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Original Article
1 (
1
); 50-54
doi:
10.25259/FH_20230101_43

Comparison of Intranasal Versus Intravenous Dexmedetomidine to Attenuate Haemodynamic Response of Laryngoscopy and Endotracheal Intubation in Elective Lumbar Spine Surgery: A Randomized Controlled Study

Department of Anaesthesiology, Chirayu Medical College & Hospital, Bhopal, Madhya Pradesh, India 462020
Department of Anaesthesiology, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India 462020
Department of Anaesthesiology, RIMS, Ranchi, Jharkhand, India 834009
Corresponding Author Dr. Harish Kumar Address: Department of Anesthesiology 3rd Floor, Hospital building, AIIMS, Bhopal Email: harish.anesth@aiimsbhopal.edu.in Phone no- 9471300943
Licence
This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

How to cite: Ankita, Kumar H, Kumar M. Comparison of Intranasal Versus Intravenous Dexme-detomidine to Attenuate Haemodynamic Response of Laryngoscopy and Endotra-cheal Intubation in Elective Lumbar Spine Surgery: A Randomized Control Study. Future Health 2023; 1(1):43-49.

Abstract

Background:

In general anaesthesia, hemodynamic alterations during endotracheal intubation are vital concerns. The efficacy of intranasal and intravenous Dexmedetomidine (DEX) in decreasing the stress response generated by laryngoscopy and endotracheal intubation was investigated in this study.

Methods:

Seventy adults were randomised into two groups in this prospective, randomised, double-blind study: Group DIV (n=35) and Group DIN (n=35). Dexmedetomidine (DEX) infusion (0.5 μg /kg) was administered intravenously over 40 minutes to the DIV group and intranasally (1 μg /kg) to the DIN group 40 minutes before induction.

The primary outcome was to compare the mean arterial pressure (MAP) between the two groups starting 40 minutes before induction and continuing every 10 minutes until induction of anaesthesia, at the time of intubation, and then every minute afterwards until 5 minutes, 7 minutes, and 10 minutes following intubation. Comparisons of heart rate (HR), systolic (SBP) and diastolic blood pressure (DBP), sedation and any adverse effects were the secondary outcomes.

Results:

The two groups had no statistically significant difference in MAP, HR, SBP and DBP. The DIV group's preoperative sedation score before induction was significantly higher than the DIN group's (P = 0.014).

Conclusion:

This study demonstrates that dexmedetomidine administered intravenously is equally efficient as intranasal dexmedetomidine in attenuating hemodynamic response during laryngoscopy and intubation.

Keywords

laryngoscopy
intubation
dexmedetomidine
premedication
spine surgery

Introduction

The augmented cardiovascular responses in the form of tachycar-dia, hypertension, and even myocar-dial infraction brought about by the noxious stimulus of laryngoscopy and intubation may be detrimental for patients with cardiovascular and cerebrovascular diseases.1

Adequate premedication is neces-sary for stable haemodynamics during laryngoscopy and intubation, which is an integral component of general anaesthesia.

A perfect premedication should be anxiolytic, sedative, analgesic, and antisialagogue. It should have a brief duration of action, a rapid onset, be administered non-parenterally, and have no adverse hemodynamic or respiratory effects2

Dexmedetomidine (DEX) is a highly selective, short-acting, alpha 2-adrenoreceptor agonist used for conscious sedation, and analgesia perioperatively. The intranasal mode of administration of dexmedetomidine has advantage over the intravenous mode in respect to ease of administration.

There needs to be more literature regarding compari-son of the efficacy between intranasal (IN) and intravenous (IV) DEX as a premedication to attenuate haemodynamic response during laryngoscopy and endotracheal intubation in lumbar spine surgery.

So, this study intends to compare the efficacy of IN dexmedetomidine and IV dexmedetomidine for the prevention of haemodynamic surges during laryngoscopy and endotracheal intubation in patient undergoing lumbar spine surgery.

Materials and Methods

A double-blind, randomised control study was con-ducted in a teaching institution of tertiary care after approval of the Institutional Ethical Committee (RmC/IHEC/2021/93) and the informed consent of the participants.

Seventy adults, 18 to 60 years of age, ASA (American Society of Anaesthesiologists physical status) I and II, undergoing elective lumbar spine surgery under general anaesthesia with endotracheal intubation, were included in this study.

