3754 PART 18 Aging

is normal, a residual between 100 and 200 mL must be interpreted

based on symptoms, and a value >200 mL is abnormal and usually

influences treatment.

Management Patients who meet certain criteria should be referred

for further urologic, gynecologic, and/or urodynamic evaluation before

initiating specific therapy. Examples include history of lower urinary

tract surgery or radiation or recurrent symptomatic urinary tract infections, marked pelvic prolapse on physical examination of a woman,

suspected prostate cancer, and sterile hematuria.

Potentially reversible conditions should be addressed, including

the many types of medications that can affect bladder function,

which should be eliminated if possible (Table 477-11). Table 477-13

lists treatments for different types of incontinence. Many patients

respond well to properly taught and adhered to behavioral interventions. Physical therapists and nurses who specialize in treating lower

urinary tract symptoms can be very helpful and should be consulted

if available. Pharmacologic treatment of incontinence and overactive

bladder is dictated by the innervation of the lower urinary tract.

α-Adrenergic stimulation increases tone in the smooth muscle of the

urethra; thus, α agonists have been used to treat stress incontinence

in women (although none are approved by the U.S. Food and Drug

Administration for this indication), and alpha blockers are used to

decrease urethral tone in men with overactive bladder associated with

prostate enlargement. Anticholinergic/antimuscarinic agents and β-3

stimulation inhibit bladder contraction and are used for overactive

bladder and urge incontinence. In men with overactive bladder and

normal postvoid residual who do not respond to an alpha blocker

(with or without a 5α-reductase inhibitor), adding an antimuscarinic

or β-3-adrenergic agent may improve symptoms with a very low risk

of causing urinary retention. Patients with severe cognitive impairment

and/or immobility can generally be managed effectively by prompted

voiding and/or incontinence undergarments, as long comfort, dignity,

and safety are maintained.

■ SLEEP DISORDERS

Sleep disorders are discussed in more detail for the general adult population in Chap. 31. Because they are so common and have some unique

features in older patients, they are discussed briefly here.

TABLE 477-11 Reversible Conditions That Cause or Contribute to Urinary Incontinence and Overactive Bladder Symptoms in Older People

CONDITION MANAGEMENT

Lower urinary tract conditions

 Urinary tract infection (symptomatic with frequency,

urgency, dysuria, etc.)

Antimicrobial therapy

Atrophic vaginitis/urethritis Topical estrogen (not a primary treatment for incontinence but may help prevent recurrent infections and

ameliorate symptoms of overactive bladder; oral estrogens can cause or worsen incontinence)

 Stool impaction with irritation of bladder/urethral

innervation and/or partial bladder outlet obstruction

Disimpaction; appropriate use of stool softeners, bulk-forming agents, and laxatives if necessary; implement

bowel regimen

Increased urine production

Metabolic (hyperglycemia, hypercalcemia) Better control of diabetes mellitus

Therapy for hypercalcemia depends on underlying cause

Excess caffeine or fluid intake Reduction in intake of caffeinated beverages; reduction in fluid intake (most older people with incontinence

or overactive bladder self-restrict fluid intake)

 Volume overload with increased urine production at

night

Support stockings

Venous insufficiency with edema Leg elevation

Sodium restriction

Diuretic therapy (late afternoon dose may be effective)

Congestive heart failure Medical therapy

Impaired ability or willingness to reach a toilet

Delirium Diagnosis and treatment of underlying cause(s)

 Chronic illness, injury, or restraint that interferes with

mobility

Regular toileting

Use of toilet substitutes

Environmental alterations (e.g., bedside commode, urinal)

Remove restraints if possible

Psychological (depression, anxiety) Appropriate nonpharmacologic and/or pharmacologic treatment

Drug side effects Remove offending drug(s) if feasible; modification of dose, frequency, or timing may also reduce symptoms for

some drugs:

Diuretics (polyuria, frequency, urgency)

Anticholinergics (constipation, incomplete bladder emptying)

Psychotropic drugs

Tricyclic antidepressants (anticholinergic effects)

Antipsychotics (immobility, sedation)

Sedative-hypnotics (immobility, sedation)

Narcotic analgesics (constipation, incomplete bladder emptying)

α-Adrenergic blockers (urethral relaxation)

α-Adrenergic agonists (urethral contraction and potential incomplete bladder emptying)

Cholinesterase inhibitors (urinary frequency, urgency)

Angiotensin-converting enzyme inhibitors (cough precipitating stress incontinence)

Calcium channel blockers, gabapentin, pregabalin, glitazones (edema with nocturia)

Alcohol (polyuria, frequency, urgency, sedation, delirium, immobility)

Caffeine (polyuria, bladder irritation)

Source: Reproduced with permission from RL Kane et al (eds): Essentials of Clinical Geriatrics, 8th ed. New York, McGraw-Hill, 2017.

3755Caring for the Geriatric Patient CHAPTER 477

The 3IQ is a patient questionaire that helps your doctor distinguish urge incontinence from stress

incontinence. It should take no more than a couple of minutes. Complete the quiz and bring it to your

next appointment.

(if this response is marked, the 3IQ test is complete)

1. During the last 3 months, have you leaked urine (even a small amount)?

2. During the last 3 months, did you leak urine (check all that apply):

3. During the last 3 months, did you leak urine most often (check only one):

Definitions of type of urinary incontinence are based on responses to question 3.

Response to Question 3 Type of incontinence

Most often with physical activity Stress only or stress predominant

Without physical activity or sense of urgency Other cause only or other cause predominant

Most often with the urge to empty the bladder Urge only or urge predominant

About equally with physical activity and

sense of urgency

Mixed

Yes

When you were performing some physical activity, such as coughing,

sneezing, litting, or exercising?

When you had the urge or the feeling that you needed to empty your

bladder, but you could not get to the toilet fast enough?

When you were performing some physical activity, such as coughing,

sneezing, litting, or exercising?

When you had the urge or the feeling that you needed to empty your

bladder, but you could not get to the toilet fast enough?

Without physical activity and without sense of urgency?

Without physical activity and without sense of urgency?

About equally as often with physical activity as with a sense of urgency?

No

FIGURE 477-9 The 3 Incontinence Questions (3IQ) Assessment Tool. (From Annals of Internal Medicine, JS Brown JS et al: The sensitivity and specificity of a simple test

to distinguish between urge and stress urinary incontinence. 144 (10):715, 2006. Copyright © 2006 American College of Physicians. All Rights Reserved. Reprinted with the

permission of American College of Physicians, Inc.)

Epidemiology and Impact Aging is associated with multiple

changes in sleep architecture as well as multiple diseases and disorders

that can disrupt sleep. Thus, complaints of sleep difficulty are common in older adults. Consequences of sleep difficulty include lower

health-related quality of life, increased medication use, more cognitive

decline, and greater health care utilization. Four types of primary

sleep disorders are common in the geriatric population: insomnia,

sleep-disordered breathing due to obstructive sleep apnea (OSA), restless leg syndrome (RLS), and periodic leg movements in sleep (PLMS).

Complaints of bothersome insomnia—the inability to fall asleep or

stay asleep despite a conducive environment—increase with age and

occur in close to 30% of people older than 65. Insomnia is commonly

associated with depression, anxiety, alcohol intake, and ingestion of

caffeinated beverages later in the day. OSA occurs in ~10% of older

adults but is probably underreported and underdiagnosed. It is associated with medical comorbidities, such as obesity and congestive heart

failure. RLS occurs in 5–10% of adults, and its prevalence increases in

those older than 70. It is almost twice as common in women than men;

family history, iron deficiency, and intake of antihistamines and most

antidepressants are risk factors. PLMS can be found in up to 45% of

older people but is often of unknown clinical consequence and remains

undiagnosed.

Evaluation Older people should be screened for sleep difficulty

with questions such as, “Do you often feel sleepy during the day?” and

“Do you have difficulty falling asleep at night?” Further evaluation of

the nature and impact of the complaints can be accomplished with

standardized questionnaires (Table 477-3). Patients with significant

sleep complaints should be asked about conditions that can interrupt

sleep, such as nocturia, gastroesophageal reflux, chronic pain, and

caffeine and alcohol intake. Specific questions characterizing the

complaints should include inquiring about loud snoring (for OSA),

the urge to move legs associated with uncomfortable sensations (RLS),

and leg movements during sleep (PLMS; which may result in kicking

a bed partner).

Management Patients suspected of having OSA, RLS, or PLMS

should be referred for formal sleep evaluation. While hypnotics are

among the most commonly prescribed drugs in the geriatric population, nonpharmacologic management of sleep should be the initial

and primary approach, as many patients can benefit from properly

taught and adhered to interventions (Table 477-14). Benzodiazepine

hypnotics should be avoided whenever feasible because they are

associated with next-day hangover effects, which may manifest as

cognitive impairment and can precipitate falls and car crashes and

rebound insomnia. Patients with sleep-onset insomnia may respond to

melatonin or low-dose trazadone, both of which are safer than using a

benzodiazepine chronically.

■ FRAILTY

Definition, Epidemiology, and Impact The term frail is often

used to describe older adults. However, over the past several years,

frailty has been defined as a specific syndrome, and the word frail is

3756 PART 18 Aging

TABLE 477-12 Key Aspects of the History and Physical Examination of an Older Patient with Symptoms of Urinary Incontinence and Overactive

Bladder

History

Active medical conditions, especially neurologic disorders, diabetes mellitus, congestive heart failure, venous insufficiency

Medication review for drugs that can contribute (see Table 477-11)

Fluid intake pattern

Type and amount of fluid (especially caffeine and fluids before bedtime)

Past genitourinary history, especially childbirth, surgery, dilatations, urinary retention, recurrent urinary tract infections

Symptoms of incontinence

Onset and duration

Type—stress vs urge vs mixed vs other (see Fig. 477-10)

Frequency, timing, and amount of incontinence episodes and of continent voids (a voiding diary may be useful)

Other lower urinary tract symptoms

Irritative—dysuria, frequency, urgency, nocturia

Voiding difficulty—hesitancy, slow or interrupted stream, straining, incomplete emptying

Other—hematuria, suprapubic discomfort

Other symptoms

Neurologic (indicative of stroke, dementia, parkinsonism, normal-pressure hydrocephalus, spinal cord compression, multiple sclerosis)

Psychological (depression)

Bowel (constipation, stool incontinence)

Symptoms suggestive of volume-expanded state (e.g., lower extremity edema, shortness of breath while horizontal or with exertion)

Environmental factors

Location of bathroom

Availability of toilet substitutes (e.g., urinal, bedside commode)

Perceptions of incontinence

Patient’s concerns or ideas about underlying cause(s)

Most bothersome symptom(s)

Interference with daily life

Severity (e.g., “Is it enough of a problem for you to consider surgery?”)

Physical Examination

Mobility and dexterity

Functional status compatible with ability to self-toilet

Gait disturbance (e.g., that may suggest parkinsonism, normal-pressure hydrocephalus)

Mental status

Cognitive function compatible with ability to self-toilet

Motivation

Mood and effect

Neurologic

Focal signs (especially in lower extremities) that could suggest a central nervous system condition

Signs of parkinsonism

Sacral arc reflexes (e.g., loss of perianal sensation or an anal wink in response to perianal stimulation)

Abdominal

Bladder distensiona

Suprapubic tenderness

Lower abdominal mass

Rectal

Perianal sensation

Sphincter tone (resting and active)

Impaction

Masses

Size and contour of prostate (neither is diagnostic of urethral obstruction)

Pelvic

Perineal skin condition

Perineal sensation

Atrophic vaginitis (friability, inflammation, bleeding)

Pelvic prolapse or mass

Other

Lower extremity edema or signs of congestive heart failure (if nocturia is a prominent complaint)

a

Clinically significant degrees of urinary retention may be difficult to detect on physical examination; many incontinent patients should have a postvoid residual

determination done by ultrasound (see text).

Source: Reproduced with permission from RL Kane et al (eds): Essentials of Clinical Geriatrics, 8th ed. New York, McGraw-Hill, 2017.

3757Caring for the Geriatric Patient CHAPTER 477

Prevalence of pituitary incontinence

35

30

25

20

15

10

5

30–39 40–49 50–59 60–69 70–79 80+

0

Age group

Urge

Stress

Mixed

FIGURE 477-10 Rates of urge, stress, and mixed incontinence, by age group, in a sample of 3552 women.

*Based on a sample of 3553 participants. (Adapted from JL Melville, W Katon, K Delaney, K Newton: Urinary

incontinence in US women: A population-based study. Arch Intern Med 165:537, 2005.)

