Hypercapnia Research Papers - Academia.edu (original) (raw)

Objective: We propose that higher airway occlusion pressure (P0.1) responses to hypercapnic challenge (HC) indicate less severe injury. The study aim was to determine whether P0.1 responses to HC were associated with successful weaning after prolonged mechanical ventilation (PMV) in patients with brainstem lesions and to determine a reference value for clinical use. Design and setting: Forty-two patients with brainstem lesions on PMV were recruited. Breathing parameters and P0.1 were measured before HC. Three-minute HC challenges with increasing CO 2 concentrations were initiated and P0.1, respiratory rate, minute ventilation (V e), tidal volume (V t) and end tidal CO 2 were measured. Measurements and results: Patients were classified into high (group I) and low (group II) response groups on the basis of P0.1 responses to HC. Increases in V e and V t after HC were significantly greater in group I patients (12.22 ± 8.22 vs. 3.08 ± 4.84 L/min, P \ 0.001 and 399.11 ± 278.18 vs. 110.54 ± 18.275 ml, P \ 0.001). P0.1 levels were significantly higher in group I compared to group II before HC (2.69 ± 1.81 vs. 1.28 ± 1.04 cmH 2 O, P = 0.003). The increase in P0.1 following HC was significantly greater in group I compared to group II patients (11.05 ± 4.06 vs. 2.90 ± 2.53 cmH 2 O, P \ 0.001). Weaning success was significantly higher in group I compared to group II patients (72.2% vs. 33.3%, P = 0.02). A P0.1 increase of [6 cmH 2 O following HC was significantly associated with successful weaning. Conclusions: Assessing the P.01 response to serial increases in the level of HC may be a safe means to ascertain whether patients with brainstem lesions are ready for ventilator weaning.

- by
- •
- Medicine, Prospective studies, Young Adult, Clinical Sciences

The interactions between the acid-base variables that contribute to exudate acidosis were studied in the subcutaneous air-pouch after carrageenan injection in rats. We studied the concurrent changes of exudate gases (Pco2 and Po2), main ions ([Na+], [K+], [Ca2+], [Mg2+], [C1-] and [Lac-]), inorganic phosphate (Pi) and albumin in acutely inflamed rats (4, 8, 12, 24 and 48h of inflammation). A notable hypercapnia was found in the exudate after only 8 h (exudate Pco2 = 64.3 • 2.9 mm Hg) but this hypercapnia decreased after 48 h (32.9 • 12.7 mm Hg), coincident with the greatest increase in exudate cells. With respect to the metabolic acid-base variables, the most important changes found were a parallel decrease in the strong ion difference ([SID]) and exudate pH, as well as increases in the exudate weak acid buffers ([AToT]) due to albumin and inorganic phosphate (Pi) increases. However, after 12h, the exudate acidosis was stable at around pH 7. A similar acid pH was obtained after 24 h of inflammation when the carrageenan solution injected was previously adjusted to a physiological pH (7.4). This pH, analogous to that of the exudate, was the result of compensation by the acid-base independent variables, a fact which suggests that acid pH may be a beneficial condition for cells taking part in inflammatory processes.

- by Teresa Carbonell
- •
- Inflammation, Proteins, Clinical Sciences, Rats

A recent modification of the Kety-Schmidt wash-out technique for ' 33xenon was used to measure whole-brain blood flow (CBF) and oxygen consumption (CMR,,) 1 to 4 hours after termination of halothane anesthesia in 15 Wistar rats. I n this 3-hour experimental period, mean CBF and CMRo, were reduced to 29 and 43% of control values, respectively. CBF and CMR,, determincd at the beginning and end of the experimental period were not significantly different from each other. Cerebral venous O2 tension was significantly higher than in the control group, supporting recent suggestions of a primary, intrinsic effect of halothane on the homeostatic control of this variable. It is concluded that halothane is not useful for cerebral metabolic studies in the rat.

- by Albert Gjedde
- •
- Carbon Dioxide, Brain, Blood Pressure, Medical Physiology
- by Angel Carrillo
- •
- Transcription Factors, Child, Pediatric, Pediatric Pulmonology

Background: Ventilation using low tidal volumes with permission of hypercapnia is recommended to protect the lung in acute respiratory distress syndrome. However, the most lung protective tidal volume in association with hypercapnia is unknown. The aim of this study was to assess the effects of different tidal volumes with associated hypercapnia on lung injury and gas exchange in a model for acute respiratory distress syndrome.

