PART 1: CLINICAL AND ANESTHETIC IMPLICATION
Q1. Define chronic renal failure.
Ans. Chronic kidney disease (CKD) is defined as gradual and progressive decline of renal function taking several years leading to accumulation of excess fluid, electrolyte, and waste product of metabolism in blood.
Chronic kidney disease can also be defined as the presence of renal damage characterized by abnormal excretion of albumin or reduced kidney function quantified by measured or estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 that persists for more than 3 months.
Q2. What are the causes of chronic kidney disease?
Ans. Most important causes are:
- Diabetes mellitus
- Chronic glomerulonephritis
- Polycystic kidney disease
- Hypertension
- Systemic lupus erythematosus (SLE)
- Interstitial nephritis.
Q3. What are the stages of chronic kidney disease?
Ans. Stages of CKD (National Kidney Foundation) are as follows:
- Stage 1: Normal eGFR ≥90 mL/min/1.73 m2 and persistent albuminuria
- Stage 2: eGFR between 60 and 89 mL/min/1.73 m2
- Stage 3: eGFR between 30 and 59 mL/min/1.73 m2
- Stage 4: eGFR between 15 and 29 mL/min/1.73 m2
- Stage 5: eGFR of <15 mL/min/1.73 m2 or end-stage renal disease (ESRD).
Q4. What are the clinical manifestations of chronic renal failure?
Ans. Fluid
Over the period of time, CKD patients develop fluid overload as they are not able to adapt to varying amount of salt intake and have reduced capacity to concentrate or dilute urine which makes these patients vulnerable to volume overload when large amount of fluid is given.
Infusion of large amount of normal saline in patients with CKD leads to development of hyperchloremic metabolic acidosis having deleterious effect like reduced cardiac contractility, cardiac output, renal blood flow, and GFR.2
Electrolytes
Potassium: Potassium concentration in the body usually remains within normal limit until CKD stage 5 by increasing the excretion through remaining functioning nephron and by increasing excretion of potassium in stool.
Patients with CKD may develop hyperkalemia if there is exogenous intake of potassium or if there is transcellular shift which may occur in acidemia, insulin therapy, IV beta blocker use, etc.
Sodium: Chronic kidney disease may be associated with normal sodium balance, sodium retention or sodium excretion. Sodium homeostasis is also influenced by medication like diuretics, cardiac function, and fluid status of the body.
Magnesium: Patients with CKD have altered magnesium clearance leading to muscle weakness and increased action of nondepolarizing muscle relaxant (NMDR).
Calcium and phosphorous: Chronic kidney disease patients are more prone to hypocalcemia because of decreased absorption of calcium from the gut due to fall in production of vitamin D3.
There is hyperphosphatemia which causes calcium phosphate to be deposited in soft tissue further causing hypocalcemia.
Chronic hypocalcemia causes secondary hyperparathyroidism leading to activation of osteoblast and osteoclast causing osteitis fibrosa cystica.
Hematological
Chronic kidney disease is associated with normocytic and normochromic anemia which has multifactorial origin. These are:
- Reduced erythropoietin production
- Ineffective erythropoiesis
- Bone marrow suppression
- Iron, vitamin B12, and folic acid deficiency
- Reduced life span of red blood cell
- Blood loss from gastrointestinal tract and dialysis
- Hemolysis
- Increased sampling in admitted patients
- Anemia of chronic disease
- Bone marrow fibrosts.
Coagulation
Patients with CKD usually have normal tests of coagulation and platelet count is usually within normal limit. Defective is the qualitative function of platelet. They have decreased adhesiveness and aggregation due to impaired release of von Willebrand and factor eight complex, reduced adenosine diphosphate (ADP), and thromboxane A2 leading to increased risk of bleeding.
Thromboelastographic indices show that each aspects of coagulation are increased, including initial fibrin formation, fibrin–platelet interaction, and qualitative platelet function.
Cardiovascular system
Cardiovascular diseases like myocardial infarction, heart failure, and stroke are more common as well as the leading cause of death in end-stage CKD patients.3
Pressure and volume overload are responsible for left ventricular hypertrophy in patients with long-standing history of CKD. Fluid retention is responsible for volume overload while hypertension and arteriosclerosis for pressure overload. Myocardial fibrosis associated with left ventricular hypertrophy (LVH) results in diastolic dysfunction and arrhythmias including high prevalence of second- and third-degree atrioventricular (AV) block and permanent pacing.
Long-standing CKD patents also have compromised endothelial function, low grade inflammation as well as dyslipidemia which lead to accelerated atherosclerosis and calcification of major blood vessels (Calciphylaxis).
Hypertension may be the cause or manifestation of kidney disease. Hence, controlling blood pressure is of prime importance in preserving residual renal function in both diabetic and nondiabetic renal disease (Cardio renal syndrome—effect of cardiac system on renal failure and vice versa).
