Journal of Critical Care (2012) 27, 739.e7–739.e13

Prognostic factors and outcomes of patients withpulmonary hypertension admitted to the intensivecare unit☆,☆☆

Thanh N. Huynh MDa,⁎, S. Sam Weigt MDa, Catherine A. Sugar PhDb,c,Shelley Shapiro MD, PhDd, Eric C. Kleerup MDa

aDivision of Pulmonary and Critical Care Medicine, Department of Medicine, David Geffen School of Medicine, UCLA,BOX 951690, 37-131 CHS, Los Angeles, CA 90095-1690, USAbDepartment of Biostatistics, UCLA School of Public Health, Los Angeles, CA 90095-1772, USAcDepartment of Psychiatry and Biobehaviorial Sciences, David Geffen School of Medicine, UCLA, BOX 951690, 37-131 CHS,Los Angeles, CA 90095-1690, USAdDepartment of Cardiology, UCLA-VA Greater LA Healthcare Systems, Los Angeles, CA 90095-1691, USA

0h

Keywords:Pulmonary hypertension;Intensive care unit;Pulmonary arterycatheterization

AbstractPurpose: Patients with pulmonary hypertension (PH) can decompensate to the point where they requirecare in the intensive care unit (ICU). Our objective is to examine the outcomes and characteristics ofpatients with PH admitted to the ICU.Methods: This is a retrospective study of 99 patients with PH who were admitted to the medical ICU ofa single tertiary care center. Baseline characteristics, interventions during ICU admission, and ICU and6-month outcome were documented. Univariate and multivariate logistic regressions were used toevaluate association of patient characteristics with mortality.Results: Intensive care unit mortality was 30%, and 6-month mortality was 40%. Acute Physiology andChronic Health Evaluation II score, World Health Organization Group 3 PH, and preexisting treatmentwith a prostacyclin at time of ICU admission were associated with worse outcome. Patients whoreceived cardiopulmonary resuscitation had 100% mortality. The requirement for mechanical ventilationand dialysis was also associated with increased mortality. Pulmonary artery catheter placement wasassociated with reduced mortality, specifically if it was placed early during ICU admission and ifassociated with a change in the present management.Conclusions: Mortality is high in critically ill patients with PH. The identification of prognostic baselinecharacteristics and interventions in the ICU is important and warrants further investigation.© 2012 Elsevier Inc. All rights reserved.

☆ Institution where work was performed: University of California, Los Angeles.☆☆ There is no financial support or conflicts of interest to disclose.⁎ Corresponding author. Tel.: +1 310 825 5316; fax: +1 310 206 8622.E-mail address: thuynh@mednet.ucla.edu (T.N. Huynh).

883-9441/$ – see front matter © 2012 Elsevier Inc. All rights reserved.ttp://dx.doi.org/10.1016/j.jcrc.2012.08.006

739.e8 T.N. Huynh et al.

1. Introduction

Pulmonary hypertension (PH) is a progressive diseasecharacterized by sustained elevations in pulmonary arterialpressures and increased pulmonary vascular resistance [1,2].This results in right heart failure (RHF); impairment inoxygenation; exercise limitation; and, ultimately, death.Therapeutic improvements have targeted reduction inpulmonary vascular resistance in an effort to unload theright ventricle and improve cardiac output [3]. Three classesof medications, phospodiesterase inhibitors, endothelin re-ceptor antagonists, and prostacyclin analogs increase exer-cise capacity and stabilize disease progression [3-6]. Despitethese advances, patients with PH continue to require admis-sion to the hospital and often to the intensive care unit (ICU),most commonly for decompensated RHF [7,8].

