DOI 10.1378/chest.102.3.725 1992;102;725-731Chest

 M Lahav, A Regev, P Ra'anani and E Theodor for congestive heart failure.continuous infusion preceded by a loading dose Intermittent administration of furosemide vs

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) ISSN:0012-3692http://chestjournal.chestpubs.org/site/misc/reprints.xhtml(without the prior written permission of the copyright holder.reserved. No part of this article or PDF may be reproduced or distributedChest Physicians, 3300 Dundee Road, Northbrook, IL 60062. All rights

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Several reports have suggested that continuous intravenousadministration of loop diuretics may be superior to intermittent administration. We performed a prospective randomized crossover study comparing intermittent intravenow administration (IA) of furosemide with continuousinfusion following a single loading dose (LDCI) in ninepatients with severe congestive heart failure. At the time

of hospital admission, patients were randomly assigned toone of two treatment groups. One group (four patients)received an 1V bolus injection of furosemide followed imme

diately by a continuous infusion for 48 h. The second group(five patients) was treated with three IV bolus injections aday for 48 h. Total doses of furosemide were equivalent in

the two groups. After 48 h, each patient was crossed overto the other method and treated for an additional 48 h.LDCI produced significantly greater diuresis and natriuresis than IA (total urine output increased by 12 to 26percent, total sodium excretion increased by 11 to 33percent) (p<O.Ol). There were no significant differences in

side effects between the two methods. These results indicatethat LDCI may be a preferred method for administrationof furosemide in patients with congestive heart failure.

(Chest 1992;102:725-31)

IA= intermittent administration; LDClcontinuous infusionfollowingloading dose

F urosemide is a potent loop diuretic that is widelyemployed in the treatment of congestive heart

failure (CHF). When administered intravenously (IV),it induces a prompt and vigorous diuresis with a widerange dose response curve.'

In severe heart failure, relatively high doses offurosemide are used. These doses are often associatedwith significant side effects, including hypovolemia,electrolyte disturbances, hyperuricemia, and metabolic alkalosis.2'3

Furosemide is usually administered intermittentlyby IV bolus injections. This mode of administrationmay lead to marked fluctuations in intravascularvolume and to high peak serum levels of furosemide,increasing its toxicity.4

It seems conceivable that continuous furosemideinfusion may decrease the fluctuations in intravascularvolume causing a relatively constant hourly urineoutput.5 It may also prevent the accumulation of toxiclevels of furosemide, thus causing fewer and lesssevere side effects.6 Moreover, this method of administration would allow rapid termination of an undesirably vigorous diuresis or a side effect. In patientsrefractory to conventional doses offurosemide, continuous IV administration may allow gradual increase ofinfusion rate until the desirable hourly diuresis occurs.6'7

Several reports have suggested that continuous IV

administration of loop diuretics may also lead toincreased diuretic and natnuretic effects comparedwith intermittent schedule.@9 This concept receivedtheoretical support from several authors'°'2 but onlytwo prospective controlled clinical studies addressedthis issue directly.5―3One of these studies demonstrated no significant difference in the diuretic andnatriuretic effects of the two modes of administrationin patients after open heart surgery.5 The other studydemonstrated superior efficacy of the continuous IVadministration in patients with chronic renal@However, the patients examined in this study did nothave CHF. Since the dose response relationship offurosemide is altered considerably in CHF,'2 theresults ofthis study cannot be extrapolated to patientswith CHF. Furthermore, in both of these studies,furosemide was administered for relatively short periods.

It has been demonstrated that continuous administration of furosemide causes a gradual increase inurine output that may reach a peak only several hoursafter the initiation ofinfusion.5 This lag period may becritically important in patients with severe CHF.

Based on these observations, we postulated thatcontinuous infusion of furosemide preceded by an IVloading dose may induce increased diuresis with fewerside effects compared with the conventional intermittent mode ofadministration in patients with CHF.

Ihtietzts

METHODS

All the patients included in this study were admitted to the

Fromthe Department oflnternal Medicine E, Beilinson MedicalCenter, Petahliqva and Tel Aviv UniversitySadder SchoolofMedicine, Israel.

Manuscript received October 9; revision accepted February 25.

CHEST I 102 I 3 1 SEPTEMBER, 1992 725

IntermittentAdministrationof Furosemidevs ContinuousInfusionPrecededbyaLoadingDosefor CongestiveHeartFailure*Mel,' La/wv, M.D.; Arie Regev, M.D.; Pia Ra'anani, M.D.;and Emanuel Theodor, M.D.

