Download Anesthesia for patients with pulmonary hypertension

Anesthesia for patients with pulmonary hypertension
Chad D. Pritts and Ronald G. Pearl
Stanford University, Stanford, California, USA
Correspondence to Ronald G. Pearl, MD, PhD,
Professor and Chair of Anesthesia, Department of
Anesthesia, H3589, 300 Pasteur Drive, Stanford,
CA 94305-5640, USA
Tel: +1 650 723 5024; fax: +1 650 725 0009;
e-mail: [email protected]
Current Opinion in Anaesthesiology 2010,
23:411–416
Purpose of review
Patients with pulmonary hypertension who undergo anesthesia and surgery have high
morbidity and mortality. Recent advances in our understanding of pulmonary
hypertension and its therapy provide an opportunity to improve outcomes.
Recent findings
Pulmonary hypertension can be classified into several subtypes, each with its own
causes, pathophysiology, and therapy. Echocardiography remains a critical aspect of
the evaluation of patients with pulmonary hypertension, but estimation of right ventricular
systolic pressure is often inaccurate. Inhaled vasodilators can produce selective and
potent pulmonary vasodilation.
Summary
The cause of pulmonary hypertension should be defined in perioperative patients with
pulmonary hypertension, and therapy should be optimized prior to anesthesia.
Pulmonary artery catheterization may be required to confirm the presence of pulmonary
hypertension and its severity. The focus of anesthetic management is to maintain
right ventricular cardiac output and avoid systemic hypotension. Inhaled vasodilators
such as nitric oxide and prostacyclin can be life-saving when perioperative right
heart failure occurs due to exacerbation of pulmonary hypertension.
Keywords
anesthesia, pulmonary hypertension, right heart failure, vasodilators
Curr Opin Anaesthesiol 23:411–416
ß 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
0952-7907
Introduction
In 1973, when the World Health Organization (WHO)
organized the first international conference on pulmonary
hypertension, there were no effective therapies for pulmonary hypertension, and patients with primary pulmonary hypertension [now termed idiopathic pulmonary
arterial hypertension (PAH)] had a median survival of
less than 3 years. Today, there are multiple diseasemodifying therapies, and median survival has more than
doubled. As a result, more patients with pulmonary
hypertension undergo anesthesia and surgery. Successful
management of the perioperative patient with pulmonary
hypertension requires multiple steps: recognizing the
disorder, diagnosing the cause, assessing the severity of
the disease, assessing the risks and benefits of anesthesia
and surgery, developing an anesthetic plan, and managing
the perioperative complications of systemic hypotension
and right heart failure.
Definition and classification of pulmonary
hypertension
An approach to the patient with pulmonary hypertension
begins with understanding the different causes. In 2008,
the Fourth World Symposium on Pulmonary Hyperten0952-7907 ß 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
sion, held in Dana Point, California, extensively reviewed
all aspects of pulmonary hypertension, including classification, diagnosis and evaluation, and therapy [1]. In
contrast to prior symposia and guidelines which focused
mainly on PAH (described below), the recent symposium
also extensively covered pulmonary hypertension due to
left heart disease, lung disease, and pulmonary thromboembolic disease, causes which are more common in
patients requiring surgery [2]. In addition to guidelines
from this symposium [3], guidelines for the diagnosis
and treatment of pulmonary hypertension have been
recently published by several European societies [4]
and by a consortium of American societies [5].
The Fourth World Symposium defined pulmonary hypertension as a mean pulmonary artery pressure (mPAP)
greater than 25 mmHg at rest, based on a review demonstrating that the normal mPAP is 14.0 3.3 mmHg [6].
Although the previously accepted definition of pulmonary hypertension also included mPAP during exercise
above 30 mmHg, this definition was discontinued since
these values can occur in normal patients [6].
