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Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is clear that mechanical ventilation strategies influence the course of lung disease, and the choice of a ventilation strategy that avoids volutrauma and atelectrauma is firmly based on experimental literature and clinical experience. The application of a lung-protective strategy with reduced tidal volumes, effective lung recruitment, adequate PEEP to minimize alveolar collapse during expiration, and permissive hypercapnia has been shown to be advantageous in adult patients who have ARDS, although it has not been systematically studied in children. A significant body of literature confirms the beneficial effects of hypercapnic acidemia in the setting of acute lung injury. As a corollary, experimental evidence indicates that buffering hypercapnic acidosis abrogates its protective effects. The use of permissive hypercapnia as part of a lung-protective strategy in children should be accepted and perhaps even desired, provided it does not result in significant hemodynamic instability. This acceptance should be tempered with the recognition that a low-stretch, reduced-tidal volume strategy without hypercapnia has also been shown to improve outcomes in adults who have ARDS and that HFOV can generally provide lung-protective ventilation without necessarily inducing hypercapnia. Thus, a synthesis of the available clinical and research data strongly supports a graded approach to managing patients who have acute lung injury requiring intubation. The highest priority should be a mechanical ventilation strategy that limits the tidal volume, with the allowance of hypercapnia to a degree that does not compromise hemodynamic status.
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PMID:Is permissive hypercapnia a beneficial strategy for pediatric acute lung injury? 1695 99

Respiratory failure from causes exclusive of intrinsic lung disease is rare in systemic sclerosis. We report an unusual case of a young woman with diffuse systemic sclerosis who presented with proximal muscle weakness, dyspnea, weight loss, and nasal regurgitation. On physical examination, she had normal breath sounds but severe limitation of chest wall expansion. Pulmonary function tests (PFTs) were consistent with restrictive lung disease. Pulmonary pressures were normal on right heart catheterization and chest radiography and high-resolution computed tomography showed no evidence of intrinsic lung disease. Quadriceps muscle biopsy was consistent with type II atrophy, without any element of inflammatory myositis. After a meal, the patient aspirated, developed severe persistent hypercapnia, and required ventilatory support. Therapy with corticosteroids and intravenous gamma globulin failed to improve her condition, and the patient subsequently expired. Hypercapnic respiratory failure on the basis of chest wall involvement from systemic sclerosis may occur in the absence of intrinsic lung disease, and the prognosis, as in this case, may be grave.
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PMID:Hypercapnic respiratory failure in systemic sclerosis. 1704 22

Preterm birth and chronic lung disease may increase the risk of hypertension and cardiovascular disease in infancy and adolescence. Here we looked for evidence of early circulatory dysfunction associated with these perinatal complications. We compared infants born at term (n = 12) with those born preterm with an uncomplicated neonatal course (n = 12) or diagnosed with bronchopulmonary dysplasia (BPD) (n = 10). We measured blood pressure (BP) (Finometer), and heart rate (HR) responses to 4 min of breathing 4% CO2 during quiet sleep. Hypercapnia accelerated HR and increased BP of term infants. Preterm infants either (i) had an exaggerated pressor but little or no HR response to CO2 (healthy or mild-moderate BPD) or (ii) had a diminished pressor response and accompanying decrease in HR (severe BPD). Short-term reflex cardiovascular control was consequently altered by premature birth, with potentially more serious aberrations associated with severe BPD. Most anomalies had not resolved by the time infants born preterm reached term age; some may be early signs of emerging long-term cardiovascular dysfunction.
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PMID:Abnormal circulatory stress responses of preterm graduates. 1731 92

Chronic obstructive pulmonary disease (COPD) is a slowly progressive lung disease that results in several complications, including cognitive dysfunction. Some evidences support that cognitive impairment is common and clinically important in COPD, but the exact mechanism is still unclear. It has been confirmed that chronic hypoxia-hypercapnia contributes a lot to the development in pathophysiology of COPD. Data from some pilot studies indicated that chronic hypoxia-hypercapnia influences cognitive functions both in patients and in animals, which includes some distinctive pattern of cognitive dysfunction in human being or impairment of spatial learning-memory in rat. Therefore, we propose that cognitive impairment is strongly related to combination of chronic hypoxia and hypercapnia, and chronic hypoxia-hypercapnia-induced animal models may mimic the cognitive dysfunction of COPD. Attempts to confirm this hypothesis may lead to new model of cognitive dysfunction in COPD.
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PMID:Chronic hypoxia-hypercapnia influences cognitive function: a possible new model of cognitive dysfunction in chronic obstructive pulmonary disease. 1833 81

