BibliU-Print-9781259644047.pdf

1578185 – McGraw-Hill Professional ©

PART 19 Consultative Medicine

465 Approach to Medical ConsultationJack Ende, Jeffrey Berns

Effective health care requires teams of generalists and specialists with complementaryexpertise. Many clinical conditions require the input of more than one clinical provider,either because the diagnosis and recommended treatment is uncertain or because apatient may have multiple diseases that may be best managed by involving multiplespecialists.

To consult is to seek advice from someone with expertise in a particular area, whereasconsultation refers to the meeting or comparable outcome arising from that request.Medical consultation takes several forms. Its most traditional forms include in-hospitalconsultation in which physicians provide recommendations or perform procedures for ahospitalized patient, and out-patient consultations, in which patients are seen in the officesetting. More contemporary forms of consultation include e-consultations, telemedicineevaluations (see “Consultation Involving Telemedicine,” below), and remote medicalsecond 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 appropriaterecommendations.

While forms of medical consultation evolve, basic responsibilities associated withmedical consultation endure. These responsibilities can be divided into those that fall tothe requesting physician or non-physician practitioner; the consultant, who provides theconsultation; and the health system, hospital, or organization that must support thisimportant medical encounter (Table 465-1).

TABLE 465-1 Stakeholder Responsibilities in the Medical Consultation Process

1578185 – McGraw-Hill Professional ©

RESPONSIBILITIES OF THE REQUESTING PRACTITIONERBefore requesting a consultation, the provider should ensure that the patient endorses thepurpose of the consultation, understands the role of the consultant, and anticipates thelikely outcomes of the encounter. Further responsibilities of the requesting practitionerinclude being specific and communicating clearly the reason for the consultation. Vaguemessages such as, “Please evaluate” are not as helpful as more specific inquiries such as,“What is the cause of the declining kidney function?” or, “How should this asymptomaticpulmonary nodule be evaluated?” To the extent possible, the requesting practitionershould provide the relevant clinical information, summarized as succinctly as possible.Urgency should be clearly conveyed, typically with a phone call or other directcommunication.

The requesting practitioner should be explicit regarding the intended outcome of theconsultation, i.e., is this for a single evaluation or ongoing co-management?Communication between the requesting and the consulting providers is paramount.Whether this communication includes direct contact is less important than that therelevant information and desired outcome be explicit and clear, regardless ofcommunication medium. Consultations should be requested for clinical purposes andalways directed to qualified consultants; they should not be driven by entrepreneurial orrelationship-building purposes. Another responsibility of the referring provider is not to“over- consult.” Medical care should be focused on value, not volume.

RESPONSIBILITIES OF THE CONSULTANTJust as the referring provider should attend to clear and explicit communication, so tooshould the consultant follow the precepts of effective interactions between professionals,which include courtesy, availability, and clarity. Particularly on the inpatient service, whereconsultants may receive several requests each day, it is important that the incomingconsultations are triaged and dispatched as clinically appropriate. Consultants also needto determine the requested level of involvement going forward and not assume that long-

1578185 – McGraw-Hill Professional ©

term co- management is being sought. While consultants can and should make use ofavailable clinical data, they should also assemble independently their own database,including taking a history, performing a physical exam, and reviewing pertinent clinicalstudies. Absent that, they may be unable to provide an independent and actionablesynthesis. Just as the referring provider needs to be clear and concise, so too should theconsultant be specific and focused in the recommendations provided. “Possible malignantascites” is less helpful than, “I will arrange for paracentesis to exclude the possibility ofmalignant ascites.” For the most part, recommendations to “consider” some diagnosis ortest are less helpful than more specific and concrete advice. Some referring practitionerswish to be called after a patient is seen; others prefer that communication be handled aspart of the medical record. How this communication is handled must also align with thecomplexity and urgency of the consultation and clinical circumstances.

RESPONSIBILITIES OF HEALTH SYSTEMS, HOSPITALS, AND MEDICALORGANIZATIONSHealth systems, hospitals, and medical organizations also have responsibilities in theconsultation process. This responsibility includes ensuring that qualified consultants areaccessible and available on the medical staff. Consultations within a single system areaided by common shared electronic medical records, particularly when consultationsoriginate in the hospital, but can also involve care in the outpatient setting. Finally, healthcare entities should strive to foster a culture of team-based care and collegiality.

SPECIAL ISSUES IN MEDICAL CONSULTATION

Curbside Consults        Curbside consults are requests from one practitioner to another foran informal and unwritten opinion about a specific patient care matter. They are typicallylimited in scope, mostly regarding management or questions regarding procedures, anddeveloped from information provided by the consulting practitioner and perhaps themedical record (such as labs and imaging studies), but without a comprehensive review ofthe record or any direct contact with the patient. Although often viewed as convenient,efficient, and a common aspect of clinical care, by their very nature, curbside consultshave been found to often be incomplete or even flawed. It is not uncommon for thequestion being asked to be deemed too complex for a curbside consult, or for it not to bethe 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 reasonto limit curbside consults, the risk is actually negligible as U.S. courts have ruled thatcurbside consults do not establish a doctor-patient relationship necessary for creating thebasis for medical malpractice litigation. An important exception, however, is when acurbside consult is provided by a resident or fellow in training; in this circumstance thetrainee’s supervising physician, whether aware of the curbside consult or not, isresponsible for the recommendations of the trainee.

Second Opinions    Physicians may find themselves providing consultations requested bypatients who have already been evaluated for the same problem by another physician. Nota “consult” in the usual context of one physician referring a patient to another, the serviceprovided by the consultant here 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

1578185 – McGraw-Hill Professional ©

recommendation is correct, out of dissatisfaction with the initial physician, or with thehope of an entirely different opinion and recommendation. The physician providing thesecond opinion should strive to understand the patient’s motivations for seeking theadditional opinion. While a second opinion may have been initiated by the patient ratherthan referral from another physician, it is recommended that the consulting physiciancommunicate with the patient’s primary physician or specialist as would be donefollowing a standard consultation unless the patient insists otherwise. In addition,professional behavior in how the consulting physician refers to the recommendations oractions of previously consulted physicians is important, even when there is disagreement.Likewise, it is important that a transfer of care from prior consultants to the one providinga second opinion be enacted only if specifically requested by the patient or the physicianwho encouraged the second opinion.

Consults Involving Mid-Level Providers Increasingly, specialist physicians may findthemselves being consulted by nurse practitioners and physician assistants rather thanother physicians. Whether the quality of the information provided to the consultantphysician by a mid-level provider is different from physician-to-physician referrals has notbeen studied. Consulting physicians should know whether they should respond back tothe mid-level provider or to the supervising physician. As with physician-to-physicianconsults, it is also important for the consultant to know whether the individual calling forthe consult has an ongoing role in the care of the patient or is simply covering for a limitedperiod of time. Finally, the consultant, if responding back to the mid-level provider, shouldmake sure that the information provided meets the needs of that provider, and thatquestions are answered as they would be if responding back to another physician.

Consultation Involving Telemedicine        Consultations making use of electronic healthrecords, patient portals, and various forms of telecommunication technology, includingvideo conferencing or cell phone communication, can improve access to care, reduce cost,and improve outcomes. This is particularly true when employed in geographic areas ofhealth care shortage and when the clinical issues can be handled without direct contactwith the patient, e.g., radiology or dermatology. However, the absence of direct contactbetween patient and consultant introduces special issues related to diagnostic accuracyand physician-patient relationship. Regulatory issues, liability, security, and confidentialityissues arise as well. Consultation via telemedicine holds considerable promise, but theaforementioned concerns will need to be better understood.

FURTHER READINGDANIEL H, SULMASY LS: Policy recommendations to guide the use of telemedicine in

primary care: An American College of Physicians Position Paper. Ann Intern Med163:787, 2015.

PEARSON SD: Principles of generalist-specialist relationships. J Gen Intern Med 14(Suppl1):S13, 1999.

466 Medical Disorders During PregnancyRobert L. Barbieri, John T. Repke

1578185 – McGraw-Hill Professional ©

Each year, approximately 4 million births occur in the United States, and more than 130million births occur worldwide. A significant proportion of births are complicated bymedical disorders. Advances in medical care and fertility treatment have increased thenumber of women with serious medical problems who attempt to become pregnant.Medical problems that interfere with the physiologic adaptations of pregnancy increasethe risk for poor pregnancy outcome; conversely, in some instances, pregnancy mayadversely impact an underlying medical disorder.

HYPERTENSION(See also Chap. 271) In pregnancy, cardiac output increases by 40%, with most of theincrease due to an increase in stroke volume. Heart rate increases by ~10 beats/minduring the third trimester. In the second trimester, systemic vascular resistance decreases,and this decline is associated with a fall in blood pressure. During pregnancy, a bloodpressure of 140/90 mmHg is considered to be abnormally elevated and is associated withan increase in perinatal morbidity and mortality. In all pregnant women, the measurementof blood pressure should be performed in the sitting position, because the lateralrecumbent position may result in a lower blood pressure. The diagnosis of hypertensionrequires the measurement of two elevated blood pressures at least 4 h apart. Hypertensionduring pregnancy is usually caused by preeclampsia, chronic hypertension, gestationalhypertension, or renal disease.

