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OLEH:
AGUSTIAN DENY
(I11109090)
I K A P U R WA N T I ( I 1 1 1 1 0 0 5 7 )
WENDY WONGSO
(I11111025)

S M F I L M U P E N YA K I T D A L A M
PROGRAM STUDI KEDOKTERAN
U N I V E R S I TA S TA N J U N G P U R A
R U M A H S A K I T A B D U L A Z I S S I N G K AWA N G
2016

REVIEW ARTICLE

Fluid Management and Use of

Diuretics in Acute Kidney Injury
ANNIE-CL AIRE NADEAU-FREDETTE AND JOSEE BOUCHARD
D I V I S I O N O F N E P H R O L O G Y, D E PA R T M E N T O F M E D I C I N E ,
H O P I TA L D U S A C R E - C O E U R D E M O N T R E A L
UNIVERSITE DE MONTREAL, MONTREAL, CANADA .
A D VA N C E S I N C H R O N I C K I D N E Y D I S E A S E , VO L 2 0 , N O 1
(JANUARY), 2013: PP 45-55

Introduction
Acute

kidney injury (AKI) is a frequent condition

encountered in hospitalized patients, especially in
critically ill adult patients in which its incidence can
reach 65%.
However, few therapeutic interventions have been
successful in treating or preventing AKI, often because
of delayed diagnosis and interventions.
Patients at risk for or with AKI require careful attention
to their hemodynamic status because hypovolemia can
decrease kidney perfusion and contribute to kidney
injury.

Introduction
Early

fluid administration aims to prevent and/or

minimize the effects of AKI.
However, recent observational studies in critically ill
patients have suggested that fluid overload may have a
negative influence on kidney function and mortality.
This journal will review recent literature on
1. Volume resuscitation
in critically ill
2. Fluid management
adult patients
with AKI
3. Use of diuretics

Introduction
Volume resuscitation

Volume Resuscitation
Rivers et al (2001), In severe sepsis and septic shock,

the administration of intravenous fluids and

vasopressors in the first hours of an acute critical
illness has been considered one of the most
important interventions toward better outcomes.
This trial on EGDT performed at one emergency
department
randomized.
The
mortality
was
significantly lower in the EGDT group (30.5% vs
46.5%, P 0.009).

Crystalloids vs Colloids
In volume resuscitation, the optimal repletion fluid

remains controversial subject.

Crystalloids are thought to exacerbate pulmonary and
peripheral edema by increasing fluid extravasation.
Whereas colloids tend to remain in a larger proportion
in the intravascular space, reducing the amount of
replacement
fluid
required,
the
degree
of
hypoalbuminemia, and perhaps pulmonary leakiness.
However, colloids have been associated with an
increased risk of complications and adverse effects
on kidney function.

 Kidney

Disease Improving Global Outcome (KDIGO)

Clinical Practice Guidelines for AKI have suggested that
isotonic crystalloids should be used ahead of synthetic
and nonsynthetic colloids for intracellular volume
expansion in patients at risk or presenting with AKI, in
the absence of hemorrhagic shock.
In 2011, the Cochrane Collaboration group systematically
reviewed 56 randomized controlled trials (RCTs) and
concluded that colloids are not superior to isotonic
crystalloids in terms of mortality whenused for
intravascular volume repletion in patients with trauma,
burns, or after surgery.

 In summary, we do agree with the KDIGO and Cochrane

group recommendations and favor the use of isotonic

crystalloids over colloids in patients at risk or with AKI.
Synthetic colloid solutions should be avoided because
of their negative effect on kidney function and survival.
Hypooncotic albumin could be used in patients with sepsis
bearing in mind their infectious risk and should be
avoided in traumatic brain injury.
Hypooncotic albumin may also have a role in patients
requiring large amounts of fluid, and hyperoncotic
albumin should probably be avoided except for cirrhotic
patients.

Late Fluid Management

Over the last years, a few RCTs and several observational

studies have shown that excessive fluid repletion

leading to fluid overload may have a negative influence
on survival, cardiopulmonary complications, kidney
function, and wound healing in critically ill adult patients.
In AKI, once hemodynamic status is stabilized, we usually
aim for a neutral or restrictive fluid balance depending
on the clinical context to prevent or treat significant fluid
overload despite the lack of randomized data.
However, the safety and efficacy of this procedure need to
be confirmed with RCTs. This journal will review this
procedure.

