Renal

Question 1

What Is the Definition of Chronic Kidney Disease (CKD) and What Are the Common Causes?

Answer 1

Kidney Disease Improving Global Outcomes (KDIGO) defines CKD as abnormalities of kidney structure or function, present for greater than 3 months, with implications for health (Table 26.2).
CKD is classified based on cause, glomerular filtration rate (GFR), and albuminuria category.
These factors also determine prognosis (Fig. 26.1).
DM and hypertension are two of the most common causes of CKD in the United States [2] and the developed world.
Other causes include chronic glomerulonephritis (e.g., IgA nephropathy); autoimmune diseases (e.g., systemic lupus erythematosus); genetic disorders (e.g., polycystic kidney disease); urinary tract diseases (e.g., infection, obstruction); toxin exposure (e.g., heavy metals, drugs); and infectious
diseases (e.g., tuberculosis, human immunodeficiency virus, hepatitis B and C).

Question 2

When Is Dialysis Indicated in CKD Patients?

Answer 2

KDIGO guidelines and the Canadian Society of Nephrology are largely in agreement in recommending that the decision to initiate renal replacement therapy (RRT) is based on signs and symptoms of CKD and the GFR. Clinical indications to commence dialysis include symptomatic uremia, fluid overload, and refractory hyperkalemia or acidemia.
Asymptomatic patients with GFR of 5–15 mL/min/1.73m2 are closely followed on a monthly basis, and dialysis is not initiated until symptoms develop that are refractory to medical therapy. Dialysis is initiated in patients with a GFR <5 mL/min/1.73m2 irrespective of the clinical status.

Question 3

What Complications Is the Patient with CKD Subject to in the Perioperative Period?

Answer 3

In general, morbidity and mortality are increased compared to patients without CKD.
• Cardiovascular events are increased as a result of CKD, independent of other commonly associated cardiovascular risk factors. These represent the leading cause of mortality, which increases with declining GFR.
• Worsening electrolyte disturbance, particularly hyperkalemia. Blood calcium levels can become high or low.
• Worsening metabolic acidosis with reduced capacity for further respiratory compensation. Work of breathing and hypoxia are further increased if pulmonary edema is
present.
• Impaired sodium and water excretion can lead to hypervolemia if there is excess intravenous (IV) fluid
administration. Issues with fluid and electrolyte disturbances are further worsened by sub-optimal dialysis
planning.
• Acute on chronic kidney injury from multiple causes, such as ischemia (e.g., intra-operative hypotension,
aortic cross-clamping) and known nephrotoxic drugs (e.g., non-steroidal anti-inflammatories, aminoglycoside
antibiotics, IV contrast). Fluorinated volatile anesthetics such as methoxyflurane and enflurane can cause nephrotoxicity. Sevoflurane appears to be safe despite concerns
with compound A production, as are isoflurane and desflurane.
• Bleeding due to platelet dysfunction caused by uremic toxins. Blood transfusion is more likely in the presence of pre-existing chronic anemia secondary to erythropoietin
insufficiency and decreased red cell survival.
• Cognitive dysfunction and encephalopathy become more
apparent in late-stage CKD. Delayed emergence from anesthesia and postoperative delirium are more common than in the general population.
• Autonomic neuropathy as a result of CKD can lead to delayed gastric emptying and cardiovascular instability.
• Pain management may be difficult, as chronic pain may be present secondary to calciphylaxis (calcification of the small blood vessels of the skin and subcutaneous fat) or peripheral neuropathy due to CKD.
• Undesired or serious adverse effects from common anesthesia drugs can occur due to altered pharmacokinetics such as varied protein binding and impaired renal clearance.
• Impaired wound healing and risk of infection are increased due to impaired immunity.
• Complications associated with the underlying cause of CKD

Question 4

What Specific Considerations Should
Be Evaluated During the Preoperative Assessment of CKD Patients?

Answer 4

Relevant history, physical examination, and investigations
pertaining to the CKD illness, treatment, and associated conditions will be considered in the following sections.

