Received: 6 September 2019 | Accepted: 3 April 2020

DOI: 10.1002/ppul.24776

REVIEW

Intensive care management of right ventricular failure and

pulmonary hypertension crises

Ryan D. Coleman MD1,2 | Corey A. Chartan DO1,2 | Peter M. Mourani MD3

1
Section of Critical Care Medicine, Department
of Pediatrics, Baylor College of Medicine, Abstract
Houston, Texas
2 Pulmonary hypertension (PH), an often unrelenting disease that carries with it
Section of Pulmonary Medicine, Department
of Pediatrics, Baylor College of Medicine, significant morbidity and mortality, affects not only the pulmonary vasculature but,
Houston, Texas
in turn, the right ventricle as well. The survival of patients with PH is closely related
3
Section of Critical Care Medicine and
Pediatric Heart Lung Center, Department of to the right ventricular function. Therefore, having an understanding of how to
Pediatrics, University of Colorado School of manage right ventricular failure (RVF) and acute pulmonary hypertensive crises is
Medicine and Children's Hospital Colorado,
Aurora, Colorado imperative for clinicians who encounter these patients. This review addresses the
management of these patients in detail, addressing: (a) the pathophysiology of RVF,
Correspondence
Ryan D. Coleman, MD, Right Ventricular (b) intensive care monitoring of these patients in the intensive care unit, (c) imaging
Failure Program, Pediatric Critical Care of the right ventricle, (d) intubation and mechanical ventilation, (e) inotrope and
Medicine, Texas Children's Hospital, 6651
Main St, MC E1420, Houston, TX 77030. vasopressor selection, (f) pulmonary vasodilator use, (g) interventional and surgical
Email: ryanc@bcm.edu procedures for the acutely failing right ventricle, and (h) mechanical support for RVF.

KEYWORDS

critical care, mechanical ventilation, pharmacology, pulmonary hypertension, pulmonary

physiology, right ventricular failure

1 | INTRODUCTION
Pulmonary arterial hypertension is a disease of the pulmonary vas-
culature that, regardless of the specific etiology, often leads to ma-
ladaptive behavior of the right ventricle, with both the pulmonary
circulation and right ventricle demonstrating pathologic remodeling
over time (Table 1). The pulmonary endothelium and arterial smooth
muscle cells undergo abnormal proliferation and become resistant to
apoptosis, with dysregulated angiogenesis throughout the micro-
circulation, increased interstitial fibrosis, glycolytic shift towards less
efficient metabolic pathways, significant inflammation, increased
oxidative stress and abnormal neurohormonal modulation, and
receptor regulation.1‐3 Within 5 years of diagnosis, between 25%
and 60% of patients with pulmonary hypertension (PH) will die from
their disease.4
The right ventricle has evolved to rely on functioning in its low
resistance, high compliance pulmonary circulation. Thus, even subtle
increases in afterload can cause significant decreases in right ven-
tricular (RV) output with RV ejection fraction having been shown to
5,6
be inversely proportional to pulmonary arterial pressure. Multiple
drug classes exist for the treatment of pulmonary arterial hy-
pertension, but these drugs mainly target the pulmonary vasculature
with the goal of increasing vasodilation of the pulmonary arterial
bed.7,8 Though certain medications may have some beneficial ven-
tricular remodeling effects, the data supporting these effects are
limited, not consistently demonstrated and at the best show these
therapies only delay the inevitable ventricular dysfunction that oc-
curs over time.9‐11 Ultimately, regardless of the specific etiology of a
patient's PH, it is the progressive RV dysfunction and failure that
makes PH fatal.12‐14
Because right ventricular failure (RVF) is a common reason for
patient death, it is imperative physicians become familiar with the
basic pathophysiology and treatment options for addressing RVF.
With an increasing number of patients who carry the diagnosis of PH
being admitted, particularly to large urban teaching hospitals, it is
becoming more likely that these patients will be encountered in any
given intensive care unit (ICU).15,16 These patients are at increased
risk of death compared to general ICU patients, with an overall
mortality rate of between 5.9% and 6.8% for patients with PH as
compared to 0.6% to 2.3% for those without PH.16,17 Among patients

636 | © 2020 Wiley Periodicals, Inc. wileyonlinelibrary.com/journal/ppul Pediatric Pulmonology. 2021;56:636–648.

