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378
CIRCULATION
Sperelakis N: Mechanism for the inotropic effect of angiotensin II on
isolated cardiac muscle. Circ Res 39: 178, 1976
25. Khairallah PA, Davila D, Papilolaou, Glende NM, Meyer P: Effects of
angiotensin infusion on catecholamine uptake and reactivity in blood
vessels. Circ Res 28: 96, 1971
26. Thompson JL: Effect of angiotensin on the cardioaccelerator response to
sympathetic nerve stimulation in isolated rabbit hearts (35152). Proc Soc
Exp Biol Med 135: 825, 1970
27. Ljungqvist A: The effect of angiotensin infusion, sodium loading and
sodium restriction on the renal and cardiac adrenergic nerves. Acta
Pathol Microbiol Scand, Sect A, 83: 661, 1975
VOL 57, No 2, FEBRUARY 1978
28. Bickerton RK, Buckley JP: Evidence for a central mechanism in
angiotensin induced hypertension. Proc Soc Exp Biol Med 106: 834, 1961
29. Sweet CS, Ferrario CM, Khosla MC, Bumpus FM: Antagonism of
peripheral and central effects of angiotensin II by (1-sarcosine, 8isoleucine) angiotensin II. J Pharmacol Exp Ther 185: 35, 1973
30. Hoffman WE, Phillips MI: Evidence for Sarl-Ala'-angiotensin crossing
the blood cerebrospinal fluid barrier to antagonize central effects of
angiotensin II. Brain Res 109: 541, 1976
31. Buggy J, Fink GD, Johnson AK, Brody MJ: Prevention of the development of renal hypertension by anteroventral third ventricular tissue
lesions. Circ Res 40 (suppl I): I-I 10, 1977
Efficacy of Dopamine, Dobutamine, and Epinephrine
During Emergence from Cardiopulmonary Bypass in Man
PETTER A. STEEN, M.D., JOHN H. TINKER, M.D., JAMES R. PLUTH, M.D.,
DONALD A. BARNHORST, M.D., AND SAIT TARHAN, M.D.
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SUMMARY Hemodynamic effects of dobutamine and dopamine
(both 5, 10, 15 ,ug/kg/min) and epinephrine (0.04 Ag/kg/min) were
studied immediately following cessation of cardiopulmonary bypass
in 34 patients with preoperative evidence of left ventricular dysfunction. Significant increases in mean cardiac index were seen with
dobutamine (15, 25, and 26% respectively), and epinephrine (30%).
The largest increases occurred with dopamine (44, 53, and 64 percent
respectively). Responses varied from patient to patient, however.
Seven patients developed marked output increases without concomi-
MANY STUDIES OF THE HEMODYNAMIC EFFECTS of various inotropic agents have been conducted in
patients following open cardiac surgery.1"6 Most investigators have examined only one drug in each patient, and
have studied patients several hours'14 to days5 following termination of bypass, often in the intensive care unit.
Undeniably, this timing and setting provide more stable and
controlled conditions. However, a critical time for many of
these patients is that period immediately following cessation
of cardiopulmonary bypass, when workload is re-imposed
on the myocardium. Adequacy of cardiac performance is
usually monitored by observing arterial pressure in conjunction with left atrial pressure. Patients are given transfusions
until certain arterial and/or left atrial pressures are reached;
the target pressures are set rather arbitrarily. Inotropic
agents are widely used during this period, often briefly, to
permit "satisfactory" acceptance of that workload. Choice
of inotropic drug is largely based on personal preference
because there is little available information on what happens
during this period. Efficacy of inotropic drug administration
is also usually judged by arterial and atrial pressure
responses. Cardiac output is seldom monitored immediately
following bypass.
We previously reported" that dobutamine was associated
From the Departments of Anesthesiology and Surgery, Mayo Medical
School and Mayo Clinic, Rochester, Minnesota.
Address for reprints: Dr. Tinker, Mayo Clinic, 200 First Street S.W.,
Rochester, Minnesota 55901.
