The Effect of Magnesium Sulphate on Hemodynamics and Its Efficacy in Attenuating the Response to Endotracheal Intubation in Patients with

Coronary Artery Disease

G. D. Puri, MD, PhD*, K. S. Marudhachalam, MD, DA, DNB*, Pramila Chari, MD, FAMS, MAMS, DA?, and R. K. Suri, MS, FAMst
Departments of *Anaesthesia and Intensive Medical Education & Research, Chandigarh, Care and tcardiothoracic India and Vascular Surgery, Postgraduate Institute of

Laryngoscopy and endotracheal intubation may produce adverse hemodynamic effects. Magnesium has direct vasodilating properties on coronary arteries and inhibits catecholamine release, thus attenuating the hemodynamic effects during endotracheal intubation. We studied 36 patients with coronary artery disease (CAD) scheduled for elective coronary artery bypass grafting to evaluate the hemodynamic effects of magnesium and its efficacy in attenuating the response to endotracheal intubation. Patients received either 0.1 mL/kg (50%) magnesium sulfate (50 mg/kg) (Group A, n = 19) or isotonic sodium chloride solution (Group B, n = 17) before the induction of anesthesia and 0.05 mL/kg of isotonic sodium chloride solution (Group A) or lidocaine 2% (1 mg/kg) (Group B) before intubation. The hemodynamic variables were recorded before induction, after the trial drug, after induction, and after endotracheal intubation. Automatic ST segment analysis was performed throughout the study period. Magnesium sulfate administration was associated with

increased cardiac index (P < O.Ol), a minimal increase in heart rate, and a significant decrease in mean arterial pressure (MAP) and systemic vascular resistance (SVR) (P < 0.001). None of the patients in the magnesium group had significant ST depression compared with three patients in the control group. The magnesium group patients had a significantly lesser increase in MAP (P < 0.05) and SVR (P < 0.01) compared with the control group patients who received lidocaine before endotracheal intubation. Thus, magnesium is an useful adjuvant to attenuate endotracheal intubation response in patients with CAD. Implications: Endotracheal intubation produces adverse hemodynamic effects, which may be more detrimental in patients with coronary artery disease than in healthy patients. The present study shows that magnesium administered before endotracheal intubation can attenuate this response better than lidocaine. (Anesth Analg 1998;87:808-11)

and endotracheal intubation are associated with an increase in heart rate (HR), systemic arterial pressure, pulmonary arterial pressure (PAP), and capillary wedge pressures.Many pharmacologic techniques using adrenoreceptor blockers, calcium channel blockers, opioids, and vasodilators have been used to attenuate these responses, which indicates the lack of an ideal drug for this purpose (l-3). Magnesium inhibits catecholamine release from the adrenergic nerve terminals and from the adrenal medulla in vitro and has been used to attenuate adverse
aryngoscopy

cardiovascular effects during laryngoscopy and intubation (4,5). Several authors have suggested that magnesium may exert a vasodilator effect on human coronary arteries (6,7) in addition to catecholamine suppression. The purpose of this study was to evaluate the effects of magnesium on hemodynamics during the induction of anesthesia and its efficacy in attenuating pressor response to laryngoscopy and endotracheal intubation in patients with coronary artery disease(CAD) undergoing coronary artery bypass grafting (CABG). Lidocaine 2% was used as the standard regimen for attenuating the intubation response in the control group.

Methods
Accepted for publication June 10, 1998. Address correspondence and reprint requests to G. D. Puri, Department of Anaesthesia and Intensive Care Unit, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India.

After obtaining hospital ethics committee clearance, we studied 36 patients with CAD scheduled for elective CABG. Informed, written consent was obtained, and patients were randomly assigned to receive either
01998 by the International Anesthesia Research Society 0003.2999/98/$5.00

