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Year : 2008  |  Volume : 52  |  Issue : 1  |  Page : 38 Table of Contents     

Prevention of Perioperative Renal Failure

1 Professor & Head, Department of Anaesthesiology & Critical Care, Bhopal Memorial Hospital & Research Centre, Bhopal, M.P., India
2 Associate Professor, Department of Anaesthesiology & Critical Care, Bhopal Memorial Hospital & Research Centre, Bhopal, M.P., India
3 Assistant Professor, Department of Anaesthesiology & Critical Care, Bhopal Memorial Hospital & Research Centre, Bhopal, M.P., India

Date of Acceptance13-Dec-2007
Date of Web Publication19-Mar-2010

Correspondence Address:
R C Agarwal
Professor & Head, Dept. of Anaesthesiology & Critical Care, Bhopal Memorial Hospital & Research Centre, Bhopal - 462 038, M.P.
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Source of Support: None, Conflict of Interest: None

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Acute renal failure in the perioperative setting is a significant complication of anaesthesia and surgery. Preventive strate­gies may be considered the best strategy to prevent renal impairment and consequent renal failure. The anaesthesiologist must identify high risk patients preoperatively to prevent postoperative renal dysfunction along with optimizing intravascular volume status and cardiac output as well as renal function and avoiding nephrotoxins in the perioperative period. This can best be accomplished if the clinician understands the pathophysiological basis of the disease process.

Keywords: Acute renal failure, Perioperative, Nephrotoxin

How to cite this article:
Agarwal R C, Jain RK, Yadava A. Prevention of Perioperative Renal Failure. Indian J Anaesth 2008;52:38

How to cite this URL:
Agarwal R C, Jain RK, Yadava A. Prevention of Perioperative Renal Failure. Indian J Anaesth [serial online] 2008 [cited 2020 Dec 4];52:38. Available from: https://www.ijaweb.org/text.asp?2008/52/1/38/60596

   Introduction Top

Development of acute renal failure (ARF) perioperatively is associated with considerable mortality and often with incomplete recovery regardless of baseline renal function. Surgery represents a point in the disease process of critically ill patients when they are most sus­ceptible to an ischaemic injury of vital organs. The anaesthesiologist has a unique opportunity to reduce the perioperative mortality of high risk patients from renal failure by anticipating problems preoperatively and re­sponding aggressively to unanticipated complications during the critical perioperative period. Preventive strat­egies comprehend volume loading to correct hypovolemia, optimizing cardiac output and systemic blood pressure by use of inotropes and vasopressors, use of renal va­sodilators to augment renal blood flow and use of diuret­ics to decrease medullary oxygen consumption. [1] Thera­peutic implications relate to this pathophysiological se­quence and several physiological and pharmacological considerations are discussed in this review.

   Etiology Top

The etiology of acute oliguria must be investigated promptly in the perioperative setting. In cases of severe renal hypoperfusion, there is a narrow window of only 30-60 minutes between the onset of oliguria and the ini­tiation of ischaemic acute tubular necrosis (ATN). [2] Perioperative ARF results from many etiologies, how­ever, more than 90 percent of cases of perioperative ARF are due to relative hypovolemia and inadequate renal perfusion. [3] The causes of oliguria can be defined as pre renal, intrarenal or post renal. This classification provides a useful structure for the systematic approach to therapy and is summarized in [Table 1].

   Risk factors Top

Proper preoperative management of patients at high risk for perioperative ARF includes the following steps:

  1. Identification of patients at high risk for ARF.
  2. Evaluation of intravascular volume status.
  3. Optimization of pre-existing medical conditions.
  4. Review of medications with discontinuation of any non­-essential medications associated with renal insufficiency.

Pre-existing renal disease is the most important preoperative risk factor for the development of perioperative ARF. [5] [Table 2] reviews the multitude of risk factors for the development of postoperative ARF (PO­ARF). [2] Early recognition and optimization of these con­ditions is of paramount importance in order to avoid or limit perioperative renal dysfunction.

