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Prevention of Contrast Media–Associated Nephropathy
Randomized Comparison of 2 Hydration Regimens in 1620 Patients Undergoing Coronary Angioplasty
Christian Mueller, MD;
Gerd Buerkle, MD;
Heinz J. Buettner, MD;
Jens Petersen, MD;
André P. Perruchoud, MD;
Urs Eriksson, MD, PhD;
Stephan Marsch, MD, PhD;
Helmut Roskamm, MD
Arch Intern Med. 2002;162:329-336.
ABSTRACT
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Background The administration of radiographic contrast agents remains an important
cause of acute renal failure. The optimal infusion for hydration has not been
evaluated.
Objective To compare the incidence of contrast media–associated nephrotoxicity
with isotonic or half-isotonic hydration.
Design Prospective, randomized, controlled, open-label study.
Methods Patients scheduled for elective or emergency coronary angioplasty were
randomly assigned to receive isotonic (0.9% saline) or half-isotonic (0.45%
sodium chloride plus 5% glucose) hydration beginning the morning of the procedure
for elective interventions and immediately before emergency interventions.
An increase in serum creatinine of at least 0.5 mg/dL (44 µmol/L) within
48 hours was defined as contrast media–associated nephrotoxicity. Secondary
end points were cardiac and peripheral vascular complications.
Results A total of 1620 patients were assigned to receive isotonic (n = 809)
or half-isotonic (n = 811) hydration. Primary end point analysis was possible
in 1383 patients. Baseline characteristics were well matched. Contrast media–associated
nephropathy was significantly reduced with isotonic (0.7%, 95% confidence
interval, 0.1%-1.4%) vs half-isotonic (2.0%, 95% confidence interval, 1.0%-3.1%)
hydration (P = .04). Three predefined subgroups benefited
in particular from isotonic hydration: women, persons with diabetes, and patients
receiving 250 mL or more of contrast. The incidence of cardiac (isotonic,
5.3% vs half-isotonic, 6.4%; P = .59) and peripheral
vascular (isotonic, 1.6% vs half-isotonic, 1.5%, P
= .93) complications was similar between the 2 hydration groups.
Conclusion Isotonic hydration is superior to half-isotonic hydration in the prevention
of contrast media–associated nephropathy.
INTRODUCTION
PREVENTION OF disease should always be the highest priority, particularly
if there is no effective therapy and the disease is iatrogenic. The administration
of radiographic contrast agents remains an important cause of hospital-acquired
acute renal failure, which contributes to morbidity and mortality during hospitalization,
prolongs hospital stay, and increases the incidence of chronic end-stage renal
disease and costs of health care.1-5
However, coronary angiography and angioplasty, diagnostic and interventional
studies in other vascular territories, and computed tomography rely on the
use of radiographic contrast agents. The incidence of contrast media–associated
nephropathy depends on its definition and the patient cohort studied. Chronic
renal insufficiency, diabetes mellitus, contrast media volume, and recurrent
administration are considered important risk factors.5-13
These risk factors have a high prevalence in patients undergoing coronary
angioplasty, rendering it a high-risk intervention for the development of
contrast media–associated nephropathy.12-13
Several agents have been suggested for the prevention of contrast media–associated
nephropathy, including hydration, furosemide, mannitol, dopamine hydrochloride,
aminophylline, atrial natriuretic peptide, acetylcysteine, alprostadil, and
captopril.12-23
Only hydration with isotonic sodium chloride is uniformly accepted and used
in clinical practice. The optimal infusion for hydration (isotonic or hypotonic),
however, has not been evaluated. Most authorities recommend hydration with
half-normal isotonic sodium chloride 12 hours before and after the administration
of radiocontrast.12-16,24-25
We aimed in a randomized controlled study to test the hypothesis that
isotonic hydration is superior to half-isotonic hydration in the prevention
of contrast media–associated nephropathy. Because these hydration regimens
may differ in their effects on platelet aggregation, the coagulation system,
and arterial blood pressure, cardiac and peripheral vascular complications
were analyzed as secondary end points.
