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Ann Thorac Surg 2000;69:501-506
© 2000 The Society of Thoracic Surgeons

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Original Articles

Mannitol, furosemide, and dopamine infusion in postoperative renal failure complicating cardiac surgery

^a Department of Cardiovascular and Thoracic Surgery, Newark Beth Israel Medical Center, Newark, New Jersey, USA

Address reprint requests to Dr Gielchinsky, Department of Cardiovascular and Thoracic Surgery, Newark Beth Israel Medical Center, 201 Lyons Ave, Newark, NJ 07112
e-mail: gielchinsky{at}worldnet.att.net

	Abstract

Top Abstract Introduction Material and methods Results Comment References

 
Background. Acute renal failure occurring in the postoperative period, requiring dialysis after cardiac surgery is an important risk factor for an early mortality, and the overall mortality of this complication is as high as 40% to 60%. Dialysis in the early postoperative period is often complicated by acute hemodynamic, metabolic, and hematologic effects that adversely affect cardiopulmonary function in patients stabilizing from recent surgery. The purpose of this study was to avoid the need for dialysis by infusion of the solution of mannitol, furosemide, and dopamine in the early postoperative period in oliguric renal failure.

Methods. One hundred patients with postoperative oliguric or anuric renal failure despite adequate postoperative cardiac output and hemodynamic function were randomized. Forty patients (group A) were given intermittent doses of diuretics (furosemide, bumetadine, and ethracrynic acid) and fluids. Sixty patients (group B) were given continuous infusion of the solution of mannitol, furosemide, and dopamine; the infusion was started within 6 hours (mean 3.5 hours) in subgroup B1 (n = 30), and later than 6 hours (mean 7.5 hours) in subgroup B2 (n = 30) after the onset of renal failure.

Results. Diuresis occurred in 93.3% of group B (n = 56) versus 10% in group A (n = 4; patients with preop normal renal function). Ninety percent of group A (n = 36) required dialysis versus only 6.7% of group B (n = 4; patients with preexisting renal disease of subgroup B2). Renal function returned to preoperative normal (serum creatinine 0.9 ± 0.05, p < 0.0001) or baseline value (serum creatinine 2.5 ± 0.01, p < 0.0001) after first postoperative week in subgroup B1 and third postoperative week in subgroup B2.

Conclusions. Infusion of solution of mannitol, furosemide, and dopamine promoted diuresis in patients with acute postoperative renal failure with adequate postoperative cardiac output and had decreased the need for dialysis in the majority of patients. Early administration of this solution in acute renal failure caused early restoration of renal function to normal or baseline status. It remains to be determined whether routine administration of this solution in the early postoperative period for oliguric renal failure influences the long-term mortality and morbidity in those patients who do require dialysis.

	Introduction

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Occurrence of acute oliguric renal failure in the immediate postoperative period carries important morbidity and mortality after a successful cardiac surgical procedure. Adult cardiac and aortic surgical procedures are especially prone to this complication with the incidence varying between 2% to 15% and the mortality rate as high as 40% to 60% [1–5]. Some of the factors that contribute to renal failure in the postoperative period are advanced age, preexisting renal insufficiency, preoperative left ventricular dysfunction, low cardiac output in the perioperative period, and performance of operations other than isolated CABG, prolonged aortic cross-clamp, and cardiopulmonary bypass time [6–10]. Factors that have potential to adversely affect renal function in the postoperative period are fluid shifts with altered hemodynamics, atheroembolic disease, angiographic dyes, and use of medications such as antihypertensives and antibiotics [11, 12]. Acute renal failure may also ensue despite adequate cardiac and hemodynamic function in the postoperative period. In patients with adequate cardiac output, the onset of oliguria (urine volume < 0.5 mL/kg/hour) and rising serum potassium concentration (k > 5.3 meq/L) suggests an underlying intrinsic renal dysfunction, not related to the blood flow.

It is conventional to administer intermittent doses of diuretics and fluids in the early postoperative period in acute renal dysfunction until dialysis is mandatory to correct fluid, electrolyte, and metabolic disorder, and rising blood urea nitrogen and creatinine. In our experience, intermittent administration of diuretics were usually unsuccessful, and use of dialysis in the early postoperative period compromised cardiopulmonary function, especially in patients with marginal cardiopulmonary reserve and in patients who had undergone complex cardiac surgical procedures. To address this issue, we have started using continuous infusion of the solution of mannitol and furosemide in addition to renal doses of dopamine in patients with acute postoperative renal failure with adequate cardiac output. This infusion has established diuresis and obviated the need for dialysis in a majority of the patients. Since 1985, many cardiac surgical patients with a acute postoperative renal failure were given this infusion with a substantial decrease in need for dialysis in the immediate postoperative period.