COLEMAN ET AL. | 637

T A B L E 1 Basic mechanisms of pulmonary hypertension

Mechanism Common examples

Increased precapillary resistance Constriction Hypoxemia

BMPR2 mutation
Obstruction Pulmonary embolism
Abnormal development or destruction of vasculature Bronchopulmonary dysplasia
Connective tissue diseases

Increased postcapillary resistance Pulmonary vein abnormalities Pulmonary vein stenosis

Pulmonary veno‐occlusive disease
Left‐sided heart disease Mitral valve stenosis
Shone's complex
Abnormal development of vasculature Alveolar‐capillary dysplasia

Increased pulmonary blood flow Increased cardiac output Hyperthyroidism

Vein of Galen malformation
Systemic‐to‐pulmonary shunts Ventricular septal defect
Atrioventricular septal defect
Patent ductus arteriosus

Abbreviation: BMPR2, bone morphogenetic protein receptor type II.

with PH, those with primary PH have a reported a mortality rate of
8.4%, while those with secondary PH have a mortality rate of 6.5%.16
2 | PATHOPHYSIOLOGY OF ACUTE RVF
Changes in RV function and composition occur throughout disease
progression, with changes in preload, afterload, and contractility in-
terplaying with alterations in coronary blood flow, myocardial me-
tabolism, receptor regulation, and neurohormonal shifts18‐22
(Table 2). RV remodeling is also affected by time and speed with
which the changes in pulmonary vascular resistance (PVR) occur,
specific etiology, potential genetic and epigenetic factors, and any
number of other potential disease components. These changes can
then be further broken down into adaptive vs maladaptive re-
modeling, with the type of remodeling affecting the progression to
frank ventricular failure.
Adaptive ventricular remodeling to increased PVR, such as that
seen in classic Eisenmenger syndrome, is characterized by concentric
hypertrophy, preservation of both systolic and diastolic function, and
maintenance of relatively normal RV dimensions with preserved
cardiac output.20,23
Maladaptive remodeling, often associated with a worse prog-
nosis, consists of more eccentric hypertrophy, right vs left ventricular
dyssynchrony (thought to potentially be due to myocyte stretch),
diminished systolic and diastolic function, and, therefore, decreased
cardiac output.12,24‐26 The right ventricle becomes dilated, with his-
topathology demonstrating myocardial apoptosis, fibrosis, and a de-
crease in capillary density.1,12
Ventriculoarterial coupling, wherein the right heart and pul-
monary vasculature are treated as an interdependent system rather
than separate entities, has become a common framework for
analyzing acute stressors placed on the right ventricle and its
function.27,28 When an acute increase in afterload occurs, in order to
maintain cardiac output, the right ventricle must immediately in-
crease its contractile strength to compensate. Through the use of
magnetic resonance imaging‐generated pressure‐volume (PV) loops,
ventricular elastance (Ees), arterial elastance (Ea), and their relation-
ship to one another can be quantified.29,30 Ees is the slope of the
end‐systolic PV relationship, and is considered a load‐independent
measure of RV function. Ea reflects the pulmonary vascular re-
sistance times the heart rate and represents a ventricular‐
independent assessment of vascular load. Under normal loading
conditions, the end‐systolic ventricular elastance to arterial elastance

T A B L E 2 Causes of acute right ventricular failure

Decrease in contractility Increase in afterload Volume overload

RV ischemia/infarction Pulmonary embolus Fluid bolus

Sepsis Acidosis Transfusion

Postcardiotomy low cardiac output syndrome Alveolar hypoxia

Myocarditis ARDS

Post heart transplant Mechanical (positive pressure) ventilation

Abbreviations: ARDS, acute respiratory distress syndrome; RV, right ventricular.

638 | COLEMAN ET AL.

