ACUTE RENAL INSUFFICIENCY IS A CHALLENGING PROBLEM AFTER CARDIAC SURGERY

LITHUANIAN UNIVERSITY OF HEALTH SCIENCE

MEDICAL ACADEMY FACULTY OF NURSING

DEPARTMENT OF NURSING AND CARE

DILSON DAVIS

ACUTE RENAL INSUFFICIENCY IS A CHALLENGING PROBLEM

AFTER CARDIAC SURGERY

The graduate thesis of the Master’s degree study program “Advanced Nursing Practice” (State Code 6211GX008)

Tutor of graduate thesis,

PhD MD, MildaŠvagždienė

TABLE OF CONTENTS

ABSTRACT...3

ABBREVATIONS ...6

INTRODUCTION ... 7

1. REVIEW OF LITERATURE ... 9

M

Pathologic changes in renal failure after cardiac surgery ... 11

Other events associated with CPB ... 15

Strategies to reduce the risk of renal failure ... 20

2. OBJECTIVES ... 26

3. ORGANISATION & METHODOLOGY ... 26

4. DISCUSSION OF RESULTS ... 27

5. CONCLUSION ... 37

6. PRACTICAL RECOMMENDATION ... 37

LIST OF SCIENTIFIC REPORTS PUBLICATIONS ... 41

LIST OF LITERATURE RESOURCES ... 42

ANNEXS… ... 46

DECLARATION OF THE AUTHOR’S CONTRIBUTION AND ACADEMIC

HONESTY

ABSTRACT

Dilson Davis. Acute renal insufficiency is a challenging problem after cardiac surgery. The graduate

Master’s thesis. The tutor - Dr. MildaŠvagždienėMD, Lithuanian University of Health

Sciences,Medical Academy, the Faculty of Nursing, Department of Nursing and Care. Kaunas, 2019. 48p.

Acute renal failure (ARF) refers to the abrupt loss of kidney function. There are many possible causes of acute renal failure categorized into three major areas prerenal, intrarenal, and postrenal. Acute kidney injury following major cardiovascular surgery has a complex and multifactorial etiology which includes pre-operative renal insufficiency, advanced age, history of congestive heart failure, diabetes mellitus, recent exposure to nephrotoxic agents such as contrast dye, intra-aortic balloon pump, emergency operation, prolonged cardiopulmonary bypass (CPB) time, low urinary output during CPB, and need for deep hypothermic circulatory arrest. The twentieth international consensus conference of acute disease quality initiative group found that acute kidney injury is a common perioperative complication for patients undergoing cardiovascular surgery. When renal failure after cardiac surgery is severe enough to require renal replacement therapy, the mortality rate is close to 60%. The successful prevention and management of acute kidney injury involves identifying patients at risk for acute kidney injury, recognizing subtle abnormalities in a timely manner, performing basic clinical assessments and responding appropriately to the data obtained.

OBJECTIVES OF THE PRESENT STUDY:

1.

2. To find the possibilities to reduce the risk of renal failure in the patient undergoing elective cardiac surgery

3. Prepare a plan for reducing the risk of renal insufficiency in the patient undergoing elective cardiac surgery.

MATERIALS AND METHODS:For this research, the literature search was conducted in the

PubMed, Medline updates from web sites, library data base, science direct and 30 literature sources where reviewed. Studies published in English between 2009–2019 have been reviewed.

RESULTS:56 years old white male patient arrived for elective cardiac surgery due to coronary artery

disease. He complains for shortness of breath during physical activity. He was scheduled to elective coronary artery bypass grafting surgery. The patient has history of chronic renal failure, chronic atrial fibrillation. Preoperative heart ultrasound – Showed moderately reduced systolic LV function, concentric LV hypertrophy, MV fibrocalcinosis, degenerative changes in leaflets, II-III degree MV regurgitation, II degree TV regurgitation. Max. pressure in RV about 46 mmHg, moderately pulmonary hypertension. Elective MV and TV reconstruction and coronary artery bypass grafting surgery was performed under standard anesthesia.

Duration of cardiopulmonary bypass (CPB) was 172 min. Ao cross-clamping time – 99 min.

After the surgery the patient was hemodynamicallystabel and recovery of normal muscle tone and consciousness the patient was safely extubated. Patient in sinus rhythm, breathing spontaneous oxygen via the face mask 10–8–6 l/min, diuresis > 50–100 ml/hour. During the night period blood gases showed respiratory acidosis due to increased pCO2 (up to 65 mmHg). Oxygen therapy was changed to oxygen via nasal cannulas 5–6 l/min.On the second postoperative day the patient added to his history the episodes of bronchospasms. During auscultation the wheeze was found and the treatment was supplemented by inhalations of salbutamol. Blood gases were returning to normal ranges, hypercapnia decreasing (48 mmHg), but there was still non lactic metabolic acidosis. Laboratory exams revealed the increase in serum creatinine (310 mol/l) and urea . Blood pressure remained within normal ranges, heart rate was sinus rhythm. Diuresis was adequate. The patient started to drink clear fluids. Infusion therapy was still continued with crystalloid solutions at the rate of 150 ml/hour. On the third postoperative day the condition of the patient was gradually improving. He started to eat solid food. He had mild respiratory failure, which was compensated by additional oxygen via nasal cannulas (6 l/min). The blood gases remained within normal limits. The patient remained haemodynamically stable, heart rate – normarythmic atrial fibrillation. As the patient had AF before the surgery, the recovery of sinus rhythm was ineffective. Though diuresis was still adequate serum levels of creatinine increased to 336mol/l. Metabolic non lactic acidosis was still persistent as well. In order to maintain diuresis infusion therapy with crystalloids was still continued at the rate of 100 ml/hour. On the fourth postoperative day serum creatinine levels started to decrease, ie 281mol/l, as well as

metabolic non lactic acidosis. And on the sixth postoperative day the patient was transferred to the Department of Cardiac surgery for further treatment.

SUMMARY: Medical management measures like diuretic therapy, crystalloid administration, constant

monitoring and early prompt management is essential to prevent renal insufficiency after cardiac surgery. A compassionate and knowledgeable and skilled nurse who cares for the patient after cardiac surgery is an asset in the achievement of positive outcome for the patient and family.

ABBREVIATIONS

ARF : Acute renal failure CPB : Cardio pulmonary bypass MV : Mitral valve

TV : Tricuspid valve RV : Right ventricle AO : Aorta

CVP :Central venous pressure RBC : Red blood cell corpuscles

ACEI :Angiotensin converting enzyme inhiitors CVS : Cardiovascular surgery

RCRI : Revised cardiac risk index

ASA : American society of anesthesiologists PACU : Post anesthesia care unit

NSAID : Non steroidalanti inflammatory drugs ARB : Angiotensin receptor blocker

GFR : Glomerular filtration rate

VO2 : Minute volume of oxygen consumption

ATP : Adenosine triphosphate ANP : Atrial natriuretic peptide DA : Dopamine agonist N-AC : N acetyl cysteine

INTRODUCTION

Cardiac surgery associated acute kidney injury is a common and serious postoperative complication of cardiac surgery requiring cardiopulmonary bypass and it is the second most common cause of acute kidney injury in intensive care unit[1]. Acute kidney injury following major cardiovascular surgery has a complex and multifactorial etiology which includes pre-operative renal insufficiency, advanced age, history of congestive heart failure, diabetes mellitus, recent exposure to nephrotoxic agents such as contrast dye, intra-aortic balloon pump, emergency operation, prolonged cardiopulmonary bypass (CPB) time, low urinary output during CPB, and need for deep hypothermic circulatory arrest[2].

