|Year : 2015 | Volume
| Issue : 4 | Page : 573-579
Propofol versus dexmedetomidine as a sole sedative for diagnostic flexible bronchoscopy: a randomized double-blind study
Balaji Mani1, Sagiev Koshy George1, Mohd Saif Khan MD, DNB, PDFCC 1, H Kisku King2
1 Department of Anesthesiology and Critical Care, Pondicherry Institute of Medical Sciences, Puducherry, India
2 Department of Pulmonary Medicine, Pondicherry Institute of Medical Sciences, Puducherry, India
|Date of Submission||31-Jan-2015|
|Date of Acceptance||04-Jun-2015|
|Date of Web Publication||29-Dec-2015|
Mohd Saif Khan
No. 3-A, D Block, PIMS Staff Quarters, P.I.M.S. Hospital, Kalapet, Puducherry 605014
Source of Support: None, Conflict of Interest: None
Clinical trial registration CTRI:REF/2013/10/005804
Sedation is commonly used to improve patients' tolerance and comfort during flexible bronchoscopy (FB). Dexmedetomidine is a relatively novel sedative for use in FB.
The aim of this study was to compare dexmedetomidine and propofol as sole sedative agent in terms of hemodynamics, efficacy, safety and tolerance to the procedure among patients undergoing FB.
Settings and design
This study was carried out in a tertiary care teaching hospital, and was a double-blind randomized-controlled trial.
Patients and methods
Sixty patients were analyzed. Group 1 received propofol (1 mg/kg bolus, then 5 mg/kg/h infusion); group 2 received dexmedetomidine (1 mg/kg bolus, followed by 0.7 mg/kg/h infusion). Intraoperative (IOP) SpO 2 , heart rate, mean arterial pressure, and respiratory rate were recorded at nine time points. Primary outcome variables were hemodynamic variables, level of sedation, and recovery time (to reach an Aldrete score 10/10).
The dexmedetomidine group showed significantly lower mean heart rate than the propofol group at IOP 0 , IOP 2 , and IOP 4 . The mean arterial pressure was significantly higher throughout the procedure in the dexmedetomidine group compared with the propofol group (P < 0.001). A significant decrease in respiratory rate was noted in the dexmedetomidine group at IOP 4 and IOP 6 (P < 0.001). The lowest mean SpO 2 was noted in the dexmedetomidine group (97.0 ± 1.1). Incidences of bucking and coughing were significantly higher in the dexmedetomidine group. Bronchoscopist visual analogue scale scores for coughing and satisfaction were significantly lower in the propofol group (P < 0.001). Recovery time was shorter in the propofol group [3 (1.2) vs. 4.5 (1.1) min] (P < 0.001).
Propofol showed superiority over dexmedetomidine in terms of safety, efficacy, adverse-effect profile, and tolerance to the procedure in patients undergoing diagnostic flexible bronchoscopy.
Keywords: dexmedetomidine, flexible bronchoscopy, propofol, sedation
|How to cite this article:|
Mani B, George SK, Khan MS, King H K. Propofol versus dexmedetomidine as a sole sedative for diagnostic flexible bronchoscopy: a randomized double-blind study. Ain-Shams J Anaesthesiol 2015;8:573-9
|How to cite this URL:|
Mani B, George SK, Khan MS, King H K. Propofol versus dexmedetomidine as a sole sedative for diagnostic flexible bronchoscopy: a randomized double-blind study. Ain-Shams J Anaesthesiol [serial online] 2015 [cited 2019 Jun 25];8:573-9. Available from: http://www.asja.eg.net/text.asp?2015/8/4/573/172743
| Introduction|| |
Flexible bronchoscopy (FB) is an outpatient procedure performed for a variety of diagnostic as well as therapeutic indications  . Despite the claim that FB can be performed without sedation, certain problems cannot be ignored such as cough, breathing difficulty, nasopharyngeal irritation and pain, and procedure-related phobia ,, . Moreover, FB induces a stress response with the release of endogenous catecholamines  . Therefore, current ACCP (American College of Chest Physicians) guidelines recommend the use of sedation with the aim of improving patient comfort and reducing adverse events related to the procedure  . However, an optimal sedative for FB remains elusive and most bronchoscopies are performed under different combinations of sedatives and analgesics. Propofol is favored because of its short half-life, titrability, and rapid recovery profile , . Dexmedetomidine, being a highly selective a2 -agonist, uniquely blunts the hemodynamic response of tracheal stimulation at the time of introduction of the bronchoscope and does not cause respiratory depression  . Several studies have reported the efficacy and safety of dexmedetomidine in combination with other sedative agents ,, . However, no data are available comparing dexmedetomidine and propofol as the sole sedative during flexible bronchoscopy. Therefore, this study aimed to compare the hemodynamics, efficacy, safety, and recovery profile of dexmedetomidine and propofol as the sole sedative agent in patients undergoing diagnostic FB.