The management of a critically ill PH patient is chal-lenging. With very little physiologic reserve, they maydeteriorate rapidly into irreversible hemodynamic collapse[9]. Treatment often involves high-dose intravenous di-uretics; vasopressor support; escalation or initiation of newPH therapy; and, possibly, mechanical ventilation andhemodialysis. Few studies describe the prognostic factors,course, and outcomes of these patients or the ICU man-agement [10,11], and none evaluate the efficacy of thevarious interventions initiated in the critical care setting.Evaluation of the impact of these interventions on mortalityis important, especially because they are often costly andinvasive. In an effort to address these questions, we retro-spectively assessed the clinical characteristics and mortalityoutcome of a group of patients with PH who requiredadmission to the ICU.

2. Patients and methods

2.1. Study design

This is a retrospective study at a single tertiary care centerto identify the characteristics and the ICU interventionsassociated with in-hospital and 6-month mortality afteradmission to the ICU. Our study was approved by the UCLAInstitutional Review Board (IRB no. 11-001695).

2.2. Patients

The first admission of all patients with PH who requiredadmission to the UCLA medical ICU between July 2004 andJune 2009 was identified via International Classification ofDiseases, Ninth Revision, codes (416.0 and 416.8). Afterexclusion of patients with PH from left heart failure (DanaPoint Group 2), 99 patients were included in the study. Morethan 900 patients with PH were seen in the outpatient settingat UCLA during the same 5-year study period.

2.3. Data

Data were abstracted from electronic medical records. Age,sex, and type of PH (Dana Point Group classification) weredocumented. To estimate the severity of PH, we recorded theduration or PH diagnosis before ICU admission, the rightventricular systolic pressure estimated on their most recentechocardiogram, and prior treatment of PH. These medica-tions were endothelin receptor antagonists, phosphodiesteraseinhibitors, and prostacyclin analogues (at this center, the localpractice is to start patients on epoprostenol while they are inthe ICU and transition to treprostinol once pumps areavailable). Because PH therapies may take 3 months foronset and stabilization [12], the duration of PH diagnosis wasdichotomized at this time point. Biologic markers within thefirst 24 hours of ICU admission, such as brain natriureticpeptide (BNP), troponin, partial pressure of CO2, and liverfunction tests (alanine aminotransferase/aspartate aminotrans-ferase), were recorded but were not performed consistently.The indication for admission was classified into 4 groups:RHF, respiratory failure from causes other than RHF, sepsis,and other (which included arrhythmia, syncope, postoperativemonitoring, and gastrointestinal bleed). Severity of illness atthe time of admission, assessed by the Acute Physiology andChronic Health Evaluation (APACHE) II score was obtainedwithin the first 24 hours.

The interventions and therapy used during each patient'sICU stay were documented including initiation of a new PHmedication, vasopressor use, mechanical ventilation, hemo-dialysis, cardiopulmonary resuscitation (CPR), and the place-ment of a pulmonary artery catheter (PAC). The treatmentsadministered following PAC placement included diuresisand/or initiation of a PH medication.

2.4. Statistical analysis

Using 6-month mortality as the main outcome variable,patient baseline characteristics and ICU interventions werefirst individually evaluated by univariate logistic regression.Analyses were repeated for ICU mortality. Kaplan-Meiersurvival curves were generated for 6-month survival byAPACHE II quartiles. Next, block stepwise logistic regres-sion was used to model the joint relationship between thepredictors and 6-month mortality (P b .05). In the first block,significant baseline characteristics were identified. Wedecided a priori that the significant baseline characteristicswill then be used in a stepwise model to evaluate ICUinterventions. This allowed us to determine whether theinterventions provided additional information about mortal-ity beyond the baseline characteristics with which thepatients presented. To evaluate only patients with DanaPoint Group 1 PH, this analysis was then repeated afterexcluding patients with group 3 PH.

A secondary analysis was performed on the subset ofpatients who received a PAC within the first 3 days of

Table 1 Baseline characteristics of patients with PH requiringICU admission

Sex (female/male) 64/35Age, y, mean (SD) 51.9 (13.6)

739.e9Patients with PH in teh ICU

admission. Logistic models using 6-month and ICU mor-tality as the outcome variables were created to evaluatewhich treatments driven by PAC data were associated withimproved survival after adjustment for APACHE.