PREECLAMPSIAApproximately 5–7% of all pregnant women develop preeclampsia, the new onset ofhypertension (blood pressure >140/90 mmHg) and proteinuria (either a 24 h urinaryprotein >300 mg/24 h, or a protein- creatinine ratio ≥0.3) after 20 weeks of gestation.Recent revisions to the diagnostic criteria include: proteinuria is no longer an absoluterequirement for making the diagnosis; the terms mild and severe preeclampsia have beenreplaced; and the disease is now termed preeclampsia either with or without severefeatures and fetal growth restriction is no longer a defining criterion for preeclampsia withsevere features. Although the precise pathophysiology of preeclampsia remains unknown,recent studies show excessive placental production of antagonists to both vascularendothelial growth factor (VEGF) and transforming growth factor β (TGF-β). Theseantagonists to VEGF and TGF-β disrupt endothelial and renal glomerular function resultingin edema, hypertension, and proteinuria. The renal histological feature of preeclampsia isglomerular endotheliosis. Glomerular endothelial cells are swollen and encroach on thevascular lumen. Preeclampsia is associated with abnormalities of cerebral circulatoryautoregulation, which increase the risk of stroke at mildly and moderately elevated bloodpressures. Risk factors for the development of preeclampsia include nulliparity, diabetesmellitus, a history of renal disease or chronic hypertension, a prior history of preeclampsia,extremes of maternal age (>35 years or <15 years), obesity, antiphospholipid antibodysyndrome, and multiple gestation. Low-dose aspirin (81 mg daily, initiated at the end ofthe first trimester) modestly reduces the risk of preeclampsia in pregnant women at highrisk of developing the disease.

Preeclampsia with severe features is the presence of new-onset hypertension andproteinuria accompanied by end-organ damage. Features may include severe elevation ofblood pressure (>160/110 mmHg), evidence of central nervous system (CNS) dysfunction(headaches, blurred vision, seizures, coma), renal dysfunction (oliguria or creatinine >1.5

1578185 – McGraw-Hill Professional ©

mg/dL), pulmonary edema, hepatocellular injury (serum alanine aminotransferase levelmore than twofold the upper limit of normal), hematologic dysfunction (platelet count<100,000/L or disseminated intravascular coagulation [DIC]). The HELLP syndrome(hemolysis, elevated liver enzymes, low platelets) is a special subtype of severepreeclampsia and is a major cause of morbidity and mortality in this disease. Plateletdysfunction and coagulation disorders further increase the risk of stroke.

TREATMENT

PreeclampsiaPreeclampsia resolves within a few weeks after delivery. For pregnant women withpreeclampsia prior to 37 weeks of gestation, delivery reduces the mother’s morbiditybut exposes the fetus to the risk of premature birth. The management of preeclampsiais challenging because it requires the clinician to balance the health of the mother andfetus simultaneously. In general, prior to term, women with preeclampsia withoutsevere features may be managed conservatively with limited physical activity, althoughbed rest is not recommended, close monitoring of blood pressure and renal function,and careful fetal surveillance. For women with preeclampsia with severe features,delivery is recommended unless the patient is eligible for expectant management in atertiary hospital setting. Expectant management of preeclampsia with severe featuresremote from term affords some benefits for the fetus, but significant risks for themother. Postponing delivery beyond 34 weeks gestation in this group of patients is notrecommended. In preeclampsia without severe features delivery at 37 weeks isrecommended.

The definitive treatment of preeclampsia is delivery of the fetus and placenta. Forwomen with preeclampsia with severe features, aggressive management of bloodpressures >160/105 mmHg reduces the risk of cerebrovascular accidents. IV labetalolor hydralazine is most commonly used to acutely manage severe hypertension inpreeclampsia; labetalol is associated with fewer episodes of maternal hypotension.Elevated arterial pressure should be reduced slowly to avoid hypotension and adecrease in blood flow to the fetus.

Magnesium sulfate is the preferred agent for the prevention and treatment ofeclamptic seizures. Large, randomized clinical trials have demonstrated the superiorityof magnesium sulfate over phenytoin and diazepam in reducing the risk of seizure and,possibly, the risk of maternal death. Magnesium may prevent seizures by interactingwith N-methyl-D-aspartate (NMDA) receptors in the CNS. The universal use ofmagnesium sulfate for seizure prophylaxis in preeclampsia without severe features isno longer recommended by most experts. There is consensus that magnesium sulfateshould be used in all cases of preeclampsia with severe features, or in cases ofeclampsia. Women who have had preeclampsia appear to be at increased risk ofcardiovascular and renal disease later in life.

CHRONIC ESSENTIAL HYPERTENSIONPregnancy complicated by chronic essential hypertension is associated with intrauterinegrowth restriction and increased perinatal mortality. Pregnant women with chronic

1578185 – McGraw-Hill Professional ©

hypertension are at increased risk for superimposed preeclampsia and abruptio placentae.Women with chronic hypertension should have a thorough prepregnancy evaluation, bothto identify remediable causes of hypertension and to ensure that the prescribedantihypertensive agents (e.g., angiotensin-converting enzyme [ACE] inhibitors, angiotensin-receptor blockers) are not associated with an adverse outcome of pregnancy. Labetaloland nifedipine are the most commonly used medications for the treatment of chronichypertension in pregnancy. The target blood pressure is in the range of 130–150 mmHgsystolic and 80–100 mmHg diastolic. Should hypertension worsen during pregnancy,baseline evaluation of renal function (see below) is necessary to help differentiate theeffects of chronic hypertension from those of superimposed preeclampsia. There are noconvincing data that the treatment of mild chronic hypertension improves perinataloutcome.

GESTATIONAL HYPERTENSIONThe development of elevated blood pressure after 20 weeks of pregnancy or in the first 24h post-partum in the absence of preexisting chronic hypertension or proteinuria is referredto as gestational hypertension. Mild gestational hypertension that does not progress topreeclampsia has not been associated with adverse pregnancy outcome or adverse long-term prognosis.

RENAL DISEASENormal pregnancy is characterized by an increase in glomerular filtration rate andcreatinine clearance. This increase occurs secondary to a rise in renal plasma flow andincreased glomerular filtration pressures. Patients with underlying renal disease andhypertension may expect a worsening of hypertension during pregnancy. If superimposedpreeclampsia develops, the additional endothelial injury results in a capillary leaksyndrome that may make management challenging. In general, patients with underlyingrenal disease and hypertension benefit from aggressive management of blood pressure.Preconception counseling is also essential for these patients so that accurate riskassessment and medication changes can occur prior to pregnancy. In general, aprepregnancy serum creatinine level <133 μmol/L (<1.5 mg/dL) is associated with afavorable prognosis. When renal disease worsens during pregnancy, close collaborationbetween the internist and the maternal-fetal medicine specialist is essential so thatdecisions regarding delivery can be weighed to balance the sequelae of prematurity for theneonate versus long-term sequelae for the mother with respect to future renal function.

CARDIAC DISEASE

VALVULAR HEART DISEASE(See also Chaps. 256–263) Valvular heart disease is the most common cardiac problemcomplicating pregnancy.

Mitral Stenosis    This is the valvular disease most likely to cause death during pregnancy.The pregnancy-induced increase in blood volume, cardiac output, and tachycardia canincrease the transmitral pressure gradient and cause pulmonary edema in women withmitral stenosis. Women with moderate to severe mitral stenosis (mitral valve area ≤1.5cm2) who are planning pregnancy and have either symptomatic disease or pulmonary

1578185 – McGraw-Hill Professional ©

hypertension should undergo valvuloplasty prior to conception, preferably withpercutaneous balloon valvotomy (PBV). Pregnancy associated with long-standing mitralstenosis may result in pulmonary hypertension. Sudden death has been reported whenhypovolemia occurs. Careful control of heart rate, especially during labor and delivery,minimizes the impact of tachycardia and reduced ventricular filling times on cardiacfunction. Pregnant women with mitral stenosis are at increased risk for the developmentof atrial fibrillation and other tachyarrhythmias. The immediate postpartum period is atime of particular concern secondary to rapid volume shifts. Careful monitoring of cardiacand fluid status should be observed.

Mitral Regurgitation and Aortic Regurgitation and Stenosis        The pregnancy-induceddecrease in systemic vascular resistance reduces the risk of cardiac failure with theseconditions, especially in women with chronic lesions. Acute onset of mitral or aorticregurgitation may not be well tolerated during pregnancy. For women with severe aorticstenosis, treatment before pregnancy should be considered for a peak-to-peak valvegradient >50 mmHg. In women with aortic stenosis and a mean valve gradient <25 mmHg,pregnancy is likely to be well tolerated. For women with mitral or aortic regurgitation andleft ventricular dysfunction (LVEF <30%) pregnancy should be avoided.

CONGENITAL HEART DISEASE(See also Chap. 264) Reparative surgery has markedly increased the number of adultwomen with surgically repaired congenital heart disease. Maternal morbidity and mortalityare greater among these women than among those without surgical cardiac repair. Whenpregnant, these patients should be jointly managed by a cardiologist and an obstetricianfamiliar with these problems. The presence of a congenital cardiac lesion in the motherincreases the risk of congenital cardiac disease in the newborn. Prenatal screening of thefetus for congenital cardiac disease with ultrasound is recommended.

