1032 Volume 7 - Number 7 ‘ 1996

Dopamine Does Not Enhance Furosemide-InducedNatriuresis in Patients with Congestive Heart Failure1Dennis L. Vargo, D. Craig Brater,2 David W. Rudy, and Suzanne K. Swan

DL. Vargo. D. Craig Brater, D.W. Rudy, S.K. Swan.Clinical Pharmacology Division, Department of Medi-cine. Indiana University School of Medicine, Indianap-ohs, IN

(J. Am. Soc. Nephrol. 1996; 7:1032-1037)

ABSTRACTThe objective of this study was to determine whetherthe addition of low-dose (renal-dose) dopamine tofurosemide therapy enhances natriuresis In patientswith compensated congestive heart failure, New York

Heart Association Class II or III. We performed arandomized, controlled, open-label, crossover studywherein urinary sodium, creatinine, and furosemide

excretion rates and GFR determined by inulin clear-ance rates were measured during each of threetreatment interventions: furosemide infusion alone,dopamine infusion alone, and furosemide and dopa-mine infusions administered concurrently. Six of eightrecruited subjects (4 male, 2 female) were able tocomplete the study. The baseline sodium excretionrate after equilibration on a metabolic diet was 6.7 ±

0.7 mEq (mean ± SE) over 3 h. Infusion of dopaminealone caused a slight nonsignificant increase In na-triuresis to 36.7 ± 8.5 mEq/3 h. Furosemide alonemarkedly increased sodium excretion to 276.6 ± 47.2

mEq/3 h. No significant additional increment in natri-uresis occurred when dopamine and furosemidewere administered concurrently (253.8 ± 73.6 mEq/3h). Neither dopamine, furosemide, or their coadmin-Istration affected GFR. In conclusion, infusion of low-dose dopamine does not enhance furosemide-in-duced urinary sodium excretion rates in patients withcompensated congestive heart failure, New YorkHeart Association Class II or Ill.

Key Words: oop diuretics, edema, diuretic combinations,

pharmacodynamics, GFR

A common clinical challenge that arises in pa-

tients with congestive heart failure (CHF) is the

establishment and maintenance of effective natriure-sis, particularly in the intensive care setting. Patients

� ReceIved October 27, 1995. Accepted February 26, 1996.2 Correspondence to Dr. D.C. Brater, Department of Medicine, Indiana UniversIty

School of MedIcine, ClInIcal Pharmacology DivIsion, West OutpatIent Building.

Room 320, 1001 W. Tenth Street, Indianapolis, IN 46202.

1046.6673/0707-1032$03.00/0Journal of the AmerIcan Society of Nephrologycopy�ght C 1996 by the American Society of Nephrology

frequently receive high doses ofboop diuretics to whicha law-dose (“renal-dose”) dopamine infusion is added

to promote and/or maintain an adequate diureticresponse. For example, a recent survey of patients in

the medical intensive care unit at our county hospital

showed that half of our patients received this combi-nation. Data such as this, coupled with anecdotes andrecent editorial commentary ( 1 ), suggest that this

practice is common. Little, if any, data support this

practice ( 1 ). As such, we undertook a study to criti-

calby examine whether concurrent therapy with intra-

venous low-dose dopamine and furosemide infusionsis more efficacious than furosemide infusion alone. To

do so, we conducted a prospective, controlled, ran-domized trial in patients with stable CHF, New York

Heart Association (NYHA) Class II or III, comparing theeffects ofbow-dose dopamine (1 to 3 pg/kg per mm) orfurosemide (0.25 to 0.5 mg/kg per h) to their coad-ministration in a crossover fashion. We discontinued

this trial after completing study of six patients be-

cause two additional patients enrolled in the study

experienced adverse events during the dopamine in-fusion phase, and no improvement in natriuretic effi-cacy was observed with the addition of dopamine to a

continuous infusion of furosemide in the other partic-

ipants.

METHODS

Patients

Entry criteria included a diagnosis of chronic CHF as aresult of severe left ventricular dysfunction, NYHA Class II orIII, and no other significant medical conditions or pharma-cobogic therapy that would impair the subject’s ability torespond to diuretic therapy. All of these patients had beenfollowed chronically in our Cardiology and General InternalMedicine Clinics. The patients’ characteristics are listed inTable 1 . All had left ventricular systolic dysfunction byechocardiography (nuclear scmntigraphy in Patient 5), allwere receiving angiotensmn-converting enzyme inhibitors anddiuretics chronically, and most were also receiving digoxmn.

