Rapid and reliable smooth extubation - Comparison of fentanyl with dexmedetomidine: A randomized, double-blind clinical trial.

BACKGROUND: Fentanyl and dexmedetomidine have been tried to attenuate airway and circulatory reflexes during emergence and extubation individually but have not been compared with respect to the level of sedation to evolve a reliable technique for rapid and smooth extubation. AIM: To compare the effects of fentanyl and dexmedetomidine in attenuating airway and circulatory reflexes during emergence and extubation of the endotracheal tube. SETTING AND
DESIGN: This double-blind, randomized, controlled study was done in patients undergoing surgery under general anesthesia belonging to the American Society of Anesthesiologists physical status 1 or 2.
METHODOLOGY: All patients received a standardized anesthetic protocol. Patients were randomized to receive either fentanyl 1 μg/kg or dexmedetomidine 0.75 μg/kg. Fifteen minutes before expected last surgical suture, isoflurane was cutoff and equal amount of test solution was given when train-of-four ratio was 0.3. The degree of sedation, airway, and circulatory responses at the time of suction and extubation were analyzed. STATISTICAL ANALYSIS USED: Chi-square test for nonparametric data and t-test for parametric data.
RESULTS: Heart rate (HR) was comparable in both the groups until endotracheal extubation. Later, there was rise in HR in fentanyl group. There was stastisticaly significant drop in blood pressure at 5 min after test drug administration in both the groups. Airway response for suctioning and extubation was better in dexmedetomidine group and it was associated with better sedation score than fentanyl group.
CONCLUSION: Single dose of 0.75 μg/kg dexmedetomidine given 15 min before extubation provides smooth extubation when compared to fentanyl.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

Tracheal extubation can be associated with detrimental airway and hemodynamic responses. Smooth extubation requires the absence of straining, movement, coughing, breath holding and laryngospasm.[1] Many theories have been described for sudden increase in heart rate (HR) and blood pressure (BP) during intubation and extubation such as surge of catecholamines,[2] airway irritation, intense pain following surgery, and emergence. Although these changes are transitory, it could be a major concern for an anesthesiologist. Many drugs are used to attenuate the intubation response such as intravenous lignocaine,[3] short-acting opioids such as fentanyl and remifentanil,[45] esmolol,[6] labetalol,[7] intratracheal local anesthetic instillation,[8] dexmedetomidine[9] which can be used during extubation also. Extensive research has been done to attenuate hemodynamic responses to intubation, but the same care and precautions are seldom carried out for extubation. A reliable technique for rapid and smooth extubation is still not fully evolved. The aim of this study was to compare the effect of sedation with single-dose dexmedetomidine and fentanyl on the attenuation of circulatory and airway response to endotracheal extubation.

METHODOLOGY

After Ethical Committee approval and obtaining written informed consent from patients, this double-blind, randomized, prospective clinical trial was carried out over a period of 6 months on fifty patients of American Society of Anesthesiologists (ASA) Grades 1 and 2 of either sex, aged above 18 years undergoing surgery under general anesthesia. Patients with active upper respiratory tract infection and those required intra-operative nasogastric tube were excluded from the study. Patients were randomized into two groups by sealed envelope technique; Group D received dexmedetomidine 0.75 µg/kg and Group F received fentanyl µg/kg.

