Salutary effect of reduced glutathione on renal function in coronary artery bypass operation. Effect of calcium antagonist diltiazem on renal function in open heart surgery. Effects of a continuous diltiazem infusion on renal function during cardiac surgery. Low-dose dopamine during cardiopulmonary bypass in patients with renal dysfunction. Diltiazem infusion for renal protection in cardiac surgical patients with preexisting renal dysfunction. Evaluation of dopexamine hydrochloride as a renoprotective agent during aortic surgery. A randomised, clinical study of the effect of low-dose dopamine on central and renal haemodynamics in infrarenal aortic surgery. Effect of felodipine on renal function and vasoactive hormones in infrarenal aortic surgery. Low-dose continuous infusion of human atrial natriuretic peptide during and after cardiac surgery. Randomized controlled trial of the effect of mannitol on renal reperfusion injury during aortic aneurysm surgery. A prospective randomized study to evaluate the renoprotective action of beating heart coronary surgery in low risk patients. Dopamine therapy for patients at risk of renal dysfunction following cardiac surgery: science or fiction? Role of dopamine in renal dysfunction during laparoscopic surgery. Effect of dexamethasone on perioperative renal function impairment during cardiac surgery with cardiopulmonary bypass. Renal function and cardiopulmonary bypass: effect of perfusion pressure. Preoperative intravenous hydration confers renoprotection in patients with chronic kidney disease undergoing cardiac surgery. Hypertonic sodium lactate versus lactated ringer's solution for intravenous fluid therapy in operations on the abdominal aorta. Haemodynamic and renal effects of intravenous enalaprilat during coronary artery bypass graft surgery in patients with ischaemic heart dysfunction. A randomized trial on the effect of mannitol on postoperative renal function in patients with obstructive jaundice. The effect of dopamine on renal function in solitary partial nephrectomy surgery. Renal protection by radical scavenging in cardiac surgery patients. The effect of mannitol on oxygenation and creatine kinase MB release in patients undergoing multivessel off-pump coronary artery bypass surgery. Dexamethasone: benefit and prejudice for patients undergoing on-pump coronary artery bypass grafting: a study on myocardial, pulmonary, renal, intestinal, and hepatic injury. Lack of renoprotective effect of theophylline during aortocoronary bypass surgery. Preoperative inhibition of angiotensin-converting enzyme improves systemic and renal haemodynamic changes during aortic abdominal surgery. Lack of renoprotective effect of i.v. N-acetylcysteine in patients with chronic renal failure undergoing cardiac surgery. Haemodynamics and 'optimal' hydration in aortic cross clamping. Prophylactic dialysis in patients with renal dysfunction undergoing on-pump coronary artery bypass surgery. Effect of "renal-dose" dopamine on renal function following cardiac surgery. Extraperitoneal approach reduces intestinal and renal dysfunction in elective abdominal aortic aneurysm repair. Preoperative alpha2-adrenergic receptor agonists prevent the deterioration of renal function after cardiac surgery: results of a randomized, controlled trial. Can renal dysfunction after infra-renal aortic aneurysm repair be modified by multi-antioxidant supplementation? Ringer's lactate with or without 3% dextran-60 as volume expanders during abdominal aortic surgery. Perioperative N-acetylcysteine to prevent renal dysfunction in high-risk patients undergoing cabg surgery: a randomized controlled trial. Mannitol and dopamine in patients undergoing cardiopulmonary bypass: a randomized clinical trial. The effect of 'renal-dose' dopamine on renal tubular function following cardiac surgery: assessed by measuring retinol binding protein (RBP). Effect of angiotensin converting enzyme inhibition on blood pressure and renal function during open heart surgery. Prospective study of postoperative renal function in obstructive jaundice and the effect of perioperative dopamine. Renal dose dopamine in open heart surgery. Does it protect renal tubular function? Effects of dopexamine on creatinine clearance, systemic inflammation, and splanchnic oxygenation in patients undergoing coronary artery bypass grafting. A randomized clinical trial of oral ursodeoxycholic acid in obstructive jaundice. On-pump versus off-pump coronary revascularization: evaluation of renal function. Perioperative renal protection in patients with obstructive jaundice using drug combinations. Mechanisms of renal hemodynamic impairment during infrarenal aortic cross-clamping. Oliguria during corrective spinal surgery for idiopathic scoliosis: the role of antidiuretic hormone. Impairment of renal function after cardiopulmonary bypass is not influenced by dopexamine. The effects of fenoldopam on renal function in patients undergoing elective aortic surgery. Low-dose prostacyclin preserves renal function in high-risk patients after coronary bypass surgery.
Renal dysfunction and acute renal failure are serious complications of open heart operations. Previous reports have suggested beneficial effects of exogenous glutathione for preservation of renal function after ischemic renal injury. We prospectively studied the effect of perioperative administration of glutathione on renal function in patients who underwent coronary artery bypass operation.
                Two hundred mg per kg of glutathione was administered to the treated group (n = 10) before cardiopulmonary bypass, and on the first and second postoperative days. The control group was administered placebo in the same volume. Hemodynamics, renal function, and plasma hormone levels were measured consecutively.
                In the glutathione group, the mean arterial pressure and systemic vascular resistance index were lower than in the control group. Urine volume, creatinine clearance, and renal excretory index were well preserved in the group treated with glutathione. Moreover, the fractional excretion of sodium was lower and urine and plasma osmolarity was higher in the group treated with glutathione. No differences in plasma renin activity, angiotensin II, or aldosterone concentrations between the two groups were observed.
                Perioperative glutathione treatment has a salutary effect on perioperative renal function through effects on both renal hemodynamics and tubular mechanism. Acute renal failure, which is a serious complication following open heart surgery, has a high mortality rate. Previous reports have shown that the calcium antagonist diltiazem is beneficial either as an adjunct to cardioplegic solution or perioperative treatment for preservation of postoperative cardiovascular function. We studied the effects of diltiazem on renal function, plasma atrial natriuretic peptide levels, and the renin-angiotensin-aldosterone system in patients who had undergone coronary artery bypass grafting.
                Diltiazem was administered, 0.1 mg/kg, in a bolus injection followed by continuous infusion at a rate of 2 micrograms/kg/min during surgery, and 30 mg through a nasogastric tube at every 8 h. Hemodynamics, renal function, and plasma hormone levels were measured in the diltiazem-treated group (n = 13) and the nontreated group (n = 10).
                Heart rate, mean arterial pressure, and systemic vascular resistance index in the diltiazem-treated group were significantly lower than those in the nontreated group following cardiopulmonary bypass. Urine volume, creatinine clearance, and free water clearance were well preserved in the diltiazem-treated group. However, plasma renin activity and aldosterone levels were significantly higher in the diltiazem-treated group with the same changes in plasma atrial natriuretic peptide levels.
                Perioperative treatment with diltiazem has a beneficial effect on postoperative renal function, and reflex sympathetic activation induced by peripheral vasodilation activated the renin-angiotensin-aldosterone system. Thirty-five male patients undergoing coronary artery surgery were studied to investigate renal function during a continuous infusion of the calcium channel blocker diltiazem. All patients had preoperative renal function within normal limits (serum creatinine below 0.133 mmol/L) and were randomly divided into three groups: Control (C), Diltiazem 1 (D1), and Diltiazem 2 (D2). Diltiazem was infused in D1 (1 microgram/kg/min) and D2 (2 micrograms/kg/min) patients throughout surgery and during the following 36 hours. Glomerular function was investigated using the endogenous creatinine clearance while tubular function was assessed by means of water and sodium reabsorption tests, as well as urinary enzyme activity measurements. Hemodynamic monitoring was performed using a pulmonary artery catheter. The glomerular filtration rate of C and D1 patients showed a significant fall during cardiopulmonary bypass (CPB) with respect to the prebypass period and returned to the baseline values only in the postoperative period. A similar change was not observed in D2 patients. The analysis of variance demonstrated that the glomerular filtration rate was significantly higher in Group D2 versus Group C during and after CPB (P = 0.03 and P = 0.04, respectively). Furthermore, after CPB, urinary output was significantly improved in D2 patients, both versus C and D1 patients (P = 0.003), notwithstanding a lower mean arterial pressure in the D2 Group (P = 0.04 v C Group). Tubular function was not influenced by diltiazem infusion. It is concluded that a continuous diltiazem infusion, at a dose of 2 micrograms/kg/min during cardiac surgery, may be useful to prevent a decrease in glomerular function secondary to cardiopulmonary bypass. Thirty-six patients with preoperative renal dysfunction were studied to evaluate the effects of dopamine (D) and dopamine-nitroprusside (DN) on renal function during cardiopulmonary bypass (CPB). No differences from the control group (C) were found in creatinine clearance, fractional sodium excretion, osmolarity and free-water clearance. Sodium output/intake ratio during CPB was higher in group D than in groups C and DN (P less than 0.05); water output/intake ratio was higher in group D than in group C (P less than 0.05). Urine lysozime levels and alpha-glycosidase/creatinine ratios increased similarly in the three groups, suggesting ischemic tubular cell damage. No patients showed acute postoperative renal failure or a worsening of their renal dysfunction. The data suggest an increased water and sodium excretion during CPB with a dopamine infusion, possibly resulting from a renal vasodilator effect that was abolished by simultaneous nitroprusside administration. To evaluate if the calcium channel blocker diltiazem protects postoperatively renal function in cardiac surgical patients with preexisting mild-to-moderate renal dysfunction.
