Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In chronic obstructive pulmonary disease (COPD), the neuromuscular response to an acute increase in airflow produced by external flow resistive loads (FRL) is impaired. The present study compared the response to FRL of 15 subjects with airway obstruction due to asthma and that of 15 normal subjects. FRL were applied during progressive hypercapnia and isocapnic hypoxia produced by rebreathing techniques to permit the response to be assessed at the same degree of CO2 or O2 drive. The neuromuscular response to FRL was assessed from the airway occlusion pressure developed 100 msec after the onset of inspiration (P100), as well as ventilation. During control rebreathing, ventilatory responses to hypercapnia (ratio of change in minute ventilation to change in PCO2, delta VE/delta PCO2) and hypoxia (ratio of change in VE to the change in percentage of O2 saturation, delta VE/deltaSO2) were the same in asthmatic and normal subjects despite differences in the mechanics of breathing. The P100 response to hypercapnia delta P100/delta PCO2) and hypoxia (delta P100/delta SO2) as well as absolute P100 at any given degree of O2 and CO2 drive was greater during control rebreathing in asthmatics than in normal subjects (P less than 0.05). FRL values of 9 and 18 cm H2O per L per sec applied during either hypercapnia or hypoxia increased the occlusion pressure to a greater extent in asthmatics than in normal subjects. Methacholine-induced bronchoconstriction was used to test the effect of acute airway obstruction on the response to FRL. Bronchoconstriction was associated with an increase in the P100 response to hypercapnia and to FRL, despite increases in lung volume and decreases in inspiratory muscle force. We conclude that: (1) asthmatics with airway dysfunction have an increased nonchemical drive to breathe mediated at least in part by sensory receptors in the airways; (2) asthmatics with airway obstruction respond supernormally to acute changes in resistance to airflow, unlike subjects with COPD. The failure of COPD subjects with prolonged airway obstruction to respond to FRL may be due to adaptation of the sensory mechanisms that respond to changes in airway resistance.
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PMID:The respiratory neuromuscular response to hypoxia, hypercapnia, and obstruction to airflow in asthma. 48 28

This analysis of asthma mortality has emphasized the roles played in its pathogenesis by different modes of therapy as reported in the literature. In addition attention was directed towards yet another potentially lethal therapeutic modality, IPPB, the efficacy and potential benefits of which are critically questioned. IPPB treatments were related to every fatal episode of asthma which made up the entire asthma mortality experience during a 12 month period at Morrisania Hospital. The adverse consequences of IPPB therapy were reviewed and it was further suggested that its use in acute asthma attacks was related to lethal episodes of hypoxia and pneumothorax. The patient must, in order to trigger an IPPB apparatus, create a pre-determined negative pressure to initiate inflation. The machine may, therefore, be ineffective in a patient with severe obstruction and greatly increased airway resistance either because of the inability to trigger it or with adequate triggering the subsequent delivery of an inadequate tidal volume at the pressure limitation set. Thus, severe hypercapnia and hypoxia may result especially if oxygen enriched gas mixtures are not used. This may occur even with the delivery of an adequate tidal volume since its distribution within the lungs is poor resulting in a worsening of ventilation-perfusion relationships as evidenced by an increase in the measured physiologic dead space. This experience and review of the literature suggests that IPPB treatment in asthma, especially during an acute attack, should always be administered with small doses of nebulized bronchodilators and oxygen with careful monitoring of arterial blood gases. This will allow for the detection of the adverse effects of this mode of therapy which may exceed the hoped for benefits, the most important being bronchodilatation and subsequent mobilization of secretions with continued treatment.
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PMID:Asthma mortality: an analysis of one years experience, review of the literature and assessment of current modes of therapy. 110 38

Because of the previous finding of an attenuated hypoxic ventilatory drive in a teenager with severe asthma, the ventilatory responses to hypoxia and hypercapnia were examined during remission in 16 patients with the history of severe asthma. Spirometric and body plethysmographic pulmonary functions were normal or nearly normal just prior to ventilatory drive testing. The ventilatory responses to progressive isocapnic hypoxia and to hyperoxic hypercapnia were studied. Both hypoxic and hypercapnic drives were significantly depressed in the asthmatic patients. Factors known to blunt the ventilatory drives were not present in this group of patients. Hence, the etiology of these changes is unclear. In some patients, these depressed respiratory drives might contribute to hypoventilation, to severe hypoxemia, and to respiratory failure during severe asthma.
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PMID:Depression of hypoxic and hypercapnic ventilatory drives in severe asthma. 117 5

