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ORIGINAL ARTICLE
Year : 2014  |  Volume : 41  |  Issue : 3  |  Page : 151-155

A comparative clinical study of dexmedetomidine versus placebo to attenuate hemodynamic response to endotracheal intubation in patients undergoing off pump coronary arterial bypass grafting


Department of Cardiothoracic and Vascular Anesthesiology and Surgery, KLE University's Jawaharlal Nehru Medical College, Nehrunagar, Belgaum, Karnataka, India

Date of Web Publication19-Sep-2014

Correspondence Address:
Soniya R Sulhyan
C/O Dr. M. D. Dixit, Director, KLE Heart Foundation, Krishna Floor, Near Intensive Therapy Unit, Krishna Floor, Dr. Prabhakar Kore Hospital and Medical Research Centre, Nehrunagar, Belgaum - 590 010
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0974-5009.141198

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  Abstract 

Context: Direct laryngoscopy and endotracheal intubation are the most stressful periods during induction of anesthesia. These events can lead to hypertension, tachycardia, arrhythmias and myocardial ischaemia. Aims: (1) To evaluate the haemodynamic response to laryngoscopy and endotracheal intubation with a single preinduction infusion of dexmedetomidine (DEX) 1 μg/kg over a 10 min period, (2) To assess the incidence of side effects, that is, rebound hypertension, bradycardia and hypotension etc., associated with the use of DEX. Settings and Design: This was a prospective, double-blind, parallel group randomized clinical trial of DEX (1 μg/kg) before anesthetic induction to study the attenuation of hemodynamic response to endotracheal intubation in 60 adult patients undergoing elective off pump coronary arterial bypass grafting. Materials and Methods: Patients were randomly allocated to receive either DEX (DEX group, n = 30) or 0.9% normal saline (PLA group, n = 30). Hemodynamic variables were recorded at baseline (Abbreviated as TB), after completion of drug infusion (Abbreviated as TC), 3 min after induction and immediately before intubation (T0), at the 1 st (T1), 3 rd (T3) and 5 th (T5) min after intubation. Statistical Analysis Used: The data are presented as mean ± standard deviation. Demographic data were analysed by Student's t-test between the two groups. Analysis of variance for repeated measures f-test was used to analyze changes over time. A P < 0.05 was considered as significant and P < 0.01 or 0.001 was considered as highly significant. Results: All the hemodynamic variables were comparable in both groups at baseline. Heart rate values were statistically significantly lower in the DEX group at TC and highly statistically significantly lower at T1, T3 and T5 values. Systolic blood pressure values were statistically significantly lower in the DEX group at T0 and highly statistically significantly lower at T1, T3 and T5. Diastolic blood pressure and mean blood pressure values and systolic pulmonary artery pressure values were highly statistically significantly lower in the DEX group at T1, T3 and T5. Diastolic pulmonary artery pressure were statistically significantly lower in the DEX group at TC, T0 and T1 and highly statistically significantly lower at T3. Mean pulmonary artery pressure were statistically significantly lower in the DEX group at T0 and highly statistically significantly lower at TC, T1 and T3. Arterial oxygen saturation was statistically significantly lower in the DEX group at TC. There was no case of hypotension or bradycardia in our case series. Conclusions: Dexmedetomeditine (1 μg/kg) attenuates hemodynamic response to laryngoscopy and intubation in elective surgery for off pump coronary artery bypass grafting.

Keywords: Dexmedetomidine, intubation, off pump coronary artery bypass grafting


How to cite this article:
Sulhyan SR, Vagarali AT, Patil SS, Dixit MD. A comparative clinical study of dexmedetomidine versus placebo to attenuate hemodynamic response to endotracheal intubation in patients undergoing off pump coronary arterial bypass grafting. J Sci Soc 2014;41:151-5

How to cite this URL:
Sulhyan SR, Vagarali AT, Patil SS, Dixit MD. A comparative clinical study of dexmedetomidine versus placebo to attenuate hemodynamic response to endotracheal intubation in patients undergoing off pump coronary arterial bypass grafting. J Sci Soc [serial online] 2014 [cited 2020 May 27];41:151-5. Available from: http://www.jscisociety.com/text.asp?2014/41/3/151/141198


