Perioperative Management of Patients With End-Stage Renal Disease

Journal of Cardiothoracic and Vascular Anesthesia 31 (2017) 2251–2267
Contents lists available at ScienceDirect
journal homepage: www.jcvaonline.com
Review Article
Perioperative Management of Patients With

End-Stage Renal Disease
Hirotsugu Kanda, MD, PhDn,1, Yuji Hirasaki, MD†,‡,
Takafumi Iida, MD, PhDn, Megumi Kanao-Kanda, MD, PhDn,
Yuki Toyama, MDn, Takashi Chiba, MD§,
Takayuki Kunisawa, MD, PhDn
n
Department of Anesthesiology and Critical Care Medicine, Asahikawa Medical University, Asahikawa,
Hokkaido, Japan
†
Department of Anesthesiology, Tokyo Women’s Medical University, Tokyo, Japan
‡
Department of Anatomy, The Jikei University School of Medicine, Tokyo, Japan
§
Iwamizawa Dialysis Center, Jinyukai, Iwamizawa, Hokkaido, Japan
End-stage renal disease (ESRD) is associated with significant alterations in cardiovascular function; homeostasis of body fluid, electrolytes,
and acid-base equilibrium; bone metabolism, erythropoiesis; and blood coagulation. The prevalence of ESRD is increasing rapidly worldwide, as
is the number of patients requiring surgery under general anesthesia. Patients with ESRD have significantly higher risks of perioperative
morbidity and mortality due to multiple comorbidities. The perioperative management of patients with ESRD under general anesthesia therefore
requires special considerations and a careful multidisciplinary approach. In this review, the authors summarize the available literature to address
common issues related to patients with ESRD and discuss the best perioperative approach for this patient subgroup.
& 2017 Elsevier Inc. All rights reserved.
Key Words: hemodialysis; end-stage renal disease; stroke-volume variation; general anesthesia; goal-directed therapy
THE NUMBER OF patients with chronic kidney disease of the non-ESRD population.1 As such, perioperative manage-
(CKD) dependent on hemodialysis (HD) is increasing rapidly ment of patients with ESRD requires special considerations
all over the world due to the increasing prevalence of regarding disease pathophysiology, including cardiovascular
hypertension, type-2 diabetes mellitus, and the aging popula- dysfunction, volume disturbances, anemia, and electrolyte
tion. For example, more than 600,000 patients in the United disorders, and pharmacokinetic/pharmacodynamic alterations
States currently are receiving long-term HD for end-stage renal (Fig 1). In particular, fluid management to prevent both fluid
disease (ESRD).1 The extended lifespan prolonged by HD has overload and hypovolemia is one of the greatest challenges in
increased the need for surgery to address complications of the ESRD patients. A persistent fluid overload may lead to
underlying disease. Patients with ESRD have a higher risk of hypertension, pulmonary edema, and congestive heart failure
cardiovascular disease and other coexisting diseases2 and an and a greater risk of mortality.3 Therefore, ESRD patients
adjusted all-cause mortality rate at least 10-fold higher than that usually undergo HD the day before surgery to achieve
euvolemia, the so-called “dry weight.”4 On the other hand,
1
ESRD patients sometimes exhibit significant hypotension after
Address reprint requests to Hirotsugu Kanda, MD, PhD, Department of
Anesthesiology and Critical Care Medicine, Asahikawa Medical University,
the induction of general anesthesia.5 Surprisingly, little evidence
Midorigaoka-higashi 2-1-1-1, Asahikawa, Hokkaido, 078-8510, Japan. related to perioperative fluid management in ESRD patients has
E-mail address: h.kanda0629@nifty.com (H. Kanda). been published.
http://dx.doi.org/10.1053/j.jvca.2017.04.019
1053-0770/& 2017 Elsevier Inc. All rights reserved.
2252 H. Kanda et al. / Journal of Cardiothoracic and Vascular Anesthesia 31 (2017) 2251–2267
Fig 1. Main systemic complications of ESRD and the treatment of these abnormalities. BP, blood pressure; HF, heart failure; ESA, erythropoietin stimulating
agents; SVV, stroke-volume variation; ScvO2, central venous oxygen saturation; Hyp.K þ , hyperkalemia.
In this review, the authors summarize the available literature renal transplant still are considered to have CKD. The term
to address common issues related to patients with ESRD and “ESRD” corresponds to CKD grade 5, for which lifelong renal
discuss the best perioperative approach for this patient replacement therapy (RRT), including peritoneal dialysis, HD,
subgroup. In particular, the authors focus on fluid/blood or transplantation, is necessary for survival.
management, including dry weight, choice of fluid, transfu-
sion, and parameters to guide volume replacement therapy. Epidemiology
Generation Status and Vital Prognosis

