Pharmaceutical News

Airway Pressure Release Ventilation (APRV)

Airway Pressure Release Ventilation (APRV)A Human TWal
Airway pressure release ventilation (APRV) is a new approach to ventilatory support that provides artificial ventilation of the lungs by releasing positive airway pressure (Paw), thereby acutely reducing lung volume below functional residual capacity (FRC). The APRV system delivers continuous positive airway pressure (CPAP) and augments ventilation as an adjunct to CPAP In dogs with normal lungs, APRV provided ventilation and oxygenation equivalent to that provided by conventional positive pressure ventilation (PPV) and was superior to conventional ventilatory support with positive end-expiratory pressure (PEEP) in dogs with acute lung injury (ALI). We sought to determine APRVs ability to support ventilation and oxygenation of patients recovering from the mild pulmonary dysfunction which follows cardiopulmonary bypass. Continue reading

Pulmonary Hypertension and Right Ventricular Function in Patients with COPD: Conclusion

However, as in the left ventricle, it is probable that the slope of the end-systolic FfV relationship is a more accurate measure of ventricular contractility than is the position of the P/V relationship alone. This relationship is linear in the left ventricle and is independent of the ventricular loading conditions. It is difficult to measure end-systolic pressure precisely, but it has been shown, again for the left ventricle, that the slope of the P/V relationships measured when using either peak or end-systolic pressure are closely correlated. Therefore, we substituted peak right ventricular pressure for end-systolic pressure in our study. We have also previously demonstrated the linearity of the right ventricular end-systolic PA relationship in patients with hypoxic COPD by off loading the ventricle with an intravenous infusion of sodium nitroprusside, and have shown that this relationship is sensitive to changes in right ventricular contractility. Values for the slope of the RV PA relationship are not available in normal subjects for comparison with our patients. Continue reading

Pulmonary Hypertension and Right Ventricular Function in Patients with COPD: Outcome

Pulmonary Hypertension and Right Ventricular Function in Patients with COPD: OutcomeRight ventricular function is difficult to assess, principally due to the variation in shape of the right ventricle even in normal subjects. Although radionuclide measurements of RVEF are independent of the geometric configuration of the ventricle, RVEF is influenced by ventricular loading conditions, independent of changes in muscle function, and is therefore, an inaccurate assessment of ventricular contractility in patients with increased afterload. Simultaneous measurements of right ventricular pressure, Cl, and RVEF have allowed us to calculate the right ventricular end-systolic pressure volume ratio in patients with COPD. For ethical reasons, we have not been able to compare the results of P/V measurements in patients with COPD with those in normal subjects. However, we have calculated the mean systolic PA relationship in the right ventricle from right ventricular hemodynamic data obtained by Gurtner et al in 20 normal subjects and the mean RVEF from a similar number of normal subjects which we have studied previously. Continue reading

Pulmonary Hypertension and Right Ventricular Function in Patients with COPD: Ventricular function

We believe, however, that there may be a more fundamental reason why RVEF and Ppa are not significantly correlated. Ventricular function is influenced by ventricular afterload, preload, and contractility. Which of these factors is the most important determinant of RVEF is still debated. Studies showing a highly significant correlation between RVEF and Ppa imply that RVEF is mostly dependent on afterload. However, the true ventricular afterload is defined as the stress acting on the ventricular wall immediately after ventricular muscle shortening. The assumption that Ppa relates to the right ventricular afterload requires that intracavity pressure closely approximates transmural pressure, but this may not apply in patients with chronic airflow limitation. Pulmonary vascular resistance, which we found did correlate with RVEF, may reflect the right ventricular afterload more accurately, but this is still an approximation. Moreover, in a study by Gunther and Grossman, in patients with aortic stenosis in whom the left ventricular afterload was augmented, there was no significant correlation between left ventricular ejection fraction (LVEF) and peak left ventricular systolic pressure. However, there was a highly significant correlation between LVEF and the mean left ventricular midwTall circumferential wall stress, which is a measure of the true ventricular afterload. The complex and variable shape of the right ventricle has so far precluded measurements of right ventricular wall stress. Thus, we believe that RVEF cannot be used as a noninvasive estimate of Ppa in patients with COPD. Continue reading

Pulmonary Hypertension and Right Ventricular Function in Patients with COPD: Discussion

Pulmonary Hypertension and Right Ventricular Function in Patients with COPD: DiscussionWe found no correlation between simultaneous measurements of RVEF and the Ppa (Fig 1) in 100 patients with COPD who had a wide range of both Ppa and RVEF (Table 1). This represents the largest group of patients with COPD where a correlation between these simultaneously measured variables has been made. Previous studies have shown correlation coefficients between Ppa and RVEF varying from + 0.23 to — 0.86. Several factors may account for this variability. In only four of these studies were the measurements made exclusively in patients with COPD. In most previous studies, Ppa and RVEF were not measured simultaneously. Moreover, the technique of measurement of RVEF is not consistent in these studies and may account for some of the variability in the relationship between RVEF and Ppa. Indeed, one group of authors has published two studies in patients with COPD which describe a significant correlation between Ppa and RVEF in one study and an insignificant correlation in the other. The technique which we employed to measure RVEF is reproducible in our hands and correlates well with the first pass technique considered by some authors to be more reproducible.
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Pulmonary Hypertension and Right Ventricular Function in Patients with COPD: Results