   Pathophysiology Top

The most common cause of perioperative ARF is ATN caused by ischaemia. [6],[7] Although this process is commonly called "necrosis", tubular epithelial cell loss after ischaemia results from both necrosis and apoptosis. Damaged tubular cells slough and obstruct the narrow portion of the descending part of the loop of Henle, caus­ing the filtrate to leak back into the renal interstitium (backleak). [7] A secondary contribution to the injury is activation of the renin angiotensin system, constricting glomerular vessels and reducing glomerular filtration. The luminal cells of the proximal convoluted tubule and med­ullary thick ascending limb of Henle are very active and thus most susceptible to ischaemia. Nearly 90-95% of the blood flows to the cortex while the medulla receives only 5-10%, resulting in a regional PaO2 of 10 mmHg in the medulla compared to 50 mmHg in the cortex. [8] Oxy­gen extraction on the other hand is much greater due to active water and salt reabsorption. This explains the ease with which medullary hypoxia can develop.

After ATN is triggered by acute ischaemia, a main­tenance phase of 1-2 weeks usually follows when the GFR decreases markedly. During this time, renal vaso­motor tone depends upon the opposing influences of ni­tric oxide and the very potent and long acting endog­enous vasoconstrictor endothelin (ET1). Other than the degree and duration of the initial insult, the factors which determine whether renal function recovers are poorly understood. If recovery of renal function is going to oc­cur, it is usually detectable within three weeks days of the initial injury.

   Preventive strategies Top

Most current practices used to provide 'renal pro­tection' are based on tradition, anecdotal information, or extrapolation from animal models. However logic sug­gests that the aim of the anaesthesiologist during the perioperative period should be to maintain a urine flow greater than 0.5 ml.kg -1 .h -1 , although there are no ran­domized studies to confirm this assertion.

A number of possible strategies aimed at alleviat­ing the development of renal dysfunction are shown be­low.

Treatment modalities to reduce or prevent the de­velopment of PO-ARF.

  1. Maintain adequate oxygen delivery - by ensuring adequate cardiac output, adequate oxygen carrying capacity, and proper haemoglobin saturation.
  2. Suppression of renovascular constriction - by en­suring adequate volume preload, use of infusions of mannitol, calcium entry blockers, and angiotensin converting enzyme inhibitors (ACE inhibitors).
  3. Renal vasodilation- by dopaminergic agents, pros­taglandins, and atrial natriuretic peptide (ANP).
  4. Maintain renal tubular flow - by loop diuretics and mannitol.
  5. Decrease oxygen demand - by use of loop diuret­ics and mild cooling.
  6. Attenuate ischaemic reperfusion injury - as a re­sult of the release of oxygen free radicals and cal­cium ion.

   Therapeutic implications for the anaesthesiologist Top

The prevention of pre-renal causes of ATN must begin before surgery. It is of utmost importance to iden­tify high risk patients preoperatively where risk is assessed and perfusion is optimized. In high risk patients, this should mandate an intravenous infusion the night before surgery. The maintenance of renal function after an ischaemic in­sult appears to be critically dependent on the speed with which perfusion is re-established. [9]

Essential preliminary monitoring includes an elec­trocardiogram, noninvasive blood pressure monitoring and pulse oximetry. Whether monitoring with invasive devices such as pulmonary artery catheters, arterial cannulae ac­tually reduces the incidence of ARF has never been dem­onstrated. The overwhelming consensus among clinicians is that these devices have improved our ability to maintain perfusion during major surgery. However, it must be em­phasized that unless data from invasive monitoring is ap­propriately used to maintain perfusion, the risk of compli­cations (e.g. sepsis) may negate any benefits.

   Physiological considerations Blood gas tensions Top

Decreases of arterial oxygen tensions alter renal blood flow (RBF) by either local effects or by the sec­ondary haemodynamic response to hypoxemia. Severe arterial hypoxemia to PaO2 values less than 40 mmHg are associated with decreases of RBF and enhanced renal vasoconstriction. [10] Hypercapnia has also been as­sociated with decreased sodium excretion, and RBF in patients requiring mechanical lung ventilation. [11] Thus the maintenance of perioperative RBF is best accomplished if the anaesthesiologist ensures adequate ventilation pre­venting hypoxaemia and hypercarbia.

