As per the American Society of Anesthesiologists (ASA), difficult airway guidelines awake fiberoptic intubation (AFOI) is most appropriate and recommended for the management of anticipated difficult airway. It is the most reliable and safe modality. However, this can be a tightrope walk for the anesthesiologist to strike a balance between patient comfort by providing sedation and at the same time maintaining a patent airway with spontaneous breathing to avoid the complications of respiratory depression and pulmonary aspiration.
Many drugs have been studied to facilitate this process such as benzodiazepines, local anesthetic agents, and opioid agonists. However, most of them are respiratory depressants. Dexmedetomidine is a popularized drug for its sympatholytic, anxiolytic, analgesic, and sedative properties, with its uniqueness of being devoid of respiratory depressant effect.
Recently, Mirkheshti et al. in 2017 evaluated the effects of local (transtracheal block) dexmedetomidine on sedation and hemodynamic changes in patients undergoing fiberoptic nasotracheal intubation and concluded that the use of local dexmedetomidine during fiberoptic bronchoscopy decreases sudden changes in hemodynamic values, decreases coughing, and improves patient tolerance and intubation score.
However, most of the research has been done on dexmedetomidine through the intravenous route and not much has been studied through alternative routes in adults.
Hence, in our study, we have compared the effects of dexmedetomidine through intravenous and local routes, i.e., through nebulization and in transtracheal block during awake fiberoptic intubation.
SUBJECTS AND METHODS
A prospective, randomized, double-blind study was done within the duration from January 2020 to May 2021 in a tertiary care hospital. After approval from institutional ethical committee (BVDUMC/IEC/89), patients aged between 18 and 75 years, belonging to ASA PS classes I, II, and III requiring elective fiberoptic nasotracheal intubation were included in this study. Indication, risks, and benefits of fiberoptic nasotracheal intubation were explained. Patients not willing to participate, hemodynamically unstable (systolic blood pressure <90 mmHg, heart rate <50/min, or patients with conduction block on electrocardiography), and patients allergic to local anesthetic agents were excluded from the study. Written informed consent was taken. Detailed preoperative anesthesia checkup of all patients was done before the day of surgery.
The sample size was calculated based on the standard deviation from previous study, keeping power at 80% and confidence intervals at 95% (Type I alpha error at 0.05%), a sample of 76 patients would be required. They were divided into two groups: Group I and Group L as shown in Figure 1 by computer-generated randomization table of 38 patients in each group.
Group I: patients received intravenous dexmedetomidine 1 μg.kg−1 over 10 min as an infusion before fiberoptic intubation, followed by 2 mL of 4% lignocaine as nebulization and 2 mL of 2% lignocaine as transtracheal injection. Normal saline 0.05 mL.kg−1 was added in both injections.
Group L: patients received an intravenous infusion of normal saline for 10 min, followed by nebulization with dexmedetomidine 0.5 μg.kg−1 added to 2 mL of 4% lignocaine and transtracheal injection of dexmedetomidine 0.5 μg.kg−1 added to 2 mL of 2% lignocaine 10 min before fiberoptic intubation.
Awake fiberoptic nasotracheal intubation was performed in both groups and parameters were recorded at baseline and every 5 min during intubation. The intubating conditions were assessed by patient tolerance score (PTS) (1 – no reflex from the patient, 2 – a mild grimace, 3 – significant grimace, 4 – verbal complaining, and 5 – defensive posture and movement of the patient) and cough score (1 – no cough, 2 – mild cough, 3 – moderate cough, and 4 – severe cough). Coughing was considered mild if no more than two coughs in sequence, moderate if three to five coughs in sequence, and severe if more than five coughs in the sequence occurred.
Sedation was assessed with Ramsay Sedation Score (RSS). Hemodynamic response – heart rate, blood pressure, blood oxygen saturation (SpO2), and total time duration required from the beginning of fiberoptic nasotracheal intubation till successful intubation was also noted.
The assessment of all scores was carried out by an independent faculty member who was blind about the group to which the patient belongs.
The entire data were statistically analyzed using Statistical Package for the Social Sciences (SPSS version 22.0, IBM Corporation, USA) for MS Windows. In the entire study, the P < 0.05 was considered to be statistically significant. The intergroup statistical comparison of the distribution of categorical variables was tested using the Chi-Square test or Fisher's exact probability test if more than 20% of cells have expected frequency <5. The intragroup statistical comparison of means of normally distributed continuous variables is done using paired t-test. The underlying normality assumption was tested before subjecting the study variables to t-test.
At the end of the clinical trial, all the data were unblinded and entered into an Excel sheet according to the group they belong.
After analysis, demographic data (age and gender) as shown in [Table 1] were found to be comparable between both the groups and were statistically insignificant.
