Why there is a need to discuss pulmonary hypertension other than pulmonary arterial hypertension?

Pulmonary hypertension(PH) is a condition characterized by the elevation of the mean pulmonary artery pressure above 25 mm Hg and the pulmonary vascular resistance above 3 wood units. Pulmonary arterial hypertension(PAH) is an uncommon conditionwith severe morbidity and mortality, needing early recognition and appropriate and specific treatment. PH is frequently associated with hypoxemia, mainly chronic obstructive pulmonary disease and DPLD and/or left heart diseases(LHD), mainly heart failure with reduced or preserved ejection fraction. Although in the majority of patients with PH the cause is not PAH, a significant number of published studies are still in regard to group Ⅰ PH, leading to a logical assumption that PH due to other causes is not such an important issue. So, is there a reason to discuss PH other than PAH? Chronic lung diseases, mainly chronic obstructive lung disease and DPLD, are associated with a high incidence of PH which is linked to exercise limitations and a worse prognosis. Although pathophysiological studies suggest that specific PAH therapy may benefit such patients, the results presented from small studies in regard to the safety and effectiveness of the specific PAH therapy are discouraging. PH is a common complication of left heart disease and is related to disease severity, especially in patients with reduced ejection fraction. There are two types of PH related to LHD based on diastolic pressure difference(DPD, defined as diastolic pulmonary artery pressure- mean PAWP): Isolated post-capillary PH, defined as PAWP 15 mm Hg and DPD 7 mm Hg, and combined post-capillary PH and pre-capillary PH, defined as PAWP 15 mm Hg and DPD ≥ 7 mm Hg. The potential use of PAH therapies in patients with PH related to left heart disease is based on a logical pathobiological rationale. In patients with heart failure, endothelial dysfunction has been proposed as a cause of PH and hence as a target for treatment, supported by the presence of increased endothelin-1 activity and impaired nitric oxide-dependent vasodilation. Unfortunately, so far, there is no evidence supporting the use of specific PAH therapies in patients with PH related to left heart disease. In conclusion, the presence of PH in patients with conditions other than PAH contributes to the severity of the disease, affecting the outcome and quality of life. The disappointing results regarding the effectiveness of specific PAH therapies in patients withchronic lung diseases and LHD underline the need for seeking new underlying mechanisms and thus novel therapies targeting PH due to left heart disease and/or lung diseases.     

B-type natriuretic peptide: issues for the intensivist and pulmonologist

OBJECTIVE: B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP), although promising as biomarkers for heart failure, are affected by multiple confounders. The purpose of this article is to review the literature on the utility of BNP and NT-proBNP as biomarkers, with a focus on their role in critical illness and pulmonary diseases. DATA SOURCE: Published articles on BNP and NT-proBNP. DATA ANALYSIS: Multiple disorders in the intensive care unit cause elevated BNP and NT-proBNP levels, including cardiac diseases, shock, pulmonary hypertension, acute respiratory distress syndrome, acute pulmonary embolism, chronic obstructive pulmonary disease, renal failure, and other conditions. CONCLUSIONS: Intensivists and pulmonologists should understand that BNP and NT-proBNP levels might be raised to different degrees not only in heart failure but also in critical illness and various pulmonary diseases; in these situations, BNP and NT-proBNP may also serve as markers of severity and prognosis.     

Noninvasive ventilation in acute respiratory failure

BACKGROUND: Noninvasive ventilation has assumed an important role in the management of respiratory failure in critical care units, but it must be used selectively depending on the patient's diagnosis and clinical characteristics. DATA: We review the strong evidence supporting the use of noninvasive ventilation for acute respiratory failure to prevent intubation in patients with chronic obstructive pulmonary disease exacerbations or acute cardiogenic pulmonary edema, and in immunocompromised patients, as well as to facilitate extubation in patients with chronic obstructive pulmonary disease who require initial intubation. Weaker evidence supports consideration of noninvasive ventilation for chronic obstructive pulmonary disease patients with postoperative or postextubation respiratory failure; patients with acute respiratory failure due to asthma exacerbations, pneumonia, acute lung injury, or acute respiratory distress syndrome; during bronchoscopy; or as a means of preoxygenation before intubation in critically ill patients with severe hypoxemia. CONCLUSION: Noninvasive ventilation has assumed an important role in managing patients with acute respiratory failure. Patients should be monitored closely for signs of noninvasive ventilation failure and promptly intubated before a crisis develops. The application of noninvasive ventilation by a trained and experienced intensive care unit team, with careful patient selection, should optimize patient outcomes.     