All subjects underwent a screening physical and labora-tory examination before enrollment in the study. Thisincluded routine chemistries, a 24-h urine collection forcreatinine clearance rate determination, and an electracar-diagram. Qualifying subjects were admitted to the GeneralClinical Research Center at Indiana University Medical Cen-ter and remained as inpatients for the duration of the study.All prescribed medications were continued during the study,with the exception of nonsteroidal anti-inflammatory drugs(NSAID), which were stopped at least 1 wk before admission,and diuretics, which were held upon admission to the re-search unit. To prevent weight gain in the absence of thediuretic, patients were placed on a controlled, low-sodiumdiet (see below). Cardioprotective doses of aspirin (�325mg/day) were allowed.

Vargo et al

Journal of the American Sociely of Nephrology 1033

TABLE 1 . Patient characterlsticsa

Patient

#

Age

(yr)Sex Race

CrCI(mi/mm)

NYHAClass

.

Systolic Function Diagnoses .

Medications

1 56 M W 40 III Severe generalized LVhypokinesis; LV dilation; LVfractional shortening = 4%

Coronary artery disease,hypertension, ethanolabuse history

Digoxin,nitroglycerIn,aspirin, benazepril

2 69 M B 102 II Generalized LV hypokinesis;Lv dilation; LV fractionalshortening = 10%

Diabetes mellitus, arthritis,coronary artery disease

Nitroglycerin,calcium channelantagonist, insulin,captopril

3 48 M W 1 19 II Generalized LV hypokinesis;LV dilation; LV fractionalshortening = 13%

Hypertension, ethanolabuse, tobacco abusehistory, gout

Dlgoxln, Ibuprofen,enalapril

4 48 F W 55 Ill Akinetic inferior wall; LVfractional shortening =

18%

Hypertension, reactiveairway disease, diabetesmellltus, hepatlc injuryhistory

Digoxin,13-adrenergicantagonist, aspirin,insulin, albuterol,acetaminophen,benazepril

5 56 F B 94 III Global hypokinesis; LVEF =

26%

Myocardial infarction,hypertensIon, diabetesmellitus, peripheralvascular disease,diverticulosls, bronchitis

Nitroglycerin, aspirin,ferrous sulfate,histamineH2-antagonlst, oralhypoglycemicagent,benzodlazaplne,

propoxyphene,benazepril

6 68 M W 80 III Reduced LV systolic function;LV fractional shortening =

4%

Coronary artery disease,myocardlal Infarctionhistory, hypertension,abdominal aortlcaneurysm, emphysema

Nitroglycerin,digoxln, aspirin,antacids, enalapril

a CrCl, creatinine clearance: NYHA. New York Heart Association; LV. left ventricular: LVEF, left ventricular ejection fraction.)

Study Arms

Upon admission, subjects began a controlled metabolicdiet that included strict water and electrolyte compositionconsisting of 60 mEq Na� , 80 mEq K� , and up to 3 L ofdistilled water per day. After documenting sodium balance byquantifying total daily urinary sodium excretion values. bodyweight, and vital signs, subjects received (in random order)each of three study treatments on separate study days.Before each treatment, three 20-mm control collections wereobtained to determine baseline renal function and sodiumexcretion rates, after which treatments were as follows:

1 . Dopamine. A 30-min titration per�ad was utilized in whichdopamine was infused intravenously and titrated to amaximally tolerated dose ( 1 to 3 .�g/kg per mm). A maxi-mally tolerated dose was considered to be one that did notinduce tachycardia or significant changes in blood pres-

sure. This infusion was maintained for a minimum of 210mm. The cumulative dose of dopamine for each subject islisted in Table 2.

2. Furosemide. A 30-mm intravenous placebo infusion of0.45% normal saline at 20 mL/h was administered tocorrespond with the dopamine titration period. This infu-sian also matched the small amount of sodium receivedwith dopamine infusion. This was followed by an intrave-nous loading dose of 40 mg furosemide (given over 5 mm),

TABLE 2. Cumulative amount (mg) of dopamineand furosemide Infused during the study

PatientNumber

DopamineAlone

FurosemideAlone

Combination

Dopamine Furosemide

1 47.3 95.8 47.3 123.72 31.8 86.2 31.8 86.2

3 51.0 133.6 51.0 102.44 53.8 99.4 53.8 99.45 43.5 1 16.5 43.5 116.56 40.3 112 40.3 112

which was followed by a continuous intravenous Infusionof 0.25 mg/kg per h of furosemide for 90 mm. If the urineoutput had not doubled from baseline by this time, theinfusion was increased to 0.5 mg/kg per h for an addi-tional 90 mm. If urine output had doubled with the lowerinfusion rate, this rate was continued for a total durationof 180 min. The cumulative furosemide doses for eachpatient are listed in Table 2.