- by Michael Ebsen
- •
- Engineering, Physics, Chemistry, Carbon Dioxide
- by Edgar Chedrawy and +1
- •
- Nursing, Patient Safety, Critical Care, Length of Stay

Results: MMT patients and normal subjects were 35 ± 9 years old (mean ± SD), and BMI values were 27 ± 6 kg/m 2 and 27 ± 5 kg/m 2 , respectively. Thirty percent of MMT patients had a central apnea index (CAI) > 5, and 20% had a CAI >... more

- by Olaf Drummer
- •
- Hypoxia, Anoxia, Sleep, Heroin Dependence

A diving fatality at the extreme depth of 264 m fresh water is described. The diver was equipped with an underwater video camera which recorded events leading to his death. These events corroborated predictions about respiratory complications at extreme pressure made by early researchers. Review of the video and relevant literature resulted in the following physiological interpretation: an increase in respired gas density during descent caused a progressive increase in resistance to flow in both the airways and the breathing circuit. Initially, this was associated with a shift to ventilation at higher lung volumes, a relative degree of hypoventilation, and mild permissive hypercapnia. The promotion of turbulent airway flow by increasing gas density resulted in effort-independent expiratory flow at lower flow rates than usual. The consequent inability to match ventilation to the demands of physical work at the bottom precipitated a spiraling crisis of dyspnea, increasing PaCO2, and w...

- by Frans Cronje
- •
- Diving, Atmospheric Pressure, Medical Physiology, Oxygen
- by Angel Cogolludo
- •
- Carbon Dioxide, Neonatology, Peptides, Norepinephrine

Obesity is becoming a major medical concern in several parts of the world, with huge economic impacts on health-care systems, resulting mainly from increased cardiovascular risks. At the same time, obesity leads to a number of sleep-disordered breathing patterns like obstructive sleep apnea and obesity hypoventilation syndrome (OHS), leading to increased morbidity and mortality with reduced quality of life. OHS is distinct from other sleep-related breathing disorders although overlap may exist. OHS patients may have obstructive sleep apnea/hypopnea with hypercapnia and sleep hypoventilation, or an isolated sleep hypoventilation. Despite its major impact on health, this disorder is under-recognized and under-diagnosed. Available management options include aggressive weight reduction, oxygen therapy and using positive airway pressure techniques. In this review, we will go over the epidemiology, pathophysiology, presentation and diagnosis and management of OHS.

- by Kenneth Berger
- •
- Chronic Disease, Sleep, Clinical Sciences, Wakefulness

Bronchopulmonary dysplasia Hypercapnia Hypocapnia Mechanical ventilation Premature infant s u m m a r y Lung injury in ventilated premature infants occurs primarily through the mechanism of volutrauma, often due to the combination of high tidal volumes in association with a high end-inspiratory volume and occasionally end-expiratory alveolar collapse. Tolerating a higher level of arterial partial pressure of carbon dioxide (PaCO 2 ) is considered as 'permissive hypercapnia' and when combined with the use of low tidal volumes may reduce volutrauma and lead to improved pulmonary outcomes. Permissive hypercapnia may also protect against hypocapnia-induced brain hypoperfusion and subsequent periventricular leukomalacia. However, extreme hypercapnia may be associated with an increased risk of intracranial hemorrhage. It may therefore be important to avoid large fluctuations in PaCO 2 values. Recent randomized clinical trials in preterm infants have demonstrated that mild permissive hypercapnia is safe, but clinical benefits are modest. The optimal PaCO 2 goal in clinical practice has not been determined, and the available evidence does not currently support a general recommendation for permissive hypercapnia in preterm infants.

- by Ulrich Thome
- •
- Brain, Developmental disabilities, Clinical Sciences, Newborn Infant

Morbid obesity adversely affects respiratory physiology, leading to reduced lung volumes, decreased lung compliance, ventilation perfusion mismatch, sleepdisordered breathing and the impairment of ventilatory control, and neurohormonal and neuromodulators of breathing. Therefore, morbidly obese subjects are at increased risk of various pulmonary complications that can present either acutely or chronically. Respiratory failure is one of the most common pulmonary complications related to morbid obesity. Both acute hypoxaemic and hypercapnic respiratory failure are more common among obese patients. The management pathway of respiratory failure depends, to a large extent, on the underlying cause, primarily due to the diversity of the underlying triggering diseases, the pathophysiology and the prognosis associated with each disease. Morbidly obese patients with hypoventilation have an increased risk of acute hypercapnic respiratory failure. Early diagnosis of this disorder and the application of non-invasive ventilation in this group of patients have been shown to improve respiratory parameters, decrease the need for invasive mechanical ventilation and improve survival.

- by Ahmed BaHammam
- •
- Anoxia, Risk factors, Risk Factors, Disease Management

Although lifesaving, mechanical ventilation can result in lung injury and contribute to the development of bronchopulmonary dysplasia. The most critical determinants of lung injury are tidal volume and end-inspiratory lung volume. Permissive hypercapnia offers to maintain gas exchange with lower tidal volumes and thus decrease lung injury. Further physiologic benefits include improved oxygen delivery and neuroprotection, the latter through both avoidance of accidental hypocapnia, which is associated with a poor neurologic outcome, and direct cellular effects. Clinical trials in adults with acute respiratory failure indicated improved survival and reduced incidence of organ failure in subjects managed with low tidal volumes and permissive hypercapnia. Retrospective studies in low birth weight infants found an association of bronchopulmonary dysplasia with low PaCO 2 . Randomized clinical trials of low birth weight infants did not achieve sufficient statistical power to demonstrate a reduction of BPD by permissive hypercapnia, but strong trends indicated the possibility of important benefits without increased adverse events. Herein, we review the mechanisms leading to lung injury, the physiologic effects of hypercapnia, the dangers of hypocapnia, and the available clinical data.

