From the Pulmonary and Critical Care Division, Department of Internal
Medicine, University of Texas Southwestern Medical Center at Dallas.
Correspondence to Robert L. Johnson, Jr, MD, Pulmonary and Critical Care Division, Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75235-9034. E-mail rjohn2{at}mednet.swmed.edu
Dopamine
is an endogenous catecholamine that
preferentially reduces renal vascular resistance and increases
glomerular filtration rate, urine flow, and solute
excretion in normal subjects.1 In contrast to
norepinephrine, it increases cardiac output and aortic
pressure without raising systemic vascular resistance
(Table
The article by van de Borne et al10 brings
these observations into a clearer clinical perspective with better
quantification and a more unified interpretation of the different
effects of low-dose dopamine on gas exchange. They are not trivial. The
effects on carotid body function and on efficiency of alveolar
capillary gas exchange have been well documented in the past but are
not widely recognized clinically. In the late 1960s, high
concentrations of dopamine were measured in the carotid body, higher
than any other catecholamine.14 It
was later shown that dopamine inhibits chemoreceptor discharge from the
carotid body and very likely has the same effect on aortic
bodies.15 In 1975, Zapata16
reported that superfusion of isolated carotid bodies with dopamine in
Locke solution depresses the frequency of chemoreceptor discharges
recorded from the nerve trunk. Complete inhibition of chemoreceptor
discharges from the in situ carotid body of the cat could be elicited
by infusing a 2-µg bolus of dopamine into the carotid
artery.17 Depression of the ventilatory response
to hypoxia by intravenous dopamine infusion in
normal humans was reported first in 1978 by Welsh et
al.11 In their study, dopamine also caused a
slight but significant decrease in ventilation and an increase in
PaCO2 in normal subjects breathing
air.
Huckauf et al13 reported that dopamine infusions
induced hypoxemia in patients with left heart failure, which was
primarily explained by an increased alveolar-arterial
O2 tension difference
(A-aPO2), presumably from uneven
regional matching of blood flow to alveolar ventilation (ie, uneven
distribution of
In summary, available data from multiple sources now indicate that
dopamine infusions in critically ill patients can interfere with 2
important protective mechanisms against a fall in arterial
O2 saturation in the presence of uneven
distribution of alveolar ventilation: it can (1) depress local
vasoconstriction in response to alveolar hypoxia, which
normally keeps perfusion appropriately matched to ventilation in the
lung, and (2) depress the chemoreceptor drive to ventilation normally
induced by arterial hypoxemia and probably hypercapnia. As
pointed out by van de Borne et al,10 the 2
effects are synergistic. Both mechanisms can usually be counterbalanced
by modest use of supplemental oxygen if substantial anatomic
right-to-left shunts are not present. In mechanically ventilated
patients, depression of ventilatory drive is not a problem. In some
instances, reduced ventilatory drive during mechanical ventilation can
be beneficial by reducing any tendency to fight the ventilator.
However, problems can arise when the patient is taken off mechanical
support. The patient in whom the carotid body is functionally ablated
by a continuous dopamine infusion actually may be easier to remove from
mechanical support than one with an intact carotid body because the
former does not feel the conscious discomfort from hypoxemia and
possibly also from hypercapnia. This blunting of conscious discomfort
evoked by arterial hypoxemia and hypercapnia reflects the
loss of another protective mechanism provided by normal carotid body
function. In the study by van de Borne et al,10
normal subjects could hold their breath longer and allow their
O2 saturation to fall to significantly lower
levels during low-dose dopamine infusion than under control conditions.
Thus, the patient being weaned from ventilatory support while still
receiving dopamine may not be able to give the physician important
symptomatic feedback of impaired gas exchange; the
physician must depend on objective measurements. This potential problem
is not generally recognized, as is evident from a recent article in
The New England Journal of Medicine.18 The
article concerns recognition of patients for "earlier discontinuation
of mechanical ventilation, without harm to the patient." In the study
protocol, it is stated that during weaning no infusions of vasopressor
agents or sedatives are allowed (with the exception of renal-dose
dopamine). Paradoxically, as suggested above, the patient receiving
low-dose dopamine may be easier to wean than a patient with normal
peripheral chemoreceptor drive, but with the potential
danger of precipitating respiratory failure.