OTHER CARDIAC DISORDERSSupraventricular tachycardia (Chap. 241) is a common cardiac complication ofpregnancy. Treatment is the same as in the nonpregnant patient, and fetal tolerance ofmedications such as adenosine and calcium channel blockers is acceptable. Whennecessary, pharmacologic or electric cardioversion may be performed to improve cardiacperformance and reduce symptoms. This intervention is generally well tolerated by motherand fetus.

Peripartum cardiomyopathy (Chap. 254) is an uncommon disorder of pregnancy andits etiology remains unknown. Approximately 10% of women with peripartumcardiomyopathy carry a truncating mutation in the gene encoding the titin sarcomereprotein. Treatment is directed toward symptomatic relief and improvement of cardiacfunction. Many patients recover completely; others are left with progressive dilatedcardiomyopathy. Recurrence in a subsequent pregnancy has been reported, and womenwho do not have normal baseline left-ventricular function after an episode of peripartumcardiomyopathy should be counseled to avoid pregnancy.

SPECIFIC HIGH-RISK CARDIAC LESIONS

Marfan Syndrome (See also Chap. 406)        This autosomal dominant disease isassociated with an increased risk of aortic dissection and rupture. An aortic root diameter

1578185 – McGraw-Hill Professional ©

<40 mm is associated with a favorable outcome of pregnancy; conversely, an aortic rootdiameter >40 mm is associated with an increased risk of aortic dissection. Prophylactictherapy with beta blockers has been advocated to reduce aortic dilation and the risk ofdissection. A “cardiac delivery” with reduced pushing and early intervention with operativedelivery is often recommended to reduce increases in aortic wall stress caused by theValsalva maneuver.

Ehlers-Danlos syndrome (EDS) may be associated with premature labor, and in type IVEDS there is increased risk of organ or vascular rupture that may cause death. For womenwith vascular EDS, pregnancy is relatively contraindicated because of the high risk ofvascular and uterine rupture.

Pulmonary Hypertension (See also Chap. 277)        Maternal mortality in the setting ofsevere pulmonary hypertension is high, and primary pulmonary hypertension is acontraindication to pregnancy. Termination of pregnancy may be advisable in thesecircumstances to preserve the life of the mother. In the Eisenmenger syndrome, i.e., thecombination of pulmonary hypertension with right-to-left shunting due to congenitalabnormalities (Chap. 264), maternal and fetal deaths occur frequently. Systemichypotension may occur after blood loss, prolonged Valsalva maneuver, or regionalanesthesia; sudden death secondary to hypotension is a dreaded complication.Management of these patients is challenging, and invasive hemodynamic monitoringduring labor and delivery is recommended in severe cases.

In patients with pulmonary hypertension, vaginal delivery is less stressfulhemodynamically than cesarean section, which should be reserved for accepted obstetricindications.

DEEP VENOUS THROMBOSIS AND PULMONARY EMBOLISM(See also Chap. 273) Pregnancy is associated with venous stasis, endothelial injury and ahypercoagulable state. Inherited thrombophilias and the presence of antiphospholipidantibodies increase the risk of venous thromboembolism (VTE) in pregnancy. Deepvenous thrombosis (DVT) or pulmonary embolism (PE) occurs in about 1 in 500pregnancies, with DVT being three times more common than PE. VTE occurs morecommonly in the 6 weeks post-partum than antepartum. In pregnant women, mostunilateral DVTs occur in the left leg because the left iliac vein is compressed by the rightiliac artery and the uterus compresses the inferior vena cava.

TREATMENT

Deep Venous ThrombosisAggressive diagnosis and management of DVT and suspected pulmonary embolismoptimize the outcome for mother and fetus. In general, all diagnostic and therapeuticmodalities afforded that the nonpregnant patient should be utilized in pregnancyexcept for D-dimer measurement, in which values are elevated in normal pregnancy.Anticoagulant therapy with low-molecular-weight heparin (LMWH) or unfractionatedheparin is indicated in pregnant women with DVT. LMWH may be associated with anincreased risk of epidural hematoma in women receiving an epidural anesthetic inlabor and must be discontinued at least 24 h before placement of an epidural catheter.

1578185 – McGraw-Hill Professional ©

Warfarin therapy is contraindicated in the first trimester due to its association with fetalchondrodysplasia punctata. In the second and third trimesters, warfarin may causefetal optic atrophy and mental retardation. In pregnancy the use of warfarin isrestricted to women with mechanical heart valves. Warfarin is not contraindicated inbreast-feeding women. For women at moderate or high risk of DVT who have acesarean delivery, mechanical and/or pharmacologic prophylaxis is warranted.

ENDOCRINE DISORDERS

DIABETES MELLITUS(See also Chaps. 396–398) In pregnancy, the fetoplacental unit induces major metabolicchanges, the purpose of which is to shunt glucose and amino acids to the fetus while themother uses ketones and triglycerides to fuel her metabolic needs. These metabolicchanges are accompanied by maternal insulin resistance caused in part by placentalproduction of steroids, a growth hormone variant, and placental lactogen. Althoughpregnancy has been referred to as a state of “accelerated starvation,” it is bettercharacterized as “accelerated ketosis.” In pregnancy, after an overnight fast, plasmaglucose is lower by 0.8–1.1 mmol/L (15–20 mg/dL) than in the nonpregnant state. Thisdifference is due to the use of glucose by the fetus. In early pregnancy, fasting may resultin circulating glucose concentrations in the range of 2.2 mmol/L (40 mg/dL) and may beassociated with symptoms of hypoglycemia. In contrast to the decrease in maternalglucose concentration, plasma hydroxybutyrate and acetoacetate levels rise to two to fourtimes normal after a fast.

TREATMENT

Diabetes Mellitus in PregnancyPregnancy complicated by diabetes mellitus is associated with higher maternal andperinatal morbidity and mortality rates. Preconception counseling and treatment areimportant for the diabetic patient contemplating pregnancy and can reduce the risk ofcongenital malformations and improve pregnancy outcome. Folate supplementationreduces the incidence of fetal neural tube defects, which occur with greater frequencyin fetuses of diabetic mothers. In addition, optimizing glucose control during keyperiods of organogenesis reduces other congenital anomalies, including sacralagenesis, caudal dysplasia, renal agenesis, and ventricular septal defect.

Once pregnancy is established, glucose control should be managed moreaggressively than in the nonpregnant state. In addition to dietary changes, thisenhanced management requires more frequent blood glucose monitoring and ofteninvolves additional injections of insulin or conversion to an insulin pump. Fastingblood glucose levels should be maintained at <5.8 mmol/L (<105 mg/dL), withavoidance of values >7.8 mmol/L (140 mg/dL). Sequential measurement ofhemoglobin A1c is of minimal value for monitoring glucose control during pregnancybecause of the higher rate of red blood cell turnover during pregnancy. Commencing inthe third trimester, regular surveillance of maternal glucose control as well asassessment of fetal growth (obstetric sonography) and fetoplacental oxygenation

1578185 – McGraw-Hill Professional ©

(fetal heart rate monitoring or biophysical profile) optimize pregnancy outcome.Pregnant diabetic patients without vascular disease are at greater risk for delivering amacrosomic fetus, and attention to fetal growth via clinical and ultrasoundexamination is important. Fetal macrosomia is associated with an increased risk ofmaternal and fetal birth trauma, including permanent injury to the brachial plexus.Pregnant women with diabetes have an increased risk of developing preeclampsia, andthose with vascular disease are at greater risk for developing intrauterine growthrestriction, which is associated with an increased risk of fetal and neonatal death.Excellent pregnancy outcomes in patients with diabetic nephropathy and proliferativeretinopathy have been reported with aggressive glucose control and intensive maternaland fetal surveillance.

As pregnancy progresses, glycemic control may become more difficult to achievedue to an increase in insulin resistance. In pregnant women with Type 1 diabetes,closed-loop insulin delivery with both continuous interstitial glucose monitoring andsensor-augmented insulin pump therapy is helpful in normalizing circulating glucosewith few episodes of hypoglycemia. In general, efforts to control glucose and avoidpreterm delivery result in the best overall outcome for both mother and newborn.Preterm delivery is generally performed only for the usual obstetric indications (e.g.,preeclampsia, fetal growth restriction, non-reassuring fetal testing) or for worseningmaternal renal or active proliferative retinopathy.

GESTATIONAL DIABETES (GDM)GDM occurs in ~4% of pregnancies. Because about 90% of women have at least one riskfactor for GDM, all pregnant women should be screened for GDM. A typical two-stepstrategy for establishing the diagnosis of GDM is performed at 24–28 weeks of gestationand involves administration of a 50-g oral glucose challenge with a single serum glucosemeasurement at 60 min. If the plasma glucose is <7.8 mmol/L (<130 mg/dL) the test isconsidered normal. Plasma glucose >7.8 mmol/L (>130 mg/dL) warrants administrationof a 100-g oral glucose challenge with plasma glucose measurements obtained in thefasting state and at 1, 2, and 3 h. Normal plasma glucose concentrations at these timepoints are <5.3 mmol/L (<95 mg/dL), <10 mmol/L (<180 mg/dL), <8.6 mmol/L (<155mg/dL), and <7.8 mmol/L (<140 mg/dL) as the upper norms for a 3-h glucose tolerancetest. Two elevated glucose values indicate a positive test. Adverse pregnancy outcomesfor mother and fetus appear to increase with glucose as a continuous variable; thus it ischallenging to define the optimal threshold for establishing the diagnosis of GDM.

