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RESEARCH ARTICLE
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Year : 2021  |  Volume : 53  |  Issue : 6  |  Page : 440--447

Clinical usefulness of intermediate-dose dexmedetomidine (0.75 μg/kg) in flexible bronchoscopy – A prospective, randomized, double-blinded study

Rahul Magazine1, Thomas Antony1, Bharti Chogtu2, Amithash Marulaiah Prabhudev1, Vyshak Uddur Surendra1, Vasudeva Guddattu3,  
1 Department of Respiratory Medicine, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
2 Department of Pharmacology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
3 Department of Data Science, Prasanna School of Public Health, Manipal Academy of Higher Education, Manipal, Karnataka, India

Correspondence Address:
Dr. Bharti Chogtu
Department of Pharmacology, Kasturba Medical College, Manipal, Manipal, Manipal Academy of Higher Education, Manipal - 576 104, Karnataka
India

Abstract

BACKGROUND: Dexmedetomidine, although an effective drug for conscious sedation during flexible bronchoscopy, has occasional side effects on the cardiovascular system which need to be addressed. MATERIALS AND METHODS: Patients between 18 and 65 years, requiring diagnostic flexible bronchoscopy, found eligible, after screening, were randomized to either receive 0.75 μg/kg intravenous dexmedetomidine over 10 min or intravenous midazolam 0.035 mg/kg over 1 min. Composite score was used as the primary outcome measure. Additional parameters recorded were: Hemodynamic variables, oxygen saturation, Ramsay sedation score, for pain intensity and distress Numerical Rating Scale, number of rescue medication doses, ease of doing bronchoscopy, Visual Analog Scale score for cough and response of the patient 24 h after bronchoscopy. RESULTS: In each group, 24 patients were enrolled. The composite score was in the ideal category in 24 patients in dexmedetomidine group and 21 in midazolam group, at nasopharynx (P = 0.234). The corresponding values at the level of trachea were 23 and 16 (P = 0.023). In dexmedetomidine group, patient response after 24 h of bronchoscopy showed quality of sedation to be excellent in 0 subjects, good in 13, fair in 9 and poor in 2 and discomfort to be nil in 7, mild 10, moderate in 7 and severe in 0. The corresponding values in midazolam group for quality of sedation were 0, 4, 14, 6, and for discomfort 0, 10, 14, 0. The Visual Analog Scale (VAS) for cough revealed a mean score of 0.800 and 1.812 (P = 0.011) during and 2.092 and 3.542 (P = 0.016) 24 h after bronchoscopy in the respective study groups. CONCLUSION: Low-dose dexmedetomidine (0.75 μg/kg single dose) appears to provide better patient comfort and equivalent safety profile when compared with midazolam.



How to cite this article:
Magazine R, Antony T, Chogtu B, Prabhudev AM, Surendra VU, Guddattu V. Clinical usefulness of intermediate-dose dexmedetomidine (0.75 μg/kg) in flexible bronchoscopy – A prospective, randomized, double-blinded study.Indian J Pharmacol 2021;53:440-447


How to cite this URL:
Magazine R, Antony T, Chogtu B, Prabhudev AM, Surendra VU, Guddattu V. Clinical usefulness of intermediate-dose dexmedetomidine (0.75 μg/kg) in flexible bronchoscopy – A prospective, randomized, double-blinded study. Indian J Pharmacol [serial online] 2021 [cited 2022 Jan 27 ];53:440-447
Available from: https://www.ijp-online.com/text.asp?2021/53/6/440/334352


Full Text



 Introduction



Sedation is now a well-established adjunct to flexible bronchoscopy, with drugs such as midazolam, fentanyl, propofol, etc., being commonly used.[1],[2],[3],[4] Proceduralist-driven sedation is fast gaining credence among the bronchoscopists in view of its cost-effectiveness, and above all the patient comfort that is achieved.[5] Notwithstanding the obvious benefits, apprehension regarding the risk of respiratory depression while administering sedation may prevent its more widespread use. Hence, there is a need for a sedating agent which not only is effective, but at the same time has minimal adverse effects on respiratory function. Dexmedetomidine is one such drug that fits the bill.[6],[7],[8],[9],[10] However, the drawback of this drug is the occasional occurrence of hypotension and bradycardia in some subjects. We hypothesized that lowering the dose of dexmedetomidine, while maintaining clinical efficacy during diagnostic flexible bronchoscopy, might prevent the cardiac side effects, thus circumventing this problem.[11],[12],[13] The present study was designed to compare the efficacy and side effect profile of a reduced dose (0.75 μg/kg) of dexmedetomidine with midazolam, a commonly used sedative in the bronchoscopy suites.

