Late Acute Respiratory Distress Syndrome Research Articles

Pulmonary capillary pressures during the acute respiratory distress syndrome.

(1). To describe the evolution of pulmonary capillary pressure (Pcap) and of the pressure drop across the pulmonary venous bed from early to established acute respiratory distress syndrome (ARDS), (2). to assess Pcap under different levels of positive end-expiratory pressure (PEEP) and (3). to compare the visual method and a mathematical model to determine Pcap. Prospective, intervention study. Intensive care unit in a teaching institution. Nine ARDS patients, according to the ARDS Consensus Conference criteria. Pulmonary arterial pressures were measured during routine respiratory mechanics measurements throughout ARDS. Four PEEP levels (6, 9, 12 and 15 cmH(2)O) were studied. Pulmonary artery occlusions were made in triplicate at each PEEP level. Pcap was determined for every occlusion trace by three observers (visual method) and a mathematical model. Diastolic pulmonary artery pressure (PAPd) and pulmonary artery occlusion pressure (PAOP) were measured. The visually determined Pcap showed a bias of 2.5+/-2.1 mmHg as compared to the mathematical estimation. PAPd, Pcap and PAOP tended to decrease from early to late ARDS ( p=0.128, 0.265, 0.121). Pcap-PAOP (6.3+/-2.7 mmHg) did not change throughout ARDS. Higher PEEP levels were associated with increased PAPd, Pcap and PAOP, as well as with larger Pcap-PAOP throughout ARDS. Pulmonary capillary pressure cannot be predicted from PAOP during early and established ARDS. The high variability in Pcap-PAOP increases the risk for underestimation of filtration pressures and consequently the risk for lung edema. Pcap can be estimated at the bedside by either the visual or mathematical methods.

Glucocorticoids and acute lung injury

To describe hypothalamic-pituitary-adrenal (HPA) activation and the role of glucocorticoids in immune modulation during critical illness, and to review clinical trials of pharmacologic and "replacement"' doses of glucocorticoids in early and late acute respiratory distress syndrome (ARDS) and sepsis. Selected review of published literature (1963 to present), clinical trials, and meta-analyses. HPA axis activation is an important component of the compensatory anti-inflammatory response to critical illness. Cortisol supports vascular tone and endothelial integrity, modulates a large number of proinflammatory cytokines, and suppresses phospholipase A(2), cyclo-oxygenase, and nitric oxide synthase. Cortisol has putative antifibrotic activities, including inhibition of fibroblast growth and collagen deposition and stimulation of T-cell and monocyte apoptosis. During critical illness, neurohumoral factors, cytokines, endothelin, and atrial natriuretic peptide all may participate in HPA axis activation, resulting in elevated plasma cortisol production and plasma concentrations. In general, cortisol concentrations correlate with severity of illness, and higher plasma concentrations are associated with a poorer outcome. Failure of adrenocorticotropic hormone to augment plasma cortisol appears to be a poor prognostic finding in vasopressor-dependent sepsis and may indicate "relative adrenal insufficiency." Replacement glucocorticoid/mineralocorticoid therapy over 7 days appears to be beneficial in such individuals. However, a meta-analysis of high-dose, short-course glucocorticoid treatment involving 1,297 patients with sepsis enrolled in nine trials showed a trend toward harm, and four trials in patients with, or at risk for, ARDS showed no benefit or a greater likelihood of progression to ARDS. In contrast, observational studies and one small randomized controlled trial suggest that lower pharmacologic doses of glucocorticoids given late (>1 wk) in the course of ARDS may be beneficial. The National Heart, Lung, and Blood Institute's ARDS Network currently is testing the use of methylprednisolone in late ARDS. This study was reviewed by an independent data safety monitoring board for safety and efficacy after enrolling 60 and 120 patients and is currently ongoing. Current evidence indicates that short-duration, high-dose glucocorticoid therapy is not effective for early ARDS or severe sepsis. One small randomized, controlled trial suggests that moderate doses of glucocorticoids may be beneficial for patients with late ARDS; a much larger randomized controlled trial is ongoing. Some patients with pressor-dependent severe sepsis appear to have relative adrenal insufficiency and benefit from replacement glucocorticoid/mineralocorticoid therapy. The accuracy of the diagnostic criteria for, and the prevalence of, relative adrenal insufficiency in patients with acute lung injury/ARDS is unknown. It is also unclear whether such a response, if present, predisposes patients to ongoing lung inflammation and the development of late fibroproliferative ARDS, or if it is predictive of a beneficial response to steroids. Studies of HPA axis activation and the role of relative adrenal insufficiency on the outcome of patients with acute lung injury are needed.

