Chapter 31: Anesthesia for Patients with Kidney Disease

Acute kidney injury (AKI) is a common problem, with an incidence of up to 5% in all hospitalized patients and up to 8% in critical illness. Postoperative AKI may occur in 1% or more of general surgery patients, and up to 30% of patients undergoing cardiothoracic and vascular procedures. Perioperative AKI is a markedly underappreciated problem that greatly increases perioperative morbidity, mortality, and costs. It is a systemic disorder that can include fluid and electrolyte derangements, respiratory failure, major cardiovascular events, weakened immunocompetence leading to infection and sepsis, altered mental status, hepatic dysfunction, and gastrointestinal hemorrhage. It is also a major cause of chronic kidney disease. Preoperative risk factors for perioperative AKI include preexisting kidney disease, hypertension, diabetes mellitus, liver disease, sepsis, trauma, hypovolemia, multiple myeloma, and age greater than 55 years. The risk of perioperative AKI is also increased by exposure to nephrotoxic agents such as nonsteroidal antiinflammatory drugs (NSAIDs), radiocontrast agents, and antibiotics (see Table 30–4). The clinician must possess a thorough understanding of the risks of AKI, its differential diagnosis, and its evaluation strategy (Figure 31–1).

Impaired kidney function may be due to glomerular dysfunction, tubular dysfunction, or urinary tract obstruction. Accurate clinical assessment of kidney function is often difficult and relies heavily on laboratory determinations of glomerular filtration rate (GFR), including creatinine clearance, and other evaluations (Tables 31–1 and 31–2). Even small postoperative increases in serum creatinine are associated with increased morbidity and mortality, although many factors may confound its measurement (Figure 31–2). Systems employed in defining and staging the degree of kidney dysfunction include the Acute Dialysis Quality Initiative Risk, Injury, Failure, Loss, End-Stage (RIFLE) criteria and the Acute Kidney Injury Network (AKIN) staging system. These systems were merged into the Kidney Disease Improving Global Outcomes (KDIGO) classification (Table 31–3). Thus, the traditional diagnosis of AKI, based upon serum creatinine and urine output, has been refined into an increase of serum creatinine of 0.3 mg/dL or more within 48 h or a 1.5-fold or greater increase in baseline within 7 days. Since AKI is a systemic disorder, it is important to recall that the kidney excretory function assessed via serum creatinine and urine output ignores endocrine, metabolic, and immunological kidney functions. A great deal of research is currently evaluating plasma and urine biomarkers associated with AKI, such as cystatin C, neutrophil gelatinase–associated lipocalin, interleukin-18, and kidney injury molecule-1, and several are now commercially available (Figure 31–3). It is likely that biomarkers will play an increasingly prominent role in the near future for diagnosis, staging, and prognostic assessment of AKI.

BLOOD UREA NITROGEN

The primary source of urea in the body is the liver. During protein catabolism, ammonia is produced from the deamination of amino acids. Hepatic conversion of ammonia to urea prevents the buildup of toxic ammonia levels:

Blood urea nitrogen (BUN) is therefore directly related to protein catabolism and inversely related to glomerular filtration. As a result, BUN is not a reliable indicator of the GFR unless protein catabolism is normal and constant. Recall that 40% to 50% of the urea filtrate is normally reabsorbed passively by the renal tubules; hypovolemia increases this fraction.

The normal BUN concentration is 10 to 20 mg/dL. Lower values may be seen with starvation or liver disease; elevations usually result from decreases in GFR or increases in protein catabolism. The latter may be due to a high catabolic state (trauma or sepsis), degradation of blood either in the gastrointestinal tract or in a large hematoma, or a high-protein diet. BUN concentrations greater than 50 mg/dL are generally associated with impaired kidney function.

SERUM CREATININE

Creatine is a product of muscle metabolism that is nonenzymatically converted to creatinine. Daily creatinine production in most people is relatively constant and related to muscle mass, averaging 20 to 25 mg/kg in men and 15 to 20 mg/kg in women. Creatinine is then filtered (and to a minor extent secreted) but not reabsorbed in the kidneys. Serum creatinine concentration is therefore directly related to body muscle mass and inversely related to glomerular filtration (Figure 31–4). Because body muscle mass is usually relatively constant, serum creatinine measurements are generally reliable indices of GFR in the ambulatory patient. However, the utility of a single serum creatinine measurement as an indicator of GFR is limited in critical illness: The rate of creatinine production, and its volume of distribution, may be abnormal in the critically ill patient, and a single serum creatinine measurement often will not accurately reflect GFR in the physiological disequilibrium of AKI.