	Material and methods

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At Newark Beth Israel Medical Center, during a period of four years, ie, from October 1994, to September 1998, an average of 730 operations per year were performed in adults for acquired cardiac disease. During this period, patients who manifested either acute oliguric or anuric renal failure in the postoperative period, with adequate postoperative cardiac output and tissue perfusion were prospectively evaluated and, in 100 patients, such acute renal dysfunction was recognized in the postoperative period. Excluded from the study were patients with acute renal failure associated with inadequate cardiac output and tissue perfusion, patients who required preoperative dialysis, and patients who depended on dialysis. This investigation was approved by the institutional review board at Newark Beth Israel Medical Center, and informed consent, obtained for surgery, also included this postoperative clinical study. We have established a protocol and enrolled these 100 patients after meeting the following criteria.

Urine volume of less than 30 mL/hour was defined as an oliguria and urine volume of less than 17 mL/hour was defined as anuria in an average adult patient. Patients who were either anuric or oliguric for a consecutive 2 to 3 hours despite volume correction and maintenance of adequate cardiac and hemodynamic function, and who fulfilled the following laboratory criteria were considered to have acute postoperative renal failure or renal dysfunction: (1) an increase in the serum creatinine level of 0.5 mg% or more; (2) an increase of more than 50% over the baseline serum creatinine; or (3) decrease in the calculated creatinine clearance of more than 50%. Though, in some of the patients in this cohort who had preoperative serum creatinine of 0.9 mg% or less, serum creatinine was only marginally elevated (ie, > 1.3 mg%) in the very early postoperative period, the free water clearance and creatinine clearance were decreased but, without significant decrease in urine volumes (probably because of osmotic diuresis induced by heart-lung prime). As the renal failure progressed into oliguria or anuria, there were further decreases in creatinine clearance with an increase in serum creatinine levels. Patients were considered to have preexisting renal disease or preoperative renal dysfunction who had a preoperative serum creatinine level of 2.5 mg% or more with evidence of glomerulopathy and without a need for preoperative dialysis.

Patients were randomized either to receive intermittent doses of diuretics (group A, 40 patients) or continuous infusion of osmitrol, furosemide, and dopamine (group B, 60 patients). The solution containing osmitrol (mannitol) and furosemide was prepared adding 1 gm of furosemide to 500 mL of 20% osmitrol solution. This constituted solution contains 0.2 gm of mannitol and 2 mg of furosemide per milliliter of fluid. This solution was given in conjunction with renal doses of dopamine (ie, 2 to 3 mcg/kg/min) at an initial rate 0.3 mL to 0.4 mL/kg/h to promote diuresis. Once the diuresis was established, the infusion rate of the solution was tailored to achieve desired urine flow.

Group A (24 patients with preoperative normal renal function and 16 with preexisting renal disease) were given intermittent doses of furosemide, ethacrynic acid, and bumetadine either alone or in combinations (Doses: furosemide 1.4 mg to 3 mg/kg ql to 2 h x 4 to 6 hours; ethacrynic acid 0.7 mg/kg q2 h x 4 to 6 hours; bumetadine 0.014 mg/kg ql h x 4 to 6 hours), as recommended by the nephrologists of this institution. Boluses of crystalloids and colloids were also given as necessary to assure adequate preload and cardiac output.

Group B patients were randomized into two subgroups. In subgroup B1 (30 patients; 14 patients with preoperative normal renal function and 16 with preexisting renal disease), the osmitrol and furosemide infusion was started within 6 hours after onset of oliguria and anuria (mean duration, 3.5 hours). In subgroup B2 (30 patients; 18 patients with preoperative normal renal function and 12 with preexisting renal dysfunction), the infusion was started later than 6 hours after the onset of oliguria or anuria (mean duration 7.5 hours). Medical measures for correction of fluid, electrolyte, and acid-based disorders were instituted in all patients when required. Criteria for dialysis were the same in both groups, and were established and carried out by the nephrologists of this institution; in none of the patients was the dialysis given either prematurely or postponed because of bias.

Postoperative care of the patients is followed according to the established standards of care of any cardiac surgical patient. Monitored were indices of cardiac and hemodynamic function (ie, cardiac output, cardiac index, central venous pressure, systemic mean arterial pressure, pulmonary artery pressure, pulmonary capillary wedge pressure, systemic and pulmonary vascular resistance) and hourly urine volume. Multiple measurements of cardiac output and hemodynamics were done along with frequent assessment of peripheral tissue perfusion to assure adequacy of cardiovascular function. Complete blood count, hematocrit, partial thromboplastin time, prothrombin time, fibrin split products, activated clotting time, serum electrolytes, blood urea nitrogen concentration, serum creatinine, serum enzymes, arterial blood gases, electrocardiograms, and chest roentgenograms were done routinely.

