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Abstract
Pulmonary hypertension occurs as the result of disease processes increasing pressure within the pulmonary circulation, eventually
leading to right ventricular failure. Patients may become critically ill from complications of pulmonary hypertension and right
ventricular failure or may develop pulmonary hypertension as the result of critical illness. Diagnostic testing should evaluate for
common causes such as left heart failure, hypoxemic lung disease and pulmonary embolism. Relatively few patients with pulmonary hypertension encountered in clinical practice require specific pharmacologic treatment of pulmonary hypertension
targeting the pulmonary vasculature. Management of right ventricular failure involves optimization of preload, maintenance of
systemic blood pressure and augmentation of inotropy to restore systemic perfusion. Selected patients may require pharmacologic therapy to reduce right ventricular afterload by directly targeting the pulmonary vasculature, but only after excluding
elevated left heart filling pressures and confirming increased pulmonary vascular resistance. Critically-ill patients with pulmonary
hypertension remain at high risk of adverse outcomes, requiring a diligent and thoughtful approach to diagnosis and treatment.
Keywords
pulmonary hypertension, pulmonary arterial hypertension, right ventricular failure, right heart failure, pulmonary vasodilators
Introduction
Pulmonary hypertension (PH) develops through a final
common pathway of myriad cardiac and noncardiac disease
processes that increase pulmonary artery (PA) pressures.1 Pulmonary hypertension contributes to critical illness primarily
via right ventricular failure (RVF), ultimately leading to hemodynamic compromise and death.2-6 Disease processes directly
impairing right ventricular (RV) contractility can produce RVF
in the absence of PH.7-10 Most cases of PH encountered in clinical practice are produced by another disease process, being
secondary to critical illness rather than causative of it.1 Identifying causes of PH requiring specific therapy can be challenging in critically ill patients, and direct treatment of PH is
often less important than correcting the underlying disease process. Several reviews have discussed various aspects of PH
and/or RVF in critical care settings.2-9 In this review, we will
focus on the diagnosis and treatment of various etiologies of
PH encountered in intensive care unit (ICU) patients, with an
emphasis on management of critically ill patients with pulmonary arterial hypertension (PAH).
Received March 25, 2014, and in revised form March 13, 2015. Accepted
for publication March 16, 2015.
Corresponding Author:
Michael A. Mathier, University of Pittsburgh Medical Center Heart and
Vascular Institute HVI at UPMC Presbyterian 200 Lothrop Street Pittsburgh,
PA 15213, USA.
Email: mathierm@upmc.edu
Venous oxygenaon
Hypoxic vasoconstricon
LV cardiac output
Systemic perfusion
Systemic BP
Heart rate
RV aerload
Coronary perfusion
RV ischemia
RV systolic funcon
RV cardiac output
LV lling
RV lling pressures
RV dilaon
Tricuspid regurgitaon
Pathophysiology
Acute RVF represents the inability of the RV to maintain normal
cardiac output at a normal right atrial pressure (RAP), and the
pathophysiology of PH-induced RVF is reviewed in detail elsewhere (Figure 1).2,3,5-7,9,10,15,26 Pulmonary hypertension is defined
by elevated PA pressures, typically resulting from increased pulmonary vascular resistance (PVR) and/or increased pulmonary
venous pressures, with elevated cardiac output contributing to
some etiologies.12 Elevated PVR results from excessive pulmonary
arteriolar vasoconstriction and/or pulmonary vascular obstruction.12 Patients with PH-induced RVF are prone to rapid deterioration through a vicious cycle of progressive shock, and even
transient hypotension or hypoxemia can trigger an inexorably fatal
downward spiral unless corrected promptly (Figure 1).2,4,5,10 Worsening hypotension in patients with RV dysfunction can result from
inadequate RV preload, excessive RV afterload, deteriorating RV
contractility, or inappropriate systemic vasodilation.8
The RV is very sensitive to changes in afterload and cannot
maintain its stroke volume if PVR rises abruptly.2,7,8 Right
ventricular dilation is characteristic of RVF, as the RV attempts
to utilize preload reserve to compensate for acutely increased
afterload from rising PVR.5,9,10,15 Right ventricular dilation
increases RV wall tension and worsens TR, further reducing
forward RV stroke volume. A distended RV can impinge on
left ventricular (LV) diastolic filling and stroke volume through
ventricular interdependence.2,5,8,10 Decreased RV output
reduces LV filling and forward LV stroke volume, leading to
systemic hypotension and RV myocardial hypoperfusion that
can induce RV ischemia and further impair RV contractility.3,5-7,10 Tachycardia is often an adaptive mechanism to
maintain cardiac output in the face of reduced stroke volume
but can worsen RV ischemia and impair RV diastolic filling.
