American Journal of Emergency Medicine 38 (2020) 1237–1244

Contents lists available at ScienceDirect

American Journal of Emergency Medicine

journal homepage: www.elsevier.com/locate/ajem

Review

Evaluation and management of pulmonary hypertension in the

emergency department setting
Erica Simon, DO, MPH, MHA a, Rachel E. Bridwell, MD a, Tim Montrief, MD b,
Alex Koyfman, MD c, Brit Long, MD a,⁎
a
Brooke Army Medical Center, Department of Emergency Medicine, 3841 Roger Brooke Dr, Fort Sam Houston, TX 78234, United States
b
University of Miami, Jackson Memorial Hospital/Miller School of Medicine, Department of Emergency Medicine, 1611 N.W. 12th Avenue, Miami, FL 33136, United States
c
The University of Texas Southwestern Medical Center, Department of Emergency Medicine, 5323 Harry Hines Boulevard, Dallas, TX 75390, United States

a r t i c l e i n f o a b s t r a c t

Article history: Background: Pulmonary hypertension (PH) is characterized by increased pulmonary vascular resistance and pul-
Received 15 January 2020 monary arterial pressure and is associated with significant morbidity and mortality.
Received in revised form 18 February 2020 Objective: This narrative review evaluates PH, outlines the complex pathophysiologic derangements, and ad-
Accepted 20 February 2020 dresses the emergency department (ED) management of this patient population.
Discussion: Approximately 10–20% of individuals in the United States suffer from PH. Each year nearly 12,000 PH
Keywords:
patients seek care in the ED for a variety of symptoms which may or may not be related to PH. There are 5 classes
Pulmonary hypertension
Idiopathic pulmonary hypertension
of PH, some of which respond to particular therapies outlined in this review. As presenting complaints are fre-
Pulmonary arterial hypertension quently vague and non-specific, emergency physicians must recognize manifestations of PH and complications
Pulmonary hypertension management related to PH to deliver appropriate care. Early imaging with chest radiograph, bedside echocardiogram, and
computed tomography can assist in determining the underlying etiology of PH exacerbation. Restarting oral or
intravenous PH medications that may have been discontinued is crucial in initial management. Immense care
should be taken to avoid hypoxia and hypercarbia as well as maintaining right ventricular preload support. In ad-
dition to correction of underlying precipitants, judicious vasopressor and inotrope use can help to correct path-
ophysiology and avoid further airway intervention.
Conclusions: An understanding of the pathophysiology of PH and available emergency treatments can assist
emergency clinicians in reducing the immediate morbidity and mortality associated with this disease. Restarting
maintenance PH medications and proper selection of vasopressors and inotropes will benefit decompensating
patients with PH.
Published by Elsevier Inc.

1. Introduction with an abbreviated review of pulmonary pathophysiology underlying

Pulmonary hypertension (PH), characterized by increased pulmo-
nary vascular resistance and pulmonary arterial pressure, is associated
with significant morbidity and mortality. The disease is heterogenous,
with varying demographics and underlying etiologies. PH affects
15–60 million individuals worldwide [1]. Although rare, with an esti-
mated 5–15 cases per 1 million adults, recent studies identify PH-
associated complaints as responsible for 64,000 ED visits over a 5 year
period [2]. In the United States, the most common cause of PH is left
sided heart failure [2,3]. In 1973, the World Health Organization
(WHO) defined a classification system for PH to design and implement
international health standards [4,5]. Published in 2013, the most recent
revision defines Groups 1–5 [4,5]. A discussion of these groups begins
⁎ Corresponding author at: 3841 Roger Brooke Dr, Fort Sam Houston, TX 78234, United
States.
E-mail address: brit.long@yahoo.com (B. Long).
PH, as an understanding of the errant physiology is crucial when ad-
dressing PH and respective therapies in the ED.
2. Methods
This narrative review provides a focused evaluation of ED-based PH
treatment. The authors searched PubMed and Google Scholar for articles
containing the key words “Pulmonary hypertension.” The PubMed
search was conducted from database inception to September 1, 2019.
The first 200 articles in Google Scholar were also evaluated for inclusion.
The literature search was restricted to studies published in English. Au-
thors evaluated case reports and series, retrospective and prospective
studies, systematic reviews and meta-analyses, and narrative reviews.
Authors also reviewed guidelines and supporting citations of included
articles. Articles with a focus on emergency medicine and critical care
were chosen based upon author consensus. When available, systematic
reviews and meta-analyses were preferentially selected. These were

