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ORIGINAL ARTICLE
Year : 2019  |  Volume : 12  |  Issue : 2  |  Page : 131-135  

Prospective randomized comparative trial of dexmedetomidine versus esmolol for attenuation of extubation response


Department of Anesthesiology, Seth GSMC and KEM Hospital, Mumbai, Maharashtra, India

Date of Submission02-Apr-2018
Date of Acceptance24-Jul-2018
Date of Web Publication25-Mar-2019

Correspondence Address:
Pushkar M Desai
A703, Noopur Apartment, Bhandarwada, Malad West - 400 064, Mumbai
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mjdrdypu.mjdrdypu_54_18

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  Abstract 


Background and Aims: General anesthesia is known to elicit stress response during endotracheal intubation, but the equally important period of extubation is usually not addressed. The aim was to compare dexmedetomidine and esmolol for attenuation of extubation response. Materials and Methods: In this prospective randomized double-blind trial, 100 American Society of Anesthesiologists I/II patients between 18 and 60 years of age undergoing abdominal and lower-limb surgeries were randomly allocated into two groups (n = 50 each). Patients in Group D received dexmedetomidine (0.5 μg/kg intravenous [IV] bolus) over 10 min and in Group E received esmolol (1 mg/kg bolus IV) before extubation. Hemodynamic parameters, namely, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP), were compared at baseline, 10 min before extubation, at extubation, and at 1, 3, 5, 10, and 15 min thereafter. Data were expressed as mean ± standard deviation and analyzed using Student's unpaired t-test and Chi-square test. P <0.05 was considered statistically significant. Results: Patients in Group D exhibited lower HR, SBP, DBP, and MAP at the time of extubation till 15 min postextubation (P < 0.001) although the difference was clinically insignificant. Incidence of hypotension was similar in both groups (6% vs. 4%). Two patients in Group D developed bradycardia which was successfully treated with injection glycopyrrolate, while none exhibited any complication in Group E. Conclusion: Dexmedetomidine is a better, effective, and safe alternative to esmolol in attenuating stress response during extubation.

Keywords: Dexmedetomidine, esmolol, extubation, stress response


How to cite this article:
Kotak N, Mamde R, Desai PM. Prospective randomized comparative trial of dexmedetomidine versus esmolol for attenuation of extubation response. Med J DY Patil Vidyapeeth 2019;12:131-5

How to cite this URL:
Kotak N, Mamde R, Desai PM. Prospective randomized comparative trial of dexmedetomidine versus esmolol for attenuation of extubation response. Med J DY Patil Vidyapeeth [serial online] 2019 [cited 2019 Apr 18];12:131-5. Available from: http://www.mjdrdypv.org/text.asp?2019/12/2/131/254773




  Introduction Top


General anesthesia with endotracheal intubation is known to elicit stress response characterized by increased sympathetic activity, leading to hypertension, tachycardia, and arrhythmia. However, equally important period of extubation too often results in stress response. Stormy extubation may predispose to pulmonary edema, myocardial insufficiency, and cerebrovascular accident in patients with cardiovascular disease.[1] Different pharmacologic methods have been described to attenuate this response, namely high dose of opioids, topical local anesthetic spray (lignocaine), deeper planes of anesthesia by inhalational agents, and vasodilators such as nitroglycerine,[2],[3] but they have got side effects such as sedation, respiratory depression, hypotension, and bradycardia.

Dexmedetomidine is a novel α2-agonist with hemodynamic stability during perioperative period by virtue of its sympatholytic effect.[4],[5] Esmolol is an ultrashort-acting β1-adrenoceptor antagonist which has been shown to blunt hemodynamic response to perioperative noxious stimuli. Both these drugs have not been compared in the literature during extubation period. Hence, we compared the safety and efficacy of single bolus intravenous (IV) dose of dexmedetomidine with that of esmolol in attenuating hemodynamic response to extubation.


  Materials and Methods Top


Institutional review board approval was obtained. One hundred American Society of Anesthesiologists (ASA) Physical Status I or II patients between 18 and 60 years of age undergoing abdominal and lower limb surgeries were prospectively randomized (n = 50 in each group) into Group D and Group E using a computer-generated table of random numbers. Hypertensive patients on beta-blockers; those with uncontrolled asthma and chronic obstructive pulmonary disease, renal impairment; and pregnant patients were excluded. The study was carried out from December 2013 to October 2014. Patients were explained about the study, and written informed consent was obtained.

