Educational

DIMENSION

Care of the Patient With

Pulmonary Arterial
Hypertension
Carol S. Smith, PhD, RN; Nancy L. York, PhD, RN;
Christy J. Kane, PhD, RRT-NPS; Frederick Weitendorf, RPh, RN

Patients presenting with pulmonary arterial hypertension (PAH), the

rarest of the groups of pulmonary hypertension diagnoses, are
infrequently seen in the critical care arena. However, when patients
with PAH present in the intensive care unit, it is generally related to
an exhaustion of treatments. This article focuses on the current state of
the literature addressing the group designation, pathophysiology,
symptom expression, and treatment modalities of the patient with PAH.
Keywords: Critical care nursing, Evidence-based practice, Pulmonary
arterial hypertension
[DIMENS CRIT CARE NURS. 2015;34(6):340/347]

Pulmonary arterial hypertension (PAH) is defined as group
1 of 5 groups related to pulmonary hypertension diagnoses
(Table 1).1 Pulmonary arterial hypertension is a serious
diagnosis generally leading to significant right-sided heart
failure and demise within 5 years of the initial diagnosis.2
Pulmonary arterial hypertension is generally diagnosed when
all else is ruled out, and the pulmonary arterial pressure
(PAP) is maintained at or greater than 25 mm Hg with a
pulmonary capillary wedge pressure (PCWP) at or less than
15 mm Hg.2,3 Critical care nurses play a pivotal role in the
management of patients with this devastating diagnosis.
This article outlines the latest diagnostic and treatment
modalities along with etiology, symptom expression, and
pathophysiology of PAH.
ETIOLOGY
Pulmonary arterial hypertension, although a nonsynony-
mous term with pulmonary hypertension, is classified as
group 1 of 5 groups under the recognized pulmonary hy-
pertension categories. This classification of group 1 re-
cently upheld during the World Symposium on pulmonary
hypertension held in Nice, France.1 These 5 pulmonary
hypertension groups address issues that may show sim-
ilarity in symptom expression, hemodynamic parameters,
and pathology, yet treatment and outcomes may vary
drastically.4
The 2 most common causes of PAH are idiopathic,
some estimating the occurrence at 1 case per million,5,6
whereas other sources state this occurrence at 15 cases per
million,3 and familial, with some estimating the occurrence
rate of 6-10% of all PAH cases,3 and other sources estim-
ating the occurrence rate as 2.9 cases per million.5,6
Currently, women are the more common gender affected,
at approximately 60% of diagnosed cases.7 Other causes
of PAH include portal hypertension, Raynaud disease,
scleroderma, systemic lupus erythematosus, human immu-
nodeficiency virus infection, thyroid disorders, chronic hemo-
lytic anemia, and certain medications, such as appetite
suppressants and chemotherapy agents.8,9 Current re-
search has defined medications to be either definite causes
of PAH, meaning there have been extensive, multisite re-
search studies supporting these claims, or possible causes,
meaning single-site studies have referenced these as

340 Dimensions of Critical Care Nursing Vol. 34 / No. 6 DOI: 10.1097/DCC.0000000000000140

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.


