The Equilibration of PCO2 in Pigs Is Independent of Lung Injury and Hemodynamics.

OBJECTIVES: In mechanical ventilation, normoventilation in terms of PCO2 can be achieved by titration of the respiratory rate and/or tidal volume. Although a linear relationship has been found between changes in respiratory rate and resulting changes in end-tidal cO2 (△PetCO2) as well as between changes in respiratory rate and equilibration time (teq) for mechanically ventilated patients without lung injury, it is unclear whether a similar relationship holds for acute lung injury or altered hemodynamics. DESIGN: We performed a prospective randomized controlled animal study of the change in PetCO2 with changes in respiratory rate in a lung-healthy, lung-injury, lung-healthy + altered hemodynamics, and lung-injury + altered hemodynamics pig model. SETTING: University research laboratory. SUBJECTS: Twenty mechanically ventilated pigs. INTERVENTIONS: Moderate lung injury was induced by injection of oleic acid in 10 randomly assigned pigs, and after the first round of measurements, cardiac output was increased by approximately 30% by constant administration of noradrenalin in both groups. MEASUREMENTS AND MAIN RESULTS: We systematically increased and decreased changes in respiratory rate according to a set protocol: +2, -4, +6, -8, +10, -12, +14 breaths/min and awaited equilibration of Petco2. We found a linear relationship between changes in respiratory rate and △PetCO2 as well as between changes in respiratory rate and teq. A two-sample t test resulted in no significant differences between the lung injury and healthy control group before or after hemodynamic intervention. Furthermore, exponential extrapolation allowed prediction of the new PetCO2 equilibrium and teq after 5.7 ± 5.6 min. CONCLUSIONS: The transition between PetCO2 equilibria after changes in respiratory rate might not be dependent on moderate lung injury or cardiac output but on the metabolic production or capacity of cO2 stores. Linear relationships previously found for lung-healthy patients and early prediction of PetCO2 equilibration could therefore also be used for the titration of respiratory rate on the PetCO2 for a wider range of pathologies by the physician or an automated ventilation system.

Independent replications reveal anterior and posterior cingulate cortex activation underlying state anxiety-attenuated face encoding.

Anxiety involves the anticipation of aversive outcomes and can impair neurocognitive processes, such as the ability to recall faces encoded during the anxious state. It is important to precisely delineate and determine the replicability of these effects using causal state anxiety inductions in the general population. This study therefore aimed to replicate prior research on the distinct impacts of threat-of-shock-induced anxiety on the encoding and recognition stage of emotional face processing, in a large asymptomatic sample (n = 92). We successfully replicated previous results demonstrating impaired recognition of faces encoded under threat-of-shock. This was supported by a mega-analysis across three independent studies using the same paradigm (n = 211). Underlying this, a whole-brain fMRI analysis revealed enhanced activation in the posterior cingulate cortex (PCC), alongside previously seen activity in the anterior cingulate cortex (ACC) when combined in a mega-analysis with the fMRI findings we aimed to replicate. We further found replications of hippocampus activation when the retrieval and encoding states were congruent. Our results support the notion that state anxiety disrupts face recognition, potentially due to attentional demands of anxious arousal competing with affective stimuli processing during encoding and suggest that regions of the cingulate cortex play pivotal roles in this.

Effects of psilocybin versus escitalopram on rumination and thought suppression in depression.

BACKGROUND: Major depressive disorder is often associated with maladaptive coping strategies, including rumination and thought suppression. AIMS: To assess the comparative effect of the selective serotonin reuptake inhibitor escitalopram, and the serotonergic psychedelic psilocybin (COMP360), on rumination and thought suppression in major depressive disorder. METHOD: Based on data derived from a randomised clinical trial (N = 59), we performed exploratory analyses on the impact of escitalopram versus psilocybin (i.e. condition) on rumination and thought suppression from 1 week before to 6 weeks after treatment inception (i.e. time), using mixed analysis of variance. Condition responder versus non-responder subgroup analyses were also done, using the standard definition of ≥50% symptom reduction. RESULTS: A time×condition interaction was found for rumination (F(1, 56) = 4.58, P = 0.037) and thought suppression (F(1,57) = 5.88, P = 0.019), with post hoc tests revealing significant decreases exclusively in the psilocybin condition. When analysing via response, a significant time×condition×response interaction for thought suppression (F(1,54) = 8.42, P = 0.005) and a significant time×response interaction for rumination (F(1,54) = 23.50, P < 0.001) were evident. Follow-up tests revealed that decreased thought suppression was exclusive to psilocybin responders, whereas rumination decreased in both responder groups. In the psilocybin arm, decreases in rumination and thought suppression correlated with ego dissolution and session-linked psychological insight. CONCLUSIONS: These data provide further evidence on the therapeutic mechanisms of psilocybin and escitalopram in the treatment of depression.

