Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
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 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 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, Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 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 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 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. Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.