                Prospective, randomized, placebo-controlled, double-blind, clinical study.
                Cardiothoracic anesthesia department at a university hospital.
                Adult patients undergoing elective cardiac surgery using cardiopulmonary bypass, with a preoperatively elevated serum creatinine level (n = 24).
                Randomized infusions of diltiazem (bolus 0.25 mg/kg followed by a continuous infusion of 1.7 microg/kg/min) (DTZ, n = 12) or placebo (C, n = 12) were started 30 minutes before induction of anesthesia and continued for 24 hours.
                Median plasma concentrations of diltiazem (DTZ group) were 79 microg/L before cardiopulmonary bypass, 67 microg/L at the end of cardiopulmonary bypass, and 164 microg/L at 24 hours postoperatively. Serum creatinine levels; on postoperative days 1, 3, and 5; and 3 weeks postoperatively were similar between groups. Iohexol clearance did not differ between the groups on day 5 but was higher in the DTZ group than in the placebo group 3 weeks after surgery (median, 51 v 40 mL/min/1.73 m(2); p < 0.05). Urinary N-acetyl-beta-glucosamidase concentrations were similar between the groups during the study but were increased from baseline on days 2 and 4 and 3 weeks postoperatively.
                Diltiazem can be safely used in patients who have mild-to-moderate renal dysfunction and undergo cardiac surgery using cardiopulmonary bypass. Within the limits of this study, the data suggest that addition of prophylactic diltiazem may prevent further glomerular damage resulting from cardiopulmonary bypass and may improve glomerular function 3 weeks after cardiac surgery.
                Copyright 2002, Elsevier Science (USA). All rights reserved. Thirty-two patients undergoing elective infrarenal aortic surgery were randomly assigned to receive a perioperative infusion of either dopexamine hydrochloride at a rate of 2 micrograms/kg/min (n = 15) or 0.9% saline solution as placebo (n = 17). Renal function was monitored by regular measurements of serum creatinine levels. There were significant mean percentage increases in serum creatinine (p < 0.001) at all time points up to 3 days postoperatively in the placebo group but only at 2 and 12 hours in the dopexamine group. It was concluded that dopexamine hydrochloride confers renal protection in patients undergoing aortic reconstruction. To determine whether dopamine prevents deterioration of central haemodynamics and renal function in aortoiliac surgery.
                Prospective, randomised and placebo-controlled.
                University hospital.
                Thirty patients for elective vascular surgery with implantation of an aortobifemoral or an aortobiiliac graft due to aortoiliac arteriosclerosis had infusion of dopamine 3 micrograms/kg/min or placebo during the operation and 24 h postoperatively. Thoracic epidural analgesia and general anaesthesia were used.
                Central haemodynamic measurements were registered. The effective renal plasma flow (ERPF), the glomerular filtration rate (GFR), angiotensin II, aldosterone, arginine vasopressin (AVP), atrial natriuretic peptide (ANP), endothelin and excretion of water and electrolytes were measured preoperatively, 1 h postoperatively and 24 h postoperatively.
                During the operation the dopamine group had higher cardiac index and heart rate together with lower pulmonary artery wedge blood pressure. ERPF and GFR did not differ between the groups. In the dopamine group ERPF was increased in all patients at the first postoperative clearance. The fractional excretion of sodium, the per- and postoperative diuresis and AVP were increased in the dopamine group as compared to the placebo group. Postoperatively, ANP in the placebo group was raised as compared to the preoperative level.
                Peroperatively, dopamine counteracted depression of left ventricular function. The increased ERPF at the first postoperative clearance in the dopamine group indicates either improved peroperative haemodynamics or a synergistic effect between dopamine and epidural sympathetic blockade. Dopamine also improved diuresis and natriuresis. We have examined the possible renoprotective effect of felodipine 5 mg orally, given daily for 5 days before operation, in 29 patients undergoing elective infrarenal aortic surgery in a randomized, blinded and placebo-controlled study. Effective renal plasma flow (ERPF), glomerular filtration rate (GFR), urine output, fractional sodium clearance and plasma concentrations of angiotensin II, aldosterone, arginine vasopressin and atrial natriuretic peptide did not differ between the felodipine and placebo groups. ERPF and GFR were not reduced after operation in the placebo group. In the felodipine group, GFR was higher 24 h after operation compared with before operation. We conclude that increased GFR in the felodipine group, measured 24 h after operation, may indicate a beneficial effect of felodipine but in the present context this was not clinically important. Felodipine had no significant effect on vasoactive hormones. We evaluated the effects of human atrial natriuretic peptide (hANP) during cardiopulmonary bypass (CPB).
                Forty patients undergoing coronary artery bypass grafting were investigated. A group of patients given hANP for 24 hours from the start of CPB (hANP group) was compared with a non-hANP group. Parameters examined were hemodynamics, urine volume, dosage of furosemide, respiratory index, pleural effusion, ANP, cyclic guanosine monophosphate, renin activity (renin), angiotensin-II, aldosterone, and glomerular filtration rate.
                Central venous pressure, systemic vascular resistance index, and pulmonary vascular resistance index were significantly lower in the hANP group than in the non-hANP group. The hANP group showed significantly higher levels of ANP, cyclic guanosine monophosphate, glomerular filtration rate, and respiratory index, and significantly lower levels of renin, angiotensin-II, aldosterone, and pleural effusion, as compared with the non-hANP group. The dosage of furosemide was significantly lower and the urine volume was significantly larger in the hANP group.
                hANP can satisfactorily compensate for the shortcomings of CPB by decreasing the peripheral vascular resistance, suppressing the renin-angiotensin-aldosterone system, and exerting a strong diuretic effect. The effects of mannitol on renal impairment following infrarenal aortic aneurysm repair were studied. Patients received either mannitol 0.3 g/kg (n = 15) or saline (n = 13) as a rapid intravenous infusion before aortic cross-clamping. One patient in the control group developed fatal postoperative renal failure but there was no renal failure in the mannitol group. Two patients treated with mannitol died from perioperative myocardial infarction. There were no significant differences in postoperative blood urea level, serum creatinine concentration or creatinine clearance between mannitol and control groups. In patients who had mannitol there was a significant diuresis on the first day after operation (mean urine output 2250 ml) compared with before operation (1557 ml) (P = 0.007). Compared with controls, patients treated with mannitol had lower mean (s.e.m.) postoperative levels of urinary albumin (160(32) versus 500(140) mg per mmol creatinine; P = 0.036) and N-acetyl glucosaminidase (143(34) versus 271(70) mumol per mmol creatinine; P = 0.04) indicating a reduced level of subclinical glomerular and renal tubular damage. These data demonstrate that mannitol reduces subclinical renal injury following infrarenal aortic aneurysm repair. Cardiopulmonary bypass (CPB) is widely regarded as an important contributor to renal failure, a well recognized complication following coronary artery surgery (coronary artery bypass grafting (CABG)). Anecdotally off-pump coronary surgery (OPCAB) is considered renoprotective. We examine the extent of renal glomerular and tubular injury in low-risk patients undergoing either OPCAB or on-pump coronary artery bypass (ONCAB).
                Forty low-risk patients with normal preoperative cardiac and renal functions awaiting elective CABG were prospectively randomized into those undergoing OPCAB (n=20) and ONCAB (n=20). Glomerular and tubular injury were measured respectively by urinary excretion of microalbumin and retinol binding protein (RBP) indexed to creatinine (Cr). Daily measurements were taken from admission to postoperative day 5. Fluid balance, serum Cr and blood urea were also monitored.
                No mortality or renal complication were observed. Both groups had similar demographic makeup, Parsonnet score, functional status and extent of coronary revascularization (2.1+/-1.0 vs. 2.5+/-0.7 grafts; P=0.08). Serum Cr and blood urea remained normal in both groups throughout the study. A significant and similar rise in urinary RBP:Cr occurred in both groups peaking on day 1 (3183+/-2534 vs. 4035+/-4079; P=0.43) before reapproximating baseline levels. These trends were also observed with urinary microalbumin:Cr (5.05+/-2.66 vs. 6.77+/-5.76; P=0.22). Group B patients had a significantly more negative fluid balance on postoperative day 2 (-183+/-1118 vs. 637+/-847 ml; P=0.03).
                Although renal complication or serum markers of kidney dysfunction were absent, sensitive indicators revealed significant and similar injury to renal tubules and glomeruli following either OPCAB or ONCAB. These results suggest that avoidance of CPB does not offer additional renoprotection to patients at low risk of perioperative renal insult during CABG. We aimed to evaluate the renoprotective role of renal-dose dopamine on cardiac surgical patients at high risk of postoperative renal dysfunction. The latter included older patients or those with pre-existing renal disease, elevated preoperative serum creatinine (Cr), poor ventricular function, hypertension, diabetes mellitus and unstable angina requiring intravenous therapy.
