Johns 

Hopkins Medical School
Access Provided by:

Morgan & Mikhail's Clinical Anesthesiology, 6e

Chapter 31: Anesthesia for Patients with Kidney Disease

KEY CONCEPTS

KEY CONCEPTS

The utility of a single serum creatinine measurement as an indicator of glomerular filtration rate (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 the serum creatinine concentration often
does not accurately reflect GFR in the physiological disequilibrium of acute kidney injury (AKI).

Creatinine clearance measurement is the most accurate method available for clinically assessing overall kidney function.

The accumulation of morphine and meperidine metabolites has been reported to prolong respiratory depression in patients with kidney
failure.

Succinylcholine can be safely used in patients with kidney failure in the absence of hyperkalemia at the time of induction.

Extracellular fluid overload from sodium retention, in association with increased cardiac demand imposed by anemia and hypertension,
makes patients with end-stage kidney disease particularly prone to congestive heart failure and pulmonary edema.

Delayed gastric emptying secondary to kidney disease–associated autonomic neuropathy may predispose patients to perioperative
aspiration.

Controlled ventilation should be considered for patients with kidney failure under general anesthesia. Inadequate spontaneous or assisted
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.

Correct anesthetic management of patients with renal insufficiency 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 nonsteroidal antiinflammatory drugs, are major risk factors for acute deterioration
in kidney function.

Kidney protection with adequate hydration and maintenance of renal blood flow is especially important for patients at high risk for AKI and
kidney failure undergoing cardiac, major aortic reconstructive, and other surgical procedures associated with significant physiological
trespass. The use of mannitol, low-dose dopamine infusion, loop diuretics, or fenoldopam for kidney protection is controversial and without
proof of efficacy.

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,
Downloaded 2020­12­20 7:2 A  Your IP is 162.129.251.104
multiple myeloma, and age greater than 55 years. The risk of perioperative AKI is also increased by exposure to nephrotoxic agents such asPage 1 / 21
Chapter 31: Anesthesia for Patients with Kidney Disease,
©2020 McGraw Hill. All Rights Reserved.   Terms of Use • Privacy Policy • Notice • Accessibility
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).
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
Johns Hopkins Medical School
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
Access Provided by:

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).

FIGURE 31–1

Differential diagnosis and evaluation of acute kidney injury (AKI). ANA, antinuclear antibody; ANCA, antineutrophil cytoplasmic antibody; Anti-ds-DNA,
anti–double stranded DNA; Anti-GMB, anti–glomerular basement membrane; C3, complement component 3; C4, complement component 4; CK,
creatine kinase; CK-MB, creatine kinase MB fraction; ENA, extractable nuclear antigen; HIV, human immunodeficiency virus; HUS, hemolytic uremic
syndrome; LDH, lactate dehydrogenase; NT-proBNP, N-terminal pro-brain natriuretic peptide; TTP, thrombotic thrombocytopenic
purpura. (Reproduced with permission from Ostermann M, Joannidis M. Acute kidney injury 2016: Diagnosis and diagnostic workup. Crit Care. 2016
Sep 27;20(1):299.)

EVALUATING KIDNEY FUNCTION

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.

TABLE 31–1
Severity of kidney injury according to glomerular function.

Creatinine Clearance (mL/min)

Normal 100–120
Downloaded 2020­12­20 7:2 A  Your IP is 162.129.251.104
Chapter 31: Anesthesia for Patients with Kidney Disease, Page 2 / 21
Decreased kidney reserve 60–100
©2020 McGraw Hill. All Rights Reserved.   Terms of Use • Privacy Policy • Notice • Accessibility

Mild kidney impairment 40–60

excretory function assessed via serum creatinine and urine output ignores endocrine, metabolic, and immunological kidney functions. A great deal of
Johns Hopkins Medical School
research is currently evaluating plasma and urine biomarkers associated with AKI, such as cystatin C, neutrophil gelatinase–associated lipocalin,
Access Provided by:
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.

TABLE 31–1
Severity of kidney injury according to glomerular function.

Creatinine Clearance (mL/min)

Normal 100–120

Decreased kidney reserve 60–100

Mild kidney impairment 40–60

Moderate kidney insufficiency 25–40

Kidney failure <25

End-stage kidney disease1 <10

1This term applies to patients with chronic kidney failure.