PATIENTS AND METHODS
PATIENT POPULATION AND CORONARY ANGIOPLASTY PROCEDURE
Patients scheduled for elective or emergency coronary angioplasty were
asked to participate in the study. End-stage renal failure with regular hemodialysis,
cardiogenic shock, and mechanical ventilation were the only exclusion criteria.
In patients with acute coronary syndromes and in selected patients with stable
coronary disease, coronary angioplasty was performed immediately after diagnostic
angiography ("emergency procedures"). Coronary angioplasty was generally scheduled
2 days after the diagnostic procedure in patients with stable angina ("elective
procedures") Eligible patients were weekly randomly assigned in equal proportions
with the use of a prespecified randomization sequence to one of the hydration
regimens. Coronary angioplasty was performed by standard technique via the
femoral artery. Decisions regarding the procedure were left to the discretion
of the investigator. To reduce the number of variables that may affect contrast
media–associated nephropathy, all procedures were performed with the
use of low-osmolar nonionic contrast media (Ultravist 370; Schering, Berlin,
Germany; and Imeron 350; Byk Gulden, Konstanz, Germany). Acetylcysteine was
not used in this study. No changes in medication were allowed during the study.
This prospective, randomized, controlled, open-label study was carried
out according to the principles of the Declaration of Helsinki and approved
by the local hospital's investigational review board. Written informed consent
was obtained from all participating patients.
HYDRATION REGIMENS
In patients scheduled for elective intervention, hydration with 0.9%
saline (the sodium concentration in isotonic saline is 154 mmol/L) or 0.45%
sodium chloride plus 5% glucose (the sodium concentration in half-isotonic
saline is 77 mmol/L) was started with an infusion rate of 1 mL/kg of body
weight per hour at 8 AM on the day of coronary angioplasty. In addition, patients
were encouraged to drink plenty of fluids (tea and mineral water). In patients
undergoing emergency intervention, no protocol-defined prehydration could
be given. However, the subgroup of patients with acute coronary syndromes
received a 500-mL crystalloidal infusion (the sodium concentration in Ringer
solution is 147 mmol/L) as their standard medical care before admission to
the hospital. The assigned infusion was started immediately on arrival in
the catheter laboratory. The infusion rate during angioplasty was adjusted
to clinical conditions by the operator. After the procedure, hydration was
continued at 1 mL/kg of body weight per hour until 8 AM the next morning.
FOLLOW-UP AND END POINTS
Serum Creatinine
A venous blood sample for serum creatinine analysis was drawn on the
morning before and 24 and 48 hours after coronary angioplasty. All samples
were analyzed in a central laboratory with the use of an enzymatic kit (CREA
Plus; Boehringer Mannheim Systems, Mannheim, Germany).
Renal insufficiency is defined as a decrease in glomerular filtration
rate.26 Glomerular filtration rate has to be
reduced by 50% before a rise in serum creatinine occurs.26-27
Therefore, we decided to use the upper limit of normal of the serum creatinine
level as the cutoff point for the definition for chronic renal insufficiency.
The most common definition of contrast media–associated nephropathy,8, 12-14,20, 22
an increase in serum creatinine concentration of at least 0.5 mg/dL (44 µmol/L)
within 48 hours, was used as the primary end point in this study. To obtain
a variable for baseline renal function independent of age and body mass, we
used a model of calculated creatinine clearance based on lean body mass.28-29 Creatinine clearance per lean body
mass (ClLBM) may be calculated according to the formula ClLBM = E/S, where E is the age-dependent urinary creatinine excretion
rate in milligrams per minute per 50 kg of lean body mass, and S corresponds
to the serum creatinine level at baseline.
Major Adverse Cardiac Events
It is unknown whether isotonic and half-isotonic infusions have different
effects on platelet aggregation and the coagulation system. Therefore, a predefined
subgroup of patients with the placement of coronary artery stents between
September 15, 1998, and February 28, 1999, had extensive clinical follow-up
to monitor major adverse cardiac events within 30 days. A major adverse cardiac
event was defined as death, myocardial infarction, urgent target vessel revascularization,
or hospitalization for unstable angina.
Peripheral Vascular Complications
Duplex sonography of the groin was performed in all patients with new
femoral bruits after removal of the pressure bandage. Peripheral vascular
events were defined as false aneurysms requiring surgery, or prolonged ultrasound-guided
compression or bleeding requiring surgery or transfusion.
