Ain-Shams Journal of Anaesthesiology

ORIGINAL ARTICLE
Year
: 2016  |  Volume : 9  |  Issue : 1  |  Page : 57--65

Controlled hypotensive anesthesia for functional endoscopic sinus surgery: a new protocol for dexmedetomidine administration


Ayman A Rayan 
 Department of Anaesthesia, Intensive Care and Pain Management, Faculty of Medicine, Menoufia University, Menoufia, Egypt

Correspondence Address:
Ayman A Rayan
Department of Anaesthesia, Intensive Care and Pain Management, Faculty of Medicine, Menoufia University, Menufia 71411
Egypt

Abstract

Objective The aim of the study was to conduct a comparative investigation to evaluate the efficacy of dexmedetomidine as a hypotensive agent by presenting a new protocol for administration versus the conventional protocol in functional endoscopic sinus surgery (FESS). Materials and methods Forty patients of ASA grade I-II scheduled for FESS were equally randomly assigned to two groups: the DEX group and the DEXnew group. The DEX group received dexmedetomidine at 1 μg/kg diluted in 10 ml normal saline 10 min before surgical incision (SI), followed by intravenous infusion of dexmedetomidine at 0.2-0.7 μg/kg/h according to the hemodynamic status and BIS. The DEXnew group received dexmedetomidine at 1 μg/kg diluted in 10 ml normal saline 10 min before SI, followed by intravenous top-up doses of 1/4 of the loading dose over 2 min in the form of intravenous shots to maintain MAP between 65 and 70 mmHg. Mean arterial blood pressure (MAP), heart rate (HR), cortisol level, fentanyl consumption, emergence time, and recovery from anesthesia (modified Aldrete score) were recorded. The sedation score and time to first analgesic request were recorded. Results In the DEX group there was a statistically significant decrease in MAP at 30, 45, 60, and 90 min after SI in comparison with preoperative MAP. In the DEXnew group also there was a statistically significant decrease in MAP at 30, 45, 60, and 90 min after SI in comparison with preoperative MAP. There was a nonsignificant difference as regards intraoperative fentanyl and postoperative pethidine consumption between the two groups. There was a significant decrease in the total amount of consumed dexmedetomidine in the DEXnew group (118 ± 14.6 μg) compared with the DEX group (189.4 ± 22.7 μg). Emergence time was significantly shorter in the DEXnew group (5.34±1.83 min) compared with the DEX group (9.45 ± 2.02 min). Conclusion This modified protocol of dexmedetomidine administration is safe and effective for controlled hypotension, providing an ideal surgical field during FESS. Compared with the conventional protocol of dexmedetomidine administration, the modified protocol offers fewer side effects; significant decrease in dexmedetomidine consumption, faster emergence time, and better modified Aldrete scores.



How to cite this article:
Rayan AA. Controlled hypotensive anesthesia for functional endoscopic sinus surgery: a new protocol for dexmedetomidine administration .Ain-Shams J Anaesthesiol 2016;9:57-65


How to cite this URL:
Rayan AA. Controlled hypotensive anesthesia for functional endoscopic sinus surgery: a new protocol for dexmedetomidine administration . Ain-Shams J Anaesthesiol [serial online] 2016 [cited 2019 Jul 23 ];9:57-65
Available from: http://www.asja.eg.net/text.asp?2016/9/1/57/178881


Full Text

 Introduction



Functional endoscopic sinus surgery (FESS) is a widely performed operation that is associated with enhanced illumination and visualization for improving surgical dissection. However, major complications have been reported for FESS under GA resulting from impaired visibility due to excessive bleeding [1] .

Controlled hypotension is a technique used to limit intraoperative blood loss to provide the best possible field for surgery, especially in FESS [2] .

An ideal hypotensive agent should be easy to administer, should have a short onset time, should have effects that disappear quickly when administration is discontinued, should be rapidly eliminated without toxic metabolites, should have negligible effects on vital organs, and should have predictable and dose-dependent effects [2] .

