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Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 11  |  Issue : 4  |  Page : 1079-1083  

A comparison of dexmedetomidine and clonidine in attenuating the hemodynamic responses at various surgical stages in patients undergoing elective transnasal transsphenoidal resection of pituitary tumors


1 Department of Anaesthesiology and Critical Care, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
2 Department of Dentistry and Maxillofacial Surgery, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India

Date of Web Publication28-Nov-2017

Correspondence Address:
Zulfiqar Ali
Department of Anaesthesiology and Critical Care, Division of Neuroanaesthesiology, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Jammu and Kashmir
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0259-1162.194575

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   Abstract 


Background: Transsphenoidal approach to pituitary tumors is a commonly performed procedure with the advantage of a rapid midline access to the sella with minimal complications. It may be associated with wide fluctuations in hemodynamic parameters due to intense noxious stimulus at various stages of the surgery. As duration of the surgery is short and the patients have nasal packs, it is prudent to use an anesthestic technique with an early predictable recovery. Materials and Methods: A total of 60 patients of either sex between 18 and 65 years of age, belonging to the American Society of Anesthesiologists I and II who were undergoing elective transnasal transsphenoidal pituitary surgery were chosen for this study. Patients were randomly allocated into two groups, Group C (clonidine) and Group D (dexmedetomidine), with each group consisting of 30 patients. Patients in Group C received 200 μg tablet of clonidine and those in Group D received a pantoprazole tablet as placebo at the same time. Patients in the Group D received an intravenous infusion of dexmedetomidine diluted in 50 ml saline (200 μg in 50 ml saline) 10 min before induction and patients in Group C received 0.9% normal saline (50 ml) as placebo. The hemodynamic variables (heart rate, mean arterial pressure) were noted at various stages of the surgery. Statistical analysis of the data was performed. Results: A total of 60 patients were recruited. The mean age, sex, weight and duration of surgery among the two groups were comparable (P > 0.05). Both dexmedetomidine and clonidine failed to blunt the increase in hemodynamic responses (heart rate and blood pressure) during intubation, nasal packing, speculum insertion and extubation. However when the hemodynamic response was compared between the patients receiving dexmedetomidine and clonidine it was seen that patients who received dexmedetomidine had a lesser increase in heart rate and blood pressure (P < 0.05) when compared to clonidine. Conclusions: A continuous intravenous infusion of dexmedetomidine as compared to oral clonidine improved hemodynamic stability in patients undergoing transnasal transsphenoidal resection of pituitary tumors.

Keywords: Clonidine, dexmedetomidine, transnasal transspenoidal resection of pituitary tumors


How to cite this article:
Jan S, Ali Z, Nisar Y, Naqash IA, Zahoor SA, Langoo SA, Azhar K. A comparison of dexmedetomidine and clonidine in attenuating the hemodynamic responses at various surgical stages in patients undergoing elective transnasal transsphenoidal resection of pituitary tumors. Anesth Essays Res 2017;11:1079-83

How to cite this URL:
Jan S, Ali Z, Nisar Y, Naqash IA, Zahoor SA, Langoo SA, Azhar K. A comparison of dexmedetomidine and clonidine in attenuating the hemodynamic responses at various surgical stages in patients undergoing elective transnasal transsphenoidal resection of pituitary tumors. Anesth Essays Res [serial online] 2017 [cited 2019 May 25];11:1079-83. Available from: http://www.aeronline.org/text.asp?2017/11/4/1079/194575




   Introduction Top


The tumors of pituitary fossa are approached through the transcranial, transsphenoidal, or transethmoidal routes. Transsphenoidal approach has the advantage of rapid midline access to the sella with the minimal risk of brain trauma, hemorrhage, and a low incidence of postoperative complications. However, transnasal transsphenoidal resection of pituitary tumor may be associated with wide fluctuations in hemodynamic parameters due to intense noxious stimulus at various stages of the surgery. There may be hypertension and tachycardia during insertion of adrenaline soaked nasal packing, nasal speculum insertion, sphenoid, and sellar dissection.[1] None of the routinely used anesthetic agents effectively blunts the undesirable hemodynamic response; hence, there is a need for increased dose of anesthetic agents during the surgery.[1] As the duration of the surgery is short and the patients have nasal packs (which makes them obligate oral breathers), it is prudent to use an anesthestic technique with an early predictable recovery with a fully conscious patient before extubation. A positive pressure ventilation with the mask has to be avoided, as there is risk of tension pneumocephalus, venous air embolism, and introduction of bacteria in subarachnoid space.

