REVIEW ARTICLE – The anesthesiologists have a role in preventing perioperative renal failure
Rudin Domi*, Ilir Ohri*, Gjergj Andrea**, Hektor Sula*, Artur Hafizi***, Aurel Janko****, Bilbil Hoxha****, Haxhire Gani*, Herion Dredha****, Rezart Xhani****
*Department of Anesthesiology, **Department of General Surgery, ***Department of Morphology, ****Service of Urology,
University Hospital Center “Mother Teresa”, Tirana (Albania)
Correspondence: Rudin Domi MD, PhD, Anesthesiologist-Intensivist, Department of Anesthesia, Intensive Care, Emergency & Toxicology, University Hospital Center “Mother Teresa”, Tirana (Albania); Cell: 00355682067003; Email: firstname.lastname@example.org; email@example.com
Acute renal failure faced in perioperative period is associated with increased morbidity and mortality. It is of great import for anesthesiologists to understand the type of the surgery or the patients, in which a risk of precipitation of perioperative renal failure is increased. The risks for renal failure have been classified as surgery-related (e.g. vascular surgery) or patient-related (e.g. preexisting renal disorder, diabetes mellitus etc). A meticulous evaluation of perioperative risks, a careful intraoperative management, and finally realizing renal protection, can guarantee a better outcome. This review is intended to describe the risks of renal injury, the mechanisms of injury and suggest interventions to prevent perioperative renal failure.
Key Words: Perioperative acute renal failure; Acute Dialysis Quality Initiative
CITATION: Domi R, Ohri I, Andrea G, Sula H, Hafizi A, Janko A et al. The anesthesiologists have a role in preventing perioperative renal failure. Anaesth Pain & Intensive Care 2012;16(1):85-90.
EPIDEMIOLOGY, MORBIDITY & MORTALITY
Perioperative acute renal failure (PARF) faced on the course of surgery or ICU stay is often considered as a complication associated with increased morbidity and mortality. PARF accounts for 20–25% of cases of hospital-acquired renal failure 1. The incidence varies between 1 and 25% depending on the type of surgery and on the definition of renal failure. PARF can cause several disorders on the other organs or being part of the multiple organ failure syndrome, so increasing the mortality of up to 60% 1. The patients with PARF are often prone of high rates of infections, cardiac arrhythmias, need of mechanical ventilation, various types of renal replacement therapies, and prolonged hospital stay. Recently has been reported that only approximately 15% of the patients with PARF, can have a full recovery. Kheterpal et al2 recently reported that in a large national database 1% of all patients undergoing general surgery developed postoperative acute renal injury, increasing 3 times higher risk of postoperative morbidity and a fivefold increase in mortality. PARF occurring during cardiac surgery is often associated with 60 % mortality 3, 4.
The hallmarks of PARF are decreased glomerular filtration rate (GFR), decreased elimination of nitrogenous wastes, and inability to maintain hydro-electrolytic balance 5. Commonly used definitions of acute renal failure (ARF) include an increase in serum creatinine of _ 0.5 mg/dL over the baseline value, a reduction in the calculated creatinine clearance rate by 50%; or a decrease in renal function needing renal replacement therapies.
The Acute Dialysis Quality Initiative (ADQI) has classified PARF as a grading system 6 using the acronym RIFLE. This acronym is composed by three grades of increasing severity of illness (R, risk; I, injury; F, failure) and two outcome parameters (L, loss; E, end-stage), basing on the serum creatinine or urine output (Table 1).
Table 1: The RIFLE classification of renal failure
|Grade||Glomerular filtration rate||Urine output|
|Serum creatinine increase:
1.5-fold; GFR decrease: .25%
|0.5 ml/ kg/h for 6 h|
|Serum creatinine increase:
2-fold; GFR decrease: .50%
|0.5 ml/ kg/h for 12 h
|Serum creatinine increase:
3-fold; GFR decrease:
.75%; serum creatinine
decrease: .350 mmol litre21
(4 mg dl21) with acute
increase .44 mmol litre21
(0.5 mg dl21)
|0.3 ml/ kg/h for 24 h
or anuria for 12 h
|L, Loss||Persistent ARF¼complete loss of renal function for .4 weeks|
|E, End-stage||ESRD¼complete loss of renal function for .3 months|
Another recently used definition is acute kidney injury (AKI) 7. Table 2 summarizes three stages of AKI. Serum creatinine and urine output are not the ideal markers for AKI. Nowadays several new biomarkers of AKI include cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), and interleukin-18.