Volatile anesthetics, sympathetic antagonists, β-adrenoreceptor antagonists, calcium channel blockers, opioids, and direct-acting vasodilators have been used to achieve controlled hypotension. Sodium nitroprusside, nitroglycerine, hydralazine, trimethaphan, adenosine, and fenoldopam and α-2 agonists are also used frequently for this purpose [3],[4],[5] .

Dexmedetomidine is a potent highly selective α2 adrenergic receptor agonist. It has sedative, analgesic, and anesthetic sparing effect as well as sympatholytic properties [6] . The central and peripheral sympatholytic action of dexmedetomidine is mediated by the α2 adrenergic receptor and is manifested by dose-dependent decrease in arterial blood pressure, heart rate, cardiac output, and norepinephrine release [7],[8] .

The present study was designed to compare the efficacy and safety of a new protocol versus a conventional protocol for dexmedetomidine administration for hypotensive anesthesia in FESS with attention focused on the amount of blood loss, hemodynamic changes, quality of the surgical field, recovery profile, and tolerability of the patients.

 Materials and methods



This clinical trial was carried out in the Armed Forces Hospital-Dhahran, KSA, from March 2012 to March 2013 after obtaining approval from the Hospital Ethics Committee and written informed consent from the patients. Forty patients aged 18-45 years, of ASA physical status I or II, scheduled to undergo FESS were enrolled in this double-blind prospective, randomized study.

Exclusion criteria included known allergy to the study medication, bronchial asthma, respiratory or cardiac dysfunction, acute infection in the upper respiratory tract, history of sleep apnea, renal insufficiency, cerebral insufficiency, liver impairment, hypertension, bleeding disorders, administered medication for psychiatric diseases, chronic or acute intake of sedative or analgesic drugs, and difficulty in understanding the study protocol.

All patients were premedicated with intravenous midazolam at 0.02 mg/kg after insertion of a 22-G peripheral intravenous catheter. Upon arrival at the operating room, another 20-G peripheral intravenous catheter was inserted. One catheter was inserted for administration of the study drug and the other for induction of anesthesia. Upon arrival at the operating room, standard monitoring (Aisys; Datex-Ohmeda Inc., a General Electric Company, doing business as GE Health Care, P.O. Box 7550, Madison, USA) in the form of a five-lead ECG to monitor HR, noninvasive blood pressure, and oxygen saturation (SpO 2 ) was continuously applied, together with monitoring of the bispectral index (BIS) (Aspect Medical System Inc., and are registered in USA, EU and other countries 194-0068 3.01). Intravenous infusion of lactated Ringer's solution (LR) at 150 ml/h was started.

Before induction of anesthesia, patients were randomly assigned according to computer-generated randomization tables to receive either a conventional protocol of dexmedetomidine (DEX group: n = 20) or a new protocol of dexmedetomidine (group DEXnew: n = 20) for controlled hypotension. The DEX group received dexmedetomidine at 1 μg/kg diluted in 10 ml normal saline (NS) 10 min before surgical incision followed by intravenous infusion of dexmedetomidine at 0.2-0.7 μg/kg/h according to the hemodynamic status and BIS score.The DEXnew group received dexmedetomidine at 1 μg/kg diluted in 10 ml NS 10 min before surgical incision, followed by intravenous top-up doses of 1/4 of the loading dose over 2 min in the form of intravenous shots (200 μg dexmedetomidine diluted in 48 ml of 0.9% NS injection for a final concentration of 4 μg/ml).