Renal perfusion is complex and highly regulated. Although 20 % of cardiac output perfuses the kidneys, the majority of blood filtered by cortex glomeruli is shunted away from the vasa recta. This shunt may help maintain the electrolyte and water concentration gradients in the renal medulla required for tubule and collecting system reabsorption, but renders the renal medulla and corticomedullary junction hypoxic relative to other tissues this may be a protective mechanism for oxidative injury but increases susceptibility to ischemia. During surgery many factors alter renal perfusion, and tubules at the corticomedullary junction and in the medulla are often damaged. Hence acute renal insufficiency after cardiac surgery is a complex and frequent clinical problem[3].

The twentieth international consensus conference of acute disease quality initiative group found that acute kidney injury is a common perioperative complication for patients undergoing cardiovascular surgery [4].

The successful prevention and management of acute kidney injury involves identifying patients at risk for acute kidney injury, recognizing subtle abnormalities in a timely manner, performing basic clinical assessments and responding appropriately to the data obtained. Nurses are an important part of the health care team. A compassionate and knowledgeable and skilled nurse who cares for the patient after cardiac surgery is an asset in the achievement of positive outcome for the patient and family. With the advancement of technology there is a continuous change in the diagnostic and treatment modalities. The medical field is a dynamic field which goes under continuous research and application of those findings in providing care. Few studies are found on the nursing care of patients undergoing cardiac

surgery though cardiothoracic nursing is a very important aspectnow days. It reflects the need to investigate on the area of cardiovascular nursing to improve a patient’s outcome after cardiac surgery.

In this context the investigator would like to conduct a study to assess the main risk factors of renal insufficiency and a perioperative plan to reduce the risk of renal insufficiency in the patient undergoing elective cardiac surgery.

Definition of acute renal insufficiency: It is defined as the sudden loss of the ability of the kidneys to

excrete wastes, concentrates urine, conserve electrolytes and maintain fluid balance[5].

Cardiac surgery: cardiac surgery is any surgery done on the heart muscle, valves, arteries or the aorta

and other large arteries connected to the heart. In open heart surgery cardiopulmonary bypass machine or octopus is used to take over the function of heart during surgery[5].

1. REVIEW OF LITERATURE

MAIN

RISK FACTORS OF RENAL FAILURE AFTER CARDIAC

SURGERY

Investigator located studies from 2009-2019 and review articles from the Web of Science databases, PubMed, Google Scholar, Medline, the Cochrane Library, Embase, and Science Citation Index for articles written in English. RVarious perioperative risk factors for postoperative renal dysfunction and failure have been identified. The important preoperative factors are advanced age, anemia,history of congestive heart failure, emergency surgery, preoperative use of intra-aortic balloon pump, preoperative renal insufficiency, elevated preoperative serum glucose and creatinine and recent exposure to nephrotoxic agents such as contrast dye. Most important intraoperative risk factor is the intraoperative haemodynamic instability, prolonged cardiopulmonary bypassand need for deep hypothermic circulatory arrest. Causes of postoperative renal failure are low output syndrome, RBC transfusion and postoperative infection [6].

A retrospective study evaluated 1056 patients undergoing cardiac surgery and identified the major risk factors for renal failure were advanced age, postoperative use of ACEI, low left ventricular ejection fraction, multiple organ dysfunction syndrome , reexploration and low CVP [7].

Recently published data suggest that perioperative BP lability influences both the risk of postoperative renal dysfunction and 30-day mortality. Future studies will determine whether the use of agents that allow improved BP control within a desirable range will reduce the incidence of postoperative AKI in cardiac surgery patients [8].

Unusual from that impairment of renal function after cardiac surgery is uncommon without preoperative renal impairment [9].

Studies revealed that many common factors contribute to the development of CVS‐AKI. Hemodynamic perturbations such as exposure to cardiopulmonary bypass (CPB), cross‐clamping of the aorta, high doses of exogenous vasopressors, and blood‐product transfusion all increase the risk of AKI. Similarly, the mechanical factors outlined may be associated with renal perfusion injury following episodes of ischemia, resulting in increased oxidative stress and associated inflammation as well as embolic disease including cholesterol emboli, all of which increase the pathological burden on

the kidney. Other mechanisms such as neurohormonal activation are relevant, as is the generation of free hemoglobin and the liberation of free iron perioperatively, all potentiating AKI. Associated tissue damage is reflected in a systemic inflammatory response, and all these factors contribute to a significant inflammatory response. Immune activation, the generation of reactive oxygen species, and upregulation of proinflammatory transcription factors all play roles[10].

Traditionally, clinicians have referred to acute renal failure as a clinical situation that leads to a decline in renal function such that nitrogenous waste accumulates in the circulation and manifests as azotemia. changes in serum creatinine occur late in the development of AKI—typically 48 hours after the initiating event (surgery in the case of cardiac surgery-associated AKI). An earlier diagnosis would surely assist with treatment and, even in the absence of demonstrably effective therapies, would at least permit avoidance of dehydration, excessive diuretic prescription, and other nephrotoxic interventions.

Neutrophil Gelatinase-Associated LipocalinNGAL is a naturally occurring protein found in tissue and circulating in very low concentrations in the plasma. In cardiac surgery-associated AKI, it has been shown to be elevated very early after surgery (2 hours after cardiopulmonary bypass in some reports), and both urinary and plasma assays are available [13]. The tests are available for clinical use in Europe and will eventually also be available for use in North America. It is currently unclear which test provides the best diagnostic performance for AKI, but there is some suggestion that the combination of the two tests might be better than either alone. In general, urine is an attractive proximal fluid for kidney biomarker discovery and development, because tubular proteins leaking from damaged nephrons are concentrated, rather than diluted, as is the case in plasma. It is also probable that plasma NGAL is a closer reflection of systemic inflammation than the extent of renal injury inflicted [16]. It is certain that once introduced into clinical practice, observational studies of this novel test will define its role in our diagnostic armory more clearly. In the meantime, it has great potential for use in intervention trials as a way of enriching the study population for randomization of putative interventions.

Kidney Injury Molecule 1 (KIM-1) is a transmembrane protein present in the renal proximal tubule whose expression is markedly upregulated in response to acute ischemia or exposure to nephrotoxins. Although several reports from noncardiac surgical patient populations have shown that KIM-1 appears to be a very sensitive indicator of AKI [17], fewer cardiac surgery studies have been

published. In one study of 103 adult patients undergoing cardiopulmonary bypass, the KIM-1 levels were significantly increased at both 2 and 24 hours after surgery in patients who subsequently developed AKI [18]. In a recent review, KIM-1 was found to be a useful diagnostic assay for AKI after cardiac surgery but was less sensitive for predicting the need for dialysis or death [19].

Cystatin C is a ―housekeeping‖ protein that is produced continuously by all nucleated cells. Because it is freely filtered at the glomerulus, is completely reabsorbed by the proximal convoluted tubule, and is not secreted, it has qualities that make it suitable for measuring the glomerular filtration rate.Compared with serum creatinine, it is less affected by age, gender, and body weight. In one prospective study, cystatin C and NGAL were measured in both the plasma and urine of 72 adults undergoing cardiac surgery. Within the first 6 hours, neither of the plasma assays for cystatin C or NGAL were predictive of AKI; however, the urinary values of both were elevated, suggesting that at least for these two candidate biomarkers, the urinary testmight be superior to the plasma assay for the early detection of AKI.