Pulmonary
Volume overload and pulmonary congestion are the main implicating factors for changes in respiratory system in patients with CKD. One of the complications of peritoneal dialysis which affect respiratory system is diaphragmatic splinting which leads to atelectasis of basal portion of the lung subsequently leading to arteriovenous shunting. CKD patients who are undergoing surgery are advised for dialysis and ultrafiltrate removal in order to reduce pulmonary congestion as well as complication (Hyperventilation as compensation for metabolic acidosis).
Immune
Humoral defense mechanism and cell-mediated immunity are defective in patients with CKD leading to poor wound healing, fistula, and catheter-related infection.
Gastrointestinal
A lot of patients with kidney failure develop uremia which subsequently leads to gastroparesis. Many patients with ESRD also suffer from diabetes mellitus and autonomic neuropathy which slow gastric emptying hence these patients should be treated as full stomach and necessary precaution should be taken during surgery.
Neurological (Dialysis Disequilibrium Syndrome and Dialysis Dementia)
Uremia associated with renal failure can lead to neurological complications like malaise, fatigue, difficulty to concentrate, seizures, and coma which can be reduced with regular dialysis. Cerebrovascular manifestations like stroke can be seen due to vascular system involvement. Peripheral and autonomic neuropathies associated with ESRD can lead to orthostatic hypotension and silent myocardial ischemia.
Endocrine
The most common disease associated with CKD is diabetes mellitus. Patients developing nephropathy due to diabetes have higher morbidity and mortality than patients with other causes of CKD. All diabetic patients undergoing transplantation should undergo detailed evaluation of cardiovascular system as they have very high prevalence of fatal cardiovascular disease which often gets masked or remains symptom free due to diabetes mellitus. Successful renal transplantation needs good glycemic control which is also associated with a lower mortality.4
Neuraxial block
Platelet dysfunction associated with CKD and use of anticoagulants like heparin during dialysis are associated with an enhanced risk of bleeding in epidural space.
Epidural anesthesia should be given carefully in ESRD as these patients with poorly controlled blood pressure may land in hemodynamic instability after administration of local anesthetic that may further compromise renal perfusion and increase the risk of developing acute kidney injury. Therefore, risk and benefit of neuraxial anesthesia in patients with CKD should be analyzed and decision should be taken on individual case scenario.
Q5. How CKD affects anesthetic drug metabolism?
Ans. Chronic kidney disease-induced alteration in the body affects both—the pharmacokinetics and the pharmacodynamics of a drug. Alteration in protein binding and hepatic metabolism is responsible for variation of clinical outcome of drugs.
Pharmacokinetic changes
Absorption: Pathophysiological manifestation of CKD like reduced gastric motility, raised gastric pH, and intestinal edema is responsible for altered absorption of many drugs.
Distribution: Changes in body composition induced by ESRD like fluctuating total body water content, plasma protein binding, tissue binding, etc., affect volume of distribution of drugs and their clinical effects.
Albumin acts as binding sites for acidic drugs. Accumulation of organic acids like lactic acid in CKD patients affects binding of acidic drugs on albumin as these organic acids also compete for the same binding site on albumin as those by acidic drugs.
Basic drugs mainly bind to alpha-1-acid glycoprotein which is an acute phase protein that is often elevated in CKD.
Elimination: Kidneys play an important role in drug metabolism as well as excretion of product of metabolism. All of these important functions of kidney are accomplished by activity of cytochrome P450 and various types of conjugation reaction.
Interestingly, nonrenal clearance of many drugs is reduced in patients with kidney disease. Hepatic clearance of drugs varies with changes in blood flow to the liver, the free fraction of a drug, and the metabolic capacity of the liver enzymes.
Changes in pharmacodynamics
Inhalation agents: All inhalational anesthetic agents cause reduction in the renal blood low as well as GFR in a dose-dependent manner. Many agents release fluoride after undergoing metabolism in the body and they are linked to high output renal failure in majority of cases. Amount of fluoride produced by isoflurane after metabolism is very small and is unlikely to cause any harm to the kidney. So isoflurane can be used as inhalational anesthetic for renal transplantation. Sevoflurane is known to produce compound A when it gets into contact with carbon dioxide absorbent used in anesthesia workstation. Studies have shown accumulation of compound A in anesthesia circuit when sevoflurane was used with low fresh gas flows. On evaluation, compound A has been found to be nephrotoxic in rats but no such association has been found in human beings with preexisting renal disease.5
Desflurane has also shown no derangements in renal function in patients with preexisting renal disease.
Hence, apart from isoflurane, sevoflurane as well as desflurane can also be used as anesthetic agent during renal transplantation.
Induction agents
End-stage renal disease has little impact on pharmacokinetics and pharmacodynamics of propofol. It is mainly metabolized in the liver and metabolites of propofol are not pharmacologically active. Infusion dose is similar in both ESRD patients as well as patients with normal kidney function.
