The toxic effects of carbon dioxide and acetazolamide in hepatic encephalopathy.

Striking alterations in respiratory gas and blood ammonia levels usually accompany hepatic coma. The arterial pH is elevated and the carbon dioxide tension reduced (1). The blood ammonia level (2-4) is increased in many instances and the brain arteriovenous ammonia difference is high (5, 6). The cerebral oxygen uptake is depressed (7, 8). Whether the pronounced alkalosis which accompanies many instances of hepatic comiia contributes to the encephalopathy is unknown. Severe blood alkalosis impairs oxyhemoglobin dissociation (9), lowers the arterial oxygen partial pressure and interferes with cerebral function in normal subjects (10). Alkalosis is reported to enhance ammonia toxicity (11-13). These effects led Roberts and associates (14) as well as others (13) to suggest using carbon dioxide inhalation to treat hepatic coma. Prelimiiinary clinical observations on our own services suggested that inhaled CO2 worsened rather than improved patients with the encephalopathy of liver disease. Accordingly, detailed clinical and cerebral metabolic studies were carried out to quantitate the effects on brain function of raising blood and tissue CO2 tensions. The results of the study are reported here. Cerebral blood flow and cerebral oxygen uptake were measured at rest in control and cirrhotic patients and the results were correlated with the patients' mental and somatic neurological function. Following the baseline study, selected patients inhaled carbon dioxide and the clinical cerebral metabolic observations were repeated. Subsequently, to eliminate the undesirable side effects of hyperpnea and dyspnea as contributing to the observed changes, similar observations were made before and after raising tissue CO2 tensions by rapidly infusing acetazolamide (Diamox).