scholarly journals Effects of PDE3 Inhibitor Olprinone on the Respiratory Parameters, Inflammation, and Apoptosis in an Experimental Model of Acute Respiratory Distress Syndrome

2020 ◽  
Vol 21 (9) ◽  
pp. 3382
Author(s):  
Petra Kosutova ◽  
Pavol Mikolka ◽  
Sona Balentova ◽  
Marian Adamkov ◽  
Andrea Calkovska ◽  
...  

This study aimed to investigate whether a selective phosphodiesterase-3 (PDE3) inhibitor olprinone can positively influence the inflammation, apoptosis, and respiratory parameters in animals with acute respiratory distress syndrome (ARDS) model induced by repetitive saline lung lavage. Adult rabbits were divided into 3 groups: ARDS without therapy (ARDS), ARDS treated with olprinone i.v. (1 mg/kg; ARDS/PDE3), and healthy ventilated controls (Control), and were oxygen-ventilated for the following 4 h. Dynamic lung–thorax compliance (Cdyn), mean airway pressure (MAP), arterial oxygen saturation (SaO2), alveolar-arterial gradient (AAG), ratio between partial pressure of oxygen in arterial blood to a fraction of inspired oxygen (PaO2/FiO2), oxygenation index (OI), and ventilation efficiency index (VEI) were evaluated every hour. Post mortem, inflammatory and oxidative markers (interleukin (IL)-6, IL-1β, a receptor for advanced glycation end products (RAGE), IL-10, total antioxidant capacity (TAC), 3-nitrotyrosine (3NT), and malondialdehyde (MDA) and apoptosis (apoptotic index and caspase-3) were assessed in the lung tissue. Treatment with olprinone reduced the release of inflammatory mediators and markers of oxidative damage decreased apoptosis of epithelial cells and improved respiratory parameters. The results indicate a future potential of PDE3 inhibitors also in the therapy of ARDS.

2016 ◽  
Vol 50 (12) ◽  
pp. 1009-1015 ◽  
Author(s):  
Lara M. Groetzinger ◽  
Ryan M. Rivosecchi ◽  
Sandra L. Kane-Gill ◽  
Michael P. Donahoe

Background: Acute respiratory distress syndrome (ARDS) is associated with a mortality rate of approximately 40%. Neuromuscular blockade is associated with an improvement in oxygenation and a reduction in mortality in ARDS. Objective: The goal of this evaluation was to determine if the depth of paralysis, determined by train-of-four (TOF) monitoring, correlates with gas exchange in moderate to severe ARDS. Methods: This was a retrospective review of moderate to severe ARDS patients who were prescribed >12 hours of continuous infusion cisatracurium between January 1, 2013, and December 31, 2014, with a PaO2:FiO2 ratio <150 and documented TOF and arterial blood gases. Patients were evaluated for inclusion at 12, 24, and 48 hours after initiation of neuromuscular blockade. Results: A total of 378 patients were screened for inclusion, with 107 evaluable patients meeting criteria at baseline. Poor correlation existed between TOF and oxygenation index (OI) at 12 (τ = 0.03), 24 (τ = 0.15) and 48 hours (τ = 0.08). When controlling for proning and baseline OI, the depth of paralysis did not have a significant effect on OI at 12, 24, or 48 hours. Conclusions: This evaluation demonstrates that the use of TOF monitoring for neuromuscular blockade does not correlate with gas exchange markers in moderate to severe ARDS.


Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Chiara Robba ◽  
◽  
Lorenzo Ball ◽  
Denise Battaglini ◽  
Danilo Cardim ◽  
...  