Type of PH (n)Dana Point Group 1 (PAH) 72Idiopathic PH 30Associated with connective tissue disease 20Drug/toxin induced 5Portopulmonary 10Associated with HIV 3Associated with congenital heart disease 4

Dana Point Group 3 (due to lung disease/hypoxia)

27

Idiopathic pulmonary fibrosis 10Obesity hypoventilation syndrome/obstructive sleep apnea

5

Bronchiolitis obliterans after lungtransplant

3

Chronic obstructive pulmonary disease 2Sarcoidosis 2Other (pulmonary alveolar proteinosis,recurrent pneumonia, radiation-inducedinterstitial lung disease,postpneumonectomy syndrome,bronchiectasis)

5

Time (mo) since PH diagnosed, median(IQR), n = 91

5.43 (0.13-29.5)

Treatment before admissionOn PH medications at admission (n) 60On prostacyclin at admission (n) 31

Reason for ICU admission (n)RHF 51Respiratory failure from causes otherthan RHF

23

Sepsis 8Other 17Postoperative observation 5Arrhythmia 4Syncope 2Miscellaneous (gastrointestinal bleeding,epistaxis, acute renal failure, subduralhematoma)

6

APACHE II, mean (SD) 17.2 (7.1)Sodium level on admission, mean (SD) 134.5 (5.1)Mean arterial pressure on admission,mean (SD)

71.6 (18.3)

Creatinine, mean (SD) 1.5 (1.7)BNP (pg/mL) on admission, n = 80Median (IQR) 384 (197-839)No. of patients with BNP N1000 19

Troponin (ng/mL), median (IQR), n = 76 0.14 (0.23-0.51)Most recent right ventricular systolicpressure (mm Hg) on echocardiogram,median (IQR), n = 94

83 (55-110)

3. Results

3.1. Baseline characteristics

After excluding elective and repeated admissions, 99patients were included in the study (Table 1). Most werefemale (64/99) and had pulmonary arterial hypertension(Dana Point Group 1) (72/99). The median length of stay inthe ICU was 10 days (interquartile range [IQR], 5-16 days).The mean APACHE II score was 17.2 (SD, 7.1). The primaryreasons for ICU admission were RHF (52%) and respiratoryfailure from causes other than RHF (23%). There were 4patients who were admitted with arrhythmias. The first patientwas admitted with a-flutter after self-discontinuing iloprost.He was cardioverted unsuccessfully. He subsequently under-went ablation and pacemaker placement but then had apulseless electrical activity cardiac arrest the next day anddied. The second patient was admitted with a-flutter withvariable block and syncope. She was diuresed, started on aprostacyclin, and converted to sinus rhythm before dis-charge. The third patient was admitted with a-flutter.Therapy with amiodarone, digoxin, sotolol, and ablationwere all unsuccessful, and she was discharged withintermittent a-fibrillation and a-flutter. The fourth patientdeveloped junctional bradycardia with hypotension during aright heart catheterization. She required atropine and adopamine drip, which then led to conversion to normal sinusrhythm. The majority of group 1 patients were admitted forRHF (57%), whereas the most group 3 patients wereadmitted for respiratory failure unrelated to RHF (63%).

3.2. Mortality associated with baselinecharacteristics

Of the 99 PH subjects, 30 died in the ICU on that ad-mission, and an additional 10 patients died within 6 months.Unadjusted odds ratios (OR) for 6-month and ICU mortalityare displayed in Table 2. Acute Physiology and ChronicHealth Evaluation II scores were positively associated withodds of death by 6 months (OR, 1.19 per point; 95% con-fidence interval [CI], 1.10-1.29; P b .0001). Six-month mor-tality significantly increases with each increase in APACHEII quartile, consistent with the logistic regression analyses(Fig. 1). Multivariable logistic regression analysis of the 12physiologic measurements included in the APACHE II scoreshowed that the association with mortality is primarily drivenby points for oxygenation (PaO2) and renal function (crea-tinine and dialysis); however, the aggregate score of theremaining 10 variables was still significantly associated with

increased mortality (P = .01, data not shown). Admissionsfor respiratory failure and sepsis were associated with higherodds of 6-month mortality (P = .01 and 0.02, respectively)