Table 2: AKI stages
|Stage||Serum creatinine||Urine output|
|1||Increased 1,5-2 fold from baseline||<0.5ml/kg/h for more than 6 h|
|2||Increased 2-3 fold from baseline||<0.5ml/kg/h for more than 12 h|
|3||Increased 4 fold from baseline, or
more than 4 mg.dl
|<0.3ml/kg/h for more than 24 h
or anuria for more than 12h
ETIOLOGY AND RISK FACTORS
PARF is multifactorial. Several situations, surgeries, or current patient’s diseases are risk factors to exacerbate PARF.
Cardiac surgery and renal failure
The incidence of PARF after cardiac surgery is estimated 1% -30% 8, with the mortality rates ranged from 28% to 63% 9, 10. The abnormal baseline creatinine, older patients, diabetes, prolonged cardiopulmonary bypass, peripherial systemic vascular diseases, and decreased ejection fraction, are generally considered as risk factors. Another study 11 has identified the cardiac catheterization performed within 5 days before operation, baseline glomerular filtration rate less than 60 mL/min, and prolonged cardiopulmonary bypass as risk factors for acute renal failure after cardiac surgery.
Vascular surgery and renal dysfunction
The rate of renal complications associated with thoracic aorta cross-clamping is estimated up to 50% and often presented as acute tubular necrosis 12. Ischemia-reperfusion injury is generally the pathogenesis mechanism.
Renal failure and sepsis
Sepsis is often complicated with renal failure, increasing mortality to 70 %, as compared with a 45 % mortality among patients with acute renal failure alone 13. Approximately 19 % of patients with moderate sepsis, 23 % with severe sepsis, and 51 % with septic shock are complicated with renal failure 14.
Liver failure/transplantation and renal dysfunction
Acute or chronic liver disease is often associated with renal failure. The mechanisms include hepatorenal syndrome, decreased systemic resistance, decreased perfusion pressure, infection induced hypotension15, 16.
Ortotopic liver transplantation (OLT) offers great challenges to the anesthesiologist. It is often with several degrees of renal dysfunction or failure. Renal dysfunction pre-OLT has been defined as a serum creatinine > 1.5 mg/dL, while PARF post-OLT has been defined as a requirement for renal replacement therapies or a doubling of serum creatinine 17, 18. Several predictive models are proposed. Several authors 19, 20 showed that an elevated pre-OLT serum creatinine or blood urea nitrogen predicted PARF requiring renal replacement therapies post-OLT.
Intrabdominal hypertension and kidney
Increased intrabdominal pressure can contribute to the development of perioperative renal failure. The abdominal compartment syndrome reduces significantly venous return, increases afterload, and decreased renal perfusion21. All the clinical situations (acute pancreatitis, abdominal trauma, mesenteric ischemia etc) that raise intrabdominal pressure can cause different grades renal dysfunction.
Nephrotoxic drugs induced renal failure
Drug toxicity is a rare complication. Aminoglycosides are well known to cause renal toxicity in 10-20% of the treated patients. The accumulation of aminoglycosides in proximal tubules may induce several intracellular processes as vacuolization, myeloid bodies, and loss of brush border. These processes damage tubular function. PARF usually develops 7- 10 days after the aminoglycosides administration. Their toxicity is usually potentiated by several situations like advance age, preexisting renal disease, sepsis, liver disease, hypovolemia, metabolic acidosis, and other drugs (loop diuretics, vancomycin, tacrolimus etc).
Non steroid antiinflamatory drugs are usually non toxic if single dose is used in healthy people. The toxicity induced by non steroid antiinflamatory drugs occur mainly when associated with other renal toxic drugs.
Radiocontrast dyes can also induce renal toxicity especially in the patients with preexisting dysfunction, hypovolemia, severe congestive heart failure, multiple myeloma, high contrast dose, and diabetes. PARF occurs mainly within 24-48 hours to intravenous contrast administration and usually recovered at 3-5 days 22.
