Academic literature on the topic 'Hypercapnia – Pathophysiology'

Abnormal central regulation of upper airway muscles may contribute to the pathophysiology of the childhood obstructive sleep apnea syndrome (OSAS). We hypothesized that this was secondary to global abnormalities of ventilatory control during sleep. We therefore compared the response to chemical stimuli during sleep between prepubertal children with OSAS and controls. Patients with OSAS aroused at a higher[Formula: see text] (58 ± 2 vs. 60 ± 5 Torr, P < 0.05); those with the highest apnea index had the highest arousal threshold ( r = 0.52, P < 0.05). The hypercapnic arousal threshold decreased after treatment. For all subjects, hypoxia was a poor stimulus to arousal, whereas hypercapnia and, particularly, hypoxic hypercapnia were potent stimuli to arousal. Hypercapnia resulted in decreased airway obstruction in OSAS. Ventilatory responses were similar between patients with OSAS and controls; however, the sample size was small. We conclude that children with OSAS have slightly blunted arousal responses to hypercapnia. However, the overall ventilatory and arousal responses are normal in children with OSAS, indicating that a global deficit in respiratory drive is not a major factor in the etiology of childhood OSAS. Nevertheless, subtle abnormalities in ventilatory control may exist.

Intermittent hypoxia-induced ventilatory neuroplasticity is likely important in obstructive sleep apnea pathophysiology. Although concomitant CO2levels and arousal state critically influence neuroplastic effects of intermittent hypoxia, no studies have investigated intermittent hypercapnic hypoxia effects during sleep in humans. Thus the purpose of this study was to investigate if intermittent hypercapnic hypoxia during sleep induces neuroplasticity (ventilatory long-term facilitation and increased chemoreflex responsiveness) in humans. Twelve healthy males were exposed to intermittent hypercapnic hypoxia (24 × 30 s episodes of 3% CO2and 3.0 ± 0.2% O2) and intermittent medical air during sleep after 2 wk washout period in a randomized crossover study design. Minute ventilation, end-tidal CO2, O2saturation, breath timing, upper airway resistance, and genioglossal and diaphragm electromyograms were examined during 10 min of stable stage 2 sleep preceding gas exposure, during gas and intervening room air periods, and throughout 1 h of room air recovery. There were no significant differences between conditions across time to indicate long-term facilitation of ventilation, genioglossal or diaphragm electromyogram activity, and no change in ventilatory response from the first to last gas exposure to suggest any change in chemoreflex responsiveness. These findings contrast with previous intermittent hypoxia studies without intermittent hypercapnia and suggest that the more relevant gas disturbance stimulus of concomitant intermittent hypercapnia frequently occurring in sleep apnea influences acute neuroplastic effects of intermittent hypoxia. These findings highlight the need for further studies of intermittent hypercapnic hypoxia during sleep to clarify the role of ventilatory neuroplasticity in the pathophysiology of sleep apnea.NEW & NOTEWORTHY Both arousal state and concomitant CO2levels are known modulators of the effects of intermittent hypoxia on ventilatory neuroplasticity. This is the first study to investigate the effects of combined intermittent hypercapnic hypoxia during sleep in humans. The lack of neuroplastic effects suggests a need for further studies more closely replicating obstructive sleep apnea to determine the pathophysiological relevance of intermittent hypoxia-induced ventilatory neuroplasticity.

Background: Obstructive sleep apnea (OSA) is a state of the occurrence of upper airway obstruction periodically during sleep that causes breathing to stop intermittently, either complete (apnea) or partial (hipopnea). Obesity hypoventilation syndrome (OHS) is generally defined as a combination of obesity (BMI ≥ 30 kg / mc) with arterial hypercapnia while awake (PaCO2 > 45 mmHg) in the absence of other causes of hypoventilation. Purpose: In order for the pulomonologis can understand the pathogenesis and pathophysiology of OSA and its complications. Literature review: Several studies have been expressed about the link between OSA, OHS with respiratory failure disease. Pathophysiology of OSA, OHS in respiratory failure were difficult to detect, can cause respiratory failure disease management becomes less effective. Conclusion: A good understanding can help with the diagnosis and management of the appropriate conduct to prevent complications of respiratory failure associated with OSA.

