Low Cardiac Output States After Open Heart Surgery

Low Cardiac Output States After Open Heart Surgery* Comparative Hemodynamic Effects of Dobutamine, Dopamine, and Norepinephrine Plus Phentolamine Ricluwd Gray, M.D., F.C.C.P.; Prediman K. Shah, M.D.; Bramah Singh, M.D., Ph.D.; Carolyn Conklin, R.N.; and Jack M. Matloff, M.D., F.C.C.P.

The hemodymunlc effects of dobutamine, dopamine,

and a combination of nonpinepbrine-phentolamlne were compared In nine padents with low cardiac oatpat llCafe after open heart SUJlery. Using a Latin ICluare dellp for drug aeqMnce, each padent w• atYen each drq at tbne levels by continuous intravenous Infusion. For dobuamtne and dopamine the doses wen 2.5, 5.0 and 10.0 µI/kg/min; for nonplnepbrine, 0.02, 0.05 and 0.10 p&/kg/ min with phentolanllne In the ratio of 1 (norepinepbrlne) to 2.5 (pbentolamlne). Dobutamlne and dopamine both produced an increase in heart rate, mean utert.I prelllUl'e, cardiac Inda, and stroke volume lndeL Both drup reduced total pulmo-

Cardiac dysfunction may occur soon after direct myocardial revascularization and/ or single and multiple valve replacement. In the former instances, transient functional derangements due to myocardial ischemic or perioperative infarction may produce a potentially reversible decline in cardiac function in addition to any ischemic or fixed contractile deficit due to coronary arterial narrowing. Such transient changes are seen even in the absence of perioperative myocardial infarction. 1 In cases of valvular heart disease, mechanical defects are associated with chronic pressure or volume overload to which similar adverse ischemic insult is added.1 •3 The resulting clinical spectrum may extend from profound circulatory collapse to the more common low output syndrome, consisting of diminished cardiac output, elevated pulmonary and systemic vascular resistances, and oliguria. In the absence of extensive preoperative depression of cardiac function or the picture of perioperative myocardial infarction with cardiogenic shock, improvement within two days of surgery is the rule. Initial therapy is aimed at correcting fluid de•From the Divisions of Cardiology and Cardiovascular Surgery, Cedars-Sinai Medical Center, Los Angeles. Supported in part by National Institutes of Health mo. SCOR grant 5 P50 HL176f51. Dr. Grar/, Cedars-Sinai Medical Cenlllr, Rqrint re~:

8100 BeoerllJ Blvd, Loa Angela 90048

18 GRAY ET Al

nary and systemic vmcular ..-.anee In the dG8e 11111p of 5.0to10.0 p&/kg/mln. When the mulmUDI tolerated dolleS were compared, the drop equally lneremed ardlac lndu: and stroke volume Inda, bat dopndM did so at a lllll8ller dG8e tban dobutmnlne. At ~ d - , dobatllmine tended to produce ae. tllcbycardla and 'YlllOCOnstrlctlon than dopamine. The Hnpinepbrlne-phentolamlne combination resulted In lncre8lell In both systemic artert.I pressure and ftl!Clllllr Nllltance with DO sipi&cant lncJUBe In arda.c lades. Its re8pOW unlq• featnre WM its predictable ~ wltb absence of cbronotropic effects and ventrlcwlar lrrffabllity.

pletion, anemia, acidosis, and optimizing cardiac rhythm. Since these measures often have limited effectiveness, further success depends on improving the myocardial contractility. Dobutamine Hcl is a relatively new agent reported to enhance contractility with less potential for chronotropic and arrhythmogenic sequelae than other cOmmonly used agents, such as isoproterenol and dopamine.t-e For this reason, the hemodynamic effects of dobutamine, dopamine, and norepinephrine plus phentolamine (a combination of drugs used commonly in our institution) were compared in nine patients with low cardiac output states after open heart surgery. Table 1-Preoperaliee Daeriplion o/ Pldien1 Populadon Patient Data (N-9)* Age, yr

Range

57

42-74

5

Previous MI Preoperative Cardiac index, L/m/m' Pulmonary capillary pressure, mm Hg Ejection fraction, % Number of diseased ve1111ela, ~75%

Mean

1.98

16 51

2.0

1.72-2.86 9-26

34-76 1-3

*Six men, three women.

