Safely guiding the patient with renal failure through the perioperative period presents a challenging set of problems such as the substantial comorbidity associated with chronic kidney disease (CKD), the risk of acute kidney injury (AKI), management of perioperative dialysis, and altered pharmacology.
Patients presenting with renal failure fall into two distinct classes: acute renal failure or chronic renal failure (CRF). Although acute and chronic renal failure are clinically separate entities, recent advances in epidemiology suggest a complex interplay between preexisting kidney disease, acute kidney injury, and the progression of CKD.
Acute Renal Failure
Patients might present with acute renal failure when arriving for surgery. This is often the case in an emergency surgery or a critically ill patient coming to the operating room from the intensive care unit. Traditionally, acute renal failure has been subdivided by etiology (prerenal azotemia, postrenal urinary tract obstruction, and intrinsic renal disease). This subdivision is helpful because it suggests a treatment approach such as percutaneous nephrostomy tube placement to treat urinary tract obstruction.
Advances in epidemiology reframed the classification system of acute renal failure by degree of injury and expected outcome. This classification system has gone through several versions in recent decades from RIFLE (risk, injury, failure, loss, end-stage renal disease [ESRD]) to AKIN (Acute Kidney Injury Network) to KDIGO (Kidney Disease: Improving Global Outcomes). All three systems share a common theme where increases in baseline creatinine or decreases in urine output are associated with adverse outcomes. The current internationally accepted grading system for AKI is provided by KDIGO ( Table 19.1 ). KDIGO stage 1 is characterized by a high sensitivity for AKI and stage 3 identifies patients at highest risk of needing renal replacement therapy. While the primary purpose of the KDIGO grading system is for research, it is useful for the perioperative physician to standardize their understanding of the degree of acute kidney injury.
|KDIGO stage||Creatinine Concentration||Urine Output|
|1||1.5–1.9 × baseline |
≥ 0.3 mg/dL above baseline
|< 0.5 mL/kg/h for 6–12 h|
|2||2.0–2.9 × baseline||< 0.5 mL/kg/h for > 12 h|
|3||≥ 3.0 × baseline |
Initiation of renal replacement therapy
|< 0.3 mL/kg/h for ≥ 24 h or anuria for ≥ 12 h|
Patients presenting for surgery with acute renal failure are a particularly comorbid group and deserve special attention. A recent large study of vascular surgery patients demonstrated AKI is an important indicator of perioperative harm in patients undergoing surgery. Managing patients with AKI is essentially the same as managing patients with CKD in that the goal is preservation of kidney function. Specific aspects of management will be discussed later in the chapter.
Chronic Renal Failure
Chronic renal failure indicates the progressive spectrum of CKD from a mild decrement in renal function to severe renal failure (also called ESRD). The term end-stage renal failure persists in the literature because it has important implications for dialysis coding in the United States. When a patient has progressed to ESRD, they require renal replacement therapy or transplantation to sustain life. Without these therapies they will die from pulmonary edema or hyperkalemia.
Physiologically, renal failure is a reduction in the number or function of nephrons in the kidney that leads to reduced ability to filter the blood. The National Kidney Foundation Disease Outcomes Quality Initiative (K/DOQI) provided a consensus definition of renal failure in 2002. This definition used a glomerular filtration rate of less than 60 mL/min/1.73m 2 lasting for more than 3 months to identify CKD. This step was important because it changed the conceptual framework for diagnosing CKD from a disease that only affected a few patients with end-stage kidney disease to a progressive disorder that affects a large percentage of the population. The K/DOQI definition further subdivided renal failure based on glomerular filtration rate into five classes ranging from CKD stage 1 (mild impairment of glomerular filtration) to CKD stage 5, more commonly referred to as ESRD as shown in Table 19.2 . In 2012, a second collaborative, Kidney Disease Improving Global Outcomes (KDIGO) issued an updated definition of chronic kidney disease that expanded on the previous definition to include albuminuria.
|Chronic Kidney Disease stage||Definition||GFR mL/min/1.73 m 2|
|1||Kidney damage with normal GFR||≥ 90|
|2||Kidney damage with mild decrease in GFR||60–89|
|3A||Mild-moderate decrease in GFR||45–59|
|3B||Moderate-to-severe decrease in GFR||30–44|
|4||Severe decrease in GFR||15–29|
|5||End-stage renal disease||< 15|
The modern perioperative physician interested in optimizing outcomes approaches CKD as a progressive spectrum rather than a dichotomous state (healthy versus renal failure) for four reasons discussed in following sections.