No statistically significant difference was found in the mean pulse rate during intubation between both the study groups (P > 0.05). The intragroup comparison showed a decreasing trend in the mean pulse rate in Group I from baseline till the end of the procedure. No patient had clinically significant bradycardia (decrease in heart rate less than 60/min). Similarly, no statistically significant difference was found in mean systolic and diastolic blood pressure between the two groups at the time of intubation as well as throughout the study. No statistically significant drop in SpO2 level was found in both groups and saturation was above 90% in all.
Mean cough score during intubation in Group I was higher (2.32 ± 0.47) compared to Group L (2.05 ± 0.23) at 5 min (P = 0.003) and at 10 min (2.61 ± 0.55 in Group I compared to 2.05 ± 0.21 in Group L) (P = 0.001) as shown in Graph 1. This difference was statistically significant. Similarly, Graph 2 shows mean PTS during intubation was significantly higher in Group I compared to Group L. At 5 min, the mean PTS in Group I was 2.61 compared to 2.05 in Group L (P = 0.001), and at 10 min, the mean PTS in Group I was 2.84 compared to 2.18 in Group L (P = 0.001).
Mean total time for intubation was significantly longer in Group I (13.16 ± 2.44 min) compared to Group L (8.29 ± 3.14 min) (P = 0.001).
Mean RSS was found to be similar between both the study groups, with a score of 2 indicating cooperative, oriented, and tranquil (P = 0.999).
AFOI is the gold standard for the management of patients with an anticipated difficult airway. It can be an unpleasant experience for the patient even with the meticulous use of local anesthetic agents.
Conscious sedation is desirable not only to make the procedure more tolerable for patients but also to ensure optimal intubating conditions. An ideal sedative agent should be short-acting, titratable, and should provide conscious sedation with adequate patient cooperation and optimal procedural conditions without any significant respiratory depression or hemodynamic changes.
Since the past decade, the practice of conscious sedation has been revolutionized by the discovery of dexmedetomidine. Dexmedetomidine is a selective alpha-2 adrenoceptor agonist with sympatholytic, anxiolytic, analgesic, and sedative properties with no significant respiratory depression. In addition, it also attenuates the sympathoadrenal response to intubation. All of these properties make it, unique and superior to other drugs which have been studied in the past. Dexmedetomidine, when administered intravenously, has the potential to produce significant bradycardia and hypotension, and hence to circumvent this problem, we studied its administration through local routes, i.e., in nebulization and transtracheal block.
Primary objective of this study was to compare patient tolerance score and secondary objectives were to compare sedation score, cough score and total duration required for awake fiberoptic nasotracheal intubation in both the groups.
Hemodynamic parameters were found to be comparable with no statistically significant difference between the groups. Similar hemodynamic findings were found by Niyogi et al. in 2019 studied the stress response of laryngoscopy and endotracheal intubation in an intravenous dexmedetomidine group receiving infusion (0.5 μg.kg−1) over 40 min and intranasal dexmedetomidine group receiving (1 μg.kg−1) 40 min before induction. The study concluded that both routes attenuated the hemodynamic stress responses of laryngoscopy and endotracheal intubation. They also observed all the hemodynamic parameters were maintained within 20% of baseline values throughout the study period. Similar findings were also found by Kumar et al.
These findings are based on the property of dexmedetomidine to modulate stress response and avoid major fluctuations in the hemodynamic parameters. Dexmedetomidine leads to a reduction in noradrenaline release due to central sympatholysis which in turn decreases the sympathetic nervous system response.
Primary outcome of our study was that the PTS was better and the cough score was less in Group L compared to Group I with a statistically significant difference. Our findings were compared with the results of a study by Kumari et al. in which 90 patients were divided into three groups: Group I nebulized with a mixture of 4% lignocaine 4 mL and fentanyl 2 μg.kg−1, Group II with a mixture of 4% lignocaine 4 mL and dexmedetomidine 1 μg.kg−1, and Group III with 4% lignocaine 4 mL and saline. Cough score and comfort scores were lower in the dexmedetomidine group as compared to other groups.
This effect can be explained by the absorption of dexmedetomidine through the nasal route, which may cross the blood–brain barrier and produce the effects on the central nervous system directly. Furthermore, through the high vascularity of the subepithelial surface of the nasal cavity, it may access systemic circulation directly, thus avoiding first-pass metabolism in the liver. Nebulized dexmedetomidine has a bioavailability of 65% through the nasal mucosa and 82% through the buccal mucosa. All of these explain the better PTS and lesser Cough Score in Group L compared to Group I.
One of our secondary objectives was to compare the total time duration for the procedure which was found to be less in Group L as compared to Group I with P = 0.001 due to the achievement of optimal intubating conditions.