Abstract Background In COVID-19 patients with acute respiratory distress syndrome (ARDS), the effectiveness of ventilatory rescue strategies remains uncertain, with controversial efficacy on systemic oxygenation and no data available regarding cerebral oxygenation and hemodynamics. Methods This is a prospective observational study conducted at San Martino Policlinico Hospital, Genoa, Italy. We included adult COVID-19 patients who underwent at least one of the following rescue therapies: recruitment maneuvers (RMs), prone positioning (PP), inhaled nitric oxide (iNO), and extracorporeal carbon dioxide (CO2) removal (ECCO2R). Arterial blood gas values (oxygen saturation [SpO2], partial pressure of oxygen [PaO2] and of carbon dioxide [PaCO2]) and cerebral oxygenation (rSO2) were analyzed before (T0) and after (T1) the use of any of the aforementioned rescue therapies. The primary aim was to assess the early effects of different ventilatory rescue therapies on systemic and cerebral oxygenation. The secondary aim was to evaluate the correlation between systemic and cerebral oxygenation in COVID-19 patients. Results Forty-five rescue therapies were performed in 22 patients. The median [interquartile range] age of the population was 62 [57–69] years, and 18/22 [82%] were male. After RMs, no significant changes were observed in systemic PaO2 and PaCO2 values, but cerebral oxygenation decreased significantly (52 [51–54]% vs. 49 [47–50]%, p < 0.001). After PP, a significant increase was observed in PaO2 (from 62 [56–71] to 82 [76–87] mmHg, p = 0.005) and rSO2 (from 53 [52–54]% to 60 [59–64]%, p = 0.005). The use of iNO increased PaO2 (from 65 [67–73] to 72 [67–73] mmHg, p = 0.015) and rSO2 (from 53 [51–56]% to 57 [55–59]%, p = 0.007). The use of ECCO2R decreased PaO2 (from 75 [75–79] to 64 [60–70] mmHg, p = 0.009), with reduction of rSO2 values (59 [56–65]% vs. 56 [53–62]%, p = 0.002). In the whole population, a significant relationship was found between SpO2 and rSO2 (R = 0.62, p < 0.001) and between PaO2 and rSO2 (R0 0.54, p < 0.001). Conclusions Rescue therapies exert specific pathophysiological mechanisms, resulting in different effects on systemic and cerebral oxygenation in critically ill COVID-19 patients with ARDS. Cerebral and systemic oxygenation are correlated. The choice of rescue strategy to be adopted should take into account both lung and brain needs. Registration The study protocol was approved by the ethics review board (Comitato Etico Regione Liguria, protocol n. CER Liguria: 23/2020).


2020 ◽  
pp. 088506662094404
Author(s):  
Shubhi Kaushik ◽  
Sindy Villacres ◽  
Ruth Eisenberg ◽  
Shivanand S. Medar

Objectives: To describe the incidence of and risk factors for acute kidney injury (AKI) in children with acute respiratory distress syndrome (ARDS) and study the effect of AKI on patient outcomes. Design: A single-center retrospective study. Setting: A tertiary care children’s hospital. Patients: All patients less than 18 years of age who received invasive mechanical ventilation (MV) and developed ARDS between July 2010 and July 2013 were included. Acute kidney injury was defined using p-RIFLE (risk, injury, failure, loss, and end-stage renal disease) criteria. Interventions: None. Measurements and Main Results: One hundred fifteen children met the criteria and were included in the study. Seventy-four children (74/115, 64%) developed AKI. The severity of AKI was risk in 34 (46%) of 74, injury in 19 (26%) of 74, and failure in 21 (28%) of 74. The presence of AKI was associated with lower Pao 2 to Fio 2 (P/F) ratio ( P = .007), need for inotropes ( P = .003), need for diuretics ( P = .004), higher oxygenation index ( P = .03), higher positive end-expiratory pressure (PEEP; P = .01), higher mean airway pressure ( P = .008), and higher Fio 2 requirement ( P = .03). Only PEEP and P/F ratios were significantly associated with AKI in the unadjusted logistic regression model. Patients with AKI had a significantly longer duration of hospital stay, although there was no significant difference in the intensive care unit stay, duration of MV, and mortality. Recovery of AKI occurred in 68% of the patients. A multivariable model including PEEP, P/F ratio, weight, need for inotropes, and need for diuretics had a better receiver operating characteristic (ROC) curve with an AUC of 0.75 compared to the ROC curves for PEEP only and P/F ratio only for the prediction of AKI. Conclusions: Patients with ARDS have high rates of AKI, and its presence is associated with increased morbidity and mortality.


2019 ◽  
Vol 7 (23) ◽  
pp. 742-742
Author(s):  
Tacyano Tavares Leite ◽  
Cícero Abdon Malheiro Gomes ◽  
Juan Miguel Cosquillo Valdivia ◽  
Alexandre Braga Libório

Author(s):  
Luciano Gattinon ◽  
Eleonora Carlesso

Respiratory failure (RF) is defined as the acute or chronic impairment of respiratory system function to maintain normal oxygen and CO2 values when breathing room air. ‘Oxygenation failure’ occurs when O2 partial pressure (PaO2) value is lower than the normal predicted values for age and altitude and may be due to ventilation/perfusion mismatch or low oxygen concentration in the inspired air. In contrast, ‘ventilatory failure’ primarily involves CO2 elimination, with arterial CO2 partial pressure (PaCO2) higher than 45 mmHg. The most common causes are exacerbation of chronic obstructive pulmonary disease (COPD), asthma, and neuromuscular fatigue, leading to dyspnoea, tachypnoea, tachycardia, use of accessory muscles of respiration, and altered consciousness. History and arterial blood gas analysis is the easiest way to assess the nature of acute RF and treatment should solve the baseline pathology. In severe cases mechanical ventilation is necessary as a ‘buying time’ therapy. The acute hypoxemic RF arising from widespread diffuse injury to the alveolar-capillary membrane is termed Acute Respiratory Distress Syndrome (ARDS), which is the clinical and radiographic manifestation of acute pulmonary inflammatory states.


