Asian Cardiovasc Thorac Ann 2005;13:302-306
© 2005 Asia Publishing EXchange Ltd
Comparison of Antihypertensives after Coronary Artery Surgery
Fevzi Toraman, MD,
Hasan Karabulut, MD1,
Onur Goksel, MD2,
Serdar Evrenkaya, MD1,
Sumer Tarcan, MD1,
Cem Alhan, MD1
Department of Cardiovascular Anesthesiology
1 Department of Cardiovascular Surgery Acibadem Hospital
2 Dr Siyami Ersek Thoracic & Cardiovascular Surgery Center Istanbul, Turkey
For reprint information contact: Onur Goksel. MD Tel: 90 532 795 9118 Fax: 90 216 348 0269 Email: onurgoksel{at}hotmail.com, 4. Gazeteciler Sitesi, C3 Blok, Da: 16,1. Levent, 80620 Istanbul, Turkey.
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ABSTRACT
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Hypertension following coronary artery bypass grafting is a common problem that may result in postoperative myocardial infraction or bleeding, Hemodynamic effects were compared in 45 hypertensive coronary bypass patients randomized to receive either diltiazem, nitroglycerin, or sodium nitroprusside. Diltiazem was administered as an intravenous bolus of 0.3 mg·kg–1 within 5 min, followed by infusion of 0.1–0.8 mg·kg–1·h–1 in group 1. Nitroglycerin was infused at a rate of 1–3 µg·kg·h–1 in group 2, and sodium nitroprusside was given at a rate of 1–3 µg·kg–1·min–1 in group 3. Hemodynamic measurements were carried out before infusion (T1) and at 30 min (T2), 2 h (T3), and 12 h (T4) after initiation of treatment in the intensive care unit. Mean arterial pressure decreased significantly in all groups. There were no differences among groups at T1 and T2. At T3, heart rate in group 2 was significantly higher than group 1. At T3 and T4, the double product was highest in group 3 (group 1 vs. 3, p < 0.001). These results suggest that the hemodynamic effects of the 3 drugs are similar within the first 30 min. However, after 30 min, diltiazem affords better myocardial performance and more effective control of hypertension.
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INTRODUCTION
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Between 50% and 70% of patients undergoing aortocoronary bypass grafting (CABG) have suffered from hypertension and used at least a single antihypertensive agent before their operation.1 Increased sympathetic activity in the early postoperative period, in addition to hypertensive history, may result in profound hypertensive periods in such patients.2 Various currently used pharmacological agents have been reported to increase the risks of postoperative hemorrhage as well as myocardial and cerebral infarctions.2–3 The homodynamic effects of the three most commonly used antihypertensive agents were investigated in this study: diltiazem, nitroglycerin, and sodium nitroprusside.
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PATIENTS AND METHODS
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Forty-five patients undergoing CABG between February 1997 and April 1998 were included in the study. The criteria for selection were systolic, diastolic, and mean arterial blood pressure (MAP) greater than 150, 90, and 110 mm Hg, respectively, for at least 15 min, with heart rate (HR) greater than 70 beats·min–1. Patients with a history of antihypertensive medication preoperatively, renal compromise (creatinine > 2 mg·dL–1), or any systemic disease (e.g., diabetes mellitus) were not included in the study group. Local Institutional Medical Ethics Committee approval and informed patient consent were obtained.
In the postoperative intensive care unit, electrocardiograms (leads II and V5) were recorded and systolic, diastolic, and mean arterial blood pressures were measured with indwelling arterial catheters; pulmonary artery pressure, pulmonary capillary wedge pressure, central venous pressure, and mixed venous oxygen saturation were determined with Swan-Ganz catheters; cardiac output, systemic vascular resistance (SVR) and pulmonary vascular resistance were assessed by the thermodilution method; rectal temperature, pulse oximetry, urine output, and arterial blood gas analyses were also noted. There were 38 males and 7 females aged 41–75 years.
The patients were randomized into three groups blinded to the investigator but not to the intensive care unit physician. Group 1 received diltiazem infusions at rates of 0.1 to 0.8 mg·kg–1·h–1 following a bolus of 0.3 mg·kg–1 within 5 min. Group 2 were given nitroglycerine infusions at rates of 1 to 3 µg·kg–1·min–1, and group 3 had sodium nitroprusside infusions at rates of 1 to 3 µg·kg–1·min–1. In all three groups, the doses were titrated according to MAP. It was intended to exclude patients receiving inotropic pharmacological support or intra-aortic balloon pump counterpulsation, those with MAP less than 70 mm Hg, or HR less than 60 or more than 130 beats·min–1; however, no patient had to be excluded from the study. Before utilization of an antihypertensive agent, hemodynamic measurements were performed in all patients at baseline (T1) and then at 30 min (T2), 2 h (T3), and 12 h (T4) after starting the infusion in the intensive care unit. The double product of heart rate and systolic pressure and the duration of intubation were recorded and compared for intra- and intergroup variations.
Intergroup findings were compared using analysis of variance; the repeated measures analysis of variance test was used for variability with time among the groups. A p value of less than 0.05 was considered significant.