- by Ulrich Thome
- •
- Clinical Trial, Carbon Dioxide, Low Birth Weight, Lung

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)-Bdependent 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-␤, which do not require NF-B. Notably, hypercapnia did not affect LPS-induced degradation of IB␣, 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.-Wang, N., Gates, K. L., Trejo, H., Favoreto, Jr., S., Schleimer, R. P., Sznajder, J. I., Beitel, G. J., Sporn, P. H. S. Elevated CO 2 selectively inhibits interleukin-6 and tumor necrosis factor expression and decreases phagocytosis in the macrophage. FASEB J. 24, 2178 -2190 (2010). www.fasebj.org

- by Silvio Favoreto
- •
- Physiology, Carbon Dioxide, Cytokines, Innate immunity

Sleep is a potentially vulnerable state for the respiratory system. Respiratory drive is determined by a central respiratory generator located within the brainstem. Withdrawal of wakefulness stimuli and the initiation of active sleep processes results in ventilation being determined primarily by metabolic demand. The respiratory system is regulated by central and peripheral chemoreceptors and mechanoreceptors that provide negative feedback to maintain ventilation. Sleep onset results in alterations in upper and lower airway physiology to maintain eucapnia.

- by Jason Kirkness
- •
- Respiratory Physiology, Anoxia, Mechanoreceptors, Sleep

This study investigated whether air leaks from the upper airway during assisted ventilatory support are associated with persistent hypercapnia (PaCO(2) >45 mmHg) in patients with neuromuscular disorders. A rehabilitation hospital. The study was performed in 95 neuromuscular patients; 52 were tracheostomized with a cuffless tracheostomy tube (invasive ventilation), and 43 received noninvasive ventilation. The volume of air leaked (VL) and arterial carbon dioxide (PaCO(2)) were routinely measured during mechanical ventilation; PaCO(2) was also measured during spontaneous breathing. VL, expressed as a percentage of tidal volume, was higher in the hypercapnic group (32+/-14%, n=20) than the nonhypercapnic group ( vs. 20+/-14%). PaCO(2) during mechanical ventilation was correlated with both VL and the duration of ventilatory support per day; PaCO(2) during spontaneous breathing was correlated only with the volume of air leaked. In stepwise multiple regression analysis, air leaks contr...

Although ventilatory failure is the most common cause of death in amyotrophic lateral sclerosis (ALS) and measurement of respiratory muscle strength (RMS) has been shown to have prognostic value, no single test of strength can predict the presence of hypercapnia reliably. RMS was measured in 81 ALS patients to evaluate the relationship between tests of RMS and the presence of ventilatory failure, defined as a carbon dioxide tension &amp;amp;amp;amp;amp;gt; or = 6 kPa. We studied the predictive value of vital capacity (VC), static inspiratory and expiratory mouth pressures (MIP, MEP), maximal sniff oesophageal (sniff P(oes)), transdiaphragmatic (sniff P(di)) and nasal (SNP) pressure, cough gastric (cough P(gas)) pressure and transdiaphragmatic pressure after bilateral cervical magnetic phrenic nerve stimulation (CMS P(di)) to identify the risk of ventilatory failure in the whole group and in subgroups of patients with and without significant bulbar involvement. For patients without significant bulbar involvement, sniff P(di) had greatest predictive power [odds ratio (OR) 57] with specificity, sensitivity and positive and negative predictive values (PPV, NPV) of 87, 90, 74 and 95%, respectively Of the less invasive tests, per cent predicted SNP had greater overall predictive power (OR 25, specificity 85%, sensitivity 81%) than per cent predicted VC (9, 89%, 53%) and per cent predicted MIP (6, 83%, 55%). No test had significant predictive power for the presence of hypercapnia when used to measure RMS in a subgroup of patients with significant bulbar weakness. Thirty-five patients underwent polysomnography. CMS P(di), sniff P(di) and per cent predicted SNP were significantly correlated with the apnoea/hypopnoea index (AHI) (P = 0.035, 0.042 and 0.026, respectively). The correlations between AHI and per cent predicted MIP and VC were less strong (both non-significant). In ALS patients without significant bulbar involvement, novel tests of RMS have greater predictive power than conventional tests to predict hypercapnia. In particular, the non-invasive SNP is more sensitive than VC and MIP, suggesting that it could usefully be included in tests of respiratory muscle strength in ALS and will be helpful in assessing the risk of ventilatory failure. In patients with significant bulbar involvement, tests of respiratory muscle strength do not predict hypercapnia. Sleep-disordered breathing is correlated with RMS and the novel tests of RMS having the strongest relationship with the degree of sleep disturbance.

