Cytokines in adult respiratory distress syndrome.
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Biomedical subjects
Publications and source records attributed to C Gibert.
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OBJECTIVE: To evaluate the sensitivity, specificity and overall accuracy of a model based on the presence or absence of organ dysfunctions and/or infection (ODIN) to predict the outcome for intensive care unit patients. DESIGN: Prospective study. SETTING: General intensive care unit in a university teaching hospital. PATIENTS: 1070 consecutive, unselected patients. INTERVENTIONS: There were no interventions. MEASUREMENTS AND MAIN RESULTS: We recorded within the first 24 h of admission the presence or absence of dysfunction in 6 organ systems: respiratory, cardiovascular, renal, hematologic, hepatic and neurologic, and/or infection (ODIN) in all patients admitted to our ICU, thus establishing a profile of organ dysfunctions in each patient. Using univariate analysis, a strong correlation was found between the number of ODIN and the death rate (2.6, 9.7, 16.7, 32.3, 64.9, 75.9, 94.4 and 100% for 0, 1, 2, 3, 4, 5, 6 and 7 ODIN, respectively; (p < 0.001). In addition, the highest mortality rates were associated with hepatic (60.8%), hematologic (58.1%) and renal (54.8%) dysfunctions, and the lowest with respiratory dysfunction (36.5%) and infection (38.3%). For taking into account both the number and the type of organ dysfunction, a logistic regression model was then used to calculate individual probabilities of death that depended upon the statistical weight assigned to each ODIN (in the following order of descending severity: cardiovascular, renal, respiratory, neurologic, hematologic, hepatic dysfunctions and infection). The ability of this severity-of-disease classification system to stratify a wide variety of patients prognostically (sensitivity 51.4%, specificity 93.4%, overall accuracy 82.1%) was not different from that of currently used scoring systems. CONCLUSIONS: These findings suggest that determination of the number and the type of organ dysfunctions and infection offers a clear and reliable method for characterizing ICU patients. Before a widespread use, this model requires to be validated in other institutions.
PURPOSE: Although nosocomial pneumonia is a common problem in intubated and ventilated patients, previous studies have not clearly demonstrated that nosocomial pneumonia actually results in increased mortality or prolongs hospitalization of these patients. In an attempt to answer these questions, we have performed a cohort study in which patients who developed nosocomial pneumonia and control subjects were carefully matched for the severity of underlying illness and other important variables. PATIENTS AND METHODS: Case patients were 48 ventilated patients with nosocomial pneumonia identified on the basis of results of protected specimen brush quantitative culture and identification of intracellular organisms in cells recovered by bronchoalveolar lavage. For matching cases and their respective controls, the following variables were used: age (+/- 5 years), Simplified Acute Physiologic Score (+/- 3 points), indication for ventilatory support, date of admission, and duration of exposure to risk. RESULTS: Successful matching was achieved for 222 of 240 (92.5%) variables. The mortality rate in cases was 26 of 48 (54.2%) compared with 13 of 48 (27.1%) in controls. The attributable mortality was 27.1% (95% confidence interval [CI], 8.3% to 45.9%; p < 0.01) and the risk ratio for death was 2.0 (95% CI, 1.61 to 2.49). The mean length of stay was 34 days for cases and 21 days for controls (p < 0.02). In the case of pneumonia due to Pseudomonas or Acinetobacter species, the mortality rate was 71.4%, the attributable mortality was 42.8% (95% CI, 14.5% to 69.0%), and the risk ratio was 2.50 (95% CI, 1.31 to 4.61). CONCLUSION: Pneumonias occurring in ventilated patients, especially those due to Pseudomonas or Acinetobacter species, are associated with considerable mortality in excess of that resulting from the underlying disease alone, and significantly prolong the length of stay in the intensive care unit.