Table 2 Bivariate baseline characteristics association with mortality

Variable 6-mo mortality ICU mortality

OR (95% CI) P OR (95% CI) P

APACHE II (per point) 1.19 (1.10-1.29) b.0001 1.21 (1.11-1.31) b.0001Reason for admission a

Respiratory failure not due to RHF 3.73 (1.33-10.5) .01 5.09 (1.71-15.1) .003Sepsis 7.20 (1.30-39.8) .02 14.0 (2.42-80.9) .003

Female sex 0.34 (0.14-0.80) .013 0.33 (0.14-0.81) .015BNP N1000 (n = 80) 2.81 (0.98-8.10) .054 2.44 (1.01-5.87) .046Dana Point Group 3 vs Group 1 2.35 (0.95-5.78) .063 2.40 (0.95-6.07) .064Age (per year) 1.03 (0.99-1.06) .091 1.02 (0.98-1.05) .23On prior prostacyclin 1.96 (0.83-4.63) .12 1.75 (0.71-4.32) .22Most recent right ventricular systolic pressureon echocardiogram (per point)

0.99 (0.97-1.00) .17 0.99 (0.97-1.01) .20

Time since PH diagnosed ≤3 months 1.55 (0.67-3.62) .31 3.33 (1.29-8.59) .013a Reference group, patients admitted for RHF.

739.e10 T.N. Huynh et al.

compared with RHF. Dana Point Group 3 patients trendedtoward being associated with increased 6-month and ICUmortality (P = .06).

Stepwise multiple regression on the baseline characteris-tics showed APACHE score, Dana Point Group 3 PH, andpreexisting treatment with a prostacyclin were significantlyassociated with increased odds of 6-month mortality(Table 3). Other baseline characteristics were not significantonce adjusting for the other variables in this model. BNP wasnot included in multivariable analysis because the number ofmissing values made the resulting models unstable. AcutePhysiology and Chronic Health Evaluation score andpreexisting treatment with a prostacyclin were also signif-icantly associated with increased odds of 6-month mortalitywhen the analysis was performed for only patients in DanaPoint Group 1.

Fig. 1 Mortality by APACHE II quartiles.

3.3. Interventions in the ICU

Of the 99 patients in the study group, 20 patients requireddialysis; 44, vasopressors; and 34, mechanical ventilation.Dopamine was the initial vasopressor in 20 patients,levophed was the initial vasopressor in 12 patients,dobutamine was the initial vasopressor in 8 patients, andthe rest of the patients were started on a combination ofvasopressors that were selected by the clinician. Seventypercent of the patients who were dialyzed died in the ICU(median no. of days on dialysis, 9.5). Fifty percent of thepatients who received vasopressors died in the ICU (medianno. of days on vasopressors, 9). Seventy-one percent of thepatients who were mechanically ventilated died in the ICU(median days on mechanical ventilation, 8). Nitric oxide(NO) was used in 35 patients. A new PH medication wasinitiated in 61 patients, 22 of which were initiated on aprostacyclin. A PAC was place in 45 patients within 3 daysof their admission. Nine patients received CPR.

Individually, the need for dialysis, vasopressors, andmechanical ventilation were all significantly associated withhigher 6-month and ICU mortality (P b .01) (Table 4). Theuse of NO was also associated with worse outcome (P =.039). Pulmonary artery catheter placement within 3 days ofadmission was significantly associated with improved 6-month mortality (P = .035) but not ICU mortality.

