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Biomedical subjects

Didier Dreyfuss

Publications and source records attributed to Didier Dreyfuss.

At least 19 recordsLinked to original sources

Levels of vancomycin in cerebrospinal fluid of adult patients receiving adjunctive corticosteroids to treat pneumococcal meningitis: a prospective multicenter observational study.

BACKGROUND: Evidence from a recent randomized controlled trial suggests that dexamethasone as adjunct therapy in adult pneumococcal meningitis reduces mortality and neurological sequelae. However, adding dexamethasone has the potential to reduce penetration of vancomycin into the cerebrospinal fluid (CSF). We sought to determine concentrations of vancomycin in serum and CSF of patients with suspected or proven pneumococcal meningitis receiving dexamethasone to assess the penetration of vancomycin into the CSF during steroid therapy. METHODS: In an observational open multicenter study, adult patients admitted to the intensive care unit because of suspected pneumococcal meningitis received recommended treatment for pneumococcal meningitis, comprising intravenous cefotaxime (200 mg per kg of body weight per day), vancomycin (administered as continuous infusion of 60 mg per kg of body weight per day after a loading dose of 15 mg per kg of body weight), and adjunctive therapy with dexamethasone (10 mg every 6 h). Vancomycin levels in CSF were measured on day 2 or day 3 of therapy and were correlated with protein levels in CSF and vancomycin levels in serum (determined at the same time as levels in CSF). RESULTS: Fourteen patients were included. Thirteen had proven pneumococcal meningitis; 1 patient, initially suspected of having pneumococcal meningitis, was finally determined to have meningitis due to Neisseria meningitidis. Mean levels of vancomycin in serum and CSF were 25.2 and 7.2 mg/L, respectively, and were positively correlated (r=0.6; P=.025). A positive correlation was also found between the ratio of vancomycin in CSF to vancomycin in serum and the level of protein in CSF (r=0.66; P=.01). CONCLUSIONS: Appropriate concentrations of vancomycin in CSF may be obtained even when concomitant steroids are used. Dexamethasone can, therefore, be used without fear of impeding vancomycin penetration into the CSF of patients with pneumococcal meningitis, provided that vancomycin dosage is adequate. This study is registered at http://www.ClinicalTrials.gov/ (registration number NCT00162578).

Adrenal Cortex Hormones↗

Evaluation of two-way protein fluxes across the alveolo-capillary membrane by scintigraphy in rats: effect of lung inflation.

Pulmonary microvascular and alveolar epithelial permeability were evaluated in vivo by scintigraphic imaging during lung distension. A zone of alveolar flooding was made by instilling a solution containing 99mTc-albumin in a bronchus. Alveolar epithelial permeability was estimated from the rate at which this tracer left the lungs. Microvascular permeability was simultaneously estimated measuring the accumulation of (111)In-transferrin in lungs. Four levels of lung distension (corresponding to 15, 20, 25, and 30 cmH2O end-inspiratory airway pressure) were studied during mechanical ventilation. Computed tomography scans showed that the zone of alveolar flooding underwent the same distension as the contralateral lung during inflation with gas. Increasing lung tissue stretch by ventilation at high airway pressure immediately increased microvascular, but also alveolar epithelial, permeability to proteins. The same end-inspiratory pressure threshold (between 20 and 25 cmH2O) was observed for epithelial and endothelial permeability changes, which corresponded to a tidal volume between 13.7 +/- 4.69 and 22.2 +/- 2.12 ml/kg body wt. Whereas protein flux from plasma to alveolar space ((111)In-transferrin lung-to-heart ratio slope) was constant over 120 min, the rate at which 99mTc-albumin left air spaces decreased with time. This pattern can be explained by changes in alveolar permeability with time or by a compartment model including an intermediate interstitial space.

Animals↗

The effect of humidification on the incidence of ventilator-associated pneumonia.

Breathing systems used with heated humidifiers are associated with a rapid and high level of bacterial colonization. This colonization is considerably reduced with the use of HMEs. Breathing systems do not need to be changed during the entire ventilation period of a given patient unless they are visibly soiled or mechanically malfunctioning. The incidence of VAP is not influenced by the type of humidification device (heated humidifier or HME). The incidence of VAP is not affected by the duration of use of HMEs or the type of HME, but prolonging the use of a HME further reduces the risk of cross-contamination and results in considerable cost savings.

Air Microbiology↗

Pneumothorax in the intensive care unit: incidence, risk factors, and outcome.