   Positive pressure ventilation (PPV) Top

A consistent decrease in renal plasma flow and sodium excretion associated with positive intra-thoracic pressure has been documented by several studies. This has been attributed to the reflex (hormonal) systemic response to a reduced cardiac output. [12] Augmentation of circulating intravascular blood volume attenuates these haemodynamic changes as well as the hormonal and renal response to PPV. [13] Deterioration of renal function is not an invariable consequence of anaesthesia or PPV if per­fusion is maintained. [13]

   Perfusion pressure Top

The anaesthesiologist must attempt to keep mean systemic pressure at a minimum value of approximately 70-80 mmHg in high risk patients by using his clinical estimate of cardiac output. Stone and Stahl studied the renal effects of haemorrhage in normal humans and con­cluded that a decrease in mean perfusion pressure from 80 mmHg to 62 mmHg resulted in a reduction of RBF of about 30% without an autoregulatory response of the renal vasculature. [14] A high perfusion pressure may also help to minimize vascular congestion and improve per­fusion of the inner medulla.

In chronically hypertensive individuals exhibiting altered vascular autoregulation, this minimal perfusion pressure may be higher, since renal function in the un­stable intraoperative period is influenced by a number of haemodynamic and hormonal factors, thus it is not pos­sible to generalize perfusion pressure requirements for all patients. [13]

   Intra-abdominal pressure (IAP) Top

A rise in the intraabdominal pressure above 18 mmHg is considered abnormal and has been associated with decreased renal function. This is a complex response to intravascular volume depletion, reduced cardiac out­put and increased renal vein and inferior venacaval pres­sure. [15] The IAP can increase due to intraabdominal bleed­ing, intestinal distension, peritonitis, paralytic ileus and ascites. Improvement in renal function only occurs after decompression. The IAP may be measured via the blad­der.

   Preservation of the transplanted kidney Top

The primary aim of the anaesthesiologist is to main­tain perfusion to the 'donor' kidney prior to removal. All means of support including augmented intravascular vol­ume, inotropic agents and even blood administration to a brain dead donor may be required to maintain a func­tioning kidney. Mannitol administration to the recipient coupled with hemodilution and maintenance of renal perfusion at a mean arterial pressure more than 80 mmHg should provide the transplanted kidney with a hyperosmotic ultrafiltrate that will flush tubules of cellu­lar debris.

   Aortic cross clamping Top

Following vascular surgery involving either supra­renal cross-clamping of the aorta, or thoracic or thoraco­abdominal aortic surgery, there is similarly high incidence of ATN. Gamulin et al, have demonstrated that decreases in GFR and renal perfusion during and after infra-renal aortic cross-clamping can occur in humans. [16] It is pos­sible that high risk patients will benefit from prophylactic pharmacologic measures if haemodynamic stability can not be maintained.

   Cardiopulmonary bypass (CPB) Top

Non-pulsatile blood flow of CPB contributes to the reduced GFR (30%) and renal plasma flow (25%). [17] The duration of extracorporeal perfusion, which corre­lates with the degree of hemolylsis, and perioperative haemodynamic stability are the major factors determin­ing the development of ATN. The prevention of ARF after CPB is nonspecific and includes intraoperative maintenance of high perfusion rates, adequate oxygen­ation and perfusion pressure, minimizing CPB duration and hemolysis as well as optimizing myocardial protec­tion. [18]

   Pharmacological considerations Top


Mannitol is an osmotic diuretic. Mannitol increases RBF secondary to release of intrarenal vasodilating pros­taglandins and ANP, decreases the production of renin and reduces endothelial cell swelling. [8] Three random­ized studies in renal transplantation patients confirm that mannitol in the presence of adequate volume expansion reduces the incidence of postoperative renal failure, underlying the importance of fluid loading.[19] However, mannitol can be injurious in large doses causing intrarenal vasoconstriction and subsequent ARF.[20]

