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Purpose: To investigate the effects of repeated-sprint training with voluntary hypoventilation at low (RSH-VHL) and high (RS-VHH) lung volume on repeated-sprint ability (RSA) in female athletes. Methods: Over a 6-week period, 24 female soccer players completed 12 sessions of repeated 30-m running sprints with end-expiratory breath holding (RSH-VHL, n = 8), end-inspiratory breath holding (RS-VHH, n = 8), or unrestricted breathing (RS-URB, n = 8). Before and after training, a running RSA test consisting of performing 30-m all-out sprints until exhaustion was implemented. Results: From before to after training, the number of sprints completed during the RSA test was increased in both RSH-VHL (19.3 [0.9] vs 22.6 [0.9]; P <.01) and RS-VHH (19.3 [1.5] vs 20.5 [1.7]; P <.01) but not in RS-URB (19.4 [1.3] vs 19.5 [1.7]; P =.67). The mean velocity and the percentage decrement score calculated over sprints 1 to 17 were, respectively, higher (82.2% [1.8%] vs 84.6% [2.1%] of maximal velocity) and lower (23.7% [3.1%] vs 19.4% [3.2%]) in RSH-VHL (P <.01), whereas they remained unchanged in RS-VHH and RS-URB. The mean arterial oxygen saturation recorded during training at the end of the sprints was lower in RSH-VHL (92.1% [0.4%]) than in RS-VHH (97.3% [0.1%]) and RS-URB (97.8% [0.1%]). Conclusions: This study shows that female athletes can benefit from the RSH-VHL intervention to improve RSA. The performance gains may have been limited by the short sprinting distance with end-expiratory breath holding, which provoked only moderate hypoxemia. The increase in the number of sprints in RS-VHH seems to show that factors other than hypoxia may have played a role in RSA improvement. [ABSTRACT FROM AUTHOR]

Astronauts experience combined exposure to a cephalad fluid shift and mild hypercapnia during space missions, potentially contributing to health problems. Such combined exposure may weaken dynamic cerebral autoregulation. The magnitude of cephalad fluid shift varies between individuals, and dynamic cerebral autoregulation may be affected more by greater cephalad fluid shift during combined exposure. We evaluated the dose‐dependent effects of head‐down tilt (HDT) on dynamic cerebral autoregulation during acute combined exposure to HDT and 3% CO2 inhalation. Twenty healthy participants were randomly exposed to three angles of HDT (−5°HDT+CO2, −15°HDT+CO2 and −30°HDT+CO2). After 15 min of rest, participants inhaled room air for 10 min in a horizontal body position, then inhaled 3% CO2 for 10 min under HDT. The last 6 min of data were used for analysis in each stage. Arterial pressure waveforms were obtained using finger blood pressure, and blood velocity waveforms in the middle cerebral artery were obtained using transcranial Doppler ultrasonography. Dynamic cerebral autoregulation was evaluated by transfer function analysis between waveforms. Statistical analysis was performed by two‐way repeated‐measures analysis of variance. The index of transfer function gain in the low‐frequency range increased significantly with −15°HDT+CO2 and −30°HDT+CO2, but no changes were seen with −5°HDT+CO2. Phase in the low‐frequency range decreased significantly with all three protocols. These results of significant changes in indexes of both gain and phase during combined exposure to steep HDT (−15° to −30°) and 3% CO2 inhalation suggest weakened dynamic cerebral autoregulation with the combination of moderate cephalad fluid shift and mild hypercapnia. [ABSTRACT FROM AUTHOR]

Background: Identification of hypoxaemia and hypercapnia is essential for the diagnosis and treatment of acute respiratory failure. While arterial blood gas (ABG) analysis is standard for PO2 and PCO2 measurement, venous blood gas (VBG) analysis is increasingly used as an alternative. Previous systematic reviews established that VBG reporting of PO2 and PCO2 is less accurate, but the impacts on clinical management and patient outcomes are unknown. Aims: This study aimed to systematically review available evidence of the clinical impacts of using ABGs or VBGs and examine the arteriovenous difference in blood gas parameters. Methods: A comprehensive search of the MEDLINE, Embase and Cochrane Library databases since inception was conducted. Included studies were prospective or cross‐sectional studies comparing peripheral ABG to peripheral VBG in adult non‐critical care inpatients presenting with respiratory symptoms. Results: Of 15 119 articles screened, 15 were included. No studies were found that examined clinical impacts resulting from using VBG compared to ABG. Included studies focused on the agreement between ABG and VBG measurements of pH, PO2, PCO2 and HCO3−. Due to the heterogeneity of the included studies, qualitative evidence synthesis was performed. While the arteriovenous difference in pH and HCO3− was generally predictable, the difference in PO2 and PCO2 was more significant and less predictable. Conclusions: Our study reinforces the notion that VBG is not comparable to ABG for physiological measurements. However, a key revelation from our research is the significant lack of data regarding the clinical implications of using VBG instead of ABG, a common scenario in clinical practice. This highlights a critical knowledge gap. [ABSTRACT FROM AUTHOR]

