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Jean-Yves Fagon

Publications and source records attributed to Jean-Yves Fagon.

36 records · Page 2Linked to original sources
PubMed2004

Nociceptin inhibits vanilloid TRPV-1-mediated neurosensitization induced by fenoterol in human isolated bronchi.

Chronic exposure to beta(2)-adrenoceptor agonists, especially fenoterol, has been shown to increase smooth muscle contraction to endothelin-1 in human bronchi partly through tachykinin-mediated pathways. The purpose of this work was to further investigate the role of sensory nerves in fenoterol-induced sensitization of human airways and the effect of nociceptin, a nociceptin/orphanin FQ (NOP) receptor agonist, on the increase in contraction after fenoterol exposure. Human bronchi from 62 patients were sensitized to endothelin-1 by prolonged incubation with fenoterol (0.1 microM, 15 h). The sensitizing effect of fenoterol was inhibited by high concentration of capsaicin (10 microM, 30 min before fenoterol sensitization), which induces depletion of mediators from sensory nerves, or co-incubation of fenoterol and capsazepine (1 microM), a vanilloid TRPV-1 receptor antagonist. Moreover, short pretreatment of bronchi with capsaicin (10 microM) or capsazepine (1 microM) after sensitization by fenoterol decreased the rise in smooth muscle contraction to endothelin-1. Nociceptin (1 microM) also inhibited the increased contraction in fenoterol-sensitized bronchi. Tertiapin (10 microM), an inhibitor of the inward-rectifier K(+) channels, but not naloxone (0.1 microM), a DOP/KOP/MOP receptor antagonist, prevented the inhibitory effect of nociceptin. In conclusion, fenoterol induces sensitization of human isolated bronchi to endothelin-1 in part through the stimulation of the vanilloid TRPV-1 receptor on tachykininergic sensory nerves. Nociceptin inhibits airway hyperresponsiveness via NOP receptor activation. This effect involves inward-rectifier K(+) channels.

Adrenergic beta-Agonists↗
PubMed2004

Impact of methicillin resistance on outcome of Staphylococcus aureus ventilator-associated pneumonia.

The impact of methicillin resistance on morbidity and mortality of patients suffering from severe Staphylococcus aureus infections remains highly controversial. We analyzed a retrospective cohort of 97 patients with methicillin-susceptible and 74 patients with methicillin-resistant Staphylococcus aureus ventilator-associated pneumonia (VAP). Initial empiric antibiotic therapy was appropriate for every patient. Patients with methicillin-resistant Staphylococcus aureus VAP were older, had higher disease-severity scores, and had been on mechanical ventilation longer at onset of VAP. Factors associated with 28-day mortality retained by multivariate logistic regression analysis were: age (odds ratio [OR] = 1.05, 95% confidence interval [CI], 1.02-1.08, p = 0.001) and Day 1 organ dysfunctions or infection (ODIN) score (OR = 1.90, 95% CI, 1.31-2.78, p = 0.001), but not methicillin resistance (OR = 1.72, 95% CI, 0.73-4.05, p = 0.22). The percentages of infection relapse or superinfection did not differ significantly between the two patient groups. In conclusion, after controlling for clinical and physiologic heterogeneity between groups, methicillin resistance did not significantly affect 28-day mortality of patients with Staphylococcus aureus VAP receiving appropriate antibiotics.

Age Distribution↗
PubMed2004

[Nosocomial pneumonia].

Nosocomial pneumonia complicates the course of a large number of hospitalized patients, associated with a higher risk of death, prolonged length of stay and over-costs. Rates of pneumonia are considerably higher in the ICU, in the post-operative period, particularly in patients treated with mechanical ventilation. Microorganisms responsible for nosocomial pneumonia are frequently multiresistant, particularly in case of late-onset pneumonia and in patients receiving prior antimicrobial therapy. Management of patients suspected of having nosocomial pneumonia aims to identify patients with true lung infection and not only colonization of the lower respiratory tract, to identify responsible pathogen(s) and to optimize the choice of antimicrobial therapy. To do that, bronchoscopic techniques with the use of bronchoalveolar lavage or protected specimen brush have the best sensitivity and specificity. Appropriate antimicrobial treatment must be initiated without delay. The potential interest of combination therapy, nebulized antibiotics needs to be clearly demonstrated by further investigations; similarly the optimal duration of treatment ensuring efficacy and avoiding the emergence and development of infections due to multiresistant pathogens remains to be more precisely evaluated.