The main aims of anesthesia for pituitary surgeries include maintenance of hemodynamic stability, provision of conditions that facilitate surgical exposure, and a smooth emergence to facilitate prompt neurological assessment. Various strategies such as local anesthetic infiltration into the nasal mucosa and maxillary nerve blocks have been attempted to blunt the stress response with variable results.[2] The stress response to surgical stimulus is characterized by activation of sympathetic nervous system and an increase in the level of pituitary hormones.[3] Centrally acting α2 adrenoceptor agonists such as clonidine and dexmedetomidine reduce noradrenaline release in the central nervous system leading to reduced sympathetic outflow.[4]

This study was designed to evaluate and compare the effect of two α2 agonists, dexmedetomidine and clonidine in attenuating the hemodynamic responses at various surgical stages in patients undergoing elective transnasal transsphenoidal resection of pituitary tumors.


   Materials and Methods Top


This prospective, randomized, comparative study was conducted in a tertiary care hospital from May 2014 to June 2015. After the Institutional Review Board approval, and informed patient consent, sixty patients of either sex between 18 and 65 years of age, belonging to the American Society of Anesthesiologists (ASA) I and II who were undergoing elective transnasal transsphenoidal pituitary surgery were selected for the study.

During preoperative visit, all patients were clinically evaluated. The study protocol was explained to all patients and a written informed consent was taken. Patients with ischemic heart disease, heart block, psychiatric or neurological illness, history of liver or renal diseases were excluded from the study. Pregnant patients and patients taking antihypertensive medication such as alpha-methyldopa, beta-blockers, calcium channel blockers, or other α2 adrenergic agonists were also excluded from the study. Patients were kept nil per oral for 6 h. In the operation theater, intra venous line was secured using 18-gauge or 20-gauge cannula. Patients were connected to the monitor for continuous monitoring of electrocardiography, heart rate (HR), noninvasive blood pressure, and oxygen saturation. Radial artery was cannulated for continuous measurement of arterial blood pressure after induction of anesthesia. Patients were randomly allocated into two groups, Group C (clonidine) and Group D (dexmedetomidine), with each group consisting of thirty patients. Patients were assigned to groups using randomized computer generated chart. Ninety minutes before entering the operating room, patients in Group C received 200 μg tablet of clonidine and those in Group D received a pantoprazole tablet as placebo at the same time. Patients in the Group D received intravenous infusion of dexmedetomidine diluted in 50 ml saline (200 μg in 50 ml saline) 10 min before induction and patients in Group C received 0.9% normal saline (50 ml) as placebo (dexmedetomidine infusion was prepared by diluting 2 ml [200 μg] dexmedetomidine in 48 ml of 0.9% normal saline, [1 ml = 4 μg]). The dose of dexmedetomidine given was 1 μg/kg over 10 min as intravenous loading dose before induction followed by 0.5 μg/kg/h till the end of surgical procedure (till the last surgical stitch was applied). Anesthesia was induced with fentanyl 2 μg/kg and propofol titrated with the loss of verbal response. Tracheal intubation was facilitated with intravenous vecuronium 0.15 mg/kg. Anesthesia was maintained with a mixture of nitrous oxide, oxygen, and isoflurane. Intermittent positive pressure ventilation with tidal volume of 7–8 ml/kg body weight was done to maintain end-tidal carbon-dioxide between 30 and 35 mmHg. The total fresh gas flow rate was kept constant at 1 L/min using a closed circle absorber. Posterior pharynx was packed with moist cotton gauze under direct laryngoscopy, to avoid entry of surgical bleed into the esophagus and stomach. Repeated doses of fentanyl were given hourly. Intravenous paracetamol 1 g was given over a period of 30 min toward the end of surgery. At the end of the surgery, the drug infusion was discontinued. Similarly, isoflurane was stopped, and the lungs were ventilated with 100% oxygen. Injection ondansetron 4 mg was prophylactically administered as an antiemetic agent in all patients. The neuromuscular blockade was antagonized with injection neostigmine 50 μg/kg and glycopyrrolate 10 μg/kg. The patient's trachea was extubated when the patient was generating an adequate tidal volume (>6 mg/kg) and able to open the eyes spontaneously or obey simple commands. After extubation, all patients were transferred to high dependency unit in neurosurgical ward for overnight observation. In the postoperative period, analgesics were administered on the basis of patient demand analgesia. Injection paracetamol 15 μg/kg was used 8 hourly for the first 24 h to 48 h. Similarly, injection fentanyl 1–2 μg/kg was administered if the patient had pain and demanded additional analgesics. The hemodynamic variables (HR, mean arterial pressure) were noted during the following stages of the surgery:

  1. Baseline
  2. Before and after intubation (preintubation and postintubation – maximal rise within 3 min of tracheal intubation)
  3. Before and after nasal packing of saline swabs soaked in adrenaline (prenasal packing and postnasal packing – maximal rise within 3 min)
  4. Insertion of Hardy's self-retaining nasal speculum (pre- and post-speculum maximal rise within 3 min)
  5. Extubation and postextubation (maximal rise within 3 min of postextubation).


The sample size for the study was calculated from the software G power 3.1.5. G* Power (Faul, Erdfelder, Lang, and Buchner, 2007) is a stand-alone power analysis program for many statistical tests commonly used in the social, behavioral, and biomedical sciences. It is available free of charge via the Internet for both Windows and Mac OS X platforms. For an α value of 5% and keeping the power of the study (1−β) equal to 80%, it was found that a minimum of thirty patients are required to be recruited in each group.

Data were summarized as mean ± standard deviation. Statistical analysis of the data was performed using Student's t-test for difference of means and paired sample t-test. For quantitative analysis of nominal data, Chi-square test was used. These tests were two-sided and were referenced for P values for their significance. Any P < 0.05 was taken to be statistically significant and P < 0.001 as highly significant.


   Results Top


Demographic data

A total of 60 patients were recruited and taken for final analysis [Table 1]. The mean age in patients receiving dexmedetomidine was 43.93 while as the mean age was 47. Sixty in patients receiving clonidine. Similarly, the mean weight was 64.55 in patients receiving clonidine and 63.13 in patients receiving dexmedetomidine. The mean age, sex, weight, and duration of surgery among the two groups were comparable (P > 0.05).
Table 1: Comparison of age, weight, and duration of surgery between the two groups

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Hemodynamic variables

The HR in both groups increased at various stages of anesthesia and surgical stimulation as during tracheal intubation, insertion of nasal packs, insertion of nasal speculum and during extubation. This increase was significant in both groups when it was compared with the respective baseline responses [Table 2] and [Table 3]. In other words, both dexmedetomidine and clonidine failed to blunt the increase in hemodynamic responses (HR and blood pressure) during intubation, nasal packing, speculum insertion, and extubation. However, when the hemodynamic response was compared between the patients receiving dexmedetomidine and clonidine, it was seen that patients who received dexmedetomidine had a lesser increase in HR and blood pressure when compared to clonidine [Table 4]. In other words, an intravenous infusion of dexmedetomidine blunted effectively the stress responses at various surgical stages when compared to oral clonidine.
Table 2: Comparison of hemodynamic variables between the two groups at various stages

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Table 3: Intra group comparison of hemodynamics at different stages of surgery in dexmedetomidine group

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Table 4: Intra group comparison of hemodynamics at different stages of surgery in clonidine group

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However at 10 min after extubation, the mean HR in dexmedetomidine and clonidine group was 74.07 ± 5.66 beats/min and 76.10 ± 6.08 beats/min, respectively, and the difference in the two groups was statistically insignificant. However, the patients who received dexmedetomidine had a lower blood pressure when compared to the clonidine group.


