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Evaluation of the progress and prognosis of adult respiratory distress syndrome. Simple respiratory physiologic measurement.

In our study of 14 patients with adult respiratory distress syndrome (ARDS), we measured A-aDO2, VD/VT, arterial-to-end tidal PCO2 ), effective dynamic compliance, and pulmonary vascular resistance on a daily basis. At the onset of ARDS, all patients showed bilateral interstitial edema on the chest X-ray films, P(A-a)O2 of more than 500 mm Hg, marked decrease in effective dynamic compliance, a moderate increase in VD/VT, and a normal value of a-etPCO2. Pulmonary vascular resistance was low. After seven days, all of those who subsequently died and developed persistent elevation of P(A-a)O2, significant increase in VD/VT, a-etPCO2 and pulmonary vascular resistance, and significant decrease in effective dynamic compliance compared to the values at the onset of ARDS. Those abnormalities diverged significantly from the findings in those who survived. By evaluating sequential changes of those parameters, we might be able to predict an accurate prognosis of ARDS.

Acute Disease

Current concepts of the adult respiratory distress syndrome.

The adult respiratory distress syndrome (ARDS) is a sequel to pulmonary injury that may be direct, closed chest trauma or indirect, through air or vascular passages, aspiration, or fat embolization. An understanding of this syndrome is essential for the oral surgeon who not only manages severe maxillofacial injuries but is also a member of a trauma team that manages multisystem injuries. Emphasis on pathophysiologic pathways resulting in ARDS is presented with a discussion on oxygenation and ventilation abnormalities. Application of these guidelines will assist the oral surgeon in understanding the management of patients with this acute progressive syndrome.

Adrenal Cortex Hormones

Rare genetic variant risks in patients with sepsis-associated acute respiratory distress syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a complex, heterogeneous, and deadly condition often resulting from pulmonary lesions due to sepsis, among other causes. There is a lack of targeted therapies to specifically treat the patients. Common genetic factors in the population (frequency&#x2009;>&#x2009;1%) have been associated with ARDS susceptibility, but systematic genetic screens of the role of rare genetic variants are lacking. We used the network of known molecular interactions to identify ARDS risks from clusters of biologically related genes containing qualifying variants (QVs) with frequency&#x2009;<&#x2009;1% likely affecting function. METHODS: We conducted whole-exome sequencing in sepsis patients from the GEN-SEP cohort (n&#x2009;=&#x2009;822, of which 272 developed ARDS). A network-based heterogeneity clustering algorithm was used to discover significant gene clusters (p&#x2009;<&#x2009;1&#x2009;&#xd7;&#x2009;10&#x2013;5). Gene-set enrichment analysis and logistic regression models aggregating QVs were used for cross-verification to confirm consistency and deepen understanding of the effect sizes of gene clusters. RESULTS: We identified 19 significant clusters (plowest&#x2009;=&#x2009;3.29&#x2009;&#xd7;&#x2009;10&#x2013;10), each containing an average of 102 genes (11.6% mean similarity). QVs in nine gene clusters were associated with sepsis-associated ARDS (plowest&#x2009;=&#x2009;1&#x2009;&#xd7;&#x2009;10&#x2013;5) but were not associated with 28-day survival. Clusters were enriched in several biological pathways, notably the Toll-like receptor cascades. CONCLUSIONS: These results support a marked genetic heterogeneity underlying ARDS susceptibility and the presence of rare risk variants involving multiple biological processes that are associated with sepsis outcomes. Particularly, they underscore the importance of rare variants in genes of the Toll-like receptor cascades in the risk for sepsis-associated ARDS.

Humans

Maternal intravenous ethanol in the prevention of respiratory distress syndrome.

The occurrence of respiratory distress syndrome (RDS) was studied in 68 premature neonates whose mothers were treated with at least one six-hour course of intravenous ethyl alcohol within 48 hours before delivery. At the gestational interval of 28 to 32 weeks, significant differences were observed in the incidence of RDS (p = less than 0.05), in severe RDS (p = less than 0.005), and in the mortality rate from RDS ( = less than 0.05), when compared to premature neonates not treated with alcohol and delivered during the same time interval. Several high-risk factors were found unevenly distributed between treated and control groups of patients, and their relevance to RDS was discussed. Premature rupture of membranes of more than 24 hours did not protect infants from RDS in the patients studied. Explanations for possible mechanisms of action are discussed.

Apgar Score

Decreased angiotensin-converting enzyme in the adult respiratory distress syndrome.