                Fifty patients undergoing cardiopulmonary bypass (CPB) who fulfilled the entry criteria were prospectively randomized into two groups: Group 1 received a 'renal-dose' (3 microg kg(-1) min(-1)) dopamine infusion starting at anaesthetic induction for 48 h whilst saline infusion acted as placebo in Group 2. The anaesthetic and CPB regimes were standardized. Urinary excretion of retinol binding protein (RBP) indexed to Cr, an accurate and sensitive marker of early renal tubular damage, was assessed daily for 6 days. Additional outcome measures included daily fluid balance, blood urea and serum Cr. Statistical comparisons were made using ANOVA and Mann-Whitney U-test.
                No significant difference was found between the groups in their age, gender, preoperative NYHA class, ejection fraction, baseline serum Cr and duration of CPB and aortic cross-clamping. Renal replacement therapy was not required in any instance. Both groups demonstrated a similar and significant rise in urinary RBP throughout the study period. Dopamine-treated patients achieved more negative average fluid balance than those on placebo (5 vs. 229 ml, P<0.05).
                Renal-dose dopamine therapy failed to offer additional renoprotection to patients considered at increased risk of renal dysfunction after CPB. Sympathetic vascular insult and hemodynamic changes represent the most reliable explanation of renal impairment resulting from acute intraabdominal pressure. We evaluated the effects of low-dose dopamine administration during a long-lasting surgical laparoscopic procedure.
                For this study 40, patients submitted to a colorectal laparoscopic procedure with 15 mmHg of intraabdominal pressure were randomly allocated to two groups: 20 receiving 2 mg/kg/min of dopamine and 20 receiving the same perfusion of saline. Hemodynamic parameters, renal function, urinary output, and creatinine clearance, were studied.
                The hemodynamic parameters were similar in both groups. The urinary output decreased during the intraoperative period only the saline group (p = 0.4). Then 2 h postoperatively, it increased in both groups, and no statistically significant differences were found between the groups. The creatinine clearance decreased in both groups during the intraoperative time, but it was worse in the saline group (-28 +/- 120 vs -194 +/- 106; p = 0.022). During the postoperative period, both groups showed improvement, but in control group the values remained lower than at baseline (p = 0.04), and significantly lower than in the dopamine group (230 +/- 337 vs 100 +/- 192; p = 0.012).
                An intrabdominal pressure of 15 mmHg induces a time-limited renal dysfunction, and low doses of dopamine could prevent this undesirable effect. In cardiac surgery with cardiopulmonary bypass (CPB), corticosteroids are administered to attenuate the physiological changes caused by the systemic inflammatory response. The effects of corticosteroids on CPB-associated renal damage have not been documented. The purpose of this study was to evaluate the effects of dexamethasone on perioperative renal dysfunction in patients undergoing cardiac surgery with CPB.
                Renal damage was prospectively studied in 20 patients without concomitant morbidity undergoing coronary artery surgery with CPB. Patients were randomized in a double-blind fashion to receive dexamethasone or placebo. Markers of glomerular function (creatinine clearance) and damage (microalbuminuria), and markers of tubular function (fractional excretion of sodium and free water clearance) and damage (N-acetyl-beta-D glucosaminidase (NAG)) were evaluated in addition to plasma and urinary glucose levels. Plasma and urinary specimens were obtained at the following time periods: (1) baseline, during the 12 h before surgery; (2) skin incision before heparinization; (3) from heparinization until the end of CPB; (4) during the 2 h following weaning from CPB; (5) in the intensive care unit from 2 to 6 h after weaning of CBP; (6) and from 36 to 60 h after weaning of CPB.
                CPB was associated with an increase in markers in the placebo group, which returned to baseline during the second postoperative day, demonstrating a transient impairment of glomerular and tubular renal function. Similar patterns were observed in patients treated with dexamethasone. While postoperative glycosuria was significantly higher in the dexamethasone-treated group, no other differences between groups were observed.
                Dexamethasone administration before CPB has no protective effect on perioperative renal dysfunction in low-risk cardiac surgical patients. Controversy continues as to whether hypotension during cardiopulmonary bypass (CPB) impairs intraoperative and postoperative renal function. Therefore, 21 patients with normal renal function (plasma creatinine less than 1.2 mg/dL, creatinine clearance greater than 70 mL/min), aged 50 to 70 years, without associated pathology, scheduled for elective coronary surgery were studied prospectively. Patients were randomized into two groups: group 1 included 14 patients whose arterial blood pressure during CPB was left untreated, and group 2 consisted of 7 patients who received phenylephrine to maintain their arterial pressure above 70 mmHg. Plasma and urine creatinine, sodium, potassium, and osmolality were measured preoperatively, intraoperatively and postoperatively. Creatinine, osmolal and free water clearances, and excreted sodium fraction were calculated. Plasma creatinine remained normal throughout the study in all patients. Creatinine clearances were similar preoperatively (101.9 +/- 36.7 in group 1 and 120.6 +/- 50.7 mL/min in group 2). In group 1, creatinine clearance decreased during CPB to 88.7 +/- 39.7 mL/min, whereas in group 2 it increased to 157.6 +/- 79.5 mL/min; the difference between groups was significant. Early postoperatively, there was no difference: 136.2 +/- 86.6 mL/min in group 1 and 100 +/- 21.4 mL/min in group 2. One week postoperatively, values were 100.5 +/- 37.9 and 101.9 +/- 18.4, respectively. There was a significant correlation between the creatinine clearance and perfusion pressure intraoperatively, but not postoperatively. Osmolal clearance also correlated with perfusion pressure intraoperatively, but it was significantly lower in the phenylephrine group postoperatively. Postoperative renal function was normal in all patients; no deleterious effect of a low arterial pressure during bypass could be identified. Patients with chronic kidney disease (CKD) are at risk to develop acute renal failure (ARF) after open heart surgery. This complication is associated with high morbidity, mortality, and cost. Because the ability to concentrate urine is lost early in the progression of CKD, renal patients kept on fluid restriction prior to surgery may develop severe dehydration, a situation consistently found to be one of the most critical risk factors for postoperative ARF. Our goal was to investigate whether intravenous hydration for 12 h prior to cardiac surgery could prevent acute renal injury in patients with CKD. This is a prospective study in a tertiary cardiac surgery center. Forty-five patients admitted for elective open heart surgery with moderate-to-severe CKD, as evidenced by a quantified glomerular filtration rate less than 45 mL/min, were assigned using a 2/1 randomization process, to either receive an intravenous infusion of half-isotonic saline (1 mL/kg/h) for 12 h before the operation (hydration group, n = 30, 29 men, 64 + 1.7 years old), or to be simply kept on fluid restriction (control group, n = 15, 14 men, 64.2 + 2.8 years old). Groups were not different in clinical and intraoperative variables associated with postoperative renal injury. ARF developed in 8 of 15 (53%) patients in the control group, but in only 9 of the 30 (30%) patients in the hydration group. Four patients in the control group (27%), but no one in the hydration group, required dialysis after the operation (P < 0.01). Peak creatinine and blood urea nitrogen values were two to three times higher in the control group than in the hydration group. Preoperative intravenous hydration may ameliorate renal damage in patients with moderate-to-severe renal insufficiency undergoing cardiac surgery. Fifty-eight patients who were to undergo aortic reconstruction were prospectively randomized into two groups to compare the effects of perioperative fluid replacement with isotonic and hypertonic crystalloid solutions. Blood loss was replaced with packed red blood cells, and additional fluid was given as either Ringer's lactate solution (RL, 130 mEq sodium/L, 274 mOsm/L) or a hypertonic balanced salt solution (HSL, 250 mEq sodium/L, 514 mOsm/L). Fluid was administered to maintain the cardiac filling pressure within 3 torr of the preoperative level and the cardiac output (CO) at or above the preoperative level. The groups were similar with respect to age, preexisting disease, duration of operation, and operative blood loss. During the operation, the RL group required 9.5 +/- 0.8 L of fluid, whereas the HSL group required 4.5 +/- 0.3 L (P less than 0.001). Pulmonary, cardiac, and renal functions were adequately maintained in both groups. There were no significant differences between the groups with regard to CO, urine output, or creatinine clearance during the operation and early postoperative period. Postoperatively, the intrapulmonary shunt was 20 +/- 1% in the RL group and it was 16 +/- 1% in the HSL group (P less than 0.05). The amount of sodium infused and the cumulative sodium balance at the completion of the study period were similar in both groups. Serum sodium and osmolarity were significantly greater in the HSL group (P less than 0.001), reaching a maximum of 151 +/- 1 mEq/L and 305 +/- 2 mOsm/L, respectively. Two patients in the HSL group had a persistent elevation in serum osmolarity (greater than 320 mOsm/L) during operation, for which they received RL for the balance of the resuscitation. There were no complications that could be attributed to the hypertonicity of the solution. HSL is effective for resuscitation of patients with extracellular fluid deficit and is safe provided that the serum sodium and osmolarity are monitored during periods of large volume administration. Renal dysfunction occurring after open heart surgery is multifactorial in origin but activation of the renin-angiotensin system may have a prominent role. Fourteen patients with ischaemic heart dysfunction scheduled for elective coronary artery bypass graft (CABG) surgery were allocated to a treatment group [enalaprilat for 2 days; ACEI (angiotensin-converting enzyme inhibitor) group, n=7] or a control group (n=7). The cardiac index was significantly higher in ACEI-treated patients than in the controls before and after cardiopulmonary bypass (CPB) (P<0.05) and on postoperative day 2 (P<0.05). The systemic vascular resistance was significantly lower in the ACEI-treated patients than in the controls before and after CPB (P<0.05). Renal plasma flow, measured as [131I]orthoiodohippuran clearance (ClH), was higher in the ACEI group than in the control group before CPB, as was endogenous creatinine clearance after CPB (P<0.05). On post-operative day 7, ClH was significantly higher in the ACEI group than in the control group (P<0.05). Plasma renin activity and vasopressin concentration increased in both groups during CPB (P<0.05). The study demonstrates that administration of an i.v. ACEI, enalaprilat, improves cardiac output during CABG surgery in patients with ischaemic heart dysfunction. Moreover, renal perfusion was better maintained during surgery, and this effect was sustained up to post-operative day 7. A randomized trial was undertaken to reassess the effectiveness of mannitol in preventing postoperative renal impairment in patients with obstructive jaundice. The study included 31 patients with obstructive jaundice (bilirubin, 3 mg/dl or higher) randomly allocated in two groups to receive (n = 17) or not receive (n = 14) preoperative mannitol. Sixty-five percent of patients had a creatinine clearance below 70 ml/min before surgery. Serum bilirubin and bacteribilia had no relation with preoperative renal function. No relation was found between serum bilirubin value and the percentage fall in postoperative creatinine clearance. Compared with the preoperative values, the postoperative creatinine clearance was significantly impaired in the mannitol group (p = 0.03) and remained almost unaltered in the no-mannitol group. Three patients (9.7%) died of acute renal failure; two were in the mannitol group and one was in the no-mannitol group. Serum fibrin degradation products were not sensitive markers for impending renal failure. There was no significant difference in postoperative serum sodium concentration or in the urinary sodium excretion. Administration of mannitol did not improve the postoperative renal function of jaundiced patients, nor did it prove beneficial in preventing renal failure. Our results suggest that severe disturbances of body-fluid compartments may be the basic mechanism underlying kidney dysfunction in obstructive jaundice and that further water depletion induced by mannitol may indeed prove detrimental. Dopamine continues to be used for preventing and treating acute renal failure. We determined the effects of dopamine on postoperative renal function in patients with a solitary kidney undergoing partial nephrectomy.
