Comparison between dexmedetomidine and midazolam premedication in pediatric patients undergoing ophthalmic day-care surgeries.

UNLABELLED: Midazolam is the most commonly used premedication in children. It has been shown to be more effective than parental presence or placebo in reducing anxiety and improving compliance at induction of anesthesia. Clonidine, an a2 agonist, has been suggested as an alternative. Dexmedetomidine is a more a2 selective drug with more favorable pharmacokinetic properties than clonidine. AIMS: To compare i.v. Dexmedetomidine and Midazolam as premedication in pediatric patients. SETTINGS AND
DESIGN: Open label single blind study.
MATERIAL AND METHODS: 60 patients were randomly allocated to group D(n=30) and group M(n=30) and given Inj Dexmedetomidine 0.4 μg/kg diluted in 10 ml slowly i.v. and Inj Midazolam 0.05mg/kg i.v. accordingly. Level of sedation, parent separation, response to induction, blood pressure, pulse, oxygen saturation, post operative agitation and shivering was noted. STATISTICAL ANALYSIS USED: Unpaired student's t-test and chi square test used in this study. P value <0.05 was considered significant.
RESULTS: There were significant differences in parental separation acceptance,Response to induction and wake-up behavior score. When compared with group M, patients in groupD were significantly more sedated % minutes after premedication (P<0.001). Post operative agitation and shivering was low in group D in comparision with group M. Though blood pressure and pulse were on lower side in group D than in group M, oxyden saturation remained same in both the groups having no statistical significance.
CONCLUSIONS: Dexmedetomidine is superior than Midazolam as premedication in pediatric patients with more intense sedation, excellent parent separation, favourable induction conditions, lower incidence of postoperative agitation and shivering along with hemodynamic stability and no respiratory depression.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

One of the challenges for pediatric anesthesiologists is to minimize distress for children in the operating room (OR) environment and to facilitate smooth induction of anesthesia. This is often accomplished by prior administration of a sedative drug before transfer to the OR. Midazolam is the most commonly used drug for this purpose.[12] Premedication with midazolam has been shown to be more effective than parental presence or placebo in reducing anxiety and improving compliance at induction of anesthesia.[34] The beneficial effects of midazolam include sedation, anxiolysis, and reduction of postoperative vomiting.[456789] Undesirable effects, including restlessness, paradoxical reaction, and negative postoperative behavioral changes, have made it a less than ideal premedication.[101112] Although amnesia is considered an advantage by some authorities, it has also been regarded as a possible disadvantage by others[13] Clonidine, an α2 agonist, has been suggested as another option for premedication in children.[14] Dexmedetomidine is a newer α2 agonist with a more selective action on the α2 adrenoceptor and a shorter half-life. The purpose of this investigation was to compare intravenous (I.V.) dexmedetomidine and midazolam as premedication in pediatric age group.

SUBJECTS AND METHODS

After approval from the ethical committee, written informed consent was obtained from the patients’ parents. Sixty children of ASA physical status I or II aged between 5 and 12 years were scheduled to undergo ophthalmic day-care surgery.

Children were randomly allocated to group-D and group-M. The children were taken to the preoperative holding area in the presence of one parent. All children received EMLA® cream unless contraindicated and then a 24-G I.V. line was secured after 15 min. Baseline heart rate, oxygen saturation (SpO2), and blood pressure (BP) were measured before any drug administration. Group-D patients received inj. dexmedetomidine 0.4 mg/kg diluted in 10 ml given slowly I.V. Group-M patients received inj. midazolam 0.05 mg/kg I.V. as premedication. Inj. glycopyrolate 0.004 mg/kg I.V. was given.

Sedation score was noted at 5 min after premedication. At 10 min, response to parent separation was noted. The patients were taken to OR and ECG, SpO2, and NIBP monitors were applied. Response to induction in the form of mask acceptance was noted at 15 min. They were induced using propofol and scoline was given as a muscle relaxant. They underwent intubation and an endotracheal tube was fixed after checking proper placement. Anesthesia was maintained using 50% oxygen and sevoflourane as the inhalational agent, with inj. atracurium as muscle relaxant. Surgeries were mostly of 45-90-min duration. Intra-operative BP, SpO2, and pulse were noted. After that the patients were reversed with inj. glycopyrolate and inj. neostigmine, and extubated. They were observed for postoperative agitation and shivering till 2 h, and were discharged after fulfillment of modified Aldrete score ≥9 points.

The demographic data of the patients will be studied for each group.

The means of continuous variables (age, weight, pulse rate, BP, oxygen saturation) were compared using Student's t-test.

The demographic data for categorical variables (sex, ASA class, shivering) were compared using χ2-test.

P < 0.05 was considered significant.

RESULTS

The demographic characteristics for all the patients have been summarized in Table 1.

