LMNOP in ADHF: Should Lasix
Stay in the Acronym?
EVIDENCE IN THE ED
AMOS SHEMESH, MD, PGY-III
MARCH 2014
Diuretics and ADHF
 Mainstay for the treatment for the past four decades
 Data on dosing strategies is lacking
 A few studies have examined the potential toxicities
 May have a number of adverse effects on patients
with HF, including direct activation of RAAS,
increased ADH, increased norepi levels, decreased
GFR, increased SVR, and electrolyte disturbances.
 Acute isn’t the same as chronic
The Guidelines
 Evaluation and management of patients with ADHF: Heart Failure Society
of America 2010 comprehensive heart failure practice guideline
 LOE = C
 It is recommended that patients admitted with ADHF and evidence of fluid overload be
treated initially with loop diuretics—usually given intravenously rather than orally.
 Careful observation for development of side effects, including renal dysfunction,
electrolyte abnormalities, symptomatic hypotension, and gout is recommended in
patients treated with diuretics, especially when used at high doses and in combination.
 When congestion fails to improve in response to diuretic therapy, the following options
should be considered
 Re-evaluating presence/absence of congestion
 Sodium and fluid restriction
 Increasing doses of loop diuretic
 Continuous infusion of a loop diuretic
 Addition of a second type of diuretic
 Another option, ultrafiltration, may be considered
Question
 Are loop diuretics clinically indicated and beneficial
in patients who present with acute cardiogenic
pulmonary edema?
Articles
 Hoffman JR, Reynolds S. Comparison of
nitroglycerin, morphine and furosemide in treatment
of presumed pre-hospital pulmonary edema. Chest
1987; 92: 586-93.
 Cotter G, Metzkor E, Kaluski E, et al. Randomized
trial of high-dose isosorbide dinitrate plus low-dose
furosemide versus high-dose furosemide plus lowdose isosorbide dinitrate in severe pulmonary
oedema. Lancet 1998; 351:389-93.
Articles
 Hoffman JR, Reynolds S. Comparison of
nitroglycerin, morphine and furosemide in
treatment of presumed pre-hospital
pulmonary edema. Chest 1987; 92: 586-93.
 Cotter G, Metzkor E, Kaluski E, et al. Randomized
trial of high-dose isosorbide dinitrate plus low-dose
furosemide versus high-dose furosemide plus lowdose isosorbide dinitrate in severe pulmonary
oedema. Lancet 1998; 351:389-93.
Hoffman, et al - Methods
 Prospective non-randomized sequential prehospital
trial evaluating various combinations of therapy for
presumed pre-hospital cardiogenic pulmonary
edema in LA county
 Study patients got 1 of 4 therapeutic regimens
 Compared NTG, furosemide, morphine in 57
presumed pulmonary edema patients (Best outcome
with NTG)
Group B pts were 27x more likely to worsen than group A patients by odds ratio
testing, and 17.9x more likely to worsen than all groups combined.
Group A pts were 13x more likely to improve than group B patients, and any patient who
got nitro (A,B,D) was 6.5 times more likely to improve than those who didn’t.
No significant differences in objective response to therapy between the groups of
patients who received Lasix (A, B, and C) compared to the group that didn’t (D)
Hoffman, et al –Results
Fluid/Electrolyte complications in the first 24h were related primarily to Lasix.
Arrhythmias with hypokalemia in 3 pts
Fluid repletion needed in 13 pts for hypotension/tachycardia
The one group D patient (did not get lasix in the field) who developed
hypotension to an SBP of 80 did so after getting 70mg lasix in the ED
Hoffman, et al - Conclusions
 23% of patients were misdiagnosed, didn’t have pulmonary edema
 Furosemide may have caused adverse effects with fluid and electrolyte
management in some patients
 Patients in nitro group had no adverse effects
 Findings are more dramatic for morphine than furosemide. However,
>25% who received lasix in the field later required fluid repletion, and
several developed important adverse consequences, including severe
volume-related hypotension (three).
 “May be no apparent therapeutic advantage to early use of furosemide”
 Use caution:
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Small study (N=57), multiple treatment arms
Comparing groups with drug combos is not the same as comparing the drugs
Didn’t validate the final diagnoses of hospital physicians
It’s a pre-hospital treatment study… from 1987.
Articles
 Hoffman JR, Reynolds S. Comparison of nitroglycerin,
morphine and furosemide in treatment of presumed prehospital pulmonary edema. Chest 1987; 92: 586-93.
 Cotter G, Metzkor E, Kaluski E, et al.
Randomized trial of high-dose isosorbide
dinitrate plus low-dose furosemide versus highdose furosemide plus low-dose isosorbide
dinitrate in severe pulmonary oedema. Lancet
1998; 351:389-93.
Cotter, et al - Methods
Pts recruited 1996-1997 from EMS in Israel
EMT-P & MD screened for si/sx of
cardiogenic pulmonary edema
CXR confirmed, Sats <90%
All get oxygen, lasix 40mg, morphine 3mg
Then Randomized
8x more nitrate
4x more lasix
Group A: 3mg nitrate q5 min+40mg lasix
Group B: 80mg lasix q15min+nitrate
1mg/h increased by 1 mg/h q10 min
Continue until sats >96%, MAP<90 or
decreases by 30%.
Cotter, et al - Results
Mechanical ventilation was required
in 7 (13%) patients in the nitrate
group and 21 (40%) in the
furosemide group (P=0.0041).
MI occurred in 9 (17%) and 10 (37%)
patients (P=0.047), respectively.
Composite end-point (i.e. one or
more of the 3 main outcome
measures) was recorded in 13 (25%)
from group A, and 24 (46%) in
group B.
Secondary outcome of O2 sats were
significantly better in group A than
group B.
Cotter, et al - Results
 Intubation and MI occurred in significantly fewer
patients in nitrate group than in lasix group
 Nitrate group more effective than lasix group in
controlling severe pulmonary edema
 Use caution:
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Small study
Combination regimens
Lasix dosing in this study was pretty high – mean doses were
56mg (SD 28) and 200mg (65), respectively.
Ideal dosing of lasix remains to be determined
 National Registry of >100K pts– 89% got IV diuretics
 Stratified into low <160 mg and high >160mg groups
according to cumulative dose of IV lasix in first 24h
 High dose group had a significantly greater
decline in renal function, a longer length of
stay, and a higher in-hospital mortality rate
(OR 0.87; 95% CI 0.78-0.97, P=0.1)
HUPism
 Loop diuretics are a Level C recommendation in
ADHF and are appropriate to use, though high doses
early in management of acute cardiogenic pulmonary
edema may be harmful or lead to further
complications.
… and maybe consider holding off on diuretics in
patients with ADHF and worsening renal function
Lasix and Decreased Cardiac Output
 Braunwald and colleagues demonstrated an average fall in CO
of 20% following diuresis inpatients with impaired cardiac
function both at rest and during exercise.
 Nelson and coworkers compared the hemodynamic effects of
IV lasix (1mg/kg) with that of IV isosorbide dinitrate (50-200
ug/kg/min) in pts with LV failure following MI. The PAOP fell
in both groups, but the CO was maintained in the nitrate
group, whereas it fell by about 10% in the furosemide group.
 Hutton and colleagues compared the effects of IV lasix (0.5
mg/kg) and isosorbide 5-mononitrate (15mg) at the time of
cardiac cath in patients with LV dysfunction; furosemide
induced acute vasoconstriction with a reduction in CO; in
contrast, isosorbide 5-mononitrate maintained CO while
reducing the PAOP.