Background: Flow-controlled ventilation is a novel ventilation method which allows to individualize ventilation according to dynamic lung mechanic limits based on direct tracheal pressure measurement at a stable constant gas flow during inspiration and expiration. The aim of this porcine study was to compare individualized flow-controlled ventilation (FCV) and current guideline-conform pressure-controlled ventilation (PCV) in long-term ventilation.Methods: Anesthetized pigs were ventilated with either FCV or PCV over a period of 10 h with a fixed FiO₂of 0.3. FCV settings were individualized by compliance-guided positive end-expiratory pressure (PEEP) and peak pressure (P_peak) titration. Flow was adjusted to maintain normocapnia and the inspiration to expiration ratio (I:E ratio) was set at 1:1. PCV was performed with a PEEP of 5 cm H₂O andP_peakwas set to achieve a tidal volume (V_T) of 7 ml/kg. The respiratory rate was adjusted to maintain normocapnia and the I:E ratio was set at 1:1.5. Repeated measurements during observation period were assessed by linear mixed-effects model.Results: In FCV (n = 6), respiratory minute volume was significantly reduced (6.0 vs 12.7, MD − 6.8 (− 8.2 to − 5.4) l/min;p < 0.001) as compared to PCV (n = 6). Oxygenation was improved in the FCV group (paO₂119.8 vs 96.6, MD 23.2 (9.0 to 37.5) Torr; 15.97 vs 12.87, MD 3.10 (1.19 to 5.00) kPa;p = 0.010) and CO₂removal was more efficient (paCO₂40.1 vs 44.9, MD − 4.7 (− 7.4 to − 2.0) Torr; 5.35 vs 5.98, MD − 0.63 (− 0.99 to − 0.27) kPa;p = 0.006).P_peakand driving pressure were comparable in both groups, whereas PEEP was significantly lower in FCV (p = 0.002). Computed tomography revealed a significant reduction in non-aerated lung tissue in individualized FCV (p = 0.026) and no significant difference in overdistended lung tissue, although a significantly higherV_Twas applied (8.2 vs 7.6, MD 0.7 (0.2 to 1.2) ml/kg;p = 0.025).Conclusion: Our long-term ventilation study demonstrates the applicability of a compliance-guided individualization of FCV settings, which resulted in significantly improved gas exchange and lung tissue aeration without signs of overinflation as compared to best clinical practice PCV.

The influence of adrenaline during cardiopulmonary resuscitation (CPR) on the neurological outcome of cardiac arrest survivors is unclear. As little is known about the pathophysiological effects of adrenaline on cerebral oxygen delivery and cerebral metabolism we investigated its effects on parameters of cerebral oxygenation and cerebral metabolism in a pig model of CPR. Fourteen pigs were anesthetized, intubated and instrumented. After 5 min of cardiac arrest CPR was started and continued for 15 min. Animals were randomized to receive bolus injections of either 15 or 30 μg/kg adrenaline every 5 min after commencement of CPR. Measurements included mean arterial pressure (MAP), intracranial pressure (ICP), cerebral perfusion pressure (CPP), cerebral regional oxygen saturation (rSO2), brain tissue oxygen tension (PbtO2), arterial and cerebral venous blood gases and cerebral microdialysis parameters, e.g. lactate/pyruvate ratio. Adrenaline induced a significant increase in MAP and CPP in all pigs. However, increases in MAP and CPP were short-lasting and tended to decrease with repetitive bolus administration. There was no statistical difference in any parameter of cerebral oxygenation or metabolism between study groups. Both adrenaline doses resulted in short-lasting CPP peaks which did not translate into improved cerebral tissue oxygen tension and metabolism. Further studies are needed to determine whether other dosing regimens targeting a sustained increase in CPP, may lead to improved brain oxygenation and metabolism, thereby improving neurological outcome of cardiac arrest patients.

The endothelial glycocalyx is a thin layer consisting of proteoglycans, glycoproteins and glycosaminoglycans that lines the luminal side of vascular endothelial cells. It acts as a barrier and contributes to the maintenance of vascular homeostasis and microperfusion. During solid organ transplantation, the endothelial glycocalyx of the graft is damaged as part of Ischemia Reperfusion Injury (IRI), which is associated with impaired organ function. Although several substances are known to mitigate glycocalyx damage, it has not been possible to use these substances during graft storage on ice. Normothermic machine perfusion (NMP) emerges as an alternative technology for organ preservation and allows for organ evaluation, but also offers the possibility to treat and thus improve organ quality during storage. This review highlights the current knowledge on glycocalyx injury during organ transplantation, presents ways to protect the endothelial glycocalyx and discusses potential glycocalyx protection strategies during normothermic machine perfusion.