TABLE 477-13 Primary Treatments for Different Types of Geriatric

Urinary Incontinence

TYPE OF

INCONTINENCE PRIMARY TREATMENTS

Stress Pelvic muscle (Kegel) exercises

Other behavioral interventions including timed voiding and

double voiding to avoid residual urine

α-Adrenergic agonist (none are approved by the U.S. Food

and Drug Administration for this purpose)

Topical estrogen to strengthen periurethral tissue (not

effective alone; oral estrogens contraindicated)

Periurethral injections to provide bulking and support

Surgical bladder neck suspension or sling for severe

incontinence, based on patient preference

Urge and

overactive bladder

symptoms

Pelvic muscle (Kegel) exercises

Other behavioral interventions: timed voiding and double

voiding to avoid residual urine

Antimuscarinic and β-3-adrenergic drugs

Incontinence with

incomplete bladder

emptying

α-Adrenergic antagonists in men with a 5α-reductase

inhibitor if the prostate is enlarged); an antimuscarinic or

β-3-adrenergic drug can be added if unresponsive to the

α-adrenergic agonist

Bladder training, double voiding

Intermittent catheterization

Indwelling catheterization in selected patients in whom

risks and discomforts of urinary retention outweigh risks of

a chronic indwelling catheter

Incontinence with

impaired physical

and/or cognitive

function

Behavioral interventions (prompted voiding, habit training)

Environmental manipulation including use of urinal or

bedside commode, safe lit path to bathroom)

Incontinence undergarments and pads

Source: Reproduced with permission from RL Kane et al (eds): Essentials of Clinical

Geriatrics, 8th ed. New York, McGraw-Hill, 2017.

TABLE 477-14 Nonpharmacologic Management of Insomnia in Older

Adults

Sleep Hygiene Rules

Check effect of medication on sleep and wakefulness

Avoid caffeine, alcohol, and cigarettes after lunch

Limit liquids in the evening

Keep a regular bedtime-waketime schedule

Avoid naps or limit to 1 nap a day, no longer than 30 min

Spend time outdoors (without sunglasses), particularly in the late afternoon or

early evening

Exercise—but limit exercise immediately before bedtime

Instructions for Stimulus-Control Therapy

Only go to bed when tired or sleepy

If unable to fall asleep within 20 min, get out of bed (and bedroom if possible);

while out of bed, do something quiet and relaxing

Only return to bed when sleepy

If unable to fall asleep within 20 min, again get out of bed

Repeat these behaviors until able to fall asleep within a few minutes

Get up at the same time each morning (even if only a few hours of sleep)

Avoid naps

Source: Adapted from JB Halter et al (eds): Hazzard’s Geriatric Medicine and

Gerontology, 7th ed. New York, McGraw-Hill, 2016.

more appropriately used to describe people who meet frailty criteria.

Frailty is a state of increased vulnerability characterized by a decline

in physiologic reserve and function across multiple systems. Many

different definitions and tools to define frailty exist. Fried criteria

based on the Cardiovascular Health Study (see below) and the Frailty

Index (a list of several specific diagnoses developed by Rockwood and

colleagues) have been used to screen for frailty in clinical settings. The

importance of screening for frailty is to mitigate

disability and adverse health outcomes as well

as for the assessment of benefits and risks of

treatment decisions. The prevalence of frailty is

higher among women and increases with age.

The overall prevalence of frailty in communitydwelling adults aged 65 and older varies considerably but, on average, is 10–14% depending

on the definition. The prevalence of frailty

increases with age, reaching close to 16% in

individuals age 80–84 and 26% in those aged

85 or older. In older hospitalized patients and

institutionalized older people, the frailty prevalence varies from about 27% to up to 80%.

Irrespective of the definition, the prevalence of

frailty shows a U-shaped relationship with body

mass index (BMI), with higher levels of frailty

in individuals with both low and very high BMI.

Pathophysiology Frailty is a three-dimensional process that involves changes at the

cellular, physiologic, and phenotypical levels.

At the cellular level, frailty manifests as changes

in mitochondrial function, the development of

oxidative stress and DNA damage, and telomere

shortening and stem cell exhaustion. These changes at the cellular level

result in physiologic alterations including inflammation, cell mediator

dysfunction such as low production of nitric oxide by the endothelium,

sarcopenia, and energy unbalance. Fried and colleagues conceptualize

frailty as a vicious circle of declining energetics and reserve, whose

elements represent both the diagnostic criteria for the syndrome identification and the core elements of its pathophysiology. The process

manifests phenotypically as overall decline in physical function and

cognitive impairment. In particular, the phenotype of frailty has been

defined by Fried and colleagues by the five following characteristics:

unintentional weight loss, weakness, exhaustion, slowness, and low

activity (with specific operational definitions of each).

Management Although there is conflicting evidence regarding the

effectiveness of specific interventions to treat or prevent frailty, personcentered physical activity programs and nutritional supplementation

appear to improve components of frailty such as muscle strength, gait

speed, and overall mobility. In addition, optimizing the management

3758 PART 18 Aging

of chronic conditions, medication management including mitigation

of polypharmacy, and identifying the individual’s priorities could lead

to reversing or slowing progression of frailty.

■ ELDER ABUSE AND NEGLECT

Epidemiology and Impact The incidence of elder abuse and

neglect and self-neglect are unknown because they are often unrecognized. The best data suggest that the incidence over 12 months is

at least 8–10%. Abuse and neglect can result in physical injuries and

related pain, worsening of chronic medical conditions, dehydration

and pressure ulcers, emotional distress, and loss of income and savings.

Evaluation Because abuse and neglect are underreported, are unsuspected, and have such devastating consequences, older adults should be

screened (without the presence of caregivers) with questions such as,

“Do you ever feel unsafe where you live?” “Has anyone ever threatened or

hurt you?” “Has anyone been taking your money without your permission?” (Table 477-3). Table 477-15 outlines the definitions, symptoms

and signs, and key aspects of evaluating suspected abuse and neglect.

TABLE 477-15 Elder Abuse and Neglect

CATEGORY DEFINITION AND EXAMPLES SYMPTOMS AND SIGNS KEY ASPECTS OF EVALUATION

Physical Abuse Acts of violence that may result in pain,

injury, or impairment

• Pushing, slapping, hitting,

force-feeding

• Improper positioning or use of

restraints

• Improper use of medications

Abrasions

Lacerations

Bruises

Fractures

Use of restraints

Burns

Pain

Depression

Delirium or onset or worsening of

dementia-related behavioral symptoms

The interview should be conducted alone with the patient; it

may reveal discordant histories or findings inconsistent with

the history provided by the caregiver.

Ankles and wrists should be examined for abrasions

suggestive of the use of restraints.

Findings that are discordant with the mechanism of injury

reported or multiple injuries in various stages of healing should

raise the suspicion of abuse.

Injuries to the head, neck, and upper arms occur in victims of

physical elder abuse but must be distinguished from accidental

injuries.

Jaw and zygomatic fractures are more likely to be sustained

from a punch than from a fall, which more typically result in

fractures to orbital and nasal bones.

Psychological or

Verbal Abuse

Conduct that causes mental or

emotional distress

• Verbal harassment or intimidation

• Threats of punishment or deprivation

• Isolation

Direct observation of verbal abuse

Subtle signs of intimidation, such as

deferring questions to a caregiver or

potential abuser

Evidence of isolation

Depression, anxiety, or both

Assess the size and quality of the patient’s social network

(beyond the suspected abuser).

Conduct standardized assessments of depression, anxiety, and

cognition, directly or through referral.

Ask specifically about verbal or psychological abuse with

questions such as “Does your relative/caregiver ever yell or

curse at you?”; “Have you been threatened with being put into

a nursing home?”; or “Are you ever prevented from seeing

friends and family members whom you wish to see?”

Financial Abuse Misuse of the person’s income or

resources for the financial or personal

gain of a caregiver or advisor

• Stealing money or possessions

• Denying a home

• Coercing to sign contracts or spend

money

Inability to pay for medicine, medical

care, food, rent, or other necessities

Failure to renew prescriptions,

adhere to medication regimens or

other treatments, or keep medical

appointments

Malnutrition, weight loss, or both,

without an obvious medical cause

Evidence of poor financial

decision-making

Firing of home care or other service

providers by abuser

Unpaid utility bills

Initiation of eviction proceedings

Ask about financial exploitation with questions such as

“Has money or property been taken from you without your

consent?”; “Have your credit cards or automated teller

machine card been used without your consent?”; and “At the

end of the month, do you have enough money left for food and

other necessities?”

Abrupt changes in financial circumstances of the caregiver

in either direction may herald an increased risk of financial

exploitation or exploitation already under way.

Abuse of the power of attorney; if the person with power of

attorney or health care proxy is suspected of not acting in the

best interest of the patient, documents necessary to ensure

that the assumption of fiduciary responsibilities is authorized.

Sexual Abuse Sexual coercion or assault Bruising, abrasions, lacerations in the

genital or anal areas or abdomen

Newly acquired sexually transmitted

diseases, especially in nursing home

Urinary tract infection

Inquire directly about sexual assault or coercion.

For patients with dementia, direct queries to caregivers about

hypersexual behavior as part of a larger history regarding

dementia-related behaviors and assess patient’s capacity for

decision-making about sexual activity.

If indicated, refer to an emergency department for assessment

for sexual assault and collection of specimens (forensic

evidence should be collected by experienced professionals,

such as nurses who have undergone Sexual Assault Nurse

Examiners [SANE] training).

Neglect (by

caregiver or

self-neglect)

Failure to provide the materials,

supplies, food and drink, or services

necessary for optimal functioning or to

avoid harm

Malnutrition

Dehydration

Poor hygiene

Pressure ulcers

Nonadherence to medication regimen

or other treatments

Worsening of dementia-related

behavioral symptoms

Interview primary caregiver about his or her understanding

of the nature of the patient’s care needs and how well care is

being rendered.

Neglect by a caregiver may be intentional or unintentional.

Assess hygiene, cleanliness, and appropriateness of dress.

Examine the skin for pressure ulcers, infections, and

infestations.

Assess nutrition and hydration, including measuring body

mass index and blood urea nitrogen and creatinine to assess

hydration.

3759Caring for the Geriatric Patient CHAPTER 477

Management In addition to treating the physical, medical, and

emotional consequences, patients suspected of elder abuse or neglect

should be reported to the appropriate local or state agency to investigate

and ensure the patient’s safety. The reader is referred to two reviews of

this topic for further information on specific aspects of management.

■ SEVERE ACUTE RESPIRATORY SYNDROME

CORONA VIRUS (SARS-COV-2) INFECTION AND

COVID-19 DISEASE

(See Chaps. 122 and 199) The COVID-19 pandemic has disproportionately affected the older population, especially those residing in

nursing homes and assisted living facilities. Compared with those

between the ages of 18 and 29 years old, older adults are at greater

risk for adverse outcomes after infection with SARS-CoV-2, especially

those with multiple comorbidities. Mortality ratios are 200 and 600

times higher among those aged 75–84 and >85, respectively, with 8 and

13 times the risk of hospitalization. While some older patients survive

with minimal symptoms and residual effects, others deteriorate rapidly

into respiratory distress, and if they survive, many have prolonged

effects in multiple systems. For these reasons, patients in this age group

should have an advance care planning discussion regarding goals of

care if they get infected with SARS-CoV-2 or similar infections that

cause widespread life-threatening illnesses. Screening older adults for

SARS-CoV-2 is challenging as some of the cardinal symptoms are often

not present, especially among frail older adults living in LTC institutions. For example, temperature elevations do not reach threshold for

fever of 38°C in a significant portion of older adults with COVID-19.

The pandemic has had devasting consequences in nursing homes

and assisted living facilities. Tragic outbreaks causing dozens of hospitalizations and deaths in a single facility over a short period of time

have been widely reported, even in the highest quality facilities. Staff

and clinicians working in nursing homes and assisted living in many

areas have suffered from a shortage of accurate testing capability and

personal protective equipment that has put their own health and the

health of their families at risk, especially in facilities that serve more

diverse and socioeconomically disadvantaged populations. Because of

restrictions on visitation and social distancing policies, the pandemic

has had a tremendous negative psychological effect on residents and

their loved ones. Owners and operators of these institutions have

suffered severe financial consequences, and many may not be able to

continue operating without ongoing state and/or federal assistance.

COVID-19 has taught us many lessons for the future care of our

growing geriatric population. These lessons go well beyond the need

for intensive education on and implementation of intensive infection

control policies and procedures. The way that our society organizes

and funds care for vulnerable older people who cannot live independently, trains health care professionals to care for this population, and

measures the quality of care needs careful rethinking to meet the needs

of older people over the next several decades.