                We performed a prospective randomized controlled study at a tertiary care referral center involving 24 patients with a solitary kidney undergoing partial nephrectomy secondary to malignancy. Patients were randomized to receive dopamine (11) [corrected] or no dopamine (13) [corrected]. Intraoperatively those assigned to the dopamine group received a 3 microg./kg. per minute dopamine infusion. Patients in each group received an adequate amount of fluid to maintain good urine production, systemic blood pressure and central venous pressure. Serum electrolytes, blood urea nitrogen, creatinine, serum and urine osmolality, and urine output were measured at baseline, intraoperatively and through postoperative day 4. Preoperatively and postoperatively renal blood flow and the glomerular filtration rate were measured.
                In the 2 groups blood urea nitrogen and serum creatinine increased postoperatively. Although the degree of this increase showed a trend to be lower in the dopamine group, the difference did not reach statistical significance. There was no difference in renal blood flow or the glomerular filtration rate in the treatment groups.
                Administering dopamine to patients with a solitary kidney undergoing partial nephrectomy provided no renoprotective effect. Renal function impairment is a common complication in cardiac surgery patients. Because cardiopulmonary bypass and cardioplegic arrest are associated with formation of free radicals, which have been shown to impair various organs including the kidneys, radical scavenging may protect renal function. Therefore, the purpose of our study was to evaluate the impact of the radical scavenger N-acetylcysteine (NAC) versus placebo on peri-operative renal function in cardiac surgery patients.
                We reanalyzed the data of our previous study in which 40 coronary artery surgery patients (66 +/- 9 [SD] years, 9 women and 31 men) with normal pre-operative renal function had been randomized in a double-blind fashion to receive either NAC (100 mg/kg into the cardiopulmonary bypass prime followed by infusion at 20 mg/kg/h; n = 20) or placebo (n = 20). We determined serum creatinine levels as an indicator for renal function pre- and at 1 day post-surgery as well as peri-operative urinary output and diuretic medication. Creatinine clearance was calculated according to Cockcroft and Gault.
                Biometric and intra-operative patient data were similar between both groups. In the placebo group, serum creatinine increased from 93.1 +/- 35.4 micromol/L pre-operatively to 115.9 +/- 47.2 micromol/L on post-op day 1 (p < 0.001). In contrast, serum creatinine in the NAC group remained unchanged (92.3 +/- 31.3 micromol/L pre-op; 99.3 +/- 25.4 micromol/L on post-op day 1; p = 0.084). Accordingly, creatinine clearance decreased by 16.9 +/- 14.3 mL/min in the placebo group as compared to 7.5 +/- 17.7 mL/min in the NAC group (p = 0.039). Urinary output and diuretic medication were similar between NAC and placebo.
                Our data suggest that free radical-scavenging using NAC protects renal function in patients subjected to cardiac surgery on cardiopulmonary bypass. Despite avoiding cardiopulmonary bypass, off-pump coronary artery bypass surgery is associated with reduction in PaO2 and postoperative respiratory compliance. Also, transient interruption of coronary flow is necessary during distal anastomoses and may impose ischemia-reperfusion myocardial injury. Mannitol is an osmotic diuretic with free radical scavenging properties, and we have evaluated the effects of mannitol on oxygenation and cardiac enzyme release in patients undergoing multivessel off-pump bypass surgery in a prospective, randomized, controlled, double-blind trial.
                Fifty patients were randomly allocated to receive either 20% mannitol 0.5 g/kg (n = 25) or normal saline 2.5 mL/kg (n = 25) during Y-graft construction. Pulmonary variables and serum sodium concentrations were measured 15 minutes after induction of anesthesia and sternum closure. Creatine kinase MB was measured before and after the operation. Intraoperative and postoperative fluid input and output, time to extubation, and intraoperative hemodynamic variables were also recorded.
                PaO2 after sternum closure was significantly higher in the mannitol group, with faster time to extubation and shorter length of stay in the intensive care unit. Intraoperative urine output was significantly greater in the mannitol group, without significant differences in fluid input, serum sodium concentration, and hemodynamic variables. Number of patients with a creatine kinase MB level more than 3 times the upper limit of normal was significantly higher in the control group.
                Mannitol could be safely used without adverse side effects in patients undergoing multivessel off-pump bypass surgery with beneficial effects in terms of preserving oxygenation, earlier extubation, and fewer patients with significant creatine kinase MB elevation. Cardiac surgery with cardiopulmonary bypass (CPB) results in perioperative organ damage caused by the systemic inflammatory response syndrome (SIRS) and ischemia/reperfusion injury. Administration of corticosteroids before CPB has been demonstrated to inhibit the activation of the systemic inflammatory response. However, the clinical benefits of corticosteroid therapy are controversial. This study was designed to document the effects of dexamethasone on cytokine release and perioperative myocardial, pulmonary, renal, intestinal, and hepatic damage, as assessed by specific and sensitive biomarkers.
                A prospective, double-blind, placebo-controlled, randomized trial for dexamethasone was conducted in 20 patients receiving either dexamethasone (1 mg/kg before anesthesia induction and 0.5 mg/kg after 8 h; n = 10) or placebo (n = 10). Different markers were used to assess the SIRS: interleukin (IL)-6, IL-8, IL-10, C-reactive protein (CRP), and tryptase; and organ damage: heart (plasma heart-type fatty acid binding protein, cardiac troponin I [cTnI], creatine kinase-MB), kidneys (N-acetyl-glucosaminidase [NAG], microalbuminuria), intestine (intestinal-type fatty acid binding protein [I-FABP]/liver-type fatty acid binding protein [L-FABP]), and liver (alpha-glutathione S-transferase).
                Dexamethasone modulated the SIRS with lower proinflammatory (IL-6, IL-8) and higher antiinflammatory (IL-10) IL levels. CRP and tryptase were lower in the dexamethasone group. cTnI values were lower in the dexamethasone group at 6 h in the ICU (p = 0.009). Patients in the dexamethasone group had a longer time to tracheal extubation (18.86 +/- 1.13 h vs 15.01 +/- 0.99 h, p = 0.02 [mean +/- SEM]), with a lower oxygenation index at that time: Pa(O2)/fraction of inspired oxygen ratio, 37.17 +/- 1.8 kPa vs 29.95 +/- 2.1 kPa (p = 0.009). The postoperative glucose level (10.7 +/- 0.6 mmol/L vs 7.4 +/- 0.5 mmol/L, p = 0.005) was higher in the dexamethasone group. Serum glucose was independently associated with intestinal injury (urine I-FABP peak, R2 = 42.5%, beta = 114.4 +/- 31.4, significant at p = 0.002; urine L-FABP peak, R2 = 47.3%, beta = 7,714.1 +/- 1,920.9, significant at p = 0.001) and renal injury (urine NAG, R2 = 32.1%, beta = 0.21 +/- 0.07, significant at p = 0.009). Tryptase peaks correlated negatively with peaks of intestinal and renal injury biomarkers.
