Pulmonary Hypertension

Chris Nickson ●
Nov 3, 2020

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OVERVIEW
Pulmonary hypertension (PH) is a
pathophysiological disorder that may involve
multiple clinical conditions and can complicate
many cardiovascular and respiratory diseases (Galie
et al, 2019).

Pulmonary arterial hypertension (PAH) is

traditionally defined as an increase in mean
pulmonary arterial pressure (PAPm) ≥25 mmHg
at rest as assessed by right heart catheterization
(RHC) (Galie et al, 2019)
Recently it has been proposed to include
pulmonary vascular resistance (PVR) ≥3 
Wood Units (WU) into the definition of pre-
capillary PH associated with mPAP >20 
mmHg, irrespective of aetiology (Galie et al,
2019)
normal PAPm at rest is 14+3 mmHg with an
upper limit of normal of approximately 20
mmHg (97.5th percentile) (Simmonaeu et al,
2019)
PH on exercise is not well defined and should
not be used for diagnosis

In many cases PH is an incurable, chronic and

progressive disease

therapy is focussed on symptomatic relief and

delaying progression
lung transplantation is a potential option for
refractory PH

CLASSIFICATION AND CAUSES

PH is classified by the World Symposia on
Pulmonary Hypertension (WSPH) into 5 groups,
with distinct clinical, haemodynamic, pathological,
and therapeutic characteristics (Simmonaeu et al,
2019).

1. Pulmonary arterial hypertension

1.1 Idiopathic
1.2 Heritable
1.2.1 BMPR2 mutation
1.2.2 Other mutations
1.3 Drugs and toxins induced
1.4 Associated with:
1.4.1 Connective tissue disease
1.4.2 HIV
1.4.3 Portal hypertension
1.4.4 Congenital heart disease (subgroups:
Eisenmenger syndrome, left-to-right shunts,
coincidental or small defects and post-
operative/closed defects)
1.4.5 Schistosomiasis
1.5 PAH long-term responders to calcium
channel blockers
1.6 PAH with overt features of venous/capillaries
involvement (pulmonary veno-occlusive
disease/pulmonary capillary haemangiomatosis
(PVOD/PCH))
1.7 Persistent PH of the newborn syndrome

2. Pulmonary hypertension due to left heart disease

2.1 Left ventricular systolic dysfunction

2.2 Left ventricular diastolic dysfunction
2.3 Valvular disease obstruction and congenital
cardiomyopathies
2.4 Congenital/ acquired left heart inflow/
outflow tract obstruction and congenital
cardiomyopathies
2.5 Congenital /acquired pulmonary veins
stenosis

Pulmonary hypertension due to lung diseases

and/or hypoxia

3.1 Chronic obstructive pulmonary disease

3.2 Interstitial lung disease
3.3 Other pulmonary diseases with mixed
restrictive and obstructive pattern
3.4 Sleep-disordered breathing
3.5 Alveolar hypoventilation disorders
3.6 Chronic exposure to high altitude
3.7 Developmental lung diseases (Web Table III)

4. Chronic thromboembolic pulmonary

hypertension and other pulmonary artery
obstructions

4.1 Chronic thromboembolic pulmonary

hypertension
4.2 Other pulmonary artery obstructions
4.2.1 Angiosarcoma
4.2.2 Other intravascular tumors
4.2.3 Arteritis
4.2.4 Congenital pulmonary arteries stenoses
4.2.5 Parasites (hydatidosis)

5. Pulmonary hypertension with unclear and/or

multifactorial mechanisms

5.1 Haematological disorders: chronic

haemolytic anaemia, myeloproliferative disorders
5.2 Systemic and disorders: sarcoidosis,
pulmonary histiocytosis, neurofibromatosis,
glycogen storage disease, Gaucher disease
5.3 Others: fibrosing mediastinitis, chronic renal
failure (with/without dialysis),
5.4 Complex congenital heart disease