- by Rebecca Lyall and +1
- •
- Nonparametric Statistics, Carbon Dioxide, Amyotrophic Lateral Sclerosis, Brain

Compared to sham operated controls, myofilaments from hearts of ovariectomized ( OVX) rats demonstrate an increase in Ca 2+ sensitivity with no change in maximum tension (Wattanapermpool and Reiser, Am J Physiol 1999;277:H467-73). To test the significance of this modification in intact cells, we compared intracellular Ca 2+ transients and shortening of ventricular myocytes isolated from sham and 10

- by Beata Wolska
- •
- Kinetics, Calcium, Sex Hormones, Cell separation

This paper presents technical foundations for a new technique of near-infrared transillumination-backscattering sounding, which is designed to enable noninvasive detection and monitoring of changes in the width of the subarachnoid space (SAS) and magnitude of cerebrovascular pulsation in humans. The key novelty of the technique is elimination of influence of blood flow in the scalp on the signals received from two infrared sensors-proximal and distal. A dedicated digital algorithm is used to estimate on line the ratio of the powers of received signals, referred to as two-sensor distal-to-proximal received power quotient, TQ ( ). The propagation duct for NIR radiation reaching the distal sensor is the SAS filled with translucent cerebrospinal fluid. Information on slow fluctuations of the average width of the SAS is contained in the slow-variable part of the TQ ( ), called the subcardiac component, and in TQ itself. Variations in frequency and magnitude of faster oscillations of the width of that space around the baseline value, dependent on cerebrovascular pulsation, are reflected in instantaneous frequency and envelope of the fast-variable component. Frequency and magnitude of the cerebrovascular pulsation depend on the action of the heart, so this fast-variable component is referred to as the cardiac component.

- by Andrzej Frydrychowski
- •
- Algorithms, Biomedical Engineering, Signal Processing, Near Infrared

La lesió n pulmonar aguda es una enfermedad con alta mortalidad, que afecta a gran cantidad de pacientes y cuyo tratamiento continú a en debate. Recientemente, se ha postulado que la hipercapnia podría atenuar la respuesta inflamatoria durante la lesió n pulmonar, lo que le otorgaría un papel específico dentro de las estrategias de protecció n pulmonar durante la asistencia respiratoria mecá nica. En el presente trabajo revisamos la evidencia actual sobre el papel que altos niveles de CO 2 en sangre desempeñ an en la lesió n pulmonar. Concluimos que, si bien existen reportes que demuestran beneficios, evidencia má s reciente sugiere que la hipercapnia puede ser nociva, contribuyendo a agravar el dañ o pulmonar.

- by Arturo Briva
- •
- Carbon Dioxide, Forecasting, Cytokines, Inflammation

Background: Hypercapnic Chronic Obstructive Pulmonary Disease (COPD) exacerbation in patients with comorbidities and multidrug therapy is complicated by mixed acid-base, hydro-electrolyte and lactate disorders. Aim of this study was to determine the relationships of these disorders with the requirement for and duration of noninvasive ventilation (NIV) when treating hypercapnic respiratory failure.

- by Claudio Terzano
- •
- Carbon Dioxide, Multidisciplinary, PLoS one, Aged

nia induces injury to alveolar epithelial cells via a nitric oxide-dependent pathway. Am J Physiol Lung Cell Mol Physiol 279: L994-L1002, 2000.-Ventilator strategies allowing for increases in carbon dioxide (CO 2 ) tensions (hypercapnia) are being emphasized to ameliorate the consequences of inflammatory-mediated lung injury. Inflammatory responses lead to the generation of reactive species including superoxide (O 2 Ϫ ), nitric oxide (⅐NO), and their product peroxynitrite (ONOO Ϫ ). The reaction of CO 2 and ONOO Ϫ can yield the nitrosoperoxocarbonate adduct ONOOCO 2 Ϫ , a more potent nitrating species than ONOO Ϫ . Based on these premises, monolayers of fetal rat alveolar epithelial cells were utilized to investigate whether hypercapnia would modify pathways of ⅐NO production and reactivity that impact pulmonary metabolism and function. Stimulated cells exposed to 15% CO 2 (hypercapnia) revealed a significant increase in ⅐NO production and nitric oxide synthase (NOS) activity. Cell 3-nitrotyrosine content as measured by both HPLC and immunofluorescence staining also increased when exposed to these same conditions. Hypercapnia significantly enhanced cell injury as evidenced by impairment of monolayer barrier function and increased induction of apoptosis. These results were attenuated by the NOS inhibitor N-monomethyl-L-arginine. Our studies reveal that hypercapnia modifies ⅐NOdependent pathways to amplify cell injury. These results affirm the underlying role of ⅐NO in tissue inflammatory reactions and reveal the impact of hypercapnia on inflammatory reactions and its potential detrimental influences. carbon dioxide; nitration; inflammation; superoxide; free radical; peroxynitrite DESPITE SIGNIFICANT ADVANCES in understanding the pathophysiology of acute respiratory distress syn-Address for reprint requests and other correspondence:

- by Alvaro Estevez
- •
- Physiology, Carbon Dioxide, Cytokines, Apoptosis
- by Ahmed S BaHammam
- •
- Respiratory Medicine, Obesity, Treatment Outcome, INTENSIVE CARE

s u m m a r y Daytime hypercapnia that develops in morbidly obese individuals in the absence of concurrent lung or neuromuscular disease is referred to as the obesity hypoventilation syndrome (OHS). The characteristic polysomnographic (PSG) abnormality is marked sleep hypoxemia. Although the likelihood of hypoventilation increases with increasing body mass index (BMI), it is too simplistic to think of this disorder arising merely from chest wall restriction due to excess weight. Rather, this is a disorder which emerges when the compensatory mechanisms that normally operate to maintain ventilation appropriate for the level of obesity are impaired. OHS develops from a complex interaction between abnormal respiratory function, sleep disordered breathing and diminished respiratory drive. Irrespective of the mechanisms underlying the development of this disorder, early recognition of the problem and institution of effective therapy is important to reduce the significant clinical and societal repercussions of OHS. While therapy directed at improving sleep disordered breathing is effective in reversing daytime respiratory failure, it is not universally successful and information regarding longer term clinical outcomes is limited. Attention to weight reduction strategies are also necessary to reduce comorbid conditions and improve quality of life, but data regarding how successful and sustained this is in obesity hypoventilation are sparse.

- by Amanda Piper
- •
- Comorbidity, Body Mass Index, Risk factors, Lung
- by Andrea Messori
- •
- Treatment Outcome, Coma, Anoxia, Chronic Disease

Keywords: retina blood flow laser Doppler flowmetry hypercapnia P ET CO 2 P ET O 2 a b s t r a c t

- by Chris Hudson
- •
- Carbon Dioxide, Capillaries, Young Adult, Optometry and Ophthalmology

Near-infrared spectroscopy (NIRS) enables continuous non-invasive quantification of blood and tissue oxygenation, and may be useful for quantification of cerebral blood volume (CBV) changes. In this study, changes in cerebral oxy-and deoxyhemoglobin were compared to corresponding changes in CBF and CBV as measured by positron emission tomography (PET). Furthermore, the results were compared using a physiological model of cerebral oxygenation. In five healthy volunteers changes in CBF were induced in a randomized order by hyperventilation or inhalation of 6% CO . Arterial content of O and CO was measured several times during each scanning. Changes in 2 2 2 deoxyhemoglobin (DHb), oxyhemoglobin (DHbO ) and total hemoglobin (DHb ) were continuously recorded with NIRS equipment.

The term permissive hypercapnia defines a ventilatory strategy for acute respiratory failure in which the lungs are ventilated with a low inspiratory volume and pressure. The aim of permissive hypercapnia is to minimize lung damage during mechanical ventilation; its limitation is the resulting hypoventilation and carbon dioxide (CO 2 ) retention. In this article we discuss the rationale, physiologic implications, and implementation of permissive hypercapnia. We then review recent clinical studies that tested the effect of various approaches to permissive hypercapnia on the outcome of patients with acute respiratory failure. Curr Opin Crit Care 2001, 7:34-40

- by Fabio Sangalli
- •
- Treatment Outcome, Risk assessment, Newborn Infant, Risk Assessment

Intensivists and respirologists are very likely to encounter patients with OHS and AHRF. A high index of suspicion is needed to avoid misdiagnosis and delayed treatment that can only worsen morbidity and mortality and increase healthcare costs. Despite a lack of relevant RCTS, there is now a consensus that NIV is the first-line treatment for OHS presenting with acute-on-chronic hypercapnic respiratory failure. In this setting, NIV improves alveolar ventilation, hypercapnia, and hypoxemia, avoids invasive ventilation, and probably decreases the frequency of adverse outcomes.

- by Ahmed S BaHammam
- •
- Obesity, Critical Care, COPD, Hypertension
- by Murray Altose
- •
- Electrophysiology, Carbon Dioxide, Asthma, Dogs