808

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magnesium sulfate (Group A, M = 19) or placebo (Group B, n = 17). Persons allocating and preparing the drugs were not involved in administering the drug and observing the cardiovascular responses. Patients with an ejection fraction <40%, associated valvular lesions, left ventricular aneurysm, shock, unstable blood pressure (hyper-/hypotension), and poor left ventricular function, as well as those undergoing emergency surgery, were excluded from our study. Patients received their cardiovascular drugs on the morning of surgery. They received diazepam 0.2 mg PO the night before and the morning of surgery. They also received morphine 0.1 mg/kg and promethazine 0.5 mg/kg IM 45 min before going to the operating room. Peripheral, central venous, and arterial cannulations were performed under local anesthesia. Electrocardiogram, oximetry, intraarterial blood pressure, central venous pressure, and PAP were monitored. After 5 min of stable cardiovascular variables, cardiac output was measured using a thermodilution technique. Mean arterial pressure (MAP), PAP, capillary wedge pressures, and HR were recorded. Automated ST segment analysis was performed in all patients. An ST segment depression of >l mm at 60 ms after the J-point was considered significant. Group A patients received magnesium sulfate (50%) 0.1 mL/kg (50 mg/ kg), and Group B patients received 0.1 mL/kg isotonic sodium chloride solution IV over 1 min. The hemodynamic variables were recorded again, and anesthesia was induced with 0.15 mg/kg morphine, 3-5 m&kg thiopental, and 0.12 mg/kg pancuronium IV. Ventilation was assisted/controlled with O,/N,O (33%:66%) with halothane 0.5% using a Bains circuit with a fresh gas flow of approximately 110 mL * kg-l * mini. The trachea was intubated 3-4 min after pancuronium administration, and 0.05 mL/kg isotonic sodium chloride solution (Group A) or lidocaine 2% (1 g/kg) (Group B) was injected 1 min before endotracheal intubation. Hemodynamic variables were again recorded immediately before and after tracheal intubation, as well as 3 min after intubation. Systemic vascular resistance (SVR) and cardiac index (CI) were calculated. Untoward effects such as hypotension (systolic blood pressure ~25% of baseline), arrhythmias, and significant ST changes (~1 mm depression below baseline) were also recorded. If active intervention required to keep the patients systolic blood pressure >90 mm Hg, the drug card was opened and necessary treatment was given. The patient was then excluded from subsequent analysis. Statistical analysis for intraindividual variability was performed by using repeated-measurement analysis of variance followed by Students t-test for continuous quantitative data. 2 test was used for qualitative data.

Table

1. Demographic Data

Group A Variable
(n = 16) 51.2 k 6.4 61.8 t 7.5

Group B
(n = 14) 54.9 ? 5.5 62.0 ? 3.1

Age (yr)
Weight (kg) Height (cm) BSA (m)
Data BSA are mean -t SD. = body surface area

166.52 9.3 1.7 * 0.13

168.2? 4.7 1.7 ? 0.1

Results
The groups were well matched for their demographic data (Table 1) and preoperative cardiovascular medications (Table 2). The baseline HR, MAP, CI, and SVR were similar in both groups (Table 3). Three patients in the magnesium group and two patients in the control group required pharmacological management for hypotension. In addition, another patient in the control group had to be given an increasing concentration of halothane and nitroglycerin IV to decrease the blood pressure, which went up to 200 mm Hg systolic during the study period. These patients were excluded from analysis. HR tended to increase after magnesium administration, but not significantly. It decreased toward the baseline after the induction of anesthesia in the magnesium group, whereas it increased significantly in the control group (P < 0.001). HR further increased after endotracheal intubation in both the groups. It was significantly more rapid immediately after and 3 mm after endotracheal intubation from the baseline (P < 0.001). MAP decreased (P < 0.001) after magnesium administration alone compared with the control group (P < 0.05) at preinduction stage. It decreased after the induction of anesthesia,but the decreasewas significant (P < 0.01) only in the control group and there was no significant difference between the two groups immediately before intubation. MAP increased after intubation and was significantly higher in control group compared with the magnesium group immediately after and 3 min after intubation (P < 0.01). Compared with baseline, the postintubation MAP values were significantly higher only in the control group (P < 0.01). CI increased significantly (P < 0.01) after magnesium administration and was significantly higher (P < 0.05) compared with the control group at all subsequent stages of induction and endotracheal intubation. The CI decreased (P < 0.05) after induction in both groups. The CI was not significantly different from baseline after induction and intubation in the magnesium group, whereas it was low in the control group compared with baseline CI (P < 0.001). SVR showed a significant decrease (P < 0.001) after magnesium administration and increased toward baseline after endotracheal intubation, but SVR was significantly lower (P < 0.05) in Group A compared

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with Group B at all stages except baseline. The increase in SVR was significant after induction (P < 0.05) and immediately after endotracheal intubation (P < 0.001) in both the groups. The SVR in the magnesium group was significantly (P < 0.05) lower 3 min after intubation compared with the baseline value, whereas it was significantly higher (P < 0.05) than baseline in the control group. Automated ST segment trend analysis revealed significant ST depression in three patients of the control group compared with none in the magnesium group.

Discussion
The ability of magnesium ions to inhibit the release of catecholamines has been known for many years (4). More recent studies have shown that magnesium may exert a vasodilator effect on human coronary arteries (6-8). However, a systematic evaluation of its effect on cardiovascular hemodynamics has not been reported in patients with CAD.
Table 2. Preoperative Cardiovascular Medications Group A Group B

Medication P-adrenergicblockers Nitrates Calcium channelblockers Angiotensin-converting enzyme inhibitors

