John F. Murray

Bio: John F. Murray is an academic researcher from University of California, San Francisco. The author has contributed to research in topics: Respiratory distress & Pulmonary edema. The author has an hindex of 12, co-authored 17 publications receiving 3133 citations.

An Expanded Definition of the Adult Respiratory Distress Syndrome

Abstract: More than twenty years ago, Ashbaugh and coworkers, (1), in a now classic article, described. 12 patients whose striking but uniform clinical, physiologic, roentgenographic,and pathologic abnormalities distinguished them from among 272adult patients who had received respiratory support in the intensive care units of Colorado General Hospital and Denver General Hospital. The 12patients all had severedyspnea, tachypnea, cyanosis that was refractory to oxygen therapy, decreased respiratory system compliance, and diffuse alveolar infiltrations on their chest radiographs. Pathologic examination in seven patients who died revealed atelectasis, vascular congestion and hemorrhage, severe pulmonary edema and hyaline membranes. Shortly afterward, Petty and coworkers (2), called this constellation of findings the adult respiratory distress syndrome (ARDS). Since then, ARDS has been recognized as an entity throughout the world and has been the subject of numerous conferences, hundreds of articles, and several books. As a result of this activity, much descriptive information has been obtained about ARDS, and we have learned a lot about its clinical features, physiologic disturbances, prognosis, and pathologic findings. And yet formidable problems remain: there is disagreement about exactly what ARDS is and on what causes it; more importantly, available empiric treatment is inadequate, and mortality remains unacceptably high (600/0 or more) (3). This appears to be one of the few points of agreement among investigators, but even that statement is arguable (4). We believe that much of the controversy concerning ARDS is explained by the lack of a satisfactory definition of this elusivesyndrome. How can you collect, much less compare, epidemiologicdata and mortality figures when there is no uniformly accepted (and used) definition? How can you study basic pathophysiologic mechanisms, understand natural history, and above all, evaluate new therapeutic approaches in what appears now to be an amalgam of many different disorders? The purpose of this article, therefore, is to propose an expanded definition of ARDS that takes into account new knowledge about

Plasma tumor necrosis factor in patients with septic shock. Mortality rate, incidence of adult respiratory distress syndrome, and effects of methylprednisolone administration

Abstract: We assayed serial plasma samples from 86 patients, who were enrolled in a prospective randomized trial of the effects of methylprednisolone (MPSS) in septic shock, for the presence of cytokine tumor necrosis factor (TNF) using an enzyme-linked immunosorbent assay. TNF was present in the plasma of 27 of the 74 patients with septic shock, but in only 1 of the 12 patients with shock due to other causes. TNF was detected with equal frequency in patients with shock from gram-negative or from gram-positive bacillary sepsis. TNF levels were highest on the initial sample and decreased significantly over the subsequent 24 h in both the patients treated with MPSS and in those given placebo. Patients with detectable TNF had a higher incidence and severity of the adult respiratory distress syndrome and a higher mortality rate than did patients without detectable TNF.

Biologically active products of complement and acute lung injury in patients with the sepsis syndrome.

Abstract: To determine if biologically active products of complement appear during sepsis and to establish the relationship of these components to the respiratory and hemodynamic complications of sepsis, we measured C5a des Arg and C3a des Arg (radioimmunoassay), neutrophil chemotaxis, and neutrophil-aggregating activity in plasma obtained from 40 patients at the time sepsis was suspected clinically. Levels of C3a des Arg and C5a des Arg were elevated in 35 and 38 patients, respectively, and in all 25 with positive blood cultures. Highest C5a des Arg levels occurred in patients with hypotension (less than 90 mmHg) and/or acidemia. The C5a des Arg concentrations were significantly higher in patients with than in those without neutrophil-chemotactic activity. Neutrophil-aggregating activity was less sensitive an index of complement activation, as it was positive in only 8 patients and correlated poorly with C5a des Arg and C3a des Arg values. Using a composite scoring system to quantify sepsis-related pulmonary abnormalities, we found that neither biologic nor immunologic assays of complement activation products correlated with the initial severity nor predicted the development or worsening of associated acute lung injury.

Diagnostic utility of fiberoptic bronchoscopy in patients with Pneumocystis carinii pneumonia and the acquired immune deficiency syndrome.

Abstract: The records of 35 adult male patients with suspected Pneumocystis carinii pneumonia and the acquired immune deficiency syndrome were reviewed to determine the diagnostic utility of fiberoptic bronchoscopy. Twenty-two of the 24 patients (92%) shown to have Pneumocystis pneumonia were diagnosed by bronchoscopy; 20 patients were diagnosed after 1 bronchoscopy and 2 patients after 2 bronchoscopies. The sensitivity of bronchoscopy specimens for diagnosing Pneumocystis pneumonia was 79% for transbronchial biopsies (19 of 24), 78% for transbronchial biopsy touch preparations (7 of 9), 55% for bronchial washings (11 of 20), and 39% for bronchial brushings (7 of 18). The overall sensitivity of fiberoptic bronchoscopy was 85% (22 positive of 26 total bronchoscopies). Complications, occurring during 6 of the 37 bronchoscopies, were slight hemoptysis (1 patient), fever (2 patients), septic shock (1 patient), and pneumothorax (2 patients). Fiberoptic bronchoscopy is a safe and effective procedure for making the early diagnosis of Pneumocystis carinii pneumonia in adult male patients with the acquired immune deficiency syndrome.