Pregnant women with GDM are at increased risk of stillbirth, preeclampsia, and deliveryof infants who are large for their gestational age, with resulting birth lacerations, shoulderdystocia, and birth trauma including brachial plexus injury. These fetuses are at risk ofhypoglycemia, hyperbilirubinemia, and polycythemia. Tight control of blood sugar duringpregnancy and labor can reduce these risks.

TREATMENT

Gestational Diabetes

1578185 – McGraw-Hill Professional ©

Treatment of GDM with a two-step strategy—dietary intervention followed by insulininjections if diet alone does not adequately control blood sugar (fasting glucose <5.6mmol/L [<100 mg/dL] and 2-h postprandial glucose <7.0 mmol/L [<126 mg/dL])—isassociated with a decreased risk of birth trauma for the fetus. Oral hypoglycemicagents such as glyburide and metformin have become more commonly utilized formanaging GDM refractory to nutritional management, but most experts favor insulintherapy. For women with GDM, there is a 40% risk of being diagnosed with diabeteswithin the 10 years after the index pregnancy. All women with GDM should have aformal glucose tolerance test (GTT) to screen for T2DM at ~6 weeks post-partum. Inwomen with a history of GDM, exercise, weight loss, and treatment with metforminreduce the risk of developing diabetes. Lactation also reduces the risk of GDMprogressing to T2DM. All women with a history of GDM should be counseled aboutprevention strategies and evaluated regularly for diabetes.

OBESITY(See also Chap. 395) Pregnant women who are obese have an increased risk of stillbirth,congenital fetal malformations, GDM, preeclampsia, urinary tract infections, preterm andpost-date delivery, and cesarean delivery. Women contemplating pregnancy shouldattempt to attain a healthy weight prior to conception. For morbidly obese women whohave not been able to lose weight with lifestyle changes, bariatric surgery reduces the risksfor GDM, macrosomia, and preterm delivery. Following bariatric surgery, women shoulddelay conception for 1 year to avoid pregnancy during an interval of rapid metabolicchanges. The National Academy of Medicine guidelines for weight gain during pregnancyrecommend that for BMI ranges of <18.5, 18.5–24.9, 25.0–29.9, and ≥30 kg/m2, weightgain targets should be 12.5–18 kg, 11.5–16 kg, 7–11.5 kg, and 5–9 kg, respectively.

THYROID DISEASE(See also Chap. 375) In pregnancy, the estrogen-induced increase in thyroxine-bindingglobulin increases circulating levels of total T3 and total T4. Placental human chorionicgonadotropin (hCG) directly stimulates the thyroid causing an increase in free T3 and T4.Interpretation of the measurement of free T4, free T3, and thyroid-stimulating hormone(TSH) should use trimester-specific ranges.

TREATMENT

Hyperthyroidism in Pregnancy

HYPERTHYROIDISMMethimazole crosses the placenta to a greater degree than propylthiouracil and hasbeen associated with fetal aplasia cutis. However, propylthiouracil can be associatedwith liver failure. Some experts recommend propylthiouracil in the first trimester andmethimazole thereafter. Radioiodine should not be used during pregnancy, either forscanning or for treatment, because of effects on the fetal thyroid. In emergentcircumstances, additional treatment with beta blockers may be necessary.Hyperthyroidism is most difficult to control in the first trimester of pregnancy and

1578185 – McGraw-Hill Professional ©

easiest to control in the third trimester. In women with high-titer thyroid stimulatingantibodies, the newborn may be born with neonatal Graves’ disease.

HYPOTHYROIDISMThe goal of therapy for hypothyroidism is to maintain the serum TSH in the normalrange, and thyroxine is the drug of choice. During pregnancy, the dose of thyroxinerequired to keep the TSH in the normal range rises. In one study, the mean replacementdose of thyroxine required to maintain the TSH in the normal range was 0.1 mg dailybefore pregnancy and increased to 0.15 mg daily during pregnancy. Since theincreased thyroxine requirement occurs as early as the fifth week of pregnancy, oneapproach is to increase the thyroxine dose by 30% (two additional pills weekly) as soonas pregnancy is diagnosed and then adjust the dose by serial measurements of TSH.

HEMATOLOGIC DISORDERSPregnancy has been described as a state of physiologic anemia. Part of the reduction inhemoglobin concentration is dilutional, but iron and folate deficiencies are major causesof correctable anemia during pregnancy.

In populations at high risk for hemoglobinopathies (Chap. 94), hemoglobinelectrophoresis should be performed as part of the prenatal screen. Hemoglobinopathiescan be associated with increased maternal and fetal morbidity and mortality.Management is tailored to the specific hemoglobinopathy and is generally the same forboth pregnant and nonpregnant women. Prenatal diagnosis of hemoglobinopathies in thefetus is readily available and should be discussed with prospective parents either prior toor early in pregnancy.

Thrombocytopenia occurs commonly during pregnancy. The majority of cases arebenign gestational thrombocytopenias, but the differential diagnosis should includeimmune thrombocytopenia (Chap. 111), preeclampsia, and thrombotic thrombocytopenicpurpura. Benign gestational thrombocytopenia is unlikely if the platelet count is <100,000per μL.

NEOPLASIACancer complicates ~1 in every 1000 pregnancies. Of all the cancers that occur in women,<1% complicate pregnancies. The four cancers that occur most commonly in pregnancyare cervical cancer, breast cancer, melanoma, and lymphomas (particularly Hodgkin’slymphoma); however, virtually every form of cancer has been reported in pregnant women(Table 466-1). In addition to cancers developing in other organs of the mother, gestationaltrophoblastic tumors can arise from the placenta.

TABLE 466-1 Incidence of Malignant Tumors During Gestation

1578185 – McGraw-Hill Professional ©

aThese are estimates based on extrapolations from a review of more than 3 million pregnancies (LH Smith et al:Am J Obstet Gynecol 184:1504, 2001).bBased on accumulating case reports from the literature; the precision of these data is not high.

Managing cancer in a pregnant woman is complex. One must take into account (1) thepossible influence of the pregnancy on the natural history of the cancer, (2) effects on themother and fetus of complications from the malignancy (e.g., anorexia, nausea, vomiting,malnutrition), (3) potential effects of diagnostic and staging procedures, and (4) potentialeffects of cancer treatments on both the mother and the developing fetus. Generally, themanagement that optimizes maternal physiology is also best for the fetus. The dilemmaoccasionally arises that what is best for the mother may be harmful to the fetus, and whatis best for the fetus may compromise the ultimate prognosis for the mother. The best wayto approach management of a pregnant woman with cancer is to ask, “What would one doin this clinical situation if she was not pregnant? Then, which, if any aspect of those plansneed to be modified because she is pregnant?”

TREATMENT

Special Therapeutic Considerations in PregnancyExposure of developing fetuses to ionizing radiation may cause adverse fetal effects;awareness of this potential toxicity has resulted in a disproportionate aversion todiagnostic imaging in pregnancy. The fetus is most sensitive to teratogenesis duringorganogenesis in the first trimester. Imaging that uses ionizing radiation should not bedone without a compelling reason and due consideration to obtaining the necessaryinformation by alternative imaging modalities. Exposure to diagnostic and therapeuticradionuclides, especially radioactive iodine, poses unique risks, but a full discussion ofthese is beyond the scope of this chapter.

Generally, toxic chemotherapy should be avoided during pregnancy, if at all possible.It should virtually never be given in the first trimester. A variety of single agents andcombinations have been administered in the second and third trimesters, without ahigh frequency of toxic effects to the pregnancy or the fetus, but data on safety aresparse. A database on the risks associated with individual chemotherapy agents isavailable(http://ntp.niehs.nih.gov/ntp/ohat/cancer_chemo_preg/chemopregnancy_monofinal_508.pdf). If the malignancy is slowly progressive, and if the patient is near her deliverydate, and if waiting until delivery to begin treatment is not anticipated to compromisematernal prognosis, then delaying treatment until after delivery to avoid fetal exposureto chemotherapy is desirable. If there is a greater sense of urgency to begin definitive

1578185 – McGraw-Hill Professional ©

treatment to avoid compromising maternal prognosis, and the patient is beyond 24weeks of gestation but remote from her delivery date, then treatment (surgical, medical,or both) might be initiated during pregnancy and plans made to deliver the fetus earlyto avoid exposure to more chemotherapy than absolutely necessary. Since neonatalprognosis is most closely linked to gestational age at delivery, decisions regardingtiming of delivery should include input from Maternal-Fetal Medicine, Neonatology, andOncology. Finally, if the patient is in her first trimester and toxic chemotherapy must beinitiated promptly to avoid a very poor maternal outcome, then it may be necessary toconsider therapeutic abortion to avoid maternal disaster and fetal survival with injuryresulting in long-term morbid sequelae. In general, pregnancy has relatively little or noimpact on the natural history of malignancies, despite the hormonal influences. Spreadof the mother’s cancer to the fetus (so-called vertical transmission) is exceedingly rare.