Definition of CKD
Hill et al performed a systematic review and meta-analysis on
The Kidney Disease Improving Global Outcomes (KDIGO) 100 articles and reported the prevalence of CKD using the Kidney
2012 Clinical Practice Guidelines for the Evaluation and Disease Outcomes Quality Initiative criteria in a general popula-
Management of Chronic Kidney Disease proposed a 5-stage tion.7 They demonstrated an estimated mean prevalence (95%
classification for CKD based on the glomerular filtration rate confidence interval) of CKD at any stage of 13.4% (11.7%-
(GFR) (Table 1).6 CKD is defined as either a history of kidney 15.1%) worldwide, which is higher than the prevalence of
transplantation or a GFR o60 mL/min/1.73 m2 for more than diabetes (8.5% in 2014),8 and a prevalence of ESRD (CKD
3 months in the presence of additional markers of kidney stage 5) of 0.1%. The prevalence and prognosis of ESRD are
damage, such as albuminuria (albumin excretion rate highly modified by socioeconomic background.9 The main causes
4 30 mg/24 h, albumin-to-creatinine ratio 4 30 mg/g of ESRD in the United States, in order, are diabetes, hypertension,
[ 4 3 mg/mmol]); urine sediment abnormalities; electrolyte glomerulonephritis, and cystic kidney disease.1 Liyanage et al
and other abnormalities due to tubular disorders; tissue reported that more than 2.6 million patients with ESRD received
abnormalities detected using histology; and structural abnor- RRT in 2010 worldwide,10 but the actual prevalence of ESRD is
malities detected using imaging. Patients with a functioning deemed to be higher than the reported numbers. Furthermore,
they estimated that as many as 9.7 million patients worldwide
Table 1 required RRT in 2010 and the number is projected to double by
GFR Categories in CKD
2030. The current total Medicare cost for ESRD patients in the
GFR Category GFR (mL/min/1.73 m2) Terms United States already has reached $32.8 billion.1
Life on dialysis is not straightforward; patients on HD have
Grade 1 Z90 Normal or high a higher risk of developing comorbidities such as stroke, acute
Grade 2 60-89 Mildly decreased
Grade 3a 45-59 Mildly to moderately decreased
coronary events, heart failure, vascular access–related infec-
Grade 3b 30-44 Moderately to severely decreased tion, endocarditis, cancer, bowel ischemia/bleeding, limb
Grade 4 15-29 Severely decreased ischemia/necrosis, and bone fractures requiring emergency
Grade 5 o15 Kidney failure medical or surgical interventions.9,11
From KDIGO 2012 Clinical Practice Guidelines for the Evaluation and
The prognosis of ESRD thus is poor. The World Health
Management of Chronic Kidney Disease.6 Organization reported that 864,226 deaths (12.2 deaths per
Abbreviations: CKD, chronic kidney disease; GFR, glomerular filtration rate. 100,000 people; 1.5% of global deaths) worldwide were
H. Kanda et al. / Journal of Cardiothoracic and Vascular Anesthesia 31 (2017) 2251–2267 2253
attributable to CKD in 2012.12 The United States Renal Data metabolism via activation of vitamin D. These functions,
System annual data report demonstrated that the expected however, are disrupted significantly in patients with ESRD,
remaining lifetime and unadjusted annual mortality rate of leading to retention of water and urea toxin, hyperkalemia,
dialysis patients in 2014 was 6.9 years and 180.0 per 1,000 acidosis, anemia, and osteomalacia, which are discussed in
patient-years, respectively.1 Robinson et al found high 5-year detail in the following.
mortality rates ranging between 39% and 60%, primarily due
to cardiovascular complications.13
Cardiovascular Disease
Impact of ESRD on Perioperative Outcomes Cardiovascular diseases due to atherosclerosis and cardiac
remodeling commonly occur in patients with CKD.24 Accel-
Considering their severe comorbidities, it is not surprising erated atherosclerosis is a feature of CKD that may be related
that patients with ESRD have considerable perioperative risks. to impaired endothelial function, low-grade inflammation, and
Indeed, the literature consistently demonstrated a higher risk of dyslipidemia.25 Patients with CKD generally exhibit lower
mortality in ESRD patients compared with non-ESRD levels of high-density lipoprotein and higher levels of
patients, both in the cardiac and noncardiac perioperative intermediate-density lipoprotein.25 Another potential contribu-
periods (Table 2).14–23 Gajdos et al demonstrated that the ting factor to cardiovascular disease in CKD is activation of
30-day mortality rates of patients with ESRD undergoing the renin-angiotensin system. Angiotensin Ⅱ, especially that
elective vascular procedures were 4-fold higher than those of acting at angiotensin-1 receptors, promotes the production of
their non-ESRD cohorts.17 Furthermore, they found that older reactive oxygen species, leading to endothelial dysfunction
patients (4 65 years) with ESRD had remarkably higher risks and vascular remodeling. Under normal conditions, a wide
of postoperative pulmonary complications and death than the range of systemic mean arterial pressures (MAPs) autoregulate
younger subgroup, suggesting that the indications for perform- renal blood flow; however, arterial hypertension and renal
ing these procedures in this subgroup requires careful disease disrupt this autoregulatory mechanism, with renal
consideration. Moran-Atkin et al also reported higher mortality blood flow becoming more directly proportional to the
rates in older patients with ESRD in elective and emergency MAP.26 The relative risk for ESRD is 4 20-fold higher for
colon surgery for diverticulitis.18 patients with high-risk hypertension (systolic blood pressure
[SBP] 4 210 mmHg or diastolic blood pressure 4120
Pathophysiology mmHg) than for patients with normal blood pressure (BP)
levels.27,28
Kidneys play essential physiologic roles, including excre- Progressive dysfunction of the cardiovascular system, espe-
tion of excessive water and water-soluble waste (eg, urea); ion cially left ventricular hypertrophy (LVH) resulting from high
metabolism; acid-base balance; erythropoiesis; and bone pressure and volume overload, occurs in patients with ESRD.
Table 2
Postoperative Mortality of Patients With ESRD in Various Surgical Settings
Author (yr) Procedure Number (With ESRD) Mortality Rate (Non-ESRD Patients) Odds Ratio (95% CI)
Parikh et al14 (2010) CABG 3485 5.4% in 2003 (1.8%) NA

