# 26 - PART 19 Consultative Medicine

# 01 - 490 Approach to Medical Consultation

## 490 Approach to Medical Consultation

Jeffrey S. Berns, Jack Ende

Approach to Medical 
Consultation
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 the required diagnos­
tic procedure or management lie outside the principal provider’s area 
of expertise.
To consult is to seek advice from someone with expertise in a par­
ticular 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 non­
physician practitioner; the consultant, who provides the consultation; 
and the health system, hospital, or organization that must support this 
important medical encounter (Table 490-1).
■
■RESPONSIBILITIES OF THE REQUESTING 
CLINICIAN
Before requesting a consultation, the physician or other provider 
should ensure that the patient endorses the purpose of the consulta­
tion, 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 
TABLE 490-1  Stakeholder Responsibilities in the Medical Consultation 
Process
REFERRING 
PHYSICIAN OR 
PROVIDER
CONSULTANT PHYSICIAN
HEALTH SYSTEM, 
HOSPITAL, OR CARE 
ORGANIZATION
• Ensure patient 
• Maintain standards of 
• Maintain adequate 
participation and 
engagement
• Be specific 
professionalism, including 
those pertaining to 
availability, communication, 
respect, and collegiality
• Appreciate levels of urgency 
specialty 
workforce to 
enable appropriate 
access
• Support systems 
regarding clinical 
question and 
desired outcome
• Communicate level 
and respond appropriately
• Assemble and develop one’s 
for efficient 
exchange of 
clinical information
• Develop culture 
of urgency
• Avoid consulting 
own database
• Be specific in synthesis and 
of collegiality and 
team-based care
for nonclinical 
purposes
recommendations
• Understand desired 
outcomes, including 
arrangements for follow-up
• Communicate with referring 
provider in whatever manner 
is mutually desirable

Consultative Medicine
PART 19
as helpful as more specific inquiries such as “What is the cause of the 
declining kidney function?” or “How should this asymptomatic pulmo­
nary nodule be evaluated?” To the extent possible, the requesting phy­
sician 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 communi­
cation 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 clini­
cal 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 com­
munication, 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 incom­
ing 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 clini­
cal 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 pro­
vided. “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 respon­
sibilities 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 con­
sultations 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 con­
sultations 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.
■
■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 devel­
oped from information provided by the consulting physician and per­
haps the medical record (such as labs and imaging studies). Although

# 02 - 491 Medical Disorders During Pregnancy

## 491 Medical Disorders During Pregnancy

often viewed as convenient, efficient, and a common aspect of clinical 
care, without a comprehensive review of the record or any direct con­
tact 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 gastroen­
terologist 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.
PART 19
Consultative Medicine
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 con­
sultations 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 physician-referred 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 cor­
rect, 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 opin­
ion 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 impor­
tant 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 
Increas­
ingly, 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 physician-tophysician referrals has not been studied. Consulting physicians should 
know whether they should respond back to the advanced practice pro­
vider or to the supervising physician, if there is one. As with physicianto-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 and Electronic Health 
Records (EHRs) 
Consultations making use of EHRs, patient 
portals, and various forms of telecommunication technology, includ­
ing 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 access to telemedicine tech­
nologies and willingness and ability to use them among some patient 
populations.
■
■FURTHER READING
Ahmed S et al: Utility, appropriateness, and content of electronic con­
sultations across medical subspecialties. A cohort study. Ann Intern 
Med 172:641, 2020.
Pearson SD: Principles of generalist-specialist relationships. J Gen 
Intern Med 14:S13, 1999.
Sulmasy DH: Policy recommendations to guide the use of telemedi­
cine in primary care: An American College of Physicians Position 
Paper. Ann Intern Med 163:787, 2015.
Sarah Rae Easter, Robert L. Barbieri

Medical Disorders 

During Pregnancy
Each year, ~3.7 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 fertil­
ity treatment have increased the number of people with serious medi­
cal 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. 288) 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 systolic 
≥140 and/or diastolic ≥90 mmHg on two measurements 4 h apart after 
20 weeks’ gestation is abnormal and is associated with an increase in 
perinatal morbidity and mortality. 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). The 
prevalence of hypertensive disorders in pregnancy (HDP) is rising. The 
Centers for Disease Control and Prevention (CDC) estimated that in 
2019, 16% of deliveries in the United States were complicated by a HDP.
■
■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

protein-creatinine 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, includ­
ing severe hypertension (blood pressure ≥160/110 mmHg), new-onset 
symptoms (headache not responsive to medications, visual changes, or 
unremitting severe epigastric pain), pulmonary edema, or laboratory 
abnormalities signifying thrombocytopenia (platelets <100 × 109/L), 
renal insufficiency (creatinine >1.1 mg/dL), or liver impairment (eleva­
tion of transaminases to twice the normal concentration). Eclampsia 
is diagnosed when a pregnant person with preeclampsia develops 
generalized seizures. 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 placen­
tal abruption are additional end-organ complications of preeclampsia.
The precise pathophysiology of preeclampsia remains unknown, but 
chronic uteroplacental ischemia, an exaggerated maternal inflamma­
tory response, and/or imbalance of angiogenic factors likely contribute 
to the clinical syndrome. In preeclampsia, there is excess production of 
an antiangiogenesis factor, soluble fms-like tyrosine kinase 1 (sFlt-1), 
and decreased production of an angiogenic factor, placental growth 
factor (PlGF). A ratio of circulating sFlt-1/PlGF ≥40 is associated with 
an increased risk of developing preeclampsia with severe features in 
the 2 weeks following the measurement. Abnormalities of cerebral 
circulatory autoregulation explain some of the neurologic manifesta­
tions of the disease and can increase the risk of stroke at even modestly 
elevated blood pressures. In the absence of treatment, 1 in 100 cases of 
preeclampsia may progress to eclampsia—new-onset generalized tonicclonic seizures in a patient with preeclampsia. Low-dose aspirin initi­
ated 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 preg­
nancy in the absence of preexisting chronic hypertension or protein­
uria is referred to as gestational hypertension. Gestational hypertension 
with severe features of the disease is best classified as preeclampsia. 
Both gestational hypertension and preeclampsia are associated with 
an increased risk of developing chronic hypertension, cardiovascular 
disease, chronic kidney disease, or diabetes mellitus later in life.
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, but preterm delivery exposes the fetus to 
the risks of prematurity. In preeclampsia without severe features, 
delivery at 37 weeks is recommended. People with preeclampsia 
without severe features may be managed expectantly until 37 weeks 
with close monitoring for development of severe features or labora­
tory abnormalities, frequent 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 sig­
nificant 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 unremit­
ting 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 neo­
natal outcomes. Therefore, concerns about fetal well-being, such 
as severe fetal growth restriction or placental abruption, may also 
prompt delivery before 34 weeks. Timely management of blood 
pressures ≥160/110 mmHg reduces the risk of CVAs. Labetalol and 

hydralazine IV are the first-line agents to manage severe hyperten­
sion in preeclampsia with consideration of oral agents once blood 
pressure is controlled.