(Ees/Ea) ratio remains between 1.5 and 2, representing a balance
between oxygen consumption and mechanical workload demand.28,30
When the vascular load is increased, the right ventricle will in-
itially hypertrophy to decrease the wall stress (Law of LaPlace) and
attempt to restore coupling. However, when faced with a sustained
increase in vascular load, the right ventricle dilates and the wall thins
(via the Frank‐Starling mechanism), while the heart rate increases to
try to maintain the same cardiac output, resulting in an increased Ea.
Eventually, this ratio becomes altered, demonstrating the uncoupling
that occurs in the setting of PH, with the Ees/Ea decreasing. Values
less than 1.3 have been associated with decoupling and worse
outcomes.28,31
Changes in the PVR, particularly abrupt rises, can cause sig-
nificant alterations of cardiac septal geometry. An abrupt rise in
afterload can cause the right ventricle to dilate and shift the
interventricular septum (IVS) from right to left, increasing left
ventricular end‐diastolic pressure, decreasing left ventricular
diastolic filling, decreasing left ventricular transmural pressures,
and ultimately results in decreased systemic cardiac output.19 The
right ventricle, accustomed to coronary blood flow in both systole
and diastole, when faced with increased wall stress, diminished
coronary flow, increased coronary sinus congestion and decreased
left‐sided cardiac output, can quickly become ischemic.32 The
decrease in left ventricular output and increase in end‐diastolic
volume and pressure that accompanies the IVS shift only further
decrease RV performance, due to interventricular dependence
and 20% to 40% of RV function being directly related to left
33,34
ventricular function.
3 | C L I N I C A L D I A G N O SI S O F AC U T E R V F
Patients with RVF, depending on the speed of onset, can demon-
strate a myriad of symptoms (Table 3). Because it reflects both de-
creased cardiac output and increased systemic venous pressures
both at rest and with stress, the clinical course can be insidious
depending on the time course of the heart failure.
Acute right heart failure often presents rather dramatically, with
patients exhibiting the typical signs of low cardiac output—syncope,
near‐syncope, hypotension, tachycardia, diaphoresis, cyanosis, and
cool extremities. Patients may experience chest pain secondary to
right coronary ischemia, as well as shortness of breath. Right upper
quadrant pain caused by hepatic congestion and stretch of the liver
capsule may be present, as well as nausea and/or vomiting. Atrial and
ventricular dysrhythmias may be present secondary to atrial stretch
and ventricular ischemia.35 Peripheral edema, ascites, and hepato-
megaly may or may not be present, depending on whether or not
there is an underlying component of chronic heart failure. The phy-
sical exam may reveal jugular venous distention, the characteristic
holosystolic murmur of tricuspid regurgitation, a gallop, a prominent
fixed split‐second heart sound and/or RV heave.
Chronic right heart failure has a more subdued clinical pre-
sentation. By history, patients will complain of decreased exercise
tolerance, increasing fatigue, dyspnea, and increasing peripheral
edema. Exercise limitation is of particular importance, as there is a
well‐documented relationship between poor exercise tolerance and
decreased overall survival in both pediatric and adult patients.36‐38
Decreased flow reserve, related to a decreased peak cardiac index,
can also result in syncope.39 Pulmonary edema may occur, particu-
larly if there is a postcapillary component of PH, due to decreased
lung lymphatic flow and development of pleural effusions. Because of
the elevated central venous pressures (CVP) and diminished cardiac
output, there may be evidence of kidney injury, with studies having
established both a relationship between acute kidney injury and right
heart failure and blood urea nitrogen and creatinine values and
survival in chronic disease.40‐42 Patients with chronic RVF may also
have abnormal liver function assays. Hyperbilirubinemia and elevated
markers of cholestasis, secondary to diminished liver perfusion and
increased hepatic congestion, have also been shown to have
worsened survival.43,44
4 | IN TEN SI V E CA R E M O N ITO R I NG
OF PATIENT S WITH RVF

Accurate real‐time hemodynamic data are necessary to monitor a

T A B L E 3 Indices of right ventricular failure
Signs and symptoms
Gallop rhythm (S3)
Accentuated S2
Hepatomegaly/ascites
Pleural effusion
Clinical indices
Poor weight gain/failure to thrive
Fatigue
Cardiorenal syndrome
Cardiohepatic syndrome
patient with RVF in the ICU. Without invasive hemodynamic data, it
is difficult to understand where the ventricle is on its Frank‐Starling
curve, and, thus, management decisions regarding volume status and
inotropic and vasopressor support can be difficult. Beyond the
standard practice of continuous arterial blood pressure monitoring,
there are a number of other invasive and noninvasive modalities that
can be of great utility in patients with acute RVF.