All patients were anesthetized following a standard anesthetic technique after 5 min of preoxygenation with intravenous fentanyl at 2 μg/kg, ondansetron at 0.1 mg/kg, dexamethazone at 0.1-0.2 mg/kg, and propofol at 1-2 mg/kg until loss of verbal response. Endotracheal intubation was facilitated by the use of cisatracurium at 0.15 mg/kg. Anesthesia was maintained by one MAC sevoflurane in oxygen/nitrous oxide flow (FiO 2 35%). Adequate muscle relaxation was maintained with 0.05 mg/kg of cisatracurium every 30 min. Increments of fentanyl at 1 μg/kg were given when there were signs of inadequate analgesia (increases in noninvasive blood pressure 20% greater than baseline blood pressure, and/or tachycardia more than 90 beats/min for 10 min). The lungs were mechanically ventilated using volume-controlled mode to maintain end-tidal CO 2 (30-35 mmHg).

Approximately 20 min before the end of surgery, top-up doses of cisatracurium were stopped and intravenous infusion of paracetamol at 15 mg/kg over 15 min was given. At the end of the surgery, intravenous infusion was stopped in both groups and the residual neuromuscular blocker was antagonized when spontaneous breathing movements began, and muscle paralysis was reversed with neostigmine at 0.04 mg/kg and atropine at 0.02 mg/kg. After extubation, patients were transferred to the postanesthesia care unit (PACU) to be observed for 1 h for postoperative monitoring of hemodynamic changes and time to first rescue analgesia, which was pethidine at 0.5 mg/kg intramuscularly given on demand, with a maximum dose of 1 mg/kg every 6 h for the first 24 h.

Values of HR, MAP, and SpO 2 before induction of anesthesia were taken as baseline values. BIS reading after intubation was taken as baseline. Stress response was assessed by comparing the serum level of cortisol intraoperatively and postoperatively with preoperative levels.

Intraoperative fluid administered for all patients included LR as a maintenance fluid and NS for deficits and losses. The intraoperative estimated blood loss for each procedure was calculated by weighing the surgical gauze pads and measuring the contents of the suction bottle (with adjustment made for the amount of saline irrigation used) by the same anesthesiologist for all patients who was unaware of the study details.

The same surgical team performed all operations to ensure consistency of the surgical technique and duration of surgery. During the course of induced hypotension, if the MAP decreased below 60 mmHg, the dose of the studied drug was gradually tapered, and ephedrine shots (5-10 mg) and fluid bolus were started; the study drug was stopped if needed and those patients were excluded from the study. Bradycardia (HR <50 beats/min) was treated with 10 μg/kg atropine intravenously.

The serum level of cortisol preoperatively, during the hypotensive period, and postoperatively were measured and recorded. The two groups were compared with reference to patient characteristics, intraoperative clinical data (operative time, estimated blood loss, surgeon satisfaction, intraoperative fentanyl consumption), and emergence time (first response to commands after endotracheal extubation). Incidences of postoperative nausea and vomiting were recorded and the requirement for antiemetics was also noted. Total consumption of pethidine over 24 h, time to first request for analgesia, and pain intensity were also measured and recorded.

Pain intensity was assessed on the verbal numerical rating scale (VNRS: 0, no pain; 10, the severest pain imaginable) upon arrival at the PACU (time 0) and at 1, 3, 6, 12, and 24 h postoperatively. Every assessment of VNRS was performed by a blinded interviewer, and pain was scored at rest. When the VNRS was greater than 4 in the PACU, pethidine at 0.5 mg/kg was given IM as rescue analgesia. After being transferred to the ward, the patient was managed with a standard protocol including injection of pethidine at 0.5 mg/kg intramuscularly on demand with a maximum dose of 1 mg/kg intramuscularly every 6 h for the first 24 h. Surgeon satisfaction [Table 1] was assessed using satisfaction scores in which 4 = excellent, 3 = good, 2 = fair, and 1 = bad. The percentage of satisfaction was calculated for both groups.{Table 1}

After extubation and full recovery, patients were transferred to the PACU; recovery was evaluated using a modified Alderet score [9] , and time needed to achieve at least 9 was recorded. Sedation score was measured using the Ramsay Sedation Scale [10] [Table 2] and [Table 3].{Table 2}{Table 3}