Thiopental is also used during induction of patients with ESRD. Thiopental is metabolized entirely in the liver and its metabolites are excreted by the kidneys and the gastrointestinal tract. No harmful effects of thiopental on kidney function have been recorded so far.
Neuromuscular blocking and reversal agents
Succinylcholine is used as muscle relaxant in order to facilitate tracheal intubation. Succinylcholine has rapid onset of muscle relaxation and brief duration of action which make it ideal agent for tracheal intubation. But bolus dose of scoline is associated with rise in serum potassium concentration which can cause cardiac arrhythmias and in some cases even cardiac arrest especially in CKD patients. Hence, a caution should be exercised while using scoline in patients with ESRD.
Use of pancuronium in patients with CKD is associated with the problems of prolonged neuromuscular block and postoperative residual curarization (PORC) as pancuronium has a decreased clearance and increased half-life in patients with ESRD.
End-stage renal disease has little impact on pharmacokinetics and pharmacodynamics of atracurium. It is not dependent upon either renal or hepatic function for its metabolism and excretion. Atracurium mainly undergoes spontaneous breakdown at body temperature and pH which is known as Hofmann degradation, and some part of atracurium is also metabolized by nonspecific esterases. Hence, it can be safely used in patients with ESRD.
Cisatracurium which is cis isomer of atracurium is also metabolized by Hofmann degradation and ester hydrolysis. Many anesthetists prefer using cisatracurium as it is more potent and the plasma concentration of laudanosine after cisatracurium administration is lower than after an equipotent dose of atracurium.
Use of mivacurium in patients with ESRD is associated with slow recovery as a result lower infusion rates are required in these patients.
Vecuronium mainly undergoes biliary excretion but around 30% of drug is excreted by the kidney. Hence, use of vecuronium in ESRD patients is associated with prolonged duration of its action.
Rocuronium also undergoes primary bile excretion with up to 33% of drug being excreted in the urine within 24 hours. So the duration of action and time to recovery are significantly prolonged in patients with ESRD.
Patients with CKD have reduced clearance and prolonged half-life of neostigmine. Hence, while reversing the patient's neostigmine should be used with longer acting glycopyrrolate 6rather than atropine in order to avoid parasympathomimetic response, including bradycardia and AV block.
Sugammadex may prove useful in preventing PORC when patients have received an amino steroid NMBA (neuromuscular blocking agent). Its efficacy as a reversal agent does not appear to rely on renal excretion of the cyclodextrin-relaxant complex.
Analgesic agents
Paracetamol: Occasional use of paracetamol in normal subjects and in patients with ESRD showed no evident change in glomerular or tubular function but prolonged use has been associated with analgesic nephropathy. Intraoperative use of paracetamol is safe and does not require dose alteration.
Nonsteroidal anti-inflammatory drugs: The use of nonsteroidal anti-inflammatory drug (NSAID) in patients with ESRD is more likely to cause harm than any benefit during perioperative period. Their use is associated with acute reduction in GFR and in rare cases acute interstitial nephritis.
Opioids: Morphine is metabolized by the liver but its active metabolites are excreted by the kidney. Patients with ESRD receiving morphine will have prolonged effect due to accumulation of active metabolite of morphine, i.e., morphine 6 glucuronide. In the same way, repeated doses of meperidine may lead to seizures because of accumulation of normeperidine. There is no change in pharmacokinetics of fentanyl, alfentanil, and sufentanil in ESRD patients as their metabolites are inactive and have no effect on opioid receptors even if they accumulate due to repeated doses. As far as remifentanil is concerned, it is a very short-acting opioid which is metabolized by tissue esterases and do not require change in dose in ESRD patients as compared to normal patients.
Immunosuppression therapy: All ESRD patients post-transplantation require immunosuppression. Traditional regimens consist of—calcineurin inhibitor (ciclosporin or tacrolimus), antiproliferative agent (azathioprine or mycophenolate mofetil), and a corticosteroid while newer regimens try to avoid or remove corticosteroids and calcineurin inhibitors. Polyclonal and monoclonal antibodies also form part of treatment protocol post-transplantation.
Local anesthetics: The duration of action of local anesthetic is reduced in patients with CKD due to altered protein binding. Local anesthetic needs dose reduction by 25% because of altered protein binding and a lower seizure threshold.
FURTHER READING
- How prostaglandin mediated injury?
- Types of dialysis, flow rates, advantages and disadvantages, quality of dialysis.
- Routes of dialysis.
- Order of access for dialysis.
- Symptoms which improve/not improve/develop after dialysis.
PART 2: ANESTHESIA FOR RENAL TRANSPLANT
Q1. Who is expanded criteria kidney donor?
Ans. An expanded criteria donor is donor who is either:
- Age of donor: 60 years or more
- Age: 50–59 years having two or more of the following criteria:
- History of hypertension
- Death from cardiovascular accident
- Serum creatinine level >1.5 mg/dL.