Women who have had preeclampsia are at increased risk of 
cardiovascular disease later in life. Interventions to reduce cardio­
vascular risk can be initiated in health encounters following birth.
■
■CHRONIC HYPERTENSION
Pregnant people with chronic hypertension are at increased risk for 
superimposed preeclampsia and placental complications such as fetal 
growth restriction and placental abruption. These complications may 
necessitate preterm birth, which is associated with newborn respira­
tory distress syndrome. People with chronic hypertension should have 
a thorough prepregnancy evaluation to identify remediable causes of 
hypertension and to transition off antihypertensive agents associated 
with adverse outcomes in pregnancy. Angiotensin-converting enzyme 
inhibitors and angiotensin-receptor blockers are contraindicated in 
pregnancy because of an increased risk of stillbirth and congenital 
fetal anomalies. Labetalol and extended-release nifedipine are the most 
commonly used medications for the treatment of chronic hypertension 
in pregnancy. The optimal target blood pressure is <140/90 mmHg, 
which reduces the risk of developing preeclampsia and preterm birth. 
A preconception or early pregnancy assessment for end-organ impacts 
of hypertension, including the presence of proteinuria, may help differ­
entiate the effects of chronic hypertension from those of superimposed 
preeclampsia.
CHAPTER 491
■
■RENAL DISEASE
Normal pregnancy is characterized by a 40% increase in glomerular fil­
tration rate and creatinine clearance secondary to a rise in renal plasma 
flow. Patients with underlying renal disease may expect a worsening 
of existing hypertension or development of preeclampsia during preg­
nancy. A prepregnancy serum creatinine level ≥133 μmol/L (≥1.5 mg/dL) 

and low C4 levels are associated with adverse pregnancy outcomes. 
Certain pathologies, such as those associated with glomerular disease, 
increase the risk of adverse outcomes. Neither hemodialysis nor prior 
renal 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 regard­
ing 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.
Medical Disorders During Pregnancy 
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. 
Patients with pulmonary hypertension (Chap. 294), 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 severe complications are at the highest risk of 
maternal mortality. Pregnancy is contraindicated in these women, with 
termination of pregnancy as an option to reduce maternal risk. Risk 
stratification including a detailed history with attention to symptoms, 
echocardiography, and cardiopulmonary exercise testing guides moni­
toring and management for most patients. Contemporary guidelines 
support continuing most nonteratogenic prepregnancy medications 
and reserving cesarean delivery for obstetric indications with few 
exceptions.
■
■VALVULAR HEART DISEASE
(See also Chaps. 272–279.)
Mitral Stenosis 
The pregnancy-induced increase in blood volume, 
cardiac output, and tachycardia can increase the transmitral pres­
sure gradient and cause pulmonary edema or tachyarrhythmias in

women with mitral stenosis. People 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 percutane­
ous 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 sec­
ondary to rapid volume shifts.

Aortic Stenosis 
People with aortic stenosis, a mean valve gradient 
<25 mmHg, and normal left ventricular function are likely to tolerate 
pregnancy. Symptomatic aortic stenosis or severe aortic stenosis with 
a peak gradient >50 mmHg should be evaluated for correction prior 
to pregnancy.
Mitral and Aortic Regurgitation 
The pregnancy-induced 
decrease in systemic vascular resistance reduces the risk of cardiac fail­
ure with these conditions, especially in those 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 
People 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 popula­
tion and avoided in the first trimester due to its association with fetal 
chondromalacia punctata. 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 
in the second and third trimesters. Bridging from warfarin to heparin 
infusion at 36 weeks’ gestation minimizes bleeding risk and facilitates 
neuraxial analgesia at delivery.
PART 19
Consultative Medicine
■
■CONGENITAL HEART DISEASE
(See also Chap. 280) Reparative surgery has markedly increased the 
number of adults 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. People 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 Eisen­
menger’s syndrome, i.e., the combination of pulmonary hypertension 
with right-to-left shunting due to congenital abnormalities (Chap. 280), 
maternal and fetal deaths occur frequently, informing the recommenda­
tion 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 predis­
pose to aortic dissection, the majority of which occur in people with 
underlying aortopathies (Chap. 291). Although dissection may occur 
in the absence of aortic root enlargement in some genetic syndromes, 
sequential transthoracic echocardiographic (TTE) monitoring during 
pregnancy for evolution of the aortic root diameter is the mainstay of 
monitoring those at risk. Aortic magnetic resonance imaging (MRI) 
without gadolinium is useful to define thoracoabdominal 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 block­
ers are a mainstay of therapy for most patients. A high clinical suspi­
cion for dissection in patients presenting with chest pain is mandatory.
Marfan Syndrome 
(See also Chap. 425) This autosomal domi­
nant 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. 425) Vascular 
EDS (vEDS, type IV) is an autosomal dominant disease associated with 
an increased risk of uterine or vascular rupture that may cause death. 
For people with vEDS, 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. Treat­
ment is generally the same as in the nonpregnant patient, and fetal tol­
erance 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 (PPCM) (Chap. 269) 
This 
uncommon but life-threatening condition should be considered in 
patients presenting in the third trimester or postpartum period with 
unexplained cardiogenic pulmonary edema. Treatment is directed 
toward symptomatic relief and improvement of cardiac function. The 
majority of patients recover completely. The subset of patients with 
left ventricular ejection fraction <30% are at high risk of progressive 
dilated cardiomyopathy. People with a history of PPCM may carry a 
genetic mutation that influences cardiac function. Approximately 10% 
of people with a history of PPCM have a truncating mutation in the 
titin gene encoding the sarcomere protein and experience higher rates 
of ongoing cardiomyopathy. Recurrence in a subsequent pregnancy is 
a risk, with a left ventricular ejection fraction of <50% 12 months post­
partum as the threshold to advise against another pregnancy.
ENDOCRINE AND METABOLIC DISORDERS
The fetoplacental unit induces major metabolic changes to shunt glu­
cose 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 maternal state of accelerated ketosis during maternal 
fasting, characterized by lower 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. 415–417) Pregnancy complicated by pregestational 
diabetes mellitus (pgDM), either type 1 or type 2 diabetes, complicates 
~1% of pregnancies and is associated with increased maternal and peri­
natal morbidity and mortality rates. The prevalence of pgDM is greater 
among patients who are obese compared to normal weight (2.2 vs 
0.5%). The metabolic changes of pregnancy can precipitate hyper­
glycemia requiring increased insulin needs, development of diabetic 
ketoacidosis, or hypoglycemia. Impaired glycemic control during the 
critical first 5–8 weeks of embryonic growth leads to an increased risk 
of spontaneous abortion and congenital malformations and highlights 
the importance of prepregnancy glycemic control. pgDM increases the 
risk of stillbirth, preeclampsia, and large for gestational age infants. 
Macrosomia increases the risk of shoulder dystocia and birth trauma, 
including brachial plexus injury and obstetric lacerations. Neonates 
are at risk of hypoglycemia, hyperbilirubinemia, polycythemia, and 
respiratory distress. An assessment of end-organ complications of 
pgDM including nephropathy, retinopathy, and neuropathy is essential 
to understanding the patient’s risk profile.
■
■GESTATIONAL DIABETES
Gestational diabetes mellitus (GDM) occurs in ~8% of pregnancies, and 
screening for GDM is a routine part of prenatal care, recommended by 
the U.S. Preventive Services Task Force with a B recommendation. The 
typical two-step strategy to diagnose GDM is performed at 24–28 weeks of

