The Effect of Sodium Glutamate on Hepatic Coma 12

Abnormalities of nitrogen metabolism may be important in the production of hepatic coma (1).This concept is supported by the following: 1) Elevated blood "ammonia" 8 concentrations have been described in patients with cirrhosis of the liver, many of whom were in hepatic coma; the highest values have occurred in comatose patients.2) Some alcoholic patients with cirrhosis given nitrogenous substances including ammonium ca- tion-exchange resins, ammonium salts, urea, and increments of dietary protein have developed im- pending hepatic coma (mental confusion and of- ten the characteristic "flapping" tremor) which usually terminated after discontinuing these sub- stances (2, 3). 3) A similar state occurred also in Eck fistula dogs and man after feeding incre- ments of dietary protein and other nitrogenous substances (4-6).Ammonium may react with glutamic acid to form glutamine or precursors of urea.Glutamic acid is used more than any other amino acid in brain energy metabolism, and has been reported to improve insulin coma in psychotic patients (7, 8).Walshe first used glutamic acid in the treat- ment of hepatic coma with encouraging results (9).Other investigators have since reported variable findings (10-20).This paper evaluates the effect of intravenous sodium glutamate ad- ministered to eleven patients with cirrhosis of the liver.Five were comatose, six showed signs of 1 This work was supported in part by the Office of The Surgeon General, Department of the Army, and in part by a grant from Merck and Company, Inc., Rahway, New Jersey, to Harvard University.2A preliminary report of part of this investigation is included in the Proceedings of the Forty-Sixth Annual Meeting of the American Society of Clinical Investigation, Atlantic City, May 4, 1954 (J.Clin.Invest., 1954, 33, 971).8 Whether free ammonium exists in shed blood or forms after shedding is argued.If it does exist it is present as ammonium ion.Therefore, when referring to plasma or blood, we have put the word ammonia in quotes.