Anti-Bacterial Agents↗
PubMed2004

Value of the clinical pulmonary infection score for the identification and management of ventilator-associated pneumonia.

OBJECTIVE: To evaluate the potential ability of an algorithm based on the clinical pulmonary infection score (CPIS) to identify and treat patients with bacterial ventilator-associated pneumonia (VAP) compared to a strategy based on quantitative cultures of bronchoscopic specimens. DESIGN: Retrospective cohort study. SETTING: Thirty-one critical care units across France. PATIENTS: Two hundred and one patients clinically suspected of having VAP who had been included in the "invasive strategy" group of the French multicenter randomized trial and for whose quantitative cultures bronchoscopic specimens were obtained. CPIS was determined retrospectively, based on data that had been collected for the initial study. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The clinical pulmonary infection score was determined on days 1 and 3, and compared in patients identified as having developed VAP or not, as defined by bronchoscopic specimen culture results. On day 3 138 of the 201 patients (69%) had a CPIS of more than 6 that would have required prolonged antimicrobial therapy based on the algorithm. In contrast, based on bronchoscopy, only 88 (44%) patients were considered to have VAP (kappa coefficient for concordance between the two strategies, 0.33). While the sensitivity of CPIS more than 6 on day 3 for identifying VAP was 89%, its specificity was only 47%, leading to potentially unnecessary treatment of 60 (53%) of the 113 patients without VAP as diagnosed by bronchoscopy. CONCLUSION: A strategy based on the CPIS to decide which patients with suspected VAP should receive prolonged administration of antibiotics would appear to over-prescribe these agents, as compared to a strategy based on bronchoscopy.

Algorithms↗
PubMed2003

Airway colonisation in long-term mechanically ventilated patients. Effect of semi-recumbent position and continuous subglottic suctioning.

OBJECTIVE: To evaluate the impact of continuous subglottic suctioning and semi-recumbent body position on bacterial colonisation of the lower respiratory tract. DESIGN: A randomised controlled trial. SETTING: The ten-bed medical ICU of a French university hospital. PATIENTS: Critically ill patients expected to require mechanical ventilation for more than 5 days. INTERVENTIONS: Patients were randomly assigned to receive either continuous suctioning of subglottic secretions and semi-recumbent body position or to receive standard care and supine position. MEASUREMENTS AND RESULTS: Oropharyngeal and tracheal secretions were sampled daily and quantitatively cultured. All included patients were followed up from day 1 (intubation) to day 10, extubation or death. Ninety-seven samples of oropharynx and trachea were analysed (40 for the suctioning group and 57 for the control group). The median bacterial counts in trachea were 6.6 Log10 CFU/ml (interquartile range, IQR, 4.4-8.3) in patients who received continuous suctioning and 5.1 Log10 CFU/ml (IQR 3.6-5.5) in control patients. Most of the patients were colonised in the trachea after 1 day of mechanical ventilation (75% in the suctioning group, 80% in the control group). No significant difference was found in the daily bacterial counts in the oropharynx and in the trachea between the two groups of patients. CONCLUSION: Tracheal colonisation in long-term mechanically ventilated ICU patients was not modified by the use of continuous subglottic suctioning and semi-recumbent body position.

Aged↗
PubMed2003

Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial.

