The effects of perfluorocarbon dosing strategy on cerebral blood flow when starting partial liquid ventilation: A randomized, controlled, experimental study

Abstract

Introduction: Partial liquid ventilation may benefit the lung disease in preterm neonates but intratracheal instillation of perfluorocarbon increases cerebral blood flow and may cause brain injury. We aimed to determine if the effects of perfluorocarbon administration on cerebral blood flow vary by dose-volume, rate of administration, endotracheal tube portal of entry, or closely targeting PaCO<sub>2</sub>. Methods: Forty-two dosing events (in eleven rabbits) were randomised to different dosing strategies, including a sham (<i>i.e.</i>, placebo/control) dose of air over 20 min, 20 mL/kg of perfluorocarbon slowly over 20 min, 10 mL/kg of perfluorocarbon slowly over 20 min, 10 mL/kg of perfluorocarbon moderately fast over 10 min, 10 mL/kg of perfluorocarbon rapidly over 5 min, 10 mL/kg of perfluorocarbon slowly over 20 min via the endotracheal tube tip lumen (as opposed to the proximal end of the tube used in all other groups), or 10 mL/kg of perfluorocarbon slowly over 20 min whilst targeting a PaCO<sub>2</sub> of 45 - 50 mmHg. Blood gases, haemodynamics, cortical cerebral blood flow and carotid flow were recorded continuously for 30 minutes from the start of each dose. Results: Carotid flow increased with 20 mL/kg perfluorocarbon and cortical cerebral blood flow was significantly more variable. Carotid and cortical cerebral blood flow increased using 10 mL/kg or 20 mL/kg with no difference between the two dose-volumes. There was no difference in cerebral blood flow by rate of administration, but carotid blood flow was more variable during slow administration. There were no differences in the increase in cerebral blood flow by portal of entry. If PaCO<sub>2</sub> was maintained between 45 - 50 mmHg there was no increase in cerebral blood flow and there was less variable carotid flow. Conclusions: Cerebral blood flow increases with perfluorocarbon dosing. This occurs regardless of the dose-volume of perfluorocarbon. These effects were mitigated by closely targeting PaCO<sub>2</sub>

Cerebral blood flow is not affected during perfluorocarbon dosing with volume‐controlled ventilation

“…The lack of changes seen in cerebral blood flow while using volume‐controlled ventilation are in stark contrast to the large increases seen in carotid blood flow and cortical cerebral blood flow (and the variability of both) in our previous studies using pressure‐controlled ventilation without adjustment. In those studies, the increases in cerebral blood flow correlated strongly with decreases in tidal volumes and increased PaCO 2 (and less so with a drop in oxygenation).…”

“…After each event, any remaining FC‐77 was sucked out of the airway with the residual left to evaporate. The completeness of perfluorocarbon washout was confirmed when the measured expired tidal volumes equalled those set on the ventilator (as previously described).…”

“…Before our previous rabbit studies were done, we had already demonstrated that there was an effect of perfluorocarbon dosing on cerebral blood flow in animals with lung disease . One of the specific aims of those rabbit studies was to confirm that similar effects are seen in the adult rabbits without lung disease and to study a large number of different dosing strategies, particularly the acute dose effects on cerebral blood flow (not lung function). A simple and reliable model of the effects of perfluorocarbon administration on cerebral blood flow was needed.…”

“…In our current studies, as well as our previous rabbit studies, we investigated the effects of different dosing strategies in multiple sequences in single animals; others have also used this approach . Individual rabbits were not allocated dosing strategies: each dosing event was randomly allocated a different dosing strategy.…”

“…Our previous studies have shown that perfluorocarbon administration at the start of PLV increases cerebral blood flow . We have also shown that this effect can be mitigated with the use of continuous monitoring of arterial carbon dioxide allowing continuous adjustment of mechanical ventilation to prevent a rise in carbon dioxide . However, continuous arterial carbon dioxide monitoring is not available clinically.…”