STATISTICAL ANALYSIS
The primary analysis compared the incidence of contrast media–associated
nephropathy with isotonic or half-isotonic hydration. The sample size was
determined on the assumption that isotonic hydration would lower the incidence
of contrast media–associated nephropathy by 40%. The expected event
rate for half-isotonic hydration was 6% ( error of .05,  error
of .20). Patients who underwent coronary artery bypass grafting or a second
catheterization within 48 hours of coronary angioplasty were analyzed for
secondary end points only to exclude the effect of extracorporeal circulation
and the second contrast challenge on serum creatinine values. Predefined subgroups
were those undergoing elective procedures, women, persons with diabetes, patients
with preexisting renal dysfunction, and patients receiving higher contrast
volumes ( 250 mL of contrast medium).
Discrete variables were expressed as counts, and continuous variables
were expressed as means ± SDs. Comparisons were made among continuous
variables using analysis of variance for independent samples and repeated-measures
analysis of variance for paired samples (change in serum creatinine level).
Comparison of discrete variables was made by  2 test. All hypothesis
testing was 2-tailed. To identify independent risk factors for the development
of contrast media–associated nephropathy, patients of both hydration
groups were analyzed together. For multivariate analysis, backward stepwise
logistic regression analysis was used (SPSS version 9.0; SPSS Inc, Chicago,
Ill).
RESULTS
BASELINE PATIENT CHARACTERISTICS AND PROCEDURAL DETAILS
From April 1, 1998, to May 31, 1999, 1620 patients scheduled for elective
or emergency angioplasty were enrolled in the study. Eight hundred nine patients
were initially assigned to receive isotonic hydration, and 811 patients were
to receive half-isotonic hydration (Figure
1). Of these, 237 patients had to be excluded from the analysis
of the primary end point because of coronary artery bypass grafting (n = 1),
a second catheterization (n = 137), or incomplete data (n = 99). Therefore,
685 patients assigned to receive isotonic infusion and 698 patients assigned
to receive half-isotonic infusion remained for the analysis of contrast media–associated
nephropathy.
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Figure 1. Patient flow through the study.
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The demographic characteristics of these 1383 patients were well balanced
across treatment groups (Table 1).
Three hundred fifty-four patients (25.6%) were women, 286 (20.7%) had chronic
renal insufficiency, and 217 (15.7%) had diabetes. Most patients had multivessel
coronary artery disease with preserved left ventricular function.
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Table 1. Baseline Clinical Characteristics*
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Angiographic and procedural details were similar in both groups (Table 2). About 50% of coronary lesions
were complex (lesion type B2 or C). Emergency interventions accounted for
almost 60% of all procedures. The mean volume of contrast used in the isotonic
group was 232 mL vs 236 mL in the half-isotonic group. The total amount of
intravenous hydration (2022 mL vs 2028 mL) and the volumes administered before
(443 mL vs 428 mL), during (362 mL vs 369 mL), and after angioplasty (1217
mL vs 1229 mL) were comparable in both groups. The baseline characteristics
of the patients who were excluded from the analysis of the primary end point
were similar between the 2 treatment groups (data not shown) and were similar
to those shown in Table 1 and Table 2.
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Table 2. Angiographic and Procedural Characteristics*
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Baseline renal function was normal in most patients. In addition, renal
insufficiency was predominantly mild in 288 patients defined as having chronic
renal insufficiency. Baseline creatinine (Table 3) was in the normal range, and mean baseline creatinine clearance
per 50 kg of lean body mass was 84 mL/min in both groups.
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Table 3. Outcome Variables (for All Interventions)*
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PRIMARY END POINT
Contrast media–associated nephropathy developed in 5 patients
with isotonic infusion vs 14 patients with half-isotonic infusion. Therefore,
as shown in Figure 2, the incidence
of contrast media–associated nephropathy was significantly reduced with
isotonic (0.7%, 95% confidence interval [CI], 0.1%-1.4%) vs half-isotonic
(2.0%, 95% CI, 1.0%-3.1%) hydration (P = .04). Three
predefined subgroups benefited in particular from isotonic hydration (Table 4): women (reduction in contrast
media–associated nephropathy from 5.1% [95% CI, 1.8%-8.4%] to 0.6% [95%
CI, 0%-1.7%]; P = .01), persons with diabetes (reduction
from 5.5% [95% CI, 1.1%-9.8%] to 0%; P = .01), and
patients receiving 250 mL or more of contrast (reduction from 3.0% [95% CI,
0.9%-5.0%] to 0%; P = .01).