The normal serum creatinine concentration is 0.8 to 1.3 mg/dL in men and 0.6 to 1 mg/dL in women. Note from Figure 31–4 that each doubling of the serum creatinine represents a 50% reduction in GFR. As previously noted, many factors may affect serum creatinine measurement.

GFR declines with increasing age in most individuals (5% per decade after age 20), but because muscle mass also declines, the serum creatinine remains relatively normal; creatinine production may decrease to 10 mg/kg. Thus, in elderly patients, small increases in serum creatinine may represent large changes in GFR. Using age and lean body weight (in kilograms), GFR can be estimated by the following formula for men:

For women, this equation must be multiplied by 0.85 to compensate for a smaller muscle mass.

The serum creatinine concentration requires 48 to 72 h to equilibrate at a new level following acute changes in GFR.

CREATININE CLEARANCE

Creatinine clearance measurement is the most accurate method available for clinically assessing overall kidney function (actually, GFR). Although measurements are usually performed over 24 h, 2-h creatinine clearance determinations are reasonably accurate and easier to perform. Mild impairment of kidney function generally results in creatinine clearances of 40 to 60 mL/min. Clearances between 25 and 40 mL/min produce moderate kidney dysfunction and nearly always cause symptoms. Creatinine clearances less than 25 mL/min are indicative of overt kidney failure.

Later stage kidney disease leads to increased creatinine secretion in the proximal tubule. As a result, with declining kidney function the creatinine clearance progressively overestimates the true GFR. Moreover, relative preservation of GFR despite progressive kidney disease may result from compensatory hyperfiltration in the remaining nephrons and increases in glomerular filtration pressure. It is therefore important to look for other signs of deteriorating kidney function such as hypertension, proteinuria, or abnormalities in urine sediment.

BLOOD UREA NITROGEN:CREATININE RATIO

Low renal tubular flow rates enhance urea reabsorption but do not affect creatinine excretion. As a result, the ratio of BUN to serum creatinine increases to more than 10:1. Decreases in tubular flow can be caused by decreased kidney perfusion or obstruction of the urinary tract. BUN:creatinine ratios greater than 15:1 are therefore seen in volume depletion and in edematous disorders associated with decreased tubular flow (eg, congestive heart failure, cirrhosis, nephrotic syndrome) as well as in obstructive uropathies. Increases in protein catabolism can also increase this ratio.

URINALYSIS

Urinalysis continues to be routinely performed for evaluating kidney function. Although its utility and cost-effectiveness for this purpose are questionable, urinalysis can be helpful in identifying some disorders of renal tubular dysfunction as well as some nonrenal disturbances. A routine urinalysis typically includes pH; specific gravity; detection and quantification of glucose, protein, and bilirubin content; and microscopic examination of the urinary sediment. Urinary pH is helpful only when arterial pH is also known. A urinary pH greater than 7.0 in the presence of systemic acidosis is suggestive of renal tubular acidosis (see Chapter 50). Specific gravity is related to urinary osmolality; 1.010 usually corresponds to 290 mOsm/kg. A specific gravity greater than 1.018 after an overnight fast is indicative of adequate renal concentrating ability. A lower specific gravity in the presence of hyperosmolality in plasma is consistent with diabetes insipidus.

Glycosuria is the result of either a reduced tubular threshold for glucose (normally 180 mg/dL) or hyperglycemia. Proteinuria detected by routine urinalysis should be evaluated by means of 24-h urine collection. Urinary protein excretions greater than 150 mg/d are significant. Elevated levels of bilirubin in the urine are seen with biliary obstruction.

Microscopic analysis of the urinary sediment detects the presence of red or white blood cells, bacteria, casts, and crystals. Red cells may be indicative of bleeding due to tumor, stones, infection, coagulopathy, or trauma (commonly, urinary catheterization). White cells and bacteria are generally associated with infection. Disease processes at the level of the nephron produce tubular casts. Crystals may be indicative of abnormalities in oxalic acid, uric acid, or cystine metabolism.

Most drugs commonly employed during anesthesia (other than volatile anesthetics) are at least partly dependent on renal excretion for elimination. In the presence of kidney impairment, dosage modifications may be required to prevent accumulation of the drug or its active metabolites. Moreover, the systemic effects of AKI can potentiate the pharmacological actions of many of these agents. This latter observation may be the result of decreased protein binding of the drug, greater brain penetration due to some breach of the blood–brain barrier, or a synergistic effect with the toxins retained in kidney failure.

