Hemodynamic effects of dopexamine in patients following coronary artery bypass surgery

Hemodynamic Effects of Dopexamine in Patients Following Coronary Artery Bypass Surgery J.I.T. Poelaert, MD, H.E. Mungroop, MD, J.J. Koolen, MD, and P.C.M. Van den Berg, MD Dopexamine is a new dopamine analogue, with combined agonist properties on dopamine receptors and the beta2-adrenoceptor. The aim of this study was to evaluate the short-term hemodynemic effects of dopexamine at different dosage rates in postoperative coronary artery bypass (CABG) patients, especially with respect to the right ventricle, using a right ventricular ejection fraction pulmonary artery catheter. With a dose of 2 # g / k g / m i n of dopexamine, significant increases in heart rate (25%), cardiac

index (33%), and right ventricular ejection fraction (20%) were observed. Pulmonary vascular resistance decreased with a dose over 1 # g / k g / m i n (15%). Mean arterial blood pressure and pulmonary artery pressures were not affected. A t 4 # g / k g / m i n , cardiac index was further increased. In conclusion, dopexamine could be beneficial to patients with a compromised right ventricle by lowering afterload and improving ventricular performance after CABG. © 1989 by W.B. Saunders Company.

OPEXAMINE hydrochloride (DX) is a

measured and derived parameters calculated: heart rate (HR), mean arterial blood pressure (MAP), right atrial pressure (RAP), pulmonary capillary wedge pressure (PCWP), cardiac index (CI), REF, stroke volume index (SVI), end-diastolic volume index (EDVI), end-systolic volume index (ESVI), PVR, and systemic vascular resistance (SVR). In nine patients, DX was administered by infusion over 10 minutes at a dose of 1 and 2 #g/kg/min. At the end of the 10-minute period, measurements were carried out. In another comparable group of seven patients, measurements were carried out at a dose of l, 2, and 4 ~tg/kg/min. Statistical analysis was carried out with the Wilcoxon matched-pair signed rank test.

D recently introduced, inotropic analogue of dopamine. It has potent B2-adrenergic and peripheral dopaminergic (DA-1) agonist properties, along with prejunctional DA-2 receptor stimulation resulting in peripheral vasodilation of the renal and mesenteric vascular beds.l-4 In contrast to dopamine and dobutamine, it lacks a-adrenergic receptor agonist activity and is only a weak agonist at 8l-adrenergic receptors. This study was designed to examine the acute hemodynamic effects of DX in patients following coronary artery bypass grafting (CABG), especially its effects on the right ventricle and pulmonary vascular resistance (PVR). By reducing right ventricular (RV) afterload, DX could be beneficial, since RV dysfunction can be an important factor in some patients after CABG. 5-6 MATERIALS AND METHODS Studies were carried out in 16 patients undergoing CABG. They gave informed consent, and the study was approved by the Local Ethical Committee. There were nine male and seven female patients; the mean age was 63 years (range, 53 to 77). Patients with valvular heart disease and ventricular aneurysms were excluded. All patients had sinus rhythms, and no patients were included who received a right CABG. Patients received lorazepam as premedieation and underwent an intravenous (IV) anesthetic with fentanyl and pancuronium bromide. After the induction of anesthesia, an arterial catheter and a triple-lumen pulmonary artery catheter with a rapid-response thermistor for measuring RV ejection fraction (REF) were placed. After surgery, patients were transported to the intensive care unit. They were ventilated and allowed to stabilize. Measurements were carried out within six hours after surgery, during apnea, and at a body temperature of at least 36°C. Before starting the DX infusion, the following hemodynamic parameters were

RESULTS

Results of the 16 patients with a dose of 0, 1 and 2 izg/kg/min are shown in Table 1. Of the seven patients who also received a dose of 4 #g/kg/min, measurements could only be carried out in five due to hypertension. Results of this group are shown in Table 2. Heart rate rose from 85 _+ 12 BPM to 112 _+ 15 BPM (P<0.05). Cardiac index rose from 1.8 ___0.2 L / m i n / m 2 to 2.2 _+0.7 L / m i n / m 2 at 1 #g/kg/min (/' < 0.05), and to 2.3 _+ 0.6 L / m i n / m 2 at 2 ~:g/kg/min ( P < 0.01). Right ventricular ejection fraction increased from 0.36 +_ 0.15 to 0.42 ___ 0.13 ( P < 0.05). Right atrial pressure and PCWP were not significantly altered by DX. Enddiastolic volume index and ESVI decreased signif-