Loop diuretics

Drugs such as furosemide cause renal vasodila­tion as well as increasing sodium, potassium, urine out­put and creatinine clearance. Furosemide induced diuresis without maintenance of volume expansion may be detri­mental. [21] There are no controlled trial data to show the efficacy of continuous infusions of loop diuretics in over­coming diuretic tolerance or resistance. [22] Furthermore, recent studies by Lassnigg and colleagues have shown furosemide ( at a dose of 0.5 mcg.kg -1 .min -1 for 48 h) to have no renal protective effect after cardiac surgery, and to, perhaps, be causative of renal impairement. [23] Prophylaxis using loop diuretics is, however, effective against pigment nephropathies. [24]

Dopaminergic drugs

acts on the population of dopamine re­ceptors, DA1 and DA2. The use of low dose dopamine (1­3 mcg.kg -1 .min -1 ) was widely accepted in common clinical practice in an attempt to prevent or treat renal dysfunction. A systematic review of 58 studies concludes that there is no evidence, despite, its widespread use to support the use of low dose dopamine to prevent or to treat ARF. [25]

The improvement in urine output of non-shocked patients is only an expression of the diuretic effect of dopamine rather than its protective effect on renal func­tion. [26] The natriuretic effect of dopamine increases sol­ute delivery to the distal tubular cells, which may increase medullary oxygen consumption and exacerbate the is­chaemia during hypotension. This effect could explain why increases in RBF are not protective. [27] Furthermore, Perdue and colleagues have reported 'renal doses'of dopamine to be associated with an increased incidence of arrhythmias and worsening renal function. [28]

Dopexamine also increases splanchnic and renal perfusion, via a dopaminergic effect. [27] Despite some authors suggesting that dopexamine may protect renal function in patients undergoing cardiac surgery; there is no evidence to suggest a protective role in critically ill patients. [29]


Fenoldopam mesylate is a dopamine analogue, which stimulates postsynaptic peripheral dopamine-1 receptor only. The potential advantages of fenoldopam over dopamine include: increase in dopaminergic potency, lack of tachyarrhythmias and ability to safely infuse through a peripheral vein. [30] Two studies reported the beneficial role of fenoldopam in the prevention of PO­ARF in patients undergoing abdominal aortic aneurysm repair and CABG. [31] However, further randomized stud­ies are required before one can advocate the use of fenoldopam in the prevention of ARF.

Calcium channel blockers

These drugs exert direct vascular effect with pres­ervation of renal autoregulation and enhanced recovery of RBF, GFR and natriuresis. Calcium channel blockers have been tried successfully in the prevention of radiocontrast induced nephropathy, [32] but others have failed to confirm this. [33] Critically ill patients may not tol­erate high doses of these drugs which may further com­promise their haemodynamic status. As of now, calcium channel blockers can not be recommended for the pre­vention of renal function.

Atrial natriuretic peptide (ANP)

ANP is a potent endogenous renal protective hor­mone and diuretic. This hormone is produced in the car­diac atria in response to volume overload. ANP acts on the renal glomeruli to increase glomerular hydrostatic pressure by dilating afferent arterioles, constricting ef­ferent arterioles and increasing GFR. [34]

The synthetic ANP analogue anaritide and a renally produced natriuretic peptide ularitide have been tried in preventing or improving renal failure. A preliminary study was promising; however, large prospective positive stud­ies are required to warrant clinical use of the drug. [35]

   Future considerations Top

   Endothelin receptor antagonists (ET antagonists) Top

ET are potent vasoconstrictor peptides secreted by many types of cells. In the kidney, ET1 causes dose dependent vasoconstriction. Cross-clamping can in­crease plasma ET concentrations, the resulting renal vasoconstriction being preventable by nifedipine, thus either ET receptor antagonists or ET antibodies might offer amelioration of hypoxic renal injury. [36]

   Prostaglandins Top

Prostaglandin E1 is an endogenous renal vasodila­tor, but evaluation of three dosage regimens in patients with chronic renal insufficiency undergoing radiocontrast studies showed no effect on creatinine clearance although the serum creatinine increased more in the placebo group. [37]

   Acetylcysteine Top

The benefits associated with the administration of N-acetylcysteine in patients of radiocontrast nephropa­thy remains debatable. One cohort study found that N­acetylcysteine could independently decrease serum crea­tinine without any effect on GFR. The role of this agent to prevent ARF therefore remains unclear. This drug is currently under investigation, and conclusions are still uncertain. [38]