END-OF-LIFE AND PALLIATIVE CARE

End-of-life and palliative care are critical aspects of caring for the geriatric population and require a comprehensive, person-centered approach.

End-of-life and palliative care are addressed in detail in Chap. 12, and

pain management is addressed in Chap. 13. For geriatric patients,

limited life expectancy is a critical factor to consider when making

end-of-life care decisions. General principles of decision-making are

especially relevant when considering palliative and/or end-of-life care

in older patients (Fig. 477-5). Decision-making becomes complicated,

however, among older patients with multimorbidity. Without a clear

terminal diagnosis, when to start palliative care/end-of-life care could

be challenging. While it is sometimes clear when an older patient

has a terminal condition, such as end-stage congestive heart failure

or chronic obstructive pulmonary disease, many older patients with

multimorbidity have combinations of conditions of varying severity.

Moreover, neurogenerative disorders, including most forms of dementia, Parkinson’s disease, and patients with multiple strokes, commonly

have a gradually progressive course, and it can be challenging to determine when discussions about palliative and end-of-life care should be

initiated. Dementia, however, should be considered a terminal illness

in the advanced stages.

Internists should play a pivotal role in making the decision when

to initiate these discussions and should be proactive in encouraging

patients and their families to execute advance directives before a health

care crisis occurs. There are good data that bear on some of the decisions. For example, the survivability of cardiopulmonary resuscitation

(CPR) in hospitalized patients age 65 and older is <20%; among the

old-old with multimorbidity, it is much lower. The survivability of

CPR in nursing home residents is almost zero, making it a futile intervention for most in this setting. Data and recommendations of major

organizations suggest that enteral feeding tubes should not be placed

in patients with end-stage dementia (Table 477-2). Tools for the estimation of prognosis such as ePrognosis, for holding conversations with

older people and their families about advance care planning, and for

documentation of advance directives (e.g., living will, durable power

of attorney for health care, Physician Orders for Life-Sustaining Treatments [POLST], and other order sets) will assist internists in paying

careful attention to factors that contribute to person-centered care and

in dealing with these challenging issues in end-of-life geriatric care.

■ FURTHER READING

AMDA—The Society for Post-Acute and Long-Term Care

Medicine: Ten things clinicians and patients should question. http://

www.choosingwisely.org/societies/amda-the-society-for-post-acuteand-long-term-care-medicine/. Accessed September 20, 2020.

American Diabetes Association: Older adults: Standards of medical care in diabetes—2020. Diabetes Care 43(Suppl 1):S152, 2020.

American Geriatrics Society: Choosing Wisely: Ten things clinicians and patients should question. http://www.choosingwisely.org/

societies/american-geriatrics-society/. Accessed September 20, 2020.

American Geriatrics Society Panel on Pharmacologic

Management of Persistent Pain in Older Persons: Pharmacologic management of persistent pain in older persons. J Am Geriatr

Soc 46:1331, 2009.

Centers for Disease Control and Prevention: CDC Immunization Schedules–Feb, 2020. https://www.cdc.gov/vaccines/schedules/

hcp/imz/adult.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc

.gov%2Fvaccines%2Fschedules%2Fhcp%2Fadult.html#table-age.

Accessed September 21, 2020.

Clinician’s Guide to Assessing and Counseling Older Drivers.

http://www.michigan.gov/documents/sos/Clinicians_Guide_To_

OlderDrivers_3rd_edition_523147_7.pdf. Accessed September 20,

2020.

Halter JB et al (eds): Hazzard’s Geriatric Medicine and Gerontology,

7th ed. New York, McGraw-Hill, 2018.

Institute for Healthcare Improvement: Age-friendly health

systems. http://www.ihi.org/Engage/Initiatives/Age-Friendly-HealthSystems/Pages/default.aspx. Accessed September 20, 2020.

Kane RL et al (eds): Essentials of Clinical Geriatrics, 8th ed. New York,

McGraw-Hill, 2017.

The 2019 American Geriatrics Society Beers Criteria® Update

Expert Panel: American Geriatrics Society 2019 Updated AGS

Beers Criteria® for potentially inappropriate medication use in older

adults. J Am Geriatr Soc 67:674, 2019.

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Consultative Medicine PART 19

Approach to Medical

Consultation

Jeffrey Berns, Jack Ende

478

Effective health care requires teams of generalists and specialists with

complementary expertise. Many clinical conditions require the input

of more than one clinical provider, either because the diagnosis and

recommended treatment is uncertain or because a patient may have

multiple diseases that may be best managed by involving multiple

specialists.

To consult is to seek advice from someone with expertise in a particular area, whereas consultation refers to the meeting or comparable

outcome arising from that request. Medical consultation takes several

forms. Its most traditional forms include in-hospital consultation, in

which physicians provide recommendations, typically recorded in the

medical record, or perform procedures for a hospitalized patient, and

outpatient consultations, in which patients are seen in the office setting.

More contemporary forms of consultation include e-consultations,

telemedicine evaluations (see “Consultation Involving Telemedicine,”

below), and remote medical second opinions. In these forms, the consultant may not actually see the patient but, nonetheless, assumes the

responsibility of evaluating the patient’s clinical condition, assessing

and analyzing pertinent clinical data, and offering a synthesis and

appropriate recommendations.

While forms of medical consultation evolve, basic responsibilities

associated with medical consultation endure. These responsibilities

can be divided into those that fall to the requesting physician or nonphysician practitioner; the consultant, who provides the consultation;

and the health system, hospital, or organization that must support this

important medical encounter (Table 478-1).

■ RESPONSIBILITIES OF THE REQUESTING

CLINICIAN

Before requesting a consultation, the physician or other provider

should ensure that the patient endorses the purpose of the consultation, understands the role of the consultant, and anticipates the likely

outcomes of the encounter. Further responsibilities of the requesting

physician include being specific and communicating clearly the reason

for the consultation. Vague messages such as “Please evaluate” are not

as helpful as more specific inquiries such as “What is the cause of the

declining kidney function?” or “How should this asymptomatic pulmonary nodule be evaluated?” To the extent possible, the requesting physician should provide the relevant clinical information, summarized as

succinctly as possible. Urgency should be clearly conveyed, typically

with a phone call or other direct communication.

The requesting physician should be explicit regarding the intended

outcome of the consultation, i.e., is this for a single evaluation or

ongoing co-management? Communication between the requesting

and the consulting physicians is paramount. Whether this communication includes direct contact is less important than that the relevant

information and desired outcome be explicit and clear, regardless of

communication medium. Consultations should be requested for clinical purposes and always directed to qualified consultants; they should

not be driven by entrepreneurial or relationship-building purposes.

Another responsibility of the referring physician is not to “overconsult.” Medical care should be focused on value, not volume.

■ RESPONSIBILITIES OF THE CONSULTANT

Just as the referring physician should attend to clear and explicit communication, so too should the consultant follow the precepts of effective

interactions between professionals, which include courtesy, availability,

and clarity. Particularly on the inpatient service, where consultants

may receive several requests each day, it is important that the incoming consultations are triaged and dispatched as clinically appropriate.

Consultants also need to determine the requested level of involvement

going forward and not assume that long-term co-management is being

sought. While consultants can and should make use of available clinical data, they should also assemble independently their own database,

including taking a history, performing a physical exam, and reviewing

pertinent laboratory, imaging, and pathology studies. Absent that, they

may be unable to provide an independent and actionable synthesis. Just

as the referring physician needs to be clear and concise, so too should

the consultant be specific and focused in the recommendations provided. “Possible malignant ascites” is less helpful than, “I will arrange

for paracentesis to exclude the possibility of malignant ascites.” For the

most part, recommendations to “consider” some diagnosis or test are

less helpful than more specific and concrete advice. Some referring

physicians wish to be called after a patient is seen; others prefer that

communication be handled as part of the medical record. How this

communication is handled must also align with the complexity and

urgency of the consultation and clinical circumstances.

■ RESPONSIBILITIES OF HEALTH SYSTEMS,

HOSPITALS, AND MEDICAL ORGANIZATIONS

Health systems, hospitals, and medical organizations also have responsibilities in the consultation process. This responsibility includes

ensuring that qualified consultants are accessible and available on

the medical staff. Consultations within a single system are aided by

common shared electronic medical records, particularly when consultations originate in the hospital, but then also involve care in the

outpatient setting. Finally, health care entities should strive to foster

a culture of team-based care and collegiality. Reimbursement for consultations varies among payors and may have implications for self-pay

or unreimbursed expenses for providers or health systems. While it is

important to understand reimbursement models, the clinical needs of

the patient should be prioritized.

TABLE 478-1 Stakeholder Responsibilities in the Medical Consultation

Process

REFERRING PHYSICIAN

OR PROVIDER

CONSULTANT

PHYSICIAN

HEALTH SYSTEM,

HOSPITAL, OR CARE

ORGANIZATION

• Ensure patient

participation and

engagement

• Be specific regarding

clinical question and

desired outcome

• Communicate level of

urgency

• Avoid consulting for

nonclinical purposes

• Maintain standards

of professionalism,

including those

pertaining to

availability,

communication,

respect, and

collegiality

• Appreciate levels of

urgency and respond

appropriately

• Assemble and develop

one’s own database

• Be specific in

synthesis and

recommendations

• Understand desired

outcomes, including

arrangements for

follow-up

• Communicate with

referring provider in

whatever manner is

mutually desirable

• Maintain adequate

specialty workforce

to enable appropriate

access

• Support systems for

efficient exchange of

clinical information

• Develop culture of

collegiality and teambased care

3762 PART 19 Consultative Medicine

Each year, ~3.75 million births occur in the United States, and

>130 million births occur worldwide. A significant proportion of births

are complicated by medical disorders. Advances in medical care and

fertility treatment have increased the number of women with serious

medical problems seeking pregnancy. Medical problems that interfere

with the physiologic adaptations of pregnancy increase the risk for

poor pregnancy outcome. Conversely, in some instances, pregnancy

events may have implications for an individual’s long-term health.

HYPERTENSION

(See also Chap. 277) Cardiac output increases by 40% in pregnancy,

with most of the increase due to an increase in stroke volume. Heart

rate increases by ~10 beats/min during the third trimester. In the

second trimester, systemic vascular resistance decreases, and this

decline is associated with a fall in blood pressure. A blood pressure of

≥140/90 mmHg is abnormal and is associated with an increase in perinatal morbidity and mortality. The diagnosis of hypertension requires

the measurement of two elevated blood pressures at least 4 h apart.

Hypertension during pregnancy is classified as preeclampsia, gestational hypertension, or chronic hypertension. These classifications

are distinguished based on timing in pregnancy and the presence of

associated features (see below).

479 Medical Disorders

During Pregnancy

Sarah Rae Easter, Robert L. Barbieri

■ SPECIAL ISSUES IN MEDICAL CONSULTATION

Curbside Consults Curbside consults are requests from one

physician to another for an informal and unwritten opinion about a

specific patient care matter. They are typically limited in scope, mostly

regarding management or questions regarding procedures, and developed from information provided by the consulting physician and perhaps the medical record (such as labs and imaging studies). Although

often viewed as convenient, efficient, and a common aspect of clinical

care, without a comprehensive review of the record or any direct contact with the patient, curbside consults have been found to often be

incomplete or even flawed. It is not uncommon for the question being

asked to be deemed too complex for a curbside consult or for it not to

be the actual or only issue the consultant feels needs to be addressed. As

a general rule, curbside consults should be avoided. While medicolegal

liability is often cited as a reason to limit curbside consults, the risk

is actually negligible as U.S. courts have ruled that curbside consults

do not establish a doctor-patient relationship necessary for creating

the basis for medical malpractice litigation. An important exception,

however, is when a curbside consult is provided by a resident or fellow

in training; in this circumstance, the trainee’s supervising physician,

whether aware of the curbside consult or not, is responsible for the

recommendations of the trainee.

Advice Related to curbside consultation, but decidedly different,

are instances when one physician reaches out to another, often one

in another specialty, for advice. Examples include an internist turning

to a radiologist for guidance on what is the most appropriate imaging

study to diagnose a deep tissue abscess; a general internist asking a

gastroenterologist for advice on management of acute diverticulitis;

a hospitalist asking a neurologist for guidance on management of a

patient with Parkinson’s disease who is NPO; or a nephrologist asking

an infectious disease specialist about immunizations in a kidney transplant recipient.