Low cardiac output results in venous blood oxygen desaturation, which worsens arterial hypoxemia when pulmonary
reserve is compromised. Hypoxia-induced pulmonary vasoconstriction constricts pulmonary arterioles in hypoxic lung segments to improve physiologic ventilationperfusion (V/Q)
matching and systemic oxygenation at the expense of increased
PVR.23 Inflammatory cytokine release (ie, from sepsis or cardiopulmonary bypass) worsens RVF by producing pulmonary
vasoconstriction, microvascular obstruction, myocardial
depression, and systemic vasodilation.8,10,15
Clinical Presentation
Acute RVF produces symptoms through systemic congestion
and/or low cardiac output. Typical symptoms of isolated RVF
include dyspnea and gastrointestinal symptoms, usually without orthopnea or paroxysmal nocturnal dyspnea.2,13 Signs and
symptoms of low output include exertional light-headedness or
PH not likely
TR jet velocity <3m/s
Normal RV structure
and funcon
Evaluate alternave
causes of symptoms
Consider RHC if
no other cause
PH likely
TR jet velocity >=3m/s
Abnormal RV structure
Abnormal RV funcon
Addional causes?
Elevated PAWP
Hypoxemia
Concomitant PE
Pulmonary congeson
PVOD
Idiopathic PAH
Associated PAH
Figure 2. Diagnostic approach to newly recognized pulmonary hypertension in acutely ill patients. TTE indicates transthoracic echocardiogram;
TR, tricuspid regurgitation; RV, right ventricle; LV, left ventricle; RHC, right heart catheterization; PAWP, pulmonary artery wedge pressure; PE,
pulmonary embolism; PAP, pulmonary artery pressure; PVR, pulmonary vascular resistance; CT, computed tomography; CTA, CT angiography;
PVOD, pulmonary veno-occlusive disease.12,41
Diagnostic Evaluation
In the ICU, patients may present with RVF from de novo
acute PH (newly diagnosed PH) or acute-on-chronic PH
(deterioration of prior chronic PH), along with patients having
incidentally discovered PH without overt RVF. The diagnostic assessment in de novo PH seeks to identify treatable
secondary causes and recognize patients who are likely to
benefit or be harmed by PAH-specific therapy (Figure 2),
while the diagnostic assessment in patients with established
PH aims to identify factors triggering decompensation
(Table 2). Distinguishing patients who are critically ill because
of PH (and will require PH treatment) from patients whose PH is
secondary to critical illness (who are more common in our experience) remains challenging. In critically ill patients, multiple
underlying disease processes often contribute to worsening PH
and/or RVF rather than a single correctible factor.
Transthoracic echocardiography remains the first-line test
for patients with suspected PH and/or RVF to estimate PA
systolic pressure (PASP) and assess RV structure and function.41-43 Echocardiographic assessment of PASP depends on
the peak TR jet Doppler velocity plus an estimate of the RAP,
although this method lacks both sensitivity and specificity for
PH.12,42,43 Patients with an estimated PASP >40 mm Hg or
peak TR jet velocity 3 m/s on echocardiogram are likely to
have PH at right heart catheterization (RHC), with higher
specificity at higher PASP values.41-43 In our medical ICU
patients, a TR jet velocity 3 m/s on TTE had up to 90% positive predictive value for PH in patients undergoing RHC,
despite a poor negative predictive value.11 Because of the limited ability of the RV to tolerate acute increases in afterload,
severe elevations in PA pressures generally represent a more
chronic disease process, allowing time for the RV to adapt
(especially in the presence of RV hypertrophy). Echocardiographic RV dysfunction is characterized by a dilated, hypocontractile RV with flattening or paradoxical motion of the
interventricular septum, and these findings are characteristic
of decompensated RVF.4,5,25 Echocardiographic evidence of
PH-LHD includes LV systolic or diastolic dysfunction, mitral
valve disease, left atrial enlargement, and/or Doppler evidence
of elevated LV filling pressures.13,43,44 Mild LV diastolic dysfunction (abnormal relaxation) can be induced by ventricular
interdependence from RV dilation, but higher degrees of LV
diastolic dysfunction suggest PH-LHD.13,44 Echocardiography
often identifies pericardial effusions in patients with PH, which
rarely cause tamponade but are associated with adverse prognosis and a high mortality rate after drainage.25,45
In critically ill patients with PH and/or RVF, we favor early
RHC to establish the diagnosis, determine the etiology, and
assess the filling pressures (Figure 2). This includes patients
in whom clinical suspicion for PH remains high, despite normal TR jet velocity (ie, an abnormal RV on echocardiogram).