The symposium developed an updated clinical classification of pulmonary hypertension in five groups [7]
(Table 1). In groups 1, 3, 4, and 5, the pulmonary
DOI:10.1097/ACO.0b013e32833953fb
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412 Anaesthesia and medical disease
Table 1 Clinical classification of pulmonary hypertension as
developed by the Fourth World Symposium on Pulmonary
Hypertension
1. Pulmonary arterial hypertension (PAH)
1.1 Idiopathic (IPAH)
1.2 Heritable
1.2.1 BMPR2
1.2.2 ALK1, endoglin (with or without hereditary hemorrhagic
telangectasia)
1.2.3 Unknown
1.3 Drug and toxin-induced
1.4 Associated with:
1.4.1 Connective tissue diseases
1.4.2 HIV infection
1.4.3 Portal hypertension
1.4.4 Congenital heart disease
1.4.5 Schistosomiasis
1.4.6 Chronic hemolytic anemia
1.5 Persistent pulmonary hypertension of the newborn
1’. Pulmonary veno-occlusive disease (PVOD) and/or pulmonary
capillary hemangiomatosis
2. Pulmonary hypertension owing to left heart disease
2.1 Systolic dysfunction
2.2 Diastolic dysfunction
2.3 Valvular disease
3. Pulmonary hypertension owing 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 abnormalities
4. Chronic thromboembolic pulmonary hypertension (CTEPH)
5. Pulmonary hypertension with unclear multifactorial mechanisms
5.1 Hematologic disorders: myeloproliferative disorders,
splenectomy
5.2 Systemic disorders: sarcoidosis, pulmonary Langerhans cell
histiocytosis
5.3 Metabolic disorders: glycogen storage disease, Gaucher
disease, thyroid disorders
5.4 Others: tumoral obstruction, fibrosing mediastinitis, chronic
renal failure on dialysis
Reproduced with permission from [7].
hypertension is precapillary, with a pulmonary artery
wedge pressure 15 mmHg or less. In group 2 (left heart
disease), patients have postcapillary pulmonary hypertension, but the pulmonary hypertension may be either
passive or reactive based upon whether the transpulmonary gradient (mPAP minus left atrial pressure) is
below or above 12 mmHg. The five clinical classes of
pulmonary hypertension have differing causes and
clinical courses.
Pulmonary arterial hypertension
PAH is a clinical condition characterized by the presence
of precapillary pulmonary hypertension in the absence of
other causes such as pulmonary hypertension due to lung
disease, chronic thromboembolic disease, or other rare
diseases. PAH includes different forms that share a
similar clinical picture and virtually identical pathological
changes of the lung microcirculation. Idiopathic pulmonary arterial hypertension (IPAH) was once considered a
rare disorder, but recent epidemiologic data suggest a
prevalence of approximately 15 per million. When PAH
occurs in a familial context, 50–90% of these individuals
have mutations in the BMPR2 gene, a member of the
TGF-beta superfamily [8,9]. Heritable PAH is an autosomal dominant disease with incomplete penetrance and
genetic anticipation. BMPR2 mutations and mutations in
related signaling receptors such as activin receptor like
kinase type 1 and endoglin have also been discovered in
up to 40% of PAH patients without a family history
of PAH.
PAH also occurs in association with multiple other disorders, including congenital heart disease and connective
tissue diseases such as systemic sclerosis (formerly known
as CREST). The incidence of PAH in patients with HIV
is approximately 0.5%, which is 6–12 times that of the
general population, and has not decreased despite effective antiretroviral therapy [10]. Patients with portal
hypertension have a 2–6% incidence of pulmonary hypertension, frequently contraindicating liver transplantation [11]. PAH has been linked to exposure to drugs and
toxins, including appetite suppressants such as fenfluramine and dexfenfluramine, rapeseed oil, and amphetamines. Hemoglobinopathies, such as sickle cell disease,
have been associated with PAH, with an incidence of 10–
30% in patients with sickle cell disease.
Prognosis in PAH is influenced by the underlying cause.
The progression with the scleroderma spectrum of diseases appears to be worse than for IPAH. Patients with
HIV-associated PAH have similar survival to those with
IPAH. Patients with PAH due to congenital heart disease
have a markedly better prognosis than those with IPAH
[12]. Predictors for poor prognosis in PAH include poor
functional status, poor exercise capacity as measured by
the 6 min walk test, elevated right atrial pressure, significant right ventricular (RV) dysfunction, evidence of RV
failure, low cardiac index, elevated brain natriuretic peptide (BNP), C-reactive protein, and an underlying diagnosis of scleroderma [13].
Pulmonary hypertension due to left heart disease
This classification group now includes three distinct
causes: left heart systolic dysfunction, left heart diastolic
dysfunction, and left heart valvular disease [2,7]. In all
three settings, backward transmission of increased left
atrial pressure results in increased pulmonary artery pressure. Initially, the transpulmonary gradient (mPAP minus
pulmonary capillary wedge pressure) is low, and the
increase in PAP is passive. In some patients, the increase
in PAP is out of proportion to the increased left atrial
pressure and the transpulmonary gradient is increased,
indicating remodeling of the pulmonary circulation or an
abnormal vasoconstrictor response. In patients with pulmonary hypertension associated with left heart disease,
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Anesthesia for patients with pulmonary hypertension Pritts and Pearl 413
therapy is primarily directed towards the underlying
heart disease.