 Materials and Methods



This randomized, prospective, double-blinded study was conducted after getting permission from the Institutional Ethics Committee (IEC: 608/2017 Dated 20-9-2017). The study was done at respiratory medicine department of a tertiary care teaching hospital in Southern India.

Screening

Inpatients requiring flexible bronchoscopy from October, 2017 to March, 2019 were screened for the study. Those who met the inclusion criteria were enrolled in the study.

Patients aged 18–65 years requiring flexible bronchoscopy were included in the study. The exclusion criteria included known allergy to Midazolam or Dexmedetomidine, COPD (chronic obstructive pulmonary disease) with FEV1 <50%, hepatic or renal insufficiency, any seizure disorder, psychiatric disorder, hemodynamic instability including heart rate <50 beats/min or heart block of second or third degree, heart failure, hypovolemia, oxygen saturation (SpO2 <90%), body weight more than 70 kg, pregnancy and lactation.

The informed written consent was taken in the language understood by the patients. Then the patients were enrolled and randomized into two study groups, as per computer-generated randomization table, and were randomly allocated to any of the two groups (Group A: Dexmedetomidine or Group B: Midazolam.).[14] The following parameters of the patients were monitored: Pulse rate (PR), noninvasive blood pressure (BP), respiratory rate, SpO2, and Ramsay Sedation Score (RSS) for sedation status. The baseline values of these parameters were noted.

To ensure double blinding, before the procedure, the study drugs were prepared in two syringes labeled as 1 and 2, ensuring the name of the drug is not written on the syringes. Syringe 1 contained either Dexmedetomidine (0.75 μg/kg) in normal saline and then diluted to make a total of 10 ml or Normal saline 10 ml. Syringe 2 contained either Midazolam (0.035 mg/kg) diluted in normal saline to make a total of 4 or 4 ml of normal saline. At the outset, contents of syringe 1 were infused slowly over 10 min and contents of syringe 2 were injected at the beginning of 9th min. Bronchoscopy commenced at the end of 10th min.

Procedure: Lignocaine jelly 2% (2 ml) was administered into one of the patent nostrils of the patient. Then 2% of lignocaine spray (2 ml) was sprayed at the level of oropharynx and another 2 ml at the vocal cords, via the bronchoscope. After that at 1st min, bronchoscope was passed below the level of vocal cords and 2% of lignocaine (1 ml) was sprayed over trachea. After spraying 2% lignocaine (1 ml), the bronchoscope was introduced into the main bronchi, on cessation of coughing. Next the bronchial tree was examined and the planned sampling procedure was completed. In case, the patient developed recurrent cough, additional lignocaine spray 2% was sprayed. The rescue medication (intravenous Midazolam 0.5 mg bolus) was administered with an interval of at least 2 min between the doses. It was kept as an open-labeled syringe.

The hypotension (systolic BP <90 mm Hg) was to be managed with intravenous crystalloids. Bradycardia (<50 bpm) was to be treated with atropine (0.01 mg/kg) intravenously.[15] The level of sedation of the patient was continuously assessed and kept 2–3 as per RSS.

In this study, there were three observers. Observer A: The person, who randomized the patients as per computer-generated randomization table, prepared the study drug, labeling syringes as 1 and 2 and was not involved in the further study. Observer B-performed the bronchoscopy and Observer C after explaining study methodology took consent, assessed the patient, gave the study medication and ultimately recorded the parameters. B and C observers were blinded to the study drug.

Composite score during the flexible bronchoscopy was the primary outcome measure. Higher score indicated worse performance of the drug.[6]

“SpO2, hemodynamic variables, Numerical Rating Scale (NRS) for pain intensity and distress, number of doses of rescue medication of intravenous midazolam during the procedure, time of bronchoscopy procedure, and dose of lignocaine used” were noted.

NRS 0 stands for no pain/discomfort and 10 for unbearable pain/discomfort. VAS was used to gauge cough and ease of doing bronchoscopy. Twenty 4 h postprocedure, patient response was assessed.[6],[16],[17],[18],[19]

Sample size: Anticipating a standard deviation (SD) of 3.65 and a minimum clinically significant difference of 3 in composite score for a power of 80% at 95% confidence level, a minimum of 24 subjects in each group were recruited.

