End-tidal CO2 Partial Pressure Research Articles

The aging brain and cerebrovascular reactivity

Cerebrovascular reactivity (CVR) is a measure of vascular response to a vasoactive stimulus, and can be used to assess the health of the brain vasculature. In this current study we used different analyses of BOLD fMRI responses to CO2 to provide a number of metrics including ramp and step CVR, speed of response and transfer function analysis (TFA). 51 healthy control volunteers between the ages of 18–85 (26 males) were recruited and scanned at 3T field strength. Atlases reflecting voxel-wise means and standard deviations were compiled to assess possible differences in these metrics between four age cohorts. Testing was carried out using an automated computer-controlled gas blender to induce hypercapnia in a step and ramp paradigm, and monitoring end-tidal partial pressures of CO2 (PETCO2) and O2 (PETO2). No significant differences were found for resting PETCO2 values between cohorts. Ramp CVR decreased significantly with age in white matter frontal regions comprising the ACA-MCA watershed area, a finding that may be indicative of age related changes. Similarly, TFA showed that gain was reduced in the left white matter ACA-MCA watershed area as well as the posterior and anterior cingulate cortex, and superior frontal gyrus in the oldest compared to youngest cohort. These findings, detailing changes in cerebrovascular regulation in the healthy aging brain should prove useful in mapping areas of dysregulated blood flow in individuals with vascular risk factors especially those at risk for developing vascular dementia.

A high-flow nasal cannula system with relatively low flow effectively washes out CO2 from the anatomical dead space in a sophisticated respiratory model made by a 3D printer

BackgroundAlthough clinical studies of the high-flow nasal cannula (HFNC) and its effect on positive end-expiratory pressure (PEEP) have been done, the washout effect has not been well evaluated. Therefore, we made an experimental respiratory model to evaluate the respiratory physiological effect of HFNC.MethodsAn airway model was made by a 3D printer using the craniocervical 3D-CT data of a healthy 32-year-old male. CO2 was infused into four respiratory lung models (normal-lung, open- and closed-mouth models; restrictive- and obstructive-lung, open-mouth models) to maintain the partial pressure of end-tidal CO2 (PETCO2) at 40 mmHg. HFNC flow was changed from 10 to 60 L/min. Capnograms were recorded at the upper pharynx, oral cavity, subglottic, and inlet sites of each lung model.ResultsWith the normal-lung, open-mouth model, 10 L/min of HFNC flow decreased the subglottic PETCO2 to 30 mmHg. Increasing the HFNC flow did not further decrease the subglottic PETCO2. With the normal-lung, closed-mouth model, HFNC flow of 40 L/min was required to decrease the PETCO2 at all sites. Subglottic PETCO2 reached 30 mmHg with an HFNC flow of 60 L/min. In the obstructive-lung, open-mouth model, PETCO2 at all sites had the same trend as in the normal-lung, open-mouth model. In the restrictive-lung, open-mouth model, 20 L/min of HFNC flow decreased the subglottic PETCO2 to 25 mmHg, and it did not decrease further. As HFNC flow was increased, PEEP up to 7 cmH2O was gradually generated in the open-mouth models and up to 17 cmH2O in the normal-lung, closed-mouth model.ConclusionsThe washout effect of the HFNC was effective with relatively low flow in the open-mouth models. The closed-mouth model needed more flow to generate a washout effect. Therefore, HFNC flow should be considered based on the need for the washout effect or PEEP.

Isocapnic buffering phase: a useful indicator of exercise endurance in patients with coronary artery disease

ABSTRACTObjectives: The significance of the isocapnic buffering (IB) phase – the period between the first ventilatory threshold (1st VT) and respiratory compensation point (RCP) – has not been adequately established in patients. This study aimed to determine the clinical significance of the IB phase in patients with coronary artery disease (CAD).Methods: This retrospective study included data of sixty-two CAD patients after coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI) performed in a single medical center between 2010 – 2014. According to their physical conditions, the patients performed incremental cardiopulmonary exercise test (CPET) using a cycle ergometer by the ramp of 5–20 W/min. Correlations between the corrected IB phase duration and age, body mass index (BMI), left ventricular ejection fraction (LVEF), and CPET parameters were evaluated using Pearson correlation coefficients. Variables predicting peak oxygen consumption (VO2) were evaluated using multiple regression.Results: Peak VO2 (p < 0.001), VO2 at RCP (p < 0.001), ∆O2/∆WR slope (p < 0.001), maximal partial pressure of end tidal CO2 (PetCO2) (p = 0.0012), VE/VCO2 slope (p = 0.010), BMI (p = 0.012), and age (p = 0.017) were significantly correlated, whereas LVEF (p = 0.246) and VO2 at 1st VT (p = 0.179) were not significantly correlated with the corrected IB phase duration. In multiple regression analysis, the corrected IB phase duration, VO2 at 1st VT, and ∆O2/∆WR slope were significantly associated with peak VO2.Conclusion: The findings indicate that the IB phase duration is a useful indicator of peripheral cardiopulmonary function and endurance performance in CAD patients. These findings could assist the exercise prescription of cardiac rehabilitation for patients with CAD.