Vancomycin penetration into the fluid lining the epithelial surface of the lower respiratory tract was studied by performing fiberoptic bronchoscopy with bronchoalveolar lavage on 14 critically ill, ventilated patients who had received the drug for at least 5 days. The apparent volume of epithelial lining fluid (ELF) recovered by bronchoalveolar lavage was determined by using urea as an endogenous marker. Vancomycin levels in ELF ranged from 0.4 to 8.1 micrograms/ml (mean, 4.5 micrograms/ml), while the mean simultaneous level of the drug in plasma was 24 micrograms/ml (range, 9 to 37.4 micrograms/ml). There was a significant relationship (r = 0.64, P < 0.02) between vancomycin levels in plasma and those in ELF, with a correlation whose slope (0.15) indicated that the blood-to-ELF ratio of drug penetration was 6:1. Using the albumin concentration in ELF as a marker of lung inflammation, we found that vancomycin penetration was higher in patients with ELF albumin values of > or = 3.4 mg/ml than in patients with normal values (< 3.4 mg/ml) (P < 0.02). These results suggest that the vancomycin distribution includes the ELF of the lower respiratory tract at a concentration that is dependent upon the levels in blood and the alveolar capillary membrane protein permeability. These concentrations were well above the MICs for most staphylococci and enterococci.
There is ample experimental evidence that polymorphonuclear neutrophils (PMN) play a critical role in the pathogenesis of the adult respiratory distress syndrome (ARDS). Since interleukin-8 (IL-8) is a strong chemotactic factor for PMN, we measured IL-8 levels in plasma and bronchoalveolar lavage (BAL) fluid of 18 patients, 12 with ARDS and 6 with severe pneumonia uncomplicated by ARDS, all of whom had an increased number of PMN in BAL fluid. Seven healthy subjects served as controls. We found elevated levels of IL-8 in the alveolar spaces of all patients tested. Elevated BAL IL-8 levels were related to a fatal outcome and the presence of shock and correlated with a general clinical severity index (simplified acute physiological score). BAL fluid levels of IL-8 were significantly higher in patients with ARDS than in patients with pneumonia. In plasma, IL-8 levels were increased similarly in all patients and did not correlate with survival or the presence of shock. The BAL fluid-to-plasma ratio of IL-8 was significantly greater than that of tumor necrosis factor alpha, indicating higher local production of IL-8. Moreover, the presence of a primed subpopulation of blood PMN with respect to H2O2 production indicates that IL-8 may contribute to the neutrophil-mediated process in the pathogenesis of ARDS and pneumonia.
To prospectively determine the bacteriologic and clinical efficacy of antimicrobial therapy for nosocomial bacterial pneumonia selected based upon information provided by cultures of protected specimen brush (PSB) samples obtained during bronchoscopy, 76 consecutive patients with ventilator-associated pneumonia were studied using follow-up quantitative PSB cultures obtained after 3 days of treatment. Of the 173 microorganisms initially present in the PSB samples, only 11 (6%) were not eradicated by antimicrobial therapy, including three recovered at high (> or = 10(3) cfu/ml) concentrations. Thirty-two emerging pathogens, including nine at high concentrations, were also detected; 26 of them (81%) were resistant to the initial antibiotics administered. Of the 76 patients included in the study, cultures of follow-up PSB samples identified 51 in whom the infection site in the lung was completely sterilized, 16 with low-grade infection, and only nine with persistent high-grade infection. Analysis of clinical outcome within the 15 days after the initiation of antimicrobial therapy demonstrated clinical improvement in 62 of 67 (93%) patients in whom the site of infection was contained by treatment as compared with four of 9 (44%) patients with persistent high-grade infection (p < 0.01). These data suggest that appropriate antimicrobial therapy for ventilator-associated pneumonia results in the control of the initial infection in 88% of the patients. However, an early superinfection caused by multiresistant pathogens can occur in a small subset of these patients. When follow-up PSB cultures were negative, an improved outcome was noted.
