FUROSEMIDE IN CRITICALLY ILL –

“When truth is replaced by silence,the silence is a lie.”

The dual effect of furosemide in refilling

intravascular in managing sepsis/septic shock
with fluid overload

Courtessy of george
CLINICAL TRIAL AND THE
CONTROVERSIES
 Loading dose of 0.4 mg/kg followed by a continuous infusion commenced at a dose of 0.05 mg/kg/h.
 Target urine output in the range of 1.0–2.0 mL/kg/h. The maximum infusion rate was 0.40 mg/kg/h. Urine
output was assessed hourly.
 Infusion was continued for a minimum of 24 h and discontinued if any one of the following events
occurred: 1) kidney recovery; 2) decision to start RRT; 3) death; 4) adverse reaction attributed to study
intervention; 5) ICU discharge; or 6) a total of 7-days of study drug had been administered.
 Five trial enrolling 555 patients
 “We found no statistical difference in mortality (oods ration [OR], 1.28,
p=0.18) or renal recovery (OR, 0.88,p=0.5) with use of loop diuretics compare
with control.”
 However, loop diuretics were associated with
 Shorter duration of RRT (-1.4 days, p=0.02),
 Shorter time to spontaneous decline in serum creatinin (-2.1 days, p=0.01)
 Greater increase in urine output from baseline (OR, 2.6, p=0.004)).
Post hoc analysis from FACtt trial
Clin J Am Soc Nephrol 6: 966-973, 2011
Conclusion:
….with caveat that these data were obtained in a
randomized clinical trial of patients with AKI,
clinicians may be reassured that, in appropriate
patients, diuretics may not be contraindicated
In summary, both fluid
balance and urine volume
were found to be independent
predictors of mortality in Diuretics

adult critically ill patients with

AKI.
No-
diuretics
Of interest, diuretic use
appeared to be independently
associated with better survival
in this study

Teixeira et al. Critical Care 2013, 17:R14

Figure 1: Changes in hourly (a) plasma furosemide concentration, (b) urinary furosemide
excretion and (c) urine output over the six hour period following a single bolus dose of
intravenous furosemide, stratified by measured creatinine clearance. Error bars signify 95%
confidence interval.
 Low GFR = No furosemide in urine

No furosemide in urine = no UO
THE EFFECT OF FUROSEMIDE ON TOTAL
BLOOD VOLUME AND PLASMA VOLUME
 The findings suggest that the rate of fluid refill into
the intravascular compartment exceeded the net volume of
fluid excreted in the urine.
 Total blood volume No
Change post furosemide
FUROSEMIDE-INDUCED SHIFT OF FLUID FROM THE
EXTRAVASCULAR TO THE INTRAVASCULAR

 Hemodynamic /Vascular effect of furosemide:

 Furosemide increases in venous compliance and therefore reduced venous
vein pressure  reduction in capillary hydrostatic pressure  Starling forces
favoring transcapillary refill.
 Furosemide increases of plasma protein concentration  increase in the
total circulating plasma protein mass  increased colloid osmotic pressure.

Diffusion of fluid into the intravascular compartment is therefore favored not only by
hydrostatic forces but by increases in colloid osmotic pressure, with this dual
mechanism accounting for an increase in colloid hydrostatic gradient.
 CONCLUSION IN THIS STUDY

 Furosemide may have a selective capability for expanding blood

volume independently of its diuretic action.
 The extrarenal actions of furosemide all serve to reduce edema
formation and augment the intravascular volume.
 Therefore, in the setting of clinical edema states, the action of furosemide
is such that intravascular volume is replenished at a rate that is equal to or
that exceeds volume removal due to diuresis.
 Rationale for using diuretics:
 to ameliorate AKI includes prevention of tubular obstruction,
 reduction in medullary oxygen consumption and increase in renal blood flow
 reducing fluid overload and venous congestion
 Surrogate Parameter for fluid overload;
 Increased CVP
 peripheral edema
 increased intra-abdominal pressure
 Diuresis responsiveness; urinary output of at least 100 ml/h following a test
dose of 1.0–1.5 mg furosemide/kg BW predicted reduced progression to a
higher stage of AKI in oliguric patients
1. Pasien A, laki laki 46 tahun paska prosedur appendektomi laparoskopi dengan sepsis
intraabdominal berat.
2. Pasien B, laki-laki berusia 58 tahun sepsis pneumonia paska syok kardiogenik disebabkan
oleh infark miokardium anterior luas.
3. Pasien C, anak 12 tahun paska laparotomi eksplorasi karena peritonitis generalisata.
4. Pasien D, anak 10 tahun dengan sindroma syok dengue, efusi pleura dan sepsis
pneumonia.
 KESIMPULAN
 Loop diuretics are commonly prescribed in ICU
 They appear to be mostly prescribed to control fluid balance
 The effect of a standard dose of furosemide (40 mg IV) varies
greatly in different individuals and is modulated by renal function,
blood pressure, and albumin level.
 Such a dose leads to changes in acid base status (alkalosis) due to
its effect on chloride excretion
 In patients with established AKI there is limited logic to such
treatment as urinary furosemide is the major driver of diuresis and
its concentration in urine is very low
 Whether loop diuretics are the best diuretics to use in ICU patients
remains untested