Ann Thorac Surg 1995;60:1741-1744
© 1995 The Society of Thoracic Surgeons
Original Articles: Cardiovascular
Effects of Dopamine on Liver Blood Flow in Children With Congenital Heart Disease
Ian M. Mitchell, FRCS,
James C. S. Pollock, FRCS,
Morgan P. G. Jamieson, FRCS
Department of Cardiac Surgery, Royal Hospital for Sick Children, Glasgow, Scotland
Accepted for publication August 3, 1995.
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Abstract
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Background. A reduction in liver function is common after cardiac operations, particularly in children with preexisting cardiac failure. The etiology is multifactorial, but the redistribution of organ blood flow that occurs during cardiopulmonary bypass implicates ischemia as one of the principal causes of injury. Dopamine hydrochloride is known to have specific effects on the renal circulation, and the aim of this study was to investigate its effects on hepatic perfusion.
Methods. Eight children with congenital heart disease were studied 6 hours after the end of cardiopulmonary bypass when they were fully rewarmed and hemodynamically stable. Using noninvasive auricular densitometry, we determined the percent disappearance rate of indocyanine green as an index of liver blood flow both before and 1 hour after commencing an infusion of dopamine at 4 µg•kg-1•min-1.
Results. Results showed an increase of approximately 31% in the percent disappearance rate of indocyanine green with the addition of low-dose dopamine (4 µg •kg-1•min-1) (p < 0.01).
Conclusions. Dopamine may have a therapeutic role in increasing hepatic perfusion and minimizing any loss in liver function.
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Introduction
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Hepatic injury after cardiopulmonary bypass is a well-recognized phenomenon of multifactorial etiology, although ischemia is usually the principal factor involved [1, 2]. In view of the reduction in liver blood flow observed during cardiopulmonary bypass [2–6] and the possibility of this persisting (in certain circumstances) into the early postoperative period [3, 6, 7], there is clearly a role for any therapeutic measure that either reverses or alleviates this situation.
General measures to increase the cardiac output may improve overall systemic perfusion, but in view of the changes in the systemic distribution of the blood supply during cardiopulmonary bypass [8, 9], this may be of limited benefit to individual organs, in particular the liver. A specific measure able to alter the blood flow to an individual organ would be more desirable. Dopamine hydrochloride is an agent known to exert a specific effect on at least one vascular bed, as it is well established that it can increase renal blood flow [10, 11]. Although it is possible that this increase is achieved at the expense of splanchnic blood flow, there is some evidence that it may actually increase as well [12, 13].
The aim of this study was to investigate the effects of dopamine on liver blood flow after cardiopulmonary bypass in children, because surgical intervention in this group has been shown to be associated with reduced hepatic perfusion and loss of function [6, 7].
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Patients and Methods
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This study was approved by the hospital ethics committee, and informed consent was obtained from the parents of each child involved.
Eight children with congenital heart disease were studied on the intensive care unit once they were fully rewarmed and hemodynamically stable, approximately 6 hours after the end of cardiopulmonary bypass. Each had undergone operation with standard anesthesia and bypass techniques and had had total correction of the cardiac defect. Patient and operative details are shown in Table 1
. Each operation was judged to be of similar complexity and resulted in similar bypass times. Each child was ventilated and sedated in a standard fashion using midazolam hydrochloride and morphine sulfate until the end of the study period, and no child received any inotropic or vasoactive drug other than the dopamine used for this study. Heart rate, blood pressure, urine output, and peripheral temperature were monitored throughout the study period in each patient.
Liver blood flow was estimated by calculation of the percent disappearance rate (PDR) of indocyanine green using noninvasive auricular densitometry. A Waters XE-302 earpiece (Waters Instruments Inc, Rochester, MN) was attached to the patient's ear after the latter was cleaned with an alcohol swab and rubbed briskly. The earpiece was covered with a cloth to reduce interference from background light and connected to a D-402A dichromatic densitometer (Waters Instruments Inc). We switched this apparatus on and allowed it to warm up for 10 minutes before adjusting the baseline to zero.
Indocyanine green (0.5 mg/kg; Hynson, Westcott and Dunning, Baltimore, MD) was then rapidly injected as a bolus dose into a central venous catheter. A printer attached to the densitometer recorded the changes in dye concentration monitored by the earpiece. The initial deflection provided an index of cardiac output (calculated from the area under the first curve), and the subsequent decline followed hepatic excretion. The hepatic clearance curve was analyzed by noting the densitometer deflection at 2-minute intervals starting with the third minute and plotting these points against time on the y-axis of semilogarithmic paper so as to produce a straight line. The half-life for clearance of the dye (t
) was measured in minutes, and the PDR was calculated using the following formula:
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Calculating the PDR rather than the clearance itself eliminates the need to ensure that an accurate dose of indocyanine green is given to each child, as clearance is calculated from the product of k, the elimination rate constant (Loge 2/t) and the volume of distribution (dose of dye/concentration at time zero). This technique has previously been validated for use in the context of cardiac surgery [6, 14].
Once a reliable measurement had been obtained, an infusion of dopamine, 4 µg•kg-1•min-1, was started through a primed central venous catheter. After 1 hour, another injection of dye was given and the PDR, recalculated.
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Results
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The results are summarized in Table 2 and displayed graphically in Figure 1. Each patient was fully rewarmed prior to the initial PDR measurement. Heart rate, blood pressure, urine output, and peripheral temperature were stable throughout the study period in each patient. In 7 children, there was a significant mean increase of approximately 31% in the PDR of indocyanine green with the addition of low-dose dopamine (4 µg•kg-1•min-1) (p < 0.01 by t test). The management and the postoperative course of the remaining patient, patient 4, were no different from those in the rest of the group. Inclusion of this atypical result does not significantly detract from the probability value and overall conclusion.
