BACKGROUND: Overlap syndrome (OS), the coexistence of chronic obstructive pulmonary disease and obstructive sleep apnea, is frequently characterized by the presence of daytime hypercapnia (pCO2 ≥ 45 mmHg). The aim of this study was to investigate potential differences in anthropometric, sleep and respiratory characteristics between hypercapnic and normocapnic patients with OS.
METHODS: Consecutive patients who underwent polysomnography, pulmonary function testing and arterial blood gases and had been diagnosed with OS were enrolled in the study.
RESULTS: According to pCO2 levels in wakefulness, the patients were divided into group A, consisting of OS patients without hypercapnia (n = 108) or group B, consisting of OS patients with hypercapnia (n = 55). The majority of included patients in both groups were males (n = 92 in group A vs. n = 50 in group B). Group B had increased BMI (p = 0.001), neck (p = 0.017) and waist circumference (p = 0.013), higher scores in Epworth sleepiness scale (ESS) (p = 0.008), increased sleep efficiency (p = 0.033), oxygen desaturation index (p = 0.004) and time with oxyhemoglobin saturation <90% (p = 0.006) than group A. Also, Group B had decreased average and minimum oxyhemoglobin saturation during sleep (p < 0.001). Hypercapnic patients had lower FEV1% (p = 0.003), FVC% (p = 0.004), pO2 and pCO2 (p < 0.001 for both) values compared with normocapnic patients. In binary regression analysis, which assessed various predictors on the likelihood of having hypercapnia, it was found that BMI (OR: 1.313, 95% CI: 1.048-1.646, p = 0.018) and FVC (OR: 0.913, 95% CI: 0.845-0.986, p = 0.020) were the major determinants of hypercapnia in OS patients.
CONCLUSIONS: Hypercapnic OS patients were more obese and sleepy and presented worse respiratory function in wakefulness and sleep hypoxia characteristics compared with normocapnic OS patients.

The review discusses the potential relationship between hypoxia resistance and longevity, the influence of carbon dioxide on the mechanisms of aging of the mammalian organism, and intermittent hypercapnic-hypoxic effects on the signaling pathways of aging mechanisms. In the article, we focused on the potential mechanisms of the gero-protective efficacy of carbon dioxide when combined with hypoxia. The review summarizes the possible influence of intermittent hypoxia and hypercapnia on aging processes in the nervous system. We considered the perspective variants of the application of hypercapnic-hypoxic influences for achieving active longevity and the prospects for the possibilities of developing hypercapnic-hypoxic training methods.

Humidified high-flow nasal oxygen therapy (HFNO) has, in recent years, come to assume a key role in the management of hypoxemic acute respiratory failure (ARF). While non-invasive ventilation (NIV) currently represents the first-line ventilatory strategy in patients exhibiting hypercapnic ARF, the operating principles and physiological effects of HFNO could be interesting and useful in the initial management of hypercapnic ARF and/or after extubation, particularly in acute exacerbations of chronic obstructive pulmonary disease. Under these conditions, HFNO could be used either alone continuously or in combination with NIV during breaks in spontaneous breathing, depending on the severity and etiology of the underlying hypercapnic ARF.

CO2 exposure has been used to investigate the panicogenic response in patients with panic disorder. These patients are more sensitive to CO2, and more likely to experience the \"false suffocation alarm\" which triggers panic attacks. Imbalances in locus coeruleus noradrenergic (LC-NA) neurotransmission are responsible for psychiatric disorders, including panic disorder. These neurons are sensitive to changes in CO2/pH. Therefore, we investigated if LC-NA neurons are differentially activated after severe hypercapnia in mice. Further, we evaluated the participation of LC-NA neurons in ventilatory and panic-like escape responses induced by 20% CO2 in male and female wild type mice and two mouse models of altered LC-NA synthesis. Hypercapnia activates the LC-NA neurons, with males presenting a heightened level of activation. Mutant males lacking or with reduced LC-NA synthesis showed hypoventilation, while animals lacking LC noradrenaline present an increased metabolic rate compared to wild type in normocapnia. When exposed to CO2, males lacking LC noradrenaline showed a lower respiratory frequency compared to control animals. On the other hand, females lacking LC noradrenaline presented a higher tidal volume. Nevertheless, no change in ventilation was observed in either sex. CO2 evoked an active escape response. Mice lacking LC noradrenaline had a blunted jumping response and an increased freezing duration compared to the other groups. They also presented fewer racing episodes compared to wild type animals, but not different from mice with reduced LC noradrenaline. These findings suggest that LC-NA has an important role in ventilatory and panic-like escape responses elicited by CO2 exposure in mice.