3. Combination Therapy. A 30-mm dapamine titration pe-nod was initiated as in the previously described dopammnetreatment phase, followed by maintenance of the dopa-

C

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E

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zz

_� �__ou �:i� �

60Baseline �A Dopamine + Furosemide�

40 � + Furosemide�* Dopamine

20

-50 �30 � 3OTIM:A:min)9o 120 150 180

Dopamtn. Furosernlde

(A,*) (+,A)

Dopamine-Furosemide in CHF

1034 Volume 7 . Number 7 - 1996

mine Infusion for an additional 180 mm. After the dopa-mine titration, furosemide was administered in a fashionidentical to the previously described furosemide-treat-ment phase. Total dopamine and furosemide doses in thisphase of the study were similar to those for single-drugadministration and are listed in Table 2.

Study Protocol

At the beginning of each study day, baseline urine andblood samples were collected and patients were given a 15mL/kg distified-water load orally to ensure adequate urineoutput. An intravenous bobus dose of inulin followed by acontinuous infusion were administered at a dosage calcu-lated to maintain a serum inubin concentration of approxi-mately 20 mg%. The infusion was maintained throughoutthe course of the study. Urine output was carefully moni-tored and replaced in an equivobume manner with an intra-venous infusion of 0.45% normal saline throughout thecourse afthe study. After the bolus dose ofinulin, 1 h elapsedso that achieve steady-state inulin concentrations could beachieved and the oral water load could be completed. Then,three 20-mm inubin-clearance determinations were obtainedto establish baseline renal function. After this. dopamine orplacebo was administered as described above. For the re-mainder of the study, urine collections occurred every 30mm.

As noted previously, subjects were not studied until so-dium balance was attained. Each study day was separatedby 2 to 5 days to regain sodium balance as documented bystable body weight and 24-h sodium excretion (Table 3). Thetreatment sequence was administered in a single-blind. ran-domized fashion. After the completion of each study day, netsodium balance was calculated and any sodium deficits werereplaced with intravenous normal saline the following day.

Measurements

In addition to the urine collections previously described,serum samples were obtained at the beginning and end ofeach urine collection and 5 and 15 mm after the 40-mgfurosemide bolus for electrolyte, creatinine, inulmn, and furo-semide concentration determinations using standard meth-ods in our laboratory. These data were used to calculatesodium (mEq/min) and furasemide (j�g/min) excretion rates.Serum and urine sodium concentrations were determined byflame photometry (Instrumentation Laboratories 943; In-strumentation Laboratories, Lexington, MA). Inulin concen-

trations were determined by a Technicon Autoanalyzer II(Technicon Instruments, Ebmhurst, IL) using the anthronemethod (2). Serum and urine creatinine concentrations weredetermined with the Technicon Autoanalyzer using the Jaffereaction (3). Urinary furosemide concentrations were mea-sured with HPLC using previously described methods (4).

TABLE 3. Prestudy body weight and sodiumexcretion rate (mean ± SE)

TreatmentWeight

(kg)

Sodium ExcretionRate (mEq/24 h)

Dopamine 77.1 ± 3.9 58.2 ± 5.2Furosemide 77.2 ± 4.0 60.5 ± 6.5Combination 77.5 ± 4.1 48.0 ± 3.4

Statistical Analysis

All values are expressed as mean ± SE. Natriuretic re-sponse was determined as cumulative urinary sodium excre-tion and as sodium excretion rates over time. GFR wasdetermined by inulin clearance rates using the standardformula. In the two studies that included furosemide, adose-response relationship was defined as the excretion rateof sodium as a function of urinary furosemide excretion rate.Statistical analysis was performed by analysis of varianceusing PC-SAS (SAS, version 6.08; SAS Institute, Inc., Cary,NC). Duncan’s multiple range tests were used on all van-

ables. In addition, sodium excretion at baseline and duringthe treatment phases was compared using Tukey’s RangeTest and Newman-Keuls test. Statistical significance wasassumed for P values < 0.05.