OBJETIVO: La CPAP en ventilación no invasiva es utilizada ampliamente en el paciente pediátrico con insuficiencia respiratoria aguda. Sin embargo la escasez de interfases específicas, respiradores adecuados y la escasa tolerancia de la técnica en estos pacientes pueden hacer fracasar su aplicación. El objetivo de este estudio fue analizar la eficacia de un sistema de CPAP formado por un circuito respiratorio de Mapleson modificado, durante la IRA en pediatría. MATERIAL Y MÉTODOS: Estudio prospectivo observacional realizado en niños con insuficiencia respiratoria aguda con indicación de ventilación no invasiva. La CPAP se aplicó mediante un circuito respiratorio Mapleson D provisto de un manómetro y un tubo nasofaríngeo como interfase. Se recogieron previo al tratamiento y 2 horas después, frecuencia cardiaca, frecuencia respiratoria, fracción inspirada de oxígeno, presión arterial de oxígeno, de dióxido de carbono y pulsioximetría. RESULTADOS: Se incluyeron 16 pacientes de edad media 3,8 años durante un periodo de 18 meses. Observamos una disminución PaCO 2 desde 66,8±18,08 mmHg a 46,48±5,9 mmHg tras CPAP (p=0,16) y un aumento en la relación PaO 2 /FiO 2 de 201±111 a 262±115 mm Hg tras CPAP (p=0,30). La FC descendió de 156±22 a 127±18 l/min (p=0,05) y la FR de 53±15 a 33±13 resp/min (p<0,05). No se registraron complicaciones graves y la tolerancia fue adecuada. La técnica se consideró exitosa en 12 pacientes (75%). CONCLUSIONES: La aplicación de CPAP sin respirador mediante circuito Mapleson D puede ser utilizado como ventilación no invasiva en pacientes pediátricos con insuficiencia respiratoria aguda con elevada tasa de éxito. Palabras clave: Insuficiencia Respiratoria aguda. Ventilación no invasiva. Circuito Mapleson. Circuito Mapleson tipo D. CPAP. Aceptado para su publicación en diciembre de 2008.

- by Penny Stabler
- •
- Traumatic Brain Injury, Carbon Dioxide, Dysarthria, Prospective studies

This study examined the effect of anxiety on cerebral blood flow at different levels of pCO 2 in healthy participants (N = 29). Three types of breathing were used to manipulate pCO 2 in a within-subject threat-of-shock paradigm: spontaneous breathing, CO 2 -inhalation and hyperventilation resulting in normo-, hyper-and hypocapnia. Transcranial Doppler ultrasonography was used to measure CBF velocity (CBFv) in the right middle cerebral artery, while breathing behavior and end-tidal pCO 2 were monitored. During normocapnia, elevated anxiety was clearly associated with increased CBFv. Consistent with the cerebral vasoconstrictive and vasodilating effects of, respectively, hypo-and hypercapnia, we observed a positive linear association between CBFv and pCO 2 . The slope of this association became steeper with increasing anxiety, indicating that anxiety enhances the sensitivity of CBFv to changes in pCO 2 . The findings may elucidate conflicting findings in the literature and are relevant for brain imaging relying on regional cerebral blood flow.

- by Ilse Van Diest
- •
- Psychophysiology, Fear, Carbon Dioxide, Adolescent

Hypercapnia increases core temperature cooling rate during snow burial.

- by Martin Radwin
- •
- Carbon Dioxide, Biological Sciences, Disasters, Mountaineering

The consistent determination of changes in the transverse relaxation rate R 2 Ã (DR 2 Ã ) is essential for the mapping of the effect of hyperoxic and hypercapnic respiratory challenges, which enables the noninvasive assessment of blood oxygenation changes and vasoreactivity by MRI. The purpose of this study was to compare the performance of two different methods of DR 2 Ã quantification from dynamic multigradient-echo data: (A) subtraction of R 2 Ã values calculated from monoexponential decay functions; and (B) computation of DR 2 Ã echo-wise from signal intensity ratios. A group of healthy volunteers (n ¼ 12) was investigated at 3.0 T, and the brain tissue response to carbogen and CO 2 -air inhalation was registered using a dynamic multigradient-echo sequence with high temporal and spatial resolution. Results of the DR 2 Ã quantification obtained by the two methods were compared with respect to the quality of the voxel-wise DR 2 Ã response, the number of responding voxels and the behaviour of the 'global' response of all voxels with significant R 2 Ã changes. For the two DR 2 Ã quantification methods, we found no differences in the temporal variation of the voxel-wise DR 2 Ã responses or in the detection sensitivity. The maximum change in the 'global' response was slightly smaller when DR 2 Ã was derived from signal intensity ratios. In conclusion, this first methodological comparison shows that both DR 2 Ã quantifications, from monoexponential approximation as well as from signal intensity ratios, are applicable for the monitoring of R 2 Ã changes during respiratory challenges.

- by Stefanie Remmele and +2
- •
- Biomedical Engineering, Carbon Dioxide, Magnetic Resonance Imaging, Brain Mapping

1. Martin-Caraballo M, Greer JJ: Electrophysiological properties of rat phrenic motoneurons during the perinatal development. J Neurophysiol 1999, 81:1365-1378 2. Greer JJ, Allan DW, Martin-Caraballo M, Lemke RP: Invited Review: An overview of phrenic nerve and diaphragm muscle development in the perinatal rat. J Appl Physiol 1999, 86:779-786 3. Martin-Caraballo M, Campagnaro PA, Gao Y, Greer JJ: Contractile properties of the rat diaphragm during the perinatal period. J Appl Physiol 2000, 88:573-580 4. Martin-Caraballo M, Greer JJ: Development of potassium conductances in perinatal rat phrenic motoneurons. J Neurophysiol 2000, 83:3497-3508 5. Martin-Caraballo M, Greer JJ: Voltage-sensitive calcium currents and their role in regulating phrenic motoneuron electrical excitability during the perinatal period. J Neurobiol 2001, 46:231-248 Acknowledgements: Funded by CIHR, AHFMR and Alberta Lung Association.