Received June 9, 1977; revision accepted September 6, 1977.
tant increases in arterial pressure, whereas seven others showed
"satisfying" increases in arterial pressure without appreciable output
increases. Heart rate increases were small and few arrhythmias were
noted. We conclude that dopamine, epinephrine, and dobutamine all
are effective inotropic agents during the immediate post-bypass
period, with variations discussed in detail. None possess the disturbing chronotropic and arrhythmogenic effects of isoproterenol
(previously studied). Efficacy of administration of inotropic drugs
seems best assessed by serial output measurements during this period.
with moderate increases in cardiac index without significant
heart rate increases, in sharp contrast to isoproterenol.
Isoproterenol (0.02 jAg/kg/min) caused a mean heart rate increase of 43.9%, with multiple premature ventricular contractions, and little change in output.
In this study, our objectives were twofold: first, to provide
a comparison of the effects of three inotropic agents
(dobutamine, dopamine, and epinephrine) during the period
immediately following emergence from cardiopulmonary
bypass; and second, to make recommendations regarding
appropriate methods of monitoring the efficacy of inotropic
drug administration in this specific situation.
Methods
Thirty-four patients were studied, usually with two of the
three drugs in each patient. Dopamine and dobutamine were
usually studied in two infusion rates, epinephrine in one infusion rate. This resulted in 56 patient-inotropic drug exposures, and a total of 81 inotropic drug dosages. Patients
were studied who had documented evidence of left ventricular dysfunction preoperatively, based upon review of
catheterization data and history/physical exam. Elevated
left ventricular end diastolic pressure ( > 15 torr), ventricular hypokinesia, and/or ejection fraction < 50% were present. All patients were New York Heart Association functional class III or IV. Twenty-three underwent valve
replacement, seven had coronary artery bypass grafting, and
four had both. Table 1 summarizes patient data.
INOTROPIC DRUGS AFTER BYPASS/Steen et al.
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The protocol was reviewed and approved by the institutional Human Studies Committee. Patients were visited
preoperatively and informed written consent obtained.
Anesthesia was induced with thiopental 2-4 mg/kg and
maintained prior to bypass with nitrous oxide 50%,
diazepam (0.15-0.4 mg/kg) and incremental doses of
meperidine (3-7 mg/kg). Pancuronium 0. 15-0.3 mg/kg
provided neuromuscular blockade. A catheter was placed in
the thoracic aorta from the femoral artery for dye-dilution
sampling and measurement of arterial pressure. Left and
right atria were cannulated directly by the surgeon before
cessation of bypass. The left atrial catheter was used for
pressure measurements and dye-injections. Infusions of inotropic agents were given by calibrated drug pump via an external or internal jugular line used for no other purpose.
For emergence from bypass, the venous outflow line to the
bypass pump was gradually occluded and the patient
received transfusion until systolic arterial pressure reached
80-120 torr, unless left atrial pressure increased to greater
than 25 torr. At either point, transfusion was stopped,
arterial, left and right atrial pressures were recorded, and
control cardiac outputs were measured in duplicate by dilution with Cardio-green. Patients whose systolic arterial pressures rose above 120 torr following the initial transfusion
and whose left atrial pressures remained below 25 torr were
not given inotropic drugs. Infusion with inotropic agents was
begun in all other cases.
Control cardiac outputs were always obtained within four
minutes of cessation of bypass and were computed by a
Waters Cardiac Output Computer (checked daily by manual
extrapolation and calculation from obtained curves). During
inotropic drug infusion, cardiac outputs and pressures were
measured at 5 and 10 min. After 10 min the first drug dosage
was changed to the next higher increment of the same drug
unless systolic arterial pressure was greater than 140 torr, in
which case the initial dosage was halved. After an additional
5 min at this second dosage, outputs were again measured,
and the first drug was then discontinued over a 5 min period.
