|Year : 2017 | Volume
| Issue : 1 | Page : 103-108
Efficacy of adding fixed dose dexmedetomidine to nitroglycerin for controlled hypotension in functional endoscopic sinus surgery
Eslam N Nada
Anaesthesia and Intensive Care Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
|Date of Web Publication||3-Aug-2018|
Eslam N Nada
Flat 702, El Hedaya Tower 1, Moahada Street, El Sharkia 44519, Zagazig
Source of Support: None, Conflict of Interest: None
Background Functional endoscopic sinus surgery (FESS) is a surgical procedure during which all possible measures to minimize bleeding should be considered, as even small amount of blood may obstruct vision. Controlled hypotension is one of these measures used to limit intraoperative blood loss to provide the best possible surgical field. The aim of this study was to compare the effect of a fixed dose of dexmedetomidine (DEX) and nitroglycerin (NTG) with NTG alone on hemodynamic parameters, NTG dose, surgeon satisfaction, and blood loss during controlled hypotensive anesthesia in FESS.
Patients and methods Fifty patients of both sexes, classified as American Society of Anesthesia physical status I and II, aged between 20 and 50 years, and candidates for FESS were randomly allocated into two groups by using the sealed envelope method. Group I (n=25) received hypotensive anesthesia with NTG and group II (n=25) received hypotensive anesthesia with NTG and DEX. DEX 1 μg/kg over 10 min was given, and then infused by a syringe pump at a fixed rate of 0.5 μg/kg/h before induction of anesthesia in group II only. After induction and intubation NTG was infused in both groups and titrated to obtain a target mean arterial blood pressure (MAP) of 55–65 mmHg. The MAP and heart rate (HR) were measured at baseline, and then periodically. The following parameters were also recorded: duration of surgical interference (time from the beginning to the end of surgical intervention), blood loss volume, surgeon satisfaction, time to achievement of the target MAP, time to reversibility of MAP to baseline, and the highest dose of NTG needed to reach target MAP.
Results There was no significant difference between two groups regarding demographic data, basal hemodynamics, duration of surgical intervention, American Society of Anesthesia physical status, surgeon satisfaction, and all measurements of MAP except time of intubation, which was significantly less in group II. On the other hand, there was a significant difference between both groups regarding HR, time to achievement and reversibility of MAP, blood loss volume, and the highest dose of NTG needed to reach the target MAP, as all of these measurements were significantly lower in group II.
Conclusion DEX (1 μg/kg bolus, followed by 0.5 μg/kg/h infusion) and NTG is superior to NTG alone in rapid achievement of target MAP with lower HR and lower NTG doses and in reducing blood loss volume during FESS.
Keywords: controlled hypotension, dexmedetomidine, functional endoscopic sinus surgery, intraoperative blood loss, nitroglycerin
|How to cite this article:|
Nada EN. Efficacy of adding fixed dose dexmedetomidine to nitroglycerin for controlled hypotension in functional endoscopic sinus surgery. Ain-Shams J Anaesthesiol 2017;10:103-8
|How to cite this URL:|
Nada EN. Efficacy of adding fixed dose dexmedetomidine to nitroglycerin for controlled hypotension in functional endoscopic sinus surgery. Ain-Shams J Anaesthesiol [serial online] 2017 [cited 2018 Oct 15];10:103-8. Available from: http://www.asja.eg.net/text.asp?2017/10/1/103/238473
| Introduction|| |
Complications of functional endoscopic sinus surgery (FESS) like hemorrhage, cerebrospinal fluid leak, or orbital complications are usually due to poor visualization of the surgical field from bleeding. Thus, reducing bleeding by local vasoconstriction, positioning, and controlled hypotension is important to reduce the risk for these complications .
Controlled (deliberate/induced) hypotension is a technique by which the arterial blood pressure is lowered in a controllable manner to reduce surgical blood loss and improve the operative field visibility. However, it is not without potential complications including permanent cerebral damage, delayed awakening, cerebral thrombosis, brain ischemia, and death ,,.