It is reported that age, emergency and high risk surgery, ischemic heart disease, congestive heart disease, ASA physical status and RCRI score were considered risk factors for the development of AKI, in patients needing intensive care after surgery. AKI has serious impact on PACU length of stay and mortality. AKI was an independent risk factor for hospital mortality [11].

PATHOLOGIC CHANGES IN RENAL FAILURE AFTER CARDIAC

SURGERY

Clinically, the pathogenesis of ARF associated with CPB can be divided into preoperative, intraoperative, and postoperative events. The sum of all of these various insults is ultimately reflected in the development of tubular injury that when severe enough is manifested as a rise in serum creatinine often associated with a decreased urine output.

Patients have had recent myocardial infarctions or severe valvular disease with reduced left ventricular function and reduced renal perfusion. In the extreme, patients may be in cardiogenic shock and require inotropic support or an intra-aortic balloon pump. This pre-existing prerenal state may be exacerbated by the use of diuretics, nonsteroidal anti-inflammatory drugs (NSAID), angiotensin- converting enzyme inhibitors (ACEI), or angiotensin receptor blockers (ARB), which impair the autoregulation of renal blood flow. Furthermore, episodes of preoperative hypotension may lead to sublethal endothelial injury, which may impair the production of vasodilatory substances such as

endothelial nitric oxide and promote vasoconstriction as a result of the release of endothelin, catecholamines, and angiotensin II, promoting further tubular ischemia and injury [12]. Compounding these factors may be a lack of renal functional reserve as a result of underlying chronic kidney disease, including small- and large-vessel renovascular disease. These hemodynamic alterations in the preoperative setting may increase the vulnerability of the kidney (particularly the inner stripe of the outer medulla, where metabolic demands are high and the pO2 is between 10 and 20 mmHg) to any

further ischemic or nephrotoxic insult[13].

There may be activation of inflammatory mediators in the preoperative period that also serve to prime the kidney for subsequent injury. Endotoxin levels have been noted to be elevated in some patients in the preoperative period, despite no evidence of active infection, and these levels have been correlated to postoperative myocardial dysfunction. The elevation in preoperative endotoxin levels may reflect the effect of poor cardiac output states’ contributing to intestinal ischemia and bacterial translocation or may be related to the preoperative care of patients (e.g., subclinical catheter infections). Levels of TNF-α have also been shown to be elevated in patients with pre-existing congestive heart failure and may also play a role in stimulation of the immune system[14].

Nephrotoxic medications or intravenous contrast that is given in the immediate preoperative period may also lead to overt or occult tubular injury that can interact with other factors to lead to ARF. These medications include vasoactive (pressor) drugs, NSAID, ACEI, ARB, and antibiotics.

Thus, the preoperative period is a critical time when events (hemodynamic, nephrotoxic, and inflammatory) can occur and can lead to subtle renal injury that is not necessarily reflected by changes in GFR. This subtle injury is likely substantiated by the fact that the preoperative risk scoring systems all rely on factors that ultimately act to reduce renal perfusion, result in lack of renal functional reserve, or set up a proinflammatory milieu[15].

Intraoperative Events

The intraoperative period is a critical time when patients are exposed to anesthesia and cardiopulmonary bypass. These events lead to dramatic hemodynamic effects as well as activation of both innate and adaptive immune responses that can initiate or extend renal injury.

CPB is associated with significant hemodynamic changes, and the maintenance of cardiovascular stability during CPB requires interplay between the function of the CPB machine and patient factors such as systemic vascular resistance, venous compliance, and autoregulatory capacity of

various vascular beds. The ultimate goal is to maintain regional perfusion at a level that supports optimal cellular and organ function. Thus, any decrease in renal perfusion during CPB, depending on its magnitude and duration, can lead to significant cellular injury.

Minute oxygen consumption (VO2) is the major determinant of blood flow requirements

normally and during CPB. Experimentally, CPB flow rates have been determined by calculating VO2 at

different perfusion rates. Perfusion is increased until VO2 reaches a plateau, after which further

increases in CPB flow rates do not lead to increases in oxygen consumption. In general, CPB flow rates of 1.8 to 2.2 L/min per m2 are recommended on the basis of this analysis..

In addition to CPB flow rates, perfusion pressure during CPB is an important determinant of adequate nutrient delivery to vascular beds. Perfusion pressure is determined by the interaction of blood flow and overall arterial resistance. Resistance, in this case, is related to actual friction resistance because of the steady, nonpulsatile nature of CPB, which negates the elastance, inertial, and reflective components of arterial resistance during normal pulsatile flow . Friction resistance is primarily a function of vasomotor tone and blood viscosity (which is further dependent on hematocrit and

temperature). Importantly, both variables are changing during CPB (e.g., blood viscosity increases as hypothermia is induced and vasomotor tone is affected by anesthesia) and lead to associated changes in perfusion pressure. In general, a mean perfusion pressure of 50 to 70 mmHg is maintained during CPB Given hemodynamic goals of a mean perfusion pressure of 50 to 70 mmHg and CPB flow rates of 1.8 to 2.4 L/min per m2, it is not known what effect these goals have on renal perfusion and oxygen delivery. The majority of studies on autoregulation of regional blood flow during CPB has focused on the cerebral circulation and demonstrates preserved cerebral autoregulation with these parameters Small studies have suggested that mean arterial pressures on CPB >70 mmHg lead to higher

intraoperative creatinine clearances but without a change in postoperative renal function as compared with pressures between 50 and 60 mmHg. Thus, it is likely that renal perfusion and autoregulation are also maintained as long as these hemodynamic goals are met. However, these values are likely near the minimum blood flows that support normal organ function, and any perturbation may lead to ischemia and cellular damage. Furthermore, the effect of these parameters in patients with impaired baseline renal function is not known. In patients with pre-existing hypertension, the relationship between renal blood flow and mean arterial pressure is shifted such that falls in BP that normally would not impair renal perfusion now do so. This means that higher mean pressure may be required to maintain adequate renal perfusion in these patients.Furthermore, if there is any degree of pre-existing acute tubular

necrosis, then autoregulatory capacity of the kidney may be lost and renal blood flow becomes linearly dependent on pressure[16].

Whether alterations of these CPB flow and pressure goals would lead to improved renal outcomes is not known. Gold et al. reported that maintenance of higher perfusion pressures in the range of a mean perfusion pressure of 70 mmHg was associated with a reduced incidence of cardiac and neurologic complications when compared with patients whose pressures were maintained at 50 to 60 mmHg. Renal function was not assessed in this study.

Other procedural factors that likely have an impact on renal hemodynamics include hemodilution (oxygen delivery capacity), hypothermia (oxygen consumption), the absence of pulsatile perfusion, and the use of crystalloid versus colloidal prime solutions. As discussed above, with the exception of hemodilution, no deleterious effects on renal function have been found associated with alterations in body temperature or in the absence of pulsatile flow.

In total, these hemodynamic changes may lead to regional renal ischemia and cellular injury that could either initiate acute kidney injury (AKI) or extend pre-existing renal injury. Furthermore, these hemodynamic changes are potentially modifiable[17].