Statistical analysis

Data were analyzed using SPSS statistics for Windows, version 17.0. (Chicago, SPSS Inc, USA). Results were presented as mean ± SD, number, and percentage. A power analysis for sample size suggested a minimum of 20 patients in each group with a error level 5% corresponding to a 95% confidence and a mean total dexmedetomidine dose in the DEX group of 189.4 and that in the DEXnew group of 118 μg with SD 22.7 and 14.6, respectively. The statistical power was 100%. The t-test was used to compare the two groups with respect to age, weight, and intraoperative clinical data (operative time and occurrence of reflex tachycardia). The Mann-Whitney U-test was used to compare the two groups with respect to estimated blood loss and intraoperative fentanyl consumption. MAP and HR were analyzed using the paired t-test for comparison in each group. P values less than 0.05 were considered significant.

 Results



Forty-five patients were evaluated for study eligibility. Two patients refused to sign the consent form and three patients failed to meet the inclusion criteria. The remaining 40 patients who fulfilled the entry criteria were enrolled in this study. Patients were able to complete the entire study and their data were included in the final analysis [Table 4].{Table 4}

In both groups there was a significant decrease in HR at 30 min (70.5 ± 8.2 beats/min in the DEX group and 75.13 ± 6.5 beats/min in the DEXnew group), at 45 min (67.6 ± 8.3 beats/min in the DEX group and 73.9 ± 5.9 beats/min in the DEXnew group), at 60 min (71.6 ± 9.5 beats/min in the DEX group and 71.2 ± 6.9 beats/min in the DEXnew group), and at 90 min (72.07 ± 8.4 beats/min in the DEX group and 73.5 ± 4.7 beats/min in the DEXnew group) compared with preoperative HR (84.5 ± 8.7 beats/min in the DEX group and 83.3 ± 7.5 beats/min in the DEXnew group), as shown in [Table 5].{Table 5}

In both groups there was a significant decrease in MAP at 30 min (70.9 ± 6.8 mmHg in the DEX group and 71.6 ± 6.8 mmHg in the DEXnew group), at 45 min (69.2 ± 7.3 mmHg in the DEX group and 68.4 ± 5.7 mmHg in the DEXnew group), at 60 min (68.4 ± 6.9 mmHg in the DEX group and 73.7 ± 6.5 mmHg in the DEXnew group), and at 90 min (68.2 ± 5.7 mmHg in the DEX group and 73.5 ± 5.9 mmHg in the DEXnew group) compared with preoperative MAP (85.7 ± 7.5 mmHg in the DEX group and 87.5 ± 8.6 mmHg in the DEXnew group), as shown in [Table 6].

There was a statistically nonsignificant difference as regards intraoperative fentanyl (μg) and postoperative pethidine (mg) supplementation between the two groups [Table 7] [Table 8] [Table 9]; [Figure 1].{Figure 1}{Table 6}{Table 7}{Table 8}{Table 9}

Emergence time (first response to commands after endotracheal extubation) was significantly shorter in the DEXnew group (5.34 ± 1.83 min) compared with the DEX group (9.45 ± 2.02 min) [Table 10].{Table 10}

No statistically significant difference was seen between the two groups as regards the time of first postoperative analgesic dose (P = 0.979). No postoperative nausea or vomiting was observed in the two groups, and surgeon satisfaction was comparable in the two groups; it was 90% in the DEX group and 95% in the DEXnew group.

In the DEX group hypotension was reported in five patients (25%). MAP reached 55 mmHg and four patients (20%) developed bradycardia (HR reached 45 beats/min), which was treated with 10 mg ephedrine intravenously and 0.4 mg atropine intravenously as well as by reducing the rate of dexmedetomidine to 0.2 μg/kg/h or stopping the infusion accordingly. In contrast, in the DEXnew group, hypotension and bradycardia were reported in two patients after the loading dose, who were treated accordingly with ephedrine and atropine.