All patients were premedicated with oral diazepam 10 mg in the night and tablet ranitidine 150 mg in the morning of the surgery. On the operating room table, after securing an intravenous access, injection midazolam 1 mg and injection ondansetron 4 mg were given. Base line hemodynamic parameters such as HR, BP, oxygen saturation were recorded with a multiparameter monitor. All participants were anesthetised using standard anesthesia technique. All patients were induced with thiopentone 5 mg/kg, morphine 0.1 mg/kg. Tracheal intubation was done using vecuronium (loading dose of 0.1 mg/kg, intermittent bolus of 0.02 mg/kg) and anesthesia was maintained on O2:N2O (0.3 L: 0.3 L) and isoflurane 1.5% dial concentration adjusted to maintain minimum alveolar concentration. An additional dose of morphine was given depending on hemodynamics. Fifteen minutes before expected last surgical suture, ensuring train-of-four (TOF) ratio 0.3 (TOF watch), isoflurane was stopped, and equal amount of test solution (10 ml) was given over a period of 5 min by infusion (Baxter infusion syringe pump). The test solution was prepared by anesthesiologist who was not involved in the study. Five minutes after the infusion, the patient was reversed from muscle relaxant effect with injection neostigmine 50 µg/kg and glycopyrrolate 10 µg/kg. Hemodynamics was assessed at 5 min interval from the time of study drug administration up to 15 min after extubation. The level of sedation during suction and extubation was assessed using observer assessment sedation score [Table 1]. The level of sedation during suction was assessed, and airway response under direct laryngoscopy to suction was noted by five-point scale [Table 2]. After 5 min interval, the level of sedation was assessed, and smoothness of extubation was noted by four-point scale [Table 3]. When mean arterial BP fall more than 10% of baseline value, 200 ml fluid bolus was given, and injection mephentermine was supplemented intravenously if there was no improvement. Drop in HR more than 20% from baseline was treated with injection atropine 0.6 mg intravenously.

Table 1

Observer assessment sedation score

Table 2

Grading of airway reflexes

Table 3

Smoothness of extubation

Statistical analysis

Based on our pilot study, 15% difference in HR and BP between baseline and extubation between two groups was observed. For α 0.05 and β 80%, 23 patients per treatment group were needed. Assuming a 5% dropout rate, fifty patients (25 patients per group) were recruited for the study.

The parameters were recorded, and data were entered into Microsoft Excel 2016. Statistical analysis is done using Statistical Package for Social Sciences (SPSS Version 19, IBM Corporation, Armonk, North Castle, New York, United States). Statistical analysis was done using paired-samples t-test for between group comparisons. The Chi-square test was used to analyze extubation quality, sedation scores, and adverse events. P < 0.05 was considered as statistically significant.

RESULTS

Age, weight, gender, airway, and ASA physical status were comparable in both groups. The total dose of morphine consumed by the patients was not statistically significant [Table 4].

Table 4

Demographic data and total morphine consumption

Both groups showed decrease in HR from the time of test drug administration to extubation. However, dexmedetomidine produced a significant drop in HR when compared to fentanyl. After extubation, there was statistically significant increase in HR in fentanyl group [Figure 1].

Figure 1

Hemodynamic variations over time

Statistically significant reduction in BP was observed in both groups at 5 min after drug administration, which improved with fluid bolus and was maintained within 10% of baseline value throughout the study in both the groups [Figure 1].

Patients in dexmedetomidine group showed greater degree of sedation during suctioning of airway and extubation when compared to fentanyl. In dexmedetomidine group, the patients were arousable but not awake, whereas in fentanyl group, the patients were awake and this could be the reason for significant increase in HR in fentanyl group after extubation [Figures 2 and 3].

Figure 2

Level of sedation and grading of smoothness during extubation

Figure 3

Level of sedation and grading of airway reflexes during suction

More number of patients in dexmedetomidine group tolerated laryngoscopy and suction. In both groups, none of the patients had breath holding or difficulty in tolerating the endotracheal tube [Figure 3]. Smoothness during extubation without coughing on tube was comparable between the groups.

DISCUSSION

Recovering from anesthesia often results in elevated catecholamine concentration following anesthetic withdrawal which is further aggravated by laryngeal manipulation occurring during extubation. Dexmedetomidine, a potent alpha-adrenoceptor agonist, decrease the sympathetic outflow and noradrenergic activity thereby counteracting the hemodynamic fluctuation occurring at the time of extubation[9], and fentanyl is a proven drug to attenuate the intubation and extubation response. We compared the effects of dexmedetomidine and fentanyl in attenuation of hemodynamic and airway reflexes during emergence and extubation.

