IMPORTANCE: Acute respiratory distress syndrome (ARDS) is a life-threatening form of respiratory failure that affects approximately 200 000 patients each year in the United States, resulting in ...nearly 75 000 deaths annually. Globally, ARDS accounts for 10% of intensive care unit admissions, representing more than 3 million patients with ARDS annually. OBJECTIVE: To review advances in diagnosis and treatment of ARDS over the last 5 years. EVIDENCE REVIEW: We searched MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews from 2012 to 2017 focusing on randomized clinical trials, meta-analyses, systematic reviews, and clinical practice guidelines. Articles were identified for full text review with manual review of bibliographies generating additional references. FINDINGS: After screening 1662 citations, 31 articles detailing major advances in the diagnosis or treatment of ARDS were selected. The Berlin definition proposed 3 categories of ARDS based on the severity of hypoxemia: mild (200 mm Hg<Pao2/Fio2≤300 mm Hg), moderate (100 mm Hg<Pao2/Fio2≤200 mm Hg), and severe (Pao2/Fio2 ≤100 mm Hg), along with explicit criteria related to timing of the syndrome’s onset, origin of edema, and the chest radiograph findings. The Berlin definition has significantly greater predictive validity for mortality than the prior American-European Consensus Conference definition. Clinician interpretation of the origin of edema and chest radiograph criteria may be less reliable in making a diagnosis of ARDS. The cornerstone of management remains mechanical ventilation, with a goal to minimize ventilator-induced lung injury (VILI). Aspirin was not effective in preventing ARDS in patients at high-risk for the syndrome. Adjunctive interventions to further minimize VILI, such as prone positioning in patients with a Pao2/Fio2 ratio less than 150 mm Hg, were associated with a significant mortality benefit whereas others (eg, extracorporeal carbon dioxide removal) remain experimental. Pharmacologic therapies such as β2 agonists, statins, and keratinocyte growth factor, which targeted pathophysiologic alterations in ARDS, were not beneficial and demonstrated possible harm. Recent guidelines on mechanical ventilation in ARDS provide evidence-based recommendations related to 6 interventions, including low tidal volume and inspiratory pressure ventilation, prone positioning, high-frequency oscillatory ventilation, higher vs lower positive end-expiratory pressure, lung recruitment maneuvers, and extracorporeal membrane oxygenation. CONCLUSIONS AND RELEVANCE: The Berlin definition of acute respiratory distress syndrome addressed limitations of the American-European Consensus Conference definition, but poor reliability of some criteria may contribute to underrecognition by clinicians. No pharmacologic treatments aimed at the underlying pathology have been shown to be effective, and management remains supportive with lung-protective mechanical ventilation. Guidelines on mechanical ventilation in patients with acute respiratory distress syndrome can assist clinicians in delivering evidence-based interventions that may lead to improved outcomes.
IMPORTANCE: The substantial growth over the last decade in the use of extracorporeal life support for adults with acute respiratory failure reveals an enthusiasm for the technology not always ...consistent with the evidence. However, recent high-quality data, primarily in patients with acute respiratory distress syndrome, have made extracorporeal life support more widely accepted in clinical practice. OBSERVATIONS: Clinical trials of extracorporeal life support for acute respiratory failure in adults in the 1970s and 1990s failed to demonstrate benefit, reducing use of the intervention for decades and relegating it to a small number of centers. Nonetheless, technological improvements in extracorporeal support made it safer to use. Interest in extracorporeal life support increased with the confluence of 2 events in 2009: (1) the publication of a randomized clinical trial of extracorporeal life support for acute respiratory failure and (2) the use of extracorporeal life support in patients with severe acute respiratory distress syndrome during the influenza A(H1N1) pandemic. In 2018, a randomized clinical trial in patients with very severe acute respiratory distress syndrome demonstrated a seemingly large decrease in mortality from 46% to 35%, but this difference was not statistically significant. However, a Bayesian post hoc analysis of this trial and a subsequent meta-analysis together suggested that extracorporeal life support was beneficial for patients with very severe acute respiratory distress syndrome. As the evidence supporting the use of extracorporeal life support increases, its indications are expanding to being a bridge to lung transplantation and the management of patients with pulmonary vascular disease who have right-sided heart failure. Extracorporeal life support is now an acceptable form of organ support in clinical practice. CONCLUSIONS AND RELEVANCE: The role of extracorporeal life support in the management of adults with acute respiratory failure is being redefined by advances in technology and increasing evidence of its effectiveness. Future developments in the field will result from technological advances, an increased understanding of the physiology and biology of extracorporeal support, and increased knowledge of how it might benefit the treatment of a variety of clinical conditions.
