Secondary Logo

Journal Logo

EACTA Original Article

The use of esmolol and magnesium to prevent haemodynamic responses to extubation after coronary artery grafting

Arar, C.*; Colak, A.*; Alagol, A.*; Uzer, S. S.*; Ege, T.; Turan, N.; Duran, E.; Pamukcu, Z.*

Author Information
European Journal of Anaesthesiology: October 2007 - Volume 24 - Issue 10 - p 826-831
doi: 10.1017/S0265021507000865



Patients are commonly extubated following open-heart surgery in the intensive care unit. Haemodynamic responses occur during laryngoscopy, intubation and extubation [1]. In patients having coronary artery bypass graft (CABG) surgery, tachycardia and hypertension may occur resulting in silent myocardial ischaemia [2,3]. Esmolol, is a short acting, highly cardioselective β-adrenergic receptor antagonist which is rapidly metabolized to inactive metabolites by plasma esterases [4,5].

Magnesium (Mg) has been used to inhibit haemodynamic response to intubation, as it has been shown to inhibit catecholamine release from adrenal medulla and adrenergic nerve endings in in vitro studies [6,7]. Mg administration is also recommended since it causes coronary artery vasodilatation in addition to catecholamine inhibition [8-11].

In this study, we aimed to compare the effects of esmolol and Mg on haemodynamic response in the pre-extubation period in the intensive care unit following CABG surgery.


Following written informed consent by the patients and Trakya University Medical Faculty Local Ethics Committee, 120 consecutive cases undergoing CABG surgery which would be extubated in the intensive care unit were included in this double blind study. Patients received their routine medications before the operation. For premedication, diazepam (Diazem tablet, Deva, Istanbul, Turkey) 5-10 mg was orally administered the night before the operation, and diazepam (Diazem tablet, Deva) 5-10 mg with morphine (Morphine HCL, Galen, Istanbul, Turkey) 5-10 mg was administered intramuscularly 1 h prior to operation. Anaesthesia induction was performed with fentanyl (Fentanyl Citrate, USP, Abbott, Istanbul, Turkey) 10 μg kg−1 and pancuronium bromide (Pavulon, Organon, Istanbul, Turkey) 0.1 mg kg−1 intravenous. Controlled ventilation was undertaken with an oxygen-air mixture in order to maintain end tidal carbon dioxide tension between 30-35 mmHg. For maintenance of anaesthesia, sevoflurane (Sevorane, Abbott, Istanbul, Turkey) 2-3% with fentanyl 5 μg kg−1 and pancuronium bromide were used. Coronary revascularization was performed in all cases under cardiopulmonary bypass. After the operation, the patients were transferred to the intensive care unit where they were attached to a ventilator providing intermittent positive pressure ventilation.

Those patients who had a preoperative ejection fraction <40%, a history of asthma, were receiving vasodilatator and inotropic support by infusion or were allergic to the drugs used were excluded from the study. All patients were on treatment with a β-blocker agent until 8 h prior to operation. In accordance with the routine procedure of the clinic, the patients who were awake, had spontaneous respiration, adequate muscular strength and a rectal temperature of 36.5-37°C were randomly divided into three groups once the decision to extubate had been made. The drugs were prepared by one anaesthesiologist and administered by another who did not know its identity. Group I received esmolol (Brevibloc; Baxter, Deerfield, IL, USA) 1 mg kg−1, group II (n = 40) received Mg 30 mg kg−1 and Group III (n = 40) received normal saline. Each drug was diluted to 20 mL and administered over 5 min. Extubation was performed at the end of the infusion. Nitroglycerin (Perlinganit, Melusin, Istanbul, Turkey) infusion was available and administered at the dose of 0.5-5 μg kg−1min−1 if there was a more than 20% increase in heart rate (HR), systolic arterial pressure (SAP), diastolic arterial pressure (DAP) or mean arterial pressure (MAP) until the haemodynamic status turned to that prior to medication before extubation. HR, SAP, DAP, Peripheral Oxygen Saturation (SPO2), Central Venous Pressure (CVP) and side effects were recorded before medication (t1), before extubation (t2), during extubation (t3) and 1 min after extubation (t4).