Intravenous infusion of salbutamol 10 mug/min in seven healthy subjects significantly increased their ventilatory responses to inhaled CO2 in both hypoxia and hyperoxia. These changes in chemical control of breathing are unlikely to be significant when the drug is used in severe asthma but may benefit patients with acute exacerbations of chronic ventilatory failure. The infusion also increased heart rate, which was most pronounced when hypoxia was combined with hypercapnia. The infusion produced an average fall in plasma potassium from 3-99 to 3-10 mmol/l, which was associated with an increase in plasma glucose and serum insulin, suggesting that this arose from a shift of potassium from the extracellular to the intracellular space. Routine monitoring of plasma potassium and the electrocardiogram is indicated when an intravenous salbutamol infusion is used to treat severe asthma as the drug may predispose to cardiac dysrhythmias.
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PMID:Effect of intravenous infusion of salbutamol on ventilatory response to carbon dioxide and hypoxia and on heart rate and plasma potassium in normal men. 124 57

Charts of all children with severe acute asthma admitted to the Pediatric Intensive Care unit (PICU) of this hospital between January 1987 and December 1990 were reviewed retrospectively. There were 47 admissions for life threatening asthma to the PICU over this period, representing about 2% of all acute asthma admissions to our hospital. The mean duration of symptoms in these patients before admission was 54 hours. Only 55% of the PICU admissions had received bronchodilators before coming to our hospital emergency room from where they were admitted. From arterial blood gas analysis, 57% of the patients had hypercapnia (PaCO2 > 45 mmHg). All the patients received nebulized salbutamol frequently as well as intravenous aminophylline and hydrocortisone. Mechanical ventilation was used in only 8.5% of the patients. Only two patients developed pneumothorax, neither of whom had been mechanically ventilated, but they did not require surgical intervention for drainage. There was only one death in a patient who was known to have sickle cell anemia and developed sagittal sinus thrombosis. We conclude from our series that the mortality for children with life threatening asthma admitted to PICU is very low if bronchodilators and steroids are used optimally in their management, along with judicious selection of those requiring mechanical ventilation.
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PMID:Four-year experience with bronchial asthma in a pediatric intensive care unit. 147 85

We performed inhalation anesthetic therapy in an attempt to produce improvement in cause of life-threatening asthma, which were standard pharmacological therapy. We analysed the results obtained in 6 cases given inhalation anesthetic therapy (4 cases were treated with halothane and 2 cases with enflurane). The following observations were made: 1) The criteria for starting inhalation anesthetic therapy were persistent hypoxycemia or hypercapnia, persistently high inspiratory intra-airway pressure, clinical exhaustion and bronchial toilet with bronchofiberscope. 2) We treated the patients with halothane concentrations of between 1.0 and 2.0% and enflurane concentrations of between 1.0 to 4.2%. 3) No major complications were observed in inhalation anesthetic therapy.
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PMID:[Halothane or enflurane treatment in life-threatening asthma]. 179 65

Bronchial lavage was performed in 10 cases with status asthmaticus who were mechanically ventilated. The mean value of PaCO2 was 64.4 +/- 17.4 Torr before bronchial lavage, and it significantly decreased to 51.9 +/- 11.0 Torr after lavage. In 7 out the 10 cases, bronchial lavage was judged to be effective from the clinical point of view. In 5 cases with values of PaCO2 of over 55 Torr before lavage, massive mucus plugs were recovered. Bronchial lavage was judged to be effective in all of them, whereas three out of the another five cases whose values of PaCO2 were less than 55 Torr showed exacerbation of hypercapnia, and the state of asthma worsened and/or continued for a longer period. The ratio of PaO2/FiO2 did not improve even in effective cases. These results indicated that bronchial lavage is a useful tool to improve the hypercapnic state in patient with status asthmaticus being mechanically ventilated, if the value of PaCO2 is over 55 Torr.
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PMID:[Bronchial lavage in the treatment of status asthmaticus]. 192 Sep 75