RESULTS

Patient Outcome

We completed studies in six of eight adults (fourmale, two female) between the ages of 48 and 69 yr

with stable CHF (Table 1). Two additional subjects,

4 1 - and 6 1 -year-old men with left ventricular functionsimilar to the other six patients were withdrawn when

they had adverse effects upon infusion of dopamine.

One subject had asymptomatic ventricular bigeminy;

the other became hypotensive. Both subjects recov-

ered quickly an cessation of the dopamine infusion.One of the six subjects completing the study devel-

oped a recurrence of atrial fibrillation after completingthe combined furosemide and dopamine treatment;this resolved with volume replacement and an addi-

tional dose of digoxin. All other subjects maintained

stable vital sign measurements, and electrolyte con-

centrations were stable in all subjects throughout the

course of the study.

Glomerular Filtration Rate

There was no significant change in GFR as deter-

mined by inubin clearance rates during any of thestudy days (Figure 1 ). The same findings were ob-

120

100

0 #{149} #{149}

Figure 1 . Lack of effect of dopamine, furosemide, and thecombination on GFR as measured by Inulin clearance.

1.8I

I

.c

wE

z0

C.)xUI

0

UI

I

350

0

I

Vargo et al

Journal of the American Society of Nephrology 1035

,.u

EBRS.Nfl. r �:: I, {*DoPai�+Furos�d�

:: ___

I I TIME (mm)Dopimin. Furos.mld.

(A,*) (+,A)

Figure 2. Effect of dopamine, furosemide, and the combina-tion on sodium excretion rate over time.

served when renal function was assessed by creati-

nine clearance (data not shown).

Sodium Excretion

Figure 2 illustrates sodium excretion rates over timethroughout each of the treatment periods. Dopamine

infusion alone caused a slight increase in sodium

excretion rate from baseline levels that persisted forthe duration of the infusion. Furosemide alone causeda more marked increase in sodium excretion, whichremained constant throughout the infusion period.

The addition of dopamine to furosemide did not en-

hance excretion rates.Figure 3 shows the cumulative natriuretic response.

In this analysis, baseline sodium excretion rate (6.7 ±0.7 mEq/3 h) was calculated during the 48 h preced-ing the first study day, a time in which sodium bal-ance was maintained. Dopamine alone slightly in-

350

300 � *

250

200

150

100

50

DOPAMINE + FUROSEMIDE DOPAMINE BASEUNEFUROSEMIDE

TREATMENT

Figure 3. CumulatIve effect of dopamine, furosemide, andthe combination on sodium excretion rate. (Asterisks denotesignificance of differences.)

creased sodium excretion to 36.7 ± 8.5 mEq/3 h,

which was not significantly different from baseline.Furosemide alone caused a marked increase in so-dium excretion, which was significantly greater thanvalues at baseline or with dopamine alone. Sodiumexcretion after coadministration of dopamine and fu-

rosemide was not different from furosemide alone(253.8 ± 73.6 versus 276.6 ± 47.2 mEq/3 h, respec-

tively). Changes in urine volume paralleled those ofsodium (data not shown).

Furosemide Pharmacodynamics

Cumulative furosemide excretion in urine was 32.9

± 4.3 mg after furosemide alone and 27.8 ± 3.4 mg

after dopamine plus furosemide. Figure 4 illustrates

furosemide excretion rates during the furosemide in-fusion periods ( 180 mm) and demonstrates the lack of

effect ofdopamine on furosemide elimination. Figure 5shows the dose-response relationship between so-

dium excretion rate and furosemide excretion rate foreach treatment arm involving furosemide. No signifi-

cant difference was observed between the two dose-response curves.

DISCUSSION

The findings of our study challenge the commonclinical practice of using “renal-dose” infusions ofdopamine to promote or enhance the natriuretic effect

of loop diuretics in patients with compensated CHF.Although the infusion of dopammne alone appeared toincrease sodium excretion by a small degree com-pared with baseline values, the addition of dopamine

to a continuous infusion of furosemide did not in-crease the natriuresis induced by furosemide alone. Infact, a slight decrease in natriuresis was observedwhen these agents were administered concomitantly,but this difference did not reach statistical signifi-

cance. This lack of natriuretic enhancement could notbe explained by alterations in the delivery of furo-semide to its site of action, because furosemide excre-

300

250 //t\:\\ � Dop.mIne+ Furos.mIde_

200

�/, ,

0 30 60 90 120 150 180

TIME (mm)

Figure 4. UrInary furosemide excretion rates after furosemidealone and combined with dopamine.

