Hypercapnia

Katsura K, Rodriguez de Turco EB, Siesjo BK, Bazan NG. Effects of hyperglycemia and hypercapnia on lipid metabolism during complete brain ischemia. Brain Res 2004 1030 133-140. 

In advanced COPD, airflow obstruction, damaged bronchioles and alveoli, and pulmonary vascular abnormalities lead to impaired gas exchange. This results in hypoxemia and eventually hypercapnia. Hypoxemia is initially present only during exercise but occurs at rest as the disease progresses. Inequality in the ventilation/perfusion ratio (VAQ) is the major mechanism behind hypoxemia in COPD. 

The goal of oxygen therapy is to maintain Pao2 above 60 mm Hg (8 kPa) or Sao2 above 90% in order to prevent tissue hypoxia and preserve cellular oxygenation.1 Increasing the Pao2 much further confers little added benefit and may increase the risk of C02 retention, which may lead to respiratory acidosis. An arterial blood gas should be obtained after 1 to 2 hours to assess for hypercapnia. 

In advanced COPD, caution should be used since overly aggressive administration of oxygen to patients with chronic hypercapnia may result in respiratory depression and respiratory failure. In these patients, mild hypoxemia, rather than carbon dioxide accumulation, triggers their drive to breathe. 

Respiratory acidosis is characterized by a reduced arterial pH, a primary increase in the arterial PaC02 and, when present for sufficient time, a compensatory rise in the HCOf concentration. Because increased C02 is a potent respiratory stimulus, respiratory acidosis represents ventilatory failure or impaired central control of ventilation as opposed to an increase in C02 production. As such, most patients will have hypoxemia in addition to hypercapnia. The most common etiologies of respiratory acidosis are listed in Table 25-6. 

The goals of therapy in patients with chronic respiratory acidosis are to maintain oxygenation and to improve alveolar ventilation if possible. Because of the presence of renal compensation it is usually not necessary to treat the pH, even in patients with severe hypercapnia. Although the specific treatment varies with the underlying disease, excessive oxygen and sedatives should be avoided, as they can worsen C02 retention. 

Polak A, Haynie GD, Hays RM, Schwartz WB. Effects of chronic hypercapnia on electrolyte and acid-base equilibrium. J Clin Invest 1961 40 1223-1237. 

PN therapy is associated with significant complications, both with short- and long-term therapy. Many complications are related to overfeeding (Table 97—7). Metabolic complications include hyperglycemia, hypoglycemia, hyperlipidemia, hypercapnia, electrolyte disturbances, refeeding syndrome, and acid-base... 

Dextrose Hyperglycemia, hypertriglyceridemia, hepatic steatosis, hypercapnia hyperglycemia may cause fluid and electrolyte disturbances and increased infection risk... 

Total calories Hepatic steatosis, cholestasis, hypercapnia... 

Hypercapnia (abnormally high concentration of carbon dioxide in the blood) can develop as a result of overfeeding with both dextrose and total calories.1,37 Excess carbon dioxide production and retention can lead to acute respiratory acidosis. The excess carbon dioxide also will stimulate compensatory mechanisms, resulting in an increase in respiratory rate in order to eliminate the excess carbon dioxide via the lungs. This increase in respiratory workload can cause respiratory insufficiency that may require mechanical ventilation. Reducing total calorie and dextrose intake would result in resolution of hypercapnia if due to overfeeding. 

Hypercapnia Abnormally high concentration of carbon dioxide in the blood. 

Chemoreceptors. The peripheral chemoreceptors include the carotid bodies, located at the bifurcation of the common carotid arteries, and the aortic bodies, located in the aortic arch. These receptors are stimulated by a decrease in arterial oxygen (hypoxia), an increase in arterial carbon dioxide (hypercapnia),... 

Hepatic encephalopathy Hyperbilirubinemia Hypocalcemia Hypercalcemia Hyperparathyroidism Hypoparathyroidism Thiamine deficiency (Wernicke s) encephalopathy Diabetic ketoacidosis Nonketotic hyperosmolar coma Phosphate depletion Hypoglycemia Hypoxemia Hypercapnia... 

Patients with chronic pulmonary disorders may exhibit lethargy, confusion, memory loss and stupor. The combined insults of hypoxia and hypercapnia, which result in C02 retention, contribute to the encephalopathy but neurological symptoms correlate best with the degree of C02 retention. Acute moderate hypercapnia associated with 5-10% C02 in the expired air, leads to arousal and excitability whereas higher C02 concentrations, >35% in the expired air, are anesthetic. 

Although C02 is a normal metabolite, it is toxic at elevated levels. C02 exists in equilibrium with carbonic acid (H2C03) and with bicarbonate (HCO, ), a major H+ buffer. Renal conservation of HCO, is generally sufficient to buffer hypercapnia however, an added insult, such as... 

The combination of hypoxia and hypercapnia in pulmonary insufficiency results in cerebral vasodilation and increased CBF and may lead to increased intracranial pressure. Arteriovenous differences for oxygen across the brain generally decrease as a function of increased CBF, leaving CMR02 unchanged [6]. 

Neuromuscular symptoms include altered mental status, abnormal behavior, seizures, stupor, and coma. Hypercapnia can mimic a stroke or CNS tumor by producing headache, papilledema, focal paresis, and abnormal reflexes. CNS symptoms are caused by increased cerebral blood flow and are variable, depending in part on the acuity of onset. 

Significant changes in arterial blood gases are not usually present until the FEV is less than 1 L. At this stage, hypoxemia and hypercapnia may become chronic problems. Hypoxemia usually occurs initially with exercise but develops at rest as the disease progresses. 

