Arterial CO2 Partial Pressure Research Articles

Association of dynamic changes in arterial partial pressure of carbon dioxide with neurological outcomes in aneurysmal subarachnoid hemorrhage

BackgroundCerebral blood flow (CBF) is closely regulated by carbon dioxide (CO2). In patients with aneurysmal subarachnoid hemorrhage (aSAH), abnormal arterial partial pressure of CO2 (PaCO2) might deteriorate brain injuries. Nevertheless, the impact of dynamic PaCO2 fluctuations on neurological outcomes in aSAH patients has not been extensively studied. Our study aimed to investigate the association between dynamic PaCO2 levels and unfavorable neurological outcomes in aSAH patients. MethodsIn this retrospective observational study, we consecutively enrolled 159 aSAH patients from December 2019 to July 2021. Arterial blood gas measurements within 10 days after intensive care unit (ICU) admission for each patient were recorded to calculate the time-weighted average (TWA)-PaCO2, an indicator representing the dynamic changes in PaCO2 levels. For the association between TWA-PaCO2 levels and unfavorable neurological outcomes in aSAH patients, multivariable logistic analysis was used to explore TWA-PaCO2 levels as categorical variables, and restricted cubic spline (RCS) was used to explore TWA-PaCO2 levels as continuous variables. ResultsIn multivariable logistic analysis, after adjusting confounders, when TWA-PaCO2 35–45 mmHg was as a reference, TWA-PaCO2 < 35 mmHg (odds ratio [OR] 2.15, 95 % confidence interval [CI] 0.83–5.55, P = 0.113) and TWA-PaCO2 > 45 mmHg (OR 8.31, 95 % CI 0.72–96.14, P = 0.090) were not independently associated with unfavorable neurological outcomes (modified Rankin score of 3–6). The RCS shows a “U” shape curve between TWA-PaCO2 levels and unfavorable neurological outcomes, with a nonlinear P-value of 0.023. The lowest ORs of unfavorable neurological outcomes were within PaCO2 32.8–38.1 mmHg. ConclusionsBoth lower and higher PaCO2 levels are harmful to aSAH patients. PaCO2 in the range of 32.8–38.1 mmHg is associated with lowest unfavorable neurological outcomes.

Imitating the respiratory activity of the brain stem by using artificial neural networks: exploratory study on an animal model of lactic acidosis and proof of concept.

Artificial neural networks (ANNs) are versatile tools capable of learning without prior knowledge. This study aims to evaluate whether ANN can calculate minute volume during spontaneous breathing after being trained using data from an animal model of metabolic acidosis. Data was collected from ten anesthetized, spontaneously breathing pigs divided randomly into two groups, one without dead space and the other with dead space at the beginning of the experiment. Each group underwent two equal sequences of pH lowering with pre-defined targets by continuous infusion of lactic acid. The inputs to ANNs were pH, ΔPaCO2 (variation of the arterial partial pressure of CO2), PaO2, and blood temperature which were sampled from the animal model. The output was the delta minute volume (ΔVM), (the change of minute volume as compared to the minute volume the animal had at the beginning of the experiment). The ANN performance was analyzed using mean squared error (MSE), linear regression, and the Bland-Altman (B-A) method. The animal experiment provided the necessary data to train the ANN. The best architecture of ANN had 17 intermediate neurons; the best performance of the finally trained ANN had a linear regression with R2 of 0.99, an MSE of 0.001 [L/min], a B-A analysis with bias ± standard deviation of 0.006 ± 0.039 [L/min]. ANNs can accurately estimate ΔVM using the same information that arrives at the respiratory centers. This performance makes them a promising component for the future development of closed-loop artificial ventilators.

Exposure to passive heat and cold stress differentially modulates cerebrovascular-CO2 responsiveness.