Outreach such as this is typically triggered by a specific patient

encounter, but the request is more for general information that the

requesting physician may use for the encounter at hand as well as for

similar encounters going forward. Thus, reaching out for advice differs

from formal consultation and from curbside consultation, which are

specific for a particular patient. As such, requests for advice fall within

the realm of collegial communication and not necessarily within that

of clinical consultation per se.

Second Opinions Physicians may find themselves providing consultations requested by patients who have already been evaluated for the

same problem by another physician. Not a “consult” in the usual context

of one physician referring a patient to another, the service provided

by the consultant is, nonetheless, very much aligned with a physicianreferred consult. Second opinions, which often are encouraged by the

patient’s physician, may be sought by patients for reassurance that a

diagnosis and treatment recommendation are correct, out of dissatisfaction with the initial physician, or with the hope of an entirely

different opinion and recommendation. The physician providing the

second opinion should strive to understand the patient’s motivations

for seeking the additional opinion. While a second opinion may have

been initiated by the patient rather than referral from another physician, it is recommended that the consulting physician communicate

with the patient’s primary physician, as would be done following a

standard consultation, unless the patient insists otherwise. In addition, professional behavior in how the consulting physician refers to

the recommendations or actions of previous physicians is important,

including when there is disagreement. Likewise, it is important that a

transfer of care from the prior physician to the one providing a second

opinion be enacted only if specifically requested by the patient or the

physician who encouraged the second opinion.

Consults Involving Advanced Practice Providers Increasingly,

specialist physicians may find themselves being consulted by

nurse practitioners and physician assistants rather than other physicians. Whether the quality of the information provided to the

consultant physician by these providers is different from physicianto-physician referrals has not been studied. Consulting physicians

should know whether they should respond back to the advanced practice provider or to the supervising physician, if there is one. As with

physician-to-physician consults, it is also important for the consultant

to know whether the individual calling for the consult has an ongoing

role in the care of the patient or is simply covering for a limited period

of time. Finally, the consultant, if responding back to the advanced

practice provider, should make sure that the information provided

meets the needs of that provider and that questions are answered as

they would be if responding back to another physician.

Consultation Involving Telemedicine Consultations making

use of electronic health records, patient portals, and various forms of telecommunication technology, including video conferencing or cell phone

communication, can improve access to care, reduce cost, and improve

outcomes. This is particularly true when employed in geographic areas of

health care shortage and when the clinical issues can be handled without

direct contact with the patient, i.e., radiology or dermatology. However,

the absence of direct contact between patient and consultant introduces

special issues related to diagnostic accuracy and physician-patient relationship. Regulatory, liability, security, and confidentiality issues arise

as well, as do concerns about disparities related to in access to telemedicine technologies and willingness and ability to use them among some

patient populations.

■ FURTHER READING

Daniel H, Sulmasy LS: Policy recommendations to guide the use of

telemedicine in primary care: An American College of Physicians

Position Paper. Ann Intern Med 163:787, 2015.

Pearson SD: Principles of generalist-specialist relationships. J Gen

Intern Med 14(Suppl 1):S13, 1999.

3763 Medical Disorders During Pregnancy CHAPTER 479

pressures >160/110 mmHg reduces the risk of CVAs. Labetalol or

hydralazine IV are the first-line agents to manage severe hypertension in preeclampsia with consideration of oral agents once blood

pressure is controlled. Elevated arterial pressure should be reduced

slowly to avoid hypotension and a decrease in blood flow to the

fetus.

Magnesium sulfate is the preferred agent to prevent eclampsia in

patients with preeclampsia with severe features and for treatment

and prevention of recurrent seizures in patients with eclampsia.

Magnesium sulfate is administered as an IV loading dose followed

by a continuous infusion, with care taken in patients with impaired

renal function or pulmonary edema. Randomized trial data demonstrate that magnesium is superior to phenytoin and diazepam in

reducing the risk of seizure. Women who have had preeclampsia

appear to be at increased risk of cardiovascular disease later in life.

■ CHRONIC HYPERTENSION

Pregnancy complicated by chronic hypertension is associated with

risks to mother and neonate. Pregnant women with chronic hypertension are at increased risk for superimposed preeclampsia and placental

complications including intrauterine growth restriction and placental

abruption. Women with chronic hypertension should have a thorough

prepregnancy evaluation to identify remediable causes of hypertension

and to transition off of antihypertensive agents associated with adverse

outcomes in pregnancy. Labetalol and extended-release nifedipine are

the most commonly used medications for the treatment of chronic

hypertension in pregnancy. The target blood pressure is in the range

of 130–150 mmHg systolic and 80–100 mmHg diastolic to balance

maternal safety with fetal perfusion. A preconception or early pregnancy assessment for end-organ impacts of hypertension, including

the presence of proteinuria, may help differentiate the effects of chronic

hypertension from those of superimposed preeclampsia. There are

no convincing data that the treatment of mild chronic hypertension

improves perinatal outcome.

■ RENAL DISEASE

Normal pregnancy is characterized by an increase in glomerular filtration rate and creatinine clearance secondary to a rise in renal plasma

flow and increased glomerular filtration pressures. Patients with underlying renal disease may expect a worsening of existing hypertension

or development of preeclampsia during pregnancy. A prepregnancy

serum creatinine level <133 μmol/L (<1.5 mg/dL) is associated with a

favorable prognosis, whereas certain pathologies, such as those associated with glomerular disease, increase the risk of adverse outcomes.

Neither hemodialysis nor transplant is a contraindication to pregnancy,

but both require close multidisciplinary management. When renal

disease worsens during pregnancy, close collaboration between the

internist and the maternal-fetal medicine specialist is essential so that

decisions regarding delivery can be weighed to balance the sequelae of

prematurity for the neonate versus long-term sequelae for the mother

with respect to future renal function.

CARDIAC DISEASE

Cardiac disease is the leading cause of maternal mortality in the

United States. Prepregnancy cardiac disease and cardiac disease caused

by pregnancy are both major contributors. Patient education, risk

stratification, optimization of hemodynamics, and multidisciplinary

planning with a pregnancy heart team are the tenets of management independent of etiology. Patients with pulmonary hypertension

(Chap. 283), severe ventricular dysfunction (ejection fraction <30%

or New York Heart Association class III–IV), severe mitral or aortic

stenosis, severe aortic dilation, or Fontan circulation with any complication are at the highest risk of maternal mortality. Pregnancy is

contraindicated in these women, with most experts recommending termination of pregnancy due to maternal risk. Risk stratification including a detailed history with attention to symptoms, echocardiography,

and cardiopulmonary exercise testing guides monitoring and management for most patients. Contemporary guidelines support continuing

■ PREECLAMPSIA

Approximately 5–7% of all pregnant women develop preeclampsia,

the new onset of hypertension (blood pressure ≥140/90 mmHg) and

proteinuria (either a 24-h urinary protein >300 mg/24 h or a proteincreatinine ratio ≥0.3) after 20 weeks of gestation. Preeclampsia can be

diagnosed without proteinuria in the presence of symptoms or laboratory abnormalities raising concern for end-organ damage. Specific

clinical features qualify as evidence of severe disease, including severe

hypertension (blood pressure ≥160/110 mmHg), new-onset symptoms

(headache not responsive to medications, visual changes, unremitting

severe epigastric pain, or pulmonary edema), or laboratory abnormalities signifying thrombocytopenia (platelets <100 × 109

/L), renal

insufficiency (creatinine >1.1 mg/dL), or liver impairment (elevation

of transaminases to twice the normal concentration). The HELLP

syndrome (hemolysis, elevated liver enzymes, low platelets) is a special

subtype of preeclampsia with severe features and is a major cause of

morbidity and mortality. Coagulopathy, cerebrovascular accidents

(CVAs), hepatic capsule rupture, and placental abruption are additional end-organ complications of preeclampsia.

The precise pathophysiology of preeclampsia remains unknown,

but chronic uteroplacental ischemia, an exaggerated maternal inflammatory response, and/or imbalance of angiogenic factors likely contribute to the clinical syndrome. Excessive placental production of

antagonists to both vascular endothelial growth factor (VEGF) and

transforming growth factor β (TGF-β) and subsequent endothelial

injury may underlie the pathophysiology in more severe presentations

of the disease. Abnormalities of cerebral circulatory autoregulation

explain some of the neurologic manifestations of the disease and can

increase the risk of stroke at even modestly elevated blood pressures.

In the absence of treatment, 1 in 200 cases of preeclampsia may progress to eclampsia—new-onset generalized tonic-clonic seizures in a

patient with preeclampsia. Low-dose aspirin initiated between 12 and

14 weeks of gestation reduces the risk in women at high risk of developing preeclampsia.

■ GESTATIONAL HYPERTENSION

The development of elevated blood pressure after 20 weeks of pregnancy in the absence of preexisting chronic hypertension or proteinuria

is referred to as gestational hypertension. Gestational hypertension with

severe features of the disease is best classified as preeclampsia, whereas

gestational hypertension in the absence of severe features has a similar

rate of adverse outcomes to the general obstetric population.

TREATMENT

Preeclampsia

The management of preeclampsia is challenging because it requires

the clinician to balance the health of the mother with the health

of the fetus. The definitive treatment of preeclampsia is delivery

of the fetus and placenta. This reduces the mother’s morbidity but

exposes the fetus to the risks of prematurity. In preeclampsia without severe features, delivery at 37 weeks is recommended. Women

with preeclampsia without severe features may be managed conservatively until 37 weeks with close monitoring for development

of severe features, careful fetal surveillance, and limited physical

activity to reduce blood pressure.

Expectant management of preeclampsia with severe features

remote from term affords some benefits for the fetus but at significant risk to the mother. For women with preeclampsia with severe

features, delivery is recommended unless the patient is <34 weeks

and eligible for expectant management in a tertiary hospital setting.

Indications for delivery prior to 34 weeks include unremitting

symptoms, development of laboratory abnormalities, or severe

range blood pressures refractory to medical management. The goal

of prolonging pregnancy to this gestational age is to improve neonatal outcomes. Therefore, concerns about fetal well-being, such as

severe intrauterine growth restriction or placental abruption, may

also prompt delivery before 34 weeks. Timely management of blood

3764 PART 19 Consultative Medicine

most nonteratogenic prepregnancy medications and reserving cesarean

delivery for obstetric indications with rare exceptions.

■ VALVULAR HEART DISEASE

(See also Chaps. 261–268.)

Mitral Stenosis The pregnancy-induced increase in blood volume, cardiac output, and tachycardia can increase the transmitral

pressure gradient and cause pulmonary edema or tachyarrhythmias in

women with mitral stenosis. Women with moderate to severe mitral

stenosis (mitral valve area ≤1.5 cm2

) who are planning pregnancy and

have either symptomatic disease or pulmonary hypertension should

undergo valvuloplasty prior to conception, preferably with percutaneous balloon valvotomy. Careful control of heart rate and avoidance of

hypovolemia, especially during labor and delivery, mitigate the risk of

tachycardia and reduced ventricular filling times on cardiac function.

The immediate postpartum period is a time of particular concern secondary to rapid volume shifts.

Aortic Stenosis Women with aortic stenosis and a mean valve

gradient <25 mmHg are likely to tolerate pregnancy. For women with

symptomatic aortic stenosis or severe aortic stenosis with a peak gradient >50 mmHg, treatment before pregnancy should be considered.

Mitral and Aortic Regurgitation The pregnancy-induced

decrease in systemic vascular resistance reduces the risk of cardiac failure with these conditions, especially in women with chronic lesions. As

a general rule, regurgitant lesions are well tolerated in pregnancy with

acute onset of mitral or aortic regurgitation as an exception.

Mechanical Heart Valves Women with mechanical heart valves

are at high risk of valve thrombosis in pregnancy and warrant special

consideration. Use of warfarin in pregnancy is limited to this population and still avoided in the first trimester due to its association with

fetal chondrodysplasia punctate. The risk of serious neonatal bleeding

and associated neurologic injury persists throughout pregnancy, but

the superiority of warfarin in preventing valve thrombosis merits its

use. Bridging from warfarin to heparin infusion just prior to delivery

minimizes bleeding risk and facilitates neuraxial analgesia.