Pulmonary hypertension due to lung diseases and/or
hypoxia
The main cause of pulmonary hypertension in this setting
is alveolar hypoxia from lung disease, impaired control of
breathing, or high altitude [14]. In most patients with
parenchymal lung disease, pulmonary hypertension is
modest with mPAP of 25–35 mmHg. However, in some
patients the elevations can be more substantial. A retrospective study of 998 patients with chronic obstructive
pulmonary disease (COPD) who underwent right heart
catheterization found that only 1% had severe pulmonary
hypertension with mPAP greater than 40 mmHg [14].
Chronic thromboembolic pulmonary hypertension
Chronic thromboembolic pulmonary hypertension
(CTEPH) is a frequent cause of pulmonary hypertension
[2]. CTEPH occurs in up to 4% of patients after an
acute pulmonary embolism, but half of the patients with
CTEPH have no prior history of pulmonary embolism.
Since patients with CTEPH who have involvement of
the proximal pulmonary arterial tree may be candidates
for surgical thromboembolectomy, it is recommended
that patients with CTEPH be referred to a center with
expertise in dealing with this disease [15,16].
Diagnosis and evaluation of patients with
pulmonary hypertension
When pulmonary hypertension is suspected based on
history and physical examination, chest radiograph, or
ECG, the initial diagnostic test is normally an echocardiogram [3,4,5,17]. Evaluation for other potential
causes, such as thromboembolic disease by ventilation–
perfusion scan, is appropriate in all patients suspected of
having PAH. The diagnosis of PAH requires confirmation
with right heart catheterization, including measurement
of right atrial pressure, mPAP, and pulmonary capillary
wedge pressure. Diagnosis of PAH requires that the
pulmonary vascular resistance (PVR) be greater than 3
Wood units (240 dynes s/cm5). High-resolution CT scan
may be useful in diagnosing interstitial lung disease or in
demonstrating pulmonary edema in patients with pulmonary veno-occlusive disease [14]. Left heart catheterization is important in patients who may have pulmonary hypertension due to left heart disease, since many
such patients will have elevated left ventricular enddiastolic pressure (LVEDP) without elevated wedge
pressure [18]. Differentiating pulmonary hypertension
due to left heart disease from PAH is critical since
standard treatment for PAH with prostanoids or endothelin antagonists either increases mortality or has no benefit
in patients with left heart disease. Sleep studies should be
performed in patients with pulmonary hypertension
when there is a suspicion of obstructive sleep apnea
[19]. Although Doppler echocardiography reliably estimates pulmonary artery pressure in other settings,
multiple studies indicate significant errors, both underestimation and overestimation, in patients with pulmonary hypertension [19,20]. However, other aspects of
the echocardiography examination, such as RV function
assessed by measurement of TAPSE or the Tei index,
may influence diagnostic and therapeutic decisions [21].
Cardiac MRI and newer CT techniques are emerging as
effective imaging modalities in patients with pulmonary
hypertension [22,23]. Lung biopsy is rarely indicated in
patients with pulmonary hypertension.
In patients with newly diagnosed PAH, acute vasodilator
testing has prognostic value and should be performed in
all patients who are candidates for long-term calcium
channel blocker treatment [3,5,17,24]. Inhaled
nitric oxide is the preferred agent for acute vasodilator
testing, but adenosine and prostacylin can also be used.
A meaningful acute vasodilator response requires a
decrease in mPAP by at least 10 mmHg to a value below
40 mmHg with no decrease in cardiac output. Vasodilator
testing should be performed at experienced centers.
Pathophysiology
In PAH, pulmonary hypertension is due to a combination
of pulmonary arteriolar vasoconstriction, vascular proliferation, and in-situ thrombosis. The increased RV
afterload eventually leads to RV hypertrophy, chamber
dilation, and RV dysfunction [25,26,27]. Multiple
mediators have been implicated in the development of
PAH [28,29]. Although endothelial cell injury or dysfunction is part of the initiating process, the specific
events remain a subject of intense investigation.
Treatment of pulmonary hypertension
Management of the patient with pulmonary hypertension
begins with treatment of the underlying cause and symptomatic therapy, including diuretics for volume overload
and oxygen to maintain arterial saturation above 90%.
Coumadin is recommended in all patients with idiopathic
PAH based on one prospective and two retrospective
observational, uncontrolled trials. Calcium channel blockers are indicated only for patients with PAH who demonstrate a positive response to acute vasodilator testing [24].
Patients on calcium channel blocker therapy require frequent assessment for deterioration. Percutaneous pulmonary valve implantation may be an option for patients with
severe pulmonary regurgitation and pulmonary hypertension associated with congenital heart disease [30].
