Editorial
Low-Dose Dopamine and Oxygen Transport by the Lung
Robert L. Johnson, Jr, MD
D
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cation 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-mg 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 V̇/Q̇ 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 V̇/Q̇ matching in the lung.
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
opamine 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) 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 mg z kg21 z min21), 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 –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
(V̇/Q̇) matching in the lung9,13 (Table).
See p 126
The article by van de Borne et al10 brings these observations into a clearer clinical perspective with better quantifiThe opinions expressed in this editorial are not necessarily those of the
editors or of the American Heart Association.
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 [email protected]
(Circulation. 1998;98:97-99.)
© 1998 American Heart Association, Inc.
97
98
Low-Dose Dopamine
Comparing Effects of Catecholamines on Hemodynamics and Gas Exchange
Dopamine
Norepinephrine
Low-Dose
(,5 mg z kg21 z min21)
High-Dose
(.5 mg z kg21 z min21)
Dobutamine
Cardiac output
7
7
1
_
Systemic blood pressure
_
7
1
7
Heart rate
2
7
1
1
Systemic vascular resistance
_
7
2
+
Renal blood flow
2
_
1
7
Glomerular filtration rate
7
1
1
7
Chemoreceptor function
7
2
2
7
A-aPO2
7
1
_
7
O2 transport
7
2
1
_
A-aPO2 indicates alveolar-arterial O2 tension difference; 7, no change; 1, increase; 2, decrease; _, more
profound increase; +, more profound decrease.
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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 –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
Acknowledgment
My thanks to Dr Orson Moe for his helpful critique of the
manuscript.
References
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KEY WORDS: Editorials
n V̇/Q̇ mismatch
n lung n
ventilation
n hypoxia n chemoreceptors
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Low-Dose Dopamine and Oxygen Transport by the Lung
Robert L. Johnson
Circulation. 1998;98:97-99
doi: 10.1161/01.CIR.98.2.97
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