BACKGROUND: The risk factors and outcomes of critically ill patients with iatrogenic pneumothorax (IP) have not been studied in a large unselected intensive care unit (ICU) population. METHODS: The authors studied a prospective cohort of adults admitted for more than 24 h. Data were collected at ICU admission and daily by senior physicians until ICU discharge. Risk factors for IP were identified in the entire cohort. A matched nested case-control study was used to evaluate the excess risk of IP in decedents. RESULTS: Of the 3,499 patients, 69 with pneumothorax before ICU admission were excluded. Of the remaining 3,430 patients, 94 experienced IP within 30 days (42 due to barotrauma and 52 due to invasive procedures). The cumulative incidence of IP was 1.4% (95% confidence interval [CI], 1.0-1.8) on day 5 and 3.0% (95% CI, 2.4-3.6) on day 30. Risk factors for IP (hazard ratio [95% CI]) were body weight less than 80 kg (2.4 [1.3-4.2]), history of adult immunodeficiency syndrome (2.8 [1.2-6.4]), diagnosis of acute respiratory distress syndrome (5.3 [2.6-11]) or cardiogenic pulmonary edema at admission (2.0 [1.1-3.6]), central vein or pulmonary artery catheter insertion (1.7 [1.0-2.7]), and use of inotropic agents during the first 24 h (2.1 [1.3-3.4]). Excess risk of IP in decedents was 2.6 (95% CI, 1.3-4.9; P = 0.004). CONCLUSION: Iatrogenic pneumothorax is a life-threatening complication seen in 3% of ICU patients. Incorporating risk factors for IP into preventive strategies should reduce the occurrence of IP.

Aged↗

Control and outcome of a large outbreak of colonization and infection with glycopeptide-intermediate Staphylococcus aureus in an intensive care unit.

BACKGROUND: Glycopeptide-intermediate Staphylococcus aureus (GISA) is emerging as a cause of nosocomial infection and outbreaks of infection and colonization in intensive care units (ICUs). We describe an outbreak of GISA colonization/infection and the ensuing control measures in an ICU and investigate outcomes of the affected patients. METHODS: We describe an outbreak of GISA colonization and infection that affected 21 patients in a medical ICU at a tertiary care teaching hospital, as well as the measures taken to eradicate the GISA strain. RESULT: Recognition of the outbreak was difficult. Infections, all of which were severe, were diagnosed in 11 of 21 patients. Patient isolation and barrier precautions failed when used alone. Addition of a stringent policy of restricted admissions, twice daily environmental cleaning, and implementation of hand decontamination with a hydroalcoholic solution led to outbreak termination. This was associated with increases in workload, despite a marked decrease in the number of admissions. CONCLUSION: This first description of a large outbreak of GISA colonization and infection underlines the importance of routine GISA-strain detection when methicillin-resistant S. aureus is isolated. Outbreak control may be difficult to achieve.

Anti-Bacterial Agents↗

Acute lung injury and bacterial infection.

The relationships between acute lung injury and bacterial infection are complex. Indeed, sepsis and in particular pneumonia are leading causes of acute lung injury. Bacterial superinfection of the lung is a frequent complication of acute lung injury. Because of impaired host defenses and prolonged mechanical ventilation, more than one third of patients with the acute respiratory distress syndrome acquire ventilator-associated pneumonia, with resistant pathogens in most instances. This complication is responsible for more than a doubling of the time on mechanical ventilation but does not seem to increase mortality.

Animals↗

Noninvasive evaluation of acute capillary permeability changes during high-volume ventilation in rats with and without hypercapnic acidosis.

OBJECTIVE: To evaluate whether hypercapnic acidosis attenuates acute alterations of pulmonary capillary permeability due to high lung stretch in rats using a simple, noninvasive, scintigraphic method. DESIGN: Prospective, randomized, controlled animal study. SETTING: University research laboratory. SUBJECTS: Male adult Wistar rats weighing 291 +/- 7.5 g. INTERVENTIONS: Three groups of rats were studied: controls ventilated with a low (6 mL/kg body weight) tidal volume and rats ventilated with a high (38 mL/kg body weight) tidal volume under normocapnic (Paco(2) = 35.2 +/- 1.65 mm Hg) or hypercapnic (Paco(2) = 102.5 +/- 5.63 mm Hg) conditions. MEASUREMENTS AND MAIN RESULTS: Pulmonary capillary permeability alterations were assessed by monitoring the rate of (111)In-transferrin accumulation in lung tissue. Respiratory system pressure-volume curves were registered and analyzed. High tidal volume ventilation increased In-transferrin plasma to lung flux in such a way that I(111)In-transferrin behaved like a marker of water. The rate of initial (first 30 mins of high tidal volume ventilation) lung transferrin accumulation measured by scintigraphy (standardized lung/heart ratio) was steady, correlated with the percent decrease in respiratory system compliance (a marker of edema progression), and did not differ between normocapnic and hypercapnic groups (18.9 +/- 3.97 vs. 14.2 +/- 2.89%/hr, not significant). However, lung In-tranferrin accumulation rate was highly scattered due to variable interindividual mechanical properties of the respiratory system. This rate was correlated with initial values of volume of the upper inflection point of the pressure-volume curve (r = -.53, p < .001) and end-inspiratory pressure (r = .54, p < .001). Mechanical properties were similar in normocapnic and hypercapnic rats. There was no difference between In-transferrin accumulation rates in these rats when a stringent selection was made based on end-inspiratory pressure (28-32 cm H(2)O) or body weight (330-360 g). CONCLUSIONS: Hypercapnic acidosis does not influence in vivo the acute increase in pulmonary capillary permeability due to high-volume ventilation.