INTRAVENOUS AGENTS

Propofol & Etomidate

The pharmacokinetics of both propofol and etomidate are minimally affected by impaired kidney function. Decreased protein binding of etomidate in patients with hypoalbuminemia may enhance its pharmacological effects.

Barbiturates

Patients with kidney disease often exhibit increased sensitivity to barbiturates during induction, even though pharmacokinetic profiles appear to be unchanged. The mechanism appears to be an increase in free circulating barbiturate from decreased protein binding. Acidosis may also favor a more rapid entry of these agents into the brain by increasing the nonionized fraction of the drug (see Chapter 26).

Ketamine

Ketamine pharmacokinetics are minimally altered by kidney disease. Some active hepatic metabolites are dependent on renal excretion and can potentially accumulate in kidney failure.

Benzodiazepines

Benzodiazepines undergo hepatic metabolism and conjugation prior to elimination in urine. Because they are highly protein bound, increased benzodiazepine sensitivity may be seen in patients with hypoalbuminemia. Diazepam and midazolam should be administered cautiously in the presence of kidney impairment because of a potential for the accumulation of active metabolites.

Opioids

Most opioids used in anesthetic practice (morphine, meperidine, fentanyl, sufentanil, and alfentanil) are inactivated by the liver; some of these metabolites are then excreted in urine. Remifentanil pharmacokinetics are unaffected by kidney function due to rapid ester hydrolysis in blood. With the exception of morphine and meperidine, significant accumulation of active metabolites generally does not occur with these agents. Accumulation of morphine (morphine-6-glucuronide) and meperidine (normeperidine) metabolites may prolong respiratory depression in patients with kidney failure, and increased levels of normeperidine are associated with seizures. The pharmacokinetics of the most commonly used opioid agonist–antagonists (butorphanol, nalbuphine, and buprenorphine) are unaffected by kidney failure.

Anticholinergic Agents

In doses used for premedication, atropine and glycopyrrolate can generally be used safely in patients with kidney impairment. Because up to 50% of these drugs and their active metabolites are normally excreted in urine, however, the potential for accumulation exists following repeated doses. Scopolamine is less dependent on renal excretion, but its central nervous system effects can be enhanced by decreased kidney function.

Phenothiazines, H₂ Blockers, & Related Agents

Most phenothiazines, such as promethazine, are metabolized to inactive compounds by the liver. Droperidol may be partly dependent on the kidneys for excretion. Although their pharmacokinetic profiles are not appreciably altered by kidney impairment, potentiation of the central depressant effects of phenothiazines by the systemic effects of kidney disease may occur.

All H₂-receptor blockers are dependent on kidney excretion, and their dose must be reduced for patients with kidney disease. Proton pump inhibitor dosage does not need to be reduced for patients with kidney disease. Metoclopramide is partly excreted unchanged in urine and will accumulate in kidney failure. Although up to 50% of dolasetron is excreted in urine, no dosage adjustments are recommended for any of the 5-HT₃ blockers in patients with kidney disease.

INHALATION AGENTS

Volatile Agents

Volatile anesthetic agents are ideal for patients with kidney disease because of lack of dependence on the kidneys for elimination, ability to control blood pressure, and minimal direct effects on kidney blood flow. Although patients with mild to moderate kidney impairment do not exhibit altered uptake or distribution, accelerated induction and emergence may be seen in severely anemic patients (hemoglobin <5 g/dL) with chronic kidney failure; this observation may be explained by a decrease in the blood:gas partition coefficient or by a decrease in minimum alveolar concentration. Some clinicians avoid sevoflurane (with <2 L/min gas flows) for patients with kidney disease who undergo lengthy procedures (see Chapters 8 and 30).

Nitrous Oxide

Some clinicians omit entirely or limit the use of nitrous oxide (or air) to maintain an FiO₂ of 50% or greater in severely anemic patients with end-stage kidney disease in an attempt to increase arterial oxygen content. This may be justified in patients with hemoglobin less than 7 g/dL, in whom even a small increase in the dissolved oxygen content may represent a significant percentage of the arterial to venous oxygen difference (see Chapter 23).