potential causes (Table 2).1,8,9 Even less frequently, PAH is
associated with pulmonary veno-occlusive disease and
pulmonary capillary hemangiomatosis.9
While idiopathic PAH has no known cause, familial
PAH is inherited as an autosomal dominant trait with a
low penetrance, meaning some people who inherit the trait
will remain disease-free.10 Familial PAH is most often
caused by a mutation in BMPR2 (bone morphogenetic
protein receptor type II), a member of the tumor necrosis
factor " super family, which helps regulate the growth of
cells in the small arterial walls in the lungs.11,1
Pathophysiology
Pathophysiologic changes seen with PAH culminate in a
decrease in pulmonary artery breadth via vasoconstriction,
intimal proliferation, and fibrosis.12 Vasoconstriction is
multifaceted and thought to be an imbalance in the sub-
stance thromboxane, a known vasoconstrictor, compara-
tive to the availability of prostacyclin, a known vasodilator.
Concurrently, an overproduction of endothelin 1, also
known to cause vasoconstriction, is noted, while a sig-
nificant decrease in the synthesis of endothelium-derived
nitric oxide (NO), known to cause vasodilation, exists.10
Intimal proliferation and ultimate fibrosis formation are
thought to trigger significant imbalances in the above
substances.3,10 Other causes, thought to be related to the
use of certain appetite suppressants, are known to decrease
serotonin reuptake and thereby promote unwanted vaso-
constriction. Along with vasoconstriction, potential thrombi
formation and plexogenic arterial changes occur, leaving the
pulmonary artery narrowed and thickened with a high risk
of thrombi formation potentially leading to a sudden and
significant decrease in pulmonary arterial diameter.3
Hemodynamic Parameters
Hemodynamically, the right side of the heart enjoys sig-
nificantly less pressure than does the left side; however, in
PAH, consistently high right-sided heart pressure exists.
This increase in pressure is obtained through continual
pulmonary artery vasoconstriction, smooth muscle hyper-
trophy, and intimal proliferation.10 Classic diagnosis, gen-
erally obtained via right-heart catheterization, reveals a
consistently high PAP of 25 mm Hg or greater at rest or
30 mm Hg or greater with activity. This increase in PAP
is noted with normalized PCWP of 15 mm Hg or less and
a pulmonary vascular resistance of greater than 3 wood
units.1,3 Generally, a diagnosis of PAH is ruled out if the
PCWP is determined to exceed 15 mm Hg as this calls into
question other pulmonary hypertension diagnoses.13,14
Diagnosis is generally obtained with the above hemody-
namic parameters following a ruling out of other scenarios
known to cause an increase in PAP.3,10
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Care of the Patient With PAH
TABLE 1 Current Diagnostic Classification of
Pulmonary HypertensionYRelated
Diagnoses
1. Pulmonary arterial hypertension (PAH)
1.1 Idiopathic PAH
1.2 Heritable PAH
1.2.1 BMPR (bone morphogenic protein receptor type II)
1.2.2 ALK-1 (anaplastic lymphoma kinase), ENG (endoglin),
SMAD9, CAV1 (caveolin 1), KCNK3
1.2.3 Unknown
1.3 Drug and toxin induced
1.4 Associated with
1.4.1 Connective tissue disease
1.4.2 Human immunodeficiency virus infection
1.4.3 Portal hypertension
1.4.4 Congenital heart disease
1.4.5 Schistosomiasis
1¶. Pulmonary veno-occlusive disease and/or pulmonary capillary
hemangiomatosis
1µ. Persistent pulmonary hypertension of the newborn
2. Pulmonary hypertension due to left-sided heart disease
2.1 Left ventricular systolic dysfunction
2.2 Left ventricular diastolic dysfunction
2.3 Valvular disease
2.4 Congenital/acquired left-sided heart inflow/outflow tract
obstruction and congenital cardiomyopathies
3. Pulmonary hypertension due to lung diseases and/or hypoxia
3.1 Chronic obstructive pulmonary disease
3.2 Interstitial lung disease
3.3 Other pulmonary diseases with mixed restrictive and
obstructive pattern
3.4 Sleep-disordered breathing
3.5 Alveolar hypoventilation disorders
3.6 Chronic exposure to high altitude
3.7 Developmental lung diseases
4. Chronic thromboembolic pulmonary hypertension
5. Pulmonary hypertension with unclear multifactorial mechanisms
5.1 Hematologic disorders: chronic hemolytic anemia,
myeloproliferative disorders, splenectomy
5.2 Systemic disorders: sarcoidosis, pulmonary histiocytosis,
lymphangioleiomyomatosis
5.3 Metabolic disorders: glycogen storage disease, Gaucher disease,
thyroid disorders
5.4 Others: tumoral obstruction, fibrosing mediastinitis, chronic renal
failure, segmental pulmonary hypertension
Table created with information from Simonneau et al.1
November/December 2015 341
 Care of the Patient With PAH