NEUROLOGIC DISORDERSFor women with epilepsy planning pregnancy, consideration should be given to switchingfrom valproate, a known teratogen, to another medication. If valproate is continued duringpregnancy, folic acid supplementation should be increased to 4 mg daily.

Patients with preexisting multiple sclerosis (Chap. 436) experience a gradual decreasein the risk of relapses as pregnancy progresses and, conversely, an increase in attack riskduring the postpartum period. Disease-modifying agents, including interferon β, should notbe administered to pregnant multiple sclerosis patients, but moderate or severe relapsescan be safely treated with pulse glucocorticoid therapy. Finally, certain tumors, particularlypituitary adenoma and meningioma (Chap. 373), may manifest during pregnancybecause of accelerated growth, possibly driven by hormonal factors.

Peripheral nerve disorders associated with pregnancy include Bell’s palsy (idiopathicfacial paralysis) (Chap. 438), which is approximately threefold more likely to occur duringthe third trimester and immediate postpartum period than in the general population.Therapy with glucocorticoids should follow the guidelines established for nonpregnantpatients. Entrapment neuropathies are common in the later stages of pregnancy,presumably as a result of fluid retention. Carpal tunnel syndrome (median nerve) presentsfirst as pain and paresthesia in the hand (often worse at night) and later with weakness inthe thenar muscles. Treatment is generally conservative; wrist splints may be helpful, andglucocorticoid injections or surgical section of the carpal tunnel can usually be postponed.Meralgia paresthetica (lateral femoral cutaneous nerve entrapment) consists of pain andnumbness in the lateral aspect of the thigh without weakness. Patients are usuallyreassured to learn that these symptoms are benign and can be expected to remitspontaneously after the pregnancy has been completed. Restless leg syndrome is themost common peripheral nerve and movement disorder in pregnancy. Disordered ironmetabolism is the suspected etiology. Management is expectant in most cases.

GASTROINTESTINAL AND LIVER DISEASEUp to 90% of pregnant women experience nausea and vomiting during the first trimesterof pregnancy. Hyperemesis gravidarum is a severe form that prevents adequate fluid andnutritional intake and may require hospitalization to prevent dehydration and malnutrition.

Crohn’s disease may be associated with exacerbations in the second and thirdtrimesters. Ulcerative colitis is associated with disease exacerbations in the first trimester

1578185 – McGraw-Hill Professional ©

and during the early postpartum period. Medical management of these diseases duringpregnancy is similar to management in the nonpregnant state (Chap. 319).

Exacerbation of gallbladder disease is common during pregnancy. In part, thisaggravation may be due to pregnancy-induced alteration in the metabolism of bile andfatty acids. Intrahepatic cholestasis of pregnancy is generally a third-trimester event.Profound pruritus may accompany this condition, and it may be associated with increasedfetal mortality. Placental bile salt deposition may contribute to progressive uteroplacentalinsufficiency. Therefore, regular fetal surveillance should be undertaken once thediagnosis of intrahepatic cholestasis is made, and delivery should be planned once thefetus reaches about 37 weeks of gestation. Favorable results with ursodiol have beenreported.

Acute fatty liver is a rare complication of pregnancy. Frequently confused with theHELLP syndrome (see “Preeclampsia” above) and severe preeclampsia, the diagnosis ofacute fatty liver of pregnancy may be facilitated by imaging studies and laboratoryevaluation. Acute fatty liver of pregnancy is generally characterized by markedly increasedserum levels of bilirubin and ammonia and by hypoglycemia. Management of acute fattyliver of pregnancy is supportive; recurrence in subsequent pregnancies has been reported.

All pregnant women should be screened for hepatitis B. This information is importantfor pediatricians after delivery of the infant. All infants receive hepatitis B vaccine. Infantsborn to mothers who are carriers of hepatitis B surface antigen should also receivehepatitis B immune globulin as soon after birth as possible and preferably within the first72 h. Screening for hepatitis C is recommended for individuals at high risk for exposure.

INFECTIONS

BACTERIAL INFECTIONSOther than bacterial vaginosis, the most common bacterial infections during pregnancyinvolve the urinary tract (Chap. 130). Many pregnant women have asymptomaticbacteriuria, most likely due to stasis caused by progestational effects on ureteral andbladder smooth muscle and later in pregnancy due to compression effects of theenlarging uterus. In itself, this condition is not associated with an adverse outcome ofpregnancy. If asymptomatic bacteriuria is left untreated, symptomatic pyelonephritis mayoccur. Indeed, ~75% of pregnancy-associated pyelonephritis cases are the result ofuntreated asymptomatic bacteriuria. All pregnant women should be screened with a urineculture for asymptomatic bacteriuria at the first prenatal visit. Subsequent screening withnitrite/leukocyte esterase strips is indicated for high-risk women, such as those with sicklecell trait or a history of urinary tract infections. All women with positive screens should betreated. Pregnant women who develop pyelonephritis need inpatient IV antibioticadministration due to the elevated risk of urosepsis and acute respiratory distresssyndrome in pregnancy. Pregnant women with recurrent urinary tract infections, or oneepisode of pyelonephritis, should be considered for daily antibiotic suppressive treatmentthroughout the remainder of their pregnancy.

All pregnant patients are screened prenatally for syphilis, gonorrhea, and chlamydialinfections, and the detection of any of these should result in prompt evaluation andtreatment (Chaps. 151 and 184).

VIRAL INFECTIONS

1578185 – McGraw-Hill Professional ©

Zika Virus (ZV)        ZV can be transmitted from mother to fetus throughout gestation andoften results in fetal death, severe microcephaly, or other malformations of the centralnervous system. Pregnant symptomatic women with relevant epidemiologic exposurewithin 2 weeks of symptom onset should have serum and urine tested for ZV ribonucleicacid by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Testing 2–12weeks after symptom onset utilizes serum measurement of Zika and dengue virus IgM.Sequential obstetrical ultrasound is recommended to assess for fetal growth andanomalies. Couples considering pregnancy should avoid travel to areas with knownmosquito transmission of ZV.

Influenza (See also Chap. 195) Pregnant women with influenza are at increased risk ofserious complications and death. All women who are pregnant or plan to becomepregnant in the near future should receive inactivated influenza vaccine. The promptinitiation of antiviral treatment is recommended for pregnant women in whom influenza issuspected. Treatment can be reconsidered once the results of high- sensitivity tests areavailable. Prompt initiation of treatment lowers the risk of admission to an intensive careunit and death.

Cytomegalovirus Infection The most common cause of congenital viral infection in theUnited States is cytomegalovirus (CMV) (Chap. 190). As many as 50–90% of women ofchildbearing age have antibodies to CMV, but only rarely does CMV reactivation result inneonatal infection. More commonly, primary CMV infection during pregnancy creates arisk of congenital CMV. No currently accepted treatment of CMV infection duringpregnancy has been demonstrated to protect the fetus effectively. Moreover, it is difficultto predict which fetus will sustain a life-threatening CMV infection. Severe CMV disease inthe newborn is characterized most often by petechiae, hepatosplenomegaly, and jaundice.Chorioretinitis, microcephaly, intracranial calcifications, hepatitis, hemolytic anemia, andpurpura may also develop. CNS involvement, resulting in the development of psychomotor,ocular, auditory, and dental abnormalities over time, has been described. Women with aprimary CMV infection should delay conception for 6 months.

Rubella (See also Chap. 201)    Rubella virus is a known teratogen; first-trimester rubellacarries a high risk of fetal anomalies, though the risk significantly decreases later inpregnancy. Congenital rubella may be diagnosed by percutaneous umbilical-bloodsampling with the detection of IgM antibodies in fetal blood. All pregnant women and allwomen of childbearing age should be tested for their immune status to rubella. All womenwho might become pregnant and who are not immune to rubella should be vaccinated atleast 3 months before conception.

Herpesvirus Infection (See also Chap. 187) The acquisition of genital herpes duringpregnancy is associated with spontaneous abortion, prematurity, and congenital andneonatal herpes. A cohort study of pregnant women without evidence of previousherpesvirus infection demonstrated that ~2% acquired a new herpesvirus infection duringthe pregnancy. Approximately 60% of the newly infected women had no clinicalsymptoms. Infection occurred with equal frequency in all three trimesters. If herpesvirusseroconversion occurred early in pregnancy, the risk of transmission to the newborn wasvery low. In women who acquired genital herpes shortly before delivery, the risk oftransmission was high. The risk of active genital herpes lesions at term can be reduced by

1578185 – McGraw-Hill Professional ©

prescribing acyclovir for the last 4 weeks of pregnancy to all women who had an episodeof genital herpes during the pregnancy.

Herpesvirus infection in the newborn can be devastating. Disseminated neonatalherpes carries with it high mortality and morbidity rates from CNS involvement. It isrecommended that pregnant women with active genital herpes lesions at the time ofpresentation in labor be delivered by cesarean section.