Creatinine clearance and free water clearance were estimated from random urine samples. Frequent estimation of serum creatinine and creatinine clearance were done in the early postoperative period to monitor progress in acute renal dysfunction. In selected patients, urine was examined for myoglobin and hemoglobin pigments and casts. Renal scans (technetium scan) were done after the onset of renal failure only in patients with preoperative normal renal function (n = 56) of both groups A and B, and the scans were repeated after the second postoperative week only in patients who had adequate diuresis without a need for dialysis (group B: n = 32; group A: n = 4). Renal scan examinations were not done in patients with preexisting renal disease as to avoid errors in interpretation and with the assumption that some abnormalities were already existent in the preoperative period. Demographics and patient clinical characteristics of both group A and group B are shown in Table 1.

	Results

Top Abstract Introduction Material and methods Results Comment References

 
Preoperative patient characteristics, associated comorbid features, did not assume statistical significance between groups A and B, and patients had mean age of 71 years with moderately depressed left ventricular ejection fraction (EF 0.35). In patients with preoperative normal renal function (n = 56), the preoperative mean serum creatinine was 0.9 ± 0.03. In patients with preexisting renal disease (n = 44), the preoperative mean serum creatinine was 2.7 ± 0.03. After the onset of acute renal failure, free water clearance was decreased in all patients (mean 8 mL/min). Creatinine clearance obtained from random urine samples also showed a significant decrease (mean 30 mL/min). Serum potassium was either normal or mildly elevated (5.4 ± 0.2). In the early postoperative period before significant decrease in urine volume, serum creatinine elevations were just above the baseline values, but after progression of renal failure and onset of oliguria and anuria, the serum creatinine levels were further increased (mean 2.9 mg%) in patients of both groups (Table 2). On the first postoperative day in patients with good preoperative renal function (n = 56), the serum creatinine was elevated to a mean of 1.9 ± 0.03, and in patients with preexisting renal disease (n = 44), the serum creatinine level was mean 3.2 ± 0.05) (Table 3). Multiple measurements of cardiac output and hemodynamic indices performed during the postoperative course in both groups A and B indicate adequate cardiac and hemodynamic function (Table 2).

In all patients (n = 30) of subgroup B1, adequate urine flow was established within 2 to 4 hours after the infusion was started. In patients with preoperative normal renal function (n = 14), the serum creatinine was returned to normal after the first postoperative week (0.9 mg%; p < 0.0001 from early postop value). Renal scans were also returned to normal with adequate perfusion after the second postoperative week. In patients with preexisting renal disease (n = 16), the serum creatinine was returned to preoperative baseline levels after the first postoperative week (2.5 mg%; p < 0.0001 from early postop value) with establishment of normal electrolyte balance (Table 3).

In group B2, the majority of the patients (n = 26; 86.6%) also established adequate urine flow 4 to 6 hours after infusion was begun. All patients (n = 18) with preoperative normal renal function of this subgroup responded with diuresis (B1 versus B2, p = NS), but developed high output renal failure and serum creatinine returned to normal only after the third postoperative week (1.1 mg% p < 0.0001 from early postop value). Repeat renal scans performed after the second postoperative week showed defects in perfusion. Only 8 patients with preexisting renal disease of this subgroup responded with an adequate diuresis, (B1 versus B2, p = 0.024), and on postoperative day 21, the serum creatinine was 2.9 ± 0.2, which was a slight elevation above the preoperative levels, and had a normal potassium and electrolyte balance (Table 3). Serum creatinine levels returned to baseline only after the third postoperative week. Four patients with renal disease of this subgroup (33.3%) did not establish adequate urine flow, and fluid and electrolyte balance was abnormal requiring dialysis (B1 versus B2, p = 0.024). The overall outcome in 100 patients with acute renal failure was shown in Figure 1.

View larger version (20K): [in this window] [in a new window]   Fig 1. Outcome in acute postoperative renal failure in 100 patients: Group A (n = 30) were given intermittent administration of diuretics. Subgroup B1 (n = 30) and subgroup B2 (n = 30) were given infusion of mannitol, furosemide, and dopamine 3.5 hours (mean) and 7.5 hours (mean), respectively, after the onset of renal failure. p Values represent group A versus B1 and group A versus B2 both for normal renal function and renal dysfunction. (*) High output renal failure occurred in subgroup B2 despite diuresis. Renal function returned to preoperative baseline after first postoperative week in subgroup B1 and third postoperative week in subgroup B2. (B1 versus B2 for preop normal renal function: p = NS. B1 versus B2 for preop renal dysfunction: p = 0.024 by Fisher’s exact test.)