Between the first and second inotropic drug dose the appropriate dose of protamine for heparin reversal was administered. The second inotropic drug was then given in the
same fashion after cardiac outputs had returned to ± 10% of
the first control value. For dobutamine and dopamine 10
,gg/kg/min was the starting infusion rate, going either to 15
or to 5 tg/kg/min. Only one dose of epinephrine, 0.04
ug/kg/min, was studied.
Left atrial (LAP), right atrial (RAP), and aortic pressures were continuously recorded. Left atrial pressure was
maintained at control levels during the study period by appropriate additional transfusion if needed. The electrocardiogram was monitored throughout the period for
arrhythmias and heart rate.
During the test period, patients were ventilated with oxygen only; no inotropic agents other than the drug studied
were given. After the second drug was studied, nitrous oxide
was started and the inotropic drug tapered or continued at
the discretion of the attending anesthesiologist. Diazepam
and meperidine were administered before termination of
bypass and provided adequate hypnosis and analgesia. No
patient had any recall of the procedure.
Drug dilutions were: dopamine and dobutamine 1 mg/ml
379
TABLE 1. Drug Administered by Type of Surgery
MV replacement
AV replacement
Double valve
replacement
TV replacement
CABG
Coronary + valve
Dobutamine
Dopamine
Epinephrine
6
10
6
6
2
3
2
1
2
1
4
4
1
3
3
2
Abbreviations: MV = mitral valve; AV = aortic valve; TV = tricuspid
valve; CABG = coronary artery bypass graft.
and epinephrine 16 jig/ml, all in 5% dextrose in water. The
following formulae and units were used for calculated
values:
(CI) = CO/BSA
SVR = (MAP - RAP) * 79.98/CO
SVI = CI/HR
LVSWI - (MAP - LAP) . SVI * 14.4
1000
where CI = cardiac index; BSA = body surface area;
SVR = systemic vascular resistance in dynes. sec * cm-5;
CO = cardiac output, SVI = stroke volume index in L/min
* M2l* beat; MAP = mean arterial pressure; RAP = right
atrial pressure; LVSWI = left ventricular stroke work index
in gram-meters/m2 beat.
Data for each drug given before protamine were compared to that for the same drug given to other patients after
protamine by Student's t-test for unpaired values. Data for
each drug exposure were compared to the appropriate control value by Student's t-test for paired values.
-
Results
No significant differences in any measured parameters
were noted to depend upon whether a drug was given first or
second in the sequence, therefore all results for each drug are
taken together. For the first drug dose (10,ug/kg/min for
dopamine and dobutamine; 0.04 Ag/kg/min for epinephrine) data reported were obtained after the 10-min test
period. For the second dose of dopamine and dobutamine (5
and 15 Ag/kg/min) data reported were obtained after 5 min.
Epinephrine 0.04 Ag/kg/min was studied in ten patients;
dobutamine 5 ,ug/kg/min in 11 patients, 10 jg/kg/min in 17
patients, 15 Ag/kg/min in ten patients; dopamine 5
,ug/kg/min in seven patients, 10 ,ug/kg/min in 20 patients,
and 15 ,Mg/kg/min in six patients.
Cardiac Index (CI)
Most but not all patients responded to the inotropic drugs
with an increase in cardiac index (table 2, fig. 1). In three instances, during infusion of dobutamine 5 ,Mg/kg/min, three
instances during infusion of dobutamine 10 ,Mg/kg/min
(total of four different patients), and in one patient receiving
dopamine 10 ,g/kg/min, there was no increase or a slight
decrease in cardiac index. In each instance of failure to respond to either dobutamine or dopamine, cardiac index did
increase in response to the other drug. There were no instances in which epinephrine failed to elicit an increase in
cardiac index.
380
CIRCULATION
Mean CI increased 15%, 25%, and 26% with dobutamine,
at 5, 10 and 15 Ag/kg/min, respectively. With dopamine the
mean increases in cardiac index were 44%, 53%, and 64% at
5, 10 and 15 Ag/kg/min, respectively. The mean increase in
Cl with epinephrine 0.04 gg/kg/min was 30%. All mean
values were significantly different from mean control values
(P < 0.01 for all except dobutamine 5 Ag/kg/min, which
was significant at P < 0.05).