The current standard treatment for obstructive sleep apnea (OSA), continuous positive airway pressure (CPAP), is characterized by a low adherence rate due to various factors including circuit-dependent carbon dioxide (CO 2) rebreathing, which can exacerbated by disparate factors, such as low PAP, use of auto-titrating PAP or ramps. However, risk factors for rebreathing are often overlooked or poorly understood in clinical practice. Therefore, our objective was to evaluate the extent of rebreathing occurring with commonly used CPAP masks across varying PAPs, tidal volumes, and respiratory rates. In a bench study, we assessed the rebreathing rate of nine masks interfacing a CPAP with a lung simulator providing different breathing respiratory rates (15 or 20 breaths/min) and tidal volumes (400, 500, 600, 700 and 750 mL). Additionally, a theoretical model was developed to describe the likelihood of CO 2 rebreathing from four different masks at various breathing settings. Overall, all masks performed worse in situations characterized by low PAPs, high tidal volumes, and high respiratory rates. However, Dreamwear, Nuance, Siesta, Vitera, and particularly V2 masks exhibited greater susceptibility to rebreathing compared to F20, P10, Brevida, and Rio masks for the same variations of PAPs or ventilatory parameters. The mathematical model suggested that the risk of rebreathing for Rio, P10 and Nuance mask is negligible for respiratory rates of 10 breaths/min or below. Circuit-dependent CO 2 rebreathing can be a common occurrence and warrants careful mask selection upon CPAP therapy initiation for optimal clinical outcomes. • Circuit rebreathing may subtly affect CPAP adherence, yet is poorly investigated. • Mask models exhibit varied CO 2 rebreathing risks depending on different factors. • Higher rebreathing rates are at low PAPs, high tidal volumes/breathing frequencies. • Rebreathing risk is low for specific masks, perhaps apt for CPAP naïve patients. • Mask with higher rebreathing rates might be indicated for mask noise complaints. [ABSTRACT FROM AUTHOR]

Background: Cerebrovascular reactivity (CVR) is a measure of the change in cerebral blood flow (CBF) in response to a vasoactive challenge. It is a useful indicator of the brain's vascular health. Purpose: To evaluate the factors that influence successful and unsuccessful CVR examinations using precise arterial and end‐tidal partial pressure of CO2 control during blood oxygen level–dependent (BOLD) MRI. Study Type: Retrospective. Subjects: Patients that underwent a CVR between October 2005 and May 2021 were studied (total of 1162 CVR examinations). The mean (±SD) age was 46.1 (±18.8) years, and 352 patients (43%) were female. Field Strength/Sequence: 3 T; T1‐weighted images, T2*‐weighed two‐dimensional gradient‐echo sequence with standard echo‐planar readout. Assessment: Measurements were obtained following precise hypercapnic stimuli using BOLD MRI as a surrogate of CBF. Successful CVR examinations were defined as those where: 1) patients were able to complete CVR testing, and 2) a clinically useful CVR map was generated. Unsuccessful examinations were defined as those where patients were not able to complete the CVR examination or the CVR maps were judged to be unreliable due to, for example, excessive head motion, and poor PETCO2 targeting. Statistical Analysis: Successful and unsuccessful CVR examinations between hypercapnic stimuli, and between different patterns of stimulus were compared with Chi‐Square tests. Interobserver variability was determined by using the intraclass correlation coefficient (P < 0.05 is significant). Results: In total 1115 CVR tests in 662 patients were included in the final analysis. The success rate of generating CVR maps was 90.8% (1012 of 1115). Among the different hypercapnic stimuli, those containing a step plus a ramp protocol was the most successful (95.18%). Among the unsuccessful examinations (9.23%), most were patient related (89.3%), the most common of which was difficulty breathing. Data Conclusion: CO2‐BOLD MRI CVR studies are well tolerated with a high success rate. Evidence Level: 4 Technical Efficacy: Stage 3 [ABSTRACT FROM AUTHOR]