CHEST, 80: 1, JULY, 1981

All patients were studied fn the supine position at nor-

MATERIALS AND METHODS

motbermia within M hours of surgery Uive within four boon)•· nti. ·lbldy took appmdm•tely two hours to complete. During this time adequate ftafd replacement ( 150 to 200 ml/hr) was continued. The hematocrit level was greater than 25 percent, and no patient was bleeding at the time of the study. Hemodynamic data included l)'ltemic arterial, right atrial, and pulmonary arterial and pulmonary capillary wedge pressures. Cardiac output was measured fn duplicate by thermodilution. Derived hemodynamic indices were calculated as follows:

The patient population (Table 1) consisted of ~ ~and three women with a mean age of st years. Five 'pal tients had had a prior myocardial fnfarc:tion, and two llWltained a perioperative myocardial fnfarction as indicated by typical ECG and myocardial-spedflc enzyme patterns. The mean preoperative cardiac inda: was 1.98 L/m/mz, with a pulmonary capillary wedge pressure of 16 mm Hg and a venbiculographic ejection fraction of 51 percent. In those patients with coronary disease ( de&ned as coronary arterial crou-sectional area uarrowinl of 75 percent or greater), the mean number of dUeued veueJs was 2.0. Patient selection for drug therapy was hued on a cardiac index below 2.5 L/m/m1, with systolic arterial pressure below 90 mm Hg, in the absence of hypovolemfa. Patients were excluded from the study if they had arterial pressures below 70/30 mm Hg, more than six premature ventricular contractions (PVCs)/mfD, or heart rates above 125 beats/ min. Once drug therapy was begun, it was discontinued ff any of the exclusion criteria occurred during the administration of any of the agenbl. Surgical procedures fncluded double valve replacement (aortic and mitral) in . , patient and single valve replacement (one aortic, one mitral) with coronary bypass in two. Six patients had isolated coronary artery bypass grafts. An average of 3.4 grafts per patient were imerted in those having myocardial revascularfzation. Surgical techniques included the U1e of bubble oxygenator with nonblood prime and intermittent aortic croll-clamping. Mild systemic hypothermia was used, the average lowest temperature being ao·c. The mean pump and fschemic (aortic croas-clamp) times were 146 and 46 min, respectively.

Systemic vascular resistance in dynes•sec•cm·ll =

(MAP~RA)

X SO

=

Total pulmonary resistance in dynea•sec•cm-11

(~~)xso =

Left ventricular stroke work index in gm•m/M2 stroke volume index X0.0136X [4/5(SAP-DAP)+DAP-PCW] where MAP, SAP and OAP are mean, systolic and diastolic arterial pressures, respectively, PAP is pulmonary arterial

pressure. PCW is pulmonary capillary wedge pressure, RA is mean right abial pressure, and CO is cardiac output.

After control hemodynamic data had been obtained, measurements were repeated following ten minutes of steady-state infusion at each dosage. Hemodynamic variables were allowed to return to control leveJs between administration of different drugs. An attempt was made to give each patient each drug at each dose. The sequence of

Table l--llernodTfUIJflfe DON Raporue to Tlree Lnela o/ Dobutandne, Dopamine, and Norepineplarine-Plaentolamine• Dopamine

Dobutamine

N orepinephrine-Phentolamine

(N-5) (N-7) (N-9) III I II III I II I II III 2.5 2.5 5.0 10.0 0.02 0.05 0.10 5.0 10.0 Control Control Control pg/kg/min ,.g/kg/min pg/kg/min Heart rate, beats/min