TABLE 31–2

Laboratory evaluation of kidney impairment.1 , 2

Diagnostic Test Strenghts Weaknesses

Serum creatinine Easily available Not renal-specific

Low cost Late marker after renal injury

Serum levels confounded by muscle mass, drugs,

laboratory technique, fluid status

Blood urea nitrogen Easily available Not renal-specific

Low cost Serum levels confounded by liver disease,

gastrointestinal bleed, and hypovolemia

FeNa Easily available Difficult to interpret in patients with chronic kidney

disease

Low cost Confounded by diuretic treatment

Urine microscopy Noninvasive Operator-dependent

Low cost Requires training and experience

Can provide very valuable information if done properly, (i.e., red cell
casts in case of glomerulonephritis)

Renal histology Can provide very valuable information about cause of AKI and Invasive
degree of chronic changes Requires competency
Downloaded 2020­12­20 7:2 A  Your IP is 162.129.251.104 Bleeding complications
Chapter 31: Anesthesia for Patients with Kidney Disease, Page 3 / 21
©2020 McGraw Hill. All Rights Reserved.   Terms of Use • Privacy Policy • Notice • Accessibility
Novel AKI biomarkers Opportunity to diagnose AKI before creatinine rise Costs
 End-stage kidney disease1 <10
Johns Hopkins Medical School
Access Provided by:

1This term applies to patients with chronic kidney failure.

TABLE 31–2

Laboratory evaluation of kidney impairment.1 , 2

Diagnostic Test Strenghts Weaknesses

Serum creatinine Easily available Not renal-specific

Low cost Late marker after renal injury

Serum levels confounded by muscle mass, drugs,

laboratory technique, fluid status

Blood urea nitrogen Easily available Not renal-specific

Low cost Serum levels confounded by liver disease,

gastrointestinal bleed, and hypovolemia

FeNa Easily available Difficult to interpret in patients with chronic kidney

disease

Low cost Confounded by diuretic treatment

Urine microscopy Noninvasive Operator-dependent

Low cost Requires training and experience

Can provide very valuable information if done properly, (i.e., red cell
casts in case of glomerulonephritis)

Renal histology Can provide very valuable information about cause of AKI and Invasive
degree of chronic changes Requires competency
Bleeding complications

Novel AKI biomarkers Opportunity to diagnose AKI before creatinine rise Costs

May provide additional diagnostic and prognostic information Significant confounders

Techniques to measure Opportunity to monitor GFR in real time and to diagnose AKI early Costs
real-time GFR Not yet available in clinical practice
Requires training and experience

1Reproduced with permission from Ostermann M. Diagnosis of acute kidney injury: Kidney Disease Improving Global Outcomes criteria and beyond. Curr Opin Crit.

2014 Dec;20(6):581-587.

2AKI, acute kidney injury; FeNa, fractional excretion of sodium; GFR, glomerular filtration rate.

TABLE 31–3

RIFLE, AKIN, and KDIGO classifications for acute kidney injury.1 , 2

Serum Creatinine Criteria Urine Output

Downloaded 2020­12­20 7:2 A  Your IP is 162.129.251.104
Criteria of All
Chapter 31: Anesthesia for Patients with Kidney Disease, Page 4 / 21
RIFLE Classification AKIN Classification KDIGO Classification
©2020 McGraw Hill. All Rights Reserved.   Terms of Use • Privacy Policy • Notice • Accessibility Classifications

Definition Increase in serum creatinine of either ≥0.3 Rise in serum creatinine by ≥26
 1Reproduced with permission from Ostermann M. Diagnosis of acute kidney injury: Kidney Disease Improving Global Outcomes criteria and beyond. Curr Opin Crit.
Johns Hopkins Medical School
2014 Dec;20(6):581-587. Access Provided by:

2AKI, acute kidney injury; FeNa, fractional excretion of sodium; GFR, glomerular filtration rate.

TABLE 31–3

RIFLE, AKIN, and KDIGO classifications for acute kidney injury.1 , 2

Serum Creatinine Criteria Urine Output

Criteria of All
RIFLE Classification AKIN Classification KDIGO Classification Classifications

Definition Increase in serum creatinine of either ≥0.3 Rise in serum creatinine by ≥26
of AKI mg/dL (≥26.4 μmol/L) or a percentage μmol/L over ≤48 h, or to ≥1.5-fold
increase of ≥50% (1.5-fold from baseline) in from baseline which is known or
48 h presumed to have occurred in the
preceding 7 days

Stage I or Increase in serum creatinine to Increase in serum creatinine by ≥26 μmol/L Rise in serum creatinine by ≥26.5 <0.5mL/kg/h for
RIFLE risk ≥1.5 to 2-fold from baseline, or (>0.3mg/dL) or increase to more than or μmol/L in 48 h, or rise to 1.5–1.9 >6 h
GFR decrease by >25% equal to 1.5-fold to 2-fold from baseline times from baseline

Stage II Increase in serum creatinine to Increase in serum creatinine to more than 2- Rise in serum creatinine 2.0–2.9 <0.5 mL/kg/h for
or RIFLE >2-fold to 3-fold from baseline, fold to 3-fold from baseline times from baseline >12 h
injury or GFR decrease by >50%

Stage III Increase in serum creatinine to Increase in serum creatinine to more than 3- Rise in serum creatinine three times <0.3 mL/kg/h for
or RIFLE >3-fold from baseline, or to ≥354 fold from baseline, or to ≥354 μmol/L with an from baseline, or increase in serum 24 h or more, or
failure μmol/L with an acute rise of at acute rise of at least 44 μmol/L, or treatment creatinine to ≥353.6 μmol/L, or anuria for 12 h
least 44 μmol/L, or GFR decrease with RRT irrespective of the stage at the time initiation of RRT irrespective of
by >75% of RRT serum creatinine

RIFLE Complete loss of kidney — —

loss function for >4 wk

End- End-stage kidney disease for >3 — —

stage mo
kidney
disease

1Reproduced with permission from Ostermann M. Diagnosis of acute kidney injury: Kidney Disease Improving Global Outcomes and beyond. Curr Opin Crit Care.