Correlation between gallium lung scans and fiberoptic bronchoscopy in patients with suspected Pneumocystis carinii pneumonia and the acquired immune deficiency syndrome.

Abstract: We retrospectively examined the sensitivity and specificity of gallium lung scans for detecting Pneumocystis carinii pneumonia in 22 patients with known or suspected acquired immune deficiency synd...

The American-European Consensus Conference on ARDS: Definitions, mechanisms, relevant outcomes, and clinical trial coordination

Abstract: The acute respiratory distress syndrome (ARDS), a process of nonhydrostatic pulmonary edema and hypoxemia associated with a variety of etiologies, carries a high morbidity, mortality (10 to 90%), and financial cost. The reported annual incidence in the United States is 150,000 cases, but this figure has been challenged, and it may be different in Europe. Part of the reason for these uncertainties are the heterogeneity of diseases underlying ARDS and the lack of uniform definitions for ARDS. Thus, those who wish to know the true incidence and outcome of this clinical syndrome are stymied. The American-European Consensus Committee on ARDS was formed to focus on these issues and on the pathophysiologic mechanisms of the process. It was felt that international coordination between North America and Europe in clinical studies of ARDS was becoming increasingly important in order to address the recent plethora of potential therapeutic agents for the prevention and treatment of ARDS.

The acute respiratory distress syndrome

Abstract: The acute respiratory distress syndrome is a common, devastating clinical syndrome of acute lung injury that affects both medical and surgical patients. Since the last review of this syndrome appeared in the Journal, 1 more uniform definitions have been devised and important advances have occurred in the understanding of the epidemiology, natural history, and pathogenesis of the disease, leading to the design and testing of new treatment strategies. This article provides an overview of the definitions, clinical features, and epidemiology of the acute respiratory distress syndrome and discusses advances in the areas of pathogenesis, resolution, and treatment. Historical Perspective and Definitions . . .

Effect of a Protective-Ventilation Strategy on Mortality in the Acute Respiratory Distress Syndrome

Abstract: Background In patients with the acute respiratory distress syndrome, massive alveolar collapse and cyclic lung reopening and overdistention during mechanical ventilation may perpetuate alveolar injury. We determined whether a ventilatory strategy designed to minimize such lung injuries could reduce not only pulmonary complications but also mortality at 28 days in patients with the acute respiratory distress syndrome. Methods We randomly assigned 53 patients with early acute respiratory distress syndrome (including 28 described previously), all of whom were receiving identical hemodynamic and general support, to conventional or protective mechanical ventilation. Conventional ventilation was based on the strategy of maintaining the lowest positive end-expiratory pressure (PEEP) for acceptable oxygenation, with a tidal volume of 12 ml per kilogram of body weight and normal arterial carbon dioxide levels (35 to 38 mm Hg). Protective ventilation involved end-expiratory pressures above the lower inflection poin...

Prone Positioning in Severe Acute Respiratory Distress Syndrome

Abstract: In this multicenter, prospective, randomized, controlled trial, we randomly as signed 466 patients with severe ARDS to undergo prone-positioning sessions of at least 16 hours or to be left in the supine position. Severe ARDS was defined as a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (Fio2) of less than 150 mm Hg, with an F io2 of at least 0.6, a positive end-expira tory pressure of at least 5 cm of water, and a tidal volume close to 6 ml per kilogram of predicted body weight. The primary outcome was the proportion of patients who died from any cause within 28 days after inclusion. Results A total of 237 patients were assigned to the prone group, and 229 patients were as signed to the supine group. The 28-day mortality was 16.0% in the prone group and 32.8% in the supine group (P<0.001). The hazard ratio for death with prone position ing was 0.39 (95% confidence interval [CI], 0.25 to 0.63). Unadjusted 90-day mortal ity was 23.6% in the prone group versus 41.0% in the supine group (P<0.001), with a hazard ratio of 0.44 (95% CI, 0.29 to 0.67). The incidence of complications did not differ significantly between the groups, except for the incidence of cardiac arrests, which was higher in the supine group. Conclusions In patients with severe ARDS, early application of prolonged prone-positioning ses sions significantly decreased 28-day and 90-day mortality. (Funded by the Programme Hospitalier de Recherche Clinique National 2006 and 2010 of the French Ministry of Health; PROSEVA ClinicalTrials.gov number, NCT00527813.)