Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Theophylline is a bronchodilator used extensively in the management of obstructive pulmonary disease. Factors implicated in altered theophylline clearance include smoking, age, concomitant drug intake, liver disease and left ventricular heart failure. However, evidence now suggests that theophylline clearance may be altered by changes in severity of the pulmonary obstruction, hypoxia and variation in arterial pH. The in vitro disposition of theophylline has been evaluated in isolated rat livers and mouse hepatocytes. In vivo studies have assessed the metabolism of theophylline under hypoxia in rats, rabbits and dogs. In isolated mouse hepatocytes and rat livers, low oxygen concentrations resulted in higher theophylline concentrations, a longer elimination half-life and a decrease in the production of the metabolite 1,3-dimethyl uric acid, suggesting impaired metabolism of theophylline. In rabbits, hypoxia, hypercapnia and respiratory acidosis decreased total body clearance and increased plasma theophylline concentrations. On the other hand, experiments involving dogs showed no significant changes in theophylline concentrations or pharmacokinetic parameters with hypoxia. At present, animal studies remain inconclusive. This can be attributed to the use of different animal models and variations in study methodology, including the extent and duration of hypoxia and acidaemia, concurrent acid-base disorders such as hypercapnia, as well as the severity of pulmonary obstruction. Human studies assessing alterations in theophylline disposition secondary to the hypoxia present in pulmonary disease are few and include mostly case reports and observational studies. There is evidence suggesting decreased theophylline clearance and protein binding during acute illness and some consensus can be achieved using case reports and controlled studies. There is additional evidence that drug clearance decreases with age and that elderly patients may have a decreased theophylline clearance at baseline. However, the most obvious markers appear to be the severity of pulmonary disease and the rate of change in the patient's condition. Caution should be exercised when administering theophylline to elderly patients with chronic obstructive pulmonary disease presenting with acute exacerbations of a concomitant respiratory illness, as these patients appear to be most likely to exhibit altered theophylline metabolism. Therefore, they would be at increased risk for toxicity should conventional dosages be used during an acute respiratory event.
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PMID:Hypoxia, arterial pH and theophylline disposition. 826 13

Conventional pharmacotherapy of severe asthma and status asthmaticus includes beta2-sympathomimetics, theophylline, corticosteroids and occasionally topical anticholinergics (ipratropium bromide). Since hypoxemia is the most severe phenomenon in status asthmaticus the administration of oxygen is mandatory. However, if the bronchodilating therapy fails and hypoxemia continues, usually respiratory failure develops due to progressive respiratory muscle failure. An increasing PaCO(2) and respiratory acidosis are indications for mechanical ventilatory support to unload the failing respiratory pump. Nowadays, there is increasing consensus that ventilatory support should be administered primarily as non-invasive ventilation (NIV) via a face mask1. However, in a significant number of patients with severe asthma NIV is either contraindicated or insufficient. In this case usually the patient must be endotracheally intubated and mechanically ventilated "invasively". Intubation and ventilation of patients with severe asthma or status asthmaticus is associated with a high incidence of complications compared to patients ventilated for other causes of respiratory failure2,3. Therefore the risks of invasive mechanical ventilation have to be weighted carefully to ongoing conservative therapy and NIV. Cardiopulmonary arrest and severe hypoxemia in spite of O2 supplement and NIV are absolute criteria for intubation and ventilation. Mostly deterioration in mental status and exhaustion are the clinical findings leading to mechanical ventilation. Decision is guided rather by the course of the deterioration (how fast the patient's condition is worsening) than by pathological values alone. An increased PaCO(2) with moderate respiratory acidosis alone is not per se an indication for mechanical ventilation. However, a continuously rising PaCO(2) or the development of a severe metabolic acidosis after 1 hour of NIV is a strong argument for invasive mechanical ventilation. Other criteria are evidence of cardiac failure with fall in pulse volume and dysrhythmias, pneumomediastinum or pneumothorax (which has to be drained before mechanical ventilation!).
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PMID:Ventilating the patient with severe asthma: nonconventional therapy. 1276 62

The cardiovascular and respiratory systems act as a functional unit. Mechanical ventilation modifies pulmonary volumes, which generates changes in autonomic nervous system reactivity and provokes tachy- or brady-cardia (depending on the tidal volume used). Mechanical ventilation also decreases cardiac filling volumes (pre-load) and alters pulmonary vascular resistances. In addition, intrathoracic pressures are enlarged, which usually produces a decrease in right atrium filling and an increase in right ventricle afterload. If coronary flow is impaired, myocardial contractility is reduced. However, if cardiac failure is present, mechanical ventilation is especially beneficial because it corrects hypoxia and respiratory acidosis, decreases the work of breathing, and improves stroke volume. Mechanical ventilation in congenital heart diseases is indicated either as lifesaving support or as physiopathological treatment to modify the ratio between pulmonary and systemic flow. As a general rule, if excessive pulmonary blood flow is present, the aim of respiratory support is to increase pulmonary vascular resistance by using high levels of airway pressure and even by delivering FiO2<21%. When there is low pulmonary flow, the lowest possible intrathoracic pressures should be used, especially in cases of pulmonary hypertension, which will also require high FiO2. However, mechanical ventilation has adverse effects and consequently it must be stopped as early as possible, once the child is stable and requires minimal cardiopulmonary support. Weaning can even be performed in the operating room, when the surgical procedure is finished. When this is not possible, weaning should be performed in the pediatric intensive care unit. Because there are no criteria for successful withdrawal of mechanical support in congenital heart disease, general pediatric criteria should be used.
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PMID:[Ventilation in special situations. Mechanical ventilation in congenital cardiopathies and pulmonary hypertension]. 1464 24