Diabetic ketoacidosis is a frequent complication of type 1 diabetes mellitus in children and adolescents. One of the leading causes of death in this pathology is cerebral edema. This complication is often asymptomatic, which makes it difficult to diagnose. The main risk factors for cerebral edema in children include the true factors (low partial pressure of carbon dioxide, high blood urea nitrogen, concomitant psychiatric pathology, etc.) and iatrogenic factors (large volume of infusion therapy, rapid decrease in blood glucose levels, administration of bicarbonate, etc.). The pathophysiology of this complication is not yet fully understood. The main pathophysiological elements of cerebral edema in children with DKA include the disruption of blood-brain barrier permeability, edema of brain cells, and dysfunction of cell membranes. Important roles are also played by hypercapnia and reduction of osmotic pressure. Based on the character of pathophysiologic changes, cerebral edema in children and adolescents with DKA is subdivided into vasogenic and cytotoxic. Gaining a better understanding of the pathophysiological mechanisms of this complication will increase the quality of care provided in pediatric practice.

Diabetic ketoacidosis is a frequent complication of type 1 diabetes mellitus in children and adolescents. One of the leading causes of death in this pathology is cerebral edema. This complication is often asymptomatic, which makes it difficult to diagnose. The main risk factors for cerebral edema in children include the true factors (low partial pressure of carbon dioxide, high blood urea nitrogen, concomitant psychiatric pathology, etc.) and iatrogenic factors (large volume of infusion therapy, rapid decrease in blood glucose levels, administration of bicarbonate, etc.). The pathophysiology of this complication is not yet fully understood. The main pathophysiological elements of cerebral edema in children with DKA include the disruption of blood-brain barrier permeability, edema of brain cells, and dysfunction of cell membranes. Important roles are also played by hypercapnia and reduction of osmotic pressure. Based on the character of pathophysiologic changes, cerebral edema in children and adolescents with DKA is subdivided into vasogenic and cytotoxic. Gaining a better understanding of the pathophysiological mechanisms of this complication will increase the quality of care provided in pediatric practice.

Alterations of intracranial vessel tone have been implicated in the pathophysiology of migraine. The cerebrovascular reactivity was measured by means of transcranial Doppler in 60 migraine patients with ( n = 30) or without aura ( n = 30) during the headache-free interval and in 30 healthy controls. The vasomotor response was evaluated during hypercapnia induced by inhalation of a mixture of CO2 5% and O2 95% and during hypocapnia obtained after voluntary hyperventilation. To improve the power of the study in detecting possible abnormalities of cerebrovascular reactivity, two different measures were performed at 1 week intervals in migraine patients and controls. Reactivity index values during CO2 inhalation were significantly different ( p=0.01) among the three groups during the first and second measurements; in particular, lower values were found in patients suffering from migraine without aura with respect to controls ( p<0.05, Scheffe's test). Values of reactivity index obtained following induction of hypocapnia did not differ between migraine patients and controls (all p values >0.05). Our data suggest a reduced vasodilatory response to hypercapnia of cerebral arterioles in patients suffering from migraine without aura with respect to controls that might be related to baseline arteriolar vasodilation.

Obstructive sleep apnea (OSA) is a common disorder of upper airway obstruction during sleep. The effects of intermittent upper airway obstruction include alveolar hypoventilation, altered arterial blood gases and acid-base status, and stimulation of the arterial chemoreceptors, which leads to frequent arousals. These arousals disturb sleep architecture and cause hypersomnolence. Chronic intermittent alveolar and systemic arterial hypoxia-hypercapnia can cause pulmonary and systemic hypertension, with effects on the right and left ventricles, and even the renal system. The pathophysiology of OSA can therefore be used to review and integrate many topics in pulmonary and cardiovascular physiology in the context of problem-based learning, a guided discussion, or a formal lecture. The discussion begins with a case scenario, followed by a definition of the disorder, the common symptoms and signs of OSA, and a description of an apneic event. These are related to the physiology of the upper airway in OSA, normal alterations in the respiratory system during sleep, the effects of apnea on gas exchange and arterial blood gases, and the cardiovascular consequences of alterations in alveolar and systemic arterial Po2 and Pco2. The treatment of OSA, particularly how the use of continuous positive airway pressure relates to the pathophysiology of the disorder, is discussed briefly.