Excluded from this study were patients who refused to participate, had a known allergy or hypersensitivity to dexmedetomidine, had severe cardiac and respiratory disease, and were predicted to have a difficult airway. All patients were assessed for intranasal pathology during the preoperative visit. Patients with nasal ulcers, nasal polyps, or nasal septum deviation were pre-cluded from the study. Individual patients underwent a comprehensive pre-operative evaluation and any necessary investigations. Both groups of patients fasted for six hours and received ranitidine (150 mg) and alprazolam (0.5 mg) the night before surgery as premedication.

The randomization was based on a computer-generated random number table. This randomisation schedule allowed for the assignment of patients in two equal groups (Group -DIV and Group DJ. The list was concealed in opaque, sealed envelopes that were numbered and unsealed sequentially after obtaining patient consent.

On the day of the operation, all participants were moved to the preparatory area two hours beforehand. In the preoperative room, all standard monitors, including pulse oximetry, noninvasive blood pressure (NIBP), and electrocardiogram (ECG), were affixed, and baseline haemodynamic parameters were recorded. An 18G peripheral venous cannula administered 80ml/h of Ringer's lactate solution as maintenance fluid.

Group DIV received intravenous DEX (0.50 μg /kg) over the course of 40 minutes before induction. The equiva-lent volume of NS was intravenously administered to the Din group.

Patients in Group -DIN- received IN DEX (1 μg /kg) in its undiluted, parenteral formulation (100 g/ml) form. Intranasal medication was administered into both nostrils using a 1 ml syringe in the supine, head-down position approximately 40 minutes prior to induction. The equivalent volume of NS was intranasally adminis-tered to the DIV group. All patients were instructed to avoid sucking and sneezing following intranasal drug administration. Neither the person administering the medication nor the patients were informed of their group assignment during the course of the study.

Heart rate (HR), mean arterial pressure (MAP), systolic blood pressure (SBP), diastolic blood pressure (DBP), and SpO2 were measured in the preoperative room at 10-minute intervals until induction of anaesthesia.

In the operating room, hemodynamic parameters were recorded during intubation, then every minute for the next five minutes, at seven minutes, and ten minutes after intubation. Using the Ramsay sedation scale (RSS), an observer evaluated the sedation status of both groups at baseline and 40 minutes after drug administration.

After transferring the patient to the operating room, general anaesthesia techniques were standardised for both groups. In the operating room, additional monitors, such as a neuromuscular monitor and an ETCO2 monitor, were affixed, and monitoring continued until the end of the procedure. The monitoring of hemodynamics was maintained throughout the perioperative period. After 3 minutes of preoxygenation with 100% oxygen, all patients were induced with propofol (2 mg/kg) and fentanyl (1 μg /kg) administered intravenously. The administration of intravenous rocuronium bromide (1 mg/kg) facilitated tracheal intubation. When the train of four (tOF) count was zero, an experienced anesthesiologist performed laryngoscopy with a Macintosh laryngoscope blade and endotracheal (ET) intubation with an appropriate size cuffed-disposable armoured ET tube. The laryngoscopy & intubation time limit was 15-20 sec-onds. If laryngoscopy & intubation were not completed within 15 to 20 seconds, the data were excluded from the study analysis. No surgical procedure was permit-ted until 10 minutes after intubation. Anaesthesia was maintained with (40% O2 and N2O with sevoflurane) and repeated intermittent bolus doses of rocuronium in both groups. All patients were ventilated utilising volume-controlled ventilation with a closed circuit to maintain an EtCO2 level between 35 and 40 mm Hg. The timing of extubation was determined by neuromuscular surveil-lance (TOF watch).

The primary outcome was to compare the mean arterial pressure (MAP) between the two groups starting 40 minutes before induction and continuing every 10 minutes until induction and at the time of intubation, and then every minute afterwards until 5 minutes, 7 minutes and 10 minutes following intubation. Comparisons of heart rate, systolic and diastolic blood pressure, sedation, and other adverse effects were the second-ary outcomes.

During the study period, episodes of hypotension (MAP 20% of baseline), bradycardia (HR 50/min), and hypoxia (SPO2 90%) were recorded and treated accordingly.

Infusions of neostigmine (0.05 mg/kg) and glycopyrrolate (0.01 mg/kg) were administered intravenously to reverse neuromuscular block after surgery. After extubation, the patient was transferred to the recovery area. When the patient's Aldrete score was > 9, he was transferred to the ward and his vital signs were monitored for 12 hours.