Parvovirus Infection (See also Chap. 192)        Parvovirus infection (caused by humanparvovirus B19) may occur during pregnancy. It rarely causes sequelae, but susceptiblewomen infected during pregnancy may be at risk for fetal hydrops secondary to erythroidaplasia and profound anemia.

HIV Infection (See also Chap. 197)    The predominant cause of HIV infection in childrenis transmission of the virus from mother to newborn during the perinatal period. Allpregnant women should be screened for HIV infection. Factors that increase the risk ofmother-to-newborn transmission include high maternal viral load, low maternal CD4+ Tcell count, prolonged labor, prolonged duration of membrane rupture, and the presence ofother genital tract infections, such as syphilis or herpes. Prior to the widespread use ofantiretroviral treatment, the perinatal transmission rate was in the range of 20%. In womenwith a good response to antiretroviral treatment, the transmission rate is about 1%.Measurement of maternal plasma HIV RNA copy number guides the decision for vaginalversus cesarean delivery. For women with <1000 copies of plasma HIV RNA/mL who arereceiving combination antiretroviral therapy, the risk of transmission to the newborn is~1% regardless of mode of delivery or duration of membrane rupture. These women mayelect to attempt a vaginal birth following the spontaneous onset of labor. For women witha viral load of ≥1000 copies/mL prior to 38 weeks of gestation, a scheduled prelaborcesarean at 38 weeks is recommended to reduce the risk of HIV transmission to thenewborn.

VACCINATIONS(See also Chap. 118) For rubella-nonimmune individuals contemplating pregnancy,measles-mumps-rubella vaccine should be administered, ideally at least 3 months prior toconception, but otherwise in the immediate postpartum period. In addition, pregnancy isnot a contraindication for vaccination against influenza, tetanus, diphtheria, and pertussis(Tdap), and these vaccines are recommended for appropriate individuals.

MATERNAL MORTALITYMaternal death is defined as death occurring during pregnancy or within 42 days ofcompletion of pregnancy from a cause related to or aggravated by pregnancy, but not dueto accident or incidental causes. The maternal mortality ratio is the number of maternaldeaths per 100,000 live births. From 1935 to 2007, the U.S. maternal mortality ratiodecreased from nearly 600/100,000 births to 12.7/100,000 births. Since 2007, the U.S.maternal mortality ratio has increased to 21.5/100,000 births. There are significant healthdisparities in the maternal mortality ratio. In the United States, in the period from 2005 to2014, the maternal mortality ratios (per 100,000 live births) by race were 11.3 amongHispanic women, 14.1 among non-Hispanic white women, and 40.2 among non-Hispanicblack women. The most common causes of maternal death in the United States today arepulmonary embolism, obstetric hemorrhage, hypertension, sepsis, cardiovascular

1578185 – McGraw-Hill Professional ©

conditions (including peripartum cardiomyopathy and stroke), and ectopic pregnancy.Specialists in internal medicine play an important role in national efforts to reduce thematernal mortality ratio.

As stated above, the maternal mortality ratio in the United States is about21.5/100,000 live births. In some countries in sub-Saharan Africa and southern Asia, thematernal mortality ratio is >500/100,000 live births. The most common causes ofmaternal death in these countries are maternal hemorrhage, hypertensive disorders,infection, obstructed labor, and complications from unsafe pregnancy termination. Thehealth interventions that would have the greatest impact on maternal health includeimproving the following components of the health system: (1) access to contraceptiveservices in order to space births and limit total family size; (2) access to safe pregnancytermination; (3) presence of trained birth attendants at all deliveries; and (4) transportationto emergency obstetrical centers that can provide intensive medical and surgical services,including cesarean delivery. Maternal death is a global public-health tragedy that could bemitigated with the application of modest resources.

SUMMARYWith improved diagnostic and therapeutic modalities as well as advances in the treatmentof infertility, more patients with serious medical complications will be seeking to becomepregnant and will require complex obstetric care. Improved outcomes of pregnancy inthese women will be best attained by a team of internists, maternal- fetal medicine (high-risk obstetrics) specialists, pediatricians and anesthesiologists assembled to counselthese patients about the risks of pregnancy and to plan their treatment prior to, andfollowing, conception. The importance of preconception counseling cannot be overstated.It is the responsibility of all physicians caring for women in the reproductive age group toassess their patients’ reproductive plans as part of their overall health evaluation.

ACKNOWLDGEMENTThe authors are grateful to Michael F. Greene and Dan L. Longo for their contributions tothe content on neoplasia in pregnancy based upon material from previous editions ofHarrison’s.

FURTHER READINGBRASIL P et al: Zika virus infection in pregnant women in Rio de Janeiro-preliminary report.

N Engl J Med 375:2321, 2016.ESPOSITO S et al: Chemotherapy against cancer during pregnancy: A systematic review on

neonatal outcomes. Medicine (Baltimore) 95:e4899, 2016.LEFEVRE ML et al: Low-dose aspirin use for the prevention of morbidity and mortality from

preeclampsia: U.S. Preventive Services Task Force recommendations statement. AnnInt Med 161:819, 2014.

MOADDAB A et al: Health care disparities and state-specific pregnancy- related mortality inthe United States, 2005–2014. Obstet Gynecol 126:869, 2016.

STEWART ZA et al: Closed-loop insulin delivery during pregnancy in women with Type 1Diabetes. N Engl J Med 375:644, 2016.

WARE JS et al: Shared genetic predisposition in peripartum and dilated cardiomyopathies.N Engl J Med 374:233, 2016.

1578185 – McGraw-Hill Professional ©

467 Medical Evaluation of the Surgical PatientPrashant Vaishnava, Kim A. Eagle

Cardiovascular and pulmonary complications continue to account for major morbidityand mortality in patients undergoing noncardiac surgery. Emerging evidence-basedpractices dictate that the internist should perform an individualized evaluation of thesurgical patient to provide an accurate preoperative risk assessment and stratification thatwill guide optimal perioperative risk-reduction strategies. This chapter reviewscardiovascular and pulmonary preoperative risk assessment, emphasizing the goal-directed management of patients at elevated risk for adverse cardiovascular outcomes inthe perioperative period. In addition, perioperative management of diabetes mellitus andprophylaxis of endocarditis and for venous thromboembolism are reviewed.

EVALUATION OF INTERMEDIATE- AND HIGH-RISK PATIENTSSimple, standardized preoperative screening questionnaires, such as the one shown inTable 467-1, have been developed for the purpose of identifying patients at intermediateor high risk who may benefit from a more detailed clinical evaluation. Evaluation of suchpatients for surgery should always begin with a thorough history and physicalexamination and with a 12-lead resting electrocardiogram, in accordance with theAmerican College of Cardiology/American Heart Association guidelines. The historyshould focus on symptoms of occult cardiac or pulmonary disease. The urgency of thesurgery should be determined, as true emergency procedures are associated withunavoidably higher morbidity and mortality risk. Preoperative laboratory testing should becarried out only for specific clinical conditions, as noted during clinical examination. Thus,healthy patients of any age who are undergoing elective surgical procedures withoutcoexisting medical conditions should not require any testing unless the degree of surgicalstress may result in unusual changes from the baseline state.

TABLE 467-1 Standardized Preoperative Questionnairea

1578185 – McGraw-Hill Professional ©

aUniversity of Michigan Health System patient information report. Patients who answer yes to any of questions2–9 should receive a more detailed clinical evaluation.

Source: Adapted from KK Tremper, P Benedict: Anesthesiology 92:1212, 2000; with permission.

PREOPERATIVE CARDIAC RISK ASSESSMENTA stepwise approach to cardiac risk assessment and stratification in patients undergoingnoncardiac surgery is illustrated in Fig. 467-1. The evaluation begins with characterizationof the combined surgical and clinical risk into categories of low (<1%) and elevated risk formajor adverse cardiovascular events (MACE). Select surgeries are associated with verylow risk for MACE; these surgeries and procedures include select ophthalmologic surgeries(e.g., cataract surgery), select endoscopic procedures, and select superficial procedures.Patients undergoing these low-risk procedures should proceed to surgery without furthertesting. Clinical risk may be estimated with the American College of Surgeons NationalSurgical Quality Improvement Program (NSQIP) risk calculator(http://www.riskcalculator.facs.org) or with calculation of the Revised Cardiac Risk Index(RCRI).

1578185 – McGraw-Hill Professional ©

FIGURE 467-1 Composite algorithm for cardiac risk assessment and stratification in patientsundergoing noncardiac surgery. Preoperative evaluation involves a stepwise clinical evaluation. Those

1578185 – McGraw-Hill Professional ©

individuals requiring emergency surgery should proceed without further risk stratification. Acutecoronary syndrome (step 2) should be evaluated and treated, accordingly to goal-directed medicaltherapy. For patients awaiting non-emergent 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 perioperative (<1%) risk and no further clinicaltesting is generally necessary. For those procedures associated with elevated risk, an assessment offunctional capacity informs the decision for further testing. Those individuals with moderate or greaterfunctional capacity do not require further testing and should proceed to surgery. Individuals with pooror unknown functional capacity may require pharmacologic stress testing if it would change decision-making or perioperative care. (From LA Fleisher et al: Circulation 2014;130:e278-e333, with permission.)