Q2. What is a living donor transplant program?
Ans. A living donor transplant program allows both recipient and donor surgery to be done simultaneously. It has the advantage of having minimal time for organ preservation. The time taken for removal of kidney from donor to restoration of blood supply of kidney in the recipient can be reduced to less than 1 hour which increases the chances of survival of graft and reduces the incidence of delayed graft function.
Q3. What are the preoperative workups for chronic kidney disease patient?
Ans. The recipient should undergo routine tests such as:
- ECG
- Chest radiograph
- Blood counts and platelet count
- Electrolytes like sodium, potassium, calcium, etc.
- Fasting, postprandial, and random blood sugar
- Renal function test—blood urea and serum creatinine
- Test of coagulation—prothrombin time, INR (international normalized ratio), and partial thromboplastin time
- Liver function test
Since cardiac disease is common in this patient population, a thorough cardiac evaluation is recommended.
Cardiac stress test should be done when they have:
- Age >49 years
- Diabetes mellitus
- Abnormal ECG showing findings of ischemia or old myocardial infarction, a new left bundle branch block, or diagnostic Q-wave changes in two contiguous leads
- History of ischemic heart disease, cerebrovascular disease, or peripheral vascular disease.
But all the patients are not able to undergo exercise stress test due to various limitation and disease manifestation. Such patients are required to undergo dipyridamole thallium imaging or dobutamine stress echocardiography. All the high-risk patients with previous history of cardiac disease having positive finding should undergo further evaluation with coronary angiography and cardiac catheterization.
Preemptive coronary revascularization with stent or surgery is associated with improved cardiac event-free survival rate.8
Dialysis, if indicated, is done within 24 hours of the operation. Excessive removal of ultrafiltrate should be avoided during dialysis as adequate hydration is needed for graft to function properly after anastomosis.
Dialysis itself is associated with various complications like disequilibrium syndrome, dementia and hypovolemia, peritonitis due to peritoneal dialysis, and systemic anticoagulation which should be evaluated thoroughly before proceeding with the surgery. Pre- and postdialysis body weight should be noted and it should be above dry weight.
Q4. What are the various kidney preservation solutions?
Ans.
- Euro-Collin solution: It contains phosphate as pH buffer and glucose as osmotic agent.
- University of Wisconsin: It contains cell impermeant agents like lactobionic acid, hydroxyl ethyl starch, raffinose, etc. They maintain the integrity of cell during storage of kidney during cold ischemia. Glutathione and adenosine stimulate recovery of normal metabolism after reperfusion—more hyperkalemia during reperfusion.
- Histidine-Tryptophan-Ketoglutarate:
- Histidine—acts as potent buffer
- Tryptophan—acts as membrane stabilizer and antioxidant
- Ketoglutarate—improves adenosine triphosphate (ATP) production during reperfusion.
Q5. Discuss strategies of fluid management in renal transplantation.
Ans.
Avoidance of hypovolemia
Adequate intravascular volume is required for proper functioning of graft. Perioperative fluid therapy during renal transplantation should aim at maintaining adequate hydration so that the transplanted kidney is well perfused reducing the incidence of delayed graft function and also improving graft survival. Donor kidney is generally denervated and has lost its capacity of autoregulation in case of hemodynamic instability. Hence, any decrease in blood pressure leads to reduced perfusion and repeats ischemia of transplanted kidney which necessities that perioperative fluid management should be done cautiously during kidney transplantation.
Use of crystalloid solutions
Isotonic crystalloid solutions are considered as first choice for volume replacement during kidney transplantation. Fluids such as normal saline and Ringer lactate are used for correcting hemodynamic instability during surgery, but balanced crystalloid solution are often preferred as compared to saline-based fluid because administration of large amount of normal saline may lead to development of hyperchloremic metabolic acidosis while balanced crystalloid solutions are not associated with such disturbances of electrolyte and acid-base status. But caution should be exercised while using balanced crystalloid solutions as there is risk of hyperkalemia in cases of impaired graft function. So proper monitoring of serum electrolytes is advised while using them as fluid replacement during kidney transplantation.
Use of colloid solution
Use of human albumin for volume expansion during kidney transplant has shown positive outcome with respect to urine output, renal function, and graft survival.9
Use of hetastarch has certain concern in end-stage renal disease (ESRD) patients since its use is associated with impaired platelet function and coagulation in a patient who is already prone to bleeding complication because of uremia-induced platelet dysfunction.
Mannitol, loop diuretics, and low-dose dopamine
Use of mannitol during kidney transplantation just before declamping of vascular anastomosis offers many advantages like:
- By expanding the intravascular volume of recipients it offers protection against repeat ischemia of transplanted kidney.
- By preventing water reabsorption in proximal convoluted tubule it prevents tubular obstruction and increases tubular flow rate of urine.
- It acts as free radical scavenger.