Heat and cold stress influence cerebral blood flow (CBF) regulatory factors (e.g., arterial CO2 partial pressure). However, it is unclear whether the CBF response to a CO2 stimulus (i.e., cerebrovascular-CO2 responsiveness) is maintained under different thermal conditions. This study aimed to compare cerebrovascular-CO2 responsiveness between normothermia, passive heat, and cold stress conditions. Sixteen participants (8 females; 25 ± 7 yr) completed two experimental sessions (randomized) comprising normothermic and either passive heat or cold stress conditions. Middle and posterior cerebral artery velocity (MCAv, PCAv) were measured during rest, hypercapnia (5% CO2 inhalation), and hypocapnia (voluntary hyperventilation to an end-tidal CO2 of 30 mmHg). The linear slope of the cerebral blood velocity (CBv) response to changing end-tidal CO2 was calculated to measure cerebrovascular-CO2 responsiveness, and cerebrovascular conductance (CVC) was used to examine responsiveness independent of blood pressure. CBv-CVC-CO2 responsiveness to hypocapnia was greater during heat stress compared with cold stress (MCA: +0.05 ± 0.08 cm/s/mmHg/mmHg, P = 0.04; PCA: +0.02 ± 0.02 cm/s/mmHg/mmHg, P = 0.002). CBv-CO2 responsiveness to hypercapnia decreased during heat stress (MCA: -0.67 ± 0.89 cm/s/mmHg, P = 0.02; PCA: -0.64 ± 0.62 cm/s/mmHg; P = 0.01) and increased during cold stress (MCA: +0.98 ± 1.33 cm/s/mmHg, P = 0.03; PCA: +1.00 ± 0.82 cm/s/mmHg; P = 0.01) compared with normothermia. However, CBv-CVC-CO2 responsiveness to hypercapnia was not different between thermal conditions (P > 0.08). Overall, passive heat, but not cold, stress challenges the maintenance of cerebral perfusion. A greater cerebrovascular responsiveness to hypocapnia during heat stress likely reduces an already impaired cerebrovascular reserve capacity and may contribute to adverse events (e.g., syncope).NEW & NOTEWORTHY This study demonstrates that thermoregulatory-driven perfusion pressure changes, from either cold or heat stress, impact cerebrovascular responsiveness to hypercapnia. Compared with cold stress, heat stress poses a greater challenge to the maintenance of cerebral perfusion during hypocapnia, challenging cerebrovascular reserve capacity while increasing cerebrovascular-CO2 responsiveness. This likely exacerbates cerebral hypoperfusion during heat stress since hyperthermia-induced hyperventilation results in hypocapnia. No regional differences in middle and posterior cerebral artery responsiveness were found with thermal stress.

Comparison of ventilatory parameters with nasal versus oral breathing during submaximal exercise in patients with cardiac disease and healthy people

Abstract Introduction Inefficient ventilation, namely a high ventilation/carbon dioxide production ratio (VE/VCO2) is a well established predictor for disease progression and mortality in patients with heart failure (HF). Two previous studies in healthy people have found improved ventilatory efficiency with nasal compared to oral breathing during submaximal exercise. No study has compared nasal with oral breathing in patients with HF or coronary heart disease. Method Four study groups were recruited: Patients with HF, patients with acute or chronic coronary syndrome (ACS/CCS), old healthy controls (age&amp;gt;45 years) and young healthy controls (age&amp;gt;20 years and &amp;lt;35 years). Acute measurements of 5 min (after 3 min warm-up) with nasal and 5 min with oral breathing in randomized order were performed at 50% peak power. Ventilation parameters were averaged over the last minute of each condition and analysed by linear mixed models adjusted for body mass index. Results We present data of 8 patients with HF, 8 with ACS/CCS, 10 old and 15 young healthy controls. Minute ventilation, breathing frequency and end-tidal oxygen partial pressure (PETO2) were significantly lower and tidal volume and end-tidal carbon dioxide partial pressure (PETCO2) significantly higher during nasal compared to oral breathing in all groups (Figure 1). Differences between breathing modes were between 5-20% and similar in all groups except for breathing frequency that declined more from oral to nasal breathing, namely by 27%, in patients with HF compared to the other groups. The largest discrepancies between patients and healthy controls were found for VE/VCO2 ratio, PETCO2 and PETO2. Conclusion Nasal breathing during submaximal exercise significantly improved the abnormal breathing pattern of patients with HF and ACS/CCS. Nasal breathing during exercise may be promising in patients with inefficient ventilation as it increases PETCO2 and is likely to increase arterial partial CO2 pressure, a known vasodilator, herewith facilitating perfusion of the working musculature.Figure 1

Pre-hospital endotracheal intubation in severe traumatic brain injury: ventilation targets and mortality—a retrospective analysis of 308 patients

