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Renal Function After Cardiac Surgery Adverse Effect of Furosemide
Renal Function After Cardiac Surgery Adverse Effect of Furosemide
Renal Function After Cardiac Surgery Adverse Effect of Furosemide
To cite this article: Raúl Lombardi, Alejandro Ferreiro & Cristina Servetto (2003) Renal Function
After Cardiac Surgery: Adverse Effect of Furosemide, Renal Failure, 25:5, 775-786, DOI: 10.1081/
JDI-120024293
Article views: 62
RENAL FAILURE
Vol. 25, No. 5, pp. 775–786, 2003
CLINICAL STUDY
ABSTRACT
775
in all patients: creatinemia raised from 1.04 0.2 to 1.55 0.4 mg/dL (33%),
associated with a rise in FENa. Differences between group I and group II using
univariate analysis were: baseline serum creatinine (1.01 0.23 mg/dL vs.
1.26 0.19 mg/dL, p ¼ 0.03), FENa (0.99 0.8 vs. 2.2 2.1, p ¼ 0.04), furosemide
dose during surgery normalized to body surface area (93.2 23 mg/1.73 m2 BSA
vs. 135 38 mg/1.73 m2 BSA, p<0.001), and hemodilution index (17.3 4.3% vs.
22.8 3.2%, p<0.01). In the multiple regression model, baseline creatinemia and
furosemide dose were associated to renal dysfunction.
INTRODUCTION
METHODS
Anesthesia was performed as usual (diazepam 0.3 mg/kg and morphine 0.5 mg/kg
at induction continued by isoflurane 1–2% inhalator anesthetics on maintenance);
pancuronium was employed for curarization. Mechanical ventilation during surgery
was performed with a volumetric respirator (EngströmÕ ). EKG was continuously
monitored in DII derivation. Systolic, diastolic, and mean arterial pressures were
registered through radial artery cannulation. The central venous pressure (CVP)
was monitored through subclavian or internal jugular vein catheterization. A bladder
catheter was placed for diuresis control and to collect urine along the study period.
Sodium heparin was used for anticoagulation at an initial dose of 300 UI/kg,
supplementary doses were administered to allow an activated coagulation time
higher than 480 sec. At surgery end, protamine sulfate was administered in a dose
sufficient to reach an activated coagulation time between 90 and 120 s.
Cardiopulmonary by-pass was performed in all cases, with a non-pulsatile regimen.
The system was primed with crystalloid solution, plus sodium bicarbonate and
mannitol 20%. The systemic flux during CPB was maintained close to 2.2 L/min/m2
body surface area and MAP nearby 60 10 mmHg. Membrane oxygenators were
used in all cases. All patients were operated in mild systemic hypothermia
(31–34 C). Mannitol and furosemide were used at 3 mL/kg and 1 mg/kg respectively,
at the beginning of the CPB. Supplementary doses of furosemide were administered
if diuresis on surgery was inappropriate to volume status or hemodilution.
Cefuroxime was used for antibiotic prophylaxis.
The following variables were prospectively recorded:
postoperative period at the first hour (T1), 6 h (T2), 12 h (T3), and 24 h (T4).
Urine output was measured at the same periods. Creatinine, urea, osmolar
and free water clearances, fractional excretion of sodium, potassium and
chloride, and trans tubular potassium gradient were then calculated.
STATISTICAL ANALYSIS
Data are expressed as mean SD, or median and range. For univariate analysis,
Student’s ‘‘t’’ test, ANOVA, Mann-Whitney or Wilcoxon rank tests were used for
continuous variables. Chi-square test or exact Fisher test for qualitative variables.
Multiple regression analysis and bivariate logistic regression model were used to
identify independent risk factors for renal dysfunction. Longitudinal data were ana-
lyzed with repeated measures ANOVA or Kruskall-Wallys test. A probability less
than 5% for the null hypothesis was considered of statistic significance. All tests were
two-tailed. Statistical package SPSS 9.0 (SPSS Inc., Chicago, Illinois) was used for
data processing and statistical analysis.
RESULTS
All 50 patients stayed along the study period. Thirty-two (64%) were male and
eighteen (36%) female. Mean age was 61.4 9.9 y (30–80 y). Forty-six patients had
comorbidities: hypertension (36), diabetes (12), and nephropathy (2). Underlying
cardiac disease was ischemic in the majority of cases (38) and valvular disease
(10). Thirty-two patients were treated with antiplatelet drugs prior to surgery,
twenty-three received b-blockers, fifteen ACEI, and fourteen, calcium antagonist.
In patients exposed to radiocontrast agents, the median time between exposition and
surgery was 1 day (range: 1–15 days). Tables 1 and 2 summarize intraoperative
Type of surgery
Coronary by-pass 36
Valve replacement 10
By-pass and valve replacement 2
Other 2
CPB timea (min) 77.7±34
Aortic cross clamping time (min) 42.9±19.8
Furosemide dose (mg) 101.5±28
Mannitol dose (g) 61.5±21.3
Hemodilution index 18±4.6
Autotransfusion volume (mL) 591.7±570
a
Cardiopulmonary by-pass time.
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1,8 90
1,6 80
1,4 70
CCr (ml(min)
SCr (mg/dl)
1,2 60
1 50
0,8 40
0,6 30
0,4 20
0,2 10
0 0
BAS AL TO T1 T2 T3 T4
Figure 1. Serum creatinine (SCr) (mg/dl), and creatinine clearance (CCr) (mL/min) through
the observation period.