A pilot study was conducted to ascertain the sample size based on the 15-mmHg standard deviation difference between the two groups post-intubation MAP. It was determined that 35 subjects per group were required to detect a 10-mmHg difference in MAP with 80% power and 5% type-1 error probability. The sample size calculation was performed by the nMaster 2.0 programme. [Biostatistics Department, CMC Vellore].

Statistica version 6 [Tulsa, Oklahoma: StatSoft Inc., 2001] and GraphPad Prism version 5 [San Diego, California: GraphPad Software Inc., 2007] were utilised for statistical analysis. Except for the Ramsay Sedation Score and SpO2 values, all numerical variables in the descriptive statistics were normally distributed (Kolmogorov-Smirnov goodness-of-fit test). The RSS score of 2 (awake, oriented, and cooperative) was deemed adequate for statistical analysis. Student's unpaired t-test for normally distributed data and Mann-Whitney U test for skewed data were used to evaluate comparisons of numerical variables between two groups. If the data were normally distributed, repeated measures analysis of variance (ANOVA) was followed by Tukey's test as a post hoc test; if the data were skewed, Friedman's analysis of variance (ANOVA) was followed by Dunn's test as a post hoc test. A P value of 0.05 was deemed statistically significant.

Statistical Analysis

The collected data was coded and saved within the MS Excel spreadsheet program. SPSS v23 (IBM Corp.) was utilized for information analysis. The continuous variables were analyzed by descriptive statistics and were elaborated in the form of medians/IQRs and means/standard deviations. The categorical variables were elaborated in the percentages and frequencies. To compare proportions, inferential statistics were used by using the Fisher's exact or Chi-square test. The student's t-test and Mann-Whitney U test were used for the comparison of means in the two groups as applica-ble. The paired t-test was used for the comparison of continuous variables at two points in time. Multiple logistic regression analysis was used to document independent predictors of desired outcomes.

Results

A total of 70 patients were analysed. Consort flow diagram is shown in (Figure 1). All the demographic data on patient's characteristics like age, height, weight, BMI and sex were comparable between the two groups (Table 1). In both the groups, the HR was decreased from the baseline value during the preoper-ative period, but in Group D the decrease in the HR was more (19.75% at 30 min and 23.50% at 40 min) than in Group D (15.16% at 30min and18.18% at 40 min). During intergroup comparison, a statistically significant difference in HR was shown at 30 and 40 minutes after the study drugs administration (p-value of 0.044 and 0.015 respectively). None of the patients in both groups has clinically significant bradycardia (Table 2). At 40 min intervals, 57.1% of patients in the DIN group remain in RSS stage II, whereas 77.14% of patients in the DIV group remain in RSS stage III, 77.14%. The DIV group's preoperative sedation score before induction was significantly higher than the D group's (P = 0.014). SBP, DBP and MAP were gradu-ally decreased from baseline values from 20 min onwards in both the groups, but it was more prominent in IV group than IN group. During intergroup compari-son, they found no statistically significant difference. (Maximum decrease of SBP at 40 min 11.45% in Group Din and 11.9% in Group DIV. Similarly maximum fall of dBp at 40 min 12.28% in Group DIN and 15.20% in Group D Maximum fall of MAP at 40 min for Group Din14.8% and Group DIV13.20% (Table 3). It was found that the maximal increase in HR and BP occurred during laryngoscopy and endotracheal intubation, and then it gradually came down to normal limits within 10 min in both groups. The maximal increase in heart rate was 23.7% in Group D and 20.84% in D during laryngoscopy and endotracheal intubation. During intergroup comparison, there was no statistically significant difference in HR was found during and up to 10 mins after intubation. (Table 4). Similarly, maximal increase in MAP occurred during laryngoscopy and endotracheal intubation, then it gradually came down to the normal limit within 10 min in both the group. The increase in MAP was 19% in Group DIN compared to 12.5% for MAP in Gr DIV during laryngoscopy and