TABLE 2 Medications Linked to Pulmonary of PAH is often through the exclusion of other potential
Arterial Hypertension (PAH) Diagnosis conditions and diseases. A thorough history and physical
examination assist the health care provider in determining
Known to Cause PAH Thought to Cause PAH if there is a risk of PAH and documenting baseline find-
Aminorex fumarate (Menocil) Cocaine ings. The patient should be questioned about his/her fam-
ily history of PAH or any connective tissue diseases, as well
Fenfluramine (Pondimin, Ponderax, Phenylpropanolamine
and Adifax)
as any potential exposure to human immunodeficiency
virus and known toxic agents.9 Other pertinent questions
Dexfenfluramine hydrochloride (Redux) St John’s wort
should include those related to shortness of air and ex-
Toxic rapeseed oil Interferon ! and " acerbating factors, complaints of fatigue, peripheral edema,
Benfluorex Amphetamine-like medications syncopal or near-syncopal episodes, and palpations. A fo-
cused cardiac physical examination should be performed
Table created with information from Simonneau et al,1,8,9 Gin-Sing,1,8,9 and to identify baseline heart sounds, as well as the presence
Strange et al.1,8,9
of any murmurs, jugular venous distension, and peripheral
edema.
Clinical Manifestations The initial screening for patients suspected of having
Initial signs and symptoms of PAH are often vague and PAH may include an electrocardiogram, chest radiograph,
nonspecific, making the disease difficult to recognize.2 This pulmonary function tests, arterial blood gasses, and/or
vague presentation has lent this condition to be labeled as cardiac magnetic resonance imaging.8,9 However, patients
the ‘‘other’’ high blood pressure condition and may lead to with a high suspicion of PAH typically undergo a trans-
devastating delays in seeking care and ultimate diagnosis thoracic Doppler echocardiography, followed by a right-
(Table 3).2,9 Impaired oxygenation, generally brought sided cardiac catheterization, for diagnostic confirmation.
about through ineffective cardiac output, drives the more This right-sided heart catheterization is essential for base-
common and initial symptoms of shortness of breath, dyspnea line right-sided heart readings and ruling out other potential
on exertion, chest pain, cough, fatigue, and dizziness.2 causes for the noted increase in pulmonary artery pressure.3
As the disease progresses, patients often complain of There are several cardiac catheterization findings that con-
increasing fatigue, palpitations, syncope, and increasing firm the PAH diagnosis (Table 4). As PAH progresses, car-
exercise intolerance.9,15 In addition, most patients exhibit diac magnetic resonance imaging may show a decreased
hypoxemia, jugular venous distension, peripheral edema, stroke volume, an increased right ventricular end-diastolic
and peripheral cyanosis, among others.9,15 Patients in the volume, and decreased left ventricular end diastolic volume;
advanced stages of PAH reveal symptoms such as ac- these are known poor prognostic signs and are considered
centuated S2 presentation, development of a pulmonic the triad preceding eventual right ventricular failure.
murmur, right ventricular heave, ascites, and an eventual
S3 development.3 Pharmacologic Therapy
Diagnostics GENERAL CONSIDERATIONS
While early diagnosis and treatment of PAH are critical Numerous pharmacologic agents are used to treat PAH
because of its rapid progression if untreated, the finding in the intensive care unit (ICU). Many agents target the
underlying issues and/or complications of PAH requiring
TABLE 3 Signs and Symptoms of Pulmonary
Arterial Hypertension TABLE 4 Pulmonary Artery Hypertension
Signs Symptoms Hemodynamic Findings
Jugular venous distension Exertional dyspnea Parameter Value

S3 presence Fatigue Resting mean pulmonary artery pressure >25 mm Hg

Pronounced pulmonic valve closure Dizziness Right atrial pressure >4 mm Hg
Tricuspid regurgitation murmur Angina Cardiac index <2.5 L/min per m2
Hepatomegaly Palpitations Pulmonary vascular resistance >500 dyn/s per cm5
Peripheral edema Syncope Systemic vascular resistance 800-1200 dyn/s per cm5
Peripheral cyanosis Hemoptysis Pulmonary artery wedge pressure <15 mm Hg

Table created with information from Cheever, 2005; Strange et al., 2009.9,15 Table created with information from Badesch et al,5,6 ESC,5,6 and Centeno.3