Question 5

What Specific Considerations Should
Be Evaluated During the Preoperative Assessment of CKD Patients?
1.Chronic Kidney Disease

Answer 5

The disease processes and complications due to the underlying cause of the CKD should be explored, such as the commonly associated diagnoses of DM and hypertension (see Chaps. 8 and 21).
-The onset, duration, and severity of CKD should be elicited, as well its complications in all other organ
systems (Table 26.3) [9].
-Blood urea nitrogen and creatinine are usually ordered, as their trends are used to monitor renal function.
- For pre-dialysis patients, first determine whether they have an indication for dialysis preoperatively as above.
-Discuss with renal medicine and postpone surgery if appropriate. For patients who need an upper limb arterio-venous fistula (AVF) formed in the future to allow for hemodialysis (HD), vessels at the wrist (radio-cephalic) or antecubital fossa (brachio-cephalic) are the most com-
monly chosen AVF sites. In order to preserve these veins for an AVF, dorsal veins of the hands are preferred for IV cannulation.
-Establish whether the patient is being considered for kidney transplantation. Avoiding allogenic blood transfusions is particularly important, as alloimmunization of human leukocyte antigens affects future graft success.
- In addition to the presence of poor physical health and nutrition, CKD is a chronic illness with a significant psychosocial impact on the patient. -Ensure that these are also evaluated

Question 6

What Specific Considerations Should Be Evaluated During the Preoperative
Assessment of CKD Patients?
Dialysis

Answer 6

Obtain history regarding the commencement of dialysis, complications, and previous and current treatment regimes.
Usual routes are either HD through an AVF or a central venous catheter (CVC), or peritoneal dialysis through an intra-peritoneal catheter. IV cannula insertion, phlebotomy, and blood pressure cuff placement should be avoided on the ipsilateral limb with an AVF. Superior vena cava or subclavian vein stenosis may be present due to previous repeated CVC insertions [11].
Determine the patient’s weekly dialysis schedule in order to plan perioperative dialysis effectively. Discuss with renal medicine if required

Question 7

What Specific Considerations Should Be Evaluated During the Preoperative Assessment of CKD Patients?
Electrolyte and Metabolic Abnormalities

Answer 7

Laboratory blood testing to check for any electrolyte disturbances is necessary, even for minor surgery.
Hyperkalemia is common and can be life threatening because blood potassium (K+) excretion is decreased due to impaired renal tubular function. Previous hyperkalemic events should
be noted, as some patients may be more prone than others.
Symptoms and signs of severe hyperkalemia include dyspnea,
palpitations, paresthesias, nausea, bradycardia, muscle
weakness, and depressed tendon reflexes. Early ECG changes
include narrow peaked T waves, short QT interval, and ST
depression. With worsening hyperkalemia, P waves become
absent, QRS interval widens, and conduction block develops.
Terminally, the QRS complex and T wave merge into a sine
wave, culminating in cardiac arrest. Hypermagnesemia
usually coincides with a rise in blood potassium.
Reduced production of active vitamin D3 (calcitriol) leads
to hypocalcemia, hyperphosphatemia, secondary hyperpara-
thyroidism, and renal osteodystrophy. Tertiary hyperparathy-
roidism and hypercalcemia develop after longstanding
secondary hyperparathyroidism. Although hypercalcemia
may be managed by dialysis and medications in this setting,
parathyroidectomy is the treatment of choice for long-term
control, as the hyperparathyroidism itself continues to con-
tribute to renal osteodystrophy.
Symptoms and signs of hypercalcemia include lethargy,
confusion, abdominal pain, nausea, constipation, and hypoto-
nia.
Severe complications include coma and cardiac arrhythmias (from shortened QT interval to complete heart block).
Sodium and chloride levels are usually within the normal range. Hyponatremia may coincide with hypervolemia.
Arterial blood gases may show chronic metabolic acidosis with respiratory compensation. Blood albumin level may be low due to proteinuria, malnutrition, inflammation, or other concurrent diseases.
Hypoalbuminemia will produce a higher ionized blood calcium for a given total blood calcium. Low albumin is a predictor for poor postoperative outcomes [12].

