Pulmonary Vasodilator Therapy Research Articles

Pulmonary hypertensive crises following surgery for congenital hart defects in young children

In this clinical study, 20 high risk infants and neonates were monitored to identify and characterize pulmonary hypertensive crises following surgery for congenital cardiac defects. Monitoring included right ventricular or pulmonary artery pressure catheters and transcutaneous oximetry. Eleven patients also had continuous analog recording of hemodynamic data so that antecedents of crises and the sequence of events following treatment could be reconstructed. Eleven of the 20 patients had one or more crises. Six of these ultimately died whereas 5 patients survived with aggressive vasodilator therapy. Four patients without crises but with episodic pulmonary hypertension benefitted from pulmonary vasodilator therapy to ease weaning from ventilatory support. Typically, each crisis was associated with a stress event. Crises were difficult to ablate if not rapidly treated and multiple crises would often cluster following an initial event. High dose narcotic (fentanyl) analgesia was found to be important in the postoperative management. Tolazoline and oxygen were the most consistently useful vasodilators, but isoproterenol and nitrates also played a role. Five of the children who died were examined post mortem: histologically, there was increased pulmonary arterial muscularization in 2, in none were there changes of fixed pulmonary vascular disease. The postoperative management must be individualized on the basis of monitored responses of pulmonary circulation.

Chronic Obstructive Pulmonary Disease: Current Concepts and Therapeutic Approaches

The fifth leading cause of death in the United States, chronic obstructive respiratory conditions, cannot be cured but can be considerably ameliorated by appropriate management. Many patients with COPD have a combination of chronic bronchitis, asthma, and emphysema. While the damage due to emphysema is permanent, many of the pathophysiologic changes of asthma and bronchitis can be reversed to some extent, and such reversal should be a goal of therapy. Smoking cessation will help the patient more than any other medical treatment. Bronchodilator therapy is best given by inhalation from a metered dose inhaler and on a maintenance basis. Be sure to check inhaler technique. An anticholinergic agent, eg, ipratropium bromide, is probably most effective, but many patients prefer a beta 2-selective adrenergic agent. Xanthines are currently third choice but are very useful to cover nocturnal dyspnea. Corticosteroids are usually only used in acute exacerbations and then only for short courses. If prolonged use is required, however, the inhalation route minimizes side effects to which these patients are particularly prone. Antibiotics are also usually only used in exacerbations, but one can be liberal with them. Use the less expensive broad-spectrum options for ten days. Some clinicians believe that hydration is an effective expectorant. Mucolytic therapy is extensively used outside the United States. The appropriate role of mucolytic therapy in the treatment of bronchitis remains to be more fully explored. Low-flow oxygen is only used in the prevention or treatment of cor pulmonale when the PaO2 is persistently at or below 55, or with a rising hematocrit and right-sided cardiac changes. If used, oxygen is helpful only when given long term for at least 18 h per day, not on a prn basis. Cardiac glycosides are probably of little benefit, but diuretics have an important role in treatment of fluid retention. Pulmonary vasodilator therapy is still experimental, as is almitrine. Prophylaxis with pneumococcal vaccine and annual influenza vaccine is rational but has not been proven to be of value. Exercise and activity should be encouraged for all except those with frank congestive heart failure. The role of "breathing exercises" is currently being reevaluated. Surgery has almost no place in the management of COPD. Anesthesia often results in postoperative complications in this disease. Avoid all sedatives and tranquilizers.

The pharmacological treatment of newborn diaphragmatic hernia ? update 1987

Before the mid 1970s, neonates with diaphragmatic hernias (CDH) had a survival rate of 40%. Since then increased interest has been focused on the pulmonary artery and its hypertension (the persistent fetal circulation) and the pharmacologic treatment of this pathophysiology. Our initial pharmacologic experience left us with much information and even more unanswered questions. While other series were encouraging, they also showed a survival rate of about 50%. The following problems are associated with pulmonary vasodilator therapy: (1) there is no specific pulmonary vasodilator and the response is often unpredictable; (2) the pulmonary arterioles in these babies are abnormal and appear in many instances anatomically incapable of responding; (3) cardiac output may be affected secondary to inotropic or chronotropic side effects of vasodilators; and (4) the effect of a vasodilator on the pulmonary vasculature under hypoxic conditions is unknown. Moreover, we have yet to identify at birth which CDH babies require this treatment, and we must find improved pharmacologic agents that will more specifically dilate the constricted pulmonary vascular bed with minimal effect on the systemic circulation. Although some attempts at pharmacological manipulation of the pulmonary vascular bed continue in most centers, including ours, there are many other innovations in the perioperative management which require further evaluation, among them extracorporeal membrane oxygenation, high-frequency oscillation and possibly lung transplantation in the future.