https://doi.org/10.1016/j.ajem.2020.02.041
0735-6757/Published by Elsevier Inc.
1238 E. Simon et al. / American Journal of Emergency Medicine 38 (2020) 1237–1244
followed sequentially by randomized controlled trials, prospective stud-
ies, retrospective studies, case reports, and other narrative reviews,
when alternate data were not available. Over 6000 resources were
found on initial literature search. Many of the resources found on liter-
ature search included in vivo studies, animal models, genetic studies,
case reports or series, and studies focused on outpatient management
of PH. Authors of this review focused on resources pertaining to emer-
gency medicine and critical care, resulting in selection of 89 resources
for this narrative review.
3. Discussion
3.1. Pulmonary pathophysiology
In the setting of PH, physiologic derangements represent changes in
pulmonary and systemic circulation, altering the pressures in each sys-
tem. The pulmonary circulation is normally a low-resistance, low-
pressure system, composed of thin-walled vessels capable of accommo-
dating vast alterations in preload. In patients with chronic PH, pulmo-
nary vascular resistance gradually increases with vascular remodeling
of the pulmonary arteries. This remodeling involves vascular smooth
muscle and endothelial cell proliferation, inflammation, and fibrosis. If
remodeling occurs over a prolonged period of time, the right ventricle
(RV) is able compensate, however, in the setting of RV dilation, tricuspid
regurgitation becomes common. Beyond a specific point of RV disten-
sion, RV output decreases secondary to increased pulmonary pressure
and impedance to RV outflow. This derangement sets in motion a
vicious cascade of interventricular dependence in which bulging of the
RV into the left ventricle (LV) decreases LV filling, subsequently decreas-
ing cardiac output (Fig. 1) [6-9]. As cardiac output falls, end organ
perfusion suffers, further exacerbating the pathophysiology of the in-
herent underlying disease [8].
Alterations in pulmonary system pressure and ventricular wall
thickness additionally reduce coronary artery perfusion. In a normal
physiologic setting, the coronary arteries of the RV are perfused in
both systole and diastole due to low RV wall tension as compared to
the LV [9]. In PH, as RV pressures increase, RV perfusion falls until
pulmonary artery pressures exceed systemic pressure, generating RV is-
chemia. In this under-perfused state, RV contractility declines, worsen-
ing RV overload [7,10,11]. The emergency management of PH focuses on
many of the aforementioned pathways to combat these physiologic
Fig. 1. Pathophysiology of PH.
derangements in order to improve patient hemodynamic and respira-
tory status.
3.2. WHO Groups
Most recently updated in 2013, the WHO organizes PH into 5 distinct
groups based upon pathophysiology. Group 1 is defined by pulmonary
arterial hypertension (PAH), a resting mean pulmonary artery pres-
sure ≥ 25 mmHg, and a pulmonary capillary wedge pressure ≤ 15 mmHg
as measured during right heart catheterization [1,4,12]. More than half
of all PAH cases are idiopathic [13,14]. The most common cause world-
wide is schistosomiasis. Schistosomula migrate to the lungs, heart, and
liver, causing (PAH) and portal hypertension [13,14]. While more than
half of all PAH cases are idiopathic, mutations in bone morphogenetic
protein receptor type 2 (BMPR2), a gene responsible for cell prolifera-
tion, are responsible for the majority of heritable forms [15,16]. Addi-
tional rare etiologies, such as drug associated PH, are outlined in
Table 1 [17].
Group 2 PH represents pulmonary venous hypertension (PVH) due
to left-sided heart disease, defined as mean pulmonary artery pres-
sure ≥ 25 mmHg and a pulmonary capillary wedge pressure ≥ 15 mmHg
[18]. PVH is the most common form of PH [18]. In this disease process,
elevated left atrial pressure is transmitted to the pulmonary system,
through the pulmonary capillaries, and to the pulmonary arteries –
manifestations of left heart or valvular pathologies [4,18-20]. Morbidity
and mortality in patients with PVH is related to RV dysfunction [18]. As
pulmonary compliance decreases due to PH, the work of the RV in-
creases, leading to right heart failure (RHF) and ultimately death [18].
WHO Group 3 individuals develop PH secondary to lung diseases
and/or hypoxia [4,19]. In these patients, PH occurs results from
chronic alveolar hypoxemia [21-23]. Alveolar hypoxemia induces
hypoxic pulmonary vasoconstriction, increasing pulmonary vascular
resistance [21]. WHO Group 4 includes persons who display PH
which persists for ≥6 months following anticoagulation therapy for
pulmonary emboli (PE) [24]. Chronic thromboembolic pulmonary
hypertension (CTEPH) is estimated to occur in 4.8% of survivors of
acute PE and 10% of patients with recurrent PE [25]. Surprisingly,
the majority of cases of CTEPH arise from asymptomatic venous
thromboemboli [26]. Finally, WHO Group 5 encompasses a heterog-
enous collection of disease processes in which PH results from mul-
tifactorial mechanisms (Table 1).
 E. Simon et al. / American Journal of Emergency Medicine 38 (2020) 1237–1244 1239