Some patients lose the ability to increase the rate or depth or respiration in response to persistent hypoxemia. This decreased ventilatory drive may be due to abnormal peripheral or central respiratory receptor responses. This relative hypoventilation leads to hypercapnia in this situation the central respiratory response to a chronically increased PaC02 can be blunted. Because these changes in Pa02 and PaC02 are subtle and progress over many years, the pH is usually near normal because the kidneys compensate by retaining bicarbonate. 

The most common cause of acute respiratory failure in COPD is acute exacerbation of bronchitis with an increase in sputum volume and viscosity. This serves to worsen obstruction and further impair alveolar ventilation, resulting in worsening hypoxemia and hypercapnia. Additional causes are pneumonia, pulmonary embolism, left ventricular failure, pneumothorax, and CNS depressants. 

Four cynomolgus monkeys (gender not stated) were individually exposed via a face mask to a concentration at 60 ppm for 30 min (Purser 1984). Each animal was exposed on three occasions. The same animals were used for hypoxia and hypercapnia tests. HCN, supplied from a standard gas mixture, was diluted with air the concentration was... 

The hemolytic anemia caused in pregnant rabbits by diflunisal was severe enough to explain the concomitant axial skeletal malformations (Clark et ah, 1984). Acetazolamide-induced fetal malformations in mice are apparently related to maternal hypercapnia (Weaver and Scott, 1984a, b) and hypokalemia (Ellison and Maren, 1972). The increased resorption rate induced in rabbits by the antibiotic norfloxacin depends on exposure of the maternal gastrointestinal tract (Clark et ah,... 

Epidural/Intrathecal administration Limit epidural or intrathecal administration of preservative-free morphine and sufentanil to the lumbar area. Intrathecal use has been associated with a higher incidence of respiratory depression than epidural use. Asthma and other respiratory conditions The use of bisulfites is contraindicated in asthmatic patients. Bisulfites and morphine may potentiate each other, preventing use by causing severe adverse reactions. Use with extreme caution in patients having an acute asthmatic attack, bronchial asthma, chronic obstructive pulmonary disease or cor pulmonale, a substantially decreased respiratory reserve, and preexisting respiratory depression, hypoxia, or hypercapnia. Even usual therapeutic doses of narcotics may decrease respiratory drive while simultaneously increasing airway resistance to the point of apnea. Reserve use for those whose conditions require endotracheal intubation and respiratory support or control of ventilation. In these patients, consider alternative nonopioid analgesics, and employ only under careful medical supervision at the lowest effective dose. 

Acute abdominal conditions Narcotics may obscure diagnosis or clinical course. Do not give SR morphine to patients with Gl obstruction, particularly paralytic ileus, as there is a risk of the product remaining in the stomach for an extended period and the subsequent release of a bolus of morphine when normal gut motility is restored. Special risk patients Exercise caution in elderly and debilitated patients and in those suffering from conditions accompanied by hypoxia or hypercapnia when even moderate therapeutic doses may dangerously decrease pulmonary ventilation. Also exercise caution in patients sensitive to CNS depressants, including those with cardiovascular disease myxedema convulsive disorders increased ocular pressure acute alcoholism delirium tremens cerebral arteriosclerosis ulcerative... 

Hypercapnia (hypoventilation) develops more readily in young children than in adults and adolescents ... 

E. Reduced peripheral vascular resistance occurs with most halogenated hydrocarbons, and reflex tachycardia may be a concern. Halothane may be the clearest exception, since there appears to be a balance between relaxation and constrictor influences in various vascular beds with this agent so that total peripheral resistance changes very little. Halothane is the agent of concern when sensitization of the myocardium to catecholamine-induced arrhythmias may be important, such as during incidences of hypercapnia. Sevoflurane does not directly influence sympathetic function. However, reflex tachycardia can occur. Reflex sympathetic... 

C. The purpose of this question is to clarify the functional significance of the activation of opioid receptor types. Respiratory depression and bradycardia are associated with the ji2-opioid receptor. Mydriasis is associated with the o-receptor, which is no longer thought of as opioid. Opioids, via respiratory depression, induce hypercapnia, a build-up of carbon dioxide. The clinically relevant sign of opioid overdose and opioid use is miosis, pinpoint pupils, mediated by K-receptor activation. 

T.Q. Duong, C. ladecola, S.G. Kim, Effect of hyperoxia, hypercapnia, and hypoxia on cerebral interstitial oxygen tension and cerebral blood flow, Magn. Reson. Med. 45 (2001) 61-70. 

Mecfianism of Action A methylxanthine and competitive inhibitor of phosphodiesterase that blocks antagonism of adenosine receptors. Therapeutic Effect Stimulates respiratory center, increases minute ventilation, decreases threshold of or increases response to hypercapnia, increases skeletal muscle tone, decreases diaphragmatic fatigue, increases metabolic rate, and increases oxygen consumption. Pharmacokinetics Protein binding 36%. Widely distributed through the tissues and CSF. Metabolized in liver. Excreted in urine. Half-life 3-7 hr. 

If seizures do occur, it is important to prevent hypoxemia and acidosis. Although administration of oxygen does not prevent seizure activity, hyperoxemia may be beneficial after onset of seizures. Hypercapnia and acidosis may lower the seizure threshold, and so hyperventilation is recommended during treatment of seizures. In addition, hyperventilation increases blood pH, which in turn lowers extracellular potassium. This action hyperpolarizes the transmembrane potential of axons, which favors the resting (or low-affinity) state of the sodium channels, resulting in decreased local anesthetic toxicity. 

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