gestation and involves the initial 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 indi­
cate a positive GTT diagnostic of GDM. GDM increases the risks of 
maternal and neonatal complications similar to those seen with preges­
tational diabetes. Treating GDM reduces the risk of preeclampsia, birth 
weight >4000 g, and shoulder dystocia.
TREATMENT
Diabetes Mellitus in Pregnancy
Preconception counseling to optimize glycemic control and assess for 
end-organ complications of pgDM is a cost-effective and evidencebased intervention. Guidelines encourage people with pgDM con­
sidering pregnancy to initiate insulin prior to pregnancy, targeting 
a preconception hemoglobin A1c <6% to reduce the risk of fetal 
congenital malformation. Insulin is the preferred medical therapy 
for pgDM in pregnancy due to its safety profile and lower rates of 
treatment failure compared to oral hypoglycemic medications.
Once pregnancy is established, glucose control should be man­
aged more intensively than in the nonpregnant state with assess­
ment 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 diabetes. 
Sequential measurement of hemoglobin A1c is of minimal util­
ity 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 preg­
nancy progresses due to an increase in insulin resistance. Atten­
tion to glycemic control and frequent fetal surveillance including 
ultrasounds are mainstays of management in the third trimester. 
Ultrasound identification of a large for gestational age fetus or poly­
hydramnios on antenatal ultrasound can be indicators of subopti­
mal 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 pgDM have higher rates of preterm birth, although preterm 
delivery is generally reserved for poor glycemic control, worsening 
maternal renal disease, or active proliferative retinopathy in addi­
tion 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.
TREATMENT
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 pre­
eclampsia 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 diabetes later in life, with a 10% risk within 5 years of deliv­
ery. All people with GDM should have a 2-h 75-g GTT to screen 
for diabetes or impaired glucose tolerance 4–12 weeks following 
birth. The increased long-term risks of diabetes and cardiovascular 
disease and the need for regular follow-up with a primary care 
provider should be emphasized for all people with GDM. Following 
birth, exercise, weight loss, and treatment with metformin reduce 
the risk of developing diabetes in these at-risk patients.
■
■OBESITY
(See also Chap. 414) Pregnant people who are obese have an increased 
risk for GDM, preeclampsia, cesarean delivery, congenital malforma­
tions, stillbirth, and neonatal death. A growing body of literature sug­
gests the in utero effects of excess adipose tissue may cause changes in 
fetal metabolic programming that lead to adverse health outcomes in 
adult life. People contemplating pregnancy should attempt to attain a 
healthy weight prior to conception, recognizing that even a 10% reduc­
tion in weight may significantly reduce many of these risks. Those 
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 labo­
ratory 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 diabetes.
CHAPTER 491
Medical Disorders During Pregnancy 
■
■THYROID DISEASE
(See also Chap. 394) 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, especially 
in the first trimester. Interpretation of the measurement of free T4, free 
T3, and thyroid-stimulating hormone (TSH) should use trimester-specific 
ranges. People with a history of Graves’ disease have an increased risk 
of fetal goiter and neonatal Graves’ disease independent of treatment 
status due to the transplacental passage of thyroid-stimulating antibod­
ies and stimulation of the fetal thyroid.
TREATMENT
Hyperthyroidism
Options for the treatment of symptomatic hyperthyroidism in 
pregnancy include beta blockers, propylthiouracil, and methima­
zole. Methimazole crosses the placenta to a greater degree than 
propylthiouracil and has been associated with fetal aplasia cutis. 
Propylthiouracil can be associated with maternal liver failure. Some 
experts recommend propylthiouracil in the first trimester and the 
option of continuing propylthiouracil or switching to methimazole 
thereafter. Radioiodine should not be used during pregnancy, either 
for scanning or for treatment, because of effects on the fetal thyroid.
TREATMENT
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 
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. Red 
blood cell mass increases in pregnancy but to a lesser degree than 
plasma volume. This differential increase results in a lower hemoglobin 
concentration and so-called dilutional anemia. However, iron, folate, 
and vitamin B12 deficiencies are common causes of correctable ane­
mia during pregnancy. Transfer of iron to the fetal compartment may 
explain why iron deficiency anemia is detected in ~11% of pregnant 
people in the third trimester. Screening for anemia is recommended in 
the first trimester and at 24 to 28 weeks’ gestation. Measurement of fer­
ritin can help detect iron deficiency before anemia is diagnosed. Iron 
replacement therapy is recommended in pregnancy.
Hemoglobinopathy screening is recommended for all pregnant 
women with testing of mean corpuscular volume, mean corpuscular 
hemoglobin, ferritin, and hemoglobin analysis (Chap. 103). Hemo­
globinopathies 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.
PART 19
Consultative Medicine
Thrombocytopenia occurs in 5–10% of pregnancies. The major­
ity of cases are benign gestational thrombocytopenias, but the 
differential diagnosis should include immune thrombocytopenia 
(Chap. 120), preeclampsia, and thrombotic thrombocytopenic pur­
pura. Benign gestational thrombocytopenia is unlikely if the platelet 
count is <100,000/μL.
■
■DEEP VENOUS THROMBOSIS AND 

PULMONARY EMBOLISM
(See also Chap. 290) Pregnancy is associated with venous stasis, 
endothelial injury, and a hypercoagulable state. During pregnancy, 
circulating coagulation factors II, VII, VIII, IX, X, and XII, fibrinogen, 
and von Willebrand factor increase, and protein S and antithrombin III 
decrease. Inherited thrombophilias and the presence of antiphospho­
lipid 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. In 
general, all diagnostic and therapeutic modalities afforded to the non­
pregnant patient should be utilized in pregnancy.
TREATMENT
Venous Thromboembolism
Aggressive diagnosis and management of suspected DVT or PE 
optimize outcomes for both patient and fetus. Anticoagulant ther­
apy with low-molecular-weight heparin (LMWH) or unfractionated 
heparin is indicated in pregnant people with VTE. Anticoagulants 
increase the risk of epidural hematoma in the setting of neuraxial 
analgesia (e.g., epidural or spinal anesthesia) in labor and must be 
withheld prior to placement. To ensure patient access to neuraxial 
analgesia in labor, prophylactic LMWH can be stopped 12 h before 
placement of an epidural catheter, whereas therapeutic LMWH can 
be discontinued for a full 24 h. Transition to unfractionated heparin 
as delivery approaches can shorten the time between anticoagulant 
administration and epidural placement. Unfractionated heparin 
can be used with an epidural catheter in place in those at highest 
risk of worsening thromboembolic disease.

