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doi: 10.4037/ajcc2012163 2012;21:89-98Am J Crit Care

Leah Johnson-Coyle, Louise Jensen and Alan SobeyPeripartum Cardiomyopathy: Review and Practice Guidelines

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By Leah Johnson-Coyle, RN, MN, Louise Jensen, RN, PhD, and Alan Sobey, MD

Peripartum cardiomyopathy, a type of dilated cardiomyopathyof unknown origin, occurs in previously healthy women in thefinal month of pregnancy and up to 5 months after delivery.Although the incidence is lowless than 0.1% of pregnanciesmorbidity and mortality rates are high at 5% to 32%. Theoutcome of peripartum cardiomyopathy is also highly variable.For some women, the clinical and echocardiographic statusimproves and sometimes returns to normal, whereas for oth-ers, the disease progresses to severe cardiac failure and evensudden cardiac death. In acute care, treatment may involvethe use of intravenous vasodilators, inotropic medications, anintra-aortic balloon pump, ventricular-assist devices, and/orextracorporeal membrane oxygenation. Survivors of peripartumcardiomyopathy often recover from left ventricular dysfunction;however, they may be at risk for recurrence of heart failureand death in subsequent pregnancies. Women with chronicleft ventricular dysfunction should be managed according toguidelines of the American College of Cardiology Foundationand the American Heart Association. (American Journal ofCritical Care. 2012;21(2):89-98)

PERIPARTUMCARDIOMYOPATHY: REVIEW AND PRACTICEGUIDELINES

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EpidemiologyThe reported incidence of PPCM varies because

the diagnosis is not always consistent and a com-parison with age-matched nonpregnant women doesnot exist.4,6,7 Reported incidences range from 1 in299 live births in Haiti8 to 1 in 2229 live births inSouthern California9 to 1 in 4000 live births in theUnited States.4 The wide variation most likely is the

result of geographic differences andreporting patterns.10 Also, limited accessto echocardiography in some areasmay lead to overestimation of PPCM.11

Several risk factors predispose awoman to PPCM, including increasedmaternal age, multiparity, multiplepregnancies, and pregnancies compli-cated by preeclampsia and gestationalhypertension.4,6,12 Although PPCMoccurs more frequently in women at

the upper and lower extremes of child-bearing agesand in older women of higher parity,4,13 the diseasehas also been reported in 24% to 37% of youngprimigravid women.3,6,14 In contrast, the results of alarge population-based study from Haiti suggestedthat multiparity and increasing maternal age are notrisk factors.8 Demakis et al12 and Brar et al15 found

that African American women were 2.9 times morelikely to have PPCM than were white women and 7times more likely than were Hispanic women. Thegreater incidence of hypertension in African Ameri-cans may influence this finding.4,7

EtiologyPPCM is distinguished from other forms of

cardiomyopathies by its occurrence during preg-nancy.16 Precise mechanisms that lead to PPCMremain poorly defined. Many etiological processeshave been suggested: viral myocarditis, abnormalimmune response to pregnancy, maladaptive responseto hemodynamic stresses of pregnancy, stress-activatedcytokines, excessive prolactin excretion, and pro-longed tocolysis.4,10,17,18 Also, a familial predispositionto PPCM has been reported.19-21 Although underly-ing genetic variants common to dilated cardiomy-opathies are being proposed,22 a genetic basis specificto PPCM has not been systematically studied.23 TheEuropean Society of Cardiology currently classifiesPPCM as a nonfamilial, nongenetic form of dilatedcardiomyopathy.24

Viral MyocarditisViral myocarditis has been proposed as the main

mechanism for PPCM and was first reported byGoulet et al.25 This proposal was later supported byMelvin et al,26 who found myocarditis during endomy-ocardial biopsy in 3 women with PPCM. The biopsyspecimens had dense lymphocytic infiltration witha variable amount of myocytic edema, necrosis, andfibrosis. Others27 have also reported an associationbetween PPCM and viral myocarditis. In a study byFelker et al,28 62% of women with PPCM hadmyocarditis or borderline myocarditis on biopsy;however, clinical outcomes did not differ betweenwomen with and without myocarditis.

Peripartum cardiomyopathy (PPCM) is a type of dilated cardiomyopathy of unknownorigin. It occurs in previously healthy women in the final month of pregnancy andup to 5 months after delivery.1 Although the incidence is lowless than 0.1% ofpregnanciesmorbidity and mortality rates are high, ranging from 5% to 32%.2,3

For some women, the clinical and echocardiographic status improve and mayreturn to normal, whereas for others, PPCM progresses to cardiac failure and even suddencardiac death.4 In severe cases, women experience a rapid deterioration in health, show noimprovement with medical therapy, and may require cardiac transplantation or die of heartfailure, thromboembolic events, and/or cardiac arrhythmias.5 Thus, initial severity of left ven-tricular dysfunction or dilatation is not necessarily predictive of long-term functional outcome.5

In this article, we review PPCM and present guidelines for practice.

About the AuthorsLeah Johnson-Coyle is a nurse practitioner in cardiacsciences and Alan Sobey is an intensive care physicianin the cardiovascular surgery intensive care unit at theMazankowski Alberta Heart Institute, University of AlbertaHospital, Edmonton, Alberta, Canada. Louise Jensen isa professor in the Faculty of Nursing at the University ofAlberta in Edmonton.

Corresponding author: Louise Jensen, RN, PhD, Professor,Faculty of Nursing, 3rd Floor, Edmonton Clinic HealthAcademy, University of Alberta, Edmonton, AB, CanadaT6G 1C9 (e-mail: [email protected]).

90 AJCCAMERICAN JOURNAL OF CRITICAL CARE, March 2012, Volume 21, No. 2 www.ajcconline.org

Initial severity of left ventricular

dysfunction is not necessarily

predictive of long-term outcome.


erythropoietin, and hence hematocrit levels.18 Hil-fiker-Kleiner et al31 discovered that PPCM developsin mice bred to have a cardiomyocyte-specific dele-tion of STAT3, a protein that plays a key role inmany cellular processes such as cell growth andapoptosis. The deletion of STAT3 led to enhancedexpression of cardiac cathepsin D, promoting theformation of a 16-kD form of prolactin. In womenwith PPCM, STAT3 protein levels were low in theheart, and serum levels of activated cathepsin Dand 16-kD prolactin were elevated.16,31

Selenium and MalnutritionNutritional disorders, such as deficiencies in

selenium and other micronutrients, were thoughtto play a role in the pathogenesis of PPCM.12,26 Defi-ciencies of selenium increase cardiovascular suscep-tibility to viral infections, hypertension, andhypocalcemia. However, Fett et al32 concluded thatneither low serum levels of selenium nor deficien-cies of other micronutrients (vitamins A, B12, C, E,and b-carotene), played a significant role in thedevelopment of PPCM in Haitian women. In con-trast, women with PPCM from theSahelian region of Africa had lowlevels of selenium.33

Prolonged TocolysisProlonged tocolysis refers to

the use of toco lytic agents (b-sym-pathomimetic drugs) for morethan 4 weeks.18 The associationbetween tocolytic therapies andheart failure appears to be uniqueto pregnancy. Tocolytic agents are used for the man-agement of various other conditions without theoccurrence of signs and symptoms of heart failurelike those experienced by pregnant women. Suchsigns and symptoms may develop in pregnantwomen as a result of normal physiological changesthat occur, including an increase in circulatingblood volume.18 Lampert et al34 found an associa-tion between use of tocolytic therapies and develop-ment of pulmonary edema in pregnant women andproposed a link between chronic use of b-sympath-omimetic medications and PPCM.