Statistical analysis: The SPSS version 18.0 (SPSS Inc., Chicago, IL, USA) was used for analyzing the data. The analysis between the groups for the continuous variables was done using the independent t-test. The categorical variables which included RSS, ease of bronchoscopy, etc., were analyzed using the Chi-square test. P < 0.05 was considered statistically significant.

 Results



A total of 96 patients were screened and of these 48 patients who fulfilled the study criteria were enrolled (24 in each arm). All enrolled patients completed the study and there were no dropouts [Figure 1]. The baseline characteristics of the patients are shown in [Table 1]. The comparison of composite score is shown in [Table 2]. The items under “composite score at nasopharynx and trachea” are shown in [Table 3]. The items under “NRS for Pain and Distress” are shown in [Table 4]. The rest of the study parameters are shown in [Table 5].{Figure 1}{Table 1}{Table 2}{Table 3}{Table 4}{Table 5}

At different time points, the mean heart rate (beats per minute), respectively, in dexmedetomidine group and midazolam group was as: Baseline (81.92 ± 18.533, 84.83 ± 15.670; P = 0.059), start of bronchoscopy (81.25 ± 17.662, 93.08 ± 15.581; P = 0.018), at 5 min (91.42 ± 20.502, 106.92 ± 15.174; P = 0.005), at 10 min (93.88 ± 24.027, 111.00 ± 22.055; P = 0.081)¸ at end of bronchoscopy (99.08 ± 23.413, 105.92 ± 17.619; P = 0.624), and at 10 min postbronchoscopy (87.33 ± 18.563, 95.92 ± 14.643; P = 0.082).

The mean systolic BP (mm Hg) in dexmedetomidine group and midazolam group, respectively, was as: Baseline (127.42 ± 20.930, 126.58 ± 20.905; P = 0.891), start of bronchoscopy (124.08 ± 25.053, 129.25 ± 19.929; P = 0.433), at 5 min (130.17 ± 23.331, 135.08 ± 23.136; P = 0.467), at 10 min (124.87 ± 20.119, 141.20 ± 22.768; P = 0.068)¸ at end of bronchoscopy (127.67 ± 19.611, 135.67 ± 21.130; P = 0.181), and at 10 min postbronchoscopy (117.25 ± 18.555, 125.33 ± 20.273; P = 0.156) [Figure 2].{Figure 2}

Similarly, the mean diastolic BP (mm Hg) in dexmedetomidine group and midazolam group was recorded as: Baseline (74.08 ± 11.088, 78.92 ± 9.528; P value = 0.112), start of bronchoscopy (75.75 ± 11.380, 82.50 ± 9.027; P value = 0.028), at 5 min (80.17 ± 16.258, 85.75 ± 11.844; P value = 0.181), at 10 min (79.12 ± 21.441, 92.40 ± 16.728; P = 0.109)¸ at end of bronchoscopy (81.00 ± 15.967, 90.25 ± 17.498; P = 0.062), and at 10 min postbronchoscopy (74.25 ± 10.203, 82.00 ± 11.143; P value = 0.016).

The values of the mean SpO2 (%) recorded in dexmedetomidine group and midazolam group were as: Baseline (99.92 ± 0.408, 100.00 ± 0.000; P = 0.323), start of bronchoscopy (99.96 ± 0.204, 100.00 ± 0.000; P = 0.323), at 5 min (99.92 ± 0.408, 99.67 ± 1.129; P = 0.313), at 10 min (99.50 ± 2.000, 99.60 ± 1.265; P = 0.889)¸ at end of bronchoscopy (99.50 ± 1.351, 99.25 ± 1.871; P value = 0.598) and at 10 min postbronchoscopy (99.83 ± 0.565, 99.79 ± 1.021; P value = 0.862).

Hypotension or bradycardia was not observed in either group. Two patients from the midazolam group and one from dexmedetomidine group developed oxygen desaturation with a statistically nonsignificant difference (P = 1.00). In both the groups, the dose of lignocaine used was similar, respectively (Mean ± SD was 190.00 ± 16.681 and 189.17 ± 17.673; P = 0.867).

 Discussion



In various clinical settings, it has been demonstrated that administration of dexmedetomidine (1 μg/kg) initially as loading dose and then as an infusion (0.5 μg/kg/h) is comparable, and in some cases superior, to midazolam in reducing pain and discomfort associated with invasive procedures. Moreover, this is achieved with a reduced occurrence of respiratory depression, in case of dexmedetomidine.[20],[21],[22],[23],[24] However, there are concerns regarding cardiovascular adverse events of dexmedetomidine, such as bradycardia and hypotension. This can prevent its more widespread use during common procedures such as flexible bronchoscopy. One way to get around this problem of cardiovascular side effects is to use a reduced dose of dexmedetomidine. However, two questions arise if such an approach is adopted: Is the reduced dose going to maintain clinical efficacy? And does lowering the dose lead to reduced cardiovascular side effects?