97 ±10

100 ±10

104 ±12

Mean arterial pressure, mm Hg

68 ±12

73 ±12

76t 78t ±11 ±9

Mean pulmonary arterial pressure, mm Hg

26 ±5

±6 ±6

Pulmonary capillary wedge pressure, mm Hg

18 ±4

19 ±5

Mean right atrial pressure, mm Hg

16 15 ±3 ±4

'¥1

'¥1

114t +16

98 97 ±6 ±6

105 ±6

125t ±12

60 ±16

76 ±11

89t ±16

64 ±11

28

25 ±2

66

±11 28

'¥1

±7 ±7 19 17 ±5 ±6 14 ±4

13t ±3

19 ±3

1.97 1.96 ±0.4 ±0.5

2.48t 3.0lt 1.97 ±0.7 ±0.8 ±0.2

Stroke volume index, ml/beat/m1

19.1 ±4

23.7t 26.5t ±6 ±7

Systemic vascular resistance, dyne•sec•cm·•

1284 ±356

1355 1185 ±359 ±354

Total pulmonary resistance, dyne•sec•cm·•

660 ±193

±200

645

±5 ±5

17 ±3

18 ±4

16 13 13 ±2 ±3

Cardiac index, L/m/m•

19.7 ±5

23 ±5

20.2 ±2

2.10 ±0.4

24

94 92 ±6 ±9

77t

66

±12 ±15 25 ±4

19 19 19 ±3 ±4 ±2 15 15

93 ±6

'¥1

96 ±3

94t ±13

±4

30t ±5

21 ±3

22 ±5

±2

16 ±4

16 ±4

16 ±3

3.04t 3.74t 1.88 ±0.4 ±0.7 ±0.5

1.75 ±0.4

1.83 ±0.5

2.18 ±0.7

19.9 ±4

18.8 ±3

19.5 ±4

22.5 ±7

±2 ±2

21.7 29.0t ±3 ±3

29.8t ±4

1044t 1083 ±78 ±325

952 ±354

888 ±200

879 ±190

1168 ±213

1266 ±210

1491 ±301

1758t ±569

523t 439t 605 ±217 ±206 ±140

474 ±94

350

347 ±128

630 ±222

685

±106

±338

706 ±300

696 ±363

*Mean± SD. tP<.05 from control.

CHEST, 80: 1, JULY, 1981

LOW CARDIAC OUTPUT AFTEI OPEi HEART SURGERY 17

drug administration was determined according to a Latin square design. This was done to diminish the likelihood that observed hemodynamic changes were influenced signiftcantly by the residual effects of the previous drug administration. T Doses I, n. and m represent administration of 2.5, 5.0, and 10.0 l'g/kg/min, respectively, for dobutamine and dopamine. Norepinephrine-phentol•mine doses were 0.02, 0.05, and 0.10 l'g/kg/min, respectively, in a ratio of 2.5 phentolamine to 1 norepinephrine. In aome instances the highest dose of a certain drug could not be administered safely to a given patient. The results were ezpressed as a mean ± SD and were subjected to analysis of variance, and statistically signi&cant differences were determined using the Newman-Keuls test.a This test required deletion of any patient with incomplete data, such as when the highest dose of a drug was not given. For this reason the number of patients anal)'7.ed in certain categories is less than nine.

dose III, these changes persisted, and there was also a decrease in right atrial pressure and systemic vascular resistance. However, at this dose, heart rate also increased. The hemodynamic responses to similar doses of dopamine are presented in the middle panel. Only five patients were given all three dosages, since the maximum intended dose ( 10.0 ,,.g/kg/ min) was considered clinically unsafe in four patients. Of these four, two experienced systolic blood pressure in excess of 160 mm Hg, one had multiple premature PVCs, and one a marked sinus tachycardia. At dose I, there were no statistically significant changes. At dose II, cardiac index and stroke volume index were increased. At dose m, these changes persisted, and mean arterial pressure and heart rate were also increased. Similar to the effect of dobutamine, pulmonary capillary wedge pressure remained unchanged. The effects of norepinephrine and phentolamine (1/2.5) are shown in the right panel. Only seven patients are included, since excessive blood pressure response occurred in two. At dose I, no significant differences occurred. At dose II, only mean arterial pressure was elevated. At dose Ill, mean pulmonary arterial pressure and systemic vascular resistance were also increased. But pulmonary capillary wedge pressure, cardiac index, and stroke volume index were not significantly changed. Un-

l\EsuLTS

The hemodynamic responses to the three dru~ at control and at each dose are shown in Table 2. The treabnent response is compared with control values, and differences (P<.05) are indicated by a dagger. Only significant differences will be discussed. Dobutamine at dose I produced no significant differences in any of the hemodynamic parameters. At dose II, an increase occurred in mean arterial pressure, cardiac index, and stroke volume index, with a decrease in total pulmonary resistance. At