BackgroundTraumatic brain injury (TBI) remains one of the main causes of mortality and long-term disability worldwide. Maintaining physiology of brain tissue to the greatest extent possible through optimal management of blood pressure, airway, ventilation, and oxygenation, improves patient outcome. We studied the quality of prehospital care in severe TBI patients by analyzing adherence to recommended target ranges for ventilation and blood pressure, prehospital time expenditure, and their effect on mortality, as well as quality of prehospital ventilation assessed by arterial partial pressure of CO2 (PaCO2) at hospital admission.MethodsThis is a retrospective cohort study of all TBI patients requiring tracheal intubation on scene who were transported to one of two major level 1 trauma centers in Switzerland between January 2014 and December 2019 by Swiss Air Rescue (Rega). We assessed systolic blood pressure (SBP), end-tidal partial pressure of CO2 (PetCO2), and PaCO2 at hospital admission as well as prehospital and on-scene time. Quality markers of prehospital care (PetCO2, SBP, prehospital times) and prehospital ventilation (PaCO2) are presented as descriptive analysis. Effect on mortality was calculated by multivariable regression analysis and a logistic general additive model.ResultsOf 557 patients after exclusions, 308 were analyzed. Adherence to blood pressure recommendations was 89%. According to PetCO2, 45% were normoventilated, and 29% had a SBP ≥ 90 mm Hg and were normoventilated. Due to the poor correlation between PaCO2 and PetCO2, only 33% were normocapnic at hospital admission. Normocapnia at hospital admission was strongly associated with reduced probability of mortality. Prehospital and on-scene times had no impact on mortality.ConclusionsPaCO2 at hospital admission is strongly associated with mortality risk, but normocapnia is achieved only in a minority of patients. Therefore, the time required for placement of an arterial cannula and prehospital blood gas analysis may be warranted in severe TBI patients requiring on-scene tracheal intubation.

Permissive hypercapnia and oxygenation impairment in premature ventilated infants

AimIn permissive hypercapnia high levels of carbon dioxide (CO2) are tolerated in ventilated preterm infants to minimise lung injury, but hypercapnia could directly impair oxygenation. We aimed to quantify the association of elevated CO2 with oxygenation impairment in preterm infants by measuring the right-to-left shunt and the ventilation/perfusion (VA/Q) ratio. MethodsPre-existing datasets from preterm infants during the acute phase of respiratory distress syndrome or with evolving or established bronchopulmonary dysplasia were analysed. Non-invasive paired measurements of the fraction of inspired oxygen (FIO2) and transcutaneous oxygen saturation (SpO2) were used to calculate the degree of right-to-left shunt, right shift of the FIO2 versus SpO2 curve and the VA/Q. ResultsA total of 75 infants (43 male) with a median (IQR) gestational age of 26.4 (24.7–27.7) weeks were studied at 7 (2–31) days. Thirty-six infants (48 %) had an arterial partial pressure of CO2 (PaCO2) above 6 kPa. The PaCO2 was independently associated with the right shift of the curve [adjusted p < 0.001, unstandardised coefficient; 2.26, 95 % CI: 1.51–2.95] and the right-to-left shunt [adjusted p = 0.016, unstandardised coefficient; 1.86, 95 % CI: 0.36–3.36] after adjusting for confounders. An increase of the PaCO2 from 5 to 8 kPa, corresponded to a right shift of the curve of 20.2 kPa or a decrease in the VA/Q from 0.66 to 0.24. ConclusionsIncreased carbon dioxide levels were significantly associated with impaired oxygenation in preterm infants with respiratory distress syndrome or bronchopulmonary dysplasia.

A technique to determine the end-expiratory lung volume and dead space in a ventilated patient: Theoretical considerations

The term “dead space (VD)” refers to the volume of air/gas in the respiratory tract which does not take part in gas exchange. VD can increase in some pathological settings and has been found to be a prognostic marker in acute lung injury and respiratory distress syndrome. The end-expiratory lung volume (EELV) in a mechanically ventilated patient is the volume in the lungs at the end of passive expiration which is often influenced by disease, atelectasis, airway resistance, shunt, pulmonary vascular resistance, right heart strain, etc. Measuring EELV and VD may allow monitoring of disease state and treatment effect. VD can be derived from the arterial and exhaled CO2 partial pressures. In the intensive care unit, certain ventilators can measure EELV automatically. Unfortunately, there are no means of measuring EELV in the operating room. We herein propose a technique that may theoretically allow for measurement of the EELV and VD in the operating room setting without special equipment or an arterial blood sample.