To evaluate the accuracy of clinical judgment in the diagnosis and treatment of nosocomial pneumonia in ventilated patients, we studied 84 patients suspected of having nosocomial pneumonia because of the presence of a new pulmonary infiltrate and purulent tracheal secretions. We prospectively evaluated the accuracy of diagnostic predictions and therapeutic plans independently formulated by a team of physicians aware of all clinical, radiologic and laboratory data, including the results of Gram-stained bronchial aspirates. Definite (n = 51) or probable (n = 33) diagnoses could be established in all patients by strict histopathologic and/or bacteriologic criteria. Only 27/84 patients were diagnosed as having pneumonia. Organisms responsible for pneumonias were identified by quantitative cultures of samples obtained using a protected specimen brush or pleural fluid cultures. Four hundred eight predictions were made for the 84 studied patients. Clinical diagnoses for patients subsequently diagnosed as having pneumonia were accurate in 81/131 cases (62 percent). Furthermore, only 43/131 (33 percent) therapeutic plans proposed for these patients represented effective therapy. Common causes of inappropriate treatment included failure to diagnose pneumonia (50 plans), failure to effectively treat highly resistant organisms (21 plans), and failure to treat all organisms in cases of polymicrobial pneumonia (14 plans). Therapeutic plans formulated for patients without pneumonia included the unnecessary use of antibiotics in 45/277 cases (16 percent). These findings indicate that the use of clinical criteria alone does not permit the accurate diagnosis of nosocomial pneumonia in ventilated patients, and commonly results in inappropriate or inadequate antibiotic therapy for these patients.
To gain further insight into the pathogenesis of the adult respiratory distress syndrome (ARDS), the authors studied possible relationships among the activation status of circulating polymorphonuclear neutrophils (PMN), cytokine levels, and the severity of lung injury in 31 patients: 15 with ARDS, 9 with severe pneumonia uncomplicated by ARDS, and 7 mechanically ventilated patients with neither ARDS nor pneumonia. Nine healthy subjects served as controls. Using flow cytometry, the authors identified a subpopulation of PMN with an increased capacity to generate hydrogen peroxide after stimulation ex vivo in all three patient groups; significantly higher values were found in those with ARDS. The PMN stimulation index, a reflection of the degree of hyperresponsiveness, correlated with elevated levels of tumor necrosis factor alpha (TNF-alpha) in plasma, and both spontaneous and lipopolysaccharide (LPS)-induced TNF-alpha production by cultured monocytes. These biological expressions of PMN activation and cytokine generation both correlated with indices of the severity of lung injury, but not with the overall clinical severity. In contrast, IL-6 and IL-1 beta showed little or no relationship with either the degree of lung injury or PMN hyperresponsiveness. We conclude that TNF alpha-primed PMN may play a major role in the pathogenesis of ARDS-associated lung injury.
From January 1978 to December 1988, 71 patients underwent surgical intervention at our institution for prosthetic valve endocarditis with ring abscesses. These procedures involved 59 aortic prostheses and 12 mitral prostheses. No causative agent could be identified in 19 patients (26.7%). The operation was performed during antibiotic therapy in 63 patients and after a planned course of antibiotic therapy in 8 patients. At the aortic level, abscesses were remedied by suturing in 3 cases, by pericardial patches in 34 cases, and by complex procedures in 22 cases (subcoronary valved conduit in 11 cases, supracoronary valved conduit with coronary bypass grafts in 10 cases, apicoaortic valved conduit in 1 case). At the mitral level, ring abscesses were cured in 10 cases by intraatrial implantation of the prosthesis. In one case, the prosthesis was anchored inside the left ventricle; and in one case the valve could be seated on the anulus. The overall operative mortality rate was 17%. Long-term survival was 54% +/- 8% at 6 years. Fifteen (26%) of the survivors needed a third valve replacement (four operative deaths); a complex reconstruction was performed in seven patients. Better detection of ring abscesses and earlier surgical intervention before annular destruction and hemodynamic failure can improve the operative mortality rate for prosthetic valve endocarditis. When it is necessary, complex reconstruction, in spite of a high mortality rate, seems to eradicate the infectious seat, and the outlook for the patient's condition appears good.
To gain further insight into the pathogenesis of the adult respiratory distress syndrome (ARDS), we studied possible relationships among the activation status of circulating polymorphonuclear neutrophils (PMN), cytokine levels, and the severity of lung injury in 31 patients: 15 with ARDS, nine with severe pneumonia uncomplicated by ARDS, and seven mechanically ventilated with neither ARDS nor pneumonia. Nine healthy subjects served as controls. Using flow cytometry, we identified a subpopulation of PMN with an increased capacity to generate hydrogen peroxide after stimulation ex vivo in all three patient groups; significantly higher values were found in those with ARDS. The PMN stimulation index, a reflection of the degree of hyperresponsiveness, correlated with elevated levels of tumor necrosis factor-alpha (TNF alpha) in plasma, and both spontaneous and lipopolysaccharide-induced TNF alpha production by cultured monocytes. These biologic expressions of PMN activation and cytokine generation both correlated with indices of the severity of lung injury, but not with the overall clinical severity. In contrast, IL-6 and IL-1 beta showed little or no relationship with either the degree of lung injury or PMN hyperresponsiveness. We conclude that TNF-alpha-primed PMN may play a major role in the pathogenesis of ARDS-associated lung injury.