All patients were premedicated and induced with injection midazolam (0.05 mg/kg IV), injection fentanyl (2 μg/kg IV), injection propofol (2 mg/kg IV), and injection vecuronium (0.1 mg/kg IV) as muscle relaxant. Patients were maintained on oxygen: nitrous oxide: isoflurane (monitored anesthesia care 1–1.2). Routine standard ASA monitoring was done.

Patients in Group D received IV bolus of 0.5 μg/kg dexmedetomidine over 10 min and in Group E received bolus dose of esmolol (1 mg/kg) 2 min before extubation. Anesthesiologist who administered drugs was not involved in the monitoring of hemodynamic parameters. At the end of the surgery, all patients were reversed with neostigmine 0.05 mg/kg and glycopyrrolate 10 mcg/kg IV and extubated after ensuring adequate recovery Train of four (TOF) ratio >0.9. All patients were shifted to the recovery room and observed for 2 h.

Hemodynamic parameters, namely, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP), were compared at baseline, 10 min before extubation, at extubation, and at 1, 3, 5, 10, and15 min postextubation by an anesthesiologist blinded to the drugs given.

Bradycardia (HR <45/min) was treated with injection glycopyrrolate 0.2 mg IV. Fall in blood pressure of >20% of the baseline value or SBP <90 mm/Hg was considered as hypotension and treated with fast infusion of IV fluid and ephedrine if required.

Statistical analysis

After initial pilot observations, it was decided that 20% of difference in the means of MAP and HR should be the minimum detectable difference to be considered as clinically significant. With power of study 80% and 5% Type 1 error (level of significance [α] = 0.05), the sample size required was calculated as 42 in each group, and to compensate for dropouts, a sample size of 50 participants per group was chosen.

Data were expressed as mean and standard deviation and analyzed using the Student's unpaired t-test. For categorical data such as adverse events, the Chi-square test was used. In this study, P < 0.05 was considered statistically significant.


  Results Top


Demographic variables were similar in the two groups with respect to age, sex, weight, and ASA status [Table 1]. Dexmedetomidine in Group D significantly lowered HR, SBP, DBP, and MAP at the time of extubation till 15 min postextubation [Figure 1], [Figure 2], [Figure 3], [Figure 4]. However, MAP in both groups never dropped below 65 mmHg. Incidence of hypotension was similar in both groups (6% Group D vs. 4% Group E; P = 0.68) [Table 2]. Two patients developed bradycardia with dexmedetomidine, which was successfully treated with injection glycopyrrolate. Esmolol in Group E did not cause bradycardia.
Table 1: Demographic data

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Figure 1: Comparison of heart rate

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Figure 2: Comparison of systolic blood pressure

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Figure 3: Comparison of diastolic blood pressures

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Figure 4: Comparison of mean arterial blood pressures

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Table 2: Comparison of adverse effects

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  Discussion Top


This study confirms that dexmedetomidine and esmolol were successfully used to control hemodynamic changes during extubation; however, dexmedetomidine is more effective than esmolol to attenuate these changes. In this prospective clinical study, bolus dose of dexmedetomidine 0.5 μg/kg before extubation suppressed the hemodynamics in normotensive patients and this suppression was greater than bolus dose of esmolol 1.0 mg/kg. HR, SBP, DBP, and MAPs were better controlled with dexmedetomidine after extubation.

Esmolol is a cardioselective drug with ultrashort duration of action (9 min).[6] It is routinely used to attenuate stress response in the dose ranging from 1 to 2 mg/kg intravenously; however, the optimum dose and timing of its delivery for this purpose have not been standardized.[7] Similarly, dexmedetomidine 0.5 mcg/kg given 5 min before extubation has been found to be more effective than fentanyl 1 mcg/kg in attenuating airway reflex responses to tracheal extubation and maintaining hemodynamic stability without prolonging recovery.[8],[9] Dexmedetomidine 0.5 mcg/kg given as single-dose bolus before tracheal extubation has also been shown to attenuate airway-circulatory reflexes with no difference regarding incidence of breath holding or desaturation.[10] However, the hemodynamic instability following bolus dose of dexmedetomidine 1 mcg/kg as compared to 0.5 mcg/kg has been observed which compelled us to use low dose. To our knowledge, there are no studies comparing both these drugs during extubation.

