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6/11/2019 1/33 Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8e Chapter 297: The Transplant Patient J. Hayes Calvert INTRODUCTION As of the beginning of 2013, there were 76,047 active candidates waiting for solid-organ transplants in the United States, with the kidney transplant waitlist being the largest at 57,903 candidates. 1 The kidney is the most commonly transplanted organ (58%), followed by liver (21%), heart (8%), lung (5%), pancreas (5%), and, less commonly, combined organ transplants and intestine transplants. Annually, there are around 18,000 hematopoietic stem cell transplants in the United States, with about one third of these transplants being allogenic transplants and two thirds being autologous transplants. 2 Most transplant patients require lifelong immunosuppression. Transplant patients can develop a number of acute to life-threatening emergencies, including (1) transplant-related infection, (2) medication side eects, (3) rejection, (4) gra-versus-host disease, and (5) postoperative complications or complications of altered physiology secondary to the transplanted organ. Transplant patients may also have common medical problems that require unique management. Adverse outcomes oen are directly proportional to increasing age of the recipient and the donor organ. 3 The most common acute disorders prompting ED visits are infection (39%) followed by noninfectious GI/GU pathology (15%), dehydration (15%), electrolyte disturbances (10%), cardiopulmonary pathology (10%) or injury (8%), and rejection (6%). 4,5,6,7 Acute gra-versus-host disease is an important complication, especially in those with hematopoietic stem cell transplantation. 8 Coronary artery disease, sudden cardiac death, and heart failure are results of premature cardiovascular disease in solid-organ recipients, due to underlying comorbidities and metabolic eects of immunosuppression. 9 Preoperative and regular postoperative cardiovascular assessment identifies risk factors and enables treatment to mitigate risk eects. 10 GENERAL APPROACH TO EVALUATION HISTORY AND COMORBIDITIES Key historical elements for the management of transplant patients are listed in Table 297-1.
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GENERAL APPROACH TO EVALUATION

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Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8e

Chapter 297: The Transplant Patient J. Hayes Calvert

INTRODUCTION

As of the beginning of 2013, there were 76,047 active candidates waiting for solid-organ transplants in the United

States, with the kidney transplant waitlist being the largest at 57,903 candidates.1 The kidney is the mostcommonly transplanted organ (58%), followed by liver (21%), heart (8%), lung (5%), pancreas (5%), and, lesscommonly, combined organ transplants and intestine transplants. Annually, there are around 18,000hematopoietic stem cell transplants in the United States, with about one third of these transplants being allogenic

transplants and two thirds being autologous transplants.2

Most transplant patients require lifelong immunosuppression. Transplant patients can develop a number of acuteto life-threatening emergencies, including (1) transplant-related infection, (2) medication side e�ects, (3) rejection,(4) gra�-versus-host disease, and (5) postoperative complications or complications of altered physiologysecondary to the transplanted organ. Transplant patients may also have common medical problems that requireunique management. Adverse outcomes o�en are directly proportional to increasing age of the recipient and the

donor organ.3

The most common acute disorders prompting ED visits are infection (39%) followed by noninfectious GI/GUpathology (15%), dehydration (15%), electrolyte disturbances (10%), cardiopulmonary pathology (10%) or injury

(8%), and rejection (6%).4,5,6,7 Acute gra�-versus-host disease is an important complication, especially in those

with hematopoietic stem cell transplantation.8 Coronary artery disease, sudden cardiac death, and heart failureare results of premature cardiovascular disease in solid-organ recipients, due to underlying comorbidities and

metabolic e�ects of immunosuppression.9 Preoperative and regular postoperative cardiovascular assessment

identifies risk factors and enables treatment to mitigate risk e�ects.10

GENERAL APPROACH TO EVALUATION

HISTORY AND COMORBIDITIES

Key historical elements for the management of transplant patients are listed in Table 297-1.

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TABLE 297-1

Key Historical Elements Specific to Transplant Patients

Historical Item Significance

Recent temperature increase or decrease from baseline Potential clue to onset of infection or rejection.

Changes from baseline function Decreased urine may signify rejection in renal

transplant patients or acute dehydration.

Decreased exercise tolerance may signify rejection in

heart transplant patients.

Change in skin color (jaundice specifically) may signify

rejection in liver transplant patients or gra�-versus-

host disease.

Date of transplant surgery The date from transplant helps to predict typical

infections and types of posttransplant complications

(i.e., gra�-versus-host disease).

Gra� source for solid-organ transplant, special features

of gra� if any, prior infections; donor living related vs

cadaveric

These details predict the potential for certain

infections and rejection.

Gra� source for hematopoietic stem cell transplant:

autologous, degree of match, related donor

These details predict potential gra�-versus-host

disease.

Rejection history May predict current rejection if similar presentation

and di�iculty in controlling a current episode of

rejection.

Recent changes in dosages of antirejection and other

medications

Although a planned part of transplant management,

rejection is very common when immunosuppression

doses are reduced.

Chronic infections (CMV, Epstein-Barr virus, hepatitis B

and C, other viruses)

History of chronic infections increases the chances

that current presentation is an exacerbation.

Recent exposure to infections (chickenpox, CMV,

tuberculosis)

Increases the chance of current infection.

Recent history of compliance with immunosuppressive

medications

Noncompliance increases chance of rejection.

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Abbreviation: CMV = cytomegalovirus.

Historical Item Significance

Recent travel, exposure to persons arriving from

countries with endemic infections, exposure to potential

foodborne illness or insect vectors

Exposure may predict unusual infections not

commonly considered.

Complete list of all medications, including over-the-

counter medication

Complex drug interactions are common causes of

symptoms in transplant patients and must be

evaluated.

Baseline: blood pressure, body weight, serum creatinine

(for renal transplants), and expected levels of

immunosuppressive medication

Changes in these parameters may predict rejection or

acute illness.

PHYSICAL EXAMINATION

Direct the physical examination to the chief complaint, present illness, and evidence of complications of the

transplant or immunosuppressive medications (Table 297-2).4,5,6,7,8,11,12

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TABLE 297-2

Physical Examination in Transplant Patients

Examination Comments

Volume status Check static vital signs, orthostatic blood pressures, and pulse. Use US to assess inferior vena

cava diameter as a measure of intravascular volume status.

Head, ears, eyes,

nose, and throat

Periorbital edema (glomerulonephritis), retina (CMV or toxoplasmic chorioretinitis, Listeria

endophthalmitis), sinuses (Staphylococcus aureus, mucormycosis, and invasive fungal

disease), mouth (Candida, HSV), neck (meningismus, retropharyngeal abscess),

lymphadenopathy (CMV, EBV, hepatitis, posttransplant lymphoproliferative disorder).

Lungs Pneumonia is a common source of infections in transplant patients. Streptococcus

pneumoniae and other community-acquired agents are still common sources, but

opportunistic infections, such as Pneumocystis jiroveci pneumonia, Aspergillus, tuberculosis,

coccidioidomycosis, and viral pneumonias should be suspected. Noninfectious pulmonary

infiltrates may also cause dyspnea.