Chronic Kidney Disease Is Common
The global burden of CKD is substantial with a prevalence estimated at 8%–16%. Over one million deaths have been reported worldwide from CKD and the burden of CKD is increasing. In 1990, CKD was the 27th leading cause of death in the world, but by 2013 it had become the 13th leading cause of death in the world. CKD also significantly detracts from patients’ quality of life and is associated with cardiovascular mortality. The prevalence of earlier stages of CKD is 100 times greater than the prevalence of patients with ESRD requiring dialysis or transplantation, which is 0.1%. CKD is age-related: the median prevalence of CKD was about 7% in people older than 30 years of age but about 30% among patients 64 years or older. As the population of patients presenting for surgery increases there will be an increase in the perioperative prevalence of CKD.
A diverse set of pathologies contribute to the development of CKD ( Table 19.3 ). In the developed world, the leading causes of CKD are old age, diabetes, hypertension, obesity, and cardiovascular disease. The underlying pathological process is often difficult to discern exactly, but the two most common processes are diabetic glomerulosclerosis and hypertensive nephrosclerosis.
|Fluid and electrolyte disturbances|
|Hematologic and immunologic disturbances|
|Nutritional and metabolic disturbances|
Because of its overall prevalence, many patients presenting for surgery have CKD. Among those presenting for major surgery, 8% have CKD and 4% have end-stage renal failure. Among patients presenting for vascular surgery, the rate CKD is much higher, estimated at 30% in one study of patients presenting for carotid endarterectomy, probably reflecting the association between CKD and cardiovascular disease.
Chronic Kidney Disease Increases Cardiovascular Risk
Cardiovascular mortality is 30 times higher in patients with CKD and patients with CKD are more likely to die from cardiovascular causes than to progress to ESRD. Cardiovascular disease (CVD), in the form of hypertension, coronary artery disease (CAD), and congestive heart failure are the most common causes of morbidity and mortality in patients with CKD and account for greater than 50% of the mortality in this group.
Large population studies demonstrate that even mild CKD is associated with an increased risk of cardiovascular events, death, and hospitalization. Moderate CKD (GFR 15–29 mL/min/1.73 m 2 ) and severe CKD (eGFR less than 15 mL/min/1.73 m 2 without dialysis were associated with very high rates of adverse events almost as high as those with ESRD.
For patients with ESRD who are treated with dialysis, CVD mortality is 10 to 30 times higher than for patients in the general population. The etiology of CVD in patients with CKD is multifactorial, stemming from preexisting conditions (diabetes and hypertension), uremia (toxins, hyperlipidemia, and hyperhomocysteinemia), and for those with ESRD, dialysis-related conditions such as dialysis membrane reactions and hemodynamic instability episodes. Hypertension is the most common cardiovascular problem in patients with chronic renal disease (CRD). It is associated with further impairment of renal function and progression of CVD.
Patients with CKD often have co-occurring left ventricular hypertrophy that develops secondary to long-standing pressure and volume overload. Several CKD-related factors may contribute to the development of left ventricular hypertrophy, including chronic sodium and water retention leading to volume overload, increased cardiac output from an arteriovenous fistula, and chronic anemia. Pressure overload may result from increased afterload secondary to hypertension and arteriosclerosis that develops concomitantly with progressive CKD. It is important to identify left ventricular hypertrophy because it affects intraoperative management. Important points include sensitivity to adequate preload for a stiff ventricle and diastolic dysfunction, which may lead to flash pulmonary edema.
Myocardial infarction is a risk for patients with CKD. Patients with CKD often suffer from accelerated atherosclerosis because of the combination of hypertension, dyslipidemia, and often diabetes contributing to endothelial dysfunction. CKD can also contribute to accelerated atherosclerosis via the production of reactive oxygen species. Finally, increased calcifications lead to vascular calcifications, which can precipitate vascular injury.