2014 Dec;20(6):581-587.

2AKI, acute kidney injury; AKIN, Acute Kidney Injury Network; GFR, glomerular filtration rate; KDIGO, Kidney Disease Improving Global Outcomes; RIFLE, Risk, Injury,

Failure, Loss, End-Stage; RRT, renal replacement therapy.

FIGURE 31–2

Factors affecting serum creatinine interpretation in acute kidney injury. *Edematous states: cirrhosis, nephrotic syndrome, heart failure. DKA, diabetic
ketoacidosis; eGFR, estimated glomerular filtration rate. (Reproduced with permission from Thomas MD, Blaine C, Dawnay A, et al. The definition of
acute kidney injury and its use in practice. Kidney Int. 2015 Jan;87(1):62-73.)

Downloaded 2020­12­20 7:2 A  Your IP is 162.129.251.104
Chapter 31: Anesthesia for Patients with Kidney Disease, Page 5 / 21
©2020 McGraw Hill. All Rights Reserved.   Terms of Use • Privacy Policy • Notice • Accessibility
FIGURE 31–2

Johns Hopkins Medical School
Factors affecting serum creatinine interpretation in acute kidney injury. *Edematous states: cirrhosis, nephrotic syndrome, heart failure. DKA, diabetic
Access Provided by:
ketoacidosis; eGFR, estimated glomerular filtration rate. (Reproduced with permission from Thomas MD, Blaine C, Dawnay A, et al. The definition of
acute kidney injury and its use in practice. Kidney Int. 2015 Jan;87(1):62-73.)

FIGURE 31–3

AKI biomarkers. α-GST, α-glutathione S-transferase; AAP, alanine aminopeptidase; ALP, alkaline phosphatase; γ-GT, γ-glutamyl transpeptidase; n-GST,
n-glutathione S-transferase; HGF, hepatocyte growth factor; IGFBP-7, insulin-like growth factor binding protein 7; IL-18, inteleukin-18; KIM-1, kidney
injury molecule-1; L-FABP, liver fatty acid-binding protein; NAG, N-acetyl-β-D-glucosaminidase; NGAL, neutrophil gelatinase-associated lipocalin; RBP,
retinol-binding protein; TIMP-2, tissue inhibitor metalloproteinase-2. (Reproduced with permission from Ostermann M, Joannidis M. Acute kidney
injury 2016: Diagnosis and diagnostic workup. Crit Care. 2016 Sep 27;20(1):299.)

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:

2NH3 + CO2 → H2N − CO − NH2 + H2O

Downloaded 2020­12­20 7:2 A  Your IP is 162.129.251.104
Chapter 31: Anesthesia for Patients with Kidney Disease, Page 6 / 21
©2020 McGraw Hill. All Rights Reserved.   Terms of Use • Privacy Policy • Notice • Accessibility
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
BLOOD UREA NITROGEN Johns Hopkins Medical School
Access Provided by:
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:

2NH3 + CO2 → H2N − CO − NH2 + H2O

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.

FIGURE 31–4

The relationship between the serum creatinine concentration and the glomerular filtration rate.

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.
Downloaded 2020­12­20 7:2 A  Your IP is 162.129.251.104
Chapter 31: Anesthesia for Patients with Kidney Disease, Page 7 / 21
CREATININE CLEARANCE
©2020 McGraw Hill. All Rights Reserved.   Terms of Use • Privacy Policy • Notice • Accessibility

Creatinine clearance measurement is the most accurate method available for clinically assessing overall kidney function (actually, GFR). Although
 Johns Hopkins Medical School
Access Provided by:

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.

ALTERED KIDNEY FUNCTION & THE EFFECTS OF ANESTHETIC AGENTS

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
Downloaded 2020­12­20 7:2 A  Your IP is 162.129.251.104
patients with hypoalbuminemia may enhance its pharmacological effects.
Chapter 31: Anesthesia for Patients with Kidney Disease, Page 8 / 21
©2020 McGraw Hill. All Rights Reserved.   Terms of Use • Privacy Policy • Notice • Accessibility
Barbiturates
kidney failure.
Johns Hopkins Medical School
INTRAVENOUS AGENTS
Access Provided by:

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
Downloaded 2020­12­20 7:2 A  Your IP is 162.129.251.104
Chapter 31: Anesthesia for Patients with Kidney Disease, Page 9 / 21
failure; this observation may be explained by a decrease in the blood:gas partition coefficient or by a decrease in minimum alveolar concentration.
©2020 McGraw Hill. All Rights Reserved.   Terms of Use • Privacy Policy • Notice • Accessibility
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
INHALATION AGENTS
Johns Hopkins Medical School
Volatile Agents
Access Provided by:

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
Downloaded 2020­12­20 7:2 A  Your IP is 162.129.251.104
therapy (RRT).
Chapter 31: Anesthesia for Patients with Kidney Disease, Page 10 / 21
©2020 McGraw Hill. All Rights Reserved.   Terms of Use • Privacy Policy • Notice • Accessibility
ANESTHESIA FOR PATIENTS WITH KIDNEY FAILURE
blockade are usually related to other factors (see Chapter 11). Thus, “recurarization” due to inadequate duration of reversal agent is unlikely.
Johns Hopkins Medical School
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 Access Provided by:
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).

ANESTHESIA FOR PATIENTS WITH KIDNEY FAILURE

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.

TABLE 31–4

Management priorities in patients with acute kidney failure.1

Search for and correct prerenal and postrenal causes

Review medications and patient-administered substances and stop any potential nephrotoxins
Administer medications in doses appropriate for their clearance
Optimize cardiac output and renal blood flow
Monitor fluid intake and output; measure body weight daily
Search for and treat acute complications (hyperkalemia, hyponatremia, acidosis, hyperphosphatemia, pulmonary edema)
Search for and aggressively treat infections and sepsis
Provide early nutritional support
Provide expert supportive care (management of catheter and skin care; pressure sore and deep venous thromboembolic prophylaxis; psychological
support).

1Reproduced with permission from Lameire N, Van Biesen W, Vanholder R. Acute renal failure. Lancet. 2005 Jan 29-Feb 4;365(9457):417-430.

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.
Downloaded 2020­12­20 7:2 A  Your IP is 162.129.251.104
TABLE 31–5
Chapter 31: Anesthesia for Patients with Kidney Disease, Page 11 / 21
Manifestations of chronic kidney disease.
©2020 McGraw Hill. All Rights Reserved.   Terms of Use • Privacy Policy • Notice • Accessibility
Chronic Kidney Disease
Johns Hopkins Medical School
Access Provided by:
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.

TABLE 31–5
Manifestations of chronic kidney disease.

Neurological Metabolic
 Peripheral neuropathy  Metabolic acidosis
 Autonomic neuropathy  Hyperkalemia
 Muscle twitching  Hyponatremia
 Encephalopathy  Hypermagnesemia
  Asterixis  Hyperphosphatemia
  Myoclonus  Hypocalcemia
  Lethargy  Hyperuricemia
  Confusion  Hypoalbuminemia
  Seizures Hematological
  Coma  Anemia
Cardiovascular  Platelet dysfunction
 Fluid overload  Leukocyte dysfunction
 Congestive heart failure Endocrine
 Hypertension  Glucose intolerance
 Pericarditis  Secondary hyperparathyroidism
 Arrhythmia  Hypertriglyceridemia
 Conduction blocks Skeletal
 Vascular calcification  Osteodystrophy
 Accelerated atherosclerosis  Periarticular calcification
Pulmonary Skin
 Hyperventilation  Hyperpigmentation
 Interstitial edema  Ecchymosis
 Alveolar edema  Pruritus
 Pleural effusion
Gastrointestinal
 Anorexia
 Nausea and vomiting
 Delayed gastric emptying
 Hyperacidity
 Mucosal ulcerations
 Hemorrhage
 Adynamic ileus

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.

TABLE 31–6
Complications of renal replacement therapy.

Downloaded 2020­12­20 7:2 A  Your IP is 162.129.251.104
Neurological
Chapter 31: Anesthesia for Patients with Kidney Disease, Page 12 / 21
©2020 McGraw Hill. All Rights Reserved.   Terms of Use • Privacy Policy • Notice • Accessibility
 Dialysis disequilibrium syndrome
 Dementia
Cardiovascular
hypotension during dialysis include the vasodilating effects of acetate dialysate solutions, autonomic neuropathy, and rapid removal of fluid. The
Johns Hopkins Medical School
interaction of white cells with cellophane-derived dialysis membranes can result in neutropenia and leukocyte-mediated pulmonary dysfunction
Access Provided by:
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.

TABLE 31–6
Complications of renal replacement therapy.