From the Department of Intensive Care, Academic Medical Centre, Universityof Amsterdam, Amsterdam, The Netherlands. Address reprint requests to Department of Intensive Care, UniversityHospital, Ghent, Belgium. © 1989 by W.B. Saunders Company. 0888-6296/89/0304-0010503.00/0

Journal o f Cardiothoracic Anesthesia, Vol 3, No 4 (August), 1989: pp 441-443

441

442

POELAERT ET AL

Table 1. Hemodynamic Data p.g/kg/rnin

0

1

2

HR

85 ± 12

9 4 _+ 1 2 "

101 +- 1 3 "

MAP

87 +_ 10

8 9 - 12

8 7 _+ 11

RAP

11 -+ 3

11 ± 2

11 -+ 2

PCWP

14±

13 ± 2

13 +- 2

2

PAP

22-+4

24-

CI

1.8 ± .7

2.2 ± .7"

4

2.3 +- .6"1"

REF

.36 --- .15

.42 -+ . 1 3 "

.42 --..15

SVI

21 ± 7

23-

EDVI

6 8 ± 31

59 ± 2 5 *

7

23-

7

6 0 -',- 2 8

ESVI

4 7 -+ 31

SVR

1 9 7 7 _+ 7 7 7

1631 ± 5 9 1 "

1 4 9 4 +- 560]"

2 2 8 ± 165

2 2 7 ± 108

204 ± 96*

PVR

36 ± 24*

24_+4

37 ± 2 8

Results are expressed as mean ± SD; n = 16. * P -- 0.05. t P <: 0.01.

icantly after the start of the infusion (P < 0.05). Systemic .vascular resistance decreased at all doses, whereas PVR decreased with doses above 1/~g/kg/min (P < 0.05). Dopexamine hydrochloride showed no arrhythmogenic effects. All patients tolerated the drug well, and there were no side effects. DISCUSSION

Assessing cardiac output (CO) and REF by a rapid-response pulmonary artery catheter is a reliable technique and correlates well with nuclear techniques. 7'8 A beat-to-beat temperature variation can be measured and allows calculation of EDVI and ESVI by means of the computer. To minimize the influence of ventilation on the results, measurements should be done in apnea or with an automatic phase-selected injection system. 8 The present data demonstrate an improve-

ment in systemic hemodynamics with an increase in CI, unchanged MAP, and decreased SVR. These effects were seen at the lowest dose regimen. The decrease in PVR and further increases in CI were seen at the higher dose levels. These hemodynamic changes are comparable with resuits from other studies during CABG 9 or heart failure.I°"16 The peripheral vascular effects of DX are due to DA-1 and/32-adrenergic activity, and the positive inotropic effects are probably due to /32- and /31-adrenergic myocardial agonist activity. 17-19 In studies carried out in patients with chronic heart failure, a significant decrease in SVR was seen with an increase in CI. 1°'16 In a group of cardiac patients who were catheterized for coronary artery disease, Jaski et a119 studied infusion rates of 2 ~zg/kg/min, and found an augmentation of dP/dt, suggesting positive inotropism. In patients with severe heart failure, DX preferentially increased visceral blood flow over that to the limb, 1° and improved systemic hemodynamics without adversely affecting myocardial energetics or catecholamine balance. 11 Van Der Starre and Rosseel 9 previously studied 20 patients after CABG using doses of 1 to 10 #g/ kg/min for 20 minutes. The results were almost identical to those of the present study in regards to systemic hemodynamics, but RV function was not studied. At doses over 2 ~tg/kg/min, hypertension and tachycardia were also found. Theoretically, impedance of the pulmonary circulation plays a major role in RV performance in CABG patients, and the calculated value of PVR is only a partial measure of it. 2° A much

Table 2. Hemodynamic Data p,g/kg/min

O

1

2

4

HR

9 0 -+ 9

101 _+ 1 4 "

