|Year : 2015 | Volume
| Issue : 3 | Page : 320-326
A comparative study of dexmedetomidine, magnesium sulphate, or glyceryl trinitrate in deliberate hypotension during functional endoscopic sinus surgery
Omyma S M Khalifa MD 1, Osama G Awad2
1 Department of Anesthesia, El-Minia Univeristy, Minia, Egypt
2 Department of ENT, Faculty of Medicine, El-Minia Univeristy, Minia, Egypt
|Date of Submission||02-Feb-2015|
|Date of Acceptance||10-May-2015|
|Date of Web Publication||29-Jul-2015|
Omyma S M Khalifa
Department of Anesthesia, Faculty of Medicine, El-Minia Univeristy Hospital, El-Minia Univeristy, 190 El- Horria Street, Minia city 61511
Source of Support: None, Conflict of Interest: None
Induced hypotension to minimize bleeding during functional endoscopic sinus surgery (FESS) is of vital importance to the surgeon and anesthetist to decrease the risk of complications as well as procedural failure.
This study was designed to compare the efficacy of dexmedetomidine, magnesium sulfate, or glyceryl trinitrate in inducing deliberate hypotension during FESS and their effect on postoperative recovery, discharge, and postoperative analgesic requirement.
Settings and design
This was a randomized prospective single-blind study.
Patients and methods
Sixty patients of ASA physical status I or II scheduled for FESS were equally randomly assigned into three groups. The glyceryl trinitrate group (the G group) received glyceryl trinitrate infusion of 2-10 μg/kg/min. The dexmedetomidine group (the DEX group) received dexmedetomidine bolus of 1 μg/kg, followed by 0.2-0.7 μg/kg/h infusion for maintenance, and the magnesium sulfate group (the M group) received a bolus of 50 mg/kg magnesium sulfate, followed by infusion of 15 mg/kg/h for maintenance. The target mean arterial pressure was 55-65 mmHg.
Hemodynamic parameters, blood lose, surgical field quality, intraoperative atropine, ephedrine or fentanyl use, emergence time, time to achieve an Aldrete score of 9 or greater, sedation score, time of discharge from postanesthesia care unit, and time to first analgesic request were recorded.
The studied drugs achieved the target mean arterial pressure (55-65 mmHg) with superior hemodynamic stability in the DEX group. Intraoperative blood lose and quality of the surgical field were comparable. Both dexmedetomidine and magnesium sulfate offered the advantage of inherent analgesic and sedative effect, but at the expense of longer recovery of anesthesia and discharge from postanesthesia care unit.
Dexmedetomidine, magnesium sulfate, or glyceryl trinitrate induced deliberate hypotension, with superior hemodynamic stability in dexmedetomidine. Analgesic and sedative effects were obtained with dexmedetomidine and magnesium sulfate, but with longer recovery and discharge times.
Keywords: controlled hypotension, dexmedetomidine, functional endoscopic sinus surgery, glyceryl trinitrate, magnesium sulfate
|How to cite this article:|
Khalifa OS, Awad OG. A comparative study of dexmedetomidine, magnesium sulphate, or glyceryl trinitrate in deliberate hypotension during functional endoscopic sinus surgery. Ain-Shams J Anaesthesiol 2015;8:320-6
|How to cite this URL:|
Khalifa OS, Awad OG. A comparative study of dexmedetomidine, magnesium sulphate, or glyceryl trinitrate in deliberate hypotension during functional endoscopic sinus surgery. Ain-Shams J Anaesthesiol [serial online] 2015 [cited 2019 May 20];8:320-6. Available from: http://www.asja.eg.net/text.asp?2015/8/3/320/161692
| Introduction|| |
Functional endoscopic sinus surgery (FESS) is a common successful surgical procedure for patients with medically refractory chronic rhinosinusitis  . The main obstacle to good visibility is excessive bleeding during surgery that can compromise the safety and efficiency of this surgical procedure. To ensure hemodynamic balance and patient safety, it is essential to monitor and control bleeding  .
Various agents have been used to provide controlled hypotension, including direct-acting vasodilators (sodium nitroprusside, nitroglycerin), ganglion-blocking agents, β-adrenergic blockers (esmolol), calcium channel blockers (nicardipine), α2-agonists (clonidine-dexmedetomidine), volatile agents, and magnesium sulfate , .