Background: By controlling hypercapnia, respiratory acidosis, and associated consequences, extracorporeal CO2 removal (ECCO2R) has the potential to facilitate ultra-protective lung ventilation (UPLV) strategies and to decrease injury from mechanical ventilation. We convened a meeting of European intensivists and nephrologists and used a modified Delphi process to provide updated insights into the role of ECCO2R in acute respiratory distress syndrome (ARDS) and to identify recommendations for a future randomized controlled trial. Results: The group agreed that lung protective ventilation and UPLV should have distinct definitions, with UPLV primarily defined by a tidal volume (VT) of 4–6 mL/kg predicted body weight with a driving pressure (ΔP) ≤ 14–15 cmH2O. Fourteen (93%) participants agreed that ECCO2R would be needed in the majority of patients to implement UPLV. Furthermore, 10 participants (majority, 63%) would select patients with PaO2:FiO2 > 100 mmHg (> 13.3 kPa) and 14 (consensus, 88%) would select patients with a ventilatory ratio of > 2.5–3. A minimum CO2 removal rate of 80 mL/min delivered by continuous renal support machines was suggested (11/14 participants, 79%) for this objective, using a short, double-lumen catheter inserted into the right internal jugular vein as the preferred vascular access. Of the participants, 14/15 (93%, consensus) stated that a new randomized trial of ECCO2R is needed in patients with ARDS. A ΔP of ≥ 14–15 cmH2O was suggested by 12/14 participants (86%) as the primary inclusion criterion. Conclusions: ECCO2R may facilitate UPLV with lower volume and pressures provided by the ventilator, while controlling respiratory acidosis. Since recent European Society of Intensive Care Medicine guidelines on ARDS recommended against the use of ECCO2R for the treatment of ARDS outside of randomized controlled trials, new trials of ECCO2R are urgently needed, with a ΔP of ≥ 14–15 cmH2O suggested as the primary inclusion criterion. [ABSTRACT FROM AUTHOR]

Introduction: Smooth muscle is integral to multiple autonomic systems, including cerebrovascular dynamics through vascular smooth muscle cells and in ocular muscle dynamics, by regulating pupil size. In the brain, smooth muscle function plays a role in cerebrovascular reactivity (CVR) that describes changes in blood vessel calibre in response to vasoactive stimuli. Similarly, pupil size regulation can be measured using the pupillary light response (PLR), the pupil's reaction to changes in light levels. The primary aim of this study was to explore the interplay between cerebral blood flow and pupil dynamics, evaluated using CVR and PLR, respectively. Methods: A total of 20 healthy adults took part in a CVR gas stimulus protocol and a light and dark flash PLR protocol. CVR was calculated as the blood flow velocity change in the middle cerebral artery, measured using transcranial Doppler ultrasound in response to a 5% increase in CO2. Multiple PLR metrics were evaluated with a clinical pupillometer. Results: CVR and PLRmetrics were all within the expected physiological ranges for healthy adults. Nine different PLR metrics, assessed through the light and dark flash protocols, were compared against CVR. A significant negative relationship was observed between the latency of the PLR in the dark flash protocol and CVR. No statistically significant relationshipswere found betweenCVR and other PLRmetrics. Conclusion: This is the first study to investigate the relationship between cerebral blood flow and pupil dynamics. A significant relationship between dark flash latency and CVR was observed. Future work includes evaluating these relationships using more robust CVR and PLR measurement techniques in a larger, more diverse cohort. Notably, more research is warranted into the PLR using a dark flash protocol and its connection to cerebrovascular function. [ABSTRACT FROM AUTHOR]

Abalone Haliotis midae are distributed from the cold, hypercapnic waters of the dynamic Benguela Current Large Marine Ecosystem to the relatively warm, normocapnic waters of the Agulhas Current. The species supports an important fishery as well as a thriving aquaculture industry. Due to the relatively low capacity to regulate their acid–base balance and their need to calcify shell and radula, abalone are especially vulnerable to increasing ocean acidification. Exposure to acidified seawater, i.e., hypercapnia, also occurs during the farming operation and can originate from (a) changes in influent seawater, (b) pH decrease by accumulation of waste products, and (c) intentional hypercapnia for anaesthesia using CO2-saturated seawater for size grading. Currently, these are acute exposures to hypercapnia, but increasing ocean acidification can cause chronic exposure, if not mitigated. Wild South African abalone are already exposed to periodic hypercapnia during ocean upwelling events and will be more so in the future due to progressive ocean acidification. This study investigated the acute pH effects in isolation as an initial step in studying the acute physiological response of H. midae to provide a mechanistic basis for the design of complex multifactorial studies, imitating more closely what occurs on farms and in the natural habitat. The major findings relevant to the above conditions are as follows: 1. Acute exposure to hypercapnia induces a reversible, unbuffered respiratory acidosis. 2. The impact of acute hypercapnia is size-dependent and potentially fatal. 3. Exposure to extreme, short hypercapnia during anaesthesia causes a rapid imbalance in the acid–base state but a rapid subsequent recovery. LC50 for small, medium and large abalone range from pH 6.27 to 6.03, respectively, and sub-lethal levels from pH 6.8 to 6.2. These results can be used by abalone aquaculture farms to mitigate/avoid the impact of acute (and chronic) hypercapnia but also to standardise their anaesthesia method. They are also a proxy to estimate the effects on wild populations. [ABSTRACT FROM AUTHOR]