Acidosis, Respiratory↗

Incidence and impact of organ dysfunctions associated with sepsis.

OBJECTIVE: To study the incidence and severity of organ dysfunction associated with sepsis. DESIGN: Comprehensive review of prospectively collected data from intensive care patients hospitalized between 1997 and 2001. SETTING: Thirty-five ICUs in nonuniversity and university hospitals located in the Paris area. PATIENTS: All patients hospitalized in the ICU for > 24 h meeting the criteria for severe sepsis (SS), either with only one organ dysfunction present during the ICU stay (SS1; n = 5,675) or with at least two organ dysfunction present during the ICU stay (SS2; n = 12,598), were compared to all other patients hospitalized for > 24 h in the ICU over the same time period (n = 47,637). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We collected information on demographic characteristics, type of admission, underlying disease, organ dysfunction, organ support, McCabe and Charlson-Deyo scores, simplified acute physiology score II, length of stay, and outcome. The incidence of SS was 27.7% (8.6% for SS1 and 19.1 for SS2). Compared with non-SS patients, those with SS were significantly older, were more frequently men, required organ support more frequently, had higher severity scores, and stayed longer in the ICU and hospital. Respiratory and cardiovascular dysfunction and fungal infection were strong independent risk factors for death in SS patients, with 5.64-fold, 4.35-fold, and 2.0-fold increased risks, respectively. SS2 is significantly different from SS1: older age, more surgical stays and admission from external transfer, greater number of organ supports, site of infection (less pulmonary and urinary tract infections, and more abdominal and cardiovascular infections), type of bacteria (more methicillin-resistant Staphylococcus aureus, Pseudomonas, and fungus), ICU length of stay (20.4 d vs 11.6 d), hospital length of stay (33 d vs 27.9 d), ICU mortality (42.7% vs 5.5%), and hospital mortality (49% vs 11.3%). CONCLUSIONS: Our study identifies a subgroup of patients with an ICU stay > 24 h and SS with at least two organ dysfunctions. This group of patients requires special attention since their ICU mortality is > 40% and they occupy almost 40% of all ICU beds.

APACHE↗

Infectious and inflammatory dissemination are affected by ventilation strategy in rats with unilateral pneumonia.

OBJECTIVE: To evaluate the effect of V(T) reduction and alveolar recruitment on systemic and contralateral dissemination of bacteria and inflammation during right-side pneumonia. DESIGN: Interventional animal study. SETTING. University hospital research laboratory. SUBJECTS: A total of 54 male Wistar rats. INTERVENTIONS: One day after right lung instillation of 1.4x10(7) Pseudomonas aeruginosa, rats were left unventilated or ventilated for 2 h at low V(T) (6 ml/kg) with different strategies of alveolar recruitment: no PEEP, 8 cm H(2)O PEEP, 8 cm H(2)O PEEP in a left lateral position, 3 cm H(2)O PEEP with partial liquid ventilation, or high V(T) (set such as end-inspiratory pressure was 30 cm H(2)O) without PEEP (ZEEP). After ventilation the lungs, spleen and liver were cultivated for bacterial counts. Global bacterial dissemination was scored considering the percentage of positive spleen, liver and left lung cultures. TNF-alpha was assayed in plasma before and after mechanical ventilation. MEASUREMENTS AND RESULTS: All rats had right-side pneumonia with similar bacterial counts. All mechanical ventilation strategies, with the exception of low V(T)-PEEP 8, promoted contralateral lung dissemination. Overall bacterial dissemination was less in non-ventilated controls (22%) and low V(T)-PEEP 8 (22%) than in high V(T)-ZEEP (67%), low V(T)-PEEP 8 in left lateral position (59%) and low V(T)-ZEEP (56%) ( p<0.05). Partial liquid ventilation prevented systemic bacterial translocation, but at the expense of contralateral bacterial seeding. Plasma TNF-alpha concentration increased significantly after mechanical ventilation with no PEEP at both high and low V(T). CONCLUSIONS: Our results suggest that PEEP might reduce the risk of ventilation-induced bacterial and inflammatory mediator dissemination during pneumonia.