Table 1 individuals frequently present with symptoms of RHF: ascites, periph-

Classification of WHO Groups 1–5 with underlying disease mechanisms. PH—pulmonary eral edema, and hemoptysis [39,40]. Emergency clinicians should eval-
hypertension, PVH – pulmonary venous hypertension, SSRI—selective serotonin reuptake
inhibitor, COPD—chronic obstructive pulmonary disease, ILD—interstitial lung disease,
uate for underlying precipitants of RHF including sepsis, unplanned
CTEPH—chronic thromboembolic pulmonary hypertension [17,27-31]. withdrawal of PH therapy, medication non-compliance, pregnancy,
pneumonia, anemia, and arrhythmias [41].
WHO classification Underlying disease state Additional notes or
associations
3.3.2. History
Group 1: - Schistosomiasis - Schistosomiasis most
In individuals absent a previous diagnosis of PH, initial history
Pulmonary - Idiopathic common cause globally.
arterial - Drug induced - Associated drugs: [17] should include PH risk factors including congenital heart disease, left-
hypertension - Portal hypertension sided heart disease, valvular disease, pulmonary disease, connective tis-
- Congenital heart disease sue disease, liver disease, blood dyscrasias, thyroid disorders, dialysis-
- Anorexigens – elevated
- Connective tissue diseases dependent renal disease, malignancy, stimulant use, and family history
serotonin levels stimulate
- Persistent pulmonary
hypertension of the
smooth muscle growth, of PH [39,42]. In patients diagnosed with PH, questions regarding cur-
newborn
increasing pulmonary rent therapy and medication compliance are essential to guide treat-
vascular resistance: [17] ment and specialty consultation Therapeutic side effects (Table 2)
SSRIs, tyrosine kinase
inhibitors, lithium,
should be considered diagnoses of exclusion. The possibility of preg-
buprenorphine, cocaine, nancy and vaccination status should be discussed and documented.
chemotherapy.
Group 2: PVH with - LV systolic and diastolic - In left heart disease, 69% of 3.3.3. Physical examination findings
left heart disease disease individuals will develop
Physical examination is unreliable for determining the presence of
- Valvular disease (mitral concomitant PVH [32].
and aortic) - In aortic valve disease, PH in early disease stages. In advanced PH, signs of RHF are commonly
- Congenital or acquired left development of PVH is present: elevated jugular venous pressure, hepatojugular reflex, ascites,
heart inflow/outflow tract correlated with left heart hepatomegaly, and peripheral edema [4,39,42]. On auscultation, an
obstructions dysfunction, and is an increased pulmonic component of the second heart sound (P2), an RV
indication for surgical
intervention [33].
gallop, or the murmur of tricuspid regurgitation may be present. Ar-
Group 3: PH due to - COPD - Prevalence of PH in patients rhythmias including atrial fibrillation, atrial flutter, and atrioventricular
underlying lung - ILD with ILD is 30–40% [34]. node re-entry tachycardias are common in PH patients [40]. Palpation of
disease or - Hypoxemia the precordium may reveal an RV heave. In one systematic review, au-
hypoxia - Obesity Hypoventilation
thors found that although a number of the aforementioned signs had
Syndrome
- Developmental lung high specificities (88% for an S4 on inspiration, 85% for a loud P2 on in-
disease spiration, 84% for an RV lift on inspiration), their sensitivities were low
- Chronic high-altitude (12%, 29%, and 21%, respectively) [55]. The physical examination finding
exposure with the highest positive likelihood ratio was a loud P2 on inspiration
Group 4: PH - CTEPH - Risk of CTEPH is worsened by
following prothrombotic states, post
(LR+ 1.9, 95% Credible Interval 1.2–3.1) [55]. Patients with decompen-
pulmonary splenectomy, or infection of sated PH frequently present with hypotension, displaying signs of sys-
embolism cardiac shunt or pacemaker temic hypoperfusion: diaphoresis, cool extremities, peripheral cyanosis,