Neurological
 Dialysis disequilibrium syndrome
 Dementia
Cardiovascular
 Intravascular volume depletion
 Hypotension
 Arrhythmia
Pulmonary
 Hypoxemia
Gastrointestinal
 Ascites
Hematological
 Anemia
 Transient neutropenia
 Residual anticoagulation
 Hypocomplementemia
Metabolic
 Hypokalemia
 Large protein losses
Skeletal
 Osteomalacia
 Arthropathy
 Myopathy
Infectious
 Peritonitis
 Transfusion-related hepatitis

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
Downloaded 2020­12­20 7:2 A  Your IP is 162.129.251.104
contributory.
Chapter 31: Anesthesia for Patients with Kidney Disease, Page 13 / 21
©2020 McGraw Hill. All Rights Reserved.   Terms of Use • Privacy Policy • Notice • Accessibility
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
Hypermagnesemia is generally mild unless magnesium intake is increased (commonly from magnesium-containing antacids). Hypocalcemia is
Johns Hopkins Medical School
secondary to resistance to parathyroid hormone, decreased intestinal calcium absorption secondary to decreased kidney synthesis of 1,25-
Access Provided by:
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.
Downloaded 2020­12­20 7:2 A  Your IP is 162.129.251.104
G. Neurological
Chapter 31: Anesthesia for Patients with Kidney Disease, Page 14 / 21
©2020 McGraw Hill. All Rights Reserved.   Terms of Use • Privacy Policy • Notice • Accessibility
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
 Johns Hopkins Medical School
Anorexia, nausea, vomiting, and ileus are commonly associated with uremia. Hypersecretion of gastric acid increases the incidence of peptic ulceration
Access Provided by:
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.

TABLE 31–7
Indications for renal replacement therapy.

Fluid overload
Hyperkalemia
Severe acidosis
Metabolic encephalopathy
Pericarditis
Coagulopathy
Refractory gastrointestinal symptoms
Drug toxicity

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.

TABLE 31–8
Drugs with a potential for significant accumulation in patients with renal impairment.

Downloaded 2020­12­20 7:2 A  Your IP is 162.129.251.104
Chapter 31: Anesthesia for Patients with Kidney Disease,
Muscle relaxants Antiarrhythmics Page 15 / 21
©2020 McGraw Hill. All Rights Reserved.   Terms of Use • Privacy Policy • Notice • Accessibility
 Pancuronium  Bretylium
Anticholinergics  Disopyramide
 Atropine  Encainide (genetically determined)
BUN, and creatinine measurements can assess the adequacy of dialysis. Glucose measurements guide the potential need for perioperative insulin
therapy. Johns Hopkins Medical School
Access Provided by:
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.

TABLE 31–8
Drugs with a potential for significant accumulation in patients with renal impairment.

Muscle relaxants Antiarrhythmics

 Pancuronium  Bretylium
Anticholinergics  Disopyramide
 Atropine  Encainide (genetically determined)
 Glycopyrrolate  Procainamide
Metoclopramide  Tocainide
H 2 -receptor antagonists Bronchodilators

 Cimetidine  Terbutaline
 Ranitidine Psychiatric

Digitalis  Lithium
Diuretics Antibiotics

Calcium channel antagonists  Aminoglycosides

 Diltiazem  Cephalosporins

 Nifedipine  Penicillins

β-Adrenergic blockers  Tetracycline

 Atenolol  Vancomycin

 Nadolol Anticonvulsants

 Pindolol  Carbamazepine

 Propranolol  Ethosuximide

Antihypertensives  Primidone

 Captopril Other
 Clonidine  Sugammadex

 Enalapril
 Hydralazine
 Lisinopril
 Nitroprusside (thiocyanate)

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.
Downloaded 2020­12­20 7:2 A  Your IP is 162.129.251.104
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 Page
Chapter 31: Anesthesia for Patients with Kidney Disease, hypertensive
16 / 21
response to airway instrumentation and intubation. Succinylcholine, 1.5 mg/kg, can be used to facilitate endotracheal intubation in the absence of
©2020 McGraw Hill. All Rights Reserved.   Terms of Use • Privacy Policy • Notice • Accessibility
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.
hypertension.
Johns Hopkins Medical School
Access Provided by:
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.

ANESTHESIA FOR PATIENTS WITH MILD TO MODERATE KIDNEY IMPAIRMENT

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.
Downloaded 2020­12­20 7:2 A  Your IP is 162.129.251.104
Chapter 31: Anesthesia for Patients with Kidney Disease, Page 17 / 21
Kidney protection with adequate hydration and maintenance of renal blood flow is indicated for patients at high risk for kidney injury and kidney
©2020 McGraw Hill. All Rights Reserved.   Terms of Use • Privacy Policy • Notice • Accessibility
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
cardiac and aortic reconstructive surgery. Intravascular volume depletion, sepsis, obstructive jaundice, crush injuries, and renal toxins such as
Johns Hopkins Medical School
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
Access Provided by:

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.

CASE DISCUSSION

A Patient with Uncontrolled Hypertension

A 59-year-old man with a recent onset of hypertension is scheduled for stenting of a stenotic left renal artery. His preoperative
blood pressure is 180/110 mm Hg.

What is the likely cause of this patient’s hypertension?

