|Year : 2016 | Volume
| Issue : 3 | Page : 129-137
Intranasal dexmedetomidine versus midazolam in preoperative sedation for noncomplex pediatric congenital cardiac surgeries
Hebaallah M Abdelmoneim, Saleh A Hamouda, GalalEldin A Mahfouz, Amr E Hashem
Department of Anaesthesia and Surgical Intensive Care, Faculty of Medicine, University of Alexandria, El Azerita Square, Egypt
|Date of Submission||25-Dec-2015|
|Date of Acceptance||25-May-2016|
|Date of Web Publication||4-Nov-2016|
Hebaallah M Abdelmoneim
Department of Anaesthesia and Surgical Intensive Care, Faculty of Medicine, University of Alexandria, El Azerita Square, 21131
Source of Support: None, Conflict of Interest: None
Background & objectives
Preoperative anxiety can be reduced pharmacologically. Midazolam is a benzodiazepine potent sedative, hypnotic, anaesthetic agent with strong anticonvulsant properties but does not have analgesic properties. The administration of intranasal lidocaine prior to the use of intranasal midazolam has been reported to be beneficial in reducing the burning sensation from intranasal midazolam. Dexmedetomidine, the newest sedative, is a highly selective α2 adrenergic agonist.
Materials and methods
Sixty children, aged between 3–12 years. The children were divided into two groups of 30 each. Thirty minutes before induction, Group-D (n=30) received intranasal Dexmedetomidine and Group M+L received intranasal midazolam preceeded by single puff on intranasal lidocaine spray 1% in each nostril.
Children who were premedicated with intranasal dexmedetomidine had lower sedation (MOAA/S Scale) scores, and easier child-parent separation than children who received intranasal midazolam. In addition to lower BIS measurements at the OR, after face mask application and after IV cannulation.
Intranasal Dexmedetomidine can be used effectively and safely as a preanaesthetic medication in children undergoing repair of non-complex congenital cardiac defects.
Keywords: bispectral index, dexmedetomidine, intranasal sedation, midazolam
|How to cite this article:|
Abdelmoneim HM, Hamouda SA, Mahfouz GA, Hashem AE. Intranasal dexmedetomidine versus midazolam in preoperative sedation for noncomplex pediatric congenital cardiac surgeries. Res Opin Anesth Intensive Care 2016;3:129-37
|How to cite this URL:|
Abdelmoneim HM, Hamouda SA, Mahfouz GA, Hashem AE. Intranasal dexmedetomidine versus midazolam in preoperative sedation for noncomplex pediatric congenital cardiac surgeries. Res Opin Anesth Intensive Care [serial online] 2016 [cited 2020 Jun 4];3:129-37. Available from: http://www.roaic.eg.net/text.asp?2016/3/3/129/193411
| Introduction|| |
Preoperative anxiety and maternal deprivation are challenging to anesthesiologists to be managed with premedication. Several drug routes are followed to facilitate the transfer to the operating room and for intravenous cannulation . Intranasal drug administration is a relatively easy noninvasive route with high bioavailability as it bypasses first-pass hepatic metabolism and also because of the high blood supply in the nasal mucosa . Intranasal midazolam is one of the benzodiazepines. It is characterized by rapid onset (10–12 min) and short duration, with high bioavailability (55–83%). Administration of intranasal xylocaine spray (10 mg/puff) preceding the intranasal midazolam avoids the irritation effect to the nasal mucosa and throat . Dexmedetomidine (DEX) is a new α2-agonist with a more selective action on the α2-adrenoceptor and a shorter half-life. Its onset ranges between 25 and 30 min and it has a median duration of 85 min. Bioavailability of DEX when administered intranasally ranges from 72 to 96% . Bispectral index (BIS) is a noninvasive tool that uses electromyographic and electroencephalographic data to measure the depth of sedation. It measures response of the central nervous system (CNS) response to sedation medication .
The aim of this work was to compare the effects of intranasal sedation using DEX and midazolam preceded by lidocaine spray in pediatric patients undergoing noncomplex congenital cardiac surgeries.
| Patients and methods|| |
This study was carried out in Alexandria Main University Hospital on 60 children admitted for noncomplicated congenital cardiac surgeries.
The sample size was statistically approved by the Biostatistics Department of the High Institute of Public Health, Alexandria University, and consisted of 60 patients, aged 3–12 years, scheduled for noncomplex elective cardiac surgery using cardiopulmonary bypass.