Diabetes Mellitus and renal failure
Approximately 30% of insulin-dependent diabetics and 5-10% of non insulin-dependent diabetics may develop renal disease. Hyperglycemia forces the kidney to increase filtration process. This leads to leakage of proteins in the urine. This process is known as microalbuminuria. Within 5 years of microalbuminuria, the diabetic patient progress to renal failure. Hypertension, hyperglycemia, aging, cholesterol, and smoking are considered as risk factors for development of diabetic nephropathy23. Hypertension is the most important precipitating factor.
Table 3.summarizes the risk factors, classified as patients and surgery related, and different conditions.
Table 3: Risk factors of PARF
|Patients related||Surgery related||Different conditions|
|Old people||Vascular surgery||Sepsis|
|Diabetes mellitus||Aortic cross-clamping||Hypotension, bleeding|
|Female gender||Cardiac surgery||Jaundice|
|Chronic renal disorders||Cardiopulmonary bypass||Hypoxia|
|Systemic vascular diseases||Non-renal transplantation||Multi-organ failure|
|Advance liver disease||Emergency surgery||Rhabdomyolysis|
|Drug nephrotoxicity||Contrast administration||Intra-abdominal hypertension|
Ischemic or toxic acute tubular necrosis (ATN) is the predominant cause of PARF in hospitalized patients and in the ICU, respectively accounting for 38% and 76% of cases of ARF. Prerenal azotemia accounts for 70% of the community-acquired causes of ARF, and for 40% of hospital-acquired causes. Acute tubular necrosis is caused by toxic or ischemic mediated mechanisms. The epithelial apoptosis and necrosis, tubular obstruction, and transtubular leak of glomerular filtrate, are the possible mechanisms of tubular cell damage. Inflammatory responses induced by renal ischaemia–reperfusion injury also play a significant role in the development of ATN
The hemodynamic hallmark of sepsis 24 is generalized arterial vasodilatation with a decreased systemic vascular resistance (endotoxins, inflammatory response, and nitric oxide). Arterial underfilling activates the neurohumoral axis and an increase in cardiac output secondary to the decreased cardiac afterload. Activation of the sympathetic nervous system, the renin–angiotensin–aldosterone axis, vasopressin, and an increase in cardiac output are essential in maintaining normal hemodynamic but may lead to acute renal failure if exaggerated. It is well known that glomerular filtration is determined by the difference in arterial pressure between the afferent and efferent arterioles across. During sepsis PARF can be caused not only by hypotension, but by several other mechanisms. These mechanisms include intrarenal vasoconstriction (due to imbalance between vasodilatory and vasoconstrictory substances, results in a decline in renal blood flow), release of cytokines and oxygen radicals, and finally disorders of coagulation and fibrinolysis (causing intraglomerular thrombosis).
A great number of patients awaiting OLT may have reversible renal dysfunction due to renal hypoperfusion 25, 26. While awaiting OLT, patients often develop varying degrees of renal impairment, ranging from prerenal azotemia to hepatorenal syndrome and acute tubular necrosis. These changes, which are attributable to events and/or interventions such as large-volume paracentesis, diuretic therapy, sepsis, or gastrointestinal bleeding, Intraoperatively sharp hemodynamic changes often induce renal hypoperfusion. Bleeding, great vessel clamping, anhepatic phase, lactic acidosis, and finally need for vasopressors can explain the fragile intraoperative hemodynamic of these patients.
Radiocontrast dyes can induce renal toxicity by causing hyperosmolarity and renal cell damage. Non steroid antiiflamatory drugs impair the balance between intrarenal vasodilators and vasoconstrictors, so inducing intrarenal ischemia.
GENERAL PREVENTIVE MEASURES
General preventive measures include optimizing oxygen and blood supply, decreasing the demands, and minimizing the renal perioperative insult.
Optimizing oxygen and blood supply:
Optimizing oxygen and blood supply is realized by good control of hemodynamic, cardiac output, and oxygen delivery.