 © 1992 American College of Chest Physicians by guest on July 10, 2011chestjournal.chestpubs.orgDownloaded from

Patient/Sex/

Age, yrDiagnosisMedicationsin Addition

toFurosemide1/M/69IHD,

Lt heart failure,S/P ant and inf wallMIsNitrates,

amiodarone2/Ft76IHD,

Lt heart failure,S/P ant lat wall MINitrates,

captopril,aspirin@VMfl2RHD,

Rt and Lt heartfailure, mitral valvedisease, chronic atrialfibrillationDigoxin,

warfar,n4/MfllIHD,

S/P ant and infMIs, Lt heart failureCaptopril,

thyroxine,allopurinol5fF@0COPD,

ourpulmonale, chronic

atrial fibrillation,hypertension, Lt andRt heart failureDigoxin,

nitrates@aspirin,glibenclamide&M179IHD,

hypertension,S/P ant wall MI, Ltheart failureCaptopril,

nifedipine,quinidine,

pentoxifylline7/F/74IHD,S/P ant wall

MI, acute infwall MI,Lt heart failureNitrates,

nifedipineWF/68RHD,

chronic atrialfibrillation,insufficiency ofprosthetic mitral valvedue to SBE, Lt heartfailureDigoxin,

warfarin,cefuroxime,amikacinWM178IHD,

S/P ant wallMI, Lt heart failureNitrates,

captopril

Table 1—I@ztientDatG° constant throughout the study period. None ofthe patients receivedmechanical ventilation during the study. All details of this studywere approved by the institutional clinical research committee andfully informedconsent was obtained from each patient.

Six of the nine patients included in the study had indwellingurinary catheters throughout the study period. In these patients,the urine output was measured every hour and urine samples werecollected every 2 h for sodium and potassium determination. Whenan indwelling catheter was not inserted, urine output was measuredand samples were collected after each urination. Blood sampleswere drawn at hospital admission, then once every 6 h for 12 h andevery 12 h thereafter. Each sample was analyzed for sodium,potassium, chloride, serum urea nitrogen, and creatinine levels.The pH and bicarbonate were determined in venous blood every12 h. Uric acid and calcium levels were determined every 24 h.Totalfluidintakewasmaintainedat 22ml/kgt24h in all the patients.A low-sodium diet (daily sodium chloride intake of 2 g) wasmaintained throughout the study.

The difference between the two methods of furosemide administration was assessed by net cumulative urine and sodium excretion.Statistical analysis ofpaired data was made using the Wilcoxon testfor paired data.

RESULTS

Furosemide was administered at two possible rates;six patients were treated with 120 mg/24 h. This totaldose was administered either as three bolus injectionsof 40 mg every 8 h or as a bolus of 40 mg followed bya continuous drip of 200 mg/48 h. Three patientsreceived furosemide at a rate of 90 mg/24 h , either asthree bolus injections of3O mg every 8 h or as a bolusof 30 mg followed by a continuous drip of 150 mg/48h.

Intermittent Administration (IA)

Urine output peaked within 1 to 2 h after each bolusof furosemide and declined progressively thereafter,reaching baseline levels in 3 to 4 h (Fig 1). Meanhourly urine output ranged from 35 ±18 mI/h (usually4 to 8 h after furosemide injection) to 180 ±62 mI/h (1to 2 h after injection). Hourly variations in urineoutput reached ±120 ml during the first 3 h afterbolus injections. Total urine output in 24 h rangedfrom 2,685 ml to 6,365 ml (mean, 3,790 ml) (Fig 2).Nearly 60 percent (2,230 ±698 ml) of the mean totalurine output of 48 h was excreted within the first 2-hperiods after each bolus.

Changes in sodium excretion during IA were similarto those ofurine output (Fig 3). Total sodium excretionin 48 h ranged from 115 mEq to 547 mEq (Fig 4).

Two patients were hyponatremic (130 mEqIL <Serum Na <135 mEq/L) before the initiation ofIA. Twoofthe other seven became hyponatremic during treatment. Significant elevation in serum urea nitrogenlevel was noted in two patients and elevation of serumcreatinine level was noted in one patient during IA.