Clinical Manifestations and DiagnosisFeatures of a normal pregnancy include increased

blood volume, increased metabolic demands, mildanemia, changes in vascular resistance associatedwith mild ventricular dilatation, and increased car-diac output.11 Thus, the onset of PPCM can easily bemaskedand missedbecause the manifestations

Abnormal Immune ResponseAn abnormal immune response to fetal micro -

chimerism (harboring of fetal cells in maternal cir-culation) has been studied as a cause for PPCM.29

Other researchers4,6,16,18 support this theory that dur-ing pregnancy fetal cells released into the maternalbloodstream are not rejected by the mother becauseof the natural immunosuppresion that occurs dur-ing pregnancy. However, after delivery, women losethe increased immunity, and if fetal cells reside oncardiac tissue when the fetus is delivered, a patho-logical autoimmune response can occur, leading toPPCM in the mother after birth.

Abnormal Hemodynamic ResponseDuring pregnancy, blood volume and cardiac

output increase.4 In addition, afterload decreasesbecause of relaxation of vascular smooth muscle.13

These changes cause a brief, and reversible, hyper-trophy of the left ventricle to meet the needs of themother and fetus.2 This transient left ventriculardysfunction during the third trimester and earlypostpartum period resolves shortly after birth in anormal pregnancy.2,18 Pearson et al4 suggested thatPPCM might be due, in part, to an exaggerateddecrease in left ventricular function when thesehemodynamic changes of pregnancy occur.

Apoptosis and InflammationAn increased concentration of plasma inflamma-

tory cytokines, specifically tumor necrosis factor a;C-reactive protein; and Fas/Apo-1, a plasma markerfor apoptosis (programmed cell death), have beenidentified in women with PPCM.3 Levels of Fas/Apo-1,a ligand found on cell-surface proteins that plays akey role in apoptosis, were higher in women withPPCM than in healthy volunteers.3 Furthermore, theseFas/Apo-1 levels were higher among women withPPCM who died than among those with PPCM whosurvived. However, a correlation between increasedplasma cytokine levels and left ventricular functionor outcomes has not been demonstrated. Van Hoevenet al30 further concluded that ejection fraction at thetime of clinical findings suggestive of PPCM was thestrongest predictor of outcome.

ProlactinHilfiker-Kleiner et al16,31 have proposed a new

pathogenic mechanism for PPCM: excessive pro-lactin production. Levels of prolactin are associatedwith increased blood volume, decreased bloodpressure, decreased angiotensin responsiveness, anda reduction in the levels of water, sodium, and potas-sium.31 Prolactin also increases the level of circulating


Viral myocarditishas been proposed as themain mechanismfor peripartumcardiomyopathy.


can mimic those of mild heart failure. Women withPPCM most commonly have dyspnea, dizziness,chest pain, cough, neck vein distension, fatigue,and peripheral edema.4,10,13 Women can also havearrhythmias, embolic events due to the dilated,dysfunctional left ventricle, and acute myocardialinfarction due to decreased perfusion to the coronaryarteries.4,10,35 They can also have other indicationstypical of heart failure: hypoxia, jugular venous dis-tention, S3 and S4 gallop, rales, and hepatomegaly.

35

Blood pressure is often normal or decreased, andtachycardia is common.20

PPCM was first defined in 1971 as the develop-ment of myocardial disease that occurs for the firsttime toward the end or in the early stage of thepregnancy.12 A modification of this classic definition

added a strict echocardiographic crite-rion.1 The National Heart, Lung, andBlood Institute and the Office of RareDiseases workshop adopted the modi-fied definition in 2000.4 In 2010, theEuropean Society of Cardiology Work-ing Group on Peripartum Cardiomy-opathy36 proposed a modification tothe existing definition of PPCM. PPCMis defined as an idiopathic cardiomy-opathy manifested as heart failure dueto left ventricular systolic dysfunctiontoward the end of pregnancy or in themonths after delivery when no othercause of heart failure is found. Thus,

PPCM is a diagnosis of exclusion, suggesting that abroader definition would eliminate PPCM as amissed diagnosis.36

The definitive diagnosis of PPCM depends onechocardiographic identification of new-onset heartfailure during a limited period around parturition.A diagnosis of PPCM requires the exclusion of othercauses of heart failure: myocardial infarction, sepsis,severe preeclampsia, pulmonary embolism, valvulardiseases, and other forms of cardiomyopathy.17,37

Chest radiographs should be obtained in sus-pected cases of PPCM.35 Chest radiographs may behelpful in acute pulmonary edema, but much lessso if no clinical evidence of pulmonary congestionis revealed. Radiological indications of heart failuresuch as cardiomegaly, pulmonary congestion, andpleural effusions may be evident.35 However, diag-nosing cardiomegaly on the basis of a chest radi-ograph in a pregnant patient is difficult becausethe heart is pushed upward and laterally, giving thefalse impression of cardiomegaly.

Electrocardiograms should also be obtained. InPPCM, the tracings may be normal or may show

left ventricular hypertrophy, ST-T wave abnormalities,dysrhythmias, Q-waves in the anteroseptal precor-dial leads, and prolonged PR and QRS intervals.4,38

Several laboratory tests should be performed: com-plete blood cell counts and serum levels of troponin,urea, creatinine, and electrolytes.11,20 Liver functiontests should be done, and levels of thyroid-stimulat-ing hormone should be measured. In the initialevaluation, the serum level of troponin may behelpful in ruling out myocardial infarction; how-ever an increase in troponin in the acute phase ofPPCM, without myocardial infarction, can occur.35

Levels of B-type natriuretic peptide and N-terminalpro-B-type natriuretic peptide can help in confirm-ing the diagnosis.38,39

Unlike pulmonary artery catheterization,echocardiography is noninvasive and allows serialevaluations in pregnant women.1 Serial echocardio-graphy with Doppler imaging is used to evaluateand monitor regional and global left and right ven-tricular function, valvular structure and function,possible pericardial pathological changes, andmechanical complications.11 Findings in womenwith PPCM are consistent with the findings in heartfailure: decreased ejection fraction, global dilata-tion, and thinned-out cardiac walls.4,11,38

Cardiac magnetic resonance imaging has beensuggested as a complementary tool in the diagnosisand evaluation of women with PPCM.13,21,30 Suchimaging can be used to measure global and seg-mental myocardial contraction, can help in charac-terizing the pathogenesis of the disease, and canreveal inflammatory processes.13 Baruteau et al21

maintain that because cardiac magnetic resonanceimaging can be used to distinguish inflammatoryfrom noninflammatory pathogenesis, it can behelpful at the initial evaluation of a woman withPPCM to determine the pathophysiology and toguide further therapeutic options. Ntusi and Chin40

disagree, however, and do not see a benefit forobtaining cardiac magnetic resonance images in allwomen who have PPCM. Guidelines for diagnosisof PPCM according to the American College of Car-diology Foundation (ACCF) and the American HeartAssociation (AHA)39 are provided in Figures 1 and 2.

