title: Lung protective ventilation induces immunotolerance and nitric oxide metabolites in porcine experimental postoperative sepsis.
abstract: Low tidal volume ventilation is beneficial in patients with severe pulmonary dysfunction and would, in theory, reduce postoperative complications if implemented during routine surgery. The study aimed to investigate whether low tidal volume ventilation and high positive end-expiratory pressure (PEEP) in a large animal model of postoperative sepsis would attenuate the systemic inflammatory response and organ dysfunction. Thirty healthy pigs were randomized to three groups: Group Prot-7h, i.e. protective ventilation for 7 h, was ventilated with a tidal volume of 6 mL x kg(-1) for 7 h; group Prot-5h, i.e. protective ventilation for 5 h, was ventilated with a tidal volume of 10 mL x kg(-1) for 2 h, after which the group was ventilated with a tidal volume of 6 mL x kg(-1); and a control group that was ventilated with a tidal volume of 10 mL x kg(-1) for 7 h. In groups Prot-7h and Prot-5h PEEP was 5 cmH2O for 2 h and 10 cmH2O for 5 h. In the control group PEEP was 5 cmH2O for the entire experiment. After surgery for 2 h, postoperative sepsis was simulated with an endotoxin infusion for 5 h. Low tidal volume ventilation combined with higher PEEP led to lower levels of interleukin 6 and 10 in plasma, higher PaO2/FiO2, better preserved functional residual capacity and lower plasma troponin I as compared with animals ventilated with a medium high tidal volume and lower PEEP. The beneficial effects of protective ventilation were seen despite greater reductions in cardiac index and oxygen delivery index. In the immediate postoperative phase low VT ventilation with higher PEEP was associated with reduced ex vivo plasma capacity to produce TNF-α upon endotoxin stimulation and higher nitrite levels in urine. These findings might represent mechanistic explanations for the attenuation of systemic inflammation and inflammatory-induced organ dysfunction.
authors.affiliation: Centre for Clinical Research Sörmland, Uppsala University, Uppsala, Sweden ; Department of Medical Sciences, Infectious Diseases, Uppsala University, Uppsala, Sweden.
authors.forename: Jesper
authors.initials: J
authors.lastname: Sperber
authors.affiliation: Department of Surgical Sciences, Anaesthesiology and Intensive Care, Uppsala University, Uppsala, Sweden.
authors.forename: Miklós
authors.initials: M
authors.lastname: Lipcsey
authors.affiliation: Department of Surgical Sciences, Anaesthesiology and Intensive Care, Uppsala University, Uppsala, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Larsson
authors.affiliation: Department of Medical Sciences, Biochemical Structure and Function, Uppsala University, Uppsala, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Larsson
authors.affiliation: Department of Medical Sciences, Infectious Diseases, Uppsala University, Uppsala, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Sjölin
authors.affiliation: Centre for Clinical Research Sörmland, Uppsala University, Uppsala, Sweden ; Department of Medical Sciences, Infectious Diseases, Uppsala University, Uppsala, Sweden.
authors.forename: Markus
authors.initials: M
authors.lastname: Castegren
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D007108:Immune Tolerance; D009569:Nitric Oxide / Q000276:immunology*; D010100:Oxygen / Q000276:immunology; D010366:Peak Expiratory Flow Rate / Q000276:immunology; D011183:Postoperative Complications / Q000276:immunology / Q000628:therapy; D012121:Respiration, Artificial; D018805:Sepsis / Q000209:etiology / Q000276:immunology / Q000628:therapy; D013552:Swine; D013997:Time Factors
chemical_list: D009569:Nitric Oxide; D010100:Oxygen