MUSCLE RELAXANTS

Succinylcholine

Succinylcholine can be safely used in patients with kidney failure, in the absence of hyperkalemia at the time of induction. When the serum potassium is known to be increased or is in doubt, succinylcholine should be avoided. Although decreased plasma cholinesterase levels have been reported in uremic patients following dialysis, significant prolongation of neuromuscular blockade is rarely seen.

Cisatracurium & Atracurium

Cisatracurium and atracurium are degraded by plasma ester hydrolysis and nonenzymatic Hofmann elimination. These agents are often the drugs of choice for muscle relaxation in patients with kidney failure, especially in clinical situations where neuromuscular function monitoring is difficult or impossible.

Vecuronium & Rocuronium

The elimination of vecuronium is primarily hepatic, but up to 20% of the drug is eliminated in urine. The effects of large doses of vecuronium (>0.1 mg/kg) are only modestly prolonged in patients with kidney disease. Rocuronium primarily undergoes hepatic elimination, but prolongation in patients with severe kidney disease has been reported. In general, with appropriate neuromuscular monitoring, these two agents can be used with few problems in patients with severe kidney disease.

Curare (d-Tubocurarine)

Elimination of d-tubocurarine is dependent on both kidney and biliary excretion; 40% to 60% of a dose of curare is normally excreted in urine. Increasingly prolonged effects are observed following repeated doses in patients with decreased kidney function. Smaller doses and longer dosing intervals are therefore required for maintenance of optimal muscle relaxation.

Pancuronium

Pancuronium is primarily dependent on renal excretion (60–90%). Although pancuronium is metabolized by the liver into less active intermediates, its elimination half-life is still primarily dependent on renal excretion (60–80%). Neuromuscular function should be closely monitored if these agents are used in patients with abnormal renal function.

Reversal Agents

Renal excretion is the principal route of elimination for edrophonium, neostigmine, and pyridostigmine. The half-lives of these agents in patients with renal impairment are therefore prolonged at least as much as any of the above relaxants, and problems with inadequate reversal of neuromuscular blockade are usually related to other factors (see Chapter 11). Thus, “recurarization” due to inadequate duration of reversal agent is unlikely. Sugammadex is a steroidal muscle relaxant encapsulator drug that, even after binding vecuronium or rocuronium, is rapidly and entirely eliminated (along with the neuromuscular blocker) in its unmetabolized form by the kidney (see Chapter 11). Early studies suggest that onset of sugammadex muscle relaxant reversal may be delayed and that the sugammadex–muscle relaxant complex may persist for several days in the plasma of patients with decreased kidney function. Because of the potential patient safety implications of prolonged sugammadex–muscle relaxant complex exposure in this situation, the use of sugammadex is not recommended at this time in patients with low creatine clearance (<30 mL/min) or on renal replacement therapy (RRT).

PREOPERATIVE CONSIDERATIONS

Acute Kidney Failure

This syndrome is a rapid deterioration in kidney function that results in retention of nitrogenous waste products (azotemia). These substances, many of which behave as toxins, are byproducts of protein and amino acid metabolism. Impaired kidney metabolic activity may contribute to widespread organ dysfunction (see Chapter 30).

Kidney failure can be classified as prerenal, renal, and postrenal, depending on its cause(s), and the initial therapeutic approach varies accordingly (see Figure 31–1 and Table 31–4). Prerenal kidney failure results from an acute decrease in renal perfusion; intrinsic kidney failure is usually due to underlying kidney disease, kidney ischemia, or nephrotoxins; and postrenal failure is the result of urinary collecting system obstruction or disruption. Both prerenal and postrenal forms of kidney failure are readily reversible in their initial stages but with time both progress to intrinsic kidney failure. Most adult patients with kidney failure first develop oliguria. Nonoliguric patients with kidney failure (urinary outputs >400 mL/d) continue to form urine that is qualitatively poor; these patients tend to have greater preservation of GFR. Although glomerular filtration and tubular function are impaired in both cases, abnormalities tend to be less severe in nonoliguric kidney failure.

The course of intrinsic acute kidney failure varies widely, but the oliguria typically lasts for 2 weeks and is followed by a diuretic phase marked by a progressive increase in urinary output. This diuretic phase often results in very large urinary outputs and is usually absent in nonoliguric kidney failure. Kidney function improves over the course of several weeks but may not return to normal for up to 1 year, and subsequent chronic kidney disease is common. The course of prerenal and postrenal kidney failure is dependent upon promptness in diagnosis and correction of the causal condition. Diagnostic ultrasound, including point-of-care ultrasound, is increasingly used to rapidly and noninvasively evaluate possible obstructive uropathy.