There are pharmacological and nonpharmacological techniques for inducing hypotension. The nonpharmacological methods for deliberate hypotension include positioning and positive pressure ventilation to control venous return.
On the other hand, many anesthetics and vasoactive drugs have been used to induce deliberate hypotension, including volatile anesthetics, direct-acting vasodilators, autonomic ganglion-blockers, β-adrenergic receptor blockers, α-adrenergic blocking agents, combined α and β adrenergic blocking agents, prostaglandin E1, and calcium channel blockers. Drugs used to produce controlled hypotension must be easy to administer, have a short onset time, a quick offset time on discontinuation, a rapid elimination without toxic metabolites, negligible effects on vital organs, and a predictable and dose-dependent effects .
Nitroglycerin (NTG), a directly acting vasodilator that reduces venous return with concomitant reduction in stroke volume and cardiac output, has been used to achieve induced hypotension because it could be titrated with rapid onset and rapid offset. However, it causes reflex tachycardia and venous congestion in and around the surgical site and thus may increase blood loss .
Dexmedetomidine (DEX) is a potent and highly selective α2-adrenergic agonist. It also improves perioperative hemodynamic stability and causes controlled hypotension by its central and peripheral sympatholytic action. It is also a sedative analgesic with anesthetic sparing effect. All of these actions produce dose-dependent decrease in mean arterial blood pressure (MAP), heart rate (HR), cardiac output, and norepinephrine release .
The aim of this study was to compare the effect of fixed dose DEX (1 μg/kg bolus then 0.5 μg/kg/h infusion) and NTG with NTG alone on hemodynamic parameters, surgeon satisfaction, NTG dose, and blood loss during controlled hypotensive anesthesia in FESS.
| Patients and methods|| |
This study was a randomized double-blinded clinical trial conducted in Zagazig University hospitals during the period from January 2014 to January 2016. After obtaining approval from the hospital’s ethics committee, a written informed consent was taken from 50 patients [American Society of Anesthesia (ASA) I or II, aged between 20 and 50 years, of both sexes] who were enrolled for FESS.
The exclusion criteria included BMI more than 30 kg/m2, cerebrovascular diseases, cardiovascular system disorders, hypertension, asthma or chronic obstructive lung disease, diabetes mellitus, receiving anticoagulants, anemia, hepatic or renal failure, and known drug allergy to one of the used medications.
Patients were randomly divided into two groups by using closed envelopes. Group I (n=25) received hypotensive anesthesia with NTG, and group II (n=25) received hypotensive anesthesia with NTG and DEX (1 μg/kg bolus followed by 0.5 μg/kg/h infusion).
Once patients entered the operation room, monitoring with ECG, noninvasive arterial blood pressure, and oxygen saturation measurement were carried out. Two 18-G intravenous catheters were inserted, one in each hand. Radial artery catheterization for invasive blood pressure measurement was carried out from the nondominant hand of the patient with a 20-G catheter after local anesthesia with 1 ml xilocaine.
All patients received 500 ml Voluven (Fresenius Kabi Australia Pty Limited, Australia) before induction and were premedicated with intravenous midazolam 0.05 mg/kg.
Patients in group II received DEX 1 μg/kg over 10 min (in 50 ml syringe) before induction of anesthesia, after which DEX was infused by a syringe pump at a fixed rate of 0.5 μg/kg/h in one intravenous catheter immediately after the loading dose. The infused solution was made by adding 100 µg (1 ml) of DEX to 49 ml of normal saline, with a final concentration of 2 µg/ml.
Patients in group I received intravenous normal saline over 10 min (in 50 ml syringe), followed by normal saline infusion at a fixed rate of 0.25 μg/kg/h (the same volume as in group II).
