Year : 2012  |  Volume : 15  |  Issue : 1  |  Page : 39--43

The effects of dexmedetomidine on attenuation of stress response to endotracheal intubation in patients undergoing elective off-pump coronary artery bypass grafting

Sajith Sulaiman1, Ranjith Baskar Karthekeyan1, Mahesh Vakamudi2, Ayya Syama Sundar1, Harish Ravullapalli1, Ravikumar Gandham1,  
1 Department of Cardiac Anaesthesiology, Sri Ramachandra Medical College and Research Institute, Porur, Chennai, India
2 Department of Anaesthesiology and Critical Care, Sri Ramachandra Medical College and Research Institute, Porur, Chennai, India

Correspondence Address:
Ranjith Baskar Karthekeyan
Department of Cardiac Anaesthesiology, Sri Ramachandra Medical College and Research Institute, No 1, Ramachandra Nagar, Porur, Chennai 600116


This study was designed to study the efficacy of intravenous dexmedetomidine for attenuation of cardiovascular responses to laryngoscopy and endotracheal intubation in patients with coronary artery disease. Sixty adult patients scheduled for elective off-pump coronary artery bypass surgery were randomly allocated to receive dexmedetomidine (0.5 mcg/kg) or normal saline 15 min before intubation. Patients were compared for hemodynamic changes (heart rate, arterial blood pressure and pulmonary artery pressure) at baseline, 5 min after drug infusion, before intubation and 1, 3 and 5 min after intubation. The dexmedetomidine group had a better control of hemodynamics during laryngoscopy and endotracheal intubation. Dexmedetomidine at a dose of 0.5 mcg/kg as 10-min infusion was administered prior to induction of general anesthesia attenuates the sympathetic response to laryngoscopy and intubation in patients undergoing myocardial revascularization. The authors suggest its administration even in patients receiving beta blockers.

How to cite this article:
Sulaiman S, Karthekeyan RB, Vakamudi M, Sundar AS, Ravullapalli H, Gandham R. The effects of dexmedetomidine on attenuation of stress response to endotracheal intubation in patients undergoing elective off-pump coronary artery bypass grafting.Ann Card Anaesth 2012;15:39-43

How to cite this URL:
Sulaiman S, Karthekeyan RB, Vakamudi M, Sundar AS, Ravullapalli H, Gandham R. The effects of dexmedetomidine on attenuation of stress response to endotracheal intubation in patients undergoing elective off-pump coronary artery bypass grafting. Ann Card Anaesth [serial online] 2012 [cited 2020 Jul 7 ];15:39-43
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Direct laryngoscopy and endotracheal intubation following induction of anesthesia is associated with hemodynamic changes due to reflex sympathetic discharge caused by epipharyngeal and laryngopharyngeal stimulation. This increased sympatho-adrenal activity may result in hypertension, tachycardia and arrhythmias. [1],[2] This increase in blood pressure and heart rate are usually transient, variable and unpredictable. Transient hypertension and tachycardia are probably of no consequence in healthy individuals, but either or both may be hazardous to those with hypertension, [3] myocardial insufficiency [4] and cerebrovascular diseases. [5] At least in such individuals there is a necessity to blunt this response.

The magnitude of the response is greater with increasing force and duration of laryngoscopy. [6] The elevation in arterial pressure typically starts within five seconds of laryngoscopy, peaks in 1-2 min and returns to control levels within 5 min. Reid and Brace in 1940 were the first to report the circulatory responses to laryngeal and tracheal stimulation in an anesthetized man. [7] A variety of drugs have been used to control this hemodynamic response, such as vasodilators, beta blockers, calcium channel blockers, alfa 2 agonists and opioids. However, no modality was devoid of drawbacks and limitations. Dexmedetomidine is a highly selective alfa 2 adrenergic agonist that has sedative and analgesic effects. Dexmedetomidine has been shown to decrease induction doses of intravenous anesthetics and to decrease intraoperative opioid and volatile anesthetic requirements for maintenance of anesthesia. In addition, it has been shown to decrease perioperative catecholamine concentrations and promote perioperative hemodynamic and adrenergic stability. The present study was designed to investigate the effect of dexmedetomidine on hemodynamic responses to orotracheal intubation.


