Year : 2010 | Volume
: 13 | Issue : 1 | Page : 16--21
Dexmedetomidine as an adjunct to anesthetic induction to attenuate hemodynamic response to endotracheal intubation in patients undergoing fast-track CABG
Ferdi Menda, Ozge Koner, Murat Sayin, Hatice Ture, Pinar Imer, Bora Aykac
Department of Anesthesiology, Yeditepe University, Kozyatagi, Istanbul, Turkiye, Turkey
Yeditepe Universitesi Hastanesi, Devlet yolu Ankara cad. 102/104, 34752 Kozyatagi,«SQ» Istanbul, Turkiye
During induction of general anesthesia hypertension and tachycardia caused by tracheal intubation may lead to cardiac ischemia and arrhythmias. In this prospective, randomized study, dexmedetomidine has been used to attenuate the hemodynamic response to endotracheal intubation with low dose fentanyl and etomidate in patients undergoing myocardial revascularization receiving beta blocker treatment. Thirty patients undergoing myocardial revascularization received in a double blind manner, either a saline placebo or a dexmedetomidine infusion (1 µg/kg) before the anesthesia induction. Heart rate (HR) and blood pressure (BP) were monitored at baseline, after placebo or dexmedetomidine infusion, after induction of general anesthesia, one, three and five minutes after endotracheal intubation. In the dexmedetomidine (DEX) group systolic (SAP), diastolic (DAP) and mean arterial pressures (MAP) were lower at all times in comparison to baseline values; in the placebo (PLA) group SAP, DAP and MAP decreased after the induction of general anesthesia and five minutes after the intubation compared to baseline values. This decrease was not significantly different between the groups. After the induction of general anesthesia, the drop in HR was higher in DEX group compared to PLA group. One minute after endotracheal intubation, HR significantly increased in PLA group while, it decreased in the DEX group. The incidence of tachycardia, hypotension and bradycardia was not different between the groups. The incidence of hypertension requiring treatment was significantly greater in the PLA group. It is concluded that dexmedetomidine can safely be used to attenuate the hemodynamic response to endotracheal intubation in patients undergoing myocardial revascularization receiving beta blockers.
|How to cite this article:|
Menda F, Koner O, Sayin M, Ture H, Imer P, Aykac 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
|How to cite this URL:|
Menda F, Koner O, Sayin M, Ture H, Imer P, Aykac B. Dexmedetomidine as an adjunct to anesthetic induction to attenuate hemodynamic response to endotracheal intubation in patients undergoing fast-track CABG. Ann Card Anaesth [serial online] 2010 [cited 2020 Jul 13 ];13:16-21
Available from: http://www.annals.in/text.asp?2010/13/1/16/58829
Hypertension, arrhythmias and myocardial ischemia induced by endotracheal intubation are the results of a reflex increase in sympathetic and sympathoadrenal activity.  Opioids, local anesthetics, adrenergic blocking agents and vasodilating agents have been used to attenuate this. ,,,,,,,, High-dose opioid is preferred to attenuate this response in cardiac surgery patients.  However, fast- track anesthesia with low-dose fentanyl has gained popularity in recent years. , This technique limits the use of excessive fentanyl doses during anesthesia induction and to block the hemodynamic effects of intubation, an adjunct may often be necessary.
α-2 adrenergic agonists decrease sympathetic tone , and pre-operative use of clonidine, an α-2 adrenergic agonist has been shown to blunt the hemodynamic responses to noxious stimulation and to prevent the overall hemodynamic variability. , It also reduces the need for anesthetics ,, and, therefore, can be used as an adjunct to general anesthetics. Dexmedetomidine, a more specific and selective α-2 adrenergic agonist than clonidine has a shorter duration of action than clonidine , and because of its sedative and analgesic properties it also can be used as an adjunct to general anesthetics. ,
There is a study relating to the effects of dexmedetomidine on hemodynamic response to endotracheal intubation in patients undergoing coronary artery bypass graft (CABG), however, in this study dexmedetomidine has been used with high dose fentanyl (30 µg/kg).  which may interfere with the fast track protocol routinely used in our center.
This prospective, randomized, double blinded study was planned to investigate the hemodynamic effects of intravenous dexmedetomidine used as anesthetic adjunct during induction of anesthesia. We hypothesized that, in combination with fentanyl 5 µg/kg, intravenous dexmedetomidine infusion administered prior to endotracheal intubation may attenuate the hemodynamic response to intubation without causing hemodynamic compromise.
Materials and Methods
After obtaining Ethics Committee approval, 30 patients undergoing CABG were enrolled in this study. The exclusion criteria were - ejection fraction less than 40%, age more than 60 years and body mass index (BMI) more than 30 kg/m 2 , left main coronary artery occlusion more than 50%, valvular dysfunction, preoperative medication with clonidine or alphametyl-dopa, history suggestive of sensitivity to drugs used during the study, preoperative left bundle branch block, and severe systemic disorders (e.g. insulin-dependent diabetes mellitus, kidney or liver insufficiency, severe respiratory disorder). Intubation attempt lasting longer than 20 seconds was also considered as exclusion criteria. All patients were receiving oral metoprolol (50 mg/day, if less than or equal to 70 kg, 100 mg/day, if more than 70 kg) before the surgery for at least one week. All patients received their cardiac medications two hours before surgery.
