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tion and end-tidal CO2 throughout the perioperative period. Fetal goiter may often be diagnosed by prenatal ultrasound,
Finally, the management of the hypothyroid patient is further and fetal hormone levels may be safely monitored using intra-
uterine umbilical blood sampling.21 Effective therapy is avail-
complicated by acquired VW syndrome, altered metabolism and
inactivation of drugs, primary adrenal insufficiency, electrolyte able, including the intra-amniotic injection of levothyroxine for
and free-water clearance abnormalities, hypoglycemia, and fetal hypothyroidism and the maternal administration of antith-
delayed gastric emptying. yroid drugs for fetal hyperthyroidism. If unrecognized, fetal goi-
Regional anesthesia appears to be safe provided that volume ter may interfere with vaginal delivery or obstruct the neonatal
and cardiac status are carefully monitored and maintained. airway.

4 Metabolic disorders

Table 16.2 Drugs that alter thyroid function Table 16.3 Diabetic ketoacidosis complicating pregnancy:
incidence and fetal mortality rates
A. Drugs that may potentiate or exacerbate hyperthyroidism
1. Drugs that increase TSH secretion Period Incidence Fetal mortality
Iodine, Lithium
1950“79 18/277 (7.9%) 5/18 (27.7%)
Dopamine antagonists, Tricyclic antidepressants
1971“90 11/635 (1.73%) 2/9 (22%)
2. Drugs that increase thyroid hormone secretion
1976“81 51/227 (22%) 18/51 (35%)
Iodide, Amiodarone
1986“91 9/301 (3%) 1/9 (10%)
3. Drugs that may exacerbate symptoms of hyperthyroidism
1985“95 11/520 (2%) 1/11 (9%)
Sympathomimetics, Anticholinergics
1991“01 11/2025 (0.5%) 3/11 (27.3%)
Ketamine, Pancuronium
B. Drugs that may potentiate hypothyroidism Table adapted from Kamalakannan, D., Baskar, V., Barton, D. M. &
1. Drugs that decrease TSH secretion Abdu, T. A. M. Diabetic ketoacidosis in pregnancy. Postgrad. Med. J.
Dopamine, Glucocorticoids, Octreotide 2003; 79: 454“7.
2. Drugs that decrease thyroid hormone secretion
Iodine, Lithium, Amiodarone
marked fatigue, nausea, vomiting, abdominal pain, and dyspnea.
3. Drugs that displace T4 and T3 from TBG
Signs include evidence of dehydration, hyperventilation, breath
Furosemide, Phenytoin, Sulfonylureas, Mefenamic acid,
with a ˜˜fruity™™ odor, and altered mental status that can progress
Fenclofenac, Salicylates
to coma. Hypotension with tachycardia indicates significant
4. Drugs that block gastrointestinal absorption of thyroid hormone
dehydration and electrolyte depletion. Mild hypothermia is
Ferrous sulfate, Aluminum hydroxide, Sucralfate, Cholestyramine
usually present, so normothermia or hyperthermia should raise
5. Drugs that increase hepatic T4 and T3 metabolism
suspicion of infection.
Phenobarbital, Rifampin, Phenytoin, Carbamazepine
The triad of hyperglycemia, ketonemia, or ketonuria, and an
6. Drugs that decrease T4 to T3 conversion