****
*
C)
0
e,.0
Cl CO cO )CZ
cq L
i
1-
0
Zs
0::
O; 7t
cO 0
Lf
V
"
x
Qq .-
cD
rC- o r~
Lt
C.
Mean Arterial Pressure (MAP)
0
04
0
u
0cNq O
csc
0 clr
Average MAP increased 23%, 21%, and 19% with
dobutamine, 5, 10, and 15 ,g/kg/min, respectively (table 2,
fig. 2). With dopamine, the mean increases with the same
doses were respectively 33%, 21%, and 30%, and the increase
with epinephrine 0.04 ,g/kg/min was 27%. All mean values
were significantly different from the appropriate control
values (P < 0.01 except dobutamine 15 ,g/kg/min with
P < 0.05).
kO' t +
CC
0
c)
.0
0
1.
VOL 57, No 2, FEBRUARY 1978
0D CnO
CO
C
ci ci
cO
0
CO
ci
00
b
ci
c0
Cl
_O
CC
Pulse Pressure
'*
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
*csc* tc
*N *
* ** ** * *
c:* cq*
CO
C.
CO CO
4)
e
ClJC;l '< CrN
0
0
u
c.
Mean pulse pressures increased 25%, 39%, and 30% with
dobutamine, 5, 10, and 15 gig/kg/min respectively (table 2).
With dopamine, the mean increases were respectively 52%,
46%, and 42% and the increase with epinephrine was 75%
(P < 0.05 for dobutamine 5 and 15 gg, P < 0.01 for the
rest).
CO b
CO
4- 4-4-e + + + +
o<
Cl -
fl
CO Cl
Cr
00
Heart Rate (HR)
C.
C..
00 -
ir
0
N 000 Cl NO
Cr
0
0
0000
N
C)
0--
C.
0 0 N ir******r--
6666666
*
0
a
a)
N
qU
O OCO OC z Or
i i0
cO;
Cr
000M
Mean HR increased 10%, 7% and 7% for dobutamine 5,
10 and 15 ,ug/kg/min respectively (table 3, fig. 3). For
dopamine the mean increases were respectively 9%, 12%,
and 13%. With epinephrine 0.04 Ag/kg/min, the mean increase in HR was I 1%. The increase for dobutamine 5 and
10 and dopamine 10 ,g/kg/min had a P value < 0.05, the
other heart rate changes were not significant at the P < 0.05
level.
0
Systemic Vascular Resistance (SVR)
0
0
'a
The only significant change in mean SVR seen with any of
the three drugs in any dosage was a 15% decrease with
dopamine 10 ,ug/kg/min (P < 0.01) (table 3).
S.
u
-N 0 N: 0
l
. -.
.
CO
a
CH
zI
:
D2
:4
¢.
mvv
av
c
CLrC2
>
o~6
ZZ
.
0
Crz
0>
iO.
Stroke Volume Index (SVI)
Mean SVI increased 21% and 19% with dobutamine 10
and 15 ,g/kg/min respectively (table 3). With dopamine the
increases were 38%, 51% and 49% for 5, 10, and 15
,ug/kg/min, respectively (P < 0.01 with dopamine 5 and 10
,ug/kg/min, and with dobutamine 10 ,g/kg/min; P < 0.05
with dopamine and dobutamine 15 ,g/kg/min). Mean SVI
was not changed significantly by dobutamine 5 ,ug/kg/min
or epinephrine.
Left Ventricular Stroke Work Index (LVSWI)
00 0
0
LVSWI increased 36%, 58% and 49% for dobutamine 5,
10 and 15 ,ug/kg/min respectively (table 3, fig. 4). With
dopamine the increases were respectively 82%, 74%, and
93%, and the increase for epinephrine was 52%. (P < 0.05
for epinephrine, for the other values P < 0.01).
INOTROPIC DRUGS AFTER BYPASS/Steen et al.
