Lung-protective ventilation increases cerebral metabolism and non-inflammatory brain injury in porcine experimental sepsis

Axel Nyberg1, Erik Gremo1, Jonas Blixt2, Jesper Sperber1, Anders Larsson3, Miklós Lipcsey4, Andreas Pikwer1, Markus Castegren3
1Centre for Clinical Research Sörmland, Uppsala University, Uppsala, Sweden
2Perioperative Medicine and Intensive Care (PMI), Karolinska University Hospital, Stockholm, Sweden
3Department of Medical Sciences, Uppsala University, Uppsala, Sweden
4Hedenstierna Laboratory, CIRRUS, Anesthesiology and Intensive Care, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden

Tóm tắt

Abstract Background Protective ventilation with lower tidal volumes reduces systemic and organ-specific inflammation. In sepsis-induced encephalopathy or acute brain injury the use of protective ventilation has not been widely investigated (experimentally or clinically). We hypothesized that protective ventilation would attenuate cerebral inflammation in a porcine endotoxemic sepsis model. The aim of the study was to study the effect of tidal volume on cerebral inflammatory response, cerebral metabolism and brain injury. Nine animals received protective mechanical ventilation with a tidal volume of 6 mL × kg−1 and nine animals were ventilated with a tidal volume of 10 mL × kg−1. During a 6-h experiment, the pigs received an endotoxin intravenous infusion of 0.25 µg × kg−1 × h−1. Systemic, superior sagittal sinus and jugular vein blood samples were analysed for inflammatory cytokines and S100B. Intracranial pressure, brain tissue oxygenation and brain microdialysis were sampled every hour. Results No differences in systemic or sagittal sinus levels of TNF-α or IL-6 were seen between the groups. The low tidal volume group had increased cerebral blood flow (p < 0.001) and cerebral oxygen delivery (p < 0.001), lower cerebral vascular resistance (p < 0.05), higher cerebral metabolic rate (p < 0.05) along with higher cerebral glucose consumption (p < 0.05) and lactate production (p < 0.05). Moreover, low tidal volume ventilation increased the levels of glutamate (p < 0.01), glycerol (p < 0.05) and showed a trend towards higher lactate to pyruvate ratio (p = 0.08) in cerebral microdialysate as well as higher levels of S-100B (p < 0.05) in jugular venous plasma compared with medium–high tidal volume ventilation. Conclusions Contrary to the hypothesis, protective ventilation did not affect inflammatory cytokines. The low tidal volume group had increased cerebral blood flow, cerebral oxygen delivery and cerebral metabolism together with increased levels of markers of brain injury compared with medium–high tidal volume ventilation.

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