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RESULTS
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Each of the three groups had significant differences in MAP recorded at baseline compared to the other time points (Table 1
). In group 1 only, HR showed a significant time-dependent decrease (Table 2). The mean double product, an indirect indicator of myocardial oxygen consumption, was reduced by 42% in the diltiazem group (Table 3). Mixed venous oxygen saturation and cardiac output did not vary significantly within each group (Table 4 and 5). Under basal conditions, there were no significant differences in recordings between the groups. At T2, mixed venous oxygen saturation varied significantly between group 1 and group 2. At T3, significant variations between groups were found in HR and double product (Table 6). No patient needed extra medication, other than volume replacement, as a result of antihypertensive medication. At T4, MAP, double product, and SVR were found to be different between the groups. These findings are summarized in Table 7. Intubation durations were 13.9 ± 3.2, 14.2 ± 3.1, 15.1 ± 3.9 hours for groups 1, 2, and 3 respectively, and were not found to differ significantly. Pulmonary arterial pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance, and cardiac output did not differ significantly within or between groups.
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DISCUSSION
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Use of intravenous diltiazem and its effects on hemodynamics have been reported in many studies.4–11 Joyal and colleagues4 observed that systolic, diastolic, and mean arterial blood pressure decreased significantly by 13%, 10%, 11%, respectively, following administration of diltiazem. These reductions in blood pressure correlated with initial blood pressure values, but they did not cause a significant increase in heart rate. In the same study, it was reported that diltiazem did not significantly change left ventricular end-diastolic pressure or the rate of pressure rise (dP/dt), but it caused a 16% decrease in SYR ( p < 0.001) and a 10% increase in stroke volume index ( p < 0.05). When the impact of intravenous diltiazem on the oxygen supply-demand ratio was analyzed, it was seen that coronary vascular flow did not change despite a 14% reduction in coronary vascular resistance ( p < 0.025). However, there was a 15% reduction in the double product ( p < 0.005).4 It was conducted that intravenous diltiazem caused a change in the oxygen supply-demand ratio in favor of supply by reducing demand as well as by decreasing systemic and coronary vascular resistance without increasing HR. In our study, diltiazem was found to reduce myocardial oxygen demand by reducing both HR (12%) and double product (29%).
There have been many studies on nitroglycerin and sodium nitroprusside in ischemia and their hemodynamic effects in hypertensive patients.12–19 Breisblatt and colleagues12 found in a comparative study of nitroglycerin and nitroprusside in acutely ischemic patients that these agents increased cardiac output by 28% and 35%, respectively, whereas there was a decrease in MAP of 10% and 13% for each drug. Ejection fraction increased by 0.13% with nitroglycerin and by 0.17% with nitroprusside. It was concluded that these agents had similar effects as the differences were not significant. Simon and colleagues13 showed that nitroglycerin mainly decreased systemic arterial compliance (p < 0.01) by increasing the diameter of the larger arteries and decreasing their compliance directly without changing diastolic arterial pressure, MAP, cardiac index, or total peripheral vascular resistance. The groups of Tobias14 and Flaherty15 both showed in their comparative studies on nitroglycerin and nitroprusside that these agents decreased blood pressure significantly and to a similar degree. Ruegg and colleagues16 compared isradipine, a calcium receptor antagonist, and nitroprusside in early postoperative hypertensive states. They found that MAP decreased by 24.3% with isradipine and 21.4% with nitroprusside ( p < 0.05), HR increased by 4.1% and 8.4% ( p < 0.01), double product decreased by 16.9% and 10.6% ( p < 0.001), cardiac output increased by 19.6% and 10.6% (p < 0.001), and peripheral vascular resistance decreased by 35.4% and 22% (p < 0.001). They concluded that isradipine was an effective and well-tolerated antihypertensive agent with better hemodynamic effects than nitroprusside.
In our study, HR was decreased by diltiazem in the early postoperative period after CABG, but it did not change with nitroglycerin or nitroprusside. This correlates with other studies. The MAP decreased by 22%, 17%, 18%, and double product decreased by 29%, 14%, and 13% in groups 1, 2, and 3, respectively; these decreases were slightly more pronounced in our study than in other reports where they were not significant. This may be due to the higher initial blood pressures in our patients. Our study indicates that all 3 agents have similar effects in the first 30 minutes, but in the later periods, diltiazem displays more effective blood pressure control; thus, it improves myocardial performance.
A significant limitation of this prospective study was the difficulty in randomization in terms of intention to treat. The investigator was blinded to the medication given, whereas blinding the clinician in the intensive care unit was not possible. Preventive measures such as medication for possible tachycardia caused by nitroglycerin or nitroprusside were not taken, nor were they needed. The limited number of patients fulfilling the inclusion criteria is arguably a weakness of this study. Nevertheless, we suggest that all three agents may be used for the treatment of hypertensive states in the early postoperative period after CABG operations, and that diltiazem should be preferred in those patients with accompanying tachycardia.
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REFERENCES
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ABSTRACT
INTRODUCTION