anion gap metabolic acidosis are pathognomonic for DKA (see
Propylthiouracil, Amiodarone, B-adrenergic-antagonists,
Table 16.4). It usually occurs in the later stages of pregnancy and
is also seen in newly presenting type 1 diabetics. The onset of DKA
C. Drugs that alter thyroid hormone measurement
in pregnancy can be at lower blood sugar (BS) levels and can
1. Drugs that increase TBG concentration
occur more rapidly than in nonpregnant women.23 Hence, nor-
Estrogens, Heroin, Methadone, Fluorouracil
moglycemia does not rule out DKA in pregnancy since up to one-
2. Drugs that decrease TBG concentration
third of pregnant women in DKA present with BS levels below
Androgens, Anabolic steroids, Slow-release nicotinic acid,
200 mg/dl. Significant ketonemia and an anion gap may be pre-
sent with mild acidosis (pH 7.30“7.35) if the DKA is early in its
Previously adapted from Surks, M. I. & Sievert, R. Drugs and thyroid clinical course. Leukocytosis as high as 25 000/ml with a left shift
function. N. Engl. J. Med. 1995; 333: 1688. Copyright 1995 may occur with or without associated infection.
Massachusetts Medical Society. All rights reserved.
Updated using Nader, S. Thyroid disease and pregnancy. In RK Creasy, Differential diagnosis of DKA
R. K., Resnik, R. & Iams, J. D. (eds.), Maternal“Fetal Medicine: Principles If the patient is acidotic, other causes of anion gap metabolic
and Practice, 5th edn. Philadelphia: Saunders, 2004; pp. 1063“81. acidosis include lactic acidosis (serum lactate above 5 mmol/l),
uremic acidosis (blood urea nitrogen [BUN] > 200 mg/dl) and
Pancreas drug-induced acidosis associated with a history of salicylate,
methanol, ethylene glycol, or paraldehyde ingestion. Other keto-
Diabetic ketoacidosis tic states include alcoholic ketoacidosis and starvation ketoaci-
dosis. Patients with alcoholic ketoacidosis will likely present with
Diabetic ketoacidosis (DKA) is a medical emergency, requiring
immediate treatment.22 Data collected since 1985 shows a 0.5“3% a history of alcohol ingestion and a disproportionate increase in
ß-hydroxybuterate compared with acetoacetate. Starvation keto-
incidence of DKA among all diabetic pregnancies, with a fetal loss
sis is rare, but may be more common among women with hyper-
rate of 9“27%. (see Table 16.3) Pregnant women with previously
emesis gravidarum.24 The acidosis is typically mild (pH > 7.3). A
undiagnosed diabetes may present in DKA. Precipitating events
known diabetic with altered mental status should raise suspicion
include hyperemesis gravidarum, serious infection, insulin pump
for hypoglycemic coma, hyperosmolar coma, central neurologic
dysfunction, and neglect of care. Treatment of premature labor
event, pharmacologic effects, infection, and sepsis. Sepsis and
with corticosteroids and/or ß-sympathomimetics can also preci-
lactic acidosis may coexist with DKA.
pitate DKA.