Pulmonary hypertension is defined hemodynamically by an
elevated mean PA pressure (mPAP) 25 mm Hg by RHC, and
RHC helps to differentiate common types of PH.41 We typically use a PA catheter (PAC) to guide therapy in unstable
patients with PH and/or RVF, especially if PAH-specific therapy is considered.5,8 Early use of a PAC to guide therapy was
associated with reduced mortality in 1 study of patients with
PH having RVF, despite failure of PAC-guided therapy to
reduce mortality in general critically ill patients.32,46 Caution
is required during RHC in patients with PH due to the risk of
potentially fatal PA rupture.47 The RHC allows measurement
of PA wedge pressure (PAWP) and calculation of PVR, which
corrects for elevated PAWP and cardiac output to identify
pulmonary vascular disease.12 Pulmonary hypertension
caused by left heart disease (postcapillary PH) is defined by
an elevated PAWP >15 mm Hg with normal or reduced cardiac output. Most patients have normal PVR, although
First-line therapies
Treatment goals
Second-line therapies
Normalize oxygenaon
Supplemental oxygen
Noninvasive venlaon
Mechanical venlaon
Low airway pressures
Transfusion if anemic
Ultraltraon
Stable BP inodilator
Low BP dopamine
Epinephrine
Restore systemic BP
SVR > PVR
Norepinephrine
Vasopressin
Epinephrine/dopamine
Phenylephrine
Inhaled prostanoids/NO
Add-on sildenal?
Reduce RV aerload
Selected paents
PH-LHD
Nitroglycerin
Nitroprusside
Advanced therapies
PH-PLD
Inhaled NO/prostanoids
ECMO if refractory
Figure 3. Clinical management of pulmonary hypertension-induced right ventricular failure. CVP indicates central venous pressure; BP, blood
pressure; SVR, systemic vascular resistance; PVR, pulmonary vascular resistance; CTEPH, chronic thromboembolic pulmonary hypertension;
PH-LHD, pulmonary hypertension due to left heart disease; PH-PLD, pulmonary hypertension due to parenchymal lung disease; ECMO,
extracorporeal membrane oxygenator support; NO, inhaled nitric oxide; LVAD, left ventricular assist device.2-10,12,13,22,48
Table 3. Simplified Approach to Right Ventricular Failure Etiology and Treatment.8,20
Blood pressure
Cardiac output
CVP
DPVR
Cause
Primary Treatment
#
#
#
#
$
$
#
#
#
$"
$"
$
#
"
"
$"
"
#
$"
"
$
$"
$"
$
Hypovolemia
Worsening PH
RV dysfunction
Vasodilation
Volume overload
Compensated
Volume
PAH-specific therapy
Inotropes
Vasopressors
Diuretics
None
Abbreviations: CVP, central venous pressure; DPVR, change in pulmonary vascular resistance; PAH, pulmonary arterial hypertension; PH, pulmonary hypertension; RV, right ventricular.
Note. Arrows reflect direction and magnitude of effect (# = reduction, $ = no change, $" = no change or increase, " = increase, ## = strong decrease, "" = strong
increase).
Treatment of RVF
The treatment of acute RVF involves correcting reversible
causes of decompensation (Table 2), optimizing RV preload,
supporting RV contractility, and reducing PVR while maintaining systemic vascular resistance (SVR) and mean arterial
pressure (MAP; Figure 3).2-10,14,20,24,25,51 A simplified
approach to RVF (Table 3) emphasizes the diagnosis and
Preload Optimization
Volume loading. The dysfunctional RV may require an abnormally elevated RAP (up to 12-15 mm Hg) to maintain cardiac
output due to diastolic dysfunction, so patients with RVF having hypotension and/or hypoperfusion may require volume
loading to optimize cardiac output.3,7,8 This practice is primarily based on expert opinion, with few primary data to guide the
quantity, rate, or targets of fluid therapy in patients with PH.