Stepwise multivariable logistic regression showed thateven after adjusting for the previously identified baseline risk

Table 3 Multivariate model of baseline characteristics for 6-month mortality

OR (95% CI) P

Dana Point Group 3 3.99 (1.21-13.13) .023On prior prostacyclin 3.49 (1.01-12.05) .049APACHE II (per point) 1.21 (1.10-1.33) b.001

Table 4 Bivariate association of individual ICU interventions with mortality

Intervention 6-mo mortality ICU mortality

OR (95% CI) P OR (95% CI) P

Dialysis 13.80 (3.68-51.64) b.0001 9.19 (3.05-27.67) b.0001Vasopressors 4.58 (1.94-10.84) .001 8.05 (2.98-21.73) b.0001Mechanical ventilation 9.25 (3.56-24.08) b.0001 23.6 (7.72-72.17) b.0001NO 2.43 (1.04-5.66) .039 3.01 (1.23-7.32) .015PAC within 3 d 0.41 (0.18-0.94) .035 0.59 (0.24-1.44) .25Newly initiated on prostacyclin 0.62 (0.23-1.70) .35 0.44 (0.13-1.42) .17New PH medication Initiated 0.63 (0.27-1.43) .27 0.91 (0.38-2.18) .83

739.e11Patients with PH in teh ICU

factors, the need for dialysis increased the odds of 6-monthmortality by 7.96 times (P = .017) and mechanicalventilation by 3.74 times (P = .032) (Table 5). Pulmonaryartery catheter placement within the first 3 days of admissionwas associated with reduced odds of 6-month mortality (OR,0.25; P = .028). Pulmonary artery catheters were more likelyto be placed in Dana Point Group 1 patients, specificallythose with idiopathic pulmonary hypertension, and inpatients who were not yet on a prostacyclin. Pulmonaryartery catheter placement was still significantly associatedwith improved survival when having IPH or being on aprostacyclin was adjusted for in our model (data not shown).All 9 patients who received CPR died. In the analysis of onlyDana Point Group 1 patients, mechanical ventilation wasassociated with a 10.49 increase in OR for 6-month mortality(P = .003). Pulmonary artery catheter placement within thefirst 3 days of admission trended toward improved outcome(OR, 0.26; P = .076).

3.4. Subanalysis of patients who had a PAC

A PAC was placed in 45 patients within the first 3 days ofICU admission. Mortality risk was adjusted for APACHE IIscore, which was not correlated with the placement of a PAC.The management decisions guided by PAC placement were

Table 5 Final multivariable logistic regression model ofbaseline characteristics and ICU interventions for 6-monthmortality

All patients withPH admitted tothe ICU (n = 99)

Dana Point Group 1PAH patientsonly (n = 72)

OR (95% CI) P OR (95% CI) P

ICU interventionsDialysis 7.96 (1.45-43.84) .017 7.18 (0.88-58.51) .065

PAC within3 days

0.25 (0.07-0.86) .028 0.26 (0.06-1.15) .076

Mechanicalventilation

3.74 (1.12-12.44) .032 10.49 (2.18-50.47) .003

the following: 10 patients received increased diuresis, 10patients were initiated on a new PH medication, 10 patientsreceived both increased diuresis and a new PH medication,and 15 patients had no changes in management. Patients whohad management changes, with either increased diuresis(OR, 0.03; P = .05) or the initiation of a new PH medication(OR, 0.03; P = .038), had reduced odds of 6-month mortalitywhen compared with patients who had no intervention(Table 6). There was no interaction between these 2management changes (P .69). Intensive care unit mortalitywas not affected. Actual hemodynamic measurements (rightarterial pressure, mean pulmonary arterial pressure (PAP),pulmonary capillary wedge pressure, pulmonary vascularresistance (PVR), and cardiac index (CI)) were notassociated with mortality (data not shown).

