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BACKGROUND - Routine manometry is recommended to prevent complications during therapeutic thoracentesis, but has not definitively been shown to prevent pneumothorax or reexpansion pulmonary edema. As chest discomfort correlates with negative pleural pressures, we aimed to determine whether the use of manometry could anticipate the development of chest discomfort during therapeutic thoracentesis.
METHODS - A retrospective chart review of 214 consecutive adults who underwent outpatient therapeutic thoracentesis at our institution between January 1, 2011 and June 30, 2013 was performed. We compared preprocedural to postprocedural discomfort (using a linear analog scale from 0 to 10) in patients undergoing thoracentesis with or without manometry. We used a multivariate model to adjust for possible confounders. Changes of dyspnea scores were also analyzed.
RESULTS - Manometry was performed in 82/214 patients (38%). On univariate and multivariate analyses, neither the change in chest discomfort nor dyspnea scores was significantly different in the manometry versus the control group (P=0.12 and 0.24, respectively). Similar results were also found in the subgroup of large-volume thoracentesis (P=0.32 for discomfort, P=1.0 for dyspnea).
CONCLUSIONS - In our retrospective study, the use of manometry did not appear to anticipate the development of chest discomfort during therapeutic thoracentesis. Prospective studies are needed to confirm these findings.
The rate of alveolar fluid clearance (AFC) is associated with mortality in clinical acute lung injury (ALI). Patients with ALI often develop circulatory shock, but how shock affects the rate of AFC is unknown. To determine the effect of circulatory shock on the rate of AFC in patients with ALI, the rate of net AFC was measured in 116 patients with ALI by serial sampling of pulmonary edema fluid. The primary outcome was the rate of AFC in patients with shock compared with those without shock. We also tested the effects of shock severity and bacteremia. Patients with ALI and shock (n = 86) had significantly slower rates of net AFC compared with those without shock (n = 30, P = 0.03), and AFC decreased significantly as the number of vasopressors increased. Patients with positive blood cultures (n = 21) had slower AFC compared with patients with negative blood cultures (n = 96, P = 0.023). In addition, the edema fluid-to-plasma protein ratio, an index of alveolar-capillary barrier permeability, was highest in patients requiring the most vasopressors (P < 0.05). Patients with ALI complicated by circulatory shock and bacteremia had slower rates of AFC compared with patients without shock or bacteremia. An impaired capacity to reabsorb alveolar edema fluid may contribute to high mortality among patients with sepsis-induced ALI. These findings also suggest that vasopressor use may be a marker of alveolar-capillary barrier permeability in ALI and provide justification for new therapies that enhance alveolar epithelial and endothelial barrier integrity in ALI, particularly in patients with shock.
The clinical presentation of beriberi can be quite varied. In the extreme form, profound cardiovascular involvement leads to circulatory collapse and death. This case report is of a 72 year-old male who was admitted to the Neurology inpatient ward with progressive bilateral lower extremity weakness and parasthesia. He subsequently developed pulmonary edema and high output cardiac failure requiring intubation and blood pressure support. With the constellation of peripheral neuropathy, encephalopathy, ophthalmoplegia, unexplained heart failure, and lactic acidosis, thiamine deficiency was suspected. He was empirically initiated on thiamine replacement therapy and his thiamine level pre-therapy was found to be 23 nmol/L (Normal: 80-150 nmol/L), consistent with the diagnosis of beriberi. Cardiovascular magnetic resonance (CMR) showed severe left ventricular systolic dysfunction, markedly increased myocardial T2, and minimal late gadolinium enhancement (LGE). After 5 days of daily 100 mg IV thiamine and supportive care, the hypotension resolved and the patient was extubated and was released from the hospital 3 weeks later. Our case shows via CMR profound myocardial edema associated with wet beriberi.
PURPOSE - Studies suggest that there is a sex difference in the development and outcomes of acute lung injury (ALI). Few studies have directly addressed the association of sex and alveolar fluid clearance (AFC), a process that is critical to ALI resolution.