The Changes of Physiologic Parameters with Time in Steroid treated-Late Acute Respiratory Distress Syndrome Patients

Background : The mortality from acute respiratory distress syndrome(ARDS) is >40-50%. Although some prospective trials have failed to demonstrate a survival benefit of steroids in the early stages of ARDS, there are some reports showing some success with steroids in the later stages. This study observed the changes in the physiologic parameters with time in late ARDS patients who were treated with steroids. Methods : The medical charts of 28 intensive care unit patients(male:female=24:4; mean age 64 years), who had been diagnosed with refractory late ARDS (PaO2/FIO2 <200) and were treated with corticosteroids from December 1999 to July 2002, were retrospectively reviewed. The patients were divided into two groups: the weaned group(n=14), which included the patients who had been

Metabolic correlates of oxygen debt predict posttrauma early acute respiratory distress syndrome and the related cytokine response.

The purpose of this study was to quantify the relationship between negative base excess (base deficit) and lactate as correlates of oxygen debt and the probability of the early acute respiratory distress syndrome (ARDS) response and with regard to the mediator and metabolic response characteristic of this disease. Eighty patients with multiple trauma were studied (514 samples) during their intensive care unit courses (Injury Severity Score 27.6+/-8.8, 36% deaths). Simultaneous samples of arterial base excess and lactate as correlates of oxygen debt, and enzyme-linked immunosorbent assay-measured mixed venous cytokines were obtained daily. At each sample period, the patient was categorized as having ARDS or non-ARDS. Twenty-nine patients (36%; 19 deaths) developed ARDS over the period studied: 17 in postinjury days 1 to 4 (EARLY ARDS) and 12 in postinjury days 5 or later (LATE ARDS). Patients subsequently developing ARDS had evidence of ischemic acidosis on or within the first 24 hours after hospital admission (lower base excess -7.1 mmol/L and higher lactate 5.2 mmol/L in ARDS versus base excess -3.8 mmol/L and lactate 3.6 mmol/L in non-ARDS; p < 0.05). Patients with EARLY ARDS showed even lower (p < 0.05) initial 24 hour mean base excess and higher lactate (base excess -9.1 mmol/L and lactate 6.4 mmol/L) compared with LATE ARDS (base excess -4.3 mmol/L and lactate 3.3 mmol/L). In EARLY ARDS, this degree of ischemic acidosis was followed by a greater mean IL-6 response in the postinjury days 1 to 4 (323 pg/mL) compared with the LATE ARDS response (141 pg/mL) (p < 0.05) or compared with the non-ARDS IL-6 response (67 pg/mL; p < 0.001). In addition, in EARLY ARDS, mean IL-8 levels in postinjury days 1 to 4 (264 pg/mL) were higher than in LATE ARDS (168 pg/mL) (p < 0.05) and the mean IL-1 response in postinjury days 1 to 4 of EARLY ARDS (65 pg/mL) was greater than non-ARDS (32 pg/mL) (p < 0.05). Derivation of probability curves suggests a critical threshold of base excess -6.6 mmol/L or greater for an increased risk of EARLY ARDS. These data suggest that the maximum posttrauma oxygen debt (quantified by the ischemia correlates of negative base excess and lactate) is a critical primary determinant of the later fulminant autoinflammatory EARLY ARDS response mediated by the host's endogenous cytokine mediators.

SDRA tardif chez une patiente non-neutropénique: que faire devant un prélèvement pulmonaire à Candida?