CONTEXT: The optimal duration of antimicrobial treatment for ventilator-associated pneumonia (VAP) is unknown. Shortening the length of treatment may help to contain the emergence of multiresistant bacteria in the intensive care unit (ICU). OBJECTIVE: To determine whether 8 days is as effective as 15 days of antibiotic treatment of patients with microbiologically proven VAP. DESIGN, SETTING, AND PARTICIPANTS: Prospective, randomized, double-blind (until day 8) clinical trial conducted in 51 French ICUs. A total of 401 patients diagnosed as having developed VAP by quantitative culture results of bronchoscopic specimens and who had received initial appropriate empirical antimicrobial therapy were enrolled between May 1999 and June 2002. INTERVENTION: A total of 197 patients were randomly assigned to receive 8 days and 204 to receive 15 days of therapy with an antibiotic regimen selected by the treating physician. MAIN OUTCOME MEASURES: Primary outcome measures-death from any cause, microbiologically documented pulmonary infection recurrence, and antibiotic-free days-were assessed 28 days after VAP onset and analyzed on an intent-to-treat basis. RESULTS: Compared with patients treated for 15 days, those treated for 8 days had neither excess mortality (18.8% vs 17.2%; difference, 1.6%; 90% confidence interval [CI], -3.7% to 6.9%) nor more recurrent infections (28.9% vs 26.0%; difference, 2.9%; 90% CI, -3.2% to 9.1%), but they had more mean (SD) antibiotic-free days (13.1 [7.4] vs 8.7 [5.2] days, P<.001). The number of mechanical ventilation-free days, the number of organ failure-free days, the length of ICU stay, and mortality rates on day 60 for the 2 groups did not differ. Although patients with VAP caused by nonfermenting gram-negative bacilli, including Pseudomonas aeruginosa, did not have more unfavorable outcomes when antimicrobial therapy lasted only 8 days, they did have a higher pulmonary infection-recurrence rate compared with those receiving 15 days of treatment (40.6% vs 25.4%; difference, 15.2%, 90% CI, 3.9%-26.6%). Among patients who developed recurrent infections, multiresistant pathogens emerged less frequently in those who had received 8 days of antibiotics (42.1% vs 62.0% of pulmonary recurrences, P =.04). CONCLUSIONS: Among patients who had received appropriate initial empirical therapy, with the possible exception of those developing nonfermenting gram-negative bacillus infections, comparable clinical effectiveness against VAP was obtained with the 8- and 15-day treatment regimens. The 8-day group had less antibiotic use.

Adult↗
PubMed2003

Critically ill old and the oldest-old patients in intensive care: short- and long-term outcomes.

OBJECTIVE: The purpose of this study was to examine characteristics and outcome of the old, very old and oldest-old ICU patients DESIGN. This is a cohort study. SETTING: The study was set in a ten-bed medical ICU in a university hospital. PARTICIPANTS. There were 410 patients classified in three subgroups: old, 75-79 years ( n=184; 44.4%), very old, 80-84 ( n=137, 33.4%) and the oldest-old, >or=85 ( n=91; 22.2%). MEASUREMENTS: Underlying medical conditions, organ dysfunction, severity of illness, length of stay, use of mechanical ventilation, therapeutic activity and nosocomial infections were recorded. Multivariate analysis was conducted to identify risk factors for ICU and long-term mortality. RESULTS: Characteristics at ICU admission did not differ among the three groups. ICU length of stay, therapeutic activity, mechanical ventilation and nosocomial infection(s) decreased with age. ICU survival rates for those below 75, 75-79, 80-84 and over 85 years were 80, 68, 75 and 69%, respectively; survival rates at 3 months were 54, 56 and 51%, respectively. APACHE II score [odds ratio (OR): 1.11] was identified as the only factor associated with ICU mortality, and age (OR: 2.17, for patients >or=85 years old and 1.82, for patients 80-84 years old) and limitation of activity before admission (OR: 1.74) as factors associated with long-term mortality. CONCLUSION: In a population of patients >or=75 years old, very old age is not directly associated with ICU mortality. After ICU discharge, deaths occurred predominantly during the first 3 months: age and prior limitation of activity were associated with the risk of dying.