- by Jacopo Mortola
- •
- Rhythm, Anoxia, Circadian Rhythm, Ventilation

Current protective lung ventilation strategies commonly involve hypercapnia. This approach has resulted in an increase in the clinical acceptability of elevated carbon dioxide tension, with hypoventilation and hypercapnia 'permitted' in order to avoid the deleterious effects of high lung stretch. Advances in our understanding of the biology of hypercapnia have prompted consideration of the potential for hypercapnia to play an active role in the pathogenesis of inflammation and tissue injury. In fact, hypercapnia may protect against lung and systemic organ injury independently of ventilator strategy. However, there are no clinical data evaluating the direct effects of hypercapnia per se in acute lung injury. This article reviews the current clinical status of permissive hypercapnia, discusses insights gained to date from basic scientific studies of hypercapnia and acidosis, identifies key unresolved concerns regarding hypercapnia, and considers the potential clinical implicat...

Eight men performed three series of 5-min exercise on a cycle ergometer at 65% of normoxic maximal O 2 consumption in four conditions: (1) voluntary hypoventilation (VH) in normoxia (VH 0.21 ), (2) VH in hyperoxia (inducing hypercapnia) (inspired oxygen fraction [F I O 2 ] = 0.29; VH 0.29 ), (3) normal breathing (NB) in hypoxia (F I O 2 = 0.157; NB 0.157 ), (4) NB in normoxia (NB 0.21 ). Using near-infrared spectroscopy, changes in concentration of oxy-(D[O 2 Hb]) and deoxyhemoglobin (D[HHb]) were measured in the vastus lateralis muscle. D[O 2 Hb -HHb] and D[O 2 Hb

- by Christine Lamberto
- •
- Skeletal muscle biology, Carbon Dioxide, Bicycling, Anoxia

Co-ordination of breathing and swallowing is essential for normal pharyngeal function and to protect the airway. To allow for safe passage of a bolus through the pharynx, respiration is interrupted (swallowing apnoea); however, the control of airflow and diaphragmatic activity during swallowing and swallowing apnoea are not fully understood. Here, we validated a new airflow discriminator for detection of respiratory airflow and used it together with diaphragmatic and abdominal electromyography (EMG), spirometry and pharyngeal and oesophageal manometry. Co-ordination of breathing and spontaneous swallowing was examined in six healthy volunteers at rest, during hypercapnia and when breathing at 30 breaths min -1 . The airflow discriminator proved highly reliable and enabled us to determine timing of respiratory airflow unambiguously in relation to pharyngeal and diaphragmatic activity. During swallowing apnoea, the passive expiration of the diaphragm was interrupted by static activity, i.e. an 'active breath holding', which preserved respiratory volume for expiration after swallowing. Abdominal EMG increased throughout pre-and post-swallowing expiration, more so during hyper-than normocapnia, possibly to assist expiratory airflow. In these six volunteers, swallowing was always preceded by expiration, and 93 and 85% of swallows were also followed by expiration in normo-and hypercapnia, respectively, indicating that, in man, swallowing during the expiratory phase of breathing may be even more predominant than previously believed. This co-ordinated pattern of breathing and swallowing potentially reduces the risk for aspiration. Insights from these measurements in healthy volunteers and the airflow discriminator will be used for future studies on airway protection and effects of disease, drugs and ageing.

- by Olle Ekberg
- •
- Physiology, Experimental Physiology, Young Adult, Abdominal Muscles

This study examined the time course of early scotopic threshold sensitivity during dark adaptation under mild to moderate hypoxia, moderate hypocapnia and hyperoxia, measuring detection time displacement relative to normoxia. Cone rod inXection and early rod adaptation were highlighted using progressively dimmer green Xash stimuli. Early scotopic sensitivity was signiWcantly delayed by hypoxia and hastened by hypocapnia and hyperoxia. EVects of respiratory disturbance on dark adaptation include temporal shifts of early scotopic sensitivity while human rod photoreceptors appear functionally hypoxic when breathing air at one atmosphere. At night, supplementary oxygen may beneWt aircrew visual sensitivity, even at ground level. 