Chronic Kidney Disease

The most common causes of chronic kidney disease (CKD) are hypertensive nephrosclerosis, diabetic nephropathy, chronic glomerulonephritis, and polycystic kidney disease. The uncorrected manifestations of this syndrome (Table 31–5) are usually seen only after GFR decreases below 25 mL/min. Patients with GFR less than 10 mL/min are dependent upon RRT for survival, in the form of hemodialysis, hemofiltration, or peritoneal dialysis.

The generalized effects of severe CKD can usually be controlled by RRT. The majority of patients with end-stage kidney disease who do not undergo renal transplantation receive RRT three times per week. There are complications directly related to RRT itself (Table 31–6). Hypotension, neutropenia, hypoxemia, and disequilibrium syndrome are generally transient, if they occur, and resolve within hours after RRT. Factors contributing to hypotension during dialysis include the vasodilating effects of acetate dialysate solutions, autonomic neuropathy, and rapid removal of fluid. The interaction of white cells with cellophane-derived dialysis membranes can result in neutropenia and leukocyte-mediated pulmonary dysfunction leading to hypoxemia. Dialysis disequilibrium syndrome (DDS) is most frequently seen following aggressive dialysis and is characterized by transient alterations in mental status and focal neurological deficits that are secondary to cerebral edema.

Manifestations of Kidney Failure

A. Metabolic

Multiple metabolic abnormalities, including hyperkalemia, hyperphosphatemia, hypocalcemia, hypermagnesemia, hyperuricemia, and hypoalbuminemia, typically develop in patients with kidney failure. Water and sodium retention can result in worsening hyponatremia and extracellular fluid overload, respectively. Failure to excrete nonvolatile acids produces an increased anion gap metabolic acidosis (see Chapter 50). Hypernatremia and hypokalemia are uncommon complications.

Hyperkalemia is a potentially lethal consequence of kidney failure (see Chapter 49). It usually occurs in patients with creatinine clearances of less than 5 mL/min, but it can also develop rapidly in patients with higher clearances in the setting of large potassium loads (eg, trauma, hemolysis, infections, or potassium administration).

Hypermagnesemia is generally mild unless magnesium intake is increased (commonly from magnesium-containing antacids). Hypocalcemia is secondary to resistance to parathyroid hormone, decreased intestinal calcium absorption secondary to decreased kidney synthesis of 1,25-dihydroxycholecalciferol, and hyperphosphatemia-associated calcium deposition into bone. Symptoms of hypocalcemia rarely develop unless patients are also alkalotic.

Patients with kidney failure also rapidly lose tissue protein and readily develop hypoalbuminemia. Anorexia, protein restriction, and dialysis are contributory.

B. Hematologic

Anemia is nearly always present when the creatinine clearance is below 30 mL/min. Hemoglobin concentrations are generally 6 to 8 g/dL due to decreased erythropoietin production, red cell production, and red cell survival. Additional factors may include gastrointestinal blood loss, hemodilution, bone marrow suppression from recurrent infections, and blood loss for laboratory testing. Even with transfusions, it is often difficult to maintain hemoglobin concentrations greater than 9 g/dL. Erythropoietin administration may partially correct the anemia. Increased levels of 2,3-diphosphoglycerate (2,3-DPG), which facilitates the unloading of oxygen from hemoglobin (see Chapter 23), develop in response to the decrease in blood oxygen-carrying capacity. The metabolic acidosis associated with CKD also favors a rightward shift in the hemoglobin–oxygen dissociation curve. In the absence of symptomatic heart disease, most CKD patients tolerate anemia well.

Both platelet and white cell function are impaired in patients with kidney failure. Clinically, this is manifested as a prolonged bleeding time and increased susceptibility to infections, respectively. Most patients have decreased platelet factor III activity as well as decreased platelet adhesiveness and aggregation. Patients who have recently undergone hemodialysis may also have residual anticoagulant effects from heparin.

C. Cardiovascular

Cardiac output increases in kidney failure to maintain oxygen delivery due to decreased blood oxygen-carrying capacity. Sodium retention and abnormalities in the renin–angiotensin system result in systemic arterial hypertension. Left ventricular hypertrophy is a common finding in CKD. Extracellular fluid overload from sodium retention, in association with increased cardiac demand imposed by anemia and hypertension, makes CKD patients prone to congestive heart failure and pulmonary edema. Increased permeability of the alveolar–capillary membrane may also be a predisposing factor for pulmonary edema associated with CKD (see later discussion). Arrhythmias, including conduction blocks, are common, and may be related to metabolic abnormalities and to deposition of calcium in the conduction system. Uremic pericarditis may develop in some patients, who may be asymptomatic, may present with chest pain, or may present with cardiac tamponade. Patients with CKD also characteristically develop accelerated peripheral vascular and coronary artery atherosclerotic disease.