Exclusion criteria were as follows:
- Known allergy or hypersensitivity to midazolam, DEX, or lidocaine.
- Liver or renal dysfunction.
- CNS abnormalities (tumor, ventriculoperitoneal shunt, seizure disorder, cerebral palsy).
- Low cardiac output.
Patients in this study were randomly classified into two equal groups:
Group D (30 patients):
In this group patients received intranasal DEX drops instilled at a dose of 1 μg/kg 30 min before arriving at the operating room.
Group M+L (30 patients):
Patients in this group received a single puff of lidocaine spray (10 mg/puff) intranasally in both nostrils, followed by intranasal midazolam drop instillation 60 s later, at a dose of 0.5 mg/kg (maximum dose: 10 mg=2 ml) 30 min before arriving at the operating theater.
After obtaining approval from the Ethics Committee of the Faculty of Medicine and written informed consent from the parents, every patient was subjected to a careful preanesthetic assessment that included clinical examination and routine laboratory investigations, in addition to chest radiography, ECG, echocardiography.
The intranasal DEX (100 μg/ml parenteral preparation) and midazolam (5 mg/ml parenteral preparation) was prepared in a 3-ml syringe, and 0.9% saline was added to make a final volume of 2 ml. The intranasal drug was administered in both nostrils using a 3-ml syringe, with the child in a recumbent position .
The premedication was given in the preoperative holding area in the presence of one parent .
All patients were monitored for the following:
- Heart rate (HR) and rhythm (beats/min).
- Noninvasive mean arterial blood pressure (MAP) (mmHg).
- Resuscitative drugs in the form of atropine, ephedrine, and phenylephrine were given at the appropriate dose according to the patient’s age if a decrease in the HR or mean blood pressure more than 20% of the basal value was observed.
- Oxygen saturation (SpO2) using a pulse oximeter.
- Respiratory rate (cycles/min).
- BIS index.
Peripheral intravenous cannulations
- An O2 face mask was applied on the patient, attached to the patient THROUGH the Anesthesia machine, with O2 flow of 2–5 l/min.
- Peripheral intravenous cannulation was completed as per the patient’s age.
Measurements and recording
- Demographic data: age, sex, and weight.
- Vital signs:
- HR (beats/min).
- MAP (mmHg).
- Respiratory rate (cycles/min).
- BIS measurement :
- Degree of sedation:This was scored using the Modified Observer’s Assessment of Alertness Scale :
- Assessment for separation from parents :
- Assessment of anxiety :
Anxiety was evaluated on a four-point scale.
Timing of assessment of vital signs, BIS measurements, degree of sedation, and anxiety:
- Every 10 min for 30 min in the preoperative holding area.
- On arrival at the operating room after connecting the patient to the multichannel monitor and BIS.
Vital signs and sedation level were also assessed at the following times:
- After application of the O2 face mask.
- After peripheral intravenous cannulation.
- Assessment of mask acceptance :
- Assessment of response to cannulation in order to assess the ease of cannulation :
- Assessment of amnesia :
Anterograde amnesia was assessed after extubation in the ICU by a recall questionnaire that asked the patients about events that took place after the administration of the sedation, including the last thing they remembered before ‘going to sleep’. Specific questions were asked about placement of the pulse oximeter and electrocardiography leads (‘do you remember the doctor putting something on your finger or chest?’).
- Side effects of drugs administered intranasally:
- Sneezing, coughing, nausea, vomiting, nasal burning sensation, or bitter taste .
- Reduction of HR and systolic blood pressure (SBP).
- Mild when O2 saturation was between 91 and 95%.
- Moderate when O2 saturation was between 75 and 90%.
- Severe when O2 saturation was below 75%.
Side effects were recorded if they developed.
| Results|| |
The present study was carried out on 60 children of both sexes who were operated upon for noncomplex congenital heart surgeries. Their ages ranged between 3 and 12 years and they were randomly classified into two equal groups of 30 children each.
There was no statistically significant difference between the two groups as regards age (P=0.924), sex distribution (P=0.796), and weight (P=0.117).