[35]. and tachycardia. Patients with a patent foramen ovale who suffer from
Group 5: PH - Hemolytic: Chronic - 20% of patients with
PH may exhibit symptoms of right-to-left shunting, such as systemic
secondary to hemolytic anemia, untreated thyroid disease will
multifactorial Myeloproliferative develop PH [36]. hypoxemia and cyanosis [56,57].
mechanism disorders - PH occurs in 6–10% of sickle
- Systemic Disorders: cell disease and thalassemia 3.3.4. Studies
Pulmonary histiocytosis, patients and is a major risk An electrocardiogram (ECG) should be obtained. If PH is pro-
Sarcoidosis factor for mortality [37,38].
- Metabolic: Thyroid
nounced, ECG will reveal right axis deviation and right ventricular hy-
disorders, Glycogen storage pertrophy (Fig. 2) [41,58]. In addition to a tachyarrhythmia, right
disease, Gaucher's disease atrial enlargement, and ST segment depression and T wave inversion
- Other: End stage renal in the precordial leads (right heart strain) may be present [42].
disease requiring dialysis,
Given the numerous etiologies of PH, laboratory studies should be
Tumor obstruction,
Fibrosing mediastinitis guided by the patient presentation, history, and examination findings.
In patients with chronic PH, venous blood gas frequently demonstrates
hypoxemia and respiratory alkalosis [39,42]. Brain Natriuretic Protein
3.3. ED evaluation (BNP) measurement may be useful in narrowing the differential diagno-
sis of a patient presenting with dyspnea [58]. BNP levels N400 pg/mL
3.3.1. Patient presentation suggest heart failure, but do not exclude other underlying conditions
Accounting for approximately 5 to 15 cases per one million ED visits, [59]. Normal plasma BNP levels increase with age and are higher in
PH and its associated symptoms are non-specific [3]. Dyspnea is the women than in men [60]. In the setting of renal failure, BNP should be
most common presenting complaint, though patients also report fa- interpreted with caution as reduced clearance may lead to chronic ele-
tigue, weakness, chest pain, and syncope [4,39]. Symptomatology in un- vation [58]. Evaluation of myocardial perfusion and end-organ function
diagnosed PH is insidious; many individuals experience dyspnea and is critical in patients presenting with signs and symptoms consistent
fatigue, which typically worsens over a period of weeks to months, with heart failure [59]. In this setting, a troponin, renal function panel,
and becomes apparent when limitations in daily activities occur. Angina liver function panel, and a lactate are advised [59]. An elevated troponin
results from ischemic subendocardial injury from ventilation-perfusion and abnormal liver function tests portend a poor prognosis. Elevations in
mismatch or compression of the left main coronary artery by the pul- AST, ALT, and total bilirubin signify a decreased cardiac index and in-
monary trunk [39]. Syncope, the result of decreased cerebral blood creased central venous pressure, reflecting the degree of heart failure
flow due to reduced cardiac output, is associated with a poor prognosis [60,61].
[39]. Hoarseness may occur due to compression of the recurrent laryn- Imaging may narrow the differential diagnosis among etiologies of PH
geal nerve by an enlarged pulmonary artery [4,39]. In advanced disease, and guide resuscitation. ED imaging should include a chest radiograph
1240 E. Simon et al. / American Journal of Emergency Medicine 38 (2020) 1237–1244

Table 2
Medical Management of PH, Side Effects, and Considerations [19,43-50]. It should be noted that not all of the WHO PH Groups are amenable to pharmaceutical management, as the main-
stay of treatment focuses on improving the underlying physiology based upon PH etiology. iNO—Inhaled nitric oxide, V/Q—ventilation perfusion, PDE—phosphodiesterase, PH—pulmonary
hypertension, PVR—pulmonary vascular resistance, SVR—systemic vascular resistance, sGC—soluble Guanylate Cyclase, IV—intravenous, ppm—parts per million.