ManagementCompensated Heart Failure

Management of PPCM is similar to standardtreatment for other forms of heart failure.4,39,41 How-ever, no randomized clinical trials have been doneto evaluate these therapies specifically in PPCM.Furthermore, careful attention should be paid to fetalsafety and to excretion of drug or drug metabolites


Magnetic resonance images

can be used tomeasure globaland segmental

contraction andidentify inflamma-

tory processes.


after more than 2 weeks of therapy. Digoxin, aninotropic agent, is also safe during pregnancy andshould be considered for women with left ventricu-lar systolic dysfunction and an ejection fraction ofless than 40% who have signs and symptoms ofheart failure while receiving standard therapy.42

Guidelines for management of compensated heartfailure in PPCM are presented in Table 1.

Decompensated Heart FailureIn pregnant women with acute decompensat-

ing heart failure, management begins with theABCs (airway, breathing, circulation).35 Assessmentof the airway is critical because pregnancy or recentpregnancy with associated third spacing of excessintravascular volume can result in a suboptimal air-way.35 Women with impending respiratory failurefrom pulmonary edema require rapid initiation ofsupported ventilation.44 Endotracheal intubation is

during breastfeeding after delivery.4 The goals intreating heart failure are to improve hemodynamicstatus, minimize signs and symptoms, and optimizethe long-term outcomes. Treatment focuses onreducing preload and afterload and increasing car-diac inotropy.2,4,35 Pearson et al4 reinforce that col-laboration among medical specialists, includingobstetricians, cardiologists, perinatologists, andneonatologists, is essential in care of women withPPCM. Of note, polypharmacy may be required foroptimal management, to slow progression of heartfailure and to improve outcomes in women with leftventricular systolic dysfunction.42 Medications shouldbe continued until evidence indicates improvedand/or resolved left ventricular dysfunction.4,35

Women with PPCM should be treated in the hospitalwhen they have evidence of hypotension, worseningheart failure, altered mental status, and increasedwork of breathing.42

Preload reduction is accomplished by adminis-tration of vasodilators, such as nitrates, most ofwhich are safe during pregnancy and breastfeeding.35

Loop diuretics are important for management ofsigns and symptoms and for preload reduction,although caution is warranted in antepartum womenbecause rapid changes in intravascular volume canlead to a decrease in blood supply to the uterus andtherefore the fetus.35,43 Restriction of dietary sodiumis also helpful in preload reduction.2 Bed rest wasonce standard care but is no longer recommendedbecause of the increased risk of thromboembolism.20

The current recommendation is light exercise suchas walking.4,10

Ideal medications intrapartum include hydrala -zine, nitrates, digoxin, and diuretics. Angiotensin-converting enzyme inhibitors are contraindicatedduring pregnancy because of their teratogenicity,but these medications are the mainstay of treatmentof PPCM after delivery for afterload reduction.4,13,38

Safe alternatives during pregnancy include hydrala -zine and nitrates.4,10 Aldosterone antagonists havebeen effective when angiotensin-converting enzymeinhibitors were not tolerated, but the antagonistsshould not be used during pregnancy.41

b-Adrenergic antagonists, such as extended-releasemetoprolol and carvedilol, have been approved foruse in PCCM and can improve survival.4,20,43 How-ever, b-blockers should not be given in the earlystages of PPCM because they can decrease perfusionin the acute decompensated phase of the disease.35

Pearson et al4 have proposed that carvedilol be usedin postpartum women who continue to have signsand symptoms of heart failure and have echocardio-graphic evidence of left ventricular compromise

Figure 1 Evaluation of peripartum cardiomyopathy.

Diagnostic testing

Complete family history, to identify possible familial associationSerum tests

Complete blood cell count with differentialCreatinine and urea levelsElectrolyte levels, including magnesium and calciumLevels of cardiac enzymes, including troponinLevel of B-type natriuretic peptide and/or N-terminal

pro-B-type natriuretic proteinLiver function and level of thyroid-stimulating hormone

Chest radiograph Electrocardiogram Transthoracic echocardiogramCardiac magnetic resonance imaging and/or endomyocardial

biopsy (when indicated)

Woman with signs and symptoms of heart failure who is

In last month of pregnancy or Within 5 months postpartum

Signs and symptoms of heart failure

Dyspnea CoughFatigue (at rest or exertion) Heart palpitations/tachycardiaNeck vein distention Sudden weight gain, fluid retentionExercise intolerance ArrhythmiasPeripheral edema Paroxysmal nocturnal dyspneaWeight gain (water retention) HepatomegalyChest pain Weakness



often required; however, attempts involving nonin-vasive ventilation may obviate intubation.44 Nonin-vasive ventilation must be used with caution becauseof the high risk for aspiration. Breathing is supportedwith supplemental oxygen to relieve signs and symp-toms related to hypoxemia and is assessed via con-tinuous pulse oxymetry. Women should have cardiacmonitoring, including ST-segment monitoring whenavailable.13,35 Blood pressure should be monitoredwith noninvasive blood pressure cuffs until arterialcatheters are placed. Venous and arterial accessshould be obtained early so that medications canbe administered promptly and monitoring can bestreamlined.35 Some clinicians39 advocate for the useof pulmonary artery catheters in women whose heartfailure is refractory; however, this logic has beenquestioned because many of the drugs used to treatPPCM produce benefits by mechanisms that cannotbe assessed by measurement of short-term changesin hemodynamic status. Pulmonary artery cathetersmay be beneficial in patients with heart failure, butlittle information is available on their use inwomen with PPCM.

In antepartum women, fetal heart rate monitor-ing should be started early because abnormalities infetal heart rate tracings are common when maternaloxygenation and circulation are compromised.35 Med-ical stabilization of the mothers condition is criticaland may result in resolution of fetal distress and pre-vent the need for emergency cesarean delivery thatmost likely would be poorly tolerated by the mother.35

Women with acute heart failure benefit fromintravenous administration of positive inotropicagents such as dobutamine and milrinone, none ofwhich are contraindicated in pregnancy.44 Positiveinotropic agents improve cardiac performance, facil-itate diuresis, preserve end-organ function, and pro-mote clinical stability.13,17,39 Dobutamine requiresb-receptors for its inotropic effects, whereas milrinonedoes not, an important distinction in planning carefor a patient who is being treated with b-blockingdrugs.39 Furthermore, milrinone has vasodilatingproperties for both the systemic and the pulmonarycirculation, a mechanism that may be a markedbenefit over other inotropic agents. In women withsystolic blood pressure less than 90 mm Hg, dobut-amine may be preferred over milrinone.44 Vasodilatorydrugs such as nitroglycerin and nitroprusside alsomay be of benefit.35,39 Nitroprusside should be usedwith caution in pregnant women because the toxiceffects of thiocyanate can be harmful to the fetus.20,42