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Figure 2. Incidence of contrast media–associated
nephropathy (CN), mortality, and peripheral vascular complications (Vascular).
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Table 4. Outcome Variables: Subgroup Analysis*
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In patients undergoing elective procedures and receiving study prehydration,
the superiority of isotonic infusion was more pronounced than in patients
undergoing emergency procedures, with a reduction in contrast media–associated
nephropathy to 0.7% (95% CI, 0.3%-1.6%) vs 2.7% (95% CI, 0.9%-4.6%) for half-isotonic
infusion (Table 4, P = .06). For emergency angioplasty, the incidence of contrast media–associated
nephropathy was 1.1% (95% CI, 0.4%-1.9%), with no significant difference between
the hydration groups.
Changes in serum creatinine level were small when considering all patients.
At 48 hours, serum creatinine increased in women 0.04 mg/dL (3.5 µmol/L)
(95% CI, 0.02-0.07 mg/dL [1.8-6.2 µmol/L]) with isotonic hydration vs
0.10 mg/dL (8.8 µmol/L) (95% CI, 0.05-0.15 mg/dL [4.4-13.3 µmol/L])
with half-isotonic hydration (P = .06). In persons
with diabetes, serum creatinine increased 0.04 mg/dL (3.5 µmol/L) (95%
CI, 0.01-0.07 mg/dL [0.9-6.2 µmol/L]) with isotonic hydration vs 0.12
mg/dL (10.6 µmol/L) (95% CI, 0.05-0.18 mg/dL [4.4-15.9 µmol/L])
with half-isotonic hydration (P = .04). In patients
receiving 250 mL or more of contrast, serum creatinine increased 0.05 mg/dL
(4.4 µmol/L) (95% CI, 0.03-0.07 mg/dL [2.7-6.2 µmol/L]) with isotonic
hydration vs 0.08 mg/dL (7.1 µmol/L) (95% CI, 0.05-0.11 mg/dL [4.4-9.7
µmol/L]) with half-isotonic hydration (P =
.06).
As expected, the incidence of contrast media–associated nephropathy
was higher in patients with chronic renal insufficiency and particularly high
with more advanced chronic renal insufficiency (Table 4).
SECONDARY END POINTS
Overall, 2 patients (0.1%) required dialysis during their hospitalization.
One 70-year-old woman with mild chronic renal insufficiency and mitral regurgitation
(half-isotonic hydration group) developed pulmonary edema during coronary
angioplasty that required dialysis. A 77-year-old man with severe chronic
renal insufficiency (isotonic hydration group) had already undergone a shunt
operation in the preceding week and was scheduled to begin long-term dialysis
in 4 weeks. Therefore, the arterial sheath was left for acute dialysis after
coronary angiography and coronary angioplasty.
The length of hospital stay was significantly increased in patients
developing contrast media–associated nephropathy (8.1 vs 4.7 days without
nephropathy, P<.001). However, it was similar
in both treatment groups.
For the analysis of cardiac complications, 530 consecutive patients
with stent implantation (265 with isotonic hydration and 265 with half-isotonic
hydration) had extensive clinical follow-up. Major adverse cardiac events
occurred in 14 patients (5.3%) with isotonic hydration and in 17 (6.4%) with
half-isotonic hydration (Table 3, P = .59). Mortality at 30-day follow-up was 0.4% and 1.1%,
respectively (P = .35).
Peripheral vascular complications, assessed in all 1620 patients, occurred
in 13 patients (1.6%) with isotonic hydration and 12 (1.5%) with half-isotonic
hydration (P = .93).