Pericardial effusion

Peripheral edema 4.1 | Biomarkers

Jugular venous distension
Though there are a number of potential biomarkers that can be
Exertional dyspnea
monitored in patients with RVF, currently there are no markers
Presyncope/syncope
specific to the right ventricle. Brain natriuretic peptide (BNP), a
COLEMAN ET AL.
cardiac natriuretic hormone produced by cardiac myocytes, is one
of the most commonly measured serum biomarkers in PH. BNP
levels are elevated at times of ventricular stretch secondary to in-
creased PV loads and have been shown to correlate with patient
outcomes.7,8,45,46 Depending on the type of assay and specific iso-
form of BNP measured, absolute values may vary. It is also important
to remember that BNP reflects ventricular stretch, and so patients
who have shunting lesions that offload either pressure or volume
from the right ventricle may have relatively low serum BNP con-
centrations but still have significant RV dysfunction. Other bio-
markers, such as plasma growth differentiation factor‐15, microRNA
expression, and high‐sensitivity troponin T, amongst many others, are
currently being explored to add more specificity to available bio-
markers to monitor RV performance.47‐49 Other routine biomarkers,
such as lactate, serum creatinine, and liver function assays, should
also be routinely monitored in these patients.
4.2 | Central venous pressure
CVP, a surrogate of right atrial pressure when measured via the
internal jugular vein, is a key when assessing the degree of RV dys-
function and how best to manage volume status. Though data are
not as well‐defined in pediatric patients, in adults CVP greater than
15 mm Hg or a mean arterial pressure to CVP ratio of less than 7.5
have been shown to be thresholds which raise the likelihood
of morbidity and mortality.50,51 Interventions to improve CVP (con-
trolled diuresis, improvement in contractility via alterations of the
IVS, and, thus reductions in end‐diastolic pressure) are an important
part of ICU management of these patients, but cannot be safely done
without real‐time CVP management to guide therapy. Of note, pa-
tients on increased levels of positive end‐expiratory pressure (PEEP)
may have elevated CVP readings secondary to increased in-
trathoracic pressure. CVP readings from low‐lying femoral veins or
from peripherally‐inserted central catheters do not accurately reflect
true CVP.
4.3 | Near‐infrared spectroscopy
Near‐infrared spectroscopy (NIRS) monitoring is a frequently en-
countered noninvasive monitoring modality in pediatric patients,
particularly in patients with cardiac disease.52,53 Cerebral NIRS has
been demonstrated to correlate well with invasively measured su-
perior vena cava saturations, and, thus, can accurately reflect the
oxygen extraction being undertaken by key end organs.54 This, is
turn, has been shown to be associated with morbidity and mortality
in pediatric patients undergoing surgical intervention for congenital
55
heart disease. Recent work in neonates undergoing NIRS mon-
itoring during initial resuscitation has shown that infants who do not
reach target arterial oxygen saturations have lower regional cerebral
tissue oxygenation levels that do not reach established norms. Thus,
NIRS is becoming more widely used as an adjunct marker of
| 639
hemodynamics and can detect an increased risk for cerebral injury in
this population.56,57 It has also been shown to be more sensitive
to acute changes in cerebral blood flow patterns in children under-
going Blalock‐Taussig shunt placement than traditional oximetry
readings.58 When combined with other traditional markers of
metabolic demand, such as lactate, its predictive capabilities are
even higher, with values less than 58% having worse outcomes in a
postoperative cardiac patient cohort.59 Therefore, monitoring of
NIRS trends in patients with acute hemodynamic instability can
add beneficial data to help guide management.52
4.4 | Continuous cardiac output monitors
Pulmonary artery catheters have often been considered the gold
standard for accurate measurement of real‐time hemodynamic data
in critically ill patients.60 For pediatric patients with PH, data derived
from pulmonary artery catheters were shown to potentially improve
outcomes and as such, the Society of Critical Care Medicine stated in
a position paper that this is one patient population in whom, only in
the presence of experienced attending physicians, use of a catheter
to guide management could be recommended.60‐62 As the use of
pulmonary arterial catheters has decreased over time, other invasive
measurements of cardiac output, systemic vascular resistance (SVR),
and advanced hemodynamic indices have become more common.63
The pulse index continuous cardiac output monitor is one such tool
utilized by some centers which use a combination of transcardio-
pulmonary thermodilution and pulse contour analysis to calculate
cardiac output, extravascular lung water, intrathoracic blood volume,
and SVR. Though these measurements may not always be precise and
require both user familiarity with how to interpret data and staff
comfort with frequent recalibrations of the devices when trying to
differentiate between patients who have low intravascular volume
status and may benefit from gentle volume loading vs patients who
may benefit from manipulation of their SVR, these data can be useful
to help the guide management.64,65 However, it is worth noting this
device has not been well‐studied in pediatric patients to date and is
very dependent on user familiarity.
4.5 | Capnography
Monitoring of dead space ventilation in the ICU can be a valuable
tool and has been shown to correlate with mortality.66 Capnography
can serve as a surrogate for pulmonary blood flow and cardiac out-
put, as the exhalation of carbon dioxide is dependent on perfusion of