                Even while inhibiting SIRS, dexamethasone treatment offered no protection against transient, subclinical, perioperative abdominal organ damage. Tryptase release could have a preconditioning effect, offering protection against perioperative intestinal and renal damage. Dexamethasone treatment resulted in more pronounced postoperative pulmonary dysfunction, prolonged time to tracheal extubation, and initiated postoperative hyperglycemia in patients undergoing elective on-pump coronary artery bypass graft surgery. The incidence of acute renal failure (ARF) after cardiac surgery remains high, despite improvements in surgical techniques and perioperative care, and is associated with an unacceptably high mortality. The adenosine receptor antagonist theophylline has been shown to confer some benefit in experimental and clinical ARF due to ischaemia, contrast media and various nephrotoxic agents.
                In a double-blind, randomized, placebo-controlled trial, the effectiveness of theophylline for prevention of renal impairment after elective coronary artery bypass grafting (CABG) was evaluated. Fifty-six patients with normal renal function received a bolus of 4 mg/kg and a subsequent continuous infusion of 0.25 mg/kg/h theophylline (n=28) or isotonic saline (n=28) for up to 96 h. Serum creatinine concentrations were measured preoperatively and daily until day 5 after surgery, and the glomerular filtration rate (GFR) ([(51)Cr]EDTA-clearance) was determined preoperatively, and at days 1, 3 and 5 after surgery.
                Serum creatinine and GFR were the same in both groups. The number of patients with increases of serum creatinine > or =0.4 mg/dl were five in the theophylline group and four in the placebo group. Volumes of infused fluid and urine volumes were not different between groups, both ranging from approximately 7.5 to 8 l during the first 24 h after surgery. The number of patients with termination of study medication due to presumed side effects was not different between placebo and theophylline groups.
                Theophylline administration for renal protection after CABG appears to be ineffective in a pilot study in well-hydrated patients. However, the statistical power of our study was not sufficient to exclude a possible protective effect of theophylline. The present study demonstrated the feasability of a larger trial with theophylline or one of the new specific adenosine A1 receptor antagonists in the setting of ARF after cardiac surgery. We studied 22 patients undergoing aortic surgery, allocated randomly to receive, before induction of anaesthesia, a single i.v. dose of enalapril 50 micrograms kg-1 or saline. During infrarenal aortic cross-clamping, we observed similar reductions in oxygen uptake in the two groups, despite greater systemic oxygen delivery in enalapril-treated patients; angiotensin-converting enzyme inhibition prevented the reduction in cardiac output and attenuated the decrease in glomerular filtration. Changes in glomerular filtration secondary to aortic clamping were related positively to changes in renal plasma flow (r = 0.83 (saline group) and r = 0.65 (enalapril group)). Creatinine clearance on the first day after operation was significantly higher in the enalapril compared with the saline group. We conclude that enalapril pretreatment is effective in improving systemic oxygen delivery, renal plasma flow and glomerular filtration during aortic abdominal surgery. Pre-existing chronic renal failure is a significant risk factor for acute renal failure (ARF) after cardiac surgery. N-acetylcysteine (NAC) has been shown to prevent contrast media-induced ARF. Our objective was to evaluate whether i.v. NAC has renoprotective effects in patients with mild renal failure undergoing cardiac surgery.
                In this prospective, randomized, double-blind study, 80 patients with mild to moderate renal failure undergoing elective heart surgery with cardiopulmonary bypass were recruited. All received either i.v. NAC (n=38) or placebo (n=39) at induction of anaesthesia and then up to 20 h. Urine N-acetyl-beta-D-glucosaminidase (NAG) and urine creatinine ratio, plasma creatinine, and serum cystatin C levels indicated renal function.
                Levels of urinary NAG/creatinine ratio, plasma creatinine and serum cystatin C did not significantly differ between NAC and placebo groups during five postoperative days. Urine NAG/creatinine ratio increased over 30% in 100% of patients in the NAC group vs 92.3% in the placebo group (P=0.081). Plasma creatinine increased by 25% from baseline or over 44 mumol litre(-1) in 42.1% in NAC group vs 48.7% in placebo group (P=0.560). Serum cystatin C exceeded 1.4 mg litre(-1) in 78.9% in NAC group vs 61.5% in placebo group (P=0.096).
                Prophylactic treatment with i.v. N-acetylcysteine had no renoprotective effect in patients with pre-existing renal failure undergoing cardiac surgery. The effect of optimal hydration on haemodynamics and renal function during infrarenal aortic cross clamping was studied in 26 consecutive patients operated on because of an infrarenal aortic aneurysm. The patients were randomly divided over two groups. The patients of group B (n = 13) were optimally hydrated before the operation. The Starling curve was used as standard. Patients of group A (n = 13) served as control. The pre-operative and postoperative renal functions of both groups were compared, as were the haemodynamic parameters. The haemodynamic parameters were measured at five minutes intervals during the entire procedure. During aortic clamping the heart rate was significantly lower in patients of group B, indicating a lower myocardial oxygen consumption. Neither the haemodynamic parameters nor the renal function showed other beneficial effects on optimal hydration. Preoperative creatinine values higher than 2.5 mg/dL are associated with markedly increased risk for both mortality and morbidity in patients undergoing coronary artery bypass surgery. We aimed to determine the effects of prophylactic perioperative hemodialysis on operative outcome in patients with nondialysis-dependent moderate renal dysfunction.
                Forty-four adult patients with creatinine levels greater than 2.5 mg/dL but not requiring dialysis underwent coronary artery bypass surgery with cardiopulmonary bypass. The patients were randomly divided into two groups. In group 1 (dialysis group, 21 patients), perioperative prophylactic hemodialysis was performed in all patients. Group 2 (23 patients) was taken as a control group and hemodialysis was performed only if postoperative acute renal failure was diagnosed.
                The hospital mortality was 4.8% (1 patient) in the dialysis group, and 30.4% (7 patients) in the control group (p = 0.048). Postoperative acute renal failure requiring hemodialysis was seen in 1 patient (4.8%) in the dialysis group and in 8 patients (34.8%) in the control group (p = 0.023). Thirty-three postoperative complications were observed in the control group for an early morbidity of 52.2% (12 patients) and 13 complications occurred in 8 patients in the dialysis group (38.1%). The average length of the intensive care unit and postoperative hospital stay were shorter in the dialysis group than in the control group (p = 0.005 and p = 0.023, respectively).
                Preoperative creatinine levels higher than 2.5 mg/dL, increase the risk of mortality and the development of acute renal failure and prolong the length of hospital stay after on-pump coronary artery bypass surgery. Perioperative prophylactic hemodialysis decreases both operative mortality and morbidity in these high-risk patients. The efficacy of renal-dose dopamine to improve renal function or reduce renal impairment was studied in 52 patients undergoing elective coronary artery bypass surgery. The patients were prospectively randomised in a double-blind fashion to receive dopamine at 200 micrograms/min (group D) or placebo (group P) from induction for 24 hours. Although dopamine improved haemodynamics, there was no effect on urine output at 4 hours (D = 917, P = 1231 ml: P = 0.066); urine output at 24 hours (D = 3659, P = 3304 ml: P = 0.36); creatinine clearance at 0-4 hours (D = 104, P = 127 ml/min: P = 0.27); creatinine clearance on admission to ICU-4 hours (D = 94.8, P = 83.4 ml/min: P = 0.48); creatinine clearance at 20-24 hours (D = 91.2, P = 107 ml/min: P = 0.48); free-water clearance at 0-4 hours (D = 29.6, P = -59.8 ml/hr: P = 0.069); free-water clearance at 20-24 hours (D = 43.2, P = -48.9 ml/hr: P = 0.55). The incidence of transient renal impairment was similar in both groups (D = 36%, P = 50%: P = 0.65). Our study failed to demonstrate that routine prophylactic renal-dose dopamine is associated with improvement in renal function, or with prevention of transient renal impairment in patients undergoing coronary artery bypass surgery. Intestinal mucosal barrier dysfunction observed in patients undergoing transperitoneal abdominal aortic aneurysm (AAA) repair may contribute to the development of the systemic inflammatory response syndrome and dysfunction of various organs. The aim of this study is to investigate whether an extraperitoneal approach reduces intestinal mucosal barrier and renal dysfunction in elective infrarenal AAA repair.
                Twenty patients admitted for elective infrarenal AAA repair were randomized into either the transperitoneal approach (n=10) or the extraperitoneal approach (n=10). Intestinal permeability was measured preoperatively, and at day 1 and day 3 after surgery using the lactulose/mannitol test by calculating the differential urinary excretion ratio of the two sugars after oral administration. Renal dysfunction was assessed by measuring the urinary albumin/creatinine ratio (ACR) at the same time points.