Background: Apnea testing is mandatory to confirm brain death; however, it is unsafe for patients who have substantial hypoxemia without ventilator support. We used a new modified apnea test without the need to disconnect the patient from the ventilator in the present study and compared the outcomes and complications of the new method to the widely used old method. Materials and Methods: The current study was conducted on people suspected of having brain death. Both the old and new apnea tests were carried out on the same individual. In the new modified method, instead of hyperventilating and then separating the brain death from the ventilator, the induced hypercapnia method was used, and instead of performing repeated arterial blood gas (ABG), the target ETCO2 was obtained, and at the time of the target ETCO2, ABG was also checked followed by comparing ETCO2 with PaCO2. Results: Thirty patients, including 25 (83.3%) males and 5 (16.75%) females, were included in the study. The results showed significant improvement in terms of O2 saturation and heart rate (HR) using the new modified apnea test compared to the common test. Systolic blood pressure, diastolic blood pressure, and the frequency of complications were improved in the new modified test. Conclusion: The modified apnea test produced better results in terms of O2 saturation, HR, and other clinical factors, while it does not require disconnection from the ventilator and repeated ABG assessment. Therefore, it can be used to successfully diagnose brain death in high-risk individuals suffering from severe hypoxia. [ABSTRACT FROM AUTHOR]

BACKGROUND: Noninvasive ventilation (NIV) is a widely used and well-established treatment modality for respiratory failure. In patients with increased respiratory work of breathing, accessory muscles are commonly activated along with the diaphragm. Whereas diaphragm ultrasound has been utilized to assess outcomes of mechanical ventilation, the data on intercostal muscle ultrasound remain limited. We aimed to investigate the association between intercostal muscle thickening fraction (TF) and NIV failure in critical care patients with hypercapnic respiratory failure. METHODS: Critical care subjects receiving NIV for hypercapnic respiratory failure were enrolled in the study. The intercostal muscle TF was measured on admission day (day 0) and the following day (day 1). NIV failure was defined as the need for invasive mechanical ventilation or death during NIV therapy. RESULTS: A total of 158 subjects were enrolled, and 30 experienced NIV failure. Age, sex, and body mass index (BMI) were similar in the NIV success and failure groups. Acute Physiology And Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA) scores were higher in the NIV failure group. In terms of causes of respiratory failure, the COPD exacerbation rate was higher in the NIV success group. TF was higher in the NIV failure group on both day 0 and day 1. The increased TF on the ICU admission day, with a cutoff value of 12%, was associated with NIV failure after adjusting for age, sex, BMI, APACHE II, and SOFA. Persistence of a higher TF value on both day 0 and day 1 was also associated with NIV failure risk. CONCLUSIONS: There was a positive relation between intercostal muscle TF measured by ultrasound and NIV failure, even after adjusting for APACHE II and SOFA scores. [ABSTRACT FROM AUTHOR]

Experimental studies on animals have demonstrated a higher neuroprotective efficacy of hypercapnic hypoxia compared to normocapnic hypoxia. Respiratory training with hypercapnic hypoxia has shown a positive impact on the functional state of the nervous system in children with cerebral palsy (CP). It can be presumed that the combined effect of moderate hypercapnia and hypoxia will be promising for clinical application within the context of early rehabilitation after ischemic stroke. A randomized triple-blind placebo-controlled study was conducted on 102 patients with ischemic stroke, aged 63.07 ± 12.1 years. All patients were diagnosed with ischemic stroke based on neuroimaging criteria and/or clinical criteria within the 48–72 hour timeframe. The experimental group (n = 50) underwent daily respiratory training with hypercapnic hypoxia (FetCO2 5–6%, FetO2 15–16%) using the 'Carbonic' device for 7–11 sessions of 20 minutes each day during the treatment process. The control group (placebo, n = 52) underwent training on a similar device modified for breathing atmospheric air. Neurological examinations were conducted on all patients before the study and on the day after completing the training course. The standard treatment demonstrated effectiveness in terms of neurological status scales in both groups. Intermittent exposure to hypercapnic hypoxia proved more effective in improving neurological function indicators in patients compared to the placebo group: NIHSS scale scores were 40% lower than in the placebo group (p < 0.001); mRS scale scores were 35% lower (p < 0.001); B-ADL-I and RMI indices were higher by 26% (p < 0.01) and 36% (p < 0.001), respectively; MoCA scale results were 13% higher (p < 0.05); HADS and BDI-II scale scores were lower by 35% (p < 0.05) and 25% (p < 0.05), respectively. The increase in MMSE scale scores in the intervention group was 54% higher (p < 0.001), and MoCA scale scores increased by 25% (p < 0.001). Respiratory training with hypercapnic hypoxia improves the functional state of the nervous system in patients with ischemic stroke. After conducting further clarifying studies, hypercapnic hypoxia can be considered as an effective method of neurorehabilitation, which can be used as early as 48–72 hours after the onset of stroke. [ABSTRACT FROM AUTHOR]