   Discussion Top


Control of hemodynamic parameters during neurosurgical procedures is of great concern to the neuroanesthetist whose goals include ensuring optimal cerebral perfusion pressure. Even very deep general anesthesia through inhalation or narcotics cannot reliably ablate the response to different surgical stimuli and rather, may compromise arterial blood pressure and hence cerebral blood flow in the susceptible patient. During surgery, abrupt increases in arterial blood pressure might cause bleeding or edema in the operating field. Low arterial blood pressure, on the other hand, could predispose the patients to cerebral ischemia because autoregulation of the cerebral blood flow is often impaired near tumors or traumatized areas.

Transnasal transsphenoidal resection of pituitary tumors involves wide fluctuation in hemodynamic parameter and cause hypertension and tachycardia due to intense noxious stimulus during adrenaline soaked nasal packing, nasal speculum insertion, and during sphenoid and sellar dissection. None of the routinely used anesthetic agents effectively blunt the undesirable hemodynamic responses; therefore, usually there is a need to use increased doses of anesthetic agents. An early and predictable recovery is desirable in these patients as the use of nasal packs may pose risk of airway obstruction in these patients. Hence, it is imperative that these patients should be fully awake before extubation. Several strategies have been tried to attenuate the hemodynamic and neuroendocrine response in patients undergoing transnasal transsphenoidal resection of pituitary tumor. Drugs such as clonidine, atenolol, and magnesium sulfate have been used to attenuate the hemodynamic responses during transnasal transsphenoidal pituitary surgery.[5] Bilateral maxillary nerve block and bilateral sphenopalatine ganglion block combined with general anesthesia have also been used to suppress catecholamine response and control hemodynamics in patients undergoing endoscopic endonasal transsphenoidal resection of pituitary adenoma.[2],[6] Furthermore, several reports have investigated the effects of dexmedetomidine on hemodynamics in patients undergoing neurosurgery.[7],[8]

Gopalakrishna et al. observed that the hemodynamic responses were blunted in patients undergoing transnasal transsphenoid resection of pituitary tumors when dexmedetomidine was compared with placebo.[9] Uyar et al. compared the hemodynamic and neuro-endocrinal response to skull pin head holder application during craniotomy in forty patients undergoing craniotomy who were randomized to receive either a placebo or a single bolus dose of dexmedetomidine (1 μg/kg) intravenously over 10 min before induction of anesthesia. It was seen that a single bolus of dexmedetomidine before induction of anesthesia attenuated the hemodynamic and neuro-endocrinal responses to skull pin insertion in patients undergoing craniotomy.[10]

Chiruvella et al. observed similar finding in patients undergoing laparoscopic cholecystectomy under general anesthesia. They observed that dexmedetomidine was more effective in attenuating hemodynamic response than clonidine in patients undergoing laparoscopic cholecystectomy under general anesthesia.[11] Taittonen et al. conducted a study to evaluate the effects of clonidine and dexmedetomidine premedication on perioperative oxygen consumption and hemodynamic parameters undergoing various plastic surgical procedures. Patients were premedicated with clonidine 4 μg/kg, dexmedetomidine 2.5 μg/kg or saline. It was seen that both clonidine and dexmedetomidine decreased perioperative oxygen consumption effectively. There was no difference in the hemodynamic profile. This was probably as result of lower doses of dexmedetomidine used by the authors as compared to our study and a different surgical group.[12]

Tanskanen et al. and Turan et al. observed that intraoperative dexmedetomidine infusion in craniotomy patients decreased hemodynamic responses when compared to other group of patients who received placebo.[7],[13]

There was some limitation in our study that should be considered. The study was performed in patients with low ASA scores (ASA I and II) and with good cardiac function. Indeed patients with cardiac disease may be at high risk for developing significant bradycardia and hypotension that may need intervention when using dexmedetomidine.

This study was not carried out in the postoperative period beyond 10 min due to the limitation of resources. Although we noticed an attenuation of blood pressure in the patients who received dexmedetomidine at 10 min postintubation, further studies are needed to be carried out to study the hemodynamic effects in the postoperative period.


