[Less ventilator-associated pneumonia after oral decontamination with chlorhexidine; a randomised trial]. / Minder beademingspneumonieën door orale decontaminatie met chloorhexidine; gerandomiseerde trial.

OBJECTIVE: To determine the effect of oral decontamination with either chlorhexidine (CHX, 2%) or the combination chlorhexidine-colistin (CHX-COL, 2%-2%) on the frequency and the time to onset of ventilator-associated pneumonia in Intensive Care patients. DESIGN: Double blind, placebo-controlled, multicentre, randomised trial. METHODS: Consecutive ICU patients needing at least 48 h of mechanical ventilation were enrolled in a randomized trial with 3 arms: CHX, CHX-COL, and placebo (PLAC). The trial medication was administered in the oral cavity every 6 h. Oropharyngeal swabs were obtained daily and analysed quantitatively for Gram-positive and Gram-negative microorganisms. Endotracheal colonisation was monitored twice weekly. Ventilator-associated pneumonia was diagnosed on the basis of a combination of clinical, radiological and microbiological criteria. RESULTS: Of 385 patients included, 130 received PLAC, 127 CHX and 128 CHX-COL. Baseline characteristics in the three groups were comparable. The daily risk of ventilator-associated pneumonia was reduced in both treatment groups compared to PLAC: 65% (HR= 0.352; 95% CI: 0.160-0.791; p = 0.012) for CHX and 55% (HR= 0.454; 95%/ CI: 0.224-0.925; p = 0.030) for CHX-COL. CHX-COL provided a significant reduction in oropharyngeal colonisation with both Gram-negative and Gram-positive microorganisms, whereas CHX significantly affected only colonisation with Gram-positive microorganisms. There were no differences in the duration of mechanical ventilation, ICU-stay or ICU-survival. CONCLUSION: Oral decontamination of the oropharyngeal cavity with chlorhexidine or the combination chlorhexidine-colistin reduced the incidence and the time to onset ofventilator-associated pneumonia.

Nitric oxides in plasma, urine, and cerebrospinal fluid in patients with severe falciparum malaria.

It has been suggested that nitric oxide (NO) plays an important role in the pathogenesis of severe falciparum malaria. Since NO has a very short half-life, nitrate and nitrite (NOx) levels, stable metabolites of NO, are used as measures of NO production. We measured plasma NOx levels in 24 adults with severe falciparum malaria on the Thai-Burmese border. After correction for renal function, there was no correlation between plasma NOx levels, or the total amount of NOx excreted in the urine, and disease severity. Plasma NOx levels decreased after the first 48 hr in all patients (P = 0.007), suggesting decreased NO production. The NOx levels in cerebrospinal fluid (CSF) correlated well with plasma NOx levels, but these did not show a correlation with coma depth, and were not significantly different from those in a healthy control group. These findings do not support the hypothesis that excessive NO production contributes to the pathogenesis of severe falciparum malaria. However, local changes in NO production, e.g., in the central nervous system, might not be reflected in the total NOx production or NOx levels in the CSF.