In patients with PAH, the goals of drug therapy are to
improve symptoms, quality of life, and survival. A recent
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414 Anaesthesia and medical disease
meta-analysis demonstrated a 43% reduction in mortality
with randomized controlled trials of the three diseasemodifying therapies (prostanoids, endothelin-receptor
blockers, and PDE-5 inhibitors) [31]. Although
improved hemodynamics and survival are the major
goals, most current studies focus on exercise capacity
as measured by the 6 min walk test.
Continuous intravenous epoprostenol (prostacyclin, Flolan) improves exercise capacity, hemodynamics, and
survival. Owing to its demonstrated efficacy, it is frequently the choice in the most severely ill patients.
However, because of its ultra-short half-life, need for
continuous central venous infusion, cost, and multiple
side effects, other prostanoid therapies may be preferred.
Treprostinil has a longer half-life and can be delivered
either by continuous intravenous or by subcutaneous
infusion. Inhaled iloprost, which requires administration
by an adaptive aerosolized device six times daily, may be
effective without the systemic side effects of parenteral
prostanoids [32].
Endothelin receptor antagonists are oral therapies that
improve hemodynamics and exercise capacity in PAH
[2,5]. The incidence of liver function abnormalities
may depend upon the specific endothelin receptor
antagonist. These agents may be useful in other forms
of pulmonary hypertension [33]. PDE-5 inhibitors also
improve exercise capacity and hemodynamics in PAH
[34,35,36]. PDE-5 inhibitors may be particularly useful
in the perioperative setting and for assessment of suitability for surgery [37].
Perioperative risk assessment
Patients with pulmonary hypertension have markedly
increased morbidity and mortality with anesthesia and
surgery [38]. In a recent series of patients with mild-tomoderate pulmonary hypertension, perioperative complications related to pulmonary hypertension occurred in
29% of the patients and four of the 28 patients died [39].
Emergency procedures, major surgery, and long operations were associated with increased risk. When assessing the perioperative risk, the assessment should take
into account the type of surgery, the patient’s functional
status, the severity of the pulmonary hypertension, the
function of the right ventricle and any comorbidities.
Significant pulmonary hypertension is a major contraindication to liver transplantation [37]. Thoracic surgery
is associated with changes in intrathoracic pressures, lung
volumes, and oxygenation which may cause acute
increases in PVR and decreased RV function [40,41].
Laparoscopic surgery requires pneumoperitoneum which
may be poorly tolerated because it can decrease preload
and increase afterload. Procedures associated with rapid
blood loss may be poorly tolerated. This is especially true
in patients with PAH and RV systolic and diastolic
dysfunction because they require adequate preload.
For parturients with PAH, mortality has decreased from
38% in the past to 25% with current therapies, a value
which remains prohibitively high [42]. Understanding
the interactions between pregnancy and pathophysiology
in pulmonary hypertension and the use of new therapies
may be effective in decreasing morbidity and mortality in
parturients [43,44], and in adult patients [38,40,45,46]
and pediatric patients [47] undergoing surgery. In
patients who pose an unacceptably high risk for surgery,
consideration should be given to lung or heart–lung
transplantation or chronic treatment to decrease pulmonary hypertension to acceptable levels before surgery.
Prior to anesthesia and surgery, patients with pulmonary
hypertension should have an electrocardiogram, chest
radiograph, arterial blood gas, and echocardiogram. Evidence of significant RV dysfunction should prompt reevaluation of the need for surgery. All attempts to reduce
pulmonary hypertension prior to surgery should be performed, such as the administration of oxygen, bronchodilators, antibiotics, and steroids to the patient with
obstructive lung disease, and vasodilators and inotropes
to the patient with cardiac disease. Patients receiving
chronic therapy for pulmonary hypertension should continue on such therapy throughout the perioperative
period. Patients on chronic prostacyclin (epoprostenol)
or treprostinil infusions should have the infusion continued throughout the perioperative period, and management of hypotension should be with vasopressor therapy
rather than with downward titration of the infusion.
Patients undergoing intermediate to high-risk procedures
may benefit from intraoperative pulmonary artery
catheter monitoring or transesophageal echocardiography [41]. Patients on chronic inhaled iloprost should
receive treatment prior to surgery. If they are unable
to continue inhaled iloprost after surgery, consideration
should be given to inhaled nitric oxide, nebulized iloprost, or intravenous or nebulized prostacyclin.
