dexmedetomidine as an adjunct to anesthetic induction to attenuate hemodynamic response to endotracheal intubation in patients undergoing fast track cabg

Original Article Dexmedetomidine as an adjunct to anesthetic induction to attenuate hemodynamic response to endotracheal intubation in patients undergoing fast-track CABG Ferdi Menda, Ưzge Kưner, Murat Sayın, Hatice Türe, Pınar mer, Bora Aykaỗ Department of Anesthesiology, Yeditepe University, Kozyata, stanbul, Turkiye ABSTRACT Received: 23-02-09 Accepted: 13-08-09 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 Key words: Cardiac anesthesia, dexmedetomidine, fast track DOI: 10.4103/0971-9784.58829 INTRODUCTION Hypertension, arrhythmias and myocardial ischemia induced by endotracheal intubation are the results of a reflex increase in sympathetic and sympathoadrenal activity [1] Opioids, local anesthetics, adrenergic blocking agents and vasodilating agents have been used to attenuate this [1-9] High-dose opioid is preferred to attenuate this response in cardiac surgery patients [10] However, fast- track anesthesia with low-dose fentanyl has gained popularity in recent years.[11,12] 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[13,14] 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.[15,16] It also reduces the need for anesthetics[15,17,18] and, therefore, can be used as an adjunct to general Address for correspondence: Dr Ưzge Kưner, Yeditepe Universitesi Hastanesi, Devlet yolu Ankara cad 102/104, 34752 Kozyatağı,’ İstanbul, Turkiye E-mail: ozgekoner@superonline.com 16 Annals of Cardiac Anaesthesia    Vol 13:1      Jan-Apr-2010 Menda, et al.: Dexmedetomidine use in fast-track CABG patients anesthetics Dexmedetomidine, a more specific and selective α-2 adrenergic agonist than clonidine has a shorter duration of action than clonidine[19,20] and because of its sedative and analgesic properties it also can be used as an adjunct to general anesthetics.[10,21] 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).[10] 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 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/m2, left main coronary artery occlusion more than 50%, valvular dysfunction, preoperative medication with clonidine or alphametyldopa, 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, n1=15) and dexmedetomidine (DEX, n2=15) by closed envelope method Pre-medication consisted of midazolam 0.07 mg/kg given intraAnnals of Cardiac Anaesthesia    Vol 13:1      Jan-Apr-2010 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 (SAPt0), diastolic arterial pressure (DAP t0), mean arterial pressure (MAP t0) and baseline heart rate values (HR t0) 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 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 minutes, SAP t1, DAP t1, MAP t1 and heart rate (HR t ) 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 t1 hemodynamic recordings After the loss of eyelid reflex, rocuronium mg/ kg was administered intravenously to facilitate endotracheal intubation Two minutes after administering the induction agents SAP t2, DAP t2, MAP t2 and HR t2 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(t3), (t4) and (t5) minutes after the endotracheal intubation Table 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 17 Menda, et al.: Dexmedetomidine use in fast-track CABG patients Table 1: Hemodynamic criteria and stepwise treatment of deviations throughout the operation Deviation/Threshold Treatment Hypertension SAP≥20% above BL or SAP>160 mmHg Fentanyl (5 µg/kg) - interval before next step - GTN 50 mcg/min allowed meanwhile Repeat step (3 interval) Repeat step (3 interval) Rate (↑) of propofol by mg/kg/h every one minute (after the study period) Hypotension Either SAP≤30% below BL and 90 bpm effect Bradycardia HR0.05) Figures 1-4 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 t2, 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% 3.816.3) Inter-group comparisons are shown in Figures 1-4 In DEX group, MAP was significantly lower compared to baseline values at all the measurement times, whereas in the placebo group only MAP t2 and t5 were significantly lower than the baseline value The decrease of MAP from baseline to t2 and to t5 was not different between the groups RESULTS 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 minutes after intubation From baseline to t2 and to t5 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 The groups were similar with respect to age, weight, In DEX group DAP was significantly lower compared to 18 Annals of Cardiac Anaesthesia    Vol 13:1      Jan-Apr-2010 Menda, et al.: Dexmedetomidine use in fast-track CABG patients Figure 1: Changes in the heart rate observed in the two groups during the study period *P