Chikwe et al15 (2010) CABG 96 7.3% (1.4%) NA
Thourani et al16 (2012) Valve surgery 224 18.3% (5.2%) 1.80 (1.09-2.97)
Gajdos et al17 (2013) Major vascular procedures 1409 7.25% (1.4%) All: 4.46 (3.48-5.72)
Abdominal: 4.15 (1.98-8.71)
Carotid: 3.52 (1.48-8.40)
Peripheral: 3.66 (2.67-5.03)
Moran-Atkin et al18 (2014) Colon surgery for diverticulitis 962 Elective: 25.64% (2.56%) NA
Emergency: 31.41% (7.29%)
Smith et al19 (2015) Appendectomy 5,712 NA 5.68 (3.96-8.15)
Brakoniecki et al20 (2017) General surgeries 1,163 NA 9.05 (4.09-20.0)
De la Garza Ramos et al21(2016) Anterior cervical fusion 270 o4.1% 15.2
(0.05%) (5.67-40.88)
Lin et al22 (2015) Fixation of hip fractures 2,680 Mortality rate NA
354.30/1,000 patient-years
(152.04 /1,000 patient-years)
Media survival time
1.89 years (4.68 years)
Erkocak et al23 (2016) Total joint arthroplasty 359 2% (0.6%) 10.46* (1.67-65.34)
Abbreviations: CABG, coronary artery bypass grafting; CI, confidence interval; ESRD, end-stage renal disease; NA, not applicable.
n
Result using multivariate analysis.
Sodium and water retention often lead to volume overload, Metabolic Acidosis and Electrolyte Abnormalities
increasing shunt flow through an arteriovenous fistula, or
chronic anemia, with an increased stroke volume and heart Metabolic Acidosis
rate,29 whereas hypertension and arteriosclerosis contribute to In CKD patients, impaired GFR (40-50 mL/min) limits the
pressure overload. LVH is related to myocardial fibrosis and ability of the kidneys to excrete acid.40–42 This disability
myocardial relaxation malfunction, which can cause diastolic initially leads to hyperchloremic (normal anion gap) metabolic
dysfunction and arrhythmias.29 Reduced left ventricular (LV) acidosis, which may convert to a mixed normal anion gap and
compliance may increase sensitivity to volume changes and high anion gap metabolic state when the GFR falls o15 mL/
accelerate the development of pulmonary edema. min.43 Additional abnormalities caused by acidemia and
Diastolic heart failure (ie, heart failure with a preserved metabolic acidosis include insulin resistance, thyroid dysfunc-
ejection fraction) presents clinically with symptoms and signs tion, high cortisol levels, and reduced insulin-like growth
of heart failure, including fatigue, dyspnea, palpitations, and factor-1 44–46 in conjunction with increased protein turnover,47
hypotension due to pulmonary congestion or edema, normal leading to a low serum albumin concentration.
systolic function and evidence of diastolic dysfunction.30
Glassock et al reported that subclinical diastolic dysfunction Hyperkalemia
is one of the most common echocardiographic findings in Ninety percent of potassium is excreted by the kidneys and
asymptomatic CKD patients with ESRD, together with LVH.31 10% by the intestine.48 The ability to excrete excessive
In fact, a large number of ESRD patients present with diastolic potassium is affected by CKD. Plasma potassium levels,
dysfunction and have the potential to develop diastolic heart however, are maintained within normal limits until the onset
failure. Moreover, systolic heart failure, dilated LV due to fluid of CKD grade 5. Patients have an impaired ability to excrete
accumulation, decreased ejection fraction, and mitral or potassium load, which leads to the development of
tricuspid regurgitation may present with impaired renal func- hyperkalemia.
tion.32 Eventually, diastolic heart failure contributes to the
final form of heart failure in ESRD patients, along with
progressive systolic heart failure.30,32 Disorder of Calcium, Phosphate, and Bone Metabolism
The presence of ESRD affects the excretion of phosphate
ions and activation of vitamin D at the kidneys, which
Volume Disturbance decelerates the absorption of calcium from the small intestine
and leads to an initial drop in the blood calcium level.
ESRD patients are unable to excrete salt and water Hypocalcemia may result in laryngospasm, a prolonged QT,
adequately, which results in chronic volume overload. Chronic and cardiac arrhythmias.49 This leads to secondary hyperpar-
volume overload is a common complication in HD patients in athyroidism, in which excessive excretion of parathyroid
relation to hypertension, pulmonary edema, increased arterial hormone occurs to compensate for the hypocalcemia, leading
stiffness, LVH, and heart failure and may be instrumental in to hypercalcemia and hyperphosphatemia via the mobilization
their higher mortality and morbidity.1,33 The excess fluid must of calcium and phosphate from the bone matrix.50,51 As a
be removed during each dialysis period. These clinical issues, result, the bone becomes fragile and more prone to fracture.
however, have not been resolved due to the adverse effects of On the other hand, an elevated blood calcium level leads to an
dehydration. ectopic deposition of calcium phosphate in systemic vessels
Dehydration in the HD patient often is associated with (vascular calcification)52 or soft tissues (calciphylaxis).53
hypotension, tinnitus, and dizziness (Table 3).34 Moreover, a
history of intradialytic hypotension may lead to more severe Renal Anemia and Alloimmunization
residual renal dysfunction,35 occlusion of the arteriovenous Anemia is a common complication in moderate-to-severe
access,36 cerebral or mesenteric infarction,37,38 and increased CKD,54–56 usually due to the reduced production of endogen-
morbidity and mortality.39 ous erythropoietin by the impaired kidneys.57 The reduced
aerobic capacity results in symptoms of anemia, such as
fatigue, dizziness, and palpitations, and potential aggravation
Table 3
Symptoms of Volume Overload and Dehydration of myocardial dysfunction.58 Therefore, adequate therapies,
erythropoiesis stimulating agents (ESA), red blood cell (RBC)
Overload Dehydration transfusion, and iron supplements are required to improve the
Increased body mass Decreased body mass
patient’s quality of life and outcome.59
Hypertension Hypotension Alloimmunization is defined as an immune response to
Edema Dizziness foreign antigens after exposure to genetically different cells or
Palpitation Nausea and vomiting tissues. Transfusion may induce alloimmunization targeting
Dyspnea Unsteadiness the human leukocyte antigen or RBCs, with sensitization rates
Breath shortness Torpor
Headache Syncope
ranging from 2% to 21%.60–62 Sensitized patients who
undergo kidney transplantation have a greater risk of graft
loss.63 Therefore, transfusions should be performed only in and coronary artery calcium score,72 to detect unidentified
transplantation candidates under special consideration. In cardiovascular disease preoperatively.73,74 In this context,
particular, the balance of risk and benefits before transfusion invasive diagnostic imaging, including coronary angiography,
should be assessed for potential recipients in cases of high-risk may be justified. The results should be reviewed by all care
allosensitization, previous transplantation, pregnancy, and team members and indications for the surgery should be
previous transfusion.59 discussed as long as time allows. Less-invasive catheter-based
cardiovascular interventions (percutaneous coronary interven-
Coagulopathy tion,75 endovascular stent,76 and transcatheter aortic valve
ESRD patients are at increased risk for perioperative implantation77) may lead to a lower risk of periprocedural
bleeding.64 The accumulated uremic toxins inhibit normal mortalities in some settings. Whether these procedures are
platelet function and platelet–vessel wall interactions.65 More- associated with better long-term outcomes in this patient group,
over, anemia, which commonly is seen in ESRD patients, also however, remains controversial. Marui et al demonstrated that
interferes with normal coagulation.59 A study using thromboe- coronary stenting was associated with a lower 30-day mortality,
lastography reported that coagulation abnormalities were whereas surgical revascularization was associated with a
detected in 42.9% of patients with ESRD.66 reduced risk of cardiac death in a 5-year postoperative period.75
Similarly, Yuo et al demonstrated that endovascular stenting
Pharmacology for abdominal aortic aneurysms was associated with a lower
Loss of kidney function affects drug pharmacokinetics and postprocedural mortality compared with open repair, but they
pharmacodynamics, requiring anesthesiologists to carefully found no significant difference in 1-year mortality.76 The
consider potential alterations in the distribution, metabolism decision as to whether surgery is indicated or the type of
and elimination, and protein binding, as discussed later. surgery that might be beneficial for the patient should be made
with consideration of the patient’s condition, will, and ultimate
Preoperative Considerations goal of treatment in each case.
Preoperative Evaluation and Surgical Decision-Making Management of Hypertension and Heart Failure
As mentioned previously, patients with ESRD carry higher Tailoring of BP is very important for ESRD patients to
risks of perioperative morbidity and mortality, regardless of reduce perioperative morbidity. The KDIGO clinical practice
the type of surgery. As such, a multidisciplinary team guidelines recommend treatment for blood pressure o 130/80
approach involving all medical and surgical specialties is mmHg in patients with CKD.78 Moreover, other guidelines
essential to achieve a successful postoperative outcome. The recommend predialysis and postdialysis BP goals of o 140/90
patient’s past and present history should be reviewed thor- mmHg or o 130/80 mmHg.79
oughly (Table 4).67 Physical examination focusing on the Heart failure, combined systolic heart failure and diastolic
patient’s cardiovascular status should be performed carefully to failure, is the final form of cardiovascular disease in ESRD
identify any clinical findings of cardiovascular disease. Despite patients. In patients with acute pulmonary edema or conges-
a high prevalence of coronary artery disease in patients with tion, an intravenous bolus of loop diuretics should be
ESRD, many are asymptomatic due to the presence of diabetes administered initially if urination is preserved.80 Continued
or exercise intolerance.68 The assessment, therefore, should administration of dobutamine is needed in patients with an
include objective diagnostic modalities, namely, cardiac tro- SBP o85 mmHg, or a vasodilator, such as nitroglycerin, is
ponin T,69 stress myocardial perfusion single-photon emission necessary in patients with an SBP 4 115 mmHg.80 Moreover,
computed tomography,70 dobutamine stress echocardiography,71 consideration of emergency HD is required when the hemo-
dynamics are not stable. According to the European Society of
Table 4 Cardiology guidelines, pharmacologic treatment of diastolic
Preoperative Considerations for Patients With ESRD heart failure is limited. In general, diuretics are used to control
sodium and water retention and relieve breathlessness and
Patients should be informed regarding an increased risk of complication and
mortality
edema, but the effects of diuretics are not clear in HD
Blood pressure should be controlled with predialysis and postdialysis goals of patients.80 A small study indicated that the heart rate–limiting
o140/90 and 130/80 mmHg, respectively. calcium-channel blocker verapamil may improve exercise
Patients with o4 METs or unknown functional capacity require a cardiology capacity and symptoms in diastolic heart failure patients.81,82
consultation67 Beta-blockers also may be used to control the ventricular rate
Hemoglobin level should be maintained at 9.0-10.0 g/dL using an ESA
Hemodialysis should be performed the day before surgery (elective surgery at
in patients with atrial fibrillation.80
least 6 h after dialysis with heparin)
Target range of HbA1c in ESRD patients is 6.0% to 8.0% Preoperative Dialysis
Transfusion or ESA to maintain hematocrit around 30% preoperatively reduces
the bleeding risk In general, preoperative dialysis is required to correct the
Abbreviations: ESA, erythropoiesis stimulating agents; ESRD, end-stage renal fluid status and electrolyte abnormality and to remove the
disease; HbA1c, hemoglobin A1c; METs, metabolic equivalents. uremic toxins. The appropriate timing of preoperative dialysis,
however, still is unclear due to the scarcity of clinical data. A administration of insulin and nebulized salbutamol, may be
retrospective study reported that HD within 24 hours before administered to prevent hyperkalemia. Combination therapy
surgery was associated with a lower potassium level on the with insulin and salbutamol has synergistic effects and appears
day of surgery.4 to be safe for ESRD patients.96 Emergency dialysis sometimes
Heparin is used as the first-choice anticoagulant for HD. is required in the case of severe and treatment-resistant
Because the heparin effect lasts 4 hours, elective surgery hyperkalemia.
should be scheduled at least 6 hours after dialysis to avoid The infusion of calcium salts is an appropriate therapy for
perioperative bleeding if heparin is used during HD.83 hypocalcemia that is comorbid with hyperkalemia. Calcitonin,
Heparin-free dialysis is excluded in this recommendation. bisphosphonate, and cinacalcet should be considered for
Acute removal of urea may cause dialysis disequilibrium treatment in the case of hypercalcemia.97–99
syndrome, a potentially lethal syndrome associated with In any case, frequent electrolyte checks are necessary to
various neurologic symptoms (restlessness, headache, or monitor these abnormalities during the perioperative period.
coma) after HD.84 Therefore, patients undergoing surgery
should have an adequate set period before surgery to confirm Management of Renal Anemia
the absence of these symptoms.4
Taken together, the available information suggests that HD In 1989, the US Food and Drug Administration approved
on the day before surgery is preferable to correct electrolyte the use of recombinant human erythropoietin to boost hemo-
imbalance, uremia, and excess body fluid and to minimize the globin (Hb) levels and ameliorate symptoms of anemia in
perioperative bleeding risk. patients with ESRD.100 Before the availability of ESAs,
treatment options for anemia were limited mainly to RBC
Provisions for Bleeding Risk transfusions and, in some cases, androgen and iron therapy.57
ESA therapy increases the mean Hb level in HD patients from
Adequate heparin-free dialysis that reduces the accumulated 9.8-to-11.2 g/dL and has cut the RBC transfusion rate by
urea improves platelet function.65 Preoperative transfusion or half.101 Unfortunately, however, several randomized studies
administration of ESA to maintain the hematocrit at approxi- reported that ESA treatment in predialysis patients with CKD
mately 30% may reduce the bleeding risk.85 The use of point- increased the risk of mortality and major cardiovascular
of-care tests, including thromboelastography, is expected to events.102–104 Due to the accumulation of findings that ESA
improve perioperative coagulation management in patients therapy increased the risk of adverse events, the US Food and
with ESRD.66,86 If antiplatelet agents are administered to Drug Administration introduced several major ESRD-related
prevent stroke or myocardial infarction, aspirin should be regulatory and reimbursement changes in 2011 that eventually
discontinued 6 days before surgery, clopidogrel should be led to revisions of the ESA label information. The primary
discontinued 7 days before surgery, and intravenous heparin label changes were removal of the Hb target range of 10-to-12
should be discontinued 4 hours before surgery.87Administra- g/dL and new dosing and administration language recom-
tion of 1-desamino-8-D-arginine vasopressin may reduce mending that ESA dosing be reduced or interrupted at Hb
bleeding by improving platelet function and clotting factor concentrations 11 g/dL.105,106 Revisions of the regulatory
activity in ESRD patients.88–90 However, 1-desamino-8-D- and reimbursement policies in 2011 led to subsequent
arginine vasopressin should be used with caution or avoided decreases in ESA doses and Hb concentrations in dialysis
entirely in patients with ESRD because it may lead to fluid patients in the United States and increases in the use of RBC
retention and increase BP. transfusions in chronic dialysis patients.
The 2012 KDIGO Clinical Practice Guidelines for Anemia
Treatment of Hyperkalemia and Hypercalcemia in Chronic Kidney Disease recommended initiating ESA
therapy for ESRD patients when Hb is between 9.0 and 10.0
Bolus infusion of calcium salts, calcium gluconate, or g/dL to avoid a decrease in the Hb concentration to o 9.0 g/
calcium chloride immediately decreases the potassium level.91 dL.59 In general, the KDIGO guidelines stated that ESAs
This intervention, however, increases serum calcium concen- should not be used to maintain Hb concentrations 4 11.5 g/dL
tration and thus increases the threshold for the cardiac muscle in adult patients with CKD.59 Iron therapy is considered
action potential, leading to decreased excitability.92 Several suitable adjuvant therapy for ESA therapy, whereas treatment
published studies, however, suggested that calcium should be with androgens, vitamin C, vitamin D, vitamin E, folic acid, L-
administered when the serum potassium concentration is carnitine, and pentoxifylline is not.59
4 6.0-to-6.5 mmol/L, even in the absence of electrocardio- Intravenous administration of ESA (500 IU/kg) and an
gram abnormalities.92,93 Bicarbonate infusion is the most iron supplement (200 mg) 1 day before surgery was reported
reliable treatment for acute hyperkalemia after calcium salt to significantly reduce the need for perioperative trans-
infusion. Hypertonic sodium bicarbonate (2 mmol/min over fusion in anemic patients undergoing cardiac surgery.107
1 h) or isotonic bicarbonate (1.5 mmol/min over 1 h) is Moreover, the administration of ESA before anesthesia was
effective for hyperkalemia.94,95 Therapies to increase the correlated with a reduction in cardiac surgery–associated acute
intracellular uptake of potassium, such as intravenous kidney injury.108
Blood Glucose Control Table 5