Compression garments and cerebral blood flow: Influence on cognitive and exercise performance

This study aimed to describe the effect of compression garments on middle cerebral artery blood flow velocity (MCAv) in relation to cognitive and exercise performance whilst cycling. In a randomised-controlled-cross-over design, 15 well-trained male cyclists were recruited to participate in three identical trials wearing loose fitting shorts (control), low-grade, or medium-grade compression garments. The protocol involved four 8 min increments of cycling at 30%, 50%, 70%, and 85% maximal power output and a 4 km time-trial. Participants undertook a cognitive Stroop task at baseline and at the midpoint of each increment. MCAv was monitored with Transcranial Doppler Ultrasonography. Mean arterial pressure (MAP) and partial pressure of end-tidal CO2 (PetCO2) were measured throughout. MCAv, MAP, PetCO2, and reaction time of the complex Stroop task were influenced by exercise intensity, but not compression garments. Compression garments significantly affected cognitive accuracy in the complex Stroop task such that low-grade compression appeared to enhance cognitive accuracy in comparison to the control condition at the highest intensity (p = .010). Time-trial performance did not differ between the control (338.0 ± 17.3 s), low-grade (338.7 ± 18.7 s), or medium-grade (342.2 ± 19.3 s) conditions (p = .114). Compression garments did not affect MCAv during exercise or time-trial performance, but compression may be beneficial for improved cognitive accuracy during high-intensity exercise. Further research is required to elucidate the potential impact on cognitive performance.

Effect of hypocapnia on the sensitivity of hyperthermic hyperventilation and the cerebrovascular response in resting heated humans.

Elevating core temperature at rest causes increases in minute ventilation (V̇e), which lead to reductions in both arterial CO2 partial pressure (hypocapnia) and cerebral blood flow. We tested the hypothesis that in resting heated humans this hypocapnia diminishes the ventilatory sensitivity to rising core temperature but does not explain a large portion of the decrease in cerebral blood flow. Fourteen healthy men were passively heated using hot-water immersion (41°C) combined with a water-perfused suit, which caused esophageal temperature (Tes) to reach 39°C. During heating in two separate trials, end-tidal CO2 partial pressure decreased from the level before heating (39.4 ± 2.0 mmHg) to the end of heating (30.5 ± 6.3 mmHg) ( P = 0.005) in the Control trial. This decrease was prevented by breathing CO2-enriched air throughout the heating such that end-tidal CO2 partial pressure did not differ between the beginning (39.8 ± 1.5 mmHg) and end (40.9 ± 2.7 mmHg) of heating ( P = 1.00). The sensitivity to rising Tes (i.e., slope of the Tes - V̇E relation) did not differ between the Control and CO2-breathing trials (37.1 ± 43.1 vs. 16.5 ± 11.1 l·min-1·°C-1, P = 0.31). In both trials, middle cerebral artery blood velocity (MCAV) decreased early during heating (all P < 0.01), despite the absence of hyperventilation-induced hypocapnia. CO2 breathing increased MCAV relative to Control at the end of heating ( P = 0.005) and explained 36.6% of the heat-induced reduction in MCAV. These results indicate that during passive heating at rest ventilatory sensitivity to rising core temperature is not suppressed by hypocapnia and that most of the decrease in cerebral blood flow occurs independently of hypocapnia. NEW & NOTEWORTHY Hyperthermia causes hyperventilation and concomitant hypocapnia and cerebral hypoperfusion. The last may underlie central fatigue. We are the first to demonstrate that hyperthermia-induced hyperventilation is not suppressed by the resultant hypocapnia and that hypocapnia explains only 36% of cerebral hypoperfusion elicited by hyperthermia. These new findings advance our understanding of the mechanisms controlling ventilation and cerebral blood flow during heat stress, which may be useful for developing interventions aimed at preventing central fatigue during hyperthermia.

Acidosis, but Not Alkalosis, Affects Anaerobic Metabolism and Performance in a 4-km Time Trial.