Ideally, a hypotensive agent should be easy to administer, has a short time to onset, has effects that disappear quickly when administration is discontinued, with rapid elimination without toxic metabolites, has negligible effects on vital organs, and has predictable and dose-dependent effects  .
Dexmedetomidine, is a selective, short-acting, central α2-adrenergic agonist and is characterized by dose-dependent decrease in arterial blood pressure, heart rate (HR), cardiac output, and norepinephrine release  .
Magnesium sulfate has been used to induce deliberate hypotension  . It produces its hypotensive effect by limiting the outflow of calcium from the sarcoplasmic reticulum and produces a vasodilating effect by increasing the synthesis of prostacyclin and inhibiting angiotensin-converting enzyme activity  . Magnesium reduces the need for analgesic and sedative drugs as it is an N-methyl-d-aspartate receptor antagonist  .
The glyceryl trinitrate (GTN) biotransformation pathway produces nitric oxide and contributes directly to its vasodilating effect  .
Therefore, the main objective of this study was to evaluate and compare the efficacy of dexmedetomidine and magnesium sulfate with GTN in inducing deliberate hypotension and providing better quality of the surgical field during FESS procedure under general anesthesia and their effect on postoperative recovery, discharge, and analgesia.
| Patients and methods|| |
After approval from the medical ethics committee and obtaining informed consent from all patients, this comparative study was conducted in El-Minia University Hospital during the period from August 2013 to April 2014.
Sixty patients of both sex, ASA physical status I and II, aged 18-50 years, scheduled for FESS due to chronic sinusitis resistant to medical treatment were included in this prospective single-blinded study. Patients with coagulopathies or those receiving drugs influencing blood coagulation and those with a known drug allergy or substance addiction were excluded from the study. The patients were assessed clinically, in addition to ECG, chest radiograph, and routine laboratory tests. The patients were randomly allocated into three equal groups [GTN group (the G group), the dexmedetomidine group (the DEX group), and the magnesium sulfate group (the M group)] each of 20 patients using a computer generated randomization chart. In the operating room, the patients were re-evaluated and monitored with ECG, noninvasive blood pressure, and peripheral oxygen saturation (SpO 2 ), and then two 20-G venous cannulae were inserted, one for infusion of the studied drugs and the other for administration of fluids and other drugs. A 22-G radial artery catheter was inserted for continuous measurement of invasive arterial blood pressure. For group G, GTN (Nitronal 1 mg/ml; G. Pohl-Boskamp GmbH&Co. KG, 25551 Hohenlockstedt, Germany) infusion was titrated at 25-200 μg/min, according to the response. Infusion of GTN (diluted in 0.9% saline) started after sterilization and positioning of the patient.
In the DEX group, patients received a loading dose of 1 μg/kg dexmedetomidine (Precedex; Hospira, Precedex 200 mcg/2 ml, Hospira. Inc, Lake Forest, USA) diluted in 100 ml 0.9% saline infused over 10 min just before induction of anesthesia, followed by continuous infusion of 0.2-0.7 μg/kg/h. In the M group, the infusion of magnesium sulfate (100 mg/ml, Epicio, Cairo, Egypt) was started at a loading dose of 50 mg/kg diluted in 100 ml 0.9% saline over 10 min just before induction of anesthesia, and then was sustained at a maintenance dose of 15 mg/kg/h. Infusion was performed through syringe pump (Pilote A 2 1S 2 ; Fresenius Vial France, Pilote A 2 1S 2 , Fresenius Vial l, Brezins, France). The target mean arterial pressure (MAP) for all groups was 55-65 mmHg.