Dose II (N-6)

Dose I (N-8)

Dose III (N=4)

Doh

Dop

Nor-Phen

Doh

Dop

Heart rate, beats/min

99 ±11

100 ±10

96 ±12

103 ±11

112 ±9

93 ±6

108 ±16

Mean arterial pressure, mm Hg

72 ±12

69 ±13

66 ±12

73 ±12

85 ±21

77 ±15

72 ±9

25 ±4

25 ±6

28 ±7

27 ±4

24 ±5

28 ±6

±4

19 ±5

20 ±5

21 ±3

16 19 ±4

±3 ±6

16 ±4

13 ±1

14 ±2 ±2

Mean pulmonary arterial pressure, mmHg

25

25

±4

±5

Pulmonary capillary wedge pressure, mmHg

18 ±5 ±5

Mean right atrial pressure, mmHg

14 ±3

Cardiac index, L/m/m1

Stroke volume index, ml/beat/m1

1.89 ±0.5 19.2 ±5 ±5

18 18 13 ±3 ±3

15

Nor-Phen

14 15 ±3 ±3

Doh Dop

Nor-Phen 128t ±11

95 ±2

85 ±15 ±16

91 28 ±4 22

16 2.04 ±0.4

2.11 ±0.5

1.73 ±0.4

2.39 ±0.8

3.15t ±0.4

1.83 ±0.5

2.66 ±0.7

3.83t ±0.8

21.3

18.2 ±3

23.0 ±6

28.3t ±4 ±4

19.5

24.5 ±3

21.4 29.7t ±4 ±4

Systemic vascular resistance, dyne•sec•cm·•

1397 ±360

1230 ±511

1336 ±245

1170 ±377

995 ±314

149lt ±301

992 ±247

810 ±147

1689t ±159

Total pulmonary resistance, dyne •sec•cm·•

640

552 ±199

680

±288

533 ±271

398t ±166

706 ±302

416 ±207

340

±204

±147

639t ±250

*Mean ±SD. Abbreviations: Doh indicates dobutamine; Dop, dopamine; Nor-Phen, norepinephrine-phentolamine. tP <.05 from dobutamine.

18 GRAY ET AL

CHEST, 80: 1, JULY, 1981

like effects of dobubµnine and dopamine, no change in heart rate occurred at any dose. To illustrate diJferences between dobutamine and the other two agents, the drugs were compared with one another at similar doses (Table 3). In this table, the hemodynamic response with each drug at a set equivalent dosage is compared statistically with the response with dobutamine. This diJfers from the analysis in Table 2, where the bemodynamic responses at three graduated dosages are analyzed using that patient's own control hemodynamic state for statistical comparison. Statistically significant diJferences from dobutamine (at similar dose levels) are indicated by the dagger. The data in Table 3 diJfer from Table 2 because the need to withdraw any drug at a given dosage (due to side effects) required that all responses to other drugs at that dosage be deleted in that patient for correct statistical analysis. No significant diJferences from dobutamine were seen at dose I. The comparative responses to dose II are shown in the middle panel, where a greater increase in cardiac index and stroke volume index with lower total pulmonary vascular resistance is seen with dopamine at this dose, and systemic vascular re-

LA.I

!ct c

130

0:: ·-

~~ ~~

110

I96

~

cA

90

Ir·

1~1

*p<.05FROM

j

a:

I98

~

...J cl

110

a:: ~0

E 90 E cl 70 z LA.I

li:

cl LL.I

::E

x

~ ~NE

~

4.00 3.00

~ ......