Heart Pericardial friction rubs as a complication of uremia and a wide range of viral infections. New

heart murmur can represent infection.

Abdomen Peritonitis without a defined source is one of the most common sites for infection in transplant

patients. Right upper quadrant tenderness associated with hepatitis B and C, CMV, and EBV.

Varicella-zoster virus causes pancreatitis. If le� in place, peritoneal dialysis catheters can be

sources of infection.

Flank and

suprapubic area

The urinary tract was the most common site of infection identified.

Gra� Renal gra� usually placed in abdominal flap; inspect (look for signs of wound infection),

palpate (gra� tenderness and swelling are o�en seen in acute rejection, outflow obstruction,

and pyelonephritis), and auscultate (bruits suggest renal artery stenosis and AV malformation

or AV fistula). Deep tenderness over liver gra� could indicate abscess.

Rectal Perirectal abscess is a common, yet o�en overlooked, source of infection in transplant

patients.

Extremities Access sites for hemodialysis can be sources of infection. Peripheral edema in the transplant

patient can represent a number of di�erent etiologies: recurrent versus de novo

glomerulonephritis, renal gra� failure, liver gra� failure, cirrhosis, nephrotic syndrome (from

native kidneys), renal vein thrombosis, malnutrition, hypoalbuminemia, and heart failure.

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Abbreviations: AV = atrioventricular; CMV = cytomegalovirus; EBV = Epstein-Barr virus; HSV = herpes simplex virus.

Examination Comments

Skin Rashes are commonly seen in gra�-versus-host disease, viral syndromes (hepatitis B and EBV),

cellulitis from indwelling catheter sites, nocardial cutaneous lesions, and drug reactions.

Mental

status/neurologic

examination

Cyclosporine/tacrolimus neurotoxicity, steroid psychosis, HSV encephalitis, Listeria

meningitis/encephalitis, and cryptococcal meningitis.

DIFFERENTIAL DIAGNOSIS

Consider complications of immunosuppressive medication, infection, solid-organ rejection, and gra�-versus-hostdisease (Tables 297-3 and 297-4). Chronic immunosuppressant medications, including corticosteroids, cause awide range of physical changes evident on physical examination. Medication changes should be made by, or inconsultation with, the patient's transplant team. Outpatient or inpatient management depends on the severity ofillness; the need for ongoing immunosuppression o�en requires admission when symptoms interruptmaintenance of medication.

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TABLE 297-3

Adverse Reactions to Immunosuppressant Medications

Body System Adverse E�ects

Constitutional Fever, rigors, malaise, dizziness, anorexia

Ophthalmologic Blurred vision, conjunctivitis, cataracts, papilledema, blindness

Mouth/ears Gingival hyperplasia, stomatitis, hearing loss, tinnitus

Respiratory Cough, dyspnea, interstitial lung disease, pneumonitis, pleural e�usion, noncardiogenic

pulmonary edema

Cardiovascular Hypertension, tachycardia, bradycardia, cardiomyopathy, congestive heart failure, hypotension,

syncope

GI Nausea, vomiting, diarrhea, epigastric pain, esophagitis, gastritis, hiccups, constipation,

hepatotoxicity, ascites, pancreatitis, colonic necrosis, bleeding

Musculoskeletal Myopathy, osteoporosis, tendon rupture

Hematologic Neutropenia, lymphopenia, anemia, thrombocytopenia, bleeding, thrombosis

Renal Nephrotoxicity, oliguria, dysuria, renal failure

Neurologic Headache, vertigo, paresthesias, tremors, convulsions, agitation, neuropathy, confusion,

generalized weakness, leukoencephalopathy, encephalopathy, cerebral edema

Skin Alopecia, hirsutism, thickening, thinning, necrosis, edema

Metabolic Electrolyte disturbances (sodium, potassium, calcium, magnesium, phosphorus), fluid

retention, hypercholesterolemia, hyperlipidemia, hyperglycemia, hypoglycemia

Endocrine Adrenal suppression

Immunogenic Susceptibility to infection, acute allergic reactions, anaphylaxis

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TABLE 297-4

Physical Examination Clues to Complications of Medications and Gra�-versus-Host Disease

Concern Signs and Symptoms

Edema and other

swelling

Assess symmetry, pain, color, temperature, and active range of motion. Suspect infection,

orthopedic conditions, deep vein thrombosis (due to immobility).

Skin breakdown The back, pressure points, heels, elbows, and leg ulcers (due to corticosteroid-induced

weakness).

Joint range of

motion

Shoulders, elbows, fingers, wrists, and knees (may be limited due to steroid-induced weakness

or sclerodermatous skin changes).

Thoracic

constriction

Relatively noncompliant edema like swelling on the chest wall. If present, ask about

associated dyspnea on exertion.

Abdominal

constriction

Firm skin. History of bloating, gas, constipation, diarrhea, nonspecific pains.

Sclerodermatous

skin

Sclerodermatous skin changes can a�ect joint mobility and GI and respiratory function. Note

the firmness of edema and skin, especially on the thorax and around joints. A firm, so� leather

consistency of swelling, tougher than cardiogenic pitting edema, can be a serious problem.

Assess for recent-onset dyspnea on exertion.

Dehydration Increased thirst, loss of appetite, chills, fatigue, weakness, skin flushing, dark or decrease

volume of urine, dry mouth, tachycardia, weight loss.

Electrolyte

disturbance

Signs and symptoms of dehydration above, hypotension, headache, bradycardia or

tachycardia, irregular heartbeat, tremor, muscle weakness, increased urination, constipation,

altered tendon reflexes, mood changes, abdominal pain, weight loss, muscle cramping.

Solid-organ rejection and gra�-versus-host disease are immune-medicated inflammatory reactions that maypresent with fever, signs and symptoms, and laboratory and radiographic findings that resemble infection.Infection and rejection (or an exacerbation of gra�-versus-host disease) can occur simultaneously, and treatmentshould be started for both. When suspecting acute rejection or acute gra�-versus-host disease, consult thetransplant team about treatment. Typically, high-dose corticosteroids are given, but the steroid, the dose, and theduration of therapy should be confirmed.

POSTTRANSPLANT INFECTIONS

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Infections account for a large number of deaths in transplant patients, with many undiagnosed until autopsy. Viraland bacterial illnesses may occur concurrently. Febrile episodes in the early phase a�er allogenic stem celltransplantation are likely related to infections secondary to neutropenia. Immunosuppression-induced blunting ofthe inflammatory response may mask the classic signs, symptoms, and laboratory markers of infection if thepatient presents early in the course of the illness. Later in the course of infection, patients may present with moreadvanced ominous signs such as seizure, obtundation, coma, and cardiac arrest.

CLINICAL FEATURES

The most common reason for an ED visit by a transplant recipient is fever.4,5,6,7 Fever may be masked byimmunosuppressive agents and other factors such as steroids, uremia, and hyperglycemia, and may be absent in

half of those with infection.5 Fever may be due to factors other than infection, such as drug e�ects,hypersensitivity reaction, rejection, or malignancy. Fever in a transplant patient should prompt an aggressiveworkup, even if low grade.