■ CONGENITAL HEART DISEASE

(See also Chap. 269) Reparative surgery has markedly increased the

number of adult women with congenital heart disease seeking pregnancy with a variety of disease-specific management considerations and

outcomes. Repaired septal defects are comparatively low risk, whereas

unrepaired septal lesions or repaired complex lesions such as tetralogy

of Fallot may warrant additional surveillance by a pregnancy heart team

to ensure that pregnancy is tolerated. Women with complications in the

setting of lower risk disease or with high-risk disease including uncomplicated Fontan circulation, systemic right ventricle, or cyanotic disease

require delivery at a tertiary care center with subspecialty expertise. In

Eisenmenger’s syndrome, i.e., the combination of pulmonary hypertension with right-to-left shunting due to congenital abnormalities (Chap.

269), maternal and fetal deaths occur frequently, informing the recommendation for termination of pregnancy. The presence of a congenital

cardiac lesion in the mother increases the risk of congenital cardiac disease in the newborn and is the basis for the recommendation to screen

for fetal congenital heart disease with fetal echocardiography.

■ AORTOPATHY

The physiologic cardiovascular adaptations of pregnancy can predispose women to aortic dissection, with the highest risk in women with

known aortic disease. Echocardiographic monitoring for evolution of

the aortic root diameter is essential with consideration of complete

aortic imaging with prepregnancy CT or MRI for aortic pathology in

high-risk diseases. For most diseases, an aortic root diameter <40 mm

portends a favorable pregnancy outcome, whereas a diameter >50 mm

is an indication for prepregnancy repair. Beta blockers are a mainstay

of therapy for most patients. A high clinical suspicion for dissection in

patients presenting with chest pain is mandatory.

Marfan Syndrome (See also Chap. 413) This autosomal dominant disease is associated with an increased risk of aortic dissection

and rupture. An aortic root diameter >40 mm is associated with

an increased risk of aortic dissection, and an aortic root diameter

>45 mm is an indication for surgical treatment. Operative vaginal

delivery to limit the aortic wall stress associated with Valsalva should

be considered for women with an aorta of 40–45 mm.

Ehlers-Danlos Syndrome (EDS) (See also Chap. 413) Type IV

EDS is an autosomal dominant disease associated with an increased

risk of uterine or vascular rupture that may cause death. For women

with type IV or other vascular EDS, pregnancy is relatively contraindicated because of this risk.

■ CARDIAC COMPLICATIONS IN PREGNANCY

Arrhythmias New-onset arrhythmias in healthy patients or

patients with cardiac disease are common cardiac complications.

Treatment is the same as in the nonpregnant patient, and fetal tolerance of medications such as beta blockers, calcium channel blockers,

and common antiarrhythmics is acceptable. Pharmacologic or electric

cardioversion may be performed to improve cardiac performance and

reduce symptoms according to standard indications.

Peripartum Cardiomyopathy This uncommon but life-threatening condition should be considered in patients presenting in the third

trimester or postpartum period with unexplained pulmonary edema.

Treatment is directed toward symptomatic relief and improvement of

cardiac function. Many patients recover completely; others are left with

progressive dilated cardiomyopathy. Approximately 10% of women

with peripartum cardiomyopathy carry a truncating mutation in the

gene encoding the titin sarcomere protein. Recurrence in a subsequent

pregnancy is a risk, and women who do not have normal baseline left

ventricular function after an episode of peripartum cardiomyopathy

should be counseled to avoid pregnancy.

ENDOCRINE AND METABOLIC DISORDERS

The fetoplacental unit induces major metabolic changes to shunt

glucose and amino acids to the fetus while the mother uses ketones

and triglycerides to fuel her metabolic needs. The use of glucose by

the fetus leads to a state of accelerated ketosis during maternal fasting,

characterized by lower maternal glucose concentrations and higher

hydroxybutyrate and acetoacetate levels. These metabolic changes are

accompanied by maternal insulin resistance that increases during the

course of pregnancy caused in part by placental production of steroids,

a growth hormone variant, and placental lactogen.

■ DIABETES MELLITUS

(See also Chaps. 403–405) Pregnancy complicated by diabetes mellitus (DM) is associated with higher maternal and perinatal morbidity

and mortality rates. The metabolic changes of pregnancy can precipitate hyperglycemia requiring increased insulin needs, development

of diabetic ketoacidosis, or hypoglycemia. Impaired glycemic control

during the critical first 5–8 weeks of pregnancy leads to the increased

risk of spontaneous abortion and congenital anomalies seen in pregnancies affected by DM and highlights the importance of prepregnancy

glycemic control. Pregestational DM increases the risk of stillbirth,

preeclampsia, and large for gestational age infants. Macrosomia then

increases the risk of shoulder dystocia and birth trauma, including

brachial plexus injury and maternal lacerations. Neonates are at risk

of hypoglycemia, hyperbilirubinemia, polycythemia, and respiratory

distress. An assessment of end-organ complications of DM including

nephropathy, retinopathy, and neuropathy is essential to understanding

the patient’s risk profile.

■ GESTATIONAL DIABETES

Gestational diabetes mellitus (GDM) occurs in ~4% of pregnancies,

and screening for GDM is a routine part of prenatal care. Some advocate for screening all overweight or obese women with risk factors

early in pregnancy to detect occult pregestational DM or early GDM.

Regardless of early screening, the typical two-step strategy to diagnose

3765 Medical Disorders During Pregnancy CHAPTER 479

GDM is performed at 24–28 weeks of gestation and involves administration of a 50-g oral glucose challenge with a single serum glucose

measurement at 60 min. Plasma glucose >7.2 mmol/L (>130 mg/dL)

warrants administration of a 100-g oral glucose tolerance test (GTT)

with plasma glucose measurements obtained in the fasting state and

at 1, 2, and 3 h. Normal plasma glucose concentrations at these time

points are <5.3 mmol/L (<95 mg/dL), <10 mmol/L (<180 mg/dL),

<8.6 mmol/L (<155 mg/dL), and <7.8 mmol/L (<140 mg/dL) as the

upper norms. Two elevated glucose values indicate a positive GTT

diagnostic of GDM. Rates of adverse pregnancy outcomes demonstrate a colinear increase with increasing glucose levels challenging

the optimal threshold for diagnosing GDM. GDM increases the risks

of maternal and neonatal complications associated with pregestational

diabetes, while treating GDM reduces the risk of preeclampsia, birth

weight >400 g, and shoulder dystocia.

TREATMENT

Diabetes Mellitus in Pregnancy

Preconception counseling to optimize glycemic control and

assess for end-organ complications of DM is a cost-effective and

evidence-based intervention for women with DM. Guidelines

encourage women considering pregnancy to initiate insulin prior

to pregnancy targeting a preconception hemoglobin A1C <6%. Insulin is the preferred medical therapy for pregestational DM in pregnancy due to its safety profile and lower rates of treatment failure

compared to oral hypoglycemics.

Once pregnancy is established, glucose control should be managed more intensively than in the nonpregnant state with assessment of blood glucose when fasting and either 1 or 2 h after a

meal at a minimum. Fasting blood glucose levels should be maintained at <5.3 mmol/L (<95 mg/dL), with postprandial targets of

<7.8 mmol/L (140 mg/dL) or <6.7 mmol/L (120 mg/dL) at 1 and 2 h,

respectively. Continuous glucose monitoring is an evidence-based

intervention to improve neonatal outcomes in type 1 DM. Sequential measurement of hemoglobin A1C is of minimal utility for monitoring glucose control during pregnancy because of the higher rate

of red blood cell turnover during pregnancy and resultant falsely

low values. Average daily insulin needs increase from 0.7–0.8 units/

kg in the first trimester, to 0.8–1 units/kg in the second trimester,

and 0.9–1.2 units/kg in the third trimester. Most management strategies utilize a combination of basal insulin with short-acting insulin

at mealtime or continued use of a prepregnancy insulin pump in

appropriately selected patients.

Glycemic control may become more difficult to achieve as pregnancy progresses due to an increase in insulin resistance. Attention to glycemic control and frequent fetal surveillance including

ultrasounds are mainstays of management in the third trimester.

Findings of a large for gestational age fetus or polyhydramnios

on antenatal ultrasound can be indicators of suboptimal glycemic

control. Tight glycemic control at delivery minimizes the risk of

neonatal hypoglycemia due to fetal hyperinsulinemia caused by

elevated maternal glucose levels. Infants of mothers with DM have

higher rates of preterm birth, although preterm delivery is generally

reserved for worsening maternal renal disease or active proliferative

retinopathy in addition to the usual obstetric indications. Induction of labor may be recommended in the early term period of

37–39 weeks of gestation. Cesarean delivery is reserved for cases of

suspected macrosomia based on an estimated fetal weight of 4500 g

or greater to minimize the risk of shoulder dystocia and associated

birth trauma.

Gestational Diabetes

Treatment of GDM begins with nutritional therapy to optimize normoglycemia and gestational weight gain, which is effective in the

majority of women. Insulin is the preferred therapy for patients who

exceed the aforementioned targets despite nutritional therapy. Metformin and glyburide are alternatives for patients who decline or

cannot reliably take insulin. Contemporary data demonstrate lower

mean birth weights, gestational weight gain, and rates of preeclampsia with metformin compared to both glyburide and insulin.

The unknown long-term developmental and metabolic effects of

metformin, including higher adiposity measurements in children

exposed to metformin in utero, inform the preference for insulin.

GDM confers a 7- to 10-fold increase in the risk of developing

type 2 DM later in life, with a 10% risk within 5 years of delivery.

All women with GDM should have a 4- to 12-week 2-h 75-g GTT

to screen for DM or impaired glucose tolerance. The increased

long-term risks of DM and cardiovascular disease and the need

for regular follow-up with their primary care provider should be

emphasized for all women with GDM. Exercise, weight loss, and

treatment with metformin reduce the risk of developing DM in

these at-risk women.

■ OBESITY

(See also Chap. 402) Pregnant women who are obese have an

increased risk GDM, preeclampsia, cesarean delivery, congenital

anomalies, stillbirth, and neonatal death. A growing body of literature

suggests the in utero effects of excess adipose tissue may cause changes

in metabolic programming that lead to adverse health outcomes in

adult life. Women contemplating pregnancy should attempt to attain a

healthy weight prior to conception, recognizing that even a 10% reduction in weight may significantly reduce many of these risks. Women

undergoing bariatric surgery should be counseled to avoid conception

for 12–18 months after surgery until weight stabilizes. Bariatric surgery

reduces the risks for some complications but requires increased laboratory surveillance for micronutrient deficiencies in pregnancy with

appropriate supplementation. All women should be counseled to avoid

weight gain in excess of the National Academy of Medicine guidelines

(25–35 lb for normal weight, 15–25 lb for overweight, and 11–20 lb for

obese women) with the knowledge that excess gestational weight gain

increases the risk of macrosomia and cesarean delivery, independent of

the presence of comorbid DM.

■ THYROID DISEASE

(See also Chap. 382) The estrogen-induced increase in thyroxinebinding globulin increases circulating levels of total T3

 and total T4

 in

pregnancy. Placental human chorionic gonadotropin (hCG) directly

stimulates the thyroid, causing an increase in free T3

 and T4

. Interpretation of the measurement of free T4

, free T3

, and thyroid-stimulating

hormone (TSH) should use trimester-specific ranges. There are conflicting reports about a link between subclinical hypothyroidism and/

or thyroid peroxidase antibodies and adverse pregnancy outcomes.

Women with a history of Graves’ disease have an increased risk of fetal

goiter and neonatal Graves’ disease independent of maternal treatment

status due to the transplacental passage of maternal thyroid-stimulating

antibodies and stimulation of the fetal thyroid.

TREATMENT

Hyperthyroidism

Methimazole crosses the placenta to a greater degree than propylthiouracil and has been associated with fetal aplasia cutis. However,

propylthiouracil can be associated with maternal liver failure. Some

experts recommend propylthiouracil in the first trimester and

methimazole thereafter. Radioiodine should not be used during

pregnancy, either for scanning or for treatment, because of effects

on the fetal thyroid. In emergent circumstances, including thyroid

storm, additional treatment with beta blockers may be necessary.

Hypothyroidism

The goal of therapy for hypothyroidism is to maintain the serum

TSH in the normal range, and thyroxine is the drug of choice. The

dose of thyroxine required to keep the TSH in the normal range

rises during pregnancy. Since the increased thyroxine requirement

occurs as early as the fifth week of pregnancy, one approach is to

3766 PART 19 Consultative Medicine

increase the thyroxine dose by 30% (two additional pills weekly) as

soon as pregnancy is diagnosed and then adjust the dose according

to TSH.

HEMATOLOGIC DISORDERS

Pregnancy has been described as a state of physiologic anemia. Part

of the reduction in hemoglobin concentration is dilutional, but iron,

folate, and vitamin B12 deficiencies are common causes of correctable

anemia during pregnancy.