381
5
N
**
4
'N
3
124.9%
(.Q
2
-
-9
CZ)
FIGURE 1. Changes in cardiac index with
epinephrine (0.04 gg/kg/min), dopamine (10
.tg/kg/min), and dobutamine (JO uig/kg/min)
after 10 min. Vertical lines represent standard
error of mean.
I1
n
0
Control Epinephrine
Control Dopamine
0.04 ,pg/kg/min
lOpg/kg/min
10 min
10 min
** P<0.01
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
Arrhythmias
One patient developed a brief run of ventricular tachycardia during dopamine 10 ,ug/kg/min infusion. The dopamine
dosage was reduced, lidocaine administered, and the
arrhythmias did not recur. One patient had a short run of
bigeminy during dobutamine infusion. Occasional PVCs
were seen in most patients in all groups, most commonly
with surgical manipulation. Qualitative differences between
the three agents with regard to arrhythmogenicity were not
apparent.
used. Changes in cardiac output are due to bleeding, changing ventricular function, and peripheral resistance, combined with anesthetics. Because bleeding can be considerable
during this period, we chose to transfuse in order to maintain constant left atrial pressure; thus increases in output
after inotropic drug infusion reflect increased inotropic state
at constant preload. Return of output to ± 10% of control
values after discontinuance of inotropic drugs in all cases is
evidence that output changes reported were predominantly
due to the inotropic agents themselves.
The dosages 5, 10 and 15 Ag/kg/min for dopamine4 7-10
and dobutaminel 2, 5,6 11 were chosen because similar
dosages were used in previous reports in other situations,
and to compare potencies. In open chest dogs, Tuttle and
Mills12 found dobutamine to be four times more potent than
dopamine with respect to increasing contractile tension, yet
Loeb et al.9 reported that dopamine was twice as potent as
dobutamine in increasing cardiac output in patients with
chronic low output. The epinephrine dosage of 0.04
,gg/kg/min was chosen because pilot studies indicated that it
would cause cardiac output increases similar to those caused
by 10 ,ug/kg/min dobutamine.
Cardiac index increases observed in this study with
Blood Gas, Acid Base, and Electrolyte Balance
Mean values are listed in table 4. All patients had adequate blood gas, acid-base, and electrolyte values.
Discussion
Emergence from cardiopulmonary bypass is a unique
situation with obvious potential for unstable hemodynamics.
Results of any study conducted during this period must be
interpreted with caution. This is, however, a period during
which inotropic drugs are commonly, often uncritically,
125
0
100
-
_
+1
**4
26.8%
cq
*.2
=17
Control Dobutamine
10 jiglkglmin
10 min
75
20.8%
]21.2%
-
FIGURE 2. Changes in mean arterial pressure
with epinephrine (0.04 ,ug/kg/min), dopamine (10
,ug/kg/min), and dobutamine (10 jggkg/min)
after 10 min. Vertical lines represent standard
error of mean.
(a5
9)
N.
50-
95
1.C
95
I'.
95
25
n
=10
n
ni20|
Control Epinephrine
Control Dopamine
0.04 pg kg/ min
10 ,pglkg/min
** P<0.01
10 min
0 min
1-
n1
1
Control Dobutamine
10 jiglkg/min
10 min
382
VOL 57, No 2, FEBRUARY 1978
CIRCULATION
TABLE 3. Hemodynamic Changes with Intropic Drug Administration: Heart Rate, Systemic Resistance, Stroke Volume Index. Left
Ventricular Stroke Work Index
Drug
Dosage
(sg/kg/min)
Time
(min)
N
5
10
5
11
17
10
5
10
5
10
7
Control
Systemic vascular resistance (dynes/sec/cm-')
Control
With drug
% change
Heart rate (beats/min)
With drug
% change
_
Dob utamine
Dob utamine
Dob utamine
Dop amine
Dop amine
Dop amine
Epiriephrine
5
10
15
5
10
15
0.04
102 = 5
103 3
112 * 6
110* 4
+ 7%*
106 * 4
91 6
113* 6
99 i 7
+ 7%
+ 9%
97*4
20
6
10
100 * 9
103*4
109*
5
113 12
115* 4
+10%*
1244 * 135 1390 * 121
1302* 78 1274 * 103
1353 * 146 1232 * 121
1117 * 131 1054 * 136
+12 %*
1159 * 76 982 * 87
1464 * 140 1214 * 154
1200* 80 1228 112
+13%
+11%
5
10
15
5
10
15
0.04
5
10
5
5
10
5
10
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
Values are mean sEM.
