric patients. Indian Anaesth Forum 2020;21:104-8 |
How to cite this URL:
Chouhan N, Thatte J, Phalgune D, Patkar C. Comparison of intranasal midazolam versus intranasal ketamine for preoperative anesthetic sedation in pediatric patients. Indian Anaesth Forum [serial online] 2020 [cited 2023 Jun 2];21:104-8. Available from: http://www.theiaforum.org/text.asp?2020/21/2/104/295383 |
| Introduction | |  |
Surgery and anesthesia can be a traumatic experience for a child and considerable emotional stress to both parents and children. Most of the preschool children suffer from severe anxiety and apprehension when they are separated from their parents before induction of anesthesia.[1] The unfamiliar faces and environment inside the operating room compound the sense of insecurity in the child.[2] Thus, preoperative anxiety can largely affect the smoothness of induction, emergence from anesthesia, and also the psychological and emotional state of the child in the remote future.[3] Hence, every effort should be made to make the ordeal of surgery as tolerable and pleasant as possible.
Intranasal route is easy, noninvasive, and has the rapid onset of action due to rich blood supply of the nasal mucosa and makes drugs highly bioavailable. Midazolam is water-soluble benzodiazepine with rapid onset and shorter duration of action. It produces amnesia and anxiolysis. It can be administered by intranasal, intramuscular (IM), intravenous (IV), oral and per rectal routes. Ketamine is a phencyclidine derivative. It antagonizes the N-methyl D-aspartate receptor. It produces sedation, analgesia and preserves upper airway muscle tone and respiratory drive. It can be administered by intranasal, IM, IV, oral, rectal route as preservative-free solution.
Metje et al. reported that intranasal midazolam and ketamine in pediatric patients were well accepted in both groups, and both the drugs were equally effective as sedative premedication.[4] Narendra et al. reported that midazolam was more effective than ketamine in children aged from 1 to 10 years undergoing various surgical procedures.[5] Sedative medication may be more effective in reducing the anxiety of the children during the induction of anesthesia than is the presence of parents. Keeping in view, the necessity of reducing preoperative anxiety and postoperative psychological problem in pediatric patients, this study was conducted to compare the efficacy and safety of intranasal midazolam versus intranasal ketamine for preanesthetic sedation in pediatric patients.
| Methods | | |
This prospective, randomized controlled study was conducted between April 2017 and October 2018 in the major operation theater of Poona Hospital and Research Centre, Pune, India. After approval from the scientific advisory committee and Institutional Ethics Committee, written informed consent was obtained from the parents/guardians of children. Children aged 1–5 years of either sex scheduled for the surgery lasting between 30 min and 120 min under general anesthesia, and falling into the American Society of Anesthesiologist Grades I and II were included in the study. Children with upper respiratory tract infection, congenital anomalies of nose and palate, children who had an allergy to any of the drugs used, and children with hepatic or renal derangements were excluded from this study.
Of 100 patients assessed for eligibility, after exclusion, 90 patients were randomly divided into two equal groups of 45 each, using computer-generated randomization code [Figure 1]. We used website https://www.sealedenvelope.com/simple-randomiser/v1/lists for creating a randomization list with block size four. All children were thoroughly examined before the procedure. Basic investigations were done to rule out any major systemic illness. The parents/guardians were informed about the study, and written informed consent was obtained for both the conduct of the study and administration of general anesthesia.
Group A patients received intranasal midazolam 0.2 mg/kg as premedication. (5 mg/mL ampoule), whereas Group B patients received intranasal ketamine 5 mg/kg as premedication. (50 mg/mL vial). Drugs were administered drop by drop with the help of a dropper to avoid wastage through anterior and posterior nostrils. This took 1–2 min. This was done under the supervision of a senior anesthesiologist. Researcher and children's parents were blind as to their group assignment.
Patients' vital parameters were examined before administering the premedication. Baseline heart rate, systolic blood pressure, respiratory rate, and oxygen saturation of blood were assessed just before nasal installation and at 5 min intervals till 20 min after installation. The child was taken to the operation theater after observing for 20 min.
Degree of sedation was assessed by response to separation from the parents using a 5-point sedation scale:[6]
- Agitated: Patient clinging to parents and/or crying
- Alert: Patient aware but not clinging to parents may whimper but not cry
- Calm: Lying comfortably with spontaneous eye-opening
- Drowsy: Lying comfortably with eyes closed, but responding to minor stimulation
- Asleep: Eyes closed, arousable, but does not respond to minor stimulation like touch or moving hand.