We found Ramsay's sedation score the same in both groups, with a score of 2 indicating patients were cooperative during the procedure. This is due to the potent analgesic and sedative effects of dexmedetomidine through presynaptic activation of alpha-2 adrenoceptors in the locus coeruleus. Mirkheshti et al. evaluated the effects of local dexmedetomidine on sedation and hemodynamic changes in patients undergoing fiberoptic nasotracheal intubation. They concluded that the use of local dexmedetomidine during fiberoptic bronchoscopy decreases sudden changes in hemodynamic values and decreases coughing and improves patient tolerance and intubation score. Furthermore, the local route does not have a hypnotic effect, does not decrease SpO2, and enables awake intubation.
So secondary outcome of our study was a similar sedation score in both groups while less time duration was needed for the procedure in Group L.
The limitation of the study was less sample size due to the COVID pandemic as fiberoptic intubation is an aerosol-inducing procedure, so its use was limited. Feasibility in pediatric age group and its use in emergency cases not studied.
In future whether nebulized dexmedetomidine can be used for conscious sedation in endoscopic procedures and along with regional anesthesia can be studied.
Thus, from our observations, we can conclude that dexmedetomidine through local routes, by nebulization and transtracheal block has better patient cooperation and tolerance for awake nasotracheal intubation as compared to intravenous administration. It is a better alternative route in comparison to the intravenous route in providing conscious sedation, without any significant side effects.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
1. Apfelbaum JL, Hagberg CA, Connis RT, Abdelmalak BB, Agarkar M, Dutton RP, et al 2022 American society of anesthesiologists practice guidelines for management of the difficult airway Anesthesiology. 2022;136:31–81
2. Johnston KD, Rai MR. Conscious sedation for awake fibreoptic intubation: A review of the literature Can J Anaesth. 2013;60:584–99
3. Gertler R, Brown HC, Mitchell DH, Silvius EN. Dexmedetomidine
: A novel sedative-analgesic agent Proc (Bayl Univ Med Cent). 2001;14:13–21
4. Mirkheshti A, Memary E, Honar BN, Jalaeefar A, Sezari P. The efficacy of local dexmedetomidine
during fiberoptic nasotracheal intubation: A randomized clinical trial J Anaesthesiol Clin Pharmacol. 2017;33:209–14
5. Mariyappa R, Bevinaguddaiah Y, Iyer SS. A comparison of the effectiveness of dexmedetomidine
versus propofol-fentanyl combination for sedation during awake fibreoptic nasotracheal intubation Indian J Clinl Anaesth. 2019;6:157–64
6. Xue FS, He N, Liao X, Xu XZ, Xu YC, Yang QY, et al Clinical assessment of awake endotracheal intubation using the lightwand technique alone in patients with difficult airways Chin Med J (Engl). 2009;122:408–15
7. Newton T, Pop I, Duvall E. Sedation scales and measures – A literature review SAAD Dig. 2013;29:88–99
8. Schenk A, Markus CK, Kranke P. Awake fiberoptic intubation
– Gold standard for the anticipated difficult airway Anasthesiol Intensivmed Notfallmed Schmerzther. 2014;49:92–9
9. Ahmad I, El-Boghdadly K, Bhagrath R, Hodzovic I, McNarry AF, Mir F, et al Difficult airway society guidelines for awake tracheal intubation (ATI) in adults Anaesthesia. 2020;75:509–28
10. Mondal S, Ghosh S, Bhattacharya S, Choudhury B, Mallick S, Prasad A. Comparison between dexmedetomidine
and fentanyl on intubation conditions during awake fiberoptic bronchoscopy: A randomized double-blind prospective study J Anaesthesiol Clin Pharmacol. 2015;31:212–6
11. Niyogi S, Biswas A, Chakraborty I, Chakraborty S, Acharjee A. Attenuation of haemodynamic responses to laryngoscopy and endotracheal intubation with dexmedetomidine
: A comparison between intravenous
and intranasal route Indian J Anaesth. 2019;63:915–23
12. Kumar NR, Jonnavithula N, Padhy S, Sanapala V, Naik VV. Evaluation of nebulised dexmedetomidine
in blunting haemodynamic response to intubation: A prospective randomised study Indian J Anaesth. 2020;64:874–9
13. Kumari P, Kumar A, Sinha C, Kumar A, Rai DK, Kumar R. Fentanyl versus dexmedetomidine nebulization
as adjuvant to lignocaine: A comparative study during awake flexible fiberoptic bronchoscopy Trends Anaesth Crit Care. 2021;37:18–22
14. Sdrales LM, Miller RD. Miller's Anaesthesia Review E-Book 2017 Amsterdam Elsevier Health Sciences