|
|
||||||||
Eur J Cardiothorac Surg 2002;22:106-111
© 2002 Elsevier Science NL
a Department of Cardiothoracic Surgery, Wythenshawe Hospital, Southmoor Road, Manchester, M23 9LT, UK
b Department of Cardiothoracic Surgery, Southampton General Hospital, Southampton, UK
c Department of Cardiothoracic Surgery, King's College London, London, UK
d Department of Chemical Pathology, Wythenshawe Hospital, Manchester, UK
e Department of Anaesthesia, Wythenshawe Hospital, Manchester, UK
Received 13 August 2001; received in revised form 1 April 2002; accepted 3 April 2002.
* Corresponding author. Tel.: +44-161-2912511; fax: +44-161-2912530
| Abstract |
|---|
|
|
|---|
Key Words: Anaesthesia Blood flow Cardiopulmonary bypass Kidney Vasodilation
| 1. Introduction |
|---|
|
|
|---|
Dopamine is an endogenous catecholamine (3,4-dihydroxyphenylethylamine) which when used therapeutically at renal dose (35 µg kg-1 min-1) results in dilation of the renal vasculature, reduction in renal vascular resistance and increased renal blood flow [4,5]. Its unique effect has been advocated for renal prophylaxis in various clinical settings including post-chemotherapy, contrast nephropathy, obstructive jaundice and organ transplantation. However, randomized studies failed to produce conclusive evidence in support of any benefit of dopamine under such circumstances [6,7]. In the realms of cardiac surgery, our group had previously demonstrated that far from being renoprotective, perioperative renal-dose dopamine enhanced CPB associated renal tubular dysfunction in low risk patients [8]. The present study goes on to examine this issue in patients who for specific reasons are considered at high risk of developing renal dysfunction following cardiac surgery.
| 2. Materials and methods |
|---|
|
|
|---|
|
In the first six postoperative days, daily blood and urine samples were taken for measurement of blood urea, serum creatinine, and urinary retinol binding protein to urinary creatinine ratio (Ur RBP/Ur Cr). Patients' daily fluid balance and diuretic use were also recorded.
All urine samples were collected early in the morning and a 2 ml aliquot was frozen and stored until analysis. The urinary level of RBP was measured using a commercially available reagent kit (Randox Laboratories, Antrim, UK) based on an ELISA technique. The technique details have been previously reported [8].
The statistical power calculation was performed at the conception stage utilizing expected differences in outcome based on our previous work in related subjects which employed similar methodology [8]. This suggested that a sample size of 14 in each group would have 90% power to detect a probability of 0.9 that an observation (e.g. urinary markers of differential renal injury) in the control group was less than a corresponding observation in the dopamine group using an appropriate test with a 0.05 two-sided significance level. To allow for a generous safety margin, we decided to aim for 20 patients in each study group. Chi-square tests were applied to compare differences between the groups with respect to gender, hypertensive status, and usage of aprotinin. The MannWhitney U-test was applied to non-parametric data concerning NYHA grade, Canadian Cardiovascular Society (CCS) symptom score for severity of angina and diuretic usage. The remaining data were analyzed with an unpaired two-tailed t-test and repeated measures ANOVA on raw or naturally transformed (natural log detransformed) data.
| 3. Results |
|---|
|
|
|---|
All major complications occurred in control patients: three developed neurological complications including one with mild left hemiparesis, another with previous right occipital trauma who developed left occipital infarct resulting in cortical blindness, and a third who was ventilated for 5 days whilst slowly regaining consciousness. Furthermore, an asthmatic patient had difficulty weaning from the ventilator and required respiratory support for 8 days.
The group's demographic characteristics are displayed in Table 2. There was no statistically significant difference between their age, gender, body mass index, preoperative cardiac status, and creatinine level. A borderline significant difference in preoperative diastolic blood pressure was found with higher values recorded in the controls. None of the patients received intravenous contrast media in the 5 days prior to surgery.
|
|
|
A loop diuretic was used exclusively to induce postoperative diuresis. Average diuretic usage was expressed as mg frusemide per patient per day over the study period. Patients in Group 1 received on average 19.1 mg day-1 while those in Group 2 received 19.8 mg day-1 (P=0.92) (Table 2). Not every patient received postoperative diuretic treatment.