There are studies in the literature which have used doses of dexmedetomidine lower than the usual 1 μg/kg loading dose.[25] In one such randomized double-blind study, the investigators found that there was no difference between 0.5 μg/kg of dexmedetomidine and alfentanil 10 μg/kg when used during flexible bronchoscopy.[12] Thus suggesting that a reduced dose of dexmedetomidine retains its clinical efficacy. In another randomized double-blind study from a university medical college in India, it was observed that 0.5 μg/kg of dexmedetomidine provided a clinically meaningful conscious sedation in the setting of flexible bronchoscopy, when compared to 0.035 mg/kg of midazolam.[13] Contrary to these, in a study conducted in Australia, the investigators found that 0.5 μg/kg dose of dexmedetomidine was ineffective in producing satisfactory sedation during flexible bronchoscopy, with over half of the subjects in the study requiring rescue doses of sedation.[26] In view of such a mixed picture emerging from various studies, there is a need to clarify the role of reduced dose of dexmedetomidine in the setting of flexible bronchoscopy, by finding out the appropriate dose which reduces adverse events but maintains clinical efficacy.

In this study, the dexmedetomidine group when compared with the midazolam had lower composite score both at the level of nasopharynx and trachea, although it was statistically significant only at the level of trachea. This difference could be due to the time required for the drug to take effect and hence, as more time elapsed dexmedetomidine appeared to perform better compared to midazolam at the level of trachea. The significantly lower composite scores achieved with reduced dose (0.75 μg/kg) of dexmedetomidine strengthens the assertion that dexmedetomidine maintains its clinical efficacy at such reduced doses when compared with midazolam. In a similar study, comparing single dose 0.5 μg/kg of dexmedetomidine with midazolam, there was no significant difference in the composite score between the groups, thus indicating that 0.75 μg/kg dose maybe better that 0.5 μg/kg dose of dexmedetomidine, so far as the composite score parameters are concerned.[13]

Lower doses of dexmedetomidine cause less cardiovascular effects compared to higher doses, while maintaining clinical effectiveness. In a study, done in patients undergoing upper limb surgeries, a dose of 2 μg/kg dexmedetomidine was not observed to increase the duration of analgesia when compared to a dose of 1 μg/kg dexmedetomidine. However, lower heart rate and BP was seen at higher dose.[27] Another study comparing an even lower dose, during laryngoscopy and tracheal intubation, found that 1.0 μg/kg and 0.5 μg/kg dexmedetomidine were comparable in clinical efficacy. In addition, the 0.5 μg/kg dexmedetomidine group showed lesser occurrence of cardiovascular adverse effects such as hypotension and bradycardia.[11]

In a study done at a university hospital in China, loading dose of 1 μg/kg and maintenance dose of 0.5 μg/kg/h of dexmedetomidine was compared with midazolam loading dose (2 mg) followed by need-based midazolam 1 mg intravenous boluses during flexible bronchoscopy in the postoperative setting. The investigators found that in both the groups the procedure was equally well tolerated, although dexmedetomidine group had higher incidence of bradycardia (13 vs 4) which was statistically significant (P = 0.04). Episodes of hypotension occurred in both the groups, and the difference was not statistically significant (6 vs 7; P > 0.05).[21] No patient in our study developed bradycardia or hypotension, thus further supporting the observation that dexmedetomidine at such reduced doses has a favorable side effect profile. In a similar study, 1 μg/kg dexmedetomidine group had one episode of hypotension (though not statistically significant), whereas in another study, 0.5 μg/kg of dexmedetomidine produced no event of hypotension.[6],[13] In the present study, oxygen desaturation was observed in two patients in the midazolam group and only in one patient in the dexmedetomidine group − the difference was, however, not statistically significant. These events of desaturation were transient and not clinically significant, and hence flexible bronchoscopy could be completed without any risk to the patient. This trend toward lower occurrence of the oxygen desaturation with dexmedetomidine has been observed in other similar studies as well.[6],[13]