2000
Diuresis (ml/hr)
1500 1240
1000 76 8
364
500 122 71
0
CPB 1 hr 2-6 hr 7-12 hr 13-24hr
Period
19
SCr 6 hr PO (mg/dl)
20
1 SCr 12 hr PO (mg/dl)
SCr 24 hr PO (mg/dl)
33
0 FeNa T4 (%)
Group I Group II
Figure 3. Evolution of serum creatinine (SCr) along the observation period in patients with
SCr at T4 less or equal to 2 mg/dl (Group I), or above 2 mg/dl (Group II). It is also shown
FENa at the end of the study (T4).
Variable b t P
2
SCr (mg/dl)
SCr PO 6 hr (mg/dl)
SCr PO 12 hr (mg/dl)
SCr PO 24 hr (mg/dl)
0 FENA T4 (%)
Figure 4. Evolution of serum creatinine (SCr) along the observation period in patients with
SCr at T4 less or equal to 1.5 mg/dL, or above 1.5 mg/dL. It is also shown FENa at the end of
the study (T4).
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3, 0
2, 0
1, 5
1, 0
,5
,5 1, 0 1, 5 2, 0 2, 5 3, 0 3, 5
SCr at 24 hs PO (mg/dl)
Figure 5. Multiple regression model shows association of furosemide dose and baseline
creatininemia with SCr at 24 h. There is a high correlation between observed and calculated
SCr at 24 h (r ¼ 0.836).
between group in urea, osmolar and free water clearance, potassium, chloride, and
transtubular potassium gradient.
In univariate analysis baseline SCr, FENa at T4, furosemide dose, and hemodi-
lution index were significantly different between groups (Table 3). In multivariate
logistic regression analysis only baseline SCr (GI: 1.01 0.23 mg/dL, GII: 1.26
0.19 mg/dL, p ¼ 0.03) and intraoperative furosemide dose (GI: 93.3 23 mg/
1.73 m2 BSA; GII 135 38.4 mg/1.73 m2 BSA, p<0.01) were independently
associated to renal dysfunction. Also, in multiple regression analysis, variables sig-
nificantly associated with SCr at 24 h. were furosemide dose (b ¼ 0.707) and baseline
creatinine (b ¼ 0.474) (Table 4). Observed and calculated SCr at 24 h showed a high
correlation (r ¼ 0.836, p<0.05). (Fig. 5).
DISCUSSION
It must be remarked that renal dysfunction was detected early, at the first hour
of postoperative period and was the greatest decline at six hour after surgery. At the
end of the 24-h period six patients (11.5%) had SCr higher than 2 mg/dL, 20 patients
(40%) had SCr higher than 1.5 mg/dL, but it must be noted that all but six patients
continued with a depressed creatinine clearance despite of ‘‘normal’’ creatinine
values at 24 h postoperative. Usually SCr is determined in cardiac surgery patients
after 24 h of surgery, so early and transient renal dysfunction can be overlooked.
Our data are in accordance with those of Wesslink et al.[6] who pointed out that renal
dysfunction is a result, almost unavoidable of extracorporeal circulation.
Cardiopulmonary by-pass determine negative effects on renal circulation, as a
consequence of nonpulsatile flux, decrease of renal perfusion pressure under the
autoregulation level and free hemoglobin toxicity secondary to hemolysis due to
extracorporeal circulation.[14,15] On the other hand, systemic inflammatory response
mediated by cytokines and other mediators, stimulated by bioincompatible
membranes, plus the effect of tissular injury due to surgery, hypothermia, aortic-
clamping, and myocardial reperfusion[12–14,16,17] lead to hemodynamic changes and
endothelial damage[18–21] which are in the base of renal injury.
We have not been able to demonstrate any association among variables related
to cardiopulmonary by-pass and renal dysfunction, as almost[6,13,22] but not all[8,11]
authors did. In a case-control study previously performed in our institution,[10] an
association between cardiopulmonary by-pass time and renal failure was found, but
it must be pointed out that CPB time in the past was longer than in the present study.
Similar considerations can be done regarding intraoperative MAP, which commonly
reached lower levels than nowadays.[11]
We have neither found association with postoperative hemodynamic
variables, nor the use of vasoactive drugs. Exposition to nephrotoxic drugs,
particularly radio-contrast media, showed no association with renal dysfunction.
In our opinion, the lack of association between hemodynamic variables and
renal dysfunction is relevant. One can hypothesize that progress in surgery and
anesthetic techniques, particularly reduction of operatory time, improvement in
cardiopulmonary by-pass equipment, use of more biocompatible membranes and
improvement on hemodynamic support during and after surgery, have reduced the
risk of renal injury. On the other hand, those factors related to the host, little or not
modifiable, could play a leading role in the pathogenesis of renal failure.
Percutaneous transluminal coronary angioplasty had selected patients leaving to
surgery the higher risk patients, according to the complexity and severity of illness.
In the present study, renal dysfunction at 24 h after surgery was clearly related
with baseline serum creatinine: SCr of Group II was higher than SCr of Group I
(1.26 0.13 mg/dL vs. 1.01 0.23 mg/dL, p ¼ 0.03). It must be pointed out that this
variable was predictive of renal dysfunction, in spite of being near normal values. This
predictive ability persists even if the arbitrary SCr value used to define groups is
reduced from 2 mg/dL to 1.5 mg/dL: 0.92 0.27 mg/dL vs 1.17 0.21 mg/dL;
p<0.01 (data not shown in results). In a retrospective study of 43,642 patients who
underwent cardiac surgery with cardiopulmonary by-pass, Chertow et al.[5] found that
a preoperative SCr higher than 1.5 mg/dL was a risk factor for the development of
renal failure. In the present group of patients, predictive SCr level was as lower as
1.26 mg/dL. A number of investigators have shown that previous renal disease
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diuretic. So, in the lack of evidence of the benefit of furosemide as a protector drug
in ARF, it should be avoided in cardiac surgery in the doses administered in the
present study.
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