                Intestinal permeability was significantly increased in the transperitoneal group at day 1 [0.124+/-0.035 (mean+/-s.e.m.)] compared to the preoperative level (0.020+/-0.003), (p=0.001) and to the extraperitoneal group at day 1 (0.025+/-0.008), (p<0.05) which showed no change in comparison with the preoperative level (0.020+/-0.003). The ACR was also significantly increased in the transperitoneal group at day 1 (16.69+/-5.12) compared to the preoperative level (5.71+/-2.89), (p<0.05) and to the extraperitoneal group at day 1 (4.33+/-1.49), (p<0.05) which showed no significant change at any of the times examined. No correlation was observed between the lactulose/mannitol ratio and the albumin/creatinine ratio, or between age, operating time, aortic clamping time, amount of blood lost or blood transfused.
                These results support the suggestion that minimising intestinal manipulation using an extraperitoneal approach in AAA repair preserves intestinal mucosal barrier and renal glomerular functions. To evaluate the influence of the alpha2-adrenergic receptor agonist clonidine on creatinine clearance as a measure of renal function.
                Prospective, double-blind, randomized, placebo-controlled clinical trial.
                University hospital.
                Patients undergoing coronary artery bypass graft surgery (n = 48) with normal risk.
                Administration of clonidine (4 micrograms/kg iv)) or placebo 1 hr before induction of anesthesia.
                Induction and maintenance of anesthesia (etomidate, midazolam, and fentanyl) and cardiopulmonary bypass technique (nonpulsatile, normothermic, intermittent cold blood cardioplegia) were standardized in all patients. The night before surgery and the first and third night after surgery, creatinine clearance was calculated from a 12-hr urine collection period. Venous blood samples for determination of plasma antidiuretic hormone (ADH) concentrations were taken the evening before surgery, immediately before induction of anesthesia and the evening after surgery (n = 16). Arterial catecholamine plasma concentrations were determined (high-performance liquid chromatography) before induction, 15 mins after induction of anesthesia, immediately after sternotomy, before initiation of cardiopulmonary bypass, as well as 5, 15, and 30 mins after initiation of cardiopulmonary bypass (n = 16). The total amount of anesthetics, infusions, transfusions, diuresis, and blood loss was not different between the groups. Creatinine clearance decreased over the first postoperative night from 98 +/- 18 (preoperatively) to 68 +/- 19 mL/min (p < .05) in placebo-treated patients. Creatinine clearance remained unchanged in clonidine-treated patients (90 +/- 19 [preoperatively] to 92 +/- 17 mL/min). There was a significant difference in creatinine clearance between the groups during the first postoperative night (p < .05; Mann-Whitney U test). In the third postoperative night, mean creatinine clearance of both groups was not different (75 +/- 31 vs. 86 +/- 28 mL/min). ADH concentrations were not different between the groups at any time, while plasma catecholamine concentrations were always significantly lower in clonidine-treated patients.
                Preoperative treatment with clonidine (4 microgram/kilogram) prevents the deterioration of renal function after cardiac surgery. This effect might be due to clonidine-induced reduction in the sympathetic nervous system response to coronary artery bypass graft surgery. Renal failure after lower torso ischemia is a serious problem, partly caused by hypotension and indirect reperfusion injury. This injury is partly due to the formation of oxygen free radicals by activated neutrophils. This injury results in albuminuria and renal function impairment. There are indications that free radical damage in indirect reperfusion injury can be diminished by administering extra antioxidants before and during reperfusion.
                In this prospective randomised study we have looked at the influence of a multi-antioxidant supplementation on renal function in patients undergoing an elective open infrarenal abdominal aneurysm repair. The patients received either standard treatment (n=22) or standard treatment with additional antioxidants perioperatively (Allopurinol, vitamin E and C, N-acetylcysteine and mannitol). For renal function we have looked at the albumin/creatinine ratio in urine and 24 hr creatinine clearance.
                Despite significantly increased serum total antioxidant capacity, the group receiving extra antioxidants showed no decrease in the albumin/creatinine ratio in urine. There was however a significantly higher creatinine clearance in this group at day 2.
                The results indicate that the diminished renal function after infrarenal aneurysm repair may be influenced by antioxidant therapy. To compare a solution of 3% dextran-60 (D60) in Ringer's lactate (RL) with RL alone as maintenance fluids for abdominal aortic surgery.
                Randomized control trial of 20 consecutive patients undergoing elective aortic reconstructive surgery.
                A surgical ICU in a university hospital.
                Consecutive patients, mean age 64 yr. Five patients had abdominal aneurysm, 12 had aortic obstruction disease, and three had aortic renal bypass surgery. These patients were followed for 1 month.
                Pulmonary artery occlusion pressure of at least 10 mm Hg and a urine output greater than 30 mL/h were used to guide the intraoperative fluid infusion rates, which were 36 and 104 mL/kg of D60 and RL, respectively (ratio 1:2.9).
                Body weight at 24 hr had increased more with RL (7.8 kg) than with D60 (3.2 kg) infusion (p less than .01), despite intraoperative urine volumes of 151 and 92 mg/kg with RL and D60, respectively. Total intravascular albumin decreased from 0.7 g/kg (1.4 to 0.7 g/kg) in both groups, corresponding to a plasma volume (PV) loss of 13 mg/kg without fluid infusions. A total intravascular dextran of 0.5 g/kg resulted in a PV expansion at 1 hr of 4.4 mL/kg above preoperative level, in sharp contrast to 7.0 mL/kg decrease in PV with RL. Of the intraoperative 3% D60 and RL infused, an estimated 51% D60 and 6% RL remained as PV expansion at 1 hr.
                A diluted colloid solution in Ringer's lactate is of significant value in maintaining intravascular volumes and hemodynamics during and after major operative procedures. Renal dysfunction is a complication of coronary artery bypass graft (CABG) surgery performed with cardiopulmonary bypass (CPB) that is associated with increased morbidity and mortality. N-acetylcysteine, an antioxidant and vasodilator, counteracts renal ischemia and hypoxia.
                To determine whether perioperative intravenous (IV) N-acetylcysteine preserves renal function in high-risk patients undergoing CABG surgery with CPB compared with placebo.
                Randomized, quadruple blind, placebo-controlled trial (October 2003-September 2004) in operating rooms and general intensive care units (ICUs) of 2 Ontario tertiary care centers. The 295 patients required elective or urgent CABG and had at least 1 of the following: preexisting renal dysfunction, at least 70 years old, diabetes mellitus, impaired left ventricular function, or undergoing concomitant valve or redo surgery.
                Patients received 4 (2 intraoperative and 2 postoperative) doses of IV N-acetylcysteine (600 mg) (n = 148) or placebo (n = 147) over 24 hours.
                The primary outcome was the proportion of patients developing postoperative renal dysfunction, defined by an increase in serum creatinine level greater than 0.5 mg/dL (44 micromol/L) or a 25% increase from baseline within the first 5 postoperative days. Secondary outcomes included postoperative interventions and complications, the requirement for renal replacement therapy (RRT), adverse events, hospital mortality, and ICU and hospital length of stay.
                There was no difference in the proportion of patients with postoperative renal dysfunction (29.7% vs 29.0%, P = .89; relative risk [RR], 1.03 [95% confidence interval {CI}, 0.72-1.46]) in the N-acetylcysteine and placebo groups, respectively. We noted nonsignificant differences in postoperative interventions and complications, the need for RRT (0.7% vs 2.1%; P = .37), total (6.1% vs 9.6%; P = .26) and serious adverse events, hospital mortality (3.4% vs 2.7%; P>.99), and ICU and hospital length of stay between the N-acetylcysteine and placebo groups. A post hoc subgroup analysis of patients (baseline creatinine level >1.4 mg/dL [120 micromol/L]) showed a nonsignificant trend toward fewer patients experiencing postoperative renal dysfunction in the N-acetylcysteine group compared with the placebo group (25.0% vs 37.1%; P = .29).
                N-acetylcysteine did not prevent postoperative renal dysfunction, interventions, complications, or mortality in high-risk patients undergoing CABG surgery with CPB. Further research is required to identify CABG patients at risk for postoperative renal events, valid markers of renal dysfunction, and to establish renal thresholds associated with important clinical outcomes. In this prospective, randomized, placebo-controlled, double-blinded study, we determined the effects of two commonly used adjuncts, mannitol and dopamine, on beta(2)-microglobulin (beta(2)M) excretion rates in patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass (CPB). beta(2)M excretion rate has been described as a sensitive marker of proximal renal tubular function. One-hundred patients with a preoperative serum creatinine level <or=1.5 mg/dL were prospectively randomized into 4 groups: 1). placebo, 2). mannitol 1 g/kg added to the CPB prime, 3). dopamine 2 microg kg(-1x. min(-1) from the induction of anesthesia to 1 h post-CPB, or 4). mannitol plus dopamine. The primary outcome measure was beta(2)M excretion rate at 1 h post-CPB. Secondary outcome measures included beta(2)M excretion rate at 6 and 24 h post-CPB; urinary flow rate and creatinine clearance at 1, 6, and 24 h post-CPB; and the highest postoperative serum creatinine level. Length of intensive care stay and hospitalization, as well as adverse events, were also considered secondary outcomes. Dopamine significantly increased beta(2)M excretion rate at 1 h post-CPB (2.48 +/- 3.61 microg/min) compared with placebo (0.59 +/- 1.04 microg/min; P = 0.001). This effect was not ameliorated by the addition of mannitol (beta(2)M excretion rate, 2.05 +/- 2.77 microg/min; P = 0.007 compared with placebo). beta(2)M excretion rate was similar in patients given placebo or mannitol alone (P = 0.831). Rather than being a protective drug in the setting of CPB, dopamine alone or in combination with mannitol increases beta(2)M excretion rate, which may be a measure of renal tubular dysfunction. The clinical implications of this increase and whether it is also seen in patients with established renal dysfunction undergoing CPB require additional investigation.