View larger version (17K): [in this window] [in a new window]   Fig 2. Relationship between dose of continuous infusion of solution of mannitol and furosemide with renal doses of dopamine and hourly urine volumes in 56 patients.

	Comment

Top Abstract Introduction Material and methods Results Comment References

In this study, the patients had a mean age of 70 years with moderately depressed preoperative left ventricular function with associated comorbid disease states. Renal dysfunction ensued in this cohort despite adequate postoperative cardiac output suggesting multifactorial etiology of this complication. Acute postoperative renal failure requiring dialysis is an independent risk factor for an early mortality, and several studies have shown that the overall mortality of this complication is as high as 40% to 60% [1–5]. The conduct of dialysis in the early postoperative period is often complicated by abrupt changes in cardiopulmonary and hemodynamic function despite current improvements in dialysis technology. Acute changes in blood volume, fluid, and electrolytes, and alterations in blood cellular and noncellular components and complement activation may adversely affect clinical outcomes in patients stabilizing from recent complex cardiovascular surgery [15, 16]. The investigative trials using new pharmacologic agents such as atrial natriuretic peptide, human growth factor, and epidermal growth factor for treatment of acute renal failure were done in an attempt to enhance tubular regeneration and glomerular filtration. Though these trails were encouraging, not enough data was reported on clinical renal failure [16].

The continuous infusion of the solution of furosemide (0.6 mg to 0.85 mg/kg/h) with simultaneous administration of mannitol (0.06 gm to 0.08 gm/kg/h) and renal doses (2–3 mcg/kg/min) of dopamine promoted diuresis in acute postoperative renal dysfunction with adequate postoperative cardiac output. Diuresis occurred both in patients with preoperative normal renal function and preoperative renal dysfunction and significantly decreased the need for postoperative dialysis. Diuresis was also observed in renal dysfunction complicating pigment nephropathy (ie, nephropathy induced by increased load of myoglobin and hemoglobin pigments in blood), which may occasionally complicate surgery of acute Type I aortic dissection using periods of circulatory arrest. Despite hyperosmolarity of the solution, consequent to its administration, there was improvement in pulmonary gas exchange with a decrease in edema of all tissues including the myocardium.

Mannitol is routinely used as a component of priming solution in cardiopulmonary perfusion to maintain the osmolarity of the perfusate. It obligates the renal excretion of water by nature of its pharmacokinetic properties, acting on proximal tubules and descending limb of the loop of Henle [17, 18]. The osmotic diuresis induced by mannitol decreases tissue and cellular edema. Furosemide inhibits the active resorption of sodium and chloride in the ascending limb of the loop of Henle and distal tubules causing diuresis and natriuresis [17, 18]. It also improves pulmonary congestion and reduces left ventricular filling pressures as an acute hemodynamic effect before measurable diuresis occurs. Furosemide can also be shown to increase renal blood flow and cause redistribution of blood flow within the renal cortex [17]. Low-dose dopamine, by acting through the dopaminergic receptors (DA1 and DA2) within the kidney and renal blood vessels causes diuresis and natriuresis with increases in renal blood flow and glomerular filtration [18, 19]. The cumulative effect of this solution in acute renal dysfunction was increased glomerular filtration with excretion of water and solute [17–20]. Infusion of the solution early after onset of renal dysfunction restored renal function to preoperative normal or baseline status, a finding corroborated by serum creatinine values and renal scintigraphy. Delayed administration, despite causing diuresis, resulted in either high-output renal failure, delay in return of baseline renal function, or need for dialysis.

In conclusion, acute renal failure requiring dialysis is an important risk factor for an early mortality after open-heart surgical procedures. Continuous infusion of the solution of mannitol, furosemide, and low-dose dopamine promoted diuresis in acute oliguric renal failure occurring in the early postoperative period in patients with adequate cardiac output and substantially decreased the need for dialysis. In contrast, intermittent doses of diuretics failed to induce diuresis and a majority of patients required dialysis. It remains to be determined whether routine infusion of the solution in the early postoperative period for acute oliguric renal failure influences the long-term mortality and morbidity in those patients who do require dialysis.

	References

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Srikrishna Sirivella Isaac Gielchinsky Victor Parsonnet Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sirivella, S. Articles by Parsonnet, V. Search for Related Content PubMed PubMed Citation Articles by Sirivella, S. Articles by Parsonnet, V. Related Collections Related Article