Figure 1:
Consort Diagram
Table 1: Demographic characteristics of the patients in two groups.
Demography and other parameters of patients Group DIN (n=35) Mean±SD Group DIV (n=35) Mean±SD P-value
Age (in year) 40.71±10.91 42.03±12.50 0.641
Sex(M/F) 22/13 19/16 0.642
Weight (in kgs) 60±6.894 61.03±7.350 0.548
Height (in meter) 1.623±0.075 1.625±0.065 0.892
BMI (in kg/m2) 22.75±1.7 23.10±2.388 0.980
Table 2: Comparison of heart rate between two groups at different time pointsa
Time in mins Group DIN Mean±SD Group DIV Mean±SD P-value
Basal 87.06±11.337 82.43±8.462 0.057
10min 82.31±10.715 78.80±8.213 0.128
20min 76.80±10.238 73.09±7.358 0.086
30min 73.86±9.372 69.86±6.722 0.044
40min 71.23±9.481 66.60±5.553 0.015
Table 3: Pre operative SBP, DBP and MAP at different time points
Group Basal 10min 20min 30min 40min
Din 128.20±11.749 125.03±11.449 120.20±11.483 117.26±12.793 113.54±12.181
SBP Div 126.94±10.519 123.71±9.057 118.89±10.417 116.23±10.672 111.80±9.710
p- value 0.639 0.596 0.618 0.716 0.510
Din 79.74±7.590 75.29±7.458 71.89±7.940 68.91±8.424 66.00±6.962
DBP Div 78.74±8.965 75.97±9.596 72.91±9.441 70.60±8.247 66.77±7.628
P- value 0.616 0.740 0.623 0.401 0.660
Din 94.63±8.128 90.83±8.624 87.00±8.888 84.20±9.333 81.06±7.673
MAP DiV 93.06±9.365 90.37±9.340 86.94±9.175 84.57±7.868 80.74±7.913
P- value 0.456 0.832 0.979 0.858 0.867
Table 4: Intraoperative heart rate at different time points
Time in min Group Din Mean±SD Group Div Mean±SD P-value
Intubation 84.40±9.435 79.03±5.874 0.090
1min 82.06±8.734 80.54±6.487 0.413
2min 79.74±9.082 77.94±6.063 0.333
3min 78.54±9.936 76.29±5.453 0.243
4min 77.94±10.833 75.60±5.325 0.256
5min 76.46±9.669 74.63±5.325 0.331
7min 76.09±9.633 75.09±5.883 0.602
10min 76.71±9.164 76.09±5.404 0.728
Table 5: Intraoperative MAP (mm of Hg) at different time points
Time in min Group DinMean±SD Group DivMean±SD P-value
Intubation 93.63±7.080 90.91±8.336 0.147
1min 91.97±7.833 91.26±6.853 0.682
2min 88.83±6.853 88.17±7.812 0.709
3min 86.89±7.696 86.40±7.531 0.790
4min 86.23±6.787 85.20±7.304 0.544
5min 85.49±7.089 83.97±6.640 0.360
7min 85.54±6.630 83.71±6.090 0.234
10min 83.26±5.617 84.66±7.557 0.382

Discussion

This study demonstrates that intranasal DEX adminis-tered 40 minutes before intubation is as efficacious as intravenous DEX in reducing laryngoscopic stress re-sponses. In both groups, all hemodynamic parameters (HR, SBP, DBP, MAP) remain within the permissible range during the preoperative and intraoperative phases. Preoperative sedation was substantially greater in the DIV group than in the DIN group. Laryngoscopy and endotracheal intubation are the two most consistent procedures leading to significant in-crease in heart rate and blood pressure. This has been attributed to a sympathetic response as evidenced by in-creased circulating catecholamine levels.3 These changes are found to be greatest 60 seconds after intubation and may even last for 5-10 min post-intubation. The haemodynamic changes brought about by laryngoscopy were first described by Reid and Brace Proper use of premedication may decrease this stress response.4 Numerous pharmacological agents such as opioids (fentanyl), adrenergic blocking agents (esmolol), vasodilating agents (sodium nitroprusside), and local anaesthetics drugs (intravenous lidocaine) have been attempted to attenuate these haemody-namic effects, but none have been able to attenuate these responses completely.5 Due to its unique sedative, hypnotic, anxiolytic, sympatholytic, antisecretory, and analgesic properties, DEX is widely utilised in in-tensive care units. The presynaptic activation of α-2 re-ceptors in locus caeruleus inhibits noradrenaline re-lease and causes sedation and hypnosis. Post-synaptic activation of α-2 receptors in central nervous system decreases sympathetic activity leading to bradycardia and hypotension.

Dexmedetomidine, a centrally acting α 2 agonists, of-fers a unique pharmacological profile with sedation, sympatholysis, analgesia, cardiovascular stability and with greater advantage in avoiding respiratory depression.