The association between CVD and CKD has long been recognized in the perioperative arena. The most commonly used risk stratification system, the revised cardiac risk index (RCRI) for cardiac complications after noncardiac surgery, identifies preoperative serum creatinine > 2.0 mg/dL as an independent predictor of increased risk of cardiac complications.
Long-term hemodialysis through arteriovenous (AV) fistulas is associated with a 40% incidence of development of pulmonary hypertension. The reason for this is unclear and a corresponding development in patients undergoing peritoneal dialysis has not been demonstrated. Pulmonary pressures normalize in the majority of patients after kidney transplantation. The creation of AV fistulas may also lead to increased cardiac output, which further increases the cardiac workload. Pulmonary hypertension in a patient with an AV fistula is particularly at high risk of mortality. Congestive heart failure, which has a prevalence of 40% among hemodialysis and peritoneal dialysis patients, is an independent predictor of death.
Chronic Kidney Disease Is a Risk Factor for Acute Kidney Injury
Patients with preoperatively reduced kidney function are at risk of suffering acute or chronic kidney injury in the perioperative period. Preoperative renal failure is a risk factor for postoperative renal failure. The link between CKD and AKI risk is undergoing intense research.
Acute Kidney Injury Accelerates the Progression of Chronic Kidney Disease
There is an association between acute kidney injury, even minor acute kidney injury, and the subsequent development of chronic kidney disease in hospitalized patients. Hospitalized patients with preexisting CKD and AKI are 40 times more likely to progress to ESRD as those without CKD or AKI. Several mechanisms explaining the progression of CKD after AKI have been proposed including maladaptive repair, impaired regeneration, and ongoing organ dysfunction.
Pathophysiology of Chronic Renal Failure
Uremia occurs with ESRD when the kidney can no longer adequately filter blood and organic waste products accumulate. Uremia is a combination of symptoms that presents insidiously with increasing anorexia and lethargy. The classic signs and symptoms of advanced uremia include uremic pericarditis, uremic frost on the skin, headaches, nausea, seizures, and sleep disturbances. Untreated uremia may lead to coma and even death. However, the advanced complications of uremia are rarely seen because uremia can be reversed with dialysis or renal transplantation. Although temporarily reversible with dialysis, chronic exposure to uremia is associated with insulin resistance, oxidative stress, and systemic inflammation, which can accelerate both cardiovascular disease and kidney disease.
Urea is only one of the organic waste products that accumulate and is not closely linked to the signs and symptoms of uremia. Some of the other organic waste products include guanidines, which at appreciable levels in the cerebral spinal fluid correlate with altered mental function. Other nitrogen-containing solutes that accumulate include monomethylamine, dimethylamine, and trimethylamine, which are produced by human cells and gut microbiota. They represent the basic pathophysiologic disorder of uremia, i.e., defective ion transport across cell membranes, resulting in intracellular sodium and water accumulation. The only cure is to replace renal function, i.e., dialysis or transplantation. Uremia is an indication for dialysis and a harbinger of ESRD. A uremic patient in the perioperative period should be closely evaluated.
Fluid and Electrolyte Balance
Sodium and Water Homeostasis
Patients with severe renal disease, especially those on dialysis, are extremely sensitive to excess salt and water intake, which can cause hypervolemia, hypertension, and pulmonary edema. In patients with mild or stable CKD, the body’s sodium and water content are modestly increased. This chronic mild fluid overload can stimulate chronic low level inflammation and accelerate the progression of renal disease. One proposed mechanism is that the chronic edema alters gut permeability releasing inflammatory mediators. One of the essential functions of the kidney is to manage sodium homeostasis. Patients with impaired renal function are unable to tolerate sodium loading either through dietary intake or iatrogenic from large volumes of saline solution. Large volumes of saline solution will result in hyperchloremic metabolic acidosis in patients with impaired renal function. The hypercholeremia may reduce renal blood flow and GFR.
In contrast, patients with ESRD have impaired mechanisms for conserving sodium, which can lead to volume depletion. This makes patients with ESRD particularly prone to the deleterious effects of extrarenal fluid losses such as diarrhea, vomiting, and sweating. The resulting hypovolemia can worsen prerenal kidney disease and result in acute renal failure. In some cases, gentle volume loading may be considered in the perioperative period.