Maintaining euvolemia and renal perfusion is the hallmark of care 27. The negative effect of hypotension can also be potentiated or caused by volume depletion, dialysis, sepsis, cardiac dysfunction, anesthesia, mechanical ventilation, spinal induced vasodilatation, and excessive using of antihypertensive medications. Several studies 28 confirmed that the loss of autoregulation of renal blood flow usually occurs when the mean arterial pressure drops below of 75 to 80 mm Hg. Although it has been recommended that MAP should not be increased over 65 to 70 mm Hg, whereas maintaining a MAP of 65 mm Hg may be inadequate in order to prevent renal damage in elderly patients, or in patients suffering from diabetes 29. So it is of great importance to avoid both hypovolemia and overfilling the patient. There are several clinical parameters helping us to judge the adequacy of liquid therapy such as mean arterial pressure, capillary return, heart rate, urinary output, varialbility of pulse pressure. More invasive technique include pressure measurement in left atrium (Swan Ganz), PICCO, Vigileo, mix venous saturation etc.
The blood supply generally maintained by euvolemia and vasodilatation (if necessary) of afferent arterioles. Fenoldopam, natriuretic peptide, and dopamine can induce vasodilatation of afferent arterioles, increasing renal blood flow as well. Dopamine has a dose related effect. At lower dose (2 mcg/kg/min) it acts on dopamine-receptor increasing renal blood flow, glomerular filtration, and sodium excretion. Dopamine can increase urine output, but seems not efficient to prevent the perioperative renal damage 30. Another study 31 confirmed that dopamine did not decrease the rate of renal injury and hospital stay length. Fenoldopam acts on DA-1 receptors, inducing dilatation of renal vessels and maintaining the renal perfusion 32. Fenoldopam also increases urine output and natriuresis. Several studies 33-35 found fenoldopam a suitable agent to prevent renal failure during cardiovascular surgery and radio-contrast examination.
Atrial natriuretic peptide is secreted after the right atrium is dilated as a consequence of increased filling and pressure. Its mainly pharmacological actions are vasodilatation of afferent arterioles, vasoconstriction of efferent arterioles, increasing glomerular filtration rate, and increasing urine output. The studies36 failed to prove its efficacy in prevention of PARF.
Finally increasing hemoglobin level up to 10 g/dl is essential to prevent perioperative renal ischemia and PARF. Table 4 summarizes the physiological hemodynamic goals in order to prevent PARF.
Table 4: Hemodynamic goals to prevent PARF
|Cardiac Output||≥ 4,5 L/min|
|Pression of Wedge||≥15-≤18 mmHg|
|Central Venous Pressure||≥ 5 mmHg|
|Mean Arterial Pressure||≥ 70-≤ 100 mmHg|
|Delivery O2||≥ 500 ml/min/m2|
|Partial arterial pressure O2||≥ 60 mmHg, FiO2≤ 0,5|
Good sedation and aggressive treatment usually are effective measures in order to decrease the metabolic rate and demands. Loop diuretics and mannitol are both proposed for decreasing renal oxygen consume. Decreased renal oxygen consume make the renal cortex less fragile in the course of ischemia. Mannitol seems to have several pharmacologic properties like increasing renal blood flow and free radical scanvenger37, but its use for PARF prevention is not justified by large trials 37. Loop diuretics can reduce oxygen demands because of their effect on Na/K- ATP. It is well known that this pump in order to be fully functional consumes energy, so blocking the pump can reduce the energy consume and can save energy very useful to the ischemic kidney. Conflicting results are available from studies, but the non anuric patients can benefit more than those with anuria.37, 38
Minimizing perioperative renal insult:
Minimizing perioperative renal insult is realized by using new agents (free radical scanvenger) and avoiding drug induced nephrotoxicity. Superoxide dismutase, a free-radical scavenger, has been shown to preserve renal function39 in animal models of radiocontrast-induced nephropathy. N-acetylcysteine acts as an antioxidant and has been reported to prevent a reduction in renal function in patients with contrast agents’ nephrotoxicity40, 41. Nevertheless adequate hydration is a crucial step to prevent renal failure after contrast agent administration. Avoiding non steroidal antiiflamatory drugs, aminoglycosides, convertase inhibitors are effective measures to prevent PARF.