Volumetric capnography and return of spontaneous circulation in an experimental model of pediatric asphyxial cardiac arrest

A secondary analysis of a randomized study was performed to study the relationship between volumetric capnography (VCAP) and arterial CO2 partial pressure (PCO2) during cardiopulmonary resuscitation (CPR) and to analyze the ability of these parameters to predict the return of spontaneous circulation (ROSC) in a pediatric animal model of asphyxial cardiac arrest (CA). Asphyxial CA was induced by sedation, muscle relaxation and extubation. CPR was started 2 min after CA occurred. Airway management was performed with early endotracheal intubation or bag-mask ventilation, according to randomization group. CPR was continued until ROSC or 24 min of resuscitation. End-tidal carbondioxide (EtCO2), CO2 production (VCO2), and EtCO2/VCO2/kg ratio were continuously recorded.Seventy-nine piglets were included, 26 (32.9%) of whom achieved ROSC. EtCO2 was the best predictor of ROSC (AUC 0.72, p < 0.01 and optimal cutoff point of 21.6 mmHg). No statistical differences were obtained regarding VCO2, VCO2/kg and EtCO2/VCO2/kg ratios. VCO2 and VCO2/kg showed an inverse correlation with PCO2, with a higher correlation coefficient as resuscitation progressed. EtCO2 also had an inverse correlation with PCO2 from minute 18 to 24 of resuscitation. Our findings suggest that EtCO2 is the best VCAP-derived parameter for predicting ROSC. EtCO2 and VCO2 showed an inverse correlation with PCO2. Therefore, these parameters are not adequate to measure ventilation during CPR.

Effect of external dead space removal on CO2 homeostasis in mechanically ventilated adult Covid-19 patients.

Patients with Covid-19 respiratory failure present with hypoxemia, often in combination with hypercapnia. In this prospective, observational study we examined the effect of removing external dead space (DS) on CO2 -homeostasis in mechanically ventilated Covid-19 patients. In addition, volumetric capnography was validated for its ability to estimate external DS volume using in vitro measured DS volumes as reference. In total, 10 patients with acute respiratory distress syndrome from Covid-19 were included. Volumetric capnography, mechanical ventilation, and arterial blood gas data were analyzed before and after removal of external DS and analyzed for potentially significant changes in response to DS removal. Measurements of external DS were obtained in circuit using volumetric capnography and compared to actual measured DS volumes off the circuit. After the removal of external DS, the alveolar minute ventilation and CO2 elimination improved, notwithstanding unchanged respiratory rate and tidal volumes. The increase in CO2 elimination was associated with a decrease in arterial CO2 partial pressure (PaCO2 ). The volumetric capnography method for assessment of external DS showed a low bias of -9 mL (lower limit of agreement -40, 95% CI -60 to -20 mL, upper limit of agreement 21 mL, 95% CI: 1-40 mL) and a percentage error of 48% compared to absolute values measured in vitro. Removal of external DS increased alveolar minute ventilation and CO2 elimination in Covid-19 patients with respiratory failure in the current study. This was associated with a decrease in PaCO2 . This may indicate a decreased CO2 production due to decreased work of breathing and more effective gas-exchange in response to DS removal. In addition, volumetric capnography appears to be a clinically feasible method for continuous measurement of external DS in the current study and may be of value in optimizing ventilator treatment.

Ventilatory function and oxygen delivery at high altitude in the Himalayas

This study aimed to evaluate changes in lung function assessed by spirometry and blood gas content in healthy high-altitude sojourners during a trek in the Himalayas. A group of 19 Italian adults (11 males and 8 females, mean age 43 ± 15 years, and BMI 24.2 ± 3.7 kg/m2) were evaluated as part of a Mount Everest expedition in Nepal. Spirometry and arterial blood gas content were evaluated at baseline in Kathmandu (≈1400 m), at the Pyramid Laboratory - Observatory (peak altitude of ≈5000 m), and on return to Kathmandu 2–3 days after arrival at each site. All participants took 250 mg of acetazolamide per os once daily during the ascent. We found that arterial hemoglobin saturation, O2 and CO2 partial pressures, and the bicarbonate level all decreased (in all cases, p < 0.001 with R2 =0.70–0.90), while pHa was maintained stable at the peak altitude. Forced vital capacity (FVC) remained stable, while forced expiratory volume in 1 s (FEV1) decreased (p = 0.010, n2p =0.228), resulting in a lower FEV1/FVC ratio (p < 0.001, n2p =0.380). The best predictor for acute mountain sickness was the O2 partial pressure at the peak altitude (p = 0.004, R2 =0.39). Finger pulse oximetry overestimated peripheral saturation relative to arterial saturation. We conclude that high-altitude hypoxia alters the respiratory function and the oxygen saturation of the arterial blood hemoglobin. Additionally, air rarefaction and temperature reduction, favoring hypoxic bronchoconstriction, could affect respiration. Pulse oximetry seems not enough to assist medical decisions at high altitudes.

In Vivo Testing of an Ambient Air Based, Portable, and Automated CO 2 Removal Controller for Artificial Lungs.