Author(s):  
Alma Cani ◽  
Fadil Gradica ◽  
Fahri Kokiçi ◽  
Loreta Agolli

Background: ARDS is defined as pulmonary inflammatory process characterized by increased capillary permeability associated with acute severe hypoxemia and bilateral  infiltrates on the chest radiograph. Chlinical manifestations of ARDS is associated with a reduction of  functional residual capacity and  static compliance of the respiratory system.Recently,after experimental models and physiological studies have just established the principles to understand  the potential beneficial effects  of PEEP and reduction in mortality to 22%. The benefit of PEEP has been demonstrated in terms of preventing cyclic opening and collapsing alveoli in acute respiratory distress syndrome patients (ARDS). Aim of study: To determine  the appropriate PEEP level in-patients with ARDS. Objective: By using optimal PEEP:to realize the maximal alveolar recruitment.To avoid the decrease of oxygen delivery (DO2) as result of an unfavourable reduction in cardiac output. Material and methods:Retrospectiv study of 120 patients which only 63 of them are included in study with age 18-70 years old.(2012-2014 )  The entry criteria were clinically (severe dyspnoea, tachypnea, cyanosis); PaO2/FiO2 <200mmHG, the presence of bilateral chest infiltrates. The exclusion criteria were: aged < 18 yrs, COPD in history of diseases, heart attack; PEEP was set the level that provided the greatest improvement in oxygenation. The optimal PEEP came as a result of gradual increase of PEEP from 2-5 cmH2O every 6 hours, depended on gas analyses. The right PEEP level is the PEEP allowing the highest PaO2 value without causing hemodynamic compromise. Results: During this study we conclude that the gradual increase of PEEP improves significantly arterial oxygen tension (PaO2). Per value of PEEP 9.6-15.8, CI 95% is 145.9-191.8. The  Pearson test  with a significant correlation coefficient of level 0.995 and significance level 0.000 shows also a very important result. It was considered significant statistically the value of P≤ 0.05.  Also  the value of Chi ² of PaO2 and of PEEP, has resulted significant in 0.950 with P < 0.001. Conclusion: Mechanical ventilation using optimal PEEP increases the value of PaO2. As a matter of fact 88% of cases with PaO2 > 220 mmHg survive. The role of PEEP in clinical practice is still debated but, in selected categories of patients with a careful monitoring, it may play an important role in improving outcome.


Author(s):  
Luciano Gattinon ◽  
Eleonora Carlesso

Respiratory failure (RF) is defined as the acute or chronic impairment of respiratory system function to maintain normal oxygen and CO2 values when breathing room air. ‘Oxygenation failure’ occurs when O2 partial pressure (PaO2) value is lower than the normal predicted values for age and altitude and may be due to ventilation/perfusion mismatch or low oxygen concentration in the inspired air. In contrast, ‘ventilatory failure’ primarily involves CO2 elimination, with arterial CO2 partial pressure (PaCO2) higher than 45 mmHg. The most common causes are exacerbation of chronic obstructive pulmonary disease (COPD), asthma, and neuromuscular fatigue, leading to dyspnoea, tachypnoea, tachycardia, use of accessory muscles of respiration, and altered consciousness. History and arterial blood gas analysis is the easiest way to assess the nature of acute RF and treatment should solve the baseline pathology. In severe cases mechanical ventilation is necessary as a ‘buying time’ therapy. The acute hypoxemic RF arising from widespread diffuse injury to the alveolar-capillary membrane is termed Acute Respiratory Distress Syndrome (ARDS), which is the clinical and radiographic manifestation of acute pulmonary inflammatory states.


Author(s):  
Esra Serdaroglu ◽  
Selman Kesici ◽  
Benan Bayrakci ◽  
Gulsev Kale

AbstractDiffuse alveolar damage (DAD) is one of the pathological hallmarks of acute respiratory distress syndrome (ARDS). We aimed to compare pathological findings of DAD with clinical ARDS criteria. We re-evaluated 20 patients whose clinical autopsy revealed DAD. Total 11/20 patients with DAD (55%) met the 1994 American–European Consensus Conference and 7/17 (41%) met the 2012 Berlin clinical criteria. DAD showed only moderate correlation with current clinical ARDS definition. Oxygenation index (OI), seems to be the most valuable tool in predicting pulmonary damage severity, though OI is not listed in either of the previous definitions. We support the recommended use of OI by 2015 consensus conference.


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