Chronic heart failure (CHF) is a common condition and is associated with excess morbidity and mortality, in spite of the many advances in its treatment. Chronic stable heart failure is also associated with an increased incidence of sleep-related breathing disorders, such as central sleep apnoea (CSA) and Cheyne Stokes respiration (CSR). Continuous positive airways pressure (CPAP) has been shown to alleviate the symptoms of CHF, improve left ventricular function and oxygenation. To a certain extent, CPAP also abolishes sleep-related breathing disorders in patients with chronic heart failure. In patients with acute pulmonary oedema, the use of positive pressure ventilation improves cardiac haemodynamic indices, as well as symptoms and oxygenation, and is associated with a lower need for intubation. However, some studies have cast doubts about its safety and suggest a higher rate of myocardial infarction associated with its use. In our opinion, non-invasive positive pressure ventilation and CPAP offers an adjunctive mode of therapy in patients with acute pulmonary oedema and chronic heart failure, who may not be suitable for intubation and in those not responsive to conventional therapies. Non-invasive ventilation also helps to improve oxygenation in those patients with exhaustion and respiratory acidosis. Many trials are still ongoing and the results of these studies would throw more light on the present role of non-invasive ventilation in the management of CHF.
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PMID:Positive pressure ventilation in the management of acute and chronic cardiac failure: a systematic review and meta-analysis. 1638 32

In end-stage heart failure, various acid-base disorders can be discovered due to the renal loss of hydrogen ions and hydrogen ion movements into cells, the reduction of the effective circulating volume, hypoxemia and renal failure. This justifies the occurrence of metabolic alkalosis, metabolic acidosis, respiratory alkalosis, as well as respiratory acidosis alone or in combination. Several studies have been published on the acid-base state in heart failure. In a 1951 study, Squires et al analyzed the distribution of body fluid in congestive heart failure by taking into consideration the abnormalities in serum electrolyte concentration and in acid-base equilibrium. A recent study by Milionis et al, analyzed 86 patients with congestive heart failure receiving conventional treatment; the majority of these patients exhibited hypokalemia, hyponatremia, hypocalcemia and hypophosphatemia. Disorders in acid-base balance were noted in 37.2% of patients. In a recent study, 70 patients with severe congestive heart failure before heart transplantation showed high-normal pH, slightly reduced pCO 2 and a slight loss of hydrogen ions. After heart transplantation, stability of blood pH and hydrogen ion concentrations was found. In contrast, bicarbonate and pCO 2 increased significantly. The data led us to formulate the diagnosis of a mixed acid-base disorder that includes respiratory alkalosis and metabolic alkalosis before heart transplantation. In heart failure, the presence of acid-base imbalance associated with the activation of mechanisms that lead to salt and water retention reveals evidence concerning the pivotal role of the kidney in determining the outcome of these patients.
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PMID:Acid-base balance in heart failure. 1673 34

A 63-year-old woman with confusion and disorientation was referred to the Pulmonary Medicine Department of Afyon Kocatepe University. She was uncooperative and her peripheral oxygen saturation was 75%. She was on diuretic therapy for heart failure. An emergency intubation was planned due to the development of respiratory acidosis and hypoxemia, but the patient could not be intubated. After several attempts, intubation was successful only by digital manipulation of a lateral pharyngeal mass noticed incidentally. She was inadvertently extubated on the third day of intubation and an emergency tracheotomy was performed. Otolaryngological examination revealed a mass originating from the right palatine tonsil, and a computed tomography scan showed a hypodense mass extending from the uvula to the epiglottis. Under general anesthesia, the patient underwent a right tonsillectomy and a lipomatous mass (3.6x3.2x2.2 cm) and the palatine tonsil (3.5x1.1x0.8 cm) were resected. Microscopically, the tumor consisted of mature adipocytes with thin fibrous septae. It should be borne in mind that patients may be unaware of a tonsillar mass that may lead to serious dyspnea and difficult intubation.
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PMID:Tonsillar lipoma causing difficult intubation: a case report. 1818 98

The treatment of choice for patients with respiratory failure of neuromuscular origin, especially in patients with hypercapnic respiratory acidosis, is noninvasive ventilation (NIV). Endotracheal intubation and invasive ventilation are indicated for patients with severe respiratory compromise or failure of NIV. In recent years, high-flow oxygen therapy and active humidification devices have been introduced, and emerging evidence suggests that high-flow oxygen may be effective in various clinical settings, such as acute respiratory failure, after cardiac surgery, during sedation and analgesia, in acute heart failure, in hypoxemic respiratory distress, in do-not-intubate patients, in patients with chronic cough and copious secretions, pulmonary fibrosis, or cancer, in critical areas and the emergency department. We report on a patient with amyotrophic lateral sclerosis who arrived at the emergency department with acute hypercapnic respiratory failure. She did not tolerate NIV and refused intubation, but was treated successfully with heated, humidified oxygen via high-flow nasal cannula. Arterial blood analysis after an hour on high-flow nasal cannula showed improved pH, P(aCO2), and awareness. The respiratory acidosis was corrected, and she was discharged after 5 days of hospitalization. Her response to high-flow nasal cannula was similar to that expected with NIV. We discuss the mechanisms of action of heated, humidified high-flow oxygen therapy.
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PMID:Efficacy of high-flow oxygen by nasal cannula with active humidification in a patient with acute respiratory failure of neuromuscular origin. 2365 Apr 30


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