Background Gradually changing respiratory rate (RR) over time to reduce ventilation-induced lung injury (VILI) has not been investigated. We hypothesized that gradual, compared to abrupt, increments in RR would mitigate VILI and that recruitment maneuver (RM) prior to abrupt increasing RR may prevent injurious biological impact. Methods Twenty-four hours after intratracheal administration of Escherichia coli lipopolysaccharide, 49 male Wistar rats were anesthetized and mechanically ventilated (VT=6ml/kg, PEEP=3cmH2O) with RR increase patterns as follows (n=7/group): (1)control-1, RR=70bpm for 2h; (2) and (3)abrupt increases of RR for 1h and 2h, respectively, both for 2h; (4)shorter RR adaptation, gradually increasing RR (from 70 to 130bpm over 30min); (5)longer RR adaptation, more gradual increase in RR (from 70 to 130bpm over 60min), both for 2h; (6)control-2, abrupt increase of RR maintained for 1h; and (7)control-3, RM [CPAP=30cmH2O for 30s] followed by control-2 protocol. Results At the end of 1h of mechanical ventilation, cumulative diffuse alveolar damage scores were lower in shorter (11.0 [8.0–12.0]) and longer (13.0 [11.0–14.0]) RR adaptation groups than in animals with abrupt increase of RR for 1 h (25.0 [22.0–26.0] p=0.035, and p=0.048, respectively) and 2 h (35.0 [32.0–39.0], p=0.003, and p=0.040, respectively); mechanical power and lung heterogeneity were lower, and alveolar integrity was higher, in the longer RR adaptation group compared with abruptly adjusted groups; markers of lung inflammation (IL-6), epithelial (CC-16) and endothelial cell damage (VCAM-1) were higher in both abrupt groups, but not in either RR adaptation group, compared with controls. RM prevented the increase in VCAM-1 and CC-16 gene expressions in the abruptly increased RR groups. Conclusion In mild experimental ARDS in rats, gradually increasing RR, compared with abruptly doing so, can mitigate the development of VILI. In addition, recruitment maneuver prevented the injurious biological impact of abrupt increases in RR.

Acute ischemic stroke is associated with pulmonary complications, and often dexmedetomidine and propofol are used to decrease cerebral metabolic rate. However, it is unknown the immunomodulatory actions of dexmedetomidine and propofol on brain and lungs during acute ischemic stroke. The effects of dexmedetomidine and propofol were compared on perilesional brain tissue and lung damage after acute ischemic stroke in rats. Further, the mean amount of both sedatives was directly evaluated on alveolar macrophages and lung endothelial cells primarily extracted 24-h after acute ischemic stroke. In twenty-five Wistar rats, ischemic stroke was induced and after 24-h treated with sodium thiopental (STROKE), dexmedetomidine and propofol. Dexmedetomidine, compared to STROKE, reduced diffuse alveolar damage score [median(interquartile range); 12(7.8–15.3) vs. 19.5(18–24), p = 0.007)], bronchoconstriction index [2.28(2.08–2.36) vs. 2.64(2.53–2.77), p = 0.006], and TNF-α expression (p = 0.0003), while propofol increased VCAM-1 expression compared to STROKE (p = 0.0004). In perilesional brain tissue, dexmedetomidine, compared to STROKE, decreased TNF-α (p = 0.010), while propofol increased VCAM-1 compared to STROKE (p = 0.024). In alveolar macrophages and endothelial cells, dexmedetomidine decreased IL-6 and IL-1β compared to STROKE (p = 0.002, and p = 0.040, respectively), and reduced IL-1β compared to propofol (p = 0.014). Dexmedetomidine, but not propofol, induced brain and lung protection in experimental acute ischemic stroke.

Background Obesity is associated with a chronic systemic inflammatory process. Volatile or intravenous anesthetic agents may modulate immune function, and may do so differentially in obesity. However, no study has evaluated whether these potential immunomodulatory effects differ according to type of anesthesia in obese patients undergoing laparoscopic bariatric surgery. Methods/design The OBESITA trial is a prospective, nonblinded, single-center, randomized, controlled clinical pilot trial. The trial will include 48 patients with a body mass index ≥ 35 kg/m 2 , scheduled for laparoscopic bariatric surgery using sleeve or a Roux-en-Y gastric bypass technique, who will be allocated 1:1 to undergo general inhalational anesthesia with sevoflurane or total intravenous anesthesia (TIVA) with propofol. The primary endpoint is the difference in plasma interleukin (IL)-6 levels when comparing the two anesthetic agents. Blood samples will be collected prior to anesthesia induction (baseline), immediately after anesthetic induction, and before endotracheal extubation. Levels of other proinflammatory and anti-inflammatory cytokines, neutrophil chemotaxis, macrophage differentiation, phagocytosis, and occurrence of intraoperative and postoperative complications will also be evaluated. Discussion To our knowledge, this is the first randomized clinical trial designed to compare the effects of two different anesthetics on immunomodulation in obese patients undergoing laparoscopic bariatric surgery. Our hypothesis is that anesthesia with sevoflurane will result in a weaker proinflammatory response compared to anesthesia with propofol, with lower circulating levels of IL-6 and other proinflammatory mediators, and increased macrophage differentiation into the M2 phenotype in adipose tissue. Trial registration Registro Brasileiro de Ensaios Clínicos, RBR-77kfj5 . Registered on 25 July 2018. Electronic supplementary material The online version of this article (10.1186/s13063-019-3399-z) contains supplementary material, which is available to authorized users.

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