Prior studies have identified variable effects of aging on neurovascular coupling (NVC). Carbon dioxide (CO2) affects both cerebral blood velocity (CBv) and NVC, but the effects of age on NVC under different CO2 conditions are unknown. Therefore, we investigated the effects of aging on NVC in different CO2 states during cognitive paradigms. Seventy-eight participants (18–78 yr), with well-controlled comorbidities, underwent continuous recordings of CBv by bilateral insonation of middle (MCA) and posterior (PCA) cerebral arteries (transcranial Doppler), blood pressure, end-tidal CO2, and heart rate during poikilocapnia, hypercapnia (5% CO2 inhalation), and hypocapnia (paced hyperventilation). Neuroactivation via visuospatial (VS) and attention tasks (AT) was used to stimulate NVC. Peak percentage and absolute change in MCAv/PCAv, were compared between CO2 conditions and age groups (≤30, 31–60, and >60 yr). For the VS task, in poikilocapnia, younger adults had a lower NVC response compared with older adults [mean difference (MD): −7.92% (standard deviation (SD): 2.37), P = 0.004], but comparable between younger and middle-aged groups. In hypercapnia, both younger [MD: −4.75% (SD: 1.56), P = 0.009] and middle [MD: −4.58% (SD: 1.69), P = 0.023] age groups had lower NVC responses compared with older adults. Finally, in hypocapnia, both older [MD: 5.92% (SD: 2.21), P = 0.025] and middle [MD: 5.44% (SD: 2.27), P = 0.049] age groups had greater NVC responses, compared with younger adults. In conclusion, the magnitude of NVC response suppression from baseline during hyper- and hypocapnia, did not differ significantly between age groups. However, the middle age group demonstrated a different NVC response while under hypercapnic conditions, compared with hypocapnia. NEW & NOTEWORTHY: This study describes the effects of age on neurovascular coupling under altered CO2 conditions. We demonstrated that both hypercapnia and hypocapnia suppress neurovascular coupling (NVC) responses. Furthermore, that middle age exhibits an NVC response comparable with younger adults under hypercapnia, and older adults under hypocapnia. [ABSTRACT FROM AUTHOR]

For often unclear reasons, the survival times of critically buried avalanche victims vary widely from minutes to hours. Individuals can survive and sustain organ function if they can breathe under the snow and maintain sufficient delivery of oxygen and efflux of carbon dioxide. We review the physiological responses of humans to critical avalanche burial, a model which shares similarities and differences with apnoea and accidental hypothermia. Within a few minutes of burial, an avalanche victim is exposed to hypoxaemia and hypercapnia, which have important effects on the respiratory and cardiovascular systems and pose a major threat to the central nervous system. As burial time increases, an avalanche victim also develops hypothermia. Despite progressively reduced metabolism, reduced oxygen and increased carbon dioxide tensions may exacerbate the pathophysiological consequences of hypothermia. Hypercapnia seems to be the main cause of cardiovascular instability, which, in turn, is the major reason for reduced cerebral oxygenation despite reductions in cerebral metabolic activity caused by hypothermia. ‘Triple H syndrome’ refers to the interaction of hypoxia, hypercapnia and hypothermia in a buried avalanche victim. Future studies should investigate how the respiratory gases entrapped in the porous snow structure influence the physiological responses of buried individuals and how haemoconcentration, blood viscosity and cell deformability affect blood flow and oxygen delivery. Attention should also be devoted to identifying strategies to prolong avalanche survival by either mitigating hypoxia and hypercapnia or reducing core temperature so that neuroprotection occurs before the onset of cerebral hypoxia. [ABSTRACT FROM AUTHOR]

Objectives: N95 or Type II filtering face pieces (FFP2) are often worn during work hours or on public transportation to prevent airborne infection. The aim of this randomized controlled crossover study is to assess the impact of FFP2 induced breathing resistance on pulmonary function, blood gas values and discomfort during walking and stair climbing. Methods: N = 16 healthy adults (24.8 ± 2.2 years; 10 females,) participated. Interventions included (1) six minutes of walking in a 16-meter-long hallway (612 m) and (2) eight minutes of stair climbing in a two-story staircase (420 stairs), both with and without a FFP2 (> 48 h wash-out). Spiroergometric data (Ventilation, breathing frequency, tidal volume, oxygen uptake and carbon dioxide exhalation (primary outcome), end tidal carbon dioxide- and oxygen pressure) and self-reported response (Perceived exertion, dyspnoea and pain) were assessed during activities. Blood gas analysis (capillary carbon dioxide- (pCO2) (primary outcome) and oxygen partial pressure (pO2), pH, lactate and base excess) was measured immediately after cessation of activities. Manipulation effects (FFP2 versus no mask) were tested using repeated measures analyses of variance. Results: Analysis showed no effect of FFP2 on pCO2 or other blood-gas parameters but on carbon dioxide exhalation during walking: (mean 1067, SD 209 ml/min) (mean 1908, SD 426 ml/min) (F(15) = 19.5; p < 0.001; ηp2 = 0.566) compared to no mask wearing (mean 1237, SD 173 ml/min; mean 1908, SD 426 ml/min). Ventilation was decreased and dyspnoea was increased by FFP2 during activities. FFP2 led to lower oxygen uptake and lower end tidal oxygen but higher end tidal carbon dioxide during stair climbing. Conclusions: FFP2 decreased ventilation based on slower breathing patterns and led to limitations in pulmonary gas exchange and increased subjective dyspnoea. However, invasive diagnostics revealed no signs of clinically relevant metabolic effects immediately after everyday physical activities. [ABSTRACT FROM AUTHOR]