Acute respiratory distress syndrome (ARDS) remains an important clinical challenge with a mortality rate of 35–45%. It is being increasingly demonstrated that the improvement of outcomes requires a tailored, individualized approach to therapy, guided by a detailed understanding of each patient’s pathophysiology. In patients with ARDS, disturbances in the physiological matching of alveolar ventilation (V) and pulmonary perfusion (Q) (V/Q mismatch) are a hallmark derangement. The perfusion of collapsed or consolidated lung units gives rise to intrapulmonary shunting and arterial hypoxemia, whereas the ventilation of non-perfused lung zones increases physiological dead-space, which potentially necessitates increased ventilation to avoid hypercapnia. Beyond its impact on gas exchange, V/Q mismatch is a predictor of adverse outcomes in patients with ARDS; more recently, its role in ventilation-induced lung injury and worsening lung edema has been described. Innovations in bedside imaging technologies such as electrical impedance tomography readily allow clinicians to determine the regional distributions of V and Q, as well as the adequacy of their matching, providing new insights into the phenotyping, prognostication, and clinical management of patients with ARDS. The purpose of this review is to discuss the pathophysiology, identification, consequences, and treatment of V/Q mismatch in the setting of ARDS, employing experimental data from clinical and preclinical studies as support.

Abstract Introduction Seizure-related respiratory dysfunction has been reported in patients with epilepsy(PWE) on scalp EEG. We assessed this in Stereo-EEG(SEEG) recordings in patients with pharmacoresistant focal epilepsy. Methods PWE undergoing SEEG wore temperature/pressure-based airflow,RIP belts, SpO2, and EtCO2/TcpCO2. Interpretable recordings required SpO2 and at least one airflow and effort channel. Respiratory events including apneas, hypopneas(3%) and central pauses (5 to&lt;10sec). Respiratory events, respiratory rate(RR), SpO2 nadir, total desaturation time, Peak EtCO2/TcpCO2, and hypercapnia duration were analyzed surrounding seizures. Frequency and duration of central events were compared in sleep-onset and awake seizures. Linear mixed-effects models evaluated relationships between respiratory variables and the frequency and duration of central events associated with seizures and compared respiratory variables between seizures with and without events. Results 44 seizures were recorded in 23 patients. Seizures were focal-onset in 79.5%(n=35), GTC in 20.5%(9). Respiratory events accompanied 61.4%(27) of the seizures with median duration/seizure duration of 0.40(IQR: 0.27, 0.61). Of the 47 respiratory events, 42 were central events, and 66.6%(28) were central apneas. Respiratory events occurred during the seizure in 73.8%, postictal in 26.2%; median SpO2 nadir was 90%(77.0, 93.0), total desaturation duration 104.3(50.3, 195.0)sec, peak TcpCO2 41.3(38.7, 44.8) mmHg, hypercapnia duration 157.6(51.0, 367.9) sec, and ictal-postictal RR change 3.3 ± 4.0bpm. For every 1 sec duration increase in central event duration, there was a significant increase in peak TcpCO2 0.35(95%CI [0.09,0.62],p=0.015) and TcpCO2 change 0.25(95%CI [0.02,0.49],p=0.037). Presence of central events were associated with increased peak TcpCO2(9.82[3.77,15.9], p=0.006). Seizures with central events trended greater changes in RR, SpO2, and EtCO2/TcpCO2, desaturation and hypercapnia time, with negative changes in SpO2 nadir. No significant difference on central event frequency was found between sleep-onset and awake seizures. Conclusion Central events including apneas and pauses are common in focal seizures arising from sleep and wake and are associated with hypercapnia. In addition to the significant association between TcpCO2 and the frequency and duration of central events, there is a positive trend of association of other respiratory dysfunction parameters. These findings suggest that central events may lead to a cascade of respiratory disturbance that may participate in the pathophysiology of sudden unexplained death in epilepsy. Support (if any):