alveoli.67 In children with abnormal pulmonary vascular beds who are
at risk for acute increases in PVR with subsequent decreases in
pulmonary blood flow and cardiac output, capnographic assessment
has been shown to highly correlate with both physiologic and al-
veolar dead space calculated values as well as have an association
with outcomes.68,69 Therefore, using capnography as part of the
assessment of overall pulmonary blood flow can help in the
640 | COLEMAN
management of patients with acute RVF. However, it is important to
note that in patients with underlying severe lung pathology and
do not ventilate as efficiently at baseline, the reliability of these
measurements will be more limited.
5 | I M A G I N G O F TH E P A T IE N T WI T H RV F
5.1 | Echocardiography
Echocardiography is an invaluable tool in the management of these
fragile patients. Although the complex geometry of the right ventricle
can hinder accurate quantitative assessment of ventricular ejection,
there are a number of other measurements and general observations
that can aid in the ICU assessment of the right ventricle. While
specifics of echocardiographic assessment of PH are beyond the
scope of this paper, for the acute management of a child with a failing
right ventricle, the most helpful echocardiographic views are the
four‐chamber and parasternal short access views to assess IVS po-
sition and RV free wall motion, as well as the estimated RV pressure
from Doppler interrogation of tricuspid valve regurgitation or pul-
monary insufficiency.70‐74 Measurements, such as tricuspid annular
plane systolic excursion are well‐established markers of PH severity
and ventriculo‐arterial coupling, these measurements have a fair
amount of interobserver variability and may not be as useful in the
acute setting.75 Longitudinal assessments of echocardiographic
measures are likely to provide more clinical information to guide
management rather than an individual assessment.
5.2 | Chest imaging
Imaging of the chest and pulmonary vasculature, particularly in the
setting of acute RVF, is an incredibly important part of the man-
agement and treatment. Computed tomography of the pulmonary
vasculature to evaluate for the presence of pulmonary embolism, as
well as the assessment of the more distal vasculature and pulmonary
venous anatomy can dramatically impact acute management. For
example, should acute RVF be secondary to a pulmonary embolism
that is subsequently diagnosed, immediate intervention to remove
the obstruction can be life‐saving. Chest radiographs reveal the size
and shape of the cardiac silhouette as well as the presence or ab-
sence of pulmonary edema, which can help not only to determine the
potential etiology (precapillary vs postcapillary) of undiagnosed pul-
monary vascular disease but direct potential interventions. Absence
of pulmonary vascular markings can be indicative of limited pul-
monary blood flow and elevated pulmonary arterial pressures,
whereas Kerley lines, asymmetry in pulmonary vascular markings, or
interstitial edema can be indicative of pulmonary venous hyperten-
sion. Determining precapillary vs postcapillary PH is critical for
guiding management because the strategy employed for the pre-
capillary disease can markedly worsen postcapillary disease and right
heart failure.
ET AL.
6 | INTUBATION AND M ECHANICAL
VENT IL ATION O F A P ATIENT WITH R VF
6.1 | Intubation
Patients with acute RVF can be incredibly hemodynamically unstable,
and acute changes in their intrathoracic pressure can induce cardiac
arrest. Therefore, it is imperative that the medical teams have ap-
propriate personnel, pharmacologic, and mechanical support strate-
gies prepared and ready for deployment before starting the process
if at all possible. Because of the high potential for cardiac arrest
during intubation, it is imperative to have the most experienced in-
dividual instrument the airway and a separate experienced individual
prepared to manage the potential cardiac arrest that may ensue with
the change in intrathoracic pressures.
Anesthetic and analgesic medications must be chosen wisely for
intubation, as many agents adversely affect either SVR or cardiac
contractility. Opioids tend to have minimal hemodynamic effects and
little to no effect on PVR, making high‐dose fentanyl often part of the
induction drug cocktail.76 Despite initial concerning data regarding
elevations in PVR, most recently ketamine has been shown to be safe
in patients with PH; with its quick onset of effect, it can be an ideal
agent barring catecholamine depletion.77 Propofol should be avoided,
as it causes direct myocardial depression and falls in both SVR and
mean arterial pressure, both of which only serve to exacerbate the
IVS shift and hemodynamic instability.78,79
Because of the expected physiologic instability that often occurs
with intubation, having arterial access before induction is preferable to
allow for real‐time immediate hemodynamic feedback related to any
intervention. Having either reliable large‐bore peripheral intravenous
access or central venous access before induction is ideal. The use of
epinephrine and/or vasopressin infusions initiated before in-
strumentation of the airway may help us to mitigate large fluctuations
in hemodynamics. Atropine to prevent bradycardia associated with
laryngoscopy is also particularly important in these patients, as any
decrease in cardiac output associated with bradycardia can become
quickly irrecoverable. Because of the RV's sensitivity to acute changes
in loading status, should any hemodynamic instability occur during the
intubation, fluid boluses are not advisable, as they may further distend
the RV and cause it to “fall off” the Starling curve precipitously, re-
sulting in cardiac arrest. Using small dilute doses of epinephrine (our
usual practice is 1 mL aliquots of 0.01 mg/kg diluated in 10 mL of