- by Desmond Connolly
- •
- Visual perception, Vision, Anoxia, Aerospace Medicine

Calibrated functional magnetic resonance imaging (fMRI) provides a noninvasive technique to assess functional metabolic changes associated with normal aging. We simultaneously measured both the magnitude of the blood oxygenation level dependent (BOLD) and cerebral blood flow (CBF) responses in the visual cortex for separate conditions of mild hypercapnia (5% CO 2 ) and a simple checkerboard stimulus in healthy younger (n = 10, mean: 28-years-old) and older (n = 10, mean: 53years-old) adults. From these data we derived baseline CBF, the BOLD scaling parameter M, the fractional change in the cerebral metabolic rate of oxygen consumption (CMRO 2 ) with activation, and the coupling ratio n of the fractional changes in CBF and CMRO 2 . For the functional activation paradigm, the magnitude of the BOLD response was significantly lower for the older group (0.57 ± 0.07%) compared to the younger group (0.95 ± 0.14%), despite the finding that the fractional CBF and CMRO 2 changes were similar for both groups. The weaker BOLD response for the older group was due to a reduction in the parameter M, which was significantly lower for older (4.6 ± 0.4%) than younger subjects (6.5 ± 0.8%), most likely reflecting a reduction in baseline CBF for older (41.7 ± 4.8 mL/100 mL/min) compared to younger (59.6 ± 9.1 mL/100 mL/min) subjects. In addition to these primary responses, for both groups the BOLD response exhibited a post-stimulus undershoot with no significant difference in this magnitude. However, the post-undershoot period of the CBF response was significantly greater for older compared to younger subjects. We conclude that when comparing two populations, the BOLD response can provide misleading reflections of underlying physiological changes. A calibrated approach provides a more quantitative reflection of underlying metabolic changes than the BOLD response alone.

- by Amy Lansing
- •
- Cognitive Science, Metabolism, Nonlinear dynamics, Magnetic Resonance Imaging

Background: This study aimed to assess the impact of leak compensation capabilities during pressure-and volume-limited non-invasive positive-pressure ventilation (NPPV) in COPD patients. Methods: Fourteen patients with stable hypercapnic COPD who were receiving long-term NPPV were included in the study. For both modes of NPPV, a full face mask and an artificial leak in the ventilatory circuit were used at three different settings, and applied during daytime NPPV, either without leakage (setting I), with leakage during inspiration only (setting II), and with leakage during inspiration and expiration (setting III). Ventilation pattern was pneumotachygraphically recorded. Results: NPPV was feasible with negligible leak volumes, indicating optimal mask fitting during the daytime (setting I). In the presence of leakage (settings II and III), the attempt to compensate for leak was only evident during pressure-limited NPPV, since inspiratory volumes delivered by the ventilator increased from 726 AE 129 (setting I) to 1104 AE 164 (setting II), and to 1257 AE 166 (setting III) ml during pressure-limited NPPV, respectively (all p < 0.001); however, they remained stable during volume-limited NPPV. Leak compensation resulted in a decrease in leakage-induced dyspnea. However, 83%/87% (setting II/III) of the additionally-delivered

- by Wolfram Windisch and +1
- •
- Respiratory Medicine, Reference, Millimeter Waves, Masks
- by Ahmed BaHammam
- •
- Respiratory Medicine, Obesity, Treatment Outcome, INTENSIVE CARE

In the present study, we evaluated the role of glutamatergic mechanisms in the retrotrapezoid nucleus (RTN) in changes of splanchnic sympathetic nerve discharge (sSND) and phrenic nerve discharge (PND) elicited by central and peripheral chemoreceptor activation. Mean arterial pressure (MAP), sSND and PND were recorded in urethane-anaesthetized, vagotomized, sino-aortic denervated and artificially ventilated male Wistar rats. Hypercapnia (10% CO 2 ) increased MAP by 32 ± 4 mmHg, sSND by 104 ± 4% and PND amplitude by 101 ± 5%. Responses to hypercapnia were reduced after bilateral injection of the NMDA receptor antagonist d,l-2-amino-5-phosphonovalerate (AP-5; 100 mm in 50 nl) in the RTN (MAP increased by 16 ± 3 mmHg, sSND by 82 ± 3% and PND amplitude by 63 ± 7%). Bilateral injection of the non-NMDA receptor antagonist 6,7-dinitro-quinoxaline-2,3-dione (DNQX; 100 mm in 50 nl) and the metabotropic receptor antagonist (+/−)-α-methyl-4-carboxyphenylglycine (MCPG; 100 mm in 50 nl) in the RTN did not affect sympathoexcitatory responses induced by hypercapnia. Injection of DNQX reduced hypercapnia-induced phrenic activation, whereas MCPG did not. In animals with intact carotid chemoreceptors, bilateral injections of AP-5 and DNQX in the RTN reduced increases in MAP, sSND and PND amplitude produced by intravenous injection of NaCN (50 μg kg −1 ). Injection of MCPG in the RTN did not change responses produced by NaCN. These data indicate that RTN ionotropic glutamatergic receptors are involved in the sympathetic and respiratory responses produced by central and peripheral chemoreceptor activation.

- by Thiago Moreira
- •
- Physiology, Experimental Physiology, Glutamate receptors, Medical Physiology
- by John Laffey
- •
- Endocrinology, Genetics, Cardiology, Hematology