The association between mortality and timing of PACplacement was further explored by comparing those whohad a PAC placed within 3 days of admission (n = 45), tothose who had a PAC placed later than 3 days after admission(n = 14), and those who never had a PAC (n = 40). The oddsof death were higher in patients who had a PAC placed late(OR, 5.72; P = .02) and in patients who never had a PAC(OR, 3.05; P = .04) compared with those who had a PACplaced within the first 3 days (Table 7).

4. Discussion

Patients with PH who require admission to the ICU oftenhave a dismal prognosis; our study revealed a 30% ICUmortality rate and 40% 6-month mortality, which is higherthan that of the general ICU population [13]. Given the highmortality, it is particularly important to identify thecharacteristics that will provide clinicians with prognostic

Table 6 Multivariate model of management changes guidedby PAC for 6-month mortality

OR (95% CI) P

APACHE II (per point) 1.36 (1.10-1.69) .004New PH medication 0.03 (0.00-0.82) .038Diuresis 0.03 (0.00-1.00) .050

Table 7 Pulmonary artery catheter association with mortalityanalyzed by timing of placement

6-month mortality ICU mortality

OR (95% CI) P OR (95% CI) P

APACHE II(per point)

1.18 (1.08-1.28) .000 1.21 (1.10-1.32) .000

PAC after3 days a

5.72 (1.39-23.48) .016 4.28 (1.00-18.31) .050

No PAC duringadmission

3.05 (1.07-8.73) .037 2.11 (0.66-6.73) .205

a Reference group, PAC placed within 3 days of admission.

739.e12 T.N. Huynh et al.

information and interventions that may improve survival.This is the first study to generate a mortality model afteridentifying the factors that are associated with poor outcomein patients with PH who require admission to the ICU. Theassociation of APACHE score with mortality suggests thatphysiologic scores within the first 24 hours of ICU admissionshould be routinely calculated for these patients. The find-ings that this association is mainly driven by renal failurepoints and that dialysis significantly increased the odds ofmortality are in agreement with a recent study showingthat acute kidney injury is associated with risk of death [14].Prior prostacyclin use was likely a reflection of the severityof the patient's PH because prostacyclins are only recom-mended for patients who have New York Heart Associationfunctional class III or IV symptoms [15]. Patients with DanaPoint Group 3 PH have underlying lung disease that maysignificantly contribute to their morbidity. However, studieshave shown that elevated PVR is strongly associated withearly mortality even after adjustment for other variables,suggesting it is the development of PH that significantlydecreases survival in Dana Point Group 3 patients [16,17].

Mechanical ventilation and dialysis indicate the develop-ment of end-organ failure and are associated with worseoutcome. Interestingly, the parameter estimate for mechan-ical ventilation is higher in group 1 patients (Table 5), sug-gesting that intubation in patients with pulmonary arterialhypertension (PAH) is particularly grim. Cardiopulmonaryresuscitation was performed on 9 patients, none of whomsurvived. A previous study has similarly shown that CPR inthe patient with PH is rarely successful (8/513, 6% survivalrate) [9]. Patients with PH have little reserve. Once hemo-dynamic collapse occurs, it is often irreversible. Given thepotential physical and emotional toll of CPR, this findingemphasizes the importance of addressing advanced di-rectives in critically ill patients with PH. Similar to thestudy of Sztrymf et al [11] of patients with PH with RHF, ourstudy also found that the initiation of a new PH medicationand the use of NO in the acute critical care setting were notassociated with improved outcome. Further studies are war-ranted to accurately assess these interventions.

Three other studies limited to Dana Point Group 1 PH anddecompensation due to RHF found related results [8,11,18].

Among 61 PAH patients admitted to the hospital (not neces-sarily the ICU), hyponatremia and hypotension were strongpredictors of mortality [8]. Among 119 patients who requiredeither ICU or ward admissions, respiratory rate, estimatedglomerular filtration rate, sodium level, and albumin levelswere found to be significantly associated with 90-daymortality [18]. Our study showed that APACHE II score,which captures hyponatremia, renal failure, respiratory rate,and hypotension, was predictive of poor prognosis. Inanother study, 46 patients admitted to the ICU the highmortality (41%) was significantly associated with BNP,Simplified Acute Physiology Score II scores, and escalatingdoses of ionotropes [11]. Similarly to our study, PH-specificdrugs and NO did not influence survival.