Inflammation

CPB provokes a systemic inflammatory response syndrome, Contact of blood components with the artificial surface of the bypass circuit, ischemia-reperfusion injury, endotoxemia, operative trauma, nonpulsatile blood flow, and pre-existing left ventricular dysfunction all are possible causes of SIRS in this setting. In its most severe form, a spectrum of injury that includes one or more of the following clinical manifestations may be observed: Pulmonary, renal, gastrointestinal, central nervous system, and myocardial dysfunction; coagulopathy; vasodilation and increased capillary permeability; hemolysis; pyrexia; and increased susceptibility to infection[18].

Open heart surgery, as do many surgeries, induces a generalized state of inflammation during and after surgery. Many heart surgeries require the use of a heart-lung machine, a machine that circulates blood while surgery is performed on the heart, which compounds the inflammatory response. Researchers at the Duke University Medical Center in a 2012 study reported evidence in an October 2012 "Heartwire" that this widespread inflammatory response can injure the kidneys, leading to kidney failure.

During CPB, both neutrophils and vascular endothelium are activated with upregulation of adhesion molecules such as CD11b and CD41. Platelets also undergo activation, degranulation, and

adherence to vascular endothelium. These events led to elaboration of cytotoxic oxygen-derived free radicals, proteases, cytokines and chemokines. These inflammatory mediators, such as IL-6, IL-8, and TNF-α, show a considerable rise in serum levels during CPB and generally reach peak levels 2 to 4 h after termination of CPB[19].

CPB is also a potent activator of factor XII (Hageman factor) to factor XIIa. This process initiates the intrinsic coagulation system, the kallikrein system, and the fibrinolytic system. Furthermore, complement proteins are activated through both the classical and the alternative pathways. Ultimately, this humoral response amplifies the cellular response that leads to neutrophil, endothelial, and monocyte activation and further elaboration of proinflammatory cytokines. Finally, diffuse end-organ ischemia likely causes endothelial cells, circulating monocytes, and tissue-fixed macrophages to release cytokines and oxygen-derived free radicals that further drive the inflammatory response[20].

The end result of this generalized inflammatory response induced by CPB within the kidney is not known. It is interesting that animal models of renal ischemia-reperfusion injury have clearly demonstrated the pathologic role of interstitial inflammation and the elaboration of proinflammatory cytokines and reactive oxygen species in the production of tubular injury. This local inflammatory response in experimental models is identical to that seen on a more global scale during CPB. Thus, it is likely a safe assumption that CPB-induced inflammation has significant deleterious effects on the kidney through similar mechanisms. Despite efforts to produce a CPB system that does not produce contact activation of blood components, this goal has not been realized and CPB still remains a potent proinflammatory stimulus [21].

OTHER EVENTS ASSOCIATED WITH CPB

Macroscopic and microscopic emboli, both gaseous and particulate, are often generated during CPB. These emboli are temporally related to certain intraoperative events such as aortic cannulation and aortic clamp placement and release. One study demonstrated a significant correlation between the total number of Doppler-detected emboli and postoperative changes in serum creatinine[22]. This suggests that embolic events to the renal circulation may be responsible in part for postoperative changes in GFR.

Hypotension, or decreased blood pressure, is often seen during and after open heart surgery. According to the Duke University Medical Center researchers, this decrease in blood pressure

decreases blood flow to the kidneys. Low kidney blood flow is a cause of acute renal failure and is one of the most common causes of kidney failure after open heart surgery.

Patients undergoing open heart surgery, particularly a CABG, there is diffuse plaque buildup of the major arteries including the aorta, the main artery supplying blood to the body. During surgery, pieces of plaque, called emboli, can break off and travel to various organs, decreasing blood flow. A John Hopkins University School of Medicine study published in the April 2013 issue of "Annals of Thoracic Surgery" demonstrated that 48 percent of plaque emboli during open heart surgery lodged in the kidneys. Such plaque emboli in the kidneys may lead to kidney failure and a need for dialysis.

Aprotinin is a serine protease inhibitor and potent antifibrinolytic agent that is used to attenuate blood loss and transfusion requirements during CPB. Aprotinin is eliminated by glomerular filtration and is actively reabsorbed by the proximal tubules, where it is metabolized .Aprotinin also inhibits the production of renal kallikreins and kinins involved in vasodilatoryresponses.For these reasons, there has been concern that the use of aprotinin may lead to renal injury. Several studies in patients who underwent CPB, as well as liver transplantation, did not demonstrate any renal toxicity directly attributable to aprotinin use[23].

CPB exposes blood to nonphysiologic surfaces and shear forces that lead to lysis of red blood cells with release of free hemoglobin into the circulation. In the presence of oxidants such as hydrogen peroxide and superoxide, free low molecular mass iron is released from the hemeinto the circulation. This redox active iron is able to participate in organic and inorganic oxygen radical reactions, such as stimulating lipid peroxidation and catalyzing the formation of damaging hydroxyl radicals with subsequent tissue damage. Normally, iron-transporting proteins such as transferrin and lactoferrin sequester this free iron and minimize its potential toxicity. In contradiction the release of free iron can be so great as to saturate the iron-binding capacity of transferrin. At this point, all iron-binding antioxidant capacity is lost and the serum displays pro-oxidant feature. Reperfusion injury during CPB may exacerbate further the oxidant stress in the setting of free circulating iron[24].

Tuttle et al. could not find an association between low iron-binding capacity and the risk for ARF after CPB. Although deferoxamine has been demonstrated to decrease the occurrence of lipid peroxidation during CPB, no studies have investigated any protective role of iron chelation in human kidney injury.

Postoperative Events

The postoperative events that are critical in affecting renal function are similar to traditional causative mechanisms seen in the general intensive care setting. Thus, the use of vasoactive agents,

hemodynamic instability, exposure to nephrotoxic medications, volume depletion, and sepsis/SIRS all are critical events that can lead to kidney injury. A critical factor is postoperative cardiac performance and the need for either inotropic or mechanical support. In the presence of postoperative left ventricular dysfunction, the risk for significant renal injury becomes very high as the vulnerable kidney is subjected to marginal perfusion pressures[25].

The pathologic changes in the kidney of patients with ARF following OPCAB are largely assumed to be due to acute tubular necrosis which is usually confirmed by granular casts in the urine. Hypoxia- ischemia is the predominant cause of perioperative ARF and results from low renal blood flow due to a reduced cardiac output; from regional factors reducing renal blood flow; or from disturbances ofintrarenal blood flow related to inflammation, sepsis or toxin. It was demonstrated that the transmembrane gradient for glomemlarultrafiltration was significantly diminished and there is a back- leak of glornerularultrafiltrate across the injured epithelium. ARF begins with an early phase of vasomotornephropathy in which there is associated alterations in vasoreactivity and renal perfusion leading to prerenalazotaemia and eventually cellular ATP depletion26_{. These ultimately lead to}

mitochondrial dysfunction and accumulation of intracellular sodium, calcium and reactive oxygen species. Subsequently, multiple enzyme systems are activated and cause disruption of the cytoskeleton, membrane damage, nucleic acid degradation and cell death. Vascular endothelial cell injury induces vascular congestion, edema and infiltration of inflammatory cells. Furthermore, elaborations of inflam- matory mediators lead to additional cellular injury.