Clinicians should not focus therapy on a spe-cific blood pressure value that might or might notindicate hypotension; rather, they should focus onsigns and symptoms associated with poor cardiacoutput and hypoperfusion, such as cold clammyskin, cool upper and lower extremities, decreasedurine output, and altered mental status.39 Inotropicagents are of greatest value in women who haverelative hypotension and an intolerance or noresponse to vasodilators and diuretics.42 Regardless,if invasive monitoring of hemodynamic status isused, once the clinical status of the woman hasstabilized, every effort should be made to devise anoral regimen that can maintain symptomatic improve-ment and reduce the subsequent risk of any deterio-ration in her condition.42

Left ventricular thrombus is common in womenwith PPCM whose ejection fraction is less than35%.2,38 Warfarin should be given to postpartumwomen whose ejection fraction is 35% or less, andheparin or a low-molecular-weight heparin shouldbe given to women who are pregnant and have asimilar ejection fraction.20,35 Anticoagulation therapyshould be continued until left ventricular functionis normal according to echocardiographic find-ings.13,39 Arrhythmias should be aggressively treated

Figure 2 Diagnosis of peripartum cardiomyopathy.Based on Pearson et al4 and Sliwa et al.36

Diagnostic criteria for peripartum cardiomyopathy

All 4 of the following:

Classic1. Development of cardiac failure in the last month of pregnancy or

within 5 months postpartum2. No identifiable cause for the cardiac failure3. No recognizable heart disease before the last month of

pregnancy

Additional1. Strict echocardiographic indication of left ventricular dysfunction:

a. Ejection fraction

to minimize thrombus formation and to optimizecardiac function.4,10

Immunosuppressive and anti-inflammatorytherapies have not improved the outcome in PPCMand, in general, are not recommended.45 Because ofthe various mechanisms of PPCM, immunosuppre-sion most likely would not help all women.13,35,45

In a case report, Jahns et al46 stated that bromo -criptine, a dopamine antagonist that inhibits pro-lactin secretion, prevented the expected deteriorationin the size of the left ventricle and systolic functionwhen given in addition to standard heart failuretherapy in a woman with PPCM. The treatment ofSTAT3-deficient mice with bromocriptine also pre-vented the development of PPCM in a study byHilfiker-Kleiner et al.16 The results of assessments ofthe therapeutic effects of prolactin blockade withbromocriptine are promising, and trials are beingdone in women with PPCM.16,31 In a case study, deJong et al47 argue that the benefit of using cabergo-line, another potent dopamine receptor antagonistlike bromocriptine, is the long half-life, 14 to 21days, of cabergoline, so a single dose is often enough.

Medical therapy can be unsuccessful in womenwith PPCM, and mechanical cardiovascular supportwith an intra-aortic balloon pump or ventricularassist devices may be required.48,49 Left ventricularassist devices can be a bridge to recovery or to trans-plantation.13,49-51 Use of short-term extracorporealmembrane oxygenation has also been of benefit inwomen with PPCM whose heart failure was refrac-tory to medical therapy and who had persistent pul-monary edema with hypoxemia.48,50 Extracorporealmembrane oxygenation can also serve as a bridgeto left ventricular assist devices in patients withrefractory cardiogenic shock despite use of an intra-aortic balloon pump and full inotropic support.51

Women in whom maximal medical manage-ment is unsuccessful may be candidates for cardiactransplantation.48 According to one study,14 cardiactransplantation was necessary in 4% of women withPPCM. In another study52 in which 69 women under-went cardiac transplantation for PPCM, the investi-gators concluded that heart transplantation is apractical therapeutic option for women with PPCMwho have advanced heart failure and signs andsymptoms unresponsive to medical therapies. Therisk of organ rejection in women with PPCM doesnot appear to be higher than the risk in women ofsimilar age who have a history of pregnancy andundergo transplantation for other causes. However,in an earlier study, Koegh et al48 found that the inci-dence of biopsy-proven early rejection, necessitatingincreased cytolytic therapy, was marginally higher in

Table 1 Management of compensated heart failure in peripartumcardiomyopathya

Nonpharmaceutical therapies

Low-sodium diet: limit of 2 g sodium per dayFluid restriction: 2 L/dayLight daily activity: if tolerated (eg, walking)

Oral pharmaceutical therapies

Antepartum management of peripartum cardiomyopathyb-blocker

Carvedilol (starting dose 3.125 mg twice a day, target dose 25 mg twice a day)

Extended-release metoprol (starting dose 0.125 mg daily, target dose 0.25 mg daily)

VasodilatorHydralazine (starting dose 10 mg 3 times a day, target dose 40 mg

3 times a day)

Digoxin (starting dose 0.125 mg daily, target dose 0.25 mg daily)Monitor serum levels

Thiazide diuretic (with caution) Hydrochlorothiazide (12.5-50 mg daily)

May also consider loop diuretic with caution

Low-molecular-weight heparin if ejection fraction 60 mL/min per 1.73 m2:

furosemide 20-40 mg every12-24 hGlomerular filtration rate

women with PPCM than in women with dilatedcardiomyopathy. Table 2 presents guidelines for man-agement of decompensated heart failure in PPCM.

Outcomes of PPCMPrognosis of PPCM is positively related to the

recovery of ventricular function.17 Failure of heartsize to return to normal is associated with increasedmortality and morbidity.4 Women with persistentleft ventricular dysfunction are less likely to surviveand recover normal cardiac function than are womenwith improved left ventricular function. A fractionalshortening less than 20% and a left ventriculardiastolic dimension of 6 cm or greater at the timeof diagnosis are associated with a more than 3-foldhigher risk for persistent cardiac dysfunction.53

Sliwa et al3 found that ejection fraction was thestrongest predictor of outcome in women with PPCM.Abboud et al17 reported that 50% of women withPPCM recover baseline ventricular function within6 months of delivery. In contrast, Ntusi and Mayosi18

found that only 30% of women with PPCM havecomplete recovery of cardiac function; most havepartial recovery. Medical therapy as outlined in theACCF/AHA guidelines39 should be continued whena woman does not recover function. When appropri-ate, implantation of defibrillators to prevent suddencardiac death and use of cardiac revascularizationtherapy should be considered.

Reported mortality rates for PPCM vary widely.In a study by Sliwa et al,3 the mortality rate in 29women was 32%, whereas in a large population-based study in Haiti by Fett et al,8 the mortality ratewas 15.8%. In a study of 123 women by Elkayamet al,5 the rate was 9% at a mean follow-up time of24 months. Brar et al15 concluded that mortalityrates associated with PPCM were lower than initiallyreported at 2.5%, and Mielniczuk et al9 reported amortality rate of 1.36% to 2.05%. Earlier diagnosis,coupled with modern management of heart failure,most likely has an important influence on the mor-tality associated with PPCM.9,15 Although rates haveimproved, mortality remains extremely high inwomen with PPCM.