Portable artificial lung (AL) systems are under development, but there are few technologies available that adjust the carbon dioxide (CO 2 ) removal in response to changes in patient metabolic needs. Our work describes the second generation of a CO 2 -based portable servoregulation system that automatically adjusts CO 2 removal in ALs. Four adult sheep (68 ± 14.3 kg) were used to test the servoregulator. The servoregulator controlled air sweep flow through the lung to meet a target exhaust gas CO 2 (tEGCO 2 ) level in normocapnic and hypercapnic (arterial partial pressure of CO 2 [PaCO 2 ] >60 mm Hg) conditions at varying flow rates (0.5-1.5 L/min) and at tEGCO 2 levels of 10, 20, and 40 mm Hg. In hypercapnic sheep, average post-AL blood partial pressure of CO 2 (pCO 2 ) values were 22.4 ± 3.6 mm Hg for tEGCO 2 of 10 mm Hg, 28.0 ± 4.1 mm Hg for tEGCO 2 of 20 mm Hg and 40.6 ± 4.8 mm Hg for tEGCO 2 of 40 mm Hg. The controller successfully and automatically adjusted the sweep gas flow to rapidly (<10 minutes) meet the tEGCO 2 level when challenged with changes in inlet blood flow or target EGCO 2 levels for all animals. These in vivo data demonstrate an important step toward portable ALs that can automatically modulate CO 2 removal and allow for substantial changes in patient activity or disease status in ambulatory applications.

Association between prehospital end-tidal carbon dioxide levels and mortality in patients with suspected severe traumatic brain injury

PurposeSevere traumatic brain injury is a leading cause of mortality and morbidity, and these patients are frequently intubated in the prehospital setting. Cerebral perfusion and intracranial pressure are influenced by the arterial partial pressure of CO2 and derangements might induce further brain damage. We investigated which lower and upper limits of prehospital end-tidal CO2 levels are associated with increased mortality in patients with severe traumatic brain injury.MethodsThe BRAIN-PROTECT study is an observational multicenter study. Patients with severe traumatic brain injury, treated by Dutch Helicopter Emergency Medical Services between February 2012 and December 2017, were included. Follow-up continued for 1 year after inclusion. End-tidal CO2 levels were measured during prehospital care and their association with 30-day mortality was analyzed with multivariable logistic regression.ResultsA total of 1776 patients were eligible for analysis. An L-shaped association between end-tidal CO2 levels and 30-day mortality was observed (p = 0.01), with a sharp increase in mortality with values below 35 mmHg. End-tidal CO2 values between 35 and 45 mmHg were associated with better survival rates compared to < 35 mmHg. No association between hypercapnia and mortality was observed. The odds ratio for the association between hypocapnia (< 35 mmHg) and mortality was 1.89 (95% CI 1.53–2.34, p < 0.001) and for hypercapnia (≥ 45 mmHg) 0.83 (0.62–1.11, p = 0.212).ConclusionA safe zone of 35–45 mmHg for end-tidal CO2 guidance seems reasonable during prehospital care. Particularly, end-tidal partial pressures of less than 35 mmHg were associated with a significantly increased mortality.

Out-of-Hospital Arterial to End-Tidal Carbon Dioxide Gradient in Patients With Return of Spontaneous Circulation After Out-of-Hospital Cardiac Arrest: A Retrospective Study

End-tidal carbon dioxide (etCO2) is used to guide ventilation after achieving return of spontaneous circulation (ROSC) in certain out-of-hospital systems, despite an unknown difference between arterial and end-tidal CO2 (partial pressure of carbon dioxide [paCO2]-etCO2 difference) levels in this population. The primary aim of this study was to evaluate and quantify the paCO2-etCO2 difference in out-of-hospital patients with ROSC after nontraumatic cardiac arrest. This retrospective single-center study included patients aged 18 years and older with sustained ROSC after nontraumatic out-of-hospital cardiac arrest. In patients with an existing out-of-hospital arterial blood gas analysis within 30 minutes after achieving ROSC, matching etCO2 values were evaluated. Linear regression and Bland-Altman plot analysis were performed to ascertain the primary endpoint of interest. We included data of 60 patients in the final analysis. The mean paCO2-etCO2 difference was 32 (±18) mmHg. Only a moderate correlation (R2=0.453) between paCO2 and etCO2 was found. Bland-Altman analysis showed a bias of 32 mmHg (95% confidence interval [CI], 27 to 36) [the upper limit of agreement of 67 mmHg (95% CI, 59 to 74) and the lower limit of agreement of-3 mmHg (95% CI,-11 to 5)]. The paCO2-etCO2 difference in patients with ROSC after out-of-hospital cardiac arrest is far from physiologic ranges, and the between-patient variability is high. Therefore, etCO2-guided adaption of ventilation might not provide adequate accuracy in this setting.