An important cause of AKI in cardiac surgery is cellular ischemia, which results in tubular epithelial and vascular endothelial injury and activation. Cardiac surgery heightens the risk of ischemic kidney injury by several processes. Normally, kidney perfusion is autoregulated such that glomerular filtration rate is maintained until the mean arterial blood pressure falls below 80 mm Hg. Mean arterial blood pressure during cardiac surgery is often at the lower limits or below the limits of autoregulation, especially during periods of hemodynamic instability. In addition, many cardiac surgery patients have impaired autoregulation due to existing comorbidities (eg, advanced age, atherosclerosis, chronic hypertension, or chronic kidney disease), administration of drugs that impact kidney autoregulation (eg, nonsteroidalantiinflammatory drugs, ACE inhibitors, angiotensin receptor blockers, and radiocontrast agents), or a proinflammatory state (see below). In patients with impaired autoregulation, kidney function may deteriorate even when the mean arterial blood pressure is within the normal range.

Another process by which cardiac surgery may contribute to ischemic kidney injury is by inciting a strong systemic inflammatory response. Proinflammatory events during cardiac surgery include operative trauma, contact of the blood components with the artificial surface of the CPB circuit, ischemia-reperfusion injury, and endotoxemia Inflammation plays a central role in the development of ischemic kidney injury, and it is thought that the systemic inflammatory response caused by cardiac surgery is similarly deleterious.

Perioperative anemia in cardiac surgery is independently associated with various adverse outcomes, including kidney injury. Anemia may contribute to kidney injury by reducing renal oxygen delivery, worsening oxidative stress, and impairing hemostasis.

Studies suggest that Intraoperative avoidance of the extremes of anaemia, especially during severe hypotension and avoidance of transfusion in patients with haemoglobin levels >8 g/dL (>5 mmol/L) may help decrease AKI in patients undergoing cardiac surgery and represent targets for future controlled interventions [27].

All patients in both groups received similar standardized anaesthesia management with use of propofol (1-2.5 mg/kg), remifentanil (1 mg/kg) bolus and infusion (0.4 μg/kg), and inhalational agents during CPB.Mild or modarate hypothermia (240-340) was used in all cases. Prime solution was contained 1100cc ringer lactate, 300cc mannitol, 100 mg unfractioned heparin, 250 mg methylprednisolone.Non-pulsatile perfusion techniques were used and flow rates of perfusion were1.8, 2.0, 2.2 and 2.4 L/m2/min at 240C, 300C, 340C and 370C, respectively. Crystalloid and blood cardiolegia were used for cardiac arrest. Dialysis administration criteria during CPB were based upon the institutional protocol and experience including excessive fluid volume overload (central venous pressure > 15 cmH2O), oliguria (urine output < 20 mL at the first hour of CPB), hyperkalemia (blood potassium level > 5.5 meq/L) and prolonged CPB time (> 180 min).

Tissue oxygen delivery is directly related to arterial oxygen content, which is primarily dependent on the hemoglobin concentration. Anemia would therefore decrease oxygen delivery to the kidneys, especially to the vulnerable renal medulla, where the normal partial pressure of oxygen in the renal tissue is very low. The adverse consequences of anemia are likely enhanced further during cardiac surgery, during which, for reasons outlined earlier, the kidney is more prone to renal hypoperfusion.

During CPB, hemodilution is induced to decrease blood viscosity in the hope of improving regional blood flow in the setting of hypoperfusion and hypothermia as well as limiting the need for blood

transfusion. The resulting increase in regional blood flow is thought to offset any risk of decreased oxygen carrying capacity of the blood. However, two recent studies demonstrated that hemodilution (down to hematocrits <25%) is associated with an increased risk for renal injury as measured by changes in serum creatinine. This may be due to impairment of oxygen delivery to an already hypoxic renal medulla or to alterations in systemic inflammatory mediators caused by regional ischemia.

Anemia may enhance renal oxidative stress, because RBCs serve important antioxidant functions. Anemia impairs hemostasis because normal platelet function is dependent on the presence of an adequate (but as yet undetermined) hemoglobin concentration. In cardiac surgery, during which patients are already at increased risk for bleeding due to CPB-related hemostatic defects, the added burden of anemia-induced platelet dysfunction may lead to excessive bleeding, which in turn may necessitate multiple RBC transfusions and reexploration, both of which are associated with AKI.

RBC transfusion is to improve organ function by increasing tissue oxygen delivery, there is increasing evidence that transfused RBCs may actually contribute to organ injury in susceptible patients, likely because of changes that occur to RBCs during storage. During storage, RBCs become less deformable, undergo ATP and 2,3-diphosphoglycerate depletion, lose their ability to generate nitric oxide, have increased adhesiveness to vascular endothelium, release procoagulant phospholipids, and accumulate proinflammatory molecules, as well as free iron and hemoglobin. As a result, transfused stored RBCs may impair tissue oxygen delivery, promote a proinflammatory state, exacerbate tissue oxidative stress, and activate leukocytes and the coagulation cascade. In susceptible patients, such as those undergoing cardiac surgery, these changes can lead to organ dysfunction, with the kidney seemingly at particularly high risk for injury[28].

Surgical reexploration after cardiac surgery is independently associated with various adverse outcomes, including kidney injury. Although the mechanisms by which reexploration can cause kidney injury have not been fully elucidated, it is likely a safe assumption that they involve exacerbation of many of the factors outlined above, such as hemodynamic instability and operative trauma. Surgical reexploration is also inextricably linked to both anemia and RBC transfusion, because the principal reason for reexploration after cardiac surgery is coagulopathy (which is exacerbated by anemia), which leads to excessive blood loss (and massive RBC transfusion).

It is evident that therapies aimed at mitigating preoperative anemia, perioperative red blood cell transfusions, and surgical reexploration may offer protection against acute kidney injury[28].

Strategies to reduce the risk of renal failure in the patient undergoing elective

cardiac surgery

Variety pharmacological and non-pharmacological strategies be used to prevent AKI in patients undergoing cardiac surgery.

PharmacologicInterventions

Prevention of postoperative renal dysfunction after OPCAB needs knowledge of identifyingthe preoperative risk factors.The aim is to select patients who are at risk and then to adopt strategies that would offer renal protection. Medications such as nonsteroidalantiinflammatory drugs (NSAIDs) and other nephrotoxic agents should be discontinued.

Several studies demonstrate that withholding angiotensin‐converting enzyme inhibitors and angiotensin receptor blockers in the preoperative period is associated with reduced incidence of AKI. Correction of hypoalbuminemia (level of <4 g/dL) by exogenous albumin supplementation has been shown to be renoprotective in off‐pump cardiac surgery.In contradiction it is reported that Early postoperative use of ACEI/ARB or diuretics is associated with a lower incidence of AKI after cardiac surgery with extracorporeal circulation in elderly patients[28].

Preventing significant hemodynarnic events which may insult the kidney and meticulous postoperative care including optimizing ventricular function, aggressive control of serum glucose and close monitoring of fluid and renal status, perioperative hydration and use ofhemodynamic monitoring and inotropic is agents to optimize cardiac output are of important strategies.

Several drugs have been tried in attempting to reduce postoperative renal dysfunction with inconsistent results. Loop diuretics increase renal cortical blood flow. Dopamine at low doses certainly interacts with vascular dopaminergic receptors and stimulates diuresis and natriuresis. Fenoldopam, a selective Dl receptor antagonist, has used in the prevention of contrast-induced nephropathy

Atria Natriuretic Peptide (ANP) increases natriuresis by increasing GFR as well as by inhibiting sodium reabsorption by the medullary collecting duct.