Medication Method of Mechanism of action Side effects PH Additional considerations

class administration Group

Calcium Oral Vasodilation through inhibition of Hypotension; Worsening hypoxemia and pulmonary 1 - Affordable
channel calcium channels vasoconstriction [45]
blockers
- Nifedipine
- Diltiazem
- Amlodipine
Prostacyclin Smooth muscle relaxation via direct Worsens V/Q mismatch if IV, Hypotension, Dizziness, 1,5 - Sudden withdrawal causes
Agonists Continuous arterial vasodilation [19] Flushing, Headache, Leg Pain, Jaw Pain rebound PH
- Epoprostenol infusion - Inhalational only—decreases
- Iloprost Inhalation IV Epoprostenol or Treprostinil: Bacteremia, catheter PVR
- Selexipag Oral thrombosis, fetal loss/demise - Infusion decreases SVR and
- Treprostinil Oral PVR
- Used in place of iNO in severe
RV failure [9]
Endothelin Oral Inhibition of endothelin decreases Bosentan and Ambrisentan: Peripheral edema 1,4 - Long term treatment:
Receptor vasoconstriction [51] minimal utility in emergency
Agonists situations
- Bosentan
- Macitentan
- Ambrisentan
PDE5 Oral Inhibits degradation of cGMP, Hypotension, Dizziness, Flushing, Headache, Leg pain, Back 1,5 - Do not administer nitrates
Inhibitors inducing smooth muscle relaxation pain, Myalgias
- Sildenafil [52]
- Tadalafil
iNO Inhalation Vasodilation by decrease of Free radical oxidation [53], Respiratory tract - Improves V/Q without
intracellular calcium and increased hypersensitivity in chronic use [53], N5 ppm causes changing SVR [9]
cGMP [53] pulmonary toxicity [54]

and bedside echocardiography (Fig. 3). Radiographic findings of PH in-
clude dilated pulmonary arteries, peripheral pruning, and an enlarged
right atria and RV [42]. In severe disease, pleural effusions may be pres-
ent. While chest radiography demonstrates high sensitivity (96.9%) and
specificity (99.1%) for detecting severe PH, it lacks sufficient sensitivity
for detecting mild PH (defined as 40–50 mmHg estimated pulmonary ar-
tery systolic pressure [ePASP], though this information may not be avail-
able in the ED) [62].
In the setting of PH, bedside echocardiography will demonstrate
right-sided pressure overload: right atrial enlargement, RV dilation
(RV: LV N 1:1; normal b 0.6), increased RV free wall thickness
(N5–7 mm as measured at end-diastole by M-mode or 2D echocardiog-
raphy from the parasternal long axis or subxiphoid view), end-systolic
flattening of the intraventricular septum, and interventricular interde-
pendence visualized as a “D”-shaped left ventricle in diastole (Fig. 3)
[63]. Ultrasound assessment of the inferior vena cava (IVC) may be

Fig. 2. ECG with evidence of pulmonary hypertension.