Intraoperative Considerations for Patients With ESRD
The KDIGO clinical practice guidelines suggest a target Moderate glucose control (o180 mg/dL) is recommended
hemoglobin A1c (HbA1c) of o7.0% to prevent or delay Special attention must be paid to both the type and quantity of fluid to be
progression of the microvascular complications of diabetes, administered
including diabetic kidney disease.6 On the other hand, these Stroke-volume variation is a useful indicator of hypovolemia
guidelines also recommend that the target HbA1c be extended Caution is advised to prevent acute fluid overload after preoperative fluid
removal, bleeding, and predicted insensible water loss.
to 4 7.0% in individuals with comorbidities or limited life RBC transfusion should be considered for patients with Hb o7 g/dL
expectancy and risk of hypoglycemia.6 Caution is advised when performing regional blocks and neuraxial anesthesia
Up to one-third of diabetic HD patients are considered to due to the bleeding risk
have “burnt-out diabetes.”109,110 Burnt-out diabetes presents Appropriate sites should be selected for arteriovenous fistulae, arteriovenous
with a low HbA1c level (o 6.0%) even if the diabetes mellitus grafts, a venous or arterial catheter cannulation
Intraoperative HD is not necessary except under specific situations in cardiac
is long term. Moreover, these patients have an adverse surgery
prognosis despite HbA1c o 6.0%.109,110 This adverse condi- ε-aminocaproic acid and tranexamic acid are useful against post-CPB bleeding
tion is due to multiple factors, such as malnutrition, protein-
energy wasting, reduced clearance of exogenous insulin, and Abbreviations: CPB, cardiopulmonary bypass; ESRD, end-stage renal disease;
HD, hemodialysis; RBC, red blood cells.
antihyperglycemic effects of the accumulated uremic tox-
ins.109–111 The clinical significance of this condition, however, conditions, including hypovolemia, an inadequate hemody-
remains unclear. Ricks et al reported that HD patients with namic response from the sympathetic nervous system, diastolic
HbA1c levels between o6.0% and 48.0% had increased dysfunction, autonomic dysfunction, and underlying cardiac
mortality.112 These findings indicated that ESRD patients with disease, are potential causes of intradialytic hypotension.
HbA1c levels o6.0% have a poor outcome from the view- Information obtained from physical examinations, such as
point of burnt-out diabetes.112 As previously suggested, the body mass, BP, and edema, is not adequate for accurately
authors of this review recommend a target range of HbA1c in determining the fluid status. The quantitative methods, such as
ESRD patients of 6.0% to 8.0%, especially in diabetic dialysis cardiothoracic ratio, human atrial natriuretic peptide, or brain
patients. natriuretic peptides, and inferior vena cava diameter are more
Tight glucose control (81-108 mg/dL) in critically ill credible predictors of fluid status and informative for deter-
patients, including those with renal failure, is associated with mining the dry weight.119 The equation Kt/V can be used to
an increased risk of hypoglycemia and adverse events com- estimate the volume of blood cleansed during HD and to
pared with conventional glucose control, which targets a calculate the appropriate dialysis dose, where K, t, and V are
blood glucose level of 180 mg/dL.113 Several studies have urea clearance, dialysis time, and body fluid volume, respec-
revealed that a target level o 180 mg/dL reduced periopera- tively. That is, Kt/V indicates the volume of the HD dose. The
tive morbidity and mortality.114,115 The authors recommend KDIGO clinical practice guidelines suggest a minimally
moderate glucose control (o 180 mg/dL), acceptable in adequate Kt ⁄V of 1.2 for HD treatment 3 times a week, with
general, as a suitable strategy for ESRD patients because these a target dose of 1.4 per session.120
patients have a risk for hypoglycemia, as represented by burnt- There currently is no gold standard measurement for dry
out diabetes. weight, and therefore it may be difficult for anesthesiologists
to establish the preoperative fluid status. Furthermore, it is
Intraoperative Considerations very difficult to manage fluids in HD patients intraoperatively.
Fluid Management
What is the Best Intravenous Solution for Fluid Therapy in
Dry Weight and Fluid Removal Patients With ESRD?
Anesthesiologists must estimate each patient’s fluid status To date, various types of intravenous solution have been
consistently and provide appropriate fluid therapy to maintain developed for fluid therapy.121 The effect of intravenous fluid
an adequate perfusion pressure for microcirculation (Table 5). therapy on clinical outcomes has been studied extensively over
What constitutes dry weight and euvolemia, however, is the last several decades. Perel et al performed a systematic
not clear. review of randomized controlled trials comparing colloids and
Dry weight is defined as “the lowest tolerated post-dialysis crystalloids and found no beneficial effect of colloids on
weight achieved with minimal signs or symptoms of hypo- or survival in critically ill patients.122 Furthermore, hydroxyethyl
hypervolemia.”116 This definition, however, does not ade- starch (HES) is associated with a higher risk of developing
quately apply to all patients. Fluid overload also may result acute renal insufficiency in this cohort.123,124 In the setting of
from intradialytic hypotension and/or symptoms related to kidney transplantation, Cittanova et al demonstrated that the
dialysis and ultrafiltration. Intradialytic hypotension (decrease use of high-molecular HES (200/0.6) for volume expansion
in SBP Z 20 mmHg or MAP by Z10 mmHg)117 commonly in a brain-dead donor was associated with a higher incidence
is detected in dialysis patients (15%-30% of all dialysis of postoperative graft kidney dysfunction.125 On the other
treatments) and complicates HD therapy.118 Several hand, Blasco et al revealed that the use of low-molecular
HES (130/0.4) was associated with better postoperative graft Table 6