The objective of this study was to evaluate the effect of a single preoperative dose of dexmedetomidine at a dose of 0.5 mcg/kg as 10-min infusion on hemodynamic responses to laryngoscopy and endotracheal intubation. The incidence of hypotension and bradycardia was also assessed.

 Materials and Methods

This was a prospective, double-blind, parallel-group, randomized, placebo-controlled clinical trial of dexmedetomidine for attenuation of stress response to endotracheal intubation in 60 adult patients scheduled to undergo elective off-pump coronary artery bypass grafting. The study protocol was approved by the institutional ethical committee and written informed consent was obtained from all the patients. Exclusion criteria included anticipated difficult intubation, emergency surgery, left ventricular ejection fraction <40%, left ventricular aneurysm, associated valvular lesions, left main coronary artery disease, severe systemic diseases involving the renal and hepatic systems, preoperative left bundle branch block and intubation attempt lasting longer than 15 seconds.

The day before surgery, these patients were preanesthetically evaluated. Diuretics, angiotensin- converting enzyme inhibitors and calcium channel blockers were stopped the day before surgery as per institutional protocol. Beta blockers were continued. All patients received oral diazepam 10 mg and pantoprazole 40 mg the night before and on the morning of the surgery.

Patients were randomly allocated according to computer-generated randomization to receive either dexmedetomidine (dexmedetomidine group, n=30) or 0.9% saline (control group, n=30). Syringes containing aqueous solutions of either dexmedetomidine or saline were prepared in a double-blind fashion by a team member who was not involved in data recording. Peripheral, central venous and arterial cannulations were performed under local anesthesia. Electrocardiogram, pulse oximetry, intra-arterial blood pressure, pulmonary arterial pressures nasopharyngeal temperature, urine output and capnography were also monitored. After 5 min of stable cardiovascular variables, baseline hemodynamic variables were recorded.

Before induction of anesthesia, a single dose of dexmedetomidine 0.5 mg/kg was administered intravenously using a syringe pump over 10 min. The same amount of saline was administered to the patients in the control group. After 5 min of study drug infusion, the hemodynamic variables were recorded again. Infusion of nitroglycerin - 0.2 mg/kg/min was commenced in all the patients. Induction of general anesthesia was achieved with intravenous administration of 50 mcg/kg midazolam, 4 mcg/kg fentanyl and 0.2 to 0.3 mg/kg of etodmidate. Lack of response to verbal command was considered as the end point of induction. Vecuronium bromide 0.1 mg/kg was administered intravenoulsy to facilitate tracheal intubation. The trachea was intubated after 3 min of mask ventilation. All the intubations were performed by the same anesthesiologist. Hemodynamic variables were recorded again, immediately before intubation, at the 1 st , 3 rd and 5 th min after intubation. Times for hemodynamic measurement were defined as follows: TB=baseline, prior to the start of infusion of dexmedetomidin or placebo; TA=after 5 min of study drug infusion; T0=3 min after induction and prior to intubation; T1=1 min after intubation; T3=3 min after intubation; T5=5 min after intubation.

Statistical analysis

The sample size was determined by power analysis performed by a pilot study. A sample size of 18 patients per group was required to detect a 20% change in heart rate, blood pressure and pulmonary artery pressure between baseline and intubation time, with a power of 80% at the 5% significance level. Data are expressed as the mean±standard deviation. Independent t-test was used to compare the study group and the control group. Paired t-test was used to compare the variable before and after the intervention. Chi-square test was used to analyze the categorical data and for testing the association between the variables. Nonparametric tests (Wilcoxon signed rank tests [two-tailed]) were used whenever the mean value was less than two times the standard deviation. A P value of less than 0.05 was considered statistically significant. The package SPSS 17.0 (SPSS Inc., Chicago, IL, USA) was used for statistical analysis.