N-acetylcysteine (NAC) has been shown to block oxidant stress on cardiac surgery patients and may hold promise as aprotective measure. Although it has been used in the prevention of contrast- induced nephropathy

The calcium channel blocker diltiazem has been evaluated as a renoprotective agent in cardiac surgery due to its renal vasodialatory effects. Hyperglycemia is common in cardiac surgery and increased serum glucose in pre orintraoperative period is independently known to cause ARF after cardiac surgery. So it is important to control blood glucose levels.

Glycemic Control With Intravenous Insulin is essentialReabsorption of tubular glucose is an active, energy-consuming process; thus, it is thought that reducing the metabolic burden in the tubules by reducing the concentration of urinary glucose might preferentially affect intrarenal oxygen flux. A randomized study of 1548 critically ill patients (63% of whom had undergone cardiac surgery) found a lower incidence of renal replacement therapy and improved survival with intensive (target glucose 80– 110 mg/dL) compared with conventional (target 180–200 mg/dL) glycemic control [37].However, a large clinical trial in Australia and New Zealand subsequently questioned the benefit of tight glycemic control, suggesting no benefit compared with a less-aggressive glucose target.

Urinary Alkalinization has been suggested that cardiac surgery-associated AKI is in large part a pigment nephropathy. Cold, nonpulsatile, extracorporeal circulation with passage through suction catheters, oxygenators, bubble traps, and filters is certainly a good recipe for hemolysis, and pink urine in the bladder catheter bag is indeed a familiar sight. Haase and colleagues conducted a preliminary trial of urinary alkalinization in cardiac surgery patients at high risk of AKI and showed that in patients randomized to a tonically equivalent dose of sodium bicarbonate (compared with sodium chloride), the incidence of AKI was less in the bicarbonate group. The urine of the bicarbonate patients was effectively alkalinized, which might have enhanced urinary excretion of free filtered hemoglobin. However, it is also possible that avoiding a chloride load also has beneficial effects on the kidney. A large follow-up trial is currently underway, the results of which are eagerly awaited.

Renal Replacement TherapyRRT is generally a nephrologic business; however, in the rest of the world, continuous RRT (eg, hemofiltration) is largely an intensive care unit treatment. This disconnect has resulted because of nonclinical issues and represents an unfortunate development. Extracorporeal therapywill attract an ever increasing presence in the modern intensive care unit, as the extracorporeal

philosophy leans more toward earlier, partial organ assist rather than later organ function replacement. As such, all those involved in intensive care management will require a working knowledge of partial cardiac assist, partial lung assist, partial liver assist, and partial kidney assist techniques. Although continuous venovenous hemofiltration is a physiologically simple concept (it is just like a glomerulus), it is important to consider the potential downside (ie, catheter placement complications, infection, bleeding, metabolic disturbance, fluid shifts) before its initiation.However, it is important that this technique becomes available to the wider intensive care unit community, just as ultrasonography has in recent years. In surgical practice, especially, understanding of the benefits of a zero-weight gain approach for perioperative medicine is increasing, and cardiac surgeons are well placed to lead the trend toward the earlier use of continuous venovenous hemofiltration in their volume-overloaded patients.

Research studies shows that elderly patients (above age 65) with underlying CKD preoperatively may never regain kidney function following AKI and may require lifetime renal replacement therapy. Identifying at-risk individuals and proactive early intervention to optimize outcomes is extremely important. If AKI develops, proper daily modification of medication dosing and avoidance of potentially nephrotoxic agents is mandatory. Likewise, restoration of hemodynamics using inotropic and vasopressor agents as well as intra-aortic balloon when indicated should help minimize the extent of AKI. Cautious volume replacement or the use of loop diuretics can be used depending on the clinical setting. Early termination of ventilator support as well as sepsis prevention (i.e., removing unnecessary lines, aggressive wound care) can favorably impact the course of AKI. Proper nutrition to promote tissue repair and to secure immune competence is also an important part of the overall treatment. Finally, timely initiation of HD or CVVHD to simultaneously correct fluid overload and metabolic disarray should be initiated to prevent and manage acute kidney injury[14].

New pharmacologic agents currently under investigation include levosimendan, a novel calcium sensitizer, with inotropic and vasodilatory effects that may offer protective effects in endotoxemic and ischemia-reperfusion injury and ABT-719, a novel α-melanocyte-stimulating hormone analog (α- MSH). A recent meta-analysis of 13 randomized trials involving 1345 patients undergoing cardiac surgery noted that perioperative infusion of levosimendan reduced the incidence of AKI, RRT, length of intensive care unit stay, and death. Alpha-MSH is an endogenous hormone that inhibits inflammatory, cytotoxic, and apoptotic pathways, hence prevents renal injury caused by ischemia-

reperfusion-induced AKI. In addition, α-MSH has direct protective effects on the kidney, which may result from stimulation of the melanocortin receptors in the outer renal medulla.

Non- pharmacological strategies Perioperative.

Again, results in this area are contradictory. Intravenous contrast before surgery may increase the incidence of AKI and has led to some recommendations for delaying surgery 24 to 72 hours after contrast administration. Preoperative placement of an intra‐aortic balloon pump may prevent AKI and reduce the incidence of RRT in high‐risk patients by improving perfusion and reducing endothelial activation. Contrast media used for coronary angiography may result in a contrast-induced nephropathy. It has been hypothesized that cardiac surgery in close succession to coronary angiography may increase the risk of postoperative AKI. However, data from the existing literature are conflicting. Acute kidney injury after cardiac surgery is a multifactorial event; surgery on the same day of angiography significantly increases the risk of AKI, and limiting this practice results in a containment of the postoperative AKI incidence[29].

Several studies suggest that cardiac surgery can be performed within 1 day of cardiovascular catheterization and contrast administration without an increase in the incidence of postoperative AKI. Recommendations to delay cardiac surgery for a specified period after contrast administration to reduce the risk of postoperative AKI are premature[29].

Intraoperative.

Catheter manipulation in the thoracic and abdominal aorta may lead to renal artery embolization, with aortic cross‐clamping proximal to the renal arteries associated with ischemia– reperfusion injury, further aggravated by atheroemboli secondary to aortic manipulation. Aortic clamping above bilateral renal arteries, adjunctive renal artery procedures, and left renal vein division have been found to increase the incidence of AKI. Emboli protection devices may help preserve renal function and prevent procedure‐related atheroembolism during endovascular renal interventions. Transradial coronary angiography avoids catheter manipulation in the descending and abdominal aorta, which, compounded by reduced bleeding, leads to less AKI than transfemoral angiography. Avoidance of aortic manipulation (the ―no touch‖ technique) in OPCAB has been shown to decrease the risk of postoperative stroke in several studies; however, its effect on AKI incidence remains controversial, with some studies demonstrating lower incidence, but others failing to do so.

CSA-AKI patients had significantly longer aortic cross-clamp and cardiopulmonary bypass times. Furthermore, CSA-AKI patients had higher hospital mortality (5.5% vs 1.5%, P<.001) and significantly longer ICU and hospital stays. Independent risk factors for CSA-AKI were age, peripheral vascular disease, hypertension, left ventricular ejection fraction, cardiopulmonary bypass time, and surgery on the thoracic aorta. In conclusion, patients who develop CSA-AKI have a higher preoperative risk profile, more complex surgery, and worse clinical outcomes[15].

One study of patients who underwent cardiac surgery found that more severe AKI was associated with an increased risk of progression of chronic kidney disease stage. Studies in various clinical settings found that patients with relatively small short-term changes in serum creatinine (s-Cr) levels had up to a 4-fold increase in the long-term risk of ESRD.

