scholarly journals Unsuccessful and Successful Clinical Trials in Acute Respiratory Distress Syndrome: Addressing Physiology-Based Gaps

2021 ◽  
Vol 12 ◽  
Author(s):  
Jesús Villar ◽  
Carlos Ferrando ◽  
Gerardo Tusman ◽  
Lorenzo Berra ◽  
Pedro Rodríguez-Suárez ◽  
...  

The acute respiratory distress syndrome (ARDS) is a severe form of acute hypoxemic respiratory failure caused by an insult to the alveolar-capillary membrane, resulting in a marked reduction of aerated alveoli, increased vascular permeability and subsequent interstitial and alveolar pulmonary edema, reduced lung compliance, increase of physiological dead space, and hypoxemia. Most ARDS patients improve their systemic oxygenation, as assessed by the ratio between arterial partial pressure of oxygen and inspired oxygen fraction, with conventional intensive care and the application of moderate-to-high levels of positive end-expiratory pressure. However, in some patients hypoxemia persisted because the lungs are markedly injured, remaining unresponsive to increasing the inspiratory fraction of oxygen and positive end-expiratory pressure. For decades, mechanical ventilation was the only standard support technique to provide acceptable oxygenation and carbon dioxide removal. Mechanical ventilation provides time for the specific therapy to reverse the disease-causing lung injury and for the recovery of the respiratory function. The adverse effects of mechanical ventilation are direct consequences of the changes in pulmonary airway pressures and intrathoracic volume changes induced by the repetitive mechanical cycles in a diseased lung. In this article, we review 14 major successful and unsuccessful randomized controlled trials conducted in patients with ARDS on a series of techniques to improve oxygenation and ventilation published since 2010. Those trials tested the effects of adjunctive therapies (neuromuscular blocking agents, prone positioning), methods for selecting the optimum positive end-expiratory pressure (after recruitment maneuvers, or guided by esophageal pressure), high-frequency oscillatory ventilation, extracorporeal oxygenation, and pharmacologic immune modulators of the pulmonary and systemic inflammatory responses in patients affected by ARDS. We will briefly comment physiology-based gaps of negative trials and highlight the possible needs to address in future clinical trials in ARDS.

1998 ◽  
Vol 7 (5) ◽  
pp. 335-345 ◽  
Author(s):  
MA Curley ◽  
JC Fackler

OBJECTIVE: The purpose of the study was to describe the patterns of weaning from mechanical ventilation in young children recovering from acute hypoxemic respiratory failure. METHODS: Decision-making rules on progressive weaning were developed and applied to existing data on 82 patients 2 weeks to 6 years old in the Pediatric Acute Respiratory Distress Syndrome Data Set. RESULTS: Three patterns of weaning progress were detected: sprint, consistent, and inconsistent. Length of ventilation and weaning progressively increased from the sprint, to the consistent, to the inconsistent subset. Patients in the inconsistent subset were most likely to have a systemic (sepsis or shock) trigger of acute respiratory distress syndrome and to be rated as having at least moderate disability at discharge. Hypothesis-generating univariate and then multivariate logistic regression analyses indicated that patients who experienced more days of mechanical ventilation before the start of weaning and who had a higher oxygenation index during the weaning process were most likely to have an inconsistent pattern of weaning. CONCLUSION: Patterns of weaning are discernible in a population of young children and indicate a subset at risk for inconsistent weaning. Knowing the patterns of weaning may help clinicians anticipate, perhaps plot, and then modulate a patient's weaning trajectory.


2021 ◽  
Vol 41 (6) ◽  
pp. 55-60
Author(s):  
Patrick Ryan ◽  
Cynthia Fine ◽  
Christine DeForge