Downloaded 2020­12­20 7:2 A  Your IP is 162.129.251.104
Renovascular hypertension is one of the few forms of hypertension that can be corrected with surgery or mechanical intervention. Others
Chapter 31: Anesthesia for Patients with Kidney Disease, include
Page 18 / 21
coarctation of the aorta, pheochromocytoma, Cushing disease, and primary hyperaldosteronism.
©2020 McGraw Hill. All Rights Reserved.   Terms of Use • Privacy Policy • Notice • Accessibility

Most studies suggest that renovascular hypertension accounts for 2% to 5% of all cases of hypertension. Characteristically it manifests as a relatively
 A Patient with Uncontrolled Hypertension Johns Hopkins Medical School
Access Provided by:
A 59-year-old man with a recent onset of hypertension is scheduled for stenting of a stenotic left renal artery. His preoperative
blood pressure is 180/110 mm Hg.

What is the likely cause of this patient’s hypertension?

Renovascular hypertension is one of the few forms of hypertension that can be corrected with surgery or mechanical intervention. Others include
coarctation of the aorta, pheochromocytoma, Cushing disease, and primary hyperaldosteronism.

Most studies suggest that renovascular hypertension accounts for 2% to 5% of all cases of hypertension. Characteristically it manifests as a relatively
sudden onset of hypertension in a person younger than 35 or older than 55 years of age. Renal artery stenosis can also be responsible for the
development of accelerated or malignant hypertension in previously hypertensive persons of any age.

What is the pathophysiology of the hypertension?

Unilateral or bilateral stenosis of the renal artery decreases the perfusion pressure to the kidney(s) distal to the obstruction. Activation of the
juxtaglomerular apparatus and release of renin increase circulating levels of angiotensin II and aldosterone, resulting in peripheral vascular
constriction and sodium retention, respectively. The resulting systemic arterial hypertension is often severe.

In nearly two thirds of patients, the stenosis results from an atheromatous plaque in the proximal renal artery. These patients are typically men over
the age of 55 years. In the remaining one third of patients, the stenosis is more distal and is due to malformations of the arterial wall, commonly
referred to as fibromuscular hyperplasia (or, dysplasia). This latter lesion most commonly presents in women younger than 35 years. Bilateral renal
artery stenosis is present in 30% to 50% of patients with renovascular hypertension. Less common causes of stenosis include dissecting aneurysms,
emboli, polyarteritis nodosa, radiation, trauma, extrinsic compression from retroperitoneal fibrosis or tumors, and hypoplasia of the renal arteries.

What clinical manifestations other than hypertension may be present?

Signs of secondary hyperaldosteronism can be prominent. These include sodium retention in the form of edema, metabolic alkalosis, and
hypokalemia. The latter can cause muscle weakness, polyuria, and even tetany.

How is the diagnosis made?

The diagnosis is suggested by the clinical presentation previously described. A midabdominal bruit may also be present, but the diagnosis requires
laboratory and radiographic confirmation. A definitive diagnosis is made by renal arteriography, and percutaneous balloon angioplasty with
stenting may be performed at the same time. The functional significance of the restrictive lesion(s) may be evaluated by selective catheterization of
both renal veins and subsequent measurement of plasma renin activity in blood from each kidney. Restenosis rates following angioplasty are
estimated to be less than 15% after 1 year. Patients who are not candidates for angioplasty and stenting are referred for surgery.

Should this patient undergo intervention or surgical correction given his present blood pressure?

Optimal medical therapy is important in preparing these patients for operation. Relative to patients with well-controlled hypertension, those with
poorly controlled hypertension have an increased incidence of intraoperative problems, including marked hypertension, hypotension, myocardial
ischemia, and arrhythmias. Ideally, arterial blood pressure should be well controlled prior to surgery. Patients should be evaluated for preexisting
kidney dysfunction, and metabolic disturbances such as hypokalemia should be corrected. Patients should also be evaluated as indicated for the
presence and severity of coexisting atherosclerotic disease, according to current American College of Cardiology/American Heart Association
(ACC/AHA) guidelines (see Chapter 21).

What antihypertensive agents are most useful for controlling blood pressure perioperatively in these patients?

β-Adrenergic blocking drugs are frequently utilized for blood pressure control in the perioperative period. They are particularly effective because
secretion of renin is partly mediated by β1-adrenergic receptors. Although parenteral selective β1-blocking agents such as metoprolol and esmolol
would be expected to be most effective, nonselective agents appear equally effective. Esmolol may be the intraoperative β1-blocking agent of choice
because of its short half-life and titratability. Direct vasodilators and nicardipine are also useful in controlling intraoperative hypertension (see
Chapter 15).

ACE inhibitors and angiotensin-converting enzyme receptor blockers are contraindicated in bilateral renal artery stenosis or in unilateral renal
artery stenosis where there is only one functioning kidney because they can precipitate kidney failure.

What intraoperative considerations are important for the anesthesia provider?