*p <0.05.
**p <0.01.
N = number of studies; Time
]11
I17
]10
7
20
6
I10
25.0
1.8
23.6 * 1.8
21.0 * 1.5
27.9 * 2.4
28.6 * 1.8
25.0 * 1.8
+11%
+21%**
30.0 * 3.5
24.9 * 1.9
41.4 * 4.1
37.7 * 2.7
20.2 * 2.2
26.7 * 2.4
30.0 * 4.6
29.2 * 3.3
+38%o**
+51%**
+49%*
125
Tr
*
11.4%
11.8%
100
(g.m/beat/mr2)
Control
25.9
20.4
17.3
28.3
22.1
20.7
+19%*
26.4
+ 9%0
*
*
*
*
*
With drug
2.5
2.1
1.8
4.3
2.2
1.9
35.3 * 3.7
32.2 3.7
25.7 * 2.2
51.6
5.2
38.4 * 3.9
39.9 4.7
3.8
40.1
5.1
% change
+36%**
+58%**
+49%**
+82%**
+74%**
+93%**
+52%*
twice as potent in this usage as dobutamine. This is in agreement with Loeb et al.9 who found equivalent increases in CI
for 10.3 gg/kg/min dobutamine vs 5.4 ug/kg/min
dopamine.
With epinephrine, Goldenberg et al.'4 reported a 78-98%
increase in CI with 0.15-0.30 ,g/kg/min. Barcroft and
Starr 15 found a 40% CI increase with 0.10-0.18 ,ug/kg/min,
again in circumstances other than emergence from bypass.
We interpret our results to be in general agreement.
The arterial pressure increases noted with all three drugs
are in agreement with most studies 5 6 8, 10, 11,14, 15
although some investigations4 8 18 have not observed significant increases in MAP with dopamine or dobutamine.
Despite the larger output increases seen with dopamine, the
increase in MAP with this drug was not significantly higher
than that for dobutamine or epinephrine. This is interpreted
as indicating a greater tendency of dopamine to produce
peripheral vasodilation, although a significant (P < 0.01)
decrease in calculated systemic vascular resistance was
found with the 10 Mg/kg/min dose of dopamine only. The
4S 4-
17.3%
75
FIGURE 3. Changes in heart rate with epinephrine (0.04 Aglkg/min), dopamine (10
,ug/kg/min), and dobutamine (10 Ag/kg/min)
after 10 min. Vertical lines represent standard
error of mean.
05
'5
50
05
25
oL
6%
15%**
-17%
+ 2%
time after start of administration of drug that indices were measured.
dobutamine are similar to those we previously reported during emergence from bypass' but somewhat lower than those
reported by others in other situations. Loeb et al.9 used
dobutamiiie 10.3 ,Ag/kg/min in 13 patients with chronic low
cardiac output, and reported a 34% increase in CI. Jewitt et
al.5 observed CI increases of 23 and 43% with 5 and 10
,Ag/kg/min dobutamine respectively in ten patients with coronary artery disease. Sakamoto et al.P reported 22 and 38%
CI increases with 4 and 8 Ag/kg/min dobutamine respectively in 22 patients several hours after cardiac surgery.
Kersting et al.2 found 47 and 91 % CI increases with
dobutamine 5 and 10 gg/kg/min respectively, in cardiac
surgical patients. Our lower CI increases of 15 and 25% for 5
and 10 ,g/kg/min dobutamine might in part be accounted
for by higher control cardiac indices. Also, our
measurements are not exactly comparable, being the only
ones obtained during emergence from bypass.