Clinical features Management
Signs and symptoms vary depending on the degree and stage of For both maternal and fetal well-being, DKA should be stabilized
metabolic derangement. Symptoms include polyuria, polydipsia, before delivery is attempted. Dehydration, associated with DKA,

Chapter 16

Table 16.4 Diagnostic criteria for diabetic ketoacidosis Table 16.5 Causes of hypoglycemia in diabetic pregnant
 Acidosis with blood pH < 7.3
Anion gap [Naþ “ (Kþ þ ClÀ) > 10 mEq/l]
 Serum bicarbonate < 18 mEq/l Excess activity
 Ketonemia or ketonuria (acetoacetate and ß-hydroxybuterate) Anorexia
Abnormal counterregulatory responses
Anti-insulin antibodies
Antibodies to insulin receptors
may affect uteroplacental blood flow and combined with acidosis
Impaired absorption of insulin
and ketonemia, may result in fetal demise. There may be a non-
Impaired intake (morning sickness, diarrhea, etc)
reassuring FHR pattern, with late decelerations and decreased or
Fetal death
absent beat-to-beat variability. Once dehydration, acidosis, and
Factitious insulin use
electrolyte imbalance are corrected, the FHR often reverts to a
Increased insulin sensitivity (first trimester)
normal pattern.
Treatment includes correction of dehydration, acidosis, From: Reece A. E., Homko C. H. & Wiznitzer A. Hypoglycemia in
hyperglycemia, and electrolyte imbalance. Initial hydration pregnancy complicated by diabetes mellitus. Clin. Obstet. Gynecol.
consists of one to two liters of isotonic saline over one to two 1994; 37: 50.
hours to restore intravascular volume. Following saline hydra-
tion, sufficient crystalloid is administered to maintain adequate
regional anesthesia has eliminated the counter-regulatory stress
renal and uteroplacental blood flow, as evidenced by good urine
hormones associated with pain,28 and if the patient has fasted for
output and an improved FHR pattern. The approach often
an extended period of time. Other causes of hypoglycemia are
requires six or more liters of fluid in the first 24 hours. A central
summarized in Table 16.5.
venous pressure catheter may be helpful for guiding volume
Insulin should not be given until initial serum electrolyte values
Clinical features
are obtained and rehydration has begun. After a bolus of 10 U of
Hypoglycemic coma may be preceded by irritability, tachycardia,
i.v. insulin, a continuous infusion is begun at an initial rate of
nausea, diaphoresis, and maternal confusion.29 Significant hypo-
0.1 U/kg per hour. Once the BS falls below 250 mg/dl, the insulin
glycemia (i.e. BS levels < 30 mg/dl) can lead to coma, seizures,
infusion is decreased to 0.05 U/kg per hour, and a dextrose infu-
and death. The immediate evaluation of a pregnant woman with
sion is started (100 ml/h of 5% dextrose in normal saline). Hourly
altered mental status should include an assessment of vital signs
BS checks should confirm a steady decrease of 50“70 mg/dl per
and the BS level. Other causes of altered mental status include
hour. If BS remains elevated, then ensure adequate volume repla-
hyperglycemia with or without ketonemia, infection, central neuro-
cement prior to increasing the insulin infusion rate. Potassium is
logic event, and pharmacologic effects.
added if the level is < 5.0 mEq/l and if the urine output is ade-
quate. Bicarbonate replacement is appropriate only if the pH falls
below 6.90. An underlying cause of the DKA, such as infection,
Fortunately, maternal hypoglycemia has little adverse effect on
should be sought and treated. Endotracheal intubation may be
the fetus with no evidence that it is teratogenic.26,29,30 Mild to
necessary if coma is present.
moderate hypoglycemia is not associated with an increase in the
frequency of nonreassuring FHR patterns.29 Severe hypoglycemia
Hypoglycemic coma
resulting in seizures and/or coma, however, can indirectly affect
fetal well-being.
Pregnant women with type 1 diabetes are particularly susceptible
to severe hypoglycemia (SH), especially in the first trimester.25 The If the patient is unable to swallow, the fastest treatment is i.v.
administration of 25 ml of 50% glucose. Glucagon 1 mg i.v. or i.m.
risk of SH and hypoglycemic coma is increased if there is a history
(intramuscular) requires 15 to 30 minutes to achieve a response.
of SH before pregnancy, there is a longer duration of diabetes, and
if the HbA1c is 6.5%.25 In a group of 84 women with type I Serum glucose should then be rechecked, particularly if mental
status fails to improve.
diabetes receiving intensive insulin therapy, 34% experienced at
least one episode of significant hypoglycemia resulting in seizures,
loss of consciousness, coma, injury, i.v. glucose, or glucagon
Stiff-joint syndrome (diabetic scleroderma)
treatment. Episodes peaked between 10 and 15 weeks, and became
increasingly rare as pregnancy progressed.26 In a second group of Chronic hyperglycemia may lead to glycosylation of tissue pro-
teins that can limit joint and soft tissue mobility. For this reason,
82 gestational diabetics after 24 weeks™ gestation, episodes of
type I diabetics are at risk for difficult intubation, temporo-
asymptomatic hypoglycemia (BS levels < 50 mg/dl lasting over 30
mandibular joint dysfunction, and limited cervical spine mobility.
minutes) were identified in 63% of insulin-treated patients, 28% of
glyburide-treated patients, and none in diet-controlled patients.27 Other tissues may also be involved. In one case report, anterior
spinal artery syndrome developed after epidural anesthesia in a
Hypoglycemia is possible during labor, particularly if effective