There was no significant difference between the two groups as regards HR [Figure 1] before sedation (baseline) (P=0.463), at 10 min after sedation (P=0.882), and at 20 min after sedation (P=0.193), although there was significant decrease in the DEX group when compared with group M+L at 30 min after sedation (P=0.008), in the operating room (P<0.001), after face mask application (P=0.001), and after intravenous cannulation (P<0.001).
|Figure 1: Comparison between both groups. As regards changes in the Heart rate (beats/min).|
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Similar results were noted as regards the mean blood pressure [Figure 2]. There was no significant difference as regards MAP between the two groups before sedation (baseline) (P=0.668), at 10 min after sedation (P=1.000), intraoperatively at 20 min after sedation (P=0.968), and at 30 min (P=0.081). There was a significant decrease in group D when compared with group M+L in the operating room (OR) (P=0.037), after face mask application (P=0.014), and after intravenous cannulation (P=0.015).
There was no significant difference as regards the percentage of SpO2 [Figure 3] before sedation (baseline) (P=0.427), at 10 min (P=0.466), 20 min (P=0.285), and 30 min (P=0.534) after sedation, and in the OR (P=0.501).
|Figure 3: Comparison between both groups as regards the percentage of oxygen saturation (SpO2).|
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There was no significant difference in respiratory rate, as shown in [Figure 4], before sedation (baseline) (P=0.676), at 10 min (P=0.159), 20 min (P=0.354), and 30 min (P=0.974) after sedation, in the OR (P=0.786), and after face mask application (P=0.685), but the difference in respiratory rate was significantly different after the intravenous cannulation (P=0.025).
|Figure 4: Comparison between both groups as regards the changes in the respiratory rate.|
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Concerning the BIS measurements, there was a statistically significant decrease in BIS measurement in group M+L at 10 min (P=0.024) and 20 min (P<0.001) after sedation and a statistically significant decrease in group D at 30 min after sedation (P<0.001), in the operating room (P<0.001), after the face mask application (P<0.001), and after intravenous cannulation (P<0.001) [Figure 5].
Similar results were seen as regards the sedation score. It was significantly lower in the midazolam group at 10 and 20 min after the administration of the drug. At 30 min after sedation, in the OR, after face mask application, and after intravenous cannulation there was a statistically significant decrease in sedation score in the DEX group compared with group M+L [Figure 6].
|Figure 6: Comparison between the two studied groups as regards the sedation score.|
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Concerning the parent separation score, a successful score was seen in 40% of group M+L patients compared with 60% of group D patients, as shown in [Figure 7].
|Figure 7: Comparison between the two groups as regards separation from the parent.|
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There was a statistically significantly higher mask acceptance score in the DEX group (P=0.016) compared with group M+L [Figure 8].
|Figure 8: A comparison between the two groups according tomask acceptance.|
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There was no statistically significant difference as regards the anxiety score at 10 min.
However, at 20, 30 min, and in the OR there was a statistically significant difference between the two groups, with lower anxiety score in group D (P=0.015, 0.002, and 0.01, respectively).
There was a statistically significant difference between the two groups as regards the response to cannulation (P<0.001) with a lower reactivity score in group D [Figure 9].
|Figure 9: Comparison between the two studied groups according to assessment of reactivity.|
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There was a statistically significant difference between the two groups as regards amnesia (P<0001). Forty percent of children had amnesia compared with none in group D [Figure 10].
|Figure 10: Comparison between the two studied groups according to assessment of amnesia.|
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There was no statistically significant difference between the two drugs as regards the side effects [Figure 11] and [Table 1].
|Figure 11: Comparison between the two studied groups according to assessment of the side effects.|
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|Table 1: Comparison between the two studied groups as regards the anxiety score|
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| Discussion|| |
Providing optimal preinduction sedation and analgesia for children remains an elusive goal in many situations. Intravenous administration of these agents is often preferred to ensure rapid drug delivery, but this may not always be possible. In these cases, alternatives include intramuscular, oral, buccal, and intranasal administration. The relatively rapid delivery of the drug to the blood stream and the CNS after intranasal administration produces effective sedation with minimal patient discomfort, making it a popular option. The primary disadvantage of intranasal drug administration is transient nasal irritation, with some patients also experiencing cough, vocal cord irritation, and laryngospasm .
In the present study, there was no significant demographic difference between the three groups regarding age, sex, and body weight.
In the current study, there was no statistically significant difference between the two groups as regards the HR and the mean blood pressure at 10 and 20 min after intranasal drug instillation. There was a statistically significant decrease in the DEX group at 30 min after sedation, in the OR, after face mask application, and after intravenous cannulation compared with baseline values. This difference could be attributed to the more rapid onset of midazolam. It decreased the mean HR after 10 and 20 min and its effects started to subside 30 min after sedation and in the OR. There was a statistically significant increase in the HR after face mask application and intravenous cannulation. Midazolam is characterized by short onset of action (15 min by intranasal route) .