2.0

1.5+

1.0

0.5

A DOPAMINE a FUROSEMIDE

+ FUROSEMIDE

Our results, on the surface, seem to differ from the

few publications that address the effect of dopamine

on the natriuresis caused by loop diuretics. For exam-ple, Lindner (8) and Graziani et al. (9) showed that

dopamine plus furosemide caused a natriuresis in

patients who had not responded to furosemide alone.

However, these studies differ substantially from ours.The patients had oliguric renal failure, not CHF, andthe study design was sequential, incorporated no

control of sodium intake, was not randomized, etc. Webelieve that studies such as ours need to be conductedin patients with renal insufficiency. Until such studies

50 100 150 200 250 300 occur, the utility of dopamine in that setting is stillunresolved.

FUROSEMIDE EXCRETION RATE (�tgImln)

Dopamine-Furosemide in CHF

1036 Volume 7 . Number 7 ‘ 1996

Figure 5. RelationshIp between urinary furosemide excretionrate and sodium excretion rate with and without dopamine.

tian rates were unchanged by the coadministration of

dopamine. Moreover, dopamine did not increase GFR.

The results of our study reinforce the concern ex-pressed in a recent editorial ( 1 ) that excessive or

indiscriminate use of “renal-dose” dopamine, particu-larly in critical care settings, is not substantiated by

data found in the medical literature.Our study focused on the effects of dopamine to

enhance natriuresis caused by a loop diuretic. Theresults of this primary end point are clear. The study

was not designed to address the effects of dopamine

alone in patients with CHF. As such, this secondary

end point in our study should not be overinterpreted.We observed a numeric increase in overall sodiumexcretion of about 30 mEq with dopamine alone. Thisamount was not statistically significant. However, thesmall number of patients studied makes the risk of aType 2 statistical error possible, ii not likely, for thisend point. Moreover, the effect of dopamine alone wascompared with baseline sodium excretion rate, not toa timed, placebo control. For both of these reasons,this study should not be viewed as being overly infor-

mative about the effect of dopamine alone on sodiumexcretion rates in patients such as those we studied.

On the one hand, addressing this specific questionwould require a different study design. On the other

hand, it seems that the question ofa loop diuretic plus

dopamine is most germane to the clinical setting. Assuch, it is debatable whether the former questionneeds pursuit.

It is often assumed that dopamine will induce

marked natriuresis in patients with CHF based, inpart, on early reports by Goldberg et al. (5), Beregovichet al. (6), and others (7). These reports are difficult tointerpret because of incomplete description of thepatient’s clinical status, the short duration of dopa-mine infusion (often less than 30 mm), and briefobservation periods. Moreover, these studies addressthe effects of dopamine alone on sodium excretionrate. As pointed out earlier, this was not the primaryobjective of our study. Indeed, our results with dopa-mine alone are not inconsistent with this prior work.

In contrast, in patients with CHF, we are aware ofonly two studies that are somewhat similar to ourown. Marchionni et at. ( 10) administered ibopamine topatients with CHF, all of whom were receiving “stan-

dard therapy” of digoxin, furosemide, and captopril.

Natriuresis was assessed as total sodium excreted

over 24 h. Ibopamine caused an increase over baselinethe first day with progressively less effect over subse-quent days. The study was nat randomized, crossover,

or controlled in terms of sodium intake. Moreover, thefurosemide dose ranged from 25 to 250 mg orally/day.Whether the diuretic dose was optimized in all pa-tients is unlikely. This may well explain why our

results differ. In contrast, Robinson et al. studied 17

elderly patients hospitalized for CHF ( 1 1). These pa-

tients were “resistant” to diuretic therapy. All received

angiotensin-converting enzyme inhibitors. Dopamineadministered at a rate of 2.5 pg/kg per mm caused no

increase in GFR and 24- h sodium excretion was not

increased. Interestingly, one patient suffered an ar-rhythmia. The diuretic doses were not described.