In these 100 patients with COPD, there was a wide range of ventilatory function, arterial blood gas values, Ppa and RVEF (Table 1). There was no correlation between mean pulmonary arterial pressure and simultaneous measurements of RVEF (Fig 1) (r= —0.07), nor between RVEF and systolic pulmonary arterial pressure (r= —0.02). However, there was a weak but significant correlation between the total pulmonary vascular resistance and the RVEF (r= — 0.40,p<0.05,n = 52). In addition, RVEF did not correlate with Pa02, (r = 0.09), PaC02, (r = 0.08), or FEVj, (r = 0.006). Cardiac index was within the normal range (>2 L min-um) in all but three patients in which it was measured (mean Cl = 2.7 ±0.5 L min“l*m~2, n = 52). Continue reading

Pulmonary Hypertension and Right Ventricular Function in Patients with COPD: Hemodynamic Techniques

Pulmonary Hypertension and Right Ventricular Function in Patients with COPD: Hemodynamic TechniquesHemodynamic Techniques
Each patient was studied semisupine when breathing room air. A fine arterial line (Vigon 18 gauge) was inserted into the nondominant brachial or radial artery under local anesthesia, in order to measure blood gas tensions in arterial blood. A Swan-Ganz (SG) balloon-tipped thermodilution pulmonary arterial catheter (No 5-7F) was passed from either the right antecubital vein or the femoral vein to the pulmonary artery under local anesthetic. Heart rate and rhythm were monitored continuously by an ECG. The SG catheter, filled with fluid, was attached to a hemodynamic cart to measure pressure and cardiac output. Pressure measurements were zero-referenced to a point 5 cm below the sternal angle. All intracardiac pressures were measured by averaging over at least three respiratory cycles. Mean pressures were calculated by electronic integration. Cardiac output was measured in 52 of 100 patients at rest by the thermodilution technique. The average of three measurements with a variability of < 10 percent was used in the analysis. Continue reading

Pulmonary Hypertension and Right Ventricular Function in Patients with COPD: Materials and Methods

One hundred patients were studied (66 men and 34 women, mean age 62, SD eight years) who had a history of cough and sputum production for three months per year for at least two consecutive years. The patients had airflow limitation (FEV/FVC <60 percent predicted) which was largely irreversible (<15 percent change in FEVi in response to two puffs of a p-2 agonist), indicating COPD. Most had severe airflow limitation (although we wished to have a wide range of disability), with hypoxemia, but variable C02 retention when breathing room air (Table 1). Sixty-two of these patients had a documented past history of peripheral edema, when a diagnosis of ”cor pulmonale” was made, other causes of edema having been excluded on clinical grounds. Continue reading

Pulmonary Hypertension and Right Ventricular Function in Patients with COPD

Pulmonary Hypertension and Right Ventricular Function in Patients with COPDOver the past 15 years, radionuclide ventriculography has been used extensively to study left ventricular function. Accurate measurements of the right ventricular ejection fraction (RVEF) using this technique can be achieved with a little more difficulty. Several studies have shown a correlation between the mean pulmonary arterial pressure (Ppa) and the RVEF, suggesting that RVEF is largely dependent on right ventricular afterload. However, the relationship between these two variables is not strong enough to allow substitution of the noninvasive measurement of RVEF for invasive measurements of Ppa. Moreover, the RVEF depends not only on the right ventricular afterload, but also on the ventricular preload and contractility. Thus, RVEF may not be a good indicator of right ventricular function in the face of an augmented afterload. Continue reading

Effect of Platelet-activating Factor Inhalation on Nonspecific Bronchial Reactivity in Man: Discussion

Our study provides contrasting evidence to the concept that PAF can increase bronchial reactivity in normal subjects, as shown by Rubin et al and Cuss et al. For their study of the effect of PAF on airway reactivity, Cuss et al used a mean dose of inhaled PAF of 57 μg, given as five single breaths over 1 h. Rubin et al utilized a single breath of 1,000μ/ml. From a previous report, their nebulizer delivers .023 ml to the mouth. This would result in a single delivered dose of 23 μg. In this report all subjects inhaled ten consecutive breaths of 200 μg/ml, a total of 60 μg delivered to the mouth. The total 60 μg was delivered over 5 min using a timed inhalation method. The difference in our results is not likely due to a discrepancy in the amount of inhaled PAF. Continue reading