Randomized double-blind study, comparing dexmedetomidine (1 μg/kg) single dose with 0.02 mg/kg midazolam, revealed the NRS for pain and distress scores to be lower in dexmedetomidine group.[6] Whereas in another randomized double-blind study, no significant difference was observed in NRS for pain and distress on comparing 0.5 μg/kg dexmedetomidine single dose with 0.035 mg/kg midazolam between the study groups.[13] In the former, lower scores in favor of dexmedetomidine could have been due to the fact that a higher dose of dexmedetomidine was compared with a lower dose of midazolam in that study, thus exaggerating the difference. Nevertheless, we can safely surmise that dexmedetomidine at doses of 0.5 and 1 μg/kg appear to be comparable to or better than midazolam, respectively, in terms of NRS scores.[6],[13] In the present study, 0.75 μg/kg dexmedetomidine single dose resulted in NRS scores which were not significantly different from those observed in the midazolam group.

Ease of doing bronchoscopy has been shown to be better with dexmedetomidine at 1 μg/kg when compared to midazolam.[6] However, dexmedetomidine, when used at 0.5 μg/kg dose, gave inconclusive results in a similar clinical setting.[13] In our study, there is a trend toward better ease of doing bronchoscopy, even though it did not reach statistical significance.

Limitations

Midazolam, being the most common intravenous sedative used during flexible bronchoscopy, was compared with dexmedetomidine in our study.[28] Its lack of analgesic property becomes a disadvantage for it when compared with dexmedetomidine. Hence, comparing midazolam-fentanyl combination, instead of only midazolam, with dexmedetomidine, would have created a more balanced study design. In most of the studies, dexmedetomidine has been used as a loading dose followed by a maintenance dose. However, in the present study we used only the loading dose, and hence, this approach could potentially lead to early loss of clinical efficacy of the drug during the procedure. However, considering the fact that we conducted the study during diagnostic flexible bronchoscopy, which has a relatively shorter procedure time, the drug is expected to remain effective for such short duration.