1. Fluid Management in Critically Ill Adult Patients

. Patients in the conservative fluid management strategy had an

increased number of ventilator-free days and a shorter length of

ICU stay.
. Negative fluid balance 24 hours before breathing trial and
negative cumulative fluid balance were independently associated
with first-day weaning success.
. Positive cumulative balance within the first 72 hours was
associated with an increased risk of mortality in sepsis.

consider the timing of the critical illness when making

decisions on fluid administration and supports the importance
of a rapid and adequate fluid repletion in the first hours of
septic shock, and, if feasible, a subsequent neutral fluid
balance.

Fluid Management in Critically Ill Adult Patients with AKI

Positive fluid balance after AKI was strongly
associated with mortality. Negative fluid balance
during RRT (Renal Replacemnet Therapy) was
associated with a decreased risk of death and increased
RRT-free days in AKI
The PICARD study showed that fluid overload, defined
as a percentage of fluid accumulation more than 10%
over baseline weight at hospital admission, was also
associated with a significantly higher mortality at 60
days and at hospital discharge.

 Fluid overload at the time of AKI diagnosis was not

associated with recovery of kidney function; however,

patients with fluid overload at their peak serum creatinine
were significantly less likely to recover kidney function
A retrospective study showed that dialyzed patients who
subsequently
became
dialysis
independent
had
significantly less fluid overload at the time of RRT
initiation (3.5% vs 9.3%, P: 0.004).
Each rise in percent of fluid overload at dialysis initiation
was a significant negative predictor of kidney recovery

Diuretics
Patients

with AKI can develop oliguria and fluid

retention,which are associated with further complications
such as respiratory failure.
In many studies, oliguric AKI has been associated with
worse outcomes than nonoliguric AKI.
The use of diuretics in oliguric AKI is frequent; however, the
benefit associated with this intervention remains unproven.
Experimental studies have shown that furosemide could
reduce AKI risk by inhibiting the Na-K-2Cl cotransporter to
reduce tubular medullar oxygen demand.
Although interesting, the results of these experimental
animal studies might not translate in humans

Diuretics in Prevention of AKI

Several years ago, RCTs reported that loop diuretics do not

prevent AKI.
More recently, Mahesh and colleagues evaluated the
renoprotective effect of lowdose furosemide or saline
infusion for 12 hours in 42 cardiac surgical patients. There
were no differences in kidney function between groups, and
urine output was higher in the furosemide group.
A recent meta-analysis by Ho and Power also concluded
that preventive furosemide administration does not improve
the risk of RRT or mortality.
On the basis of these results, the recent KDIGO guidelines
recommended not using furosemide to prevent AKI

Diuretics in Treatment of AKI

KDIGO guidelines that diuretics should not be used to

treat AKI, except for the management of volume overload

In the meta-analysis by Ho and Power, the use of diuretics in
the treatment of AKI was not associated with a significant
modification of the risk of mortality or RRT requirement.
More recently, data from the FACTT trial were used to assess
the association between fluid balance and diuretic use in
mortality. Higher furosemide doses were associated with
decreased mortality at 60 days (OR 0.38; 95% CI 0.23-0.63)
In contrast, an older retrospective study found that diuretic
use was associated with an increased risk of death (OR 1.68;
95% CI 1.06-2.64)

Diuretics in Treatment of AKI with RRT

Two RCTs recently showed that loop diuretics do not

improve recovery of kidney function in AKI requiring

RRT.
In the largest RCT on furosemide in AKI, patients were
randomized
to
furosemide
at
25
mg/kg/day
intravenously, or furosemide at 35 mg/kg/day orally, or
matched placebo
There were no differences in survival or kidney
recovery rates between the groups.
Patients with high-dose furosemide had a higher urine
output, but this did not translate into differences in the
number of dialysis sessions or time on dialysis.

 In summary, the use of diuretics in AKI has no clear

benefit on the recovery of kidney function and

mortality, and their role in preventing or treating
fluid overload needs to be evaluated.
Therefore, we agree with the KDIGO guidelines that
diuretics should not be used to treat AKI, except for
treating volume overload.

 Two ongoing studies might bring new insights to these

clinically relevant questions.

The SPARK study is a phase II randomized, blinded,
placebo-controlled trial of a low-dose infusion of
furosemide titrated to urine output in critically ill
patients with early AKI. The study is expected to enroll
216 critically ill patients and its primary outcome is
progression in AKI severity.
Another study, The Effect of Loop Diuretics on Severity
and Outcome of Acute Kidney Injury, will evaluate the
effect of 1.0 or 1.5 mg/kg/hour of intravenous
furosemide on kidney recovery.

Conclusion

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