This study aimed to determine the effect of preexercise metabolic acidosis and alkalosis on power output (PO) and aerobic and anaerobic energy expenditure during a 4-km cycling time trial (TT). Eleven recreationally trained cyclists (V˙O2peak 54.1 ± 9.3 mL·kg·min) performed a 4-km TT 100 min after ingesting in a double-blind matter 0.15 g·kg of body mass of ammonium chloride (NH4Cl, acidosis), 0.3 g·kg of sodium bicarbonate (NaHCO3, alkalosis), or 0.15 g·kg of CaCO3 (placebo). A preliminary study (n = 7) was conducted to establish the optimal doses to promote the desirable preexercise blood pH alterations without gastrointestinal distress. Data for PO, aerobic and anaerobic energy expenditure, and blood and respiratory parameters were averaged for each 1 km and compared between conditions using two-way repeated-measures ANOVA (condition and distance factors). Gastrointestinal discomfort was analyzed qualitatively. Compared with placebo (pH 7.37 ± 0.02, [HCO3]: 27.5 ± 2.6 mmol·L), the NaHCO3 ingestion resulted in a preexercise blood alkalosis (pH +0.06 ± 0.04, [HCO3]: +4.4 ± 2.0 mmol·L, P < 0.05), whereas NH4Cl resulted in a blood acidosis (pH -0.05 ± 0.03, [HCO3]: -4.8 ± 2.1 mmol·L, P < 0.05). Anaerobic energy expenditure rate and PO were reduced throughout the trial in NH4Cl compared with placebo and NaHCO3, resulting in a lower total anaerobic work and impaired performance (P < 0.05). Plasma lactate, V˙CO2, and end-tidal CO2 partial pressure were lower and the V˙E/V˙CO2 higher throughout the trial in NH4Cl compared with placebo and NaHCO3 (P < 0.05). There was no difference between NaHCO3 and placebo for any of these variables (P > 0.05). Minimal gastrointestinal distress was noted in all conditions. Preexercise acidosis, but not alkalosis, affects anaerobic metabolism and PO during a 4-km cycling TT.

Continuous coloured light altered human brain haemodynamics and oxygenation assessed by systemic physiology augmented functional near-infrared spectroscopy

Exposure to artificial coloured light is unavoidable in our modern life, but we are only just beginning to understand the impact of coloured light on human physiology. The aim of the present study was to determine effects of coloured light exposure on human systemic and brain physiology using systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS). We measured changes in haemoglobin concentrations and tissue oxygen saturation in the left and right prefrontal cortices (L-PFC, R-PFC) by fNIRS, and also recorded skin conductance (SC), partial pressure of end-tidal CO2 (PETCO2), and heart-rate variability variables. 17 healthy adults (median age: 29 years, range: 25–65 years, 6 women) were exposed to blue, red, green, or yellow light for 10 minutes. Pre-light and post-light conditions were in darkness. In the L-PFC the yellow evoked a brain activation. SC and PETCO2 did not change during any of the coloured light exposures, but SC increased and PETCO2 decreased for all colours (except green) in the post-light period. Changes in L-PFC haemoglobin concentration were also observed during the post-light period but have to be interpreted with care, because heart rate and SC increased while PETCO2 decreased. The detected effects are potentially of high relevance for choosing room lighting and may possibly be applied therapeutically.

Effectiveness of Underbody Forced-air Warming System in Preventing Hypothermia in Patients Undergoing Major Surgeries.

Objective To compare the effectiveness of the forced-air warming system and the conventional warming care practice in preventing hypothermia in patients undergoing major surgeries.Methods A total of 62 patients were enrolled in this study. Patients of both sexes,aged≥18 years,and with an ASA physical status Ⅰ-Ⅲ were included and allocated randomly into intervention group(n=30)or control group(n=32). Patients in the intervention group were provided forced-air warming,either prior to induction or during the surgery procedure depending on core temperature monitoring results. In the control group,patients were warmed with conventional warming care without any intervention. Core temperature was measured by Spot-On sensor and tympanic membrane thermometer,blood pressure,the electrocardiogram,heart rate,pulse oxygen staturation,and partial pressure of end-tidal CO2 were also monitored continuously in the two groups.Crystalloid,colloid,and allogeneic blood were also recorded by strict protocol. Results Intraoperative hypothermia monitored with tympanic thermometer was observed in 23 patients(71.87%)in the control group,which was significantly higher than that (0) in the intervention group(P=0.00). In addition,the incidence of hypothermia monitored by Spot-On sensor was 81.25%(n=26)in control group and 13.33%(n=4)in intervention group(P=0.00). Conclusion Compared with the conventional warming care,forced-air warming system is more effective in preventing hypothermia during major surgeries.

Effects of Hypercapnia on Myocardial Blood Flow in Healthy Human Subjects.

