Abstract

BackgroundProtective 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.ResultsNo 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.ConclusionsContrary 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.

Highlights

  • Protective ventilation with lower tidal volumes reduces systemic and organ-specific inflammation

  • Mechanical ventilation (MV) carries the risks of cyclic atelectasis and overdistension of alveoli, events that add to a pro-inflammatory response [1]

  • Three animals in the Medium high V­ T group and two animals in the Low ­Tidal volume (VT) group received noradrenalin during the experiment according to the protocol

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Summary

Introduction

Protective ventilation with lower tidal volumes reduces systemic and organ-specific inflammation. The aim of the study was to study the effect of tidal volume on cerebral inflammatory response, cerebral metabolism and brain injury. Protective ventilation, i.e. the avoidance of iatrogenic harm by the use of higher than traditional positive end-expiratory pressure (PEEP) levels and smaller than traditional tidal volumes ­(VT), has an established role in the care of patients with acute respiratory distress syndrome (ARDS) [2]. Experimental large animal studies have shown strong associations between lower tidal volumes and decreased systemic and organ-specific inflammation, as well as decreased microbiological growth [4,5,6]. The pathophysiology of SAE is highly complex and not fully understood, but proposed mechanisms include alterations in the blood–brain barrier, effects of local and systemic inflammatory cytokines, cerebral metabolism disruption and imbalance of neurotransmitters [8, 9]

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