  Introduction Top


Securing the airway during general anesthesia is best provided by endotracheal intubation assisted by a direct laryngoscopy, but is associated with profound adverse hemodynamic changes [1] like hypertension, arrhythmias and myocardial ischemia. [2],[3] A number of pharmacological drugs like lidocaine, esmolol, nitroglycerine, magnesium sulphate, verapamil, nicardipine and diltiazem, opioids, β-blockers, gabapentin have been used to attenuate this response. [2],[3],[4],[5]

The major determinants of myocardial oxygen demand are heart rate (HR) and blood pressure. Since, endotracheal intubation causes marked increase in arterial pressure and HR, the increase in myocardial oxygen demand must be met by an increase in supply of oxygenated blood through coronary circulation. When one or more occlusive lesions occur in the coronary arteries, the ability to increase myocardial oxygen supply is minimal and abrupt increase in myocardial demand results in ischemia and myocardial dysfunction or overt tissue infarction.

α2 adrenergic agonists decrease sympathetic tone and blunt the hemodynamic responses to noxious stimulation and prevent the overall hemodynamic variability. It also reduces the need for anesthetics and therefore can be used as an adjunct to general anesthetics.

Dexmedetomidine (DEX), a more specific and selective α2 adrenergic agonist than clonidine has a shorter duration of action. [2] The present study is designed to assess the effects of DEX to attenuate the haemodynamic responses to endotracheal intubation as follows:

  1. To evaluate the haemodynamic response to laryngoscopy and endotracheal intubation with a single preoperative dose of DEX in a dose of 1 μg/kg over a 10 min infusion period
  2. To assess the incidence of side effects, that is, rebound hypertension, bradycardia and hypotension etc., associated with the use of DEX.



  Materials AND METHODS Top


This was a prospective, double-blind, parallel group randomized clinical trial of DEX to study the attenuation of hemodynamic response to endotracheal intubation in 60 adult patients undergoing elective off pump coronary arterial bypass grafting. The study protocol was presented to the institutional ethical committee for their approval. Written explained informed consent was taken from all the patients.

Exclusion criteria included anticipated difficult intubation, ejection fraction <40%, age >70 years and body mass index >30 kg/m 2 , left main coronary artery occlusion, combined operations, history of sensitivity to drugs during study, severe systemic renal and hepatic diseases, preoperative left bundle branch block, intubation attempt lasting longer than 20 s, emergency surgeries.

These patients underwent preanesthetic evaluation the day before surgery. Diuretics, angiotensin converting enzyme inhibitors, angiotensin receptor antagonists and calcium channel blockers were stopped the day before surgery as per institutional protocol. Tablet clopidogrel was stopped 72 h before the surgery. All patients received tablet pantoprazole 40 mg and tablet lorazepam 1 mg on the night before and on the morning of day of surgery.

Patients were randomly allocated to receive either DEX (DEX group, n = 30) or 0.9% normal saline (PLA group, n = 30). Syringes containing aqueous solutions of the study drugs were prepared in double blind fashion. Peripheral, central venous and arterial cannulations were performed under local anesthesia using 2% lignocaine. Electrocardiogram, pulse oximetry for oxygen saturation (SpO 2 ), intraarterial blood pressure, pulmonary arterial pressures, nasopharyngeal temperature and capnography were also monitored. After 3 min of stable cardiovascular variables, hemodynamic variables were recorded as baseline (TB).

