February 1998
Renal protection in patients undergoing cardiopulmonary bypass with preoperative abnormal renal function.

Lema G, Urzua J, Jalil R, Canessa R, Moran S, Sacco C, Medel J, Irarrazaval M, Zalaquett R, Fajardo C, Meneses G; ; Anesth Analg 1998; 86:3-8.

[ see abstract below ]

In patients whose preoperative renal function is normal, acute renal failure is a rare complication of cardiac surgery with cardiopulmonary bypass (CPB). However, the risk of postoperative oliguria and renal dysfunction increases exponentially with increasing preoperative serum creatinine above 1.5 mg/dL (1). Established acute renal failure requiring dialysis after cardiac surgery has a forbiddingly high mortality - about 60% - whether or not it is of the oliguric or nonoliguric type.

Low-dose dopamine (1-3 mcg/kg/min) has long been advocated as a renal protective agent. Through its agonist effect on dopaminergic receptors in the renal vasculature and tubular cells of the nephron, it increases renal blood flow (RBF), glomerular filtration rate (GFR), urine flow (diuresis) and salt excretion (saliuresis). However, there are actually few outcome data in clinical studies that support a perioperative renal protective effect for dopamine, and studies in patients with normal or mildly abnormal renal dysfunction have not demonstrated any benefit for the prophylactic administration of low dose dopamine during CPB (2,3).

Renal autoregulation implies the maintenance of RBF and GFR despite a reduction in renal perfusion pressure (note that this does not apply to urine flow, which is very pressure dependent). In certain states, renal autoregulation is impaired or lost; for example, acute renal failure and septic shock. In these situations, RBF and GFR decline with hypotension and measures to maintain renal perfusion pressure, e.g. the infusion of vasopressor agents, may actually enhance renal protection. An analogous situation may apply to CPB.

An interesting prospective study published in the January 1998 issue of Anesthesia and Analgesia investigates these questions. Lema et al. examined the hypothesis that in patients with preexisting renal dysfunction, low dose dopamine provides greater renal protection during CPB than maintenance of perfusion pressure with phenylephrine (4). They studied 17 patients with a serum creatinine > 1.5 mg/dL undergoing elective coronary artery bypass surgery with nonpulsatile hypothermic CPB. Patients were randomized to receive an infusion of dopamine 2 mcg/kg/min throughout the surgical procedure, or phenylephrine infusion to maintain a perfusion pressure > 70 mmHg during CPB. The bypass pump was primed with 0.5-0.75 g/kg mannitol. Fluid and inotropic support were provided to maintain a cardiac index > 2.2 L/min/m2 and a urine flow > 1 mL/kg/hr (> 2 mL/kg/hr during CPB). If these parameters could not be met, the patient was withdrawn from the study.

Essentially, the study revealed no significant difference in renal function during or after CPB between the two groups. GFR decreased significantly from baseline after anesthetic induction and toward the end of CPB; renal plasma flow (RPF) increased after surgery, and the filtration fraction (GFR/RPF) decreased during and after CPB. However, except for GFR in the pre-CPB period (see below), these changes were similar whether patients received perioperative dopamine or phenylephrine during CPB.

However, the study did reveal that in the pre-CPB period, patients appeared to have a prerenal syndrome that was partially relieved in the group receiving low dose dopamine.

In the period after surgery was begun, but before CPB, patients receiving dopamine had a significantly higher GFR, urine flow rate (2.0 vs 0.3 mL/min) and lower urine osmolarity (370 vs 627 mOsm/L). The implication is that fluid restriction in patients presenting for cardiac surgery creates a prerenal state in which the tubular concentration is "switched on", resulting in oliguria and a concentrated urine. In this study, the diuretic effect of low dose dopamine overcame tubular concentrating ability before CPB. Presumably the administration of mannitol in the pump prime in both groups had a similar effect during and after CPB.

In another study on patients who were scheduled as a "late start" (after 12 p.m.) for cardiac surgery, Bryan et al. demonstrated the creation of a prerenal state (urine osmolarity > 750 mOs/L) which was resistant to the diuretic and saliuretic effects of low dose dopamine (5). In contrast, dopamine infusion resulted in the expected diuresis and salt excretion only in those patients who had been fluid loaded with a saline infusion during the time preceding surgery.

Lema et al. conclude that a prerenal state exists prior to CPB that is improved by low dose dopamine, although this did not appear to have any effect on ultimate renal outcome. Indeed, any implications on outcome in this study are severely restricted by two important limitations. First, it is extremely unlikely that the small size of the study (n = 17) had the power to determine such differences even if they existed. Second, the actual difference in mean arterial pressure during CPB between the two groups (60 mmHg in the dopamine group, 71 mmHg in the phenylephrine group), although statistically significant, is probably too small to have revealed any putative benefit from maintenance of perfusion pressure.

What can we "take home" from all this? Perhaps the most important message is that many patients presenting for cardiac surgery are in a prerenal state that could have adverse implications for perioperative renal outcome, although this remains to be proved. But, as Lema et al. suggest, the "benefit" of low dose dopamine in reversing this state could equally (and perhaps more physiologically) be achieved by shortening the preoperative fasting period, and by paying more attention to the adequacy of preoperative hydration in patients undergoing cardiac surgery, especially in those with preexisting renal dysfunction.


References:
1. Higgins TL, Estafanous FG, Loop FD et al. Stratification of morbidity and mortality outcome by preoperative risk factors in coronary artery bypass procedures. JAMA 1992; 267:2344-8.
2. Costa P, Ottino GM, Matani A, et al. Low-dose dopamine during cardiopulmonary bypass in patients with renal dysfunction. J Cardiothoracic Anesth 1990;4:469-73.
3. Myles PS, Buckland MR, Schenk NJ, et al. Effect of "renal-dose" dopamine on renal function following cardiac surgery. Anaesth Intens Care 1993;21:56-61.
4. Lema G, Urzua J, Jalil R et al. Renal protection in patients undergoing cardiopulmonary bypass with preoperative abnormal renal function. Anesth Analg 1998; 86:3-8.
5. Bryan AG, Bolsin SN, Vianna PTG and Haloush H. Modification of the diuretic and natriuretic effects of a dopamine infusion by fluid loading in preoperative cardiac surgical patients. J Cardiothorac Vasc Anesth 1995;9:158-63.


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