Question 8

What Specific Considerations Should Be Evaluated During the Preoperative Assessment of CKD Patients?
Fluid Status

Answer 8

Patients on dialysis usually have a target or dry weight (base-
line euvolemic weight) to which they are dialyzed. Any acute
and significant weight gain preoperatively most likely indi-
cates an increase in total body water. Other symptoms and
signs of fluid overload include increased dyspnea, hyperten-
sion, elevated jugular venous pressure (JVP), and peripheral
and pulmonary edema.
Chest radiograph may show signs of cardiac failure, e.g.,
cardiomegaly, pleural effusions, and pulmonary vascular
congestion.
The ability to concentrate or dilute urine is impaired.
Some patients, even while on dialysis, can still produce a
“normal” amount of urine per day. This may mean a urinary
catheter is required perioperatively. Caution is needed when
interpreting urine output as marker of intravascular fluid
status

Question 9

What Specific Considerations Should
Be Evaluated During the Preoperative
Assessment of CKD Patients?
Cardiovascular System

Answer 9

With accelerated atherosclerosis and associated cardiovascu-
lar diseases (e.g., hypertension, DM) being major underlying
causes of CKD, a thorough cardiovascular and respiratory
assessment is required. Importantly, the severity and stability
of cardiopulmonary pathologies need to be established,
along with functional status. The latest American College of Cardiology/American Heart Association guidelines should
be employed (discussed in Chap. 2) [13].
Symptoms and signs such as angina, dyspnea, orthopnea,
palpitations, syncope, peripheral edema, lethargy, postural
hypotension, elevated JVP, displaced apex beat, cardiac mur-
murs, extra heart sounds, and pulmonary edema should be
explored at a minimum.
Plasma cardiac troponin and brain-natriuretic peptide lev-
els help to assess dyspnea, ischemic heart disease (IHD), left
ventricular (LV) strain, and perioperative risk stratification.
However, levels need to be interpreted carefully in the setting
of declining GFR and dialysis [14]. Obtaining preoperative
baseline levels assists with interpreting postoperative trends.
Baseline ECG without hyperkalemia may show pre-
existing conduction abnormalities (e.g., arrhythmias, heart
block), decreased R-R variability (from autonomic dysfunc-
tion), and left ventricular hypertrophy (LVH).
Bedside echocardiography is useful to assess patients
with valvular heart disease and cardiac failure. LVH is com-
mon [4] and its extent can be quantified. LV ejection fraction
can be calculated, along with evidence of any diastolic dys-
function. Rarely, uremic pericarditis may be present [15]

Question 10

What Specific Considerations Should Be Evaluated During the Preoperative Assessment of CKD Patients?
Bleeding and Blood Loss

Answer 10

Any history of bleeding diathesis should be sought, and a complete blood count ordered as a minimum. Chronic anemia is ubiquitous and usually physiologically compensated.
Blood transfusion may be required, depending on the surgery. A blood group and screen should be considered.
Platelet levels are typically within the normal range, but platelet dysfunction occurs due to the presence of uremic toxins. In vitro laboratory tests such as partial thromboplastin time and international normalized ratio are usually within normal limits. The effects of CKD on in vivo coagulation and fibrinolytic pathways are complex. Patients are usually considered to be in a prothrombotic state [6].
Neuraxial anesthesia techniques are generally considered safe in uremic patients with no other coagulopathy. Benefits and risks should be tailored to each patient

Question 11

What Specific Considerations Should Be Evaluated During the Preoperative Assessment of CKD Patients?
Surgical Factors

Answer 11

If a pre-dialysis patient is due to undergo major surgery with a high likelihood of requiring RRT postoperatively (e.g., supra-inguinal vascular surgery), the patient may benefit from a dialysis CVC inserted before surgery. This possibility should be discussed with relevant specialties, such as renal and intensive care medicine.
For peritoneal dialysis patients undergoing intraabdominal surgery, an alternative route of dialysis is required postoperatively. For patients needing bowel preparation preoperatively, phosphate-based preparations may
cause acute phosphate nephropathy and are not recommended. If surgery is for AVF formation, assess the patient’s suitability for regional anesthesia, as it may provide better fistula outcomes.

Question 12

What Medications Should We Expect to See
in the Preoperative CKD Patient?

