In our institution, there has been a general preference of conscious sedation during the performance of awake diagnostic flexible bronchoscopy (ADFB). A wide variety of therapeutic agents, either as sole agents or in combination, have been used to provide conscious sedation for this procedure. We were interested in using dexmedetomidine as a sole agent to provide conscious sedation in view of case reports of its successful use in providing sedation during awake fiberoptic intubation.1,2 Dexmedetomidine has also been safely used as a sedative agent during awake fiberoptic intubation in a randomized trial comparing it with remifentanil.3
Despite local anesthetic topicalization of the airway, ADFB is associated with coughing, hypertension, and patient distress. Dexmedetomidine, a parenteral α-2 agonist used for sedation in the intensive care unit, has favorable properties as a sedative for awake bronchoscopy. In addition to its sedative effects, dexmedetomidine has rapidly titratable sympatholytic and analgesic properties that would be useful during an ADFB,4,5 with a low risk of apnea.6 It has also been shown to be a reasonable alternative for sedation in upper gastrointestinal endoscopies for which the requirements for sedation are similar.7 We therefore conducted a prospective trial to determine the feasibility of dexmedetomidine sedation for ADFB.
All patients presenting for diagnostic flexible bronchoscopy were identified and approached to participate in the trial that had been approved by the Human Research Ethics Committee of the investigating institution (Melbourne Health Human Research Ethics Committee). As our aim was to determine the feasibility of dexmedetomidine in providing sedation for ADFB, we intended to recruit approximately 50 patients, with no randomization of treatment groups. Only a core group of anesthetic specialist consultants (3) was involved in the provision of sedation during the study. Patients who had any of the exclusion criteria below or who refused consent were not included in the trial.
- Allergy to dexmedetomidine
- Heart rate <50 beats/min
- Second-degree and third-degree heart block (allpatients 50 y and above would automatically havean electrocardiogram performed preprocedure)
- Severe cardiac failure: grade 3 or 4 ventricularfunction
- Hypotension (systolic blood pressure <90 mm Hg)
- American Society of Anesthesiologists IV(physical status)
- On an α-agonist currently or within the past 2weeks
According to routine institutional guidelines for patients presenting for diagnostic bronchoscopy, all patients were fasted for 6 hours from solids and 2 hours from clear fluids. Intravenous access was established and monitoring for hemodynamic and oxygenation status was performed in all patients. This included an electrocardiogram trace, heart rate, noninvasive blood pressure (systolic blood pressure, mean arterial blood pressure, diastolic blood pressure) and pulse oximetry (SpO2) measurements.
After baseline parameters were obtained, patients were premedicated with 0.2 mg of glycopyrrolate intravenously. This was then followed by the initial intravenous dexmedetomidine bolus of 0.5 μg/kg for 10 minutes followed by a constant infusion of 0.2 to 0.7 μg/kg/h (Alaris PK syringe pump, Cardinal Health, UK) titrating to a Ramsay Sedation Scale score of 3 (Table 1).8 We had chosen a bolus dose of 0.5 μg/kg to reduce the possibility of hypotension that had been observed earlier.9,10
Topicalization of the airways with a local anesthetic was performed during the initial loading infusion of dexmedetomidine. This was achieved by using a De Vilbiss atomizer device. This device enables quick and efficient topicalization of the airways.11 The atomizer device was loaded with 4% lignocaine with a precalculated limit of 9 mg/kg.12,13 The end-points for adequate topicalization were a change in voice and a lack of response to tactile stimulation of the pharynx. The total dose of local anesthetic used for topicalization was recorded.
Once topicalization was completed and the patient sedated to a Ramsay Sedation score of 3, ADFB was performed. Hemodynamic and oxygenation parameters were recorded before glycopyrrolate administration (baseline), every 2 minutes during the dexmedetomidine infusion, and every 5 minutes after the procedure for 30 minutes or until the return to baseline (<10% variation from baseline parameters).