Acute respiratory distress syndrome (ARDS) is a clinical and pathophysiologic entity characterized by an acute and diffuse injury of the endothelial and epithelial surfaces of the lung, leading to respiratory failure. During the late phase of ARDS, glucocorticoids could have a beneficial effect on lung fibroproliferation but predispose to the development of pneumonia and sepsis. Alterations in cellular immunity observed in intensive care unit patients facilitate the progression from Candida colonization to Candida infection. However, in these critically ill patients, it remains difficult to distinguish colonization from invasive infection. As illustrated by this case report of a late ARDS successfully treated by glucocorticoids, the presence of Candida in bronchoalveolar lavage of ARDS in non-neutropenic patients should be considered with care before interpreting it as a colonization of the airways.

Modulation of neutrophil apoptosis by granulocyte colony-stimulating factor and granulocyte/macrophage colony-stimulating factor during the course of acute respiratory distress syndrome.

To determine whether bronchoalveolar lavage fluid (BALF) from patients either at risk for the acute respiratory distress syndrome (ARDS) or with sustained ARDS modulates neutrophil apoptosis; to measure the BALF concentrations of the apoptosis inhibitors granulocyte colony-stimulating factor (G-CSF) and granulocyte/macrophage colony-stimulating factor (GM-CSF) before and after the onset of ARDS; and to determine whether the BALF concentrations of G-CSF and/or GM-CSF are associated with clinical outcome. Prospective cohort study. Tertiary university hospital. Twenty patients at risk for ARDS and 45 patients with established ARDS. Patients at risk for ARDS underwent bronchoalveolar lavage within 24 hrs of being identified, then again 72 hrs later. Patients with ARDS underwent bronchoalveolar lavage within 24 hrs of meeting ARDS criteria, then again on days 3, 7, and 14 of the disease. Normal peripheral blood neutrophil were incubated overnight in BALF from normal volunteers, from patients at risk for ARDS, or from patients with ARDS. neutrophil apoptosis was determined by flow cytometric analysis of annexin V binding. G-CSF and GM-CSF were measured in BALF by immunoassays. Compared with normal BALF, BALF from patients on days 1 and 3 of ARDS inhibited neutrophil apoptosis, but BALF from patients at later stages of ARDS, or from patients at risk for ARDS, did not. The BALF concentrations of both G-CSF and GM-CSF were elevated early in ARDS and decreased toward later stages. Patients who lived had significantly higher concentrations of GM-CSF in the BALF than those who died. We conclude that the antiapoptotic effect of ARDS BALF on normal neutrophil is highest during early ARDS, and decreases during late ARDS. G-CSF and GM-CSF are present in BALF from patients with ARDS, and their concentrations parallel the antiapoptotic effect of ARDS BALF. These data support the concept that the life-span of neutrophil in the air spaces is modulated during acute inflammation. GM-CSF in the air spaces is associated with improved survival in patients with ARDS.

Early and late acute respiratory distress syndrome: two distinct clinical entities.