Answer 12

• Angiotensin-converting enzyme (ACE) inhibitors and
angiotensin II receptor blockers (ARBs) slow the progres-
sion of CKD, particularly in patients with proteinuria [4].
They are also used as anti-hypertensives. However, they
can contribute to nephrotoxicity and may cause potassium
retention.
• Loop diuretics are used to prevent hypervolemia and
hypertension, as well as to promote the urinary excretion
of potassium.
• Statins are used for treatment of dyslipidemia and to
lower cardiovascular risk, especially in patients with
established IHD. They may decrease proteinuria [4].
• Erythropoiesis-stimulating agents (ESA), iron, folate, and
vitamin B12 can be used to treat anemia once hemoglobin
level drops below 100 g/L. Over-treatment of hemoglobin
back to the normal range is paradoxically detrimental due
to the increased risk of thrombotic events [10]. ESA and
the improvement in red cell mass help to reduce uremic
bleeding [17].
• Vitamin D3 and calcium for treatment of hypocalcemia
and secondary hyperparathyroidism.
• Dietary phosphate binders for treatment of hyperphos-
phatemia. Older preparations containing aluminum
hydroxide should not be given with sodium citrate.
Increased aluminum absorption can occur when they are
given together, causing neuro-toxicity [18].
• Bicarbonate for treatment of metabolic acidosis when
blood bicarbonate levels reach <22 mmol/L [1].

Question 13

How Should CKD Patients Be Optimized Prior
to Elective Surgery?

Answer 13

Optimization of associated cardiovascular risk factors such
as hypertension and DM is advisable. Cases involving symp-
tomatic and unstable IHD, arrhythmias, valvular lesions, and
cardiac failure should be discussed with the cardiology
service.
Ensure the patient is euvolemic and has no significant
electrolyte abnormalities. Dialysis patients should be close
to their dry weight. A repeat check of blood electrolyte levels
on the day of surgery should be considered in all patients.
Patients normally on HD should be dialyzed within 24
hours before elective surgery but not immediately before.
Hypotension, hypoxemia, neutropenia, coagulopathy, and
dialysis disequilibrium syndrome [19] are possible immedi-
ately after HD.
Guidance from renal medicine should be sought regard-
ing the need for additional treatments for peritoneal dialysis
patients prior to surgery [20]. Dialysate should be drained to
decrease intra-abdominal pressure on the day of surgery.
Other causes of chronic anemia, e.g., iron deficiency ane-
mia, should be identified and managed to ensure optimal red
cell mass, thus reducing the need for blood transfusion.
Minimization of perioperative blood loss is paramount.
Any coexisting coagulopathy should be identified and cor-
rected. In addition to ESA and dialysis, specific treatments to
reduce uremic bleeding include desmopressin, cryoprecipi-
tate, and conjugated estrogens [17].
The risk of perioperative thrombosis versus bleeding
should be considered when deciding whether to cease aspirin
therapy preoperatively. It would be safe to withhold aspirin
preoperatively in CKD patients with low risk of thrombosis.
The continued administration of aspirin perioperatively has
been associated with increased bleeding, while having no
benefit in reducing a composite of death and non-fatal myo-
cardial infarction [21].
Diuretic medications are normally withheld on the day of
surgery. However, if the patient is due to undergo minor day
surgery, diuretics may be continued to help maintain
euvolemia and potassium excretion postoperatively.
ACE inhibitors and ARBs should be withheld on the day
of surgery to prevent intra-operative hypotension.
Pharmacological kidney protection such as the adminis-
tration of N-acetyl cysteine, sodium bicarbonate, loop diuret-
ics, mannitol, and dopamine have been studied. No clear
benefit has been shown for these therapies [22].
Appropriate antibiotic prophylaxis should be prescribed
to prevent surgical site infections.
Patients with suspected delayed gastric emptying should
be treated with aspiration prophylaxis.
A CKD Patient on Dialysis Presents
for Surgery with a K+ of 6.2 mmol/L. How
Would You Proceed?
Ensure that this result is from a recent sample. Blood K+
level may have increased further with elapsed time. Check
whether the blood sample is hemolyzed — release of potas-
sium from red blood cells will give a falsely high K+.
Concurrent 12-lead ECG should be reviewed and compared
to the patient’s baseline ECG.
There is currently no established consensus as to what
constitutes a safe level of K+ prior to elective surgery. The
decision will mainly be based on the chronicity of the hyper-
kalemia for the particular patient (increased tolerance to ECG
changes) and the type of surgery (anticipated tissue damage
and metabolic impact). Generally, a K+ of ≤5.5 mmol/L
would be acceptable to proceed with elective surgery.
Consider postponing surgery if K+ is >6.0 mmol/L with ECG
changes where urgent preoperative dialysis is not feasible. A
multidisciplinary discussion is vital. Ensure improved preop-
erative optimization prior to rescheduled surgery.
Similar considerations apply for emergency surgery. The
urgency of surgery largely dictates the preoperative manage-
ment. Surgery can proceed if K+ is ≤6.0 mmol/L with no
ECG changes, as this should be tolerated well by most
patients. Patients with a K+ >6.0 mmol/L and ECG changes
should be dialyzed preoperatively if possible. Dialysis for 2
hours can sufficiently improve hyperkalemia and reverse
ECG changes [20]. Ensure that anticoagulation is not used or
that it has been reversed to prevent subsequent surgical
bleeding. If dialysis before emergency surgery is not feasible
or if the hyperkalemia worsens intra-operatively, pharmaco-
logical treatment and physiological manipulation are
required until the patient can receive RRT postoperatively. It
may be possible to provide continuous RRT intra-operatively
in exceptional cases.
The acute management of severe hyperkalemia is sum-
marized in Table 26.4 [23]. In addition, mechanical hyper-
ventilation in intubated patients can help temporize
hyperkalemia by compensating for metabolic acidosis, shift-
ing K+ back into cells.