Table

(n = 16) (n = 14) 16 16 7
5

14 14 7
5

Magnesium should produce bradycardia by slowing the atria1 rate (9). However, in intact animals, the ability of magnesium to inhibit the release of acetylcholine from the vagus nerve predominates, resulting in a mild increase in HR (10). In our study, there was initial insignificant increase in HR rate and no further increase after endotracheal intubation in the magnesium group. This may be because magnesium decreases epinephrine levels, thus attenuating the endotracheal intubation response (11). Magnesium produces vasodilation by a direct action, as well indirectly by sympathetic blockade and inhibition of catecholamine release. Parenteral magnesium administration resulted in a rapid but transient decrease in SVR, whereas arterial pressures did not show any appreciable increase after endotracheal intubation in magnesium-treated patients, compared with those in the control group. The reduction in arterial pressure associated with a greater decrease in SVR is consistent with a predominant peripheral vasodilator action of magnesium. Clinical observations of cutaneous flushing and experimental data from animal studies are consistent with this vasodilator action (12). Some of our patients complained of warmth in the body after magnesium injection. After the magnesium infusion, there was a significant increase in cardiac output, and CI was maintained at a higher level than that of the control group during the induction of anesthesia and endotracheal intubation. The increase in cardiac output may be a consequence of the increase in HR, as well as reduced left ventricular afterload (13).

3. Hemodynamic ChangesDuring the Induction of Anesthesiaand Endotracheal Intubation

Basal
HR @pm) w C 65.2 2 12.7 64.3 + 7.5

After drug
70.5 + 15.6 64.2 -+ 8.8 76.2 1. 15.6$ * 91.5 2 7.8 * 3.2 ? 0.8t * 2.7 ? 0.5 1050.3 + 286.2$ t 1530.0 ? 263.6
index, SVR

After induction immediately before ET1

69.7 i- 13.7 67.9 -t 7.4$ 75.5 2 13.4$ t * $ * t 80.4 2 lO.Ot 2.7 ? 0.8 * 2.1 ? 0.4$ 1225.1 5 322.1* t 1754.9 ? 310.9t
vascular resistance,

Immediately after intubation

t t $ $ 74.5 2 11.1* 72.9 ? 8.8$ 92.2 -+ 16.5 * 109.7 t 19.6t 2.7 ? 0.8 * 2.1 ? 0.4$ 1534.5 454.4 t $ 2233.5 ? 388.7$
ET1 = endotracheal

3 min after ET1 74.5 -i- 10.3$ 73.6 k 7.7$ * * 86.6 i 14.5 * 104.8 2 16.0 2.8 2 0.7 * 2.3 2 0.4

MAP (mmHg) Mg
C

91.7 t 14.5
92.6 ? 8.7 2.8 ? 0.7 2.7 ? 0.5 1412.9 2 286.1 1525.4 ? 272.4
pressure,

CI (L/sq.m) M!s
C SVR (dyne-sec/cm5) w C

* 1349.7 ? 367.9* t t 1987.1 t 344.0*

intubation, Mg = magnesium

Values are mean + SD. HR = heart rate, MAP = mean arterial (Group A), C = control (Group 8). * P < 0.05. t P i 0.01. f P < 0.001.

CI = cardiac

= systemic

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The absence of significant ST segment changes during induction and endotracheal intubation in the study group may be the result of a decrease in afterload and coronary vasodilation produced by magnesium administration (13). The mechanism of magnesium-induced coronary and systemic dilation is probably related to the calcium antagonist effects of magnesium ions at the level of vascular smooth muscle cells (14), with considerable evidence of modulating coronary vascular tone both in isolated coronary strips (6,14) and in patients with angina (7). Some of the difference in cardiovascular responses to endotracheal intubation between the two groups may be due to the IV lidocaine injection in the control group. Lidocaine has been used to attenuate cardiovascular responses during endotracheal intubation with varied results (15,16). Magnesium was injected before induction so that we could evaluate the cardiovascular effects of this drug alone. The present study shows that magnesium is significantly better in attenuating the cardiovascular responses to induction and endotracheal intubation with favorable hemodynamits, compared with IV lidocaine. An enhancing effect of magnesium on neuromuscular block (17) was not seen in our study, as all patients ventilation was controlled postoperatively. However, we also did not monitor neuromuscular block routinely in all patients. Three patients who were receiving calcium channel blockers, P-adrenergic blockers, and angiotensin-converting enzyme (ACE) inhibitors, which probably potentiated the myocardial depressive effect of magnesium in addition to blocking the compensatory mechanism of hypotension, experienced hypotensive episodes. In conclusion, magnesium administration at the time of the induction of anesthesia improves hemodynamics in patients with CAD undergoing CABG and is associated with lesser hemodynamic and ST segment changes compared with lidocaine at the time of endotracheal intubation in these patients. When administering magnesium sulfate, however, one should be aware of the adverse hemodynamic interactions in patients with CAD receiving calcium channel blockers, P-adrenergic blockers and ACE inhibitors for antihypertensive therapy.

We acknowledge for his assistance

K. Thennarasu, PhD, in statistical analysis.

Department

of Biostatistics,

References
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