106 _+ 1 3 "

112 _ 1 5 "

MAP

8 5 ± 12

9 2 + 13

84_+ 13

82±

RAP

11 - 2

11 _ 1

11 - 1

11 _+ 2

14

PCWP

15 ± 2

14 _ 3

14 - 3

14 ± 4

MPAP

25-+4

27 ± 4

25 + 4

25 + 4

CI

1.8 ± .2

2.4 ± .8*

2.5 ± .7"

2.8 _+ 1 . 1 "

REF

.35 ± .13

.41 ± . 0 9 *

.41 -+ .04

.43 +_ , 0 6 *

SVI

20 ± 3

23_+ 6 *

24_+ 5

25 ± 8

EDVI ESVI

6 2 -+ 21 4 2 +- 21

5 7 +- 1 4 " 34 ± 11"

6 2 ± 13 3 9 +- 8

5 9 _+ 15 3 4 _+ 9

SVR

1793 +- 5 0 8

1627 ± 6 9 5 *

1 3 4 4 _+ 5 8 8 *

1 2 2 0 +_ 6 6 2 *

PVR

227 - 82

241 ± 111

198 ± 7 8 *

184 _+ 7 1 "

Results are expressed as mean _+ SD; n = 5. * P _ 0.05.

DOPEXAMINE AFTER CABG

443

better p a r a m e t e r for considering R V afterload is R V wall tension, which can be derived from m e a s u r e d values of R V E D V I and R V E S V I . In the present study group, a c o n c o m i t a n t decrease of these p a r a m e t e r s was observed. Moreover, the R V is more sensitive to changes in afterload, due to its thin wall a n d constrained contractile reserve. This has i m m e d i a t e implica-

tions on the R E F , to a relatively greater degree t h a n on the left side of the heart. D X could be beneficial to patients with a compromised R V by lowering R V afterload and improving R V performance. This is especially true in cold postoperative C A B G patients, 21 where afterload reduction leads to unloading of both ventricles and improvem e n t in right and left ventricular performance.

REFERENCES

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12. Colardyn FA, VandenbogaerdeJF: Use of dopexamine hydrochloride in intensive care patients with lowoutput left ventricular heart failure. Am J Cardiol 62: 68C-72C, 1988 13. Jackson NC, Taylor SH, Frais MA: Hemodynamic comparison of dopexamine hydrochloride and dopamine in ischemic left ventricular dysfunction. Am J Cardiol 62:73C-77C, 1988 14. Gollub SB, Emmott WW, Johnson DE, et al: Hemodynamiceffects of dopexaminehydrochlorideinfusions of 48 to 72 hours' duration for severecongestiveheart failure. Am J Cardio162:83C-88C, 1988 15. Tan LB, Littler WA, Murray RG: Beneficial hemodynamic effects of intravenous dopexamine in patients with low-output heart failure. J Cardiovasc Pharmacol 10: 280-286, 1987 16. Svensson G, Sjogren A, Erhardt L: Short-term hemodynamiceffects of dopexaminein patients with chronic congestiveheart failure. Eur Heart J 7:697-703, 1986 17. Bass AS, Kohli JD, Lubbers NL, et al: Cardiovascular evaluation of dopexamine, an unusual dopamine receptor agonist. Clin Res 34:941A, 1986 18. Mitchell PD, Smith GW, Well E, et al: Inhibition of uptake by dopexaminehydroehloridein vitro. Br J Pharmacol 92:265-270, 1987 19. Jaski BE, Wijns W, Foulds R, et al: The hemodynamic and myocardial effects of dopexamine: A new beta2adrenoceptor and dopaminergicagonist. Br J Clin Pharmacol 21:393-400, 1986 20. VersprilleA: Physiologicalmeaningof intravascular pressure, in Vincent JL (ed): Update in Intensive Care and Emergency Medicine,vol 5. New York, Springer-Verlag, 1988, pp 369-384 21. Gonzales AC, Brandon TA, Fortune RL, et al: Acute right ventricular failure is caused by inadequate right ventricular hypothermia. J Thorac Cardiovasc Surg 89: 386-398, 1985