Anesthetic management
Anesthetic management for patients with pulmonary hypertension has been extensively reviewed [40,45,
46,47,48]. In general, the way a specific anesthetic technique is managed is as important as the choice of the
technique. Etomidate is an ideal agent for induction of
general anesthesia, and a balanced maintenance technique
is generally tolerated in patients with pulmonary hypertension. Similar to aortic stenosis, the goal is to maintain
adequate preload, systemic vascular resistance (SVR), and
contractility in order to allow the right ventricle to maintain
cardiac output; in addition, it is essential to prevent
increases in PVR from hypoxia, hypercarbia, acidosis,
agitation, pain, and hypothermia. Hypotension should
be aggressively treated with systemic vasoconstrictors such
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Anesthesia for patients with pulmonary hypertension Pritts and Pearl 415
as phenylephrine or vasopressin in order to avoid
decreased RV coronary perfusion and loss of the contribution of the interventricular septum to RV ejection
(paradoxical septal motion). Since hypotension can produce a rapid downward spiral, continuous blood pressure
monitoring with an arterial catheter should be considered
in all patients with significant pulmonary hypertension.
In patients with pulmonary hypertension, the most
dangerous perioperative complication is systemic hypotension due to RV failure from exacerbation of pulmonary
hypertension [49]. Although combined inovasodilators
such as dobutamine and milrinone can be effective in
increasing cardiac output in patients with pulmonary
hypertension, owing to their systemic vasodilating effects
they will not improve and may even exacerbate systemic
hypotension. Systemic hypotension due to RV failure
from pulmonary hypertension should be treated with
inhaled vasodilators such as inhaled nitric oxide or
inhaled iloprost [50,51,52,53]. PDE-5 inhibitors may
be useful preoperatively in preventing exacerbation of
pulmonary hypertension or postoperatively in allowing
weaning from inhaled pulmonary vasodilators [54].
Barst RJ, Gibbs SR, Ghofrani HA, et al. Updated evidence-based treatment
algorithm in pulmonary arterial hypertension. J Am Coll Cardiol 2009;
54:S78–S84.
The newest evidence-based treatment recommendations for the management of
PAH.
3
Galiè N, Hoeper MM, Humbert M, et al. Guidelines for the diagnosis and
treatment of pulmonary hypertension: the Task Force for the Diagnosis and
Treatment of Pulmonary Hypertension of the European Society of Cardiology
(ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). Eur Heart J 2009;
30:2493–2537.
Superb evidence-based guidelines on pulmonary hypertension which include
clinical classification, diagnosis, evaluation, and therapy.
4
McLaughlin VV, Archer SL, Badesch DB, et al. ACC/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. Circulation 2009; 119:2250–
2294.
This consensus document representing four different societies is a comprehensive
summary of pathology, pathogenesis, classification, natural history, diagnostic
assessment, and evidence-based treatment of pulmonary hypertension, including
both PAH and other forms of pulmonary hypertension.
5
Kovacs G, Berghold A, Scheidl S, Olschewski H. Pulmonary arterial pressure
during rest and exercise in healthy subjects: a systematic review. Eur Respir J
2009; 34:888–894.
The new definition of pulmonary hypertension is based on this review demonstrating that normal mPAP is 14.0 3.3 mmHg but can increase significantly above
30 mmHg during exercise.
6
7 Simonneau G, Robbins IM, Beghetti M, et al. Updated clinical classification of
pulmonary hypertension. J Am Coll Cardiol 2009; 54:43–54.
This article describes the most recent scheme (from the 2008 Fourth World
Symposium) for the clinical classification of pulmonary hypertension, including the
rationale for the changes from prior classifications.
Machado RD, Eickelberg O, Elliott CG, et al. Genetics and genomics of
pulmonary arterial hypertension. J Am Coll Cardiol 2009; 54 (1 Suppl):S32–
S42.
Genetic abnormalities, particularly mutations in the BMPR2 gene, account for a
substantial number of patients with PAH.
8
Conclusion
Major advances have occurred in our understanding of
the different causes responsible for pulmonary hypertension and the resulting pathophysiology. The development of three disease-modifying therapeutic classes
(prostanoids, endothelin antagonists, and PDE-5 inhibitors) has markedly improved quality of life and survival
for patients with pulmonary hypertension. Anesthetic
management of patients with pulmonary hypertension
is based on understanding the underlying pathophysiology and avoiding RV failure and systemic hypotension.
The currently available inhaled vasodilators can be
effective in reversing life-threatening pulmonary hypertension during the perioperative period. Future developments will result in more effective acute and chronic
therapies.
References and recommended reading
Papers of particular interest, published within the annual period of review, have
been highlighted as:
of special interest
of outstanding interest
Additional references related to this topic can also be found in the Current
World Literature section in this issue (pp. 437–438).
