Helium in the adult critical care setting

Helium is a low-density inert gas whose physical properties are very different from those of nitrogen and oxygen. Such properties could be clinically useful in the adult critical care setting, especially in patients with upper to more distal airway obstruction requiring moderate to intermediate levels of FiO2. However, despite decades of utilization and reporting, it is still difficult to give any firm clinical recommendation in this setting. Numerous case reports are available in the context of upper airway obstruction of different origins, but there is a lack of controlled studies for this indication. One study reported a helium-induced beneficial effect on surrogates of work of breathing after extubation in non-COPD patients, possibly in relation to laryngeal consequences of tracheal intubation. Physiological benefits of helium-oxygen breathing have been demonstrated in the context of acute severe asthma, but there is a lack of large controlled studies demonstrating an effect on pertinent clinical endpoints, except for a study reported only as an abstract, which mentioned a reduction in the intubation rate in helium-treated patients. Finally, there are a number of physiological studies in the context of COLD-COPD patients demonstrating a beneficial effect, mainly by a reduction in the resistive inspiratory work of breathing but also by a reduction in hyperinflation. Reduction of hypercapnia was mainly observed in spontaneously breathing and noninvasively ventilated helium-treated patients but not in intubated patients during controlled ventilation, suggesting that the decrease in PaCO2 was mainly in relation to a diminution in CO2 production, related to the diminution in work of breathing and not an improved alveolar ventilation. Moreover, there is little evidence that helium-oxygen could improve parameters of heterogeneity in such patients. Two RCTs were unable to demonstrate a reduction in the intubation rate in such setting, but they were likely underpowered. An adequately powered international multicentric study is ongoing and will help to determinate the exact place of the helium-oxygen mixture in the future. The place of the mixture during the weaning period will deserve further evaluation

Therapeutic effect of neutralizing endogenous IL-18 activity in the collagen-induced model of arthritis.

Contains fulltext : 134210.pdf (publisher's version ) (Open Access)Two distinct IL-18 neutralizing strategies, i.e. a rabbit polyclonal anti-mouse IL-18 IgG and a recombinant human IL-18 binding protein (rhIL-18BP), were used to treat collagen-induced-arthritic DBA/1 mice after clinical onset of disease. The therapeutic efficacy of neutralizing endogenous IL-18 was assessed using different pathological parameters of disease progression. The clinical severity in mice undergoing collagen-induced arthritis was significantly reduced after treatment with both IL-18 neutralizing agents compared to placebo treated mice. Attenuation of the disease was associated with reduced cartilage erosion evident on histology. The decreased cartilage degradation was further documented by a significant reduction in the levels of circulating cartilage oligomeric matrix protein (an indicator of cartilage turnover). Both strategies efficiently slowed disease progression, but only anti-IL-18 IgG treatment significantly decreased an established synovitis. Serum levels of IL-6 were significantly reduced with both neutralizing strategies. In vitro, neutralizing IL-18 resulted in a significant inhibition of TNF-alpha, IL-6, and IFN-gamma secretion by macrophages. These results demonstrate that neutralizing endogenous IL-18 is therapeutically efficacious in the murine model of collagen-induced arthritis. IL-18 neutralizing antibody or rhIL-18BP could therefore represent new disease-modifying anti-rheumatic drugs that warrant testing in clinical trials in patients with rheumatoid arthritis

Hélium en réanimation : de la mécanique des fluides à la clinique

En raison de sa faible densité, l'hélium tend à favoriser la présence de conditions d'écoulement laminaires dans les voies aériennes, tout en diminuant la résistance à l'écoulement en conditions turbulentes. Cette propriété rend compte de son intérêt potentiel lors d'atteintes obstructives des voies aériennes supérieures ou inférieures. Plusieurs études ont démontré des effets cliniques et physiopathologiques favorables dans ces situations, tant en respiration spontanée qu'en ventilation mécanique, invasive ou non invasive. Pour l'heure, nous manquons d'études bien conduites démontrant que ces effets favorables s'accompagnent d'un impact bénéfique sur le devenir des patients. Dans cette attente, le recours de routine aux mélanges hélium-oxygène (He-O2) ne peut être préconisé et son utilisation doit être limitée à des situations cliniques individuelles avec des objectifs ciblés