Transcript Diapositiva 1

ULTRAFILTRAZIONE EXTRACORPOREA NELLA
SINDROME CARDIORENALE ACUTA
(Lo Studio CARRESS-HF)
Aurelio Limido
UO Nefrologia e Dialisi
AO Fatebenefratelli e Oftalmico
Milano
2012;367 24 december :2296-304.
The acute cardiorenal syndrome (type 1) is defined as worsening renal function
in patients with acute decompensated heart failure.
It occurs in 25 to 33% of patients with acute decompensated heart failure and
is associated with poor outcomes.
Multiple processes contribute to the development of the acute cardiorenal
syndrome, including extrarenal hemodynamic changes, neurohormonal
activation, intrarenal microvascular and cellular dysregulation, and oxidative
stress.
In some cases, intravenous diuretics, which are often administered in patients
with acute decompensated heart failure, may directly contribute to worsening
renal function.
The use of diuretics to treat persistent congestion after the onset of worsening
renal function may lead to further kidney injury.
Current treatment guidelines state that ultrafiltration is a reasonable
approach in patients with congestion that is not responding to
medical therapy (class IIa, level of evidence B).
Potential advantages of ultrafiltration include greater control over the
rate and volume of fluid removal, greater net loss of sodium, and less
neurohormonal activation.
However, little is known about the safety and efficacy of ultrafiltration
as compared with pharmacologic therapy in patients with acute
decompensated heart failure complicated by acute cardiorenal
syndrome and persistent congestion.
Methods
We randomly assigned a total of 188 patients with acute decompensated
heart failure, worsened renal function, and persistent congestion to a
strategy of stepped pharmacologic therapy (94 patients) or ultrafiltration
(94 patients).
The primary end point was the bivariate change from baseline in the serum
creatinine level and body weight, as assessed 96 hours after random
assignment.
Patients were followed for 60 days.
Patients who were hospitalized with acute decompensated heart failure as the
primary diagnosis were eligible for enrollment. There was no exclusion
criterion that was based on ejection fraction.
All patients had worsened renal function (increase in the serum creatinine
level of at least 0.3 mg per deciliter) within 12 weeks before or 10 days after
the index admission for heart failure.
All patients were required to have at least two of the following conditions at
the time of randomization: at least 2+ peripheral edema, jugular venous
pressure greater than 10 cm of water, or pulmonary edema or pleural
effusion on chest radiography.
Patients with a serum creatinine level of more than 3.5 mg per deciliter at the
time of admission and those receiving intravenous vasodilators or inotropic
agents were excluded from the study.
For patients assigned to ultrafiltration therapy, loop diuretics were
to be discontinued for the duration of the ultrafiltration intervention.
Ultrafiltration was performed at a fluid-removal rate of 200 ml per
hour.
For patients assigned to stepped pharmacologic therapy,
intravenous diuretics were used to manage signs and symptoms of
congestion. Investigators were encouraged to decrease doses, increase
doses, or continue current doses of diuretics as necessary to maintain
a urine output of 3 to 5 liters per day.
Results
Ultrafiltration was inferior to pharmacologic
therapy with respect to the bivariate end point
of the change in the serum creatinine level and
body weight 96 hours after enrollment (P =
0.003), owing primarily to an increase in the
creatinine level in the ultrafiltration group.
At 96 hours, the mean change in the creatinine
level was −0.04±0.53 mg per deciliter in the
pharmacologic therapy group, as compared with
+0.23±0.70 mg per deciliter in the ultrafiltration
group (P = 0.003).
There was no significant difference in weight
loss 96 hours after enrollment between patients
in the pharmacologic-therapy group and those
in the ultrafiltration group (a loss of 5.5±5.1 kg
and 5.7±3.9 kg, respectively; P = 0.58).
Conclusions
In a randomized trial involving patients hospitalized for acute decompensated
heart failure, worsened renal function, and persistent congestion, the use of a
stepped pharmacologic-therapy algorithm was superior to a strategy of
ultrafiltration for the preservation of renal function at 96 hours, with a similar
amount of weight loss with the two approaches.
Our study has several limitations.
First, although the trial was randomized, the treatment assignments were not
blinded, and biases on the part of study investigators may have affected the
duration or relative intensity of ultrafiltration and pharmacologic therapy.
Second, the safest and most effective rates of fluid removal, the duration of
therapy, and the conditions for termination of ultrafiltration are unknown.
Finally, the results of the strategies tested here may not apply to other patient
populations with acute decompensated heart failure, such as patients with less
severe cardiorenal syndrome.
NEJM 367; 24 december 13, 2012 (Editorial Comment)
CARRESS-HF illustrates overall dismal outcomes in patients with acute cardiorenal
syndrome. Regardless of treatment strategy … more than a third of the patients died or
were readmitted to the hospital for acute decompensated heart failure within 60 days,
despite substantial overall weight loss.
We simply do not know whether a rise in serum creatinine level during treatment
represents desired effects of hemoconcentration (when therapy is efficacious) or undesired
deterioration of renal function (when therapy is ineffective). In fact, transient changes in
serum creatinine levels during therapy for acute decompensated heart failure may not
necessarily reflect substantial underlying renal injury or adverse longterm consequences.
The effect of therapy on the bivariate primary end point of change in weight and change in
serum creatinine level may be dependent on the rate at which congestion is being relieved.
It is conceivable that a slower but steady ultrafiltration rate may help maintain an adequate
plasma refill rate. This may result in longer duration of ultrafiltration and greater volume
removal without inducing azotemia.
NEJM 368;12 march 21, 2013
Ultrafiltration presumably should be restricted to patients with impairment of
renal function, cardiac function, or both that is more severe than the
impairment in patients involved in the current trial.