One of the most frequently cited issues forwomen who survive PPCM is whether or not theycan safely become pregnant again.5,14 No clearlyestablished recommendations for future pregnanciesin these women exist.20 Left ventricular recovery andfunction are considered the most reliable prognosticfactors and predictors of survival in subsequentpregnancies.20 Future pregnancies are not recom-mended in women with persistent heart failure,because the heart most likely would not be able to

Table 2 Management of decompensated heart failure in peripartum cardiomyopathya

If no improvement clinically: Consider cardiac magnetic resonance imagingPerform endomyocardial biopsy to detect viral myocarditis

(if not previously completed)

Assist devices:Intra-aortic balloon pumpLeft ventricular assist devicesExtracorporeal membrane oxygenationTransplantation

If a woman remains refractory to therapy, consult your institutions guidelines for bromocriptine or cabergoline administration forsuppression of prolactin production

AirwayIntubate promptly upon distress for increased work of breathing

to prevent complications with difficult airway later in treatment Breathing

Provide supplemental oxygenMaintain continuous pulse oximetry to monitor SaO2Measure arterial blood gases (if available) every 4-6 h until

breathing is stableCirculation

Start cardiac and blood pressure monitoringInsert arterial catheter for accurate blood pressure monitoringand blood sampling

Obtain central venous access with central venous pressure monitoring

In antepartum women, obtain fetal monitoring

Pharmacological management of acute heart failure in peripartumcardiomyopathy

Intravenous loop diuretic (caution is advised in antepartumwomen)Furosemide: dosing considerations should be made on the

basis of creatinine clearanceGlomerular filtration rate >60 mL/min per 1.73 m2:

furosemide 20-40 mg intravenously every 12-24 hGlomerular filtration rate

FINANCIAL DISCLOSURESNone reported.

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8. Fett JD, Christie LG, Carraway RD, Murphy JG. Five-yearprospective study of the incidence and prognosis of peri-partum cardiomyopathy at a single institution. Mayo ClinProc. 2005;80(12):1602-1606.

9 Mielniczuk LM, Williams K, Davis DR, et al. Frequency ofperipartum cardiomyopathy. Am J Cardiol. 2006;97(12):1765-1768.

10. Ro A, Frishman W. Peripartum cardiomyopathy. CardiolRev. 2006:14(1):35-42.

11. Sliwa K, Tibazarwa K, Hilfiker-Kleiner D. Management ofperipartum cardiomyopathy. Curr Heart Fail Rep. 2008;5(5):238-244.

12. Demakis JG, Rahimtoola S, Sutton GC, et al. Natural courseof peripartum cardiomyopathy. Circulation. 1971;44(6):1053-1061.

13. Ramaraj R, Sorrell VL. Peripartum cardiomyopathy: causes,diagnosis, and treatment. Cleve Clin J Med. 2009;76(5):289-296.

14. Elkayam U, Akhter MW, Singh H, et al. Pregnancy-associatedcardiomyopathy: clinical characteristics and a comparisonbetween early and late presentation. Circulation. 2005;111(16):2050-2055.

15. Brar SS, Khan SS, Sandhu GK, et al. Incidence, mortality,and racial differences in peripartum cardiomyopathy. AmJ Cardiol. 2007;100(2):302-304.

16. Hilfiker-Kleiner D, Sliwa K, Drexler H. Peripartum cardiomy-opathy: recent insights in its pathophysiology. Trends Car-diovasc Med. 2008;18(5):173-179.

17. Abboud J, Murad Y, Chen-Scarabelli C, Saravolatz L,Scarabelli TM. Peripartum cardiomyopathy: a comprehen-sive review. Int J Cardiol. 2007;118(3):295-303.

18. Ntusi NB, Mayosi BM. Aetiology and risk factors of peripar-tum cardiomyopathy: a systematic review. Int J Cardiol.2009;131(2):168-179.

19. Pearl W. Familial occurrence of peripartum cardiomyopathy.Am Heart J. 1995;129(2):421-422.

20. Moioli M, Menada MV, Bentivoglio G, Ferrero S. Peripartumcardiomyopathy. Arch Gynecol Obstet. 2010;281(2):183-188.doi:10.1007/s00404-009-1170-5.

21. Baruteau AE, Leurent G, Martins R, et al. Peripartum car-diomyopathy in the era of cardiac magnetic resonanceimaging: first results and perspectives. Int J Cardiol. 2010;144(1):143-145.

22. van Spaendonck-Zwarts KY, van Tintelen P, van VeldhuisenDJ, et al. Peripartum cardiomyopathy as a part of familialdilated cardiomyopathy. Circulation. 2010;121:2169-2175.

23. Burkett EL, Hershberger RE. Clinical and genetic issues infamilial dilated cardiomyopathy. J Am Coll Cardiol. 2005;45(7):969-981.

24. Elliott P, Andersson B, Arbustini E, et al. Classification ofthe cardiomyopathies: a position statement from the Euro-pean Society of Cardiology Working Group on Myocardialand Pericardial Disease. Eur Heart J. 2008;29(2):270-276.

25. Goulet B, McMillan T, Bellet S. Idiopathic myocardial degen-eration associated with pregnancy and especially the puer-

tolerate the increased cardiovascular workload asso-ciated with the pregnancy.5,13 Women whose car-diomyopathy appears to have resolved are a moredifficult group to counsel.4 Because multiparity hasbeen associated with PPCM, subsequent pregnan-cies can increase the risk for recurrent episodes ofPPCM, irreversible cardiac damage and decreasedleft ventricular function, worsening of a womansclinical condition, and even death.4,14

Williams et al35 have suggested that dividingwomen into 2 categories (recovered vs nonrecoveredleft ventricular function) is most appropriate forcounseling on future pregnancy. Even though thecardiac function has normalized in the group ofwomen with recovered cardiac function, the leftventricular contractile reserve may remain impaired,and recurrence of PPCM is still possible.4,5 The sub-set of women with persistent left ventricular systolicdysfunction should be counseled against subse-quent pregnancies; the risks are 19% higher formaternal death than among women with PPCMwhose heart failure has resolved.35

ConclusionPPCM affects previously healthy women in the

final month of pregnancy and up to 5 months afterdelivery.4 The diagnosis is based on 4 criteria.1,4 Forsome women, the clinical and echocardiographicstatus improve rapidly and sometimes return tonormal. In other women, the clinical condition rap-idly worsens, no improvement occurs with medicaltherapy, and chronic heart failure from persistentventricular dysfunction develops.5 No single expla-nation of the pathogenesis of PPCM is relevant forall women; the disease has a multifactorial origin.In acute care, treatment may involve the use ofintravenous vasodilators, inotropic medications, anintra-aortic balloon pump, ventricular assist devices,and/or extracorporeal membrane oxygenation.20,50

Survivors of PPCM often recover from left ventricu-lar dysfunction; however, they may be at risk forrecurrence of heart failure and death in subsequentpregnancies. Women with chronic left ventriculardysfunction should be managed according toACCF/AHA guidelines.39 Careful assessment of riskfactors in pregnant women could help in the preven-tion of PPCM. Tools to stratify women by risk whohave recovered from PPCM are needed to predictthe risk of future pregnancies.

eLettersNow that youve read the article, create or contribute to anonline discussion on this topic. Visit www.ajcconline.organd click Submit a response in either the full-text orPDF view of the article.



pernium. Am J Med Sci. 1937;194(2):185-199.26. Melvin KR, Richardson PJ, Olsen EG, Daly K, Jackson G.