Question 14

A CKD Patient on Dialysis Presents
for Surgery with a K+ of 6.2 mmol/L. How
Would You Proceed?

Answer 14

Ensure that this result is from a recent sample. Blood K+
level may have increased further with elapsed time. Check
whether the blood sample is hemolyzed — release of potas-
sium from red blood cells will give a falsely high K+.
Concurrent 12-lead ECG should be reviewed and compared
to the patient’s baseline ECG.
There is currently no established consensus as to what
constitutes a safe level of K+ prior to elective surgery. The
decision will mainly be based on the chronicity of the hyper-
kalemia for the particular patient (increased tolerance to ECG
changes) and the type of surgery (anticipated tissue damage
and metabolic impact). Generally, a K+ of ≤5.5 mmol/L
would be acceptable to proceed with elective surgery.
Consider postponing surgery if K+ is >6.0 mmol/L with ECG
changes where urgent preoperative dialysis is not feasible. A
multidisciplinary discussion is vital. Ensure improved preop-
erative optimization prior to rescheduled surgery.
Similar considerations apply for emergency surgery. The
urgency of surgery largely dictates the preoperative manage-
ment. Surgery can proceed if K+ is ≤6.0 mmol/L with no
ECG changes, as this should be tolerated well by most
patients. Patients with a K+ >6.0 mmol/L and ECG changes
should be dialyzed preoperatively if possible. Dialysis for 2
hours can sufficiently improve hyperkalemia and reverse
ECG changes [20]. Ensure that anticoagulation is not used or
that it has been reversed to prevent subsequent surgical
bleeding. If dialysis before emergency surgery is not feasible
or if the hyperkalemia worsens intra-operatively, pharmaco-
logical treatment and physiological manipulation are
required until the patient can receive RRT postoperatively. It
may be possible to provide continuous RRT intra-operatively
in exceptional cases.
The acute management of severe hyperkalemia is sum-
marized in Table 26.4 [23]. In addition, mechanical hyper-
ventilation in intubated patients can help temporize
hyperkalemia by compensating for metabolic acidosis, shift-
ing K+ back into cells.

Question 15

True/False Questions
1. (a) Perioperative risk of cardiovascular events is
increased in CKD patients.
(b) Tertiary hyperparathyroidism causes hypocalcemia
and hypophosphatemia.
(c) Indications for dialysis in CKD patients include
refractory hyperkalemia and fluid overload.
(d) Daily urine production reduces in proportion to
declining GFR.
(e) ACE inhibitor therapy helps decrease proteinuria in
CKD patients.

Question 16

2. (a) Treatment of anemia in CKD patients should aim for
   a target hemoglobin level back in the normal refer-
   ence range.
   (b) For elective surgery, end-stage CKD patients should
   be dialyzed immediately before surgery to achieve
   optimal fluid and electrolyte status.
   (c) CKD patients with a preoperative K+ level of 6.0 mmol/L
   should always have their surgery postponed.
   (d) ECG signs of severe hyperkalemia include absent P
   waves, QRS interval widening, and conduction block.
   (e) The prevention of uremic bleeding involves the infu-
   sion of functional allogenic platelets.

Question 17

Does This Patient Need to Be Referred
to a Center That Does Transplant Surgery
to Have His Hip Surgery?

Answer 17

This is not essential but the patient needs to be reviewed and
treated by a perioperative medical team who are experienced
in managing post-heart transplant patients. In particular, the
team should have expertise in the assessment of cardiac and
immunosuppressive status preoperatively and of supervising
anti-rejection therapy postoperatively.