Furthermore, it is unclear at first sight why renal function should be
different at 96 hours only when serum creatinine concentrations are used as
a marker of renal function, but not when the level of cystatin C or the
glomerular filtration rate are used. How can this discrepancy be explained?
Jenny Haas, M.D.
Bernhard K. Krämer, M.D.
Urs Benck, M.D.
NEJM 368;12 march 21, 2013
Given the bivariate primary end point that entailed the serum creatinine level for
the comparison of ultrafiltration with pharmacologic therapy … this trial could not
have had different results.
In the ultrafiltration group, most of the fluid removal was achieved with
ultrafiltration, which implied that less fluid was eliminated by the kidney through
glomerular filtration. By contrast, in the pharmacologic-therapy group, the
excess fluid was eliminated exclusively through the kidney. Since, according to
the manufacturer, creatinine is not removed with the ultrafiltration procedure
used in the study, it could be anticipated that a smaller amount of creatinine was
excreted through glomerular filtration and tubular secretion.
Gian Paolo Rossi, M.D.
Antonio Piccoli, M.D., D.Sc.
Lorenzo A. Cal, M.D., Ph.D.
NEJM 368;12 march 21, 2013
As manufacturers of the Aquadex FlexFlow ultrafiltration system, we
would like to highlight some points.
First, the study population in this trial had more advanced disease than
that which is indicated for this therapy.
Second, ultrafiltration was performed at a fluid removal rate of 200 ml
per hour, which may have been inappropriate for this patient population.
Third, rates of intravascular volume refill were not monitored.
Juan Bosch, M.D.
Luis A. Rios-Nogales Garces, M.D., Ph.D.
NEJM 368;12 march 21, 2013
Transient increases in the creatinine level may not portend a poor prognosis.
Whereas doses of diuretics were adjusted in the pharmacologic-therapy group, the
ultrafiltration rate was uniformly 200 ml per hour, which may be excessive … in
patients with low blood pressure or right ventricular dysfunction.
In contemporary ultrafiltration devices, hematocrit sensors estimate blood volume so
that the capillary refill time is not exceeded and hypovolemia is prevented.
A total of 12% of patients in the pharmacologic-therapy group received inotropic
agents, which are prohibited in ultrafiltration; this may have attenuated hypotensionrelated worsening renal function.
A total of 23% of patients in the ultrafiltration group crossed over to alternative
therapy, and 39% received intravenous diuretics before the 96-hour assessment,
which may have contributed to worsening renal function.
Maria Rosa Costanzo,
Gregg C. Fonarow,
Gerasimos S. Filippatos, M.D.
NEJM 368;12 march 21, 2013 (Reply)
The diversity of responses to the results of our trial highlights the uncertainty in
clinical practice for patients with acute decompensated heart failure and kidney
disease. Haas et al. recommend that ultrafiltration be reserved for patients with
more advanced kidney disease or cardiac dysfunction, whereas Bosch and RN
Garces suggest that the patients in our trial had disease that was more advanced
than the disease stage for which ultrafiltration is recommended.
Both Haas et al. and Rossi et al. question the use of the serum creatinine level to
assess renal function. We selected change in the creatinine level as a key
component of the primary end point in our trial because it is one of the few
measures routinely used ... .
Bosch and RN Garces, and Costanzo et al., raise important issues related to the
application of ultrafiltration in our trial. We acknowledge that the ideal rate of fluid
removal, supportive medical therapy, monitoring measures, and the conditions
used to determine the best time for discontinuing acute decongestive therapies for
ultrafiltration are unknown.
2013;62(3):453-456
2013;62(3):453-456
As shown in CARRESS-HF, when diuretic dosages are titrated effectively and in a
timely manner that uses a continuous infusion of loop diuretics and adds distalacting diuretics, it is possible in many patients to remove an amount of fluid
similar to ultrafiltration.
At the present time, we can recommend ultrafiltration only in patients with ADHF
who are unable to achieve decongestion with a rational stepped-up diuretic
regimen and usual hemodynamic care.
Because readmission and mortality rates remain high for patients with ADHF and
cardiorenal syndrome, further studies are needed to guide clinicians in the use
of diuretics and ultrafiltration. In order to improve care, we need methods that
optimize active monitoring of congestion and the hemodynamic and kidney
responses to treatment that go beyond measurement of body weight and SCr
Benjamin J. Freda, DO
Jaya Mallidi, MD
Gregory L. Braden, MD
Baystate Medical Center
Springfield, Massachusetts
Open questions remain. First, is UF really justified in congested patients who still
have daily urine output greater than 2.5-3 L during medical therapy, as in the
CARRESSHF study? On the basis of the available data, the answer is probably no …
Second, is there a threshold level of renal dysfunction beyond which UF should not
be used? Albeit definite clinical evidence is limited, most of the trials excluded
patients with sCr values exceeding 3 mg/dL. Quite obviously, UF is not indicated in
the presence of metabolic derangements (azotemia, hyperkalemia, metabolic
acidosis) requiring different techniques of RRT.
Third, how could the fluid removal rate by UF be optimized in order to match the
capillary refilling rate in individual patients? Despite the availability of infrared
hemoglobinometry to estimate relative blood volume decrease in modern UF
devices, clinical experience in the nephrology field suggests that this approach does
not invariably obviate hemodynamic instability during extracorporeal procedures.
On the whole, the available evidence suggests that clinicians should adopt
a very selective and targeted approach to performing UF in patients with
ADHF – e.g., as emergency treatment in the presence of acute pulmonary
edema with respiratory failure in oliguric ADHF, or when congestion is
really unresponsive to maximal and appropriate diuretic treatment.
Along the same line of reasoning, UF is not indicated as an alternative
strategy to diuretic therapy.