All patients were preoxygenated and premedicated with intravenous midazolam 0.05 mg/kg and fentanyl 2 μg/kg. Induction of anesthesia was accomplished with 2 mg/kg intravenous propofol 2% supplemented, if necessary, with 0.2 mg/kg aliquots until loss of verbal response. Endotracheal intubation was facilitated with 0.6 mg/kg rocuronium bromide with suitable-sized cuffed tube that was fixed with adhesive tape around the mouth and oropharyngeal pack was inserted. Normocapnic mechanical ventilation (ETCO 2 32-35 mmHg) was performed, and anesthesia was maintained with sevoflurane 1-3% and muscle relaxation with 0.15 mg/kg rocuronium bromide when needed. After induction and intubation, all patients were laid in an approximately 30° reverse Trendelenburg position and a standard dose of adrenaline (1 : 200 000 adrenaline) was administered at the surgical site. Patients received lactated Ringer's at 3 ml/kg. In all groups, signs of inadequate anesthesia as increase in the arterial pressure greater than the targeted were treated with titration of the hypotensive agents, increased sevoflurane concentration, and additional dose of fentanyl. An intravenous bolus of 0.5 mg atropine was administered in case of bradycardia. If MAP became less than 55 mmHg, the administered infusion dose of the hypotensive agent was reduced or discontinued. If no response was obtained, an intravenous bolus of ephedrine 10 mg was administered.
To ensure consistency in the estimation of the surgical field, the same surgeon who was blinded to the hypotensive agent used performed all operations. The surgeon estimated the quality of the surgical field using a predefined category scale adopted from that described by Fromme et al.  [Table 1].
|Table 1: Average category scale for assessment of intraoperative surgical field|
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The ideal values of category scale for surgical field assessment were predetermined to be 2-3. Infusion of the hypotensive drugs was stopped 5 min before the anticipated end of surgery. Sevoflurane was stopped at the end of the surgery and the residual neuromuscular blockade was reversed with the use of atropine 0.01 mg/kg and neostigmine 0.05 mg/kg. The amount of blood lost was measured from the suction apparatus and recorded, and the total duration of surgery and anesthesia were also recorded.
Patients' hemodynamics were recorded preoperatively (baseline), after induction, after intubation, during the hypotensive period (at 10, 20, 30, 40, 50, and 60 min of onset of the hypotensive effect of the studied drug), before extubation, and lastly 5 min after extubation. As most of the cases ended around that time, analysis of the hypotensive period was up to 60 min. The time needed to restore the baseline blood pressure was recorded. Minimum alveolar concentration (MAC) of sevoflurane during the hypotensive period, the score of surgical field quality (average category scale), intraoperative use of atropine, ephedrine and/or fentanyl, and total blood loss were also recorded.
Anesthesia time (defined as the interval between the induction and discontinuation of anesthesia), surgery time, and emergence time (defined as the interval between the discontinuation of anesthesia to the response of eye opening to verbal command) were recorded.
After recovery, patients were transferred to the postanesthesia care unit (PACU) to be followed up, and postoperative recovery was evaluated using a modified Aldrete score (0-10)  . The time needed to achieve an Aldrete score of 9 or greater and the discharge time of PACU were recorded. Postoperative sedation was measured using the Ramsay scale  at 15, 30, and 60 min after tracheal extubation [Table 2].
The time to the first analgesic requirement, postoperative antiemetic use, and hemoglobin level preoperatively, and postoperatively at 2 and 24 h were recorded. For postoperative analgesia, 1 mg/kg of pethidine HCl was given intramuscularly. For nausea/vomiting, 0.25 mg/kg of metoclopramide was administered intravenously.
The collected data were coded, tabulated, and statistically analyzed using (statistical package for the social sciences (SPSS, version 20; SPSS Inc., Chicago, Illinois, USA) software.
Descriptive statistics were carried out for numerical data using mean, SD, and minimum and maximum of the range, whereas for categorical data number and percentage were used.
Analyses were performed for quantitative variables using the one-way ANOVA test for parametric data between the three groups and using post-hoc analysis for two groups.
Paired sample t-test was used for parametric data between two variables in each group. The χ2 -test was used for qualitative data between groups.
The level of significance was taken at P value less than 0.05.
Sample size calculation
On comparing cases administered with GTN, dexmedetomidine, or magnesium, a significant difference between the groups as regards hypotension required 19 cases per group (power 0.84, α = 0.05, β = 0.16).
| Results|| |
Demographic data were comparable among the study groups [Table 3].
Baseline values of MAP were comparable in the three groups. On intergroup comparison, there was a significant reduction in MAP compared with baseline values after induction of anesthesia and during the hypotensive period in all groups. This reduction extended until extubation in the DEX and M groups. However, in the G group a rise in MAP was noticed before extubation, followed by a significant reduction at 5 min after extubation. The studied drugs reached the desired MAP (55-65 mmHg) with significant differences detected between the three groups during the hypotensive period from 20 up to 60 min and extended until extubation, with the lowest values observed in the DEX group, followed by the M group and lastly the G group in almost all times [Table 4].