Patients with acute PH (particularly acute PE) may be more
likely to respond favorably to volume administration compared
to patients with chronic PH who usually have elevated RV filling pressures even in the absence of gross volume overload.3,7,14,15,24,52 Despite favorable effects in animal models,
patients with acute RV dysfunction caused by RV infarction
may not consistently respond to volume loading and responded
more reliably to inotropic support in some studies.53-55 Volume
loading is considered more appropriate when CVP is low but
should be discontinued if CVP rises without improved systemic
hemodynamics. Cautious fluid administration can be continued
if the CVP remains low without pulmonary congestion.7,14,24,52
Based on expert opinion, a reasonable fluid challenge for a
patient with acute RV dysfunction or acute PH is up to 500
mL over 15 to 20 minutes, while the fluid challenge in a patient
with chronic PH should be smaller (up to 250 mL).5,9,7,14,24,52
A CVP >15 mm Hg is rarely needed to optimize RV stroke
volume, and markedly elevated CVP (especially >20 mmHg)
can impair RV function via increased RV wall stress and functional TR, leading to worsening systemic hemodynamics.3,4,7
Empiric fluid administration can worsen decompensated RVF
and is not recommended without assessment of CVP.5-9
Volume removal. Patients with systemic congestion in the
absence of hypotension or hypoperfusion typically improve
with volume removal alone and may not need vasoactive drugs.
Relief of RV volume overload can improve RV function by
reversing RV overdistention and septal shift, so volume
removal may be warranted even in patients with hypotension
having low output and high CVP.3,4 Most acutely ill patients
with PH-induced RVF warrant empiric diuresis, particularly
with worsening hypoxemia, gross fluid overload, or elevated
CVP.3 Intravenous loop diuretics are first line for volume
overload and titrated to the lowest filling pressures that relieve
congestion while maintaining adequate systemic hemodynamics.51 We prefer a continuous furosemide infusion to allow
gradual diuresis and avoid abrupt swings in filling pressures.
Furosemide infusion rates 30 mg/h have been reported in the
literature.33,56 Resistance to an adequate loop diuretic dose
(10-20 mg/h furosemide infusion) can often be overcome
by adding a thiazide-type diuretic.33,51,56 In our experience,
diuretic resistance in RVF is usually due to low cardiac output,
especially in the presence of hypotension, hyponatremia, and/or
worsening renal function. Extracorporeal fluid removal via ultrafiltration can be used for persistent volume overload, despite
combination diuretic therapy, although the need for dialysis
or ultrafiltration to manage refractory cardiorenal syndrome
portends a grim prognosis.4,32,51,57
Vasoactive Therapies
Support with vasoactive drugs including vasodilators, inotropes, and/or vasopressors may be required to reverse severe
RVF with low output and/or systemic hypotension when preload optimization is inadequate to restore hemodynamics. The
goals of vasoactive drug therapy are to reduce PVR, maintain
SVR, and increase cardiac output to improve MAP and organ
perfusion.2 Most patients with hypotension having RVF have
low cardiac output, but hypotension with preserved cardiac
output and low SVR suggests inappropriate vasodilation
requiring vasopressor therapy (Table 3).20 Hypotension with
reduced cardiac output and adequate/increased CVP suggests
worsening RVF from excessive RV afterload (increased PVR)
and/or reduced RV contractility (stable PVR; Table 3).20 Pulmonary arterial hypertensionspecific therapies can be effective monotherapy for worsening RVF when elevated PVR is
the dominant etiology. Inotropic support is often required for
low-output RVF, especially if RV contractility is impaired.