- It increases the release of vasodilatory prostaglandins in the kidney.
Loop diuretics like furosemide are generally given during period of vascular anastomosis to promote urine production but it is unclear whether it improves graft function or simply increases urine production from a functioning kidney.
Studies on the use of dopamine infusion during kidney transplantation have failed to show any significant benefit.
Q6. Perioperative hydration policy during kidney transplantation.
Ans. The most important goal of fluid administration during kidney transplantation is to maintain adequate intravascular volume status as well as stable hemodynamics. Both overhydration and underhydration should be avoided. It is pertinent to note that adequate hydration of donor as well as recipient is important for success of renal transplantation and for proper functioning of graft after surgery.
Fluid strategy in donors
It is recommended to give fluid generously in all cases of donor nephrectomy in order to main good diuresis before clamping of renal vessels. Balanced crystalloid solutions are preferred as compared to saline-based fluid. Good hydration along with stable hemodynamics helps the graft to tolerate ischemia time after nephrectomy with less damage till vascular anastomosis is completed in the recipient.
Fluid strategy in recipient
Proper fluid management leads to stable hemodynamics in surgical patients. Maintaining adequate hydration of recipients during vascular anastomosis and declamping is an essential part of anesthetic management during kidney transplantation. Good hydration of recipient leads to good cardiac output, tissue perfusion, and stable hemodynamics which are very essential for good graft function in early postoperative period. To reduce the incidence of delayed graft function recipients are given unrestricted fluid intraoperatively. Systolic blood pressure is targeted between 130 and 160 mm Hg while central venous pressure (CVP) is targeted between 10 and 15 mm Hg. Declamping of renal vessels followed by reperfusion of graft may be associated with sudden hypotension. It is important to maintain blood pressure in order to avoid any injury to transplanted organ due to hypoperfusion.10
The important factors leading to postrevascularization hypotension are:
- Rapid shift of 25% of cardiac output to the renal graft
- Release of vasodilator mediators accumulated during renal ischemia period.
Hence, adequate precaution should be taken to avoid hypotension and subsequent injury to transplanted organ.
Q7. What are the intraoperative concerns and precautions during transplant surgery?
Ans. The main anesthetic goal is to maintain renal perfusion and prevent harm to the donated kidney by avoiding hypoxia, hypovolemia, hypotension, and nephrotoxic drugs.
Some important concerns are:
- Cadaveric renal transplants are usually done on emergency basis. Recipients of cadaveric renal transplants should be evaluated by proper history, examination, and investigation before taking them to surgery.
- Antihypertensive medications should be continued perioperatively.
- Central venous cannulation and arterial cannulation should be done on extremities other than arteriovenous (AV) fistula. The AV fistula should be protected by cotton pad.
- Adequate blood and blood products should be made available in operating room (OR).
- Intravenous (IV) methylprednisolone is usually given after induction.
- Invasive monitoring (CVP and arterial) is established to guide fluid therapy.
- Postdeclamping adequate hydration should be maintained.
- Mannitol and furosemide may be given during anastomosis to stimulate urine formation and to restore function in the transplanted kidney after reperfusion.
- Hyperkalemia should be treated promptly.
- If the kidney function is not restored, some patients may need dialysis in the postoperative period for hyperkalemia and fluid overload.
- Regional anesthesia/analgesia can be administered after weighing the risks and the benefits.
Q8. What is cold and warm ischemia time?
Ans. Ischemia time during kidney transplantation starts with clamping of renal vessels in the donor to the end of vascular anastomosis in the recipient. The whole period is divided into warm and cold ischemia time. Warm ischemia time starts with clamping of renal vessels in the donor being interrupted by preservation of graft in low temperature and starts again with start of vascular anastomosis in recipients and ends with declamping of renal vessels.
Cold ischemia is the time during which graft is usually preserved by storing it at 4°C generally for less than 24 hours.
FURTHER READING
- Expected GFR in a post-transplant donor and recipient.
- Optimization of donor.
- Maastricht classification of DCD.
- Anesthesia management of brain dead donor.
- Criteria for live donors for transplantation.
- Role of antithymocyte globulin.
- HLA matching, PRA.
- Brain death diagnosis.
PART 3: ACUTE KIDNEY INJURY
Q1. Define RIFLE criteria for AKI.
Ans.
Stage | GFR criteria | Urine output criteria |
|---|---|---|
Risk | Serum creatinine increased × 1.5 Or GFR decrease >25% | <0.5 mL/kg/h for ≥6 h |
Injury | Serum creatinine increased × 2 Or GFR decrease >50% | <0.5 mL/kg/h for ≥12 h |
Failure | Serum creatinine increased × 3 Or GFR decrease ≥75% Or an absolute serum creatinine ≥354 μmol/L With an acute rise ≥4 μmol/L | <0.3 mL/kg/h for ≥24 h or anuria for >12 h |
Loss | Persistent AKI, requiring renal replacement therapy for >4 weeks | |
ESRD | Requiring dialysis for >3 months | |
| (ESRD: end-stage renal disease; GFR: glomerular filtration rate; AKI: acute kidney injury) | ||
Q2. Define AKIN classification of acute kidney injury (AKI).