1 Humbert M, McLaughlin VV. The 4th World Symposium on Pulmonary
Hypertension. J Am Coll Cardiol 2009; 54:S1–S2.
An overview of this pivotal conference which will affect all aspects of the management of patients with pulmonary hypertension.
Hoeper MM, Barbera JA, Channick RN, et al. Diagnosis, assessment, and
treatment of nonpulmonary arterial hypertension, pulmonary hypertension.
J Am Coll Cardiol 2009; 54:S85–S96.
Management of the patient with pulmonary hypertension in groups 2–5 of the new
classification (‘non-PAH pulmonary hypertension’) differs significantly from that of
patients with PAH.
2
9
Geraci MW, Bull TM, Tuder RM. Genomics of pulmonary arterial hypertension: implications for therapy. Heart Fail Clin 2010; 6:101–114.
10 Sitbon O, Lascoux-Combe C, Delfraissy JF, et al. Prevalence of HIV related
PAH in the current antiretroviral therapy era. Am J Respir Crit Care Med 2008;
177:1133–1141.
Despite effective antiretroviral therapy, the prevalence of HIV remains at 0.46%
and has not decreased.
11 Ramsay M. Portopulmonary hypertension and right heart failure in patients
with cirrhosis. Curr Opin Anaesthesiol 2010 [Epub ahead of print].
12 Beghetti M, Galie N. Eisenmenger syndrome: a clinical perspective in a new
therapeutic era of pulmonary arterial hypertension. J Am Coll Cardiol 2009;
53:733–740.
13 Quarck R, Nawrot T, Meyns B, Delcroix M. C-reactive protein: a new predictor
of adverse outcome in pulmonary arterial hypertension. J Am Coll Cardiol
2009; 53:1211–1218.
14 Weitzenblum E, Chaouat A, Canuet M, Kessler R. Pulmonary hypertension in
chronic obstructive pulmonary disease and interstitial lung diseases. Semin
Respir Crit Care Med 2009; 30:458–470.
Although pulmonary hypertension due to COPD and interstitial lung disease is
usually only mild to moderate in severity, it is associated with a markedly decreased
prognosis.
15 Roscoe A, Klein A. Pulmonary endarterectomy. Curr Opin Anaesthesiol 2008;
21:16–20.
16 Keogh AM, Mayer E, Benza RL, et al. Interventional and surgical modalities of
treatment in pulmonary hypertension. J Am Coll Cardiol 2009; 54:S67–S77.
Pulmonary endarterectomy for CTEPH, atrial septostomy, bilateral sequential lung
or heart–lung transplantation, and RV assist devices can be successful interventions in patients with severe pulmonary hypertension.
17 Badesch DB, Champion HC, Sanchez MAG, et al. Diagnosis and assessment
of pulmonary arterial hypertension. J Am Coll Cardiol 2009; 54:S55–S66.
The recommendations for diagnosis and assessment of PAH from the Fourth
World Symposium.
18 Halpern SD, Taichman DB. Misclassification of pulmonary hypertension due
to reliance on pulmonary capillary wedge pressure rather than left ventricular
end-diastolic pressure. Chest 2009; 136:37–43.
In a large series of patients with pulmonary hypertension, over half the patients with
a pulmonary capillary wedge pressure 15 mmHg or less had an LVEDP greater
than 15 mmHg and would have been presumed to have PAH based on PCWP
alone rather than pulmonary hypertension due to left heart disease.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
416 Anaesthesia and medical disease
19 Minai OA, Ricaurte B, Kaw R, et al. Frequency and impact of pulmonary
hypertension in patients with obstructive sleep apnea syndrome. Am J Cardiol
2009; 104:1300–1306.
Pulmonary hypertension is common among patients with obstructive sleep apnea
and results in functional limitations and increased mortality. Estimation of RV
systolic pressure by echocardiography is frequently inaccurate.
20 Fisher MR, Forfia PR, Chamera E, et al. Accuracy of Doppler echocardio graphy in the hemodynamic assessment of pulmonary hypertension. Am J
Respir Crit Care Med 2009; 179:615–621.
Although Doppler echocardiography is frequently used for noninvasive assessment of right ventricular pressure in patients with or at risk for pulmonary
hypertension, significant overestimation or underestimation occurred in almost
half the patients.
21 Cacciapuoti F. Echocardiographic evaluation of right heart function and
pulmonary vascular bed. Int J Cardiovasc Imaging 2009; 25:689–697.
Newer echocardiographic measurements can provide better evaluation of right
ventricular function in patients with pulmonary hypertension.
22 McLure LE, Peacock AJ. Cardiac magnetic resonance imaging for the
assessment of the heart and pulmonary circulation in pulmonary hypertension.