In the analysis of HR, significant difference was detected between the groups at 50 and 60 min of the hypotensive period, before extubation, and at 5 min after extubation (with P values 0.043, 0.034, <0.001, and <0.001, respectively), with slower and more steady rate observed in the DEX group. Intergroup comparison showed a significant reduction in HR in all groups after induction and throughout the hypotensive period in comparison with the basal HR. This significant reduction continued until extubation and 5 min after extubation in the DEX group. However, it showed significant increase in the G group and nonsignificant increase in the M group at those two times [Figure 1].
|Figure 1: Comparison of heart rate (HR) (beats/min) in the studied groups. Significant in comparing G versus the DEX group at 40, 50, 60 min before and after extubation. Signifi cant in comparing M versus the DEX group at 60 min of hypotension before and after extubation. DEX, dexmedetomidine; G, glyceryl trinitrate; M, magnesium sulfate.|
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|Table 4: Comparison of mean arterial blood pressure (mmHg) between and within the studied groups (mean ± SD)|
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The studied groups were comparable in terms of duration of anesthesia and surgery, intraoperative blood loss, hemoglobin concentration (preoperatively and postoperatively), and intraoperative use of atropine or ephedrine [Table 5]. However, significant difference between the groups was present in analysis of emergence time, the time needed to restore the basal values of MAP (longer time in the DEX group), and intraoperative fentanyl need (more in the G group). The end-tidal concentrations of sevoflurane and average category scale for quality of the surgical field during the hypotensive period were comparable in the three groups [Table 6].
|Table 6: End-tidal concentrations of sevofl urane and average category scale of surgical field (0– 5) during hypotensive period|
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The DEX group showed significantly longer time to achieve a modified Aldrete score of 9 or greater and to discharge the patients from the PACU, together with significantly higher postoperative sedation scores at 15 and 30 min, compared with the G and M groups and was longer in the M group compared with the G group However, no significant difference was observed in sedation at 60 min. The time to first analgesic request was significantly shorter in the G group. No significant difference was found as regards the use of postoperative antiemetic [Table 7].
|Table 7: Postanesthesia care unit data, time to first analgesic request, and antiemetic use|
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| Discussion|| |
FESS is a surgical procedure, during which all necessary manipulations are performed while using a fiberoptic camera. During the surgery, bleeding has to be minimized, as even a small amount of blood may completely obstruct vision through the endoscope. Various approaches have been used to secure a dry operating field  .
In this prospective randomized study, dexmedetomidine, magnesium sulfate, or GTN was used to induce hypotension in an attempt to provide a good surgical field. The results revealed that the three drugs reached the desired MAP (55-65 mmHg) with significant differences detected during the hypotensive period from 20 up to 60 min and extended until extubation with the lowest values in the DEX group, followed by the M group and lastly the G group in almost all times. For HR, significant reduction in all groups was detected during the hypotensive period; this reduction continued until extubation and 5 min after extubation in the DEX group only. However, it showed a significant increase in the G group and nonsignificant increase in the M group at those two times - that is, slower and steadier rate in the DEX group. Intraoperative blood loss and quality of the surgical field during the hypotensive period were comparable in the three groups, but emergence time and the time needed to restore the basal values of MAP were longer in the DEX group.
The target MAP between 55 and 65 mmHg was decided after revising previous studies in which metabolic and hormonal responses were investigated in patients who were subjected to induced hypotension in an attempt to provide bloodless field without the hazard of tissue ischemia. Newton et al.  investigated in 30 patients the metabolic and hormonal responses to middle ear surgery using induced hypotension to a MAP of 55 mmHg and concluded that this level of deliberate hypotension produced an endocrine and metabolic response of small magnitude and short duration that did not affect tissue oxygenation but kept it adequate.