Ans.
Stage | GFR criteria | Urine output criteria |
|---|---|---|
Stage 1 | Serum creatinine increased ≥26.2 μmol/L Or × 0.5–2 baseline | <0.5 mL/kg/h for ≥6 h |
Stage 2 | Serum creatinine increased × 2–3 baseline | <0.5 mL/kg/h for ≥12 h |
Stage 3 | Serum creatinine increased >× 3 baseline Or serum creatinine ≥354 μmol/L with an acute rise ≥44 μmol/L or initiation of renal replacement therapy (RRT) |
Q3. Define KDIGO classification of AKI.
Ans.
Stage | GFR criteria | Urine output criteria |
|---|---|---|
Stage 1 | Serum creatinine increased × 1.5–1.9 baseline | <0.5 mL/kg/h for 6–12 h |
Stage 2 | Serum creatinine increased × 2–2.9 baseline | <0.5 mL/kg/h for ≥12 h |
Stage 3 | Serum creatinine increased >× 3 baseline Or serum creatinine ≥354 μmol/L with an acute rise ≥44 μmol/L or initiation of RRT | <0.3 mL/kg/h for ≥24 h or anuria for ≥12 h |
Q4. Define AKI.
Ans. The AKI network defines AKI as presence of one of the following criteria:
- An absolute rise in serum creatinine level of ≥0.3 mg/dL (≥26.4 μmol)
- A percentage rise in serum creatinine level of ≥150% (>1.5-fold from the baseline)
Q5. Why serum creatinine is neither sensitive nor specific marker for AKI?
Ans.
- Serum creatinine level in a patent is affected by many factors such as age, sex, ethnicity, muscle bulk, volume status of body, treatment, and diet like amount of protein intake.
- No change in serum creatinine level is observed till glomerular fitration rate (GFR) is reduced by >50% from baseline.
Q6. What are the risk factors for AKI?
Ans.
Patient-related factors | Surgical factors |
|---|---|
Age | Length of surgery |
Hypertension | Major abdominal surgery |
Diabetes mellitus | Duration of cardiopulmonary bypass (CPB) |
Pulmonary disease like chronic obstructive | Cross clamp time |
pulmonary disease (COPD) | |
Cardiac causes like heart failure | Hemolysis (cardiac surgery) |
Chronic kidney disease | Hemodilution during cardiac surgery |
Emergency operation | Use of intra-aortic balloon pump |
Sepsis | |
Peripheral vascular disease | |
Cerebrovascular disease | |
Ascites |
Q7. What should be the characteristics of ideal biomarker of AKI?
Ans. An ideal biomarker should have following characteristics:
- It should be highly sensitive as well as specific.
- It should have rapid and consistent response to injury.
- It should have normal values for age, sex, and race already established.
- Its level should correlate with the severity of the disease.
- Its detection should be quick, reliable, and cost-effective.
Q8. Elaborate some novel biomarkers of AKI.
Ans.
Neutrophil gelatinase-associated lipocalin
Neutrophil gelatinase-associated lipocalin (NGAL) cannot be detected in urine or in plasma of all those patients having normal kidney function. Studies have shown that urinary NGAL has higher sensitivity and specificity in pediatric population undergoing cardiac surgery for predicting postoperative AKI as compared to adult population.
Plasma NGAL level has demonstrated low sensitivity for detecting AKI following cardiac surgery hence limiting its use as single biomarker for predicting AKI.13
KIM-1
It is a transmembrane glycoprotein which is generally not expressed in normal renal tissue. Various human and animal studies have shown that soluble form of KIM-1 molecule is readily detectable in urine following injury to kidney due to ischemia and nephrotoxins. It is also found to be highly sensitive marker for AKI following cardiac surgery.
Interleukin-18
Interleukin-18 (IL-18) is an inflammatory cytokines which is raised in a number of inflammatory diseases but it has found to be early biomarker for AKI in patients with chronic kidney disease (CKD), postcardiac surgery, etc.
Cystatin C
Cystatin C is produced by all nucleated cells of the body. It is freely filtered by the kidney and undergoes complete reabsorption in the renal tubules. Various studies have shown no clear association between plasma cystatin C level and AKI but urinary cystatin level was associated with AKI and correlated with severity of injury.
Q9. What are the management strategies for AKI?
Ans. Avoidance of AKI remains the cornerstone of management.
