Effect of Acetazolamide vs Placebo on Duration of Invasive Mechanical Ventilation Among Patients With Chronic Obstructive Pulmonary Disease: A Randomized Clinical Trial.

IMPORTANCE: Acetazolamide has been used for decades as a respiratory stimulant for patients with chronic obstructive pulmonary disease (COPD) and metabolic alkalosis, but no large randomized placebo-controlled trial is available to confirm this approach. OBJECTIVE: To determine whether acetazolamide reduces mechanical ventilation duration in critically ill patients with COPD and metabolic alkalosis. DESIGN, SETTING, AND PARTICIPANTS: The DIABOLO study, a randomized, double-blind, multicenter trial, was conducted from October 2011 through July 2014 in 15 intensive care units (ICUs) in France. A total of 382 patients with COPD who were expected to receive mechanical ventilation for more 24 hours were randomized to the acetazolamide or placebo group and 380 were included in an intention-to treat analysis. INTERVENTIONS: Acetazolamide (500-1000 mg, twice daily) vs placebo administered intravenously in cases of pure or mixed metabolic alkalosis, initiated within 48 hours of ICU admission and continued during the ICU stay for a maximum of 28 days. MAIN OUTCOMES AND MEASURES: The primary outcome was the duration of invasive mechanical ventilation via endotracheal intubation or tracheotomy. Secondary outcomes included changes in arterial blood gas and respiratory parameters, weaning duration, adverse events, use of noninvasive ventilation after extubation, successful weaning, the duration of ICU stay, and in-ICU mortality. RESULTS: Among 382 randomized patients, 380 (mean age, 69 years; 272 men [71.6%]; 379 [99.7%] with endotracheal intubation) completed the study. For the acetazolamide group (n = 187), compared with the placebo group (n = 193), no significant between-group differences were found for median duration of mechanical ventilation (-16.0 hours; 95% CI, -36.5 to 4.0 hours; P = .17), duration of weaning off mechanical ventilation (-0.9 hours; 95% CI, -4.3 to 1.3 hours; P = .36), daily changes of minute-ventilation (-0.0 L/min; 95% CI, -0.2 to 0.2 L/min; P = .72), or partial carbon-dioxide pressure in arterial blood (-0.3 mm Hg; 95% CI, -0.8 to 0.2 mm Hg; P = .25), although daily changes of serum bicarbonate (between-group difference, -0.8 mEq/L; 95% CI, -1.2 to -0.5 mEq/L; P < .001) and number of days with metabolic alkalosis (between-group difference, -1; 95% CI, -2 to -1 days; P < .001) decreased significantly more in the acetazolamide group. Other secondary outcomes also did not differ significantly between groups. CONCLUSIONS AND RELEVANCE: Among patients with COPD receiving invasive mechanical ventilation, the use of acetazolamide, compared with placebo, did not result in a statistically significant reduction in the duration of invasive mechanical ventilation. However, the magnitude of the difference was clinically important, and it is possible that the study was underpowered to establish statistical significance. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01627639.

Pulmonary superinfection by trichomonads in the course of acute respiratory distress syndrome.

The finding of trichomonads in bronchoalveolar lavage fluid (BALF) samples from an acute respiratory distress syndrome (ARDS) patient, never previously reported, incited us to search for these parasites retrospectively in the BALF of patients with ARDS or related pathologies. Eighty-four consecutive BALF samples have been reviewed. Results were compared with data from clinical files of patients included in this study. Detection and identification of trichomonads were based on cytologic characteristics. Subsequently, immunocytochemistry and in situ hybridization were performed in the last case of the series. Our results were as follows: (1) Trichomonads were detected in 25/84 BALFs (20/77 patients). Among the patients testing positive, 17 suffered from ARDS, about 30% of the ARDS patients included in the study. (2) Trichomonads were detected more frequently at a late ARDS stage. (3) No correlation was found between trichomonad detection and other data. (4) Within the group of trichomonad-infected ARDS patients, density of infection correlated with higher mortality. The late detection of these microorganisms in the course of ARDS suggested that trichomonad development is a secondary event. As BALFs obtained early in the course of ARDS were also included in the study, trichomonad incidence could be underestimated. The significance of trichomonad lung colonization in ARDS and its potential pathogenic role are unclear. Nevertheless, the question of an active role of trichomonads in the extension of alveolar lesions or in the limitation of recovery is clearly raised.

Respiratory changes in inferior vena cava diameter are helpful in predicting fluid responsiveness in ventilated septic patients.

OBJECTIVE: To evaluate the extent to which respiratory changes in inferior vena cava (IVC) diameter can be used to predict fluid responsiveness. DESIGN: Prospective clinical study. SETTING: Hospital intensive care unit. PATIENTS: Twenty-three patients with acute circulatory failure related to sepsis and mechanically ventilated because of an acute lung injury. MEASUREMENTS: Inferior vena cava diameter (D) at end-expiration (Dmin) and at end-inspiration (Dmax) was measured by echocardiography using a subcostal approach. The distensibility index of the IVC (dIVC) was calculated as the ratio of Dmax - Dmin / Dmin, and expressed as a percentage. The Doppler technique was applied in the pulmonary artery trunk to determine cardiac index (CI). Measurements were performed at baseline and after a 7 ml/kg volume expansion using a plasma expander. Patients were separated into responders (increase in CI > or =15%) and non-responders (increase in CI <15%). RESULTS: Using a threshold dIVC of 18%, responders and non-responders were discriminated with 90% sensitivity and 90% specificity. A strong relation (r = 0.9) was observed between dIVC at baseline and the CI increase following blood volume expansion. Baseline central venous pressure did not accurately predict fluid responsiveness. CONCLUSION: Our study suggests that respiratory change in IVC diameter is an accurate predictor of fluid responsiveness in septic patients.

Fatal acute cellulitis due to Neisseria meningitidis.

We describe the first fatal evolution of cellulitis due to Neisseria meningitidis serogroup Y involving an 85-year-old woman. She presented with an extensive cellulitis of the left side of the face, neck, and thorax and septic shock. In spite of active antibiotic therapy, evolution was rapidly fatal.