Perioperative renal failure is a major complication that can dramatically increase morbidity and mortality. Indentifying the patients on risk, current diseases, and surgical procedures that can induce PARF, are important steps to prevent this complication. Adequate hydration, maintaining good blood pressure, and avoiding nephrotoxic drugs can ameliorate the prognosis.
- Webb S, Allen S. Perioperative renal protection. Continuing Education in Anaesthesia, Critical Care & Pain 2008; 8(5): 176-180
- Kheterpal S, Tremper KK, Heung M, et al. Development and validation of an acute kidney injury risk index for patients undergoing general surgery: results from a national data set. Anesthesiology 2009; 110:505–15.
- Hoste EA, Cruz DN, Davenport A, et al. The epidemiology of cardiac surgery associated acute kidney injury. Int J Artif Organs 2008; 31:158–65.
- Shaw A, Swaminathan M, Stafford-Smith M. Cardiac surgery-associated acute kidney injury: putting together the pieces of the puzzle. Nephron Physiol 2008; 109: 55–60.
- Thadhani R, Pascual M, Bonventre J. Acute renal failure. N Engl J Med 1996; 334:1448–1460
- Bellomo R, Ronco C, Kellum JA, et al. Acute renal failure—definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 2004; 8: R204–R212
- Kellum JA. Acute kidney injury. Crit Care Med 2008; 36: S141–5
- Bove T, Calabro MG, Landoni G, et al. The incidence and risk of acute renal failure after cardiac surgery. J Cardiothorac Vasc Anesthe 2004; 18:442–5
- Chertow GM, Levy EM, Hammermeister KE, Grover F, Daley J. Independent association between acute renal failure and mortality following cardiac surgery. Am J Med 1998; 104:343–8
- Boldt J, Brenner T, Lehmann A, Suttner SW, Kumle B, Isgro F. Is kidney function altered by the duration of cardiopulmonary bypass? Ann Thorac Surg 2003; 75:906–12
- Del Duca D, Iqbal S, Rahme E, Goldberg P, de Varennes B. Renal Failure After Cardiac Surgery: Timing of Cardiac Catheterization and Other Perioperative Risk Factors Ann Thorac Surg 2007; 84:1264 –71
- Aronson S, Blumenthal R. Perioperative renal dysfunction and cardiovascular anesthesia: Concerns and controversies. J Cardio Vasc Anesth 1998; 12(5): 567-586
- Edelstein CL, Schrier RW. Pathophysiology of ischemic acute renal failure. In: Schrier RW, ed. Diseases of the kidney and urinary tract. 7th ed. Vol. 2. Philadelphia: Lippincott Williams & Wilkins, 2001:1041-69
- Riedemann NC, Guo RF, Ward PA. The enigma of sepsis. J Clin Invest 2003;112: 460-7
- Montoliu S, Balleste´ B, Planas R, et al. Incidence and prognosis of different types of functional renal failure in cirrhotic patients with ascites. Clin Gastroentero Hepatol 2010; 8:616–622
- Cardenas A, Gine P. Acute-on-chronic liver failure: the kidneys. Current Opinion in Critical Care 2011, 17:184–189
- Velidedeoglu E, Bloom RD, Crawford MD, Desai NM, Campos L, Abt PL, Markmann JW, Mange KC, Olthoff KM, Shaked A, et al: Early kidney dysfunction post liver transplantation predicts late chronic kidney disease. Transplantation 2004; 77(4):553-556
- Campbell MS, Kotlyar DS, Brensinger CM, Lewis JD, Shetty K, Bloom RD, Markmann JF, Olthoff KM, Shaked A, Reddy KR: Renal function after orthotopic liver transplantation is predicted by duration of pretransplantation creatinine elevation. Liver Transpl 2005; 11(9):1048-1055
- Contreras G, Garces G, Quartin AA, Cely C, LaGatta MA, Barreto GA, Roth D, Gomez E: An epidemiologic study of early renal replacement therapy after orthotopic liver transplantation. J Am Soc Nephrol 2002; 13(1):228-233