Using hippuryl-L-histidyl-L-leucine as substrate, serum angiotensin-converting enzyme was measured in 13 patients who had adult respiratory distress syndrome, eight patients with respiratory failure without adult respiratory distress syndrome, and two groups of controls: 24 healthy blood donors and 24 hospitalized patients with a variety of conditions but without respiratory failure or adult respiratory distress syndrome. Serum angiotensin-converting enzyme expressed in units/ml was 14.60 +/- 5.60 for adult respiratory distress syndrome compared with 28.92 +/- 6.60 for the blood donors, 20.76 +/- 5.87 for the patients with respiratory failure without adult respiratory distress syndrome and 20.20 +/- 5.94 in the hospitalized patients without respiratory failure or adult respiratory distress syndrome. These differences were significant, P less than .001 when adult respiratory distress syndrome was tested against the blood donors and P less than .01 against the other two groups. The significance of these findings is not clear, but the possibility is raised that the decrease of angiotensin-converting enzyme in adult respiratory distress syndrome results from a loss of pulmonary endothelial cells, which are known both to produce angiotensin-converting enzyme and to be damaged in adult respiratory distress syndrome.

Adolescent

[Prevention and therapy of respiratory distress syndrome in premature infants by means of bromhexine metabolite VIII. Animal experimental studies on the therapeutic efficacy of bromhexine metabolite VIII in premature respiratory distress syndrome].

In preparing a clinical study 14C-labelled bromhexine metabolite VIII was applied intraamnially in animal experiments. The distribution was measured in different maternal and fetal organs by thinlayer chromatography and autoradiography. A complete placental passage was found in both directions. An organspecific accumulation in the fetal lungs could not be demonstrated.

Ambroxol

Adult respiratory distress syndrome.

Treatment of the adult respiratory distress syndrome requires an understanding of the current concepts of the pathogenesis of this syndrome. The clinical features and pathophysiology are briefly discussed. Differential diagnosis requires the exclusion of pulmonary infection and left heart failure. Therapy is aimed at correction of the associated initiating disease process and the maintenance of tissue oxygenation. The latter requires increased inspired oxygen concentration, maintenance of an adequate cardiac output, and maintenance of a normal hematocrit level and body temperature. The therapeutic role of intravenous albumin, diuretics, and steroids in this syndrome is still controversial. Currently accepted modalities for improving oxygenation, when oxygen by face mask proves inadequate, include intubation and ventilation with postiive end-expiratory pressure. Other promising technics for improving oxygenation which do not require intubation are continuous positive airway pressure applied by face mask, continuous negative chest wall pressure, and alterations in posture. The long-term prognosis in survivors appears to be good, with only mild residual pulmonary functional abnormalities.

Adult

Detection of left ventricular failure in patients with adult respiratory distress syndrome.

Fourteen patients with adult respiratory distress syndrome were admitted to the medical intensive care unit and received bedside heart catheterization with the use of a balloon-tipped, flow directed catheter. Four of the 14 (29 percent) were found to have left ventricular failure (LVF), defined as a pulmonary artery wedge pressure greater than 12 mm Hg. Analysis of the standard clinical and laboratory data demonstrated no criteria which could differentiate those patients with LVF from those without. Three of the four patients indentified as having LVF responded to therapy directed toward LVF with substantial clinical improvement.

Adolescent

[The protease inhibitor potential in newborns with respiratory distress syndrome].

In 70 newborns with respiratory distress syndrome (RDS) and in roughly the same number of eutrophic mature newborns the total antiplasmin, progressive antithrombin and alpha 2-macroglobulin was determined, the latter in an enzymatical as well as immunochemical way. In healthy mature newborns the progressive antithrombin was somewhat below the level of adults, alpha 2-macroglobulin was above it in both methods and total antiplasmin within it. All parameters of protease inhibitory capacity were significantly lowered in newborns with RDS. Smaller values could be found in patients with bleedings and in those who died later on. Even in those patients with a birth weight under 2,000 g there was a tendency to lower values which can only be partially due to the specificity of development of inhibitors. Progressive antithrombin, total antiplasmin and alpha 2-macroglobulin determined enzymatically are correlated in newborns with RDS jointly and with numerous other parameters of the coagulation system. These relations point to the fact that all components are included in the same consumption process, viz. in the process of disseminated intravascular coagulation. Alpha 2-macroglobulin values determined immunochemically do not correlate with coagulation parameters determined enzymatically as well as with other parameters. They lay partially above or below those determined enzymatically. This behaviour can only be explained by a partial enzyme complex binding of alpha 2-macroglobulin in newborns with RDS.

Antithrombins

Adult respiratory distress syndrome.

Many causes for the adult respiratory distress syndrome (ARDS) have been reported, all with common pathologic, pathophysiologic and biochemical end results. The final common pathway may involve changes in lung content of a critical enzyme, superoxide dismutase, or alterations in surfactant metabolism, or both. The early assumption that the disorder is partially due to oxygen toxicity from inspired oxygen concentrations greater than 60 percent is consistent with findings of recent biochemical studies. Although the lung normally maintains its alveoli dry, during ARDS increased permeability of small pulmonary vessels results in primary pulmonary edema, in contrast to edema from increased vascular pressure. These data have been obtained mainly in animals; whether they apply to humans with ARDS is not certain. Tissue oxygenation is improved by increasing end-expiratory pressure in an animal model of ARDS, more effectively during spontaneous breathing than during mechanical ventilation. During spontaneous breathing, adverse ventilatory effects were caused by stimulation of pulmonary reflexes.

