Low-Dose Dopamine and Oxygen Transport by the Lung
1998; Lippincott Williams & Wilkins; Volume: 98; Issue: 2 Linguagem: Inglês
10.1161/01.cir.98.2.97
ISSN1524-4539
Autores Tópico(s)Renal function and acid-base balance
ResumoHomeCirculationVol. 98, No. 2Low-Dose Dopamine and Oxygen Transport by the Lung Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBLow-Dose Dopamine and Oxygen Transport by the Lung Robert L. Johnson Robert L. JohnsonRobert L. Johnson From the Pulmonary and Critical Care Division, Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas. Originally published14 Jul 1998https://doi.org/10.1161/01.CIR.98.2.97Circulation. 1998;98:97–99Dopamine 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,23 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.4567 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 body1112 and (2) to reduce arterial oxygen saturation at a given alveolar oxygen tension by impairing regional ventilation/perfusion (V̇/Q̇) matching in the lung913 (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 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 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.19None 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.202122 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.22The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association. Table 1. Comparing Effects of Catecholamines on Hemodynamics and Gas ExchangeNorepinephrineDopamineDobutamineLow-Dose ( 5 mg · kg−1 · min−1)Cardiac output↔↔↑⇈Systemic blood pressure⇈↔↑↔Heart rate↓↔↑↑Systemic vascular resistance⇈↔↓⇊Renal blood flow↓⇈↑↔Glomerular filtration rate↔↑↑↔Chemoreceptor function↔↓↓↔A-aPo2↔↑⇈↔O2 transport↔↓↑⇈A-aPo2 indicates alveolar-arterial O2 tension difference; ↔, no change; ↑, increase; ↓, decrease; ⇈, more profound increase; ⇊, more profound decrease.My thanks to Dr Orson Moe for his helpful critique of the manuscript.FootnotesCorrespondence 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] References 1 McDonald RH Jr, Goldberg LI, McNay JL, Tuttle EP Jr. Effects of dopamine in man: augmentation of sodium excretion, glomerular filtration rate and renal plasma flow. J Clin Invest..1964; 43:1116–1124.CrossrefMedlineGoogle Scholar2 Goldberg LI. Cardiovascular and renal actions of dopamine: potential clinical applications. Pharmacol Rev.1972; 24:1–29.MedlineGoogle Scholar3 Goldberg LI. Dopamine: clinical uses of an endogenous catecholamine. N Engl J Med.1974; 291:707–710.CrossrefMedlineGoogle Scholar4 Lindner A, Cutler RE, Goodman G. Synergism of dopamine plus furosemide in preventing acute renal failure in the dog. Kidney Int.1979; 16:158–166.CrossrefMedlineGoogle Scholar5 Parker S, Carlon GC, Isaacs M, Howland WS, Kahn RC. Dopamine administration in oliguria and oliguric renal failure. Crit Care Med.1981; 9:630–632.CrossrefMedlineGoogle Scholar6 Varriale P, Mossavi A. The benefit of low-dose dopamine during vigorous diuresis for congestive heart failure associated with renal insufficiency: does it protect renal function? Clin Cardiol.1997; 20:627–630.CrossrefMedlineGoogle Scholar7 Flancbaum L, Choban PS, Dasta JF. Quantitative effects of low-dose dopamine on urine output in oliguric surgical intensive care unit patients. Crit Care Med.1994; 22:61–66.CrossrefMedlineGoogle Scholar8 Tuttle RR, Mills J. Dobutamine: development of a new catecholamine to selectively increase cardiac contractility. Circ Res..1975; 36:185–196.CrossrefMedlineGoogle Scholar9 Shoemaker WC, Appel PL, Kram HB, Duarte D, Harrier HD, Ocampo HA. Comparison of hemodynamic and oxygen transport properties of dopamine and dobutamine in critically ill surgical patients. Chest.1989; 96:120–126.CrossrefMedlineGoogle Scholar10 van de Borne P, Oren R, Somers VK. Dopamine depresses minute ventilation in patients with heart failure. Circulation..1998; 98:126–131.CrossrefMedlineGoogle Scholar11 Welsh MJ, Heistad DD, Abboud FM. Depression of ventilation by dopamine in man: evidence for an effect on the chemoreceptor reflex. J Clin Invest..1978; 61:708–713.CrossrefMedlineGoogle Scholar12 Lahiri S, Nishino T, Mokashi A, Mulligan E. Interaction of dopamine and haloperidol with O2 and CO2 chemoreception in carotid body. J Appl Physiol Respir Environ Exerc Physiol..1980; 49:45–51.MedlineGoogle Scholar13 Huckauf H, Ramdohr B, Schröder R. Dopamine induced hypoxemia in patients with left heart failure. Int J Clin Pharmacol Biopharm.1976; 14:217–224.MedlineGoogle Scholar14 Zapata P, Hess A, Bliss EL, Ezaguirre C. Chemical, electron microscopic and physiological observations on the role of catecholamines in the carotid body. Brain Res.1969; 14:473–496.CrossrefMedlineGoogle Scholar15 Lahiri S, Nishino MT, Mokashi A. Aortic body chemoreceptor responses to changes in Pco2 and Po2 in the cat. J Appl Physiol Respir Environ Exerc Physiol.1979; 47:858–866.MedlineGoogle Scholar16 Zapata P. Effects of dopamine on carotid chemo- and baroreceptors in vitro. J Physiol (Lond)..1975; 244:235–251.CrossrefGoogle Scholar17 Llados F, Zapata P. Effects of dopamine analogues and antagonists on carotid body chemosensors in situ. J Physiol (Lond). 