254
Subramaniam
hyperventilation to keep EtCO2 30–35 mmHg,
use of total intravenous anesthesia with propo-
fol in place of the inhalational agent, and man-
nitol 0.25–1 g/kg slow IV before the opening
of the dura.
• The position of the patient depends on the sur-
gical approach chosen. For craniotomy, sub-
frontal, pterional, transcallosal, transcortical,
lamina terminalis, and bifrontal approaches [9]
may be used depending upon the tumor loca-
tion and size. For smaller intrasellar tumors, an
endoscopic approach in the supine position
with the head flexed to one side and reverse
Trendelenburg position is required. A Mayfield
frame is used to stabilize the head which can
cause intracranial bleed, dural tear, or skull
fractures in small children. Hence it invites
extreme caution! Local infiltration or scalp
block may be given. After proper positioning,
eyes and all pressure points must be padded.
• Intraoperative bleeding should be managed
with fluids, blood, and blood products.
Persistent hypotension despite adequate resus-
citation should raise suspicion of hypoadre-
nalism and warrants steroid replacement. Inj.
hydrocortisone 0.5–1 mg/kg IV should be
given and continued in the postoperative
period for at least 72 h.
• Given the proximity of the lesion to vital neuro-
logical structures, surgery can lead to damage
to the optic chiasm, thalamus, mammillotha-
lamic tract, and forebrain causing neurological
deficits in the postoperative period.
• Temperature homeostasis may be disturbed
due to hypothalamic injury. Hence tempera-
ture should be closely monitored and hypo-
thermia/hyperthermia prevented.
• The trans-sphenoidal approach may lead to
CSF leaks which should be watched for in the
postoperative period.
17.2.2 Postoperative Management
Postoperative management remains crucial and
the following are the important concerns:
• Diabetes insipidus should be suspected if
urine output >4 m/kg/h and treated with fluid
R.
replacement and desmopressin. Its incidence
is highest in the postoperative period
(70–90%).
• Adequate analgesia must be provided with
multimodal techniques including opioids,
NSAIDs, and scalp blocks.
• Steroid and hormone replacement should be
continued for at least 72 h or even later as per
need.
• Cerebral edema reduction measures should be
continued along with seizure prophylaxis.
• Hypopituitarism and hypothalamic dysfunc-
tion should be watched for and managed.
• Postoperatively, certain high-risk patients
including major blood loss intraoperatively,
suspicion of increased intracranial pressures,
and extensive tumor resection should be man-
aged in critical care setup and may require the
need for mechanical ventilation.
• Postoperative MRI is done to look for residual
lesions and to plan adjuvant RT.
• Long-term endocrinology follow-up is
required for the management of hormonal
imbalances.
In summary, a dedicated multidisciplinary
approach toward the management of craniopha-
ryngiomas is essential for successful postoperative
outcomes. This requires in-depth knowledge about
the associated endocrinopathies and the periopera-
tive involvement of various brain centers.
Preoperative optimization of the hormonal dys-
function and dyselectrolytemia with a high index
of suspicion for diabetes insipidus in the postop-
erative period is key to successful management.
17.3 Adrenocortical Tumors
Adrenocortical carcinoma (ACC) may be secre-
tory (producing cortisol and/or mineralocorticoid
and/or androgen) resulting in Cushing’s or
Conn’s syndrome or nonsecretory. It is com-
monly seen in females of less than 40 years.
Overt clinical symptoms, due to hypersecretion
of the adrenal hormones, are the most common
presentation (nearly 60% of cases). ACC hyper-
secretion is the etiological factor for Cushing’s
syndrome in almost 10–15% of cases [11]. About
17 Anesthetic Concerns in Endocrine Cancers
30% of patients of ACC have symptoms related
to mass effect without clinical manifestation
related to the secretory tumor. Most ACCs result-
ing in Cushing’s syndrome (80%) are ACTH
dependent, the source being the pituitary. Adrenal
hyperplasia resulting from excess ACTH from
the pituitary is termed Cushing’s disease. About
10% result from an ectopic ACTH source, usu-
ally small cell Ca of the lung. The remaining 10%
are ACTH independent.
Conn’s syndrome (primary hyperaldosteron-
ism) is manifested usually from a single ade-
noma. The excessive ACTS production from the
pituitary gland may lead to adrenal hyperplasia,
and the condition is labeled as Cushing’s
disease.