Background Manual prone positioning has been shown to reduce mortality among patients with moderate to severe acute respiratory distress syndrome, but it is associated with a high incidence of pressure injuries and unplanned extubations. This study investigated the feasibility of safely implementing a manual prone positioning protocol that uses a dedicated device. Review of Evidence A search of CINAHL and Medline identified multiple randomized controlled trials and meta-analyses that demonstrated both the reduction of mortality when prone positioning is used for more than 12 hours per day in patients with acute respiratory distress syndrome and the most common complications of this treatment. Implementation An existing safe patient-handling device was modified to enable staff to safely perform manual prone positioning with few complications for patients receiving mechanical ventilation. All staff received training on the protocol and use of the device before implementation. Evaluation This study included 36 consecutive patients who were admitted to the medical intensive care unit at a large academic medical center because of hypoxemic respiratory failure/acute respiratory distress syndrome and received mechanical ventilation and prone positioning. Data were collected on clinical presentation, interventions, and complications. Sustainability Using the robust protocol and the low-cost device, staff can safely perform a low-volume, high-risk maneuver. This method provides cost savings compared with other prone positioning methods. Conclusions Implementing a prone positioning protocol with a dedicated device is feasible, with fewer complications and lower costs than anticipated.


2019 ◽  
Vol 40 (01) ◽  
pp. 081-093 ◽  
Author(s):  
Michael Sklar ◽  
Bhakti Patel ◽  
Jeremy Beitler ◽  
Thomas Piraino ◽  
Ewan Goligher

AbstractMechanical ventilation practices in patients with acute respiratory distress syndrome (ARDS) have progressed with a growing understanding of the disease pathophysiology. Paramount to the care of affected patients is the delivery of lung-protective mechanical ventilation which prioritizes tidal volume and plateau pressure limitation. Lung protection can probably be further enhanced by scaling target tidal volumes to the specific respiratory mechanics of individual patients. The best procedure for selecting optimal positive end-expiratory pressure (PEEP) in ARDS remains uncertain; several relevant issues must be considered when selecting PEEP, particularly lung recruitability. Noninvasive ventilation must be used with caution in ARDS as excessively high respiratory drive can further exacerbate lung injury; newer modes of delivery offer promising approaches in hypoxemic respiratory failure. Airway pressure release ventilation offers an alternative approach to maximize lung recruitment and oxygenation, but clinical trials have not demonstrated a survival benefit of this mode over conventional ventilation strategies. Rescue therapy with high-frequency oscillatory ventilation is an important option in refractory hypoxemia. Despite a disappointing lack of benefit (and possible harm) in patients with moderate or severe ARDS, possibly due to lung hyperdistention and right ventricular dysfunction, high-frequency oscillation may improve outcome in patients with very severe hypoxemia.


2021 ◽  
Vol 8 ◽  
Author(s):  
Sébastien Gibot ◽  
Marie Conrad ◽  
Guilhem Courte ◽  
Aurélie Cravoisy

Introduction: The best way to titrate the positive end-expiratory pressure (PEEP) in patients suffering from acute respiratory distress syndrome is still matter of debate. Electrical impedance tomography (EIT) is a non-invasive technique that could guide PEEP setting based on an optimized ventilation homogeneity.Methods: For this study, we enrolled the patients with 2019 coronavirus disease (COVID-19)-related acute respiratory distress syndrome (ARDS), who required mechanical ventilation and were admitted to the ICU in March 2021. Patients were monitored by an esophageal catheter and a 32-electrode EIT device. Within 48 h after the start of mechanical ventilation, different levels of PEEP were applied based upon PEEP/FiO2 tables, positive end-expiratory transpulmonary (PL)/ FiO2 table, and EIT. Respiratory mechanics variables were recorded.Results: Seventeen patients were enrolled. PEEP values derived from EIT (PEEPEIT) were different from those based upon other techniques and has poor in-between agreement. The PEEPEIT was associated with lower plateau pressure, mechanical power, transpulmonary pressures, and with a higher static compliance (Crs) and homogeneity of ventilation.Conclusion: Personalized PEEP setting derived from EIT may help to achieve a more homogenous distribution of ventilation. Whether this approach may translate in outcome improvement remains to be investigated.


Author(s):  
Richard K. Patch ◽  
James Y. Findlay

Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by acute hypoxemic respiratory failure. Patients with ARDS have pulmonary damage from an acute, usually severe, diffuse inflammatory lung injury that leads to increased vascular permeability and loss of aerated tissue. Mortality from ARDS is estimated to range from 26% to 58%, and in-hospital mortality is high (46.1%) for those with severe ARDS. Survivors have extensive morbidity, including neurocognitive dysfunction, physical disabilities, and psychiatric illnesses such as depression, anxiety, and posttraumatic stress disorder. Lung function may be compromised for as long as 5 years.


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