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We administered dichloroacetate, which prevents or reverses hyperlactatemia in animals and lowers plasma lactate levels in human beings, to 13 patients with lactic acidosis of various causes. All had hypotension, and their acidemia had resisted treatment with sodium bicarbonate. The metabolic effects of dichloroacetate were evaluated in 11 patients. In seven dichloroacetate significantly reduced the level of arterial blood lactate (P less than 0.005) from the base-line value and raised the levels of arterial blood bicarbonate (P less than 0.02) and arterial pH (P less than 0.005). In six of these seven, the acidemia resolved completely with therapy. In 10 of the 13 patients systolic blood pressure increased by 10 to 40 mm Hg, and 4 patients had a 21 per cent increase in cardiac output (P less than 0.02). Despite improvement in their lactic acidemia, all patients but one died of their underlying disease. No serious drug-related toxicity occurred. We conclude that dichloroacetate is a safe and effective adjunct in the treatment of patients with lactic acidosis, although the ultimate prognosis may depend on the underlying disease.

Since phenformin's introduction into clinical medicine, a total of 552 cases of lactic acidosis have been reported in patients taking this hypoglycemic agent. In 306 cases, sufficient documentation was available to establish the diagnosis with reasonable certainty (blood lactate, 6 meq/litre or greater, and blood pH, 7.33 or less). The mortality rate among insulin-treated patients (15%) was considerably less than the mortality rate in the group as a whole (42%). Taken together with results from animal studies, these data suggest that insulin is the treatment of choice for phenformin-associated lactic acidosis. Sodium bicarbonate should be administered to patients with severe acidosis, but should be withheld from patients with mild acidosis. Overly aggressive administration of sodium bicarbonate can be deleterious and should be avoided. Although dialysis has been suggested by some authors for the treatment of phenformin-associated lactic acidosis, the mortality rate among dialyzed patients (48%) was roughly the same as for the group as a whole (42%).

The efficacy and tolerability of aminoglutethimide for the treatment of Cushing's syndrome was assessed in 66 cases three of which are described in the present paper. Aminoglutethimide provided palliation from the signs and symptoms of hypercorticism in 13 of 21 patients with metastatic adrenocortical carcinoma and four of six patients with ectopic ACTH production due to metastatic carcinomas. All six of the patients with adrenal adenomas showed clinical and biochemical improvement, while 14 of the 33 patients with bilateral adrenal hyperplasia of pituitary origin improved. Adverse reactions attributed to aminoglutethimide such as drowsiness, rash, and nausea occurred in 58 per cent of cases. These data suggest that aminoglutethimide has a place in controlling the signs and symptoms of adrenocorticoid excess in patients with Cushing's syndrome due to malignancy and is effective preoperative therapy for patients with adrenal adenomas and bilateral hyperplasia.