Comparison of the Efficacy of Intravenous Dexmedetomidine versus Intravenous Clonidine for Controlled Hypotension during Functional Endoscopic Sinus Surgery: A Prospective Observational Study

Abstract

Background:

Periprocedural hemorrhage is common during functional endoscopic sinus surgeries (FESSs) owing to the rich vascularity of the nose, which obscures the surgical field and increases the time of the procedure with complications. Controlled hypotension can be employed to mitigate the problem.

Objective:

Comparison of clonidine and dexmedetomidine as an infusion dose to effectuate controlled hypotension during sinus surgery.

Patients and Methods:

A prospective observational study was done between Group Dexmedetomidine and Clonidine who were posted for FESS with 40 participants per group. Both the groups received the allocated drugs in 100 ml of normal saline 15 min before induction. The patient’s hemodynamics, Nasal bleeding, and surgeon’s satisfaction score were noted.

Results:

Both Groups showed a drop in hemodynamics after induction, but a higher drop was seen in Group D. Nasal bleeding and Surgeon’s satisfaction scores were better in Group D compared to Group C.

Conclusions:

Controlled hypotension can be achieved with the preinduction infusion of either clonidine 3 μg/kg or dexmedetomidine 1 μg/kg. Dexmedetomidine provides better hemodynamic stability, decreased bleeding, and an excellent surgical field when compared to clonidine.

INTRODUCTION

Periprocedural hemorrhage is common during functional endoscopic sinus surgeries (FESSs) owing to the rich vascularity of the nose, which seriously hampers the surgeon’s view of the field. It also is a source of apprehension to the patient in the postoperative period, often delaying discharge from the hospital, especially in the setting of day-care procedures. To mitigate this concern, controlled hypotension was suggested and is employed by many anesthesiologists. Controlled hypotension is clinically acceptable where mean arterial blood pressure (MAP) can be lessened by 30% below the patient’s baseline MAP, with a MAP of 60–70 mmHg in the American Society of Anesthesiologists (ASA) Physical Status (PS) Class I patients.[1,2,3]

Many drugs and anesthetic techniques have been employed for controlled hypotensive anesthesia in endoscopic sinus surgeries, among which none comprehensively serve the purpose. Various drugs such as sodium nitroprusside, nitrates, beta blockers, and anesthetic agents have been used before but have their shortcomings which make them less of an ideal agent for achieving controlled hypotension.[4]

Alpha-2 agonists have a favorable drug profile compared to other drugs. Alpha-2 agonists have analgesic, amnestic, and anesthetic-sparing actions, rendering them an important option for controlling hypotension in endoscopic sinus surgeries.[5] This group of drugs also decreases the requirement for anesthetic agents and sudden changes in hemodynamic parameters.[6] Our study aimed to compare the two Alpha-2 agonists, clonidine and dexmedetomidine, as an infusion dose to effectuate hypotension during sinus surgery. The primary objective was to achieve a target MAP of 60–70 mmHg intraoperatively, and the secondary objectives were to assess the parameters such as nasal bleeding score, surgeon’s satisfaction score, and discharge time from the postoperative intensive care unit.

PATIENTS AND METHODS

Study design

This prospective observational case–control trial was in a tertiary hospital from December 2018 to September 2020. Our study commenced on obtaining sanction from the appropriate governing bodies of the institution. The study was registered with the Clinical Trials Registry, India (CTRI/2019/02/017662). We have included patients of either gender aged between 18 and 60 years, ASA-PS I or II diagnosed with rhinosinusitis unamenable to medical therapy and required FESS surgery. Exclusion criteria include patients with known or suspected allergies to the study drugs, patients with uncontrolled hypertension, beta-blockers, patients with heart blocks, ischemic heart disease, or pacemaker in-situ, patients with bilateral ethmoidal polyposis or extensive sinusitis, pregnant women, and patients with significant neurological, psychiatric, liver or kidney diseases. The study was carried out with respect to the principles of the Declaration of Helsinki, 2013.

RAMDOMIZATION

After recruitment, preanesthetic evaluation was done a day before surgery and all patients were assured that the study would, in no way have any impact on their course of treatment. The participants were allocated randomly into two groups by computer-generated random number method by the consultant anesthesiologist preoperatively, and accordingly, data were collected from the groups formed.

• Group C: IV Clonidine 3 mcg/kg

• Group D: IV Dexmedetomidine 1 mcg/kg.