■
■NEOPLASIA
Cancer complicates ~1 in 1400 pregnancies. The four cancers that 
occur most commonly in pregnancy are cervical cancer, breast cancer, 
melanoma, and lymphoma. Also, cancer rates in pregnancy vary across 
the globe depending on local medical practices and exposures. In addi­
tion to cancers developing in other organs, 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. People with a history 
of active or treated hormonally responsive breast cancer who choose to 
pursue pregnancy have similar rates of cancer-related events as those 
who do not. Spread of the cancer to the fetus (so-called vertical trans­
mission) is exceedingly rare. However, managing cancer in a pregnant 
people 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 situa­
tion 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 therapeutic doses of ionizing 
radiation may cause adverse effects and is generally avoided during 
pregnancy.
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 adminis­
tered in the second and third trimesters, without a high frequency 
of toxic effects to the pregnancy or the fetus. Whether the asso­
ciation 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 treat­
ment until after delivery to avoid fetal exposure to chemotherapy 
may be desirable. If delaying therapy may compromise maternal 
prognosis, then treatment might be initiated after the first trimester 
of pregnancy with plans to deliver the fetus preterm to avoid excess 
cumulative 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, safety of the proposed treatment, and the 
person’s goals of care.
NEUROLOGIC DISORDERS
Neurologic complaints such as headaches or neuropathies are common 
in pregnancy, and differentiating bothersome symptoms from lifethreatening pathology is challenging (Chap. 437). While most com­
plaints are benign, cerebrovascular accidents (CVAs) should be high on 
the differential diagnosis and evaluated with MRI without gadolinium 
or a head computed tomography (CT) in cases of suspected stroke. 
Noncontrast MRI is more sensitive than CT in identifying early and 
small infarcts and cerebral venous thrombosis.
Exclusion of preeclampsia is important for any patient present­
ing 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 or the postpartum period with neurologic 
complaints. Peripheral nerve disorders associated with pregnancy include

Bell’s palsy (idiopathic facial paralysis) (Chap. 452), carpal tunnel syn­
drome (median nerve entrapment), or meralgia paresthetica (lateral 
femoral cutaneous nerve entrapment). Restless leg syndrome (RLS) is 
the most common peripheral nerve and movement disorder in preg­
nancy, affecting up to 20% of patients. If serum ferritin is low, oral iron 
supplementation is a first-line treatment option.
Pregnancy is safe for most people with neurologic disorders, with 
management considerations focusing on medication safety, the impact 
of pregnancy on the disease, and potential neonatal consequences. For 
those with epilepsy planning pregnancy, lamotrigine and levetiracetam 
are first-line monotherapies due to the abundance of safety data. Val­
proate is known to be associated with congenital malformations and 
should be discontinued in favor of another medication for people plan­
ning to conceive. Folic acid supplementation of 4 mg daily is recom­
mended for those taking antiepileptic drugs (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. 455) experience 
a gradual decrease in the risk of relapses as pregnancy progresses and, 
conversely, an increase in attack risk during the postpartum period. 
Prior to conception, disease-modifying therapies (DMTs) should 
be used to gain control of the disease. DMTs are typically withheld 
in pregnancy due to the decreased risk of relapse alongside limited 
neonatal safety data. Relapses should be treated with glucocorticoids, 
which may be given prophylactically after birth to reduce the risk of 
postpartum relapse. Finally, certain tumors, particularly pituitary ade­
noma (Chap. 392) and meningioma, 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 central nervous system (CNS) tumors to facilitate neuraxial 
analgesia.
GASTROINTESTINAL AND LIVER DISEASE
Up to 90% of pregnant people experience nausea and vomiting dur­
ing the first trimester of pregnancy. Hyperemesis gravidarum (HG) is 
a severe form that prevents adequate fluid and nutritional intake and 
may require hospitalization to prevent dehydration and malnutrition. 
GDF15, which is produced by the placenta and is known to suppress 
appetite, may be involved in the pathogenesis of HG. Thiamine and 
folate supplementation and monitoring of electrolytes for evidence of 
refeeding syndrome should be considered in severe cases with evalua­
tion for supplemental enteral nutrition in refractory disease.
Exacerbation of inflammatory bowel disease is common, and medi­
cal management, including the use of anti–tumor necrosis factor 
agents, parallels the nonpregnant state (Chap. 337). 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 cho­
lestasis of pregnancy is generally a third-trimester event presenting with 
profound pruritus 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 before term. 
Symptoms can be improved with the use of ursodiol.
Acute fatty liver is a rare complication of pregnancy on the spec­
trum 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. Most people recover within 7–10 days after delivery, 
but reports of fulminant liver failure requiring transplant under­
score the importance of prompt diagnosis and management. The 
association between acute fatty liver in pregnancy and long-chain 
3-hydroxyacyl CoA dehydrogenase (LCHAD) deficiency in the fetus 
inform the recommendation for close monitoring in the newborn 
with consideration of genetic testing.
All pregnant people should be screened for hepatitis B virus with 
HBsAg testing and hepatitis C virus (Chap. 350). 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 the risk of vertical transmission. Strategies 
to decrease vertical transmission of hepatitis C are limited to avoid­
ing 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. 161, 187, and 194). 
Other than bacterial vaginosis, the most common bacterial infections 
during pregnancy involve the urinary tract (Chap. 140). All pregnant 
people should be screened with a urine culture for asymptomatic 
bacteriuria at the first prenatal visit. Pregnancy is an indication for treat­
ment of asymptomatic bacteriuria to avoid pyelonephritis. Progesteronemediated 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 pyelone­
phritis 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 people 
with recurrent urinary tract infections or one episode of pyelonephri­
tis should receive daily antibiotic suppressive treatment throughout 
the remainder of their pregnancy. Options for suppressive treatment 
include nitrofurantoin (50 or 100 mg at bedtime) or cephalexin (250 
or 500 mg at bedtime).
CHAPTER 491
Medical Disorders During Pregnancy 
■
■VIRAL INFECTIONS
All pregnant people should be screened for hepatitis B virus, hepa­
titis C virus, and HIV as well as immunity to rubella and varicella. 
Screening for varicella immunity begins with obtaining a history of 
varicella immunization or infection. Testing for antibodies to varicella 
is reserved for cases where there is no history of prior immunization or 
infection, because the available varicella antibody test has low sensitiv­
ity and does not reliably detect antibodies in people who have been 
immunized.
Influenza 
(See also Chap. 206) Pregnant people with influenza are 
at increased risk of serious complications and death. All people 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 people 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.
COVID-19  
Pregnancy is a risk factor for severe COVID-19 infec­
tion. All unvaccinated people planning pregnancy or who are pregnant 
should receive a COVID-19 vaccine.
Cytomegalovirus Infection 
The most common cause of con­
genital viral infection in the United States is cytomegalovirus (CMV) 
(Chap. 200). 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. CNS 
involvement can result in the development of psychomotor, ocular, 
auditory, and dental abnormalities over time. People with a primary 
CMV infection should delay conception for 6 months.
Herpesvirus Infection 
(See also Chap. 197) The acquisition 
of genital herpes during pregnancy is associated with spontaneous

abortion, prematurity, and congenital and neonatal herpes. Dissemi­
nated neonatal herpes carries with it high mortality and morbidity 
rates from CNS involvement. A cohort study of pregnant people with­
out 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 (400 mg three times daily) for the last 4 weeks of 
pregnancy to all people who had an episode of genital herpes during 
the pregnancy. Those with active genital herpes lesions at the time of 
presentation in labor should be delivered by cesarean section.