Intravascular volume depletion may occur in high-output acute kidney failure if fluid replacement is inadequate. Hypovolemia may occur secondary to excessive fluid removal during dialysis.

D. Pulmonary

Without RRT or bicarbonate therapy, CKD patients may be dependent on increased minute ventilation as compensation for metabolic acidosis (see Chapter 50). Pulmonary extravascular water is often increased in the form of interstitial edema, resulting in a widening of the alveolar to arterial oxygen gradient and predisposing to hypoxemia. Increased permeability of the alveolar–capillary membrane in some patients can result in pulmonary edema even with normal pulmonary capillary pressures.

E. Endocrine

Abnormal glucose tolerance is common in CKD, usually resulting from peripheral insulin resistance (type 2 diabetes mellitus is one of the most common causes of CKD). Secondary hyperparathyroidism in patients with chronic kidney failure can produce metabolic bone disease, predisposing to fractures. Abnormalities in lipid metabolism frequently lead to hypertriglyceridemia and contribute to accelerated atherosclerosis. Increased circulating levels of proteins and polypeptides normally degraded by the kidneys are often present, including parathyroid hormone, insulin, glucagon, growth hormone, luteinizing hormone, and prolactin.

F. Gastrointestinal

Anorexia, nausea, vomiting, and ileus are commonly associated with uremia. Hypersecretion of gastric acid increases the incidence of peptic ulceration and gastrointestinal hemorrhage, which occurs in 10% to 30% of patients. Delayed gastric emptying secondary to kidney disease–associated autonomic neuropathy may predispose patients to perioperative aspiration. Patients with CKD also have an increased incidence of hepatitis B and C, often with associated hepatic dysfunction.

G. Neurological

Asterixis, lethargy, confusion, seizures, and coma are manifestations of uremic encephalopathy, and symptoms usually correlate with the degree of azotemia. Autonomic and peripheral neuropathies are common in patients with CKD. Peripheral neuropathies are typically sensory and involve the distal lower extremities.

Preoperative Evaluation

Most perioperative patients with acute kidney failure are critically ill, and their kidney failure is frequently associated with trauma or perioperative medical or surgical complications. They are typically in a state of metabolic catabolism. Optimal perioperative management is dependent upon RRT. Hemodialysis is more effective than peritoneal dialysis and can be readily accomplished via a temporary internal jugular, subclavian, or femoral dialysis catheter. Continuous renal replacement therapy (CRRT) is often used when patients are too hemodynamically unstable to tolerate intermittent hemodialysis. Indications for RRT are listed in Table 31–7.

Patients with chronic kidney failure commonly present to the operating room for creation or revision of an arteriovenous dialysis fistula under local or regional anesthesia. Preoperative dialysis on the day of surgery or on the previous day is typical. However, regardless of the intended procedure or the anesthetic employed, one must be certain that the patient is in optimal medical condition; potentially reversible manifestations of uremia (see Table 31–5) should be addressed.

The history and physical examination should address both cardiac and respiratory function. Signs of fluid overload or hypovolemia should be sought. Patients are often relatively hypovolemic immediately following dialysis. A comparison of the patient’s current weight with previous predialysis and postdialysis weights may be helpful. Hemodynamic data and a chest radiograph, if available, are useful in confirming clinical suspicion of volume overload. Arterial blood gas analysis is useful in evaluating oxygenation, ventilation, hemoglobin level, and acid–base status in patients with dyspnea or tachypnea. The electrocardiogram should be examined for signs of hyperkalemia or hypocalcemia (see Chapter 49) as well as ischemia, conduction block, and ventricular hypertrophy. Echocardiography can assess cardiac function, ventricular hypertrophy, wall motion abnormalities, and pericardial fluid. A friction rub may not be audible on auscultation of patients with a pericardial effusion.

Preoperative red blood cell transfusions are usually administered only for severe anemia as guided by the patient’s clinical status. Bleeding time and coagulation studies (or perhaps a thromboelastogram) may be advisable, particularly if neuraxial anesthesia is being considered. Serum electrolyte, BUN, and creatinine measurements can assess the adequacy of dialysis. Glucose measurements guide the potential need for perioperative insulin therapy.