BACKGROUND: 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 (CO2) 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.
METHODS: 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 CO2 rebreathing from four different masks at various breathing settings.
RESULTS: 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.
CONCLUSIONS: Circuit-dependent CO2 rebreathing can be a common occurrence and warrants careful mask selection upon CPAP therapy initiation for optimal clinical outcomes.

Therapeutic hypercapnia has been proposed as a potential strategy to enhance cerebral perfusion and improve outcomes in patients after cardiac arrest. However, the effects of targeted hypercapnia remain unclear. We conducted a systematic review and meta-analysis to evaluate the impact of hypercapnia compared to normocapnia on mortality and length of stay in post-cardiac arrest patients. We searched major databases for randomized controlled trials and observational studies comparing outcomes between hypercapnia and normocapnia in adult post-cardiac arrest patients. Data on in-hospital mortality and the ICU and hospital length of stay were extracted and pooled using random-effects meta-analysis. Five studies (two randomized controlled trials (RCTs) and three observational studies) with a total of 1,837 patients were included. Pooled analysis showed hypercapnia was associated with significantly higher in-hospital mortality compared to normocapnia (56.2% vs. 50.5%, OR 1.24, 95% CI 1.12-1.37, p<0.001). There was no significant heterogeneity (I2 = 25%, p = 0.26). No statistically significant differences were found for ICU length of stay (mean difference 0.72 days, 95% CI -0.51 to 1.95) or hospital length of stay (mean difference 1.13 days, 95% CI -0.67 to 2.93) between the groups. Sensitivity analysis restricted to mild hypercapnia studies did not alter the mortality findings. This meta-analysis did not find a mortality benefit with targeted hypercapnia compared to normocapnia in post-cardiac arrest patients. The results align with current guidelines recommending a normal partial pressure of arterial carbon dioxide (PaCO2) target range and do not support routinely targeting higher carbon dioxide levels in this setting.

Oxygen, like all medicines, is a drug which needs moderation. Hypoxia, as well as excess oxygen supplementation, can be harmful in a patient with chronic obstructive pulmonary disease (COPD). Both the European and the British guidelines recommend a target oxygen saturation of 88-92% in patients with COPD. Hypoxia can result in symptoms, such as restlessness, anxiety, agitation, and headache, while excess oxygen can lead to altered sensorium due to the retention of carbon dioxide (CO2) in patients with COPD. We often come across patients who come with breathlessness and have hypoxia, and the knee-jerk reaction is to start the patient on oxygen support to maintain an oxygen saturation of >95%, and this may result in hypercapnia and type II respiratory failure. Here, we present a descriptive review of the proper application of oxygen therapy in a patient presenting with acute exacerbation of COPD, the rationale behind the target oxygen saturations, and the mechanisms of type II respiratory failure due to hyperoxygenation.

We aimed to determine the relative contribution of hypercapnia and hypoxia to the bradycardic response to apneas. We hypothesized that apneas with hypercapnia would cause greater bradycardia than normoxia, similar to the response seen with hypoxia, and that apneas with hypercapnic hypoxia would induce greater bradycardia than hypoxia or hypercapnia alone. Twenty-six healthy participants (12 females; 23 ± 2 years; BMI 24 ± 3 kg/m2) underwent three gas challenges: hypercapnia (+5 torr end tidal partial pressure of CO2 [PETCO2]), hypoxia (50 torr end tidal partial pressure of O2 [PETO2]), and hypercapnic hypoxia (combined hypercapnia and hypoxia), with each condition interspersed with normocapnic normoxia. Heart rate and rhythm, blood pressure, PETCO2, PETO2, and oxygen saturation were measured continuously. Hypercapnic hypoxic apneas induced larger bradycardia (-19 ± 16 bpm) than normocapnic normoxic apneas (-11 ± 15 bpm; p = 0.002), but had a comparable response to hypoxic (-19 ± 15 bpm; p = 0.999) and hypercapnic apneas (-14 ± 14 bpm; p = 0.059). Hypercapnic apneas were not different from normocapnic normoxic apneas (p = 0.134). After removal of the normocapnic normoxic heart rate response, the change in heart rate during hypercapnic hypoxia (-11 ± 16 bpm) was similar to the summed change during hypercapnia+hypoxia (-9 ± 10 bpm; p = 0.485). Only hypoxia contributed to this bradycardic response. Under apneic conditions, the cardiac response is driven by hypoxia.