To conclude, the determinants of renal function are complex and are profoundly altered in the perioperative period. The process to limit perioperative renal impairment begins with the identification of risk factors preoperatively, understanding basic renal physi­ology, the influence of perioperative events and drugs on the pathophysiology of renal function. Pre-operative measures to reduce risk of ARF include optimizing vol­ume and solute status, ensuring adequate urine flow, avoiding high doses of diuretics, optimizing hematocrit levels, and avoiding contrast agents. Although a number of preventive strategies have been described, none apart from maintenance of normovolemia appears to be ef­fective. A number of new therapies have been identi­fied, but these must await the outcome of randomized clinical trials with large number of patients.

   References Top

1.Tang IY, Murray PT. Prevention of perioperative acute renal failure: what works? Best pract & Res clin Anesth 2004; 18:91­1-11.  Back to cited text no. 1      
2.Wilson WC, Aronson S. Oliguria, a sign of renal success or impending renal failure? Anesthesiol Clin North Am 2001; 19: 841.  Back to cited text no. 2      
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4.Nightingale P, Edward DJ. Critical care In: Wylie and Churchill Davidson's. A practice of anesthesia 6 th edition 1995: 1335­-1337.  Back to cited text no. 4      
5.Novis BK, Roizen MF, Aronson A, et al. Association of pre­operative risk factors with postoperative ARF. Anesth Analg 1994; 78:143-9.  Back to cited text no. 5      
6.Welch M, Knight DG, Carr HMH, et al. Influence of renal artery blood flow on renal function during aortic surgery. Sur­gery 1994; 115: 46-51.  Back to cited text no. 6      
7.7.Sladen RN, Prough DS. Perioperative renal protection. Prob­lems in anesthesia 1997; 9: 314-331.  Back to cited text no. 7      
8.Simon G. Does mannitol save the kidney? Anesth Analg 1996; 82:899-901.  Back to cited text no. 8      
9.Brezis M, Rosen S, Silva P, et al. Selective vulnerability of the thick ascending limb to anoxia in the isolated perfused rat kid­ney. J Clin Invest 1984; 73:182-90.  Back to cited text no. 9      
10.Kilbern KH, Dowell AR. Renal function in respiratory failure: effects of hypoxia, hyperoxia and hypercapnia. Arch Intern Med 1971; 127:754-62.  Back to cited text no. 10      
11.Sladen A, Laver MG, Pontopiddan H. Pulmonary complica­tions and water retention in prolonged mechanical ventilation. N Engl J Med 1968; 279:448-53.  Back to cited text no. 11      
12.Venus B, Mathru M, Smith RA, et al. Renal function during the application of PEEP in swine: effects of hydration. Anesthesi­ology 1985; 62:765-9.  Back to cited text no. 12      
13.Mazze RI. Renal physiology and the effects of anesthesia In: Miller RD (Ed.).Anesthesia.2 nd ed. 1986:1223-48.  Back to cited text no. 13      
14.Stone AM, Stahl WM. Renal effects of hemorrhage in normal man. Ann surg 1970; 172:825-36.  Back to cited text no. 14      
15.Richards WO, Scovill W, Shin B, et al. Acute renal failure asso­ciated with increased intra-abdominal pressure. Ann surg 1983; 197:183-7.  Back to cited text no. 15      
16.Gamulin Z, Forster A, Morel D, et al. Effects of infrarenal aortic cross-clamping on renal hemodynamics in humans. An­esthesiology 1984; 61:394-9.  Back to cited text no. 16      
17.Krian A. Incidence, prevention and treatment of ARF follow­ing cardiopulmonary bypass. Int Anesthesiol clin 1976; 14:87.  Back to cited text no. 17      
18.Geha A. ARF in cardiovascular and other surgical patients. Surg clin N Amer 1980; 60:1151-66.  Back to cited text no. 18      