Can Alterations in Cerebrovascular CO2 Reactivity Be Identified Using Transfer Function Analysis without the Requirement for Carbon Dioxide Inhalation?

The present study aimed to examine the validity of a novel method to assess cerebrovascular carbon dioxide (CO2) reactivity (CVR) that does not require a CO2 inhalation challenge, e.g., for use in patients with respiratory disease or the elderly, etc. In twenty-one healthy participants, CVR responses to orthostatic stress (50° head-up tilt, HUT) were assessed using two methods: (1) the traditional CO2 inhalation method, and (2) transfer function analysis (TFA) between middle cerebral artery blood velocity (MCA V) and predicted arterial partial pressure of CO2 (PaCO2) during spontaneous respiration. During HUT, MCA V steady-state (i.e., magnitude) and MCA V onset (i.e., time constant) responses to CO2 inhalation were decreased (p < 0.001) and increased (p = 0.001), respectively, indicative of attenuated CVR. In contrast, TFA gain in the very low-frequency range (VLF, 0.005-0.024 Hz) was unchanged, while the TFA phase in the VLF approached zero during HUT (-0.38 ± 0.59 vs. 0.31 ± 0.78 radians, supine vs. HUT; p = 0.003), indicative of a shorter time (i.e., improved) response of CVR. These findings indicate that CVR metrics determined by TFA without a CO2 inhalation do not track HUT-evoked reductions in CVR identified using CO2 inhalation, suggesting that enhanced cerebral blood flow response to a change in CO2 using CO2 inhalation is necessary to assess CVR adequately.

Effect of high ambient temperature on physiological responses during incremental exercise in Thoroughbred horses

Several reports have suggested that the risk of exertional heat illness (EHI) in Thoroughbred racehorses increases in high ambient temperatures. Heat dissipation in horses during exercise becomes less efficient when the body temperature and ambient temperature are close. Therefore, we hypothesised that exercise at 40 °C may increase body temperature, oxygen consumption, and cardiac output during incremental exercise tests compared to 20 and 30 °C. Six trained Thoroughbred horses were studied in a randomised, crossover design at three ambient temperatures with a 6-day washout period. Using a 3% inclined treadmill, horses performed incremental exercise tests at 1.7, 3.5, 6, 8, and 10 m/s for 90 s at ambient temperatures of 20, 30, and 40 °C. The effects of ambient temperature at 10 m/s on physiological variables were analysed using mixed models (P&lt;0.05). Pulmonary arterial temperature and rectal temperature at 40 °C were higher than those at 20 °C (P&lt;0.001) and 30 °C (P&lt;0.001). Similarly, oxygen consumption (vs 20 °C, P=0.009; vs 30 °C, P=0.006) and cardiac output (vs 20 °C, P=0.001; vs 30 °C, P=0.001) at 40 °C were higher than those at 20 and 30 °C. Arterial O2 partial pressure, O2 saturation, and pH at 40 °C were lower than those at 20 and 30 °C. Arterial CO2 partial pressure at 40 °C was higher than that at 20 and 30 °C. No differences were observed in arterial-mixed venous O2 concentration difference (P=0.391) and plasma lactate concentration (P=0.134) at different ambient temperatures. These results indicate that exercise at 40 °C causes excessive high body temperature, decreased running economy, and increased cardiac output compared to exercise at 20 and 30 °C. We strongly suggest that trainers and veterinarians should anticipate the occurrence of increased thermal stresses when ambient temperature is extremely high even in dry conditions and prepare to mitigate the risk of EHI from the perspective of equine welfare.

Pulmonary ventilation and gas exchange during prolonged exercise in humans: Influence of dehydration, hyperthermia and sympathoadrenal activity.

