Adaptive Brain Shut-Down Counteracts Neuroinflammation in the Near-Term Ovine Fetus

Objective: Repetitive umbilical cord occlusions (UCOs) in ovine fetus leading to severe acidemia result in adaptive shut-down of electrocortical activity (ECOG) as well as systemic and brain inflammation. We hypothesized that the fetuses with earlier ECOG shut-down as a neuroprotective mechanism in response to repetitive UCOs will show less brain inflammation and, moreover, that chronic hypoxia will impact this relationship.Methods: Near term fetal sheep were chronically instrumented with ECOG leads, vascular catheters and a cord occluder and then underwent repetitive UCOs for up to 4 hours or until fetal arterial pH was < 7.00. Eight animals, hypoxic prior to the UCOs (SaO2< 55%), were allowed to recover 24 hours post insult, while 14 animals, five of whom also were chronically hypoxic, were allowed to recover 48 hours post insult, after which brains were perfusion-fixed. Time of ECOG shut-down and corresponding pH were noted, as well as time to then reach pH<7.00 (ΔT). Microglia (MG) were counted as a measure of inflammation in grey matter layers 4-6 (GM4-6) where most ECOG activity is generated. Results are reported as mean±SEM for p<0.05.Results: Repetitive UCOs resulted in worsening acidosis over 3 to 4 hours with arterial pH decreasing to 6.97±0.02 all UCO groups’ animals, recovering to baseline by 24 hours. ECOG shut-down occurred 52±7 min before reaching pH < 7.00 at pH 7.23±0.02 across the animal groups. MG counts were inversely correlated to ΔT in 24 hours recovery animals (R=-0.84), as expected. This was not the case in normoxic 48 hours recovery animals, and, surprisingly, in hypoxic 48 hours recovery animals this relationship was reversed (R=0.90).Conclusion: Adaptive brain shut-down during labour-like worsening acidemia counteracts neuroinflammation in a hypoxia- and time-dependent manner

Impact of ventilatory modes on the breathing variability in mechanically ventilated infants.

Objectives: Reduction of breathing variability is associated with adverse outcome. During mechanical ventilation, the variability of ventilatory pressure is dependent on the ventilatory mode. During neurally adjusted ventilatory assist (NAVA), the support is proportional to electrical activity of diaphragm (EAdi), which reflects the respiratory center output. The variability of EAdi is therefore translated into a similar variability in pressures. Contrastingly, conventional ventilatory modes deliver less variable pressures. The impact of the mode on the patient’s own respiratory drive is less clear. This study aims to compare the impact of NAVA, pressure-control (PCV) and pressure-support ventilation (PSV) on the respiratory drive patterns in infants. We hypothesized that on NAVA, EAdi variability resembles most the endogenous respiratory drive pattern seen in a control group.Methods: EAdi was continuously recorded in 10 infants ventilated successively on NAVA (5 hours), PCV (30 min), and PSV (30 min). During the last 10 minutes of each period, the EAdi variability pattern was assessed using non-rhythmic to rhythmic index (NRR). These variability profiles were compared to the pattern of a control group of 11 spontaneously breathing and non-intubated infants.Results: In control infants, NRR was higher as compared to mechanically ventilated infants (p<0.001), and NRR pattern was relatively stable over time. While the temporal stability of NRR was similar in NAVA and controls, the NRR profile was less stable during PCV. PSV exhibited an intermediary pattern. Perspectives: Mechanical ventilation impacts the breathing variability in infants. NAVA produces EAdi pattern resembling most that of control infants. NRR can be used to characterize respiratory variability in infants. Larger prospective studies are necessary to understand the differential impact of the ventilatory modes on the cardio-respiratory variability and to study their impact on clinical outcomes