Preventive measures
Fluids and goal-directed therapy: Maintaining renal perfusion is the most important strategy for preventing AKI as most of the patients developing postoperative AKI have episodes of hemodynamic instability during intraoperative period. Maintaining adequate hydration is vital but fluid should be given cautiously as fluid overload associated with complication like poor wound healing, gut edema, increased duration of mechanical ventilation, and length of stay in the hospital. Positive fluid balance during perioperative period has a detrimental effect on renal function. Hence, goal-directed fluid therapy is recommended during perioperative period to prevent AKI as well as to improve patient outcome.
Avoidance of nephrotoxic agents: A number of medications being used during perioperative period have lethal effect on kidney function. Drugs like angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blocker (ARB), and nonsteroidal anti-inflammatory drugs (NSAIDs) are the main culprits. Antibiotics like aminoglycosides, penicillin, fluoroquinolones, and cephalosporin's can also lead to AKI either by direct injury or by secondary interstitial nephritis.
Hemodilution and transfusion in cardiac surgery: Studies have shown association between blood transfusion and hemodilution during cardiac surgery with increased incidence of AKI. In order to prevent AKI current guidelines suggest to maintain hemoglobin >7 g/dL and hematocrit >21%.
Pharmacological interventions
Dopamine: Studies have shown no benefit for using dopamine either for the treatment or prevention of AKI.14
Fenoldopam: Fenoldopam has conflicting results when it is used for the management of AKI. When used during cardiac surgery, it has reduced the incidence of AKI, need for RRT and mortality.
Diuretics (furosemide/mannitol): Use of diuretics during AKI may improve urine output but studies have not shown any survival benefit or reduced the need for hemodialysis after their use in AKI.
Atrial natriuretic peptide: Atrial natriuretic peptide (ANP) is an endogenous diuretic and natriuretic which is produced by cardiac atria in response to stretching and dilation. Use of recombinant ANP in postoperative period of cardiac surgery patients with decompensated heart failure has reduced the need for RRT, but it has shown no such benefit in other patient's population.
Nesiritide (recombinant human β natriuretic peptide): Further studies are needed before any recommendation can be made about its use in AKI patients.
N-acetylcysteine: Use of N-acetylcysteine in perioperative period has not shown any survival and protective benefit, but there is some protective role of N-acetylcysteine in contrast-induced nephropathy.
Prophylactic RRT: Prophylactic RRT is not recommended in high-risk patients undergoing major surgery because of insufficient evidences.
RRT in established AKI: Patients with established AKI need RRT for definite management.
2013 - Cochrane analysis on perioperative renal protective strategies concluded that no pharmacological intervention is effective. Prevention of hypovolemia is the single best strategy for renal protection.
FURTHER READING
- Significance of FeNa.
- Early diagnosis of complications like sepsis, abdominal, HTN and hemorrhage.
PART 4: CLINICAL CASE SCENARIO
Q1. Anesthesia for arteriovenous fistula surgery. Why is it created for dialysis?
Ans. A fistula is surgically created between radial artery and cephalic vein. Other sites include brachial and the basilic vein. They have the advantage of long-term patency, lower infection and reduced mortality but they need at least 1–4 for maturation.
Complications of arteriovenous (AV) fistula consist of infection, stenosis, thrombosis, aneurysm, and limb ischemia.
Anesthetic options include:
- General anesthesia (GA)
- Local infiltration
- Brachial plexus block.
15General anesthesia has a lot of concern and complications in view of significant comorbidities, but may have to be administered if patient refuses or is not willing for regional anesthesia (RA).
Local infiltration anesthesia is other option which requires patient cooperation. Repeated injections may be required; this can increase the chances of systemic local anesthetic toxicity.
Regional anesthesia with brachial plexus block is an effective and preferred alternative to GA and infiltration anesthesia. RA has various advantages such as vasodilatation, better hemodynamic stability and good postoperative analgesia, but the maximum dose of the local anesthetic drug should be reduced by 25% because of their altered pharmacokinetics in chronic renal failure (CRF) and lower seizure threshold.
Q2. Anesthetic management for nontransplant surgery.
Ans. Our main goal is to avoid hypoxia, hypovolemia, and hypotension.
Preoperative evaluation
History should consist of:
- Proper history regarding onset of disease
- Disease process leading to CRF
- Requirements and schedule of dialysis (dry weight, native urine output)
- Comorbidities
- Detailed history of drug therapy including antihypertensive and oral hypoglycemic agent
- Assessment of fluid and electrolyte status
- Assessment of renal function
- Blood pressure (BP) and sugar trends
- Use of radiocontrast
- Previous surgical history
- Bleeding disorders, blood transfusion
- Allergies
- Use of nephrotoxic agents
- Significant history of cardiac disease and peripheral vascular disease
- Any symptoms of congestive heart failure
- Functional capacity.
General examination (Examination of AV fistula)
- Build
- Nutritional status
- Pallor, periorbital and peripheral edema
- Features of uremic syndrome
- Raised jugular venous pressure (JVP).