Clinical studies have demonstrated an arousal deficit in infants suffering Obstructive Sleep Apnoea (OSA), and that treatment to alleviate the symptoms of OSA appears to reverse the deficit in arousability. Some sudden infant deaths are thought to be contingent upon such an arousal deficit. This research utilised young piglets during early postnatal development, and exposed them to intermittent hypercapnic hypoxia (IHH) as a model of clinical respiratory diseases. Arousal responses of control animals were compared to the animals exposed to IHH. Comparisons were also made between successive exposures on the first and the fourth consecutive days of IHH. Time to arouse after the onset of the respiratory stimulus, and frequency of arousals during recovery, demonstrated that arousal deficits arose after successive exposures and that these were further exacerbated on the fourth study day. After an overnight recovery period, the arousal deficit was apparently dormant, and only triggered by HH exposure. These studies confirm that both acute and chronic deficits can be induced on a background of otherwise normal postnatal development, suggesting that deficits observed in the clinical setting may be a secondary phenomenon.

Master of Science (Medicine)
Clinical studies have demonstrated an arousal deficit in infants suffering Obstructive Sleep Apnoea (OSA), and that treatment to alleviate the symptoms of OSA appears to reverse the deficit in arousability. Some sudden infant deaths are thought to be contingent upon such an arousal deficit. This research utilised young piglets during early postnatal development, and exposed them to intermittent hypercapnic hypoxia (IHH) as a model of clinical respiratory diseases. Arousal responses of control animals were compared to the animals exposed to IHH. Comparisons were also made between successive exposures on the first and the fourth consecutive days of IHH. Time to arouse after the onset of the respiratory stimulus, and frequency of arousals during recovery, demonstrated that arousal deficits arose after successive exposures and that these were further exacerbated on the fourth study day. After an overnight recovery period, the arousal deficit was apparently dormant, and only triggered by HH exposure. These studies confirm that both acute and chronic deficits can be induced on a background of otherwise normal postnatal development, suggesting that deficits observed in the clinical setting may be a secondary phenomenon.