Since the introduction of oxygen as a therapeutic agent 70 years ago, much has been learned regarding the detrimental effects of hypoxemia and the beneficial impact of oxygen therapy. It is projected that there are close to 800,000 patients receiving long-term oxygen therapy (LTOT) in the United States, at a cost of approximately $1.8 billion annually. The large numbers of patients receiving supplemental oxygen as treatment and the high costs incurred in providing oxygen therapy necessitate the practitioner to know the indications for LTOT as well its effects on survival, pulmonary hemodynamics, sleep, and exercise capacity. It is now recognized that the basis for LTOT prescription for all patients is founded on data that are over 25 years old and that only involve a very select cohort of patients. It is clear that further studies are required to assess the effects of oxygen on patients with chronic obstructive pulmonary disease with only mild hypoxemia, not only survival but also on neurocognitive function, quality of life, exercise physiology, and sleep quality. In addition, although proven to be safe when prescribed long term to individuals with lung disease, there are some concerns about worsening carbon dioxide retention and increased oxidant injury. The goals of this article are to briefly describe the indications for chronic oxygen administration, the physiologic effects of treatment, and potential toxicities, as well as its effect on morbidity and mortality.
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PMID:Oxygen therapy in chronic obstructive pulmonary disease. 1845 64

Chronic neonatal lung disease (CNLD) is defined as a supplemental oxygen requirement beyond 36 weeks' postmenstrual age, with more severely affected infants requiring oxygen beyond a full-term-equivalent age. Low-flow supplemental oxygen facilitates discharge from hospital of infants with CNLD who develop hypoxia in air. There is a lack of data on the most appropriate minimum mean target oxygen saturation (Spo(2)) level. Reflecting a variety of clinical practices and infant comorbidities (frequency of oxygen desaturation, presence of pulmonary hypertension, retinopathy of prematurity, and adequacy of growth), the minimum mean target range for Spo(2) during overnight oximetry should be 93%-95%. The effect of supplemental oxygen on carbon dioxide retention should be considered before deciding on an oxygen flow. Most infants with CNLD are not ready for discharge until their supplemental oxygen requirement is < or = 0.5 litres per minute delivered through a nasal cannula. The safety of short-term disconnection from supplemental oxygen should be assessed before discharge. Assessment of oxygenation during sleep with continuous overnight oximetry or polysomnography is recommended when weaning infants from supplemental oxygen. Discontinuation of oxygen therapy is based on clinical assessments and documentation of adequate oxygenation in room air. There is limited objective evidence on which to base recommendations.
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PMID:Infants with chronic neonatal lung disease: recommendations for the use of home oxygen therapy. 1901 58

Respiratory-induced changes in the partial pressures of arterial carbon dioxide (PaCO2) and oxygen (PaO2) play a major role in cerebral blood flow (CBF) regulation. Elevations in PaCO2 (hypercapnia) lead to vasodilatation and increases in CBF, whereas reductions in PaCO2 (hypocapnia) lead to vasoconstriction and decreases in CBF. A fall in PaO2 (hypoxia) below a certain threshold (<40-45 mmHg) also produces cerebral vasodilatation. Upon initial exposure to hypoxia, CBF is elevated via a greater relative degree of hypoxia compared with hypocapnia. At this point, hypoxia-induced elevations in blood pressure and loss of cerebral autoregulation, stimulation of neuronal pathways, angiogenesis, release of adenosine, endothelium-derived NO and a variety of autocoids and cytokines are additional factors acting to increase CBF. Following 2-3 days, however, the process of ventilatory acclimatization results in a progressive rise in ventilation, which increases PaO2 and reduces PaCO2, collectively acting to attenuate the initial rise in CBF. Other factors acting to lower CBF include elevations in haematocrit, sympathetic nerve activity and local and endothelium-derived vasoconstrictors. Hypoxia-induced alterations of cerebrovascular reactivity, autoregulation and pulmonary vascular tone may also affect CBF. Thus, the extent of change in CBF during exposure to hypoxia is dependent on the balance between the myriad of vasodilators and constrictors derived from the endothelium, neuronal innervations and perfusion pressure. This review examines the extent and mechanisms by which hypoxia regulates CBF. Particular focus will be given to the marked influence of hypoxia associated with exposure to high altitude and chronic lung disease. The associated implications of these hypoxia-induced integrative alterations for the regulation of CBF are discussed, and future avenues for research are proposed.
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PMID:Regulation of cerebral blood flow in mammals during chronic hypoxia: a matter of balance. 1961 69