Peripartum cardiomyopathy due to myocarditis. N Engl JMed. 1982;307(12):731-734.

27. Midei MG, DeMent SH, Feldman AM, Hutchins GM, Baugh-man KL. Peripartum myocarditis and cardiomyopathy. Circulation. 1990;81:922-928.

28. Felker GM, Jaeger CJ, Klodas E, et al. Myocarditis andlong-term survival in peripartum cardiomyopathy. AmHeart J. 2000;140(5):785-791.

29. Ansari AA, Fett JD, Carraway RE, Mayne AE, Onlamoon N,Sundstrom JB. Autoimmune mechanisms as the basis forhuman peripartum cardiomyopathy. Clin Rev AllergyImmunol. 2002;23:301-324.

30. van Hoeven KH, Kitsis RN, Katz SD, Factor SM. Peripartumversus idiopathic dilated cardiomyopathy in young womena comparison of clinical, pathological and prognostic fac-tors. Int J Cardiol. 1993;40(1):57-65.

31. Hilfiker-Kleiner D, Kaminski K, Podewski E, et al. A cathepsinD-cleaved 16 kDa form of prolactin mediates postpartumcardiomyopathy. Cell. 2007;128(3):589-600.

32. Fett J, Ansara A, Sundstrom J, Combs G Jr. Peripartumcardiomyopathy: a selenium disconnection and an autoim-mune connection. Int J Cardiol. 2002;86(2):311-316.

33. Cnac A, Simonoff M, Moretto P, Djibo A. A low plasmaselenium is a risk factor for peripartum cardiomyopathy: acomparative study in Sahelian Africa. Int J Cardiol. 1992;36(1):57-59.

34. Lampert MB, Hibbard J, Weinert L, Briller J, Lindheimer M,Lang RM. Peripartum heart failure associated with prolongedtocolytic therapy. Am J Obstet Gynecol. 1992;168(2):493-495.

35. Williams J, Mozurkewich E, Chilimigras J, Van De Ven C.Critical care in obstetrics: pregnancy-specific conditions.Best Pract Res Clin Obstet Gynaecol. 2008;22(5):825-846.

36. Sliwa K, Hilfiker-Kleiner D, Petrie MC, et al; Heart FailureAssociation of the European Society of Cardiology WorkingGroup on Peripartum Cardiomyopathy. Current state ofknowledge on aetiology, diagnosis, management, and ther-apy of peripartum cardiomyopathy: a position statementfrom the Heart Failure Association of the European Societyof Cardiology Working Group on Peripartum Cardiomyopa-thy. Eur J Heart Fail. 2010;12(8):767-778.

37. Pyatt JR, Dubey G. Peripartum cardiomyopathy: currentunderstanding, comprehensive management review andnew developments. Postgrad Med J. 2011;87(1023):34-39.

38. Lata I, Gupta R, Sahu S, Singh H. Emergency managementof decompensated peripartum cardiomyopathy. J EmergTrauma Shock. 2009;2(2):124-128.

39. Jessup M, Abraham W, Casey D, et al. 2009 Focused update:ACCF/AHA guidelines for the diagnosis and managementof heart failure in adults: a report of the American Collegeof Cardiology Foundation/American Heart Association TaskForce on Practice Guidelines Developed in CollaborationWith the International Society for Heart and Lung Trans-plantation. J Am Coll Cardiol. 2009;53(15):1343-1382.

40. Ntusi NB, Chin A. Characterisation of peripartum cardiomy-opathy by cardiac magnetic resonance imaging. Eur Radiol.2009;19(6):1324-1325.

41. Carlin AJ, Alfirevic Z, Gyte ML. Interventions for treatingperipartum cardiomyopathy to improve outcomes forwomen and babies. Cochrane Database Syst Rev. 2010(9):CD008589. doi:10.1002/14651858.CD008589.pub2.

42. Heart Failure Society of America. Executive summary:HFSA 2006 comprehensive heart failure practice guideline.J Card Fail. 2006;12(1):10-38.

43. Egan DJ, Bisanzo MC, Hutson HR. Emergency departmentevaluation and management of peripartum cardiomyopathy.J Emerg Med. 2009;36(2):141-147.

44. Arnold JM, Liu P, Demers C, et al; Canadian CardiovascularSociety. Canadian Cardiovascular Society consensus con-ference recommendation on heart failure 2006: diagnosisand management. Can J Cardiol. 2006;22(1):23-45.

45. McNamara DM, Holubkov R, Starling, RC, et al. Controlledtrial of intravenous immune globulins in recent-onsetdilated cardiomyopathy. Circulation. 2001;103:2254-2259.

46. Jahns BG, Stein W, Hilfiker-Kleiner D, Pieske B, Emons G.Peripartum cardiomyopathya new treatment option byinhibition of prolactin secretion. Am J Obstet Gynecol.2008;199(4):e5-e6.

47. de Jong JS, Rietveld K, van Lochem LT, Bouma BJ. Rapid leftventricular recovery after cabergoline treatment in a patientwith peripartum cardiomyopathy. Eur J Heart Fail. 2009;1(2):220-222.

48. Keogh A, Macdonald P, Spratt P, Marshman D, Larbalestier R,Kaan A. Outcome in peripartum cardiomyopathy after hearttransplantation. J Heart Lung Transplant. 1994;13(2):202-207.

49. Smith IJ, Gillham MJ. Fulminant peripartum cardiomyopathyrescue with extracorporeal membranous oxygenation. IntJ Obstet Anesth. 2009;18(2):186-188.

50. Palanzo DA, Baer LD, El-Banayosy A, et al. Successful treat-ment of peripartum cardiomyopathy with extracorporealmembrane oxygenation. Perfusion. 2009;24(2):75-79.

51. Gavaert S, van Belleghem Y, Bouchez S, et al. Acute andcritically ill peripartum cardiomyopathy and bridge totherapeutic options: a single center experience with intra-aortic balloon pump, extra-corporeal membrane oxygena-tion and continuous-flow left ventricular assist devices. CritCare. 2011;15(2):R93.

52. Rasmusson K, de Jong M, Doering L. Update on heart failuremanagement. current understanding of peripartum cardiomy-opathy. Prog Cardiovasc Nurs. 2007;22(4):214-216.

53. Chapa JB, Heiberger HB, Weinert L, Decara J, Lang RM, Hib-bard JU. Prognostic value of echocardiography in peripartumcardiomyopathy. Obstet Gynecol. 2005;105(6):1303-1308.

To purchase electronic or print reprints, contact TheInnoVision Group, 101 Columbia, Aliso Viejo, CA 92656.Phone, (800) 899-1712 or (949) 362-2050 (ext 532); fax,(949) 362-2049; e-mail, [email protected].



Letters

Delirium Diagnosis: What You DoWith the Information Matters Most

The articles by Guenther et al1 and Gesin et al2

published in the January edition of the AmericanJournal of Critical Care are important contributions tothe discussion of how best to identify delirium in theintensive care unit (ICU).