Drugs with significant renal elimination should be avoided if possible (Table 31–8). Dosage adjustments and measurements of blood levels (when available) are necessary to minimize the risk of drug toxicity.

Premedication

Alert patients who are stable can be given reduced doses of a benzodiazepine, if needed. Chemoprophylaxis for patients at risk for aspiration is reviewed in Chapter 17. Preoperative medications—particularly antihypertensive agents—should be continued until the time of surgery (see Chapter 21). The management of diabetic patients is discussed in Chapter 35.

INTRAOPERATIVE CONSIDERATIONS

Monitoring

Patients with kidney disease and failure are at increased risk for perioperative complications, and their general medical condition and the planned operative procedure dictate monitoring requirements. Because of the risk of thrombosis, blood pressure should not be measured by a cuff on an arm with an arteriovenous fistula. Continuous invasive or noninvasive blood pressure monitoring may be indicated in patients with poorly controlled hypertension.

Induction

Patients with nausea, vomiting, or gastrointestinal bleeding should undergo rapid-sequence induction. The dose of the induction agent should be reduced for debilitated or critically ill patients, or for patients who have recently undergone hemodialysis and who remain relative hypovolemic. Propofol, 1 to 2 mg/kg, or etomidate, 0.2 to 0.4 mg/kg, is often used. An opioid, β-blocker (esmolol), or lidocaine may be used to blunt the hypertensive response to airway instrumentation and intubation. Succinylcholine, 1.5 mg/kg, can be used to facilitate endotracheal intubation in the absence of hyperkalemia. Rocuronium (1 mg/kg), vecuronium (0.1 mg/kg), cisatracurium (0.15 mg/kg), or propofol–lidocaine induction without a relaxant may be considered for intubation in patients with hyperkalemia.

Anesthesia Maintenance

The ideal anesthetic maintenance technique should control hypertension with minimal deleterious effect on cardiac output, because increased cardiac output is the principal compensatory mechanism for tissue oxygen delivery in anemia. Volatile anesthetics, propofol, fentanyl, sufentanil, alfentanil, and remifentanil are satisfactory maintenance agents. Meperidine should be avoided because of accumulation of its metabolite normeperidine. Morphine may be used, but prolongation of its effects may occur.

Controlled ventilation should be considered for patients with kidney failure under general anesthesia. Inadequate spontaneous ventilation with progressive hypercarbia under anesthesia can result in respiratory acidosis that may exacerbate preexisting acidemia, lead to potentially severe circulatory depression, and dangerously increase serum potassium concentration (see Chapter 50). On the other hand, respiratory alkalosis may also be detrimental because it shifts the hemoglobin dissociation curve to the left, can exacerbate preexisting hypocalcemia, and may reduce cerebral blood flow.

Fluid Therapy

Superficial procedures involving minimal physiological trespass require replacement of insensible fluid losses only. In situations requiring significant fluid volume for maintenance or resuscitation, isotonic crystalloids, colloids, or both may be used (see Chapter 51). Current evidence suggests balanced crystalloids such as Plasma-Lyte or lactated Ringer’s solution are preferable in such circumstances to chloride-rich crystalloids such as 0.9% saline because of the deleterious effects of hyperchloremia on kidney function. However, 0.9% saline is preferable to balanced crystalloids in patients with alkalosis and hypochloremia. Lactated Ringer’s solution should be avoided in hyperkalemic patients when large fluid volumes are required, because it contains potassium 4 mEq/L. Glucose-free solutions should generally be used because of the glucose intolerance associated with uremia. Blood that is lost should generally be replaced with colloid or packed red blood cells as clinically indicated. Allogeneic blood transfusion may decrease the likelihood of kidney rejection following transplantation because of associated immunosuppression. Hydroxyethyl starch has been associated with increased risk of AKI and death when administered to critically ill patients or those with preexisting impaired kidney function, or when used for volume resuscitation. Its use in other circumstances is controversial at this time and the subject of many investigations. Intraoperative fluid therapy can be guided by noninvasive measurements of stroke volume and cardiac output.

PREOPERATIVE CONSIDERATIONS

The kidney normally possesses large functional reserve. GFR, as determined by creatinine clearance, can decrease from 120 to 60 mL/min without clinical signs or symptoms of diminished kidney function. Even patients with creatinine clearances of 40 to 60 mL/min usually are asymptomatic. These patients have only mild kidney impairment but should still be thought of as having decreased kidney reserve. Preservation of remaining kidney function is paramount, and best accomplished by maintaining normovolemia and normal kidney perfusion.