Patients in both groups were comparable with respect to age, weight, gender and ASA status.

Sedation scores at the end of 5 min have been summarized in Figure 1.

Figure 1

shows 5 minute sedation after both drugs

In group-D, 53% and 13% patients were drowsy and asleep, whereas in group-M 37% and 10% patients were drowsy and asleep accordingly.

Mean sedation score in group-D was 3.63 ± 0.04 and in group-M it was 3.12 ± 1.2, with P value being 0.038, which was statistically significant, as shown in Table 2.

Table 2

shows Response to sedation

Figure 2 shows that in the dexmedetomidine group, 90% children could be separated easily from parents (grading being excellent and good) at the end of 10 min, whereas in the midazolam group, separation was not satisfactory for 54% children (grading being fair and poor), needing further convincing and persuasion. The mean value of separation score in group-D was 1.60 ± 0.67 whereas in group-M it was 2.51 ± 0.89, with P < 0.001, which is statistically very highly significant, as shown in Table 2.

Figure 2

It shows drug sedative response to parent separation

Table 1

Demographic distribution. This Table shows all demographic datas were comparable.

Patients in group-D were much feasible to separate as sedation was intense. In group-M, in comparison with group-D, patients were sedated but not as in group-D because in group-M, patients were able to separate but with added persuasion. So we can say that patients in group-D were much more sedated than those in group-M.

Figure 3 shows that the in dexmedetomidine group, there was excellent favorable response to mask placement in 24 children, whereas in the midazolam group only 10 showed excellent favorable response and 11 children were cooperative on assurance. P value was found to be < 0.001, which is very highly significant, as shown in Table 2.

Figure 3

Shows Response to induction. X axis shows time in minutes. Y axis shows favourable response to mask

Figure 4 shows that in the dexmedetomidine group, 67% children were calm postoperatively and in the midazolam group only 17% children were calm, although 70% children in the midazolam group were calm on consolation. P < 0.0001, which is statistically significant, as shown in Table 2.

Figure 4

It show postoperative agitation

Figure 5 shows that shivering occurred only in 27% children in group-D and in 63% children in the midazolam group, with P < 0.001.

Figure 5

It shows drug effects on shievering

Figure 6 and Table 3 shows that pulse rate decreased significantly in the dexmedetomidine group than in the midazolam group. There were no changes in pulse during intubation as well as extubation. Bradycardia was noted in the post-operative period till 2 h, which was responsive to inj. Atropine I.V. stat. Stress response was observed in the form of increased pulse rate in the midazolam group.

Figure 6

It shows pulse changes during anaesthesia

Table 3

Dexmedetomidine group significant decrease in pulse rate after induction compare to midazolam group

Figures 7 and 8, and Tables 4 and 5 show that BP decreased significantly after administration of the drug in the dexmedetomine group than in the midazolam group. There were no changes in systolic and diastolic blood pressure during intubation as well as extubation in the dexmedetomidine group. Postoperatively mild hypotension was noted in the dexmedetomidine group, which was responsive to I.V. fluids. Stress response was noted in the midazolam group in the form of increased systolic and diastolic BP. There were no significant changes in BP postoperatively in the midazolam group.

Figure 7

Shows systolic blood pressure during anaesthesia. X axis shows time in minutes. Y axis shows systolic blood pressure in mmhg

Figure 8

Shows diastolic blood pressure changes during anaesthesia. X axis shows time in minutes. Y axis shows diastolic blood pressure in mmhg

Table 4

Systolic blood pressure

Table 5

Diastolic blood pressure

Figure 9 and Table 6 shows that there were no significant changes in O2 saturation throughout the peri-operative period, with P value being > 0.05, which is statistically non-significant.

Figure 9

Shows mean oxygen saturation during anaesthesia

Table 6

Both groups there were no much difference in oxygen saturation during anaesthesia

DISCUSSION

The concept of day-care surgery in children is not new. There is a general as well as financial benefit to the family unit in that there is reduced dislocation to family life relating to parent's time off work, travel to and from hospital, arranging baby-sitters, etc., Parents are actively and continuously involved with the care of their child in day-care surgery units as opposed to their peripheral role when children are admitted as inpatients. There is a decreased risk of hospital-acquired infections because of reduced contact with potentially infectious hospital staff and inpatients. Finally, there is financial saving for both the institution and the parent.

Dexmedetomidine is a highly selective α2-adrenoceptor agonist that has sedative, anxiolytic, and analgesic effects.[15] Here in this study we compared dexmedetomidine and midazolam as premedication in pediatric patients undergoing ophthalmic day-care surgery.