Question 18

Which Surgical Post-transplant Patients
Should Be Referred to a Transplant
Surgery Center to Have Non-transplant
Surgery

Answer 18

If the non-transplant surgery involves the transplanted organ,
may significantly affect the function of the transplanted
organ, or if the patient appears unstable, referral to a trans-
plant center is advisable.
In the case described, the patient has a complication that
is common in the general population, likely has no relation-
ship to the transplanted organ, and the surgery will be
unlikely to affect the transplanted organ directly. It should be
possible to perform the orthopedic intervention in a non-
transplant center, assuming appropriate team expertise in
post-transplant management.

Question 19

This Patient at Increased Risk for Traumatic
Hip Fracture?

Answer 19

Long-term immunosuppressive therapy is required following
organ transplantation and is associated with the development
of osteoporosis and bone demineralization, which increase
the risk of fractures and avascular necrosis of the femoral
head.

Question 20

What Are the Physiological Features
of the Transplanted Heart?

Answer 20

Transplant surgery requires removal of all neural and vascu-
lar connections from the donor organ and restoring the vas-
cular connections but not the neural connections [1–5].
Partial cardiac reinnervation may occur in many patients and
the higher resting rate of the transplanted heart may trend
downward with time. The transplanted heart is preload-
dependent to maintain cardiac output and blood pressure.
Hemodynamics are very sensitive to vasodilated conditions
such as septic shock and neuraxial anesthesia.

Question 21

Are There Any Unique ECG Features That
May Be Seen Following Orthotopic Heart
Transplant?

Answer 21

If a biatrial surgical approach has been used, there will be
two P waves visible on the ECG. With the biatrial technique,
remnants of the native atria, including tissue that contains the
native sinus node and the pulmonary venous ostia remain in
situ and are anastomosed to parts of the donor atria
including on the right side, tissue containing the donor sinus
node. Both sinus nodes retain automaticity and excite the
surrounding tissue, hence the two P waves. Propagation of
conduction of the native node is impeded by the suture line;
consequently, the resting heart rate is determined by the
donor node. The bicaval surgical technique, where the
recipient atria are excised, is more popular today and under
these circumstances there will be only one P wave.
It is common to observe right bundle branch block and/or
right intraventricular delay on the ECG of a recently trans-
planted patient, this is a benign finding.
Acute rejection is usually manifest on an ECG as low
QRS voltage and concomitant atrial fibrillation/flutter.

Question 22

Describe a General Approach
to Preoperative Evaluation of this Patient

Answer 22

Preoperative evaluation of transplant patients undergoing
non-transplant surgery includes assessment of graft function,
indicators of rejection, presence of infection, and other organ
function. Solid organ transplant recipients may be at
increased risk for atherosclerotic coronary artery disease and
should be assessed accordingly [6]. Changes in immunosup-
pressive medication and a history of rejection episodes
requiring rescue immunosuppressive therapy should be
noted [7]. During the preoperative workup, the perioperative
team must be mindful that patients on chronic immunosup-
pressive therapy are predisposed to diabetes, epilepsy, hyper-
tension, renal insufficiency, hyperkalemia, hypomagnesemia,
pancytopenia, and poor wound healing.

Question 23

What Blood Tests Should He Have Before
Surgery?

Answer 23

In general, testing should be directed by the likelihood of
detecting abnormalities that affect management either preop-
eratively or in anticipation of postoperative abnormalities for
which a baseline comparison may be useful [1–5].
In this case, most testing can be guided by the probability
of abnormalities caused by the immune-modulating drugs.
Since this immune regimen can affect renal function, and
steroids have been associated with gastric ulcerations,
evaluation of the complete blood count, electrolytes, and
creatinine are appropriate.

Question 24

Should This Patient Have an Echocardiogram
or Chest Radiograph?

Answer 24

These tests are not likely to be useful in the absence of spe-
cific symptoms suggestive of an acute change in the status of
the patient, but review of the most recent echocardiogram
findings is appropriate. It is helpful to be aware of the ven-
tricular and valvular function.

Question 25

Do Other Transplanted Solid Organs Differ
from Native Organs?