- Sanchez EQ, Gonwa TA, Levy MF, Goldstein RM, Mai ML, Hays SR, Melton LB, Saracino G, Klintmalm GB: Preoperative and perioperative predictors of the need for renal replacement therapy after orthotopic liver transplantation. Transplantation 2004; 78(7):1048-1054
- Walker J, Criddle LM. Pathophysiology and management of abdominal compartment syndrome. Am J Crit Care 2003; 12:367—371 Walker J, Criddle LM. Pathophysiology and management of abdominal compartment syndrome. Am J Crit Care 2003; 12:367—371
- Aspelin P, Aubry P, Fransson S et al. Nephrotocsic effects in high risk patients undergoing angiography. N Eng J Med 2003; 348: 491
- Ueda H, Ishimura E, Shoji T, Emoto M, Morioka T, Matsumoto N, Fukumoto Sh, Miki T, Masaaki Inaba M, Nishizawa Y, Factors Affecting Progression Of Renal Failure In Patients With Type 2 Diabetes. Diabetes Care , 200326:1530–1534
- Schrier R, Wei Wang W. Acute Renal Failure and Sepsis. N Engl J Med 2004; 351:159-69
- Aberg F, Koivusalo AM, Hockerstedt K, Isoniemi H: Renal dysfunction in liver transplant patients: comparing patients transplanted for liver tumor or acute or chronic disease. Transpl Int 2007; 20(7):591-599
- Marik PE, Wood K, Starzl TE: The course of type 1 hepato-renal syndrome post liver transplantation. Nephrol Dial Transplant 2006; 21(2):478-482
- Esson ML, Schrier RW. Diagnosis and treatment of ATN. Ann Intern Med 2002; 379:744–752
- Ronco C, Bellomo R. Prevention of acute renal failure in the critically ill. Nephron Clin Pract 2003; 93:C13–C20
- Lee RW, Di Giantomasso D, May C, et al. Vasoactive drugs and the kidney. Best Pract Res Clin Anaesthesiol 2004; 18:53–74
- Lassnigg A, Donnor E, Grubhofer G, et al. Lack of renoprotectiveeffects of dopamine and furosemide during cardiacsurgery. J Am Soc Nephrol 2000; 11:97–104
- Bellomo R, Chapman M, Finfer S, et al. Low dose dopamine in patients with early renal dysfunction: a placebo controlled randomized trial: Australian and New Zealand Intensive Society (ANZICS) Clinical Trials Group. Lancet 2000; 356:2139–2143
- Mathur VS, Swan SK, Lambrecht LJ, et al. The effects of fenoldopam, a selective dopamine receptor aginist, on systemic and renal hemodynamics in normotensive subjects. Crit Care Med 1999; 27:1832–1837
- Kini AS, Mitre CA, Kim M, et al. A protocol for prevention of radiocontrast nephropathy during percutaneous coronary intervention: effect of selective dopamine receptor agonist fenoldopam. Catheter Cardiovasc Interv 2002; 55:169–173
- Garwood S, Swamidass CP, Davis EA, et al. Case series of low dose fenoldopam in seventy cardiac surgical patients at increased risk of renal dysfunction. J Cardiothorac Vasc Anesth 2003; 17:17–21
- Gilbert TM, 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; 6:31–36
- Lewis J, Salem MM, Chertow GM, et al. ANP is oliguric ARD: Anaritide ARF Study Group. Am J Kidney Dis 2000; 36:767–774
- Venkataraman R, Kellum J. Prevention of Acute Renal Failure. Chest 2007; 131:300–308
- Uchino S, Doig GS, Bellomo R, et al. Diuretics and mortality in acute renal failure. Crit Care Med 2004; 32:1669–1677
- Bakris GL, Lass N, Gaber AO, et al. Radiocontrast mediuminduced declines in renal function: a role for oxygen free radicals. Am J Physiol 1990; 258:115–120
- Hoffmann U, Fischereder M, Kruger B, et al. The value of N-acetylcysteine in the prevention of radiocontrast agentinduced nephropathy seems questionable. J Am Soc Nephrol 2004; 15:407–410
- Pannu N, Manns B, Lee H, et al. Systematic review of the impact of N-acetylcysteine on contrast nephropathy. Kidney Int 2004; 65:1366–1374.