Signs and symptoms of infection depend on the type of infection and can, in part, be predicted by the time frame

since the transplant (Table 297-5).13 Combining all posttransplant period groups, urinary tract infections (43%)

and pneumonia (23%) are likely to be the most common infections.11 In contrast, a study of 238 ED presentationsof febrile pediatric heart transplant patients found pneumonia in 24%, bacteremia in 3%, cellulitis in 2%, and

urinary tract infection in 1%; the majority had a negative workup.12

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TABLE 297-5

Infections Stratified by Posttransplant Period

Period a�er

Transplant/ConditionsInfection Comments

<1 mo: resistant

organisms

MRSA

Vancomycin-resistant

Enterococcus faecalis

Candida species

(including non-

albicans)

Opportunistic infections are generally absent during this

period as full e�ect of immunosuppression not complete.

MRSA important in HSCT patients.

<1 mo: complications

of surgery and

hospitalization

Aspiration

Catheter infection

Wound infection

Anastomotic leaks and

ischemia

C. di�icile colitis

Clostridium di�icile common during this period. Early gra�

injuries may abscess. Unexplained early signs of infection such

as hepatitis, encephalitis, pneumonitis, or rash may be donor

derived.

<1 mo: colonization of

transplanted organ or

HSCT neutropenia

Aspergillus

Pseudomonas

Klebsiella

Legionella

Microbiologic analysis of aspirates or biopsy from surgery

essential for therapeutic decisions.

<1 mo: HSCT-specific

infections

Additional bacterial

pathogens:

Streptococcus

viridans and

enterococci

Viral infections

include respiratory

syncytial virus and

HSV

Neutropenia and mucocutaneous injury increase risk for HSCT

patients. Lungs, bloodstream, and GI tract most commonly

a�ected sites.

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Period a�er

Transplant/ConditionsInfection Comments

1–6 mo: in patients

with Pneumocystis

jiroveci pneumonia

and antiviral (CMV,

HBV) prophylaxis

Polyomavirus BK

infection,

nephropathy

C. di�icile colitis

HCV infection

Adenovirus infection,

influenza

Cryptococcus

neoformans infection

Mycobacterium

tuberculosis infection

Anastomotic

complications

Activation of latent infections, relapse, residual, and

opportunistic infections occur during this period. Viral

pathogens and allogra� rejection cause the majority of febrile

episodes during this period. Polyomavirus BK, adenovirus

infections, and recurrent HCV are becoming more common.

1–6 mo: in patients

without prophylaxis

Pneumocystis

Infection with

herpesviruses (HSV,

varicella-zoster virus,

CMV, Epstein-Barr

virus)

HBV infection

Infection with Listeria,

Nocardia,

Toxoplasma,

Strongyloides,

Leishmania,

Trypanosoma cruzi

Discontinuation of prophylaxis at the end of this period may

prompt active infection, especially CMV. Gra�-versus-host

disease and mucocutaneous injury increase risk for HSCT

patients.

>6 mo: general Community-acquired

pneumonia and

urinary tract

infections

Infection with

Aspergillus, atypical

molds, Mucor species

Infection with

Nocardia,

Rhodococcus species

Community-acquired organisms dominate during this period.

Transplant recipients have a persistently increased risk of

infection due to community-acquired pathogens.

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Abbreviations: CMV = cytomegalovirus; HBV = hepatitis B virus; HCV = hepatitis C virus; HSCT = hematopoietic stem cell

transplant; HSV = herpes simplex virus; MRSA = methicillin-resistant Staphylococcus aureus; PTLD = posttransplantation

lymphoproliferative disorder.

Period a�er

Transplant/ConditionsInfection Comments

>6 mo: late viral

infections

CMV infection (colitis

and retinitis)

Hepatitis (HBV, HCV)

HSV encephalitis

Community-acquired

viral infections (severe

acute respiratory

syndrome, West Nile)

JC polyomavirus

infection (progressive

multifocal

leukoencephalopathy)

Skin cancer,

lymphoma (PTLD)

In some patients, chronic viral infections may cause allogra�

injury (e.g., cirrhosis from HCV infection in liver transplant

recipients, bronchiolitis obliterans in lung transplant

recipients, accelerated vasculopathy in heart transplant

recipients with CMV infection) or a malignant condition such as

PTLD or skin or anogenital cancers.

DIAGNOSIS AND TREATMENT

The evaluation should include routine testing as well as additional tests based on complaint, history, and physical

examination (Table 297-6).14

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TABLE 297-6

Diagnostic Tests to Consider in the Evaluation of Infections in the Transplant Patient

Test Comments

CBC Leukocytosis or le� shi� of the WBC count may be blunted by immunosuppressive

agents.

Renal function tests:

BUN, creatinine

Essential in the evaluation of renal transplant patients, may help determine dosing of

antibiotics in all transplant patients.

Liver function tests May show mild transaminase elevations with cytomegalovirus and Epstein-Barr virus

infections, and much higher elevations with hepatotropic viruses such as hepatitis B and

C viruses. May be elevated in Legionella infections.

C-reactive protein Significant elevations more likely in infections versus noninfectious infiltrates.

Procalcitonin level Significant elevations more likely in infections versus noninfectious infiltrates.

CT of the brain Focal infections in the brain are much more common in this population, but CT should

be used only as clinically indicated.

Cyclosporine or

tacrolimus level or

other levels of

immunosuppressants

These levels may be deliberately low depending on the desired level of

immunosuppression. Bioavailability may be variable.

Cultures of mouth,

sputum, urine, blood,

stool, vascular access,

and wound sites

Collect as indicated by history and physical. Urine Legionella antigen should be

considered before treatment of patients with pneumonia with GI complaints. Bacterial

and fungal cultures of blood and urine should be obtained on all patients.

Cerebrospinal fluid

cultures and antigen

tests

Collect as indicated by history and physical.

Serology:

cytomegalovirus,

Epstein-Barr virus,

hepatitis,

toxoplasmosis,

cryptococcosis

Because viral and fungal cultures are not very sensitive, clinicians should rely on their

acumen to order organism-specific antigen assays and antibody titers. When

contemplating viral or parasitic infections, these tests should be obtained to allow

identification of bacterial, fungal, and viral pathogens.

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Test Comments

Chest radiograph Infiltrates on chest radiograph may reflect infectious or noninfectious complications of

hematopoietic stem cell transplant or organ transplant.

CT of the chest Patients with evidence of pulmonary infiltrates on chest x-ray or high-resolution CT, but

without productive sputum, may ultimately require bronchoscopy with bronchoalveolar

lavage and transbronchial biopsy for definitive diagnosis.

CT or US to include the

gra�

These scans can be used to identify likely abscess formation or possible anastomotic

leaks.