Hypokalemia (serum K <3.5 mEq/L) occurred intwo patients and hypocalcemia (serum Ca <8.5 mg/dl) occurred in two patients. Hyperuricemia (uric acid>8.0 mg/dl), hypochloremic alkalosis(pH >7.45), or

*IHD = ischemic heart disease; RHD rheumatic heart disease;S/P = state post; Ltleft; Rt = right; MI = myocardial infarction;COPD =chronic obstructive pulmonary disease; SBE subacutebacterial endocarditis; ant = anterior; inf inferior; lat lateral.

hospital with class 3-4 CHF (New York Heart Association classification) that was refractory to conventional oral therapy (ie, combinations of oral diuretics, nitrates, angiotensin-converting enzyme[ACE]inhibitors,and digoxin).

Relevant clinical data are presented in iuible 1. Patients wereexcluded from the study furthe followingreasons:serum creatininelevels of >2.0 mg/dl, serum sodium concentration <130 mEq/L,liver disease, history of allergic reaction to flirosemide, and additional medical therapy known to influence urine output, eg,aminophyiline, dopamine, or thiazide diuretics.

At the time of hospital admission, patients were randomlyassigned to one of two treatment groups. One group received IVbolus injection of 30 to 40 mg of flirosemide as a loading dosefollowed immediately by a continuous infusion of 2.5 to 3.3 mg/h(60 to 80 mg/day) for 48 h.

The second group was treated with three IV bolus injections of3oto40mgevery8hfor48h.

Forty-eight hours after initiation of furosemide therapy, eachpatient was crossed over to the other treatment group and wastreated for an additional 48 h.

The total doses of furosemide were equivalent in the two modesofadministration.Switchingfromthe intermittent to the continuousmode ofadministration was done 8 h after the last IV bolus. Beforecrossing over from continuous infusion to intermittent administration, the patients were allowed a washout period of 3 h, duringwhich they were not given furosemide. Each patient's regularmedications (1€,nitrates, ACE inhibitors, or digoxin) were held

726 IntermittentvsContinuousFurosernideinCHF(Lahavet a!)

 © 1992 American College of Chest Physicians by guest on July 10, 2011chestjournal.chestpubs.orgDownloaded from

CC

4 4 4 1 1 bokaI@FIGURE 1. Mean hourly urine output in six catheterized patients during intermittent furosemide

administration (open circles) and continuous infusion with a loading dose (black circles).

hypomagnesemia (serum Mg <1.9 mEq/L) were notrecorded during IA. None ofthe less common systemicside effects (eg, tinnitus, deafuess, gastrointestinalsymptoms, skin rash) developed during the treatment.

Continuous Infusionfollowing Loading Dose (LDCI)

As in the intermittent mode ofadministration, urineoutput peaked 1 to 2 h after IV furosemide loadingdose (Fig 1). After the second hour, there was a gradualdecrease in hourly urine volumes, but diuresis was

maintained above preinfusion levels throughout the48-h period.

Mean hourly urine output ranged from 41 ±13 ml!h (before the initiation of flirosemide) to 170 ±55 ml!h (2 h after IV loading dose). Hourly variations inurine output were maximal during the first 2 h afterthe IV loading dose (135 mI/h) but did not exceed 25mI/h thereafter.

Total urine output in 48 h ranged from 3,215 ml to7,365 ml (mean, 4,490 ml) (Fig 2).

7!5 @Contlnuous

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CHEST I 102 I 3 I SEPTEMBER, 1992 727

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2000

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FIGURE 2. Total 48-h urine output with intermittent furosemide administration (IA) vs continuous infusionpreceded by a loading dose (LDCI).

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4 4 4 4 4 boiusLV.FIGURE 3. Mean hourly sodium excretion in six catheterized patients during intermittent furosemideadministration (open circles) and continuous infusion with loading dose (black circles).

5

As in intermittent administration, changes in hourlysodium excretion during continuous furosemide infusion paralleled those of urine output. Total sodiumexcretion in 48 h ranged from 135 mEq to 677 mEq.

There was no significant difference in patterns ofresponse between patients who were receiving ACE

inhibitors or nitrates and those who were not.Two patients were hyponatremic (130 mEq!L <Se

rum Na <135 mEq/L) before the initiation of LDCI.One of the other seven became hyponatremic duringtreatment. Significant elevation in serum urea nitrogen level was noted in one patient and elevation of

C

E

I

serum creatinine concentration was noted in oneduring LDCI. Hypokalemia occurred in two patientsand hypocalcemia occurred in one. Hypochloremicalkalosis, hyperuricemia, or hypomagnesemia werenot recorded during LDCI and none of the lesscommon side effects were recorded during treatment.