 E. Simon et al. / American Journal of Emergency Medicine 38 (2020) 1237–1244
Fig. 3. Ultrasound depicting RV dilatation. A. Apical 4 chamber echocardiography. B. Notice the end-systolic flattening of the intraventricular septum, and interventricular interdependence
visualized as a “D”-shaped left ventricle in diastole (Red). A markedly thickened moderator band (blue), indicative of RV hypertrophy, is located in the right ventricular apex connecting the
interventricular septum to the anterior papillary muscle. When looking within the RV, the moderator band appears similar to other trabecula except that it does not seem to be attached to
one single side, but rather crosses the lower portion of the RV. RV: right ventricle; LV: left ventricle; RA: right atrium; LA: left atrium.
misleading in PH patients, especially those with mitral regurgitation or
aortic stenosis (Group 2 PH), revealing plethora that may not reflect in-
travascular volume status [9,64].
Computed Tomography (CT) plays an essential role in identifying
potential etiologies underlying PH (Fig. 4). A CT demonstrating right
atrial enlargement, RV dilation, and main pulmonary artery/ascending
aorta diameter ratio ≥ 1 is suggestive of PH, with a positive predictive
value of 96% (Fig. 3) [65]. On CT, the pulmonary trunk should be no
larger than 2.8 cm at the level of its bifurcation. Measurements
N2.8 cm suggest PH with a sensitivity of 69%–87% and a specificity of
89%–100% [66]. For individuals with CTEPH, CT angiography may reveal
thrombi in the pulmonary vasculature and identify intra- and extra-
cardiac shunts contributing to the patient's presentation. In this patient
population, non-enhanced CT may reveal a mosaic pattern of variable
attenuation in the lung parenchyma with evidence of irregular pulmo-
nary perfusion due to chronic thromboemboli.
LV dysfunction is suggested on CT by the presence of a mosaic pulmo-
nary perfusion pattern and pulmonary ground-glass opacities (indica-
tive of chronic pulmonary edema). The use of high-resolution CT in
patients with PAH, without co-existing lung disease, should demonstrate
normal lung parenchyma. Interstitial pulmonary abnormalities revealed
by CT may point to an intrinsic lung disease as the etiology of the PH.
3.4. ED management
The primary goal of the emergency clinician is the identification and
treatment of the underlying etiologies of PH (e.g. alveolar hypoxia in
Fig. 4. CT of the chest demonstrating evidence of PH.
1241
COPD, hyperthyroidism, etc.). For individuals presenting with RHF, trig-
gering factors should be addressed: antibiotic therapy administered for
infections, transfusions given as indicated for anemia to maintain a he-
moglobin of N10 g/dL, and arrhythmias treated [60,67]. New-onset atrial
fibrillation or flutter are common in PH patients. In the absence of ran-
domized controlled trials, observational studies suggest improved sur-
vival with a rhythm control strategy [68]. Rate control with calcium
channel blockers or β-blockers is not advised, as these medications fur-
ther impair RV function [60]. Although digoxin may slow the ventricular
rate in patients with supraventricular tachyarrhythmias associated with
RV dysfunction, cardioversion is the preferred therapy for PH patients
given this population's propensity for digoxin toxicity [69]. Electrical
cardioversion is favored, as prolonged atrial arrhythmias in patients
with PH are associated with rapid decompensation. Pharmacologic car-
dioversion with Class III agents, such as amiodarone and sotalol, have
been reported [70-72]. While Class IC agents may theoretically be uti-
lized, data in PH patients are lacking. In individuals with atrial arrhyth-
mias lasting N48 h, anticoagulation is advised prior to cardioversion
[68].
In PH patients who present due to an unexpected discontinuation in
oral or IV PH therapy, every effort should be made to contact the
patient's PH specialist to initiate ED treatment and prevent acute de-
compensation. While prostacyclins, endothelin receptor agonists, and
phosphodiesterase inhibitors may not be immediately available in the
ED, initiating these therapies early in the ED course may improve pa-
tient hemodynamics, though optimizing oxygenation and circulation
should take priority [19,43,45]. In individuals with PH, supplemental
oxygen is indicated to maintain an oxygen saturation N 90% [51,60].
Hypercapnia should be avoided as it results in further pulmonary vaso-
constriction [6,41,51,60]. Continuous non-invasive positive pressure
ventilation may be considered, though fluid balance must be optimized
prior to initiation to eliminate dangerous decreases in cardiac output
[60]. Although data are limited in the setting of acute exacerbations,
non-invasive positive pressure ventilation in Group 3 PH patients with