Certain vasoactive drugs including PAH-specific therapies
can simultaneously increase RV inotropy and reduce PVR
to reverse RVF.8,10,13,58-60 Vasopressors may be required to support MAP in patients with severe hypotension, especially with
inadequate vascular tone. In-hospital mortality approaches
50% in patients with severe PAH-induced RVF who require
support with vasopressors and/or inotropes, especially at
higher doses.27,29,30,32,34,61
Pulmonary arterial hypertensionspecific therapies. The underlying
etiology of PH determines the need for therapy targeting the
pulmonary vasculature and the most appropriate type of drug
(if indicated; Figure 3). Treatment with PAH-specific drugs has
only been associated with improved outcomes in outpatients
with chronic PAH, representing a minority of all patients with
PH.12 Relatively few critically ill patients with PH and/or RVF
will have an underlying etiology that warrants PAH-specific
therapy, so PH is not always a plausible target for therapy and
PAH-specific therapies are unlikely to improve outcomes in
unselected patients.2 Appropriate use of PAH-specific therapy
can be lifesaving in severe RVF due to PAH and may obviate
the need for inotropic therapy, but off-label use of systemic
PAH-specific drugs in patients with other forms of PH may
lead to life-threatening complications when used injudiciously.12 In his article, we discuss off-label uses of these drugs
in selected non-PAH patient subsets based on evidence from
clinical studies and personal experience supporting a limited
role in certain situations, but PAH-specific drugs should not
be used routinely in non-PAH patients. Importantly, there is
no evidence supporting any outcomes benefit for off-label use
Dobutamine58-60,81-83
Milrinone59,60,84,85
Norepinephrine65,92
Dopamine
Epinephrine
Vasopressin85,86
Phenylephrine65,92
#$a
##
"
"
"
#
""
#$a
#
"
"
"
"
"
$
#
$
$
$
#
"
Supportive Care
Oxygenation. Oxygen is the most important physiologic pulmonary vasodilator, and increased fraction of inspired oxygen
(FIo2) can counter hypoxic pulmonary vasoconstriction and
reduce PVR, making supplemental oxygen the first-line therapy for patients with hypoxemia having PH.95 Worsening
hypoxemia is common in decompensated PAH (see Table
2), and patients should receive supplemental oxygen to raise
SaO2 >92%.3,5,8 For selected patients with PAH having low
systemic oxygen delivery, using higher FIo2 to increase SaO2
may maximize reduction in PVR.95 For some patients with
PH-PLD, restoration of normoxia may be sufficient to reverse
PH.22 Hypoxemia in patients with PH usually responds to supplemental oxygen, although intracardiac shunting through a
patent foramen ovale can produce hypoxemia that may
resolve with lowering RAP and increasing SVR.2,7 Maintenance of normocapnia (PaCO2 35-40 mm Hg) is recommended
because hypercarbia and acidosis can further increase PVR by
augmenting hypoxic pulmonary vasoconstriction, while
hyperventilation can improve PVR transiently.2,6-8,20 Ventilator management of patients with PH is discussed subsequently
in the section on PH due to lung disease.
Arrhythmia management. Atrial fibrillation and atrial flutter are
the most frequent sustained arrhythmias in patients with
PAH-induced RVF and may be associated with increased
mortality.29,30,61 The dysfunctional RV is highly dependent
on atrial contraction to maintain adequate filling, particularly
at rapid heart rates.3,5 Cardiac arrhythmias that impair atrioventricular (AV) synchrony, such as atrial fibrillation/flutter
or complete heart block, often produce hemodynamic compromise in patients with RVF.2,7,9 Electrical therapy is the
first line for unstable patients, including cardioversion for
tachyarrhythmias, and bradyarrhythmias (i.e. after cardioversion) are poorly tolerated and respond best to AV sequential
pacing.3,7,9 Amiodarone is the first line for most tachyarrhythmias due to its lower risk of hypotension and lesser negative inotropic effects.3 Digoxin can provide rate control of
atrial arrhythmias in selected patients with preserved renal
function, but its positive inotropic effects are not clinically
relevant in severe RVF.3,96
Disease-Specific PH Therapy
Pulmonary Arterial Hypertension
Hospital admission in patients with PAH is a morbid occurrence, with in-hospital mortality of 9% overall that increases
to 14% to 17% for patients with RVF.29,30 Critically ill
patients with PAH admitted to the ICU have in-hospital mortality rates exceeding 30% to 40% plus an additional 10% to
20% mortality during the next 3 to 6 months for hospital survivors.27,29,30,32,34,61 Mortality predictors of hospitalized
patients with PAH are shown in Table 5.27,29,30,32,34,61,97
Death in hospitalized patients with PAH is most often due
to hemodynamic compromise from progressive RVF ultimately resulting in cardiac arrest, often with a bradycardic