| Patients and methods|| |
This prospective randomized double-blind controlled study was carried out during the period December 2011 to May 2013 at a tertiary care university hospital, Puducherry, India. The study protocol was approved by the institutional ethical committee (No. IEC/RC/11/64) and the trial was registered in CTRI (No. REF/2013/10/005804). After obtaining written informed consent, all patients undergoing elective diagnostic FB, ASA class 1 and 2, ranging in age from 18 to 65 years were enrolled. Patients with difficult airway (Mallampati class 3 or 4), ASA grade 3 or 4, psychiatric illnesses, known allergy to lignocaine, propofol, egg, soyabean, chronic addiction to sedative and opioid drugs, and those who were pregnant were excluded. A preanesthetic check-up was performed before the procedure, during which an explanation of the visual analogue scale (VAS) was provided to the patients. All the patients were kept nil per oral (NPO) 6 h before the procedure. Patients were transferred to the bronchoscopy suite and monitoring (ECG, pulse oximetry, non invasive blood pressure (NIBP)) was started and continued until they were shifted to the ward. The baseline values of heart rate (HR), mean arterial pressure (MAP), oxygen saturation of hemoglobin (SpO 2 ), and respiratory rate (RR) were recorded. Topical airway anesthesia was administered in the form of a 2% lignocaine jelly in a nostril and 3 ml aliquots of 1% lignocaine were instilled over the vocal cords onto the trachea using both the right and the left main bronchi by spray-as-you-go (SAYGO) technique during the procedure for all patients. Oxygen was administered to all patients at 4 l/min through a nasal prong. Sedation with either of the drug was started 5 min after the administration of topical anesthesia. Patients were assigned randomly to one of two study groups: the patients in group 1 received 1 mg/kg intravenous bolus propofol (10 mg/ml, brand name, Profol; Claris Life Sciences Ltd, Ahmedabad, Gujarat, India), followed by an infusion of 5 mg/kg/h (83.3 mg/kg/min). The patients in group 2 received 1 mg/kg intravenous dexmedetomidine (100 mg/ml, brand name, Kabimidine; Themis Medicare Ltd, Haridwar, Uttarakhand, India) for the first 10 min, followed by an infusion of 0.7 mg/kg/h. Breakthrough sedation was administered with fentanyl 25 mg intravenously. Both the bronchoscopist and the investigator were blinded to the study. Randomization to either group was performed using sealed envelopes by an anesthesiologist not otherwise involved in the study. The study drugs were prepared by the anesthesia resident, who was not aware of the study. The syringe pumps were labeled with the patient's inclusion number and passed to another anesthesia resident. Intraoperative (IOP) SpO 2 , HR, MAP, and RR were recorded at nine time points (IOP 0 , passage of the bronchoscope through the vocal cords; IOP 2 , 2 min after IOP 0 ; IOP 4 , 4 min after IOP 0 ; IOP 6 , 6 min after IOP 0 ; IOP 8 , 8 min after IOP 0 ; IOP 10 , 10 min after IOP 0 ; IOP 15 , 15 min after IOP 0 ; IOP 20 , 20 min after IOP 0 ; IOP 25 , 25 min after IOP 0 ).
The primary outcome variables were hemodynamic variables (HR, MAP, and RR), mean lowest oxygen saturation (SpO 2 ) during the procedure, level of sedation, and recovery time. The secondary objectives were cough scores, and satisfaction scores of patients and bronchoscopists. Bronchoscopists (immediately after the procedure) and patients (1 h after the procedure) were questioned on the extent of coughing and level of satisfaction, and to rate the procedures using a 10-point VAS (0, no coughing, no discomfort, or very satisfied; 10, incessant coughing, a high level of discomfort, or totally unsatisfactory). High scores indicated an unfavorable response. The patient's level of sedation was assessed using the five-grade Modified Observer Assessment of Alertness/Sedation score (MOAA/S score; 5, appropriate verbal response to patient's name, 4, lethargic response, 3, response only after name is spoken loudly and/or repeatedly, 2, response after mild prodding or shaking, 1, response after painful stimuli, 0, no response at all)  . Recovery from sedation was assessed using the modified Aldrete score, which was determined 5 min after removal of the bronchoscope and every 5 min thereafter until a discharge score of 10/10 was reached  .