Hemoglobinopathy screening with red cell indices is indicated for

all pregnant women with the addition of hemoglobin electrophoresis in populations at high risk for hemoglobinopathies (Chap. 98)

or with low mean corpuscular volume on complete blood count.

Hemoglobinopathies can be associated with increased maternal and

fetal morbidity and mortality, with sickle cell disease as a particularly

high-risk entity in pregnancy. Management is tailored to the specific

hemoglobinopathy and is generally the same for both pregnant and

nonpregnant women. Prenatal diagnosis of hemoglobinopathies in

the fetus is readily available and should be discussed with prospective

parents either prior to or early in pregnancy.

Thrombocytopenia occurs commonly during pregnancy. The majority

of cases are benign gestational thrombocytopenias, but the differential

diagnosis should include immune thrombocytopenia (Chap. 115),

preeclampsia, and thrombotic thrombocytopenic purpura. Benign gestational thrombocytopenia is unlikely if the platelet count is <100,000/μL.

■ DEEP VENOUS THROMBOSIS AND PULMONARY

EMBOLISM

(See also Chap. 279) Pregnancy is associated with venous stasis, endothelial injury, and a hypercoagulable state. Inherited thrombophilias

and the presence of antiphospholipid antibodies increase the risk of

venous thromboembolism (VTE) in pregnancy and often require

prophylactic anticoagulation during pregnancy and the postpartum

period to mitigate risk. Deep venous thrombosis (DVT) or pulmonary

embolism (PE) occurs in about 1 in 500 pregnancies with the highest risk in the postpartum state. Physiologic edema and shortness of

breath coupled with the normal elevation of d-dimer across pregnancy

can make the diagnosis challenging. In general, all diagnostic and

therapeutic modalities afforded to the nonpregnant patient should be

utilized in pregnancy.

TREATMENT

Venous Thromboembolism

Aggressive diagnosis and management of suspected DVT or PE

optimize outcomes for mother and fetus. Anticoagulant therapy

with low-molecular-weight heparin (LMWH) or unfractionated

heparin is indicated in pregnant women with VTE. Anticoagulants

increase the risk of epidural hematoma in women receiving neuraxial analgesia in labor and must be withheld prior to placement.

Prophylactic LMWH must be stopped 12 h before placement of an

epidural catheter, whereas therapeutic LMWH must be withheld

for a full 24 h. Transition to unfractionated heparin as delivery

approaches can shorten the time between anticoagulant administration and epidural placement. The variability in achieving therapeutic levels with subcutaneous heparin may prompt peripartum

transition to a heparin infusion in those at highest risk.

■ NEOPLASIA

Cancer complicates ~1 in 1000 pregnancies. The four cancers that

occur most commonly in pregnancy are cervical cancer, breast cancer,

melanoma, and lymphoma (Table 479-1). In addition to cancers developing in other organs of the mother, gestational trophoblastic tumors

can arise from the placenta.

Pregnancy has relatively little or no impact on the natural history of

malignancies, despite the hormonal influences. Spread of the mother’s

cancer to the fetus (so-called vertical transmission) is exceedingly rare.

However, managing cancer in a pregnant woman is complex, with

competing interests for mother and fetus. Generally, the management

that optimizes maternal physiology is also best for the fetus. The best

way to approach management of a pregnant woman with cancer is to

ask, “What would one do in this clinical situation if she was not pregnant? Then, which, if any aspect of those plans needs to be modified

because she is pregnant?”

TREATMENT

Malignancy

Exposure of the developing fetus to ionizing radiation may cause

adverse effects. Awareness of this potential toxicity has resulted in a

disproportionate aversion to diagnostic imaging in pregnancy. The

fetus is most sensitive to teratogenic agents in the first trimester

during organogenesis. Imaging that uses ionizing radiation should

not be done without a compelling reason and due consideration to

obtaining the necessary information by alternative modalities.

Chemotherapy is associated with adverse fetal effects, but the

significance of these depends on the specific agent and gestational

age. Cytotoxic chemotherapy should virtually never be given in the

first trimester due to risk of spontaneous abortion or malformation.

If avoiding chemotherapy during this vulnerable time period could

compromise maternal health, patients should be counseled about

the role of therapeutic abortion to avoid serious neonatal sequelae.

A variety of single agents and combinations have been administered in the second and third trimesters, without a high frequency

of toxic effects to the pregnancy or the fetus. Whether the association between chemotherapy and outcomes such as fetal growth

restriction is due to the therapy or underlying malignancy is

unknown. Literature supporting the short- and long-term neonatal

safety of common agents is growing. For malignancies diagnosed

closer to term or slowly progressive malignancies, delaying treatment until after delivery to avoid fetal exposure to chemotherapy

may be desirable. If delaying therapy may compromise maternal

prognosis and the patient is beyond the first trimester, then treatment might be initiated in pregnancy with plans to deliver the fetus

preterm to avoid excess exposure to chemotherapy. Neonatal prognosis is most closely linked to gestational age at delivery. Decisions

regarding timing of delivery should contextualize this within the

natural history of the disease and safety of the proposed treatment.

NEUROLOGIC DISORDERS

Neurologic complaints such as headaches or neuropathies are common in pregnancy, and differentiating bothersome symptoms from

life-threatening pathology is challenging. While most complaints are

benign, cerebrovascular accidents (CVAs) should be high on the differential diagnosis and evaluated with noncontrast head CT in cases

of suspected stroke. Less acute neurologic complaints are optimally

evaluated with noncontrast MRI. The increased prevalence of cerebral

venous thrombosis and arterial dissection may require additional

imaging with magnetic resonance venography or arteriography, respectively, remembering that gadolinium should be avoided in pregnancy.

TABLE 479-1 Incidence of Malignant Tumors During Gestation

TUMOR TYPE

INCIDENCE PER 10,000

PREGNANCIESa % OF CASESb

Breast cancer 1–3 25%

Cervical cancer 1.2–4.5 25%

Thyroid cancer 1.2 15%

Hodgkin’s disease 1.6 10%

Melanoma 1–2.6 8%

Ovarian cancer 0.8 2%

All sites 10 100%

a

These are estimates based on extrapolations from a review of >3 million

pregnancies (LH Smith et al: Am J Obstet Gynecol 184:1504, 2001). b

Based on

accumulating case reports from the literature; the precision of these data

is not high.

3767 Medical Disorders During Pregnancy CHAPTER 479

Exclusion of preeclampsia is important for any patient presenting

with a headache after 20 weeks of gestation with a low threshold to

assess for CVA due to the comparatively high prevalence in this population. Headache in preeclampsia can be associated with the posterior

reversible encephalopathy syndrome (PRES), which is on the spectrum

of reversible cerebral vasoconstriction syndromes (RCVS) that can

present in pregnancy with neurologic complaints. Peripheral nerve

disorders associated with pregnancy include Bell’s palsy (idiopathic

facial paralysis) (Chap. 446), carpal tunnel syndrome (median nerve

entrapment), or meralgia paresthetica (lateral femoral cutaneous nerve

entrapment). Restless leg syndrome is the most common peripheral

nerve and movement disorder in pregnancy, and complaints should

prompt an evaluation for disordered iron metabolism.

Pregnancy is safe for the majority of women with neurologic disorders with management considerations focusing on medication safety,

the impact of pregnancy on the disease, and potential neonatal consequences. For women with epilepsy planning pregnancy, lamotrigine

and levetiracetam are first-line monotherapies due to the wealth of

safety data. The decision to change antiepileptic drugs (AEDs) for

pregnancy should be individualized, with avoidance of valproate due

to known risk of congenital malformations. Folic acid supplementation

of 4 mg daily should be considered in women taking AEDs. Escalating

doses of AEDs may be required due to increased clearance in pregnancy and guided by monthly monitoring of AED levels.

Patients with preexisting multiple sclerosis (Chap. 444) experience

a gradual decrease in the risk of relapses as pregnancy progresses and,

conversely, an increase in attack risk during the postpartum period.

Disease-modifying agents should be withheld in pregnancy, and

relapses should be treated with glucocorticoids. Finally, certain tumors,

particularly pituitary adenoma and meningioma (Chap. 380), may

manifest during pregnancy because of accelerated growth, possibly

driven by hormonal factors. Neuroimaging with noncontrast MRI may

be required for women with a history of tumors to facilitate neuraxial

analgesia.

GASTROINTESTINAL AND LIVER DISEASE

Up to 90% of pregnant women experience nausea and vomiting

during the first trimester of pregnancy. Hyperemesis gravidarum is a

severe form that prevents adequate fluid and nutritional intake and

may require hospitalization to prevent dehydration and malnutrition.

Thiamine and folate supplementation and monitoring of electrolytes

for evidence of refeeding syndrome should be considered in severe

cases with evaluation for supplemental enteral nutrition in refractory

disease.

Exacerbation of inflammatory bowel disease is common, and medical management of these conditions parallels the nonpregnant state

(Chap. 326). Pregnancy is a risk factor for development or worsening

of gallbladder disease such as cholelithiasis. This aggravation may be

due to pregnancy-induced alteration in the metabolism of bile and fatty

acids. Intrahepatic cholestasis of pregnancy is generally a third-trimester

event presenting with profound pruritis and confirmed with an elevated level of bile acids with or without transaminitis. The association

between cholestasis and stillbirth merits increased fetal surveillance

and delivery by 37 weeks of gestation. Symptoms can be improved with

the use of ursodiol.

Acute fatty liver is a rare complication of pregnancy on the spectrum

with HELLP syndrome and preeclampsia. Acute fatty liver of pregnancy is generally distinguished by markedly increased serum levels

of bilirubin and ammonia and by hypoglycemia. Management of acute

fatty liver of pregnancy includes delivery accompanied by supportive

care.

All pregnant women should be screened for hepatitis B virus and

hepatitis C virus. All infants receive hepatitis B vaccine, but infants

born to mothers who are carriers of hepatitis B surface antigen should

also receive hepatitis B immune globulin as soon after birth as possible to decrease the risk of vertical transmission. The presence of the

hepatitis B E antigen in the mother and high viral load increase this

risk. Strategies to decrease vertical transmission of hepatitis C are

limited to avoiding procedures (i.e., amniocentesis) that increase the

risk. Postpartum referral to a specialist for consideration of potentially

curative therapy is indicated.

INFECTIONS

■ BACTERIAL INFECTIONS

All pregnant patients are screened prenatally for syphilis, gonorrhea,

and chlamydial infections, and the detection of any of these should

result in prompt evaluation and treatment (Chaps. 156 and 189).

Other than bacterial vaginosis, the most common bacterial infections

during pregnancy involve the urinary tract (Chap. 135). All pregnant

women should be screened with a urine culture for asymptomatic

bacteriuria at the first prenatal visit. Pregnancy is an indication for

treatment of asymptomatic bacteriuria to avoid pyelonephritis. Progesterone-mediated ureteral and bladder smooth muscle relaxation,

coupled with compression effects of the enlarging uterus, promote

stasis and increase the risk of these conditions. Pregnant women who

develop pyelonephritis should be treated with inpatient IV antibiotic

administration due to the elevated risk of urosepsis and acute respiratory distress syndrome in pregnancy-associated pyelonephritis.

Pregnant women with recurrent urinary tract infections or one episode

of pyelonephritis should be considered for daily antibiotic suppressive

treatment throughout the remainder of their pregnancy.

■ VIRAL INFECTIONS

All pregnant women should be screened for hepatitis B virus, hepatitis C

virus, and HIV. In addition, all pregnant women should be screened for

immunity to rubella and varicella.

Influenza (See also Chap. 200) Pregnant women with influenza

are at increased risk of serious complications and death. All women

who are pregnant or plan to become pregnant in the near future should

receive inactivated influenza vaccine. The prompt initiation of antiviral

treatment is recommended for pregnant women in whom influenza

is suspected. Treatment can be reconsidered once the results of highsensitivity tests are available. Prompt initiation of treatment lowers the

risk of admission to an intensive care unit and death.

Cytomegalovirus Infection The most common cause of congenital viral infection in the United States is cytomegalovirus (CMV)

(Chap. 195). As many as 50–90% of women of childbearing age have

antibodies to CMV, but only rarely does CMV reactivation result in

neonatal infection. More commonly, primary CMV infection during

pregnancy creates a risk of congenital CMV. No currently accepted

treatment of CMV infection during pregnancy has been demonstrated

to protect the fetus effectively. Severe CMV disease in the newborn is

characterized most often by petechiae, hepatosplenomegaly, and jaundice. Chorioretinitis, microcephaly, intracranial calcifications, hepatitis, hemolytic anemia, and purpura may also develop. Central nervous

system (CNS) involvement can result in the development of psychomotor, ocular, auditory, and dental abnormalities over time. Women

with a primary CMV infection should delay conception for 6 months.

