title: Sevoflurane Abolishes Oxygenation Impairment in a Long-Term Rat Model of Acute Lung Injury.
abstract: Patients experiencing acute lung injury (ALI) often need mechanical ventilation for which sedation may be required. In such patients, usually the first choice an intravenously administered drug. However, growing evidence suggests that volatile anesthetics such as sevoflurane are a valuable alternative. In this study, we evaluate pulmonary and systemic effects of long-term (24-hour) sedation with sevoflurane compared with propofol in an in vivo animal model of ALI.
  
  
  
  Adult male Wistar rats were subjected to ALI by intratracheal lipopolysaccharide (LPS) application, mechanically ventilated and sedated for varying intervals up to 24 hours with either sevoflurane or propofol. Vital parameters were monitored, and arterial blood gases were analyzed. Inflammation was assessed by the analysis of bronchoalveolar lavage fluid (BALF), cytokines (monocyte chemoattractant protein-1 [MCP-1], cytokine-induced neutrophil chemoattractant protein-1 [CINC-1], interleukin [IL-6], IL-12/12a, transforming growth factor-β, and IL-10) in blood and lung tissue and inflammatory cells. The alveolocapillary barrier was indirectly assessed by wet-to-dry ratio, albumin, and total protein content in BALF. Results are presented as mean ± standard deviation.
  
  
  
  After 9 hours of ventilation and sedation, oxygenation index was higher in the LPS/sevoflurane (LPS-S) than in the LPS/propofol group (LPS-P) and reached 400 ± 67 versus 262 ± 57 mm Hg after 24 hours (P < .001). Cell count in BALF in sevoflurane-treated animals was lower after 18 hours (P = .001) and 24 hours (P < .001) than in propofol controls. Peak values of CINC-1 and IL-6 in BALF were lower in LPS-S versus LPS-P animals (CINC-1: 2.7 ± 0.7 vs 4.0 ± 0.9 ng/mL; IL-6: 9.2 ± 2.3 vs 18.9 ± 7.1 pg/mL, both P < .001), whereas IL-10 and MCP-1 did not differ. Also messenger RNAs of CINC-1, IL-6, IL-12a, and IL-10 were significantly higher in LPS-P compared with LPS-S. MCP-1 and transforming growth factor-β showed no differences. Wet-to-dry ratio was lower in LPS-S (5.4 ± 0.2 vs 5.7 ± 0.2, P = .016). Total protein in BALF did not differ between P-LPS and S-LPS groups.
  
  
  
  Long-term sedation with sevoflurane compared with propofol improves oxygenation and attenuates the inflammatory response in LPS-induced ALI. Our findings suggest that sevoflurane may improve lung function when used for sedation in patients with ALI.
authors: From the *Institute of Anesthesiology, University Hospital Zurich, Zurich, Switzerland; and †Institute of Physiology, Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
authors: Patrick
authors: P
authors: Kellner
authors: Mattia
authors: M
authors: Müller
authors: Tobias
authors: T
authors: Piegeler
authors: Philipp
authors: P
authors: Eugster
authors: Christa
authors: C
authors: Booy
authors: Martin
authors: M
authors: Schläpfer
authors: Beatrice
authors: B
authors: Beck-Schimmer
mesh_terms: D055371:Acute Lung Injury / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology / Q000628:therapy*; D018685:Anesthetics, Inhalation / Q000008:administration & dosage*; D018686:Anesthetics, Intravenous / Q000008:administration & dosage*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D015824:Blood-Air Barrier / Q000187:drug effects / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002199:Capillary Permeability / Q000187:drug effects; D016207:Cytokines / Q000097:blood / Q000235:genetics; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects; D018836:Inflammation Mediators / Q000097:blood; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008738:Methyl Ethers / Q000008:administration & dosage*; D010100:Oxygen / Q000097:blood*; D011014:Pneumonia / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D015742:Propofol / Q000008:administration & dosage*; D017208:Rats, Wistar; D012121:Respiration, Artificial; D000077149:Sevoflurane; D013997:Time Factors
chemical_list: D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D008738:Methyl Ethers; C482199:lipopolysaccharide, E coli O55-B5; D000077149:Sevoflurane; D010100:Oxygen; D015742:Propofol