RISK FACTOR ANALYSIS
Backward stepwise logistic regression analysis revealed female sex and
baseline creatinine level as independent risk factors for contrast media–associated
nephropathy (Table 5). The odds
ratio for female sex was 3.9 (95% CI, 1.5-10.1), and the odds ratio for an
increase in baseline creatinine of 1.0 mg/dL (88 µmol/L) was 6.6 (95%
CI, 3.2-13.8). In patients with a baseline creatinine higher than 1.6 mg/dL
(141 µmol/L), the incidence of contrast media–associated nephropathy
was higher than 10%. Age, diabetes mellitus, and contrast volume were not
independent risk factors. The odds ratio for isotonic hydration was 0.3 (95%
CI, 0.1-0.9).
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Table 5. Multivariate Risk Factor Analysis (Backward Stepwise Logistic
Regression) for the Development of Contrast Media-Associated Nephropathy
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The individual risk for contrast media–associated nephropathy
(ProbCN) can be calculated using the following equations:
(1) ProbCN = 1/(1 + e-z),
where e is a constant (ie, negative exponential of z)
(2) z = -4.9 + (1.36 x sex) + (1.89 x
baseline creatinine) – (1.18 x hydration)
(3) sex = 0 for men and 1 for women, and hydration = 0 for hypotonic
and 1 for isotonic hydration.
COMMENT
Our prospective, randomized, controlled, open-label study compared isotonic
hydration with half-isotonic hydration for the prevention of contrast media–associated
nephropathy in a large cohort of patients undergoing elective or emergency
coronary angioplasty. To our knowledge, this is the largest randomized study
on the prevention of contrast media–associated nephropathy to date.
The key finding was that the incidence of contrast media–associated
nephropathy was significantly reduced with isotonic hydration. Three predefined
subgroups benefited in particular from isotonic hydration: women, persons
with diabetes, and patients receiving high volumes of contrast.
Alterations in renal hemodynamics (ischemia due to vasoconstriction)
and direct tubular toxicity are considered to be the primary factors in the
pathogenesis of contrast media–associated nephropathy.12-13,19
Atheroembolism may be of additional importance in patients undergoing invasive
contrast studies. These factors lead to a decrease in renal blood flow and
glomerular filtration rate. The predominant mechanism and the ability to affect
the predominant mechanism by hydration may differ in different patient settings.
This may in part explain the finding that isotonic hydration is particularly
more effective in certain subgroups of patients. Sodium load seems to be crucial
for the preventive effect of hydration. More potent intravascular volume expansion
and inhibition of the renin-angiotensin pathway may be achieved by higher
sodium concentration with isotonic sodium chloride solution. This hypothesis
is supported by studies showing detrimental effects of furosemide14 and beneficial effects of captopril.20
The finding that persons with diabetes appeared to benefit most from isotonic
hydration is in concordance with the documented preventive effect of captopril
in these patients. Our data suggest that isotonic hydration with 0.9% saline
should be favored for the prevention of contrast media–associated nephropathy
and raise concern about current recommendations favoring hypotonic hydration.12-16,21-22
At first glance, it is surprising that in patients undergoing emergency
coronary angioplasty the incidence of contrast media–associated nephropathy
is not higher than in patients undergoing elective coronary angioplasty. However,
319 patients with acute coronary syndromes, representing 40% of patients in
the emergency angioplasty group, received a 500-mL crystalloidal (the sodium
concentration in Ringer solution is 147 mmol/L) infusion high in sodium as
their standard medical care before admission to the hospital. Therefore, they
too had intravenous prehydration. This identical prehydration with sufficient
sodium load may have in part blunted the differences between the isotonic
and hypotonic hydration regimens started at the time of the angioplasty procedure
in the emergency group and resulted in the low incidence of contrast media–associated
nephropathy in these patients.
Although the volume of contrast media used was high and a substantial
subgroup of patients had already been exposed to contrast media in the preceding
days, the incidence of contrast media–associated nephropathy was lower
than previously reported in comparable patient cohorts.5-23
We consider 2 main factors responsible for the excellent outcome of our patients:
their normal mean baseline creatinine levels and the effective hydration regimens.