With dopamine, our CI increases of 44, 53 and 64% with
5, 10, and 15 ,/kg/min are in approximate agreement with
other reports.4 0,1 We conclude that dopamine is about
45
-
Left ventricular stroke work index
Stroke volume index (ml/stroke/m2)
Control
With drug
% change
Dobutamine
Dobutamine
Dobutamine
Dopamine
Dopamine
Dopamine
Epinephrine
+11%
- 2%
- 9%
LI
.t2I
I
n
f20
Control Epinephrine
Control Dopamine
0.04 ig/kg/min
10 yg/kg/min
*P<0.05
10 min
10 min
n 17
Control Dobutamine
10 pg/kg/min
10 min
INOTROPIC DRUGS AFTER BYPASS/Steen et al.
,c
383
50
*
**
.1
40
a
'&
c
I..
1.1X)
-
30
_FIGURE 4. Changes in left ventricular stroke
work index with epinephrine (0.04 ,ug/kg/min),
dopamine (10 ,g/kg/min). and dobutamine (10
gg/kg/min) after 10 minutes. Vertical lines represent standard error of mean.
57.9%
§
Q
20
_0
10
a
n*7
Control Epinephrine
* P<0.05
** P<0.01
0.04 pglkglmin
10 min
Control Dopamine
Control Dobutamine
10 pg/kgimin
10 pglkg/min
1 0 min
10 min
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vasodilating effects of lower doses of dopamine, especially
the renal and mesenteric vascular beds, are well
documented, and are thought to be overridden by
receptor-stimulated vasoconstriction at higher doses.4 7 8 13
In the present study, only four of 20 patients developed an
10
increase in peripheral vascular resistance at lg/kg/min
dopamine, and only one of six did so at the 15 Ag/kg/min
dosage. The failure to note increased vascular resistance in
most patients at higher dopamine doses may be due to recent
cardiopulmonary bypass, with the possibility that rewarming was not yet complete in all vascular beds, despite the fact
that nasopharyngeal temperatures were in the normal range.
Epinephrine did not alter peripheral vascular resistance,
possibly because the dose (0.04 ,g/kg/min) was sufficient to
have obtained roughly equal a and A effects. Dobutamine
has been reported to be more cardioselective than
epinephrine or dopamine, and this quality may explain the
lack of change in peripheral vascular resistance seen with
on
a
it. 12,
16
All three drugs induced significant increases in left ventricular stroke work index, roughly proportionate to the increases in cardiac index. Because the studies were carried
out with left atrial pressures held as constant as possible by
transfusion, we interpret the increases in cardiac index and
left ventricular stroke work index as evidence of increased
contractility.
Heart rate increases were approximately 10% for all three
drugs. This is in sharp contrast to the 43.9% increase in
mean heart rate we reported earlier6 with 0.02 ,ug/kg/min
isoproterenol, again during emergence from bypass.
Further, isoproterenol was associated with severe
arrhythmias in that study.8 The three drugs studied herein
were not associated with potentially dangerous arrhythmias,
except in one instance with dopamine. The marked
chronotropicity and arrhythmogenicity of isoprotere-
17. 118 are reasons why the positive inotropic effects of
this drug are often not able to be fully utilized. The
arrhythmogenicity of isoproterenol (and epinephrine) are, of
course, well known to be enhanced in the presence of
halogenated anesthetics, especially halothane. Evidence that
isoproterenol may harmfully increase 02 demand is
provided by Maroko et al.'9 who have shown in dogs that
acutely produced experimental myocardial infarctions can
be extended by treatment with the drug.