Elevation of the end-tidal partial pressure of CO2 (PETco2) increases cerebral and myocardial blood flow (MBF), suggesting that it may be a suitable alternative to pharmacologic stress or exercise for myocardial perfusion imaging. The purpose of this study was to document the pharmacodynamics of CO2 for MBF using prospective end-tidal targeting to precisely control arterial Pco2 and PET to measure the outcome variable, MBF. Methods: Ten healthy men underwent serial 82Rb PET/CT imaging. Imaging was performed at rest and during 6-min hypercapnic plateaus (baseline; PETco2 at 50, 55, and 60 mm Hg; repeat of PETco2 at 60 mm Hg; and repeat of baseline). MBF was measured using 82Rb injected 3 min after the beginning of hypercapnia and a 1-tissue-compartment model with flow-dependent extraction correction. Results were compared with those obtained during an adenosine stress test (140 μg/kg/min). Results: Baseline PETco2 was 38.9 ± 0.8 (mean ± SD) mm Hg (range, 35-43 mm Hg). All PETco2 targets were sustained, with SDs of less than 1.5 mm Hg. Heart rate, systolic blood pressure, rate × pressure product, and respiratory frequency increased with progressive hypercapnia. MBF increased significantly at each level of hypercapnia to 1.92-fold over baseline (0.86 ± 0.24 vs. 0.45 ± 0.08 mL/min/g; P = 0.002) at a PETco2 of 60 mm Hg. MBF after the administration of adenosine was significantly greater than that with the maximal hypercapnic stimulus (2.00 vs. 0.86 mL/min/g; P < 0.0001). Conclusion: To our knowledge, this study is the first to assess the response of MBF to different levels of hypercapnia in healthy humans with PET. MBF increased with increasing levels of hypercapnia; MBF at a PETco2 of 60 mm Hg was double that at baseline.

The Effect of Impella CP on Cardiopulmonary Physiology During Venoarterial Extracorporeal Membrane Oxygenation Support.

Left ventricle (LV) distension is a complication of venoarterial extracorporeal membrane oxygenation (VA-ECMO) support. The effects of Impella on the pulmonary circulatory physiology were studied in a single-center study of six consecutive patients on VA-ECMO support who had LV unloading with Impella. Right ventricular stroke volume, pulmonary hemodynamics, and partial pressure of end-tidal CO2 (PETCO2 ) were measured on echocardiogram, pulmonary artery catheter, and capnography, respectively. The addition of Impella CP increased total blood flow and reduced pulmonary artery wedge pressure. There was a small reduction in arterial oxygen saturation as Impella increased LV output. The increase in pulmonary artery capacitance (PCap) exceeded the reduction in pulmonary vascular resistance (PVR), thereby increasing the pulmonary artery time constant (product of PCap and PVR). The right ventricular stroke volume increased and the improvement in pulmonary hemodynamics and blood flow were associated with reduced arterial-PETCO2 gradient. The Impella CP unloads the LV during VA-ECMO support, increasing total flow, reducing RV afterload, and facilitating RV output and pulmonary blood flow with improvement in gas exchange.

Sex-specific cardiopulmonary exercise testing parameters as predictors in patients with idiopathic pulmonary arterial hypertension.

Cardiopulmonary exercise testing (CPET) has been used for prognosis in idiopathic pulmonary arterial hypertension (IPAH). We explored whether sex differences had an impact on prognostic assessments of CPET in IPAH. Data were retrieved from 21 male and 36 female incident IPAH patients who underwent both right heart catheterization and CPET from 2010 to 2016 at Shanghai Pulmonary Hospital. Cox proportional hazards analysis was used to assess the prognostic value of CPET. The mean duration of follow-up was 22±15 months. Nine men and 15 women had an event. The differences in clinical parameters in the whole population were not the same as the inter-subgroup differences. Event-free women had significantly higher cardiac output, lower pulmonary vascular resistance and percentage of predicted FVC compared with event men (all P<0.05). Event-free men had significantly higher end-tidal partial pressure of CO2 (PETCO2) at anaerobic threshold (AT), peak workload, PETCO2, maximum oxygen consumption (VO2)/minute ventilation (VE), and oxygen uptake efficiency slope and lower end-tidal partial pressure of O2 (PETO2) at AT, peak PETO2, and lowest VE/VCO2 compared with event men. Event-free women had dramatically higher peak VO2, VCO2, VE and O2 pulse than event women (all P<0.05). Peak PETCO2 was the independent predictor of event-free survival in all patients and males, whereas peak O2 pulse was the independent predictor of event-free survival in females. Men with peak PETCO2⩾20.50 mm Hg, women with peak O2 pulse ⩾6.25 ml per beat and all patients with peak PETCO2⩾27.03 mm Hg had significantly better event-free survival. Sex-specific CPET parameters are predictors of poor outcomes. Decreased peak PETCO2 in men and peak O2 pulse in women were associated with lower event-free survival in IPAH.