In this study, HR was significantly lower in dexmedetomidine group after extubation although clinically insignificant. This difference could be attributed to the early termination of action of esmolol due to its very short half-life (9–10 min) as compared to 2–3 h of dexmedetomidine. Furthermore, context-sensitive half-time of dexmedetomidine ranges from 4 min after 10 min infusion to 250 min after 8 h infusion.[11] Ornstein et al.[12] concluded that although esmolol has an ultrashort kinetic half-life, only the HR effect can be considered to have an ultrashort onset, but the control of MAP was delayed, which may be related to gradual decline in the plasma renin activity. An infusion of dexmedetomidine started 20 min before anesthesia and continued until the start of skin closure in patients undergoing supratentorial brain tumor surgery was also found to blunt tachycardia response to intubation and the hypertensive response to extubation.[13]

Similarly, SBP, DBP, and MAP were lower with dexmedetomidine than esmolol; however, MAP never decreased below 65 mmHg in both groups. Oxorn et al.[14] concluded that esmolol in bolus doses of 100 mg and 200 mg affects solely the chronotropic response in a significant manner. Kindler et al. found that esmolol administration before laryngoscopy was sufficient to control HR after intubation, but it did not affect SBP.[15] Our results are in accordance with other studies[16],[17],[18],[19],[20] which demonstrated better control of hemodynamics, anesthetic-sparing effect, and prolonged recovery time with dexmedetomidine. Ghodki et al.[16] used dexmedetomidine as an anesthetic adjuvant in laparoscopic surgery using entropy monitoring with loading dose 1 mcg/kg over 15 min and observed smooth extubation in all patients with minimal change in hemodynamics, good recovery without residual effects of dexmedetomidine, and no adverse reactions such as nausea and vomiting, hypotension, bradycardia, or respiratory depression. Even a single dose of dexmedetomidine before anesthesia induction is an effective method for attenuating the hemodynamic response to tracheal intubation in hypertensive patients with anesthetic-sparing effect.[17] Both esmolol and dexmedetomidine are safe agents for producing controlled hypotension during functional endoscopic sinus surgery, and dexmedetomidine offers added advantage of an inherent analgesic, sedative, and anesthetic-sparing effect than esmolol.[18],[19]

Regarding adverse effects and complications, we found extremely lower incidence of bradycardia and hypotension which can be explained by Aho et al.,[20] who demonstrated that dexmedetomidine causes bradycardia at a dose of >2.4 mcg/kg, while Wiest[21] demonstrated that esmolol causes bradycardia at a dose of 150 mcg/kg/min.

Limitations of this study include lack of comparison of extubation quality and recovery parameters; however, authors think that additional sedative, analgesic property of dexmedetomidine cannot be compared to esmolol which lacks it. Further, high-risk patients with cardiovascular disease were not included in whom even a small difference in hemodynamics might have greater impact on the outcome. Furthermore, cost could be an important factor in choosing the drug, and authors did not perform cost analysis too.


  Conclusion Top


Dexmedetomidine is a better, effective, and safe alternative to esmolol in attenuating the stress response during extubation.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Fox EJ, Sklar GS, Hill CH, Villanueva R, King BD. Complications related to the pressor response to endotracheal intubation. Anesthesiology 1977;47:524-5.  Back to cited text no. 1
    
2.
Devault M, Greifenstein FE, Harris LC Jr. Circulatory responses to endotracheal intubation in light general anesthesia-the effect of atropine and phentolamine. Anesthesiology 1960;21:360-2.  Back to cited text no. 2
    
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Prys-Roberts C, Foëx P, Biro GP, Roberts JG. Studies of anaesthesia in relation to hypertension. V. Adrenergic beta-receptor blockade. Br J Anaesth 1973;45:671-81.  Back to cited text no. 3
    
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Málek J, Marecek F, Hess L, Kurzová A, Ocadlík M, Votava M, et al. Acombination of dexmedetomidine with ketamine and opioids results in significant inhibition of hemodynamic changes associated with laparoscopic cholecystectomy and in prolongation of postoperative analgesia. Rozhl Chir 2010;89:275-81.  Back to cited text no. 4
    