342 Dimensions of Critical Care Nursing Vol. 34 / No. 6

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

 Care of the Patient With PAH

continuous assessment/monitoring by the intensive care
registered nurse (Table 5). For example, positive inotropic
agents may assist with optimizing cardiac output for those
with right-sided and/or left-sided heart dysfunction seen in
patients with PAH.17 Anticoagulation therapy should also
be considered for certain PAH patients but should not be
used in patients with secondary PAH caused by an under-
lying disease process such as scleroderma or congenital
heart defects.5,18 Careful fluid management is imperative
to avoid an unwanted increase in PAP or right ventricular
pressure, which can ultimately lead to increased right-sided
stress and eventual right-sided heart failure. As with all
patients in the ICU, maintaining adequate oxygenation is
paramount. Supplemental oxygen via oxygen device or
mechanical ventilator, as discussed below, should be used
to maintain oxygen saturation greater than 90%.5 In ad-
dition, the patients’ arterial partial pressure of oxygen and
hemoglobin levels should be monitored while also maxi-
mizing their cardiac output.5 For the purpose of this ar-
ticle, pharmacologic therapy will focus on vasodilator
agents used to decrease the pulmonary hemodynamic pres-
sures and/or pulmonary vascular resistance in patients
with PAH.
VASOREACTIVITY TESTING AND
CALCIUM-CHANNEL BLOCKERS
During the initial evaluation of patients with PAH, vaso-
reactivity testing is recommended. These tests are per-
formed in the cardiac catheterization laboratory while
monitoring pulmonary pressure during the right-sided heart
catheterization.19 In patients with pulmonary hypertension
associated with venous occlusion, vasoreactivity testing
should be avoided because of possible severe pulmonary
edema.5,6 Primarily, 3 drugs are used to evaluate pulmonary
vasoreactivity. Epoprostenol, adenosine, and NO are used
for 10, 2, and 5 minutes, respectively.5,6,20 Patients with
PAH showing a positive result, or hemodynamic impro-
vement, as a result of their vasoreactivity study may ulti-
mately benefit from the usage of calcium-channel blockers
(CCBs), such as nifedipine, diltiazem, and amlodipine, to
treat their PAH with a potential improved prognosis.5,20
Conversely, patients whose vasoreactivity studies produce
a negative result, those who have no hemodynamic impro-
vement, or those who have not undergone a vasoreactivity
study should not be started on a CCB because of potential
severe adverse effects, such as hypotension, syncope, and
right ventricular failure.3,12 Patients with PAH who do not
respond favorably or sufficiently to CCB therapy are typi-
cally placed on 1 of the agents discussed in the following
section.5,6
A primary goal in treating the patient with PAH is to
achieve pulmonary vasodilation, improving ventilation/
perfusion matching and reducing workload of the right
side of the heart, without causing systemic vasodilation,
leading to hypotension. The vasodilator agents used in
treating patients with PAH can be categorized by the
pathways they influence.18 Endothelin receptor antagonists
block the vasoconstriction caused through the endothelin

TABLE 5 Agents Used to Treat Pulmonary Arterial Hypertension

Possible Complications/Special
Agent Pathway Route Monitoring Considerations

Ambrisentan Endothelial Oral BP, CO, Hgb, LFT Not used in pregnant women, headache, flushing,
tachycardia constipation, pale skin
Bosentan Endothelial Oral BP, CO, LFT, Hgb Not used in pregnant women, headache, flushing,
heartburn, cold-like symptoms, liver damage
Nitric oxide Nitric oxide Inhaled gas (delivered with Continuous administration, Methemoglobinemia, formation of nitrogen dioxide,
INOMaxB) BP, CO, ABG and rebound pulmonary hypertension when
weaned or stopped
Sildenafil Nitric oxide Oral or intravenous BP, CO Use with caution with nitrates as profound
hypotension can occur
Epoprostenol Prostacyclin Intravenous or inhaled aerosol Continuous administration, Nausea, diarrhea, flushing, headaches, muscle pain
BP, CO
Iloprost Prostacyclin Inhaled aerosol, delivered with BP, CO, LFT, BUN/Cr, Jaw pain, flushing, sleep issues, cough, nausea,
adaptive aerosol delivery system vomiting, blurred vision, development of
pulmonary edema
Treprostinil Prostacyclin Inhaled aerosol subcutaneous (via BP, CO, LFT, BUN, Cr Risk of gram negative infection with intravenous
pump) or intravenous usage, increased risk of bleeding