no LV dysfunction is typically well tolerated and improves hypercapnia
[73,74]. There are no current recommendations regarding the use of
bilevel positive pressure ventilation in PH patients given the paucity of
data [69,74]. High-flow nasal cannula (HFNC) is an alternative therapy
that may improve hypoxemia, especially if patients are unable to toler-
ate the mask utilized for NIPPV.
Intubation should be avoided if possible, as the effect of sedatives
and positive intrathoracic pressure may reduce cardiac function and
cause peripheral vasoconstriction, resulting in hypotension and cardio-
vascular collapse [9]. If intubation is required, etomidate is recom-
mended for induction, given its limited effects on cardiac contractility
and vascular tone. Hemodynamic optimization prior to intubation is
recommended. If the patient is hemodynamically unstable, vasopres-
sors should be initiated before attempts to establish a definitive airway
1242 E. Simon et al. / American Journal of Emergency Medicine 38 (2020) 1237–1244
are made [59,75]. Awake intubation with topical anesthetics is an alter-
native that should be considered given the reduced risk of hemody-
namic decompensation as compared to rapid sequence intubation.
Medications administered during rapid sequence induction will likely
result in profound hemodynamic collapse, hypercarbia, hypoxemia,
and acidosis [9]. Ventilator settings should target 6–8 mL/kg of ideal
body weight and plateau pressures b30 cm H2O. Low positive end expi-
ratory pressures should be utilized to minimize decreases in preload
and increases in RV afterload [7,59]. Hypoxemia and hypercapnia
should be avoided [9,42,51,58].
In the majority of cases, RV failure will be associated with fluid over-
load [69]. IV diuretics should be used cautiously to obtain a negative
fluid balance, optimizing circulating blood volume and reducing RV
preload, and thus improving cardiac output [76]. For patients not previ-
ously receiving oral diuretics, an initial dose of 20–40 mg IV furosemide
is recommended for hypervolemia [76]. In individuals utilizing home di-
uretic therapy, the initial IV dose should be at least equivalent to the oral
dose [75]. Consultation may be required for ultrafiltration in patients
who are resistant to diuretic therapy [75]. In hypovolemic patients, vol-
ume should be delivered conservatively, with boluses of 250 mL over
15–30 min [76].
In the setting of hemodynamic instability, vasopressors should be
initiated. Vasopressors increase aortic root pressure, increasing RV
perfusion [9]. Norepinephrine is an effective first-line vasopressor
for patients with PH [76-78]. Although norepinephrine primarily tar-
gets α 1 receptors, with limited β1 stimulation to increase cardiac
contractility, studies in heart failure patients have demonstrated im-
proved RV myocardial oxygen delivery following administration
(dose: 0.01–0.03 μg/kg/min IV) [77]. The addition of low dose vaso-
pressin (0.01–0.03 U/min) may be considered if the aforementioned
therapies fail to result in hemodynamic improvement. Higher doses
should be avoided, which result in pulmonary and coronary vaso-
constriction [75,77].
Epinephrine may benefit PH patients given the combined alpha
and beta stimulation which provides systemic vascular support
with inotropy, though this may increase myocardial oxygen demand.
To date, there have been no trials regarding epinephrine use in adult
PH patients. In a pilot study of hemodynamically stable children, epi-
nephrine demonstrated an increase in systemic vascular resistance,
though it worsened the systolic pulmonary artery pressure: aortic
pressure ratio [79]. Additionally, two patients experienced brief
dysrhythmias, atrial bigeminy and ventricular bigeminy following
administration of epinephrine [79]. Animal models suggests that
epinephrine improves cardiac index through inotropy, with systemic
vascular resistance increasing in a dose dependent fashion [79,80]. In
contrast, sole α stimulation from phenylephrine should not be used
in the unstable PH patient as it increases pulmonary vascular resis-
tance and may induce reflex bradycardia [81]. Dopamine should be
also avoided given β2-mediated decreases in systemic vascular resis-
tance and possible arrhythmias [77].
Inotropes increase the risk of tachyarrhythmias and should only
be utilized in the setting of inadequate oxygen delivery, despite
correction of abnormalities in RV preload, and conditions causing
ischemia [77]. If inotrope support is required, dobutamine is the
agent of choice [75,76]. At low doses (5–10 μg/kg/min), dobuta-
mine improves RV contractility and increases cardiac output
through β 1 receptor stimulation [75,76]. Higher doses should be
avoided, given increased stimulation of β2 receptors, causing vaso-
