Impact of positive end-expiratory pressure on autonomic nervous system activity and its interaction with cerebrovascular reactivity – an experimental study

Mechanical ventilation requires positive end-expiratory pressure (PEEP), which has shown to improve lung recruitment and gas exchange. However, the increase in intrathoracic pressure might impact cardiac function and autonomic nervous system (ANS) activity. This post hoc analysis aimed to evaluate the impact of incremental PEEP on ANS activity and to examine its relationship with cerebrovascular reactivity in an experimental model. Twelve anesthetized, mechanically ventilated pigs were studied in both the supine and prone positions at baseline PEEP (5 cmH₂O) and at incremental PEEP levels (10, 15, 20 cmH₂O). ANS parameters included time-domain heart rate variability (HRV): the standard deviation of normal pulse intervals (SDNN), the root mean square of successive differences between normal heartbeats (RMSSD), HRV entropy measures: fuzzy entropy (FuzzyEn) and sample entropy (SampEn), heart rate asymmetry indices: Guzik's index (GI) and Porta's index (PI), and baroreflex sensitivity (BRS). Cerebrovascular reactivity was assessed using the pressure reactivity index (PRx). Relationships between ANS metrics and PRx were analyzed using univariate and multivariate linear mixed-effects models (LMEMs), adjusted for PEEP. Increasing PEEP significantly altered HRV entropy (FuzzyEn: p = 0.006; SampEn: p = 0.018) and BRS (p = 0.013) in the supine position, with similar trends observed in the prone position. In the univariate LMEM analyses, all ANS metrics significantly influenced PRx in both positions. However, in the multivariate LMEM models, only SDNN (p = 0.001), RMSSD (p = 0.001), GI (p = 0.003), and PI (p = 0.007) remained significantly associated with PRx in the prone position, whereas no ANS metrics remained significant in the supine position. Incremental PEEP modifies ANS activity, as reflected by changes in HRV entropy and BRS. Prone positioning appears to preserve the autonomic modulation of cerebrovascular reactivity under PEEP. These findings underscore the importance of considering ventilatory settings when assessing heart-brain interactions.