1978;274:487–499.Google Scholar18 Ely EW, Baker AM, Dunagan DP, Burke HL, Smith AC, Kelly PT, Johnson MM, Browder RW, Bowton DL, Haponik EF. Effect on the duration of mechanical ventilation of identifying patients capable of breathing spontaneously. N Engl J Med..1996; 335:1864–1869.CrossrefMedlineGoogle Scholar19 Johnson RL Jr, Ramanathan M. Buffer equilibria in the lungs. In: Seldin DW, Giebisch G, eds. The Kidney, Physiology and Pathophysiology. 2nd ed. New York, NY: Raven Press; 1992;1:193–218.Google Scholar20 Swygert TH, Roberts LC, Valek TR, Brajtford D, Brown MR, Gunning TC, Paulsen AW, Ramsey MAE. Effect of intraoperative low-dose dopamine on renal function in liver transplant recipients. Anesthesiology.1991; 75:571–576.CrossrefMedlineGoogle Scholar21 Baldwin L, Henderson A, Hickman P. Effect of postoperative low-dose dopamine on renal function after elective major vascular surgery. Ann Intern Med.1994; 120:744–747.CrossrefMedlineGoogle Scholar22 Denton MD, Chertow GM, Brady HR. "Renal-dose" dopamine for treatment of acute renal failure: scientific rationale, experimental studies and clinical trials. Kidney Int.1996; 49:4–14.Google Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Lomivorotov V, Efremov S, Kirov M, Fominskiy E and Karaskov A (2017) Low-Cardiac-Output Syndrome After Cardiac Surgery, Journal of Cardiothoracic and Vascular Anesthesia, 10.1053/j.jvca.2016.05.029, 31:1, (291-308), Online publication date: 1-Feb-2017. Hebert K, Franco Ladron de Guevara E, Macedo Dias A and Vilches E (2015) Adrenergic Agents PanVascular Medicine, 10.1007/978-3-642-37078-6_237, (931-951), . TEERLINK J, SLIWA K and OPIE L (2013) Heart failure Drugs for the Heart, 10.1016/B978-1-4557-3322-4.00015-6, (169-223), . Hebert K, de Guevara E, Dias A and Vilches E (2014) Adrenergic Agents PanVascular Medicine, 10.1007/978-3-642-37393-0_237-1, (1-26), . POOLE-WILSON P and OPIE L (2009) Acute and Chronic Heart Failure: Positive Inotropes, Vasodilators, and Digoxin Drugs for the Heart, 10.1016/B978-1-4160-6158-8.50011-3, (160-197), . Karajala V, Raghavan M, Venkataraman R and Kellum J (2008) Therapeutic Role of Dopamine in Acute Heart Failure Syndrome Acute Heart Failure, 10.1007/978-1-84628-782-4_53, (577-582), . Ciarka A, Vincent J and van de Borne P (2007) The effects of dopamine on the respiratory system: Friend or foe?, Pulmonary Pharmacology & Therapeutics, 10.1016/j.pupt.2006.10.011, 20:6, (607-615), Online publication date: 1-Dec-2007. Boersma E (2006) Prehospital triage and treatment of suspected acute myocardial infarction Coronary Reperfusion Therapy in Clinical Practice, 10.1201/b15780-3, (19-41), Online publication date: 17-Jan-2006. Karthik S and Lisbon A (2006) CRITICAL CARE ISSUES FOR THE NEPHROLOGIST: Low-dose Dopamine in the Intensive Care Unit, Seminars in Dialysis, 10.1111/j.1525-139X.2006.00208.x, 19:6, (465-471) Debaveye Y and Van den Berghe G (2004) Is There Still a Place for Dopamine in the Modern Intensive Care Unit?, Anesthesia & Analgesia, 10.1213/01.ANE.0000096188.35789.37, (461-468), Online publication date: 1-Feb-2004. Opasich C, Russo A, Mingrone R, Zambelli M and Tavazzi L (2001) Intravenous inotropic agents in the intensive therapy unit: do they really make a difference?, European Journal of Heart Failure, 10.1016/S1388-9842(99)00061-6, 2:1, (7-11), Online publication date: 1-Mar-2000. Merekin D, Lomivorotov V, Efremov S, Kirov M and Lomivorotov V (2019) Low cardiac output syndrome in cardiac surgery, Almanac of Clinical Medicine, 10.18786/2072-0505-2019-47-035, 47:3, (276-297) July 14, 1998Vol 98, Issue 2 Advertisement Article InformationMetrics Copyright © 1998 by American Heart Associationhttps://doi.org/10.1161/01.CIR.98.2.97 Originally publishedJuly 14, 1998 KeywordsEditorialschemoreceptorsV̇/Q̇ mismatchhypoxiaventilationlungPDF download Advertisement
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