   Conclusions Top


A continuous intravenous infusion of dexmedetomidine as compared to oral clonidine improved hemodynamic stability in patients undergoing transnasal transsphenoidal resection of pituitary tumors. Hence, we recommend the addition of an intravenous dexmedetomidine infusion, intraoperatively in clinical practice, by the neuroanesthesiologists or the occasional anaesthesiologist who anesthetise the patients for transnasal transsphenoidal resection of pituitary tumors, for optimization of intraoperative hemodynamics in healthy patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Ali Z, Prabhakar H, Bithal PK, Dash HH. Bispectral index-guided administration of anesthesia for transsphenoidal resection of pituitary tumors: A comparison of 3 anesthetic techniques. J Neurosurg Anesthesiol 2009;21:10-5.  Back to cited text no. 1
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2.
Chadha R, Padmanabhan V, Rout A, Waikar HD, Mohandas K. Prevention of hypertension during trans-sphenoidal surgery – The effect of bilateral maxillary nerve block with local anaesthetics. Acta Anaesthesiol Scand 1997;41(1 Pt 1):35-40.  Back to cited text no. 2
    
3.
Desborough JP, Hall GM. Endocrine response to surgery. In: Kaufman L, editor. AnaesthesiaReview. Vol. 10. Edinburgh: Churchill Livingstone; 1993. p. 131-48.  Back to cited text no. 3
    
4.
Gertler R, Brown HC, Mitchell DH, Silvius EN. Dexmedetomidine: A novel sedative-analgesic agent. Proc (Bayl Univ Med Cent) 2001;14:13-21.  Back to cited text no. 4
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Gupta D, Srivastava S, Dubey RK, Prakash PS, Singh PK, Singh U. Comparative evaluation of atenolol and clonidine premedication on cardiovascular response to nasal speculum insertion during trans-sphenoid surgery for resection of pituitary adenoma: A prospective, randomised, double-blind, controlled study. Indian J Anaesth 2011;55:135-40.  Back to cited text no. 5
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6.
Ali AR, Sakr SA, Rahman MA. Bilateral sphenopalatine ganglion block as adjuvant to general anaesthesia during endoscopic trans-nasal resection of pituitary adenoma. Egypt J Anaesth 2010;26:273-80.  Back to cited text no. 6
    
7.
Tanskanen PE, Kyttä JV, Randell TT, Aantaa RE. Dexmedetomidine as an anaesthetic adjuvant in patients undergoing intracranial tumour surgery: A double-blind, randomized and placebo-controlled study. Br J Anaesth 2006;97:658-65.  Back to cited text no. 7
    
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Talke P, Chen R, Thomas B, Aggarwall A, Gottlieb A, Thorborg P, et al. The hemodynamic and adrenergic effects of perioperative dexmedetomidine infusion after vascular surgery. Anesth Analg 2000;90:834-9.  Back to cited text no. 8
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Gopalakrishna KN, Dash PK, Chatterjee N, Easwer HV, Ganesamoorthi A. Dexmedetomidine as an anesthetic adjuvant in patients undergoing transsphenoidal resection of pituitary tumor. J Neurosurg Anesthesiol 2015;27:209-15.  Back to cited text no. 9
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10.
Uyar AS, Yagmurdur H, Fidan Y, Topkaya C, Basar H. Dexmedetomidine attenuates the hemodynamic and neuroendocrinal responses to skull-pin head-holder application during craniotomy. J Neurosurg Anesthesiol 2008;20:174-9.  Back to cited text no. 10
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Chiruvella S, Donthu B, Siva JV, Dorababu S. Comparative study of clonidine versus dexmedetomidine for haemodynamic stability during laparoscopic cholecystectomy. Int J Sci Stud 2014;2:186-90.  Back to cited text no. 11
    
12.
Taittonen MT, Kirvelä OA, Aantaa R, Kanto JH. Effect of clonidine and dexmedetomidine premedication on perioperative oxygen consumption and haemodynamic state. Br J Anaesth 1997;78:400-6.  Back to cited text no. 12
    
13.
Turan G, Ozgultekin A, Turan C, Dincer E, Yuksel G. Advantageous effects of dexmedetomidine on haemodynamic and recovery responses during extubation for intracranial surgery. Eur J Anaesthesiol 2008;25:816-20.  Back to cited text no. 13
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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