Abbreviations: ABG, arterial blood gas; BP, blood pressure; BUN/Cr, Blood, urea, nitrogen/creatinine; CO, cardiac output; Hgb, hemoglobin; LFT, liver function test.
Table created with information from Badesch et al,5,6 ESC,5,6 and the US National Library of Medicine.16

November/December 2015 343

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

 Care of the Patient With PAH
pathway. Inhaled NO and prostacyclin agents cause vaso-
dilation through their respective pathways.18
ENDOTHELIAL RECEPTOR ANTAGONISTS
Two endothelial receptors antagonists are currently on the
market. Ambrisentan and bosentan are oral medications
used to treat patients with significant, chronic PAH. Both
medications appear to improve symptoms and limitations
caused by PAH.18,21-23 Patients with PAH may use these
medications as part of their home regimen.18
NITRIC OXIDE PATHWAY
A second mechanism to facilitate pulmonary vasodilation
is the NO pathway.18 Nitric oxide is produced naturally
in the human body, and diminished NO levels in the lung
may be 1 possible component of PAH. Nitric oxide exists
as a gas, both colorless and odorless, which makes it ideal to
administer directly to the lungs.24 Dosages are administered
by a specialized machine, INOMax by IKARIA (Hampton,
New Jersey), and with parts per million (ppm) dosages
varying depending on the protocol used. Nitric oxide readily
crosses the alveolar-capillary membrane and quickly binds
with hemoglobin, making it inactive, thus making it a
selective pulmonary vasodilator.25
Five potential issues with NO exist. First, NO has an
extremely short half-life, a few seconds, requiring contin-
uous administration of NO. Second, patients on NO may
cause increased levels of methemoglobin, but this is rarely
an issue for patients receiving less than 100 ppm.25 Third,
NO may combine with oxygen to form nitrogen dioxide,
a potentially toxic gas.24 Care must be used to limit the
time NO is exposed to oxygen, and nitrogen dioxide levels
should be monitored, which is standard with the INOMax
delivery system. Fourth, patients using NO may experi-
ence a rebound increase in pulmonary artery pressures as
the NO is weaned and/or removed, so close monitoring
is necessary as the patient is weaned from the gas.24,26,27
Finally, NO delivery is expensive, costing several thou-
sand dollars per day.28,29
Even with the potential challenges of delivering this
gas, NO is extensively and safely used in the neonatal ICU
for the treatment of persistent pulmonary hypertension of
the newborn.24,30 In adults, current research focuses on
the ability of NO to be used for long-term therapy. Nitric
oxide can be safely delivered by pulsed nasal cannula or
face mask to patients with chronic PAH.25 Finally, short-
term NO, in combination with oxygen, can be used to
determine the patient’s vasoreactivity at the time of diagnosis,
which may predict a patient’s long-term prognosis.20,31
Sildenafil works indirectly on the NO pathway. Silden-
afil is a phosphodiesterase type 5 inhibitor and prevents the
breakdown of guanosine monophosphate. This process
344 Dimensions of Critical Care Nursing Vol. 34 / No. 6
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
results in vasodilation. Sildenafil is available by tablet,
liquid suspension, and by intravenous routes.18
PROSTACYCLIN PATHWAY
Three prostanoid derivatives vasodilate the pulmonary
circulation through the prostacyclin pathway and are cur-
rently used for the treatment of PAH.20 The first prostanoid
derivative, epoprostenol, is a vasodilator and also diminishes
platelet aggregation, requiring aggressive monitoring to
avoid unwanted bleeding.27 Epoprostenol is administered
by continuous intravenous route or by continuous inhalation
via aerosol delivery. Continuous administration is neces-
sary because of the drug’s short half-life.5,6 The inhalation
route offers direct administration to the lung and the
target organ and may minimize systemic adverse effects, such
as vasodilation of the systemic circulation.32 Infusion issues,
such as infiltration, can be catastrophic to the patient be-
cause of the ultrashort half-life this medication exhibits.20
As with NO, sudden disruption in epoprostenol admin-
istration may result in rebound increased pulmonary hemo-
dynamic values. Adverse effects of epoprostenol include
gastrointestinal upset, including nausea, diarrhea, flushing,
headaches, and general muscle pain.20
Iloprost, a prostacyclin analog, is also used to vasodilate
pulmonary vessels. Iloprost is primarily used as a long-
term treatment of chronic PAH, but may also be beneficial
in treating some patients with acute PAH exacerbations.5,27
Inhaled iloprost requires administration by a specialized
adaptive aerosol delivery system.33 Because of its longer
half-life, as compared with epoprostenol, iloprost may be
given intermittently throughout the day. Jaw pain and
flushing are the most common adverse effects noted.5,6
Treprostinil, the third drug in this class, can be given by
inhalation, intravenously, or subcutaneously, via a pump.
When given intravenously, adverse effects of this medi-
cation are similar to epoprostenol.20 In addition, patients
receiving intravenous treprostinil may have a higher inci-
dence of gram-negative infections, including sepsis.20 Be-
cause of its longer half-life, initial studies demonstrate the
home care regimen of patients with PAH may require only
4 doses of inhaled treprostinil throughout the day.32
Off-label medication usage refers to the prescribing of
Federal Drug AdministrationYapproved medications that
are used in a form or administrative route not specifically
approved for usage. Current statistics reveal that up to
23% of all medications used for inpatient scenarios in-
clude off-label medications or off-label administration
route usage of prescribed medications.34 The 3 prostanoid
derivatives mentioned previously all have off-label usage
in the treatment of group 1 PAH patients. Epoprostenol
intravenously administered, inhaled iloprost, and treprostinil
administered either intravenously, subcutaneously, or
inhaled are considered off-label usage via administration
 Care of the Patient With PAH