The children were shifted to the operation theater, and preoxygenation was done by holding the face mask.
The response to the face mask was assessed as follows:[7]
- Refuses mask
- Accepts with persuasion
- Accepts readily.
IV access was secured. Response to IV access was assessed by venipuncture score. It was assessed as follows:[8]
- Crying, uncooperative not able to start IV access
- Withdrawal for painful stimuli but allows to crying
- Calm, no withdrawal for painful stimuli and IV cannulation
- Asleep: No response to painful stimuli and IV cannulation.
Children were given premedication in the form of injection glycopyrrolate 5 μg/kg IM. Induction was done with injection thiopentone sodium 5 mg/kg IV and injection succinylcholine 2 mg/kg IV. Intubation was done with an appropriately sized portex endotracheal tube. Maintenance was done with O2: N2O = 50:50 + sevoflurane as an inhalational agent + injection atracurium 0.5 mg/kg IV as neuromuscular blocker.
At the end of the surgery, residual neuromuscular blockade was reversed with injection glycopyrrolate 10 μg/kg IV and injection neostigmine 0.04 mg/kg IV. The child was extubated after performing thorough oropharyngeal suction.
After extubation, postoperative sedation was assessed with a 3-point scale as follows:
0: Spontaneous eye-opening
1: Eye-opening to speech
2: Eye-opening in response to physical stimulation.
Patients were observed in the recovery unit for a period of 2 h. During this time, any side effects to the drugs used in the study were noted such as nausea, vomiting, respiratory depression, tachycardia/bradycardia, hypertonia, involuntary movements, shivering, and rash.
The primary outcome measures were the comparison of degree of sedation of intranasal midazolam versus intranasal ketamine for preanesthetic sedation in pediatric patients by accessing parental separation, acceptance of face mask, venipuncture score, and postoperative sedation, whereas the secondary outcome measures were the comparison of side effects and vital parameters. On the basis of a previously published study,[9] a sample size of 45 patients in each group was calculated by a formula,[10] with 80% power and 5% probability of Type I error to reject the null hypothesis.
Statistical analysis
Data collected were entered in Excel 2007, and analysis of the data was done using the Statistical Package for the Social Sciences software for Windows, version 20.0. IBM Corporation Armonk, NY, USA. The comparison of quantitative variables between the groups such as mean age, mean duration of surgery, mean pulse rate, mean systolic blood pressure, mean respiratory rate, and mean oxygen saturation was done using the unpaired t-test, whereas the comparison of qualitative variables such as weight, gender, type of surgery, parental separation score, venipuncture score, acceptance of mask, postoperative sedation score, and postoperative side effects was done using the Chi-square test or Fisher's exact test. The confidence limit for significance was fixed at 95% level with P < 0.05.
| Results | | |
The present research was conducted to compare the degree of preanesthetic sedation of intranasal midazolam versus intranasal ketamine in 90 children between the age group of 1 and 5 years by accessing parental separation, acceptance of face mask, venipuncture score, and postoperative sedation. Out of 100 patients assessed for eligibility, 10 were excluded because of upper respiratory tract infection (8) and congenital anomaly of nose or palate (2). Group A (45 patients) received intranasal midazolam, whereas Group B (45 patients) received intranasal ketamine as premedication. There was no statistically significant difference between Group A and Group B in relation to weight, mean age, gender, mean duration of surgery, and type of surgery [Table 1].
At 5 m and 10 m, pulse rate and systolic blood pressure in the ketamine group were significantly higher than that in the midazolam group. Mean respiratory rate, mean oxygen saturation, acceptance of face mask, response to venipuncture, postoperative sedation, and postoperative side effects were comparable between the two groups. The percentage of children with parental separation score more than 2 was higher in Group B as compared to Group A [Table 2]. There was no statistically significant difference in postoperative sedation, and postoperative side effects between the two groups [Table 3].
| Discussion | | |
The present randomized controlled study was conducted to compare the efficacy and safety of intranasal midazolam versus intranasal ketamine for preanesthetic sedation in pediatric patients. In our study, the percentage of patients in the ketamine group with parental separation score more than 2 was significantly higher as compared to the midazolam group. Acceptance of face mask, response to venipuncture, postoperative sedation, and postoperative side effects were comparable between the two groups.