Before induction of anesthesia, a single dose of injection DEX 1 μg/kg diluted in 10 ml of 0.9% normal saline was administered over 10 min in DEX group and 10 ml of 0.9% normal saline in the PLA group through the central venous pressure measuring port of the pulmonary artery pressure catheter inserted through the right internal jugular vein. Haemodynamic variables were recorded again at the end of 5 min of completion of study drug infusion (TC). Induction of general anesthesia was achieved with intravenous (IV) injection fentanyl 10 μg/kg and injection midazolam 0.1 mg/kg. Lack of response to verbal command followed by loss of corneal reflex was considered as the end point of induction. Injection vecuronium 0.1 mg/kg was administered intravenously to facilitate tracheal intubation. Trachea was intubated after 3 min of mask ventilation with 100% oxygen. All intubations were performed by the same senior anaesthesiologist. Hemodynamic variables were recorded 3 min after induction, that is, immediately before intubation (T0), at the 1 st (T1), 3 rd (T3) and 5 th (T5) min after intubation.

The data are presented as mean ± standard deviation. Demographic data were analysed by Student's t-test between the two groups. Analysis of variance for repeated measures f-test was used to compare between groups and with groups. Chi-square test was used to analyse the categorical data and for testing the association between the variables. A P < 0.05 was considered as significant and P < 0.01 or 0.001 was considered as highly significant. The package IBM SPSS Statistics Data Editor 20.0 (SPSS Inc., Chicago, IL, USA) was used for statistical analysis.


  Results Top


The groups had no significant differences in terms of age [Table 1], gender, ejection fraction, number of diseased coronary vessels, regional wall motion abnormality. Risk factors like hypertension, diabetes mellitus and old history of myocardial infarction [Table 2] were comparable between the groups.

All the hemodynamic variables were comparable in both the groups at baseline.
Table 1: Age wise comparison of DEX and PLA

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Table 2: Comparison of DEX and PLA according to HTN
and IHD variables


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Heart rate values were statistically significantly lower in the DEX group at TC and highly statistically significantly lower at T1, T3 and T5 values.

Systolic blood pressure values were statistically significantly lower in the DEX group at T0 and highly statistically significantly lower at T1, T3 and T5.

Diastolic and mean blood pressure values and systolic pulmonary artery pressure values were highly statistically significantly lower in the DEX group at T1, T3 and T5.

Diastolic pulmonary artery pressures were statistically significantly lower in the DEX group at TC, T0 and T1 and highly statistically significantly lower at T3.

Mean pulmonary artery pressures were statistically significantly lower in the DEX group at T0 and highly statistically significantly lower at TC, T1 and T3.

SpO 2 was statistically significantly lower in the DEX group at TC [Table 3].
Table 3: Comparison of hemodynamic variables between dexmedetomidine & placebo

Click here to view


There was no case of hypotension or bradycardia or hypertension in our case series in either group.


  Discussion Top


Direct laryngoscopy and endotracheal intubation are the most stressful events during induction of anesthesia. They lead to a transient but marked stimulation of the sympathetic system leading to tachycardia and hypertension and arrhythmias. Such events can be catastrophic in cardiac surgery patients who are at risk of developing myocardial ischaemia during these events. α adrenergic agonists like clonidine and its newer congener DEX are capable of attenuating these unwanted harmful events during periods of direct laryngoscopy and intubation.

They also decrease the anesthetic requirements, increase hemodynamic stability and decrease circulating catecholamines upto 90%. [6],[7],[8] DEX has analgesic and sedative properties. [7] It produced similar levels of sedation and times to extubation, with less opioid requirements compared with propofol in postoperative patients. [9],[10] It is also associated with easy arousability and minimal respiratory depression. [11],[12] It has been used for adjunctive sedation in alcohol withdrawal, mechanical ventilation in Intensive Care Unit, awake carotid endarterectomy, for bariatric and cosmetic procedures [12] and lowering postoperative delirium after surgery. [13],[14],[15]

In our present study, we compared hemodynamic characteristics of DEX in attenuating the hemodynamic responses to direct laryngocopy and intubation.