The study was designed in a placebo controlled, double blinded, randomized, prospective fashion. The patients were randomly seperated into two groups: placebo (PLA, n 1 =15) and dexmedetomidine (DEX, n 2 =15) by closed envelope method. Pre-medication consisted of midazolam 0.07 mg/kg given intra-muscularly 30 minutes before the surgery. Before arriving, at the operating room, a 16- gauge peripheral venous cannula was inserted into the right antecubital vein and according to study protocol all patients were prehydrated with 500 ml Lactated Ringer's solution. In the operation room, monitoring of 12 leadelectrocardiogram (ECG) , invasive blood pressure obtained via the right radial artery catheter, urinary output, pulse oxymetry, neuromuscular block level via train of four (TOF) Watch (Organon TOF-Watch® SX, Ireland) was initiated. All cannulations were performed under local anesthesia. In all patients, baseline systolic arterial pressure (SAPt 0 ), diastolic arterial pressure (DAP t 0 ), mean arterial pressure (MAP t 0 ) and baseline heart rate values (HR t 0 ) were recorded after a three minute resting period following the insertion of the radial artery catheter. The drug infusion (dexmedetomidine or saline placebo similar in appearance) was then commenced in a double blinded fashion. DEX group received a total dose of 1 µg/kg dexmedetomidine diluted in 100 ml sodium chloride (NaCl) solution in 15 minutes and the patients in PLA group received 100 ml NaCl solution in 15 minutes. After a stabilization period of 5 minutes, SAP t 1 , DAP t 1 , MAP t 1 and heart rate (HR t 1 ) were recorded. All the hemodynamic measurements were made by yet another anesthesiologist who was blinded to the groups.
A mixture of etomidate (0.3 mg/kg) and fentanyl (5 µg/ kg) was prepared for the induction of anesthesia. This mixture was infused via an infusion pump in three minutes immediately after t 1 hemodynamic recordings. After the loss of eyelid reflex, rocuronium 1 mg/ kg was administered intravenously to facilitate endotracheal intubation. Two minutes after administering the induction agents SAP t 2 , DAP t 2 , MAP t 2 and HR t 2 recordings were done and the trachea was intubated. Each intubation was performed by an anesthesiologist and accomplished within 20 seconds. Hemodynamic measurements were repeated after completion of administration of dexmedetomidine or placebo infusion and 1(t 3 ), 3 (t 4 ) and 5 (t 5 ) minutes after the endotracheal intubation. [Table 1] shows the definition criteria and stepwise treatment of hypotension, hypertension, bradycardia and tachycardia.
After the last recordings propofol 6-12 mg/kg/h and remifentanil 0.05-0.25 mcg/kg/min infusions were administered for maintenance of general anesthesia, troughout. Three minutes after the beginning of total intravenous anesthesia a 7-F central venous catheter was inserted into the right internal jugular vein. Nasogastric tubing, nasopharyngeal temperature monitoring and urinary catheterization were performed. Ringer's Lactate solution was infused at an approximate rate of 5 ml/kg/h. The total amount of intravenous fluids given administered was limited to 1000 ml prior to institution of cardiopulmonary bypass (CPB). Controlled mechanical ventilation was adjusted to maintain end-tidal carbon dioxide between 35-45 mmHg. During hypothermic (32 o C) CPB, propofol (2-3 mg/kg/h) and remifentanil (0.05-0.10 µg/kg/min) infusion was continued. At the end of the surgery patients were transferred to the surgical intensive care unit with propofol and remifentanil infusion running.
All data are presented as mean ± SD (standard deviation). Demographic data were analyzed by Student's t test. Analysis of variance for repeated measures (ANOVA) was used to analyze changes over time. When statistical significance was found, the difference between two different data for each variable was analyzed by Mann Whitney-U test. Inter-group comparisons for hemodynamic parameters were made with Mann Whitney-U test. To compare the incidence of hypertension, hypotension, bradycardia and tachycardia between the groups, Fisher's exact test was used, P ® and while a= 0.10, 1-â=0.80, d= 0.8 and allocation ratio n 1 /n 2 =1 the effective sample size was 30 for comparison of independent means.
The groups were similar with respect to age, weight, gender [Table 2]. Post-operative mechanical ventilation time and intensive care unit stay were identical among the groups. Postoperative mechanical ventilation time was 240.7 ± 37.9 min in PLA group and 244.7 ± 41.5 min in DEX group ( P > 0.05). Intensive care unit (ICU) stay was 1.3 ± 0.5 days in PLA group and 1.3 ± 0.4 days in DEX group ( P > 0.05).