Basic demographics of age, sex, American Society of Anesthesiologists status, weight, and reason for the ADFB was recorded. As this trial was to determine the feasibility of dexmedetomidine sedation for ADFB, we recorded any adverse event that was likely to occur from earlier experience of its use, such as apnea, bradycardia, hypotension, nausea, or any other adverse event. We had allowed for the use of rescue sedation to be used at the discretion of the sedating anesthetist should the anesthetist feel that unnecessary distress was present at any point during the procedure. The dose of any rescue medications used was documented.
Patient satisfaction and comfort were recorded during the postprocedure interview focusing on memory, discomfort, pain, and acceptability of the sedation using a visual analog scale. The satisfaction of the proceduralist was also recorded by using a visual analog scale.
A total of 9 patients were recruited before the early termination of the trial. The trial was terminated early owing to the high proportion of patients requiring rescue sedation (55.6%; Table 2).
No episodes of desaturation (SpO2≤94%) were noted during the dexmedetomidine loading infusion except in patient 9, who had a baseline SpO2 of 92% (Table 3). Patients 1 and 4 developed episodes of desaturation during the procedure that was also present during the recovery phase. This is despite these 2 patients not having received rescue sedatives. In addition, patients 2, 6, and 7 also had at least one episode of desaturation during the recovery phase. These patients did receive additional rescue sedation. Patient 9, who had a baseline oxygen saturation of 92%, unsurprisingly had episodes of desaturation throughout the study. There were, however, no apneas in any of the patients during the study.
No episodes of bradycardia were observed during all 3 phases (loading, continuous infusion during the procedure, recovery phases) of the trial (Table 4). There were also no episodes of hypotension or hypertension during the loading infusion of dexmedetomidine. However, 5 patients developed at least one episode of hypotension during the procedure and an additional 3 patients developed at least 1 episode of hypotension during the recovery phase. Of these, 4 of 5 and 5 of 8 patients, respectively, had received rescue medications during the procedure. Two patients developed episodes of hypertension during the procedure and recovery phases.
Two of 9 patients developed nausea during the trial. However, all patients reported a dry mouth (Table 5).
Seven patients rated their memory of the procedure ≥7 (Table 6). Seven rated their discomfort during bronchoscopy as ≥3. Eight patients reported a pain rating of more than ≤3 during bronchoscopy and 6 gave a score of ≥7 when asked whether they would have the procedure performed in the same way again. Of the 4 patients who received dexmedetomidine sedation only, all rated their memory of the procedure as ≥7 and all rated their discomfort during bronchoscopy ≥3. Three patients rated their pain ≤3 and 3 gave a score ≥7 when asked whether they would have the procedure performed in the same way again.
The proceduralists gave a score of ≥7 for 6 patients when asked how satisfied they were with the sedation (Table 7). For 5 patients, the proceduralists gave a score of ≥7 when asked whether they would do the procedure the same way again.
For the 4 patients who received dexmedetomidine sedation only, the proceduralists gave a score of ≥7 when asked how satisfied they were with the sedation provided by dexmedetomidine and also when asked whether they would do the procedure the same way again.
Topicalization of the airways before bronchoscopy was performed by the anesthetist using 4% lignocaine administered through a De Vilbiss atomizer. Additional local anesthetic (2% lignocaine) was given to patients as required during bronchoscopy through the bronchoscope. Eight of 9 patients required supplemental lignocaine (Table 8). The amount of supplemental 2% lignocaine given by the proceduralist ranged from 0 up to 240 mg. The total dose of dexmedetomidine given to patients for sedation ranged from 24.5 to 78.5 μg.