Hyperkalemia is a frequent safety event for patients with CKD. One reason that patient with CKD are at risk of hyperkalemia is that many of the medications that treat CKD increase the risk of hyperkalemia (potassium > 5.5). Acute hyperkalemia may suppress electrical conduction in the heart leading to asystolic cardiac arrest. Hyperkalemic asystolic cardiac arrest is often preceded by prolonged PR interval, widened QRS, and tall peaked T waves, but be aware that hyperkalemic asystole has been reported without these electrocardiogram (ECG) changes.
Patients with stage 5 CKD are at risk of developing hyperkalemia for several reasons either from exogenous potassium or transcellular potassium shifts caused by acidosis or insulin deficiency. Beta blockers may increase the risk of hyperkalemia. Other important causes of hyperkalemia in a patient with CKD include: rhambomyolysis secondary to trauma or major surgery, catabolic state such as sepsis, non-steroidal anti-inflammatory drugs (NSAIDS), angiotensin-converting enzyme inhibitors, potassium sparing diuretics, nephrotoxic drugs such as cyclosporine or aminoglycosides, or radiocontrast material ( Table 19.4 ).
Hyperkalemia is an indication for perioperative dialysis. Some patients with CRF tolerate stable potassium levels of 6 to 6.5 mmol/L without showing any conduction disturbances. However, if potassium levels increase to higher than that, these patients may rapidly show signs of hyperkalemia.
A preoperative potassium level of 6 mmol/L or greater should be corrected before the start of anesthesia unless there is a dire emergency. Treatment alternatives for lowering potassium level consist of normalizing pH if acidosis is present, and intravenous administration of insulin or glucose and/or a beta-2-adrenergic agonist, all of which work by shifting potassium into the cells. Dialysis or administration of sodium polystyrene sulfonate, either orally or as an enema, removes potassium ions.
Hypokalemia in patients with CKD usually reflects diuretic use. A study in cardiac surgery patients demonstrated that preoperative hypokalemia was associated with serious perioperative arrhythmias. More rarely, hypokalemia is associated with primary renal potassium wasting, as seen in Fanconi syndrome, Bartter syndrome, and renal tubular acidosis. Acute hypokalemia increases excitability and lowers the arrhythmia threshold. Both supraventricular and ventricular arrhythmias may occur. These may be refractory to normal antiarrhythmic treatment until the serum potassium concentration is normalized.
Magnesium dysregulation in CKD can result in complications and may result from inadequate dialysis. Hypermagnesemia may cause muscle weakness and potentiate nondepolarizing muscle relaxants. Hypomagnesemia may result in the development of both supraventricular and ventricular arrhythmias.
Calcium Phosphate Balance
Secondary hyperparathyroidism is common in patients with CKD. Dysregulated calcium and phosphate balance is a hallmark of CKD. Phosphate is regulated by renal extraction. A decrement in glomerular filtration rate allows for the accumulation of phosphate. Retained phosphate directly stimulates parathyroid hormone (PTH) synthesis and indirectly causes PTH release by lowering ionized calcium levels and suppressing calcitriol production. Calcitriol is necessary for calcium absorption from the gastrointestinal (GI) tract. Without calcitriol, ionized calcium levels fall, stimulating PTH secretion and proliferation of parathyroid cells. This syndrome is called hyperparathyroidism.
Secondary hyperparathyroidism ultimately leads to high bone resorption and turnover, abnormal osteoid production, and weak bone strength. Consequently, these patients are at high risk of fractures.
A rare but interesting complication of abnormal calcium-phosphate production is calciphylaxis in which extraosseous calcifications accumulate in soft tissues and blood vessels. This can even cause a painful itchy rash when deposited in the skin. Accelerated calcification of coronary arteries may be one factor predisposing progressive coronary artery disease in patients with CKD and similarly accelerate deposition in arteries and arterioles, causing stiff arterioles and blood vessels. Phosphate binders such as sevelamer are typically given to these patients. Sometimes these patients are also treated with bisphosphonates.