normal saline) to address hypotension preserves blood pressure and
contractility without overshooting and causing a profound hyperten-
sive event and its resulting sequelae. Sodium bicarbonate and calcium
chloride/calcium gluconate boluses to ensure optimal pH and con-
tractility capabilities are also helpful in acute settings.
6.2 | Mechanical ventilation
With intubation, the intrathoracic pressure changes from negative
to positive, which results in impaired venous return to the right side
COLEMAN ET AL.
of the heart with a subsequent decrease in cardiac output, a finding
first described in 1948 by Cournand et al.80 Shekerdemian et al
then applied this concept in patients with pulmonary circulations
requiring passive pulmonary blood flow, demonstrating negative‐
pressure ventilation strategies improved cardiac output in patients
with Fontan circulations and early extubation promoted cardiac
output in patients undergoing repair of heart defects associated
with RV dysfunction.81‐83 When choosing a ventilation strategy,
because of the increased afterload placed on the RV by positive‐
pressure ventilation, it is imperative to choose a PEEP that achieves
an end‐expiratory lung volume that approximates functional re-
sidual capacity. Overdistention raises PVR via compression of the
alveolar vessels, whereas atelectasis raises PVR via the collapse of
the extra‐alveolar vessels in combination with the collapse of
terminal airways and resultant alveolar hypoxia. A tidal volume and
intermittent mandatory ventilation rate should be chosen to
achieve effective minute ventilation and maintain lung recruitment
without overdistention of lung units.
7 | INOTROPE/VASOPRESSOR SELECTION
7.1 | Epinephrine
Epinephrine is well‐established as the first‐line therapy for children
with hypotension and is the resuscitation drug of choice for pediatric
advanced life support. Because it can have both α‐ and β‐adrenergic
effects depending on the dose, it is possible that high‐dose epi-
nephrine could induce tachycardia or even become arrhythmogenic,
increasing myocardial oxygen demand, decreasing coronary blood
flow, and ultimately have worsened overall function. Siehr et al84
nicely demonstrated epinephrine was beneficial in pediatric patients
with PH in that it was able to improve systolic blood pressures, but of
note, it also increased PVR with escalating doses; therefore, the dose
should be carefully titrated.
7.2 | Vasopressin
Vasopressin works well in patients with PH who have a normal left
ventricular function. Vasopressin, via the V1 receptor, induces nitric
oxide release in the pulmonary artery vascular endothelium, re-
sulting in a decrease in pulmonary artery pressure via vessel dila-
tion.85 However, it maintains SVR and thus, by increasing the
afterload with which the left ventricle has to pump against, it can
help us to shift the IVS rightward and improve both left ventricular
filling and ejection. In the study by Siehr et al84, vasopressin was
found to favorably decrease the systolic pulmonary artery to sys-
temic aortic pressure, making it seem to be an ideal agent for
children with PH who are in the ICU. Beneficial effects have also
been seen in neonates with a persistent PH of the newborn, with
improvement in oxygenation and the ability to wean inhaled nitric
86
oxide (iNO).
| 641
7.3 | Milrinone
Milrinone works via the phosphodiesterase pathway and has both
inotropic and lusotropic effects. It is a well‐established tool for
supporting patients after surgical repair of congenital heart disease
and has been actively investigated in the neonatal population with
some data suggesting an improvement in both oxygenation and
overall hemodynamics after milrinone initiation.87,88 Because of the
significant vasodilatory properties of the drug, it can cause significant
decreases in both the right and left ventricular end‐diastolic pres-
sures, however. Lowering of the SVR can then adversely affect the
IVS position and worsen overall hemodynamic stability in these pa-
tients, and thus may not be an ideal agent in patients who are he-
modynamically unstable. Should milrinone be used, adding either
epinephrine or vasopressin may be necessary to maintain appro-
priate SVR and ensure adequate systemic and coronary perfusion
pressures. Milrinone also has a long half‐life of 2 hours, and is renally
cleared; because patients with RVF often have kidney injury, this
drug must be used with caution.89,90
8 | PULMONARY VASODILATORS
Selective pulmonary vasodilators given via inhalation are an attrac-
tive group of agents, as they often have minimal systemic side effects
but can dramatically improve overall hemodynamics and RV function.
However, it is imperative to understand the etiology of the patient's
PH (precapillary vs postcapillary) before these therapies are started.
Should the patient have a postcapillary disease, the addition of in-
haled vasodilators may ultimately worsen their RV function and
promote pulmonary edema formation.91 There are times when there
may be a “necessary evil” and tight fluid balance control is necessary
so that pulmonary edema is minimized. These therapies should only
be used sparingly and in experienced centers familiar with the
management of patients with postcapillary PH.
8.1 | Inhaled nitric oxide
Nitric oxide is an endogenous and potent vasodilator derived from
vascular endothelium that works via the cyclic guanosine mono-
phosphate pathway to induce vascular smooth muscle relaxation.92
iNO has a well‐established role in the treatment of persistent PH of
the newborn and is approved by the Food and Drug Administration
for this indication.8,93 However, it has become often the first‐line
treatment employed for nearly all patients in any ICU with known
or suspected PH with acute RVF. Doses greater than 20 ppm have
not been shown to increase oxygenation or improve outcomes, but