No studies have examined the relationship between PACplacement and mortality in critically ill patients with PH.The placement of a PAC has fallen out of favor overall in theICU due to studies showing a lack of efficacy [19-21].Although the diagnosis of PH is contingent upon finding amean PAP greater than 25 on right heart catheterization, theutility of the PAC to guide management during acutedecompensations requiring ICU level care has not beenevaluated. Recently, a review by Hoeper and Granton [22]has advocated the use of invasive hemodynamic monitoringin patients with severe PH and RHF. Our study is the firststudy to demonstrate data to support this recommendation.The improved survival seen with PAC placement within 3days of admission is interesting and should be furtherevaluated. Our study showed that PAC placement wasassociated with improved survival when its placement led tomanagement changes that might have not been otherwisepursued (increased diuresis or initiation of new PHmedication). The initiation of a new PH medication wasnot associated with better outcome in the entire cohort,which suggests that PH therapy is particularly beneficialwhen its initiation was guided by hemodynamic measure-ments. Furthermore, the PAC was only associated withimproved outcome when it was placed early in theadmission, at a time when management decisions may bemore crucial and less of a “last ditch effort.” Lastly, it isinteresting to note that early PAC placement improved 6months but not ICU outcomes. We believe that it is theinitiation of PH therapy, which can take several months toshow benefit, that likely improves long-term survival. Thisis supported by the observation that patients who had nochange in management after PAC placement did not havereduced mortality. The use of a PAC in this populationdeserves to be prospectively evaluated in a randomizedmanner or pre-PAC/post-PAC therapeutic plan comparison.

There are several limitations to our study. First, oursample size is small, particularly in subanalyses. Second, ourstudy is retrospective and, hence, cannot provide conclusiveevidence about the efficacy of specific interventions. How-ever, the observed associations certainly validate the needfor larger, prospective studies on this patient population.Third, there were a few parameters that were missing or

739.e13Patients with PH in teh ICU

incomplete in our analysis (such as BNP and functionalclass). Although these factors have been evaluated in pre-viously studies [8,11,23], the results have been conflicting.There are a larger number of patients with PH followed inour telemetry unit who receive high levels of interventionthat may provide more insight into the inpatient interventionsthat affect outcome.

5. Conclusions

In conclusion, our study shows that the mortality ofpatients with PH who require admission to the ICU is high.Patients with high APACHE scores, Dana Point Group 3 PH,and patients already on treatment with prostacyclins are atincreased risk for death. Pulmonary artery catheter placementwithin 3 days of admission that leads to a change in medicalmanagement may be associated with reduced mortality.Nonetheless, our study is retrospective, small, and at a singlecenter. Intensive care unit interventions in patients with PHwarrant further evaluation in prospective trials.

References

[1] Farber HW, Loscalzo J. Pulmonary arterial hypertension. N Engl JMed 2004;351:1655-65.

[2] Chin KM, Kim NH, Rubin LJ. The right ventricle in pulmonaryhypertension. Coron Artery Dis 2005;16:13-8.

[3] Oudiz RJ, Schilz RJ, Barst RJ, et al. Treprostinil, a prostacyclinanalogue, in pulmonary arterial hypertension associated with connec-tive tissue disease. Chest 2004;126:420-7.

[4] Galie N, Ghofrani HA, Torbicki A, et al. Sildenafil citrate therapyfor pulmonary arterial hypertension. N Engl J Med 2005;353:2148-57.

[5] Channick RN, Simonneau G, Sitbon O, et al. Effects of the dualendothelin-receptor antagonist bosentan in patients with pulmonaryhypertension: a randomised placebo-controlled study. Lancet2001;358:1119-23.