Eur Respir J 2009; 33:1454–1466.
Cardiac MRI provides a morphological and functional assessment of the right
ventricle and the pulmonary circulation and may become the primary modality for
evaluation of patients with pulmonary hypertension.
23 Revel MP, Faivre JB, Remy-Jardin M, et al. Pulmonary hypertension: ECGgated 64-section CT angiographic evaluation of new functional parameters as
diagnostic criteria. Radiology 2009; 250:558–566.
24 Tonelli AR, Alnuaimat H, Mubarak K. Pulmonary vasodilator testing and use of
calcium channel blockers in pulmonary arterial hypertension. Respir Med
[Epub ahead of print].
A recent review of the literature regarding pulmonary vasodilator testing and use of
calcium channel blockers in PAH.
37 Ajami GH, Borzoee M, Radvar M, Amoozgar H. Comparison of the effectiveness of oral sildenafil versus oxygen administration as a test for feasibility of
operation for patients with secondary pulmonary arterial hypertension. Pediatr
Cardiol 2008; 29:552–555.
38 Hill NS, Roberts KR, Preston IR. Postoperative pulmonary hypertension:
etiology and treatment of a dangerous complication. Respir Care 2009;
54:958–968.
Postoperative pulmonary hypertension has high morbidity and mortality and
treatment requires an understanding of the pathophysiology and available treatment options.
39 Price LC, Montani D, Jaı̈s X, et al. Noncardiothoracic nonobstetric surgery in
mild-moderate pulmonary hypertension: perioperative management of 28
consecutive individual cases, Eur Respir J [Epub ahead of print].
In a series of 28 patients with mostly nonsevere pulmonary hypertension (75%
functional class 1 or 2, 25% class 3, and no patients in class 4) and a large
proportion of minor surgical procedures (43%) and regional anesthesia (50%),
perioperative complications related to pulmonary hypertension occurred in 29% of
all patients and four of the 28 patients (14%) died. Emergency procedures, major
surgery and long operations were associated with increased risk.
40 Ross AF, Ueda K. Pulmonary hypertension in thoracic surgical patients. Curr
Opin Anaesthesiol 2010; 23:25–33.
Management of patients with pulmonary hypertension undergoing thoracic surgery
requires identification of potential problem areas such as one-lung ventilation and
knowledge of new pharmacological options, particularly inhaled vasodilators.
41 Pedoto A, Amar D. Right heart function in thoracic surgery: role of echocardiography. Curr Opin Anaesthesiol 2009; 22:44–49.
42 Bédard E, Dimopoulos K, Gatzoulis MA. Has there been any progress made
on pregnancy outcomes among women with pulmonary arterial hypertension?
Eur Heart J 2009; 30:256–265.
Although maternal mortality in parturients with PAH remains prohibitively high
(25%), it has improved from the 38% mortality rate in the period from 1978 to
1996.
25 Greyson CR. Pathophysiology of right ventricular failure. Crit Care Med 2008;
36 (1 Suppl):S57–S65.
Right ventricular failure in the critical care setting commonly involves a combination
of pressure overload and decreased contractility, requiring management markedly
different from left ventricular failure.
43 Madden BP. Pulmonary hypertension and pregnancy. Int J Obstet Anesth
2009; 18:156–164.
Pulmonary hypertension results in high maternal and fetal morbidity and mortality
and may require specific targeted therapy.
26 Afifi S, Shayan S, Al-Qamari A. Pulmonary hypertension and right ventricular
function: interdependence in pathophysiology and management. Int Anesthesiol Clin 2009; 47:97–120.
44 Higton AM, Whale C, Musk M, Gabbay E. Pulmonary hypertension in
pregnancy: two cases and review of the literature. Intern Med J 2009;
39:766–770.
27 Bogaard HJ, Abe K, Noordegraaf AV, Voelkel NF. The right ventricle under
pressure cellular and molecular mechanisms of right-heart failure in pulmonary
hypertension. Chest 2009; 135:794–804.
45 Fox C, Kalarickal PL, Yarborough MJ, Jin JY. Perioperative management
including new pharmacological vistas for patients with pulmonary hypertension for noncardiac surgery. Curr Opin Anaesthesiol 2008; 21:467–
472.
28 Morrell NW, Adnot S, Archer SL, et al. Cellular and molecular basis of
pulmonary arterial hypertension. J Am Coll Cardiol 2009; 54:S20–S31.