Anesthesia was induced by propofol 2 mg/kg and fentanyl 1 μg/kg. Rocuronium 1 mg/kg was given to facilitate endotracheal intubation and end-tidal carbon dioxide was applied. Patients were ventilated with 100% oxygen and isoflurane 1 MAC was used for maintaining anesthesia. Top up doses of rocuronium 0.3 mg/kg were given every 30 min. All patients were positioned in a 30° reverse Trendelenburg position. The nasal mucosae of all the patients were infiltrated using 4 ml of 2% xylocaine with adrenaline (1 : 200 000).
In both groups, after endotracheal intubation, NTG was infused by a syringe pump and titrated to obtain a target MAP of 55–65 mmHg. The starting dose was 0.5 μg/kg/min and the maximum allowed dose was 10 μg/kg/min; the highest infusion dose for each patient was recorded. Patients who might need more than maximum dose or experienced tachycardia more than 120 beats/min were excluded and managed by other medications (anesthetic drugs or other antihypertensive drugs).
If severe hypotension below the targeted level occurred, hypotensive drugs were discontinued as a first step, and if there was no response within 1 min, ephedrine 0.1 mg/kg was given, which could be repeated to achieve a desirable blood pressure, and the patient was excluded from the study. Moreover, if any patient developed bradycardia (<50 beats/min), atropine was given 0.01 mg/kg and the patient was excluded from the study.
All operations were done by the same surgeon and the duration of surgical intervention (from beginning to end of surgical procedure) and surgeon satisfaction were recorded.
Blood loss volume, measured in suction bottle and by the visual estimation of the soaked swaps if present (depending on the swap size and soaking percentage), was recorded.
Infusion of the hypotensive agent was stopped 5 min before the anticipated end of surgery.
MAP and HR measurements were recorded at the following time points: baseline (Tb), immediately after intubation (Ti), immediately after the start of infusion of NTG (Ts), then at 5 min after start (T5), then at 10 min (T10), at 15 min (T15), at 30 min (T30), at 45 min (T45), at 60 min (T60), at 75 min (T75), and at the end point of administration of both hypotensive agents (Te).
The time from the start of infusion of hypotensive agents to achievement of target MAP was recorded (time to achievement).
Time to reversibility, which is the time taken to reach the baseline MAP readings after stopping of hypotensive agent, was also recorded.
Any complications (surgical or anesthetic) were recorded.
The primary outcome was the highest dose of NTG infusion needed to achieve the target MAP. Analyses were performed using the Statistical Package for Social Science version 16 (SPSS Inc., Chicago, IL , USA). A sample size of 20 patients per group was needed to detect an intergroup difference of 50% in the highest NTG doses needed to achieve target MAP with a power of 80% and level of significance of 5%. Twenty-five patients were included per group to replace any dropouts.
The χ2-test was performed for statistical analysis of sex, ASA physical status, and surgeon satisfaction where the data were expressed as numbers. Meanwhile, all other measurements were analyzed using Student’s t-test and data were expressed as mean±SD. A P-value of less than 0.05 was considered statistically significant.
| Results|| |
The two groups did not differ significantly in terms of age, sex distribution, BMI, ASA physical status, and time of surgery scores ([Table 1]).
|Table 1 Demographic data, American Society of Anesthesia physical status, and duration of surgical intervention|
Click here to view
There was a statistically significant difference between both groups (P<0.0001) regarding the highest dose of NTG needed to achieve the target MAP, the time needed to achieve this target pressure (time of achievement), and the time needed for reversal to the baseline MAP measurements (time of reversibility) ([Table 2]).
|Table 2 Highest nitroglycerin dose, time to achievement, and time to reversibility of hypotension|
Click here to view
When hemodynamics were compared between both groups, there was no significant difference between them in baseline measurements of both MAP (P=0.696) and HR (P=0.543).