-E 0'

8...J

2.00

t

1~ r ~ 178

I· I·~ ~· I I. 82

2.06

*p<.05 FROM

20

CONTROL

(/)

a..

sistance is increased with norepinephrine-phentolamine. At dose III, a higher heart rate, cardiac index, and stroke volume index are seen with dopamine; norepinephrine with phentolamine is associated with higher systemic and total pulmonary vascular resistances. At this dose, statistically significant elevations in mean arterial and pulmonary capillary wedge pressures are not reached with either dopamine or norepinephrine-pbentolamine compared with dobutamine. Based on the foregoing type of comparison, individual patients were then treated clinically with whichever drug most readily improved the end:. points of cardiac index or systemic arterial pressure. It soon became evident that to achieve a given cardiac index or arterial pressure, dopamine was more potent on a milligram-for-milligram basis. After the standard comparison of drugs, a deviation in dosage from the initial protocol allowed for higher doses of dobutamine to be given. The hemodynamic effects of the three drugs at this maximum dose were than compared (Fig 1-3). Differences from control ( P < .05) are indicated by the asterisk. The average maximum dose for dobutamine was 11.3; for dopamine 7.2; and for nore-

~

-

jtR

&:I

I

a:

10

1~

IM

1·

36 ~ E E

28

I25

20

_,Ii~

C(

~,_

l·s

15

I

I! ~i

~ E E

CONTROL

!• M soo

It

1641

Ia In

129

I42o 1~4 l™

i

1.00 ~=:.., 11.3 7.2 .08 Jll/llg/mkl FmtJBB 1. Comparative hemodynamic response of three drugs at muimum safe dose. Mean ± SD;• = P < .05 fMm C0DtroL ContlolDobutcrninl Doparnne

CHEST, 80: 1, JULY, 1981

Norepilephrine/ DcpamN Phentolamine Dobutaminl .11Q/k9/mln 7.2 11.3 Flcom: 2. Comparative hemodynamic response of three drugs

Cclnlnll

at maximum safe dose. Mean ± SD;• = P

0.8

< .05 fMm control

LOW CARDIAC OUTPUT Arni OPEi HWT SURGERY

19

32 26

20 14

if11900

*

1908

lhl300 700

24 16

8 Control Dopamine Dobutamine 11.3

7.2

Noreplnephrine I Phentolomlne 0.8 j11J/k91min

FJGUBB 3. Comparative hemodynamic response of three drugs at muimum safe dose. Mean ± SD;• P < .05 from control

=

pinephrine with phentolamine 0.08 pg/kg/min. At these doses, heart rate (Fig 1, top panel) was increased by dopamine and to a slightly lesser extent by dobutamine. Mean arterial pressure (middle panel) was slightly elevated with dobutamine but significantly altered only by dopamine and norepinephrine-phentolamine. Cardiac index increased to a simliar degree with both dobutamine and dopamine, but was not changed by the norepinephrine combination (bottom panel). Right atrial pressure (Fig 2, top panel) was lowered only by dobutamine, while mean pulmonary arterial pressure (middle panel) remained unchanged by all drugs. Total pulmonary resistance (lower panel) was lowered by both dobutamine and dopamine. Stroke volume index (Fig 3, top panel) improved to a similar degree with both dobutamine and dopamine, but was unchanged by the norepinephrine combination. Increased systemic vascular resistance (middle panel) was seen only with norepinephrine-phentolamine. No significant changes in pulmonary capillary wedge pressure was seen (bottom panel), although dobutamine appeared less likely to result in its elevation. DISCUSSION