MATERIALS AND METHODS - To test the hypothesis that female sex is associated with an increased AFC rate, we measured AFC rates in 150 mechanically ventilated patients with acute pulmonary edema and a pulmonary edema fluid-to-plasma protein ratio (EF/PL) diagnostic of low permeability (EF/PL <0.65, n = 69) or high permeability (EF/PL ≥0.65, n = 81) edema. We measured protein concentration in serial samples of undiluted EF collected within 6 hours of intubation and calculated net rate of AFC. In addition, plasma levels of receptor for advanced glycation end products were measured as a surrogate marker for alveolar epithelial injury.
RESULTS - In patients with ALI, women had higher rates of net AFC at 4 hours compared to men (11.9% per hour vs 4.3% per hour, P = .017) and more women had maximal rates of AFC. There were no differences in circulating levels of receptor for advanced glycation end products between men and women.
CONCLUSIONS - These findings may have significant implications for future ALI studies and potential therapies.
Published by Elsevier Inc.
We hypothesised that the oedema fluid-to-plasma protein (EF/PL) ratio, a noninvasive measure of alveolar capillary membrane permeability, can accurately determine the aetiology of acute pulmonary oedema. 390 mechanically ventilated patients with acute pulmonary oedema were enrolled. A clinical diagnosis of acute lung injury (ALI), cardiogenic pulmonary oedema or a mixed aetiology was based on expert medical record review at the end of hospitalisation. The EF/PL ratio was measured from pulmonary oedema fluid and plasma samples collected at intubation. 209 patients had a clinical diagnosis of ALI, 147 had a diagnosis of cardiogenic pulmonary oedema and 34 had a mixed aetiology. The EF/PL ratio had an area under the receiver-operating curve of 0.84 for differentiating ALI from cardiogenic pulmonary oedema. Using a predefined cut-off of 0.65, the EF/PL ratio had a sensitivity of 81% and a specificity of 81% for the diagnosis of ALI. An EF/PL ratio >/=0.65 was also associated with significantly higher mortality and fewer ventilator-free days. Noninvasive measurement of the EF/PL ratio is a safe and reliable bedside method for rapidly determining the aetiology of acute pulmonary oedema that can be used at the bedside in both developed and developing countries.
Coagulation and fibrinolysis abnormalities are observed in acute lung injury (ALI) in both human disease and animal models and may contribute to ongoing inflammation in the lung. Tissue factor (TF), the main initiator of the coagulation cascade, is upregulated in the lungs of patients with ALI/acute respiratory distress syndrome (ARDS) and likely contributes to fibrin deposition in the air space. The mechanisms that govern TF upregulation and activation in the lung are not well understood. In the vascular space, TF-bearing microparticles (MPs) are central to clot formation and propagation. We hypothesized that TF-bearing MPs in the lungs of patients with ARDS contribute to the procoagulant phenotype in the air space during acute injury and that the alveolar epithelium is one potential source of TF MPs. We studied pulmonary edema fluid collected from patients with ARDS compared with a control group of patients with hydrostatic pulmonary edema. Patients with ARDS have higher concentrations of MPs in the lung compared with patients with hydrostatic edema (25.5 IQR 21.3-46.9 vs. 7.8 IQR 2.3-27.5 micromol/l, P = 0.009 by Mann-Whitney U-test). These MPs are enriched for TF, have procoagulant activity, and likely originate from the alveolar epithelium [as measured by elevated levels of RAGE (receptor for advanced glycation end products) in ARDS MPs compared with hydrostatic MPs]. Furthermore, alveolar epithelial cells in culture release procoagulant TF MPs in response to a proinflammatory stimulus. These findings suggest that alveolar epithelial-derived MPs are one potential source of TF procoagulant activity in the air space in ARDS and that epithelial MP formation and release may represent a unique therapeutic target in ARDS.