Rubella 
(See also Chap. 212) Rubella virus is a known terato­
gen; first-trimester rubella carries a high risk of fetal malformations, 
although the risk significantly decreases later in pregnancy. Congenital 
rubella infection may be diagnosed by percutaneous umbilical-blood 
sampling with the detection of IgM antibodies in fetal blood. All preg­
nant people or those considering pregnancy should be tested for their 
immune status to rubella.
Parvovirus Infection 
(See also Chap. 202) Infection with human 
parvovirus B19 may occur during pregnancy with the possibility of 
fetal transmission in the absence of immunity. It rarely causes sig­
nificant maternal sequelae but can lead to erythroid aplasia in the fetus 
with resultant anemia, fetal hydrops, and death. Management includes 
screening for fetal anemia with Doppler assessment of the middle cere­
bral artery and consideration of intrauterine transfusion of red blood 
cells to the fetus to avoid the physiologic consequences of anemia while 
awaiting recovery of the fetal bone marrow.
PART 19
Consultative Medicine
HIV Infection 
(See also Chap. 208) 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-tonewborn 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 those receiving ante­
partum ART, viral load guides the decision for vaginal versus cesarean 
delivery and need for adjunct intrapartum zidovudine. People with 
an undetectable viral load are at the lowest risk of transmission and 
require no additional therapy, whereas 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 indi­
cations for women with ≥50 but ≤1000 copies/mL, and intrapartum 
zidovudine can be considered.
Zika Virus 
Zika virus (ZIKV) can be transmitted from mother to 
fetus throughout gestation and often results in severe microcephaly, 
CNS malformations, and fetal death. Symptomatic pregnant people 
with relevant epidemiologic exposure within 2 weeks of symptom 
onset should have serum and urine tested for ZIKV and dengue nucleic 
acids by nucleic acid amplification test and IgM serology. 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 ZIKV.
■
■VACCINATIONS
(See also Chap. 129) For rubella-nonimmune individuals contemplat­
ing pregnancy, measles-mumps-rubella vaccine should be adminis­
tered, ideally at least 3 months prior to conception, but otherwise in 
the immediate postpartum period. All pregnant people should be vac­
cinated against influenza and COVID-19. 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 pro­
duction 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 rate is the number of maternal deaths per 
100,000 live births. From 1935 to 2007, the U.S. maternal mortality rate 
decreased from nearly 600/100,000 births to 12.7/100,000 births, rising 
thereafter. In 2021, the U.S. maternal mortality rate was 32.9/100,000 
births. An increasingly complex patient population, with multiple 
comorbidities, and the COVID-19 pandemic likely contributed to the 
high rate of maternal death in 2021. There are significant racial and 
ethnic disparities in the maternal mortality rate, with a nearly fourfold 
increased risk of death for non-Hispanic black women compared to 
non-Hispanic white women (69.9 vs 26.6 deaths per 100,000 live births, 
respectively) (Chap. 11). Women over 40 years of age had a maternal 
mortality rate of 139 per 100,000 live births.
Pregnancy-related death is defined as the death of a person while 
pregnant or within 1 year of the end of pregnancy from any cause 
related to or aggravated by pregnancy. Cardiovascular disease, includ­
ing 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 rate 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 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 people will be best attained by a multidisciplinary team of 
internists, maternal-fetal medicine (high-risk obstetrics) specialists, 
pediatricians, and anesthesiologists assembled to counsel these patients 
about the risks of pregnancy and to optimize interconception care. The 
importance of preconception counseling and the impact of events of 
pregnancy on lifelong disease cannot be overstated. It is the responsi­
bility of all physicians caring for women in the reproductive age group 
to assess their patients’ reproductive plans as part of their overall health 
evaluation and to integrate pregnancy-related diagnoses into their 
assessment of future risk for cardiovascular disease.
■
■FURTHER READING
Crisafulli F et al: Variations of C3 and C4 before and during preg­
nancy in systemic lupus erythematosus: Association with disease 
flares and obstetric outcomes. J Rheumatol 50:1296, 2023.
Ford ND et al: Hypertensive disorders in pregnancy and mortality 
at delivery hospitalization-United States, 2017-2019. Morb Mortal 
Week Report 71:585, 2022.
Fu J et al: Increased risk of major congenital malformations in early 
pregnancy uses of angiotensin-converting enzyme inhibitors or 
angiotensin receptor blockers: A meta-analysis. Diabetes Metab Res 
Rev 37:e3453, 2021.
Hoyert DL: Maternal mortality rates in the United States, 2021. NCHS 
Health E-Stats. 2023. DOI: https://dx.doi.org/10.15620/cdc:124678.

# 03 - 492 Medical Evaluation of the Patient Undergoing Noncardiac Surgery

## 492 Medical Evaluation of the Patient Undergoing Noncardiac Surgery

Parikh NI et al: Adverse pregnancy outcomes and cardiovascular dis­
ease risk: Unique opportunities for cardiovascular disease prevention 
in women: A scientific statement from the American Heart Associa­
tion. Circulation 143:e902, 2021.
Regitz-Zagrosek V et al: 2018 ESC guidelines for the management of 
cardiovascular diseases during pregnancy. Eur Heart J 39:3165, 2018.
Tita AT et al: Treatment for mild chronic hypertension during preg­
nancy. N Engl J Med 386:1781, 2022.
Verlohren S et al: Clinical interpretation and implementation of the 
sFlt-1/PlGF ratio in prediction, diagnosis and management of pre­
eclampsia. Pregnancy Hypertens 27:42, 2022.
Prashant Vaishnava, David I. Sahar, Kim A. Eagle

Medical Evaluation of 

the Patient Undergoing 
Noncardiac Surgery
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 prophy­
laxis 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 492-1, 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 sur­
gery should always begin with a thorough history and physical exami­
nation 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 
morbidity and mortality risk. Preoperative laboratory testing should be 
carried out only for specific clinical conditions, as noted during clini­
cal 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. 492-1. 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 endo­
scopic procedures, and select superficial procedures. Patients under­
going these low-risk procedures should proceed to surgery without 

TABLE 492-1  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 
CHAPTER 492
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:
Medical Evaluation of the Patient Undergoing Noncardiac Surgery 
aUniversity 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.
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). Additional tools 
include the Surgical Outcome Risk Tool (SORT) or the American 
University of Beirut (AUB)-HAS2 Cardiovascular Risk Index. The 
former is based, in part, on the American Society of Anesthesiologists 
Physical Status (ASA-PS) grade; the latter provides for estimation of 
30-day death, myocardial infarction (MI), or stroke risk.
Previous studies have compared several cardiac risk indices. The 
American College of Surgeons’ NSQIP prospective database has 
identified five predictors of perioperative MI and cardiac arrest based 
on increasing age, American Society of Anesthesiologists class, type 
of surgery, dependent functional status, and abnormal serum cre­
atinine level. However, given its accuracy and simplicity, the RCRI 
(Table 492-2) 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, cerebrovas­
cular disease, diabetes mellitus treated with insulin, and renal insuf­
ficiency 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 pres­
ence of none, one, two, three, or more of these clinical predictors, the 
rate of development of one of these four major cardiac events is esti­
mated to be 0.4%, 0.9%, 7%, and 11%, respectively (Fig. 492-2). 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 manage­
ment, or avoidance of surgery.
For patients at elevated combined clinical and surgical risk for 
MACE, the stepwise perioperative cardiac assessment for coronary