Patients with mild CKD typically present with a mild, chronic anion-gap metabolic acidosis. These patients are unable to excrete acid adequately because the failing kidney cannot synthesize ammonia. Consequently, they develop a metabolic acidosis with reduced plasma bicarbonate. This chronic metabolic acidosis is often treated in the outpatient setting with oral sodium bicarbonate. A recent systemic review allayed concerns that IV sodium bicarbonate caused hypotension and volume overload. It may be necessary to treat patients with IV sodium bicarbonate in the perioperative period.
But be aware that the reduced bicarbonate leads to the CKD patient’s reduced ability to buffer an acid load. Therefore, postoperative respiratory or lactic acidosis can quickly become severe. A common consequence of this is severe hyperkalemia.
Vascular access can be particularly vexing for the perioperative physician taking care of the patient with ESRD. Patients treated with dialysis or those soon to need dialysis require preservation of vascular access. Vascular access can be maintained either through arteriovenous fistula (AVF), arteriovenous graft (AVG), or long- or short-term catheters. Long-term catheters are often tunneled. For long-term dialysis, AVF is preferable to tunneled catheters because it has demonstrated reduced mortality probably because of a reduced risk of infection. However, creating an arteriovenous fistula requires surgery and several months to mature before it can be used. Importantly, in patients who might need dialysis, the cephalic vein should be preserved by limiting access.
When AVF may take too long to develop, the K/DOQI guidelines suggest using a tunneled dialysis catheter for dialysis. These may be cuffed or uncuffed. It is recommended to avoid using these for indications other than dialysis and the patient will require that catheter for life-sustaining dialysis treatment. The preferred placement for tunneled catheters is the inferior jugular vein because subclavian vein placement can lead to stenosis with nearly 50% of patients with subclavian vein catheters demonstrating subclavian vein stricture, which can make fistulas unusable. Femoral placement should be avoided in patients who may receive renal transplant because external iliac vein stenosis will interfere with blood flow to the graft.
Anemia is common among patients with CKD and particularly severe among those with ESRD. The main culprit for anemia in this population is depressed erythropoietin-stimulating agent (ESA) production by failing kidneys where it is synthesized. The situation is exacerbated by vitamin deficiencies such as B12, iron, and folate deficiency. Furthermore, chronic blood loss and hemolysis from dialysis reduce red blood cells. Finally, chronic inflammation induces a perpetual anemia of chronic disease. The typical anemia in CKD/ESRD is normochromic, normocytic anemia. The introduction of erythropoietin in 1989 and the analog darbopoetin alpha, into the treatment of patients with ESRD has improved quality of life and reduced the need for transfusions. For patients who are chronically anemic, current guidelines suggest maintaining blood levels at 9.5–11 g per 100 mL. Lower hemoglobin levels constitute a perioperative risk.
Uremic Bleeding Diathesis
Patients with CKD tend to have a bleeding diathesis, which can be severe. The bleeding tendency is primarily related to platelet dysfunction, specifically decreased activity of platelet factor III, abnormal platelet aggregation, abnormal interaction between platelets and vessel walls, and defective release of von Willebrand factor. Patients with CRF are therefore at risk of surgical bleeding, GI tract bleeding, intracranial hemorrhage, and hemorrhagic pericardial effusion. Despite the hemostatic effect there is also a tendency toward hypercoagulability and thrombosis. The bleeding tendency is improved by dialysis, which is the principal treatment, but infusion of desmopressin (DDAVP), cryoprecipitate, and conjugated estrogens may be of value for temporary treatment.
Gastritis, peptic ulcer disease, and mucosal ulcerations, which can occur at any level of the GI tract, are common in uremic patients. Symptoms include abdominal pain, hiccups, nausea, vomiting, and bleeding. Bleeding may be exacerbated by uremic hemostasis defects and use of heparin during hemodialysis. Central nervous system effects of uremia contribute to worsening of hiccups, nausea, and vomiting. Patients with ESRD are therefore at increased risk of regurgitation and aspiration at induction of and emergence from anesthesia.