These data show that the administration of both

20 DAY ET AL

dobutamine and dopamine results in an increase in heart rate, mean arterial pressure, cardiac index, and strolce volume index. Both drugs reduced total pulmonary and systemic vascular resistance in the dose range of 5.0 to 10.0 pg/kg/min. When :maximum "safe dose" effects were compared, both drugs increased cardiac index and stroke volume index to a similar degree, but dopamine did so at a smaller dose than dobutamine (7.2 vs 11.3 pg/kg/ min). At this dose, dobutamine had a tendency to produce less tachycardia and slightly less vasoconstriction than that seen with dopamine. In 4/9 patients, the maximum intended dose of dopamine could not be used because of multiple PVCs in one patient, marked sinus tachycardia in another, and systolic arterial hypertension in two patients. In another drug study with dopamine in this setting, deletion of patients began as dopamine was given in doses as small as 8 pg/kg/min. Tachycardia and, to a lesser extent, hypertension were reasons for deletion. 9 The norepinephrine-phentolamine combination predictably resulted in increases in systemic arterial pressure and systemic vascular resistance, with no significant increase in cardiac index. No change in heart rate or ventricular irritability was noted. Development of systemic hypertension prevented the use of the maximum intended dose of norepinephrine-phentolamine in two patients. Although the overall number of patients is too small to contrast the drug response in patients with differing surgical procedures, it is possible that differences may emerge in a larger study population. Limiting side effects occurred in two of the three patients with valve replacement Unwanted hypertension resulted from both dopamine and the norepinephrine combination in one patient with aortic and mitral valve replacement, and excessive heart rate was seen with dopamine in a patient with coronary bypass and mitral valve replacement. On the basis of this experience, it is clear that there is no drug of choice for the low cardiac output state after cardiac surgery. Rational therapy should be individualized based on bedside measurement of cardiac output, pulmonary and systemic pressures and vascular resistances. From these measurements one then chooses an agent (or combination of agents) with the desired a- or ,8-adrenergic ef. fects. Although a set dose range may be useful as a guideline, eventual success in selecting a dosage depends on titration of the chosen agent with repeated hemodynamic measurenients to serve as endpoints of therapy. Dobutamine played a signiflcant role in management of several, but not all, of these patients. It seemed most useful in patients

CHEST, 80: l, JULY, 1981

NOREPINEPHRINE /Pt£NTOLAMINE

DOPAMINE

DOBUTAMINE

N

~

......

.

E

-s

50

10

18

10

26

PCW (mmHQ)

26

18

10

PCW (mmHg)

10

26

18 PCW (mmHg)

4. Hemodynamic response of left ventricular stroke worlc index and simultaneous pulmonary capillary wedge pressure before and after maximum dose of each drug. Closed circles control; open circles maximum dose response; LVSWI left ventricular ll:roke work indez; PCW pulmonary capillary wedge pressure. FIGVRB

=

=

=

=

with depressed cardiac output with only mild to moderate hypotension. It was particularly advantageous in this setting when the patient had sinus tachycardia or a tendency toward ectopic dysrhythmias. The mechanism of action of dobutamine relates to its potent direct cardiac p stimulation and is not dependent on endogenous norepinephrine stores. 10011 This, coupled with a lack of direct vasoconstriction and a reflex decrease in peripheral vascular resistance, results in the limited increases seen in systemic arterial pressure. Dobutamine may have direct vasoconstrictor effects at higher doses, but no such tendency was seen in our group of patients using a dose of 10.0 µ.g/kg/min. For this reason dobutamine is not likely to be useful in the patient with shock or marked hypotension, as in cardiogenic shock following acute myocardial infarction or perioperative infarction. Although dopamine remains a popular and effective means of augmenting cardiac performance in both acute myocardial infarction11 and chronic congestive heart failure, 11 especially in combination with nitroprusside, our experience in the cardiac surgical patient indicates that its tendency to produce tachycardia and ventricular arrhythmias is significant and may limit its use in many patients. Dopamine is useful, however, in the patient who requires both a pressor effect and an increase in cardiac output but does not exhibit tachycardia or ventricular irritability. These data indicate that the combination of norepinephrine-phentolamine has effects quite different from those of dobutamine and dopamine.