Open surgical revascularization of a kidney is a major procedure, with the potential for major blood loss, fluid shifts, and hemodynamic changes.
One of several procedures may be performed, including transaortic renal endarterectomy, aortorenal bypass (using a saphenous vein, synthetic
graft, or segment of the hypogastric artery), a splenic to (left) renal artery bypass, a hepatic or gastroduodenal to (right) renal artery bypass, or
Downloaded 2020­12­20 7:2 A  Your IP is 162.129.251.104
excision of the stenotic segment with reanastomosis of the renal artery to the aorta. Rarely, nephrectomy may be performed. Isolated stenosis
Chapter 31: Anesthesia for Patients with Kidney Disease, Page 19 of /a21
renal artery may be corrected with stenting performed with local anesthesia and sedation.
©2020 McGraw Hill. All Rights Reserved.   Terms of Use • Privacy Policy • Notice • Accessibility

With all “open” procedures, an extensive retroperitoneal dissection often necessitates relatively large volumes of intravenous fluid replacement.
 artery stenosis where there is only one functioning kidney because they can precipitate kidney failure.
Johns Hopkins Medical School
What intraoperative considerations are important for the anesthesia provider? Access Provided by:

Open surgical revascularization of a kidney is a major procedure, with the potential for major blood loss, fluid shifts, and hemodynamic changes.
One of several procedures may be performed, including transaortic renal endarterectomy, aortorenal bypass (using a saphenous vein, synthetic
graft, or segment of the hypogastric artery), a splenic to (left) renal artery bypass, a hepatic or gastroduodenal to (right) renal artery bypass, or
excision of the stenotic segment with reanastomosis of the renal artery to the aorta. Rarely, nephrectomy may be performed. Isolated stenosis of a
renal artery may be corrected with stenting performed with local anesthesia and sedation.

With all “open” procedures, an extensive retroperitoneal dissection often necessitates relatively large volumes of intravenous fluid replacement.
Large-bore intravenous access is mandatory because of the potential for extensive blood loss. Heparinization contributes to increased blood loss.
Depending on the surgical technique, aortic cross-clamping, with its associated hemodynamic consequences, often complicates anesthetic
management (see Chapter 22). Continuous intraarterial blood pressure monitoring will nearly always be used, and central venous pressure
monitoring is often helpful. Goal-directed hemodynamic and fluid therapy utilizing arterial pulse contour analysis, esophageal Doppler, or
transesophageal echocardiography should be considered for patients with poor ventricular function and may be advisable in most patients to guide
fluid management (see Chapter 51). The choice of anesthetic technique is generally determined by the patient’s cardiovascular function.

Generous hydration and maintenance of adequate cardiac output and blood pressure are important to protect both the affected and the normal
kidney against acute ischemic injury. Topical cooling of the affected kidney during the anastomosis may also be employed.

What postoperative considerations are important?

Although in most patients hypertension is ultimately cured or significantly improved, arterial blood pressure is often quite labile in the early
postoperative period. Close hemodynamic monitoring should be continued well into the postoperative period. Reported operative mortality rates
range from 1% to 6%, and most deaths are associated with myocardial infarction. The latter probably reflects the relatively high prevalence of
coronary artery disease in older patients with renovascular hypertension.

SUGGESTED READINGS

Ahn HJ, Kim JA, Lee AR, et al. The risk of acute kidney injury from fluid restriction and hydroxyethyl starch in thoracic surgery. Anesth Analg .
2016;122:186. [PubMed: 26418125]

Allen CJ, Ruiz XD, Meizoso JP, et al. Is hydroxyethyl starch safe in penetrating trauma patients? Mil Med . 2016;181:152. [PubMed: 27168566]

Bie P, Evans RG. Normotension, hypertension and body fluid regulation: Brain and kidney. Acta Physiol . 2017;219:288.

Fuhrman D, Kellum J. Biomarkers for diagnostic, prognosis and intervention in acute kidney injury. Contrib Nephrol . 2016;187:47. [PubMed:
26881914]

Goldstein SL. Automated/integrated real-time clinical decision support in acute kidney injury. Curr Opin Crit Care . 2015;21:485. [PubMed: 26539921]

Green RS, Butler MB, Hicks SD, et al. Effect of hydroxyethyl starch on outcomes in high-risk vascular surgery patients. A retrospective analysis. J
Cardiovasc Vasc Anesth . 2016;30:967.

Hoste EAJ, Bagshaw SM, Bellomo R, et al. Epidemiology of acute kidney injury in critically ill patients: The multinational AKI-EPI study. Intens Care
Med . 2015;41:1411.

Ince C, Groeneveld ABJ. The case for 0.9% NaCl: Is the undefendable, defensible? Kidney Int . 2014;86:1087. [PubMed: 25007167]

Kashy BK, Podolyak A, Makarova N, et al. Effect of hydroxyethyl starch on postoperative kidney function in patients having noncardiac surgery.
Anesthesiology . 2014;121:730. [PubMed: 25054470]

KDIGO Workgroup. AKI definition. Kidney Int Suppl . 2012;2:19.