Humans

Continuous positive airway pressure versus positive end-expiratory pressure in respiratory distress syndrome.

The hemodynamic and respiratory effects of spontaneous ventilation with continuous positive airway pressure (CPAP) and mechanical ventilation with positive end-expiratory pressure (PEEP) were compared in nine patients who had adult respiratory distress syndrome. These patients were capable of maintaining spontaneous ventilation (tidal volume above 300 ml. and PaCO2 below 45 torr). Arterial and mixed venous blood gases, cardiac output, oxygen delivery and consumption, pulmonary artery pressure, and pulmonary wedge pressure were measured in 11 instances, with each patient on 5 or 10 cm. H2O CPAP or PEEP, and in nine instances, with each patient on the ventilator but without PEEP (O PEEP). During CPAP, when compared to PEEP at the same level of end-expiratory pressure, mean PaO2 increased significantly (p less than 0.05) and mean physiological shunt decreased (p less than 0.05). In nine of 11 instances, cardiac output was higher on CPAP than on a corresponding level of PEEP. Thus CPAP was more effective than the same amount of PEEP in improving arterial oxygenation by the lung without adversely affecting cardiac output.

Adolescent

Gas exchange, pulmonary mechanics and haemodynamics in adult respiratory distress syndrome: experimental results in Lewe miniature pigs.

Adult respiratory distress syndrome (ARDS) is a common medical emergency in respiratory care complicating a great variety of traumas and diseases. An animal model from Lewe miniature pigs has been developed to study the ARDS under standardized conditions; it is based on aspiration pneumonitis, a disorder often observed in ARDS, injuring the lung alveolar surfactant system. The experimental study was conducted under neuroleptanalgesia. ARDS was produced by intratracheal application of hydrochloric acid (0.2 mol/l) in an amount of 1.0 ml/kg body wt. The animals were ventilated automatically by a standardized ventilatory pattern in IPP mode. In all animals the time course of oxygenation ratio (Pa,O2/F1O2), arterial CO2 tension (Pa,CO2), ratio of alveolo--arterial oxygen tension difference to inspired oxygen fraction (Aa,DO2/F1O2), oxygen exchange ratio ((AaDO2/Pa,O2), lung compliance (CL), inspiratory airway resistance (RrsI), dead space ratio VD/VT), pulmonary artery pressure (PAP) and systemic blood pressure were studied. Changes in quasi-static volume--pressure curves, percentage change in lung water content and gross pathological finding were used to integrate the findings into a system of pathophysiological changes in ARDS. The animal group to which hydrochloric acid was administered shows severe pulmonary distress leading to death within 3.5--7.5 h. No significant changes in the measured parameters could be observed in the control group over a 14 h period. The results suggest that aspiration pneumonitis in Lewe miniature pigs is very suitable to investigate various problems in pathogenesis of ARDS. The model provides reproducible results which correlate very well with findings in different ARDS states. The models serves both to compare clinical states and to search for newer therapeutic manoeuvres.

Animals

How to manage adult respiratory distress syndrome.

The key clinical features of adult respiratory distress syndrome are increasing dyspnea, tachypnea, and work of breathing; diffuse pulmonary infiltrations on chest radiographs; severe hypoxemia; and absence of a classic diagnosis. Adequate tissue oxygenation is the cornerstone of therapy. Therapeutic modalities include mechanical ventilation, fluid restriction, diuretics, and cardiotonic and vasopressor agents.

Adult

Inflammatory and tissue injury marker dynamics in pediatric acute respiratory distress syndrome.

BACKGROUNDThe molecular signature of pediatric acute respiratory distress syndrome (ARDS) is poorly described, and the degree to which hyperinflammation or specific tissue injury contributes to outcomes is unknown. Therefore, we profiled inflammation and tissue injury dynamics over the first 7 days of ARDS, and associated specific biomarkers with mortality, persistent ARDS, and persistent multiple organ dysfunction syndrome (MODS).METHODSIn a single-center prospective cohort of intubated pediatric patients with ARDS, we collected plasma on days 0, 3, and 7. Nineteen biomarkers reflecting inflammation, tissue injury, and damage-associated molecular patterns (DAMPs) were measured. We assessed the relationship between biomarkers and trajectories with mortality, persistent ARDS, or persistent MODS using multivariable mixed effect models.RESULTSIn 279 patients (64 [23%] nonsurvivors), hyperinflammatory cytokines, tissue injury markers, and DAMPs were higher in nonsurvivors. Survivors and nonsurvivors showed different biomarker trajectories. IL-1&#x3b1;, soluble tumor necrosis factor receptor 1, angiopoietin 2 (ANG2), and surfactant protein D increased in nonsurvivors, while DAMPs remained persistently elevated. ANG2 and procollagen type III N-terminal peptide were associated with persistent ARDS, whereas multiple cytokines, tissue injury markers, and DAMPs were associated with persistent MODS. Corticosteroid use did not impact the association of biomarker levels or trajectory with mortality.CONCLUSIONSPediatric ARDS survivors and nonsurvivors had distinct biomarker trajectories, with cytokines, endothelial and alveolar epithelial injury, and DAMPs elevated in nonsurvivors. Mortality markers overlapped with markers associated with persistent MODS, rather than persistent ARDS.FUNDINGNIH (K23HL-136688, R01-HL148054).