Total urine output with LDCI was consistentlyhigher (by 12 to 26 percent; mean, 18.5 percent) thanwith IA (p'<O.Ol) (Fig 3).

Total sodium excretion was also consistently higher(by 11 to 33 percent; mean, 21.5 percent) with LDCIthan with IA (p<O.Ol) (Fig 4).

FIGURE 4. Total 48-h sodium excretion with intermittent furosemide administration (1A) vs continuousinfusion preceded by a loading dose (LDCI).

Intermittentvs ContinuousFurosemide @iCHF (Lahav et a!)

Continuous

@ Intermfttsntp'ic0.01

 © 1992 American College of Chest Physicians by guest on July 10, 2011chestjournal.chestpubs.orgDownloaded from

SourceNo.of

SubjectsDiagnosisPreinfusion/ Control DosageInfusionRateFurosemideKrasna

et aI@3Acute renal failure after cardiac surgery40 mg x 3/day IV0.38-0.75mgfkg/hAmielet al@4Malignant ascites80-120 mg/day orally100 mg/24hCerland

andClass IV congestive heart failure250-4,000mg/dayvanMeijel@Lawson

et alb10Congestive heart failure120 mg/day orally4-16mg/bCopelandet a?18Postcardiac surgery

Bumetanide0.3mg/kg x 2/12 h IV0.05mg/kg/hRudy

et al's8Chronic renal failure6 mg X2/12 h1 mg holus, 0.918 mg/h

DISCUSSION

Loop diuretics cause their natriuretic effect predominantly by decreasing chloride reabsorption in thethick ascending ioop of Henle. Like several otherdiuretics, loop diuretics must reach the tubular lumento be @4@5They reach the luminal compartment by being actively secreted from the blood intothe urine at the organic acid transport pathway of thestraight segment of the proximal ,0

Using probenecid as a means to alter the relationshipbetween serum and urine concentrations of furosemide, Chennavasin et al'@ have confirmed previousanimal data suggesting that urinary furosemide is thebest correlate of response.

The relationship between urinary furosemide excretion rate and response is characterized by a sigmoidshaped 14,16This curve is suppressed in manypatients with CHF and may occasionally lose itssigmoidal configuration in these patients.'2―6

Pretreatment of subjects with probenecid has beendemonstrated to increase the overall natriuretic response to furosemide. This difference was attributedto the changed time course of delivery of furosemideinto urine.'7 A similar phenomenon has been demonstrated by Kaojarern et al―when comparing overallresponse to oral IV dosing of furosemide.

Brater'°used the concept of sodium to furosemideexcretion ratio to describe the efficiency of the diuretic. By applying this approach, he found that theamount ofurinary furosemide with maximal efficiency(21 .5 p@g/min)was considerably less than the amountof drug causing half maximal response (ED5O) (69.8p.g/min). Brater has also demonstrated that after oralfurosemide administration, the amount of furosemidein urine more persistently approached that amountwith maximal efficiency. Thus, overall natriuresis wasgreater relative to the total amount of drug deliveredto the acitve site. A similar effect was caused bypretreatment with probenecid. Based on these data,it seems conceivable that during slow IV infusion, theamount of furosemide in urine may approach theamount with maximal efficiency for longer periods oftime.

This concept may explain greater overall diuresiswith continuous infusion compared with IV bolusinjections.‘¿�@

Recent publications dealing with continuous IVadministration of furosemide include mostly casereports and uncontrolled studies of which only a fewdeal with patients with CHF (Table 2). Krasna et al7reported a prompt resolution ofoliguria by continuousfurosemide administration in three cardiac surgicalpatients with acute postoperative renal failure that didnot respond to bolus injections of furosemide. Amielet al@reported rapid relief of tense ascites by IVinflusion offurosemide in four patients with abdominalmalignant neoplasms. Gerland and van Meijel9 treated35 patients with CHF who were refractory to conventional therapy with high doses of furosemide (250 to4,000 mg/day) either orally or IV (as bolus injections

or continuous infusion). They did not conduct acomparative study between the different modes ofadministration, but they pointed out that slow continuous IV infusion seemed the most effective and leasttoxic.