Overall, these data are consistent with ours.Indeed, as shown in Figure 5, our study explored the

effect of dopamine on response to doses of furosemidethat were maximally effective; in other words,

amounts of furosemide were used that reached the

upper plateau of response to furosemide. When dopa-mine is superimposed upon such doses, it causes no

increase in response. It is possible that dopamine may

enhance response to lower, submaximal doses of fu-rosemide. However, we would argue that this is a moot

point, because clinically it makes more sense to attainthe desired response to the loop diuretic alone rather

than using a combination. The former strategy entails

a lower risk of adverse effects as shown in our study,

and is less expensive.Yet another question with dopamine is its ability to

protect the kidney ( 1). Intriguing data have raised thisquestion. For example, low-dose dopamine is effectivein preserving renal blood flow in dogs receiving nor-

epinephrine ( 1 2). However, low-dose dopamine offers

no added benefit in preserving renal function when

compared with saline infusion in other animal models( 13). We emphasize that our study does not addressthe potential protective effect of dopamine on renal

function; rather, it specifically questions the empiric

Vargo et al

Journal of the American Society of Nephrology 1037

practice of using dopamine to enhance responsive-ness to a loop diuretic.

What are the potential flaws in our study? First, our

subjects were not representative of those in criticalcare settings. Though their cardiac disease was se-vere, they were clinically stable and were studied in ahighly controlled setting. In addition, none were cate-gorized as NYHA Class IV. Under the conditions of ourstudy, there was no appreciable enhancement of fu-rosemide-induced natriuresis with the addition of acontinuous infusion of low-dose dopamine. Differenttypes of patients may respond differently.

Second, although the results in the six patients whocompleted the study are clear, our study was con-ducted in a small number of patients. Should morepatients be studied to avoid a false conclusion? Be-cause two additional patients (25% of those enrolled)had to be dropped from the study because of adverse

effects, and because another patient suffered adverseeffects, we felt that we needed to stop the study withonly six patients. We were not willing to risk such anadverse event rate in view of simply increasing thenumber of patients. We believe that our results aresufficiently clear to motivate a definitive study in acritical care setting. More patients would not havemade the need for a definitive study less compelling;our data are sufficient to justify ethically such a studynow.

In conclusion, the addition of a low-dose (“renal-dose”) dopamine infusion to a continuous infusion offurosemide at a maximally effective dose in patientswith compensated CHF did not enhance urinary so-dium excretion rate. Whether this lack of enhance-ment applies to unstable patients with end-stage CHFin the critical care setting remains to be determined.We hope that the results of this report stimulateconduct of such a study; routine use of renal dose

dopamine in critical care settings for its diuretic effectshould await results of such a trial.

ACKNOWLEDGMENTSThe General Clinical Research Center at Indiana University School ofMedicine is supported by Grant MO 1 RO0750 from the National

Institutes of Health (Bethesda, MD). Dr. Brater is supported by

Grants ROl AG0763 1 and ROl DK37994, and Dr. Vargo is supportedby Clinical Pharmacology Training Grant T32 GM08425. all from the

National Institutes of Health.

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4. Smith DE, Lin ET, Bennet LZ: Absorption and distribu-tian of furosemide in healthy volunteers measured with ametabolite specific assay. Drug Metab Dispos 1980;3:337-342.

5. Goldberg LI, McDonald RH, Jr. Zimmerman AM: Sodiumdiuresis produced by dapamine in patients with conges-tive heart failure. N Engl J Med 1963;269: 1060-1064.

6. Beregovich J, Bianchi C, Rubler S. Lomnitz E, Cagin N,Levitt B: Dose-related hemodlalysis and renal effects ofdapamine in congestive heart failure. Am Heart J 1974;87:550-557.

7. Sen I: Dopamine and natriuresis-mechanism of actionand developmental aspects. Am J Hypertens 1990;3:82S-86S.

8. Lindner A Synergism of dopamine and furosemide indiuretic-resistant, oligunic acute renal failure. Nephron1983;33: 12 1-126.

9. Graziani G, Cantaluppi A, Casati S, et aL: Dopamine andfurasemide in oligunic acute renal failure. Nephron 1984;37:39-42.

10. Marchionni N, Conti A, Dc Alfieri W, et aL: Ibopamine incongestive heart failure refractory to digitalis, diuretics,and captapril. J Clin Pharmacol 1986;26:74-77.

1 1 . Robinson T, Gariballa S, Fancourt G, Potter J, Castle-den M: The acute effects of a single dopammne infusion inelderly patients with congestive cardiac failure. Br J ClinPharmacol 1994;37:261-263.

12. Schaer GL, Parillo JE: Narpmnephrine alone versus nor-epmnephrine plus low-dose dopamine: Enhanced renalblood flow with combination pressor therapy. Crit CareMed 1985;13:492-496.

13. Casson IF, Claydon DA, Cope GF, Lee MR: The pratec-tive effect ofy-glutamyl L-dopa an the glycerol treated ratmodel of acute renal failure. Clmn Sci 1983;65: 159-164.