The sample size was calculated for a two-sided significance a level of 0.05 and a power of 0.8 to detect a 9.5 mmHg difference in the average of MAP between the two groups. Assuming an SD of 12.2 mmHg with a 10% loss to follow-up, the minimum number of patients required was 29 in each group.
The data were entered in EPIINFO software (Centers for Disease Control and Prevention, Atlanta, GA) and analyzed using the Statistical Package for Social Sciences software (SPSS version 17 for Windows; SSPS Inc., Chicago, Illinois, USA). The continuous data were summarized using mean and SD and dichotomous and categorical data were described using percentages. The tests of significance used were an independent-sample t-test to compare the means of two groups of continuous data and the c2 -test for categorical and dichotomous data. A P value less than 0.05 was considered significant.
| Results|| |
We screened 70 patients for inclusion in the study; of these, 60 patients were analyzed (CONSORT flow, [Figure 1]. The dexmedetomidine group showed a significantly lower mean HR than the propofol group at 0, 2, and 4 min. No episode of desaturation was noted in both groups. No significant change in SpO 2 was observed in both groups. The lowest mean SpO 2 was noted in the dexmedetomidine group (97.0 ± 1.1). The mean MAP was significantly higher throughout the procedure in the dexmedetomidine group compared with the propofol group (P < 0.001). The mean HR was significantly lower in the dexmedetomidine group during the first 4 min of FB. Significant depression in the RR was noted in the dexmedetomidine group at IOP 4 and IOP 6 (P < 0.001; [Figure 2].
|Figure 1: CONSORT flow diagram. Sixty-two patients were randomized into two groups of 30 patients each to receive either propofol or dexmedeto midine|
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|Figure 2: Physiological changes (mean ± SD) during flexible bronchoscopy in patients undergoing elective flexible bronchoscopy receiving propofol (n = 30) or dexmedetomidine (n = 30) as sedation: (a) heart rate, (b) mean arterial pressure, (c) respiratory rate, and (d) oxygen saturation (SpO2)|
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A moderate sedation level (MOAA/S score 3 or 4) was achieved within 5 min of the procedure in a significantly larger proportion of the patients in the propofol group compared with the dexmedetomidine group [Table 1]. Bronchoscopist VAS scores for coughing and satisfaction were significantly lower in the propofol group (P < 0.001). Patients in the dexmedetomidine group required a higher but statistically insignificant dose of fentanyl for breakthrough sedation (P = 0.266). Hemodynamic and airway adverse events are summarized in [Table 2]. Although the incidences of hypertension, tachycardia, and bradycardia were higher in the dexmedetomidine group, there were no significant differences. Incidences of bucking and coughing were significantly higher in the dexmedetomidine group [Table 2]. The recovery time (to reach an Aldrete score of 10/10) was shorter in the propofol group [3 (1.2) vs. 4.5 (1.1) min] (P < 0.001, [Table 1].
| Discussion|| |
The present study was carried out to compare the hemodynamics, efficacy, safety, recovery time, tolerance, and adverse events related to the administration of propofol or dexmedetomidine in patients undergoing flexible bronchoscopy. Our principal findings were that the administration of propofol during flexible bronchoscopy led to significantly faster induction time, early recovery, and lower adverse events compared with the administration of dexmedetomidine as the sole anesthetic agent. Moreover, patients' tolerance and bronchoscopist's satisfaction were better in the propofol group. Overall, no episode of desaturation was noted in both the groups. This could have been because of the exclusion of patients with severe lung disease (FEV 1 < 1 l) and the use of a low-dose opioid. This is not in agreement with various studies in which desaturation was commonly reported ,, .