In the present study, the trends of change in the respiratory rate were comparable between the two groups. The trends were similar, and the difference between these two groups was not statistically significant. The above-mentioned findings indicate that there was no fall in the respiratory rate in both the groups. These results are in accordance with Wilton et al. who reported that there was no change in the respiratory rate after the administration of intranasal midazolam.[6]
In our study, blood pressure at 5 and 10 min, in children of the ketamine group was significantly higher than that in the midazolam group. The results are comparable with the study conducted by Metje et al., where nasal ketamine was compared with nasal midazolam as premedication in pediatrics.[4] They observed that the systolic arterial pressure was higher in the ketamine group as compared to the midazolam group 20 m after the administration of the drug and upon arrival in the operating theater.
The difference between parental separation scores of both the groups was statistically significant. Percentage of patients in the ketamine group with parental separation score more than 2 was significantly higher as compared to the midazolam group. Bhakta et al. reported that 80% of patients receiving intranasal midazolam had the scores of three or more and that they separated easily from their parents.[11] However, in our study, parental separation was better in ketamine than midazolam group.
In each of the groups, majority (80%) of the patients had the acceptance of face mask score of more than 2. This shows that most of the children accepted the face mask well. The response in both the groups was similar, and the difference in response to face mask was not statistically significant. Our results are comparable with Weksler et al. who conducted a study 1993 in preschool children posted for elective surgeries.[12] The patients received 6 mg/kg of nasally administered ketamine as premedication. In their study, 67/86 (78%), mask acceptance was rated either excellent or adequate.[12]
The incidence of side effects in both the groups was found to be statistically nonsignificant. Emergence reactions are commonly seen with ketamine. However, emergence reactions were not detected in any of our patients. This finding is in accordance with Weksler et al.,[12]
Limitations
Intranasal midazolam has a low pH and itself may be very uncomfortable for a small child and cause irritation. To prevent irritation, we have not used previous instillation of intranasal lignocaine. We did not get the spray of ketamine; therefore, we put drug drop by drop in to the nostrils. Some children tolerated well but some cried during the procedure. The study of the intranasal route is still in its infancy. However, the intranasal administration of drugs for sedation and analgesia has some promising features, especially in preschool children with fear of separation from parents and unfamiliar surroundings. Further randomized controlled trials at multiple centers with larger sample size are needed.
| Conclusions | | |
Percentage of patients in the ketamine group with parental separation score more than 2 was significantly higher as compared to the midazolam group. Acceptance of face mask, response to venipuncture, postoperative sedation, and postoperative side effects were comparable between the two groups. Both groups had minimal side effects.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflict of interest.
| References | | |
| 1. | Beeby DG, Hughes JO. Behaviour of unsedated children in the anaesthetic room. Br J Anaesth 1980;52:279-81.  |
| 2. | Korsch BM. The child and the operating room. Anesthesiology 1975;43:251-7. |
| 3. | Kain ZN. Perioperative psychological trauma in children. In: Atlee JL, editor. Complication in Anesthesia. 1 st ed. Philadelphia: W.B. Saunders; 1990. |
| 4. | Metje T, Velasco PG, Roman J, de Heredia BB. Comparison of nasal ketamine and midazolam for pediatric premedication. Spanish Journal of Anesthesiology and Reanimation 1998;45:122. |
| 5. | Narendra PL, Naphade RW, Nallamilli S, Mohd S. A comparison of intranasal ketamine and intranasal midazolam for pediatric premedication. Anesth Essays Res 2015;9:213-8. [Full text] |
| 6. | Wilton NC, Leigh J, Rosen DR, Pandit UA. Preanesthetic sedation of preschool children using intranasal midazolam. Anesthesiology 1988;69:972-5. |
| 7. | 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. |
| 8. | Khatavkar SS, Bakhshi RG. Comparison of nasal midazolam with ketamine versus nasal midazolam as a premedication in children. Saudi J Anaesth 2014;8:17-21. |
| 9. | Kazemi AP, Kamalipour H, Seddighi M. Comparison of intra nasal midazolam verses Ketamine as premedication in 2-5 year old paediatric surgery patients. Pak J Med Sci 2005;21:460-4. |
| 10. | Motulsky H. Intuitive Biostatics. Oxford: Oxford University Press; 1995. |
| 11. | Bhakta P, Ghosh BR, Roy M, Mukherjee G. Evaluation of intranasal midazolam for preanesthetic sedation in pediatric patients. Indian J Anaesthesia 2007;51:111. |
| 12. | Weksler N, Ovadia L, Muati G, Stav A. Nasal ketamine for paediatric premedication. Can J Anaesth 1993;40:119-21. |
[Figure 1]
[Table 1], [Table 2], [Table 3]
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