New horizons: NT-proBNP for risk stratification of patients with shock in the intensive care unit

B-type natriuretic peptide (BNP) and amino-terminal pro-BNP (NT-proBNP) are promising cardiac biomarkers that have recently been shown to be of diagnostic value in decompensated heart failure, acute coronary syndromes and other conditions resulting in myocardial stretch and volume overload. In view of the high prevalence of cardiac disorders in the intensive care unit, the experience of elevated natriuretic peptide levels in the critically ill might be of enormous diagnostic and therapeutic value. BNP and NT-proBNP levels rise to different degrees in critical illness and may also serve as markers of severity and prognosis in diseases beyond acute or chronic heart failure. The diagnostic and prognostic use of natriuretic peptides in the intensive care setting for patients with various forms of shock could be an attractive alternative as noninvasive markers of cardiac dysfunction that could obviate the need for pulmonary artery catheterization in some patients.     

Intensive care for severe acute pneumonia using hemodynamic pulmonary circulatory unloading

Pulmonary hypertension (PH) and its direct sequel, namely progressive arterial hypoxemia, is one of the severe complications of acute severe pneumonia (ASP). The paper presents the view of the pathogenesis of PH in patients with ASP and discusses a treatment for this complication. Based on the results of their own studies, the authors propose one of the effective methods for decreasing pulmonary vascular resistance. This method is based on the vasoconstrictor concept of the pathogenesis of PH in PH and includes therapy with nitrates. The authors propose to use drugs ameliorating pulmonary arterial hypertension, particularly intravenous nitrates in a dose of 0.2-0.3 mg/kg/day, as a part of intensive care.     

先天性心脏病伴重度肺动脉高压术后早期并发症分析

目的 探讨先天性心脏病（CHD）伴重度肺动脉高压（PH）体外循环（CPB）术后早期并发症及处理。方法对本科2003年6月至2009年6月行CPB手术的45例CHD伴重度PH患者进行回顾分析,讨论术后早期主要并发症和死亡原因。结果术后早期主要并发症有严重低氧血症（13．33％）、缺氧发作（11．11％）、低心排（6．67％）。住院死亡率6．67％,死亡原因均为低心排,主要为右心室功能失代偿。多因素分析显示,低温CPB（OR=0．56;95％CI0．35-0．89）是严重低氧血症的一个危险因素。结论术后早期并发症主要由术后PH为基础的心肺功能不全所导致,对术后高危患者动态监测肺动脉压、右心功能和延长呼吸机支持,有助于防治并发症。     

Metalloproteinase-9 in circulating monocytes in pulmonary hypertension

The role of matrix metalloproteinases (MMPs) in pulmonary hypertension (PH) is complex as MMPs are involved in both the vascular and cardiac remodelling associated with PH. To gain insight into this problem, monocytes were isolated from pulmonary arterial blood in patients suffering from PH, related to chronic obstructive pulmonary disease (n = 6), chronic pulmonary thromboembolism (n = 3) or pulmonary arterial hypertension (n = 8). The severity of PH was associated with decreases in cardiac index (CI) and mixed venous blood oxygen saturation (SO(2)), and an increase in right atrial pressure (). Monocyte pro-MMP-9 content (zymography) was positively correlated with SO(2) (r = 0.73, P < 0.05) and CI (r = 0.66, P < 0.05), and negatively with (r = 0.54, P < 0.05); there was no significant correlation with pulmonary vascular resistance. In conclusion, the pro-MMP-9 content of circulating monocytes was lower in the more severe forms of PH which showed heart failure suggesting that such MMP enzymatic activity reflects heart failure following pulmonary vascular and myocardial remodelling in PH.     

Management strategies for patients with pulmonary hypertension in the intensive care unit