Adrenocortical carcinoma (ACC): The com-
monest etiology of corticotropin-independent
Cushing’s syndrome is ACC. The majority (80%)
are secondary to elevated ACTH from a pituitary
tumor. The remaining small proportion is second-
ary to ectopic ACTH-producing sites (10%).
ACC manifests as “metabolic syndrome,” and
impaired glucose levels, increased blood pres-
sure, hyperlipidemia, hypercoagulability, and
central obesity are the usual manifestations [12].
Other important clinical findings include hirsut-
ism, amenorrhea in females, striae, and bruising
[11]. High serum cortisol levels lead to hyperco-
agulability secondary to hyper-homocysteinemia,
increased clotting factors, impaired fibrinolysis,
and abnormalities in von Willebrand factor
(vWF). These factors mandate a thorough preop-
erative evaluation to identify any of these abnor-
malities for optimal perioperative planning and
risk stratification [12]. An extensive preoperative
cardiac evaluation, including assessment of car-
diac risk factors, ECG, and echocardiography, is
also required.
Hypercortisolism also has an impact on psy-
chological and cognitive abnormalities. Patients
have mood fluctuations, depression, and suicidal
thoughts. A preoperative psychiatric evaluation
may be needed. About 50% have osteoporosis,
and so all patients must be questioned about bone
pains/backache to rule out vertebral collapse/
fractures which can affect perioperative care
[13].
255
Rarely symptoms escalate over a few weeks,
leading to a “cortisol crisis,” which requires
emergent adrenalectomy as a lifesaving mea-
sure [14].
Nearly half of the ACCs are functional. The
most common hormone secreted is cortisol fol-
lowed by androgens, aldosterone, and estrogen.
Almost 15% of patients of ACC may have raised
more than one hormone, and thus biochemical
profiling for serum cortisol, plasma ACTH, 24-h
free urinary cortisol, and 1 mg dexamethasone
suppression test should be done [15]. Also, the
elevation of sex steroids and/or their precursors
and mineralocorticoids are indicative of
malignancy.
Imaging with MRI/CT is the next step and is
necessary to see the precise location, size, metas-
tases, homogeneity, contrast enhancement, and
contrast washout [16]. Typically malignant
lesions have a slower washout time.
17.3.1 Preoperative Optimization
These patients need optimization of blood pres-
sure and glucose, often on an urgent basis, before
surgery. The use of angiotensin-converting
enzyme (ACE) inhibitors and angiotensin
receptor-­blocking (ARB) drugs are effective for
symptom control. It is important to withhold
ARB dose on the day of surgery to avoid the
severe and often refractory hypotension seen in
these patients following induction [17], neurax-
ial blockade, or adrenalectomy, compounded by
suppression of the HPA axis due to hypercorti-
solemia. Electrolyte abnormalities should be
corrected. Severe metabolic alkalosis (due to
intracellular acidosis and HCO3−reabsorption)
may lead to compensatory respiratory depres-
sion, atelectasis, and hypoxemia [14].
Hypokalemia can increase myocardial irritabil-
ity and predispose to arrhythmias. Preexisting
anemia is not uncommon; also, there is a poten-
tial for significant blood loss. Blood and blood
products should therefore be typed and cross-
matched before surgery. Consideration should be
also given for DVT prophylaxis preoperatively.
In case neuraxial blockade is planned, pharma-
256
cological thromboprophylaxis can be initiated
following surgery. Vascular access may be diffi-
cult due to peripheral edema/easy bruisability of
skin [18]. Fungal infections are common in the
neck/axillae and should be considered before
placing central venous access. Stress doses of
steroids should be given intravenously in the
perioperative period in patients with hypercorti-
solism, to reduce postoperative adrenal
insufficiency.
17.3.2 Induction and Maintenance
of Anesthesia
For IV induction in patients with cortisol excess,
etomidate is avoided. Both propofol and thiopental
are suitable. Depending on the indication, either
non-depolarizing or depolarizing muscle relaxants
can be used. In patients with predominant cortisol
excess, central obesity and “buffalo hump” may
cause difficulty with laryngoscopy, which can be
overcome by placing the patient in the “ramped”
position employed for bariatric patients.
