Selective CB2 Receptor Agonist, HU-308, Reduces Systemic Inflammation in Endotoxin Model of Pneumonia-Induced Acute Lung Injury.

Acute respiratory distress syndrome (ARDS) and sepsis are risk factors contributing to mortality in patients with pneumonia. In ARDS, also termed acute lung injury (ALI), pulmonary immune responses lead to excessive pro-inflammatory cytokine release and aberrant alveolar neutrophil infiltration. Systemic spread of cytokines is associated with systemic complications including sepsis, multi-organ failure, and death. Thus, dampening pro-inflammatory cytokine release is a viable strategy to improve outcome. Activation of cannabinoid type II receptor (CB2) has been shown to reduce cytokine release in various in vivo and in vitro studies. Herein, we investigated the effect of HU-308, a specific CB2 agonist, on systemic and pulmonary inflammation in a model of pneumonia-induced ALI. C57Bl/6 mice received intranasal endotoxin or saline, followed by intravenous HU-308, dexamethasone, or vehicle. ALI was scored by histology and plasma levels of select inflammatory mediators were assessed by Luminex assay. Intravital microscopy (IVM) was performed to assess leukocyte adhesion and capillary perfusion in intestinal and pulmonary microcirculation. HU-308 and dexamethasone attenuated LPS-induced cytokine release and intestinal microcirculatory impairment. HU-308 modestly reduced ALI score, while dexamethasone abolished it. These results suggest administration of HU-308 can reduce systemic inflammation without suppressing pulmonary immune response in pneumonia-induced ALI and systemic inflammation.

Randomized trial of three airway management techniques for restricted access in a simulated pediatric scenario.

PURPOSE: Emergency pediatric airway management during restricted access to the head is challenging and may relate to an entrapped motor vehicle trauma. Video laryngoscopy and supraglottic airways have separately been described to facilitate face-to-face airway management. We hypothesized that video laryngoscopy might be superior to direct laryngoscopy or supraglottic device use to establish ventilation during face-to-face airway management, studied in a simulated pediatric entrapped motor vehicle scenario. METHODS: Ethics approval was obtained from local REB. 45 experienced airway practitioners managed the airway of a pediatric manikin representing a 6 year old (SimJunior). With a cervical collar applied and in the sitting position, the manikin's head was only accessible from the left anterolateral side. Following a standardized demonstration, airway management using a Macintosh #2 blade (DL), a Storz C-MAC® D-Blade (VL) and a #2.5 LMA Supreme™ (SGD) was performed once each in a random order. Outcomes included success rate, time to ventilation (TTV), percentage of glottic opening (POGO) for DL and VL and ease of use on a 10-point Likert scale (VAS). Data was analyzed using analysis of variance for TTV and VAS and t-test for POGO. Statistical significance was deemed at P < 0.05. Data are presented as median and interquartile range. RESULTS: Success rate was 95% for both DL and SGD and 93% for VL. TTV was significantly less with SGD compared to DL and VL. TTV was 31 s (28, 35) for DL, 46 s (31, 62) for VL and 20 s (17, 24) for SGD. POGO was significantly improved with VL (100%) compared to DL (80%). Participants rated SGD significantly easier to use than VL, but not easier than DL. DISCUSSION: All three techniques have high success rates. Time to establish ventilation with the SGD was significantly faster compared to DL and VL and participants rated SGD easiest to use. The utility of VL was limited due to significantly longer time to ventilation, despite significantly improved view compared to DL, similar to adult studies. Since time and success are clinically important, this study suggests that supraglottic devices should be considered for primary emergency pediatric airway management in situations with restricted access to the head.