The alveolar compartment in acute lung injury contains high levels of tissue factor (TF) procoagulant activity favoring fibrin deposition. We previously reported that the alveolar epithelium can release TF procoagulant activity in response to a proinflammatory stimulus. To test the hypothesis that the alveolar epithelium further modulates intra-alveolar fibrin deposition through secretion of an endogenous inhibitor to TF, tissue factor pathway inhibitor (TFPI), we measured TFPI levels in edema fluid (EF) from patients with acute respiratory distress syndrome. To determine whether the alveolar epithelium can release TFPI, both full-length TFPI and truncated TFPI were measured (ELISA) in pulmonary edema fluid from patients with acute respiratory distress syndrome (ARDS) and a control group of patients with hydrostatic pulmonary edema (HYDRO). TFPI protein was also measured in conditioned media (CM) and cell lysates (CL) from human alveolar epithelial cells (A549) after exposure to cytomix (TNF-alpha, IL-1 beta, IFN-gamma). TFPI protein levels were higher in pulmonary edema fluid from patients with ARDS vs. HYDRO. TFPI protein was increased in CM and did not change in CL after cytomix treatment; TFPI mRNA levels (RT-PCR) did not change. Despite the high levels of TFPI, both the EF and CM retained significant TF procoagulant activity as measured by plasma recalcification time. The majority of intra-alveolar TFPI was in a truncated, inactive form, whereas the majority of TFPI released from cells was full length, suggesting different mechanisms of inactivation. In summary, the alveolar epithelium releases TFPI in response to an inflammatory stimulus but does not increase TFPI gene transcription or protein production. Levels of intra-alveolar TFPI in ARDS are not sufficient to block intra-alveolar TF procoagulant activity due to truncation and inactivation of intra-alveolar TFPI.
BACKGROUND - The alveolar compartment is a procoagulant antifibrinolytic environment in acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). A study was undertaken to test the hypothesis that the alveolar epithelium can initiate intra-alveolar coagulation by expressing active tissue factor (TF).
METHODS - Using an in vitro cell surface TF assay and TF ELISA, the activity and production of TF in cultured alveolar epithelial (A549) cells following exposure to cytomix (tumour necrosis factor alpha, interleukin 1beta and interferon gamma) was measured. TF gene transcription was measured by semi-quantitative reverse-transcription PCR. Immunohistochemistry for TF was performed on lung sections from patients with ARDS and controls. TF protein levels were measured by ELISA in undiluted pulmonary oedema fluid from patients with ALI/ARDS and compared with control patients with hydrostatic pulmonary oedema.
RESULTS - TF activity, mRNA and protein levels increased in A549 cells after stimulation with cytomix. Increased TF activity was also seen in A549 cells following incubation with pulmonary oedema fluid from patients with ALI/ARDS. Immunohistochemistry for TF in human lung tissue from patients with ARDS showed prominent TF staining in alveolar epithelial cells as well as intra-alveolar macrophages and hyaline membranes. TF antigen levels in oedema fluid (median 37 113 (IQR 14 956-73 525) pg/ml) were significantly higher than in plasma (median 336 (IQR 165-669) pg/ml, p<0.001) in patients with ALI/ARDS, and TF procoagulant activity in oedema fluid was much higher than in plasma of these patients. Higher plasma levels were associated with mortality.
CONCLUSIONS - The alveolar epithelium is capable of modulating intra-alveolar coagulation through upregulation of TF following exposure to inflammatory stimuli and may contribute to intra-alveolar fibrin deposition in ARDS.
Intra-alveolar fibrin deposition is a common response to localized and diffuse lung infection and acute lung injury (ALI). We hypothesized that the alveolar epithelium modulates intra-alveolar fibrin deposition through activation of protein C. Our objectives [corrected] were to determine whether components of the protein C activation pathway are present in the alveolar compartment in ALI and whether alveolar epithelium is a potential source. In patients with ALI, pulmonary edema fluid levels of endothelial protein C receptor (EPCR) were higher than plasma, suggesting a source in the lung. To determine whether alveolar epithelial cells are a potential source, protein C activation by A549, small airway epithelial, and primary human alveolar epithelial type II cells was measured. All three cell types express thrombomodulin (TM) and EPCR, and activate protein C on the cell surface. Activation of protein C was inhibited by cytomix (TNF-alpha, IL-1beta, and IFN-gamma). Release of EPCR and TM into the conditioned medium was inhibited by the metalloproteinase inhibitors tumor necrosis factor protease inhibitor (TAPI) and GM6001, indicating that the shedding of EPCR and TM from the alveolar epithelium is mediated by a metalloproteinase. These findings provide new evidence that the alveolar epithelium can modulate the protein C pathway and thus could be an important determinant of alveolar fibrin deposition. Local fibrin deposition may be a fundamental mechanism for the lung to localize and confine injury, thus limiting the risk of dissemination of injury or infection to the systemic circulation.