Propofol is the most commonly used sedative after midazolam in our setup and the use of dexmedetomidine in the sedation protocol has been introduced recently. Despite similar efficacy and safety of sedation with propofol and midazolam, propofol has been the preferred sedative owing to its faster onset of action and better recovery profile, leading to early discharge and improved patient tolerance  . The use of propofol can reduce instances of cough, pain, and sensation of asphyxiation in FB compared with no sedation ,, . Similarly, we found a lower incidence of bucking and coughing in the propofol group. Good cough control improves the quality of a bronchoscopy because of better visualization of the bronchial tree and aids in better sampling. Contamination with blood and bronchial secretions because of cough decreases the diagnostic yield of broncho alveolar lavage (BAL) fluid. Furthermore, incessant cough can halt the bronchoscopy  . A latest randomized study by Liao et al.  , comparing dexmedetomidine and midazolam in 198 postoperative patients undergoing flexible bronchoscopy, reported significantly higher cough scores in the dexmedetomidine group. Another study by Clark et al.  , comparing midazolam and propofol for flexible bronchoscopy, reported significantly better tolerance with the use of propofol. The reason for better tolerance with propofol compared with dexmedetomidine could be the difference between the pharmacodynamic effects of the drugs. Probably, the maintenance dose rate of dexmedetomidine used in our study was lower, which could have resulted in the higher incidence of adverse events and lower tolerance and satisfaction levels. In future, a dose-finding study can be planned to determine the optimal safe dose of dexmedetomidine that can suppress cough and bucking and improve tolerance and satisfaction from both the patient's and the bronchoscopist's perspective.
Flexible bronchoscopy is performed as a daycare or ambulatory procedure. It is imperative that the sedative used in such procedures should have an ultra-short recovery profile. In the present study, the time taken to reach a modified Aldrete score of 10/10 during the recovery period was significantly shorter in the propofol group (P = 0.0001). Similarly, a study carried out by Clark et al.  reported shorter recovery time with propofol compared with that with the midazolam group as evidenced by the bispectral (BIS) index (5.4 ± 4.7 vs. 11.7 ± 10.2 min; P = 0.001). One study reported longer recovery time in the propofol-dexmedetomidine group (18.4 ± 5.8 min) compared with the propofol-remifentanil group  . The longer recovery time in the propofol-dexmedetomidine group may have been because of the higher dose rate of dexmedetomidine in that study  (1.0 mg/kg/h) compared with the lower dose rate used in our study (0.7 mg/kg/h). However, the recovery time in the dexmedetomidine group in our study was not too prolonged as to be unacceptable.
Major limitations with the use of propofol are, first, its narrow margin of safety between moderate sedation and deep sedation and, second, unavailability of an antidote and, hence, it is recommended that it must be administered by either an anesthesiologist or formally trained users. Dexmedetomidine is a selective a2 -agonist with sedative and analgesic properties with the advantage of causing only mild respiratory depression at higher doses  . Its sympatholytic property is utilized in blunting of a sympathetic tracheal response to the introduction of a flexible bronchoscope  . Dexmedetomidine has been reported to be more effective than remifentanil and results in a lower incidence of oxygen desaturation and reduced need for oral cavity suction (reduced salivation and airway secretions)  . In another study, dexmedetomidine and midazolam were associated with better patient cooperation and higher patient satisfaction than midazolam alone  . However, in our study, dexmedetomidine showed a less favorable satisfaction score in both patients and bronchoscopists because it was used as a sole sedative agent, without any amnesic premedication.
The limitations of our study were that it was a single-center study with a small sample size and ASA class 3 or grade 4 patients were excluded. Hence, the result of this study cannot be extrapolated to high-risk patients such as those with liver disease, severe lung disease, and the elderly. In such situations, there would be complications and hence, sedative dose should be curtailed. There is a definite but slight possibility of interobserver bias as FB was performed by two bronchoscopists. However, both study groups did not differ significantly in terms of the bronchoscopist's experience and durations of the procedure. Finally, the cost of sedation regimens could not be assessed and compared, which needs further research.
The strengths of our study were its resilient design with a definite protocol, adequately powered, and double-blinded randomization. It compared two sedatives as sole agents without using any combination because drug interactions leading to synergism or antagonism may confound the outcome. Our study was carried out in India, where flexible bronchoscopy is usually performed without sedation and under local anesthesia alone because of fears related to oversedation. No standard guideline exists for the use of sedation in bronchoscopy in India. Further studies with multicenter data involving large numbers of patients are needed to prove our inferences and to guide the development of standard guidelines for the use of sedation safely in flexible bronchoscopy.
| Conclusion|| |
Propofol is superior to dexmedetomidine in terms of safety, efficacy, adverse effect profile, and tolerance to the procedure in patients undergoing diagnostic flexible bronchoscopy. Future clinical trials should be designed to determine the optimal dose of dexmedetomidine required to achieve sedative goals and improved patient satisfaction.
The authors thank Dr. Bridgitte Akila for the statistical analysis of the data and Dr. Tahmina S. for correcting grammatical errors and reviewing the article.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2]