There is another intriguing aspect of the results obtained by van de
Borne et al10 in patients with heart failure that
was not discussed in detail. Ventilation was significantly depressed in
normoxic patients with heart failure by low-dose dopamine infusion,
which resulted in a fall of arterial
O2 saturation and a significant rise in end-tidal
PCO2. The latter results suggest a
significant depression of the ventilatory response not only to
O2 but also to
CO2. The data of Huckauf et
al13 also suggest that dopamine suppresses the
carotid body response to hypercapnia as well as hypoxemia. This is
consistent with observations in cats that dopamine
significantly reduces chemoreceptor drive in response to both hypoxemia
and hypercapnia.12 This has not been
systematically examined in humans, particularly in patients with
mechanically abnormal lungs. An increase in mechanical load imposed on
respiratory muscles can amplify an impaired ventilatory response to
CO2, whereas the effect may be
difficult to detect in subjects with normal lung
mechanics.19
None of the data presented by van de Borne et
al10 imposes a contraindication to appropriate
use of low-dose dopamine in critically ill patients as long as the
possible side effects on gas exchange are recognized and avoided. It
seems prudent to avoid low-dose dopamine when weaning patients from
mechanical ventilation unless arterial
O2 saturation is closely monitored.
Perhaps the most important message that should be derived from the
study by van de Borne et al10 is an expanded need
to define more clearly the appropriate clinical uses for renal-dose
dopamine. Although there is a theoretical rationale for use of low-dose
dopamine, its clinical efficacy remains largely unsupported by
data.20 21 22 In view of the potentially
detrimental effects, the clinical rationale for use of renal-dose
dopamine should be more clearly defined, as pointed out in an excellent
review by Denton et al.22
Acknowledgments
My thanks to Dr Orson Moe for his helpful critique of the
manuscript.
Footnotes
The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.
References
© 1998 American Heart Association, Inc.
Editorials
Low-Dose Dopamine and Oxygen Transport by the Lung
Key Words: Editorials • lung • ventilation • hypoxia • chemoreceptors • 
/
mismatch
) and increases rather than
decreases renal blood flow. Hence, dopamine was suggested as a
potentially valuable pharmacological agent for treatment of cardiogenic
and septic shock,2 3 particularly in patients who
were oliguric. Even at low doses (ie, <5 µg ·
kg-1 · min-1), at
which hemodynamic effects are relatively small, it
raises glomerular filtration and causes modest
diuresis in normal subjects that might protect against acute
renal failure in oliguric patients who are in shock or heart
failure.4 5 6 7 The synthetic
catecholamine dobutamine was introduced later
and had many features similar to those of dopamine but without
preferential renal vasodilation.8 However, at
high infusion rates, dobutamine enhances cardiac output,
stroke index, and O2 transport more effectively
than dopamine,9 and it also minimizes afterload
on the left ventricle. Dobutamine now is more often used
for hemodynamic support in heart failure or cardiogenic
shock, although the 2 drugs are sometimes used together for their
complementary effects. Low-dose or so called "renal-dose" dopamine,
however, has become widely used in intensive care units for its
presumed protective effect on renal function in patients undergoing
major surgical procedures, patients with refractory heart failure, and
patients with cardiorespiratory failure who are receiving ventilatory
support. In these settings, it is often considered to be relatively
free of serious adverse effects. However, as pointed out by van de
Borne et al10 in this issue of
Circulation, there are two potentially detrimental effects
of low-dose dopamine on oxygen transport that are often overlooked.
Dopamine has been shown (1) to impair the ventilatory response to
hypoxemia and hypercapnia by a depressive effect on the carotid
body11 12 and (2) to reduce arterial
oxygen saturation at a given alveolar oxygen tension by impairing
regional ventilation/perfusion (/) matching in the
lung9 13 (Table).
View this table:
[in a new window]
Table 1. Comparing Effects of Catecholamines on Hemodynamics and Gas
Exchange / ratios). However, hypoxemia was
aggravated by a small but statistically significant rise in
arterial PCO2. Shoemaker
et al9 have reported a progressive decrease in
arterial PO2 with
increasing rates of dopamine infusion in critically ill patients after
major surgery, which was also attributed to uneven /
matching in the lung.
This article has been cited by other articles:
 |
|
 |
|
  Y. A. Debaveye and G. H. Van den Berghe Is There Still a Place for Dopamine in the Modern Intensive Care Unit? Anesth. Analg., February 1, 2004; 98(2): 461 - 468. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||