4 Metabolic disorders

pregnant patient with poorly controlled diabetes. According to the Labor has a glucose-lowering effect and rapid changes in BS
authors, the injection of a large volume of epidural solution may occur. For many gestational diabetics, no insulin is required
(35 ml) into the noncompliant epidural space may have com- once labor is established. For type I diabetics, a continuous infu-
pressed the vascular supply to the spinal cord.31 Other potential sion of insulin and dextrose in labor improves maternal glucose
complications include restrictive pulmonary disease, difficult i.v. control and limits the risk of neonatal hypoglycemia. Blood sugar
and potassium (Kþ) should be checked every 30“60 minutes for
access due to thickened skin, and poorly compressible arm tis-
sues leading to erroneously high noninvasive blood pressure (BP) any actively laboring patient on an insulin infusion. Insulin infu-
readings. sions should be administered through a dedicated i.v. line as
blood products, in particular, will break down insulin enzymati-
cally. Normal saline should be used for acute administration of
Hyperglycemic hyperosmolar state
i.v. fluids, because rapid infusions of lactated Ringer™s or dextrose
Hyperglycemic hyperosmolar state (HHS) is far less common solutions may precipitate hyperglycemia.
than diabetic ketoacidosis. There has been one case report of
HHS in a pregnant woman who had severe preeclampsia, but
no previous history of diabetes. This woman reverted to a nor-
moglycemic state after delivery.32 Normal pregnancy stimulates hyperplasia of the lactotrophic
Hyperglycemic hyperosmolar state is characterized by serum cells in the pituitary.33 As a result, previously asymptomatic
osmolality > 310 mOsm/kg, BS levels > 600 mg/dl, and normal women with pituitary adenomas may develop symptoms of pitu-
blood pH (> 7.3). In this disease process, hyperglycemia leads to itary enlargement during pregnancy, including headache, visual
profound osmotic diuresis, dehydration, and hyperosmolality. disturbance, and diabetes insipidus (DI). Computed tomography
Coma can occur if osmolality exceeds 320“330 mOsm/kg. and magnetic resonance imaging (MRI) are helpful for tracking
Hyperglycemic hyperosmolar state is typically precipitated by growth of the pituitary gland through pregnancy. Differentiating
an event such as infection, therapy with glucocorticoids, stroke, between pituitary disorders requires endocrinologic evaluation or
pulmonary embolism, or recent operation. As with DKA, stabili- transphenoidal biopsy, because radiologic appearance does not
zation of the metabolic derangements, particularly dehydration, necessarily differ between types of adenoma.
should precede delivery. Intubation for airway protection may be
Anesthetic considerations for patients with diabetes Prolactinomas are pituitary adenomas that oversecrete prolactin,
leading to amenorrhea, infertility, galactorrhea, and hyperpro-
The timing of delivery is determined jointly by the obstetrician
lactinemia. Dopamine receptor agonists, including bromocrip-
and anesthesiologist to ensure that the patient™s condition is
tine and cabergoline, suppress prolactin secretion and improve
optimal. The preanesthetic evaluation should be completed as
conception rates.34 Bromocriptine appears to be safe in preg-
early as possible to allow assessment and correction of acid-base
nancy, although asymptomatic women discontinue therapy
status, and fluid and electrolyte abnormalities. Serious metabolic
once pregnancy is confirmed. Data are less extensive for caber-
derangements should be managed before attempting delivery,
goline, but preliminary evidence does not suggest any adverse
even if fetal status is not reassuring. Because of the potential for
fetal effects.35
stiff-joint syndrome and difficult intubation, a careful airway
Women with macroadenomas (!10 mm) are more likely than
examination is essential prior to any anesthetic intervention.
those with microadenomas (< 10 mm) to present with symptoms
If nonpharmacologic methods of pain control do not provide
of pituitary enlargement during pregnancy (23% versus 1.3%).36 If
adequate relief in labor, continuous epidural analgesia is beneficial.
symptoms develop, headaches usually precede visual changes,
Pain can lead to stimulation of the hypothalamic-hypophyseal axis,
with a mean onset time of 14 weeks™ gestation. In such cases,
causing excess release of catecholamines, which oppose insulin
therapy with bromocriptine can be continued in pregnancy to
activity. Effective regional anesthesia decreases circulating levels
control symptoms and reduce pituitary size. Adjunctive glucocor-
of catecholamines, reducing the potential for critical decreases in
ticoids accelerate resolution of visual symptoms. Patients who fail
uteroplacental blood flow in patients with chronic uteroplacental
to improve on bromocriptine may benefit from cabergoline,37
insufficiency. Abrupt onset of regional anesthesia may precipitate
radiation therapy, or transphenoidal hypophysectomy.
hypoglycemia in a fasted diabetic woman, so a BS should be
checked if diaphoresis or dizziness develop after neuraxial block.28
Anesthetic implications
If a C/S under GA is planned, women with stiff-joint syndrome
may benefit from awake fiberoptic intubation. If significant tissue Pregnant women with prolactinoma should be evaluated for
turgidity is present, concerns with neuraxial block include the symptoms of increased intracranial pressure (ICP), DI, and visual
possibility of noncompliance of the epidural space. In such disturbances. In asymptomatic women, there are no anesthetic
cases, a combined spinal“epidural technique with low-dose implications. For parturients with symptoms, MRI or CT of the
spinal anesthesia may be preferred over epidural anesthesia, sella tursica is used to measure pituitary enlargement and to look
because of the smaller volume of anesthetic solution. for increased ICP. Women with increased ICP who expect to