OBJECTIVE: Pulmonary hypertension may be encountered in the intensive care unit in patients with critical illnesses such as acute respiratory distress syndrome, left ventricular dysfunction, and pulmonary embolism, as well as after cardiothoracic surgery. Pulmonary hypertension also may be encountered in patients with preexisting pulmonary vascular, lung, liver, or cardiac diseases. The intensive care unit management of patients can prove extremely challenging, particularly when they become hemodynamically unstable. The objective of this review is to discuss the pathogenesis and physiology of pulmonary hypertension and the utility of various diagnostic tools, and to provide recommendations regarding the use of vasopressors and pulmonary vasodilators in intensive care. DATA SOURCES AND EXTRACTION: We undertook a comprehensive review of the literature regarding the management of pulmonary hypertension in the setting of critical illness. We performed a MEDLINE search of articles published from January 1970 to March 2007. Medical subject headings and keywords searched and cross-referenced with each other were: pulmonary hypertension, vasopressor agents, therapeutics, critical illness, intensive care, right ventricular failure, mitral stenosis, prostacyclin, nitric oxide, sildenafil, dopamine, dobutamine, phenylephrine, isoproterenol, and vasopressin. Both human and animal studies related to pulmonary hypertension were reviewed. CONCLUSIONS: Pulmonary hypertension presents a particular challenge in critically ill patients, because typical therapies such as volume resuscitation and mechanical ventilation may worsen hemodynamics in patients with pulmonary hypertension and right ventricular failure. Patients with decompensated pulmonary hypertension, including those with pulmonary hypertension associated with cardiothoracic surgery, require therapy for right ventricular failure. Very few human studies have addressed the use of vasopressors and pulmonary vasodilators in these patients, but the use of dobutamine, milrinone, inhaled nitric oxide, and intravenous prostacyclin have the greatest support in the literature. Treatment of pulmonary hypertension resulting from critical illness or chronic lung diseases should address the primary cause of hemodynamic deterioration, and pulmonary vasodilators usually are not necessary.     

Pulmonary vascular and right ventricular dysfunction in adult critical care: current and emerging options for management: a systematic literature review

Introduction  

Pulmonary vascular dysfunction, pulmonary hypertension (PH), and resulting right ventricular (RV) failure occur in many critical illnesses and may be associated with a worse prognosis. PH and RV failure may be difficult to manage: principles include maintenance of appropriate RV preload, augmentation of RV function, and reduction of RV afterload by lowering pulmonary vascular resistance (PVR). We therefore provide a detailed update on the management of PH and RV failure in adult critical care.     

Spurious hypoxemia

OBJECTIVE: To discuss the pathophysiology and clinical implications of spurious hypoxemia in the setting of hyperleukocytosis. DESIGN: Case report and review of the literature. SETTING: A 22-bed, adult neurosciences critical care unit at a tertiary care hospital. PATIENT: A 49-yr-old male with chronic myelogenous leukemia. INTERVENTIONS: Administration of hydroxyurea and imatinib mesylate. MEASUREMENTS AND MAIN RESULTS: The patient was admitted to the neurosciences critical care unit with an acute nontraumatic subdural hematoma that required emergent surgical evacuation. His clinical course was notable for neurologic deterioration, sepsis, hyperleukocytosis, severe hypoxemia, and prolonged mechanical ventilation. An inverse relationship was observed between arterial oxygen tension and the magnitude of hyperleukocytosis. Hypoxemia resolved after the institution of chemotherapy and normalization of white cell count. Pulse oximeter saturation was normal throughout. CONCLUSIONS: Patients with hyperleukocytosis are at risk for severe hypoxemia, which may be real or spurious. Failure to recognize spurious hypoxemia can lead to unnecessary diagnostic tests and therapeutic interventions, exposing patients to avoidable risk. A diagnostic algorithm is proposed.     

Chronic oxygen therapy.

Chronic low flow oxygen is useful therapy for patients with chronic obstructive lung disease who are crippled by hypoxemia despite optimal programs of usual respiratory care. Patients should be considered for chronic oxygen therapy who have (a) a resting Pao2 less than 55 mm Hg while breathing room air; or (b) profound tissue hypoxemia measured by mixed venous Pao2 and suggested by symptoms such as cor pulmonale and congestive heart failure; or (c) pulmonary hypertension or polycythemia even though daytime Pao2 is greater than 55 mm Hg. Arterial blood must be obtained to demonstrate hypoxemia and assess the benefits of oxygen therapy. Patients on chronic oxygen must remain under close medical supervision. There are no absolute contraindications to chronic oxygen therapy, other than refusal of the patient to quit smoking. Complications of therapy appear to be negligible. The exciting suggestion of improved prognosis in patients with chronic obstructive lung disease on oxygen therapy and the possibility of delaying the long-term sequelae of chronic respiratory failure bear careful watching in the future.     

