Biological markers and diagnosis of ventilator-associated pneumonia

Evaluation of a new biomarker from bronchoalveolar fluid, the Clara cell protein 10, adds data to the search for a diagnostic marker for ventilator-associated pneumonia (VAP). For more than 15 years, investigators tried to identify such a marker for predicting or diagnosing VAP. Unfortunately, the results of a number of these studies are disappointing. For optimal management of critically ill, ventilated patients with clinical suspicion of VAP, clinicians need accurate microbiological information to decide to treat in case of confirmed infection and to guide the initial choice of antibiotic therapy with identification of the responsible pathogen(s). Thus, today, the potential advantages of biomarkers are to improve the rapidity and performance of current diagnostic procedures and to reduce antibiotic exposure and selective pressure

Is bronchoalveolar lavage with quantitative cultures a useful tool for diagnosing ventilator-associated pneumonia?

The results of a recently published Canadian study suggest that bronchoalveolar lavage and endotracheal aspiration are associated with similar clinical outcomes and similar overall use of antibiotics in critically ill patients with suspected ventilator-associated pneumonia (VAP). The study, however, does not provide convincing information on the best strategy to diagnose VAP, to accurately choose initial treatment and to exclude VAP in order to avoid administering antibiotics to patients without bacterial infection. In fact, this trial has several limitations or drawbacks: patients at risk for developing VAP due to Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus were excluded, far from the real-life scenario; a significant number of patients were receiving recent antimicrobial therapy at the time of sampling, with, consequently, difficult-to-interpret culture results; randomization of included patients for initial treatment – meropenem plus ciprofloxacin or meropenem alone – resulted in a high rate of inappropriate initial empirical therapy due to the absence of customization to local epidemiology; and the initial decision to treat and the re-evaluation at day 3 were, in fact, based on clinical judgment and not on direct examination and quantitative culture results. In summary, because antimicrobial treatment was initiated in all suspected patients and was rarely withheld in patients with negative cultures, the study does not suggest an appropriate strategy for improving the use of antibiotics in intensive care unit patients. Such a strategy has two requirements: immediate administration of adequate therapy in patients with true VAP, and avoidance of administering antibiotics in patients without bacterial infection

New approach to modulate retinal cellular toxic effects of high glucose using marine epa and dha

<p>Abstract</p> <p>Background</p> <p>Protective effects of omega-3 fatty acids against cellular damages of high glucose were studied on retinal pigmented epithelial (RPE) cells.</p> <p>Methods</p> <p>Retinal epithelial cells were incubated with omega-3 marine oils rich in EPA and DHA and then with high glucose (25 mM) for 48 hours. Cellular responses were compared to normal glucose (5 mM): intracellular redox status, reactive oxygen species (ROS), mitochondrial succinate deshydrogenase activity, inflammatory cytokines release and caveolin-1 expression were evaluated using microplate cytometry, ELISA and flow cytometry techniques. Fatty acids incorporation in retinal cell membranes was analysed using chromatography.</p> <p>Results</p> <p>Preincubation of the cells with fish oil decreased ROS overproduction, mitochondrial alterations and TNFα release. These protective effects could be attributed to an increase in caveolin-1 expression induced by marine oil.</p> <p>Conclusion</p> <p>Marine formulations rich in omega-3 fatty acids represent a promising therapeutic approach for diabetic retinopathy.</p

Validation of a predictive method for an accurate assessment of resting energy expenditure in medical mechanically ventilated patients