Methodology

Both the drugs were diluted in 100 mL of normal saline and were given 15 min before induction as per the groups allocated. Anesthetic induction was done with injection fentanyl 2 mcg/kg, injection propofol 2 mg/kg till loss of verbal response, and injection atracurium 0.5 mg/kg for muscle relaxation. After ensuring complete neuromuscular blockade as monitored by a neuromuscular monitor, laryngoscopy, and orotracheal intubation were performed, and ventilation was confirmed with capnography. A sterile throat pack was inserted with the aid of Magill’s forceps to prevent airway soilage. Anesthesia was maintained with isoflurane in a mixture of 33% oxygen and 66% nitrous oxide. The patient was mechanically ventilated to maintain normocapnia (ETCO₂ 35–45 mmHg). Surgeons infiltrated the surgical field with adrenaline which was done just before starting the procedure. The concentration used was 2 mcg/mL (100 mcg of adrenaline in 50 mL of 0.9% sterile normal saline).

After surgery, inhalational anesthetics were gradually tapered and cutoff. After a thorough suctioning, the throat pack was removed. MAC was decremented to 0.3, and the residual neuromuscular blockade was antagonized with IV neostigmine 0.05 mcg/kg and glycopyrrolate 0.01 mcg/kg after the train of four counts digressed to 3 or >3. The patient was extubated once they started obeying verbal commands and other extubation criteria were met. After extubation, patients were shifted to the postanesthesia care unit (PACU).

Parameters assessed were the hemodynamics (heart rate [HR] and MAP) at baseline and postadministration of the allocated drug and then after every 10 min, Nasal bleeding score every 10 min intraoperatively[7] and surgeons satisfaction score via a 4-graded Likert scale.[8]

Intraoperative data such as the duration of surgery and anesthesia and the duration of induced hypotension (induced hypotension till the return of blood pressure to >70 mmHg at the end of surgery) (min), any additional requirement of propofol/fentanyl for perpetuating hypotension, and time to reach modified Aldrete score ≥9 (min) for discharge from PACU were noted. Any adverse events (hypotension, bradycardia, nausea, vomiting, and shivering) were also documented and dealt accordingly by the concerned anesthesia team.

Statistics

The sample size was calculated to detect a significant difference of 20% in MAP between the two groups for a type I error of 0.05.

The formula used (with usual notations) is as under:

Where P = (P₁ + P₂)/2

So if you replace the P with P₁ and P₂

• Group 1 = Dexmedetomidine group

• Group 2 = Clonidine group.

From the review of the literature and the previous article.[7]

The proportion of hypotension during FESS in Group 1 (P₁) = 6.0%. The proportion of hypotension during FESS in Group 2 (P₂) =30.3%. Z_1-α/2 = Value of standard normal variate corresponding to α level of significance = 1.96. Z_1-β= The standard normal deviation for desired power = 0.84. With these assumptions, the minimum sample size calculated came to 37 for each group. We decided to recruit 40 subjects in each group. There were no dropouts. Forty patients in Group D (Group Dexmedetomidine) and 40 in Group C (Group Clonidine) were eligible for final analysis.

Quantitative parameters were tested for normality using the Kolmogorov–Smirnov test. Descriptive analysis of quantitative parameters was expressed as means and standard deviation. Categorical data were expressed as absolute number and percentage. Cross tables were generated, and the Chi-square test was used for testing the association for categorical variables. Independent Student’s t-test was used for testing of mean value of study parameters between independent groups. P < 0.05 was considered statistically significant.

RESULTS

Forty participants in Group D (Group Dexmedetomidine) and 40 in Group C (Group Clonidine) were enrolled for final analysis [Figure 1].

Figure 1.

Consort flow diagram

The demographic variables for both groups were similar as shown in Table 1.

Table 1.

Demographic details

Variable	Group C (n=40)	Group D (n=40)	P
Age (years)	31.8±7.3	33.9±6.8	0.171*
Weight (kg)	57.2±7.5	60.6±9.5	0.082*
Sex (male/female)	17/23	15/25	0.648+
ASA I/II	28/12	25/15	0.503+

*Student’s t-test, ⁺Chi-square test. ASA=American Society of Anaesthesiologists

The duration of surgery and anesthesia were similar in both groups. The duration of induced hypotension and time taken to reach modified Aldrete score ≥9 for discharge from the postoperative care unit (minutes) were significantly higher in Group C when compared to Group D (P < 0.05) [Table 2].

Table 2.