Patient
Needs emergency
noncardiac
surgery
Needs elective
noncardiac
surgery
Exhibits evidence
of acute coronary
syndrome
Perioperative risk
for MACE* <1%
Perioperative risk
for MACE* >1%
PART 19
Consultative Medicine
Consider
noninvasive
testing if results
would change
management
Proceed
to surgery
Proceed to ACS
evaluation
Proceed
to surgery
Proceed
to surgery
Proceed
to surgery
PERIOPERATIVE MEDICAL INTERVENTION WHEN CONSIDERING NONCARDIAC SURGERY
Beta-blockers
Statin
Alpha agonist
• 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
Initiation not 
recommended prior
to noncardiac surgery
FIGURE 492-1  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 according 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. ACE, angiotensin-converting enzyme; ACS, acute 
coronary syndrome; MACE, major adverse cardiovascular event. (Reproduced with permission from AY Patel et al: Cardiac risk of noncardiac surgery. J Am Coll Cardiol 
66:2140, 2015.)
artery disease (CAD) proceeds with consideration of functional 
capacity. Participation in activities of daily living offers an expres­
sion 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 492-3). 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 pharmacologic stress 

* 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
No evidence of
ongoing ACS
Functional
capacity:
Unknown
Functional
capacity:
Excellent
Functional
capacity:
Moderate – Good
Functional
capacity:
Poor
Consider
noninvasive
testing if results
would change
management
ACE inhibitor
Aspirin
Continued, or if held
before surgery, restart
postoperatively as soon
as clinically feasible
Continued when the risk
of increased cardiac
events outweights the
risk of increased bleeding
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 preopera­
tive noninvasive cardiac testing for all patients undergoing major sur­
gery. The current paradigm to guide the need for noninvasive cardiac 
testing is to perform such testing in patients with poor or unknown 
capacity if it would alter clinical management or modify perioperative 
care. Options for pharmacologic stress testing include dobutamine 
stress echocardiography or myocardial perfusion imaging with coro­
nary vasodilator stress (dipyridamole, adenosine, or regadenoson) 
with thallium-201 and/or technetium-99m. Similarly, there is a limited

TABLE 492-2  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.
role for perioperative coronary computed tomography angiography 
(CCTA) in patients undergoing noncardiac surgery. While some inves­
tigators have shown in observational studies that CCTA may improve 
prediction of MACEs perioperatively when compared to RCRI, there 
are few data to demonstrate that such improved prognostication trans­
lates to improved outcomes. 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 
RCRI 
 

≥3
Event Rate 
0.50% 
1.30% 
6.00% 
11%
Std Dev  
0.45% 
1.10% 
5.30% 
10.00%
15%
Risk stratification
Risk of cardiac events
10%
4–7
5%
0.9–1.3
0.4–0.5
0%
Low risk
Intermediate risk
High risk

≥3
Revised Cardiac Risk Index (RCRI)
FIGURE 492-2  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 492-3  Assessment of Cardiac Risk by Functional Status
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
Risk
Lower
• Performs regular vigorous exercises
Abbreviation: MET, metabolic equivalent.
Source: From LA Fleisher et al: Circulation 116:1971, 2007.
be indicated regardless of the surgery planned and instead according to 
clinical practice guidelines. In the Coronary Artery Revascularization 
Prophylaxis trial, there were no differences in perioperative and longterm cardiac outcomes with or without preoperative coronary revascu­
larization; of note, patients with left main disease were excluded.
■
■RISK MODIFICATION: PREVENTIVE STRATEGIES 
TO REDUCE CARDIAC RISK
Perioperative Coronary Revascularization 
Prophylactic coro­
nary 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 coro­
nary 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 
(Chap. 287). It is recommended that, if possible, elective noncardiac 
surgery be delayed for 6 months after elective PCI and 12 months 
after acute coronary syndrome. Contemporary stent platforms allow 
for greater flexibility in the earlier interruption of DAPT; accordingly, 
time sensitive noncardiac surgery could be a consideration as soon as 
1 month of treatment with DAPT has passed. For patients who must 
undergo noncardiac surgery early (>14 days) after PCI, balloon angio­
plasty without stent placement appears to be a reasonable alternative 
because DAPT is not necessary in such patients.
CHAPTER 492
Medical Evaluation of the Patient Undergoing Noncardiac Surgery 
PERIOPERATIVE PREVENTIVE MEDICAL THERAPIES  The goal of peri­
operative 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 inflam­
mation, all of which are heightened during the perioperative 
period.
a-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, 
first, to the publication of the PeriOperative Ischemic Evalu­
ation (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 scrutinized 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 sur­
gery. Second, research misconduct has discredited the Dutch 
Echocardiographic Cardiac Risk Evaluation Applying Stress 
Echocardiography (DECREASE) family of studies, which pre­
viously contributed to the bedrock of data supporting the use 
of perioperative beta blockade but have now been retracted.
9–11

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 prospec­
tive and retrospective studies support the perioperative prophylactic 
use of statins for reduction of cardiac complications in patients with 
established atherosclerosis. For patients undergoing noncardiac sur­
gery 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. There is equipoise about the perioperative initiation of 
statin therapy in patients undergoing other elevated-risk procedures. In 
the Lowering the Risk of Operative Complications Using Atorvastatin 
Loading Dose (LOAD) randomized, placebo-controlled trial, the use 
of 80 mg of atorvastatin within 18 h before surgery and then followed 
by 40 mg daily for 7 days in statin-naïve patients (24% of whom had 
a history of cardiovascular disease) did not reduce the risk of major 
adverse events.
PART 19
Consultative Medicine
ANGIOTENSIN-CONVERTING ENZYME (ACE) INHIBITORS  It is impor­
tant to maintain continuity of therapy with inhibitors of the reninangiotensin-aldosterone system (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, noncardiac surgery should be avoided 
in this vulnerable period. The duration of DAPT thereafter is dictated 
by the circumstances in which PCI was performed and whether the 
indication was stable ischemic heart disease or acute coronary syn­
drome. For the former among patients treated with a drug-eluting 
stent (DES), DAPT should be given for at least 6 months. For the latter, 
DAPT should be given for at least 12 months. However, DAPT may be 
interrupted to allow for noncardiac surgery 30 days after bare metal 
stent (BMS) and 6 months after DES, respectively. Elective, noncardiac 
surgery should be delayed for 5 days since the last dose of clopidogrel; 
7 days since the last dose of prasugrel; and 3–5 days since the last dose 
of ticagrelor. The use of cangrelor, an intravenous reversible P2Y12 
receptor antagonist, may be an appealing bridging strategy, although 
studies of its use in those undergoing cardiac and noncardiac sur­
gery are limited. If P2Y12 inhibitor therapy (clopidogrel, prasugrel, or 
ticagrelor) is interrupted or discontinued in patients who have received 
intracoronary stents, aspirin should be continued perioperatively (save 
select circumstances where the risk of bleeding may be catastrophic as 
in neurosurgical or spinal procedures) and the P2Y12 receptor inhibitor 
should be restarted as soon as possible postoperatively. Decisions sur­
rounding antiplatelet management in the perioperative setting among 
patients who have received intracoronary stents are complex and 
should involve multidisciplinary decision-making.
`2 AGONISTS  Based on the results of POISE-2 (a large multicenter, 
international, blinded randomized clinical trial of aspirin and clonidine), 
α2 agonists for prevention of cardiac events are not recommended in 
patients who are undergoing noncardiac surgery. In this trial, clonidine 
increased the rate of nonfatal cardiac arrest and clinically important 
hypotension, while reducing the rate of death or nonfatal MI.
CALCIUM CHANNEL BLOCKERS  Evidence is lacking to support the 
use of calcium channel blockers as a prophylactic strategy to decrease 
perioperative risk in major noncardiac surgery.
SODIUM-GLUCOSE COTRANSPORTER 2 INHIBITORS  The use of 
sodium-glucose cotransporter 2 (SGLT-2) inhibitors has grown in 