arrest rhythm.29,30,97 Patients with PAH having cardiac arrest
have dismal outcomesonly 21% of resuscitative attempts
are initially successful, with 90-day survival of 6%.32,97 The
most common reason for hospital admission in patients with
PAH is RVF, followed by infection/sepsis (especially line
sepsis and pneumonia), medication noncompliance, respiratory failure, bleeding (especially gastrointestinal), syncope,
10
patients with PAH on chronic oral PAH-specific therapy decompensate and develop RVF, initiation of prostanoid therapy is
indicated, but preexisting oral PAH-specific drugs can be continued in the absence of adverse effects.12,98 Hypotension from
oral PAH-specific therapy is typically mild and may not warrant
drug discontinuation, but holding oral PAH-specific drugs when
the patient is hypotensive (ie, from sepsis) is reasonable and
rarely associated with rebound worsening of PH, especially if
the patient is receiving an alternative PAH-specific drug. The
phosphodiesterase (PDE)-5 inhibitor sildenafil is the only oral
PAH-specific drug we consider using in the acute setting due
to its rapid onset (15-30 minutes) and short duration of action
(up to 4-6 hours).2,8,62,98 Sildenafil at usual doses of 20 to 40
mg every 8 hours can improve hemodynamics in selected
patients with PAH, PH-LHD, or postoperative PH and can facilitate weaning of inhaled pulmonary vasodilators at a modest risk
of systemic hypotension.6,8,13,101-103,105,106 Both milrinone and
PDE-5 inhibitors may synergistically augment the effects of
prostanoids and inhaled NO, suggesting a role for combination
therapy.66,101-105 We avoid endothelin receptor antagonists
(ERAs) in acutely ill patients due to their prolonged duration
of action, delayed onset of effect, and risk of fluid retention and
hepatoxicity.8,12,13 The new guanlyate cyclase activator riociguat mimics the effect of a PDE-5 inhibitor by directly stimulating guanlyate cyclase.107,108 Studies of oral PAH-specific
drugs in critically ill patients are lacking, except for studies
examining off-label use in selected patient populations that
have not shown an outcome benefit.
Disease-specific considerations in PAH. Hemoptysis is an uncommon but potentially fatal complication of PAH, related to bronchial artery hypertrophy and/or hemodynamic progression
complicated by coagulopathy from chronic anticoagulation and
antiplatelet effects of prostanoid therapy.109,110 Bronchial artery
embolization may be effective for terminating acute episodes of
hemoptysis but recurrent hemoptysis is frequent.110,111 Pulmonary arterial hypertension associated with connective tissue disease (particularly systemic lupus erythematosus) may worsen
during disease flares, requiring augmented immunosuppression.3 Pulmonary veno-occlusive disease is a dangerous subtype
of PAH producing postcapillary pulmonary vascular obstruction
resulting in hydrostatic pulmonary edema in response to dilation
of pulmonary arterioles by PAH-specific therapy.2,12,49 With
aggressive diuretic therapy, some patients with PVOD may tolerate low-dose intravenous prostanoid therapy but prognosis
remains poor.3,12,49 The following 3 PAH scenarios require
especially careful management in conjunction with a PAH specialist and will not be discussed in detail here: portopulmonary
hypertension, PAH from congenital heart disease complicated
by right-to-left shunting (Eisenmenger syndrome), and management of patients with PAH in the peripartum period.
11
Thromboembolic PH
Acute PE is a common cause of new-onset PH and RVF, and
patients with PE complicated by RVF are at increased risk of
death.14 Antithrombotic therapy is the cornerstone of acute
PE therapy, including thrombolytic therapy or embolectomy
for massive PE causing hemodynamic instability or refractory
hypoxemia.14,120 With appropriate antithrombotic therapy, RV
dysfunction from acute PE typically improves or resolves,
although a minority of patients will go on to develop
CTEPH.12,14 Fluid resuscitation with or without inotrope and/
or vasopressor therapy is typically adequate for hemodynamic
stabilization in acute PE.52 Systemic PAH-specific therapy
may worsen V/Q mismatch, so inhaled pulmonary vasodilator
therapy is preferable when necessary. Patients with CTEPH
may present with severe PH and low-output RVF, warranting
PAH-specific therapies including off-label parenteral prostanoids and riociguat (Figure 3).3,12,108 Pulmonary thromboendarterectomy can significantly improve symptoms and
outcomes in selected patients with CTEPH.12,14 Patients with
Postoperative PH
Postoperative PH after cardiothoracic surgery occurs due to
acutely raised PVR from lung injury and adverse effects of
cardiopulmonary bypass superimposed on preexisting pulmonary vascular disease and/or elevated LV filling pressures.2,21,25 Abnormalities in RV filling and contractility
may drive postoperative RVF without overt PH.25,123 Risk