vehicle, while the medications are recognized by the tions.5,6 A pharmacist or pharmacology database should
FDA.16 be consulted to determine if any drug interactions exist.

COMBINATION THERAPY AND DRUG COST

INTERACTIONS
As with other medical conditions, a combination-drug ap-
proach may be more beneficial than a single-drug ap-
proach.5,18,20 Typically, 2 drugs are administered, 1 each
from 2 of the 3 classes discussed previously. Matamis et al35
found, in cardiac surgery patients with PAH, an improve-
ment in pulmonary pressure when a combination of in-
haled NO and sildenafil was administered, as compared
with the drugs being administered alone. A few studies have
shown a positive impact of adding inhaled treprostinil to
sildenafil or bosentan as well as the benefits of combining
sildenafil with epoprostenol.5,6,20 Further data from on-
going random clinical trials are necessary to determine best
practices of combination therapy, in particular when to add
an additional medication as well as which combination of
agents is best.5,6,20
Drug interactions may occur when administering PAH
pharmacologic agents.5,6 For example, significant hypo-
tension may occur in patients who take sildenafil with
nitrates.5,6 For this reason, these 2 drugs should not be
administered together. Multiple other medication interac-
tions exist, and the registered nurse should be aware of
these at all times. Table 6 lists the more common medica-
tions seen within the intensive care arena that may pose
issues if used concurrently with the known PAH medica-
As mentioned earlier, NO administration is quite costly.
Mullin et al28 compared the use of aerosolized epoprostenol
with inhaled NO. No significant clinical difference was
observed in this small study; however, the aerosolized epo-
prostenol saved approximately $10 000 per patient, as
compared with inhaled NO. Torbic et al29 also found no
clinical difference between inhaled epoprostenol and in-
haled NO. In addition, they noted that ‘‘inhaled NO was
4.5 to 17 times more expensive than inhaled epoprostenol,
depending on contract pricing.’’29(p844) For facilities that
treat large number of patients needing NO, the savings
of using epoprostenol, or other similar agents, should be
considered.
Mechanical Ventilation in PAH Patients
Appropriate mechanical ventilation settings depend on the
patient’s underlying pathology; however, as with other
critical care patients, maintaining adequate oxygenation is
paramount. In PAH patients with right ventricular fail-
ure, invasive ventilation should be avoided because of the
possible sedative agent’s adverse effects, such as hypoten-
sion, which may be necessary for patients on invasive me-
chanical ventilation. However, if sedation is needed, the
use of low-dose opioids concurrently given with benzodi-
azepines or the use of propofol is preferred.17