Tests a�er admission Beyond the scope of this chapter, but may include biopsy of the transplanted organ,

bronchoalveolar lavage on bronchoscopy, and focused imaging of suspected sites of

infection.

Creatine kinase May have increased levels in infections with certain organisms, such as Legionella.

Leukopenia can represent acute bacterial infection,5 and leukopenia with an increase in atypical lymphocytes iscommonly seen with viral infections, especially cytomegalovirus. Pulmonary infections that are encounteredfrequently include Pneumocystis jiroveci, Nocardia, Legionella pneumophila, and Aspergillus; these requirespecial stains and studies for accurate diagnosis.

Treatment recommendations should be determined by careful analysis of each individual patient for potentialatypical infections requiring specific coverage. Empiric antimicrobial therapy for transplant patients is outlined in

Table 297-7.15,16,17 Empiric treatment prior to confirmatory studies centers first on antibacterial agents, and then,especially if there is concern for meningitis/encephalitis, on antiviral agents such as acyclovir. Discuss treatmentof suspected fungal infections or atypical infections with the transplant team.

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TABLE 297-7

Empiric Antimicrobial Therapy

Condition Antimicrobial Agent Comments*

All patients Discuss agent(s) with

transplant team.

The transplant team caring for the patient should always be consulted as

soon as possible; however, in certain life-threatening situations, empiric

broad-coverage therapy may be indicated immediately.

Suspected

infection

site based

on history

and physical

examination

Site-specific agents

are preferable if

predicted by initial

findings, balanced by

known pathogens as

listed in Table 297-5.

The urgency for treatment should be based on the patient's presenting

condition; bacterial infections are the most aggressive organisms

requiring coverage, but some fungal infections may yield sepsis. In

general, broad coverage for any suspected site infection is recommended

initially pending cultures and further workup to define noninfectious

causes of fever.

Neutropenia

in the

absence of

symptoms

suggesting

site-specific

infection

Third-generation

cephalosporin such

as ce�azidime or a

carbapenem plus

coverage for MRSA

below.

Multiple alternative agents used, including an aminopenicillin plus a β-

lactam inhibitor such as piperacillin-tazobactam or cefepime.

Monotherapy has fewer complications, but concern for MRSA remains

high. Addition of antiviral and antifungal agents should be at the

discretion of the transplant team.

Suspected

MRSA

Vancomycin In the majority of patients, MRSA infection should be seriously considered

as a potential cause of infection, pending cultures. Linezolid is an

alternative antibiotic.

Parasitic

infections

Trimethoprim-

sulfamethoxazole

a�er discussion with

transplant team

Consider Toxoplasma gondii, Pneumocystis jiroveci.

Viral

infections

Ganciclovir or

valganciclovir for

CMV, acyclovir for

herpes simplex and

varicella-zoster

Consider treatment for CMV pneumonia, CMV chorioretinitis, CNS or

disseminated herpes simplex or varicella-zoster.

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Abbreviations: CMV = cytomegalovirus; MRSA = methicillin-resistant Staphylococcus aureus.

*Standard doses apply but may be altered by transplant team recommendations.

Condition Antimicrobial Agent Comments*

Fungal

infections

Discuss with

transplant team;

agent depends on site

and severity of illness

Consider Aspergillus, Candida albicans, Cryptococcus neoformans.

GRAFT-VERSUS-HOST DISEASE

Gra�-versus-host disease is a major cause of morbidity and mortality a�ecting approximately 50% of allogeneic

hematopoietic stem cell transplantation patients,18 but it also occurs a�er small bowel or liver transplantation.19

Hyperacute gra�-versus-host disease is an unusual and severe form of acute gra�-versus-host disease. Onsetoccurs in the first week a�er hematopoietic stem cell transplantation and is characterized by fever, generalized

erythroderma, severe hepatitis, fluid retention, widespread inflammation, and shock.20

Acute gra�-versus-host disease is classified as appearance of the disease up to 100 days a�er transplant. A well-appearing hematopoietic stem cell transplantation recipient with a nonspecific rash (most common symptom) ordiarrhea (second most common symptom) should be suspected of having new-onset or an exacerbation of gra�-

versus-host disease.20 The most widely used gra�-versus-host prophylaxis includes a combination of a calcineurin

inhibitor (e.g., cyclosporine, tacrolimus) with methotrexate.20 In patients who recover from acute gra�-versus-hostdisease, later long-term complications from chronic gra�-versus-host disease are common.

Chronic gra�-versus-host disease is a late complication characterized by immune dysregulation.21 It results insevere morbidity, with complications a�ecting skin (sclerodermatous contractures), muscles (myopathy), bone

(osteoporosis), nerves (peripheral neuropathy), and the cardiopulmonary system (physical deconditioning).22

ACUTE GRAFT-VERSUS-HOST DISEASE

Consider gra�-versus-host disease in any patient with a rash. Rash is o�en misattributed as a drug reaction. Thetypical rash is maculopapular, frequently demonstrating a brownish hue and slight scaling (Figure 297-1). The rashcan be pruritic and painful. The distribution varies greatly but o�en a�ects palms and soles initially, and laterprogresses to cheek, ears, neck, trunk, chest, and upper back. In the more severe forms, erythroderma or bullae

develop.8 Mucositis has been reported to occur in 35% to 70% of patients.

FIGURE 297-1.

Rash of acute cutaneous gra�-versus-host disease. The maculopapular lesions have acquired a brownish hue, andthere is slight scaling. [Reproduced with permission from Wol� KL, Johnson R, Suurmond R: Fitzpatrick's Color

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Atlas & Synopsis of Clinical Dermatology, 6th ed. © 2009, McGraw-Hill, New York.]

Diarrhea, GI bleeding, or hepatic dysfunction can occur. Diarrhea, with or without upper GI symptoms such asanorexia, nausea, and emesis, is common. Symptoms include painful cramping, ileus, and, sometimes, life-threatening hemorrhage from the colon. Hepatic involvement is characterized by increase in liver function studies.GI hemorrhage in the early posttransplant period may be a result of coagulation abnormalities, especiallythrombocytopenia. The di�erential diagnosis of GI bleeding in this setting includes all the usual causes of GIbleeding in addition to bleeding due to acute gra�-versus-host disease–related damage to colonic tissues and

infection (viral, fungal, or bacterial).18,23 Diagnosis requires endoscopy.

Treatment is directed by the transplant team, typically PO prednisone or IV methylprednisolone, at 1 to 2

milligrams/kg daily, and possibly adjustment of other immunosuppressant doses.8

Disposition and interval for follow-up are also determined by the transplant team.

TRANSFUSION-ASSOCIATED GRAFT-VERSUS-HOST DISEASE

Most living cells that are in transfused blood survive for no more than a few days or weeks. However, in somepatients, transfused cells engra�, expand, and circulate. When immunocompetent T lymphocytes engra� in animmune-suppressed patient, transfusion-associated gra�-versus-host disease may occur and is almost always

fatal.24,25 It is possible to avoid transfusion-associated gra�-versus-host disease by irradiating blood productsbefore transfusion. Patients with immunocompromise or other risk factors (Table 297-8) should receive irradiatedblood products.