In a recently published randomized, controlled trial, the risk of AKI and loss of renal function was investigated after off-pump versus on-pump CABG. The authors found that off-pump surgery reduced the risk of postoperative AKI but not loss of renal function at 1 year after surgery. In summary, studies of various cohorts found an increased risk of ESRD in patients with AKI. To the best of our knowledge, no previously reported studies investigated the relationship between AKI after CABG and the risk of ESRD. This study used a large nationwide cohort of patients who underwent primary isolated CABG to investigate the long-term risk of ESRD in patients who developed postoperative AKI[17].

Moderate hypothermic circulatory arrest with antegrade cerebral perfusion during complex aortic surgery has been embraced by an increasing number of surgical groups, with data suggesting that this is not associated with an increased AKI risk. Conversely, hyperthermic perfusion during CPB, defined as a cumulative time at >37°C, is associated with an increase in AKI incidence. In a study achieving clinical equipoise through propensity score matching, duration of hyperthermic perfusion was independently associated with severity of AKI, with a 51% increase in the incidence for every 10 minutes of hyperthermic perfusion. Cold renal perfusion has been suggested for pararenal abdominal aorta aneurysm surgery to reduce the incidence of AKI associated with juxtarenal and thoracoabdominal aortic operations.

Pulsatile perfusion provides surplus mechanical energy transmission to the vascular endothelium. Its impact on clinical outcomes has been extensively studied in a variety of settings; however, the data on renal outcomes are conflicting because of the lack of uniformity in pulsatility

delivery. A retrospective analysis showed pulsatile CPB conferred a renoprotective effect in higher risk patients undergoing cardiac surgery. However, the contemporary use of implantable continuous‐flow left ventricular assist devices challenges this concept. The improvement in the hemodynamic environment provided by continuous‐flow left ventricular assist devices leads to better renal function in heart failure patients, implying that the theoretical importance of pulsatility is superseded by increased cardiac output.

Hemodilution during CPB is an independent risk factor for AKI in adult cardiac surgery, with improved outcomes for cases in which significant hemodilution (hematocrit <24%) is avoided during CPB Although lower hemoglobin (8.8 versus 13.1 g/dL) preoperatively and on arrival to the intensive care unit has been associated with persistent AKI after cardiac surgery, transfusion of at least 2 U of packed red blood cells has also been associated with higher incidence of CVS‐AKI. In 2 recent RCTs in which patients were randomized to a liberal (Hg <9.5 g/dL) or restrictive (Hg <7.5 g/dL) transfusion policy intraoperatively and postoperatively, there was no difference in postoperative outcomes including AKI. Conventional ultrafiltration has been used to treat the hemodilutional effects of CPB circuits. The risk of developing severe AKI depended on the type of cardiac surgical procedure. Thirty- day mortality was associated with severe perioperative circulation impairment or bleeding, but overall long-term mortality was additionally predicted by age, postoperative myocardial infarct, and preoperative circulation status [15].

Postoperative.

Implementation of a ―KDIGO bundle of care‖—consisting of avoidance of nephrotoxic agents, discontinuation of angiotensin‐converting enzyme inhibitors and angiotensin receptor blockers for the first 48 hours after surgery, close monitoring of renal function, avoidance of hyperglycemia for the first 72 hours after surgery, consideration of alternatives to radiocontrast agents, and close hemodynamic monitoring using a prespecified algorithm—prevented CVS‐AKI in high‐risk patients defined as biomarker positive. According KDIGO acute kidney injury is the presence of increase in serum creatinine 0.3 mg/dL or more within 48 hours or increase in serum creatinine to 1.5 times or more than base line data or urine volume less than 0.5 ml/kg/h for at least 6 hours[29].

Recent literature offers hope that understanding of the pathogenesis of AKI after cardiac surgery continues to improve, new directions for the prevention and amelioration of AKI will emerge. Approaches to the prevention of postoperative AKI include careful risk stratification of patients,

allowing adequate recovery following a prior AKI, consideration of less extensive surgical procedures, avoidance of cardiopulmonary bypass, minimizing injury from radiocontrast dyes or other nephrotoxic agents, and optimizing cardiovascular function and oxygen delivery. Early identification of AKI and prompt, judicious application of RRT may also improve outcomes. Interest in pharmacologic renoprotection is currently directed toward statins and sodium bicarbonate[30].

2. OBJECTIVES OF THE PRESENT STUDY :

1. To find the main risk factors of renal failure after cardiac surgery

2. To find the possibilities to reduce the risk of renal failure in the patient undergoing elective cardiac surgery

3. Prepare a plan for reducing the risk of renal insufficiency in the patient undergoing elective cardiac surgery.

3. ORGANISATION AND METHODOLOGY OF A RESEARCH

Qualitative research approach and case study method is used

56 years old white male patient arrived for elective cardiac surgery due to coronary artery disease. He complains for shortness of breath during physical activity. He was scheduled to elective coronary artery bypass grafting surgery. The patient has history of chronic renal failure, chronic atrial fibrillation.

Preoperative heart ultrasound – Showed moderately reduced systolic LV function, concentric LV hypertrophy, MV fibrocalcinosis, degenerative changes in leaflets, II-III degree MV regurgitation, II degree TV regurgitation. Max. pressure in RV about 46 mmHg, moderately pulmonary hypertension.

Elective MV and TV reconstruction and coronary artery bypass grafting surgery was performed under standard anesthesia.

Duration of cardiopulmonary bypass (CPB) was 172 min. Ao cross-clamping time – 99 min. After the surgery the patient was hemodynamicallystable and recovery of normal muscle tone and consciousness the patient was safely extubated. Patient in sinus rhythm, breathing spontaneous oxygen via the face mask 10–8–6 l/min, diuresis > 50–100 ml/hour. During the night period blood gases showed respiratory acidosis due to increased pCO2 (up to 65 mmHg). Oxygen therapy was changed to oxygen via nasal cannulas 5–6 l/min.

On the second postoperative day the patient added to his history the episodes of bronchospasms. During auscultation the wheeze was found and the treatment was supplemented by inhalations of salbutamol. Blood gases were returning to normal ranges, hypercapnia decreasing (48 mmHg), but there was still non lactic metabolic acidosis. Laboratory exams revealed the increase in serum creatinine (310 mol/l) and urea. Blood pressure remained within normal ranges, heart rate was sinus rhythm. Diuresis was adequate. The patient started to drink clear fluids. Infusion therapy was still continued with crystalloid solutions at the rate of 150 ml/hour.

On the third postoperative day the condition of the patient was gradually improving. He started to eat solid food. He had mild respiratory failure, which was compensated by additional oxygen via nasal cannulas (6 l/min). The blood gases remained within normal limits. The patient remained haemodynamically stable, heart rate – normarythmic atrial fibrillation. As the patient had AF before the surgery, the recovery of sinus rhythm was ineffective. Though diuresis was still adequate serum levels of creatinine increased to 336mol/l. Metabolic non lactic acidosis was still persistent as well. In order to maintain diuresis infusion therapy with crystalloids was still continued at the rate of 100 ml/hour[31].

On the fourth postoperative day serum creatinine levels started to decrease, ie 281mol/l, as well as metabolic non lactic acidosis. And on the sixth postoperative day the patient was transferred to the Department of Cardiac surgery for further treatment.