The time needed to achieve a score of at least 9 on the modified Aldrete scale was 9.8 (3.3) min in the DEX group versus 7.2 (2.1) min in the DEXnew group. This difference was statistically significant, indicating faster recovery (P < 0.01) [Figure 2].{Figure 2}

In the DEX group, there was no statistically significant change as regards serum cortisol level between preoperative periods in comparison with 1 h after induction and 1 h postoperatively, whereas in the DEXnew group there was a highly significant decrease in serum cortisol 1 h after induction in comparison with the preoperative period.

There was a highly significant decrease in the total amount of dexmedetomidine consumed in the DEXnew group (118 ± 14.6 μg) compared with the DEX group (189.4 ± 22.7 μg) [Figure 3].{Figure 3}

There was a statistically nonsignificant difference as regards VNRS at rest in both groups postoperatively but there was significant difference between the two groups immediately postoperatively in the PICU [Table 11] [Table 12] [Table 13] [Table 14]; [Figure 4] and [Figure 5].{Figure 4}{Figure 5}{Table 11}{Table 12}{Table 13}{Table 14}

There was a nonsignificant difference as regards sedation in both groups postoperatively. The median postoperative sedation scores were statistically comparable in the DEX group versus the DEXnew group immediately after extubation, and 15 min and 30 min after transfer to the PACU.

 Discussion



Many methods have been adopted for optimization of the surgical conditions in special surgical procedures; FESS is the most common surgical procedure with a need to control intraoperative bleeding. Induced hypotension has been widely advocated to control bleeding during FESS to improve the quality of the surgical field [11],[12] . In our study we used dexmedetomidine in controlled hypotension in both groups but with different protocols of administration, with the aim of providing an optimal surgical field. Both drugs were effective in achieving MAP at 65-70 mmHg, and lowering the HR ensured a good surgical condition and provided a dry surgical field during the surgical procedure.

Patients of both groups were treated with dexmedetomidine 10 min before induction of anesthesia. They had a significant decrease in MAP and HR after administration of the loading dose. This dexmedetomidine-induced hemodynamic profile can be attributed to the known sympatholytic effect of α2 agonists. The α2-receptors are involved in regulating the autonomic and cardiovascular systems. α2-receptors are located in blood vessels, where they mediate vasoconstriction, and in the sympathetic terminal, where they inhibit norepinephrine release [13] . The dominant actions of α2 agonists comprise sedation, analgesia, anxiolysis, perioperative sympatholysis, cardiovascular stabilizing effects, reduced anesthetic requirements, and preservation of respiratory function [14],[15] .

This effect coincided with the result of our study: there was a significant decrease in MAP and HR after the loading dose of dexmedetomidine in both groups.

Dexmedetomidine exerts sedative and analgesic sparing effects through central actions in the locus ceruleus and in the dorsal horn of the spinal cord [16] .

Because dexmedetomidine reduced HR and MAP, it was thought to be a beneficial agent for controlled hypotension. It was useful especially as it did not cause reflex tachycardia and it blocked the sympathetic system leading to reducing HR. Reduction of both MAP and HR improved the surgical field. Although the MAP was reduced with an infusion of dexmedetomidine, there was no reflex tachycardia and this was very advantageous in hypotensive anesthesia [17] .

In the DEX group, during the intraoperative infusion of dexmedetomidine, five patients (25%) developed hypotension and were treated with 10 mg ephedrine intravenously and four patients (20%) developed bradycardia and were treated with 0.4 mg atropine intravenously as well as by reducing the rate of dexmedetomidine to 0.2 μg/kg/h or stopping the infusion accordingly.

This in agreement with the study conducted by Abdullah et al. [18] , in which bradycardia was the most frequent adverse effect in the dexmedetomidine group (24%).

This was in contrast to the study conducted by Richa et al. [19] , in which atropine was not used and only one patient (8.3%) needed one dose of ephedrine for treatment of hypotension.

