Effects of Intravenous Zaprinast and Inhaled Nitric Oxide on Pulmonary Hemodynamics and Gas Exchange in an Ovine Model of Acute Respiratory Distress Syndrome

2000 ◽  
Vol 93 (2) ◽  
pp. 422-430 ◽  
Author(s):  
Christophe Adrie ◽  
Alexandra Holzmann ◽  
W. Mona Hirani ◽  
Warren M. Zapol ◽  
William E. Hurford
Keyword(s):  
Nitric Oxide ◽  
Acute Respiratory Distress Syndrome ◽  
Gas Exchange ◽  
Lung Injury ◽  
Pulmonary Artery ◽  
Distress Syndrome ◽  
Pulmonary Vasculature ◽  
Beneficial Effects ◽  
Before And After ◽  
Inhaled No

Background Inhaled nitric oxide (No) selectively dilates the pulmonary vasculature and improves gas exchange in acute respiratory distress syndrome. Because of the very short half-life of NO, inhaled NO is administered continuously. Intravenous Zaprinast (2-o-propoxyphenyl-8-azapurin-6-one), a cyclic guanosine monophosphate phosphodiesterase inhibitor, increases the efficacy and prolongs the duration of action of inhaled NO in models of acute pulmonary hypertension. Its efficacy in lung injury models is uncertain. The authors hypothesized that the use of intravenous Zaprinast would have similar beneficial effects when used in combination with inhaled NO to improve oxygenation and dilate the pulmonary vasculature in a diffuse model of acute lung injury. Methods The authors studied two groups of sheep with lung injury produced by saline lavage. In the first group, 0, 5, 10, and 20 ppm of inhaled NO were administered in a random order before and after an intravenous Zaprinast infusion (2 mg/kg bolus followed by 0.1 mg. kg-1. min-1). In the second group, inhaled NO was administered at the same concentrations before and after an intravenous infusion of Zaprinast solvent (0.05 m NaOH). Results After lavage, inhaled NO decreased pulmonary arterial pressure and resistance with no systemic hemodynamic effects, increased arterial oxygen partial pressure, and decreased venous admixture (all P < 0.05). The intravenous administration of Zaprinast alone decreased pulmonary artery pressure but worsened gas exchange (P < 0.05). Zaprinast infusion abolished the beneficial ability of inhaled NO to improve pulmonary gas exchange and reduce pulmonary artery pressure (P < 0. 05 vs. control). Conclusions This study suggests that nonselective vasodilation induced by intravenously administered Zaprinast at the dose used in our study not only worsens gas exchange, but also abolishes the beneficial effects of inhaled NO.

Short-term Cardiorespiratory Effects of Proportional Assist and Pressure-support Ventilation in Patients with Acute Lung Injury/Acute Respiratory Distress Syndrome

2006 ◽  
Vol 105 (4) ◽  
pp. 703-708 ◽  
Author(s):  
Eumorfia Kondili ◽  
Nectaria Xirouchaki ◽  
Katerina Vaporidi ◽  
Maria Klimathianaki ◽  
Dimitris Georgopoulos
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Acute Lung Injury ◽  
Gas Exchange ◽  
Lung Injury ◽  
Respiratory Distress Syndrome ◽  
Pressure Support Ventilation ◽  
Pressure Support ◽  
Distress Syndrome ◽  
Short Term ◽  
Support Ventilation

Background Recent data indicate that assisted modes of mechanical ventilation improve pulmonary gas exchange in patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Proportional assist ventilation (PAV) is a new mode of support that amplifies the ventilatory output of the patient effort and improves patient-ventilator synchrony. It is not known whether this mode may be used in patients with ALI/ARDS. The aim of this study was to compare the effects of PAV and pressure-support ventilation on breathing pattern, hemodynamics, and gas exchange in a homogenous group of patients with ALI/ARDS due to sepsis. Methods Twelve mechanically ventilated patients with ALI/ARDS (mean ratio of partial pressure of arterial oxygen to fractional concentration of oxygen 190 +/- 49 mmHg) were prospectively studied. Patients received pressure-support ventilation and PAV in random order for 30 min while maintaining mean airway pressure constant. With both modes, the level of applied positive end-expiratory pressure (7.1 +/- 2.1 cm H2O) was kept unchanged throughout. At the end of each study period, cardiorespiratory data were obtained, and dead space to tidal volume ratio was measured. Results With both modes, none of the patients exhibited clinical signs of distress. With PAV, breathing frequency and cardiac index were slightly but significantly higher than the corresponding values with pressure-support ventilation (24.5 +/- 6.9 vs. 21.4 +/- 6.9 breaths/min and 4.4 +/- 1.6 vs. 4.1 +/- 1.3 l . min . m, respectively). None of the other parameters differ significantly between modes. Conclusions In patients with ALI/ARDS due to sepsis, PAV and pressure-support ventilation both have clinically comparable short-term effects on gas exchange and hemodynamics.