function compared with high-molecular HES.126 Estimated Risks Associated With Blood Transfusions per Unit Transfused
As for crystalloids, studies have demonstrated that hyper- Risks Associated with Transfusions Estimated Risk
chloremia secondary to the use of 0.9% saline was associated
with poor postoperative outcomes in noncardiac surgery.127,128 Infections
On the other hand, the use of balanced solutions was Hepatitis B 1 in 282,000 to 1 in 357,000
West Nile virus 1 in 350,000
associated with better kidney function and a better 24-hour Death from bacterial sepsis 1 in 1,000,000
survival rate in a rat sepsis model.129 In clinical trials, the use Hepatitis C 1 in 1,149,000
of balanced solutions was associated with better control of the Human immunodeficiency virus 1 in 1,467,000
plasma acid-base and electrolyte balances;130,131 it remains Immunologic response
unclear, however, whether the use of balanced solutions is Fever/allergic reaction 1 in 100-200
Hemolytic reaction 1 in 6,000
associated with better clinical outcomes.
Transfusion-related acute lung injury 1 in 12,350
Scarce information is available regarding the best practice Anaphylaxis 1 in 50,000
for intravenous fluid therapy in patients with ESRD. It is Fatal hemolysis 1 in 1,250,000
unknown whether colloid solutions have any adverse effects in Graft-versus-host disease Rare
patients with ESRD who already have limited renal function. Other
Mistransfusion 1 in 14,000-19,000
Colloid infusions, including HES, however, should not be
used in ESRD patients. Crystalloids should be used as first-line Taken from the KDIGO Clinical Practice Guidelines for Anemia in Chronic
fluid replacement therapy. Considering the presence of meta- Kidney Disease.60
bolic acidosis de novo, a balanced solution may be preferable
to prevent further exacerbation of acidosis. On the other hand, The risk of blood transfusion must be considered in clinical
balanced solutions often contain potassium, which potentially practice. Improved blood screening methods through the donor
can lead to potassium retention. These issues should be history questionnaire and strict laboratory screening have
addressed in future studies. Therefore, the type of fluids decreased the risk of transfusion-transmitted viral infections
administered intraoperatively should be selected carefully on greatly (Table 6).59 Bacterial and parasitic contamination now
the basis of the patient’s perioperative status, including pose a greater threat in transfusion medicine than does viral
volume, electrolyte status, and hemodynamics. contamination.133 The risks associated with blood transfusion
include hemolytic or febrile transfusion reactions, allergic
Intraoperative Transfusion reaction, transfusion-related acute lung injury, transfusion-
RBC transfusion increases the oxygen-carrying capacity, associated circulatory overload, post-transfusion purpura,
thereby improving anemia-related symptoms.132 In patients graft-versus-host disease, iron overload, alloimmunization,
with symptomatic anemia, RBC transfusion leads to an citrate toxicity, and hyperkalemia.133
immediate increase in the RBC mass and, as mentioned
previously, transfusion of RBCs again has become more Hemodynamic Management and Monitoring
common on the basis of findings from clinical trial data and In general, hemodynamic management in ESRD patients
the recent revision of regulatory and reimbursement policies means achieving the appropriate preload and afterload and
for ESA. The use of RBC transfusions again should be maintaining BP. There are no available data, however,
considered with regard to the risk and benefit, based on the regarding the outcome of ESRD patients undergoing peri-
guidelines. operative hemodynamic management. Currently, both static
According to the 2012 KDIGO clinical practice guidelines, and dynamic monitoring are used for hemodynamic manage-
acute clinical situations, acute severe hemorrhage, unstable ment, especially fluid responsiveness.
coronary artery disease, and the need for rapid preoperative Hb Static monitoring or invasive monitoring requires a catheter
correction should be treated with RBC transfusion.59 Unfortu- placement into the central veins or pulmonary artery. These
nately, the Hb threshold for transfusion in these situations is methods essentially require reaching and maintaining a certain
unclear, but the current guidelines recommend that RBC central venous pressure (CVP) or pulmonary arterial wedge
transfusion be considered for patients with Hb o 7 g/dL.59 pressure (PAWP), indicating an adequate preload. Evaluating
RBC transfusion also is necessary for clinical conditions such intravascular volume status based on CVP or PAWP is of
as hemoglobinopathies, bone marrow failure, and ESA resis- limited use, however, because the measures are poorly related
tance. Indications for transfusion outside of acute situations are to the patient’s fluid responsiveness.134,135 Moreover, insertion
not established, but the rate of transfusion markedly increases of a pulmonary artery catheter, which is invasive, does not
when Hb falls o 10 g/dL (100 g/L).59 The guidelines improve the outcome in critically ill patients.136 Therefore,
recommend that RBC transfusion in a CKD patient with pulmonary artery catheters are not recommended for peri-
nonacute anemia should be based on symptoms of anemia operative hemodynamic monitoring in ESRD patients. Goal-
rather than an arbitrary Hb threshold.59 Taken together, acute directed therapy (GDT) based on dynamic monitoring of
transfusion is absolutely necessary for ESRD patients in the systolic-pressure variation, pulse-pressure variation, and
perioperative period if Hb o 7 g/dL, and even earlier in some stroke-volume variation (SVV) improves outcomes in high-
severe cases. risk patients compared with a standard management protocol
with static monitoring.137,138 In other words, these dynamic cardiopulmonary bypass (CPB) in cardiac surgery. Takami et
parameters could be better correlated with fluid responsiveness al reported a retrospective study finding that regular inter-
than static measurements, CVP, and PAWP.139,140 SVV can be mittent HD after cardiac surgery could be performed safely in
used to replace CVP in the volume management of patients most HD-dependent patients compared with intraoperative
who have undergone kidney transplantation.141 The authors of hemofiltration during CPB.147 On the other hand, some studies
this study found that SVV was decreased after a 500-mL fluid have indicated that intraoperative HD could be used to manage
infusion in patients with ESRD, but LV end-diastolic volume the water and electrolyte balance in case of emergency surgery
measured using 3-dimensional transesophageal echocardiogra- with severe hyperkalemia or CPB with potassium-rich cardi-
phy was not changed after infusion in these patients due to oplegia.148,149 Taken together, intraoperative HD is not
diastolic disfunction.142 In addition, low venous oxygen necessary, except under specific conditions.
saturation (SvO2) was associated with high mortality in cardiac Postbypass bleeding is a common problem in cardiac
or major surgery and sepsis patients.143 In fact, adequate tissue surgery, especially in ESRD patients, due to coagulation
oxygenation is dependent on oxygen delivery (cardiac output abnormalities.150 Several studies have revealed that ε-amino-
or Hb) and extraction (metabolic demands).144 Impaired tissue caproic acid and tranexamic acid reduced bleeding and
oxygenation results in hypoxic tissue injury and organ improved patient outcome in cardiac surgery.151–153 Moreover,
dysfunction. Therefore, it is important to maintain tissue appropriate use of clotting factor replacement therapy or blood
oxygenation using SvO2 as an indicator, even if the MAP transfusions has the potential to decrease the postoperative
targets are achieved using vasopressors.143 There were several bleeding risk and redo surgery. On the other hand, antifibrin-
protocols and studies of GDT using SVV, cardiac index, or olytic therapy using aprotinin to limit blood loss should not be
SvO2 showing improved outcome, including in-hospital mor- performed in cardiac surgery because aprotinin is associated
tality, hospital stay, and transfusion dose.145 Taken together, with the risk of renal failure requiring dialysis.153,154
vasopressors or rapid fluid infusion should be performed if the
cardiac index is o2.5 L/m2 or SVV is 4 10%. In addition, if Regional and Neuraxial Anesthesia
central venous oxygen saturation (ScvO2) is o70%, transfu- Brachial plexus block is useful for the formation of an
sion or inotropic agents should be administered. arteriovenous fistula in patients with ESRD.155 Moreover,
Inducing general anesthesia in ESRD patients is a clinical regional or neuraxial anesthesia or in combination with general
challenge because anesthetic agents reduce both cardiac output anesthesia are an appropriate anesthetic management for other
and afterload (ie, systemic vascular resistance). Ickx et al types of surgery.156–158 Special attention, however, is required
reported that there was no major hemodynamic instability in when using local anesthetic agents or neuraxial anesthesia to
ESRD patients without cardiac complications compared with a avoid adverse complications. Low bicarbonate value due to
healthy control group if low-dose and long-term infusion of ESRD leads to a delayed onset of local anesthetics, and a low
propofol was administered for induction anesthesia.146 In that protein binding effect increases the duration of their effects.159
study, however, treatment with ephedrine was more common These pharmacodynamic changes may increase the possibility
in the ESRD group. There is no gold standard anesthetic agent of local anesthetic intoxication, and careful administration is
for ESRD patients. The details of anesthetic agents are required. Epidural anesthesia has been performed successfully
described in the Pharmacology section. It is very important to for surgery of body trunk and inferior limbs to achieve safe
monitor the hemodynamic status and to be prepared to provide and effective analgesia. The risks and benefits must be
the appropriate treatment, infusion, or vasopressor during considered carefully when administering epidural anesthesia
induction anesthesia. The authors’ institutional policy suggests to a patient with a platelet count of o100,000/mm. That is,
that an arterial line catheter be inserted before anesthesia to these patients have an increased risk of neuraxial hematoma
provide real-time BP, SVV, cardiac output, or cardiac index associated with neuraxial anesthesia.160,161
monitoring and that a novel CV catheter, which is able to ESRD patients frequently receive antiplatelet medication
measure ScvO2, be inserted to administer vasopressor or (eg, aspirin or clopidogrel) because of coronary artery disease
inotropes in ESRD patients with the severe clinical triad of or cerebrovascular disease. As discussed, the antiplatelet
severe aortic valve stenosis, atrial fibrillation, and low ejection medication must be discontinued if a neuraxial block or deep
fraction. The authors of the study presented here revealed that plexus block is indicated.87
SVV is a useful indicator of hypovolemia or fluid responsive-
ness in ESRD patients.142 Although there is no suitable method Vascular Access
for monitoring perioperative fluid overload, anesthesiologists
should be alert to the potential for acute fluid overload, Appropriate vascular access is required for long-term
including congestion or hemodynamic instability, if the volume survival and quality of life. Anesthesiologists must be familiar
of intravenous infusion exceeds the total dose of preoperative with vascular access sites to prevent complications. Arterio-
fluid removal, bleeding, and predicted insensible water loss. venous fistula (AVF), arteriovenous grafts (AVG), tunneled
cuffed catheters, and port catheter systems are well-known
Specific Considerations for Cardiac Surgery options for permanent access.162 Short-term noncuffed cathe-
There are no randomized clinical trials evaluating whether ters are used for acute dialysis and for a limited duration in
intraoperative dialysis should be performed during hospitalized patients.
Arteriovenous Fistula resumed 12 hours after surgery until stable hemostasis is