19.Nicholson ML, Baker DM, Hopkinson BR, et al. Randomized controlled trial of the effect of mannitol on renal reperfusion injury during aortic aneurysm surgery. Br J Surgery 1996; 83:1230-3.  Back to cited text no. 19      
20.Doi K, Ogawa N, Suzuki E, et al. Mannitol induced ARF. Am J Med 2003; 115:593-594.  Back to cited text no. 20      
21.Gadallah MF, Lynn M, Work J. Mannitol nephrotoxicity syn­drome: role of hemodialysis and postulate of mechanism. Am J Med Sc 1995; 309:219-22.  Back to cited text no. 21      
22.Barter DC. Diuretic therapy. N Engl J Med 1998; 339:387-95.  Back to cited text no. 22      
23.Lassnigg A, Donner E, Grubhofer G, et al. Lack of renoprotective effects of dopamine and furosemide during cardiac surgery. J Am Soc Nephrol 2000; 11:97-104.  Back to cited text no. 23      
24.Homsi E, Barreiro MF, Orlando JM, et al. Prophylaxis of ARF in patients with rhabdomyolysis. Renal Fail 1997; 19:283-8.  Back to cited text no. 24      
25.Kellum JA, Decker M, Janine RN. Use of dopamine in ARF: A Meta-analysis. Crit Care Med 2001; 29:1526-1531.  Back to cited text no. 25      
26.Mehta RL, Pascual MT, Soroko S, et al. Diuretics, mortality and nonrecovery of renal function in ARF. J Am Med Ass 2002; 288:2547-2553.  Back to cited text no. 26      
27.Girbes AR. Prevention of ARF: role of vasoactive drugs, man­nitol and diuretics. Int J Arti Organs 2004; 27:1049-1053.  Back to cited text no. 27      
28.Perdue PW, Balser JR, LipSett PA, et al. 'Renal dose' dopam­ine in surgical patients: dogma or science? Ann Surg 1998; 227:470-3.  Back to cited text no. 28      
29.Ralph CJ, Tanser SJ, MacNaughton PD. A randomized con­trolled trial investigating the effects of dopexamine on gas­trointestinal function and organ dysfunction in the critically ill. Int Care Mes 2002; 28:884-890.  Back to cited text no. 29      
30.Lokhandwala MF. Preclinical and clinical studies on the cardio­vascular and renal effects of fenoldopam: a DA-1 receptor ago­nist. Drug Devel Res 1987; 10:123-34.  Back to cited text no. 30      
31.Gilbert TB, Hasnain JU, Flinn WR, et al. Fenoldopam infusion associated with preserving renal function after aortic cross clamping for aneurysm repair. J Cardiovasc Pharmacol Ther 2001; 6:31-6.  Back to cited text no. 31      
32.Ladefoged SD, Anderson CB. Calcium channel blockers in kid­ney transplantation. Clin Transplant 2000; 8: 128-33.  Back to cited text no. 32      
33.Neumayer HH, Junge W, Kufner A. Prevention of radiocontrast media induced nephrotoxicity by the calcium channel blocker nitrendipine: a prospective randomized clinical trial. Nephrol Dial Transplant 1989; 4:1030-6.  Back to cited text no. 33      
34.Maack T, Camargo MJ, Kleinert HD, et al. Atrial natriuretic factor: structure and functional properties. Kidney Int 1985; 27: 607-15.  Back to cited text no. 34      
35.Allgren RL, Marbury TC, Rahman SN, et al. Anaritide in acute tubular necrosis. New Engl J Med 1997; 336:828-34.  Back to cited text no. 35      
36.Antonucci F, Bertolissi M, Calo L. Plasma endothelin and renal function during infra-renal aortic cross clamping and nifedipine infusion. Lancet 1990; 336:1449.  Back to cited text no. 36      
37.Koch J, Plum J, Grabenesse B, et al. Prostaglandin E1: a new agent for the prevention of renal dysfunction in high risk pa­tients caused by radiocontrast media? Nephrol Dial Trans­plant 2000; 15:43-9.  Back to cited text no. 37      
38.Hoffman U, Fischereder M, Kruger, B et al. The value of N­acetylcysteine in the prevention of radiocontrast agent induced nephropathy seems questionable. J Am Soc Nephrol 2004; 15: 407-410.  Back to cited text no. 38      


  [Table 1], [Table 2]


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