When creatinine clearance decreases to 25 to 40 mL/min, kidney impairment is moderate, and patients are said to have renal insufficiency. Azotemia is always present, and hypertension and anemia are common. Correct anesthetic management of this group of patients is as critical as management of those with frank kidney failure, especially during procedures associated with a relatively high incidence of postoperative kidney failure, such as cardiac and aortic reconstructive surgery. Intravascular volume depletion, sepsis, obstructive jaundice, crush injuries, and renal toxins such as radiocontrast agents, certain antibiotics, angiotensin-converting enzyme inhibitors, and NSAIDs (see Table 30–4) are additional major risk factors for acute deterioration in kidney function. Hypovolemia and decreased kidney perfusion are particularly important causative factors in the development of acute postoperative kidney failure. The emphasis in management of these patients is on prevention, because the mortality rate of postoperative kidney failure may surpass 50%. The combination of diabetes and preexisting kidney disease markedly increases perioperative risk of kidney function deterioration and of kidney failure.

Kidney protection with adequate hydration and maintenance of renal blood flow is indicated for patients at high risk for kidney injury and kidney failure. The use of mannitol, low-dose dopamine or fenoldopam infusion, loop diuretics, or bicarbonate infusion for kidney protection is controversial and without proof of efficacy (see earlier discussion). N-acetylcysteine, when given prior to the administration of radiocontrast agents, reduces the risk of radiocontrast agent–induced AKI (see Chapter 30).

INTRAOPERATIVE CONSIDERATIONS

Monitoring

The American Society of Anesthesiologists’ basic monitoring standards are used for procedures involving minimal fluid losses. For procedures associated with significant blood or fluid loss, close monitoring of hemodynamic performance and urinary output is important (see Chapter 51). Although maintenance of urinary output does not ensure preservation of kidney function, urinary outputs greater than 0.5 mL/kg/h are preferable. Continuous invasive blood pressure monitoring is also important if rapid changes in blood pressure are anticipated, such as in patients with poorly controlled hypertension and in those undergoing procedures associated with abrupt changes in sympathetic stimulation or in cardiac preload or afterload.

Induction

Selection of an induction agent is not as important as ensuring an adequate intravascular volume prior to induction; induction of anesthesia in hypovolemic patients with impaired kidney function frequently results in hypotension. Unless a vasopressor is administered, such hypotension typically resolves only following intubation or surgical stimulation. Kidney perfusion, which may already be compromised by preexisting hypovolemia, may then deteriorate further, first as a result of hypotension, and subsequently from sympathetically or pharmacologically mediated renal vasoconstriction. If sustained, the decrease in renal perfusion may contribute to postoperative kidney impairment or failure. Preoperative hydration usually prevents this sequence of events.

Maintenance of Anesthesia

All anesthetic maintenance agents are acceptable, with the possible exception of sevoflurane administered with low gas flows over a prolonged time period (see Chapter 30). Intraoperative deterioration in kidney function may result from adverse effects of the operative procedure (hemorrhage, vascular occlusion, abdominal compartment syndrome, arterial emboli) or anesthetic (hypotension secondary to myocardial depression or vasodilation), from indirect hormonal effects (sympathoadrenal activation or antidiuretic hormone secretion), or from impeded venous return secondary to positive-pressure ventilation. Many of these effects are avoidable or reversible when adequate intravenous fluids are given to maintain a normal or slightly expanded intravascular volume. The administration of large doses of predominantly α-adrenergic vasopressors (phenylephrine and norepinephrine) may also be detrimental to preservation of kidney function. Small, intermittent doses, or brief infusions, of vasoconstrictors may be useful in maintaining renal blood flow until other measures (eg, transfusion) are undertaken to correct hypotension.

Fluid Therapy

As reviewed earlier, appropriate fluid administration is important in managing patients with preexisting AKI or kidney failure or who are at risk for AKI. We find guidance from noninvasive monitors of stroke volume and cardiac output useful. Concern over fluid overload is justified, but acute problems are rarely encountered in such patients with normal urinary outputs if rational fluid administration guidelines and appropriate monitoring are employed (see Chapter 51). Moreover, the adverse consequences of excessive fluid overload are far easier to treat than those of AKI and kidney failure.