This feasibility trial was terminated early after only 9 patients were recruited because of the high proportion of patients requiring rescue sedation (55.6%). On preliminary review of the first 9 patients, we felt that the use of rescue sedation in such a high proportion of patients placed future patients at unnecessary and potential risk of additional discomfort prior to the use of rescue medication. We feel that as a sole sedative, dexmedetomidine at this dose was unable to provide sufficient sedation to allow ADFB to proceed comfortably in our patients. Perhaps if we had increased the dose to a bolus dose of 1.0 μg/kg over 10 minutes, we might have found a more favorable result. This higher dose had been used earlier with reasonable success as an alternative to midazolam in the provision of sedation for diagnostic upper gastrointestinal endoscopy.7 We were, however, cautious in our approach because of findings of hemodynamic instability with the use of dexmedetomidine infusions.9,10 Another explanation for unsatisfactory sedation by dexmedetomidine for ADFB when compared with earlier reports of its successful use during awake fiberoptic intubations could be the high intensity of stimulation resulting from diagnostic bronchoscopy, which involves prolonged stimulation of the subglottic airway with associated instrumentation.
Although we accept that our threshold of interventions with rescue sedation is subjective in response to observed patient discomfort and distress during this study, we feel that our findings are still relevant as the core group of anesthetists involved in the study regularly provide sedation for ADFB and are reasonably experienced in the provision of sedation in these circumstances.
Although there were episodes of desaturation during the procedure and recovery period, there was no episode of apnea at any point during the study. Desaturation during ADFB is not uncommon.14 The desaturation could have been related to procedural causes, including bronchoalveolar lavage,15 airway instrumentation, and coughing associated with the procedure. This finding of limited respiratory compromise from dexmedetomidine sedation has been documented earlier.6,10
There were no episodes of clinically relevant bradycardia at any point. This may have been because of the use of glycopyrrolate premedication attenuating the propensity of dexmedetomidine in causing bradycardia. Five of 9 patients, however, developed at least 1 episode of hypotension during bronchoscopy and the recovery phase. Of these 5, 4 had received rescue sedation, which may have contributed to the episodes of hypotension. These patients were asymptomatic and did not require any intervention. Bradycardia and hypotension are well-known adverse effects of dexmedetomidine sedation.10 All patients developed a dry mouth after the procedure. This could have been caused by glycopyrrolate administration, prior fasting and dexmedetomidine itself.
A common sedation technique for bronchoscopy is the use of a combination of a benzodiazepine and an opioid. The benzodiazepine provides the sedative and amnestic components and the opioid provides the analgesic and antitussive components.16 Dexmedetomidine with its sedative, amnestic, and analgesic properties would be useful in this setting.5 However, we have found that at the dose used in our study, a high proportion required rescue sedation, and a large number of patients gave a high rating for memory of the procedure as well. The high requirement for rescue sedation could be because of the lack of antitussive effect of dexmedetomidine in our study. The minimal amnesic effect could be related to a greater intensity of stimulation from diagnostic bronchoscopy and the conservative dosing regimen used here. Nevertheless, a large proportion of patients gave a high score in response to whether they would have the procedure performed the same way again. Surprisingly, as well, the proceduralist also gave a high satisfaction rating in 66.7% of patients.
Although we did not collect any data on the duration of recovery before fitness for discharge, we suspect that there would potentially be a prolonged recovery phase with the use of dexmedetomidine sedation. When dexmedetomidine was used to provide conscious sedation in colonoscopy, it was found to have a prolonged recovery than when compared with a pethidine and midazolam combination or fentanyl boluses.10
The use of single agents alone provides simplicity and minimizes the potential for cumulative adverse effects associated with the use of multiple agents. Both midazolam and propofol have been used as single-agent sedatives for flexible bronchoscopy, with propofol being shown to be superior in achieving the required level of sedation faster and having a faster offset compared with midazolam.17 As a single agent, propofol has also been shown to provide safe effective sedation with faster recovery when compared with a combination of a benzodiazepine and an opioid.18 Thus, the use of single agents alone is not unusual. We had hoped that our pilot trial would have been favorable in showing the use of dexmedetomidine as a single agent for the provision of sedation for ADFB as well. With its useful properties of sedation, analgesia, sympatholysis, and lack of respiratory depression, it seemed an ideal drug for this clinical situation.