[6] Barst RJ, Rubin LJ, Long WA, et al. A comparison of continuousintravenous epoprostenol (prostacyclin) with conventional therapy forprimary pulmonary hypertension. The Primary Pulmonary Hyperten-sion Study Group. N Engl J Med 1996;334:296-302.

[7] Wax D, Garofano R, Barst RJ. Effects of long-term infusion ofprostacyclin on exercise performance in patients with primarypulmonary hypertension. Chest 1999;116:914-20.

[8] Campo A, Mathai SC, Le Pavec J, et al. Outcomes of hospitalisationfor right heart failure in pulmonary arterial hypertension. Eur Respir J2011;38:359-67.

[9] Hoeper MM, Galie N, Murali S, et al. Outcome after cardiopulmonaryresuscitation in patients with pulmonary arterial hypertension. Am JRespir Crit Care Med 2002;165:341-4.

[10] Zamanian RT, Haddad F, Doyle RL, Weinacker AB. Managementstrategies for patients with pulmonary hypertension in the intensivecare unit. Crit Care Med 2007;35:2037-50.

[11] Sztrymf B, Souza R, Bertoletti L, et al. Prognostic factors of acuteheart failure in patients with pulmonary arterial hypertension. EurRespir J 2010;35:1286-93.

[12] Benedict N, Seybert A, Mathier MA. Evidence-based pharmacologicmanagement of pulmonary arterial hypertension. Clin Ther 2007;29:2134-53.

[13] Zimmerman JE, Kramer AA, McNair DS, Malila FM. AcutePhysiology and Chronic Health Evaluation (APACHE) IV: hospitalmortality assessment for today's critically ill patients. Crit Care Med2006;34:1297-310.

[14] Haddad F, Fuh E, Peterson T, et al. Incidence, correlates, and conse-quences of acute kidney injury in patients with pulmonary arterialhypertension hospitalized with acute right-side heart failure. J CardFail 2011;17:533-9.

[15] Shapiro SM, Oudiz RJ, Cao T, et al. Primary pulmonary hypertension:improved long-term effects and survival with continuous intravenousepoprostenol infusion. J Am Coll Cardiol 1997;30:343-9.

[16] Nadrous HF, Pellikka PA, Krowka MJ, et al. Pulmonary hyperten-sion in patients with idiopathic pulmonary fibrosis. Chest 2005;128:2393-9.

[17] Corte TJ, Wort SJ, Gatzoulis MA, Macdonald P, Hansell DM, WellsAU. Pulmonary vascular resistance predicts early mortality in patientswith diffuse fibrotic lung disease and suspected pulmonary hyperten-sion. Thorax 2009;64:883-8.

[18] Haddad F, Peterson T, Fuh E, et al. Characteristics and outcome afterhospitalization for acute right heart failure in patients with pulmonaryarterial hypertension. Circ Heart Fail 2011;4:692-9.

[19] Richard C, Warszawski J, Anguel N, et al. Early use of the pulmonaryartery catheter and outcomes in patients with shock and acute respi-ratory distress syndrome: a randomized controlled trial. JAMA 2003;290:2713-20.

[20] Shah MR, Hasselblad V, Stevenson LW, et al. Impact of the pul-monary artery catheter in critically ill patients: meta-analysis ofrandomized clinical trials. JAMA 2005;294:1664-70.

[21] Klings ES, Farber HW. Pulmonary hypertension as a risk factor fordeath in patients with sickle cell disease. N Engl J Med 2004;350:2521-2 [author reply −2].

[22] Hoeper MM, Granton J. Intensive care unit management of patientswith severe pulmonary hypertension and right heart failure. Am JRespir Crit Care Med 2011;184:1114-24.

[23] Leuchte HH, Holzapfel M, Baumgartner RA, Neurohr C, Vogeser M,Behr J. Characterization of brain natriuretic peptide in long-term follow-up of pulmonary arterial hypertension. Chest 2005;128:2368-74.