Mechanical ventilation is a life-saving therapy that catalyzed the development of modern intensive care units. The origins of modern mechanical ventilation can be traced back about five centuries to ...the seminal work of Andreas Vesalius. This article is a short history of mechanical ventilation, tracing its origins over the centuries to the present day. One of the great advances in ventilatory support over the past few decades has been the development of lung-protective ventilatory strategies, based on our understanding of the iatrogenic consequences of mechanical ventilation such as ventilator-induced lung injury. These strategies have markedly improved clinical outcomes in patients with respiratory failure.
IMPORTANCE: Bayesian analysis of clinical trial data may provide useful information to aid in study interpretation, especially when trial evidence suggests that the benefits of an intervention are ...uncertain, such as in a trial that evaluated early extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS). OBJECTIVE: To demonstrate the potential utility of Bayesian analyses by estimating the posterior probability, under various assumptions, that early ECMO was associated with reduced mortality in patients with very severe ARDS in a randomized clinical trial (RCT). DESIGN AND EVIDENCE: A post hoc Bayesian analysis of data from an RCT (ECMO to Rescue Lung Injury in Severe ARDS EOLIA) that included 249 patients with very severe ARDS who had been randomized to receive early ECMO (n = 124; mortality at 60 days, 35%) vs initial conventional lung-protective ventilation with the option for rescue ECMO (n = 125, mortality at 60 days, 46%). The trial was designed to detect an absolute risk reduction (ARR) of 20%, relative risk (RR) of 0.67. Statistical prior distributions were specified to represent varying levels of preexisting enthusiasm or skepticism for ECMO and by Bayesian meta-analysis of previously published studies (with downweighting to account for differences and quality between studies). The RR, credible interval (CrI), ARR, and probability of clinically important mortality benefit (varying from RR less than 1 to RR less than 0.67 and ARR from 2% or more to 20% or more) were estimated with Bayesian modeling. FINDINGS: Combining a minimally informative prior distribution with the findings of the EOLIA trial, the posterior probability of RR less than 1 for mortality at 60 days after randomization was 96% (RR, 0.78 95% CrI, 0.56-1.04); the posterior probability of RR less than 0.67 was 18%, the probability of ARR of 2% or more was 92%, and the probability of ARR of 20% or more was 2%. With a moderately enthusiastic prior, equivalent to information from a trial of 264 patients with an RR of 0.78, the estimated RR was 0.78 (95% CrI, 0.63-0.96), the probability of RR less than 1 was 99%, the probability of RR less than 0.67 was 8%, the probability of ARR of 2% or more was 97%, and the probability of ARR of 20% or more was 0%. With a strongly skeptical prior, equivalent to information from a trial of 264 patients with an RR of 1.0, the estimated RR was 0.88 (95% CrI, 0.71-1.09), the probability of RR less than 1 was 88%, the probability of RR less than 0.67 was 0%, the probability of ARR of 2% or more was 78%, and the probability of ARR of 20% or more was 0%. If the prior was informed by previous studies, the estimated RR was 0.71 (95% CrI, 0.55-0.94), the probability of RR less than 1 was 99%, the probability of RR less than 0.67 was 48%, the probability of ARR of 2% or more was 98%, and the probability of ARR of 20% or more was 4%. CONCLUSIONS AND RELEVANCE: Post hoc Bayesian analysis of data from a randomized clinical trial of early extracorporeal membrane oxygenation compared with conventional lung-protective ventilation with the option for rescue extracorporeal membrane oxygenation among patients with very severe acute respiratory distress syndrome provides information about the posterior probability of mortality benefit under a broad set of assumptions that may help inform interpretation of the study findings.