Although the three drugs were effective in achieving the target MAP, lowering the HR, and ensuring good surgical condition during the procedure, the hemodynamic profile of dexmedetomidine was steadier, which can be attributed to the known sympatholytic effect of α2 agonists. The α2 receptors are involved in regulating the autonomic and cardiovascular systems; thus, the receptors on sympathetic terminal inhibit norepinephrine release and those located on blood vessels mediate vasoconstriction  . At lower doses, DEX is predominantly sympatholytic. DEX, on binding to α2 receptors, reduces the sympathetic outflow and augments cardiac vagal activity, thus resulting in a decreased HR and cardiac output  . It causes analgesia and sympatholysis and has sedative, anxiolytic, and hypnotic effects  .
Magnesium is an agent that has been indicated to decrease MAP and HR and to reduce bleeding  . In this study, magnesium sulfate reduced MAP to the target values, which were statistically insignificant compared with those of DEX. Moreover, it significantly lowered HR and did not cause reflex tachycardia even though higher rate was detected compared with that in the DEX group at 60 min of hypotensive period, before and after extubation. In a randomized, double-blind, placebo-controlled clinical trial conducted by Elsharnouby and Elsharnouby  on 60 patients scheduled for endoscopic surgery, they found a statistically significant lower HR and MAP in the magnesium group with higher quality of vision of the surgical field and shorter operative time compared with the control group. In addition, Aboushanab and El-Shaarawy  concluded that both magnesium sulfate and dexmedetomidine were equally successful in inducing deliberate hypotension in patients undergoing middle ear surgery and produced satisfactory surgical field. In contrast, the results obtained from Akkaya et al.  have shown that dexmedetomidine provided better visual quality of the surgical field compared with magnesium when used in FESS patients under general anesthesia.
As regards GTN, Cincikas and Ivaskevicius  have shown that it reduced bleeding and improved surgical view quality with MAP 50-60 mmHg during endoscopic nasal surgery. However, Jamaliya et al.  found that a continuous infusion of DEX is effective in minimizing blood loss and maintaining superior hemodynamics as compared with GTN in posterior fixation spine surgeries. GTN produces its hypotensive action by liberating nitric oxide, which has a half-life of 0.1 s, whereas DEX acts by selectively binding to α2 receptors with great affinity , . This could explain our findings, which is in agreement with those of Jamaliya et al.  , in which longer time to restore the baseline MAP and more hemodynamic stability were observed during extubation in the DEX group compared with the GTN group even after the hypotensive drugs were stopped.
On evaluating the intraoperative fentanyl and first postoperative analgesic request, this study showed that fentanyl was significantly lower, together with longer time to require postoperative analgesia, in the DEX and M groups compared with the G group. In accordance with our results, several studies have demonstrated the analgesic properties of both drugs , , whereas others showed that perioperative use of dexmedetomidine was associated with a significant reduction in the consumption of fentanyl in a dose-dependent manner , .
This can be explained by the sedative and analgesic sparing effects of dexmedetomidine through central actions in the locus coeruleus and in the dorsal horn of the spinal cord  .
Ryu et al.  concluded that magnesium sulfate was associated with better postoperative analgesia compared with remifentanyl in inducing deliberate hypotension for middle ear surgery.
As regards emergence time, our findings are consistent with those of Durmus et al.  and Bulow et al.  , who reported significantly longer emergence time in patients who received dexmedetomidine for induced hypotension when compared with the control group and the remifentanyl group, respectively.
Lastly, due to the higher sedation score observed in the DEX group, earlier discharge from the PACU was recorded in the G group, followed by the M group. These findings were supported by other studies in which longer time of recovery and discharge from the PACU were recorded in patients who received dexmedetomidine , .
In conclusion, dexmedetomidine, magnesium sulfate, or GTN successfully induced deliberate hypotension and were effective in providing good surgical field during FESS, but dexmedetomidine showed superior hemodynamic profile. Compared with GTN, both dexmedetomidine and magnesium sulfate offered the advantage of inherent analgesic and sedative effect. Limitation of this study was the lack of a bispectral index monitoring to assess the depth of anesthesia; however, on analyzing end-tidal sevoflurane concentrations between the groups during the hypotensive period, no significant difference was detected between the studied drugs. We did not use a control group in the study because it is unethical not to try to control bleeding in such procedures during which even small amounts of bleeding can restrict surgical vision. Moreover, the effect of the studied drugs on the release of catecholamine and other stress hormones either intraoperatively or postoperatively was not investigated. Lastly, the intraoperative and postoperative effect of inducing hypotension on organ perfusion was not followed.
| Acknowledgements|| |
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]