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TABLE 297-8

Significant Risk Factors for the Development of Transfusion-Associated Gra�-versus-Host Disease

Congenital and acquired immunodeficiency syndromes

History of bone marrow (stem cell) transplantation, whether allogeneic or autologous

Transfusions from blood relatives ("directed donation")

Transfusions with fresh whole blood

Premature infants receiving any sort of transfusion

Human leukocyte antigen–matched platelet transfusions

Hodgkin's disease, even when in remission

Leukemia not in remission

Patients treated with purine analogs; the e�ects of fludarabine and cladribine (2-CdA) persist for a year

SPECIFIC TYPES OF TRANSPLANTATION

RENAL TRANSPLANTATION

Renal transplantation is the preferred treatment for end-stage renal disease. Vascular complications that occurfollowing renal transplantation include renal artery stenosis, allogra� infarction, arteriovenous fistulas,pseudoaneurysm, and renal vein thrombosis. Nonvascular complications include ureteral obstruction, urine leak,periallogra� fluid collections (hematomas, lymphoceles, and abscesses), neoplasms, GI complications, and

posttransplant lymphoproliferative disease.26 The major causes of renal transplant loss are death from vascular,malignant, or infectious disease, and loss of the allogra� from chronic renal dysfunction associated with thedevelopment of gra� fibrosis and glomerulosclerosis. Medication changes, as well as imaging contrast agent usethat may a�ect renal function (including gadolinium-based contrast agents), should be discussed with thepatient's transplant team.

DIAGNOSTIC TESTING

Table 297-6 lists recommendations on diagnostic testing in transplant patients, including renal transplantpatients. The serum creatinine level is the most valuable prognostic marker of gra� function at all times a�ertransplantation and should be obtained whenever renal failure or infection is suspected. The urinalysis providesimportant clues to acute changes in gra� viability. Red blood cell casts and proteinuria are commonly seen inrecurrent or de novo glomerulonephritis. The presence of WBCs, bacteria, and nitrites is helpful in diagnosingurinary tract infections. Proteinuria may signal rejection, drug toxicity, glomerular disease, or other gra�nephropathy, although proteinuria from a remaining native kidney should also be considered. Obtaincyclosporine or tacrolimus blood levels for all patients on these medications. Contact the patient's transplantteam regarding abnormal drug levels, because low drug levels are sometimes deliberately used to reduce sidee�ects.

IMAGING

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Ultrasonography is the best test to detect urinary obstruction. Renal gra� ultrasonography can also be useful inpatients suspected of having pyelonephritis, vascular abnormalities (stenosis, thrombosis, pseudoaneurysm, andarteriovenous fistula), perinephric abscess, urine leak, wound infection, or an episode of rejection.

MRI can be helpful in evaluating hematomas and other fluid collections, vascular abnormalities, and small infarctscaused by medication-induced vasculitis. Magnetic resonance angiography has the advantage of requiring eitherno contrast material or a gadolinium chelate that is less nephrotoxic than other agents. However, gadolinium-based contrast agents can cause acute renal failure in up to 3.5% of patients with underlying chronic renal

insu�iciency.27 Therefore, the patient's transplant team should be consulted before using gadolinium-basedcontrast agents.

GRAFT DYSFUNCTION AND FAILURE

Chronic renal dysfunction precedes the majority of gra� failures. Acute renal failure in transplant patients isdefined as a 20% rise from baseline serum creatinine levels, as opposed to a 50% rise in other patients with acuterenal failure. Consider the conditions described in Table 297-9 when evaluating possible gra� dysfunction or even

a small increase in serum creatinine.28,29

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TABLE 297-9

Di�erential Diagnosis of Renal Allogra� Dysfunction

Deferential Disorder Comments

Mechanical At ultrasonography, a urine leak (i.e., urinoma) appears as a

well-defined, anechoic fluid collection with no septations

that increases in size rapidly. Complications of surgery

Ureteral obstruction

Urine leak: urinoma, ascites, or abscess

Vascular The transplanted kidney is usually placed extraperitoneally

in the right iliac fossa. End-to-side anastomosis to the

external iliac vasculature provides circulation. Color duplex

imaging of the renal artery and vein is helpful in assessing

renal vascular stenosis or thrombosis.

Renal artery stenosis or thrombosis (12%)

Renal vein thrombosis

Renal artery and renal vein thrombosis are

uncommon; they usually occur in the first month

a�er transplant.

Glomerulonephritis

Infection Urinary tract infections are the most common source of

bacteremia in renal transplant recipients, and infectious

diseases are the second leading cause of death in this

population. See "Posttransplant Infections" section.

Urinary tract infection

Interstitial nephritis from polyoma BK virus,

cytomegalovirus, herpes viruses 1 and 2, and

adenovirus

Rejection Most common presentation of rejection in renal transplant

patients is hypertension and falling urine output.

Comparison of creatinine at the time of presentation to

prior levels is critical. Fever may be a presentation for

rejection.

Hyperacute

Acute

Late (recurrent acute)

Chronic cellular

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Deferential Disorder Comments

Chronic humoral

Recurrent pyelonephritis/vesicoureteral reflux —

Nephrotoxic agents Drug serum levels do not correlate well with the degree of

renal damage. Nonsteroidal anti-inflammatory drugs are

contraindicated in this group. Avoid contrast agents if

possible.

Aminoglycosides, fluoroquinolones, cidofovir,

foscarnet, sulfonamides, calcineurin inhibitors

(cyclosporin A and tacrolimus), nonsteroidal anti-

inflammatory drugs, gadolinium-based and some

other contrast agents, herbal preparations

Noncompliance with Diabetes o�en follows transplantation; marked

exacerbations in hypertension are frequently associated

with gra� failure. Medications

Management of risk factors such as diabetes and

hypertension

Chronic allogra� nephropathy —

LIVER TRANSPLANTATION

The most common reasons for ED visits are fever and abdominal pain.6 Complications include bleeding, rejection,and infection, as well as biliary, vascular, and wound complications. Bacterial infection may accompany acute

rejection.30 Specific complications of liver transplantation are listed in Table 297-10. Obtain a CBC with plateletcount and di�erential; serum chemistries, including electrolytes, BUN, creatinine, basic coagulation studies, liverfunction tests, amylase, and lipase levels; and cultures of blood, urine, bile, and ascites. Radiographic testing asindicated may include chest x-ray and abdominal ultrasonography with Doppler flow studies. US with Doppler canidentify fluid collections, thrombosis of the hepatic artery or portal vein, and dilatation of the biliary tree(although the absence of biliary dilatation does not exclude obstruction or other posttransplantation pathology).With partial obstruction, the intrahepatic ductal system o�en does not appear to be dilated appreciably by US.With complete obstruction, duct dilation is usually seen. Patients o�en require cholangiography for completeevaluation. Patients with choledochocholedochostomy may be best evaluated by endoscopic retrogradecholangiopancreatography because it permits both a radiographic diagnosis and the potential for nonoperativeintervention. Patients with a Roux-en-Y hepaticojejunostomy or those who cannot have endoscopic retrogradecholangiopancreatography must undergo percutaneous cholangiography. Early, broad-spectrum prophylacticantibiotics should be administered before any biliary tract manipulation. Discuss treatment and disposition withthe transplant team.