[Figure 1],[Figure 2],[Figure 3],[Figure 4] show HR, MAP, SAP and DAP values of the two groups during the study. In the DEX group (HR) was significantly lower than the baseline in all measurement times. In the placebo group all the HR values, except for t 2 , were higher than the baseline value. In the placebo group, HR increased significantly after the intubation compared to baseline (P = 0.03, mean difference of 6.8, CI 95% (0.6-13)) (but not compared to the baseline), whereas it decreased in the DEX group at the same time interval (P = 0.004, mean difference of 10.0, CI 95% 3.8-16.3). Inter-group comparisons are shown in [Figure 1],[Figure 2],[Figure 3],[Figure 4].
In DEX group, MAP was significantly lower compared to baseline values at all the measurement times, whereas in the placebo group only MAP t 2 and t 5 were significantly lower than the baseline value. The decrease of MAP from baseline to t 2 and to t 5 was not different between the groups.
In DEX group SAP was significantly lower throughout the study in comparison to the baseline values, whereas in the PLA group SAP significantly decreased compared to baseline only after induction of anesthesia and 5 minutes after intubation. From baseline to t 2 and to t 5 the SAP decrease was similar in both groups (P > 0.05). In the PLA group SAP increased significantly after the intubation compared to post-induction period (P = 0.008, mean difference of 24.6, CI 95% (7.4-41.9), whereas it did not change significantly in DEX group after the intubation.
In DEX group DAP was significantly lower compared to baseline values at all the measurement times, while in the PLA group only DAP t2 and DAP t5 were significantly lower than the baseline value. The decrease of DAP t2 and DAP t5 from the baseline values (ÄDAP t 0 -t 2 and ÄDAP t 0 -t 5 ) was not different between the two groups. There was a significant increase in DAP in the placebo group after endotracheal intubation (P=0.03, mean difference of 17, CI 95% (7- 26.9); whereas it did not change after the intubation in the DEX group.
The incidence of hypertension, hypotension, bradycardia and tachycardia in two groups are shown in [Table 3]. The incidence of tachycardia, hypotension and bradycardia was not different among the two groups. The incidence of hypertension was significantly higher in PLA group (P=0.036). In all patients hypotension was treated with 500 mL crystalloid fluid replacement and none of them required ephedrine boluses during the induction period. Fluctuation of the invasive arterial blood pressure waveform guided the fluid therapy.
The decrease in the BP and stabilization in the placebo group after induction may be related to preoperative beta blocker therapy. The heart rate, however, increased following intubation in both groups, but there was no difference in the number of patients having tachycardia in the two groups (two vs five patients). In the study group, there was a significant decrease in HR and BP at all stages. However, this change was acceptable and desirable as no bradycardia was observed in any of the patients and hypotension occurred in three patients.
Myocardial ischemia might occur during the induction - intubation sequence in patients with coronary artery disease. Intraoperative ischemia has been associated with a high rate of perioperative myocardial infarction. 
Opioids, adrenergic blocking agents, vasodilating agents and local anesthetics have been used to attenuate the hemodynamic effects of endotracheal intubation. In a study, Lidocaine and nitroglycerin were found to be ineffective in controlling the hemodynamic response to laryngoscopy and intubation. 
Dexmedetomidine has analgesic and sedative effects , in addition to blunting the hemodynamic response to endotracheal intubation as shown in our study. On the other hand, dexmedetomidine has also been shown to reduce the extent of myocardial ischemia during cardiac surgery.  The above-mentioned properties of dexmedetomidine may encourage anesthesiologists to use it in addition to low dose fentanyl and etomidate anesthetic induction to attenuate the hemodynamic response.
Jalonen et al,  used dexmedetomidine as an anesthetic adjunct in CABG patients. They used the high dose pure opioid tecnique (30 µg/kg iv fentanyl) during cardiac anesthesia induction. Since high dose opioid use during fast track cardiac anesthesia is abandoned. , , this study was planned with low dose fentanyl.
Dexmedetomidine can lead to bradycardia and hypotension. ,,,,, Erkola et al, have shown in their study that in patients undergoing abdominal hysterectomy pre-medicated with dexmedetomidine, bradycardia was more common than in those who were premedicated with midazolam. Alone  theoretically, excessive hypotension and bradycardia induced by dexmedetomidine could limit its use in patients with ischemic heart disease in patients receiving beta blocker therapymay be contra indicated. But, in our study, the incidence of hypotension was not any higher than that observed in placebo group patients, and none of the patients experienced bradycardia requiring treatment. Jalonen et al,  used dexmedetomidine as an anesthetic adjunct in CABG patients receiving beta blockade and reported that the intraoperative incidence of bradycardia requiring treatment was not more common in the dexmedetomidine group than in the placebo group. The authors suggested that, with the beta-receptors already blocked, additional sympathetic blockade with dexmedetomidine did not appear to decrease the heart rate further. The suggestion by Jalonen and coworkers appear relevant to our study as well.
This study investigated the hemodynamic effects of dexmedetomidine during induction and intubation period, further studies investigating the myocardial protecting properties of dexmedetomidine during this stage of anesthesia may be needed to provide information about that aspect of the drug.
We conclude that dexmedetomidine effectively blunts the hemodynamic response to endotracheal intubation in patients undergoing myocardial re-vascularization and can be safely used at induction of general anesthesiain combination with fentanyl, even among patients receiving beta blockers.
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