Simonneau et al (2019) identify the following drugs

and toxins associated with PAH (group 1.3):

Definite Possible

Aminorex Cocaine

Fenfluramine Phenylpropanolamine

Dexfenfluramine l-tryptophan

Benfluorex St John’s wort

Methamphetamines Amphetamines

Dasatinib Interferon-α and -β

Toxic rapeseed oil Alkylating agents

Bosutinib

Direct-acting antiviral
agents against
hepatitis C virus

Leflunomide

Indirubin (Chinese
herb Qing-Dai)

PATHOPHYSIOLOGY
Cardiac causes

LA or LV disease -> ↑ LA pressure -> ↑

pulmonary venous pressure -> ↑ PAP -> ↑PVR
L to right shunt will also cause high PVP

Respiratory causes

hypoxic vasoconstriction increases pulmonary

hypertension

Which leads to:

vasoconstriction
altered vascular endothelium and smooth
muscle function
cellular remodelling
increased vascular contractility
lack of relaxation in response to various
endogenous vasodilators
fibrosis of vascular tissue

DIAGNOSIS
Right heart catheterization is the gold standard
investigation for diagnosis. Haemodynamic
definitions of PH, from Simmonaeu et al, (2019),
are:

Clinical
Definitions Characteristics
groups

mPAP >20 
mmHg
Pre-capillary 1, 3, 4
PAWP ≤15 
PH and 5
mmHg
PVR ≥3 WU

mPAP >20 
Isolated
mmHg
post-
PAWP >15  2 and 5
capillary PH
mmHg
(IpcPH)
PVR <3 WU

Combined mPAP >20 

pre- and mmHg
post- PAWP >15  2 and 5
capillary PH mmHg
(CpcPH) PVR ≥3 WU

Severity

Mild = 20-40mmHg
Moderate = 41-55mmHg
Severe = > 55mmHg

Functional assessment

I – no limitation on physical activity (no SOB,

fatigue, chest pain or syncope)
II – minimal limitation of physical activity
(comfortable @ rest, but develop symptoms on
normal physical activity)
III – marked limitation of physical activity
(comfortable @ rest but symptoms on less than
normal activity)
IV – unable to perform any physical activity, RHF,
symptoms @ rest

ASSESSMENT
History

Non-specific
progressive dyspnea (initially exertional)
fatigue
weakness
chest pain (like angina)
syncope or pre-syncope
cough
Symptoms of underlying causes (e.g. collagen
disease, valve pathology, VTE, OSA, alcohol
consumption, chronic respiratory disease)
Progressive right heart failure occurs later or in
accelerated disease
Rarely
haemoptysis
Ortner’s syndrome/hoarseness (unilateral
vocal chord paralysis)
arrhythmias

Examination

prominent ‘a’ wave

augmented P2 heart sound (palpable in severe
cases)
right heart failure – increased JVP and jugular
distention (large V waves), hepatojugular reflux,
parasternal heave (RV lift), tricuspid or
pulmonary regurgitant murmur, S3 gallop,
hepatomegaly, ascites, splenomegaly, peripheral
oedema
other signs of CHF
hypoxaemia

INVESTIGATIONS
Bedside

ECG
A normal ECG does not exclude PH
Findings may include: RVH, RAD, p-
pulmonale, tall R waves in V1, right ventricular
strain
ABG (hypoxia, acidosis, lactate)

Laboratory

Cardiac biomarkers (N-terminal pro-brain

natriuretic peptide/brain natriuretic peptide,
troponin)
Electrolytes and renal function (estimated
glomerular filtration rate, urea, uric acid)
Liver function (aminotransferases, bilirubin)
Inflammation/infection (C-reactive protein,
procalcitonin)
Tissue damage or hypoxia (blood gases, lactate)
Screening for connective tissue disease (CTD),
hepatitis and HIV