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TABLE 297-10

Complications of Liver Transplantation

Complication Comments

Bleeding

complications

GI bleeding should be managed in the usual fashion but may signal gra� dysfunction.

Biliary

complications

Bile leaks present early and biliary strictures present late (>2 mo from transplant). In both cases,

cholestatic liver enzymes are elevated, typically with right upper quadrant pain (more

pronounced with bile leak).

Bile leak

Biliary

stricture

Hepatic artery

complications

CT with contrast (if renal function adequate) or US is helpful in the evaluation of these conditions.

Hepatic

artery

thrombosis

Hepatic

vein

thrombosis

Portal vein

complications

Rejection Early alkaline phosphatase and bilirubin levels rise, followed by a rise in aspartate

aminotransferase and alanine aminotransferase.

Neurologic

complications

Causes include hemorrhage, cerebrovascular infarct, cerebral abscess, hypertensive

encephalopathy, osmotic demyelination syndrome, and sinus thrombosis. MRI is best for

evaluation.

Malignancy Increased risk for squamous cell carcinoma, lymphomas, and posttransplant lymphoproliferative

disorder.

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LUNG TRANSPLANTATION

Fever, cough, and increasing dyspnea are common reasons for ED visits in lung transplant patients. Importantclinical features to note are the respiratory rate, pulse oximetry measurement, and physical findings of cyanosis,diaphoresis, use of accessory muscles, signs of congestive heart failure, and adequacy of peripheral perfusion.Obtain a chest radiograph and arterial blood gas analysis when adequacy of ventilation is in question. Give β2-

agonists and anticholinergics as indicated. Signs of infection o�en overlap with the signs and symptoms ofrejection, and the management of infection is quite di�erent from that of rejection. A drop in the forced expiratoryvolume in 1 second of >10% warrants clinical investigation, but pulmonary function testing cannot distinguishbetween acute rejection, infection, and nonimmunologic causes of respiratory dysfunction such as airway

stenosis.31 Therefore, bronchoscopy is required for specific diagnosis. Lung transplant patients can deterioratevery quickly in the absence of the proper therapy. Thus, it is common practice to cover both infection and rejection

until additional histopathologic and culture results are obtained.32

COMPLICATIONS OF LUNG TRANSPLANTATION

Complications occur most frequently in the first year but can occur at any time starting from the first few weeks

a�er transplant and continue throughout the lifetime of the patient (Table 297-11).32,33 Indications for hospitaladmission are listed in Table 297-12.

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TABLE 297-11

Time Course of Lung Transplant Complications

Days a�er

TransplantComplications Most Commonly Seen in Each Time Period

0–3 d Hemorrhage from technical/mechanical problems

Reperfusion injury

Dysrhythmia

3 d–1 mo Infection: bacterial, mycoplasma, community respiratory viruses

Rejection

Anastomotic failure

Pulmonary embolism

Muscle weakness

Dysrhythmia

Starting at

1 mo

Rejection

Obliterative bronchiolitis

Infection

Bacterial, fungal, community respiratory viral (can occur at any later time)

Mycoplasma 0–4 mo

Mycobacteria a�er 4 mo

Other Cytomegalovirus infection and Pneumocystis jiroveci pneumonia may occur any time, but are more

common when prophylaxis is not being given, especially when such treatment has been recently

discontinued.

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TABLE 297-12

Indications for Hospital Admission for Lung Transplant Patients

Pretransplant patients

Respiratory failure

Infiltrate

Systemic infection

Decompensated congestive heart failure or pulmonary edema

Pneumothorax

Posttransplant patients

Respiratory failure

Acute rejection

Rapidly progressive airflow limitation (forced expiratory volume in 1 second decreases >10% over 48 h)

Infiltrate

Systemic infection

Febrile neutropenia

Pneumothorax

Acute rejection is common and may occur three to six times in the first postoperative year. A�er the first year, thefrequency of acute rejection decreases, but it can occur for several years a�er transplant. Signs of rejection includecough, chest tightness, increase or decrease in temperature from baseline of >0.28°C (0.5°F), hypoxemia, decline inforced expiratory volume in 1 second (10% or more), and infiltrates on the chest radiograph. Radiographicabnormalities are less common >6 weeks a�er transplant, and an acute rejection episode actually may be"radiographically silent" a�er this. Discuss treatment with the transplant team. If the maintenanceimmunosuppressant regimen has been tapered, it can be very helpful to return to pretaper dosages. In addition,high-dose corticosteroids are o�en used to treat acute rejection. The usual dosing regimen is 15 milligrams/kg ofIV methylprednisolone each day for 3 consecutive days. A�er the corticosteroid bolus, if the maintenanceprednisone had been tapered, increasing the prednisone to 1 milligram/kg/d and tapering over the next 10 days

may be helpful.31 Clinical response to treatment is gauged by improvements in oxygenation, spirometry, andradiographic appearance and typically occurs within 24 to 48 hours a�er treatment is initiated. Failure to improveshould suggest infection as an alternative diagnosis. A�er clinical improvement, the maintenance dose ofprednisone is increased, with a slow taper back to baseline.

Pulmonary infections from bacteria, fungi, or viruses are the most common causes of morbidity and mortality in

lung transplant patients34,35 (Tables 297-5 and 297-11). Lung transplant patients are at risk for pneumoniabecause of colonization of the recipient's airway in the setting of transplantation for bronchiectasis and cystic

fibrosis and at risk of aspiration in the presence of gastroesophageal reflux disease.33 Antibiotic selection is bestle� to the lung transplant specialist.

CARDIAC TRANSPLANTATION

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Cardiac transplantation has been applied successfully to patients of all ages, from newborns through persons intheir late 60s. Heart transplantation is indicated for patients with end-stage heart failure not remediable bystandard medical or surgical therapy. Many in the latter group will have undergone previous coronary arterybypass or valve surgery or been bridged on mechanical assist devices. The leading causes of death in those age 60

to 69 are gra� failure and infection.36

The success of a heart transplantation operation depends on the ability of the denervated heart to support thenormal circulation. The lack of sympathetic and parasympathetic innervation does, however, induce an alteredphysiologic state. The denervated heart has a normal sinus rhythm with a heart rate between 90 and 100beats/min. Denervation results in the absence of the initial centrally mediated tachycardia in response to stress orexercise, but the heart remains responsive to circulating catecholamines. Thus, the cardiac response to stress orexertion is blunted. With proper conditioning, patients are able to resume normal activity levels, includingvigorous exercise, following transplantation.