Intermittent hypoxia (IH) and unstable breathing are key features of obstructive sleep apnoea (OSA), the most common respiratory sleep disorder. Unstable ventilatory control is characterised by high loop gain (LG), and likely contributes to the propagation of apnoeas by promoting airway collapse during periods of low ventilatory drive. Currently, the contribution of inherent versus induced traits causing high LG in OSA remains unclear. OSA patients exhibit abnormal chemoreflex control which contributes to increased LG. These abnormalities normalise with continuous positive airway pressure (CPAP) treatment, suggesting induced rather than inherent trait abnormalities. Experimental IH, mimicking OSA, increases hypoxic chemosensitivity and induces long-term facilitation; a sustained increase in ventilatory neural output which outlasts the original stimulus. These neuroplastic changes induce the same abnormalities in chemoreflex control as seen in OSA patients, suggesting that high LG in OSA is largely induced by IH, and is reversible. IH protocols are typically conducted on a background of poikilocapnia or isocapnia, in contrast to combined hypoxia and hypercapnia experienced in OSA. The level of concomitant CO₂ is thought to be critical for both the induction and expression of IH induced neuroplasticity. To more accurately mimic OSA, the effects of intermittent hypercapnic hypoxia (IHH) on ventilatory neuroplasticity and LG were investigated in the first two experiments contained within this thesis. The effect of CPAP treatment on LG in untreated OSA patients was investigated in the third and final study of this thesis. In the first study, whether IHH during sleep induces LTF or increases chemosensitivity in healthy males was investigated. A randomised, separate day of intermittent medical air served as control. Unlike previous reports using isocapnic IH during sleep in healthy males, IHH did not induce LTF of ventilation or genioglossal muscle activity. Also, there was no change in the magnitude or slope of the ventilatory response to IHH from the first exposure to the last, to indicate any change in chemosensitivity. These findings suggest the effects of IHH differ to those of IH during sleep in healthy males. During wakefulness LTF in humans is only expressed during mild hypercapnia. In the second study, the effect of IHH on LG was investigated in healthy males during wakefulness using a CO₂ pseudorandom binary stimulation technique to measure LG on a background of mild hypercapnia. There was no change in chemosensitivity during IHH or ventilatory LTF following IHH. There was no change in LG and although there was a trend towards a change in the ventilatory impulse response to a sudden change in CO₂ following IHH, this was not statistically significant. These findings further support that the effects of IHH during wakefulness differ to those of IH in healthy males. In the third study, the effect of 6 weeks CPAP treatment on LG in previously untreated OSA males was investigated. Participants matched for age, sex, height, weight and BMI were also studied as controls. Helium dilution was used to assess supine functional residual capacity (FRC) and LG was compared prior to commencing CPAP treatment and at 2 and 6 weeks after starting treatment, and at the same time points but without CPAP treatment in controls. LG was higher in the OSA patients versus matched controls, but there was no effect of CPAP treatment on LG. There was also no difference between patients and controls in FRC or controller or plant gain components of LG, although given that LG is the product of controller and plant gains, this could reflect a type II error. Patients exhibited reduced FEV1 and FVC and also higher supine abdominal height which positively correlated with AHI. Thus, this study confirmed that LG is higher in OSA patients versus matched controls, and supported previous work suggesting that central adiposity contributes to upper airway collapse. However, given no effect of CPAP on LG, larger cohorts and potentially alternative measures may be required to determine mechanisms driving elevated LG in OSA patients. Although IH has previously been shown to induce neuroplastic changes to chemoreflex control that mirror abnormalities associated with high LG in OSA patients, the findings in this thesis suggest the effects of acute IHH differ to those of IH, both during sleep and wakefulness in healthy males. Potential causes for this disparity, and relevance of experimental findings to OSA pathophysiology are discussed. The effects of CPAP treatment on LG and implications for treatment options and CPAP adherence outcomes are also discussed.
Thesis (Ph.D.) (Research by Publication) -- University of Adelaide, School of Medicine, 2015.

Metabolic alkalosis occurs in up 51% of abnormal acid-base samples in the hospital. It is characterized by a primary increase in bicarbonate concentration and is always associated with chloride depletion. In critically-ill patients, it is most often generated by diuretic administration, digestive losses, alkali administration, or rapid correction of hypercapnia. Even after all causal factor are removed, it can be maintained by blood volume depletion and potassium depletion. Metabolic alkalosis results in hypercapnia, hypoxaemia, cardiac arrhythmias, altered consciousness, and neuromuscular hyperexcitability. It is first treated by removing the causal factors, whenever possible. Maintaining factors must be reversed by sodium chloride and/or potassium chloride administration. Acetazolamide and renal replacement therapy, when given for specific indications, can also correct the alkalosis. Lysine and arginine chloride are no longer used. If metabolic alkalosis is severe or when other treatments are contraindicated or ineffective, hydrochloric acid infusion is useful. Dilute hydrochloric acid can be infused safely, provided adequate precautions are taken to prevent extravascular leakage, vessel damage, and tissue necrosis.

Respiratory failure occurs when a disease process significantly interferes with the respiratory system’s vital functions and causes arterial hypoxemia, hypercapnia, or both. Typically, respiratory failure is divided into three categories based on the underlying pathophysiology: ventilation failure, oxygenation failure, and oxygenation-ventilation failure. With severe disturbances in gas exchange, mechanical ventilation is often needed to assist the respiratory system and restore the PaCO2, PaO2, or both, to normal. Respiratory Failure and the Indications for Mechanical Ventilation defines and describes the three types of respiratory failure and reviews the four indications for intubation and mechanical ventilation—acute or acute-on-chronic hypercapnia, refractory hypoxemia, inability to protect the lower airway, and upper airway obstruction.