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Fig 1. . Effects of dopamine, 4 µg•kg-1•min-1, on the percent disappearance rate (PDR) of indocyanine green 6 hours after the end of cardiopulmonary bypass.
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Comment
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Hepatic perfusion is reduced during cardiopulmonary bypass and in certain circumstances may remain low postoperatively [3, 6, 7]. Not only does this risk irreversible tissue injury and frank hepatic failure, but it also leads to an alteration in many metabolic pathways with important short-term consequences; in particular, both drug metabolism and drug pharmacokinetics [3] may be adversely affected and because of the associated gut mucosal hypoperfusion, intestinal permeability may be altered, thus leading to an increased risk of endotoxemia [15, 16]. Malabsorption may also complicate splanchnic ischemia, with direct consequences for postoperative enteral nutrition [16] in addition to the indirect consequences of impaired hepatic nutritional homeostasis [6].
In adults, there is an increasing trend toward use of the gastroepiploic artery as a conduit for coronary artery bypass grafting. Although this is technically attractive and may provide good long-term patency, there is clearly a risk of inducing splanchnic vasoconstriction and therefore reducing graft flow with an injudicious choice of inotropic agents should cardiac output fall. Any therapeutic maneuver that is able to overcome these problems associated with hepatic and splanchnic hypoperfusion is potentially of great clinical benefit, particularly if the effect is organ specific and not simply part of a systemic effect.
Dopamine is known to increase renal blood flow independent of any effect on cardiac output and probably does so by activation of DA1 receptors in the renal vascular bed, resulting in a greater degree of preglomerular than postglomerular arteriolar vasodilation [17]. There is some evidence that this response is not only dose related but may also be age related (perhaps a result of the maturation process of renal dopamine receptors) [17]. However, the question has been raised as to whether the effect on renal blood flow occurs at the expense of splanchnic blood flow [18, 19], or whether it may actually have a similar effect on this part of the circulation as well. Renal hypoperfusion is a common observation after cardiopulmonary bypass in children [17], and the therapeutic use of dopamine in reversing this is well known. A similar role in reversing hepatic hypoperfusion would be a further advantage to its use.
Investigation of the effects of dopamine administration on the splanchnic blood supply in animals has yielded inconclusive results and has demonstrated only modest dilatation of the mesenteric arteries [18, 20–23]. Four groups have studied this question in humans, and although there was no increase in liver blood flow with 4 µg•kg-1•min-1 of dopamine in one series studying adults with cardiomyopathic heart failure [24], this is in contrast to other studies.
In a series of publications, Angehrn and colleagues [12, 13, 19, 25] clearly documented an increase in hepatic perfusion after dopamine administration. In the first of these in which the indocyanine green clearance technique was used to measure liver blood flow in 9 patients without heart failure undergoing cardiac catheterization, dopamine at 4 µg•kg-1•min-1 was observed to increase hepatic perfusion by 33% and at 8 µg•kg-1• min-1, to increase perfusion by 35% [25]. The corresponding increases in the cardiac index, however, were only 17% and 20%, respectively, giving only a small, but significant increase in the liver blood flow to cardiac index ratio from 0.25 to 0.27 and from 0.23 to 0.26, respectively [25]. In a second series of patients studied 24 hours after cardiopulmonary bypass and valve replacement [19], dopamine at 6 µg•kg-1•min-1 produced an 82% increase in liver blood flow and a similar (significant) increase in the liver blood flow to cardiac index ratio as reported earlier. These results demonstrate that dopamine has a specific effect on the splanchnic circulation just as it does on the renal vasculature. The improvement in hepatic perfusion is therefore not simply the result of an increase in cardiac output.
The effects of intraoperative dopamine administration have been reported by Peschl [11] and Shimazu and co-workers [26]. In the first of these studies, dopamine was given in doses of both 4 and 8 µg•kg-1•min-1 to a small number of patients with jaundice, cirrhosis, or both. Direct measurement demonstrated an increase of up to 28.5% in intraoperative portal blood flow and up to 6.3% in hepatic artery blood flow [11]. Studying the effects of dopamine at 3 µg•kg-1•min-1 in 15 patients undergoing cholecystectomy, Shimazu and colleagues [26] demonstrated by local thermodilution and by direct measurement (respectively) that portal venous flow increased by 24% with no change in the hepatic artery flow. Because the cardiac output did not change over the study period, Shimazu and colleagues concluded that portal venous flow can increase independent of cardiac output.
The effects of dopamine on liver blood flow in children or indeed in any patient in the first few hours after cardiopulmonary bypass are important considerations in view of the suggestion that the effects of dopamine may be age related [17] and in view of the reduction in hepatic perfusion that may persist after cardiopulmonary bypass. Our results demonstrate that dopamine at 4 µg • kg-1• min-1 increases hepatic perfusion after bypass by almost one third in children between the ages of 1 year and 12 years. This is in keeping with the results in adults discussed earlier and is of particular relevance in children because of the importance of the liver in nutritional homeostasis and because of the need to reestablish adequate liver function in the early postoperative period. In the same way that dopamine has traditionally been used to improve renal function postoperatively, it would appear that this drug might have a further therapeutic role in increasing hepatic perfusion and minimizing any loss in liver function. Furthermore, dopamine does not appear to increase renal blood flow at the expense of splanchnic perfusion as has been suggested.
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Acknowledgments
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This study was funded by grants from the Association for Children with Heart Disorders and Tenovus-Scotland.
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Footnotes
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Address reprint requests to Mr Mitchell, Department of Cardiothoracic Surgery, Nottingham City Hospital, Hucknall Rd, Nottingham, NG5 1PB, England.
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Abstract
Introduction