Pulmonary hypertension

Repetitive pulmonary artery pressure(PAP) elevation during apnea is commonly reported in patients with obstructive sleep apnea syndrome(OSAS). Hypoxic pulmonary vasoconstriction(HPV) plays an important role in this PAP elevation. In addition to the HPV, augmentation of intrathoracic negative pressure which occurs concomitantly with apnea and activation of sympathetic nervous system during REM sleep, influences pulmonary blood flow, resulting in the PAP elevation. Many previous study have been declared that the daytime pulmonary hypertension(PH), which is observed in significant populations of OSAS, is related to chronic airflow limitation and/or daytime hypoxemia. Furthermore, it had been suggested that the daytime PH in OSAS can be elicited, at least in parts, by vascular remodeling together with both nocturnal and daytime hypoxemia. Such pulmonary vascular remodeling may induce greater vascular sensitivity to sympathetic stimulation and modify HPV in OSAS with daytime PH.     

呼气末正压通气治疗重度急性左心衰竭的临床研究

目的：探讨重度急性左心衰竭或急性肺水肿的机械通气治疗方法。方法：对36例重度急性左心衰竭或急性肺水肿患者行呼气末正压通气（PEEP）治疗前后的临床表现和血气结果进行分析。结果：36例重度急性左心衰竭或急性肺水肿患者经PEEP治疗后，缺氧症状明显好转，血气指标明显改善（P〈0.05）。结论：PEEP是治疗重度急性左心衰竭或急性肺水肿的有效方法。     

Severe hypertension, propranolol, and acute pulmonary edema

We describe an elderly patient with multiple risk factors for congestive heart failure (CHF) who developed severe hypertension. Treatment with 20 mg hydralazine and 0.2 mg propranolol intravenously resulted in acute pulmonary edema. We conclude that beta-blocking agents may precipitate acute heart failure in patients with compensated CHF.     

二尖瓣病变并肺动脉高压围术期低氧血症分析

目的总结二尖瓣病变并肺动脉高压患者围术期低氧血症的治疗方法。方法选择二尖瓣病变并肺动脉高压围术期发生低氧血症、低心排血量患者76例,给予呼吸机辅助呼吸、硝酸甘油0.5~1.0μg/（kg.min）持续泵入、米力农0.3~0.7μg/（kg.min）泵入。结果死亡3例,均因严重低氧血症、心衰,经治疗低氧血症等无改善,于术后7~10 d因继发多器官功能衰竭死亡;其余患者经治疗后好转出院,心功能Ⅱ、Ⅲ级。随访5月~5年,心功能Ⅰ级17例、Ⅱ级58例,术后3年死亡1例,该患者因置入生物瓣合并高血压死于脑出血。结论二尖瓣病变并肺动脉高压患者围术期易发生低氧血症,严重的低氧血症可通过扩张肺动脉降低肺动脉压并配合心功能支持药物及呼吸机治疗矫正。硝酸甘油、米力农等有效剂量泵入是降低肺动脉压改善低氧血症的有效方法。     

Pulmonary hypertension in patients with interstitial lung diseases

Pulmonary hypertension (PH) in patients with interstitial lung diseases (ILDs) is not well recognized and can occur in the absence of advanced pulmonary dysfunction or hypoxemia. To address this topic, we identified relevant studies in the English language by searching the MEDLINE database (1966 to November 2006) and by individually reviewing the references of identified articles. Connective tissue disease-related ILD, sarcoidosis, idiopathic pulmonary fibrosis, and pulmonary Langerhans cell histiocytosis are the ILDs most commonly associated with PH. Pulmonary hypertension is an underrecognized complication in patients with ILDs and can adversely affect symptoms, functional capacity, and survival. Pulmonary hypertension can arise in patients with ILDs through various mechanisms, Including pulmonary vasoconstriction and vascular remodeling, vascular destruction associated with progressive parenchymal fibrosis, vascular inflammation, perivascular fibrosis, and thrombotic angiopathy. Diagnosis of PH in these patients requires a high index of suspicion because the clinical presentation tends to be nonspecific, particularly in the presence of an underlying parenchymal lung disease. Doppler echocardiography is an essential tool in the evaluation of suspected PH and allows ready recognition of cardiac causes. Right heart catheterization is needed to confirm the presence of PH, assess its severity, and guide therapy. Management of PH in patients with ILDs is guided by identification of the underlying mechanism and the clinical context. An increasing number of available pharmacologic agents in the treatment of PH allow possible treatment of PH in some patients with ILDs. Whether specific treatment of PH in these patients favorably alters functional capacity or outcome needs to be determined.     