Sleep-disordered breathing in the obese is not a small problem. Obesity-related sleep-disordered breathing is common and may include sleep apnoea or obesity hypoventilation syndrome. Patients present with symptoms of excessive daytime sleepiness, breathlessness, and, in severe cases, hypercapnic respiratory failure. In recent decades, the prevalence of obesity has increased exponentially. Although not exclusively responsible, obesity is directly linked to the development of sleep-disordered breathing due to high resistance in the upper airway, increased work of breathing, and high neural respiratory drive. Obese patients with sleep disorders are complicated with multiple metabolic, cardiovascular, and orthopaedic co-morbidities, frequently presenting at an advanced stage. This chapter reviews a common clinical presentation of an obese patient with a respiratory condition and the difficulties in their management. The chapter explains the complex underlying pathophysiology and the long-term management of these patients, and shows how sleep-disordered breathing may develop as a consequence of obesity.

An arterial blood gas (ABG) provides clinically useful information about an individual's acid–base status, the partial pressure of arterial carbon dioxide, the partial pressure of arterial oxygen, and the arterial oxygen saturation. Hypoxia, dyspnea, or suspected acid–base disturbance are clear indications to check an ABG. Altered mental status, critical illness, and acute respiratory distress syndrome (ARDS) are specific clinical syndromes or presentations that warrant checking an ABG. An ABG is helpful in evaluating pulmonary pathophysiology as the presence and severity of hypoxia and/or hypercapnia can be quantified. Because an ABG can rapidly provide information about oxygenation, ventilation, and acid–base status, ABGs are particularly useful and common in the critical care setting.

Acute respiratory distress syndrome (ARDS) is an important condition associated with significant morbidity and mortality in both adults and children. Chapter 6 begins by explaining the definition of paediatric ARDS (PARDS), its severity stratification, risk factors for its development, and its pathophysiology. The evidence base for lung-protective ventilation strategies is covered, with recommended goals given permissive hypoxaemia and hypercapnia. Different modes of ventilation for ARDS are examined: non-invasive ventilation, conventional mechanical ventilation, high-frequency oscillatory ventilation, and neutrally-adjusted ventilator assist, and the relative merits of pressure and volume limitation for lung protection in adults and children. Adjuvant therapies for PARDS are explored: fluid restriction; neuromuscular blocking agents; prone positioning; steroids; inhaled nitric oxide; and surfactant therapy. The chapter concludes by addressing the challenges that remain in defining and managing ARDS, and suggests how patients should be followed up following discharge.

Given the increased risk prevalence of coronary artery disease, inflammatory disease, and cancer, morbidly obese patients are frequently scheduled for various types of surgery. In addition, the number of bariatric surgeries has risen almost exponentially. Therefore, the anaesthesiologist is more frequently challenged with providing general anaesthesia for this patient population. General anaesthesia comes with increased risks of events such as perioperative morbid cardiac events and postoperative respiratory failure. Postoperative respiratory failure is particularly common after cardiac, thoracic, and major abdominal surgery. Anaesthesiologists have a range of support mechanisms at their disposal to reduce postoperative respiratory failure including emergent reintubation. Apart from simple oxygen delivery via nasal cannulas or face masks, Venturi masks, and Mapleson circuits, there are various positive pressure systems available. These systems are commonly referred to as non-invasive ventilation (NIV) systems. NIV can be non-invasive continuous positive airway pressure or non-invasive intermittent positive pressure ventilation. Both types of NIV have been shown to improve oxygenation and hypercapnia in morbidly obese patients in the perioperative environment. This chapter presents the physiology and pathophysiology of the respiratory system in the morbidly obese patient. In addition, it illustrates the impact and implications of NIV systems on this patient population in the perioperative setting.