The donor heart is implanted with its own sinus node intact to preserve normal atrioventricular conduction. Thetechnique of cardiac transplantation also results in preservation of the recipient's sinus node at the superiorcavoatrial junction, and the two sinus nodes remain electrically isolated from each other. Thus, ECGs frequentlywill have two distinct P waves (Figure 297-2). The sinus node of the donor heart is easily identified by its constant1:1 relationship to the QRS complex, whereas the native P wave marches through the donor heart rhythmindependently. The presence of the two separate P waves may lead to confusion about the patient's rhythm,mistakenly interpreting sinus rhythm as second-degree heart block. The ECGs may also be interpreted erroneouslyas showing atrial fibrillation, atrial flutter, or frequent premature atrial complexes. Some patients may haveevidence of "cardiomegaly" related to the transplantation of a heart from a donor who was larger than therecipient (Figure 297-3). Clinical evaluation is based on the reason for the ED visit. Chest x-ray, ECG, and furtherevaluation are based on complications of cardiac transplantation (Table 297-13) and underlying patientcomorbidities, especially in elderly transplant recipients.

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TABLE 297-13

Complications a�er Cardiac Transplant

Complication Comments

Altered

physiology

See text in Cardiac Transplantation section.

Dysrhythmias Dysrhythmias a�er transplantation are frequently due to rejection. Treat the unstable patient

presenting in extremis with 1 gram of methylprednisolone IV; delay rejection therapy in the

stable patient for consult with the transplant team and biopsy. Atropine has no e�ect due to

denervation.

Sinus node

dysfunction

Pacemaker usually required.

Pulmonary

complications

Diagnosis may require CT or more invasive diagnostic procedures.

Pneumonia

Thromboembolic

disease

Exercise-

induced

hypoxemia

Pneumothorax

Interstitial

fibrosis

Cardiac ischemia Patients do not experience pain due to denervation; symptoms typically occur with

complications such as congestive heart failure.

Rejection Treat the patient presenting in extremis; withhold treatment for biopsy if possible.

Infection See section "Posttransplant Infections"

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Complication Comments

Congestive heart

failure

Echocardiography can help to determine etiology and therefore ideal treatment.

Ischemic stroke

and intracranial

hemorrhage

Increased risk a�er heart transplant.

Complications

specific to

ventricular assist

devices

Increased risk of infection and thromboembolism.

Cardiac

allographic

vasculopathy

Pediatric heart transplant recipients are at risk for gra� coronary artery disease and ischemia.

May require retransplantation.

FIGURE 297-2.

ECG in a heart transplant patient. ECG demonstrates donor and recipient P waves (arrowhead = donor P wave;arrow = recipient P wave).

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FIGURE 297-3.

Chest radiograph of healthy post–heart transplant patient with typical postoperative changes, including"cardiomegaly" due to transplantation of a heart from a donor who was larger than the recipient.

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1. 

2. 

3. 

4. 

CORNEAL TRANSPLANTATION

Corneal transplantation (penetrating keratoplasty) is the most common form of human solid tissuetransplantation. Unlike other tissue and organ transplants, corneal allotransplantation usually does not requiresystemic or permanent immunosuppression. Reasons for gra� failure include corneal gra� rejection (30.9%),

corneal endothelial cell failure (21.0%), glaucoma (8.5%), and other causes (26.2%).37,38 Ophthalmologyconsultation is required for any change in visual acuity or other ocular signs or symptoms in a patient with acorneal transplant.

Corneal gra� rejection is a specific process in which a gra� that has been clear suddenly develops gra� edemawith anterior segment inflammatory signs. Rejection can occur at any time starting at 10 days a�er transplant. Theinflammatory process starts at the gra� margin nearest to the most proximal blood vessels and then moves

toward the center to involve the entire gra�.37 Signs and symptoms include eye pain, photophobia, corneal orscleral injection, or decreased visual acuity. Examination may reveal unilateral anterior chamber reaction withkeratic precipitate or corneal edema in a previously clear gra�. Late gra� failure can present with gradual onset ofgra� edema with no associated inflammation or keratic precipitates. Treatment includes topical or systemicsteroids, cycloplegics, and immunosuppressive drugs such as local and systemic cyclosporine A and tacrolimus.

Wound dehiscence can occur early or late a�er corneal transplantation, as a result of infection or a�er eye trauma.Trauma may be unrecognized or be a result of events such as motor vehicle airbag deployment or a fall with thepatient's glasses impacting the eye. There may be globe rupture, slight separation of part of the suture line, or justbroken sutures.

Viral,37 bacterial,39 or fungal40 infection can threaten the transplanted cornea. In patients with a history ofherpetic keratitis, consider recurrence and examine with fluorescein for characteristic corneal staining and signs of

anterior chamber inflammation.37 Ophthalmology consultation is needed for diagnosis and treatment.

REFERENCES

2012 Annual Report of the U.S. Organ Procurement and Transplantation Network and the Scientific Registry ofTransplant Recipients: Transplant Data 2012. Department of Health Services, Health Resources and ServicesAdministration, Healthcare Systems Bureau, Division of Transplantation, Rockville, MD; United Network for OrganSharing, Richmond, VA; University Renal Research and Education Association, Ann Arbor, MI.

Zivkovic  S, Abdel-Hamid  H: Neurologic manifestations of transplant complications. Neurol Clin 28: 235, 2010. [PubMed: 19932384]  

Abecassis  M, Bridges  N, Clancy  CJ  et al.: Solid organ transplantation in older adults: Current status and futureresearch. Am J Transplant 12: 2612, 2012.

[PubMed: 22958872]

Unterman  S, Zimmerman  M, Tyo  C  et al.: A descriptive analysis of 1251 solid organ transplant visits to theemergency department. West J Emerg Med 10: 48, 2009.

Page 30: GENERAL APPROACH TO EVALUATION

6/11/2019

30/33

5. 

6. 

7. 

8. 

9. 

10. 

11. 

12. 

13. 

14. 

15. 

[PubMed: 19561769]  

Savitsky  EA, Votey  SR, Mebust  DP  et al.: A descriptive analysis of 290 liver transplant patient visits to anemergency department. Acad Emerg Med 7: 898, 2000.

[PubMed: 10958130]  

Turtay  MG, Oguzturk  H, Aydin  C  et al.: A descriptive analysis of 188 liver transplant patient visits to anemergency department. Eur Rev Med Pharmacol Sci 16 (Suppl 1): 3, 2012.

[PubMed: 22582476]  

Tokalak  I, Basaran  O, Emiroglu  R  et al.: Problems in postoperative renal transplant recipients who present tothe emergency unit: experience at one center. Transplant Proc 36: 184, 2004.

[PubMed: 15013341]  

Couriel  D, Caldera  H, Champlin  R, Komanduri  K: Acute gra�-versus-host disease: pathophysiology, clinicalmanifestations, and management. Cancer 101: 1936, 2004.

[PubMed: 15372473]  

Gillis  KA, Patel  RK, Jardine  AG: Cardiovascular complications a�er transplantation: treatment options in solidorgan recipients. Transplant Rev (Orlando) 28: 47, 2014.