Intraoperative data and intraoperative usage of propofol and fentanyl

Variable	Group C (n=40)	Group D (n=40)	Difference (Group C−Group D) (n=40)	P
Duration of surgery (min)	90.8±23.9	91.7±12	7.1±4.2	0.65*
Duration of anaesthesia (min)	100.6±9.4	98.7±9.4	6.9±2.1	0.36*
Duration of induced hypotension (min)	131.8±16.7	99±10.1	32.8±3.1	0.0001*
Time to reach modified aldrete score ≥9	52.1±9.6	38.6±12.3	13.5±2.5	0.0001*
Additional usage of propofol (mg)	5.5±11.1	8±18	−2.5±3.3	0.457*
Additional usage of fentanyl (μg)	0±0	0±0	-	-

*Student’s t-test

Both groups revealed a declining trend of MAP from baseline to preinduction, followed by a subsequent increase from the 5^th to 10^th min. Eventually, both the groups showed a subsequent drop in MAP till the 100^th min. Hence, comparing the MAP between the two groups, revealed that a higher drop was seen in Group D (as compared to the baseline) over Group C at 10, 20, 30, 40, and 50 min and was statistically significant with P < 0.05 [Figure 2].

Figure 2.

Trend of mean arterial pressure

Baseline HRs of patients were comparable with no significant intergroup difference (P = 0.569). After intubation and insertion of the throat pack, HR increased in all patients at 5 min, but the increase was not significant between the groups. After 5 min, there was a fall in mean HR in both groups and changes were not statistically significant between the groups till 60 min in the subsequent time interval (P > 0.05). After 60 min, there was a rise in mean HR observed in both the groups at 70-, 80-, and 90-min intervals, but changes were significantly higher in Group C as compared to Group D (P < 0.05) [Figure 3].

Figure 3.

Trend of heart rate

The mean bleeding score was significantly higher in patients of Group C than those in Group D (P = 0.0001) as shown in Table 3. The surgeon’s satisfaction score [Table 3] was also significantly higher in patients of Group D due to low bleeding scores than those in Group C and was statistically significant (P = 0.035).

Table 3.

Comparison of nasal bleeding score and surgeon’s satisfaction score

	Group C (n=40) n (%)	Group D (n=40), n (%)	P
Bleeding score
0=No bleeding	-	-	0.0001*
1=Minor bleeding, no aspiration required	-	21 (52.5)
2=Minor bleeding, aspiration required	20 (50.0)	18 (45.0)
3=Minor bleeding, frequent aspiration required	20 (50.0)	1 (2.5)
4=Moderate bleeding, visible only with aspiration	-	-
5=Severe bleeding, frequent aspiration required, very hard to perform surgery	-	-
Surgeon’s satisfaction score
1=Bad	-	-	0.035*
2=Moderate	12 (30.0)	6 (15.0)
3=Good	10 (25.0)	21 (52.5)
4=Excellent	18 (45.0)	13 (32.5)

*Chi-square test

Adverse effects such as bradycardia (HR <50 bpm) and hypotension (MAP < 60 mm Hg) were treated with IV atropine 0.6 mg and IV mephentermine 3 mg bolus, respectively, and the incidence was found to be similar in Group C and Group D. We also noted that the additional propofol or fentanyl requirement was similar in both groups [Table 2].

DISCUSSION

The current paradigms of surgery are shifting to day care or ambulatory procedures which “result in superior patient satisfaction in terms of recovery, cost containment, and lesser social disruption with home care and lesser chances of nosocomial infections. A common surgery incorporated into the umbrella of such procedures is FESS, which entails an oligemic surgical field. The nasal vasculature is under a tightly systematized sympathetic nervous helm comprising innervated arteries, venules, and venous sinusoids.[9]

Any manipulation of the highly vascularized and innervated nasal mucosa stimulates the sympathetic system (tachycardia and hypertension) which results in increased bleeding. The sympathetic nerves release postganglionic transmitters such as norepinephrine whose activation, causes nasal vessel constriction through an alpha adrenoceptor-mediated mechanism, which decreases mucosal engorgement. Hence, we can derive that the mucosal obstruction is caused by venous sinusoid dilatation and vein gathering. The dominance concerning the number and vasoconstrictor activity of alpha 2-adrenoceptors over alpha 1-adrenoceptors in nasal venous sinusoids is remarkably high, which makes the role of selective alpha 2-agonist very crucial by constricting the vessels directly and causing decongestion.[10,11,12] Controlled hypotensive anesthesia involves the technique of reducing the MAP and maintaining it for the desired length of time, without affecting the regional perfusion to vital organs.