All this characteristics of DEX are highly attributable as an ideal premedication agent.6,7

Lakshmi et al found that Intranasal dexmedetomidine is a better premedication agent in morbidly obese patients than oral alprazolam.8 DEX can be administered via intravenous,9 intramuscular,10 intranasal,11 and intraoral12 routes. Intranasal administration is more con-venient because it is innocuous, odourless, and re-quires no intravenous infusion. Intranasal administration of a substance allows it to cross the blood-brain bar-rier and reach the central nervous system directly 13. Be-cause of the increased vascularity of the nasal mucosa, medications can gain rapid access to the venous blood of the systemic circulation, thereby bypassing first-pass metabolism in the liver.14

Various clinical studies with intravenous DEX show that IV DEX can effectively attenuate the stress responses.

Till now intravenous DEX is most popularly used as premedication. However, it is documented that the sed-ative effect of IV DEX is more pronounced than the anal-gesic effect, accompanied by profound bradycardia and hypotension. Moreover, IV DEX may induce biphasic MAP oscillations, which are undesirable in an-aesthesia.

A study by Bloor BC et al on intravenous Dexmedeto-midine15 revealed that in spite of mild hypercapnia and hypoventilation intravenous dexmedetomidine was use-ful in providing perioperative sedation and analgesia without significant respiratory depression.

A clinical study by Sebastian B. et al documented that 0.75 μg/kg is the optimal IV dose for attenuation of stress response to laryngoscopy and endotracheal intubation without any haemodynamic disturbances.16

There is some clinical studies where intranasal DEX has been administered as a premedication especially in paediatric patients. In a study, Yuen VM, et al.17 did a randomised comparison of two intranasal dexmedeto-midine doses (1 μg /kg and 2 μg /kg) as premedication in children. They concluded that both doses produced a similar level of satisfactory sedation in children with no adverse haemodynamic effects in any of the groups. In this study, to avoid any untoward side effects, we used the lower safe dose of 1 μ/kg.

Nasal premedication with midazolam and Dexmedeto- midine has also been studied as alternative to oral premedication with comparable results18 Intranasal route has been successfully used as a sedative in chil-dren for magnetic resonance imaging, CT scan and for burn dressing.19 Noon et al found Intranasal administration of 1.5 μg/kg atomized dexmedetomidine is effective, convenient, and safe as a sedative for patients un-dergoing third molar extraction.20

A recent study by Iriola T et al,21 documented that the peak concentration of intranasal DEX was achieved with a median time range 38-45 min later. So, in our study, we administered intranasal DEX 40 mins before induction.

In our study, preoperative HR was gradually decreased in both groups of patients and this decrease was more in the IV group than intranasal group. A similar finding was found in a study by Cheung et al.22 In our study, in both the group preoperative SBP, DBP and MAP, all gradually decreased from baseline value up to 40 min after study medication. However, these de-creases were more marked in intravenous group than the intranasal group which was statistically significant differences. None of these patients, however, devel-oped clinically significant decreases that required vasopressor or anticholinergics support.

In our study, the maximal increase in HR, SBP, DBP and MAP were occurred during laryngoscopy and endotracheal intubation; then it gradually came down to the normal limit within 10 min in both the group. Though the intranasal group had slightly higher values of SBP, DBP and MAP, they were not statistically significant during intergroup comparison.

Conclusion

This study demonstrates that, dexmedetomidine ad-ministered intravenously is equally efficient as intranasal dexmedetomidine in attenuating hemodynamic response during laryngoscopy and intubation. Additionally, during the preoperative phase, intravenous dexmedetomidine induces higher sedation than intranasal method. To control haemodynamic re-sponse during laryngoscopy and endotracheal intubation, intranasal dexmedetomidine can be utilised as a safer alternative premedication in patients under-going general anaesthesia for lumbar spine surgery.

Financial Support and Sponsorship

Nil.

Conflict of Interest

There are not conflict of interest.