[PubMed: 24412041]  

Glicklich  D, Vohra  P: Cardiovascular risk assessment before and a�er kidney transplantation. Cardiol Rev 22:153, 2014.

[PubMed: 24896248]  

Trzeciak  S, Sharer  R, Piper  D  et al.: Infections and severe sepsis in solid-organ transplant patients admittedfrom a university-based ED. Am J Emerg Med 22: 530, 2004

[PubMed: 15666255]  

Yin  S, Trainor  J, Powell  EC: Serious bacterial infections in febrile outpatient pediatric heart transplantrecipients. Acad Emerg Med 16: 942, 2009

[PubMed: 19799569]  

Fishman  JA: Infection in solid-organ transplant recipients. N Eng J Med 357: 2601, 2007. [PubMed: 18094380]

Stolz  D, Stulz  A, Muller  B  et al.: BAL neutrophils, serum procalcitonin, and C-reactive protein to predictbacterial infection in the compromised host. Chest 132: 504, 2007.

[PubMed: 17573524]  

Linden  PK: Approach to the immunocompromised host with infection in the intensive care unit. Infect Dis ClinNorth Am 23: 535, 2009.

[PubMed: 19665082]  

Page 31: GENERAL APPROACH TO EVALUATION

6/11/2019

31/33

16. 

17. 

18. 

19. 

20. 

21. 

22. 

23. 

24. 

25. 

26. 

Flowers  CR, Seidenfeld  J, Bow  EJ  et al.: Antimicrobial prophylaxis and outpatient management of fever andneutropenia in adults treated for malignancy: American Society of Clinical Oncology clinical practice guideline. JClin Oncol 31: 794, 2013.

[PubMed: 23319691]  

Asberg  A, Humar  A, Rollag  H  et al.: Oral valganciclovir is non-inferior to intravenous ganciclovir for thetreatment of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant 7: 2106, 2007.

[PubMed: 17640310]  

Shidham  VB, Chang  CC, Shidham  G  et al.: Colon biopsies for evaluation of acute gra�-versus-host disease (A-GVHD) in allogeneic bone marrow transplant patients. BMC Gastroenterol 3: 5, 2003.

[PubMed: 12697049]  

Kato  T, Yazawa  K, Madono  K  et al.: Acute gra�-versus-host disease in kidney transplantation: case report andreview of literature. Transplant Proc 41: 3949, 2009.

[PubMed: 19917421]  

Vargas-Diez  E, Garcia-Diez  A, Marin  A, Fernandez-Herrera  J: Life-threatening gra�-vs-host disease. ClinDermatol 23: 285, 2005.

[PubMed: 15896544]  

Baird  K, Pavletic  SZ: Chronic gra� versus host disease. Curr Opin Hematol 13: 426, 2006. [PubMed: 17053454]  

Smith  SR, Haig  AJ, Couriel  DR: Musculoskeletal, neurologic, and cardiopulmonary aspects of physicalrehabilitation in patients with chronic gra�-versus-host disease. Biol Blood Marrow Transplant 23: 1083, 2014.

[PubMed: 25445027]

Hettinga  YM, Verdonck  LF, Fijnheer  R  et al.: Anterior uveitis: a manifestation of gra�-versus-host disease.Ophthalmology 114: 794, 2007.

[PubMed: 17187864]  

Schroeder  ML: Transfusion-associated gra�-versus-host disease. Br J Haematol 117: 275, 2002. [PubMed: 11972509]  

Frey  N, Porter  D: Gra�-versus-host disease a�er donor leukocyte infusions: presentation and management.Best Pract Res Clin Haematol 21: 206, 2008.

[PubMed: 18503987]

Venkat  K, Venkat  A: Care of the renal transplant recipient in the emergency department. Ann Emerg Med 44:330, 2004.

[PubMed: 15459617]  

Page 32: GENERAL APPROACH TO EVALUATION

6/11/2019

32/33

27. 

28. 

29. 

30. 

31. 

32. 

33. 

34. 

35. 

36. 

37. 

38. 

Akgun  H, Gonlusen  G, Cartwright  J  Jr  et al.: Are gadolinium-based contrast media nephrotoxic? Arch PatholLab Med 130: 1354, 2006.

[PubMed: 16948524]  

Chapman  JR, O'Connell  PJ, Nankivell  BJ: Chronic renal allogra� dysfunction. J Am Soc Nephrol 16: 3015,2005.

[PubMed: 16120819]  

Akbar  SA, Jafri  SZ, Amendola  MA  et al.: Complications of renal transplantation. Radiographics 25: 1335, 2005.[PubMed: 16160115]  

Blair  JE, Kusne  S: Bacterial, mycobacterial, and protozoal infections a�er liver transplantation: part I. LiverTranspl 11: 1452, 2005.

[PubMed: 16315310]  

Whelan  TP, Hertz  MI: Allogra� rejection a�er lung transplantation. Clin Chest Med 26: 599, 2005. [PubMed: 16263399]  

Taylor  JL, Palmer  SM: Critical care perspective on immunotherapy in lung transplantation critical careperspective. J Intensive Care Med 21: 327, 2006.

[PubMed: 17095497]  

Granton  J: Update of early respiratory failure in the lung transplant recipient. Curr Opin Crit Care 12: 19, 2006. [PubMed: 16394779]  

Trulock  E, Christie  J, Edwards  L  et al.: Registry of the International Society for Heart and LungTransplantation: Twenty-fourth O�icial Adult Lung and Heart–Lung Transplantation Report—2007. J Heart LungTransplant 26: 782, 2007.

[PubMed: 17692782]  

Budino  B, Martul  E, Diaz  S  et al.: Autopsy-determined causes of death in solid organ transplant recipients.Transplant Proc 36: 787, 2004.

[PubMed: 15110664]  

Salvadori  M, Bertoni  E: What's new in clinical solid organ transplantation by 2013. World J Transplant 4: 243,2014.

[PubMed: 25540734]  

Panda  A, Vanathi  M, Kumar  A  et al.: Corneal gra� rejection. Surv Ophthalmol 52: 375, 2007. [PubMed: 17574064]  

Williams  K, Esterman  A, Bartlett  C  et al.: How e�ective is penetrating corneal transplantation? Factorsinfluencing long-term outcome in multivariate analysis. Transplantation 81: 896, 2006.

Page 33: GENERAL APPROACH TO EVALUATION

6/11/2019

33/33

39. 

40. 

[PubMed: 16570014]  

Wagoner  MD, Al-Swailem  SA, Sutphin  JE  et al.: Bacterial keratitis a�er penetrating keratoplasty: incidence,microbiological profile, gra� survival, and visual outcome. Ophthalmology 114: 1073, 2007.

[PubMed: 17275089]  

Kanavi  MR, Foroutan  AR, Kamel  MR  et al.: Candida interface keratitis a�er deep anterior lamellarkeratoplasty: clinical, microbiologic, histopathologic, and confocal microscopic reports. Cornea 26: 913, 2007.

[PubMed: 17721287]  

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