The infusion rate of dexmedetomidine was adjusted between 0.3 and 0.7 μg/kg/h to achieve MAP between 65 and 70 mmHg and HR decreased from to 70-80 beats/min.

Kaygusuz et al. [20] used dexmedetomidine at 1 mcg/kg followed by a dose of 0.2 mcg/kg/h during shockwave lithotripsy combined with fentanyl at 1 mcg/kg and reported no significant difference in heart rate values during sedation and recovery; however, the heart rates in each groups decreased from baseline.

This was in agreement with the study conducted by Techanivate et al. [21] , who found that dexmedetomidine causes a significant decrease in heart rate throughout the period of colonoscopy from the time of starting the study drug (45 min). However, the average heart rate, lowest heart rate, the incidence of bradycardia, and the atropine usage in this study were not significantly different between the two groups during the intraoperative period.

In agreement with our study, Jolowiecki et al. [22] used dexmedetomidine in colonoscopy and observed 4/19 cases of hypotension (MAP = 50% of baseline), two cases of bradycardia (HR = 40 beats/min), one case of bigemini ventricular extrasystole, and nine cases of pain that required additional opioids in the postoperative period.

This in contrast to the study conducted by Nasreen et al. [23] , in which none of the patients developed heart rate less than 50 bpm following bolus or infusion of DEX at any stage during the intraoperative period. All patients were hemodynamically stable and none of them required vasopressor support or bolus administration of fluids to maintain the hemodynamic status.

In the recovery room, patients were monitored for 60 min and then shifted to the ward. During this period no complications were noted and also no adverse events were reported during their stay in the ward. This is in agreement with the study conducted by Farah et al. [23] .

The study performed by Techanivate et al. [21] demonstrates that 1 mcg/kg of dexmedetomidine added to 0.5 mcg/kg fentanyl and 20 mg propofol reduces hypotension during colonoscopy. Furthermore, the use of dexmedetomidine has faster recovery time without increasing the rate of complications, included bradycardia or delayed discharge time.

In this study, both groups had comparable emergence and recovery time from anesthesia.

No significant changes were detected in the plasma cortisol level between the two groups during the intraoperative and postoperative periods when compared with the preoperative period; this was attributed to the sympathoadrenal blocking action of dexmedetomidine leading to inhibition of the release of catecholamine and other stress hormones.

This was in agreement with the study conducted by Shams et al. [24] , who found a nonsignificant difference in the plasma cortisol level between the two groups during the intraoperative and postoperative periods.

In this study, the modified new protocol had advantages such as fewer complications in the form of bradycardia or severe hypotension as well as significant reduction in the mean amount of dexmedetomidine consumption in comparison with the conventional protocol of dexmedetomidine administration.

The time of first postoperative analgesic dose was 37.4 min in the DEX group and 35.6 min in the DEXnew group. This was in contrast to the study conducted by Shams et al. [24] , in which the time of first postoperative analgesic dose was 57.65 min on applying the conventional protocol.

In our study, the median postoperative sedation scores showed a nonsignificant difference in the DEX group compared with the DEXnew group in the immediate postextubation period, and 15 and 30 min after transfer to the PACU.

No patient complained of postoperative nausea or vomiting. This was in agreement with the study conducted by Shams et al. [24] .

Emergence time was significantly faster (5.34 min) in the DEXnew group compared with the DEX group (9.45 min). The emergence time was 7.8 min in the study conducted by Shams et al. [24] .

 Conclusion



This study reveals that the modified protocol of dexmedetomidine administration is safe and effective for controlled hypotension, providing an ideal surgical field during FESS. Compared with the conventional protocol of dexmedetomidine administration the modified protocol involves fewer side effects, significantly decreased total amount of dexmedetomidine consumed, short time to emergence, and better modified Alderete scores.

 Acknowledgements



Conflicts of interest

None declared.

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