Gesin et al performed a comprehensive evalua-tion of a multifaceted education program. Guentheret al reported the first study to identify the false-pos-itive rate of subjective delirium assessments com-pared to an objective standard. However, bothpapers fall into the common trap of confusing a disease entity with the results of a diagnostic test.

Delirium is a pathophysiologic process, themechanisms of which are poorly understood and themanifestations of which are protean, fleeting, andinfluenced by baseline cognitive state, environment,and method of assessment. As a result, comparisonsof diagnostic methods for detecting delirium willinevitably produce different results,1 and training in aparticular diagnostic method will inevitably improveagreement with other assessors using that method.2

In delirium diagnosis, it most important forclinicians and researchers to identify a diagnosticstrategy that (1) identifies patients at higher risk ofadverse outcome, independent of other markers ofdisease severity, and (2) identifies patients who willbenefit from therapy. Most methods of deliriumdiagnosis, including unstructured subjective assess-ments,3 identify patients with poor outcomes; how-ever no published study has ever convincinglydemonstrated one method does this more effectivelyor efficiently than another. Only the Intensive CareDelirium Screening Checklist (ICDSC) has everidentified patients who benefitted from an interven-tion,4 and then only as a inclusion criterion for aclinical trial, with no demonstration of comparativediagnostic effectiveness. With this background, thestudies of Guenther et al and Gesin et al warrantfurther consideration.

In a study of 160 patients, Guenther et al1 reportthe paired comparison of 436 subjective assessmentsmade by bedside nurses and assessments made usingthe Confusion Assessment Method for the ICU(CAM-ICU). In 161 unreported assessments, theCAM-ICU could not be performed as the RASS score

Letters are welcome and encouraged. They should raise points of current interest in the care of critical or high acuity patients or address topics that previously have appeared in the American Journal of Critical Care. Please be concise; letters are subject to editing for length andclarity. Include your name, credentials, title (optional), institutional affiliation, city and state, and phone number (for verification, not publication). Address letters to [email protected]. Correspondence also may be sent via eLetters from the journals Web site, www.ajcconline.org.

www.ajcconline.org AJCC AMERICAN JOURNAL OF CRITICAL CARE, May 2012, Volume 21, No. 3 151

was -4 or -5. It would be interesting to know if thebedside nurses were able to make any subjectiveassessments in these patients. It is unclear whetherthe subjective assessments were made in the courseof the usual clinical duties of the bedside nurses, andwhether they made a single snapshot assessmentor drew on observations made over the course of anursing shift. Such considerations are important, asdelirium fluctuates over time and the effort expendedin making an assessment must surely be influencedby other clinical responsibilities. In any case, theCAM-ICU was positive for delirium in 6.4% of assess-ments in which the subjective assessment was nega-tive, whereas the subjective assessment was positivein 9.6% of cases when the CAM-ICU was negative.From this, the authors conclude that use of objec-tive criteria helped detect delirium in morepatients.1(pe12) Only an analysis of paired observa-tions is presented, rather than the overall patientincidence of delirium, so it is impossible to know ifthis statement is true; however, it is clearly not cor-rect to conclude that the CAM-ICU detected delir-ium in more assessments. Indeed, as the authorspoint out in their results section, the contrary istrue. More importantly, the authors conclude thatsubjective assessments identifying delirium inpatients where the CAM-ICU was negative weremistakes, and they express concern that 8 patientswere given antipsychotic medications or sedativesthough they were not delirious.1(pe18) They implythat the CAM-ICU is the only correct method foridentifying delirium, and a positive CAM-ICUshould be the only indication for anti-delirium med-ication. These assumptions are not justified by anypublished evidence.

The term CAM-ICU delirium does not necessar-ily universally equate to the pathophysiologicalcondition being sought, just as the result of an IQtest does not necessarily equate to a persons intelli-gence or capacity to train in an occupation. Perhapsthe bedside nurse had observed features during hisor her shift that were not present at the time of theCAM-ICU assessment? Perhaps the featuresobserved required treatment to prevent self-extuba-tion? Concluding a bedside nurse was wrong toadminister sedation to an agitated patient whocould neither be safely extubated nor calmed byreassurance or analgesia, simply because their

effective diagnostic strategy. To do otherwise risksmuch wasted effort.

MICHAEL READE, MBBS, MPH, DPHIL, FANZCA, FCICM Brisbane, Queensland, Australia

FINANCIAL DISCLOSURESNone Reported

REFERENCES1. Guenther U, Weykam J, Andorfer U, Theuerkauf N, Popp

J, Ely EW, Putensen C. Implications of Objective vs Subjec-tive Delirium Assessment in Surgical Intensive CarePatients. Am J Crit Care. 2012;21:e12-e20.

2. Gesin G, Russell BB, Lin AP, Norton HJ, Evans SL, Devlin JW.Impact of a delirium screening tool and multifaceted edu-cation on nurses knowledge of delirium and ability toevaluate it correctly. Am. J. Crit Care. 2012;21:e1-e11.

3. Reade MC, Eastwood GM, Peck L, Bellomo R, Baldwin I.Routine use of the Confusion Assessment Method for theIntensive Care Unit (CAM-ICU) by bedside nurses mayunderdiagnose delirium. Crit Care Resusc. 2011;13:217-224.

4. Devlin JW, Roberts RJ, Fong JJ, et al. Efficacy and safety ofquetiapine in critically ill patients with delirium: a prospec-tive, multicenter, randomized, double-blind, placebo-con-trolled pilot study. Crit Care Med. 2010;38:419-427.

5. Godlee F. Who should define disease? BMJ. 2011;342:d2974.

doi: http://dx.doi.org/10.4037/ajcc2012826

Response:On behalf of my coauthors I would like to thank

Dr Reade for his comments and questions. He asksif nurses were able to make subjective deliriumassessments on patients who had RASS scores of -4and -5 and were thus rated as unable to assess bythe CAM-ICU raters. The answer is that it was left tothe nurses discretion not to rate patients if theywere comatose. No patients who had RASS scoresof -4 or -5 were subjectively rated by the nurses.

Reade points out a sentence in our abstractregarding the use of objective criteria with theCAM-ICU allowing detection of delirium in morepatients,1(pe12) that we could have more clearlystated as follows: While the overall delirium inci-dence found with the CAM-ICU was lower thansubjectively rated, objective criteria helped detectdelirium in a significant number of patients whowere subjectively rated non-delirious.

He states that we implied, that the CAM-ICUis the only correct method for identifying delirium.This was not our intention. In fact, we emphasizedthat the CAM-ICU is not a gold standard for diag-nosis of delirium.1(pe18) The truth is that most of theworld uses a subjective and variable method bywhich to pay attention to delirium, and thus sub-jectivity is part of usual care in many ICUs. Ourmethodology, chosen a priori and based on previ-ous literature showing that subjectivity misseshypoactive delirium,2 was to consider a formal andvalidated mechanism as the formal and definitiveapproach to study discrepancy between the two. Atthe same time, however, we clearly stated the fact

CAM-ICU was negative, ignores the realities of ICUpractice. There is every possibility that patientstreated according to subjective impressions, ratherthan their CAM-ICU diagnosis, ultimately had betteroutcomes. Unfortunately, no published study hasyet answered this question.