Physiologic Determinants of the Response to Inhaled Nitric Oxide in Patients with Acute Respiratory Distress Syndrome 

1997 ◽  
Vol 87 (2) ◽  
pp. 297-307 ◽  
Author(s):  
Claire Manktelow ◽  
Luca M. Bigatello ◽  
Dean Hess ◽  
William E. Hurford ◽  
Keyword(s):  
Nitric Oxide ◽  
Septic Shock ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Initial Response ◽  
Inhaled Nitric Oxide ◽  
Clinically Significant ◽  
Inhaled No

Background The response to inhaled nitric oxide (NO) in patients with acute respiratory distress syndrome (ARDS) varies. It is unclear which patients will respond favorably and whether the initial response persists over time. The authors defined a clinically useful response to inhaled NO as an increase of more than 20% of the ratio of the partial pressure of oxygen (Pa(O2)) to the inspiratory fraction of oxygen (FIO2), a decrease of more than 20% of pulmonary vascular resistance, or both. The authors hypothesized that patients who initially respond favorably are likely to show persistent improvements of gas exchange and hemodynamics after 48 h of NO inhalation. Methods The medical records and collected research data of 88 patients with ARDS who received 92 trials of NO inhalation between March 1991 and February 1996 were reviewed. Results Fifty-three of the 92 trials (58%) produced a clinically significant response to NO. In the responding patients who continued to receive NO therapy (n = 43), the Pa(O2)/FiO2 ratio remained higher (120 +/- 46 vs. 89 +/- 32 mmHg before NO; P < 0.01) and the mean pulmonary artery pressure remained lower (35 +/- 8 vs. 40 +/- 12 mmHg before NO; P < 0.01) at 48 h. Only 33% of the patients with septic shock responded to inhaled NO compared with 64% of those without septic shock (P < 0.02). Conclusions Most patients with ARDS had clinically useful responses to NO inhalation. Patients with an initial favorable response maintained the improvement at 48 h. Patients with septic shock were less likely to respond favorably.

scholarly journals Monitoring Expired CO2 Kinetics to Individualize Lung-Protective Ventilation in Patients With the Acute Respiratory Distress Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Fernando Suárez-Sipmann ◽  
Jesús Villar ◽  
Carlos Ferrando ◽  
Juan A. Sánchez-Giralt ◽  
Gerardo Tusman
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Gas Exchange ◽  
Lung Injury ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Lung Volume ◽  
Cyclic Deformation ◽  
Distress Syndrome ◽  
Pulmonary Ventilation ◽  
Lung Mechanics

Mechanical ventilation (MV) is a lifesaving supportive intervention in the management of acute respiratory distress syndrome (ARDS), buying time while the primary precipitating cause is being corrected. However, MV can contribute to a worsening of the primary lung injury, known as ventilation-induced lung injury (VILI), which could have an important impact on outcome. The ARDS lung is characterized by diffuse and heterogeneous lung damage and is particularly prone to suffer the consequences of an excessive mechanical stress imposed by higher airway pressures and volumes during MV. Of major concern is cyclic overdistension, affecting those lung segments receiving a proportionally higher tidal volume in an overall reduced lung volume. Theoretically, healthier lung regions are submitted to a larger stress and cyclic deformation and thus at high risk for developing VILI. Clinicians have difficulties in detecting VILI, particularly cyclic overdistension at the bedside, since routine monitoring of gas exchange and lung mechanics are relatively insensitive to this mechanism of VILI. Expired CO2 kinetics integrates relevant pathophysiological information of high interest for monitoring. CO2 is produced by cell metabolism in large daily quantities. After diffusing to tissue capillaries, CO2 is transported first by the venous and then by pulmonary circulation to the lung. Thereafter diffusing from capillaries to lung alveoli, it is finally convectively transported by lung ventilation for its elimination to the atmosphere. Modern readily clinically available sensor technology integrates information related to pulmonary ventilation, perfusion, and gas exchange from the single analysis of expired CO2 kinetics measured at the airway opening. Current volumetric capnography (VCap), the representation of the volume of expired CO2 in one single breath, informs about pulmonary perfusion, end-expiratory lung volume, dead space, and pulmonary ventilation inhomogeneities, all intimately related to cyclic overdistension during MV. Additionally, the recently described capnodynamic method provides the possibility to continuously measure the end-expiratory lung volume and effective pulmonary blood flow. All this information is accessed non-invasively and breath-by-breath helping clinicians to personalize ventilatory settings at the bedside and minimize overdistension and cyclic deformation of lung tissue.

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