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Bajwa SJ, Kaur J, Singh A, Parmar S, Singh G, Kulshrestha A, et al. Attenuation of pressor response and dose sparing of opioids and anaesthetics with pre-operative dexmedetomidine. Indian J Anaesth 2012;56:123-8.  Back to cited text no. 5
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6.
Kumar S, Mishra MN, Mishra LS, Bathla S. Comparative study of the efficacy of I.V. esmolol, diltiazem and magnesium sulphate in attenuating haemodynamic response to laryngoscopy and tracheal intubation. Indian J Anaesth 2003;47:41-4.  Back to cited text no. 6
    
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Shroff PP, Mohite SN, Panchal ID. Bolus administration of esmolol in controlling the haemodynamic response to tracheal intubation. J Anaesth Clin Pharmacol 2004;20:69-72.  Back to cited text no. 7
    
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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. 8
    
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Aksu R, Akin A, Biçer C, Esmaoǧlu A, Tosun Z, Boyaci A. Comparison of the effects of dexmedetomidine versus fentanyl on airway reflexes and hemodynamic responses to tracheal extubation during rhinoplasty: A double-blind, randomized, controlled study. Curr Ther Res Clin Exp 2009;70:209-20.  Back to cited text no. 9
    
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Guler G, Akin A, Tosun Z, Eskitascoglu E, Mizrak A, Boyaci A. Single-dose dexmedetomidine attenuates airway and circulatory reflexes during extubation. Acta Anaesthesiol Scand 2005;49:1088-91.  Back to cited text no. 10
    
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Reves JG, Glass Peter SA, Lubarsky DA, McEvoy MD, Ruiz RM. Intravenous anaesthetics. In: Miller RD editor. Miller's Anaesthesia. 7th ed., Vol. 1. Philadelphia: Churchill Livingstone Elsevier; 2010. p. 751-3.  Back to cited text no. 11
    
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Ornstein E, Young WL, Ostapkovich N, Matteo RS, Diaz J. Are all effects of esmolol equally rapid in onset? Anesth Analg 1995;81:297-300.  Back to cited text no. 12
    
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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. 13
    
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Oxorn D, Knox JW, Hill J. Bolus doses of esmolol for the prevention of perioperative hypertension and tachycardia. Can J Anaesth 1990;37:206-9.  Back to cited text no. 14
    
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Kindler CH, Schumacher PG, Schneider MC, Urwyler A. Effects of intravenous lidocaine and/or esmolol on hemodynamic responses to laryngoscopy and intubation: A double-blind, controlled clinical trial. J Clin Anesth 1996;8:491-6.  Back to cited text no. 15
    
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Ghodki PS, Thombre SK, Sardesai SP, Harnagle KD. Dexmedetomidine as an anesthetic adjuvant in laparoscopic surgery: An observational study using entropy monitoring. J Anaesthesiol Clin Pharmacol 2012;28:334-8.  Back to cited text no. 16
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Uysal HY, Tezer E, Türkoǧlu M, Aslanargun P, Başar H. The effects of dexmedetomidine on hemodynamic responses to tracheal ntubation in hypertensive patients: A comparison with esmolol and sufentanyl. J Res Med Sci 2012;17:22-31.  Back to cited text no. 17
    
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Ibraheim OA, Abdulmonem A, Baaj J, Zahrani TA, Arlet V. Esmolol versus dexmedetomidine in scoliosis surgery: Study on intraoperative blood loss and hemodynamic changes. Middle East J Anaesthesiol 2013;22:27-33.  Back to cited text no. 18
    
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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;7:175-80.  Back to cited text no. 19
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20.
Aho M, Scheinin M, Lehtinen AM, Erkola O, Vuorinen J, Korttila K, et al. Intramuscularly administered dexmedetomidine attenuates hemodynamic and stress hormone responses to gynecologic laparoscopy. Anesth Analg 1992;75:932-9.  Back to cited text no. 20
    
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Wiest D. Esmolol. A review of its therapeutic efficacy and pharmacokinetic characteristics. Clin Pharmacokinet 1995;28:190-202.  Back to cited text no. 21
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2]



 

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