Keniya et al. concluded that at DEX infusion of 1 μg/kg for 10 min followed by 0.2-0.4 μg/kg/h till skin closure, the need for thiopentone and isoflurane decreased by 30% and 32% respectively and fentanyl requirement was 100 ± 10 μg and 60 ± 10 μg in DEX group as compared to the isoflurane-opioid group. After tracheal intubation maximal increase in HR, systolic and diastolic blood pressure was 7%, 8% and 11% for DEX and 21%, 40% and 25% for isoflurane-opioid group. [16]

Menda et al. study concluded that de DEX (1 μg/kg) after etomidate (0.3 mg/kg) and fentanyl (5 μg/kg) induction can safely be used to attenuate the hemodynamic response to endotracheal intubation in patients undergoing myocardial revascularization receiving beta blockers with incidence of tacchycadia, hypotension and bradycardia not different between the two groups. This dose was similar to the dose used in our study. [2]

Sulaiman et al. concluded that DEX at a dose of 0.5 mcg/kg as 10-min infusion administered prior to induction of general anaesthesia attenuates the sympathoadrenal response to laryngoscopy and intubation in patients undergoing myocardial revascularisation and had a better control of HR and blood pressure. [3]

A study by Pandharipande et al. in septic and nonseptic patients also showed septic patients receiving DEX had 3.2 more delirium/coma-free days, 1.5 more delirium-free days and 6 more ventilator-free days. These results were more pronounced in septic than in nonseptic patients. Risk of dying at 28 days with sepsis was reduced by 70% in DEX with sepsis as compared to the lorazepam. [17] The most frequently observed side effects are hypotension, bradycardia and nausea. [18] Our results showed significant decrease in SpO 2 in DEX group at the TC. This is consistent with findings of Belleville et al. who showed that IV DEX caused marked sedation, mild hypercapnia and hypoventilation and an early transient increase in oxygen consumption in healthy young volunteers. [19]

Gu et al. showed that DEX is capable of attenuating remote lung injury induced by renal ischemia reperfusion injury via both α2 adrenoceptors dependent and independent mechanisms and exerts both antinflammatory and organoprotective effects. [20]

Yagmurdur et al. suggested that DEX may offer advantages by inhibiting lipid peroxidation in anticipated ischemia-reperfusion injury in upper-extremity surgery requiring tourniquet application. [21] But to study whether DEX protects against myocardial ischemia requires studies with large sample size. [7]

Leino et al. showed that IV DEX did not alter renal function in low risk coronary artery bypass grafting (CABG) cases although associated with increase in urinary output. [22]

Its role has also being evaluated for treatment of atrial and junctional tacchyarrhythmias during the perioperative period for congenital cardiac surgery in a dose of 1.1 ± 0.5 μg/kg and has a role for either HR control or conversion to normal sinus rhythm. [23]


  Conclusion Top


We conclude that DEX infusion at a dose of 1 μg/kg over a period of 10 min prior to induction of anesthesia is an effective method to attenuate the hemodynamic response to direct laryngoscopy and intubation in elective surgery for off pump CABG. It can be used safely before fentanyl based induction and in patients receiving β blockers.

The limitations of this study include, intraoperative and postoperative haemodynamic variables and sedation were not studied. The decrease in anesthetic dose requirements was not studied.

 
  References Top

1.Saraf R, Jha M, Sunil Kumar V, Damani K, Bokil S, Galante D. Dexmedetomidine, the ideal drug for attenuating the pressor response. Pediatr Anesth Crit Care J 2013;1:78-86.  Back to cited text no. 1
    
2.Menda F, Köner O, Sayin M, Türe H, Imer P, Aykaç B. Dexmedetomidine as an adjunct to anesthetic induction to attenuate hemodynamic response to endotracheal intubation in patients undergoing fast-track CABG. Ann Card Anaesth 2010;13:16-21.  Back to cited text no. 2
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5.Fassoulaki A, Melemeni A, Paraskeva A, Petropoulos G. Gabapentin attenuates the pressor response to direct laryngoscopy and tracheal intubation. Br J Anaesth 2006;96:769-73.  Back to cited text no. 5
    
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8.Basar H, Akpinar S, Doganci N, Buyukkocak U, Kaymak C, Sert O, et al. The effects of preanesthetic, single-dose dexmedetomidine on induction, hemodynamic, and cardiovascular parameters. J Clin Anesth 2008;20:431-6.  Back to cited text no. 8
    