Background: In advanced chronic obstructive pulmonary disease (COPD), hypercapnia may occur due to severe bronchial obstruction with lung hyperinflation. Non-invasive ventilation (NIV) provides the standard of care intended to achieve physiological PCO2 levels, thereby reducing overall mortality. The present study aimed to evaluate pulmonary function parameters derived from spirometry (forced vital capacity [FVC], forced expiratory volume in 1 s [FEV1]), body plethysmography (residual volume [RV], total lung capacity [TLC]), and lung diffusion capacity for carbon monoxide (single-breath method [DCO-SB], alveolar-volume corrected values [DCO-VA]) as predictors of chronic hypercapnia in patients with advanced COPD. Methods: This monocentric, retrospective observational study included 423 COPD patients. Receiver operating characteristic (ROC) curve analysis and cross-validation were used to assess lung function parameters' diagnostic accuracy for predicting chronic hypercapnia, with the resulting performance expressed as area under the ROC curve (AUROC). We performed univariable and multivariable binary logistic regression analysis to determine if these parameters were independently associated with chronic hypercapnia, with probabilities reported as odds ratios [OR] with 95% confidence intervals [95%CI]. Results: FVC% (AUROC 0.77 [95%CI 0.72–0.81], P < 0.01) and FEV1% (AURIC 0.75 [95%CI 0.70–0.79], P < 0.01) exhibited reasonable accuracy in the prediction of chronic hypercapnia, whereas lung diffusion capacity performed poorly (AUROC 0.64 [95%CI 0.58–0.71] for DCO-SB%, P < 0.01). FVC% (OR 0.95 [95%CI 0.93–0.97], P < 0.01) and FEV1% (OR 0.97 [95%CI 0.94–0.99], P = 0.029) were the only parameters associated independently with chronic hypercapnia in logistic regression analysis. FVC and FEV1 thresholds that best separated hypercapnic from normocapnic subjects reached 56% and 33% of predicted values. Conclusions: Routinely collected pulmonary function parameters, particularly FVC% and FEV1%, may predict chronic hypercapnia during COPD progression. [ABSTRACT FROM AUTHOR]

An open‐label, randomized, crossover study in healthy volunteers compared the reversal of remifentanil‐induced respiratory depression by intranasal (IN) naloxone hydrochloride (4 mg) to IN nalmefene (2.7 mg) (NCT 04828005). Subjects were administered a hypercapnic gas mixture which produces an elevation in minute ventilation (MV), a result of the ventilatory response to hypercapnia. Subjects breathed a hypercapnic gas mixture through a tight‐fitting mask for an initial period of 46 min prior to a series of mask "holidays" introduced to reduce subject discomfort and encourage study completion. Ten minutes after initiating the hypercapnic gas mixture, a remifentanil bolus was administered, and an infusion continued for the study duration. Subjects were administered either naloxone or nalmefene 15 min after initiating the remifentanil infusion and MV monitored for 21 min followed by a mask holiday. Both nalmefene and naloxone produced a time‐dependent reversal of remifentanil‐induced reductions in MV measured 2.5–20 min post administration. At the primary endpoint (5 min post administration), nalmefene increases in MV (5.75 L/min) were nearly twice that produced by naloxone (3.01 L/min) (P <.0009); the point estimate favors nalmefene, demonstrating non‐inferiority and superiority. In this model of opioid‐induced respiratory depression, nalmefene has a more rapid onset of action than naloxone, which required 20 min to achieve a comparable reversal of respiratory depression. Both nalmefene and naloxone were well tolerated by healthy volunteers. This rapid onset of action may prove particularly valuable in an era when over 90% of fatalities are linked to synthetic opioid overdose. [ABSTRACT FROM AUTHOR]