What is the central question of the study? Ventilation increases during prolonged intense exercise, but the impact of dehydration and hyperthermia, with associated blunting of pulmonary circulation, and independent influences of dehydration, hyperthermia and sympathoadrenal discharge on ventilatory and pulmonary gas exchange responses remain unclear. What is the main finding and its importance? Dehydration and hyperthermia led to hyperventilation and compensatory adjustments in pulmonary CO2 and O2 exchange, such that CO2 output increased and O2 uptake remained unchanged despite the blunted circulation. Isolated hyperthermia and adrenaline infusion, but not isolated dehydration, increased ventilation to levels similar to combined dehydration and hyperthermia. Hyperthermia is the main stimulus increasing ventilation during prolonged intense exercise, partly via sympathoadrenal activation. The mechanisms driving hyperthermic hyperventilation during exercise are unclear. In a series of retrospective analyses, we evaluated the impact of combined versus isolated dehydration and hyperthermia and the effects of sympathoadrenal discharge on ventilation and pulmonary gas exchange during prolonged intense exercise. In the first study, endurance-trained males performed two submaximal cycling exercise trials in the heat. On day 1, participants cycled until volitional exhaustion (135± 11min) while experiencing progressive dehydration and hyperthermia. On day 2, participants maintained euhydration andcore temperature (Tc ) during a time-matched exercise (control). At rest and during the first 20min of exercise, pulmonary ventilation ( ), arterial blood gases, CO2 output and O2 uptake were similar in both trials. At 135±11min, however, was elevated with dehydration and hyperthermia, and this was accompanied by lower arterial partial pressure of CO2 , higher breathing frequency, arterial partial pressure of O2 , arteriovenous CO2 and O2 differences, and elevated CO2 output and unchanged O2 uptake despite a reduced pulmonary circulation. The increased was closely related to the rise in Tc and circulating catecholamines (R2 ≥0.818, P≤0.034). In three additional studies in different participants, hyperthermia independently increased to an extent similar to combined dehydration and hyperthermia, whereas prevention of hyperthermia in dehydrated individuals restored to control levels. Furthermore, adrenaline infusion during exercise elevated both Tc and . These findings indicate that: (1) adjustments in pulmonary gas exchange limit homeostatic disturbances in the face of a blunted pulmonary circulation; (2) hyperthermia is the main stimulus increasing ventilation during prolonged intense exercise; and (3) sympathoadrenal activation might partly mediate the hyperthermic hyperventilation.

Utility of lactate, central venous oxygen saturation, and the difference in venous and arterial CO2partial pressures (delta pCO2) levels in quantifying microcirculatory failure

Background: The aim of the study was to evaluate the utility of lactate, central venous oxygen saturation (ScvO2), and the difference in venous and arterial CO2 partial pressures (delta pCO2) levels and their relationship with the prognosis of critically ill children with circulatory failure in the pediatric intensive care unit (PICU). Subjects and Methods: Thirty children with circulatory failure who were admitted to the PICU of a tertiary university hospital between January 15 and November 1, 2020, were evaluated in this prospective observational study. Lactate levels, ScVO2, and delta pCO2 levels were evaluated on admission and at hours 4, 12, and 24 (T0, T4, T12, T24) in the PICU. Results: The mortality of the children with circulatory failure was 30% (n = 9). Arterial and venous lactate levels were highly correlated at T0, T4, T12, T24 (P &lt; 0.001; P &lt; 0.001; P &lt; 0.001; P &lt; 0.001, respectively). Nonsurvivors had always higher arterial lactate levels (T0, T4, T12, T24) (P = 0.019, P = 0.007, P = 0.002, P = 0.0003, respectively) and higher delta pCO2 at T0 (P = 0.039) when compared with survivors. Receiver operating characteristic analysis showed that T0 arterial lactate levels (area under the curve [AUC] 0.788, P = 0.019), T24 arterial lactate (AUC 0.918, P &lt; 0,001), and T0 delta pCO2 levels (AUC 0,741, P = 0.039) and were predictive of mortality. Conclusions: Lactate remains the most important marker of microcirculatory dysfunction in critically ill children with circulatory failure. Delta pCO2 may be an additional marker of microcirculatory dysfunction in critically ill children.

Cerebral O2 and CO2 transport in isovolumic haemodilution: Compensation of cerebral delivery of O2 and maintenance of cerebrovascular reactivity to CO2

This study investigated the influence of acute reductions in arterial O2 content (CaO2) via isovolumic haemodilution on global cerebral blood flow (gCBF) and cerebrovascular CO2 reactivity (CVR) in 11 healthy males (age; 28 ± 7 years: body mass index; 23 ± 2 kg/m2). Radial artery and internal jugular vein catheters provided measurement of blood pressure and gases, quantification of cerebral metabolism, cerebral CO2 washout, and trans-cerebral nitrite exchange (ozone based chemiluminescence). Prior to and following haemodilution, the partial pressure of arterial CO2 (PaCO2) was elevated with dynamic end-tidal forcing while gCBF was measured with duplex ultrasound. CVR was determined as the slope of the gCBF response and PaCO2. Replacement of ∼20% of blood volume with an equal volume of 5% human serum albumin (Alburex® 5%) reduced haemoglobin (13.8 ± 0.8 vs. 11.3 ± 0.6 g/dL; P < 0.001) and CaO2 (18.9 ± 1.0 vs 15.0 ± 0.8 mL/dL P < 0.001), elevated gCBF (+18 ± 11%; P = 0.002), preserved cerebral oxygen delivery (P = 0.49), and elevated CO2 washout (+11%; P = 0.01). The net cerebral uptake of nitrite (11.6 ± 14.0 nmol/min; P = 0.027) at baseline was abolished following haemodilution (−3.6 ± 17.9 nmol/min; P = 0.54), perhaps underpinning the conservation of CVR (61.7 ± 19.0 vs. 69.0 ± 19.2 mL/min/mmHg; P = 0.23). These findings demonstrate that the cerebrovascular responses to acute anaemia in healthy humans are sufficient to support the maintenance of CVR.