For periodic measurements, MAP showed no significant difference between both groups except at the time of intubation (Ti) where it was 106.5±2.01 mmHg in group I and 95.25±4.44 mmHg in group II (P<0.0001) ([Table 3]).
|Table 3 Comparison of mean arterial blood pressure between the two groups at different times (mmHg)|
Click here to view
On the other hand, HR showed a significant difference between both groups at all periodic time of measurements ([Table 4]).
|Table 4 Comparison of heart rate between the two groups at different times (beats/min)|
Click here to view
Although there was significant difference between both groups regarding volume of blood loss (107±9.51 ml in group I and 91±4.47 ml in group II; P<0.0001), there was no significant difference between the two groups regarding surgeon satisfaction; the surgeon was satisfied with 23 patients in group I and with 25 patients in group II (P=0.148) ([Table 5]).
There was no need for either atropine or ephedrine and there were no detected complications in both groups.
| Discussion|| |
Many efforts have been made to optimize the surgical field conditions for FESS. Induced hypotension has been widely advocated to control bleeding and improve the quality of surgical field.
The efficacy of DEX in providing better surgical conditions and minimizing blood loss during controlled hypotension was previously reported during tympanoplasty, septoplasty and maxillofacial surgery ,,.
In this study, a target MAP of 55–65 mmHg was chosen to obtain as less a bloody surgical field as possible without the risk for tissue hypoperfusion depending on the studies conducted by Shams et al.  and Yashikawa et al. .
MAP was chosen as a parameter to quantify hypotension as it is the true measure of tissue perfusion .
Unfortunately, no sufficient clinical trials studied the effectiveness of combining DEX infusion and NTG infusion in producing controlled hypotensive anesthesia. In a study conducted by Sahin et al. , comparing DEX and alfentanil in producing hypotensive anesthesia during middle ear surgery, they had to use NTG infusion starting from a rate of 0.5 µg/kg/min in three out of 20 patients in the DEX group to achieve the target MAP of 50–65 mmHg; however, they did not comment on such combination.
In their study, Abel Rahman et al.  found that the synergistic effect of combining an infusion of DEX and NTG found in one group of their study may be explained by the different mechanisms of action of both agents, the effect of premedication with α2-agonist on baroreflex response in anesthetized patients and the patient positioning required during FESS, all of which were the same, as in the present study.
Basar et al.  investigated the effect of a single dose of DEX 0.5 µg/kg administered 10 min before induction of anesthesia and reported a significant reduction in MAP and HR. In addition, studies by Abel Rahman et al.  and Bajwa et al.  demonstrated the ability of the preinduction bolus dose of 1 µg/kg of DEX to attenuate the hemodynamic response to direct laryngoscopy and endotracheal intubation. This can explain the significant difference between the two groups in MAP and HR at the time of intubation in the present study. Furthermore, it explains the better control on hemodynamics, especially HR, and the rapid achievement of target MAP by lower doses of NTG in group II (with continuous DEX infusion) than in group I.
NTG 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. In addition, NTG infusion causes reflex tachycardia and activation of the renin–angiotensin system ,. In the present study, this could explain the longer time for restoration of baseline MAP in group II compared with group I, despite stopping the hypotensive drugs, and explain the higher HR measurements in group I.
The average blood loss was higher in group I in comparison with group II. This can be due to increased HR and venous congestion caused by NTG ,, because there was no significant difference in the MAP achieved in both groups.
Despite the less blood loss in group II, surgeon satisfaction showed no significant difference between the two groups, but still was higher in group II.
One of the limitations of this study was its end point, which was the time to reversibility without assessing time to extubation, sedation score, or pain score. However, it is known that DEX possesses sedative and analgesic effects, whereas NTG does not, and hence they are noncomparable. Another limitation was the visual assessment of blood-soaked swaps, which is a rough and inaccurate method but simple and reliable regarding our resources.
| Conclusion|| |
It was concluded that a combined infusion of DEX (1 μg/kg bolus then 0.5 μg/kg/h infusion) and NTG is an effective and safe method of producing controlled hypotension in FESS as compared with NTG infusion alone due to rapid achievement of the target MAP with a lower doses of NTG, better control on HR, and decreased blood loss.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Mafee MF, Chow JM, Meyers R. Functional endoscopic sinus surgery: anatomy, CT screening, indications, and complications. Am J Roentgenol 1993; 160:735–744.