reached to reduce the risk of bleeding.
AVF is the first choice for permanent vascular access, Special attention must be paid to fluid status, electrolyte
providing longer survival of the access, the lowest rate of balance, and blood glucose concentration. As with intraopera-
thrombosis, and a lower cost of implantation, and it is less tive fluid infusion, volume overload and hypovolemia must be
prone to infection compared with AVG or other catheters.162 avoided, and frequent checks of electrolyte status, especially
The mortality risk also is reduced in HD patients using an potassium, are needed to reduce complications. Fluid and
AVF.163 A wrist primary fistula is preferred because the access electrolyte status and urea and creatinine levels can facilitate
should be placed distally and in the upper extremities when- decisions regarding the solution type or dose and need for
ever possible. The disadvantage of AVF is long maturation urgent postoperative dialysis.
times: 1-to-4 months. The anesthesiologist should protect A multidisciplinary approach to analgesia is required to
vascular channels with the potential to become fistula con- alleviate postoperative pain. Regional and neuraxial anesthesia
traction sites, if possible. should be used from the intraoperative period to reduce
postoperative pain.155–158 These techniques diminish the
requirements for opioids, such as morphine, and thus help
Arteriovenous Grafts
avoid the risk of accumulation of the drug and its metabolites.
Intravenous patient-controlled analgesia with fentanyl may be
AVG should be considered if fistula placement is not
effective for postoperative pain in ESRD patients, with
possible because of abnormal superficial veins or an exhausted
monitoring for respiratory depression.164
AVF. The synthetic or biologic material selected for conduits
A retrospective study revealed that central venous vascular
should be based on the surgeon’s experience and preference.
access and a higher hepatic Sequential Organ Failure Assessment
subscore were independently associated with an increased risk of
Catheters for HD mortality, whereas a residual urinary output 4500 mL was
associated with a decreased risk of mortality in HD patients in the
Tunneled cuffed catheters are considered only if AVF and intensive care unit.165 These findings are helpful for postoperative
AVG cannot be used because there is a greater risk of management in ESRD patients to reduce complications.
infection, susceptibility to thrombosis, and blood flow delivery
inconsistencies compared with AVF or AVG.162 The preferred
insertion site for tunneled cuffed venous dialysis catheters is Pharmacology
the right internal jugular vein.162 Other options include the
right external jugular vein, left internal and external jugular Propofol
veins, subclavian veins, femoral veins, and translumbar and
transhepatic access to the inferior vena cava. Ultrasound Propofol commonly is used to induce and maintain peri-
imaging is useful for catheter placement. Port catheter systems operative anesthesia. Ickx et al reported that ESRD did not
sometimes are used as a bridge device until AVF maturation. markedly affect the pharmacokinetic and pharmacodynamic
Noncuffed catheters are used for acute dialysis and short term profiles of propofol.146 Dahaba et al also reported that end-
( o1 week) because of the risk of infection. stage renal failure did not increase the recovery time from total
intravenous anesthesia with propofol and remifentanil; in their
study, there was no difference in the time to maintenance of
Postoperative Considerations adequate respiration and extubation in patients with ESRD.5
Taken together, these findings suggest that propofol can be
There is no evidence regarding the optimal time to restart used safely in individuals receiving HD.
postoperative dialysis to reduce the incidence of postoperative
complications (Table 7). In general, regular HD should be
continued 3 times per week as a routine schedule except for Etomidate
urgent indications, and heparin administration should be
Etomidate is a short-acting intravenous anesthetic with a
Table 7 stable hemodynamic status for cardiac surgery compared with
Postoperative Considerations for Patients With ESRD propofol because etomidate has little or no effect on cardiac
output, peripheral resistance, and pulmonary circulation.166
Fluid status, electrolyte data, urea, and creatinine levels facilitate decisions
Etomidate causes adrenal insufficiency, however, and therefore
regarding the solution type or dose and need for urgent postoperative dialysis
Regular hemodialysis should be continued on a routine schedule of 3 times per long-term administration for anesthesia maintenance is not
week recommended.167 The possibility of adrenal inhibition by a
Heparin injections should be resumed 12 h after surgery until stable hemostasis single dose of etomidate remains unclear. There is a case
to reduce the risk of bleeding report of anesthesia induction with etomidate for HD patients
A multidisciplinary approach to analgesia is required for alleviating
with myocardial revascularization.168
postoperative pain
The risks and benefits must be considered carefully if
Abbreviation: ESRD, end-stage renal disease. etomidate is selected as the induction agent.
Ketamine hours.181 Thus, CKD patients should receive a minimum dose