Age Distribution↗
PubMed2003

Clinically significant gastrointestinal bleeding in critically ill patients with and without stress-ulcer prophylaxis.

OBJECTIVE: To compare the rates of clinically significant gastrointestinal bleeding and the number of blood units and endoscopies required for gastrointestinal hemorrhage between patients receiving or not receiving stress-ulcer prophylaxis. DESIGN: Historical observational study comparing two consecutive periods: with (phase 1) and without stress-ulcer prophylaxis (phase 2). DESIGN AND SETTING: A 17-bed intensive care unit in a university teaching hospital. PATIENTS. In phase 1 there were 736 patients and in phase 2737. Those in the two phases were comparable in age and reason for admission; clinically significant gastrointestinal bleeding rates did not differ between the two phases, but patients in phase 2 were more severely ill. MEASUREMENTS AND RESULTS: Comparable numbers of blood units were transfused per bleeding patient in the two phases, especially for patients with significant gastrointestinal bleeding. During each phase 19 fibroscopies were performed for significant bleeding, and two patients required surgery. The clinically significant gastrointestinal bleeding rate and outcome did not differ in patients with at least one risk factor. Total expenditures directly related to gastrointestinal bleeding were similar during the two phases; the total cost incurred by stress-ulcer prophylaxis was estimated at 6700. CONCLUSIONS: Our results suggest that stress-ulcer prophylaxis does not influence the clinically significant gastrointestinal bleeding rate in intensive care unit patients or the cost of its management.

Aged↗
PubMed2003

Hospital-acquired pneumonia: diagnostic strategies: lessons from clinical trials.

It should be emphasized that, for the management of VAP, like for all infectious diseases, the choice of antimicrobial treatment is much easier when the specific etiologic agents are identified by a reliable diagnostic technique. Before new antibiotics are administered, reliable pulmonary specimens (chosen according to the literature and within the capabilities of the local microbiology laboratory) must be obtained for direct examination and cultures from patients clinically suspected of having developed VAP.

Anti-Bacterial Agents↗
PubMed2003

Assessment of resting energy expenditure in mechanically ventilated patients.

BACKGROUND: Usual equations for predicting resting energy expenditure (REE) are not appropriate for critically ill patients, and indirect calorimetry criteria render its routine use difficult. OBJECTIVE: Variables that might influence the REE of mechanically ventilated patients were evaluated to establish a predictive relation between these variables and REE. DESIGN: The REE of 70 metabolically stable, mechanically ventilated patients was prospectively measured by indirect calorimetry and calculated with the use of standard predictive models (Harris and Benedict's equations corrected for hypermetabolism factors). Patient data that might influence REE were assessed, and multivariate analysis was conducted to determine the relations between measured REE and these data. Measured and calculated REE were compared by using the Bland-Altman method. RESULTS: Multivariate analysis retained 4 independent variables defining REE: body weight (r(2) = 0.14, P < 0.0001), height (r(2) = 0.11, P = 0.0002), minute ventilation (r(2) = 0.04, P = 0.01), and body temperature (r(2) = 0.07, P = 0.002): REE (kcal/d) = 8 x body weight + 14 x height + 32 x minute ventilation + 94 x body temperature - 4834. REE calculated with this equation was well correlated with measured REE (r(2) = 0.61, P < 0.0001). Bland-Altman plots showed a mean bias approaching zero, and the limits of agreement between measured and predicted REE were clinically acceptable. CONCLUSION: Our results suggest that REE estimated on the basis of body weight, height, minute ventilation, and body temperature is clinically more relevant than are the usual predictive equations for metabolically stable, mechanically ventilated patients.

Basal Metabolism↗
PubMed2002

Ventilator-associated pneumonia.