浅谈急性左心衰竭的护理

目的:探讨急性左心衰竭的护理措施及护理体会。方法:对我科54例急性左心衰竭患者的护理进行回顾性分析。结果:所有患者呼吸困难均有所缓解,可平卧或高枕卧位,肺部啰音减少或完全消失,心功能有不同程度的改善。结论:对急性左心衰竭患者进行及时的抢救和精心的护理可以明显减轻患者的症状,使患者转危为安。     

Novel therapies in acute and chronic heart failure

Despite past advances in the pharmacological management of heart failure, the prognosis of these patients remains poor, and for many, treatment options remain unsatisfactory. Additionally, the treatments and clinical outcomes of patients with acute decompensated heart failure have not changed substantially over the past few decades. Consequently, there is a critical need for new drugs that can improve clinical outcomes. In the setting of acute heart failure, new inotrops such as cardiac myosin activators and new vasodilators such as relaxin have been developed. For chronic heart failure with reduced ejection fraction, there are several new approaches that target multiple pathophysiological mechanism including novel blockers of the renin-angiotensin-aldosterone system (direct renin inhibitors, dual-acting inhibitors of the angiotensin II receptor and neprilysin, aldosterone synthase inhibitors), ryanodine receptor stabilizers, and SERCA activators. Heart failure with preserved ejection fraction represents a substantial therapeutic problem as no therapy has been demonstrated to improve symptoms or outcomes in this condition. Newer treatment strategies target specific structural and functional abnormalities that lead to increased myocardial stiffness. Dicarbonyl-breaking compounds reverse advanced glycation-induced cross-linking of collagen and improve the compliance of aged and/or diabetic myocardium. Modulation of titin-dependent passive tension can be achieved via phosphorylation of a unique sequence on the extensible region of the protein. This review describes the pathophysiological basis, mechanism of action, and available clinical efficacy data of drugs that are currently under development. Finally, new therapies for the treatment of heart failure complications, such as pulmonary hypertension and anemia, are discussed.     

Acute respiratory distress syndrome: diagnosis and management

Acute respiratory distress syndrome manifests as rapidly progressive dyspnea, tachypnea, and hypoxemia. Diagnostic criteria include acute onset, profound hypoxemia, bilateral pulmonary infiltrates, and the absence of left atrial hypertension. Acute respiratory distress syndrome is believed to occur when a pulmonary or extrapulmonary insult causes the release of inflammatory mediators, promoting neutrophil accumulation in the microcirculation of the lung. Neutrophils damage the vascular endothelium and alveolar epithelium, leading to pulmonary edema, hyaline membrane formation, decreased lung compliance, and difficult air exchange. Most cases of acute respiratory distress syndrome are associated with pneumonia or sepsis. It is estimated that 7.1 percent of all patients admitted to an intensive care unit and 16.1 percent of all patients on mechanical ventilation develop acute lung injury or acute respiratory distress syndrome. In-hospital mortality related to these conditions is between 34 and 55 percent, and most deaths are due to multiorgan failure. Acute respiratory distress syndrome often has to be differentiated from congestive heart failure, which usually has signs of fluid overload, and from pneumonia. Treatment of acute respiratory distress syndrome is supportive and includes mechanical ventilation, prophylaxis for stress ulcers and venous thromboembolism, nutritional support, and treatment of the underlying injury. Low tidal volume, high positive end-expiratory pressure, and conservative fluid therapy may improve outcomes. A spontaneous breathing trial is indicated as the patient improves and the underlying illness resolves. Patients who survive acute respiratory distress syndrome are at risk of diminished functional capacity, mental illness, and decreased quality of life; ongoing care by a primary care physician is beneficial for these patients.     

Management of pulmonary vasodilator therapy in patients with pulmonary arterial hypertension during critical illness

Pulmonary arterial hypertension (PAH) is commonly treated with pulmonary arteriolar vasodilator therapy. When a patient on PAH medication is admitted to intensive care, determining how to manage their medication during the critical illness is often complicated. There may be considerations related to the inability to take medication by mouth, related to acute renal failure or acute liver injury, related to altered mental status or delirium, or related to hypotension and bacteremia. Decisions of how to manage these medications can have a major impact on the patient’s clinical course. Presently, provider experience is the major tool in navigating the decisions regarding these medications. In this review, we offer our recommendations of how to manage PAH patients with critical illness who are on PAH medications. These recommendations include how to deliver medications via feeding tubes, how to dose medications in the setting of acute renal failure or acute liver failure, and how to manage medications during hypotension or when a tunneled catheter needs to be removed.