In conclusion, dexmedetomidine infusion with a bolus of 0.5 μg/kg for 10 minutes followed by an infusion of 0.2 to 0.7 μg/kg/h is unable to reliably provide as a sole agent adequate sedation for ADFB without the need for rescue sedation. The additional requirement for rescue sedation may have contributed to increased adverse effects. Further trials at a higher loading dose may provide better sedation, but the risk of adverse events may be increased as well.
The authors thank Jason Chen for his assistance in data collection for this trial.
1. Abdelmalak B, Makary L, Hoban J, et al. Dexmedetomidine as a sole sedative for awake intubation in management of the critical airway. J Clin Anesth. 2007;19:370–373.
2. Bergese SD, Khabiri B, Roberts WD, et al. Dexmedetomidine for conscious sedation
in difficult awake fibreoptic intubation cases. J Clin Anesth. 2007;19:141–144.
3. Hagberg CA, Lam NC, Abramson SI, et al. Dexmedetomidine versus remifentanil for sedation
in awake intubations—a randomized, double blind trial (abstract). Anesthesiology. 2008;109:A14.
4. Aantaa R, Jalonen J. Perioperative use of alpha 2-adrenoreceptor agonists and the cardiac patient. Eur J Anaesthesiol. 2006;23:361–372.
5. Hall JE, Uhrich TD, Barney JA, et al. Sedative, amnestic and analgesic properties of small dose dexmedetomidine infusions. Anesth Analg. 2000;90:699–705.
6. Venn RM, Hell J, Grounds RM. Respiratory effects of dexmedetomidine in the surgical patient requiring intensive care. Crit Care. 2000;4:302–308.
7. Demiraran Y, Korkut E, Tamer A, et al. The comparison of dexmedetomidine and midazolam used for sedation
of patients during upper endoscopy: a prospective, randomised study. Can J Gastroenterol. 2007;21:25–29.
8. Ramsay MAE, Savege TM, Simpson BRJ, et al. Controlled sedation
with alphaxalone-alphadolone. BMJ. 1974;2:656–659.
9. McCutcheon CA, Orme RM, Scott DA, et al. A comparison of dexmedetomidine versus conventional therapy for sedation
and hemodynamic control during carotid endarterectomy performed under regional anaesthesia. Anesth Analg. 2006;102:668–675.
10. Jalowiecki P, Rudner R, Gonciarz M, et al. Sole use of dexmedetomidine has limited utility for conscious sedation
during outpatient colonoscopy. Anesthesiology. 2005;103:269–273.
11. Tan H, Swart P, Lennox P, et al. Sedation
free awake fibreoptic intubation using atomised 1% cocaine and 3% lidocaine. Can J Anaesth. 2006;53(suppl 1):26391A.
12. Efthimiou J, Higenbottam T, Holt D, et al. Plasma concentrations of lignocaine during fibreoptic bronchoscopy. Thorax. 1982;37:68–71.
13. Patil V, Barker GL, Harwood RJ, et al. Training course in local anaesthesia of the airway and fibreoptic intubation using course delegates as subjects. Br J Anaesth. 2002;89:586–593.
14. Milman N, Faurschou P, Grode G, et al. Pulse oximetry during fibreoptic bronchoscopy in local anaesthesia: frequency of hypoxaemia and effect of oxygen supplementation. Respiration. 1994;61:342–347.
15. Pirozynski M, Sliwinski P, Radwan L, et al. Bronchoalveolar lavage: comparison of three commonly used procedures. Respiration. 1991;58:72–76.
16. Jantz MA. The old and the new of sedation
for bronchoscopy (editorial). Chest. 2009;135:4–6.
17. Clarkson K, Power C, O'Connell F, et al. A comparative evaluation of propofol and midazolam as sedative agents in fibreoptic bronchoscopy. Chest. 1993;104:1029–1031.
18. Stolz D, Kurer G, Meyer A, et al. Propofol versus combined sedation
in flexible bronchoscopy: a randomised non-inferiority trial. Eur Respir J. 2009;34:1024–1030.