4. DISCUSSION OF THE RESULTS

Elective cardiac surgery is highly effective in reducing complications after cardiac surgery especially in patients with advanced age and other co-morbidities. Acute renal insufficiency is a challenging problem after cardiac surgery. Investigator report a case of patient arrived for elective cardiac surgery due to coronary artery disease and also the patient has history of chronic renal failure and diabetes mellitus. Thus it aids in high risk for surgery and prone to develop renal insufficiency after cardiac surgery[31].

In patients who undergo cardiac surgery, identifying patients who are at high risk for ARF is critically important. The risk of developing myocardial ischaemia and infarction has been shown to be 16 to 19 fold more in patients with renal failure than in patients without renal failure. Many clinicians are reluctant to do coronary artery bypass grafting (CABG) in patients of CAD with CRF despite favourable surgical results in several studies. Patients with CRF on chronic haemodialysis have several physiologic abnormalities and pose a number of problems during and after cardiopulmonary bypass

(CPB) that could contribute to adverse operative outcome. These patients need special attention during and after CPB for the ongoing problems in the balance of fluid and electrolytes, the maintenance of adequate red cell mass, peri-operative bleeding diathesis and the timing and route of pre- and post- operative dialysis[32].

The author present the successful management of a case of coronary artery disease with chronic renal failure and diabetes mellitus underwent cardiac surgery. CPB procedure causes tremendous fluid shifts in the different compartments of the body. In the absence of renal function, the ability of a patient to tolerate CPB is markedly reduced. Thus patients with CRF undergoing CABG pose problems in the management of fluid and electrolytes during and after CPB procedures.

Patients with CRF undergoing CPB have risk of developing intraoperative ischaemicviscus associated with low flow state during CPB which may be exacerbated by atherosclerotic mesenteric arteries in these patients (15). To avoid such complications in the case presented had a duration of cardiopulmonary bypass (CPB) was 172 min. Ao cross-clamping time – 99 min.

Factors that alter renal blood flow and lead to prerenal azotemia should be identified and corrected. Treatment of volume depletion and congestive heart failure before cardiac surgery will increase cardiac output and renal perfusion. Perioperative hydration and the use of hemodynamic monitoring and inotropic agents to optimize cardiac output may be necessary. It is unknown whether intraoperative optimization of bypass flow, perfusion pressure, and oxygen delivery would affect the subsequent development of AKI, although conceptually this would seem to be a reasonable goal. Medications such as NSAID and other nephrotoxic agents should be discontinued. If radiographic contrast is needed, then newer isosmolar contrast agents may be less toxicIn stable patients, cardiac surgery should be postponed in patients with contrast-induced ARF. Avoided all the nephrotoxic agents in the reported case.

They also have a number of chronic conditions including their inability to excrete certain medications, bleeding diathesis secondary to coagulation defects and platelet dysfunction, and susceptibility to infections that partly account for their increased operative morbidity and mortality. Dialysis more than 24 hours before the CPB procedure to avoid haemodynamic instability that may arise immediately after dialysis, whereas others recommend to have dialysis as close to the procedure

as possible to provide the most optimal fluid and electrolyte balance at the time of operation. Some others advocate the use of intraoperative dialysis.

Dialysis was not performed in this case but after the surgery the patient was hemodynamically stable and recovery of normal muscle tone and consciousness the patient was safely extubated. Patient in sinus rhythm, breathing spontaneous oxygen via the face mask 10–8–6 l/min, diuresis > 50–100 ml/hour. During the night period blood gases showed respiratory acidosis due to increased pCO2 (up to 65 mmHg). Oxygen therapy was changed to oxygen via nasal cannulas 5–6 l/min.

Laboratory exams revealed the increase in serum creatinine (310 mol/l) and urea. Blood pressure remained within normal ranges, heart rate was sinus rhythm.

Serum Urea

Fig. 1: Above figure shows the trend of serum urea from preoperative to sixth postoperative day. From the fourth postop day serum urea level decreased

Serum Creatinine

Fig. 2: Above figure shows the trend of serum creatinine from preoperative to sixth postoperative day. From the third postop day serum creatinine level decreased

Diuresis was adequate. The patient started to drink clear fluids. Infusion therapy was still continued with crystalloid solutions at the rate of 150 ml/hour.

250 200 150 100 post op day 0 POST OP DAY 1 POST OP DAY 2 50 0

Ph pco2 po2 Hco3 LACTATE

Fig. 3: Above figure shows the trend of ABG reports from Postop day zero to two postoperative day. From the second postop day ABG values returned to normal

On the third postoperative day the condition of the patient was gradually improving. He started to eat solid food. He had mild respiratory failure, which was compensated by additional oxygen via nasal cannulas (6 l/min). The blood gases remained within normal limits. The patient remained haemodynamically stable, heart rate – normarythmic atrial fibrillation. As the patient had AF before the surgery, the recovery of sinus rhythm was ineffective. Though diuresis was still adequate serum levels of creatinine increased to 336mol/l. Metabolic non lactic acidosis was still persistent as well. In order to maintain diuresis infusion therapy with crystalloids was still continued at the rate of 100 ml/hour.

Drugs that Increase Renal Blood Flow

In low doses (3 μg/kg per min), dopamine stimulates DA-1 and DA-2 dopamine receptors, increasing renal blood flow and inhibiting proximal tubule sodium reabsorption. Although dopamine has been used extensively, studies have failed to show its efficacy in ARF after cardiac surgery or associated with other conditions. Thus, there is no role for the use of dopamine in the treatment or prevention of ARF[31].

Fenoldopam is a selective DA-1 agonist that has been used in the prevention of ARF with variable results. In patients who had chronic kidney disease and underwent cardiac angiography, fenoldopam failed to reduce renal dysfunction, 30-d morality, dialysis, or rehospitalization. However, small randomized or uncontrolled studies that used fenoldopam demonstrated a reduction of renal dysfunction in patients who underwent cardiac surgery. A potential complication is the associated systemic hypotension that occurs after administration of fenoldopam. The beneficial effect of renal vasodilation in this situation may be offset by systemic hypotension that results in an overall net reduction of blood flow to the kidney. This systemic hypotensive effect may be abrogated by local infusion of fenoldopam directly into the renal arteries using a novel vascular delivery system.

Theophylline, a nonselective adenosine antagonist, is thought to block vasoconstriction induced by A1- adenosine receptors. In a recent clinical trial, theophylline infusion in CPB was ineffective in reducing the incidence of ARF.

Drugs that Induce Natriuresis

Atrial natriuretic peptide (ANP) increases natriuresis by increasing GFR as well as by inhibiting sodium reabsorption by the medullary collecting duct. In a multicenter trial, anaritide, a 25–amino acid synthetic form of ANP was administered to critically ill patients to treat acute tubular necrosis. Whether patients received anaritide or not, the dialysis-free survival was the same in both groups. Although a subgroup of oliguric patients benefited from anaritide in the original study, this observation was not confirmed in a follow-up study. Hypotension was a complicating factor in 46% of patients who received anaritide. In a recent study, recombinant human ANP (rhANP) was used to treat ARF after cardiac surgery in patients who required inotropic support for heart failure. In patients who received rhANP, there was a significant reduction in the incidence of dialysis at day 21 after the start of treatment. In this trial, ANP was infused at a lower rate (50 as opposed to 200 ng/kg per min; thus lowering the incidence of hypotension) and for a more prolonged period than previous studies. These changes may explain the benefit seen in this study as opposed to earlier ones[32].