17.3.3 Monitoring and Ventilator
Management
Standard monitoring (SpO2, ECG, noninvasive
blood pressure, and EtCO2) is usually sufficient
for laparoscopic adrenalectomy. After induction,
arterial and central lines may be placed which
facilitate hemodynamic monitoring, accurate
titration of vasopressor therapy, and blood-gas
estimation in sicker patients [18]. Invasive hemo-
dynamic monitoring along with the noninvasive
cardiac output is useful for goal-directed fluid
therapy in patients with a poor preoperative car-
diac reserve and large tumors associated with
prolonged surgery and blood loss.
Intraoperatively, both hypertension (adrenal dis-
section and mobilization) and hypotension (blood
loss, cortisol withdrawal) may occur. Neuromuscular
monitoring is useful to guide blockade, given that
hypokalemia can prolong blockade.
Preoperative hypoventilation (secondary to
metabolic alkalosis and diminished ventilatory
drive) and resulting atelectasis can worsen
R. Subramaniam
hypoxemia and/or lung compliance after pneu-
moperitoneum, which can be managed to some
extent by using higher FiO2 and PEEP. All inha-
lational agents are suitable. Blood sugar levels
need to be monitored at frequent intervals [18]. In
the case of complex tumors with extensive vascu-
lar involvement, vascular isolation procedures
and extracorporeal membrane oxygenation may
have to be arranged.
17.3.4 Surgical Approach
The surgical excision of these tumors can be
attempted via an open or laparoscopic approach.
An open approach remains an acceptable stan-
dard modality of the management of these
tumors, especially when an infiltrating tumor or
suspected lymph nodes (presumably stage III)
are present. The laparoscopic approach may be
preferred in selected patients based on accessi-
bility and respectability [11]. Although pain
intensity in the initial postoperative period with
either technique is high, requiring frequent opi-
oids, LA has the advantages of better cosmesis,
less pain, and reduced analgesic requirement.
Further, pneumoperitoneum worsens the effects
of general anesthesia in lung mechanics, such
as reduced functional residual capacity,
increased intrapulmonary shunts, and increased
dead space. This may further increase hypox-
emia [18].
17.3.5 Analgesia
The provision of adequate analgesia cannot be
overemphasized. After open procedures, the large
incision, obese body habitus, preoperative com-
promised lung function, and edema set the stage
for the development of postoperative pneumonia
[19]. Preinduction placement of an epidural cath-
eter or a single dose of intrathecal morphine
(150–200 μg) may provide superior quality anal-
gesia without respiratory depression [14].
Multimodal analgesia with NSAIDs and
paracetamol is useful but not as effective. Early
ambulation and provision of postoperative throm-
boprophylaxis are essential [12, 19]. Parenteral
17 Anesthetic Concerns in Endocrine Cancers
steroids are administered for up to 72 h, with
gradual tapering off onto minimal maintenance
oral doses.
17.4 Malignant Adrenal
Medullary Tumors:
Malignant
Pheochromocytomas
The malignant pheochromocytoma is seen in
3–13% of the patients of pheochromocytomas
[20]. These patients may have metastases to the
lung, lymphatic nodes, muscle, or liver. These
tumors have a poor prognosis with a 5-year sur-
vival of 44%.
17.4.1 Presentation
Malignant pheochromocytomas present with all
features commonly found with the non-benign
counterparts. Also, they are significantly larger
(more than 10 cm), and the 24-h urinary vanil-
lylmandelic acid (VMA) per unit of the tumor is
often low. Hyperglycemia is frequent and may
mandate therapy with insulin. The etiology for
glucose metabolism alteration is related more to
alpha-receptor-mediated insulin inhibition than
β-insulin-releasing actions.
17.4.2 Investigations
Preoperative investigations must include an ECG,
blood pressure (BP) and heart rate (HR) record,
and echocardiography [21]. Laboratory tests
should include hematocrit, liver and renal func-
tion and baseline electrolytes. Blood sugar status
needs to be elucidated.
