A comparative study between intranasal dexmedetomidine and intranasal ketamine as a premedication in paediatric surgeries

 

Rajalakshmi J, D A¹, Lokesh Kumar K S^2*, Santosh Kumar³

 

^1,2,3Department of Anesthesiology, Dr B R Ambedkar Medical College, Bangalore, Karnataka, INDIA.

 

Abstract              Background: This prospective, randomized, double-blind study was designed to evaluate the use of intranasally administered dexmedetomidine vs intranasal ketamine as a premedication in children undergoing general surgeries Methods: 60 children of ASA physical status I and II, between the ages 2 to 8yrs were randomly assigned to 2groups. Group D- Patients received intranasal dexmedetomidine (2μg/kg). Group K- Patients received intranasal ketamine (6mg/kg). At 45 minutes after intranasal dose, sedation, ease of separation and IV cannula acceptance, was evaluated Results: The Group K had a median onset of action of 11.67 minswhen compared to Group D of 29.47 mins.57% of children in Group Kbecame significantly asleep when compared to 33% in Group D. (p=0.037). Parental separation was excellent in Group K when compared to Group D. (33.33% vs 10%) (P<0.005). Intravenous cannula acceptance was good in Group Kwhen compared to Group D (60% vs 16%). Conclusion: Ketamine (6 mg/kg) via intranasal route is better than dexmedetomidine (2μg/kg), in terms of better sedation, parental separation and IV cannula acceptance.

Keywords: Dexmedetomidine, Ketamine, Premedication, Pediatric.

 

INTRODUCTION

The preoperative period is a stressful event for the majority of the individuals undergoing surgery. This is especially true in the paediatric patients.Fear of physicians, nightmares and post operativebehavioural regression, have all been reported. Inaddition to behavioral manifestations, preoperative anxiety activates the human stress response, leading to increased serum cortisol, epinephrine, and natural killer cell activity.¹ An ideal premedicant should be available in a preparation that is readily accepted by children, should have a relatively rapid and reliable onset, should provide anxiolysis with mild sedative effect. Various drugs have been used as a premedicant in pediatric paients. In our study we chose Dexmedetomidine, a highly selective α2-adrenoreceptor agonist drug and Ketamine, a NMDA receptor antagonist as the premedicants via intranasal route. We chose intranasal route as it had a significant advantage of being non invasive, quicker onset of action, bypasses BBB and relatively less or delayed side effects. Therefore this study was conducted to compare premedicant effects of intranasal dexmedetomidine versus intranasal ketamine. The parameters which will differentiate between the two, will be- better acceptance of the drug by patients, parent separation, sedation prior to induction and intravenous cannulation.

 

METHODS

This is a prospective, randomized study to determine which is the better drug, between dexmedetomidine and ketamine, given intranasally, as a premedication. This study was conducted at Dr. B.R. Ambedkar Medical College, Bangalore. After obtaining approval from Institutional Ethics Committee and written, informed consent from patient’s parents, 60 patients of ASA I and II aged between 2-8years were enrolled into the study. The exclusion criteria included patients with cardiopulmonary ailments, hepatorenal dysfunction, mental retardation, emergency surgeries, nasal and oral deformities, history of recent nasal bleeding or discharge and allergy or hypersensitivity to Dexmedetomidine or Ketamine. Patients were randomly assigned to two study groups by computer generated random tables. Group D- Patients received intranasal dexmedetomidine (2μg/kg). Group K- Patients received intranasal ketamine (6mg/kg). Children were kept nil per oral for 6 hours prior to surgery. No premedication was given in the wards. Children were kept in holding area in comforting presence of their parents and were connected to all standard monitors. Baseline heart rate, blood pressure and oxygen saturation was measured before premedication. Intranasal dose of the drug was administered after seeking consent from the parents. The solutions were prepared in 2.5 mL syringes. Equal volumes of the prepared solution were then dripped into both nostrils of the patients. The drug was administered with patients in the supine position.Children were constantly observed for heart rate, blood pressure and saturation and the possible side effects like nausea, vomiting and increased salivation. Readings were taken at 10 minutes interval until 45 minutes, when child was separated from parents. At 45 minutes after intranasal dose, sedation, ease of separation and IV cannula acceptance, was evaluated on a four point score scale. The scoring scales² that were used are as follows:

The hemodynamic parameters taken into consideration were the blood pressure (systolic, diastolic and the mean), heart rate, respiratory rate and saturation. Statistical evaluation showed modest change from the baseline but a significant difference in HR and SBP between the groups after the respective drug administration starting at 10 minutes onwards until 45minutes. This statistical significance was due to the decrease in the heart rate caused by dexmedetomidine and increase in the heart rate caused by ketamine. Out of 30 patients 2 patients of dexmedetomidine group developed nausea and vomiting, that is around 6.7%. In the ketamine group, out of 30 patients, 4 patients developed vomiting, that is around 13.3%, 5 patients developed salivation that is around 16.7%. Two patients of the ketamine group developed tachycardia and one developed hypertension, and one patient developed involuntary movements. However none of the patients developed respiratory depression amongst the two groups.