Nutritional and Metabolic Disturbances
Patients with CRD have impaired glucose and fat metabolism and are prone to hyperglycemia and hypertriglyceridemia because of increased peripheral insulin resistance and decreased lipoprotein lipase activity. This contributes to the high incidence of CAD in patients with CRD. These patients are often on a protein-restricted diet to reduce nausea and vomiting, which, in combination with deficient caloric intake or utilization, makes them susceptible to malnutrition. Hypoalbuminemia and decreased colloid oncotic pressure tend to promote interstitial fluid accumulation. In the lungs, this leads to decreased functional residual capacity and ventilatory reserve, increasing the risk for postoperative pulmonary complications.
Central, peripheral, and autonomic nervous system neuropathies are common in patients with CRD. Retained nitrogenous metabolites and disturbed calcium homeostasis all contribute to the various manifestations of central neuropathy. Early signs and symptoms include disturbances in memory, concentration, and sleep. Later, neuromuscular irritability with hiccups, cramps and muscle fasciculations become evident. Full-blown encephalopathy with myoclonus, seizures, and coma may develop, often precipitated by major surgery or GI bleeding. Uremic encephalopathy is associated with slow delta waves on the electroencephalogram, and magnetic resonance imaging may reveal increased signal intensity in a characteristic pattern in the occipital and parietal lobes. The treatment is dialysis.
Peripheral neuropathy is very common in patients with ESRD. Manifestations include loss of vibration sense and asymmetric and symmetric neural deficits. Another common deficit is the “glove and stocking” sensory distribution, with pain or sensory loss affecting distal nerves.
The presence of peripheral neuropathy should always trigger an awareness of the possible coexistence of autonomic neuropathy. Important consequences of autonomic dysfunction include silent myocardial ischemia, orthostatic hypotension, impaired circulatory responses to anesthetic and surgical stress, and impaired gastric emptying, which increases the risk for aspiration.
The combination of uremia, anemia, and poor nutritional status induces a state of decreased resistance to infections in patients with ESRD. It is based both on leukocyte dysfunction (depressed chemotaxis, phagocytosis and bactericidal activity) and on immunosuppression (e.g., reduced interleukin-2 production and hypogammaglobulinemia) and is associated with increased mortality. Infections are particularly common, both localized at shunt and peritoneal catheter sites and disseminated in the form of sepsis. Additional infection risks stem from the impaired wound healing seen in these patients, which results in slow-healing or nonhealing wounds after surgery and a tendency for bedsore development.
Pharmacology in Chronic Renal Failure
The pharmacodynamics and pharmacokinetics of certain drugs may be affected by CKD, which may alter excretion and disposition of drugs, the latter through changes in plasma protein binding and hepatic metabolism.
Elimination of water-soluble, highly ionized drugs is highly dependent on renal excretion. Therefore, depending on the severity of renal failure, excretion of such drugs may be markedly impaired. Digoxin and certain antibiotics and muscle relaxants belong to this group. Drugs that are partially dependent on renal elimination (e.g., atropine, glycopyrrolate, neostigmine, pancuronium, and vecuronium) may show significant prolongation of action ( Table 19.5 ).
|Drugs chiefly dependent on renal excretion|
|Drugs partially dependent on renal excretion|
Thiopental and benzodiazepines, frequently used in anesthesia practice, are highly protein bound and increase their unbound free fraction in the presence of uremic conditions (hypoalbuminemia and acidemia) and may demonstrate exaggerated clinical effects. Depending on the timing and effectiveness of dialysis, the volume of distribution for drugs may be increased in addition to the plasma volume, which tends to prolong elimination half-life and also counteracts the effects of the increased free fraction of protein-bound drugs.
Many drugs are lipid soluble and depend on hepatic metabolism and/or glucuronization to generate water-soluble compounds that can be excreted by the kidneys. If these compounds maintain some or all of the parent drug’s pharmacologic activity, their clinical effects may be quite prolonged ( Table 19.2 ). Another risk is that such accumulated metabolites may have toxic effects when their concentrations increase ( Table 19.2 ).
CRF is often a debilitating condition. Many patients have reduced muscle mass and other characteristics, with the result that pharmacodynamic effects are altered. It is therefore prudent, when the clinical situation allows, to titrate drugs to effect rather than to administer “normal” doses of drug.
Choice of Anesthetic Technique
Patients with ESRD pose a significant challenge to the perioperative clinician. Dialysis increases not only the risk of comorbidities but also the challenges of renal replacement therapy before, after, and even during surgery.