Simultaneous monitoring of intratidal compliance and resistance in mechanically ventilated piglets: A feasibility study in two different study groups.

Compliance measures the force counteracting parenchymal lung distension. In mechanical ventilation, intratidal compliance-volume (C(V))-profiles therefore change depending on PEEP, tidal volume (VT), and underlying mechanical lung properties. Resistance counteracts gas flow through the airways. Due to anatomical linking between parenchyma and airways, intratidal resistance-volume (R(V))-profiles are hypothesised to change in a non-linear way as well. We analysed respiratory system mechanics in fifteen piglets with lavage-induced lung injury and nine healthy piglets ventilated at different PEEP/VT-settings. In healthy lungs, R(V)-profiles remained mostly constant and linear at all PEEP-settings whereas the shape of the C(V)-profiles showed an increase toward a maximum followed by a decrease (small PEEP) or volume-dependent decrease (large PEEP). In the lavage group, a large drop in resistance at small volumes and slow decrease toward larger volumes was found for small PEEP/VT-settings where C(V)-profiles revealed a volume-dependent increase (small PEEP) or a decrease (large PEEP and large VT). R(V)-profiles depend characteristically on PEEP, VT, and possibly whether lungs are healthy or not. Curved R(V)-profiles might indicate pathological changes in the underlying mechanical lung properties and/or might be a sign of derecruitment.

Breathing-phase selective filtering of respiratory data improves analysis of dynamic respiratory mechanics.

BACKGROUND: The analysis of non-linear respiratory system mechanics under the dynamic conditions of controlled mechanical ventilation is affected by systemic disturbances of the respiratory signals. Cardio-pulmonary coupling induces cardiogenic oscillations to the respiratory signals, which appear prominently in the second half of expiration. OBJECTIVE: We hypothesized that breathing phase-selective filtering of expiratory data improves the analysis of respiratory system mechanics. METHODS: We retrospectively analyzed data from a multicenter-study (28 patients with injured lungs, under volume-controlled ventilation) and from two additional studies (3 lung healthy patients and 3 with injured lungs, under pressure-controlled ventilation). Data streams were recorded at different levels of positive end-expiratory pressure. Using the gliding-SLICE method, intratidal dynamic respiratory mechanics were analyzed with and without low-pass filtering of expiratory or inspiratory data separately. The quality of data analysis was derived from the coefficient of determination R^2. RESULTS: Without filtering, R^2 lay below 0.995 for 87 of 280 investigated data streams. In 68 cases expiration-selective low-pass filtering improved the quality of analysis to R^2 ⩾ 0.995. In contrast, inspiration-selective filtering did not improve R^2. CONCLUSIONS: The selective filtering of expiration data eliminates negative side-effects of cardiogenic oscillations thus leading to a significant improvement of the analysis of dynamic respiratory system mechanics.

The dynamics of carbon dioxide equilibration after alterations in the respiratory rate.

Manual or automated control of mechanical ventilation can be realized as an open or closed-loop system for which the regulation of the ventilation parameters ideally is tuned to the dynamics and equilibration time of the biological system. We investigated the dynamic, transient state and equilibration time (teq) of the CO2 partial pressure (PCO2) after changes in the respiratory rate (RR). In 17 anaesthetized patients without known history of lung disease, respiratory rate was alternately increased and decreased and end-tidal CO2 partial pressures (PetCO2) were measured. Linear relations were found between ΔRR and PetCO2 changes (ΔPetCO2 = 0.3 − 1.1 ΔRR) and between ΔRR and teq for increasing and decreasing RR (teq(hypervent) = 0.5 |ΔRR|, teq(hypovent) = 0.7 |ΔRR|). Extrapolation of the transition between two PCO2 steady-states allowed for the prediction of the new PCO2 steady-state as early as 0.5 teq with an error <4 mmHg. At bedside or in automated ventilation systems, the linear dependencies between ΔRR and ΔPCO2 and between ΔRR and teq as well as early steady-state prediction of PCO2 could be used as a guidance towards a timing and step size regulation of RR that is well adapted to the biological system.