On the other hand, in group D, there was no statistically significant decrease in HR at 10 min because of slower onset and a statistically significant decrease in HR after 20 and 30 min after sedation, in the OR, after face mask application and intravenous cannulation because of more prolonged duration of action compared with midazolam .
Talon et al.  observed an onset of action of 15 min for DEX administered intranasally at higher doses of 2 mcg/kg with a meter dose atomizer.
Similarly, Yuen et al.  had found that SBP decreased significantly in children after intranasal DEX, compared with that in children who received oral midazolam. SBP decreased with time and it was significantly different from baseline at 30 min (P=0.003), 45 min (P<0.001), and 60 min (P<0.001) after drug administration.
Cheung et al.  also reported that there was a modest reduction in HR and SBP at 20 and 30 min following intranasal DEX.
Sun et al.  similarly stated that intranasal DEX premedication reduced SBP [−11.47 mmHg; 95% confidence interval (CI): −13.95 to −8.98], mean blood pressure (−5.66 mmHg; 95% CI: −8.89 to −2.43), and HR (−12.71 beats/min; 95% CI: −14.80 to −10.62) at 30 and 45 min following the administration of the drug compared with intranasal midazolam.
In the present study, there was no significant difference between the two groups as regards SpO2 changes and respiratory changes except that there was an increase in the respiratory rate after intravenous cannulation in group M+L because of the short duration of action of midazolam. This increase was absent in group D because of the proposed analgesic effect of DEX. Midazolam does not have any analgesic function.
Akin et al.  similarly stated in their study that there was no statistically significant decrease in the respiratory rate or SpO2 below 95%.
In the current study as regards the BIS measurements there was a statistically significant decrease in BIS measurement in group M+L at 10 min (P=0.024) and 20 min (P<0.001) after sedation. Statistically significantly lower values were seen in group D compared with group M+L at 30 min after sedation (P<0.001), in the operation room (P<0.001), after face mask application (P<0.001), and after intravenous cannulation (P<0.001).
Cheung et al.  observed lower BIS measurements after intranasal instillation of DEX at 15, 20, and 30 min preoperatively when compared with a placebo group.
Gharde et al.  similarly stated lower BIS measurements after intranasal midazolam compared with intranasal ketamine in children with tetralogy of Fallot. Values started to decrease at 15 min after administration, until 30 min, with a P value less than 0.05. Mean BIS measurements in the intranasal midazolam group varied between 94 and 87.
In the current study, the sedation scores were statistically significantly lower in the midazolam group at 10 and 20 min after the administration of the drug. At 30 min after drug administration, in the OR, and after face mask application and intravenous cannulation there was a statistically significant decrease in sedation score in the DEX group.
Talon et al.  compared intranasal DEX with oral midazolam, which was administered before the surgery, and reported that intranasal DEX was more effective in inducing sleep preoperatively at 30 and 45 min after drug administration.
In agreement, Patel et al.  confirmed that intranasal DEX produces more effective sedation than midazolam at 45 min (P<0.0001).
Similarly, Sheta et al.  stated that intranasal DEX was more capable of inducing sleep preoperatively than intranasal midazolam at 20 and 30 min and in the OR.
In the present study, more children in group D showed better parent separation scores.
Similarly, Singla et al.  stated in their study that children who received intranasal DEX premedication had better parental separation compared with those who received intranasal midazolam. This may be attributed to the lower dose of intranasal midazolam (0.2 mg/kg).
Sun et al.  compared midazolam and DEX intranasally. They stated that the DEX group was associated with more satisfactory parent separation compared with the midazolam group.
As regards anxiety, there was no statistically significant difference as regards the anxiety score at 10 min. However, at 20 and 30 min and in the OR there was a statistically significant difference between the two groups, with lower anxiety score in group D.
In agreement, in the study by Linares Segovia et al. , in which 48.1% of the sample was treated with DEX and 51.9% with midazolam, anxiety was less frequent in the DEX group at 60 min (P=0.001) and at induction (P=0.04).
Also, Singla et al.  proved in their study that intranasal DEX was superior to midazolam as regards the anxiety score at 30 min (P=0.0234).