At the preoperative visit, the history-taking should focus on the cause of ESRD and manifestations of systemic disease, keeping in mind that myocardial ischemia may be silent in diabetic patients. The autonomic neuropathy in such patients may also impair circulatory responses to anesthesia and surgery. Bleeding, encephalopathy, and neuropathy are other possible and important complications of ESRD that should be ascertained. Whether or not the patient is anuric has significant impact on the planning of fluid management.
Patients on dialysis are not in a homeostatic state. Information on the type of dialysis, frequency, and most recent treatment is important. In most nonurgent surgery patients, the ideal timing of hemodialysis is the day before surgery. This avoids immediate dialysis-related complications, such as rebound heparinization, hypovolemia, hypokalemia, and dysequilibrium syndrome. Ideally, patients should be normovolemic and their potassium should be no higher than 6 mmol/L on the day of surgery. A blood urea nitrogen (BUN) value below 100 mg/L usually keeps coagulopathy and encephalopathy under control. However, this BUN level neither guarantees normal platelet function nor improves immunity and the impaired wound healing that often occur postoperatively.
Individuals with a prior history of perioperative uremic bleeding should be treated before surgery. In addition to dialysis, cryoprecipitate and/or intravenous or intranasal administration of desmopressin, 0.3 μg/kg, should be considered.
General anesthesia is the most common choice for surgical procedures, although regional anesthesia is successfully used in many cases (see later). Before induction of anesthesia, the patient’s volume status should be evaluated. If the patient has had recent dialysis (within 12 hours), consider fluid loading with 250 to 500 mL fluid prior to induction. Gastric emptying is delayed in uremic patients and they should always be treated as having risk of aspiration.
Thiopental has an increased free fraction in patients who have CRD and hypoalbuminemia, and it is recommended that the induction dose be decreased in these patients. Etomidate also has an increased free fraction, which does not seem to be of clinical importance. Propofol’s pharmacokinetic and pharmacodynamic properties are unchanged in patients with CRD. Its safe use in patients with renal failure has been documented. Ketamine is less extensively protein bound than thiopental and its free fraction is unaffected by renal failure. However, ketamine has the potential of causing impressive increases in blood pressure if it is used in hypertensive patients with CKD and its use should be limited to emergency anesthetic induction.
Patients with ESRD may have reduced bowel motility secondary to uremic neuropathy and co-occurring diabetes. Therefore, rapid sequence induction should be considered to reduce the risk of aspiration. Succinylcholine can be safely used in patients with ESRD. However, a serum potassium should be checked first and only used if the potassium concentration is less than 5.5 mmol/L. The effect of increased potassium with succinylcholine induction may be more pronounced in patients with ESRD because of already depressed cardiac function. Alternatively, rocuronium will not increase potassium levels but its effect will be significantly prolonged in patients with renal failure. Vecuronium effects will also be prolonged in patients with renal failure. Cisatracurium is an ideal maintenance agent for neuromuscular blockage because it undergoes Hoffman elimination in blood and tissue, a process that is totally independent of renal function, and unlike atracurium, does not cause histamine release. Caution should be used when rapid sequence induction with rocuronium is used and cisatracurium is used for maintenance as it could have synergistic effect that delays recovery from paralysis.
In all cases, neuromuscular monitoring throughout the case and full reversal is warranted. It should be noted that the suggamadex–rocuronium complex is entirely renally cleared and therefore suggamedex should not be used in patients with ESRD who have received rocuronium until further studies demonstrate safety in this regard.
The use of morphine and meperidine is of concern in patients with CRF. Both have metabolites that are dependent on renal elimination ( Table 19.6 ). Normeperidine, the active metabolite of meperidine, accumulates in patients with renal failure after repeated doses or continuous infusion and may cause seizures. About 10% of morphine is metabolized to morphine-6-glucuronide, which is a very potent sedative and dependent on excretion by the kidney. This metabolite may accumulate to 10–15 times its normal concentration in cerebrospinal fluid in patients with CRF. The pharmacokinetic and pharmacodynamic profiles of fentanyl, remifentanil, and sufentanil are not significantly influenced by renal failure. They can therefore be used with little or no modification of their dosage.