Pulmonary Vasodilator Therapy for Chronic Obstructive Pulmonary Disease and Cor Pulmonale: Treatment with Nifedipine, Nitroglycerin, and Oxygen

The present study was undertaken to evaluate the short-term effects of nitroglycerin, nifedipine, and supplemental oxygen on hemodynamics and gas exchange in 11 patients in stable condition with chronic obstructive pulmonary disease and cor pulmonale. In general, both intravenous nitroglycerin and sublingual nifedipine significantly reduced the pulmonary vascular resistance index. For the group as a whole, nifedipine decreased the pulmonary vascular resistance index by significantly increasing the cardiac index, with minimal reductions in mean pulmonary arterial pressure. Conversely, nitroglycerin decreased the pulmonary vascular resistance index by markedly reducing the mean pulmonary arterial pressure but also decreased the cardiac index in some patients. Nitroglycerin also caused a significant decrease in mixed venous oxygen tension. Administration of oxygen did not cause any clinically significant improvement in resting hemodynamics following short-term administration. During the follow-up period, eight of 11 patients who were treated with pulmonary vasodilators in addition to long-term therapy with low-flow oxygen died within a mean of six months. This rate of survival was not significantly different than an age-matched and sexmatched control group with similar severity of disease who received only long-term therapy with low-flow oxygen. Based on these data, it seems unlikely that a substantial increase in survival will be obtained by combining pulmonary vasodilators with long-term oxygen therapy in patients with stable emphysema who have cor pulmonale and carbon dioxide retention. The present study was undertaken to evaluate the short-term effects of nitroglycerin, nifedipine, and supplemental oxygen on hemodynamics and gas exchange in 11 patients in stable condition with chronic obstructive pulmonary disease and cor pulmonale. In general, both intravenous nitroglycerin and sublingual nifedipine significantly reduced the pulmonary vascular resistance index. For the group as a whole, nifedipine decreased the pulmonary vascular resistance index by significantly increasing the cardiac index, with minimal reductions in mean pulmonary arterial pressure. Conversely, nitroglycerin decreased the pulmonary vascular resistance index by markedly reducing the mean pulmonary arterial pressure but also decreased the cardiac index in some patients. Nitroglycerin also caused a significant decrease in mixed venous oxygen tension. Administration of oxygen did not cause any clinically significant improvement in resting hemodynamics following short-term administration. During the follow-up period, eight of 11 patients who were treated with pulmonary vasodilators in addition to long-term therapy with low-flow oxygen died within a mean of six months. This rate of survival was not significantly different than an age-matched and sexmatched control group with similar severity of disease who received only long-term therapy with low-flow oxygen. Based on these data, it seems unlikely that a substantial increase in survival will be obtained by combining pulmonary vasodilators with long-term oxygen therapy in patients with stable emphysema who have cor pulmonale and carbon dioxide retention.

Neonatal pulmonary hypertension: pathophysiologic-based therapy.