TABLE 492-4  Gradation of Mortality Risk of Common Noncardiac 
Surgical Procedures
Higher
• Emergent major operations, especially in the elderly
• Aortic and other noncarotid major vascular surgery 
(endovascular and nonendovascular)
• Prolonged surgery associated with large fluid shift and/or 
blood loss
Intermediate
• Major thoracic surgery
• Major abdominal surgery
• Carotid endarterectomy surgery
• Head/neck surgery
• Orthopedic surgery
• Prostate surgery
Lower
• Eye, skin, and superficial surgery
• Endoscopic procedures
Source: Reproduced with permission from LA Fleisher et al: ACC/AHA 2007 
Guidelines on perioperative cardiovascular evaluation and care for noncardiac 
surgery. Circulation 116:1971, 2007.
recent years owing to their beneficial impact in patients with and with­
out type 2 diabetes mellitus and with heart failure with either reduced 
or preserved ejection fraction. However, euglycemic diabetic ketoaci­
dosis is a known, but rare, complication with this therapy and one that 
may be precipitated by changes and fasting in the perioperative state. 
Accordingly, SGLT-2 inhibitor therapy should be interrupted for at 
least 3–4 days prior to scheduled noncardiac surgery.
ANESTHETICS  Mortality risk is low with safe delivery of modern 
anesthesia, especially among low-risk patients undergoing low-risk 
surgery (Table 492-4). Inhaled anesthetics have predictable circula­
tory and respiratory effects: all decrease arterial pressure in a dosedependent manner by reducing sympathetic tone and causing systemic 
vasodilation, myocardial depression, and decreased cardiac output. 
Inhaled anesthetics also cause respiratory depression, with diminished 
responses to both hypercapnia and hypoxemia, in a dose-dependent 
manner; in addition, these agents have a variable effect on heart rate. 
Prolonged residual neuromuscular blockade also increases the risk of 
postoperative pulmonary complications due to reduction in functional 
residual lung capacity, loss of diaphragmatic and intercostal muscle 
function, atelectasis, and arterial hypoxemia from ventilation–perfusion 
mismatch.
Several meta-analyses have shown that rates of pneumonia and 
respiratory failure are lower among patients receiving neuroaxial 
anesthesia (epidural or spinal) rather than general anesthesia. However, 
there were no significant differences in cardiac events between the two 
approaches. Evidence from a meta-analysis of randomized controlled 
trials supports postoperative epidural analgesia for >24 h for the 
purpose of pain relief. However, the risk of epidural hematoma in the 
setting of systemic anticoagulation for venous thromboembolism pro­
phylaxis (see below) and postoperative epidural catheterization must 
be considered.
PREOPERATIVE PULMONARY RISK 
ASSESSMENT
Perioperative pulmonary complications occur frequently and lead 
to significant morbidity and mortality. Clinical practice guidelines 
recommend the following:
1.	 All patients undergoing noncardiac surgery should be assessed for 
risk of pulmonary complications (Table 492-5).
2.	 While select studies have suggested that quitting smoking shortly 
before surgery increases the risk for postoperative complications 
through increased sputum production and/or decreased cough, 
meta-analysis of the available data has challenged this, and all patients 
should be advised of the imperative to stop smoking presurgically.
3.	 Patients undergoing emergency or prolonged (3–4 h) surgery; aor­
tic aneurysm repair; vascular surgery; major abdominal, thoracic, 
neurologic, head, or neck surgery; and general anesthesia should

TABLE 492-5  Predisposing Risk Factors for Pulmonary Complications
1. Upper respiratory tract infection: cough, dyspnea
2. Age >60 years
3. Chronic obstructive pulmonary disease
4. Cigarette use
5. American Society of Anesthesiologists Class ≥2
6. Functional dependence
7. Congestive heart failure
8. Serum albumin <3.5 g/dL
9. Obstructive sleep apnea
10. Impaired sensorium (confusion, delirium, or mental status changes)
11. Abnormal findings on chest examination
12. Alcohol use
13. Weight loss
14. Spirometry threshold before lung resection
a. FEV1 <2 L
b. MVV <50% of predicted
c. PEF <100 L or 50% predicted value
d. PCO2 ≥45 mmHg
e. PO2 ≤50 mmHg
Abbreviations: FEV1, forced expiratory volume in 1 s; MVV, maximal voluntary 
ventilation; PCO2, partial pressure of carbon dioxide; PEF, peak expiratory flow rate; 
PO2, partial pressure of oxygen.
Source: A Qaseem et al: Ann Intern Med 144:575, 2006. Modified from GW Smetana 
et al: Ann Intern Med 144:581, 2006, and from DN Mohr et al: Postgrad Med 100:247, 
1996.
be considered to be at elevated risk for postoperative pulmonary 
complications.
4.	 Patients at higher risk of pulmonary complications should undergo 
incentive spirometry, deep breathing exercises, cough encourage­
ment, postural drainage, percussion and vibration, suctioning and 
ambulation, intermittent positive-pressure breathing, continuous 
positive airway pressure, and selective use of a nasogastric tube for 
postoperative nausea, vomiting, or symptomatic abdominal disten­
tion to reduce postoperative risk. Multiple pulmonary risk indices 
are available to estimate the postoperative risk of respiratory failure, 
pneumonia, and other pulmonary complications; among these is 
the ARISCAT risk index, which accounts for the following seven 
risk factors: age, low preoperative oxygen saturation, respiratory 
infection within the preceding month, upper abdominal or thoracic 
surgery, surgery lasting >2 h, hemoglobin <10 g/dL, and emergency 
surgery (Table 492-6).
5.	 Preoperative spirometry and chest radiography should not be used 
routinely for predicting risk of postoperative pulmonary complica­
tions but may be appropriate for patients with chronic obstructive 
pulmonary disease or asthma.
6.	 Spirometry is of value before lung resection in determining candi­
dacy for coronary artery bypass; however, it does not provide a spi­
rometric threshold for extrathoracic surgery below which the risks 
of surgery are unacceptable.
7.	 Pulmonary artery catheterization, administration of total parenteral 
nutrition (as opposed to no supplementation), or total enteral nutri­
tion has no consistent benefit in reducing postoperative pulmonary 
complications.
PERIOPERATIVE MANAGEMENT AND 
PROPHYLAXIS
■
■DIABETES MELLITUS
(See also Chaps. 415-417) Many patients with diabetes mellitus 
have significant symptomatic or asymptomatic CAD and may have 
silent myocardial ischemia due to autonomic dysfunction. Intensive 
(vs lenient) glycemic control in the perioperative period is generally 
not associated with improved outcomes and may increase the risk 
of hypoglycemia. Practice guidelines advocate a target glucose range 
of 100–180 mg/dL in the perioperative period. Oral hypoglycemic 