TABLE 6 Medication Interactions With Commonly Seen Medications Within the Intensive Care Unit (ICU)
Pulmonary Arterial Hypertension Other Common ICU
Medication Medications Known Interactions

Ambrisentan (Letairis) Cyclosporine Increased blood level of ambrisentan

Bosentan (Tracleer) Cyclosporine/erythromycin Bosentan levels increase
Rifampicin Bosentan levels decrease
3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors Simvastatin and atorvastatin levels may decrease by 50%
Hormonal contraceptives Hormone levels decrease and contraceptive coverage may vary
Sitaxentan (Thelin) Warfarin Significantly increases prothrombin time levels
Cyclosporine Sitaxentan levels increase
Sildenafil (Revatio) 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors Simvastatin/atorvastatin levels increase with increased risk
of rhabdomyolysis
Protease inhibitors Sildenafil levels may increase
Ketoconazole Sildenafil levels may increase
Erythromycin Sildenafil levels may increase
Nitrates ethyl alcohol Profound systemic hypotension noted sildenafil levels may increase
Tadalafil (Adcirca) Nitrates Profound systemic hypotension noted

Table created with information from Badesch et al5,6 and ESC.5,6

November/December 2015 345

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

 Care of the Patient With PAH
Positive end-expiratory pressure (PEEP) can have a
positive or negative hemodynamic impact on the PAH
patient. If the patient is severely hypoxemic, the addition
of PEEP may improve pulmonary hypertension due to
the increase in oxygenation at the pulmonary capillary. In
hemodynamically unstable patients or those who require
excessive PEEP levels, the addition of high PEEP levels
may decrease venous return and further elevate pulmonary
pressures, stressing the cardiac system and lowering car-
diac output.26,27 In general, lower tidal volumes with lower
PEEP levels are recommended for the patient with PAH.26,27
Finally, permissive hypercapnia (allowing carbon dioxide
levels to climb) may cause further hemodynamic compli-
cations and should be avoided.17,26
CONCLUSIONS
Care of the patient presenting with PAH can be confusing
and highly demanding. Multiple medications, seldom seen
within the ICU, are generally employed. These medica-
tions carry multiple adverse effects and interactions with
many commonly used medications within the ICU. The
intensive care nurse is responsible for educating himself/
herself on the latest in evidence-based practice relating to
all diagnoses, including the lesser seen. The entire intensive
care team must work together when caring for patients with
PAH to avoid complications, maximize their recovery, and
attain the highest quality of life possible with a potentially
life-threatening diagnosis.
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ABOUT THE AUTHORS
Carol S. Smith, PhD, RN, is assistant professor in Lansing School of
Nursing and Health Sciences at Bellarmine University, Louisville, Kentucky.
Nancy L. York, PhD, RN, is assistant dean of Lansing School of
Nursing and Health Sciences at Bellarmine University, Louisville,
Kentucky.
Christy J. Kane, PhD, RRT-NPS, is associate professor in Lansing
School of Nursing and Health Sciences at Bellarmine University,
Louisville, Kentucky.
Frederick Weitendorf, RPh, RN, is adjunct professor of
pharmacology in Lansing School of Nursing and Health Sciences at
Bellarmine University, Louisville, Kentucky.
The authors have disclosed that they have no significant relationships
with, or financial interest in, any commercial companies pertaining to
this article.
Address correspondence and reprint requests to Carol S. Smith, PhD, RN,
Lansing School of Nursing and Health Sciences, Bellarmine University,
2001 Newburg Road, Louisville, KY 40205 (csmith@bellarmine.edu).

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DOI: 10.1097/01.DCC.0000472575.42088.18

November/December 2015 347

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