Chapter 16

deliver vaginally may benefit from regional analgesia and a shor-
Table 16.6 Anesthetic considerations for acromegaly
tened second stage to minimize the physiologic effects of pain
and pushing. Great care must be taken to avoid inadvertent dural Difficult airway:
puncture with a large-bore epidural needle in those women with  overgrowth of the tongue, epiglottis, mandible, pharyngeal tissues,
raised ICP. and vocal cords
 recurrent laryngeal nerve palsy due to overgrowth of the
cartilaginous structures, which stretch the nerve
 glottic narrowing and subglottic stenosis
Acromegaly is due to excess secretion of growth hormone by the Peripheral neuropathy
anterior pituitary in adults. Only about 100 cases of acromegaly in Glucose intolerance
pregnancy have been reported.38 Women with acromegaly may Hypertension
experience infertility or amenorrhea, but pregnancies do occur Dysrhythmia
naturally or with the help of reproductive technology.39 Ischemic heart disease
Pregnancy is associated with normal pituitary expansion due to Osteoarthritis: spinal canal stenosis
lactotrophic hyperplasia. In pregnant women with acromegaly, Skeletal muscle weakness
this may result in compression of the optic chiasm with visual
Adapted from: Stoelting, R. K. & Dierdorf, S. F. Endocrine diseases. In
field deficits. Other complications of acromegaly, particularly
Anesthesia and Co-Existing Disease, 4th edn. Philadelphia: Churchill
glucose intolerance, hypertension, and peripheral nerve com-
Livingston, 2002: pp. 395“440.
pression, may also worsen during pregnancy. Pregnancy in acro-
megalic women usually has a normal course leading to a normal
delivery. Growth hormone does not appear to cross the placenta,
and aside from maternal glucose intolerance with the potential
glands to overproduce cortisol, leading to Cushing syndrome.
for neonatal hypoglycemia, there are no known fetal effects of
Cushing syndrome refers to the group of symptoms that arise
maternal acromegaly.39
from excessive exposure to steroid hormones. Women with
In symptomatic patients during pregnancy, first-line therapy
Cushing disease have Cushing syndrome, and the systemic
consists of bromocriptine until the fetus is mature. If symptoms
effects and anesthetic considerations of Cushing syndrome are
do not improve, then transphenoidal surgery in pregnancy may be
discussed in the section on adrenal disorders.
necessary. Somatostatin analogues are an alternative to surgery,
although their safety in pregnancy is not firmly established.40
Nelson syndrome
Anesthetic implications
Nelson syndrome may develop when a patient with Cushing
Potential anesthetic complications include difficult mask ventila-
disease is treated with bilateral adrenalectomy without ade-
tion and difficult endotracheal intubation.41 In a series of 128
quate treatment of the primary pituitary lesion. The pituitary
nonpregnant patients, 10% had difficult intubation where exter-
adenoma will continue to produce ACTH leading to hyperpig-
nal laryngeal pressure alone did not improve the laryngoscopic
mentation, and may expand leading to mass effects including
view.42 Therefore, awake fiberoptic intubation should be consid-
visual field changes, headache, and DI. Amenorrhea is com-
ered. A small endotracheal tube diameter may be necessary to
mon; however, several case reports of pregnancy are available
avoid airway edema with postoperative airway obstruction.
in the literature.43,44,45 When treating parturients with Nelson
Given the risk for hypertension, left ventricular (LV) dysfunc-
syndrome, it is important to: (1) evaluate for symptoms of
tion, and ischemic heart disease, a careful cardiovascular history,
increased ICP or local mass effects from pituitary hypertrophy,
preoperative EKG, and perioperative cardiac rhythm monitoring
(2) monitor intravascular fluid volume and electrolyte distur-
are warranted. Preoperative echocardiogram or invasive cardiac
bances from DI, and (3) provide appropriate steroid supple-
monitoring may be helpful if symptoms of cardiomyopathy are
mentation including stress-dose steroids during labor and
A careful neurologic examination should precede neuraxial
blockade because acromegaly has been associated with periph-
eral neuropathy, cauda equina syndrome, and spinal canal ste-
Diabetes insipidus
nosis. We were unable to locate a case report of lumbar epidural
catheter placement in an obstetric patient with acromegaly. Diabetes insipidus is either caused by insufficient antidiuretic
Further anesthetic implications of acromegaly are listed in hormone (central DI) or by insensitivity of the renal tubules to
Table 16.6. antidiuretic hormone (nephrogenic DI). Diabetes insipidus may
be associated with pregnancy because the placenta produces
vasopressinase, an enzyme that metabolizes vasopressin
Cushing disease
(ADH).46 Women with preeclampsia, fatty liver of pregnancy,
In Cushing disease, a pituitary adenoma overproduces adreno- or hemolysis, elevated liver enzymes, and low platelets
corticotropin hormone (ACTH). This in turn stimulates the adrenal (HELLP) syndrome may accumulate vasopressinase, leading to