Lawson et al6 used a continuous IV infusion offurosemide in ten patients with CHF who failed torespond to 120 mg of furosemide orally. All patientsobtained “¿�satisfactorydiuresis― with infusion of 4 to16 mg/h. Lawson et al noted that lower plasmaconcentrations of furosemide produced considerablyhigher sodium excretion rates during continuous IVadministration. Vermeulen and Chadha'8 approachedthe same issue through the enteral route, by comparinga slow-release oral formulation with the standardformulation in patients with CHF. They found thattotal diuresis and natriuresis were equal in the twogroups while peaks of diuresis were seen only inpatients receiving the standard formulation.

Only two studies presented a prospective randomized comparison between intermittent and continuousIV administration of loop diuretics. In one study(Copelandet al@),a gentle sustaineddiuresis wasachieved by continuous infusion of furosemide inpatients after cardiac surgery, but there was nosignificant difference in total urine volume and total

Table 2—ContinuousIV Loop Diuretics: Recent Publications

CHEST I 102 I 3 I SEPTEMBER, 1992 729

 © 1992 American College of Chest Physicians by guest on July 10, 2011chestjournal.chestpubs.orgDownloaded from

sodium excretion compared with bolus furosemideadministration.

Copeland et al@measured urine output for only 12h while diuresis in the continuous infusion group didnot reach a peak until the third hour after initiation ofinfusion. In a pilot study of continuous IV administration in patients with CHF, we have seen that increasein urine output may continue for as long as 5 to 8 hafter the initiation of infusion (data not shown). Thislag period may account for the lack of significantdifference between the two modes of administrationin the study of Copeland et al. Moreover, this lagperiod may be too long for patients with severe CHF.

In a randomized crossover study published shortlyafter the initial submission of this article for publication, Rudy et@ demonstrated that continuous infusion of bumetanide preceded by a bolus loading doseresulted in a significantly greater net sodium excretioncompared with an intermittent bolus injection in eightpatients with chronic renal failure.

By using a loading dose prior to initiation of furosemide infusion, we induced prompt diuresis andtherefore could proceed with relatively slow furosemide infusion rate to achieve sustained diuresis.

In addition to inducing prompt diuresis, the initialIV bolus of furosemide has the advantage of itsextrarenal hemodynamic effects in patients withCHF.'9 These effects, though still controversial,2°'2'are probably less likely to occur with continuous, slowinfusion of furosemide.@

In our study, intermittent furosemide administration (IA) produced a series of peaks in urine outputand natriuresis (Fig 1 and 3). Each peak occurredwithin the first 2 h after the bolus injection and wasfollowed by gradual decrease, corresponding to theserum half-life of furosemide, which averages about50 mm (range, 30 to 70 min).@

LDCI produced initial peak in cliuresis and natriuresis followed also by a gradual decrease, but hereurine output and sodium excretion were maintainedat a constantly increased level throughout the administration of furosemide.

LDCI produced diuresis and natriuresis that weresignificantly and consistently greater than with IA (Fig2 and 4) regardless of initial mode of administration(IA or LDCI). Furthermore, in contrast to the largefluctuations in hourly urine output in the IA group(Fig 1), LDCI induced sustained diuresis with relatively little variation in urine output.

In our study, there were no significant differencesin side effects between the two modes of administration, but such differences may appear following administration of larger doses of furosemide or in largergroups.

There was a mild and gradual decline in hourlydiuresis and natriuresis throughout the 48-h follow-up

in both modes of administration, although it was notstatistically significant. This finding has been described by several authors and is probably related tochanges in sodium balance.4'5―°―3

We have demonstrated that LDCI of furosemideproduces a significantly greater diuresis and natriuresis than IA. It seems, therefore, that LDCI has severaladvantages over IA in CHF. We believe LDCI is alsosuperior to continuous infusion without a loading dose,since LDCI may combine the advantages of continuous infusion with those of immediate IV bolus inpatients with severe CHF.

Because oftechnical limitations, we could not measure the serum and urinary concentrations of furosemide in our patients. Results of such measurements infuture studies can conceivably provide additional dataregarding the mechanisms underlying the differentialresponses between LDCI and IA.

We also believe that further investigation of therenal and extrarenal effects ofthis method of furosemide administration is warranted.

ACKNOWLEDGMENT:We thankthe nursing staffofour department for providing help in this study.