Systemic examination
- Cardiovascular system (CVS)
- Murmurs, carotid bruits, pericardial effusion
- Respiratory
- Respiratory rate, pattern, added sounds
- Renal
- Native urine output
- Input and output charting.
Preoperative diagnostic testing
- Complete blood count
- Renal function test: Na+, K+, Cl−, blood urea nitrogen (BUN), Cr, Ca, and HCO3 levels
- Repeat electrolyte 2–3 hours before surgery/4–6 hours after last dialysis
- Chest X-ray
- Electrocardiogram (ECG)
- Arterial blood gas analysis
- Prothrombin time
- Liver function test
- Echocardiography can be done in patients with
- Hemodynamic instability
- Poor functional capacity
- Patients with long-standing end-stage renal disease (ESRD) associated with diabetes.
Preoperative optimization
For elective surgery, it is important to optimize BP, serum potassium level. Avoid unnecessary blood transfusion. The antihypertensive should be continued perioperatively. Metoclopramide and H2-receptor antagonists should be administered if patient has gastroesophageal reflux.
Care of fistula
- Avoid hypotension—prevent fistula thrombosis
- Avoid injecting any drug
- Avoid cannulation of artery or vein on same side of fistula
- Apply light bandage
- Avoid BP cuff on that side
- Adequate circulation should be maintained in that arm
- Avoid flexing or overextending the arm.
Anesthetic goals
Preoperative period:
- Maintain hydration
- Avoid acid-base and electrolyte imbalance
- Maintain hematocrit above 25%
- Coagulopathy if any should be corrected
- Adequate BP and blood sugar control
- Aspiration prophylaxis.
Intraoperative period:
- Proper care during positioning
- Appropriate drug use and dose modification
- Asepsis in placing invasive lines
- Neuromuscular monitoring
- Drugs to blunt intubation response and maintain hemodynamic stability
- Adequate hydration and goal-directed fluid therapy
- Urine output monitoring.
Postoperative period:
- Avoid aspiration
- Avoid extubation response
- Avoid respiratory depression
- Extubate only when patient is completely reversed and fully awake.
Postoperative care:
- Monitor urine output
- Postoperative analgesia—multimodal
- Intermittent boluses of fentanyl/morphine/patient-controlled analgesia
- Serum electrolytes, urea and creatinine level should be measured daily
- Maintain adequate hydration.
After minor surgery, patient should return to their preoperative regimen as soon as possible. After major surgery, some patients may require dialysis for some time in the postoperative period.
Q3. Postrenal transplant incidental surgery
Ans. The main considerations for post-transplants patients are:
- Side effects of immunosuppressant
- Potential for rejection
- Risk of infection
- Status and function of transplanted organ
- Status of other organs affected by immunosuppression or the transplanted organ
- H/s/o metabolic syndrome, CVD, obesity, OSA. 65% - new onset OM.
Anesthetic management
The main anesthetic goal is to maintain renal perfusion with least alteration in the immunosuppressive regimen.
Preoperative evaluation
- Functioning of graft and any evidence of rejection should be noted. Presence of uremia, hypertension, and proteinuria may indicate chronic graft rejection. Some postrenal transplant patients may require dialysis. There is high morbidity and mortality during rejection so elective surgery should be postponed.
- Evidence of infection: Typical signs and symptoms of intra-abdominal sepsis are often absent.
- All baseline investigations should be done including liver function test as they may be deranged secondary to immunosuppressive drugs.
Induction of anesthesia
- The choice of perioperative monitoring is determined by the nature of surgery.
- Use of LMA acceptable.
- Avoid nasal intubation.
- Regional anesthesia can be administered if the clotting studies and platelet count are normal.
- Nonsteroidal anti-inflammatory drugs (NSAIDs) are contraindicated and can augment nephrotoxicity of cyclosporine.
- Drug interactions—cyclosporine A interacts with nondepolarizing neuromuscular blockers potentiating their action, thus decreasing the dose and frequency of top-up doses is required.
- Azathioprine antagonizes neuromuscular blocking drugs.
- Immunosuppressive agent should not be stopped perioperatively.
- Perioperative steroid treatment regimen.
Patient receiving more than 10 mg prednisolone continuously for last 3 months:
Minor operation (hernias, hand surgery) | 25 mg hydrocortisone at induction |
Moderate surgery | Usual preoperative steroids + 25 mg hydrocortisone at induction + 100 mg hydrocortisone/day |
Major surgery (major trauma, prolonged surgery, or surgery where there is delayed oral intake) | Usual preoperative steroids |
+ 25 mg hydrocortisone at induction | |
+100 mg hydrocortisone/day for 2–3 day | |
All other patients—no additional steroids required |
FURTHER READING
- Analgesia options for
- Donor nephrectomy(i) open (ii) lap
- Kidney transplant surgery
- Post-transplant surgery.
- Calculate GFR.
- 2020 – AAGBI guidelines on management of patients using perioperative steroids.