Descriptive statistics, one-sample Kolmogorov-Smirnov test for normal distribution and one-way analysis of variance for continuous variables were used for comparison between the groups, Bonferroni test and Dunnett T3 test were applied as appropriate. For the qualitative data, Pearson χ2 analysis was done. The Kolmogorov-Smirnov test was applied to the ones with an expected value <5. For the other data, a Kruskal-Wallis variance analysis was used for comparisons between groups, Mann-Whitney U-test was applied to the ones with significant differences for binary comparison. For within-group comparisons, paired t-test was used where there was repeated continuous data, and for others Wilcoxon signed ranks test was used.


There was no significant difference in patient characteristics, operation time or anaesthesia time between groups (Table 1). There was a significant difference in HR between t3 (P < 0.001) and t4 (P < 0.05). Further analysis showed that the HR was significantly lower in Group I compared to Groups II (P < 0.05) or III (P < 0.001) and also that HR values were significantly lower in Group II compared to Group III (P < 0.05) at time t3. HR was significantly lower in Group I than in Group III (P < 0.05) at time t4. In the within-group comparisons, no difference was seen in Group I. A significant increase was found at t3 (P < 0.001) and at t4 (P < 0.05) compared to t1 in Group II. There was also a significant increase at t3 (P < 0.001) and t4 (P < 0.001) compared to t1 in Group III (Table 2; Fig. 1).

Table 1
Table 1:
Patient characteristics, operation time and anaesthesia time.
Table 2
Table 2:
Haemodynamic data (mean ± SD).
Figure 1.
Figure 1.:
Heart rate. t1: before infusion; t2: before extubation; t3: at extubation; t4: 1 min after extubation.*P < 0.05,**P < 0.001 when compared with Group I and†P < 0.05 when compared with Group II.

SAP was significantly lower in Group I than in Group II (P < 0.001) or III (P < 0.001) at time t3. In the within-group evaluation, no difference was seen in Group I. A significant increase was found in Group II and Group III in t3 and t4 measurements compared to t1 measurements (P < 0.001) (Table 2; Fig. 2).

Figure 2.
Figure 2.:
Systolic arterial pressure. t1: before infusion; t2: before extubation; t3: at extubation; t4: 1 min after extubation.*P < 0.001 when compared with Group I.

With respect to DAP, a significant difference was detected at times t3 (P < 0.001) and t4 (P < 0.05). On further analysis, DAP was significantly higher in Group III than in Groups I (P < 0.001) and II (P < 0.001) at time t3 and also higher in Group III than in Groups I (P < 0.05) and II (P < 0.05) at time t4. In the within-group evaluations, no difference was detected in Group I. A significant increase was detected in t3 (P < 0.001) and t4 (P < 0.05) measurements compared to t1 in Group II; in t3 (<0.001) and t4 (P < 0.001) measurements compared to t1 measurements in Group III (Table 2; Fig. 3).

Figure 3.
Figure 3.:
Diastolic arterial pressure. t1: before infusion; t2: before extubation; t3: at extubation; t4: 1 min after extubation.*P < 0.05,**P < 0.001 when compared with Group III.

When the MAP values were compared a significant difference was seen at t3 (P < 0.001) and t4 (P < 0.05). On further analysis, MAP was significantly lower in Group I than in Groups II (P < 0.001) and III (P < 0.001) and lower in Group II (P < 0.05) than in Group III at time t3 It was also lower in Group I than in Group III (P < 0.05) at time t4. In the within-group evaluations, no difference was found in Group I. A significant increase was found in t3 and t4 measurements compared to t1 measurements in Group II and III (P < 0.001) (Table 2; Fig. 4).

Figure 4.
Figure 4.:
Mean arterial pressure. t1: before infusion; t2: before extubation; t3: at extubation; t4: 1 min after extubation.*P < 0.05,**P < 0.001 when compared with Group I and†P < 0.05 when compared with Group II.

CVP values were lower in Group I than in Group III at t4 (P < 0.05). In the within-group evaluation, a significant increase was seen at t3 (P < 0.001) compared to t1 in Group I (Table 2). SPO2 was significantly lower at t4 in Group III than in Groups I (P < 0.05) and II (P < 0.05) (Table 2).

Nitroglycerin was needed in two patients in Group I, 13 patients in Group II and 27 patients in Group III (P < 0.001). Further analysis showed that it was significantly lower in Group I than in Groups II (P < 0.05) and III (P < 0.001), and significantly lower in Group II than in Group III (P < 0.05). No difference was found between the groups in terms of side effects and no hypotension or bradycardia related to esmolol was seen.