dilation and hypotension [76]. Milrinone, a selective PDE-3 inhibitor,
is recommended for PH resulting from biventricular failure (0.375–-
0.75 μg/kg/min IV). Use in the ED may be limited given the requirement
for pharmacy preparation and the drug's slow onset of action [76].
Milrinone improves inotropy and pulmonary vasodilation, but similar
to dobutamine, it may cause hypotension [75,76].
There are several other therapeutic options for patients with PH. Al-
though sildenafil reduces RV afterload through pulmonary and systemic
vasodilation, its use in critically ill patients in the ED is limited given the
risk of hypotension. Patients who fail to respond to inotrope and vaso-
pressor therapy should be considered for venoarterial extracorporeal
membrane oxygenation [76,81]. Patients with PH have a high risk of
sudden cardiac death and poor outcomes. Cardiopulmonary resuscita-
tion outcomes in PH patients with RV failure are poor: in a cohort of
3130 PH patients who required CPR, only 6% survived for N90 days
[59,82-84].
3.4.1. Special population – prostacyclin agonist pump
A life-threatening emergency can occur if the patient has been pre-
scribed IV epoprostenol or treprostinil and the IV catheter is removed
or damaged, or the pump stops working [85,86]. A PH specialist should
be consulted emergently, and if possible, the pump should not be turned
off as this may result in sudden death. If there is a problem with the line,
pump, or cassette, peripheral access should be obtained and the pump
tubing connected directly to this access [43,85,86]. The line should not
be primed or flushed, as a bolus of prostacyclin agonist may be delivered
to the patient, resulting in fatal hypotension. The patient's catheter
should be inspected for drainage and surrounding cellulitis, which sug-
gest infection. If administering medications or drawing laboratory stud-
ies, a second peripheral IV is required. An alternative infusion pump
should not be utilized unless advised by the PH specialist [85,86].
3.4.2. Inhaled therapies
Inhaled vasodilators such as nitric oxide and epoprostenol may re-
duce pulmonary vascular resistance. These medications have low sys-
temic absorption, minimal effect on blood pressure, and may improve
cardiac output [87]. These can be administered via endotracheal tube,
NIPPV, or HFNC [88]. However, inhaled vasodilators should only be ini-
tiated with PH specialist consultation, and they are not recommended in
patients with left ventricular failure [87].
3.5. Disposition
Admission and consultation are needed if new onset PH, worsening
PH, or prostacyclin agonist pump malfunction is suspected or diagnosed
during the ED course. Transthoracic echocardiography is required to as-
sess RV size and function and measure pulmonary artery systolic pressure
and tricuspid jet velocity [40,42]. In patients with PH, echocardiography
determines the extent of deterioration. In individuals without a previous
diagnosis of PH, tricuspid jet velocity N2.8 m/s estimates the likelihood of
the disease, predicting the need for right heart catheterization and ancil-
lary testing (pulmonary function tests, functional exercises tests, etc.)
[4,42,89].
4. Conclusions
Patients with new onset PH or a history of PH may present with a
myriad of chief complaints. ED evaluation and treatment center upon
identifying underlying etiologies which may trigger acute decompensa-
tion. The patient presenting with RHF is commonly critically ill. Point of
care ultrasound may be utilized to guide acute resuscitation. For this pa-
tient population, knowledge of recommendations regarding inotrope
and vasopressor therapy is essential. In the majority of cases, admission
will be warranted. The emergency medicine physician must be pre-
pared to address this complex disease process.
Declaration of competing interest
None.
Acknowledgements
All authors conceived the idea for this manuscript and contributed
substantially to the writing and editing of the review. This manuscript
 E. Simon et al. / American Journal of Emergency Medicine 38 (2020) 1237–1244
did not utilize any grants, and it has not been presented in abstract form.
This clinical review has not been published, it is not under consideration
for publication elsewhere, its publication is approved by all authors and
tacitly or explicitly by the responsible authorities where the work was
carried out, and that, if accepted, it will not be published elsewhere in
the same form, in English or in any other language, including electroni-
cally without the written consent of the copyright-holder. This review
does not reflect the views or opinions of the U.S. government, Depart-
ment of Defense, U.S. Army, U.S. Air Force, or SAUSHEC EM Residency
Program.
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