17.4.3 Preoperative Optimization
The pharmacological optimization for the effect
of excess circulating catecholamines is desirable
before surgery. Prolonged exposure to catechol-
257
amines may result in myocardial ischemia,
arrhythmias, or congestive failure (catecholamine
cardiomyopathy). These patients have pallor and
increased hematocrit due to catecholamine vaso-
constriction. A vast majority of patients with
malignant pheochromocytomas present with
severe hypertension, which needs evaluation and
control. The alpha-blockers remain the first drug
of choice to control blood pressure. Recently the
use of doxazosin, terazosin, and prazosin is pre-
ferred as compared to conventional phenoxyben-
zamine [21]. The newer agents are short-acting
and easily titratable to the target hemodynamic
status with a lesser risk of hypotensive episodes
[21]. Urapidil, a peripheral postsynaptic alpha-1
adrenergic antagonist, has been successfully used
for rapid preoperative optimization of patients
with pheochromocytomas ([22]). Calcium chan-
nel blockers and/or clonidine may be required to
optimize blood pressure control in case alpha
blockers by themselves are inadequate. Once an
appropriate alpha-blockade is achieved, beta-
blockers may be added for arrhythmia control
[21]. Patients with metastatic pheochromocy-
toma may also require alpha-methyl-para-tyro-
sine (MPT, which inhibits catecholamine
synthesis). Preoperative institution of selective
alpha-­adrenergic and subsequent beta-blockade
has several advantages (Fig. 17.1).
MPT inhibits catecholamine synthesis. Tumor
catecholamine stores are reduced by 50% after
pretreatment for 3 days. There is a good correla-
tion between catecholamine release from tumor
and perioperative cardiovascular instability. A
few patients may have refractory hypertension
not controlled by alpha-blockers. The tachycar-
dia and precipitous hypotension/QT prolonga-
tion caused by alpha-blockade (especially
phenoxybenzamine and phentolamine) may not
be well tolerated in patients with coronary artery
disease. Similarly, patients with LV dysfunction
due to catecholamine cardiomyopathy may not
tolerate beta-blockade. In these groups of
patients, MPT may be useful for blood pressure
control. The dose is 250 mg orally, increased by
250–500 mg/day to reach 1.5–2 g/day for
1–3 weeks in extensive metastatic disease. The
use of MPT combined with a-blockade (“com-
258
Pre operative preparation
Normalization of
hematocrit
Symptom Reduces intraoperative
control Hemodynamic crises
Attenuation of
vasoconstriction
Fig. 17.1 Preoperative institution of selective alpha-adrenergic and subsequent beta-blockade has several advantages
bined medical blockade”) is observed to have
stable hemodynamics [23]. Diarrhea, crystallu-
ria, galactorrhea, anxiety, and depression are
among the many side effects of MPT, frequently
leading to poor compliance: rarely extrapyrami-
dal symptoms may need treatment with carbi-
dopa. Appropriate saline hydration (2–3 L) is
required in patients who have received alpha-
blockers to prevent hypotension post-removal of
the tumor. In the face of good hemodynamic
monitoring and availability of appropriate drugs
for acute intraoperative blood pressure control,
the utility of preoperative alpha-blockade has
been questioned [24].
17.4.4 Induction and Maintenance
of Anesthesia
Probably there is no other surgical condition
than pheochromocytoma whose anesthetic
management is often described as hazardous
and discussed in great detail with a variety of
agents; in reality, however, with a better under-
standing of its pathophysiology, advanced mon-
itoring, availability of a multitude of agents,
and anesthetic management are reasonably
straightforward.
Propofol and thiopental are both useful for
anesthetic induction. Administration of a bolus of
magnesium sulfate 30 mg/kg at induction is very
effective in preventing blood pressure surges.
Vecuronium, due to its cardiovascular stability, is
R. Subramaniam
Restitution of
Vascular volume
Corrects RWMA
Reverses myocardial
ischemia
the preferred neuromuscular blocking agent.
Fentanyl in doses of 3–5 μg/kg IV attenuates
stress response to intubation.
17.4.5 Intraoperative Hypertension
The hypertensive events are observed intraopera-
tively at various time points like events causing
sympathetic stimulation, e.g., laryngoscopy, endo-
tracheal intubation, and orogastric or nasogastric
tube insertion. Also, certain drugs have a vagolytic
effect; catecholamine secretion, histamine release,
or dopamine receptor blockade can induce hyper-
tension. These agents include ketamine, morphine
in large doses, atropine, pancuronium, droperidol,
metoclopramide, and inhalational agents includ-
ing halothane and desflurane. Patient positioning
or any compression on the abdomen can lead to
tumor releases of catecholamines and thus surge in
blood pressure. Profound (>10 mm Hg) postural
fall in blood pressure after α-blockade, mean arte-
rial pressure (MAP) above 100 mm Hg, symptom-
atic high blood pressure, high plasma NE
concentration, and large tumor size have all been
seen to correlate with severe intraoperative hemo-
dynamic instability. The hypertensive episodes are
more commonly seen in familial pheochromocy-
tomas. These hypertensive episodes can lead to
various cardiac events and thus mandate vigilance.