Dexmedetomidine activates receptors in the medullary vasomotor center, reducing norepinephrine turnover and decreasing central sympathetic outflow, resulting in alterations in sympathetic function and decreased HR, and BP. In our study, patients of both groups showed drop in HR and BP throughout the study period. On comparison between the groups, dexmedetomidine group showed a significant drop in BP at 5 min interval after drug administration and improved with fluid boluses. Kothari et al.[10] compared lignocaine and dexmedetomidine and observed that single dose of dexmedetomidine 0.5 µg/kg given 5 min before extubation produced better attenuation of hemodynamic response in craniotomy patients. However, Sharma et al.[11] found an increase in mean arterial pressure for first 3 min in dexmedetomidine group which may be due to bolus drug administration effect and decreased from baseline value after 5 min.

Central stimulation of parasympathetic outflow and inhibition of sympathetic outflow from the locus ceruleous in the brainstem plays a prominent role in the sedation and anxiolysis produced by dexmedetomidine. There was increase in HR and BP in fentanyl group after extubation when compared to dexmedetomidine group which could be attributed to good sedation score provided by dexmedetomidine than fentanyl. Aksu et al.[12] also found similar hemodynamic response of increase in HR and BP after the extubation of rhinoplasty patients in fentanyl group when compared with 0.5 µg/kg dexmedetomidine.

Kim and Bishop[13] found 76% incidence of coughing during emergence. Coughing can result in hypertension, tachycardia, increased intraocular and intracranial pressure, myocardial ischemia, bronchospasm, and surgical bleeding.[14] In our study, dexmedetomidine group showed better airway response during laryngoscopy and oral suctioning when compared to fentanyl which correlated well with better sedation score in dexmedetomidine group. The smoothness of extubation was comparable between the two groups. Guler et al. observed that single dose of dexmedetomidine 0.5 µg/kg when given 5 min before extubation facilitated tolerance of endotracheal tube and significantly reduced coughing during extubation without affecting the emergence time.[15] Fan et al. did a similar study comparing remifentanil with two doses of dexmedetomidine 0.5 µg/kg and 0.7 µg/kg for otology surgery and observed that higher percentage of patients in dexmedetomidine group had smooth extubation regarding the absence of bucking and coughing with head movement during surgical dressing.[16] They also observed that incidence of postoperative nausea and vomiting was less with dexmedetomidine group.

To rule out the morphine enhancing the sedation effects during extubation, we observed total morphine consumption during the intra-operative period in both the groups and found to be comparable between the two groups.

Apart from statistically significant drop in BP at 5 min of drug administration which responded to fluid bolus in the dexmedetomidine group there were no adverse side effects during the study period. Both groups had a similar duration of recovery from anesthesia without delay in emergence. Dexmedetomidine 0.75 µg/kg given over 15 min before extubation enabled smooth extubation of the trachea and provided adequate sedation postoperatively with increase in the incidence of bradycardia and hypotension.[17]

Limitations

We studied the single dose of dexmedetomidine and fentanyl for attenuation of hemodynamic and airway reflexes. A dose-response study may be useful in determining the appropriate dose of the study drugs. Second, five point airway response to suction under direct laryngoscopy and airway response to extubation have not been validated.

CONCLUSION

Single-dose dexmedetomidine 0.75 µg/kg given 15 min before extubation produced better attenuation of airway response to laryngoscopy and airway suctioning. This resulted in smooth tracheal extubation without prolonging recovery when compared to fentanyl.

SUMMARY

This double-blind, randomized, controlled study was done in patients undergoing surgery under general anesthesia belonging to (ASA) physical status 1 or 2 to compare the effects of fentanyl 1 µg/kg and dexmedetomidine 0.75 µg/kg in attenuating airway and circulatory reflexes during emergence and extubation of the endotracheal tube. Study drug was given 15 min before the end of surgery as an infusion over 5 min. Hemodynamic parameters and patient response for laryngoscopy and oral suctioning and during extubation were graded. Dexmedetomidine was found to produce hypotension at 5 min of drug infusion and improved with fluid bolus; HR was stable throughout the study period. Extubation quality was found to be superior in dexmedetomidine group with patients arousable and tolerating suctioning and extubation. Whereas in fentanyl group, patients were awake during extubation and had tachycardia after extubation.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.