Kellum JA, Kane-Gill SL, Handler SM. Can decision support systems work for acute kidney injury? Nephrol Dial Transplant . 2015;30:1786. [PubMed:
26206764]
Downloaded 2020­12­20 7:2 A  Your IP is 162.129.251.104
Kellum JA, Shaw AD. Assessing toxicity of intravenous crystalloids in critically ill patients. JAMA . 2015;314;1695. [PubMed: 26444442]
Chapter 31: Anesthesia for Patients with Kidney Disease, Page 20 / 21
©2020 McGraw Hill. All Rights Reserved.   Terms of Use • Privacy Policy • Notice • Accessibility
Khan S, Floris M, Pani A, et al. Sodium and volume disorders in advanced chronic kidney disease. Adv Chron Kidney Dis . 2016;23:240.
 Johns Hopkins Medical School
KDIGO Workgroup. AKI definition. Kidney Int Suppl . 2012;2:19.
Access Provided by:

Kellum JA, Kane-Gill SL, Handler SM. Can decision support systems work for acute kidney injury? Nephrol Dial Transplant . 2015;30:1786. [PubMed:
26206764]

Kellum JA, Shaw AD. Assessing toxicity of intravenous crystalloids in critically ill patients. JAMA . 2015;314;1695. [PubMed: 26444442]

Khan S, Floris M, Pani A, et al. Sodium and volume disorders in advanced chronic kidney disease. Adv Chron Kidney Dis . 2016;23:240.

Legrand M, Ince C. Intravenous fluids in AKI: A mechanistically guided approach. Sem Nephrol . 2016;36:53.

Li H, Sun SR, Yap JQ, et al. 0.9% saline is neither normal nor physiological. J Zhejiang Univ Science B . 2016;17:181.

Lobo DN, Awad S. Should chloride-rich crystalloids remain the mainstay of fluid resuscitation to prevent ‘pre-renal’ acute kidney injury? Con. Kidney
Int . 2014;86:1096. [PubMed: 24717302]

Luo X, Jiang L, Du B, et al. A comparison of different diagnostic criteria of acute kidney injury in critically ill patients. Crit Care . 2014;18:R144.
[PubMed: 25005361]

McMahon BA, Koyner JL. Risk stratification for acute kidney injury: Are biomarkers enough? Adv Chron Kidney Dis . 2016;23:167.

Myburgh JA. Fluid resuscitation in acute medicine: What is the current situation? J Int Med . 2015;277:58.

Okusa MD, Davenport A. Reading between the (guide)lines—The KDIGO practice guideline on acute kidney injury in the individual patient. Kidney Int .
2014;85:39. [PubMed: 24067436]

Raghunathan K, Murray PT, Beattie WS, et al. Choice of fluid in acute illness: What should be given? An international consensus. Brit J Anaesth .
2014;113:772. [PubMed: 25326478]

Raghunathan K, Nailer P, Konoske R. What is the ideal crystalloid? Curr Opin Crit Care . 2015;21:309. [PubMed: 26103144]

Raghunathan K, Shaw A, Nathanson B, et al. Association between the choice of IV crystalloid and in-hospital mortality among critically ill adults with
sepsis. Crit Care Med . 2014;42:1585. [PubMed: 24674927]

Raiman M, Mitchell CG, Biccard BM, et al. Comparison of hydroxyethyl starch colloids with crystalloids for surgical patients. A systematic review and
meta-analysis. Eur J Anaesthesiol . 2016;33:42. [PubMed: 26351826]

Rewa O, Mottes T, Bagshaw S. Quality measures for acute kidney injury and continuous renal replacement therapy. Curr Opin Crit Care . 2015;21:490.
[PubMed: 26539922]

Severs D, Hoorn EJ, Rookmaaker MB. A critical appraisal of intravenous fluids: From the physiological basis to clinical evidence. Nephrol Dial
Transplant . 2015;30:178. [PubMed: 24463187]

Soussi S, Ferry A, Chaussard M, et al. Chloride toxicity in critically ill patients: What’s the evidence? Anaesth, Crit Care Pain Med . 2016;36:125.

Wanner C, Amann K, Shoji T. The heart and vascular system in dialysis. Lancet . 2016;388:276. [PubMed: 27226133]

Zarychanski R, Abou-Setta AM, Turgeon AF. Association of hydroxyethyl starch administration with mortality and acute kidney injury in critically ill
patients requiring volume resuscitation. A systematic review and meta-analysis. JAMA . 2013;309:678. [PubMed: 23423413]

Zazzeron L, Gattinoni L, Caironi P. Role of albumin, starches and gelatins versus crystalloids in volume resuscitation of critically ill patients. Curr Opin
Crit Care . 2016;22:428. [PubMed: 27467273]

Downloaded 2020­12­20 7:2 A  Your IP is 162.129.251.104
Chapter 31: Anesthesia for Patients with Kidney Disease, Page 21 / 21
©2020 McGraw Hill. All Rights Reserved.   Terms of Use • Privacy Policy • Notice • Accessibility