Cardiogenic shock can occur due to acute ischaemic or non-ischaemic cardiac events, or from progression of long-standing underlying heart disease. When addressing the cause of underlying disease, the ...management of cardiogenic shock consists of vasopressors and inotropes; however, these agents can increase myocardial oxygen consumption, impair tissue perfusion, and are frequently ineffective. An alternative approach is to temporarily augment cardiac output using mechanical devices. The use of these devices—known as temporary circulatory support systems—has increased substantially in recent years, despite being expensive, resource intensive, associated with major complications, and lacking high-quality evidence to support their use. This Review summarises the physiological basis underlying the use of temporary circulatory support for cardiogenic shock, reviews the evidence informing indications and contraindications, addresses ethical considerations, and highlights the need for further research.
We have previously provided the first genetic evidence that angiotensin converting enzyme 2 (ACE2) is the critical receptor for severe acute respiratory syndrome coronavirus (SARS-CoV), and ACE2 ...protects the lung from injury, providing a molecular explanation for the severe lung failure and death due to SARS-CoV infections. ACE2 has now also been identified as a key receptor for SARS-CoV-2 infections, and it has been proposed that inhibiting this interaction might be used in treating patients with COVID-19. However, it is not known whether human recombinant soluble ACE2 (hrsACE2) blocks growth of SARS-CoV-2. Here, we show that clinical grade hrsACE2 reduced SARS-CoV-2 recovery from Vero cells by a factor of 1,000–5,000. An equivalent mouse rsACE2 had no effect. We also show that SARS-CoV-2 can directly infect engineered human blood vessel organoids and human kidney organoids, which can be inhibited by hrsACE2. These data demonstrate that hrsACE2 can significantly block early stages of SARS-CoV-2 infections.
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•Soluble human ACE2 can inhibit SARS-CoV-2 infections•SARS-CoV-2 can directly infect human blood vessel and kidney organoids•Human organoids as model systems to study SARS-CoV-2 infections/COVID-19
Clinical-grade recombinant human ACE2 can reduce SARS-CoV-2 infection in cells and in multiple human organoid models.
More men than women have died from COVID-19. Genes encoded on X chromosomes, and sex hormones may explain the decreased fatality of COVID-19 in women. The angiotensin-converting enzyme 2 gene is ...located on X chromosomes. Men, with a single X chromosome, may lack the alternative mechanism for cellular protection after exposure to SARS-CoV-2. Some Toll-like receptors encoded on the X chromosomes can sense SARS-CoV-2 nucleic acids, leading to a stronger innate immunity response in women. Both estrogen and estrogen receptor-α contribute to T cell activation. Interventional approaches including estrogen-related compounds and androgen receptor antagonists may be considered in patients with COVID-19.
In this issue of the
Journal,
Papazian and colleagues
1
present intriguing results of their study examining neuromuscular blockade in patients with severe, early acute respiratory distress syndrome ...(ARDS). The investigators randomly assigned 340 patients to receive the neuromuscular blocking agent cisatracurium or placebo for a period of 48 hours. Both groups underwent mechanical ventilation according to a lung-protective strategy previously shown to decrease mortality.
2
Both the adjusted 90-day survival rate and time off the ventilator were greater in the cisatracurium group as compared with the placebo group.
ARDS is an inflammatory disease characterized by pulmonary edema, stiff lungs, and hypoxemia. . . .
Mechanical Ventilation: State of the Art Pham, Tài; Brochard, Laurent J; Slutsky, Arthur S
Mayo Clinic proceedings,
09/2017, Letnik:
92, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Mechanical ventilation is the most used short-term life support technique worldwide and is applied daily for a diverse spectrum of indications, from scheduled surgical procedures to acute organ ...failure. This state-of-the-art review provides an update on the basic physiology of respiratory mechanics, the working principles, and the main ventilatory settings, as well as the potential complications of mechanical ventilation. Specific ventilatory approaches in particular situations such as acute respiratory distress syndrome and chronic obstructive pulmonary disease are detailed along with protective ventilation in patients with normal lungs. We also highlight recent data on patient-ventilator dyssynchrony, humidified high-flow oxygen through nasal cannula, extracorporeal life support, and the weaning phase. Finally, we discuss the future of mechanical ventilation, addressing avenues for improvement.
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