 Conclusion



In the present study, 0.75 μg/kg single dose dexmedetomidine appeared to provide better patient comfort and equivalent safety profile when compared with midazolam. There also appears to be trend in favor of dexmedetomidine in ease of doing the procedure.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Du Rand IA, Blaikley J, Booton R, Chaudhuri N, Gupta V, Khalid S, et al. British Thoracic Society guideline for diagnostic flexible bronchoscopy in adults: Accredited by NICE. Thorax 2013;68 Suppl 1:i1-44.
2Prabhudev AM, Chogtu B, Magazine R. Comparison of midazolam with fentanyl-midazolam combination during flexible bronchoscopy: A randomized, double-blind, placebo-controlled study. Indian J Pharmacol 2017;49:304-11.
3Barnett AM, Jones R, Simpson G. A survey of bronchoscopy practice in Australia and New Zealand. J Bronchology Interv Pulmonol 2016;23:22-8.
4Hwang J, Jeon Y, Park HP, Lim YJ, Oh YS. Comparison of alfetanil and ketamine in combination with propofol for patient-controlled sedation during fiberoptic bronchoscopy. Acta Anaesthesiol Scand 2005;49:1334-8.
5Mohan A, Madan K, Hadda V, Tiwari P, Mittal S, Guleria R, et al. Guidelines for diagnostic flexible bronchoscopy in adults: Joint Indian Chest Society/National College of Chest Physicians (I)/Indian Association for Bronchology Recommendations. Lung India 2019;36:S37-89.
6Goneppanavar U, Magazine R, Periyadka Janardhana B, Krishna Achar S. Intravenous dexmedetomidine provides superior patient comfort and tolerance compared to intravenous midazolam in patients undergoing flexible bronchoscopy. Pulm Med 2015;2015:727530.
7Yuan F, Fu H, Yang P, Sun K, Wu S, Lv M, et al. Dexmedetomidine-fentanyl versus propofol-fentanyl in flexible bronchoscopy: A randomized study. Exp Ther Med 2016;12:506-12.
8Ryu JH, Lee SW, Lee JH, Lee EH, Do SH, Kim CS. Randomized double-blind study of remifentanil and dexmedetomidine for flexible bronchoscopy. Br J Anaesth 2012;108:503-11.
9Li H, Zhang N, Zhang K, Wei Y. Observation of the clinical efficacy of dexmedetomidine in flexible bronchoscopy under general anesthesia: Clinical case experience exchange. J Int Med Res 2019;47:6215-22.
10Niyogi S, Basak S, Acharjee A, Chakraborty I. Efficacy of intravenous dexmedetomidine on patient's satisfaction, comfort and sedation during awake fibre-optic intubation in patients with cervical spondylotic myelopathy posted for elective cervical fixation. Med Res 2019;47:6215-22.
11Sharma N, Mehta N. Therapeutic efficacy of two different doses of dexmedetomidine on the hemodynamic response to intubation, the intubating conditions, and the effect on the induction dose of propofol: A randomized, double-blind, placebo-controlled study. Anesth Essays Res 2018;12:566-71.
12Riachy M, Khayat G, Ibrahim I, Aoun Z, Dabar G, Bazarbachi T, et al. A randomized double-blind controlled trial comparing three sedation regimens during flexible bronchoscopy: Dexmedetomidine, alfentanil and lidocaine. Clin Respir J 2018;12:1407-15.
13Magazine R, Venkatachala SK, Goneppanavar U, Surendra VU, Guddattu V, Chogtu B. Comparison of midazolam and low-dose dexmedetomidine in flexible bronchoscopy: A prospective, randomized, double-blinded study. Indian J Pharmacol 2020;52:23-30.
14Wolfenden L, Nathan N, William CM. A randomized control trial of an intervention to increase the implementation of healthy canteen policy in Australian primary schools. Implement Sci 2014;9:147.
15Shoukry RA. Safety and efficacy of dexmedetomidine sedation for elective fiberoptic bronchoscopy: A comparative study with propofol. Egypt J Anaesth 2016;32:483-8.
16Breivik H, Borchgrevink PC, Allen SM, Rosseland LA, Romundstad L, Hals EK, et al. Assessment of pain. Br J Anaesth 2008;101:17-24.
17Stolz D, Chhajed PN, Leuppi JD, Brutsche M, Pflimlin E, Tamm M. Cough suppression during flexible bronchoscopy using combined sedation with midazolam and hydrocodone: A randomised, double blind, placebo controlled trial. Thorax 2004;59:773-6.
18Spinou A, Birring SS. An update on measurement and monitoring of cough: What are the important study endpoints? J Thorac Dis 2014;6:S728-34.
19Morice AH, Fontana GA, Belvisi MG, Birring SS, Chung KF, Dicpinigaitis PV, et al. ERS guidelines on the assessment of cough. Eur Respir J 2007;29:1256-76.
20Safi F, Rabiee L, Shokrpour M, Kamali A. Comparison of midazolam and dexmedetomidine for pain relief during and after hysterosalpingography in women with infertility. J Med Life 2019;12:173-7.
21Liao W, Ma G, Su QG, Fang Y, Gu BC, Zou XM. Dexmedetomidine versus midazolam for conscious sedation in postoperative patients undergoing flexible bronchoscopy: A randomized study. J Int Med Res 2012;40:1371-80.
22Tripathi M, Kumar V, Kalashetty MB, Malviya D, Bais PS, Sanjeev OP. Comparison of dexmedetomidine and midazolam for sedation in mechanically ventilated patients guided by bispectral index and sedation-agitation scale. Anesth Essays Res 2017;11:828-33.
23Yousuf A, Ahad B, Mir AH, Mir AW, Wani JG, Hussain SQ. Evaluation of effectiveness of dexmedetomidine and fentanyl-midazolam combination on sedation and safety during awake fiberoptic intubation: A randomized comparative study. Anesth Essays Res 2017;11:998-1003.
24Pushkarna G, Sarangal P, Pushkarna V, Gupta R. Comparative evaluation of dexmedetomidine versus midazolam as premedication to propofol anesthesia in endoscopic retrograde cholangiopancreatography. Anesth Essays Res 2019;13:297-302.
25Wu SH, Lu DV, Hsu CD, Lu IC. The effectiveness of low-dose dexmedetomidine infusion in sedative flexible bronchoscopy: A retrospective analysis. Medicina (Kaunas) 2020;56:E193.
26Lee K, Orme R, Williams D, Segal R. Prospective pilot trial of dexmedetomidine sedation for awake diagnostic flexible bronchoscopy. J Bronchology Interv Pulmonol 2010;17:323-8.
27Sinha C, Kumar A, Kumari P, Singh AK, Sharma S, Kumar A, et al. Comparison of two doses of dexmedetomidine for supraclavicular brachial plexus block: A randomized controlled trial. Anesth Essays Res 2018;12:470-4.
28Madan K, Mohan A, Agarwal R, Hadda V, Khilnani GC, Guleria R. A survey of flexible bronchoscopy practices in India: The Indian bronchoscopy survey (2017). Lung India 2018;35:98-107.