A comprehensive review of the multiple mechanisms responsible for the functional
and structural changes in the pulmonary vasculature in PAH, with an emphasis on
endothelial dysfunction, activation of fibroblasts and smooth muscle cells, cross-talk
between cells within the vascular wall, and recruitment of circulating progenitor cells.
29 Yildiz P. Molecular mechanisms of pulmonary hypertension. Clin Chim Acta
2009; 403:9–16.
30 Lurz P, Nordmeyer J, Coats L, et al. Immediate clinical and haemodynamic
benefits of restoration of pulmonary valvar competence in patients with
pulmonary hypertension. Heart 2009; 95:646–650.
Percutaneous pulmonary valve implantation produces clinical and hemodynamic
improvement in patients with severe pulmonary regurgitation and pulmonary
hypertension associated with congenital heart disease.
31 Galie N, Manes A, Negro L, et al. A meta-analysis of randomized controlled
trials in pulmonary arterial hypertension. Eur Heart J 2009; 30:394–403.
A meta-analysis of 21 randomized controlled trials of prostanoids, endothelinreceptor antagonists, and phosphodiesterase type-5 inhibitors in PAH demonstrated a 43% reduction in mortality.
32 Gessler T, Seeger W, Schmehl T. Inhaled prostanoids in the therapy of
pulmonary hypertension. J Aerosol Med Pulm Drug Deliv 2008; 21:1–12.
Inhaled prostacyclin and prostacyclin analogs (such as iloprost) are effective in
producing selective pulmonary vasodilation and improving outcome in patients
with pulmonary hypertension.
33 Vassallo FG, Kodric M, Scarduelli C, et al. Bosentan for patients with chronic
thromboembolic pulmonary hypertension. Eur J Intern Med 2009; 20:24–29.
34 Archer SL, Michelakis ED. Phosphodiesterase type 5 inhibitors for pulmonary
arterial hypertension. N Engl J Med 2009; 361:1864–1871.
A case-based discussion of the use of sildenafil and other PDE-5 inhibitors for PAH.
46 Gordon C, Collard CD, Pan W. Intraoperative management of pulmonary
hypertension and associated right heart failure. Curr Opin Anaesthesiol 2009;
23:49–56.
Intraoperative management of patients with pulmonary hypertension requires
knowledge of pathophysiology and available treatment modalities.
47 Friesen RH, Williams GD. Anesthetic management of children with pulmonary
arterial hypertension. Paediatr Anaesth 2008; 18:208–216.
Perioperative pulmonary hypertension is a frequent problem in pediatric anesthesia
and requires an understanding of issues specific to the pediatric population.
48 Teo YW, Greenhalgh DL. Update on anaesthetic approach to pulmonary
hypertension. Eur J Anaesthesiol 2010 [Epub ahead of print].
49 Forrest P. Anaesthesia and right ventricular failure. Anaesth Intensive Care
2009; 37:370–385.
50 Wang H, Gong M, Zhou B, Dai A. Comparison of inhaled and intravenous
milrinone in patients with pulmonary hypertension undergoing mitral valve
surgery. Adv Ther 2009; 26:462–468.
Following cardiopulmonary bypass, inhaled milrinone had similar pulmonary vasodilation to intravenous milrinone, but inhaled milrinone improved shunt fraction and
did not produce hypotension and systemic vasodilation.
51 Winterhalter M, Simon A, Fischer S, et al. Comparison of inhaled iloprost and
nitric oxide in patients with pulmonary hypertension during weaning from
cardiopulmonary bypass in cardiac surgery: a prospective randomized trial.
J Cardiothorac Vasc Anesth 2008; 22:406–413.
Although both inhaled nitric oxide and inhaled iloprost were effective in decreasing
pulmonary hypertension after weaning from cardiopulmonary bypass, iloprost was
significantly more effective.
52 Ewert R, Schäper C, Halank M, et al. Inhalative iloprost: pharmacology and
clinical application. Exp Opin Pharmacother 2009; 10:2195–2207.
35 Gailie N, Brundage BH, Ghofrani HA, et al. Tadalafil therapy for pulmonary
arterial hypertension. Circulation 2009; 119:2894–2903.
53 Creagh-Brown BC, Griffiths MJ, Evans TW. Bench-to-bedside review: inhaled
nitric oxide therapy in adults. Crit Care 2009; 13:221.
36 Jing ZC, Jiang X, Wu BX, et al. Vardenafil therapy for patients with pulmonary
arterial hypertension. A one year, multicenter, open-label study. Heart 2009;
95:1531–1536.
54 Boffini M, Sansone F, Ceresa F, et al. Role of oral sildenafil in the treatment of
right ventricular dysfunction after heart transplantation. Transplant Proc 2009;
41:1353–1356.
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