Objective: Use comparison with indirect calorimetry to confirm the ability of our previously described equation to predict resting energy expenditure in mechanically ventilated patients.Design: Prospective, validation study. Setting: Eighteen-bed, medical intensive care unit at a teaching hospital. Patients: All adult patients intubated &gt;24 hrs were assessed for eligibility. Exclusion criteria were clinical situations that could contribute to erroneous calorimetric measurements. Interventions: Resting energy expenditure was calculated using the original Harris-Benedict equations and those corrected for usual stress factors, the Swinamer equation, the Fusco equation, the Ireton-Jones equation, and our equation: resting energy expenditure (kcal/day) = 8 × weight (kg) + 14 × height (cm) + 32 × minute ventilation (L/min) + 94 × temperature (°C) − 4834. Measurements and Main Results: Resting energy expenditure was measured by indirect calorimetry for the 45 included patients. Resting energy expenditure calculated with our predictive model correlated with the measured resting energy expenditure (r2 = .62, p &lt; .0001), and Bland-Altman analysis showed a mean bias of −192 ± 277 kcal/day, with limits of agreement ranging from −735 to 351 kcal/day. Resting energy expenditure calculated with the Harris-Benedict equations was more weakly correlated with measured resting energy expenditure (r2 = .41, p &lt; .0001), with Bland-Altman analysis showing a mean bias of 279 ± 346 kcal/day between them and the limits of agreement ranging from −399 to 957 kcal/day. Applying usual stress-correction factors to the Harris-Benedict equations generated wide variability, and the correlation with measured resting energy expenditure was poorer (r2 = .18, p &lt; .0001), with Bland-Altman analysis showing a mean bias of −357 ± 750 kcal/day and limits of agreement ranging from −1827 to 1113 kcal/day. The use of the Swinamer, Fusco, or Ireton-Jones predictive methods yielded weaker correlation between calculated and measured resting energy expenditure (r2 = .41, p &lt; .0001; r2 = .38, p &lt; .0001; r2 = .39, p &lt; .0001, respectively) than our equation, and Bland-Altman analysis showed no improvement in agreement and variability between methods. Conclusions: The Faisy equation, based on static (height), less stable (weight), and dynamic biometric variables (temperature and minute ventilation), provided precise and unbiased resting energy expenditure estimations in mechanically ventilated patients

Syndrome de détresse respiratoire aiguë secondaire à une infection à Toxocara cati

Human toxocarosis is a helminthozoonosis due to the migration of toxocara species larvae throughout the human body. Lung manifestations vary and range from asymptomatic infection to severe disease. Dry cough and chest discomfort are the most common respiratory symptoms. Clinical manifestations include a transient form of Loeffler\u27s syndrome or an eosinophilic pneumonia. We report a case of bilateral pneumonia in an 80 year old caucasian man who developed very rapidly an acute respiratory distress syndrome, with a PaO2/FiO2 ratio of 55, requiring mechanical ventilation and adrenergic support. There was an increased eosinophilia in both blood and bronchoalveolar lavage fluid. Positive toxocara serology and the clinical picture confirmed the diagnosis of the "visceral larva migrans" syndrome. Intravenous corticosteroid therapy produced a rapid rise in PaO2/FiO2 before the administration of specific treatment. A few cases of acute pneumonia requiring mechanical ventilation due to toxocara have been published but this is, to our knowledge, is the first reported case of ARDS with multi-organ failure

Pharmacokinetics of epinephrine in patients with septic shock: modelization and interaction with endogenous neurohormonal status

Introduction In septic patients, an unpredictable response to epinephrine may be due to pharmacodynamic factors or to non-linear pharmacokinetics. The purpose of this study was to investigate the pharmacokinetics of epinephrine and its determinants in patients with septic shock. Methods Thirty-eight consecutive adult patients with septic shock were prospectively recruited immediately before epinephrine infusion. A baseline blood sample (C0) was taken to assess endogenous epinephrine, norepinephrine, renin, aldosterone, and plasma cortisol levels before epinephrine infusion. At a fixed cumulative epinephrine dose adjusted to body weight and under steady-state infusion, a second blood sample (C1) was taken to assess epinephrine and norepinephrine concentrations. Data were analyzed using the nonlinear mixed effect modeling software program NONMEM. Results Plasma epinephrine concentrations ranged from 4.4 to 540 nmol/L at steady-state infusion (range 0.1 to 7 mg/hr; 0.026 to 1.67 μg/kg/min). A one-compartment model adequately described the data. Only body weight (BW) and New Simplified Acute Physiologic Score (SAPSII) at intensive care unit admission significantly influenced epinephrine clearance: CL (L/hr) = 127 × (BW/70)0.60 × (SAPS II/50)-0.67. The corresponding half-life was 3.5 minutes. Endogenous norepinephrine plasma concentration significantly decreased during epinephrine infusion (median (range) 8.8 (1 – 56.7) at C0 vs. 4.5 (0.3 – 38.9) nmol/L at C1, P &lt; 0.001). Conclusions Epinephrine pharmacokinetics is linear in septic shock patients, without any saturation at high doses. Basal neurohormonal status does not influence epinephrine pharmacokinetics. Exogenous epinephrine may alter the endogenous norepinephrine metabolism in septic patients