References

  1. , . Pharmacological agents for preventing morbidity associated with the haemodynamic re-sponse to tracheal intubation. Cochrane Database Syst Rev. 2013;7:CD004087.
    [CrossRef] [Google Scholar]
  2. . Dexmedetomidine as premedication in chil-dren: Status at the beginning of 2017. Indian J Anaesth. 2017;61:101-2.
    [CrossRef] [PubMed] [Google Scholar]
  3. , , , , , . Plasma catecholamine responses to tra-cheal intubation. British Journal of Anaesthesia. 1983;55(9):855-60.
    [CrossRef] [PubMed] [Google Scholar]
  4. , . Irritation of respiratory tract and its reflex effect upon heart. Surg Gynae and Obst. 1940;70:157-6.
    [Google Scholar]
  5. , . Comparison of the Clini-cal Efficacies of Fentanyl, Esmolol and Lidocaine in Pre-venting the Hemodynamic Responses to Endotracheal Intubation and Extubation. Journal Of Current Surgery. 2012;2(1):24-28.
    [CrossRef] [Google Scholar]
  6. . Aouad MM-Perioperative uses of dexmedetomidine. Middle East J. Anaesthesiol. 2006;18:1043-58.
    [Google Scholar]
  7. , , , . Scheinin M-Rapid reversal of alpha 2-adrenoceptor ago-nist affects by atipamizole in human volunteers.Br J. Cli Pharmacl. 1991;31:160-5.
    [CrossRef] [PubMed] [Google Scholar]
  8. , . Dinesh Puhani- Acomparative study to evaluate the effect of intranasal Dexmedetomidine versus oral alprazolam as a premedication agent in morbidly obese patients under-going bariatric surgery, J. Anaesth Clin Pharmacol. 2013;29:179-82.
    [CrossRef] [PubMed] [Google Scholar]
  9. , , . Benzodiaz-epine premedication: can it improve outcome in patients undergoing breast biopsy procedures? Anesthesiology. . 1999;90(3):740-7.
    [Google Scholar]
  10. . Evaluation of Midazolam and diazepam for pre-operative sedation. MJAFI. 2000;56:287-292.
    [CrossRef] [PubMed] [Google Scholar]
  11. , , . Premedication with intranasal midazolam in pediatric anesthesia. Ann Fr Anesth Reanim. 1990;9(4):326-3.
    [CrossRef] [PubMed] [Google Scholar]
  12. , , . Oral Sedation: A primer on anxiolysis for the adult patient. Anesth Prog. 2007;54:118-129.
    [CrossRef] [PubMed] [Google Scholar]
  13. , . Intranasal delivery: an ap-proach to bypass the blood brain barrier. India J Pharmacol. 2004;36:140-7.
    [Google Scholar]
  14. , . Intranasal medication delivery for children: a brief review and update. Pediatrics. 2010;126:532-7.
    [CrossRef] [PubMed] [Google Scholar]
  15. , , , . Effects of in-travenous Dexmedetomidine in humans. II. Hemodynamic changes. Anesthesiology. 1992;77:1134-42.
    [CrossRef] [PubMed] [Google Scholar]
  16. , , . Attenuation of haemodynamic responses to laryngoscopy and endotracheal intubation with intravenous Dexmedetomidine: A comparison between two doses. Indian J Anaesth. 2017;61:48-54.
    [CrossRef] [PubMed] [Google Scholar]
  17. , , , , , , , . A randomised com-parison of two intranasal dexmedetomidine doses for premedication in children. Anaesthesia. 2012;67(11):1210-1216.
    [CrossRef] [PubMed] [Google Scholar]
  18. , . Naphade R-Dexmedetomidine at-tenuates sympathoadrenal response to tracheal intubation and reduces perioperative anaesthetic re-quirement. Indian J. Anaesth. 2011;55:352-7.
    [CrossRef] [PubMed] [Google Scholar]
  19. , , , , , , , . -Dexmedetomidine for pediat-ric sedation for computed tomography imaging studies. Anesth Analg. 2006;103:57-62.
    [CrossRef] [PubMed] [Google Scholar]
  20. , , , . - intranasal atomised Dexmedetomidine for sedation during third molar extraction. Int.J. Oral Maxillofac Surg. 2013;42:857-62.
    [CrossRef] [PubMed] [Google Scholar]
  21. , , , , , , . Bioavailability of Dexmedetomidine after intranasal administration. Eur J Clin Pharmacol. 2011;67(8):825-831.
    [CrossRef] [PubMed] [Google Scholar]
  22. , , , , , . Analgesic and sedative effects of intranasal Dexmedetomidine in third molar surgery under local an-aesthesia. Br J Anaesth. 2011;107(3):430-437.
    [CrossRef] [PubMed] [Google Scholar]
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