9.Gerlach AT, Dasta JF. Dexmedetomidine: An updated review. Ann Pharmacother 2007;41:245-52.  Back to cited text no. 9
    
10.Herr DL, Sum-Ping ST, England M. ICU sedation after coronary artery bypass graft surgery: Dexmedetomidine-based versus propofol-based sedation regimens. J Cardiothorac Vasc Anesth 2003;17:576-84.  Back to cited text no. 10
    
11.Bagatini A, Gomes CR, Masella MZ, Rezer G. Dexmedetomidine: Pharmacology and clinical application.. Rev Bras Anestesiol 2002;52:606-17.  Back to cited text no. 11
    
12.Shapiro FE, Ramsay MA, Brudney CS, Sutton TS. Special report: Surgical and medical utility of dexmedetomidine-induced sedation, a case based examination. Anesthesiol News 2010;1-12.  Back to cited text no. 12
    
13.Ten Clay SC, Liu H. Drug and innovation update. The use of α-2 adrenergic agonist dexmedetomidine in cardiac surgery. SCA Bull 2010;9 (3).  Back to cited text no. 13
    
14.Maldonado JR, Wysong A, van der Starre PJ, Block T, Miller C, Reitz BA. Dexmedetomidine and the reduction of postoperative delirium after cardiac surgery. Psychosomatics 2009;50:206-17.  Back to cited text no. 14
    
15.Riker RR, Shehabi Y, Bokesch PM, Ceraso D, Wisemandle W, Koura F, et al. Dexmedetomidine vs midazolam for sedation of critically ill patients: A randomized trial. JAMA 2009;301:489-99.  Back to cited text no. 15
    
16.Keniya VM, Ladi S, Naphade R. Dexmedetomidine attenuates sympathoadrenal response to tracheal intubation and reduces perioperative anaesthetic requirement. Indian J Anaesth 2011;55:352-7.  Back to cited text no. 16
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17.Pandharipande PP, Sanders RD, Girard TD, McGrane S, Thompson JL, Shintani AK, et al. Effect of dexmedetomidine versus lorazepam on outcome in patients with sepsis: An a priori-designed analysis of the MENDS randomized controlled trial. Crit Care 2010;14:R38.  Back to cited text no. 17
    
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19.Bloor BC, Ward DS, Belleville JP, Maze M. Effects of intravenous dexmedetomidine in humans. II. Hemodynamic changes. Anesthesiology 1992;77:1134-42.  Back to cited text no. 19
    
20.Gu J, Chen J, Xia P, Tao G, Zhao H, Ma D. Dexmedetomidine attenuates remote lung injury induced by renal ischemia-reperfusion in mice. Acta Anaesthesiol Scand 2011;55:1272-8.  Back to cited text no. 20
    
21.Yagmurdur H, Ozcan N, Dokumaci F, Kilinc K, Yilmaz F, Basar H. Dexmedetomidine reduces the ischemia-reperfusion injury markers during upper extremity surgery with tourniquet. J Hand Surg Am 2008;33:941-7.  Back to cited text no. 21
    
22.Leino K, Hynynen M, Jalonen J, Salmenperä M, Scheinin H, Aantaa R, et al. Renal effects of dexmedetomidine during coronary artery bypass surgery: A randomized placebo-controlled study. BMC Anesthesiol 2011;11:9.  Back to cited text no. 22
    
23.Chrysostomou C, Beerman L, Shiderly D, Berry D, Morell V, Munoz R. Dexmedetomidine: A novel drug for the treatment of atrial and junctional tacchyarrhythmias during the perioperative period for congenital cardiac surgery. Anesth Analg November 2008;107:1515-22.  Back to cited text no. 23
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]


This article has been cited by
1 Comparison of the efficacy of two doses of dexmedetomidine in attenuating the hemodynamic response to intubation in patients undergoing elective cardiac surgery: A randomized double-blinded study
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Journal of Anaesthesiology Clinical Pharmacology. 2020; 36(1): 83
[Pubmed] | [DOI]



 

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