This study examined the relationships between acid-base disorders, hypoxemia, electrolyte imbalances, plasma adrenaline (Ad) and noradrenaline (NAd) in 94 patients with acute severe asthma. Criteria of inclusion were [PaO2 + PaCO2/.8] less than 140 mmHg when breathing air (FiO2 = 21%) and/or PaCO2 greater than or equal to 45 mmHg. PaCO2 was closely related to H+ in those patients with hypercapnia: H+ nmol/l = 0.88 PaCO2 + 4 (r 0.91 ; n = 61; p less than 0.001). However, among the 62 acidotic cases (pH less than or equal to 7.36), 24 were classified as respiratory, 22 as mixed and 16 as metabolic. A loose though highly significant relationship was found between PaO2 and PaCO2 (when breathing air). Blood lactate, which was 3.61 +/- 1.9 mmol/l (+/- SD), was not correlated with anion gap or H+, but was loosely related to PaO2 and kalemia. Ad (1.53 +/- 1.17 nmol/l) and NAd (5.85 +/- 3.44 nmol/l), measured at the time of admission in 27 patients (FIO2 = 21%), varied significantly from those of a control group (p less than 0.01). NAd was correlated with H+, lactate and especially PaCO2, whereas no correlation could be established for Ad with these factors or NAd values. On the average, kalemia, phosphatemia and calcemia were lowered. In conclusion, mixed and metabolic acidosis were more common in this study than in a previous personal series and were not necessarily associated with an increase in blood lactate. Drugs taken prior to hospitalization must be considered in the pathophysiology of hyperlactatemia, which appears to be one among several factors linked to NAd levels.
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PMID:[Current humoral profile in acute severe asthma]. 209 10

The first part of this review deals with the basic mechanisms and factors determining hypoxaemia and hypercapnia and the different approaches used in clinical practice and in clinical research to assess the presence of ventilation-perfusion mismatching, shunt and diffusion limitation for oxygen, and more specifically the multiple inert gas elimination technique (MIGET), in pulmonary medicine. The second part reviews three different respiratory disorders where the complex interplay between intrapulmonary and extrapulmonary factors regulating oxygen are essentially interpreted through the results afforded by the MIGET over the last decade. The gas exchange response to bronchodilators in bronchial asthma, an airway disease, and then the major determinants governing abnormal gas exchange in acute pulmonary embolism, a pulmonary vascular disorder, and during haemodialysis, a respiratory entity of extrapulmonary origin, are successively explored in the light of the inert gas method.
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PMID:Clinical relevance of ventilation-perfusion inequality determined by inert gas elimination. 216 80

Respiratory disorders induce several pathophysiological changes involving gas exchange and acid-base balance, regional haemodynamics, and alterations of the alveolocapillary membrane. The consequences for the absorption, distribution and elimination of drugs are evaluated. Drug absorption after inhalation is not significantly impaired in patients. With drugs administered by this route, an average of 10% of the dose reaches the lungs. It is not completely clear whether changes in pulmonary endothelium in respiratory failure enhance lung absorption. The effects of changes in blood pH on plasma protein binding and volume of distribution are discussed, but relevant data are not available to explain the distribution changes observed in acutely ill patients. Lung diffusion of some antimicrobial agents is enhanced in patients with pulmonary infections. Decreased cardiac output and hepatic blood flow in patients under mechanical ventilation cause an increase in the plasma concentration of drugs with a high hepatic extraction ratio, such as lidocaine (lignocaine). On a theoretical basis, hypoxia should lead to decreased biotransformation of drugs with a low hepatic extraction ratio, but in vivo data with phenazone (antipyrine) or theophylline are conflicting. The effects of disease on the lung clearance of drugs are discussed but clinically relevant data are lacking. The pharmacokinetics of drugs in patients with asthma or chronic obstructive pulmonary disease are reviewed. Stable asthma and chronic obstructive pulmonary disease do not appear to affect the disposition of theophylline or beta 2-agonists such as salbutamol (albuterol) or terbutaline. Important variations in theophylline pharmacokinetics have been reported in critically ill patients, the causes of which are more likely to be linked to the poor condition of the patients than to a direct effect of hypoxia or hypercapnia. Little is known regarding the pharmacokinetics of cromoglycate, ipratropium, corticoids or antimicrobial agents in pulmonary disease. In patients under mechanical ventilation, the half-life of midazolam, a new benzodiazepine used as a sedative, has been found to be lengthened but the underlying mechanism is not well understood. Pulmonary absorption of pentamidine was found to be increased in patients under mechanical ventilation. Pharmacokinetic impairment does occur in patients with severe pulmonary disease but more work is needed to understand the exact mechanisms and to propose proper dosage regimens.
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PMID:The effect of respiratory disorders on clinical pharmacokinetic variables. 229 69


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