are more likely to cause methemoglobinemia or other complica-
tions.8 In patients with an unclear etiology of their PH, the addition
of iNO could unmask a severe postcapillary disease, such as
alveolar‐capillary dysplasia or pulmonary capillary hemangioma-
tosis, and cause an acute overall worsening of the patient's
642 | COLEMAN
hemodynamics; therefore, when initiating iNO in a patient with
severe PH and RVF of unclear etiology, patients must be carefully
monitored to assess for the development of pulmonary edema,
indicative of a postcapillary process. Abrupt discontinuation of iNO
can also cause severe rebound PH, so gradual weans with a dose of
sildenafil before discontinuation have been shown to reduce the
94
incidence of this and this approach is recommended. It is
important to note that there must be some degree of lung inflation
and the ability for gas exchange to occur if iNO is to be employed; in
patients with significant lung collapse, iNO is unlikely to be of
benefit.
8.2 | Iloprost
Iloprost is an inhaled prostacyclin that can be given intermittently
to either intubated or nonintubated patients via nebulization in
the ICU, at a usual frequency of every 2 to 3 hours.95 Because it
acts via a different mechanistic pathway than iNO, it is a useful
adjunct to further decrease pulmonary arterial pressures and
improve the RV function with minimal effects on systemic hemo-
dynamics because of its route of administration and site of action.
Iloprost has been associated with bronchospasm; therefore,
bronchodilators may be needed to prevent acute worsening of gas
exchange.95
8.3 | Inhaled epoprostenol
Continuous inhaled epoprostenol is another therapy that has been
shown to be effective at reducing pulmonary arterial pres-
96,97
sures. This therapy requires a special nebulizer system to be
implemented and can be connected to both invasive and
noninvasive support methods. Interestingly, because of the ex-
pense of iNO and the reduced cost of inhaled epoprostenol, groups
have demonstrated substantial cost savings without any increase
in patient harm with the use of inhaled epoprostenol.98,99
However, at this time, iNO remains the recommended therapy for
the acute management of PH.8,100
9 | INT ERV ENTION AL AN D S URGIC AL
PROCEDURES FOR THE ACUTELY
FAILING RV
In patients with a failing RV secondary to an abnormal pulmonary
vascular bed, creating a right‐to‐left shunt to preserve cardiac
output at the expense of oxygenation can be a necessary inter-
vention to “buy time” while specific diagnoses and therapies are
further explored. Because of the morbidity and mortality asso-
ciated with these procedures, it is the recommendation of the
authors that these interventions occur only at experienced pedia-
tric PH centers.
ET AL.
9.1 | Atrial septostomy
Atrial septostomy for severe PH with RV dysfunction has been a
well‐established intervention.7,101 These procedures have been
shown to carry significant procedure‐related mortality risk (7.1% at
24 hours); however, at expert centers, that risk can be less than
1%.101,102 It is important to remember that atrial septostomies are
volume‐unloading shunts, rather than pressure‐unloading shunts and
result in both the brain and the coronary arteries receiving deox-
ygenated blood. For the acutely failing RV facing significant pressure
overload, these shunts are not effective at aborting the pressure‐
overload resulting in ventricular failure and hemodynamic collapse.
Depending on the dilation of the right ventricle and IVS shift, the
end‐diastolic pressure and volume of the left ventricle may be high
enough that it raises the left atrial pressure higher than the right
atrium, thus preventing the decompressive right‐to‐left shunt that
these patients may need.
9.2 | Reverse Potts shunt
Reverse Potts shunt creation represents an attractive option for
patients with the acutely failing right ventricle, as the communication
between the left pulmonary artery and descending aorta results in a
right‐to‐left shunt that both unloads the high pressures the right
ventricle faces while sending deoxygenated blood to the lower body
and preserving oxygenated cardiac output for the central nervous
system and coronary artery circulations. This physiology can be
created either via surgical procedure or via catheter‐based inter-
ventions aimed at recanalization and stenting the ductus arteriosus
or through transvascular covered stent placement. The largest case
series to date discussing Potts shunt outcomes has shown promising
results, with 21 of the 24 patients (19 surgical and 5 via stenting of
the ductus) showing persistent improvement in both measures of RV
function and in functional outcomes.103
10 | PH CR I S IS : WHA T I T IS , WHA T I T IS
NOT, AND WH AT TO D O A BOUT IT
A pulmonary hypertensive crisis is the effect of an abrupt rise in PVR
and RV afterload resulting in acute right heart failure (Figure 1). It is
important to distinguish true acute RVF resulting from an acute rise
in PVR vs an acute rise in PVR that may cause systemic hypoxemia
but with a normally functioning right ventricle.
The first goal during a pulmonary hypertensive crisis should be
to decrease the abrupt increase in RV afterload and PVR (Figure 2).
This can be achieved by adding pulmonary vasodilators, preferably
inhaled agents (ie, oxygen, iNO, and inhaled prostacyclin therapy).
Inhaled therapies allow for less systemic hypotension which helps us
to maintain appropriate cardiac output and avoids ventilation/per-
fusion mismatch. It is also important to try and reverse the factors
that caused the acute rise in PVR. Additional management should aim
COLEMAN ET AL.
F I G U R E 1 Pathophysiology of a pulmonary hypertensive crisis. LV, left ventricular; PVR, pulmonary vascular resistance; RA, right atrium;
RV, right ventricular [Color figure can be viewed at wileyonlinelibrary.com]