of morphine and be monitored closely postoperatively for
Ketamine, an N-methyl-D-aspartate receptor agonist, is respiratory depression. Although ESRD is not an absolute
administered to induce or maintain anesthesia and pain control contraindication for morphine use, the drug should be admin-
for chronic pain. Ketamine has the safest pharmacologic istered to these patients with caution. A rather large fraction of
profile in patients with renal failure.169 Several studies have morphine can be eliminated by dialysis.182
reported that ketamine is a useful anesthetic agent for renal Hydromorphone has approximately 10 times greater analge-
transplant recipients or for pain management in ESRD sic effects and a shorter duration of action than morphine.
patients.170–172 Hydromorphone does not accumulate significantly in ESRD
patients, but it is metabolized to hydromorphone-3-glucoro-
Dexmedetomidine nide, which has neuroexcitatory effects and accumulates in
these patients.183 Therefore, hydromorphone should be used
Dexmedetomidine is a highly selective α2-agonist with with caution and the dosage adjusted. Hydromorphone-3-
sedative, analgesic, and sympatholytic properties. Because of glucoronide can be eliminated by dialysis.184
its minimal effects on the respiratory system, dexmedetomi- Meperidine is a synthetic opioid that is metabolized to
dine is used widely as sedative agent with or without normeperidine, which is dependent on the GFR.164 The use of
intubation. Rutkowska et al reported that intravenous dexme- meperidine in CKD patients may lead to central nervous
detomidine prolonged the duration of brachial plexus block in system and respiratory depression, seizures, and psychosis.185
patients with ESRD with appropriate sedation.173 De Wolf Although naloxone or HD are able to reverse these side
et al reported that CKD patients may be more sedated because effects,186 the use of meperidine in ESRD patients should be
of the lower plasma protein binding of dexmedetomidine, avoided if possible.
although the elimination half-life was shortened in renal Codeine and dihydrocodeine have a significantly prolonged
disease.174 In their study, there were no differences between elimination half-life in dialysis patients and sometimes cause
the CKD and control groups in either the volume of distribu- central nervous system depression.164,187,188 Therefore, these
tion at steady state or elimination clearance. Dexmedetomidine drugs should be used with caution in patients with ESRD or
can be useful for ESRD patients but must be used with caution avoided entirely, if possible.
due to its sedation-enhancing effects. Fentanyl is metabolized largely by the hepatic system with
no active metabolites. Fentanyl clearance is reduced in patients
Inhalation Agents with moderate-to-severe uremia and could depress respirations
postoperatively as a result.189 Although fentanyl can be used in
The most commonly used inhalation anesthetic agent is patients with renal failure, such patients should be monitored
sevoflurane, which reacts with carbon dioxide absorbents to for signs of gradual accumulation of the parent drug. Fentanyl
produce compound A, a substance that is nephrotoxic in is not cleared by HD because of its high protein-binding
animal models.175 A retrospective study of renal laboratory properties and low water solubility.182 Remifentanil clearance
data, however, pooled from 22 clinical trials performed to does not depend on renal function because it has an esterase-
compare sevoflurane with isoflurane, enflurane, or propofol dependent metabolism. On the other hand, patients with renal
reported a similar incidence of increased serum creatinine and failure may accumulate the remifentanil metabolite remifenta-
blood urea nitrogen concentrations.176 Isoflurane and desflur- nil acid.190 Because the effect of remifentanil acid is 1/4,600
ane are not associated with nephrotoxic potential and are that of remifentanil, remifentanil does not have toxic effects in
considered safe to use in CKD patients.177,178 In conclusion, renal impairment.190,191 Paradoxically, Dahaba et al reported
sevoflurane, desflurane, and isoflurane can be used safely in that remifentanil had reduced clearance and a prolonged
ESRD patients. elimination half-life in HD patients.192 They also reported
that a lower infusion rate of remifentanil was needed in total
Opioids intravenous anesthesia with propofol and remifentanil, but the
recovery time from general anesthesia was not prolonged
Opioids do not have direct toxic effects on the kidney. It is significantly.5
important to identify the pharmacokinetics of both the parent
drug and metabolites, however, before opioids are adminis- Neuromuscular Relaxants
tered to ESRD patients as a perioperative analgesic agent.
Morphine is metabolized to morphine-3-glucuronide and The neuromuscular-blocking agents rocuronium and vecur-
morphine-6-glucuronide by hepatic glucuronidation. onium have enhanced effects in patients with CKD as a result
Morphine-6-glucuronide is a potent μ-receptor agonist that of decreased clearance.193–195 Robertson et al reported that the
effectively provides analgesia and sedation.179 In contrast, effects of rocuronium tended to be enhanced when combined
morphine-3-glucuronide has minimal analgesic effects and is with propofol, but not when combined with inhalation agents,
neuroexcitatory.180 Renal function strongly affects the meta- in ESRD patients.195 Moreover, endogenous compounds bind
bolism of morphine-6-glucuronide, and in patients with CKD, to rocuronium; the plasma concentration is increased by the
the half-life of morphine-6-glucuronide increases from 2 to 27 urea level, concomitant medication, and diabetes, etc.195
Intraoperative use of long-acting neuromuscular blocking Nonsteroidal Anti-Inflammatory Agents (NSAIDS)