In disagreement with our study, Akin et al.  found that the anxiolysis effect was more pronounced in the midazolam group in the OR with no statistically significant difference in the preholding area between the two groups.
As regards mask acceptance in the present study, group D showed 76.7% acceptance, compared with 56.7% in group M, with significant difference between the two groups (P=0.016).
In the study by Sheta et al. , a dose of 1 μg/kg of intranasal DEX premedication was capable of producing satisfactory acceptance of the face mask compared with intranasal midazolam.
In agreement, Sun et al.  compared midazolam and DEX intranasally. They stated that the DEX group was associated with more satisfactory sedation upon mask acceptance compared with the midazolam group.
Similarly, Singla et al.  confirmed better mask acceptance after intranasal DEX compared with midazolam 30 min after drug administration (P=0.047) .
However, Akin et al.  conducted a study comparing intranasal DEX and midazolam in children, administered ∼45–60 min before the induction of anesthesia. They reported that both intranasally administered drugs were equally effective in decreasing anxiety at parental separation, whereas midazolam was capable of producing superior mask induction. In their study, a premedication time was preset to 45–60 min; within that relatively long time, the effect of intranasal midazolam would have undoubtedly worn off. Surprisingly, their results showed that midazolam was superior in providing satisfactory conditions during mask induction. In contrast, premedication time in our study was shorter because children were allowed to be transferred to the OR 30 min after the premedication .
In the present study, as regards the response to cannulation, there was a statistically significant difference between the two groups with no or mild reaction to cannulation in 60% of children in group D compared with 10% in group M+L.
In agreement, Gyanesh et al.  stated that in children given intranasal DEX 30 min before undergoing an MRI, there was no or mild reactions to intravenous cannulation in 90.4% compared with the children given intranasal ketamine.
In the present study, there was a statistically significant difference as regards anterograde amnesia. Forty percent of children in the midazolam group had anterograde amnesia when compared with 0% in the DEX group.
Kain et al.  demonstrated in their study that oral midazolam produces significant anterograde amnesia when given as early as 10 min before a surgical procedure. This study compared anterograde amnesic effects of midazolam with hydroxyzine in 30 children (mean age: 36.4 months) undergoing dental treatment. Their study comprised ASA I children with a first-time appointment with no previous dental experience. Each child was shown a picture from the Stanford–Binet Intelligence Scale Memory for Objects subtest before treatment. Recall in the treatment group was 71% for hydroxyzine and 29% for midazolam. Thus, it was found that midazolam was effective in developing amnesia compared with hydroxyzine when given as early as 10 min before surgery .
In agreement, when Cheung et al.  compared the amnesic effect of intravenous sedation by midazolam and DEX, they found a statistically significant difference (P<001). Sixty percent of the DEX group recalled pictures shown after sedation compared with 7% in the DEX group. However, DEX infusion results in impairment of memory and psychomotor performance. More than half of the patients receiving DEX remembered the pictures shown at the end of sedation drug infusion, but only two patients receiving midazolam did so. However, the amnesic effect of midazolam rapidly diminished with time, and a comparable number of patients in both groups could remember the surgical procedures. A few patients who received DEX recalled the infiltration of local anesthetic but failed to remember the surgical procedure, most likely because the former is a greater stimulus .
However, Mason et al.  proved that DEX was effective at preventing recall of these nonemotive visual stimuli even when responsiveness was present. The mechanism underlying this effect (sedation-induced inattention vs. amnesia-induced inability to remember past events) needs to be clarified in future studies.
In the current study, there was no statistically significant difference as regards the side effects. Neither group had marked side effects.
However, in the study by Sheta et al. , 13 (36.1%) children in the midazolam group showed signs of nasal irritation in the form of teary eyes, but none of these signs were seen in the DEX group.
In the present study there were no side effects such as teary eyes or nasal irritation in group M+L, which may be attributed to the use of lidocaine nasal spray 1% 60 s before the application of intranasal midazolam.
| Conclusion|| |
As proved by the sedation score and the use of BIS measurements, intranasal midazolam gives better effects than DEX after 10–20 min of administration, although DEX gives better effects thereafter. DEX is better than midazolam in producing sedation. There is less anxiety, better mask acceptance, better parent separation, and better reactivity to intravenous cannulation with DEX. Midazolam is able to produce anterograde amnesia. BIS-monitored sedation achieves best results of target sedation with the least complications.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11]