Effect of Exercise Training on Cerebral Microcirculation in Men with and without Type 1 Diabetes

PURPOSE: Effects of regular exercise on cerebral microcirculation in diabetes are unknown. We examined if exercise training leads to similar adaptations in cerebral microcirculation in men with and without type 1 diabetes (T1D). METHODS: Eight men with T1D (33±6 yrs) and eight healthy men (HC; 38±7 yrs) matched for age, anthropometry, and peak O2 uptake (VO2peak) (p>0.05), completed a 1-year individualized exercise training intervention. Individually collected data on training were similar in T1D vs. HC (mean±SD per month; p>0.05): 13±4 vs. 15±6 endurance training sessions, 3±1 vs. 3±3 resistance training sessions, 57±5 vs. 55±8 % of heart rate reserve, 16:58±6:07 vs. 16:52±4:39 h:min, 7759±4540 vs. 7762±3812 kcal, respectively. Before and after the intervention, the subjects performed step incremental cycling exercise to volitional fatigue. During exercise, alveolar gas exchange (mass spectrometry) and normalized relative concentration changes in deoxygenated hemoglobin (%Δ[HHb]) in the prefrontal cerebral cortex (near-infrared spectroscopy) were monitored; %Δ[HHb] reflects imbalance between local O2 delivery and utilization. RESULTS: Training increased VO2peak and peak work rate similarly in T1D (45±5 to 49±6 mL/min/kg fat-free mass [FFM], p<0.01; 237±34 to 254±27 W, p<0.05) and HC (48±3 to 52±5 mL/min/kg FFM, p<0.05; 255±17 to 282±36 W, p<0.05). Training also decreased minute ventilation at 160W (in T1D and HC) and 200W (in HC) (p<0.05) but had no effect on end-tidal CO2 partial pressure, which estimates arterial CO2 pressure affecting cerebral blood flow. Cerebral %Δ[HHb] did not change at any work rate in T1D but decreased at 200W in HC (p<0.05). No differences were observed between T1D and HC in the reported parameters before the intervention. CONCLUSION: Exercise training did not improve exercise-induced imbalance between local O2 delivery and utilization in prefrontal microcirculation in T1D but did so at high exercise intensity (200 W) in HC. This between-group difference was not due to different respiratory adaptations and must thus be explained by other diabetes-related mechanisms (e.g., impaired cerebrovascular autoregulation, CO2 reactivity, or neocapillarization) influencing cerebral blood flow. Supported by: Tekes, Ministry of Education and Culture, Finnish Medical Foundation.

Oral or nasal breathing? Real-time effects of switching sampling route onto exhaled VOC concentrations

There is a need for standardisation in sampling and analysis of breath volatile organic compounds (VOCs) in order to minimise ubiquitous confounding effects. Physiological factors may mask concentration changes induced by pathophysiological effects. In humans, unconscious switching of oral and nasal breathing can occur during breath sampling, which may affect VOC patterns. Here, we investigated exhaled VOC concentrations in real-time while switching breathing routes. Breath from 15 healthy volunteers was analysed continuously by proton transfer reaction time-of-flight mass spectrometry during paced breathing (12 breaths min−1). Every two minutes breathing routes were switched (Setup-1: Oral → Nasal → Oral → Nasal; Setup-2: OralinNasalout → NasalinOralout → OralinNasalout → NasalinOralout). VOCs in inspiratory and alveolar air and respiratory and hemodynamic parameters were monitored quantitatively in parallel. Changing of the breathing routes and patterns immediately affected exhaled VOC concentrations. These changes were reproducible in both setups. In setup-1 cardiac output and acetone concentrations remained constant, while partial pressure of end-tidal CO2 (pET-CO2), isoprene and furan concentrations inversely mirrored tidal-volume and minute-ventilation. H2S (hydrogen-sulphide), C4H8S (allyl-methyl-sulphide), C3H8O (isopropanol) and C3H6O2 increased during oral exhalation. C4H10S increased during nasal exhalations. CH2O2 steadily decreased during the whole measurement. In setup-2 pET-CO2, C2H6S (dimethyl-sulphide), isopropanol, limonene and benzene concentrations decreased whereas, minute-ventilation, H2S and acetonitrile increased. Isoprene and furan remained unchanged. Breathing route and patterns induced VOC concentration changes depended on respiratory parameters, oral and nasal cavity exposure and physico-chemical characters of the compounds. Before using breath VOC concentrations as biomarkers it is essential that the breathing modality is defined and strictly monitored during sampling.