Animals↗

Accuracy of delayed (24 hours) processing of bronchoalveolar lavage for diagnosing bacterial pneumonia.

OBJECTIVE: Pneumonia in the intensive care unit is associated with a high mortality rate. Diagnostic accuracy is mandatory to improve prognosis. However, in many hospitals, samples from the respiratory tract cannot be immediately processed bacteriologically around the clock. This may complicate therapeutic choice based on invasive diagnostic procedures. We evaluated the effect of storing bronchoalveolar lavage fluid at 4 degrees C for 24 hrs on direct examination and culturing for diagnosing pneumonia. DESIGN: Prospective, paired comparison study. SETTING: Intensive care unit in a university hospital. PATIENTS: A total of 93 bronchoalveolar lavages were performed on 66 intensive care unit patients who were suspected to have bacterial pneumonia. INTERVENTION: Each sample was divided into two; one half was processed immediately (H0), and the other was processed after refrigeration at 4 degrees C for 24 hrs (H24). MEASUREMENTS AND MAIN RESULTS: All negative H0 culture samples (n = 31) were also negative for pathogens in H24 samples. Sixty two bronchoalveolar lavage cultures yielded one or more microorganisms, giving a total of 113 microorganisms in one or both samples. The results of positive cultures at H0 and H24 for the culturing diagnostic threshold of 10 colony forming units/mL agreed well (Kappa coefficient, 0.84); agreement was even better (Kappa coefficient, 0.85) when possible contaminants were excluded. The bias calculated as the mean difference between paired culture results was 0.195 +/- 1.31 (Delta log). When considering the accepted threshold of 10 colony forming units/mL, specificity at H24 compared to H0 was excellent (100%), but sensitivity was slightly lower (80%). CONCLUSION: Delayed processing of bronchoalveolar lavage sampling is an acceptable alternative when immediate culturing cannot be performed because it enables antibiotic administration.

Bronchoalveolar Lavage Fluid↗

Ventilation strategy affects cytokine release after mesenteric ischemia-reperfusion in rats.

OBJECTIVE: To evaluate the impact of different ventilation modalities on lung and plasma concentrations of cytokines in a model of secondary lung inflammation, mesenteric ischemia-reperfusion, in rats. DESIGN: Prospective, randomized, controlled animal study. SETTING: Research laboratory of a university. SUBJECTS: Sixty-four male adult Wistar rats weighing 320-380 g. INTERVENTIONS: Eight groups were studied. Two groups underwent no surgical procedure: They were either not ventilated or ventilated with an injurious modality consisting of 30 mL/kg tidal volume (Vt) without positive-end expiratory pressure (PEEP). Animals of the other groups underwent laparotomy with or without 2-hr mesenteric ischemia followed by 4 hrs of reperfusion during which the rats were mechanically ventilated. Ventilation modalities were conventional (tidal volume 10 mL/kg, PEEP 3 cm H2O), protective (6 mL/kg, 6 cm H(2)O), or injurious (tidal volume 30 mL/kg and no PEEP). Rats were killed by exsanguination, and their lungs were excised and homogenized in buffer. Supernatants of lung homogenates and plasmas were stored at -80 degrees C for subsequent measurements. MEASUREMENTS AND MAIN RESULTS: Tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, macrophage inhibitory protein 2, and interleukin-10 were determined in lung supernatants and plasmas with a rat-specific enzyme-linked immunosorbent assay. Lung and plasma cytokine concentrations were not significantly different between rats ventilated with the injurious modality only and nonventilated rats. Lung and plasma cytokine concentrations were higher in rats that had undergone mesenteric ischemia-reperfusion than in rats with laparotomy only, whatever ventilation modality. Lung and plasma cytokine concentrations were higher in these rats after the injurious ventilation modality than after the other modalities. CONCLUSION: This study shows that an injurious ventilation does not produce significant in vivo release of cytokines in intact animals but promotes the release of pro- and anti-inflammatory cytokines in an inflammatory context.

Animals↗

Beyond randomized, controlled trials.

PURPOSE OF REVIEW: Most critical care physicians believe that randomized, controlled trials provide the best available evidence. This review contends that the importance of randomized, controlled trials was overemphasized and that they do not add more to knowledge and practice than physiologic and observational studies. In addition, protection of both patients and proxies may be less adequately ensured during randomized, controlled trials than during observational studies. RECENT FINDINGS: An analysis of the recent literature on critical care shows that conclusions from randomized, controlled trials are either disputable or do not affect existing practice. In addition, several papers reveal potential conflicts between randomized, controlled trials and ethical principles. SUMMARY: We may see in the future the twilight of randomized, controlled trials in critically ill patients because scientific, ethical, and sociologic substrata will be progressively lacking as will be funding.

Clinical Trials as Topic↗