Akin et al., studied intranasal dexmedetomidine vs. midazolam for premedication of pediatric patients undergoing anesthesia. Study group-M (n = 45) received 0.2 mg/kg intranasal midazolam and group-D (n = 45) received 1 μg/kg intranasal dexmedetomidine. Satisfactory mask induction was achieved by 82.2% of the patients in group-M and 60% of those in group-D (P = 0.01). There was no evidence of a difference between the groups in either sedation score (P = 0.36) or anxiety score (P = 0.56) upon separation from parents. The number of patients who required postoperative analgesia was higher in the midazolam group (P = 0.045).

Kamal et al., studied the effect of oral dexmedetomidine vs. oral midazolam as premedication in 60 pediatric patients assigned to receive either oral midazolam 0.5 mg/kg (group-M, n = 30) or oral dexmedetomidine 3 g/kg (group-D, n = 30) prior to a standardized sevoflurane anesthetic. There was no significant difference in the pre- and postoperative levels of sedation between the two groups, but onset of sedation was significantly faster in group-M (28.4 ± 13.7 vs. 39.5 ± 14.3 min; P < 0.05). Group-D showed significantly lower pain scores in the immediate postoperative period, with fewer patients requiring rescue analgesics than in group-M (10 vs. 17, P < 0.05). Incidence of postoperative agitation was significantly less in the dexmedetomidine group (23% vs. 47%, P < 0.05). Postoperative shivering and vomiting occurred less in group-D. Mean arterial pressure and heart rate were significantly lower in group-D during the intra- and postoperative periods.[15]

During induction, stress response to laryngoscopy was attenuated by dexmedetomidine and also at the time of extubation, BP and pulse did not show any variation, whereas in the midazolam group, stress response was not attenuated at both time of intubation as well as extubation. Oxygen saturation was maintained in both groups, with P > 0.05 being statistically not significant.

Munro et al., reported that reduction of BP and heart rate were <20% of baseline in children who were sedated with an initial dose of 1 μg/kg I.V. dexmedetomidine, followed by a maintenance infusion during cardiac catheterization.[16]

A pharmacokinetic study of I.V. dexmedetomidine in children done by Petroz et al., showed that 0.66 and 1 μg/kg I.V. dexmedetomidine given over 10 min produced a significant reduction of heart rate (<15% compared with baseline) and systolic BP (<25% compared with baseline).[17]

In the dexmedetomidine group, 67% patients were calm in the postoperative period, 27% patients needed assurance, and only 6% patients were agitated. So we can clearly say that postoperative agitation caused by sevoflourane is possibly reduced by dexmedetomidine. In the midazolam group, only 17% patients were calm, whereas 70% patients needed assurance. So we can say that midazolam is not effective in preventing postoperative agitation in comparison with dexmedetomidine.

Zub et al., examined anesthesia records to determine the most effective anxiety-reducing anesthesia premedicant for children prior to surgical procedures. Based on their retrospective review, Zub et al. recommended 3-4 μg/kg oral dexmedetomidine to reduce anxiety. This study used the oral dosing that Zub et al., recommended, yet there were no significant differences between dexmedetomidine and midazolam in reducing anxiety as evidenced by mask acceptance scores or parental separation scores. It should be noted, however, that children receiving dexmedetomidine were less likely to experience emergence delirium.[18]

Dexmedetomidine is also effective in prevention of postoperative shivering. Only 27% patients experienced shivering in comparison with the midazolam group, where 63% patients experienced shivering. We believe that the proven effect of dexmedetomidine on shivering prevention is by reducing vasoconstriction and shivering threshold centrally.

Bicer et al., studied the efficacy of dexmedetomidine compared with meperidine and placebo in preventing post-anesthetic shivering. They studied 120 patients (ASA I–II) scheduled for elective abdominal or orthopedic surgery of about 1-3-h duration. Forty patients in each group randomly received 1 μg/kg dexmedetomidine, 0.5 mg/kg of meperidine, or 0.9% saline as placebo, intravenously. Post-anesthetic shivering was seen in 22 patients in the placebo group, 4 patients in the meperidine group, and 6 patients in the dexmedetomidine group.[19]

Karaman et al., evaluated the efficacy of dexmedetomidine in prevention of postoperative shivering. Sixty patients undergoing gynecologic laparoscopic surgery were allocated randomly to two groups to administer either dexmedetomidine as a loading dose of 1 μg/kg for 10 min followed by a maintenance infusion of 0.5 μg/kg/h (group-D, n = 30) or a normal saline infusion (group-S, n = 30). Post-operative shivering was observed in 14 patients in group-S and three patients in group-D (P = 0.001).[20]

So by summarizing the above comparison we can conclude that dexmedetomidine by having more sedative quality, analgesic effect, no respiratory depression, decreased incidence of postoperative agitation, and shivering has proved as a superior premedication in the pediatric age group having more hemodynamic stability.