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OBJECTIVE: To evaluate the usefulness of bronchoalveolar lavage in establishing the diagnosis of the fat embolism syndrome in trauma patients with long-bone fractures. DESIGN: Case series. SETTING: Referral hospital. PATIENTS: Eighteen trauma patients with long-bone fractures, including 5 with definite fat embolism syndrome, 5 in whom the diagnosis had been clinically suspected but was impossible to confirm or exclude before bronchoscopy, and 8 with no clinical evidence of the syndrome. Control groups included 9 patients without previous trauma who developed the adult respiratory distress syndrome for various reasons and 15 normal volunteers. MEASUREMENTS AND MAIN RESULTS: Each patient had fiber-optic bronchoscopy with bronchoalveolar lavage, and the percentage of lavage cells containing intracellular fat droplets stained with oil red 0 were determined. In the five patients with definite fat embolism syndrome, light microscopic study of bronchoalveolar cells stained with oil red 0 showed many large intracellular fat droplets (mean percentage of cells containing fat droplets, 63%; range, 31% to 82%), whereas less than 2% of cells recovered by lavage from trauma patients with no clinical evidence of the syndrome, from patients with the adult respiratory distress syndrome, or from normal volunteers contained such inclusions. Use of the same technique in the five patients with possible fat embolism syndrome permitted the immediate identification of three patients in whom this diagnosis was later confirmed by subsequent autopsy or clinical follow-up. CONCLUSIONS: The identification of fat droplets within cells recovered by bronchoalveolar lavage in trauma patients may be a rapid and specific method for establishing the diagnosis of the fat embolism syndrome.
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The prevalence of human immunodeficiency virus (HIV) and hepatitis B virus in serial unselected hospital admissions was determined to examine the potential efficacy of a system of universal blood and body fluid precautions versus a system based on selected or unselected screening. Serum was obtained from 616 (97%) of the 636 patients admitted during a 1-month period and interviews were completed on 540. Of the 616, 23 (3.7%) were confirmed positive for HIV, and 12 (2.0%) of 612 for hepatitis B surface antigen. Of 33 infected persons, only 8 were known to be positive on admission and only 22 were in "high-risk" groups; therefore, selective precautions would not have been effective. Mandatory testing would have required 1216 tests to identify 25 infected persons and would leave in doubt the presence of other transmissible diseases. On the basis of these data, it appears that universal precautions are a logical system of infection control.
To obtain accurate information on distal bronchial microflora during acute exacerbation in patients with chronic bronchitis, we prospectively studied 54 such patients who had been receiving mechanical ventilation because of hypercapnic respiratory failure. Fiberoptic bronchoscopy using a protected specimen brush (PSB) was performed on each patient within the first 24 h after admission. Cultures of protected brush specimens demonstrated no growth in 27 patients (50%). With the exception of fever (38.2 +/- 0.8 versus 37.7 +/- 0.6 degrees C; p less than 0.05), the initial severity of the episode of exacerbation was similar in patients with and without infection. A total of 44 organisms were isolated in the 27 patients with positive cultures; the predominant pathogens were Hemophilus spp. and Streptococcus spp. (involved in 74% of cases), but other organisms were isolated in 12 of 27 patients. Mortality rates, duration of mechanical ventilation, and duration of hospitalization were not significantly different between patients with bronchial microflora treated with appropriate antimicrobial therapy (n = 27) and patients without bronchial microflora either receiving empirical antibiotic therapy (n = 18) or not (n = 9). These data suggest that distal bronchial infection due to the usual pathogens, as far as shown by protected specimen brush cultures, may not be the sole or even the predominant cause of acute exacerbation of chronic bronchitis in patients requiring mechanical ventilation.