Elevated CO(2) levels (hypercapnia) frequently occur in patients with obstructive pulmonary diseases and are associated with increased mortality. However, the effects of hypercapnia on non-neuronal tissues and the mechanisms that mediate these effects are largely unknown. Here, we develop Drosophila as a genetically tractable model for defining non-neuronal CO(2) responses and response pathways. We show that hypercapnia significantly impairs embryonic morphogenesis, egg laying, and egg hatching even in mutants lacking the Gr63a neuronal CO(2) sensor. Consistent with previous reports that hypercapnic acidosis can suppress mammalian NF-kappaB-regulated innate immune genes, we find that in adult flies and the phagocytic immune-responsive S2* cell line, hypercapnia suppresses induction of specific antimicrobial peptides that are regulated by Relish, a conserved Rel/NF-kappaB family member. Correspondingly, modest hypercapnia (7-13%) increases mortality of flies inoculated with E. faecalis, A. tumefaciens, or S. aureus. During E. faecalis and A. tumefaciens infection, increased bacterial loads were observed, indicating that hypercapnia can decrease host resistance. Hypercapnic immune suppression is not mediated by acidosis, the olfactory CO(2) receptor Gr63a, or by nitric oxide signaling. Further, hypercapnia does not induce responses characteristic of hypoxia, oxidative stress, or heat shock. Finally, proteolysis of the Relish IkappaB-like domain is unaffected by hypercapnia, indicating that immunosuppression acts downstream of, or in parallel to, Relish proteolytic activation. Our results suggest that hypercapnic immune suppression is mediated by a conserved response pathway, and illustrate a mechanism by which hypercapnia could contribute to worse outcomes of patients with advanced lung disease, who frequently suffer from both hypercapnia and respiratory infections.
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PMID:Elevated CO2 suppresses specific Drosophila innate immune responses and resistance to bacterial infection. 1984 71

Elevated blood and tissue CO(2), or hypercapnia, is common in severe lung disease. Patients with hypercapnia often develop lung infections and have an increased risk of death following pneumonia. To explore whether hypercapnia interferes with host defense, we studied the effects of elevated P(CO2) on macrophage innate immune responses. In differentiated human THP-1 macrophages and human and mouse alveolar macrophages stimulated with lipopolysaccharide (LPS) and other Toll-like receptor ligands, hypercapnia inhibited expression of tumor necrosis factor and interleukin (IL)-6, nuclear factor (NF)-kappaB-dependent cytokines critical for antimicrobial host defense. Inhibition of IL-6 expression by hypercapnia was concentration dependent, rapid, reversible, and independent of extracellular and intracellular acidosis. In contrast, hypercapnia did not down-regulate IL-10 or interferon-beta, which do not require NF-kappaB. Notably, hypercapnia did not affect LPS-induced degradation of IkappaB alpha, nuclear translocation of RelA/p65, or activation of mitogen-activated protein kinases, but it did block IL-6 promoter-driven luciferase activity in mouse RAW 264.7 macrophages. Elevated P(CO2) also decreased phagocytosis of opsonized polystyrene beads and heat-killed bacteria in THP-1 and human alveolar macrophages. By interfering with essential innate immune functions in the macrophage, hypercapnia may cause a previously unrecognized defect in resistance to pulmonary infection in patients with advanced lung disease.
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PMID:Elevated CO2 selectively inhibits interleukin-6 and tumor necrosis factor expression and decreases phagocytosis in the macrophage. 2018 40

Hypercapnia is regularly observed in chronic lung disease, such as bronchopulmonary dysplasia in preterm infants. Hypercapnia results in increased nitric oxide synthase activity and in vitro formation of nitrates. Neural vasculature of the immature subject is particularly sensitive to nitrative stress. We investigated whether exposure to clinically relevant sustained high CO(2) causes microvascular degeneration in the newborn brain by inducing nitrative stress, and whether this microvascular degeneration has an impact on brain growth. Newborn rat pups were exposed to 10% CO(2) as inspired gas (Pa(CO(2)) = 60-70 mmHg) starting within 24 h of birth until postnatal day 7 (P7). Brains were notably collected at different time points to measure vascular density, determine brain cortical nitrite/nitrate, and trans-arachidonic acids (TAAs; products of nitration) levels as effectors of vessel damage. Chronic exposure of rat pups to high CO(2) (Pa(CO(2)) approximately 65 mmHg) induced a 20% loss in cerebrovascular density at P3 and a 15% decrease in brain mass at P7; at P30, brain mass remained lower in CO(2)-exposed animals. Within 24 h of exposure to CO(2), brain eNOS expression and production of nitrite/nitrate doubled, lipid nitration products (TAAs) increased, and protein nitration (3-nitrotyrosine immunoreactivity) was also coincidently augmented on brain microvessels (lectin positive). Intracerebroventricular injection of TAAs (10 microM) replicated cerebrovascular degeneration. Treatment of rat pups with NOS inhibitor (L-N(omega)-nitroarginine methyl ester) or a peroxynitrite decomposition catalyst (FeTPPS) prevented hypercapnia-induced microvascular degeneration and preserved brain mass. Cytotoxic effects of high CO(2) were reproduced in vitro/ex vivo on cultured endothelial cells and sprouting microvessels. In summary, hypercapnia at values frequently observed in preterm infants with chronic lung disease results in increased nitrative stress, which leads to cerebral cortical microvascular degeneration and curtails brain growth.
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PMID:Sustained hypercapnia induces cerebral microvascular degeneration in the immature brain through induction of nitrative stress. 2035 19


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