| 4. Discussion |
|---|
|
|
|---|
The cause of renal dysfunction after open heart surgery is probably multi-factorial. Central to this is the activation of inflammatory cascades and renal ischemia from reduction of kidney blood flow during CPB. This may be exacerbated by the use of inoconstrictor or other vasopressing agents for postoperative circulatory support. Various approaches have been taken to counteract such insults with variable success. Among these dopamine through its perceived influence on renal perfusion has gained popularity with clinicians. This endogenous catecholamine is thought to exert a dose dependent effect: at levels above 7 µg kg-1 min-1 stimulation of the cardiac ß1 receptors will result in a rise in blood pressure; however, at lower dosage (25 µg kg-1 min-1) it stimulates mainly the dopaminergic receptors causing vasodilation and a reduction in diastolic blood pressure. This vasodilating effect is said to be renal specific, which in turn forms the basis for its renal protection role. Furthermore, there is a suggestion that renal-dose dopamine may also ameliorate the mesenteric and renal vaso-constrictive property of noradrenaline [9]. However, dopamine even when used at renal dose potentially has multiple unwanted effects: its systemic ß-agonist activity can increase myocardial oxygen consumption, induce sinus tachycardia and ventricular extrasystole and promote cardiac arrhythmia [10].
In clinical practice, renal-dose dopamine has been widely used for renal protection in various settings including major surgery. However, studies evaluating the role of renal-dose dopamine have so far failed to demonstrate any conclusive benefit in patients undergoing cardiac, abdominal aortic and liver transplantation surgery.
The renal vasodilating effect of dopamine is well documented [10,11]. The assumption is that the augmented renal blood flow is renal protective. However, these studies either reported concurrent augmentation of cardiac index [9,10] or no data on hemodynamic effects were given [10,11]. It is only in animal studies when the hemodynamic effect of dopamine may be excluded that its effect on renal vascular tone can be observed. Steinhausen and colleagues reported that low concentrations of dopamine (130 µM) cause an increase in the diameter of rat renal arcuate, interlobar, and afferent and efferent arterioles [12]. The enhanced renal blood flow caused by dopamine has not been translated into a reduction in renal complication in surgical patients. Recent randomized studies examining the effect of dopamine at 3 µg kg-1 min-1 have failed to demonstrate improvement in creatinine clearance, urine output and incidence of renal failure in liver transplant [7], vascular surgical [13] and jaundice [6] patients. These findings were supported by a recently published sizeable randomized study in the ICU setting. Dopamine infusion at 2 µg kg-1 min-1 confers no benefit for the patients in terms of peak creatinine rise, incidence of renal replacement therapy, and total ICU and hospital stay [14]. In the cardiac arena where the hemodynamics of critically ill patients are in constant flux, dopamine at a low dose (200 µg min-1) may confer its beneficial effect by increasing cardiac index [5]. However, in another study of patients undergoing coronary surgery, dopamine at the same dose increased cardiac index but had no effect on urine output, creatinine and free water clearance, or the incidence of renal insufficiency [15]. Evidence so far has suggested that dopamine is essentially a weak inotrope and a potent diuretic. Although laboratory data have supported dopamine's claim of renal vascular dilation, clinical studies seem to indicate that dopamine only improves renal blood flow when cardiac performance is augmented in parallel. Furthermore, we previously found that renal-dose dopamine given prophylactically in fact exacerbated the degree of renal tubular damage after CPB: patients in the treatment group had significantly higher Ur RBP/Ur Cr than well matched controls. This was observed in subjects with normal heart and kidney functions preoperatively who were not considered at risk of developing postoperative renal dysfunction [8]. The situation may be very different when pre-existing renal disease or other factors predispose them to perioperative renal failure for which renal-dose dopamine may confer a benefit. The inclusion criteria for the present study were based on published independent risk factors for post-CPB renal dysfunction. These included pre-existing renal dysfunction, age >70 years, diabetes mellitus, ejection fraction <40%, hypertension and unstable angina [1620].
Published accounts indicate that renal dysfunction post-cardiac surgery has glomerular and tubular components [21,22]. Creatinine clearance is considered a suitable surrogate for Inulin clearance in the measurement of the glomerular filtration rate (GFR). Due to the large renal reserve, any changes in serum creatinine or creatinine clearance tend to occur late and they have been considered to be less sensitive for subtle and early renal dysfunction [23]. Accurate and sensitive methods of detecting tubular injury were developed in the 1980s. These methods are based either on the ability of the proximal tubular cells to reabsorb low molecular mass proteins (e.g. ß2-microglobulin and RBP) or on the leakage of intracellular proteins of high molecular mass from the damaged tubules (e.g. N-acetyl-ß-D-glucosaminidase and glutamyltranspeptidase). Urinary excretion of RBP was chosen for our study as it was found to be the most stable in acidic urine.