UNASSIGNED: Inhalation of high concentrations of carbon dioxide (CO₂) at atmospheric pressure can be toxic with dose-dependent effects on the cardiorespiratory system or the central nervous system. Exposure to both hyperbaric and hypobaric environments can result in decompression sickness (DCS). The effects of CO₂ on DCS are not well documented with conflicting results. The objective was to review the literature to clarify the effects of CO₂ inhalation on DCS in the context of hypobaric or hyperbaric exposure.
UNASSIGNED: The systematic review included experimental animal and human studies in hyper- and hypobaric conditions evaluating the effects of CO₂ on bubble formation, denitrogenation or the occurrence of DCS. The search was based on MEDLINE and PubMed articles with no language or date restrictions and also included articles from the underwater and aviation medicine literature.
UNASSIGNED: Out of 43 articles, only 11 articles were retained and classified according to the criteria of hypo- or hyperbaric exposure, taking into account the duration of CO₂ inhalation in relation to exposure and distinguishing experimental work from studies conducted in humans.
UNASSIGNED: Before or during a stay in hypobaric conditions, exposure to high concentrations of CO₂ favors bubble formation and the occurrence of DCS. In hyperbaric conditions, high CO₂ concentrations increase the occurrence of DCS when exposure occurs during the bottom phase at maximum pressure, whereas beneficial effects are observed when exposure occurs during decompression. These opposite effects depending on the timing of exposure could be related to 1) the physical properties of CO₂, a highly diffusible gas that can influence bubble formation, 2) vasomotor effects (vasodilation), and 3) anti-inflammatory effects (kinase-nuclear factor and heme oxygenase-1 pathways). The use of O₂-CO₂ breathing mixtures on the surface after diving may be an avenue worth exploring to prevent DCS.

UNASSIGNED: Partial carbondioxide pressure of the arterial blood (PaCO2) is used to evaluate alveolar ventilation. Transcutaneous carbon dioxide pressure (TcCO2) monitoring has been developed as a non-invasive (NIV) alternative to arterial blood gas analysis (ABG). Studies have shown that decreased tissue perfusion leads to increased carbondioxide (CO2). The use of transcutaneous capnometry may be unreliable in patients with perfusion abnormalities. In this study, we aimed to evaluate the relation between TcCO2-PaCO2 and lactate level which is recognized as a marker of hypoperfusion.
UNASSIGNED: In this prospective cohort study in critical care patients with hypercapnic respiratory failure (PaCO2 ≥45 mmHg) who received NIV between April 2019 and January 2020 in the intensive care unit were enrolled in the study. Patients\' simultaneously measured TcCO2 and PaCO2 values of hypercapnic patients were recorded. Each paired measurement was categorized into two groups; normal lactate (<2 mmol/L) and increased lactate (≥2 mmol/L).
UNASSIGNED: A total of 116 paired TcCO2 and PaCO2 measurements of 29 patients were recorded. Bland-Altman analysis showed the mean bias between the TcCO2 and PaCO2 and 95% limits of agreement (LOA) in all measurements (1.75 mmHg 95% LOA -3.67 to 7.17); in the normal lactate group (0.66 mmHg 95% LOA -1.71 to 3.03); and in the increased lactate group (5.17 mmHg 95% LOA -1.63 to 11.97). The analysis showed a correlation between lactate level and the difference between TcCO2 and PaCO2 (r= 0.79, p< 0.001) and a negative correlation between mean blood pressure and the difference between TcCO2 and PaCO2 (r= -0.54, p= 0.001). Multiple regression analysis results showed that lactate level was independently associated with increased differences between TcCO2 and PaCO2 (Beta= 0.875, p< 0.001).
UNASSIGNED: TcCO2 monitoring may not be reliable in patients with increased lactate levels. TcCO2 levels should be checked by ABG analysis in these patients.