Cincikas D, Ivaskevicius J, Martinkenas JL, Balseris S. A role of anesthesiologist in reducing surgical bleeding in endoscopic sinus surgery. Medicina (Kaunas) 2011; 46:730–734.
Drozdowski A, Sieskiewicz A, Siemiatkowski A. Reduction of intraoperative bleeding during functional endoscopic sinus surgery. Anestezjol Intens Ter 2011; 43:45–50.
Morgan GE, Mikhail MS, Murray MJ. Hypotensive agents. In: Clinical anesthesiology. 4th ed. New Delhi: Tata McGraw-Hill 2012. pp. 255–262.
Degoute CS. Controlled hypotension: a guide to drug choice. Drugs 2007; 67:1053–1076.
Testa LD, Tobias JD. Pharmacologic drugs for controlled hypotension. J Clin Anesth 1995; 7:326–337.
Kaur M, Singh PM. Current role of dexmedetomidine in clinical anesthesia and intensive care. Anesth Essays Res 2011; 5:128–133. [Full text]
Durmus M, But AK, Dogan Z, Yucel A, Miman MC, Ersoy MO. Effect of dexmedetomidine on bleeding during tympanoplasty or septoplasty. Eur J Anaesthesiol 2007; 24:447–453.
Ayoglu H, Yapakci O, Ugur MB, Uzun L, Altunkaya H, Ozer Y et al.
Effectiveness of dexmedetomidine in reducing bleeding during spetoplasty and tympanoplasty operations. J Clin Anesth 2008; 20:437–441.
Richa F, Yazigi A, Hage C. Dexmedetomidine: an agent for controlled hypotension in maxilla fascial surgery: A242. Eur J Anaesthesiol 2004; 21:62.
Shams T, El Bahnasawe NS, Abu-Samra M, El-Masry R. Induced hypotension for functional endoscopic sinus surgery: a comparative study of dexmedetomidine versus esmolol. Saudi J Anaesth 2013; 7:175–180.
Yashikawa F, Kohase H, Umino M, Fukayama F. Blood loss and endocrine responses in hypotensive anaesthesia with sodium nitroprusside and nitroglycerin for mandibular osteotomy. Int J Oral Maxillofac Surg 2009; 38:1159–1164.
Shapiro DS, Loiacono LA. Mean arterial pressure: therapeutic goals and pharmacologic support. Crit Care Clin 2010; 26:285–293.
Sahin F, Deren S, Erdogan G, Ornek D, Dikmen B. Comparison of dexmedetomidine and alfentanil during middle ear surgery. Int Adv Otol 2011; 7:225–233.
Abel Rahman NI, Fouad EA, Ahmed A, Youness AR, Wahib M. Efficacy of different dexmedetomidine regimens in producing controlled hypotensive anesthesia during functional endoscopic sinus surgery. Egypt J Anaesth 2014; 30:339–345.
Basar H, Akpinar S, Doganci N, Buyukkocak U, Kaymak C, Sert O, Apan A. The effect of preanaesthetic single dose dexmedetomidine on induction, hemodynamic and cardiovascular parameters. J Clin Anesth 2008; 20:431–436.
Bajwa SJS, Kaur J, Singh A, Parmar S, Singh G, Kulshrestha A et al.
Attenuation of pressor response and dose sparing of opioids and anaesthetics with preoperative dexmedetomidine. Indian J Anaesth 2012; 56:123–128.
Bhana N, Goa KL, McClellan KJ. Dexmedetomidine. Drugs 2000; 59:263–268.
Kelm M, Schrader J. Control of coronary vascular tone by nitric oxide. Circ Res 1990; 66:1561–1575.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]