Mapping the pharmacological modulation of brain oxygen metabolism: The effects of caffeine on absolute CMRO2 measured using dual calibrated fMRI

This study aims to map the acute effects of caffeine ingestion on grey matter oxygen metabolism and haemodynamics with a novel MRI method. Sixteen healthy caffeine consumers (8 males, age=24.7±5.1) were recruited to this randomised, double-blind, placebo-controlled study. Each participant was scanned on two days before and after the delivery of an oral caffeine (250mg) or placebo capsule.Our measurements were obtained with a newly proposed estimation approach applied to data from a dual calibration fMRI experiment that uses hypercapnia and hyperoxia to modulate brain blood flow and oxygenation. Estimates were based on a forward model that describes analytically the contributions of cerebral blood flow (CBF) and of the measured end-tidal partial pressures of CO2 and O2 to the acquired dual-echo GRE signal. The method allows the estimation of grey matter maps of: oxygen extraction fraction (OEF), CBF, CBF-related cerebrovascular reactivity (CVR) and cerebral metabolic rate of oxygen consumption (CMRO2). Other estimates from a multi inversion time ASL acquisition (mTI-ASL), salivary samples of the caffeine concentration and behavioural measurements are also reported.We observed significant differences between caffeine and placebo on average across grey matter, with OEF showing an increase of 15.6% (SEM±4.9%, p<0.05) with caffeine, while CBF and CMRO2 showed differences of −30.4% (SEM±1.6%, p<0.01) and −18.6% (SEM±2.9%, p<0.01) respectively with caffeine administration. The reduction in oxygen metabolism found is somehow unexpected, but consistent with a hypothesis of decreased energetic demand, supported by previous electrophysiological studies reporting reductions in spectral power with EEG.Moreover the maps of the physiological parameters estimated illustrate the spatial distribution of changes across grey matter enabling us to localise the effects of caffeine with voxel-wise resolution. CBF changes were widespread as reported by previous findings, while changes in OEF were found to be more restricted, leading to unprecedented mapping of significant CMRO2 reductions mainly in frontal gyrus, parietal and occipital lobes.In conclusion, we propose the estimation framework based on our novel forward model with a dual calibrated fMRI experiment as a viable MRI method to map the effects of drugs on brain oxygen metabolism and haemodynamics with voxel-wise resolution.

Electroencephalographic discontinuity during sevoflurane anesthesia in infants and children.

Deep anesthesia in adults may be associated with electroencephalographic (EEG) suppression and higher rates of postoperative complications. Little is known about the impact of anesthetic depth on short- or long-term outcomes in pediatrics. Brain activity monitoring may complement clinical signs of anesthetic depth. This prospective observational study aimed to assess the frequency and degree of profound EEG suppression using multichannel EEG in children during sevoflurane general anesthesia. Children aged 0-40 months who required general anesthesia for elective surgery were included. Continuous EEG recordings were performed starting from when anesthesia began and until recovery. Discontinuity was defined as EEG amplitude <25 uV, lasting ≥2 s, and observed in all electrodes across the scalp. Frequency, duration, and inter-event interval of discontinuity events were measured. Relationships between discontinuity events and postnatal age, endtidal sevoflurane concentration (etSEVO), and multiple clinical parameters were analyzed. Discontinuity events were observed in 35/68 children, with a median duration of 10 s (95%CI: 8-12) and a median of 4 events per patient (95%CI: 2-7). Children who had discontinuity events were younger (5.5 months, 95%CI: 3.6-6.5) compared to children who did not have discontinuity events (10.2 months, 95%CI: 6.1-14); (difference between medians, 4.7 months, 95%CI: 2.3-8, P = 0.0002). Younger infants exhibited a higher number of discontinuity events, and the incidence decreased with postnatal age (r68 = -0.53, P < 0.0001). The majority of discontinuity events were observed during the first 30 min of anesthesia (66.4% total events), where etSEVO was >3%. Few discontinuity events were observed during maintenance and none during emergence. Blood pressure, heart rate, tissue oxygen saturation, and endtidal CO2 partial pressure did not change during these events. Electroencephalographic monitoring may complement clinical signs in providing information about brain homeostasis during general anesthesia. The impact of discontinuity events on immediate and long-term outcomes merits further study.

Detection of Impaired Sympathetic Cerebrovascular Control Using Functional Biomarkers Based on Principal Dynamic Mode Analysis.