The groups were well-matched for their demographic data, regional wall motion abnormality and number of coronary vessels involved. No patient was excluded from the study. Ejection fraction was significantly higher in the dexmedetomidine group [Table 1]. The presence of risk factors and preoperative cardiovascular medications were comparable between the groups [Table 2]. Except heart rate, all other baseline hemodynamic variables were similar in both groups [Table 3]. Heart rate values were statistically significantly lower in the dexmedetomidine group at all time intervals when compared with the control group. There was a statistical significance in the systolic arterial pressure, mean arterial pressure and diastolic arterial pressure between groups after drug at the 1 st , 3 rd and 5 th min post intubation. The dexmedetomidine group had a better control of heart rate and blood pressure than the control group [Table 3].{Table 1}{Table 2}{Table 3}

No statistical significance was noted in systolic pulmonary artery pressure between groups at baseline, before intubation and 3 rd and 5 th min after intubation. There was a statistical significance noted in systolic pulmonary artery pressure after drug administration and 1 min after intubation. At any time period of measurement, the mean pulmonary artery pressure was similar in both groups. Except at 5 min post intubation, diastolic pulmonary artery pressures were similar between the two groups. Overall, the dexmedetomidine group was better controlled than the control group [Table 4]. There were no incidences of hypotension (systolic blood pressure ≤25% of baseline), arrhythmias or other Electrocardiography (ST depression ≥1 mm below the baseline) observed during the study period in any group.{Table 4}


Laryngoscopy and endotracheal intubation are considered as the most critical events during general anesthesia. They provoke a transient, but marked, sympathetic and sympathoadrenal response. In patients undergoing coronary artery bypass (CABG) surgery, tachycardia and hypertension increase the risk of perioperative myocardial ischemia and infarction. Alfa 2 -adrenergic drugs, such as clonidine or dexmedetomidine, attenuate these potentially harmful cardiovascular reactions during induction of anesthesia. In our study, we compared dexmedetomidine, a newer alfa 2 -agonist, with additional properties such as sedation, anxiolysis and sympatholysis for attenuating the hemodynamic response to laryngoscopy and tracheal intubation.

Dexmedetomidine offers a unique pharmacological profile with sedation, sympatholysis, analgesia, cardiovascular stability and with great advantage to avoid respiratory depression. In particular, dexmedetomidine can provide a dose-dependent cooperative sedation that allows ready interaction with the patient. All these above-said aspects of its pharmacological profile render it suitable as an anesthetic adjuvant and also as intensive care unit sedation.

Dexmedetomidine increases the hemodynamic stability by altering the stress-induced sympathoadrenal responses to intubation during surgery and during emergence from anesthesia. [8] Jaakola et al., [9] in their study concluded that dexmedetomidine attenuates the increase in heart rate and blood pressure during intubation. The dose used for this study was 0.6 mcg/kg, which is almost similar to the dose used by us.

Scheinin et al., [8] studied the effect of dexmedetomidine on tracheal intubation, required dose of induction agent and preoperative analgesic requirements. They concluded that the required dose of thiopentone was significantly lower in the dexmedetomidine group and the drug attenuated the hemodynamic responses to intubation. The concentration of noradrenaline in mixed venous plasma was lesser in the dexmedetomidine group.

Lawrence et al., [10] found that a single dose of 2 mcg/kg of dexmedetomidine before induction of anesthesia attenuated the hemodynamic response to intubation as well as that to extubation. Bradycardia was observed at the 1 st and 5 th min after administration. This might have been due to bolus administration. The dose of dexmedetomidine in our study was 0.5 mcg/kg as an infusion over 10 min. Hemodynamic response was better in the dexmedetomidine group and bradycardia was not observed during our study.

It is a well-known fact that depression of sympathetic response against laryngoscopy and intubation is an important advantage, especially in high-risk patients. Nevertheless, the mean intubation induced pressor response was modest in our control group, which suggests that a relatively low intensity of stress is associated with the present anesthetic technique.

The hypotension and bradycardia caused by dexmedetomidine, theoretically, could limit its usage in previously beta-blocked ischemia heart patients. Few studies used dexmedetomidine as an anesthetic adjuvant in CABG patients receiving beta blockers, and reported that the intraoperative incidence of bradycardia requiring treatment was not more common in the dexmedetomidine group than in the control group. [11],[12] This finding supports and correlates to our study.

A biphasic cardiovascular response has been described after the administration of dexmedetomidine. [13] A bolus of 1 mcg/kg results in a transient increase in arterial blood pressure and reflex decrease in heart rate in young healthy patients. Initial response is due to alfa 2 receptor stimulation of vascular smooth muscle. This response can be markedly decreased by slow infusion over 10 min. In our study, this effect was not noticed due to the slow infusion of the drug over 10 min.