TABLE 492-6  Risk Modification to Reduce Perioperative Pulmonary 
Complications
Preoperatively
• Smoking cessation
• Training in proper lung expansion techniques
• Inhalation bronchodilator and/or steroid therapy, when indicated
• Control of infection and secretion, when indicated
• Weight reduction, when appropriate
Intraoperatively
• Limited duration of anesthesia
• Avoidance of long-acting neuromuscular blocking drugs, when indicated
• Prevention of aspiration and maintenance of optimal bronchodilation
Postoperatively
• Optimization of inspiratory capacity maneuvers, with attention to:
• Mobilization of secretions
• Early ambulation
• Encouragement of coughing
• Selective use of a nasogastric tube
• Adequate pain control without excessive narcotics
CHAPTER 492
Source: From VA Lawrence et al: Ann Intern Med 144:596, 2006, and WF Dunn, PD 
Scanlon: Mayo Clin Proc 68:371, 1993.
agonists should not be given on the morning of surgery. Periopera­
tive hyperglycemia should be treated with IV infusion of short-acting 
insulin or subcutaneous sliding-scale insulin. Patients whose diabetes 
is diet controlled may proceed to surgery with close postoperative 
monitoring.
Medical Evaluation of the Patient Undergoing Noncardiac Surgery 
■
■INFECTIVE ENDOCARDITIS
(See also Chap. 133) Prophylactic antibiotics should be administered 
to the following patients before dental procedures that involve manipu­
lation of gingival tissue, manipulation of the periapical region of teeth, 
or perforation of the oral mucosa: those with prosthetic cardiac valves 
(including transcatheter prosthetic valves); prosthetic material used in 
valve repair (annuloplasty ring or artificial chord); previous infective 
endocarditis; cardiac transplant recipients with valvular regurgitation 
from a structurally abnormal valve; and unrepaired cyanotic congenital 
heart disease or repaired congenital heart disease, with residual shunts 
or valvular regurgitation at the site adjacent to the site of a prosthetic 
patch or prosthetic device.
■
■AORTIC STENOSIS
Previous American College of Cardiology/American Heart Association 
guidelines have cautioned against surgery in patients with severe aortic 
stenosis, citing a 10% mortality risk. More recent guidance, rooted in 
contemporary data, offers greater latitude for noncardiac surgery in 
appropriately selected patients with severe aortic stenosis. In an analy­
sis of patients undergoing moderate- or high-risk surgery at the Mayo 
Clinic from 2000 to 2010, there was no significant difference in 30-day 
mortality between those with severe aortic stenosis and matched con­
trols (5.9 vs 3.1%, p = .13); however, those with severe aortic stenosis 
had more MACEs (18.8 vs 10.5%, p = .01), mainly due to heart failure. 
In sum, severe aortic stenosis is associated with adverse outcomes in 
patients undergoing noncardiac surgery; however, in contemporary 
cohorts, this risk is less than has previously been stated. Patients with 
severe symptomatic aortic stenosis should generally undergo aortic 
valve intervention (surgical aortic valve replacement or transcath­
eter aortic valve implantation) if noncardiac surgery can be deferred. 
Asymptomatic patients with severe aortic stenosis and preserved ejec­
tion fraction can generally safely undergo low- or intermediate-risk 
noncardiac surgery. Balloon valvotomy is usually not recommended 
but may serve a role in the minority of patients who need “bridging” to 
a necessary surgery or procedure.
■
■VENOUS THROMBOEMBOLISM
(See also Chap. 290) Perioperative prophylaxis of venous thromboem­
bolism should follow established guidelines of the American College of

Chest Physicians. Aspirin is not supported as a single agent for throm­
boprophylaxis. Low-dose unfractionated heparin (≤5000 units SC bid), 
low-molecular-weight heparin (e.g., enoxaparin, 30 mg bid or 40 mg qd), 
or a pentasaccharide (fondaparinux, 2.5 mg qd) is appropriate for patients 
at moderate risk; unfractionated heparin (5000 units SC tid) is appropri­
ate for patients at high risk. The use of direct oral anticoagulants may be 
an alternative to the use of prophylactic doses of low-dose unfractionated 
heparin and low-molecular-weight heparin; among patients immobilized 
after nonmajor orthopedic surgery, rivaroxaban 10 mg once daily when 
compared to enoxaparin was associated with a decrease in venous throm­
boembolic events, without a significant change in bleeding. Graduated 
compression stockings and pneumatic compression devices are useful 
supplements to anticoagulant therapy or as alternatives to anticoagulant 
therapy in patients at excessive bleeding risk.

■
■FURTHER READING
Eagle KA et al: Perioperative cardiovascular care for patients under­
going noncardiac surgical intervention. JAMA Intern Med 175:835, 
2015.
Fleisher LA et al: 2014 ACC/AHA guideline on perioperative car­
diovascular evaluation and management of patients undergoing 
noncardiac surgery: A report of the American College of Cardiology/
American Heart Association Task Force on Practice Guidelines. 
Circulation 130:e278, 2014.
PART 19
Consultative Medicine

Halvorsen S et al: 2022 ESC Guidelines on cardiovascular assess­
ment and management of patients undergoing non-cardiac surgery: 
Developed by the task force for cardiovascular assessment and man­
agement of patients undergoing non-cardiac surgery of the European 
Society of Cardiology (ESC) Endorsed by the European Society of 
Anesthesiology and Intensive Care. Eur Heart J 39:3826, 2022.
Hwang JW et al: Assessment of perioperative cardiac risk of patients 
undergoing noncardiac surgery using coronary computed tomo­
graphic angiography. Circ Cardiovasc Imaging 8:e002582, 2015.
Levine GN et al: 2016 ACC/AHA guideline focused update on dura­
tion of dual antiplatelet therapy in patients with coronary artery 
disease. A report of the American College of Cardiology/American 
Association Task Force on Clinical Practice Guidelines. J Am Coll 
Cardiol 68:1082, 2016.
Otto CM et al: 2020 ACC/AHA guideline for the management of 
patients of valvular heart disease: A report of the American College of 
Cardiology/American Heart Association Joint Committee on Clinical 
Practice Guidelines. Circulation 143:e72, 2021.
Smilowitz NR, Berger JS: Perioperative cardiovascular risk assess­
ment and management for noncardiac surgery: A review. JAMA 
324:279, 2020.
Tashiro T et al: Perioperative risk of major non-cardiac surgery in 
patients with severe aortic stenosis: A reappraisal in contemporary 
practice. Eur Heart J 35:2372, 2014.