The effects of adrenaline on cerebral blood vessels during cardiopulmonary resuscitation (CPR) are not well understood. We developed an extracorporeal CPR model that maintains constant low systemic blood flow while allowing adrenaline-associated effects on cerebral vasculature to be assessed at different mean arterial pressure (MAP) levels independently of the effects on systemic blood flow. After eight minutes of cardiac arrest, low-flow extracorporeal life support (ECLS) (30 ml/kg/min) was started in fourteen pigs. After ten minutes, continuous adrenaline administration was started to achieve MAP values of 40 (n = 7) or 60 mmHg (n = 7). Measurements included intracranial pressure (ICP), cerebral perfusion pressure (CePP), laser-Doppler-derived regional cerebral blood flow (CBF), cerebral regional oxygen saturation (rSO₂), brain tissue oxygen tension (P_btO₂) and extracellular cerebral metabolites assessed by cerebral microdialysis. During ECLS without adrenaline, regional CBF increased by only 5% (25th to 75th percentile: -3 to 14; p = 0.2642) and P_btO₂ by 6% (0-15; p = 0.0073) despite a significant increase in MAP to 28 mmHg (25-30; p < 0.0001) and CePP to 10 mmHg (8-13; p < 0.0001). Accordingly, cerebral microdialysis parameters showed a profound hypoxic-ischemic pattern. Adrenaline administration significantly improved regional CBF to 29 ± 14% (p = 0.0098) and 61 ± 25% (p < 0.001) and P_btO₂ to 15 ± 11% and 130 ± 82% (both p < 0.001) of baseline in the MAP 40 mmHg and MAP 60 mmHg groups, respectively. Importantly, MAP of 60 mmHg was associated with metabolic improvement. This study shows that adrenaline administration during constant low systemic blood flow increases CePP, regional CBF, cerebral oxygenation and cerebral metabolism.

Multifactorial comparison of flow-controlled ventilation (FCV) to standard of pressure-controlled ventilation (PCV) in terms of oxygenation in cardiac surgery patients after chest closure. Prospective, non-blinded, randomized, controlled trial. Operating theatre at an university hospital, Austria. Patients scheduled for elective, open, on-pump, cardiac surgery. Participants were randomized to either individualized FCV (compliance guided end-expiratory and peak pressure setting) or control of PCV (compliance guided end-expiratory pressure setting and tidal volume of 6-8 ml/kg) for the duration of surgery. The primary outcome measure was oxygenation (PaO₂/FiO₂) 15 min after intraoperative chest closure. Secondary endpoints included CO₂-removal assessed as required minute volume to achieve normocapnia and lung tissue aeration assessed by Hounsfield unit distribution in postoperative computed tomography scans. Between April 2020 and April 2021 56 patients were enrolled and 50 included in the primary analysis (mean age 70 years, 38 (76%) men). Oxygenation, assessed by PaO₂/FiO₂, was significantly higher in the FCV group (n = 24) compared to the control group (PCV, n = 26) (356 vs. 309, median difference (MD) 46 (95% CI 3 to 90) mmHg; p = 0.038). Additionally, the minute volume required to obtain normocapnia was significantly lower in the FCV group (4.0 vs. 6.1, MD -2.0 (95% CI -2.5 to -1.5) l/min; p < 0.001) and correlated with a significantly lower exposure to mechanical power (5.1 vs. 9.8, MD -5.1 (95% CI -6.2 to -4.0) J/min; p < 0.001). Evaluation of lung tissue aeration revealed a significantly reduced amount of non-aerated lung tissue in FCV compared to PCV (5 vs. 7, MD -3 (95% CI -4 to -1) %; p < 0.001). In patients undergoing on-pump, cardiac surgery individualized FCV significantly improved oxygenation and lung tissue aeration compared to PCV. In addition, carbon dioxide removal was accomplished at a lower minute volume leading to reduced applied mechanical power.