Assuming that persons with diabetes and patients receiving larger contrast
volumes are more likely to develop nephropathy, we had expected a higher incidence
of contrast media–associated nephropathy in this study. However, in
accordance with more recent analyses,12-13
our multivariate risk factor analysis showed that baseline renal function
was the most important independent risk factor for the development of contrast
media–associated nephropathy and that the implications of diabetes,
age, and contrast volume may have been overestimated. A patient with a baseline
creatinine of 2 mg/dL (177 µmol/L) had 7 times the risk of developing
contrast media–associated nephropathy of a patient with a baseline creatinine
of 1 mg/dL (88 µmol/L).
To our knowledge, this is the first study to include a sufficient number
of women to show by multivariate analysis that female sex is an independent
risk factor for the development of contrast media–associated nephropathy.
Although contrast volume was not an independent predictor of contrast media–associated
nephropathy in our study, the increased risk in women may be at least in part
explained by the higher ratio of contrast volume to body weight or body surface
area in women. In fact, for women, the risk of developing contrast media–associated
nephropathy was 4 times that of men. Additional mechanisms responsible for
this difference may include impaired thirst sensation and inadequate oral
fluid intake in women after menopause.
Our protocol did not include precatheterization overnight intravenous
hydration. The infusions were started the morning of the procedure. The PREPARED
trial25 showed in 36 patients with mild to
moderate renal insufficiency scheduled for coronary angiography that an outpatient
oral precatheterization hydration strategy is equivalent to overnight intravenous
hydration. The low incidence of contrast media–associated nephropathy
in our subgroup with predominantly mild chronic renal insufficiency at baseline
raises the possibility that neither overnight intravenous hydration nor outpatient
oral hydration may be necessary in these patients.
It was the aim of this study to compare the efficacy and safety of 2
different infusions applied in a hydration regimen that can easily be used
in daily practice. Patients did not all undergo the procedure at the same
time, nor did all patients receive the same amount of hydration. The volume
administered depended on body weight (infusion rate, 1 mL/kg per hour). The
later the angioplasty procedure was performed, the higher the volume administered
before and the lower the volume administered after the procedure. Because
of the comparable mean volumes used in both study groups, this design allows
a valid comparison between both infusions. However, it does not allow definition
of the optimal fluid volume or the optimal infusion rate for the prevention
of contrast media–associated nephropathy.
By study protocol, 137 patients undergoing a second contrast exposure
were excluded from the primary end point analysis. Two (1.5%) of these patients
developed contrast media–associated nephropathy. Therefore, the second
contrast exposure did not significantly increase the incidence of contrast
media–associated nephropathy in these patients. However, we consider
this subgroup too small and too heterogeneous to draw definite conclusions
from it.
In patients with impaired left ventricular function, oral and intravenous
hydration was adjusted to clinical conditions. With this precaution, hydration-induced
pulmonary edema was not observed. However, only 40 patients (2%) had severely
impaired left ventricular function in this study. Additional studies are necessary
in these patients.
There is considerable debate whether the preventive strategy of hydration
should be restricted to patients with preexisting renal dysfunction. Although
our results confirm previous studies4, 6-9,11, 14, 18
establishing preexisting renal dysfunction as the most important risk factor
for the development of contrast media–associated nephropathy, hydration
should not be restricted to this high-risk group. Hydration is a simple, safe,
effective, and inexpensive measure that should not be withheld from patients
in whom perhaps only minor renal damage is to be expected. Any degree of renal
damage should be prevented, if possible.
Grines and colleagues30 recently reported
a reduced risk of ischemic complications with the use of ionic contrast media
compared with nonionic contrast media. Profound platelet degranulation has
been reported as an important adverse effect of some types of contrast media
used in interventional cardiology.31 In addition,
hemodilution with isotonic sodium chloride solution was shown to exert a procoagulant
effect,32 which could not be inhibited by aspirin.33 We, therefore, sought to test the hypothesis that
isotonic and half-isotonic hydration have different effects on platelet aggregation
or the coagulation system that may eventually affect cardiac outcome. Patients
receiving coronary stents are particularly prone to acute thrombotic events
within the first month of implantation.34 However,
an intense follow-up for 30 days in this high-risk cohort showed similar rates
of major adverse cardiac events (isotonic, 5.3% vs half-isotonic, 6.4%; P = .59) with both infusions. Although this finding does
not rule out different effects on platelet aggregation or the coagulation
system, these differences do not seem to be clinically relevant in this setting.