                In many clinical settings, an increased beta-2-microglobulin (beta(2)M) excretion rate indicates renal tubular injury. In this cardiopulmonary bypass (CPB) study, a dopamine infusion (alone or with mannitol) resulted in an increased beta(2)M excretion rate. It is unclear whether this dopamine-related increase implies renal injury after CPB, and further investigations are required to examine the mechanism/clinical relevance of this observation. Acute renal failure complicating open heart surgery is not uncommon. Dopamine infusion (2.5-4.0 microg/kg per min) has often been advocated for prophylactic 'renal protection' in this setting despite little objective evidence of real benefit. We aimed to investigate whether dopamine offers any 'renal protection' in patients with normal heart and kidney functions undergoing routine coronary artery bypass grafting (CABG). Urinary excretion of retinol-binding protein (RBP), previously validated as a sensitive and accurate marker of early renal tubular injury, was used to assess the renal effects of dopamine during the first postoperative week.
                Forty consecutive patients from the elective waiting list were prospectively randomized into two equal groups: those in Group A received dopamine infusion at 'renal dose' (2.5-4.0 microg/kg per min) starting from induction of anaesthesia for 48 h, whereas those in Group B served as untreated controls. Daily measurements were made of weight-adjusted urine output (ml/kg), fluid balance (input/output), serum creatinine, blood urea and urinary RBP. Statistical comparisons were made using Mann-Whitney U-test.
                The two groups matched in terms of age, time and temperature on cardiopulmonary bypass, number of grafts performed and perioperative haemodynamic status. No differences were detected in the weight-adjusted urine output, fluid balance, serum creatinine and blood urea between the groups. Control subjects (Group B) showed an increase in urinary RBP during the first and second postoperative days (323+/-4 microg/ mmolCr and 50+/-3 microg/mmolCr; mean+/-SD). However, patients treated with dopamine (Group A) demonstrated much greater urinary excretion of RBP over the same period (1257+/-15 microg/mmolCr and 449+/-21 microg/mmolCr; P = 0.0006 and 0.03) than those in Group B.
                Dopamine given at 'renal-dose' appears to offer no renal protection in patients with normal heart and kidney functions undergoing elective coronary surgery. On the contrary, it exacerbates the severity of renal tubular injury during the early postoperative period. Based on these findings we do not recommend the use of dopamine for routine renal prophylaxis in this group of patients. Activation of the renin-angiotensin system during open heart surgery may have consequences both beneficial in sustaining blood pressure and deleterious in compromising renal hemodynamics. The influence of short-term pretreatment with captopril on blood pressure and renal function was assessed double-blind versus placebo in 18 patients without pre-existing cardiac or renal failure, and undergoing coronary artery bypass. No difference in blood pressure and fluid requirement during the surgical period was observed between groups receiving captopril or placebo. Effective renal plasma flow and glomerular filtration rate decreased in the placebo group whereas they remained unaltered in the captopril group; during cardiopulmonary bypass, urinary excretion of sodium was greater in patients receiving captopril than those receiving placebo. These results suggest that captopril pretreatment does not compromise the control of blood pressure and renal function during open heart surgery; additional studies on the protective value of angiotensin-converting enzyme inhibitors are warranted in patients at higher risk for developing renal failure. A prospective study was undertaken to assess postoperative renal dysfunction in patients with obstructive jaundice and to determine the effectiveness of dopamine in reducing its incidence. A total of 23 patients undergoing surgical relief of obstructive jaundice (serum bilirubin level above 100 mumol l-1) were randomized into two groups. Those in the control group (n = 10) received 3 litres 5 per cent dextrose intravenously during the 24 h before surgery plus a bolus of intravenous frusemide 1 mg kg-1 at induction of anaesthesia. The second group (n = 13) received a similar fluid and frusemide regimen plus an infusion of dopamine 3 micrograms kg-1 min-1 starting at induction of anaesthesia and continuing for 48 h after surgery. Postoperative oliguria occurred in two of the ten patients in the control group and in three of the 13 given dopamine (P = 0.74). No patient developed acute renal failure. There was no significant difference in mean levels of serum bilirubin, urea and creatinine, creatinine clearance and 24-h urinary output, on the day before and on days 1-5 after operation, between the two groups. It is concluded that, with careful preoperative resuscitation and control of fluid and electrolyte balance, the incidence of postoperative renal dysfunction in patients with obstructive jaundice is not as high as in some previous studies and is unaltered by administration of perioperative low-dose dopamine. This prospective, randomized study assessed the effect of dopamine on renal tubular function in patients who had coronary artery bypass grafting.
                Two groups of patients with normal preoperative renal function were randomly divided into a dopamine group (n=11), who received dopamine in a dose of 2 mg/kg x min, and a control group (n=11), who received no treatment. Dopamine infusion was initiated 24 hours before the operation and was continued for 48 hours postoperatively. Measurements of renal function obtained 2 days before the operation were considered preoperative and were repeated on the 1st, 3rd, and 7th postoperative days. Urinary excretion of b2-Microglobulin (b2-M), considered a sensitive means for diagnosing proximal tubular damage, was measured during the early (day 3) and late (day 7) postoperative period.
                There were no significant differences respect to the clearances of creatinine, osmotic, and free-water in the dopamine group compared with the control group (p>0.05). Urine microalbumin levels significantly increased on postoperative day 3 in both groups. During the early postoperative period, excretion of urine b2-M was significantly greater in the dopamine group than in the control group (p<0.05).
                Consequently, in patients with normal preoperative renal and cardiac function scheduled for elective coronary artery bypass grafting, renal dose dopamine infusion alone may not provide sufficient protection on tubular function and increases renal tubular injury during the early postoperative period. Impairment of splanchnic and peripheral tissue perfusion during cardiopulmonary bypass (CPB) may be responsible for endotoxin-mediated systemic inflammation and acute phase responses. We examined the effects of dopexamine on hemodynamic parameters, creatinine clearance, systemic and splanchnic oxygenation, gastric mucosal pH (pHi), and mixed and hepatic venous plasma levels of endotoxin, interleukin-6 (IL-6), serum amyloid A (SAA), and C-reactive protein (CRP) in 44 patients scheduled for coronary artery bypass grafting. Patients were randomized to receive continuous infusions of 0.5, 1.0, or 2 micrograms.kg-1.min-1 dopexamine (n = 10 per group) or placebo (n = 14) prior to surgery, intraoperatively, and postoperatively. Dopexamine infusion increased systemic oxygen delivery (P < or = 0.01). Hepatic venous oxygen saturation did not change, and pHi decreased during and after CPB in all patients (P < or = 0.01). Postoperative increases in IL-6 were smallest in patients who received 2.0 micrograms.kg-1.min-1 dopexamine (P < or = 0.02). SAA and CRP increases during the postoperative period were less pronounced with dopexamine throughout the study. Creatinine clearance was elevated in all dopexamine groups (P < or = 0.025). This elevation was higher with lower dopexamine doses (P < or = 0.025). We conclude that dopexamine improves creatinine clearance and reduces systemic inflammation without affecting splanchnic oxygenation. Forty patients with obstructive jaundice (bilirubin greater than 100 mumol/l) were entered into a randomized trial of oral ursodeoxycholic acid for 48 h before surgery versus no additional therapy. Pre-operative venous and operative portal total bile salt concentrations were higher in the bile salt treated patients (P less than 0.001). Portal endotoxaemia during operation was reduced in ursodeoxycholic acid treated patients (P less than 0.05). There was no significant difference in systemic venous endotoxaemia, renal function or postoperative morbidity or mortality. This study suggests pre-operative oral bile salt therapy may be of no clinical benefit in patients with obstructive jaundice. Coronary revascularization with cardiopulmonary bypass has the potential risk of renal dysfunction related to the nonphysiologic nature of cardiopulmonary bypass. Recently, there has been a revival of interest in performing myocardial revascularization on the beating heart and we investigated whether this prevents renal compromise.
                A prospective, randomized, controlled trial was performed in 50 patients (45 males, mean age 61+/-3.7 years) undergoing elective coronary artery bypass grafting. Patients were randomly assigned to conventional revascularization with cardiopulmonary bypass (on pump) or beating heart revascularization (off pump). Glomerular and tubular function were assessed up to 48 hours postoperatively.
                There were no deaths, myocardial infarctions or acute renal failure in either group. Glomerular filtration as assessed by creatinine clearance and the urinary microalbumin/creatinine ratio was significantly worse in the on pump group (p < 0.0004 and 0.0083, respectively). Renal tubular function was also impaired in the on pump group as assessed by increased N-acetyl glucosaminidase activity (p < 0.0272).
                These results suggest that off pump coronary revascularization offers a superior renal protection when compared with conventional coronary revascularization with cardiopulmonary bypass and cardioplegic arrest in first time coronary bypass patients. The effectiveness of dopamine alone or in combination with mannitol or furosemide in preventing postoperative renal dysfunction in patients with obstructive jaundice was assessed in this study.