The present study confirmed that Ur RBP/Ur Cr peaked on postoperative day 1 in both groups before returning towards preoperative baseline values on day 6, a familiar pattern observed in our previous work. There is a trend towards greater excretion in the dopamine-treated group suggesting again further exacerbation of CPB associated renal tubular injury. However, this difference was not statistically significant primarily as a result of wide data scatter, which in turn may be accountable for by our pragmatic inclusion criteria leading to a rather heterogeneous group. Whilst each subject was considered at increased risk of postoperative renal failure, they were likely to have diverse aetiology and wide-ranging renal functional reserve, an example of which is a patient with diabetes mellitus. It has been shown previously that diabetics have supra-normal urinary excretion of RBP [24]. The degree of raised urinary RBP excretion is related to the duration of diabetes and its control [24]. Diabetic subjects may have subtle proximal tubular dysfunction and remain non-microalbuminuric [25]. To overcome this limitation, it will be necessary to focus on specific groups such as those with elevated preoperative serum creatinine. An interesting observation gained from the present study and our previous work is that the peak values of Ur RBP/Ur Cr appear to be considerably higher in patients at increased risk of renal failure. The increased excretion also seems to extend further into the postoperative period. The exaggerated time-excretion integral would support a quantitative role for Ur RBP/Ur Cr in the assessment of renal tubular dysfunction.
Renal-dose dopamine may be effective in situations when the combination of an inotrope and a diuretic is required such as development of oliguria after cardiac surgery despite adequate filling. Our results indicated that patients in the treatment arm had a persistently more negative fluid balance. Since diuretic usage in both groups was comparable, the difference in fluid balance was most likely to be dopamine related. The disparity in fluid balance peaked on the 4th postoperative day (Table 3) suggesting that the diuretic action of dopamine may endure well beyond the period of its administration.
In conclusion, for cardiac surgical patients considered at increased risk of postoperative renal dysfunction, perioperative administration of renal-dose dopamine did not confer protection against CPB associated tubular damage as measured by Ur RBP/Ur Cr. We do not recommend the use of renal-dose dopamine as routine prophylaxis in this setting.
| Acknowledgments |
|---|
| References |
|---|
|
|
|---|
This article has been cited by other articles:
![]() |
B. Mahesh, B. Yim, D. Robson, R. Pillai, C. Ratnatunga, and D. Pigott Does furosemide prevent renal dysfunction in high-risk cardiac surgical patients? Results of a double-blinded prospective randomised trial Eur. J. Cardiothorac. Surg., March 1, 2008; 33(3): 370 - 376. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. H. Rosner, D. Portilla, and M. D. Okusa Analytic Reviews: Cardiac Surgery as a Cause of Acute Kidney Injury: Pathogenesis and Potential Therapies J Intensive Care Med, January 1, 2008; 23(1): 3 - 18. [Abstract] [PDF] |
||||
![]() |
Y. Abu-Omar and C. Ratnatunga Cardiopulmonary Bypass and Renal Injury Perfusion, July 1, 2006; 21(4): 209 - 213. [Abstract] [PDF] |
||||
![]() |
M. H. Rosner and M. D. Okusa Acute Kidney Injury Associated with Cardiac Surgery Clin. J. Am. Soc. Nephrol., January 1, 2006; 1(1): 19 - 32. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Gill, J. V. Nally Jr, and R. A. Fatica Renal Failure Secondary to Acute Tubular Necrosis: Epidemiology, Diagnosis, and Management Chest, October 1, 2005; 128(4): 2847 - 2863. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. O. Friedrich, N. Adhikari, M. S. Herridge, and J. Beyene Meta-Analysis: Low-Dose Dopamine Increases Urine Output but Does Not Prevent Renal Dysfunction or Death Ann Intern Med, April 5, 2005; 142(7): 510 - 524. [Abstract] [Full Text] [PDF] |
||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ANN THORAC SURG | ASIAN CARDIOVASC THORAC ANN | EUR J CARDIOTHORAC SURG |
| J THORAC CARDIOVASC SURG | ICVTS | ALL CTSNet JOURNALS |