AbstractRational management of pulmonary artery hypertension (PAH) in the newborn infant must be based on an understanding of underlying causes. When a specific diagnosis can be made, empirical treatment gives way to specific therapy. For every pathophysiologic abnormality potentially resulting in PAH, clinical entities can be identified and key therapeutic interactions can be considered.1. Pulmonary Venous Hypertension: PAH is secondary to obstruction of blood flow through the left heart. If based on anatomic abnormality (mitral or left atrial), surgical relief of obstruction is required. If PAH is the result or functional abnormality of the left ventricle (transient left ventricular ischemia), medical treatment of left ventricular failure is most important.2. Functional Obstruction of Pulmonary Vascular Bed: Hyperviscosity of blood (polycythemia ‐ HCT > 65) results in increased pulmonary vascular resistance. Treatment consists of reduction of red blood cell volume.3. Pulmonary Vascular Constriction: Hypoxemia with or without pulmonary parenchymal disease (primary or secondary persistent fetal circulation [PFC] syndrome). Therapy is directed at improvement of oxygenation and dilatation of pulmonary arteriolar bed (e.g. O2 hyperventilation and/or pulmonary vasodilator therapy).4. Decreased Pulmonary Vascular Bed: If primary pulmonary hypoplasia is present, no treatment is available. If secondary form (diaphragmatic hernia), surgical repair and pulmonary vasodilatation of contralateral lung is indicated. Extracorporeal membrane oxygenation (ECMO) can be used in severe cases.5. Increased pulmonary blood flow: Causes in the neonate include complex heart disease without pulmonary stenosis; and peripheral A—V fistula. Treatment: Surgical limitation of pulmonary blood flow may be required.Even when PAH is the result of combined etiologies, a prompt well‐organized clinical management plan can follow from understanding of pathologic principles.

Vasodilator therapy for primary pulmonary hypertension.

Primary pulmonary hypertension is a clinical syndrome characterized by pulmonary hypertension in the absence of sufficient underlying heart or lung disease to account for it (1-3). In essence, it is unexplained pulmonary arterial hypertension. Pulmonary venoocclusive disease, the etiology of which is also enigmatic, is generally considered separately because of the prospect of unique pathogenetic mechanisms and the distinctive pulmonary vascular lesions. Pulmonary vasodilator therapy is based on the premise that pulmonary vasoconstriction is an important component of the syndrome of pulmonary hypertension (1, 4). Even when the underlying disorder is predominantly one of obliterative intimal disease, it is believed that stretching of vessels due to increased intraluminal pressures leads to a secondary increase in the muscle tone of the pulmonary arteries and arterioles (5), an effect that may heighten pulmonary vascular resistance and worsen pulmonary hypertension. Unfortunately, the therapeutic use of pulmonary vasodilator agents has been hampered by difficulty in the early detection of pulmonary hypertension, by heterogeneity of the vascular lesions responsible for the clinical entity of primary pulmonary hyperten­ sion, and by uncertain criteria for a therapeutically meaningful response to pulmonary vasodilator agents. In this review, we briefly discuss the clinical diagnosis of pulmonary hypertension (PPH) and the testing of vasodilators for thera­ peutic effectiveness. In addition, we identify questions to be answered about the proper use of vasodilator agents in therapy.

RESPIRATORY FAILURE IN CONGENITAL DIAPHRAGMATIC HERNIA: VENTILATION BY HIGH FREQUENCY OSCILLATION

Congenital diaphragmatic hernia (CDH) is characterised by immaturity both of alveoli and pulmonary vasculature. In a prospective analysis of 46 infants with CDH presenting within the first 6 hours of life, simultaneous blood gases drawn from umbilical and right radial artery lines identified a group of 23 patients with severe hypoxemia due mainly to preductal rather than ductal shunting. All were treated with paralysis, hyperventilation, and vasodilator therapy. The single consistent feature in this severely affected group was hypercarbia (PaCO2>50mmHg) which remained elevated despite manipulations of both ventilator rates and mean airway pressures. All 23 patients in this group died while 21 of 23 patients with ductal shunting only, survived. In ten of the 23 patients in whom we were unable to control PaCO2 we changed from conventional ventilation (CMV) to high frequency oscillation (HFO). The mean PaCO2 on CMV was 59±15mmHg with mean PaO2 in the right radial artery of 36±11mmHg. The mean PaCO2 fell to 32±5mmHg with HFO but while there was a temporary improve ment in PaO2, this was not sustained. The fact that control of PaCO2 was readily achieved by HFO suggests that the hypercarbia and hypoxemia in this group of patients is based on intrapulmonary rather than intracardiac shunting and represents severe bilateral pulmonary hypoplasia, where pulmonary vasodilator therapy will not be of benefit.