Herpesvirus Infection (See also Chap. 192) The acquisition of

genital herpes during pregnancy is associated with spontaneous abortion, prematurity, and congenital and neonatal herpes. Disseminated

neonatal herpes carries with it high mortality and morbidity rates

from CNS involvement. A cohort study of pregnant women without

evidence of previous herpesvirus infection demonstrated that ~2%

acquired a new herpesvirus infection during the pregnancy and ~60%

of the newly infected women had no clinical symptoms. The risk of

transmission was increased in those with infections closer to delivery.

The risk of active genital herpes lesions at term can be reduced by

prescribing acyclovir for the last 4 weeks of pregnancy to all women

who had an episode of genital herpes during the pregnancy. Pregnant

women with active genital herpes lesions at the time of presentation in

labor should be delivered by cesarean section.

Rubella (See also Chap. 206) Rubella virus is a known teratogen;

first-trimester rubella carries a high risk of fetal anomalies, though

the risk significantly decreases later in pregnancy. Congenital rubella

3768 PART 19 Consultative Medicine

may be diagnosed by percutaneous umbilical-blood sampling with the

detection of IgM antibodies in fetal blood. All pregnant women and all

women of childbearing age should be tested for their immune status

to rubella.

Parvovirus Infection (See also Chap. 197) Infection with human

parvovirus B19 may occur during pregnancy. It rarely causes sequelae,

but nonimmune women infected during pregnancy may be at risk for

fetal hydrops secondary to erythroid aplasia and profound anemia.

Management includes screening for fetal anemia with Doppler assessment of the middle cerebral artery and consideration of intrauterine

transfusion of red blood cells to the fetus to avoid the physiologic

consequences of anemia while awaiting fetal recovery.

HIV Infection (See also Chap. 202) The predominant cause of HIV

infection in children is transmission of the virus from mother to newborn

during the perinatal period. All pregnant women should be screened

for HIV infection. Factors that increase the risk of mother-to-newborn

transmission include high maternal viral load, low maternal CD4+

T-cell count, prolonged labor, prolonged duration of membrane rupture, and the presence of other genital tract infections, such as syphilis

or herpes. Antiretroviral therapy (ART) has decreased the rate of perinatal transmission from 20% to ~1%. For women receiving antepartum

ART, maternal viral load guides the decision for vaginal versus cesarean delivery and need for adjunct intrapartum zidovudine. Women

with an undetectable viral load are at the lowest risk of transmission

and require no additional therapy. Those without antepartum ART

exposure or with viral loads >1000 copies/mL at delivery require IV

zidovudine and a prelabor cesarean delivery, typically scheduled at 38

weeks. Cesarean delivery should be reserved for obstetric indications

for women with ≥50 but ≤1000 copies/mL, and intrapartum zidovudine can be considered.

Zika Virus Zika virus (ZV) can be transmitted from mother to

fetus throughout gestation and often results in fetal death, severe

microcephaly, or other malformations of the CNS. Pregnant symptomatic women with relevant epidemiologic exposure within 2 weeks

of symptom onset should have serum and urine tested for ZV ribonucleic acid by real-time reverse transcriptase polymerase chain reaction

(RT-PCR). Testing 2–12 weeks after symptom onset utilizes serum

measurement of Zika and dengue virus IgM. Sequential obstetrical

ultrasound is recommended to assess for fetal growth and anomalies.

Couples considering pregnancy should avoid travel to areas with

known mosquito transmission of ZV.

■ VACCINATIONS

(See also Chap. 123) For rubella-nonimmune individuals contemplating pregnancy, measles-mumps-rubella vaccine should be administered,

ideally at least 3 months prior to conception, but otherwise in the immediate postpartum period. All pregnant women should be vaccinated

against influenza. Administration of one dose of the tetanus, diphtheria,

and pertussis (Tdap) vaccine between 27 and 36 weeks of gestation is

recommended to promote maternal IgG production and reduce the risk

of neonatal pertussis due to transplacental passage of IgG.

MATERNAL MORTALITY

Maternal death is defined as death occurring during pregnancy or

within 42 days of completion of pregnancy from a cause related to or

aggravated by pregnancy, but not due to accident or incidental causes.

The maternal mortality ratio is the number of maternal deaths per

100,000 live births. From 1935 to 2007, the U.S. maternal mortality

ratio decreased from nearly 600/100,000 births to 12.7/100,000 births.

Changes in reporting prohibited publication of a maternal mortality

ratio for >10 years until the 2020 release of the 2018 maternal mortality ratio of 17.4/100,000 births. An increasingly complex patient

population, in addition to changes in measurement, likely contributed

to this rise in maternal death. There are significant racial and ethnic

disparities in the maternal mortality ratio, with a nearly fourfold

increased risk of death for non-Hispanic black women compared to

non-Hispanic white women (37.1 vs 14.7 deaths per 100,000 live births,

respectively) (Chap. 10).

Updated data on the causes of maternal death in the new reporting

framework are forthcoming, but extrapolating evidence from causes

of pregnancy-related death is enlightening. Pregnancy-related death

is defined as the death of a woman while pregnant or within 1 year of

the end of pregnancy from any cause related to or aggravated by pregnancy. Cardiovascular disease, including cardiomyopathy, accounted

for nearly a third of pregnancy-related deaths from 2014 to 2017

followed by infection, noncardiovascular medical conditions, hemorrhage, and thrombotic events. The relative contribution of medical

disease to pregnancy-related death, coupled with knowledge that one

in three pregnancy-related deaths occur 1 week to 1 year after delivery,

highlights the role of the specialist in internal medicine in reducing

maternal mortality.

In some countries in sub-Saharan Africa and southern Asia, the

maternal mortality ratio is >500/100,000 live births. The most common

causes of maternal death in these countries are maternal hemorrhage,

hypertensive disorders, infection, obstructed labor, and complications

from unsafe pregnancy termination. The health interventions that

would have the greatest impact on maternal health include improving the following components of the health system: (1) access to

contraceptive services in order to space births and limit total family

size; (2) access to safe pregnancy termination; (3) presence of trained

birth attendants at all deliveries; and (4) transportation to emergency

obstetrical centers that can provide intensive medical and surgical

services, including cesarean delivery. Maternal death is a global public

health tragedy that could be mitigated with the application of modest

resources.

SUMMARY

With improved diagnostic and therapeutic modalities as well as

advances in the treatment of infertility, more patients with serious

medical complications will be seeking to become pregnant and will

require complex obstetric care. Improved outcomes of pregnancy in

these women will be best attained by a team of internists, maternalfetal medicine (high-risk obstetrics) specialists, pediatricians, and

anesthesiologists assembled to counsel these patients about the risks of

pregnancy and to plan their treatment prior to, and following, conception. The importance of preconception counseling and the impact of

events of pregnancy on lifelong disease cannot be overstated. It is the

responsibility of all physicians caring for women in the reproductive

age group to assess their patients’ reproductive plans as part of their

overall health evaluation.

Acknowledgment

The authors are grateful to Michael F. Greene and Dan L. Longo for their

contributions to the content on neoplasia in pregnancy based on material

from previous editions of Harrison’s.

■ FURTHER READING

American College of Obstetricians and Gynecologists et al:

Obstetric Care Consensus No. 8: Interpregnancy care. Obstet Gynecol 133:51, 2019.

Creanga AA et al: Pregnancy-related mortality in the United States,

2011-2013. Obstet Gynecol 130:366, 2017.

Feig DS et al: Continuous glucose monitoring in pregnant women with

type 1 diabetes (CONCEPTT): A multicenter international randomized controlled trial. Lancet. 390:2347, 2017.

Hoffman MK et al: Low-dose aspirin for the prevention of preterm delivery in nulliparous women with a singleton pregnancy

(ASPIRIN): A randomized, double-blind, placebo-controlled trial.

Lancet 395:285, 2020.

Honigberg MC et al: Long-term cardiovascular risk in women with

hypertension during pregnancy. J Am Coll Cardiol 74:2743, 2019.

Korakiti AM et al: Long-term neurodevelopmental outcome of

children after in utero exposure to chemotherapy. Cancers (Basel)

12:3623, 2020.

Regitz-Zagrosek V et al: 2018 ESC guidelines for the management of

cardiovascular diseases during pregnancy. Eur Heart J 39:3165, 2018.

3769 Medical Evaluation of the Surgical Patient CHAPTER 480

Cardiovascular and pulmonary complications continue to account

for major morbidity and mortality in patients undergoing noncardiac

surgery. Emerging evidence-based practices dictate that the internist

should perform an individualized evaluation of the surgical patient to

provide an accurate preoperative risk assessment and stratification that

will guide optimal perioperative risk-reduction strategies. This chapter

reviews cardiovascular and pulmonary preoperative risk assessment,

emphasizing the goal-directed management of patients at elevated risk

for adverse cardiovascular outcomes in the perioperative period. In

addition, perioperative management of diabetes mellitus and prophylaxis of endocarditis and for venous thromboembolism are reviewed.

EVALUATION OF INTERMEDIATE- AND

HIGH-RISK PATIENTS

Simple, standardized preoperative screening questionnaires, such as

the one shown in Table 480-1, have been developed for the purpose of

identifying patients at intermediate or high risk who may benefit from

a more detailed clinical evaluation. Evaluation of such patients for surgery should always begin with a thorough history and physical examination and with a 12-lead resting electrocardiogram, in accordance

with the American College of Cardiology/American Heart Association

guidelines. The history should focus on symptoms of occult cardiac or

pulmonary disease. The urgency of the surgery should be determined,

as true emergency procedures are associated with unavoidably higher

480 Medical Evaluation

of the Surgical Patient

Prashant Vaishnava, Kim A. Eagle

morbidity and mortality risk. Preoperative laboratory testing should be

carried out only for specific clinical conditions, as noted during clinical

examination. Thus, healthy patients of any age who are undergoing

elective surgical procedures without coexisting medical conditions

should not require any testing unless the degree of surgical stress may

result in unusual changes from the baseline state.

PREOPERATIVE CARDIAC

RISK ASSESSMENT

A stepwise approach to cardiac risk assessment and stratification in

patients undergoing noncardiac surgery is illustrated in Fig. 480-1. The

evaluation begins with characterization of the combined surgical and

clinical risk into categories of low (<1%) and elevated risk for major

adverse cardiovascular events (MACEs). Select surgeries are associated with very low risk for MACE; these surgeries and procedures

include select ophthalmologic surgeries (e.g., cataract surgery), select

endoscopic procedures, and select superficial procedures. Patients

undergoing these low-risk procedures should proceed to surgery without further testing. Clinical risk may be estimated with the American

College of Surgeons’ National Surgical Quality Improvement Program

(NSQIP) risk calculator (http://www.riskcalculator.facs.org) or with

calculation of the Revised Cardiac Risk Index (RCRI).

Previous studies have compared several cardiac risk indices. The

American College of Surgeons’ NSQIP prospective database has

identified five predictors of perioperative myocardial infarction (MI)

and cardiac arrest based on increasing age, American Society of

Anesthesiologists class, type of surgery, dependent functional status,

and abnormal serum creatinine level. However, given its accuracy and

simplicity, the RCRI (Table 480-2) is often the favored risk index. The

RCRI relies on the presence or absence of six identifiable predictive

factors: high-risk surgery, ischemic heart disease, congestive heart

failure, cerebrovascular disease, diabetes mellitus treated with insulin,

and renal insufficiency with a creatinine >2.0 mg/dL. Each of these predictors is assigned one point. The risk of major cardiac events—defined

as MI, pulmonary edema, ventricular fibrillation or primary cardiac

arrest, and complete heart block—can then be predicted. Based on the

presence of none, one, two, three, or more of these clinical predictors,

the rate of development of one of these four major cardiac events is

estimated to be 0.4%, 0.9%, 7%, and 11%, respectively (Fig. 480-2).

The clinical utility of the RCRI is to identify patients with three or more

predictors who are at very high risk (≥11%) for cardiac complications

and who may benefit from further risk stratification with noninvasive

cardiac testing, initiation of preoperative preventive medical management, or avoidance of surgery.