Imaging

Echocardiography
estimation of PAP (less accurate than right
heart catheterisation)
Right and left ventricle function, valve
function, pericardial effusion
Rule out other conditions mimicking right
ventricular failure, such as pericardial
tamponade
V/Q scan or CTPA: suspected pulomnary
embolism
high resolution CT: parenchymal disease
suspected
CXR – RVH on lateral (loss of retrosternal
space), prominent pulmonary vasculature

Special tests

iNO provocation test: if lowers PA pressure ->

Ca2+ antagonists may be helpful
pulmonary function tests and DLCO: mild
restrictive disease is common; DLCO <60% in
pulmonary venous disease
Cardiopulmonary exercise testing (CPET)
(severity of exercise limitation and prognosis)
Right heart catheterisation (considered
mandatory for diagnosis of PH)

MANAGEMENT
Resuscitation

CPR is often not appropriate in patients with

severe PH, endeavour to address goals of care
early
Address life threats by attempting to:
optimize PAP
optimise RV preload
decrease RV afterload
avoid RV ischaemia and failure

Specific therapy

treat underlying cause

e.g. pulmonary thromboendarterectomy for
chronic thromboembolic pulmonary
hypertension (CTEPH)
treatments for PH:
prostanoids (e.g. epoprostenol/ prostacyclin)
phosphodiesterase type 5 inhibitors (e.g.
sildenafil)
endothelin receptor antagonists (e.g.
bosentan)
refer/ consider if appropriate candidate for lung
transplantation

Management of PH with right heart failure

avoid intubation and positive pressure ventilation

(including NIV) if possible
optimise fluid status
usually requires fluid removal to prevent RV
distention compromises LV function
diuretics (e.g. frusemide)
Renal replacement therapy
decrease RV afterload, options include:
inhaled nitric oxide (iNO)
e.g. via high flow nasal prongs, NIV, or if
intubated
20-40ppm
doesn’t tend to cause systemic
hypotension as inactivated when bound to
Hb
prostacyclin
inhaled: 50mcg in saline nebulised every
hour OR 50ng/kg/min nebulised into
inspiratory limb
intravenous: 4-10ng/kg/min
other PH medications (e.g. oral
phosphodiesterase type 5 inhibitors and
endothelin receptor antagonists)
optimise cardiac output using inotropes, eg:
milrinone
dobutamine
optimise blood pressure with vasopressors:
noradrenaline if low dose (may exacerbate
pulmonary hypertension at higher doses)
vasopressin (appears to spare the pulmonary
circulation better than noradrenaline)
if realistic options, consider VA ECMO (or
temporary RVAD) – ideally in an awake, non-
intubated, spontaneously breathing patient – as
bridge to:
lung transplantation
recovery

Supportive care and monitoring

Routine ICU level monitoring (T, ECG, invasive

BP, SpO2, RR, CVP, ETCO2 if intubated)
Complex cases may be managed with
pulmonary artery catheterisation
Where possible avoid factors that exacerbate
pulmonary hypertension and right heart failure
including:
hypoxia (e.g. SpO2 <90%)
acidaemia (including hypercapnia)
raised intrathoracic pressure (e.g. high PEEP)
hypothermia
dysrhythmias
infection (consider gut translocation in right
heart failure)
VTE
pain
anaemia
Consider transition to comfort measures if not
responsive to standard therapies and not a
candidate for lung transplantation (and ECMO)
Multi-disciplinary team approach

References
LITFL

CCC — Pulmonary Hypertension

Echocardiography
Paul Young’s ICU Mind Maps — Pulmonary
Hypertension (pdf)