The present trial compared the clinical efficacy of dexmedetomidine to clonidine, as a “preinduction single dose infusion, on inducing controlled hypotension. Both act through, the alpha-2 receptors which causes a reduction in serum catecholamine levels, and attenuates sympathoadrenal responses to intraoperative stress, laryngoscopy, and intubation. Their anesthesia-sparing and opioid-sparing action is well documented. In our trial, enrolled participants (n = 80) were divided into two groups; Group C (n = 40) and Group D (n = 40). The baseline MAP (mmHg) of patients were 80.1 ± 7.2 and 80 ± 9.2 in Groups C and D, respectively, with no significant intergroup difference. MAP increased in all patients at 5 min following intubation and throat pack insertion, but the increase was not significant between the groups (P > 0.05). After 5 min, there was a fall in MAP in both groups till the 100^th min in subsequent time intervals as shown in Figure 2. MAP was significantly lower in Group D when compared to Group C till 50 min (P < 0.05) but clinically insignificant. After 50 min, changes were not significant between the groups. Target MAP was achieved in both groups, significantly earlier in Group D than in Group C. Baseline HRs of patients (bpm) were comparable between the two groups: (Group C) 73 ± 8.9 and (Group D) 74.2 ± 10.2. After intubation and insertion of the throat pack, HR increased in all patients, but the increase was neither clinically nor statistically significant between the groups (P > 0.05). After 5 min, there was a fall in mean HR in both groups and changes were similar between the groups till 60 min, followed by an increasing trend. This increasing trend changes in HR were significantly higher in Group C when compared to Group D (P < 0.05).

We found the bleeding score was significantly higher in patients of Group C than in Group D [Table 3, P = 0.0001]. This was similar to the previous trial by Das et al.[7] Among 40 patients in Group C, 20 patients had a bleeding score of 2 and the remaining 20 patients had a bleeding score of 3, whereas, in Group D (n = 40), 21 patients had a bleeding score of 1, 18 patients had a score of 2, and remaining one had a bleeding score of 3. This could be reasoned by the full agonistic property of dexmedetomidine on the alpha 2 receptors when compared to the partial agonism of clonidine, resulting in lesser bleeding by dexmedetomidine. Similarly, the surgeon’s satisfaction score was higher in Group D [Table 3, P < 0.05]. This finding was similar to the observation by Das et al. who found that the surgeon’s satisfaction score was much better in the dexmedetomidine group.[7] Guven et al. also found the beneficial effect of preoperative administration of dexmedetomidine in lowering bleeding scores in sinus endoscopic surgery when compared with the placebo group.[13] However, Escamilla et al. findings were different from our study where they did not observe a significant difference between adjuvant clonidine and dexmedetomidine in the reduction of surgical bleeding in endoscopic surgery.[14]

The duration of induced hypotension and the time taken to reach Modified Aldrete score ≥9 before discharging from PACU (minutes) was significantly higher in Group C when compared to Group D [Table 1, P < 0.05]. Hence, we can use dexmedetomidine for any day-care surgeries or short procedures and can expect a smooth postoperative recovery period. On the other hand, Mariappan et al. found that recovery quality was equal in both groups.[15]

We also noted for any adverse effects between the two groups such as nausea, vomiting, and shivering, but they were comparable and were neither clinically nor statistically significant. The usage of any additional propofol or fentanyl was also similar in both groups and was not statistically significant.

CONCLUSIONS

Controlled hypotension during FESS can be achieved with a preinduction infusion of either clonidine 3 μg/kg or dexmedetomidine 1 μg/kg. In comparison to clonidine, better hemodynamic stability is achieved with dexmedetomidine. Dexmedetomidine provides an excellent surgical field, higher Surgeon’s satisfaction score, and early discharge from the postoperative care unit when compared to clonidine.

Merits of the study

The drugs compared in the study were easily available and cost-effective. Moreover, these drugs can be administered easily and have versatile beneficial properties with minimal side effects in clinically used doses.

Limitations of our study

Limitations of our study were the absence of a placebo-controlled group, postoperative sedation scores between the two groups were not assessed, the drugs were compared using their day-to-day clinical dosage which was safe and therapeutic without the knowledge of their equipotent dosages, the surgeons were not standardized, perioperative analysis of the hemoglobin value in conjunction with intraoperative blood loss was not executed as the quantum of hemorrhage in these surgeries, is not expected to transmit significantly to the laboratory value. In the quest for augmented results, a study encompassing a larger number of subjects can be undertaken.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.