ExtractThis study was devised to ascertain (1) the extent and direction of changes in intracellular hydrogen ion activity in unmodified salicylate intoxication, and (2) whether an intracellular metabolic acidosis was unmasked or decompensated when the Pco2was maintained at normal levels. Sixteen mongrel dogs were studied in 3 groups: 1. Controls; 2. Salicylate intoxicated dogs (given 300 mg/kg of sodium salicylate intravenously; and 3. Mechanically hyperventilated dogs given no salicylate. Skeletal muscle intracellular hydrogen ion activity was determined at intervals in each group using14C-labelled 2,4-dimethyl oxazolidinedione, tritiated water and36Cl ion. In the controls the intracellular hydrogen ion activity did not deviate significantly from the average value of 130.9 nEq/1*over periods ranging from 4–12 hours. In group 2, intracellular hydrogen ion activity fell from a presalicylate value of 129.7 nEq/1 to 102.1 at 2 hours, 87.0 at 3 hours, and 81.5 at 4 hours. When 2–4% CO2was given and the Pco2was stabilized at 30–40 mm Hg, the intracellular hydrogen ion activity returned to normal. In the group 3 dogs it fell from 136.8 nEq/1 to 87.7 over 4 hours and also returned to normal when CO2was given. Results from 3 representative dogs are shown in figure 2. The authors conclude that (1) intracellular hydrogen ion activity falls significantly in salicylate intoxication due to salicylate-induced hyperventilation, and (2) no major metabolic acidosis could be demonstrated within the cells when the Pco2was held at normal levels.SpeculationThe use of THAM or large doses of sodium bicarbonate to alkalinize urine may not be entirely benign though the usefulness of these drugs as salicyluric agents is not questioned. Inhalation of CO2may warrant further research as a possible therapeutic agent for cases of salicylate intoxication in which a metabolic acidosis has not become apparent from extracellular fluid data.*nEq = 10-9equivalents.