Identifying putative ventilation-perfusion distributions in COVID-19 pneumonia.

Busana et al. (doi.org/10.1152/japplphysiol.00871.2020) published 5 patients with COVID-19 in whom the fraction of non-aerated lung tissue had been quantified by computed tomography. They assumed that shunt flow fraction was proportional to the non-aerated lung fraction, and, by randomly generating 106 different bimodal distributions for the ventilation-perfusion ([Formula: see text]) ratios in the lung, specified as sets of paired values {[Formula: see text]}, sought to identify as solutions those that generated the observed arterial partial pressures of CO2 and O2 (PaCO2 and PaO2). Our study sought to develop a direct method of calculation to replace the approach of randomly generating different distributions, and so provide more accurate solutions that were within the measurement error of the blood-gas data. For the one patient in whom Busana et al. did not find solutions, we demonstrated that the assumed shunt flow fraction led to a non-shunt blood flow that was too low to support the required gas exchange. For the other four patients, we found precise solutions (prediction error < 1x10-3 mmHg for both PaCO2 and PaO2), with distributions qualitatively similar to those of Busana et al. These distributions were extremely wide and unlikely to be physically realisable, because they predict the maintenance of very large concentration gradients in regions of the lung where convection is slow. We consider that these wide distributions arise because the assumed value for shunt flow is too low in these patients, and we discuss possible reasons why the assumption relating to shunt flow fraction may break down in COVID-19 pneumonia.

Dynamics of the cerebral autoregulatory response to paced hyperventilation assessed using subcomponent and time-varying analyses.

Cerebral blood flow (CBF) can be altered by a change in partial pressure of arterial CO2 (Pco2), being reduced during hyperventilation (HPV). Critical closing pressure (CrCP) and resistance area product (RAP) are parameters that can be studied to understand this change, but their dynamic response has not been investigated during paced HPV (PHPV). Seventy-five participants had recordings at rest and during PHPV. Blood pressure (BP) (Finometer), bilateral CBF velocity (CBFV) (transcranial Doppler), end-tidal CO2 (capnography), and heart rate (HR) were recorded continuously. Subcomponent analysis (SCA) and time-varying CrCP, RAP, and dynamic cerebral autoregulation (autoregulation index, ARI) were estimated by comparing PHPV with poikilocapnia. PHPV caused a change in CBFV (P < 0.01), EtCO2, (P < 0.01), HR (P < 0.001), and RAP (P < 0.01). SCA demonstrated RAP was the main parameter explaining the changes in CBFV due to PHPV. The time-varying step responses for CBFV and RAP during PHPV demonstrated considerable nonstationarity compared with poikilocapnia (P < 0.00001). Although time-varying ARI was temporarily depressed, after 60 s of PHPV it was significantly higher (6.81 ± 1.88) (P < 0.0001) than in poikilocapnia (5.08 ± 1.86). The mean plateau of the RAP step response was -98.3 ± 58.8% 60 s after the onset of PHPV but -71.7 ± 45.0% for poikilocapnia (P = 0.0026), with no corresponding changes in CrCP (P = 0.6). Further work is needed to assess the role of sex and aging in our findings, and the potential for using RAP and CrCP to improve the sensitivity and specificity of CO2 reactivity studies in cerebrovascular conditions.NEW & NOTEWORTHY The dynamic response of critical closing pressure (CrCP) and resistance-area product (RAP) of the cerebral circulation to a step change in mean arterial pressure can shed light on the nonstationary changes induced by paced hyperventilation and the effects of hypocapnia on the autoregulation of cerebral blood flow. Contrary to hypercapnia, where the response is dominated by CrCP, hypocapnia shows an initial depression of cerebral autoregulation, followed by improvements controlled by changes in RAP.