Answer 25

Transplanted organs, other than the heart in some cases,
remain denervated. In the lung transplant patient, normal
sensation is present at the glottis but is lost below the level of
the tracheal or bronchial anastomoses. The cough reflex is
lost below the level of the anastomosis. Mild airway hyper-
activity and impaired mucociliary clearance are features of
the transplanted lung [7]. Pulmonary function tests (PFTs)
return to near normal in double lung transplant patients at
6–12 months, and single lung transplant patients with
obstructive disease undergo a 50–60% improvement in PFTs
[8, 9].
Neither the transplanted liver nor kidney are significantly
affected by denervation. The transplanted kidney is usually
placed in the iliac fossa. The anesthesiologist delivering a
nerve block to a patient with a transplanted kidney should be
cognizant of the specific location of the transplanted kidney.

Question 26

Do the Systemic Effects of the Condition
Leading to the Organ Failure and Transplant
Persist?

Answer 26

This applies in many cases. For example, diabetes is a com-
mon condition leading to end-stage renal failure. Unless the
diabetic patient has had a pancreas transplant, the diabetes
persists. This affects preoperative testing and the probability of perioperative complications, and investigations should be
directed as appropriate.
Some conditions leading to organ failure are non-systemic
and may be largely resolved with a transplant, while others
are mixed. Primary biliary cirrhosis and progressive scleros-
ing cholangitis are conditions that often lead to liver failure
but are usually non-systemic unless associated with another
condition such as ulcerative colitis. An example of a mixed
condition is cystic fibrosis. Cystic fibrosis can affect primarily
the lung, primarily the intestine, or both. When cystic fibro-
sis leads to pulmonary failure and transplant, the pre-existing
intestinal effects persist.

Question 27

What Complications Are Common Among
Organ Transplant Patients?

Answer 27

Several complications can commonly occur. Rejection of the
transplanted organ may be a chronic condition of varying
intensity, requiring periodic adjustment of the immunosup-
pressive therapy. Hypertension, diabetes, anemia, thrombo-
cytopenia, leukopenia, neurotoxicity, renal insufficiency, and
episodic fever, among others, occur periodically. The patient
may be receiving corrective medications, and these do not
usually need perioperative adjustment

Question 28

Are There Any Special Considerations
for Liver Transplant Recipients?

Answer 28

• Liver transplant recipients recover the capacity for drug
metabolism after reperfusion of the transplanted liver [6].
• Liver transplant patients are at high risk for development
of post-transplant hypertension, acute coronary syn-
drome, and cardiac failure even when cardiac disease is
not present pre-transplant [10, 11].
• There is a significant risk of chronic renal failure after
liver transplant—the 5-year cumulative incidence of end-
stage renal disease is 18–22% [6, 12].
• Hyperlipidemia and diabetes mellitus are more common
in liver transplant patients, and those who develop
diabetes are at increased risk of cardiac disease and graft
dysfunction [13].

Question 29

Does This Patient Need a Cardiology Consult
Before Surgery?

Answer 29

This is not necessary in the case described. This patient has
been medically stable, is followed regularly, and fit for the
planned surgery. However, should the patient not be followed
carefully, or should another complicating condition be
suspected, consultation is appropriate. For example, had this
patient’s fall occurred after a loss of consciousness and
particularly if faints had become a problem for the patient,
further investigation to determine the cause of loss of
consciousness would be appropriate.

Question 30

What Immunosuppression Protocols Are
Typically Seen in Transplant Patients?

Answer 30

Rejection is one of the major barriers to long-term transplant
survival. Solid organ transplant recipients take immunosup-
pressive agents for life. Chronic exposure to immunosup-
pressants is associated with infection, lymphoproliferative
diseases, and organ dysfunction [14].
A usual regimen consists of initial administration of
intense, short-term immunosuppression during the peri-
operative and immediate postoperative period followed by
lifelong maintenance. One of the most common induction
immunosuppressive agents is basiliximab. It is an inter-
leukin-2 receptor antagonist that decreases the incidence
of acute rejection when used as induction therapy when
combined with maintenance immunosuppression. No
significant drug interactions have been reported for
basiliximab.
Maintenance immunosuppression makes use of multiple
medications that target different parts of the immune sys-
tem. A triple therapy regimen is commonly used, consisting
of the second-generation calcineurin inhibitor tacrolimus,
the antiproliferative agent mycophenolic acid, and a cortico-
steroid. The most commonly used corticosteroid agents are
prednisone, prednisolone, and methylprednisolone. As with
other immunosuppressive agents, tacrolimus can cause
nephrotoxicity and neurotoxicity and can increase the risk
of infection [14

Question 31

How Do the Immune System-Modifying
Drugs Affect Anesthetic Management?