agents or agents eliminated through the kidney should be
minimized, and continuous neuromuscular monitoring should Whether the use of NSAIDs increases the risk of ESRD
be performed to prevent postoperative residual curarization. A remains a controversial issue because previous studies have
significant hyperkalemic response to the depolarizing muscle demonstrated conflicting results. Perneger et al reported that a
relaxant suxamethonium was not observed in CKD patients if cumulative dose of 5,000 or more NSAID-containing pills was
the preoperative potassium level was within the normal associated with increased odds of developing ESRD.207
range.196 Cisatracurium, the 1R cis-10R cis isomer of atracur- Schneider et al found that both selective and nonselective
ium, is subject to Hofmann elimination, which is independent NSAIDs were associated significantly with acute renal fail-
of renal and hepatic function, making these agents useful ure.208 On the other hand, Murray et al demonstrated that
neuromuscular blockers for renal failure patients.197 Although regular analgesic agents, including NSAIDs, did not increase
the clearance is reduced by 13% and the terminal elimination the risk of developing ESRD.209 According to a recent study
half-life prolonged by 4.2 minutes,198 Dahaba et al reported of more than 100,000 selected HD patients, however, NSAID
that ESRD did not prolong recovery from total intravenous use was a significant risk factor for dialysis.210 Thus, NSAIDs
anesthesia with remifentanil and propofol or recovery from should be prescribed cautiously, especially in patients at high
cisatracurium neuromuscular block.5 These neuromuscular risk for ESRD.
relaxants should be administered with neuromuscular monitor-
ing if possible.
Local Anesthetics
Sugammadex is a selective relaxant-binding agent that
encapsulates the neuromuscular blocking agent rocuronium
As mentioned earlier, regional and neuraxial anesthesia are
for elimination by the kidneys as a sugammadex-rocuronium
effective analgesia techniques for ESRD patients. Delayed
complex. Staals et al reported no significant difference
onset and prolonged duration of local anesthetics should be
between the mean time to recovery of the train-of-4 ratio to
considered. Renal clearance of metabolites from lidocaine or
0.9 in ESRD patients and control patients after administering
ropivacaine is reduced in ESRD patients.211,212
sugammadex.199 They also reported that clearance of both
Attention must be paid to the nervous system symptoms,
rocuronium and sugammadex was reduced in patients with
especially with large doses or prolonged administration,
ESRD compared with healthy individuals.200 The
because these metabolites have central nervous system
sugammadex-rocuronium complex remains in the body for a
toxicity.
longer period in patients with ESRD. Clinical data regarding
the pharmacokinetics of this complex, however, are not yet
available. Although it is considered that sugammadex can be Conclusion
used safely in clinical practice in patients treated with HD,
detailed studies should be conducted to determine whether the In this article, the authors reviewed the literature to address
rocuronium-sugammadex complex is harmful over the long the issues related to patients with ESRD undergoing general
term in a larger population of ESRD patients. anesthesia. A careful multidisciplinary approach is mandatory
Neostigmine clearance is reduced and its elimination half- to achieve a successful surgical outcome for this high-risk
life time prolonged in CKD, including in ESRD patients.201 patient subgroup, considering comorbidities, including cardi-
Several studies, however, revealed that combined use of ovascular diseases; the risk of anemia, fluid and electrolyte
neostigmine and atropine or glycopyrronium had adequate disturbances; and drug handling malfunctions during the
reversal effects on neuromuscular blockade.202,203 On the perioperative period.
other hand, the prolonged effect of neostigmine may initiate The authors propose that dynamic parameter stroke-volume
a parasympathomimetic response, including bradycardia and variability is a useful indicator of hypovolemia for the
heart block, especially when combined with atropine, a short- intraoperative fluid management of ESRD. “Goal-directed
acting muscarinic antagonist, rather than long-acting therapy” based on cardiac output, SVV, and ScvO2 has a
glycopyrronium.204 special potential to improve patient outcome in ESRD patients.
Additional studies are needed to determine the optimal fluid
management to prevent or attenuate hypovolemia or fluid
Acetaminophen overload, which worsens the outcome of HD patients intra-
operatively. The authors believe that these special efforts can
Acetaminophen administered orally to healthy volunteers facilitate the management of ESRD patients and maximize
and CKD patients did not affect renal function, including patient outcome.
tubular and glomerular function.205 A rat model of adenine-
induced renal failure also demonstrated that acetaminophen
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Perioperative Management of Patients With End-Stage Renal Disease

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Journal of Cardiothoracic and Vascular Anesthesia 31 (2017) 2251–2267

Contents lists available at ScienceDirect

journal homepage: www.jcvaonline.com

Perioperative Management of Patients With

Generation Status and Vital Prognosis

Parikh et al14 (2010) CABG 3485 5.4% in 2003 (1.8%) NA

Blood Glucose Control Table 5

HES (130/0.4) was associated with better postoperative graft Table 6

Arteriovenous Fistula resumed 12 hours after surgery until stable hemostasis is

Ketamine hours.181 Thus, CKD patients should receive a minimum dose

Intraoperative use of long-acting neuromuscular blocking Nonsteroidal Anti-Inﬂammatory Agents (NSAIDS)

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