4 Metabolic disorders

secondary DI.47 Vasopressinase levels decline rapidly after deliv- Panhypopituitarism introduces significant perinatal risk even if
ery, with resolution of DI by the first or second postpartum day. managed appropriately. A review of eighteen pregnancies in nine
Alternative causes include head trauma, Sheehan syndrome, or women with panhypopituitarism found a high rate of pregnancy
complications despite pituitary replacement therapy.54 There
expanding pituitary lesions. There is a case of a pregnant woman
with an occluded ventriculoperitoneal shunt resulting in were eleven (61%) live births, five (28%) first trimester abortions,
increased ICP, injury to the pituitary stalk, and central DI.48 and two (11%) second trimester intrauterine fetal deaths. There
The incidence of DI is up to 4 cases per 100 000 pregnancies. were no survivors from four sets of twins. Ten of the eleven live
The main diagnostic features are polyuria, polydipsia, thirst, births were delivered by C/S, and 50% of those were small for
and hypotonic urine. Because oxytocin is produced in the same gestational age.
hypothalamic nuclei as vasopressin, some patients may benefit
Lymphocytic hypophysitis Lymphocytic hypophysitis is a rare
from perinatal oxytocin supplementation during labor or post-
autoimmune condition that most commonly presents in preg-
partum. Dehydration, hyperosmolarity, hypotension, tachy-
nancy or the postpartum period.55 Lymphocytes and plasma cells
cardia, and risk for myocardial ischemia are the primary
infiltrate the anterior pituitary or the pituitary stalk, leading to
physiologic concerns in patients with DI. Preeclamptic patients

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