to correct the metabolic derangements (acidosis), treat respiratory
failure while avoiding alveolar hypoxia, and reduce sympathetic
overstimulation via sedation and paralysis.19,104‐106
The second goal should be to augment and maximize RV con-
tractility. This can be completed by low‐dose inotropic support
(<0.05‐mcg/kg/min epinephrine infusion or small boluses of
epinephrine [0.01 mg/kg diluted in 10 mL of normal saline] to im-
prove cardiac output without a concomitant rise in PVR). Higher dose
epinephrine also places the patient at risk due to the arrhythmogenic
properties of high‐dose catecholamines.107
The third goal is to optimize the volume status of the right heart.
Most patients during a PH crisis and acute right heart failure will
have RV volume overload, leading to elevated RV end‐diastolic vo-
lume and pressure, causing increase tricuspid regurgitation and in-
creased right atrial volume/CVP. Therefore, plans should be made to
avoid fluid/volume resuscitation as this may further right atrial
dilation, more volume loading to the right ventricle and worsen RVF
and cardiac output.34,108‐110
Finally, maintaining systemic perfusion during this crisis is
extremely important. Patients with severe RVH and RV dilation,
during an acute crisis can have an IVS that bows into the left ven-
tricle during systole. This can lead to lower stroke volume and poor
cardiac output. Increasing SVR as a goal to shift the IVS using a pure
vasopressor (ie, vasopressin) can help achieve this goal and also allow
help us to improve coronary artery perfusion and avoid RV myo-
cardial ischemia.111,112
| 643
11 | MECH ANIC AL SUPP ORT FOR RVF
Mechanical circulatory support (MCS) can be utilized for patients
with acute right heart failure, but it must effectively unload the RV.
The etiology of the RVF must be determined to best decide on the
type of support necessary. The timing of initiation of support is also
extremely important, as increasing morbidity and mortality can be
seen with watchful waiting.
11.1 | Extracorporeal membrane oxygenation
Extracorporeal membrane oxygenation (ECMO) can be used as a
bridging therapy to allow for stabilization of cardiac output as ad-
ditional diagnostics or medical therapies are instituted. For patients
with RVF associated with pulmonary vascular disease, ECMO can be
used as a bridge to recovery from acute illness. It can be used as a
bridge to stabilization and addition of PH targeted therapy to max-
imize medical treatment with plans to wean off of mechanical sup-
port once RV function has been recovered. ECMO can also be
utilized as a bridge to an invasive intervention (ie, atrial septal defect
[ASD] or ventricular septal defect creation, ductus arteriosus re-
canalization, and stenting) and subsequent weaning off of MCS. In
some instances, ECMO can be used as a bridge to lung transplant.
Some patients with normal or mild RV dysfunction and hemodynamic
stability may be able to be supported with an ASD creation and
644 | COLEMAN
venovenous ECMO as a bridge to transplant, while others will re-
quire full venoarterial (VA) support to help unload the RV volume
and pressure. The intention of placing patients on VA‐ECMO support
would be to ultimately allow for the continuation of physical therapy
and rehabilitation as they wait on the mechanical support for lung
transplants.113,114 To that end, Rosenzweig et al have advocated for
the “sport model” of VA‐ECMO utilizing cannulation of the internal
jugular vein and subclavian artery to both provide venoarterial
support while allowing for full ambulation.114,115
11.2 | Paracorporeal lung support
For patients in whom it seems VA‐ECMO support may not be able to
be weaned, or if a patient is showing signs of worsening right heart
function but has not yet reached the point of needing full ECMO
support, Eghtesady, Grady et al116,117 have discussed the use of a
novel paracorporeal lung assist system. Because of the high‐risk
profile of this approach, they nicely advocated for the use of this
therapy in those patients in whom lung transplant is the destination
therapy and who otherwise have no options. Cannulation was be-
tween the pulmonary artery and the left atrium in these patients,
with their system consisting of a Quadrox oxygenator (Maquet
Cardiopulmonary AG, Hirrlingen, Germany) and Berlin cannulae
(Berlin Heart AG, Berlin, Germany). It is important to note the high
incidence of central nervous system complications in this patient
cohort, and thus, it is imperative families be counseled appropriately
before cannulation.116 Other centers have utilized the Novalung
System, particularly adult centers, as a successful bridge to lung
transplantation.118
CO N CL US I O N
Management of the acutely failing right ventricle requires particular
attention to detail, particularly with regard to the management of
volume status and selection of inotropic and vasopressor agents.
Invasive monitoring of hemodynamics, interventions made by the
most experienced of providers, and frequent titrations of both ven-
tilatory and hemodynamic support are required. Because of the high
ET AL.
F I G U R E 2 Management of a pulmonary
hypertensive crisis. iNO, inhaled nitric oxide;
NS, normal saline; PH, pulmonary
hypertension; PVR, pulmonary vascular
resistance [Color figure can be viewed at
wileyonlinelibrary.com]
acuity of these patients, management at centers with significant ex-
perience with PH, cardiac catheterization, and MCS of patients with
right‐sided failure is recommended.
ORCI D
Ryan D. Coleman http://orcid.org/0000-0002-3533-839X
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How to cite this article: Coleman RD, Chartan CA, Mourani
PM. Intensive care management of right ventricular failure
and pulmonary hypertension crises. Pediatric Pulmonology.
2021;56:636–648. https://doi.org/10.1002/ppul.24776