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| SPECIAL ARTICLE |
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| Year : 2008 | Volume
: 52
| Issue : 1 | Page : 38 |
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Prevention of Perioperative Renal Failure
RC Agarwal1, Rajnish K Jain2, Anurag Yadava3
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 Acceptance | 13-Dec-2007 |
| Date of Web Publication | 19-Mar-2010 |
Correspondence Address:
R C Agarwal
Professor & Head, Dept. of Anaesthesiology & Critical Care, Bhopal Memorial Hospital & Research Centre, Bhopal - 462 038, M.P.
India
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 |
 Introduction | |  |
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 | | |
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 | | |
Proper preoperative management of patients at high risk for perioperative ARF includes the following steps:
- Identification of patients at high risk for ARF.
- Evaluation of intravascular volume status.
- Optimization of pre-existing medical conditions.
- 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 | | |
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 | | |
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.
- Maintain adequate oxygen delivery - by ensuring adequate cardiac output, adequate oxygen carrying capacity, and proper haemoglobin saturation.
- Suppression of renovascular constriction - by ensuring adequate volume preload, use of infusions of mannitol, calcium entry blockers, and angiotensin converting enzyme inhibitors (ACE inhibitors).
- Renal vasodilation- by dopaminergic agents, prostaglandins, and atrial natriuretic peptide (ANP).
- Maintain renal tubular flow - by loop diuretics and mannitol.
- Decrease oxygen demand - by use of loop diuretics and mild cooling.
- Attenuate ischaemic reperfusion injury - as a result of the release of oxygen free radicals and calcium ion.
| Therapeutic implications for the anaesthesiologist | | |
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 | | |
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) | | |
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 | | |
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) | | |
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 | | |
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 | | |
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) | | |
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 | | |
Mannitol
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
Dopamine 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
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 | | |
| Endothelin receptor antagonists (ET antagonists) | | |
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 | | |
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 | | |
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.
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[Table 1], [Table 2]
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