Another property of isoproterenol which may set it apart
from the three drugs studied herein is the fact that the
skeletal muscular vasodilation caused by it may divert the
increased output (wastefully) to that tissue.'2 '7
Isoproterenol has been reported to induce enough skeletal
muscle vasodilation to actually decrease MAP (and coronary perfusion).' 12, 20
With respect to comparisons between dopamine,
dobutamine, and epinephrine, dopamine resulted in the
largest increases in cardiac index at the chosen dosages during emergence from bypass. However, it also resulted in
systemic vascular dilation. This may not be desirable during
this critical period because of the resultant increase in
myocardial oxygen requirement. Renal vasodilation is of
course a likely part of the dopamine effect, and is of potential longer-term benefit, but the cardioselectivity of
dobutamine might be better during the immediate postbypass period. In addition, there is evidence that dopamine
may depend upon release of endogenous catecholamines for
part of its action.'2 These catecholamine stores have been
reported to be depleted in some patients with longstanding
myocardial failure.2' It is therefore possible that the
relatively larger increases in output reported here for
dopamine may not be well sustained. We have no evidence
on this point.
Epinephrine resulted in the largest increases in pulse pres-
nol45
TABLE 4. Blood Gases, Electrolytes, and Acid Base Data Just After Emergence from Bypass
PaO2
Dobutamine
Paco,
34 - 1
195
Dopamine
Epinephrine
34
34
196
173
Values are mean ± SEM.
BE = base excess.
i
t
1
1
-
i
pHa
17
21
20
7.44 i 0.01
7.43 ' 0.01
7.44 0.03
:
Nat
BE
-0.5
-0.5
-0.5
-
i
K
0.4
140 -fi1
3.6
-
0.1
0.4
0.7
140
139
3.6
3.1
-
0.1
0.2
-
1
0
-
384
CIRCULATION
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sure. This has negative implications, especially after aortic
valve replacement, because of increased bleeding and possible compromise of aortic suture line integrity by inordinately high systolic pressure.
Monitoring arterial and atrial pressures only, as is common practice, proved to be unreliable in assessing efficacy of
inotropic drug administration. There were seven instances in
which little or no increase in mean arterial pressure was
noted during the inotropic drug administration, yet cardiac
index increased markedly. There were, by contrast, seven
other instances in which the inotropic agent led to
"satisfying" arterial pressure increases with little or no increase in cardiac index. We could not single out any of the
three drugs as more likely to be associated with such a disparity.
Increasing cardiac output and arterial pressure with inotropic drug alone may not be wise if myocardial oxygen
supply/demand ratio is unfavorably affected. Oxygen demand is increased with inotropic agent-induced increases in
contractility, heart rate, and aortic pressure. In some patients it seems beneficial to reduce aortic pressure with
vasodilators alone. In other circumstances, vasodilators
must be combined with inotropic drug to maintain adequate
perfusion pressure. No studies including vasodilators during
emergence from bypass have yet been reported. We do not
imply that inotropic drug administration, even if accompanied by satisfying increases in output and pressure, is
necessarily beneficial. Inotropic drugs are probably needed
when severe myocardial failure occurs during the emergence
period.
We conclude the following: 1) dopamine, 5-15
Ag/kg/min; dobutamine, 5-15 ,ug/kg/min; and epinephrine,
0.04 ,ug/kg/min, all are suitable for inotropic support during
emergence from cardiopulmonary bypass, to produce increases in cardiac index at constant left atrial pressures,
small increases in heart rate, and no severe arrhythmias; 2)
dopamine appears about twice as potent as dobutamine for
this purpose, although dobutamine appears to be more cardioselective; 3) considerable variance in individual patient
responses should be expected. It is recommended that cardiac performance during the period immediately following
bypass is best assessed by serial measurements of cardiac
output. Reliance upon left atrial and arterial pressures alone
may be inadequate, especially for evaluation of the results of
inotropic drug administration.
VOL 57, No 2, FEBRUARY 1978
Acknowledgment
We acknowledge the excellent technical assistance of Mr. Richard Finley
and his associates.
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Efficacy of dopamine, dobutamine, and epinephrine during emergence from
cardiopulmonary bypass in man.
P A Steen, J H Tinker, J R Pluth, D A Barnh;rst and S Tarhan
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Circulation. 1978;57:378-384
doi: 10.1161/01.CIR.57.2.378
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