In this study, we have shown that esmolol and Mg decreased haemodynamic responses during extubation and that this was more prominent in the esmolol group. Esmolol is a β-adrenergic receptor antagonist with a very short duration of action and high cardio-selectivity. The reasons for preferring esmolol in this study are that it prevents postoperative myocardial ischaemia [12,13] and its short action depending on infusion speed. It has also been used to decrease cardiovascular responses during extubation [14].

Esmolol has been used in different doses in several studies [14-16]. Dyson and colleagues [14] administered esmolol over 30 s in 1, 1.5 and 2 mg kg−1 doses for extubation in patients having non-cardiac surgery. They determined that although tachycardia was prevented with 1 mg kg−1 of esmolol, systolic hypertension could not be adequately prevented. With a dose of 1.5 mg kg−1 the increase in the HR and systolic pressure was prevented and with 2 mg kg−1 both HR and systolic pressure increased when compared to the values gained before extubation. Kurian and colleagues [15] infused esmolol 0.5 mg kg−1 dL−1 before extubation following CABG and showed that esmolol decreases the incidence of myocardial ischaemia. In a similar study, Wang and colleagues [16] administered esmolol in doses of 0.5, 1, 1.5 and 2 mg kg−1 in order to suppress the haemodynamic response to extubation following elective cardiac surgery and reported that administration of esmolol in a dose of 1.5 mg kg−1 prevented the cardiovascular response to extubation without any side effects. In our study, esmolol was administered in a dose of 1 mg kg−1 to see if that would decrease haemodynamic responses to extubation without unwanted side effects such as bradycardia and hypotension.

Mg inhibits catecholamine responses and causes dilatation in the coronary circulation [8-11]. In anaesthetized dogs, a dose-dependent decrease in HR and systolic and diastolic pressures was observed after infusion of Mg [17]. In human haemodynamic studies have shown a peripheral (predominantly arteriolar) vasodilator effect [18,19]. After the rapid infusion of a dose of 3 or 4 g of magnesium sulphate, a reduction of systolic arterial pressure occurred related to a decreased systemic vascular resistance. Positive inotropic and chronotropic effects compensated for the former by increasing the cardiac index, whereas pulmonary vascular resistance remained unchanged. In the study of Vigorito and colleagues [18] coronary vascular resistance decreased since coronary blood flow increased.

The stress of intubation and extubation is associated with catecholamine release. Mg reduces this release by an effect on the adrenal medulla and adrenergic nerve endings. In a comparative study, patients received thiopental and succinylcholine with or without Mg sulphate 60 mg kg-1 at anaesthesia induction. In the patients treated with Mg, a smaller increase in HR and systolic blood pressure was observed after intubation. Plasma concentrations of epinephrine and norepinephrine were markedly lower after intubation in the Mg-treated group [20].

In a prospective study concerning coronary patients, Puri and colleagues [21] compared haemodynamic changes during anaesthesia induction and intubation after infusion of Mg (50 mg kg−1) or lidocaine. The group treated with Mg showed a slight increase in mean arterial pressure and systemic vascular resistance and no decrease in cardiac output, as compared to the lidocaine group with equally good control of increased HR [21]. In another study, the group treated with Mg showed a smaller hypertensive response during induction compared to placebo group, whereas early-reflex tachycardia was not controlled by Mg (60 mg kg−1) [22]. Ashton and colleagues [23] found no increase in arterial pressure or HR but a moderate decrease in plasma catecholamine concentrations after intubation in a group treated with Mg (40 mg kg−1) alone before intubation. In all these studies, Mg administration before anaesthesia induction was associated with a good control of the adrenergic response during intubation.

In the previous studies, Mg was used in order to increase or prevent haemodynamic responses. The doses used in the previous studies were higher than 30 mg kg−1, the dose used in our study. The reason why we chose a lower dose was the fact that the haemodynamic response to extubation was considered to be less than the response to intubation. The low-dose Mg administration was found to decrease the haemodynamic responses better than the control group. A higher dose of Mg is recommended to inhibit haemodynamic responses.

In conclusion, we found haemodynamic responses to be decreased by the use of Mg and inhibited by the use of esmolol during extubation following CABG.