Peripheral vascular complications continue to be a considerable limitation
of percutaneous interventional procedures.34-35
Arterial blood pressure and inhibition of the coagulation system (heparin,
aspirin, and ticlopidine hydrochloride) at the time of sheath removal are
thought to be of particular importance for the development of false aneurysms
and hemorrhagic events. We hypothesized that reduced sodium load36
with half-isotonic sodium chloride solution might lead to reduced peripheral
vascular complications by reducing hypertensive episodes during sheath removal.
However, the incidence was similar in both groups (isotonic, 1.6% vs half-isotonic,
1.5%; P = .93). All patients had intensive blood
pressure monitoring in the hours after coronary angioplasty, allowing rapid
adjustments in intravenous antihypertensive medication (nitroglycerin) for
optimal blood pressure control. Therefore, a small difference in actual arterial
blood pressure may have been blunted by adjustments in antihypertensive medication.
Although this is, to our knowledge, the largest randomized study reporting
on the prevention of contrast media–associated nephropathy, there are
several limitations. First, this study included 286 patients with chronic
renal insufficiency. Renal dysfunction was predominantly mild in these patients.
Because only a small number of patients with severe renal dysfunction were
included in this study, additional studies are warranted to define the optimal
infusion for these patients at highest risk. Second, we can rule out a selection
bias in patients scheduled for elective coronary angioplasty in whom diagnostic
coronary angiography was performed in our center. Coronary angioplasty was
not delayed or canceled because of acute renal failure in any of these patients.
However, about 10% of our study patients had their diagnostic procedures performed
at another hospital. Because this proportion is small, any remaining selection
bias would be only minor and would not affect the principal findings. Third,
oral fluid intake was not quantified in this study. All patients in stable
clinical conditions were encouraged to drink plenty of tea and mineral water.
Although it is unlikely that there was a significant difference in oral fluid
intake between the 2 groups, we cannot quantify total precatheterization and
postcatheterization fluid volume and net fluid balance. Fourth, low-osmolarity
nonionic radiocontrast media were used in this study. Low-osmolarity nonionic
contrast agents differ in various aspects from high-osmolarity ionic agents.9-11 Although the preventive
strategy of hydration seems to be effective with both agents, we suggest that
our results should be only cautiously applied to procedures using high-osmolarity
agents. Fifth, in addition to the nephrotoxic effect of the contrast medium,
atheroemboli may have been dislodged into the renal arteries by the introduction
of the guiding catheter. This should be kept in mind if comparing our findings
with those of intravenous contrast studies. However, because the incidence
of contrast media–associated nephropathy was low in this study, the
clinical effects of atheroemboli were probably minor. Sixth, to obtain a variable
for baseline renal function independent of age and body mass, we used a model
of calculated creatinine clearance based on lean body mass.28-29
This calculated creatinine clearance may not be as accurate a measure of glomerular
filtration rate as an insulin clearance.
In conclusion, our findings show that the incidence of contrast media–associated
nephropathy is significantly reduced with isotonic hydration. Women, persons
with diabetes, and patients receiving large volumes of contrast seem to benefit
in particular from isotonic hydration.
AUTHOR INFORMATION
Accepted for publication June 6, 2001.
Presented in part at the 22nd Congress of the European Society of Cardiology,
Amsterdam, the Netherlands, August 30, 2000, and at the 73rd Congress of the
American Heart Association, New Orleans, La, November 14, 2000.
We thank Kika Peitz and her team for assistance in the catheter laboratories,
Ludger Kessler and his team for support in the postcatherization unit, Anita
Abels for help in data acquisition, and Dietmar Trenk, MD, Jürgen Drewe,
MD, Felix Brunner, MD, and John McB Hodgson, MD, for expert advice.
Corresponding author and reprints: Christian Mueller, MD, Department
of Internal Medicine, University Hospital, Petersgraben 4, CH-4031 Basel,
Switzerland (e-mail: chmueller{at}uhbs.ch).
From the Herz-Zentrum, Bad Krozingen, Germany (Drs Mueller, Buerkle,
Buettner, Petersen, and Roskamm), and Department of Internal Medicine, Universitätsklinik,
Basel, Switzerland (Drs Mueller, Perruchoud, Eriksson, and Marsch).
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