Ventilator-associated pneumonia (VAP) continues to complicate the course of 8 to 28% of patients receiving mechanical ventilation (MV). In contrast to infections of more frequently involved organs (e.g., urinary tract and skin), for which mortality is low, ranging from 1 to 4%, the mortality rate for VAP ranges from 24 to 50% and can reach 76% in some specific settings or when lung infection is caused by high-risk pathogens. The predominant organisms responsible for infection are Staphylococcus aureus, Pseudomonas aeruginosa, and Enterobacteriaceae, but etiologic agents widely differ according to the population of patients in an intensive care unit, duration of hospital stay, and prior antimicrobial therapy. Because appropriate antimicrobial treatment of patients with VAP significantly improves outcome, more rapid identification of infected patients and accurate selection of antimicrobial agents represent important clinical goals. Our personal bias is that using bronchoscopic techniques to obtain protected brush and bronchoalveolar lavage specimens from the affected area in the lung permits physicians to devise a therapeutic strategy that is superior to one based only on clinical evaluation. When fiberoptic bronchoscopy is not available to physicians treating patients clinically suspected of having VAP, we recommend using either a simplified nonbronchoscopic diagnostic procedure or following a strategy in which decisions regarding antibiotic therapy are based on a clinical score constructed from seven variables. Selection of the initial antimicrobial therapy should be based on predominant flora responsible for VAP at each institution, clinical setting, information provided by direct examination of pulmonary secretions, and intrinsic antibacterial activities of antimicrobial agents and their pharmacokinetic characteristics. Further trials will be needed to clarify the optimal duration of treatment and the circumstances in which monotherapy can be safely used.

Anti-Bacterial Agents↗
PubMed2002

Diagnosis and follow-up of infections in intensive care patients: value of C-reactive protein compared with other clinical and biological variables.

OBJECTIVE: To evaluate diagnostic and prognostic values of C-reactive protein (CRP) dosage in critically ill patients. DESIGN: Prospective, observational study. SETTING: Medical intensive care unit (ICU) in a university hospital. PATIENTS: A consecutive series of 74 patients admitted to the ICU. INTERVENTION: CRP measurements at admission and every 4 days thereafter. MEASUREMENTS AND MAIN RESULTS: At admission, 28 patients (38%) had microbiologically proven infections. Compared with uninfected patients, their mean +/- SD CRP level was 191 +/- 123 vs. 83 +/- 91 mg/L (p < .0001), respectively, white blood cell count was 15.3 +/- 7.5 vs. 11.4 +/- 5.3 G/L (p = .01), and the systemic inflammatory response syndrome (SIRS) was present for 96% vs. 67% (p = .008). No threshold value could be identified to discriminate between these two populations. Multivariate analysis retained CRP and SIRS as the only variables independently associated with the presence of an infection. The combination of CRP > or = 50 mg/L with SIRS was identified as the best model to diagnose infection at admission. This multivariate model performed better than temperature, CRP alone, and white blood cell count. Among the 28 infected patients, 10 recovered; CRP values decreased significantly in this population as compared with patients with persistent infection (-130 +/- 110 vs. 12 +/- 97 mg/L, respectively; p = .004). A CRP decrease > or = 50 mg/L between admission and day 4 was the best cutoff value to diagnose recovery (sensitivity 89%, specificity 79%). CONCLUSION: CRP in combination with SIRS was useful to diagnose infection in ICU patients; a CRP decrease > or = 50 mg/L between admission and day 4 was the best predictor of recovery.

Biomarkers↗
PubMed2002

[Acute complications in cocaine users].

Cocaine use has increased considerably during the last twenty years and several related complications can be identified. Clinical features of cocaine intoxication are variable, but predominantly involve cardiovascular events. Chest pain is the most main complaint; myocardial ischemia must be ruled out. Other cardiovascular manifestations are left ventricular dysfunction, arrhythmia, endocarditis and aortic dissection. Non-cardiac complications include neurological (seizures, stroke, cerebral hemorrhage), respiratory (asthma, interstitial pneumonitis, pulmonary edema), renal (acute renal failure, rhabdomyolysis) and obstetrical disorders. Detection of cocaine in the urine provides the diagnosis. Symptomatic treatment is generally given, combining conventional treatment of the complication and broad use of benzodiazepines.

Adult↗