In their 3-phase educational study of an educa-tional intervention involving 20 nurses in a singlecentre, Gesin et al2 report an effective educationalstrategy that improved interrater reliability when clin-ical nurses were trained in the ICDSC. It is importantto show that diagnostic tools developed in a researchenvironment can be taught to clinicians, and thateffective methods for teaching are described in the lit-erature. The reported results are perhaps not too sur-prisingjust as showing education in a foreignlanguage might be expected to improve communica-tion with someone who speaks that language. How-ever, in their discussion, Gesin et al2 introduce thesame thinking as Guenther et althat the ICDSCimproves the ability of nurses to evaluate patientscorrectly for delirium.2(pe8) Not only is there no evi-dence that the ICDSC always correctly diagnosesthe pathophysiological entity that is delirium, thereis nothing to suggest that the methods used by thenurses in their preeducation phase would not haveled to better patient outcomes than after they hadmastered the ICDSC. The argument is analogous tothat classically used to demonstrate the differencebetween precision and accuracy. Training in theICDSC is shown to produce a more precise assess-ment, but there is nothing to suggest that in theprocess the diagnosis has not become less accurate.Once again, concentration on process rather thanoutcome has led to overstatement of the impor-tance of a studys results.

Discussion of how to diagnose delirium is not amoot academic point. As recently identified,5 makinga diagnosis can be as beneficial or harmful as admin-istering a powerful medication, yet while we subjectdrugs to extensive trials, many diagnostic strategies,such of those for delirium, enter practice with littleunderstanding of their comparative effects on patientoutcomes. Both papers conclude that education ondelirium monitoring should be performed such thatthe CAM-ICU or the ICDSC can be more faithfullyimplemented. However, as Gesin et al point out, onecannot extrapolate results from studies using theCAM-ICU to results of studies using the ICDSC.2(pe8)

Embarking on extensive education initiativeswhen it is unsure which diagnostic tool provides thegreatest patient benefit is putting the cart beforethe horse. A better strategy would be to perform amulticenter, real-world study comparing outcomesof patients treated according to various diagnoses.We could then be sure we were teaching the most

152 AJCCAMERICAN JOURNAL OF CRITICAL CARE, May 2012, Volume 21, No. 3 www.ajcconline.org

that the CAM-ICU can miss cases of delirium. Wewould like to take the opportunity to emphasize,that any other validated delirium instrument mighthave served a similar purpose as a comparator tovariable and loose subjective guestimates.

Reade criticizes the expression CAM-ICU delir-ium, because CAM-ICU positivity does not neces-sarily universally equate to the pathophysiologicalcondition being sought. . . . The expression CAM-ICU delirium was only chosen to express exactlywhat Reade pointed out: delirium assessment wasdone with the CAM-ICU in our study. It is true,however, that out of the nearly dozen DSM-IV vali-dation studies of the CAM-ICU, it has been absolutelyconsistent that CAM-ICU specificity is exceedinglyhigh. Better said, although sometimes the CAM-ICUmay miss some delirium (eg, patients with lowerseverity of illness, whose inattention is better diag-nosed with a 10- to 30-minute instrument), when itis positive it is highly likely to represent delirium inall patient populations studied to date.

Reade stated that concluding a bedside nursewas wrong to administer sedation . . . simplybecause their CAM-ICU was negative . . . ignoresthe realities of ICU practice. The reality in manycountries is that drugs must be prescribed by physi-cians. So, it is the physicians responsibility to verifyor exclude delirium, pain, or other reasons for dis-orientation such as an underlying dementia. It isalso a reality of ICU practice that physicians mostlyrely on the nurses subjective clinical impressions,because they are present at the bedside much moreoften than physicians.

We agree with Reade that it would be interest-ing to determine whether or not patients treatedaccording to subjective impressions have better out-comes as compared to those treated according toobjective delirium criteria.

ULF GUENTHER, MDBonn, Germany


REFERENCE1. Guenther U, Weykam J, Andorfer U, Theuerkauf N, Popp J,

Ely EW, Putensen C. Implications of Objective vs Subjec-tive Delirium Assessment in Surgical Intensive CarePatients. Am J Crit Care. 2012;21:e12-e20.

2. Spronk PE, Riekerk B, Hofhuis J, Rommes JH: Occurrenceof delirium is severely underestimated in the ICU duringdaily care. Intensive Care Med. 2009;35:1276-80


Response:We thank Dr Reade for his insightful comments

regarding recognition of delirium in the ICU andfor highlighting important areas for future research.

Despite the lack of strong evidence demonstrat-ing that screening for delirium at the bedside usinga validated instrument improves patient outcome,recent European and North American consensusguidelines advocate that patients admitted to theICU be routinely screened for delirium using eitherthe ICDSC or the CAM-ICU.1,2 Realizing that bed-side delirium screening is not a replacement for aformal diagnostic evaluation by either a psychiatristor neurologist, it nevertheless remains an efficient,low-risk assessment that will help ICU cliniciansaddress reversible causes for delirium (when delir-ium is suspected), avoid treatments for agitationknown to worsen delirium (eg, benzodiazepines),and promote regular interdisciplinary discussionregarding the cognitive status of all patients.

Despite questions that remain surrounding thepsychometric properties of the ICSDC and the CAM-ICU and how one instrument compares to the other,it is well established that if adequate education isnot provided to ICU clinicians when either of theseinstruments are implemented into practice, the per-formance of each will be less than what has beenobserved in formal psychometric evaluations.3-5

Our study was not designed to answer the impor-tant questions surrounding the identification ofdelirium in the ICU that Reade raises. Instead,knowing that the ICDSC identifies delirium nearlyas well as a psychiatrist using DSM-IV criteria, wesought to measure the impact of using the ICDSC,with or without a multifaceted educational strategy,on the level of knowledge of ICU nurses regardingdelirium and its assessment and the ability of nursesto use the ICDSC correctly.6

We did not aim to determine whether use ofthe ICDSC identifies delirium correctly. Whereasthe rate of delirium detected in our study wasreported, this was not a focus and we caution read-ers not to make conclusions surrounding it. Manyof the questions Reade and others have raised sur-rounding the benefit and accuracy of using cur-rently available delirium screening instrumentsrequire further investigation.7,8

Until this research is completed, we feel ourstudy provides ICU clinicians with valuable insightregarding how nurses evaluate delirium when edu-cation and a validated instrument are not used, theintensity of any pedagogical strategy that should be employed to support ICU delirium screeningefforts, and the members of the ICU team who arebest suited to deliver education in this area.

GAIL GESIN, PHARMD; JOHN W. DEVLIN, PHARMDCharlotte, North Carolina; Boston, Massachusetts


154 AJCCAMERICAN JOURNAL OF CRITICAL CARE, May 2012, Volume 21, No. 3 www.ajcconline.org

CorrectionIn the March 2012 article by Johnson-Coyle and

colleagues, Peripartum Cardiomyopathy: Review andPractice Guidelines (Am J Crit Care. 2012;21[2]:89-98),Table 1, p. 95, line10 should have read, Extended-release metroprolol (starting dose 12.5 mg/daily,titrated up to 200 mg daily). We regret the error.


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