The mechanism of the cerebral disorder is from a direct CO2 narcosis, but the biochemical details are not known. Normally the CSF is slightly acidotic in comparison to the blood and the Pco2 of the CSF is about 10 mm Hg higher than that of the blood. With respiratory acidosis, the pH of the CSF falls (into the range of 7.15 to 7.25) and cerebral blood flow increases as a result of cerebral vasodilatation. However, the brain rapidly adapts to respiratory acidosis through the generation and secretion of bicarbonate by the choroid plexuses. Brain water content also increases, mainly in the white matter. In animal models of hypercarbia, blood and brain NH3 is elevated, which may explain the similarity of the syndrome to that of hyperammonemic liver failure (Herrera and Kazemi).
The most effective therapeutic measures are positive-pressure ventilation, using oxygen if there is also hypoxia. Oxygen supplementation is, of course, used cautiously in these patients in order to avoid suppressing respiratory drive; marginally compensated patients treated with excessive oxygen have lapsed into coma. Treatment of heart failure, phlebotomy to reduce the viscosity of the blood, and antibiotics to suppress pulmonary infection may be necessary. Often these measures result in a surprising degree of improvement, which may be maintained for months or years. If aminophylline is administered for the treatment of the underlying pulmonary airway disease, it may produce high blood levels and a tendency to produce seizures.
Unlike pure hypoxic encephalopathy, prolonged coma because of hypercapnia is relatively rare and in our experience has not led to irreversible brain damage. Papilledema, myoclonus, and especially asterixis are important diagnostic features.
This condition is now relatively infrequent but is an important cause of confusion, convulsions, stupor, and coma; as such, it merits separate consideration as a metabolic disorder of the brain. The essential biochemical abnormality is a critical lowering of the blood glucose. At a level of about 30 mg/dL, the cerebral disorder takes the form of a confusional state and one or more seizures may occur; at a level of 10 mg/dL, there is coma that may result in irreparable injury to the brain if not corrected immediately by the administration of glucose. As with most other metabolic encephalopathies, the rate of decline of blood glucose is a factor in both the depression of consciousness and residual dementia.
The normal brain has a glucose reserve of 1 to 2 g (30 mmol/100 g of tissue), mostly in the form of glycogen. Because glucose is utilized by the brain at a rate of 60 to 80 mg/min, the glucose reserve may sustain cerebral activity for 30 min or less once blood glucose is no longer available. Glucose is transported from the blood to the brain by an active carrier system. Glucose entering the brain either undergoes glycolysis or is stored as glycogen. During normal oxygenation (aerobic metabolism), glucose is converted to pyruvate, which enters the Krebs cycle; with anaerobic metabolism, lactate is formed. The oxidation of 1 mole of glucose requires 6 mole of O2. Of the glucose taken up by the brain, 85 to 90 percent is oxidized; the remainder is used in the formation of proteins and other substances, notably neurotransmitters and particularly gamma-aminobutyric acid (GABA).