Previous studies have compared several cardiac risk indices. The American College ofSurgeons’ National Surgical Quality Improvement Program prospective database hasidentified five predictors of perioperative myocardial infarction (MI) and cardiac arrestbased on increasing age, American Society of Anesthesiologists class, type of surgery,dependent functional status, and abnormal serum creatinine level. However, given itsaccuracy and simplicity, the RCRI (Table 467-2) is often the favored risk index. The RCRIrelies on the presence or absence of six identifiable predictive factors: high-risk surgery,ischemic heart disease, congestive heart failure, cerebrovascular disease, diabetesmellitus treated with insulin, and renal insufficiency with a creatinine >2.0 mg/dL. Each ofthese predictors is assigned one point. The risk of major cardiac events—defined as MI,pulmonary edema, ventricular fibrillation or primary cardiac arrest, and complete heartblock—can then be predicted. Based on the presence of none, one, two, three, or more ofthese clinical predictors, the rate of development of one of these four major cardiac eventsis estimated to be 0.4, 0.9, 7, and 11%, respectively (Fig. 467-2). An RCRI score of 0signifies a 0.4–0.5% risk of cardiac events; RCRI 1, 0.9–1.3%; RCRI 2, 4–7%; and RCRI ≥3,9–11%. The clinical utility of the RCRI is to identify patients with three or more predictorswho are at very high risk (≥11%) for cardiac complications and who may benefit fromfurther risk stratification with noninvasive cardiac testing, initiation of preoperativepreventive medical management, or avoidance of surgery.

1578185 – McGraw-Hill Professional ©

FIGURE 467-2 Risk stratification based on the revised cardiac risk index; derivation and prospectivevalidation of a simple index for prediction of cardiac risk in patients undergoing major noncardiacsurgery. Cardiac events include myocardial infarction, pulmonary edema, ventricular fibrillation, cardiacasystole, and complete heart block. (Adapted from TH Lee et al: Circulation 100:1043, 1999.)

TABLE 467-2 Clinical Markers Included in the Revised Cardiac Risk Index

High-Risk Surgical ProceduresVascular surgery (except carotid endarterectomy)Major intraperitoneal or intrathoracic proceduresIschemic Heart DiseaseHistory of myocardial infarctionCurrent angina considered to be ischemicRequirement for sublingual nitroglycerinPositive exercise testPathological Q-waves on ECGHistory of PCI and/or CABG with current angina considered to be ischemicCongestive Heart FailureLeft ventricular failure by physical examinationHistory of paroxysmal nocturnal dyspneaHistory of pulmonary edemaS3 gallop on cardiac auscultationBilateral rales on pulmonary auscultationPulmonary edema on chest x-ray

1578185 – McGraw-Hill Professional ©

Cerebrovascular DiseaseHistory of transient ischemic attackHistory of cerebrovascular accidentDiabetes MellitusTreatment with insulinChronic Renal InsufficiencySerum creatinine >2 mg/dL

Abbreviations: CABG, coronary artery bypass grafting; ECG, electrocardiogram; PCI, percutaneous coronaryinterventions.Source: Adapted from TH Lee et al: Circulation 100:1043, 1999.

For patients at elevated combined clinical and surgical risk for MACE, the stepwiseperioperative cardiac assessment for coronary artery disease (CAD) proceeds withconsideration of functional capacity. Participation in activities of daily living offers anexpression of functional capacity, often expressed in terms of metabolic equivalents(METs). For predicting perioperative events, poor exercise tolerance has been defined asthe inability to walk four blocks or climb two flights of stairs at a normal pace or to meet aMET 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 467-3).Patients with moderate or greater (≥4 METs) functional capacity (e.g., climbing up a flightof stairs, walking up a hill, or walking on level ground at 4 mph) generally should notundergo further non-invasive cardiac testing prior to elective non-cardiac surgery. Thosepatients with poor (<4 METs) or unknown functional capacity should undergopharmacological stress testing if the results of such testing would impact decision-making or perioperative care.

TABLE 467-3 Assessment of Cardiac Risk by Functional Status

PREOPERATIVE NONINVASIVE CARDIAC TESTING FOR RISKSTRATIFICATIONThere is little evidence to support widespread application of preoperative noninvasivecardiac testing for all patients undergoing major surgery. The current paradigm to guidethe need for noninvasive cardiac testing is to perform such testing in patients with poor orunknown capacity if it would alter clinical management or modify perioperative care.Options for pharmacological stress testing include dobutamine stress echocardiographyor myocardial perfusion imaging with coronary vasodilator stress (dipyridamole,adenosine, or regadenoson) with thallium-201 and/or technetium-99m. Routine screeningwith noninvasive stress testing is not recommended in patients at low risk for noncardiacsurgery. Furthermore, coronary revascularization before noncardiac surgery is not

1578185 – McGraw-Hill Professional ©

recommended for the express purpose of reducing perioperative cardiac events. That said,revascularization before noncardiac surgery should be considered in patients if it would beindicated regardless of the surgery planned and instead according to clinical practiceguidelines. In the Coronary Artery Revascular Prophylaxis trial, there were no differences inperioperative and long-term cardiac outcomes with or without preoperative coronaryrevascularization; of note, patients with left main disease were excluded.

RISK MODIFICATION: PREVENTIVE STRATEGIES TO REDUCE CARDIAC RISK

Perioperative Coronary Revascularization    Prophylactic coronary revascularization witheither 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 notrecommended for patients with stable CAD before noncardiac surgery. Although PCI isassociated with lower procedural risk than is CABG in the perioperative setting, theplacement of a coronary artery stent soon before noncardiac surgery may increase the riskof bleeding during surgery if dual antiplatelet therapy (DAPT) (aspirin and thienopyridine)is administered; moreover, stent placement shortly before noncardiac surgery increasesthe perioperative risk of MI and cardiac death due to stent thrombosis if such therapy iswithdrawn prematurely (Chap. 270). It is recommended that, if possible, electivenoncardiac surgery be delayed 30 days after placement of a bare metal intracoronarystent and ideally for 6 months after deployment of a drug-eluting stent. Contemporarystent platforms allow for greater flexibility in the earlier interruption of DAPT; currentclinical practice guidelines do suggest consideration of elective noncardiac surgery 6months after drug eluting stent (DES) implantation if the risk of further delaying surgeryexceeds the risk of stent thrombosis/myocardial ischemia. For patients who must undergononcardiac surgery early (>14 days) after PCI, balloon angioplasty without stentplacement appears to be a reasonable alternative because DAPT is not necessary in suchpatients.

PERIOPERATIVE PREVENTIVE MEDICAL THERAPIES    The goal of perioperative preventive medicaltherapies with β-adrenergic antagonists, hydroxymethylglutaryl-coenzyme A (HMG-CoA)reductase inhibitors (statins), and antiplatelet agents is to reduce perioperative adrenergicstimulation, ischemia, and inflammation, all of which are heightened during theperioperative period.

B-ADRENERGIC ANTAGONISTS    The use of perioperative beta blockade should be based on athorough 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 hasshifted in recent years owing, firstly, to the publication of the PeriOperative IschemicEvaluation (POISE) trial demonstrating that, while perioperative beta blockade reduces theperioperative risk for MI, this is at the expense of increased death and stroke. RegardingPOISE, this trial has been criticized for the use of an excessive dose of beta blocker in theperioperative period and one that may not be reflective of clinical practice, nor one thatwas titrated in the days or weeks preceding the procedure or surgery. Secondly, researchmisconduct has discredited the Dutch Echocardiographic Cardiac Risk EvaluationApplying Stress Echocardiography (DECREASE) family of studies, which previously

1578185 – McGraw-Hill Professional ©

contributed to the bedrock of data supporting the use of perioperative beta blockade buthave now been retracted.

Current guidelines emphasize the following key points:1. Continuation of beta blockade in patients undergoing surgery and who have been

receiving such therapy chronically.2. Avoidance of beta-blocker withdrawal or initiation on the day of surgery.3. Consideration of initiation of beta-blocker therapy perioperatively (ideally far enough in

advance to assess safety and tolerability) in very select high-risk patients, namely,those with intermediate- or high-risk ischemia or three more RCRI risk factors.

HMG-COA REDUCTASE INHIBITORS (STATINS)        A number of prospective and retrospectivestudies support the perioperative prophylactic use of statins for reduction of cardiaccomplications in patients with established atherosclerosis. For patients undergoingnoncardiac surgery and currently taking statins, statin therapy should be continued toreduce perioperative cardiac risk. Initiation of statin therapy is reasonable for patientsundergoing vascular surgery independent of clinical risk. Perioperative initiation of statintherapy should be considered in patients undergoing elevated risk procedures if there is anindication for such therapy separate from the surgery and according to clinical practiceguidelines.

ANGIOTENSIN-CONVERTING ENZYME (ACE) INHIBITORS It is important to maintain continuity oftherapy with ACE inhibitors (when such therapy is used for the treatment of heart failure orhypertension).