For patients at elevated combined clinical and surgical risk for

MACE, the stepwise perioperative cardiac assessment for coronary

artery disease (CAD) proceeds with consideration of functional capacity. Participation in activities of daily living offers an expression of

functional capacity, often expressed in terms of metabolic equivalents

(METs). For predicting perioperative events, poor exercise tolerance

has been defined as the inability to walk four blocks or climb two

flights of stairs at a normal pace or to meet a MET level of 4 (e.g., carrying objects of 15–20 lb. or playing golf or doubles tennis) because of

the development of dyspnea, angina, or excessive fatigue (Table 480-3).

Patients with moderate or greater (≥4 METs) functional capacity (e.g.,

climbing up a flight of stairs, walking up a hill, or walking on level

ground at 4 mph) generally should not undergo further noninvasive

cardiac testing prior to elective noncardiac surgery. Those patients with

poor (<4 METs) or unknown functional capacity should undergo pharmacological stress testing if the results of such testing would impact

decision-making or perioperative care.

■ PREOPERATIVE NONINVASIVE CARDIAC

TESTING FOR RISK STRATIFICATION

There is little evidence to support widespread application of preoperative noninvasive cardiac testing for all patients undergoing major

surgery. The current paradigm to guide the need for noninvasive

cardiac testing is to perform such testing in patients with poor or

TABLE 480-1 Standardized Preoperative Questionnairea

1. Age, weight, height

2. Are you:

Female and 55 years of age or older or male and 45 years of age or older?

If yes, are you 70 years of age or older?

3. Do you take anticoagulant medications (“blood thinners”)?

4. Do you have or have you had any of the following heart-related conditions?

Heart disease

Heart attack within the last 6 months

Angina (chest pain)

Irregular heartbeat

Heart failure

5. Do you have or have you ever had any of the following?

Rheumatoid arthritis

Kidney disease

Liver disease

Diabetes

6. Do you get short of breath when you lie flat?

7. Are you currently on oxygen treatment?

8. Do you have a chronic cough that produces any discharge or fluid?

9. Do you have lung problems or diseases?

10. Have you or any blood member of your family ever had a problem other than

nausea with any anesthesia?

If yes, describe:

11. If female, is it possible that you are pregnant?

Pregnancy test:

Please list date of last menstrual period:

a

University of Michigan Health System patient information report. Patients who

answer yes to any of questions 2–9 should receive a more detailed clinical

evaluation.

Source: Reproduced with permission from KK Tremper, P Benedict: Paper

“Preoperative Computer”. Anesthesiology 92:1212, 2000.

3770 PART 19 Consultative Medicine

unknown capacity if it would alter clinical management or modify

perioperative care. Options for pharmacological stress testing include

dobutamine stress echocardiography or myocardial perfusion imaging

with coronary vasodilator stress (dipyridamole, adenosine, or regadenoson) with thallium-201 and/or technetium-99m. Routine screening

with noninvasive stress testing is not recommended in patients at low

risk for noncardiac surgery. Furthermore, coronary revascularization

before noncardiac surgery is not recommended for the express purpose

of reducing perioperative cardiac events. That said, revascularization

before noncardiac surgery should be considered in patients if it would

be indicated regardless of the surgery planned and instead according

to clinical practice guidelines. In the Coronary Artery Revascular Prophylaxis trial, there were no differences in perioperative and long-term

cardiac outcomes with or without preoperative coronary revascularization; of note, patients with left main disease were excluded.

■ RISK MODIFICATION: PREVENTIVE

STRATEGIES TO REDUCE CARDIAC RISK

Perioperative Coronary Revascularization Prophylactic coronary revascularization with either coronary artery bypass grafting

(CABG) or percutaneous coronary intervention (PCI) provides no

short- or mid-term survival benefit for patients without left main CAD

or three-vessel CAD in the presence of poor left ventricular systolic

function and is not recommended for patients with stable CAD before

noncardiac surgery. Although PCI is associated with lower procedural

risk than is CABG in the perioperative setting, the placement of a coronary artery stent soon before noncardiac surgery may increase the risk

of bleeding during surgery if dual antiplatelet therapy (DAPT) (aspirin

and P2Y12) is administered; moreover, stent placement shortly before

noncardiac surgery increases the perioperative risk of MI and cardiac

death due to stent thrombosis if such therapy is withdrawn prematurely

Patient

Needs emergency

noncardiac

surgery

Needs elective

noncardiac

surgery

Exhibits evidence

of acute coronary

syndrome

No evidence of

ongoing ACS

Perioperative risk

for MACE* <1%

Perioperative risk

for MACE* >1%

* Estimate major adverse cardiac event

 risk using:

• American College of Surgeons National

 Surgical Quality Improvement Program

 Surgical Risk Calculator

• Revised Cardiac Risk Index, which takes

 into consideration these factors:

 - High-risk surgery

 - History of ischemic heart disease

 - History of congestive heart failure

 - History of cerebrovascular disease

 - Preoperative treatment with insulin

 - Preoperative creatinine >2 mg/dl

Functional

capacity:

Unknown

Proceed

to surgery

PERIOPERATIVE MEDICAL INTERVENTION WHEN CONSIDERING NONCARDIAC SURGERY

Beta-blockers Statin

• Start in intermediate- to

 high-risk patients

• Should not start on day

 of surgery

• Should not be withdrawn

 if taking chronically

• Continued if on

 chronically

• Start in vascular surgery

 patients

• Considered in patients

 with clinical indications,

 undergoing elevated-risk

 procedures

Alpha agonist

Initiation not

recommended prior

to noncardiac surgery

ACE inhibitor

Continued, or if held

before surgery, restart

postoperatively as soon

as clinically feasible

Aspirin

Continued when the risk

of increased cardiac

events outweights the

risk of increased bleeding

Proceed to ACS

evaluation

Proceed

to surgery

Proceed

to surgery

Proceed

to surgery

Consider

noninvasive

testing if results

would change

management

Consider

noninvasive

testing if results

would change

management

Functional

capacity:

Poor

Functional

capacity:

Moderate – Good

Functional

capacity:

Excellent

FIGURE 480-1 Composite algorithm for cardiac risk assessment and stratification in patients undergoing noncardiac surgery. Preoperative evaluation involves a stepwise

clinical evaluation. Those individuals requiring emergency surgery should proceed without further risk stratification. Acute coronary syndrome (step 2) should be evaluated

and treated, accordingly to goal-directed medical therapy. For patients awaiting nonemergent surgeries and without acute coronary syndrome, perioperative risk is a

combination of clinical and surgical risk. Select procedures and surgeries (e.g., select endoscopic procedures) are associated with low (<1%) perioperative risk and no

further clinical testing is generally necessary. For those procedures associated with elevated risk, an assessment of functional capacity informs the decision for further

testing. Those individuals with moderate or greater functional capacity do not require further testing and should proceed to surgery. Individuals with poor or unknown

functional capacity may require pharmacologic stress testing if it would change decision-making or perioperative care. (Reproduced with permission from AY Patel et al:

Cardiac risk of noncardiac surgery. J Am Coll Cardiol 66:2140, 2015.)

3771 Medical Evaluation of the Surgical Patient CHAPTER 480

TABLE 480-2 Clinical Markers Included in the Revised

Cardiac Risk Index

High-Risk Surgical Procedures

Vascular surgery (except carotid endarterectomy)

Major intraperitoneal or intrathoracic procedures

Ischemic Heart Disease

History of myocardial infarction

Current angina considered to be ischemic

Requirement for sublingual nitroglycerin

Positive exercise test

Pathological Q-waves on ECG

History of PCI and/or CABG with current angina considered to be ischemic

Congestive Heart Failure

Left ventricular failure by physical examination

History of paroxysmal nocturnal dyspnea

History of pulmonary edema

S3 gallop on cardiac auscultation

Bilateral rales on pulmonary auscultation

Pulmonary edema on chest x-ray

Cerebrovascular Disease

History of transient ischemic attack

History of cerebrovascular accident

Diabetes Mellitus

Treatment with insulin

Chronic Renal Insufficiency

Serum creatinine >2 mg/dL

Abbreviations: CABG, coronary artery bypass grafting; ECG, electrocardiogram; PCI,

percutaneous coronary intervention.

Source: Adapted from TH Lee et al: Circulation 100:1043, 1999.

10%

15%

Risk stratification

4–7

9–11

0%

5%

Risk of cardiac events

Revised Cardiac Risk Index (RCRI)

0.9–1.3 0.4–0.5

Low risk Intermediate risk High risk

0 1 2 ≥3

RCRI 0 1 2 ≥3

Event Rate 0.50% 1.30% 6.00% 11%

Std Dev 0.45% 1.10% 5.30% 10.00%

FIGURE 480-2 Risk stratification based on the Revised Cardiac Risk Index; derivation and

prospective validation of a simple index for prediction of cardiac risk in patients undergoing

major noncardiac surgery. Cardiac events include myocardial infarction, pulmonary edema,

ventricular fibrillation, cardiac asystole, and complete heart block. (Adapted from TH Lee et al:

Circulation 100:1043, 1999.)

TABLE 480-3 Assessment of Cardiac Risk by Functional Status

Risk

Higher • Has difficulty with adult activities of daily living

• Cannot walk four blocks or up two flights of

stairs or does not meet a MET level of 4

• Is inactive but has no limitations

• Is active: easily does vigorous tasks

Lower • Performs regular vigorous exercises

Abbreviation: MET, metabolic equivalent.

Source: From LA Fleisher et al: Circulation 116:1971, 2007.

(Chap. 276). It is recommended that, if possible, elective noncardiac

surgery be delayed 30 days after placement of a bare metal intracoronary stent and ideally for 6 months after deployment of a drug-eluting

stent (DES). Contemporary stent platforms allow for greater flexibility

in the earlier interruption of DAPT; current clinical practice guidelines

do suggest consideration of elective noncardiac surgery 6 months

after DES implantation if the risk of further delaying surgery exceeds

the risk of stent thrombosis/myocardial ischemia. For patients who

must undergo noncardiac surgery early (>14 days) after PCI, balloon

angioplasty without stent placement appears to be a reasonable alternative because DAPT is not necessary in such patients.

PERIOPERATIVE PREVENTIVE MEDICAL THERAPIES The goal of

perioperative preventive medical therapies with β-adrenergic antagonists, hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase

inhibitors (statins), and antiplatelet agents is to reduce perioperative

adrenergic stimulation, ischemia, and inflammation, all of which are

heightened during the perioperative period.

B-ADRENERGIC ANTAGONISTS The use of perioperative beta blockade should be based on a thorough assessment of a patient’s perioperative clinical and surgery-specific cardiac risk (e.g., as with the RCRI).

The paradigm for beta blockade in the perioperative period has shifted

in recent years owing, firstly, to the publication of the PeriOperative

Ischemic Evaluation (POISE) trial demonstrating that, while perioperative beta blockade reduces the perioperative risk for MI, this is at

the expense of increased death and stroke. Regarding POISE, this trial

has been criticized for the use of an excessive dose of beta blocker in

the perioperative period and one that may not be reflective of clinical

practice, nor one that was titrated in the days or weeks preceding the

procedure or surgery. Secondly, research misconduct has discredited

the Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress

Echocardiography (DECREASE) family of studies, which previously

contributed to the bedrock of data supporting the use of perioperative

beta blockade but have now been retracted.

Current guidelines emphasize the following key points:

1. Continuation of beta blockade in patients undergoing surgery and

who have been receiving such therapy chronically.

2. Avoidance of beta-blocker withdrawal or initiation on the day of

surgery.

3. Consideration of initiation of beta-blocker therapy perioperatively

(ideally far enough in advance to assess safety and tolerability) in

very select high-risk patients, namely, those with intermediate- or

high-risk ischemia or three or more RCRI risk factors.

HMG-COA REDUCTASE INHIBITORS (STATINS) A number

of prospective and retrospective studies support the perioperative prophylactic use of statins for reduction of cardiac

complications in patients with established atherosclerosis.

For patients undergoing noncardiac surgery and currently

taking statins, statin therapy should be continued to reduce

perioperative cardiac risk. Initiation of statin therapy is

reasonable for patients undergoing vascular surgery independent of clinical risk. Perioperative initiation of statin therapy

should be considered in patients undergoing elevated-risk

procedures if there is an indication for such therapy separate from the surgery and according to clinical practice

guidelines.

ANGIOTENSIN-CONVERTING ENZYME (ACE) INHIBITORS

It is important to maintain continuity of therapy with ACE

inhibitors (when such therapy is used for the treatment of

heart failure or hypertension).

ORAL ANTIPLATELET AGENTS The 4- to 6-week period

following implantation of an intracoronary stent (bare metal

or drug eluting) constitutes the period of time of greatest

risk for the development of stent thrombosis. If possible,