Journal articles

Bassily-Marcus AM, Yuan C, Oropello J, Manasia

A, Kohli-Seth R, Benjamin E. Pulmonary
hypertension in pregnancy: critical care
management. Pulmonary medicine.
2012:709407. 2012. [pubmed] [free full text]
Galiè N, McLaughlin VV, Rubin LJ, et al. An
overview of the 6th World Symposium on
Pulmonary Hypertension. Eur Respir
J 2019;53:1802148. 10.1183/13993003.02148-
2018 [PMC free article] [PubMed]
Gille J, Seyfarth HJ, Gerlach S, Malcharek M,
Czeslick E, Sablotzki A. Perioperative
anesthesiological management of patients with
pulmonary hypertension. Anesthesiology
research and practice. 2012:356982. 2012.
[pubmed] [free full text]
Hoeper MM, Benza RL, Corris P, et al. . Intensive
care, right ventricular support and lung
transplantation in patients with pulmonary
hypertension. Eur Respir J 2019; 53:
1801906. [PMC free article] [PubMed]
Hill NS, Roberts KR, Preston IR. Postoperative
pulmonary hypertension: etiology and treatment
of a dangerous complication. Respiratory care.
54(7):958-68. 2009. [pubmed] [free full text]
McCann C, Gopalan D, Sheares K, Screaton N.
Imaging in pulmonary hypertension, part 1:
clinical perspectives, classification, imaging
techniques and imaging algorithm. Postgraduate
medical journal. 88(1039):271-9. 2012.
[pubmed] [free full text]
McLaughlin VV, Archer SL, Badesch DB, Barst
RJ, Farber HW, Lindner JR, et al. ACCF/AHA
2009 expert consensus document on pulmonary
hypertension: A report of the American College
of Cardiology Foundation Task Force on Expert
Consensus Documents and the American Heart
Association: Developed in collaboration with the
American College of Chest Physicians, American
Thoracic Society, Inc., and the Pulmonary
Hypertension
Association. Circulation. 2009;119:2250–
94. [PubMed]
Price LC, Wort SJ, Finney SJ, Marino PS, Brett
SJ. Pulmonary vascular and right ventricular
dysfunction in adult critical care: current and
emerging options for management: a systematic
literature review. Critical care (London, England).
14(5):R169. 2010. [pubmed] [free full text]
Price LC, McAuley DF, Marino PS, Finney SJ,
Griffiths MJ, Wort SJ. Pathophysiology of
pulmonary hypertension in acute lung injury.
American journal of physiology. Lung cellular
and molecular physiology. 302(9):L803-15.
2012. [pubmed] [free full text]
Simonneau G, Montani D, Celermajer DS, et
al. Haemodynamic definitions and updated
clinical classification of pulmonary
hypertension. Eur Respir J 2019;53:1801913.
10.1183/13993003.01913-2018 [PMC free
article] [PubMed]
Vonk Noordegraaf A, Chin KM, Haddad F, et al.
. Pathophysiology of the right ventricle and of
the pulmonary circulation in pulmonary
hypertension: an update. Eur Respir J 2019; 53:
1801900. [PMC free article] [PubMed]

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Chris Nickson

Chris is an Intensivist and ECMO specialist at

the Alfred ICU in Melbourne. He is also a Clinical
Adjunct Associate Professor at Monash
University. He is a co-founder of the Australia
and New Zealand Clinician Educator
Network (ANZCEN) and is the Lead for
the ANZCEN Clinician Educator
Incubator programme. He is on the Board of
Directors for the Intensive Care Foundation and
is a First Part Examiner for the College of
Intensive Care Medicine. He is an internationally
recognised Clinician Educator with a passion for
helping clinicians learn and for improving the
clinical performance of individuals and
collectives.

After finishing his medical degree at the

University of Auckland, he continued post-
graduate training in New Zealand as well as
Australia’s Northern Territory, Perth and
Melbourne. He has completed fellowship training
in both intensive care medicine and emergency
medicine, as well as post-graduate training in
biochemistry, clinical toxicology, clinical
epidemiology, and health professional education.

He is actively involved in in using translational

simulation to improve patient care and the
design of processes and systems at Alfred
Health. He coordinates the Alfred ICU’s
education and simulation programmes and runs
Goodbye
the unit’s education website,chargebacks,
INTENSIVE. He
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created the ‘Critically Invoices
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teaches on numerous courses around the world.
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