Studies suggest that perioperative use of dexmedetomidine may result in a decreased risk of adverse cardiac events, including myocardial ischemia. [14] Alfa-adrenoreceptors stimulation can beneficially modulate coronary blood flow during myocardial ischemia by preventing transmural redistribution of blood flow away from the ischemic endocardium, by specific epicardial vasoconstrictive effects, leading to improvement in endocardial perfusion (the reverse steal effect) and by decreasing heart rate. This property along with hemodynamic stability and attenuation of intubation response makes dexmedetomidine an ideal anesthetic adjuvant, particularly for patients undergoing coronary bypass grafting.

There are three important limitations regarding this study. First, we did not measure the plasma norepinephrine levels. Secondly, extubation response, postoperative sedation and hemodynamic variations were not studied. Finally, the ejection fraction of the dexmedetomidine group was better than that of the placebo group.


It is concluded that pretreatment with dexmedetomidine at a dose of 0.5 mcg/kg as 10-min infusion prior to induction of anesthesia is a safe and effective method to attenuate the hemodynamic response to laryngoscopy and intubation. Dexmedetomidine can be considered before induction of general anesthesia in patients undergoing myocardial revascularization, even if the patients are receiving beta blockers.


1Robert K. Stoelting MD. Blood pressure and heart rate changes during short-duration laryngoscopy for tracheal intubation. Influence of viscous or intravenous lidocaine. Anaesth Analg 1978;57:197-9.
2Prys-Roberts, Greene LT, Meloche R, Foex P. Studies of anaesthesia in relation to hypertension-II. Hemodynamic consequences of induction and endotracheal intubation. Br J Anaesth 1971;43:531-47.
3Fox EJ, Sklar GS, Hill CH, Villanueva R, King BD. Complication related to the pressor response to endotracheal intubation. Anaesthesiology 1977;47:524-5.
4Dalton B, Guiney T. Myocardial ischemia from tachycardia and hypertension in coronary heart disease - Patient's undergoing anaesthesia. Ann. Mtg. Boston: American Society of Anesthesiologists; 1972. p. 201-2.
5Donegan MF, Bedford RF. Intravenously administered lignocaine prevents intracranial hypertension during endotracheal suctioning. Anaesthesiology 1980;52:516-8.
6Rose DK, Cohen MM. The airway: Problems and predictions in 18500 patients. Can J Anaesth 1991;41:372-83.
7Reid LC, Brace DE. Irritation of the respiratory tract and its reflex effect upon heart. Surg Gynaec Obst 1940;70:157-62.
8Scheinin B, Lindgren L, Randell T, Scheinin H, Scheinin M. Dexmedetomidine attenuates sympatoadrenal responses to tracheal intubation and reduces the need for thiopentone and peroperative fentanyl. Br J Anaesth 1992;68:126-31.
9Jaakola ML, Ali-Melkkilä T, Kanto J, Kallio A, Scheinin H, Scheinin M. Dexmedetomidine reduces intraocular pressure, intubation responses, and anaesthetic requirements in patients undergoing ophthalmic surgery. Br J Anaesth 1992;68:570-5.
10Lawrence CJ, De Lange S. Effects of a single pre-operative dexmedetomidine dose on isoflurane requirements and peri-operative hemodynamics stability. Anaesthesia 1997;52:736-44.
11Menda F, Köner O, Sayin M, Türe H, Imer P, Aykaç B. Dexmedetomidine as an adjuvant to anesthetic induction to attenuate hemodynamic response to endotracheal intubation in patients undergoing fast tract CABG. Ann Card Anaesth 2010;13:16-21.
12Jalonen J, Hynynen M, Kuitunen A, Heikkilä H, Perttilä J, Salmenperä M, et al. Dexmedetomidine as an anesthetic adjuvant in coronary artery bypass grafting. Anesthesiology 1997;86:331-45.
13Bloor BC, Ward DS, Belleville JP, Maze M. Effects of intravenous dexmedetomidine in humans. II. Hemodynamic changes. Anaesthesiology 1992:77;1134-42.
14Talke P, Li J, Jain U, Leung J, Drasner K, Hollenberg M, et al. Effects of perioperative dexmedetomidine infusion in patients undergoing vascular surgery. The Study of Perioperative Ischemia Research Group. Anaesthesiology 1995;82:620-33.