                Forty patients having obstructive jaundice were randomly allocated into 4 equal groups. Preoperative hydration was performed by infusing all patients 1L of 5% dextrose the night before surgery and another 1L in the morning before surgery. Intra- and postoperative maintenance of adequate intravascular volume was assured by fluid and blood replacement guided by the monitoring of central venous pressure urine output and blood pressure. The 1st group was kept as a control. The other 3 groups received dopamine 2.5 micrograms/kg/min for 2 postoperative days starting before surgery. The 2nd group was maintained on dopamine alone, while mannitol (0.25 g/kg), every 12 hours for 2 postoperative days, was added to the 3rd group. Similarly furosemide (1 mg/kg) every 12 hours for 2 postoperative days, was infused to the patients of the 4th group. Postoperative renal functions were assessed by 24-hour urine output, serum creatinine, creatinine clearance and urine to plasma osmolality ratio.
                All these tests did not show significant changes in the 1st, 2nd and 7th postoperative days. Only transient decreased creatinine clearance and elevated serum creatinine were observed in the patients of the 4th group in the 1st and 2nd postoperative days. This may be attributed to fluid imbalance induced by furosemide in these patients who were older than the other groups.
                The study showed that careful attention to perioperative hydration is the cornerstone in preserving adequate renal function following surgery in patients with obstructive jaundice. Administration of dopamine alone or in combination with mannitol or furosemide did not confer more renal protection. Infrarenal aortic cross-clamping is associated with impairment of renal hemodynamics due to vasoconstriction, the mechanism of which remains under debate. To assess the renal effect of two potent renal vasodilators (enalapril, a converting enzyme inhibitor, and nicardipine, a calcium antagonist), 24 patients scheduled for reconstructive aortic surgery were randomly allocated to one of three treatment groups (n = 8 each) and received either a placebo, nicardipine, or enalapril. Anesthesia consisted of flunitrazepam, fentanyl, pancuronium, and, occasionally, droperidol. Although aortic cross-clamping was associated with no change in mean arterial blood pressure, decreased cardiac output and increased systemic vascular resistance occurred in control patients (33% and 43%, respectively, both P less than 0.05 versus baseline) and nicardipine-treated patients (51.7% and 67.7%, respectively, both P less than 0.05 versus baseline); however, changes in cardiac output and systemic vascular resistance failed to reach significance in enalapril-treated patients. Glomerular filtration rate (technetium 99-diethylenetriaminepentacetic acid clearance) and effective renal plasma flow (iodo-Hippuran 131 clearance) decreased for the duration of aortic cross-clamping in control patients (42.9% and 18.5%, respectively, both P less than 0.05 versus baseline) and enalapril-treated patients (34.0% and 38.1%, respectively, both P less than 0.05 versus baseline), but no change was observed in nicardipine-treated patients. These results suggest that the reninangiotensin system is not an important determinant of the renal vasoconstriction associated with aortic cross-clamping. In contrast, renal dysfunction may be alleviated by the dihydropyridine derivative nicardipine, which probably acts at the level of the preglomerular resistance vessels. Patients undergoing surgery for idiopathic scoliosis were studied to determine the incidence and aetiology of oliguria during the perioperative period and to evaluate the efficacy of low dose dopamine in preventing its occurrence. Thirty patients, aged 6-18 years undergoing elective surgery were studied. Anaesthesia was standardized. Patients were randomized to receive either dopamine infusion (3 micrograms.kg-1.min-1) (Group A) (n = 15) or dextrose infusion (control) (Group B) (n = 15). Serum and urinary electrolytes and osmolalities and serum antidiuretic hormone (ADH) concentrations were measured. Urine output and haemodynamic parameters were recorded. Intraoperative oliguria occurred in 7% of patients in Group A and 47% in Group B (P < 0.05). Postoperative oliguria occurred in 20% of patients in Group A and 47% in Group B (P > 0.05). Urine and serum biochemical analysis revealed a statistically significant decrease in serum sodium and osmolality (P < 0.005) and an increase in urinary sodium and osmolality in both groups. Serum ADH concentrations were increased in both groups (P < 0.05), returning to baseline 18 h postoperatively. We conclude that oliguria during corrective spinal surgery occurs in association with excess ADH secretion as opposed to perioperative hypovolaemia. Dopamine increases urine output in the perioperative period but does not prevent the release of ADH and its subsequent biochemical effects. The objective of this study was to evaluate the effects of dopexamine on renal function in 4 groups of patients either with or without renal dysfunction. Transient renal dysfunction is often not clinically relevant in patients with normal renal function, but it is an important clinical factor in patients with pre-existing renal failure. Dopexamine (DX) is a commonly used catecholamine which probably exerts a selective effect at the splanchnic bed.
                24 patients with normal renal function and 24 patients with impaired renal function (creatinine in serum > or = 1.5 mg/dL) were each randomly allocated to 2 groups. Group 1 (control) without renal dysfunction and group 3 (control/dysfunction) with renal dysfunction were considered as control groups, while the patients in DX and DX/dysfunction groups received 1 microg/kg/min dopexamine until the end of surgery. Kidney function was investigated using standard parameters and by investigating specific proteins and enzymes.
                All patients showed pathologic excretions of the investigated parameters during cardiopulmonary bypass (CPB) with no differences between the study groups. The distal tubule, the lysosomal regions, Henle's loop and the glomerular tuft were all damaged. Heart rate and cardiac index increased significantly in the DX-groups, first until the end of surgery, second until the start of ECC.
                Dopexamine at a dose of 1 microg/kg/min had no influence on renal function and protein excretion and cannot be regarded as a kidney function protecting substance. Postoperative renal impairment is a recognized complication of infrarenal aortic cross-clamping. Our hypothesis was that the renal vasodilating and natriuretic effects of fenoldopam mesylate, a selective dopamine (DA1) agonist, would preserve renal function in patients undergoing elective infrarenal aortic cross-clamping.
                A prospective, randomized, double blind controlled clinical trial was performed. Twenty-eight ASA II-III patients undergoing elective aortic surgery requiring infrarenal aortic cross-clamping were studied. According to random allocation, patients received either fenoldopam (0.1 microg kg(-1) min(-1)) or placebo intravenously prior to surgical skin incision until release of the aortic clamp. Plasma creatinine, creatinine clearance, urinary output, fractional excretion of sodium, and free water clearance were measured: (a) prior to admission to hospital; (b) during the period from insertion of the urinary catheter until application of the aortic cross-clamp; (c) during the period of aortic cross-clamping; (d) 0-4 h, and (e) 4-8 h after release of the clamp and on days 1, 2, 3, and 5 postoperatively.
                Fenoldopam (0.1 microg kg(-1)min(-1)) administration was not associated with haemodynamic instability. On application of the aortic cross-clamp creatinine clearance decreased significantly in the placebo (83 +/- 20 to 42 +/- 29 mL min(-1) (mean +/- SD)) (P < 0.01) but not in the fenoldopam group, and this decrease persisted for at least 8 h after release of the cross-clamp (83 +/- 20 to 54 +/- 33 mL min(-1) (mean +/- SD)) (P < 0.05). Plasma creatinine concentration increased significantly from baseline on the first postoperative day in the placebo group (87 +/- 12 to 103 +/- 28 micromolL(-1) (mean +/- SD)) (P < 0.01) but not in the fenoldopam group.
                These findings are consistent with the hypothesis that fenoldopam possesses a renoprotective effect during and after infrarenal aortic cross-clamping. Renal failure after bypass is still a threatening problem prolonging hospital care and reducing overall survival. The following pilot study was aimed to analyze whether perioperative low-dose prostacyclin infusion is able to preserve renal function in a selected group of patients who according to a poor cardiac function were stratified as high risk for the development of renal failure after bypass.
                Prospective randomized study.
                Tertiary care university medical center.
                Thirty-four patients scheduled for primary cardiac bypass surgery were included in the study (prostacyclin n = 17, control n = 17). Inclusion criteria were normal renal function before surgery and a cardiac ejection fraction <40%.
                Low-dose prostacyclin (2 ng/kg/min) was added to the standard anesthetic protocol. Infusion was started immediately before surgery and was continued for a maximum of 48
                Significant differences in the endogenous creatinine clearance were found between the prostacyclin and the control group. Whereas there was a significant drop in the creatinine clearance at 6 hrs after surgery in the control group with a prolonged recovery period, values in the prostacyclin group remained stable. Creatinine clearance before intervention was 100 +/- 22 mL/min in the control group and 91 +/- 22 mL/min in the prostacyclin group, values at 24 hr were 68 +/- 34 mL/min vs. 103 +/- 37 mL/min, respectively (p < .01). Significant findings in favor for the prostacyclin group were also found for urine output and the fractional excretion rate of sodium.
                This first pilot study indicates that low-dose prostacyclin may be of substantial value for preserving renal function in high-risk patients after coronary bypass surgery.
There is no reliable evidence from the available literature to suggest that interventions during surgery can protect the kidneys from damage. There is a need for more studies with high methodological quality. One particular area for further study may be patients with pre-existing renal dysfunction undergoing surgery.