Despite numerous advances in surgical critical care and ventilatory management, mortality rates for acute respiratory distress syndrome (ARDS) have remained relatively constant. Pressure-limited and non-pressure-limited ventilatory techniques have been advocated with disparate results. We hypothesized that there are two forms of ARDS, which may account for the conflicting clinical reports. Patients with posttraumatic ARDS were identified and reviewed. ARDS was defined as PaO2/FiO2 ratio less than 200 with diffuse bilateral infiltrates on chest radiograph and no congestive heart failure. Patients were analyzed relative to injury mechanism, transfusions, fluid balance, presence of pneumonia (defined as > or =10(5) colony-forming units/mL in bronchoalveolar lavage effluent), and outcome. All were managed with a non-pressure-limited strategy. During a 5.5-year period, 178 patients with posttraumatic ARDS were identified. Mean Injury Severity Score and age were 29 and 40 years, respectively. Patients were stratified by time of ARDS diagnosis. Eighty-two patients (46%) had early ARDS (within 48 hours after admission), and 96 patients (54%) had late ARDS (>48 hours between admission and diagnosis). There were no differences in Injury Severity Score, but the late group was significantly older. The early ARDS group was characterized by profound hemorrhagic shock and had significant differences from the late group in incidence of penetrating injury (30 vs. 10%; p<0.001), admission base deficit (-7.7 vs. -4.2 mEq/L; p<0.001), 48-hour transfusions (19.7 vs. 9.4; p<0.0001), initial 5-day fluid balance (19.9 vs. 10.1 L; p<0.0001), and initial PaO2/FiO2 (121 vs. 141; p<0.007). Pneumonia before ARDS was significantly associated with late ARDS (38 vs. 9%; p<0.001). ARDS-related mortality was primarily caused by hemorrhagic shock in the early group and progressive multiple organ failure in the late group. There are two distinct forms of posttraumatic ARDS. Early ARDS is characterized by hemorrhagic shock with capillary leak. Late ARDS frequently follows pneumonia and is associated with multiple system injury. Further studies should differentiate between these two distinct syndromes.

Bronchoalveolar lavage fluid characteristics of early intermediate and late phases of ARDS. Alterations in leukocytes, proteins, PAF and surfactant components.

To determine the concentration of proteins and phospholipids, markers of inflammatory reaction such as platelet-activating factor (PAF), and cell alterations in bronchoalveolar lavage (BAL) fluid during the evolution of the acute respiratory distress syndrome (ARDS). Prospective controlled study. 14-bed medical-surgical intensive care unit in a 750-bed university teaching hospital. 19 mechanically ventilated patients, 9 patients with ARDS and 10 patients without cardiopulmonary disease (controls), were eligible for this study. BAL was performed during the early, intermediate, and late phases of ARDS. Total phospholipids and individual phospholipid classes of the surfactant, proteins, PAF, and cells were measured. High levels of PAF, an increase in neutrophils and proteins, and quantitative as well as qualitative alterations in phospholipids in BAL fluid were observed in ARDS patients compared to the control group. PAF, proteins, and neutrophils were higher in early ARDS than in intermediate or late ARDS. The surfactant pool increased in the early phase and decreased in the intermediate or late phase of the syndrome. The qualitative alterations of surfactant consist of reduced phospholipid content in the surfactant structures with good surface properties; moreover, there was a considerable decrease in the percentage of phosphatidylcholine and phosphatidylglycerol, followed by an increase in phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, and sphingomyelin in all three phases of ARDS compared to the control group. Lysophosphatidylcholine was detectable only in late ARDS. Total surfactant phospholipids, surfactant components, and inflammatory markers such as PAF, cells, and proteins were affected in patients with ARDS. These factors, undergoing quantitative alterations during the course of ARDS, could have a significant role in the pathogenesis and evolution of ARDS.

Are corticosteroids salvage therapy for refractory acute respiratory distress syndrome?

Background: Late acute respiratory distress syndrome (ARDS), characterized by progressive pulmonary interstitial fibroproliferation, is associated with mortality >80%. Although previous large prospective trials failed to show a benefit of steroids in early ARDS, recent small reports describe improved survival in patients with late ARDS. Recognizing the pathogenetic differences between early and late ARDS, we employed steroid therapy in patients with refractory late ARDS. Patients and methods: Over a 5-year period, we treated 6 patients who were dying of isolated refractory ARDS with methylprednisolone sodium succinate (1 to 2 mg/kg every 6 hours). Ventilatory parameters and lung injury scores were serially recorded, and steroids were weaned based on clinical response. Results: Steroids were instituted after 16 days of advanced mechanical ventilatory support. By day 7 of steroid therapy, there was clinically significant improvement in PaO 2 FiO 2 ratios (84 to 172) and lung injury scores (3.6 to 2.9); 5 patients (83%) survived. Conclusions: Steroid therapy appears to be effective in patients with refractory late ARDS. Prospective trials are needed to define the indications, timing of intervention, dose and duration, and precautions of steroid therapy.