 

DISCUSSION

Premedication is aimed to relieve anxiety, apprehension, fear and resistance to anaesthesia. We observed in our study that intranasal route had a significant advantage of noninvasive, quicker onset of action and relatively less or delayed side effects. The effectiveness of the premedicant was assessed mainly by sedation, parental separation and IV cannula acceptance scores. We observed that ketamine was superior to dexmedetomidine by having a faster onset of action (11.67±1.81 vs 29.47±4.13 minutes). More patients were found to be asleep in ketamine group (57% vs 33.3%). Better parental separation was seen after intranasal ketamine administration (33.33% vs 10%). The intravenous cannula acceptance was good in ketamine group (60% vs 16%). Mohamed .A.Daabisset al³ compared oral dexmedetomidine with oral combination of ketamine-midazolam and found that the ketamine-midazolam group had an earlier onset of action (18.3 minutes) compared to dexmedetomidine (24.5 minutes) Weksler, N et al⁴ in his study showed that out of 86 children who were administered intranasal ketamine at 6mg/kg, 48 patients had excellent sedation, adequate sedation was found in 19 patients. Similarly, in our study, after ketamine administration, 17(57%) patients were found to be asleep and 13(43.3%) were drowsy and after dexmedetomidine administration 10(33.3%) patients were asleep, 18(60%) were drowsy. Yuen et al ⁵ studied the effects of intranasal dexmedetomidine in various doses such as 0.5, 1 and 1.5μg/kg and inferred that the doses of 1 and 1.5μg/kg produced significant sedation in healthy volunteers but clinical sedation required for painful procedure could not be achieved. They opined that dexmedetomidine produces sedation similar to natural sleep and so patients were easily aroused at the time of IV cannulationand 2 remained awake which was statistically significant. In our study the hemodynamic parameters such as HR, SBP, DBP and MAP in intranasal ketamine group showed a significant increase. HR increased by 10% and increase in BP was 14%. It was taken as, any increase in BP above 20% of baseline as hypertension and HR by more than 140bpm in the age group of 2-5years and more than 120bpm in the age group of 6-8years as tachycardia⁶. In our study, only 2 patients showed tachycardia and 1 patient showed hypertension according to the above study criteria. The rise in hemodynamics could be attributed to the centrally mediated sympathomimetic response. Jeffrey P. Morray et al ⁷ showed there was statistically significant but clinically minor increase in heart rate, mean arterial pressure after ketamine was administered. They explained that cardiovascular effects to ketamine were due to direct effects on the heart rate and peripheral vascular resistance and indirect effects mediated through centrally induced increases in sympathetic activity which is believed to be responsible for the increase in heart rate and myocardial contractility. Yuen et al ⁴ in his study showed that there was no significant reduction in SpO₂ below 95% for dexmedetomidine with 1 and 1.5μg/kg. In the present study SpO₂ and respiratory rate did not show any significant changes from baseline in both the groups. The side effects found in our study, in both groups, included minimal amount of vomiting and salivation which did not require any intervention. In addition ketamine group had 2 patients with tachycardia and 1 patient with hypertension and 1 patient showed involuntary movements. However these side effects were statistically insignificant and no medical interventions were required. Diaz JH et al⁸ in a double blinded controlled study compared intranasal ketamine with placebo and showed that there was no significant difference in vomiting between the two groups. Therefore in our study, premedication with intranasal dexmedetomidine and intranasal ketamine showed that onset of action is faster with ketamine group .The sedation, parental separation and IV cannula acceptance is also better with the ketamine group. The statistically significant differences in hemodynamic parameters were of minor importance clinically. Also ketamine was more cost effective when compared to dexmedetomidine.

 

CONCLUSION

Both ketamine and dexmedetomidine as premedicant, provided adequate sedation with minimal side effects in paediatric patients. But ketamine when given in a dose of 6 mg/kg via intranasal route is better than that of dexmedetomidine given in a dose of 2μg/kg, in terms of better sedation, parental separation, IV cannula acceptance and is also more economical when compared to dexmedetomidine.

 

REFERENCES

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2. Gharde, P., S. Chauhan, et al. "Evaluation of efficacy of intranasal midazolam, ketamine and their mixture as premedication and its relation with bispectral index in children with tetralogy of fallot undergoing intracardiac repair." Ann Card Anaesth 2006; 9(1): 25-30.
3. Mohamed A. Daabiss., Mohamed Hashish., Dexmedetomidine versus ketamine combined with midazolam; a comparison of anxiolytic and sedative premedication in children BJMP 2011;4(4):a441
4. Weksler, N., L. Ovadia, et al "Nasal ketamine for paediatric premedication." Can J Anaesth. 1993; 40(2): 119-21.
5. V. M Yuen, Irwin MG, Hui TW, Yuen MK, Lee LH: Double-Blind, Crossover Assessment of the Sedative and Analgesic Effects of Intranasal Dexmedetomidine. AnesthAnalg 2007;105:374–80
6. Behrman, R.E. et al. Disturbances of rate and rhythm of heart. Nelson Textbook of pediatrics, 17th edition, Saunders, 2004; 428:1555-65.
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8. Diaz, J. H. "Intranasal ketamine preinduction of paediatric outpatients." PaediatrAnaesth 1997; 7(4): 273-278

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