The apolipoprotein E (APOE) gene has been studied due to its influence on Alzheimer's disease (AD) development and work in an APOE mouse model recently demonstrated impaired respiratory motor plasticity following spinal cord injury (SCI). Individuals with AD often copresent with obstructive sleep apnea (OSA) characterized by cessations in breathing during sleep. Despite the prominence of APOE genotype and sex as factors in AD progression, little is known about the impact of these variables on respiratory control. Ventilation is tightly regulated across many systems, with respiratory rhythm formation occurring in the brainstem but modulated in response to chemoreception. Alterations within these modulatory systems may result in disruptions of appropriate respiratory control and ultimately, disease. Using mice expressing two different humanized APOE alleles, we characterized how sex and the presence of APOE3 or APOE4 influences ventilation during baseline breathing (normoxia) and during respiratory challenges. We show that sex and APOE genotype influence breathing during hypoxic challenge, which may have clinical implications in the context of AD and OSA. In addition, female mice, while responding robustly to hypoxia, were unable to recover to baseline respiratory levels, emphasizing sex differences in disordered breathing. NEW & NOTEWORTHY: This study is the first to use whole body plethysmography (WBP) to measure the impact of APOE alleles on breathing under normoxia and during adverse respiratory challenges in a targeted replacement Alzheimer's model. Both sex and genotype were shown to affect breathing under normoxia, hypoxic challenge, and hypoxic-hypercapnic challenge. This work has important implications regarding the impact of genetics on respiratory control as well as applications pertaining to conditions of disordered breathing including sleep apnea and neurotrauma. [ABSTRACT FROM AUTHOR]

Peripheral hypercapnic chemosensitivity (PHC) is assessed as the change in ventilation in response to a rapid change in carbon dioxide pressures (P co 2). The increase in chemoresponse from rest to subrespiratory compensation point (RCP) exercise intensities is well-defined but less clear at intensities above the RCP when changes in known ventilatory stimulants occur. Twenty healthy subjects (n = 10 females) completed a maximal exercise test on 1 day, and on a subsequent day, transient hypercapnia was used to test PHC at multiple exercise stages. The transient hypercapnia involved two breaths of 10% CO2 repeated five times during each of the following: sitting at rest on the cycle ergometer, cycling at 40% wmax, cycling at 85% Wmax, at rest on the cycle ergometer immediately following the 85% stage, and cycling at 40% Wmax again following the postexercise rest. The PHC was not different across exercise intensities (0.98 ± 0.37 vs. 0.91 ± 0.39 vs. 0.92 ± 0.42 L·min−1·mmHg−1 for first 40% wmax, 85% wmax and second 40% Wmax, respectively (P = 0.45). There were no differences in PHC between presupra-RCP exercise rest and postsupra-RCP exercise rest (0.52 ± 0.23 vs. 0.53 ± 0.24 L·min−1·mmHg−1, P = 0.8003). Using a repeated-measures correlation to account for within-participant changes, there was a significant relationship between the end-tidal P co 2 and PHC for the 85% intensity (r = 0.5, P < 0.0001) when end-tidal P co 2 was dynamic between the trials. We conclude that the physiological changes (e.g., metabolic milieu and temperature) produced with supra-RCP exercise do not further augment PHC, and that the prestimulus end-tidal P co 2 modulates the PHC. NEW & NOTEWORTHY: Exercise at intensities above the respiratory compensation point did not further augment peripheral hypercapnic chemosensitivity (PHC). Moreover, the PHC was not different during a preexercise resting state compared with rest immediately after intense exercise. The lack of differences across both comparisons suggests that exercise itself appears to sensitize the PHC. [ABSTRACT FROM AUTHOR]

Background: Nasal high-frequency oscillatory ventilation (nHFOV) has emerged as an effective initial and rescue noninvasive respiratory support mode for preterm infants with respiratory distress syndrome (RDS); however, little is known about nHFOV use in Romanian neonatal intensive care units (NICUs). Objectives: We aimed to identify the usage extent and clinical application of nHFOV in Romania. Methods: A structured web-based questionnaire was designed to find the rate of nHFOV use and knowledge of this new method of noninvasive respiratory support in Romanian level III NICUs. Using multiple-choice, open-ended, and yes/no questions, we collected information on the NICU's size, noninvasive respiratory support modes used, nHFOV use, indications, settings, nasal interfaces, secondary effects, and equipment used. Descriptive statistics and comparisons were performed using IBM SPSS Statistics 26.0. Results: A total of 21/23 (91.3%) leaders from level III NICUs (median [IQR] number of beds of 10 [10–17.5]) responded to the survey. The most frequently used noninvasive ventilation modes were CPAP mode on mechanical ventilators (76.2%), followed by NIPPV (76.2%); heated, humidified high-flow nasal cannula (HHHFNC) (61.9%); and nHFOV (11/21 units; 52.4%). A total of 5/11 units reported frequent nHFOV use (in two or more newborns/month) in both term and preterm infants. The main indications reported for nHFOV use were CPAP failure (90.9%), hypercapnia (81.8%), and bronchopulmonary dysplasia (72.7%). Face/nasal masks and short binasal prongs are the most commonly used nasal interfaces (90.9% and 72.7%, respectively). Air leaks at the interface level (90.9%), thick secretions (81.8%), and airway obstruction (63.6%) were the most frequently mentioned adverse effects of nHFOV. Only three of the NICUs had a written protocol for nHFOV use. Most units not yet using nHFOV cited lack of equipment, experience, training, or insufficient information and evidence for the clinical use and outcome of nHFOV use in neonates as the main reasons for not implementing this noninvasive respiratory mode. Conclusions: Our survey showed that nHFOV is already used in more than half of the Romanian level III NICUs to support term and preterm infants with respiratory distress despite a lack of consensus regarding indications and settings during nHFOV. [ABSTRACT FROM AUTHOR]