Humans

Adult respiratory distress syndrome after venous air embolism.

Venous air embolism is not commonly believed to produce the adult respiratory distress syndrome. We present a nonsurgical case of venous air embolism followed by the development of this syndrome. Other causes of adult respiratory distress syndrome were excluded. Physicians should be alerted to its possible occurrence and the need for appropriate therapy.

Adult

Saturated phosphatidylcholine in amniotic fluid and prediction of the respiratory-distress syndrome.

The lecithin/sphingomyelin (L/S) ratio in amniotic fluid is widely used to predict the risk of respiratory-distress syndrome. However, the results are unreliable if the specimen is contaminated or obtained during a complicated pregnancy. We therefore compared the predictive value of the L/S ratio with that of the concentration of saturated phosphatidylcholine (SPC) in 322 amniotic-fluid samples, 75 per cent of which were contaminated or obtained during complicated pregnancies or both. A positive result is one that predicted the development of respiratory-distress syndrome, taken as an L/S ratio equal to or less than 2/1 or an SPC below 500 mug per deciliter. The respiratory-distress syndrome was correctly predicted in 25 of 45 cases (55.5 per cent) with L/S ratios equal to or less than 2/1, and in 35 of 42 cases (82 per cent) with SPC's less than 500 mug per deciliter. When L/S ratios were greater than 2/1, there were 13 of 277 (4.7 per cent) false negatives, and when SPC's were above 500 mug per deciliter, there were three of 280 (1.1 per cent) false negatives. We conclude that determination of SPC is both more specific and more sensitive as a predictor of the respiratory-distress syndrome than the techniques currently in use.

Acetone

Familial respiratory distress syndrome in three consecutive full-term infants. Case reports and documentation of lung enzyme activities.

Familial respiratory distress syndrome in full-term newborn infants is a rare occurrence. Our patient delivered three consecutive full-term infants who developed findings consistent with respiratory distress syndrome. All three died from autopsy-proven hyaline membrane disease. Analysis of the activities of four enzymes that play an important role in the biosynthesis of lecithin (choline kinase, choline phosphotransferase, phospholipase A and lysolecithin acyltransferase) failed to disclose an abnormality in lung samples in our patient with familial respiratory distress syndrome.

1-Acylglycerophosphocholine O-Acyltransferase

Interventions with a significant mortality difference in acute respiratory distress syndrome: A systematic review and comparison with Guidelines.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) has a high mortality rate. European Society of Intensive Care Medicine (ESICM) and American Thoracic Society (ATS) Guidelines are the worldwide reference for clinicians in management of ARDS. Mortality represents one of the most important outcomes in intensive care practice and randomized controlled trials (RCTs) the highest level of evidence. We compared Guidelines recommendations with RCT results to highlight differences and find potential new therapeutic opportunities. METHODS: We performed a systematic review of all RCTs reporting a statistically significant mortality difference in ARDS and a subsequent comparison with ESICM and ATS Guidelines recommendations. RESULTS: We identified 33 RCTs and 23 interventions with mortality difference in ARDS patients. Seven interventions relate to invasive ventilation strategies, two to noninvasive ventilation strategies, one to extracorporeal membrane oxygenation (ECMO), 12 to drugs and one to nutritional support. In 25/33 (76%) RCTs the intervention was associated with mortality reduction and in 8/33 with mortality increase (24%). Multicenter studies were 24/33 (73%) while blinding was adopted in 19/33 (58%) studies. Guidelines recommendations supported by RCTs with mortality impact include: the use of low tidal volume ventilation, prone positioning, venovenous ECMO, steroids and the avoidance of high frequency oscillatory ventilation. Eight of the interventions identified were not mentioned by Guidelines but demonstrated reduced mortality, and five further interventions demonstrated increased mortality. CONCLUSIONS: This systematic review highlights potential gaps between RCTs results and Guidelines that could be used to plan future research or highlight topics to be discussed in future Guidelines.

Humans