Answer 31

There are multiple perioperative effects to consider. Common
to many of these medications is induction of liver enzyme
metabolism, e.g., prednisone induces cytochrome P450. This
can lead to an interaction with other drugs metabolized by
the cytochrome P450 system, e.g., opioid analgesics, antibi-
otics, and muscle relaxants, and may lead to a reduction in
the half-life of these medications [4, 5, 15–18].
All immune modifiers suppress the immune system,
necessitating meticulous attention to sterile technique in
order to minimize risk to the patient.
Steroids are associated with glucose intolerance, and the
patient may require an insulin infusion perioperatively.
Moreover, any steroid exposure within the year prior to sur-
gery leads to the risk of adrenal suppression and requires
steroid supplementation to respond to the surgical stress. The
specific amount of steroid supplementation is controversial.
Further discussion regarding perioperative steroid manage-
ment and stress dosing can be found in Chap. 19. Awareness
of the possibility of Addisonian phenomena due to steroid
deficiency and the ability to recognize them are vital
[15–18].
Tacrolimus can occasionally produce central and periph-
eral nervous system effects characterized by denervation or
dysesthesias. If these are present, they should be documented
preoperatively so that their recognition postoperatively is not
attributed to intraoperative events [16, 17].
Cyclosporine has been associated with prolonged effects
of neuromuscular relaxants. Limitation of the dose of neuro-
muscular relaxants is prudent.

Question 32

How Should the Immune System-Modifying
Drugs Be Managed?

Answer 32

Maintenance of immune suppression is vital to organ sur-
vival. Most are available for intravenous administration, and
this substitution is advisable perioperatively to ensure ade-
quate drug levels [15–18]. It is prudent to measure blood
levels of immune suppressants to guide dosing. Prednisone
dosing may need to be adjusted to accommodate for the
stress of the perioperative period, as discussed above.

Question 33

Can This Patient Have a Regional Anesthetic,
or Should He Have a General Anesthetic?

Answer 33

In this case, regional anesthesia is an option; however, the
merits of regional anesthesia are few, while the situational
risks are notable [19]. In this patient, the transplanted
heart has been denervated and does not respond to the
neural component of the patient’s sympathetic nervous
system. As well, the heart is preload dependent to main-
tain cardiac output and blood pressure. Consequently, the
patient is not well positioned to respond to the usual
hemodynamic changes of a central neuraxial block. Also,
the decision to employ a central or peripheral block in a
patient with documented neuropathy should be taken
carefully.
By comparison, the use of general anesthesia does not
present the same concerns and may be both simpler and
safer.

Question 34

Does the Patient Need a Pacemaker
Available Perioperatively?

Answer 34

This is not required as this patient has an intact conduction
system and his heart has a normal rhythm.

Question 35

Are There Any Concerns Perioperatively
with Regard to Other Solid Organ Recipients,
for Example, Liver, Kidney, Lung?

Answer 35

The transplanted lung is affected by denervation, and
patients will not have the normal sensitivity to react to for-
eign material in the airway and will not have a reflex cough
in response.
Patients with kidney transplants are often affected by the
same systemic condition that led to the kidney failure, e.g.,
diabetes, and attention to these possible effects is
appropriate.

Question 36

True-False Questions
1. (a) The transplanted heart does not respond to the auto-
nomic nervous system of the recipient.
(b) The resting heart rate of the transplanted heart is
lower than in the non-transplanted heart.
(c) Two P waves are usually seen in the ECG of the heart
transplant recipient.
(d) Pulmonary function tests do not return to normal
after a double lung transplant.
(e) Liver transplant recipients completely recover the
capacity for drug metabolism.

Question 37

2. (a) Solid organ transplant recipients usually discontinue
   immunosuppressive medications within 5 years of
   transplant.
   (b) Basiliximab is a common induction immunosuppres-
   sive agent used perioperatively.
   (c) A corticosteroid agent is normally part of the triple
   agent anti-rejection regimen administered to solid
   organ transplant recipients.
   (d) Tacrolimus is commonly associated with neurotoxic
   adverse events.
   (e) Patients who take cyclosporine may need a larger dose
   of neuromuscular relaxants for effective paralysis.