1. Hartley M, Vaughan RS. Problems associated with tracheal extubation. Br J Anaesth 1993; 71: 561-568.
2. Barham NJ, Boomers OW, Sherry KM, Locke TJ. Myocardial ischaemia during tracheal extubation in patients after cardiac surgery: an observational study. Br J Anaesth 1998; 80: 832-833.
3. Conti J, Smith D. Haemodynamic responses to extubation after cardiac surgery with and without continued sedation. Br J Anaesth 1998; 80: 834-836.
4. Zaroslinski J, Borgman RJ, O'Donnell JP et al. Ultra-short acting beta-blockers: a proposal for the treatment of the critically ill patient. Life Sci 1982; 31: 899-907.
5. Gorczynski RJ, Shaffer JE, Lee RJ. Pharmacology of ASL-8052, a novel beta-adrenergic receptor antagonist with an ultrashort duration of action. J Cardiovasc Pharmacol 1983; 5: 668-677.
6. Douglas WW, Rubin RP. The mechanism of catecholamine release from the adrenal medulla and the role of calcium in stimulus-secretion coupling. J Physiol 1963; 167: 288-310.
7. Gambling DR, Birmingham CL, Jenkins LC. Magnesium and the anaesthetist. Can J Anaesth 1988; 35: 644-654.
8. Kimura T, Yasue H, Sakaino N, Rokutanda M, Jougasaki M, Araki H. Effects of magnesium on the tone of isolated human coronary arteries. Comparison with diltiazem and nitroglycerin. Circulation 1989; 79: 1118-1124.
9. Miyagi H, Yasue H, Okumura K, Ogawa H, Goto K, Oshima S. Effect of magnesium on anginal attack induced by hyperventilation in patients with variant angina. Circulation 1989; 79: 597-602.
10. Dube L, Granry JC. The therapeutic use of magnesium in anesthesiology, intensive care and emergency medicine: a review. Can J Anaesth 2003; 50: 732-746.
11. Horner SM. Efficacy of intravenous magnesium in acute myocardial infarction in reducing arrhythmias and mortality. Meta-analysis of magnesium in acute myocardial infarction. Circulation 1992; 86: 774-779.
12. Warltier DC, Pagel PS, Kersten JR. Approaches to the prevention of perioperative myocardial ischemia. Anesthesiology 2000; 92: 253-259.
13. Poldermans D, Boersma E, Bax JJ et al. The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery. Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group. N Engl J Med 1999; 341: 1789-1794.
14. Dyson A, Isaac PA, Pennant JH, Giesecke AH, Lipton JM. Esmolol attenuates cardiovascular responses to extubation. Anesth Analg 1990; 71: 675-678.
15. Kurian SM, Evans R, Fernandes NO, Sherry KM. The effect of an infusion of esmolol on the incidence of myocardial ischaemia during tracheal extubation following coronary artery surgery. Anaesthesia 2001; 56: 1163-1168.
16. Wang YQ, Guo QL, Xie D. Effects of different doses of esmolol on cardiovascular responses to tracheal extubation. Hunan Yi Ke Da Xue Xue Bao 2003; 28: 259-262.
17. Akazawa S, Shimizu R, Nakaigawa Y, Ishii R, Ikeno S, Yamato R. Effects of magnesium sulphate on atrioventricular conduction times and surface electrocardiogram in dogs anaesthetized with sevoflurane. Br J Anaesth 1997; 78: 75-80.
18. Vigorito C, Giordano A, Ferraro P et al. Hemodynamic effects of magnesium sulfate on the normal human heart. Am J Cardiol 1991; 67: 1435-1437.
19. Delhumeau A, Granry JC, Cottineau C, Bukowski JG, Corbeau JJ, Moreau X. Comparison of vascular effects of magnesium sulfate and nicardipine during extracorporeal circulation. Ann Fr Anesth Reanim 1995; 14: 149-153.
20. James MF, Beer RE, Esser JD. Intravenous magnesium sulfate inhibits catecholamine release associated with tracheal intubation. Anesth Analg 1989; 68: 772-776.
21. Puri GD, Marudhachalam KS, Chari P, Suri RK. The effect of magnesium sulphate on hemodynamics and its efficacy in attenuating the response to endotracheal intubation in patients with coronary artery disease. Anesth Analg 1998; 87: 808-811.
22. Yap LC, Ho RT, Jawan B, Lee JH. Effects of magnesium sulfate pretreatment on succinylcholine-facilitated tracheal intubation. Acta Anaesthesiol Sin 1994; 32: 45-50.
23. Ashton WB, James MF, Janicki P, Uys PC. Attenuation of the pressor response to tracheal intubation by magnesium sulphate with and without alfentanil in hypertensive proteinuric patients undergoing caesarean section. Br J Anaesth 1991; 67: 741-747.


© 2007 European Society of Anaesthesiology