Abstract Background By controlling hypercapnia, respiratory acidosis, and associated consequences, extracorporeal CO2 removal (ECCO2R) has the potential to facilitate ultra-protective lung ventilation (UPLV) strategies and to decrease injury from mechanical ventilation. We convened a meeting of European intensivists and nephrologists and used a modified Delphi process to provide updated insights into the role of ECCO2R in acute respiratory distress syndrome (ARDS) and to identify recommendations for a future randomized controlled trial. Results The group agreed that lung protective ventilation and UPLV should have distinct definitions, with UPLV primarily defined by a tidal volume (VT) of 4–6 mL/kg predicted body weight with a driving pressure (ΔP) ≤ 14–15 cmH2O. Fourteen (93%) participants agreed that ECCO2R would be needed in the majority of patients to implement UPLV. Furthermore, 10 participants (majority, 63%) would select patients with PaO2:FiO2 > 100 mmHg (> 13.3 kPa) and 14 (consensus, 88%) would select patients with a ventilatory ratio of > 2.5–3. A minimum CO2 removal rate of 80 mL/min delivered by continuous renal support machines was suggested (11/14 participants, 79%) for this objective, using a short, double-lumen catheter inserted into the right internal jugular vein as the preferred vascular access. Of the participants, 14/15 (93%, consensus) stated that a new randomized trial of ECCO2R is needed in patients with ARDS. A ΔP of ≥ 14–15 cmH2O was suggested by 12/14 participants (86%) as the primary inclusion criterion. Conclusions ECCO2R may facilitate UPLV with lower volume and pressures provided by the ventilator, while controlling respiratory acidosis. Since recent European Society of Intensive Care Medicine guidelines on ARDS recommended against the use of ECCO2R for the treatment of ARDS outside of randomized controlled trials, new trials of ECCO2R are urgently needed, with a ΔP of ≥ 14–15 cmH2O suggested as the primary inclusion criterion.

Abstract Objectives N95 or Type II filtering face pieces (FFP2) are often worn during work hours or on public transportation to prevent airborne infection. The aim of this randomized controlled crossover study is to assess the impact of FFP2 induced breathing resistance on pulmonary function, blood gas values and discomfort during walking and stair climbing. Methods N = 16 healthy adults (24.8 ± 2.2 years; 10 females, ) participated. Interventions included (1) six minutes of walking in a 16-meter-long hallway (612 m) and (2) eight minutes of stair climbing in a two-story staircase (420 stairs), both with and without a FFP2 (> 48 h wash-out). Spiroergometric data (Ventilation, breathing frequency, tidal volume, oxygen uptake and carbon dioxide exhalation (primary outcome), end tidal carbon dioxide- and oxygen pressure) and self-reported response (Perceived exertion, dyspnoea and pain) were assessed during activities. Blood gas analysis (capillary carbon dioxide- (pCO2) (primary outcome) and oxygen partial pressure (pO2), pH, lactate and base excess) was measured immediately after cessation of activities. Manipulation effects (FFP2 versus no mask) were tested using repeated measures analyses of variance. Results Analysis showed no effect of FFP2 on pCO2 or other blood-gas parameters but on carbon dioxide exhalation during walking: (mean 1067, SD 209 ml/min) (mean 1908, SD 426 ml/min) (F(15) = 19.5; p

Abstract Background In advanced chronic obstructive pulmonary disease (COPD), hypercapnia may occur due to severe bronchial obstruction with lung hyperinflation. Non-invasive ventilation (NIV) provides the standard of care intended to achieve physiological PCO2 levels, thereby reducing overall mortality. The present study aimed to evaluate pulmonary function parameters derived from spirometry (forced vital capacity [FVC], forced expiratory volume in 1 s [FEV1]), body plethysmography (residual volume [RV], total lung capacity [TLC]), and lung diffusion capacity for carbon monoxide (single-breath method [DCO-SB], alveolar-volume corrected values [DCO-VA]) as predictors of chronic hypercapnia in patients with advanced COPD. Methods This monocentric, retrospective observational study included 423 COPD patients. Receiver operating characteristic (ROC) curve analysis and cross-validation were used to assess lung function parameters’ diagnostic accuracy for predicting chronic hypercapnia, with the resulting performance expressed as area under the ROC curve (AUROC). We performed univariable and multivariable binary logistic regression analysis to determine if these parameters were independently associated with chronic hypercapnia, with probabilities reported as odds ratios [OR] with 95% confidence intervals [95%CI]. Results FVC% (AUROC 0.77 [95%CI 0.72–0.81], P