Because the effect here is due largely to systemic vasoconstriction, this drug combination is of value in the patient with low arterial pressure but with adequate cardiac output. An additional value is that the ratio of its two components may be individualized to produce less vasoconstriction while achieving greater increases in cardiac output. Although greater proportions of phentolamine might be associated with significant increases in cardiac output, our data showing unchanged cardiac output in the face of significantly increased systemic arterial pressure and vascular resistance indicates that an inotropic response occurs even with the relatively small proportion of phentolamine given in a fixed ratio with norepinephrine. A significant increase in cardiac index and stroke volume index was recorded by other investigators with separately controlled infusions using much higher dosages but in a ratio favoring greater amounts of norepinephrine than in our study. 14 The virtual freedom from tachycardia and arrhythmias at commonly used doses is a significant added benefit. Figure 4 shows the relationship of left ventricular stroke work index and pulmonary capillary wedge pressure for each patient before and after administration of the maximum dose of each drug. An increase in left ventricular stroke work index at the same or lower pulmonary capillary wedge pressure suggests that left ventricular performance is improved and follows a different Frank-Starling function curve. Such a response was seen with dobutamine in 7/9 patients (left panel), with dopamine in 2/9 patients (center panel), and with norepinephrine-phentolamine in 4/9 patients (right panel).

CHEST, 80: l, JULY, 1981

LOW CARDIAC OUTPUT AFTER OPEii HEART SURGERY 21

1

These data illustrate variability in individual patient responses and also conSrm that the norepinephrine combination may exhibit inotropic as well as vasopressor activity. In summary, our experience indicates that while norepinephrine-phentolamine in varying dose combinations is an effective regimen for many hypotensive patients with low cardiac output following open heart surgery, the availability of dobutamine provides an additional therapeutic approach whereby augmentation of the inotropic state can be accomplished without the propensity to induce cardiac arrhythmias. ACKNOWLEDGMENTS: The authors gratefully aclmowledge Katherine Stankus and Amy Kwan for statistical analysis and Helen Schamroth for editorial assistance.

1 Gray R, Maddabi J, Berman D, et al. Scintigraphic and hemodynamic demonstration of transient left ventricular

dysfunction immediately after uncomplicated coronary artery bypass grafting. J Thorac Cardiovasc Surg 1979; 17:504 ! Rastelli GC, Kirklin JW. Hemodynamic state early after prosthetic replacement of mitral valve. Circulation 1966; 34:448 3 Kirklin JW, Theye RA. Cardiac performance after open intra-cardiac surgery. Circulation 1963; 28:1061

22 CRAY ET Al

4 Hinds JE, Hawthorne EW. Comparative cardiac dynamic effects of dobutamine and isoprotenmol in conscious instrumented dogs. Am J Cardiol 1975; 38:894 5 Salcamoto T, Yamada T. Hemodynamic dects of dobutamine in patients following open-heart surgery. Cfr. culation 1917; 55:525 6 Gillespie TA, Roberts R, Ambos HD, et al. Salutary effects of dobutamine on hemodynamics without exacerbation of arrhythmias or myocardial injury. Circulation 1975; 52:11-76 7 Armitage P. Statistical methods in medical research. 3rd ed. Great Britain, Halsted Press Books. 1974; 239-45 8 Winer BJ. Statistical principles in experimental design. ind ed. New Yorlc: McGraw-Hill Book Co Inc, 1971; 191-96 9 Stephenson LW, Blackstone EH, Kouchoukos NT. Dopamine vs epinephrine in patients following cardiac surgery: randomi7.ed study. Surg Forum 1976; 27 :272 10 Holloway GA, Frederickson EL. Dobutamine, a new beta agonist. Anesthes Analges 1974; 53:616 11 Tuttle RR, Mills J. Dobutamine: development of a new catecholamine to selectively increase cardiac contractility. Ciro Res 1975; 38:185 12 Hol7.er J, Karliner JS, O'Rourlce RA, et al. Ef£ectiveness of dopamine in patients with cardiogenic shock. Am J Cardiol 1973; 32:79 13 Goldberg LI. Drug therapy: dopamine-clinical 111e of an endogenous catecholamine. N Engl J Med 1974; 291:707 14 Kirsh MM, Bove E, Debner M, et al. The use of lewrterenol and phentolamine in patients with low cardiac output following open-heart surgery. Ann Thorac Surg 1980; 29:26

CHEST, 80: 1, JULY, 1981

!