This study sought to determine whether models of cerebrovascular function based on Laguerre-Volterra kernels that account for nonlinear cerebral blood flow (CBF) dynamics can detect the effects of functional cerebral sympathetic blockade. We retrospectively analyzed continuous beat-to-beat blood pressure, middle cerebral blood velocity, and partial-pressure of end-tidal CO2 (PETCO2) recordings from eighteen healthy individuals who were treated with either an oral dose of the α1-adrenergic receptor blocker Prazosin or a placebo treatment. The global principal dynamic modes (PDMs) were analyzed using Laguerre-Volterra kernels to examine the nonlinear system dynamics. Our principal findings were: (1) very low frequency (<0.03 Hz) linear components of first-order kernels for BP and PETCO2 are mutually coupled to CBF dynamics with the ability to separate individuals between control and blockade conditions, and (2) the gains of the nonlinear functions associated with low-pass and ≈0.03 Hz global PDMs for the BP are sensitive to sympathetic blockade. Collectively these results suggest that very low frequency global PDMs for BP may have potential utility as functional biomarkers of sympathetic neurovascular dysfunction which can occur in conditions like autonomic failure, stroke and traumatic brain injury.

Sex-specific cardiopulmonary exercise testing indices related to hemodynamics in idiopathic pulmonary arterial hypertension.

Background:Many studies have highlighted sex preponderance in idiopathic pulmonary arterial hypertension (IPAH). It is well established that there are differences in exercise capacities in the two sexes but how much of that difference reflects on disease severity or correlates to markers of severity in the two sexes is still not clear. Right heart catheterization (RHC) and cardiopulmonary exercise testing (CPET) have been widely used for assessing functional capacity, prognosis and treatment response in IPAH. We aimed to investigate the ‘sex-specific’ CPET parameters in relation to hemodynamics in IPAH.Methods:Data were retrieved from 30 males and 53 females [mean ± standard deviation (SD) age: 39.6 ± 17.2 and 37.5 ± 12.0] stable IPAH patients who underwent both RHC and CPET at Shanghai Pulmonary Hospital from 2010 to 2016. Univariate and forward/backward multiple stepwise regression analysis was performed to assess the prognostic value of CPET and hemodynamic parameters.Results:There were no significant differences in clinical variables between men and women. Peak workload, peak oxygen uptake, anaerobic threshold (AT), peak minute ventilation, carbon dioxide output, O2 pulse and oxygen uptake efficiency slope were significantly higher in men compared with women (p < 0.05). Several CPET indexes correlated with hemodynamics. Pulmonary vascular resistance (PVR) and cardiac output (CO) were distinctly different between the sexes. Peak end-tidal partial pressure of CO2 (PETCO2) was an independent predictor of PVR elevation in all patients and in men. Peak maximum oxygen consumption (VO2) was independently predictive of CO decline in all patients and in men. Only peak O2 pulse was an independent predictor of increased PVR and decreased CO in women.Conclusions:Even after adjusting for age, body mass index and World Health Organization functional class, different CPET parameters correlated with PVR elevation and CO decline in men and women differently, which could potentially better predict severity in men and women with IPAH.

Quantifying cerebrovascular reactivity in anterior and posterior cerebral circulations during voluntary breath holding.

What is the central question of this study? We developed and validated a 'stimulus index' (SI; ratio of end-tidal partial pressures of CO2 and O2 ) method to quantify cerebrovascular reactivity (CVR) in anterior and posterior cerebral circulations during breath holding. We aimed to determine whether the magnitude of CVR is correlated with breath-hold duration. What is the main finding and its importance? Using the SI method and transcranial Doppler ultrasound, we found that the magnitude of CVR of the anterior and posterior cerebral circulations is not positively correlated with physiological or psychological break-point during end-inspiratory breath holding. Our study expands the ability to quantify CVR during breath holding and elucidates factors that affect break-point. The central respiratory chemoreflex contributes to blood gas homeostasis, particularly in response to accumulation of brainstem CO2 . Cerebrovascular reactivity (CVR) affects chemoreceptor stimulation inversely through CO2 washout from brainstem tissue. Voluntary breath holding imposes alterations in blood gases, eliciting respiratory chemoreflexes, potentially contributing to breath-hold duration (i.e. break-point). However, the effects of cerebrovascular reactivity on break-point have yet to be determined. We tested the hypothesis that the magnitude of CVR contributes directly to breath-hold duration in 23 healthy human participants. We developed and validated a cerebrovascular stimulus index methodology [SI; ratio of end-tidal partial pressures of CO2 and O2 (P ET ,CO2/P ET ,O2)] to quantify CVR by correlating measured and interpolated values of P ET ,CO2 (r=0.95, P<0.0001), P ET ,O2 (r=0.98, P<0.0001) and SI (r=0.94, P<0.0001) during rebreathing. Using transcranial Doppler ultrasound, we then quantified the CVR of the middle (MCAv) and posterior (PCAv) cerebral arteries by plotting cerebral blood velocity against interpolated SI during a maximal end-inspiratory breath hold. The MCAv CVR magnitude was larger than PCAv (P=0.001; +70%) during breath holding. We then correlated MCAv and PCAv CVR with the physiological (involuntary diaphragmatic contractions) and psychological (end-point) break-point, within individuals. There were significant inverse but modest relationships between both MCAv and PCAv CVR and both physiological and psychological break-points (r<-0.53, P<0.03). However, these relationships were absent when MCAv and PCAv cerebrovascular conductance reactivity was correlated with both physiological and psychological break-points (r>-0.42; P>0.06). Although central chemoreceptor activation is likely to be contributing to break-point, our data suggest that CVR-mediated CO2 washout from central chemoreceptors plays no role in determining break-point, probably because of a reduced arterial-to-tissue CO2 gradient during breath holding.