Rhabdomyolysis has been reported as well.
Recurrent hypertensive episodes may result in
mydriasis.
17 Anesthetic Concerns in Endocrine Cancers
17.4.6 Management of Hypertensive
Crisis
The mainstay is sodium nitroprusside (SNP)
infusion which is prepared as a 0.01% solution in
5% dextrose. It is preferably “in-line” and con-
nected to the central venous catheter, to enable
small boluses to be rapidly administered during
intraoperative hypertensive crises, e.g., in
response to tumor handling, pneumoperitoneum,
etc. [21, 25]. It brings down the blood pressure
rapidly with associated tachycardia. Milder rises
in blood pressure can be controlled by boluses of
labetalol or 200–500 μg boluses of nitroglycer-
ine. Supraventricular tachycardia can be treated
with esmolol 0.5 mg/kg; lidocaine 1–1.5 mg/kg
is indicated for ventricular arrhythmia.
Nicardipine (5–10 mg/hr) and fenoldopam
(0.2 mg/kg/min) are the preferred drugs for
patients not responding to conventional drugs.
Urapidil infusion (10–15 mg/hr) has also been
reported for hemodynamic control during laparo-
scopic pheochromocytoma excision. More
recently, the use of dexmedetomidine (0.3–
0.7 μg/kg/min) has been reported [26].
17.4.7 Postoperative Concerns
Pheochromocytoma excision is commonly asso-
ciated with significant postoperative hypoten-
sion due to acute and abrupt catecholamine
withdrawal. It is compounded by the residual
action of long-acting alpha-blockers, volume
loss and inadequate replacement, or relative
hypovolemia in the face of vasodilation resulting
from catecholamine withdrawal, and “downreg-
ulation” of peripheral adrenoceptors. Tumor size
>60 mm, urinary norepinephrine levels >600 μg/
day, and urinary epinephrine levels >200 μg/day
are independent predictors of prolonged hypo-
tension requiring postoperative vasopressor sup-
port [26, 27].
After adequate fluid replacement to correct
losses, it is advisable to initiate a low-dose nor-
epinephrine infusion which corrects hypotension
and allows the adrenoceptors to regain their
responsiveness to catecholamines. Hypoglycemia
259
tends to occur and can be severe, resulting in
obtundation. It is more common with epinephrine-­
secreting pheochromocytomas and longer opera-
tive times [28].
17.5 Malignant Carcinoid
and Carcinoid Syndrome
Carcinoid tumors are uncommon, slow-growing,
mostly asymptomatic neuroendocrine tumors of
enterochromaffin cells. Despite a benign nature,
their similarity to carcinomas gives them their
name. The incidence of these tumors is approxi-
mately 3.8–5.2/100,000. Carcinoids secrete sero-
tonin, histamine, bradykinin, and other vasoactive
peptides that are rapidly metabolized by the liver
after their release into the portal circulation.
Symptoms are therefore produced by hepatic
metastases, and by carcinoids not draining into
the liver (bronchial carcinoids), when the vasoac-
tive peptides reach the systemic circulation, pro-
ducing life-threatening perioperative
hemodynamic instability [29].
In 2000, the World Health Organization devel-
oped a classical system that recommended “neu-
roendocrine (NE) tumor” instead of “carcinoid.”
According to this classification system, these
tumors may be grouped into any of three classes
based on malignant potential as assessed
histologically:
• Well-differentiated NE tumor
• Well-differentiated NE carcinoma
• Poorly differentiated NE carcinoma
The commoner sites of carcinoids are the gas-
trointestinal (GI) tract (67.5%) and bronchopul-
monary system (25.3%). Among the GI tract, the
small intestine (40%) is commoner followed by
the rectum (27%) and stomach (10%). The
symptoms of carcinoid syndrome are due to
hepatic metastases occurring from NE tumors in
the small intestine. The vasoactive substances
released in circulation by the metastatic tumor
cells remain the reason for the manifestation of
the carcinoid syndrome in 30–50% of the
patients [30].