REFERENCES

1 Benet LZ. Pharmacokinetics/pharmacodynamics of furosemidein man: a review. J Pharmacokinet Biopharm 1979; 7:1-27

2 Plumb VJ, James TN. Clinical hazards of powerful diuretics:furosemide and ethacrynic acid. Mod Concepts CardiovascDis1978; 47:91-4

3 Lowe J, Cray J, Henry DA, Lawson DH. Adverse reactions tofurosemide in hospital inpatients. BMJ 1979; 2:360-62

4 BranckBA, RobertsCJC. Homeida M, Levine D. Determinantsof response to furosemide in normal subjects. Br J Chin Pharmacel 1977;4:121-27

5 Copeland JC, Campbell DW, Plachetka JR. Salmon NW, LarsonDF. Diuresis with continuous infusion of furosemide aftercardiac surgery. Am J Surg 1983; 146:796

6 Lawson DH, Cray JMB, Henry DA, Tilstone WJ. Continuousinfusion offurosemide in refractory oedema. BMJ 1978; 2:476

7 Krasna JM, Scott CE, SChOIZPM, Spotnitz AJ, Mackenzie JW,Penn F. Ikutoperaliveenhancement ofurinary output in patientswith acute renal failure using continuous furosemide therapy.Chest 1986; 89:295

8 Amiel FA, Blackburn AN, Rubens RD. I.V. infusion of furosemide as treatment for ascites in malignant disease. BMJ 1984;283:1041

9 Gerland PCC, van Meijel JJM. High dose furosemide in thetreatment of refractory congestive heart failure. Arch InternMed 1988; 148:286

10 Brater DC. Phannzodynamic considerations in the use ofdiuretics. Ann Rev Pharmacol Toxicol 1983; 23:45-62

11 Kaojarern5, Day B, Brater DC. The time course ofdeivery offurosemide into urine is an independent determinant of overallresponse. Kidney mt 1982; 22:69-74

12 Brater DC. Resistance to loop diuretics: why it happens andwhat to do about it. Drugs 1985; 30:427-43

13 Rudy DW, Voelker JR. Creene PK, Esparza FA, Brater DC.Loop diuretics for chronic renal insufficiency: a continuousinfusion is more efficacious than bolus therapy. Ann Intern Med1991; 115:360-66

14 Chennavasin P. Seiwell R, Brater DC, Liang WMM. Pharma

730 lntermitte@vs Continuous Furoeemide ki CHF (Lahav et a!)

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15 Odlind B, Beermann B. Renal tubular secretion and effect offurosemide. Clin Pharmacol Ther 1980; 27:784-90

16 Brater DC, Chennavasin P, Seiwell R. Furosemide in patientswith heart failure: shift of the dose-response curves. ClinPharmacol Ther 1980; 28:182-86

17 Brater DC. Effects ofprobenecid on furosemide response. ClinPharmacol Ther 1978; 23:259-65

18 Vermeulen A, Chadha DR. Diuretic effect of slow releasefurosemide in elderly patients. Eur J Clin Pharmacol 1983; 24:449-51

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Swan HJC. Renal and extrarenalhemodynamic effects of furosemide in congestive heart failure after acute myocardial infarction. N Engl J Med 1973;288:1087-90

20 Francis CS, Siegel RM, Coldsmith SR, Olivary MT, Levine TB,Cohn JN. Vasoconstrictorresponse to intravenous furosemidein patients with chronic congestive heart failure—activation ofthe neurohumoralaxis.Ann Intern Med 1985; 103:1-6

21 Kraus PA, Lipman J, Becker PJ. Acute preload effects offurosemide. Chest 1990;98:124-28

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23 LiefPD. Diuretics. Am Heart J 1978; 96:824

CHEST I 102 I 3 I SEPTEMBER, 1992 731

NinthAnnualClinicalUpdatein PulmonaryMedicineThis program will be sponsored by the Department ofPulmonary Medicine, Deborah Heart

and Lung Center. It will take place at the Trump Regency Hotel, Atlantic City, November 21.For information, contact Roberta Silver, Conference Administrator, Center for Bio-MedicalCommunication, mc, 80 West Madison Avenue, Dumont, New Jersey 07628(201:385-8080).

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DOI 10.1378/chest.102.3.725 1992;102; 725-731Chest

M Lahav, A Regev, P Ra'anani and E Theodora loading dose for congestive heart failure.

Intermittent administration of furosemide vs continuous infusion preceded by

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