ORAL ANTIPLATELET AGENTS The 4- to 6-week period following implantation of anintracoronary stent (bare metal or drug eluting) constitutes the period of time of greatestrisk for the development of stent thrombosis. If possible, noncardiac surgery should beavoided in this vulnerable period. The duration of DAPT thereafter is dictated by thecircumstances in which PCI was performed and whether the indication was stableischemic heart disease or acute coronary syndrome. For the former among patientstreated with a drug eluting stent, dual anti-platelet therapy should be given for at least 6months. For the latter, dual anti-platelet therapy should be given for at least 12 months.However, DAPT may be interrupted to allow for noncardiac surgery 30 days after BMS and6 months after DES, respectively. If P2Y12 inhibitor therapy (clopidogrel, prasugrel, orticagrelor) is interrupted or discontinued in patients who have received intracoronarystents, aspirin should be continued perioperatively (save select circumstances where therisk of bleeding may be catastrophic as in neurosurgical or spinal procedures) and theP2Y12 receptor inhibitor should be restarted as soon as possible post-operatively.Decisions surrounding antiplatelet management in the perioperative setting amongpatients who have received intracoronary stents are complex and should involvemultidisciplinary decision-making.

α2 AGONISTS Based on the results of POISE-2 (a large multicenter, international, blindedrandomized clinical trial of aspirin and clonidine), α2 agonists for prevention of cardiacevents are not recommended in patients who are undergoing noncardiac surgery. In thistrial, clonidine increased the rate of nonfatal cardiac arrest and clinically importanthypotension, while reducing the rate of death or nonfatal MI.

1578185 – McGraw-Hill Professional ©

CALCIUM CHANNEL BLOCKERS Evidence is lacking to support the use of calcium channelblockers as a prophylactic strategy to decrease perioperative risk in major noncardiacsurgery.

ANESTHETICS Mortality risk is low with safe delivery of modern anesthesia, especiallyamong low-risk patients undergoing low-risk surgery (Table 467-4). Inhaled anestheticshave predictable circulatory and respiratory effects: all decrease arterial pressure in adose- dependent manner by reducing sympathetic tone and causing systemicvasodilation, myocardial depression, and decreased cardiac output. Inhaled anestheticsalso cause respiratory depression, with diminished responses to both hypercapnia andhypoxemia, in a dose-dependent manner; in addition, these agents have a variable effecton heart rate. Prolonged residual neuromuscular blockade also increases the risk ofpostoperative pulmonary complications due to reduction in functional residual lungcapacity, loss of diaphragmatic and intercostal muscle function, atelectasis, and arterialhypoxemia from ventilation-perfusion mismatch.

TABLE 467-4 Gradation of Mortality Risk of Common Noncardiac Surgical Procedures

Several meta-analyses have shown that rates of pneumonia and respiratory failure arelower among patients receiving neuroaxial anesthesia (epidural or spinal) rather thangeneral anesthesia. However, there were no significant differences in cardiac eventsbetween the two approaches. Evidence from a meta-analysis of randomized controlledtrials 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 forvenous thromboembolism prophylaxis (see below) and postoperative epiduralcatheterization must be considered.

PREOPERATIVE PULMONARY RISK ASSESSMENTPerioperative pulmonary complications occur frequently and lead to significant morbidityand mortality. Clinical practice guidelines recommend the following:1. All patients undergoing noncardiac surgery should be assessed for risk of pulmonary

complications (Table 467-5).

TABLE 467-5 Predisposing Risk Factors for Pulmonary Complications

1578185 – McGraw-Hill Professional ©

1. Upper respiratory tract infection: cough, dyspnea2. Age >60 years3. Chronic obstructive pulmonary disease4. Cigarette use5. American Society of Anesthesiologists Class ≥26. Functional dependence7. Congestive heart failure8. Serum albumin <3.5 g/dL9. Obstructive sleep apnea10. Impaired sensorium (confusion, delirium, or mental status changes)11. Abnormal findings on chest examination12. Alcohol use13. Weight loss14. Spirometry threshold before lung resection

a. FEV1 <2 Lb. MVV <50% of predictedc. PEF <100 L or 50% predicted valued. PCO2 ≥45 mmHg

e. PO2 ≤50 mmHg

2. Patients undergoing emergency or prolonged (3–4 h) surgery; aortic aneurysm repair;vascular surgery; major abdominal, thoracic, neurologic, head, or neck surgery; andgeneral anesthesia should be considered to be at elevated risk for postoperativepulmonary complications.

3. Patients at higher risk of pulmonary complications should undergo incentivespirometry, deep-breathing exercises, cough encouragement, postural drainage,percussion and vibration, suctioning and ambulation, intermittent positive-pressurebreathing, continuous positive airway pressure, and selective use of a nasogastric tubefor postoperative nausea, vomiting, or symptomatic abdominal distention to reducepostoperative risk. Multiple pulmonary risk indices are available to estimate thepostoperative risk of respiratory failure, pneumonia, and other pulmonarycomplications; among these is the ARISCAT risk index, which accounts for thefollowing seven risk factors: age, low preoperative oxygen saturation, respiratoryinfection within the preceding month, upper abdominal or thoracic surgery, surgerylasting >2 h, and emergency surgery (Table 467-6).

TABLE 467-6 Risk Modification to Reduce Perioperative Pulmonary Complications

Preoperatively• Cessation of smoking for at least 8 weeks before and until at least 10 days after

surgery• Training in proper lung expansion techniques• Inhalation bronchodilator and/or steroid therapy, when indicated

1578185 – McGraw-Hill Professional ©

• Control of infection and secretion, when indicated• Weight reduction, when appropriateIntraoperatively• Limited duration of anesthesia• Avoidance of long-acting neuromuscular blocking drugs, when indicated• Prevention of aspiration and maintenance of optimal bronchodilationPostoperatively• 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

4. Preoperative spirometry and chest radiography should not be used routinely forpredicting risk of postoperative pulmonary complications but may be appropriate forpatients with chronic obstructive pulmonary disease or asthma.

5. Spirometry is of value before lung resection in determining candidacy for coronaryartery bypass; however, it does not provide a spirometric threshold for extrathoracicsurgery below which the risks of surgery are unacceptable.

6. Pulmonary artery catheterization, administration of total parenteral nutrition (asopposed to no supplementation), or total enteral nutrition have no consistent benefit inreducing postoperative pulmonary complications.

PERIOPERATIVE MANAGEMENT AND PROPHYLAXIS

DIABETES MELLITUS(See also Chaps. 396–398) Many patients with diabetes mellitus have significantsymptomatic or asymptomatic CAD and may have silent myocardial ischemia due toautonomic dysfunction. Intensive (versus lenient) glycemic control in the perioperativeperiod is generally not associated with improved outcomes, and may increase the risk ofhypoglycemia. Practice guidelines advocate a target glucose range from 100 to 180mg/dL in the perioperative period. Oral hypoglycemic agonists should not be given on themorning of surgery. Perioperative hyperglycemia should be treated with IV infusion ofshort-acting insulin or SC sliding-scale insulin. Patients whose diabetes is diet controlledmay proceed to surgery with close postoperative monitoring.

INFECTIVE ENDOCARDITIS(See also Chap. 123) Prophylactic antibiotics should be administered to the followingpatients before dental procedures that involve manipulation of gingival tissue,manipulation of the periapical region of teeth, or perforation of the oral mucosa: thosewith prosthetic cardiac valves (including transcatheter prosthetic valves); prostheticmaterial used in valve repair (annuloplasty ring or artificial chord); previous infectiveendocarditis; cardiac transplant recipients with valvular regurgitation from a structurallyabnormal valve; and unrepaired cyanotic congenital heart disease or repaired congenital

1578185 – McGraw-Hill Professional ©

heart disease, with residual shunts or valvular regurgitation at the site of adjacent to thesite of a prosthetic patch or prosthetic device.

VENOUS THROMBOEMBOLISM(See also Chap. 273) Perioperative prophylaxis of venous thromboembolism shouldfollow established guidelines of the American College of Chest Physicians. Aspirin is notsupported as a single agent for thromboprophylaxis. Low-dose unfractionated heparin(≤5000 units SC bid), low-molecular weight heparin (e.g., enoxaparin, 30 mg bid or 40 mgqd), or a pentasaccharide (fondaparinux, 2.5 mg qd) is appropriate for patients atmoderate risk; unfractionated heparin (5000 units SC tid) is appropriate for patients athigh risk. Graduated compression stockings and pneumatic compression devices areuseful supplements to anticoagulant therapy or in patients at excessive bleeding risk.

FURTHER READINGFLEISHER LA et al: 2014 ACC/AHA Guideline on perioperative cardiovascular evaluation

and management of patients undergoing noncardiac surgery. Circulation 130:e278,2014.

LEVINE GN et al: 2016 ACC/AHA guideline focused update on duration of dual antiplatelettherapy in patients with coronary artery disease. A Report of the American College ofCardiology/American Heart Association Task Force on Clinical Practice Guidelines. JAm Coll Cardiol 68:1082, 2016.

NISHIMURA RA et al: 2017 AHA/ACC focused update of the 2014 AHA/ACC guideline forthe management of patients with valvular heart disease. A report of the AmericanCollege of Cardiology/American Heart Association Task Force on clinical practiceguidelines. Circulation 135:1, 2017.

SMETANA GW et al: American College of Physicians. Preoperative pulmonary riskstratification for noncardiothoracic surgery: Systematic review for the AmericanCollege of Physicians. Ann Intern Med 144:581, 2006.