Efficacy of high frequency jet ventilation via nasopharyngeal catheter in assissting ventilation in patients with OSAHS undergoing gastroscopy

Objective To investigate the efficacy of high frequency jet ventilation via the nasopharyngeal catheter in assissting ventilation in patients with obstructive sleep apnea hypopnea syndrome (OSAHS) undergoing gastroscopy. Methods Eighty patients with OSAHS of both sexes, aged 40-64 yr, weighing 65-99 kg, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, with an apnea-hypopnea index 20-40 events/h, scheduled for elective painless gastroscopy, were divided into control group and test group using a random number table, with 40 patients in each group.In control group, a nasopharyngeal catheter 6.0-7.0 mm in internal diameter was inserted, and oxygen was inhaled at 4 L/min through the catheter.In test group, a nasopharyngeal catheter 4.0 mm in internal diameter was inserted, and a high frequency jet ventilator was connected (inspiratory/expiratory ratio 1.0∶1.5, frequency 150 bpm, peak pressure 0.4 kPa, tidal volume 180 ml). Anesthesia was maintained with propofol in both groups.The occurrence of hypoxemia during ventilation, and peak value of partial pressure of end-tidal CO2 before induction of anesthesia and during ventilation, and occurrence of chin lift, mask ventilation, and epistaxis after insertion of the catheter during operation were recorded. Results Compared with control group, the incidence of hypoxemia, peak value of partial pressure of end-tidal CO2 during ventilation, and incidence of chin lift, mask ventilation and epistaxis during operation were significantly decreased in test group (P<0.05). Conclusion High frequency jet ventilation via the nasopharyngeal catheter can be safely and effectively used to assisst ventilation in patients with OSAHS undergoing gastroscopy. Key words: High-frequency ventilation; Sleep apnea, obstructive; Gastroscopy

Cardiopulmonary exercise testing improves diagnostic specificity in patients with echocardiography-suspected pulmonary hypertension.

Doppler echocardiography is usually the first diagnostic investigation for patients suspected with pulmonary hypertension (PH), but it is often inaccurate when used alone, especially in mild PH. Cardiopulmonary exercise testing (CPET) may serve as a complementary tool to improve diagnostic accuracy in echocardiography-suspected "PH possible" patients. Eighty-eight consecutive patients with suspected PH (referred to as "PH possible" hereafter) based on echocardiography were included in the study. CPET was assessed subsequently and PH was confirmed by right-heart catheterization in all subjects. We analyzed CPET data from patients and derived a CPET prediction rule to hemodynamically differentiate PH. Eighty-eight patients (27 patients with confirmed PH, and PH ruled out in 61 patients) were included in the study. Compared with non-PH patients, the PH subjects had lower peak oxygen uptake (VO2 ), aerobic capacity (AT), peak partial pressure of end-tidal CO2 (PET CO2 ), oxygen uptake efficiency plateau (OUEP), and oxygen uptake efficiency slope (OUES), along with higher minute ventilation (VE)/carbon dioxide output (VCO2 ) slope and lowest VE/VCO2 (P < 0.001). VE/VCO2 slope and AT were independent predictors of PH derived from multivariate logistic regression adjusted for age and body mass index. A score combining VE/VCO2 slope and AT reached a high area under the curve value of 0.98. A score ≥0.5 had 95% specificity and 92.6% sensitivity for diagnosis of PH. A score combining VE/VCO2 slope and AT provides high specificity in screening out PH from a pool of echocardiography-suspected PH patients.