of postoperative RVF is highest after LVAD implantation and
relatively common after pneumonectomy, mitral valve surgery, and HT.12,21,25 The management of postoperative RVF
involves volume management and inotropic support, with
inhaled pulmonary vasodilators sometimes added even when
PVR is not dramatically elevated.21,25,123 Aggressive fluid
removal may be required to ameliorate elevated filling pressures, and early ultrafiltration is suggested in patients with
CVP >20 mm Hg, despite diuretic therapy.25,112 The combination of milrinone and vasopressin can support MAP and
cardiac output with favorable effects on PVR.6,21,25,85-87
Inhaled pulmonary vasodilators reduce PVR and/or improve
hypoxemia with minimal effects on systemic BP in postoperative
PH and/or RVF.2,6,8,12,21,25,66,68-74,77,100,101 Inhaled NO was more
effective than intravenous milrinone for improving postoperative
RV function without increasing the need for vasopressors.100
Perioperative off-label oral sildenafil may increase the response
to inhaled NO and facilitate weaning of NO with a low risk of
hypotension.21,25,101,103-106
Undifferentiated PH
For critically ill patients with de novo PH and/or RVF, medical stabilization may be required prior to complete diagnostic
evaluation (Figure 2). We recommend RHC and echocardiography to guide vasoactive therapies, and patients without
RV dilation or flattening of the interventricular septum generally do not require therapy to reduce PVR.3,4 Pulmonary
hypertension caused by left heart disease, PH-PLD, and PE
account for the majority of cases and rarely warrant PAHspecific therapy.2-4,12 Oxygenation should be optimized,
using RV-protective mechanical ventilator settings and adequate FIO2.23,95 Empiric diuresis is appropriate with clinical
volume overload or elevated filling pressures.3 Milrinone may
be first line for lowering PVR based on its balanced vasodilator and inotropic properties, with vasopressin added if SVR is
low due to favorable effects on PVR.5,9,85-87 Systemic PAHspecific therapy (especially intravenous prostanoids) should
be discouraged in patients with PH of unknown etiology, and
inhaled pulmonary vasodilators may be more appropriate in
selected cases where PVR must be reduced. Empiric thrombolysis for possible PE can be considered in acutely unstable
patients after weighing the risks and benefits.14
12
Perioperative PH Management
Perioperative risk of PH is proportional to the severity of PH
and the degree of RVF, and elective surgeries should generally be avoided in patients with PH-induced RVF and elevated
RAP.20 Fluid shifts, mechanical ventilation, and inflammatory mediator release can contribute to worsening PH and
RV function perioperatively.20 Patients with significant PH
have a mortality up to 7% to 10% within 1 month after major
noncardiac surgery, with frequent postoperative complications including respiratory failure and RVF.20 Patients with
decompensated RVF evidenced by elevated RAP and/or
reduced cardiac output should be stabilized prior to necessary
surgery. A recent review provides an in-depth discussion of
perioperative PH management.20
Conclusion
Pulmonary hypertension is common in critically ill patients and
may cause circulatory compromise from RVF. Numerous etiologies produce PH in critically ill patients, particularly LV failure and hypoxemic lung disease. Diagnostic evaluation in the
ICU should rapidly exclude common etiologies via RHC and
chest CT imaging. Pulmonary arterial hypertension itself is
relatively infrequent, but patients with PAH who become critically ill have poor outcomes and require aggressive treatment
including intravenous prostanoid therapy. Management of RVF
in PH involves optimization of preload, reduction in PVR, and
support of RV inotropy and systemic perfusion. Empiric PAHspecific therapy prior to diagnostic assessment can produce disastrous consequences. Many commonly used vasoactive drugs
affect the pulmonary vasculature with favorable or detrimental
effects on RV afterload. The PAH-specific therapies can be
used for carefully selected patients with severe RVF and PH
but risk systemic hypotension and worsening hypoxemia.
Inhaled pulmonary vasodilators may have greater applicability
based on their ability to improve V/Q matching and hypoxemia. Prostanoid therapy should be reserved for patients with
normal lung parenchyma and normal left ventricular filling
pressures. Highly selected patients with refractory symptoms
may be considered for advanced therapies including DLT,
ECMO, or BAS. Despite the availability of an increasing therapeutic armamentarium for chronic PAH, acutely ill patients
with PH and RVF remain challenging to manage with a high
risk of mortality.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to
the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
13
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