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ARTICLE |

Hepatic Injury Associated With Tromethamine FREE

Victor E. Goldenberg, MD; Louise Wiegenstein, MD; G. Bruce Hopkins, MD
[+] Author Affiliations

Reprint requests to 1959 NE Pacific, Seattle 98105 (Dr. Goldenberg).


JAMA. 1968;205(2):81-84. doi:10.1001/jama.1968.03140280035009
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Hemorrhagic liver necrosis of varying degrees of severity was observed in 22 (32.8%) of 67 newborn infants with idiopathic respiratory distress syndrome (IRDS) given tromethamine (Tris) and sodium bicarbonate buffers via the umbilical vein for treatment of respiratory acidosis. Identical solutions, if injected via the umbilical artery, were not associated with liver injury. Nor was liver damage observed if bicarbonate alone was injected via the umbilical vein. It is doubtful whether liver injury was a crucial factor leading to death in these seriously ill infants. However, it is felt the long-term consequences of such extensive liver damage may be serious for the survivors.

REFERENCES

Bleich, H.L., and Schwartz, W.B.:  Tris-Buffer (THAM): An Appraisal of Its Physiologic Effects and Clinical Usefulness , New Eng J Med 274:782-786 ( (April 7) ) 1966;.
Kaplan, S.A.:  Tris (Hydroxymethyl) Aminomethane (THAM)—A New Buffer for Therapeutic Use , Amer J Dis Child 103:1-3 ( (Jan) ) 1962;.
Nahas, G.G.:  Clinical Pharmacology of THAM [tris (hydroxymethyl) aminomethane] , Clin Pharmacol Ther 4:785-803 ( (Nov) -Dec) 1963;.
Moore, D., and Bernhard, W.F.:  Method for Control of Severe Alterations in Acid-Base Equilibrium , Circulation 27: 665-669 ( (April) ) 1963;.
Selmonosky, C.A.; Goetz, R.H.; and State, D.:  The Role of Acidosis in the Irreversibility of Experimental Hemorrhagic Shock , J Surg Res 3:491-496 ( (Dec) ) 1963;.
Cosby, R.S., et al:  Respiratory Effects of Tris (THAM) in Acidosis and Alkalosis , Clin Pharmacol Ther 5:185-192 ( (March) -April) 1964;.
Nahas, G.G.:  Use of Organic Carbon Dioxide Buffer in vivo , Science 129:782 ( (March 20) ) 1959;.
Kaplan, S.; Fox, R.P.; and Clark, L.C., Jr.:  Amine Buffers in the Management of Acidosis: Study of Respiratory and Mixed Acidosis , Amer J Dis Child 103:4-9 ( (Jan) ) 1962;.
Brinkman, G.L.; Brunswick, W.L.; and Whitehouse, F.W.:  Use of 2-amino-2-hydroxymethyl-1, 3-propanediol in Correction of Metabolic and Respiratory Acidosis , Ann NY Acad Sci 92: 735-742 ( (June) ) 1961;.
Hinshaw, J.R.; Cramer, L.M.; and Miller, H.C.:  Tris-Buffer in Treatment of Severely Burned Patients , Surgery 56:505-508 ( (Sept) ) 1964;.
Israels, S., in discussion, Strauss, J., et al:  Effects of 2-amino-2-hydroxymethyl-1, 3-propanediol on Renal Function in Reference to Salicylate and Glucose , Ann NY Acad Sci 92:579-595 ( (June) ) 1961;.
Peirce, E.C., II:  Correction of Acidosis With Tris (hydroxymethyl) aminomethane , Arch Surg 80:693-697 ( (April) ) 1960;.
Stahlman, M.:  Treatment of Cardiovascular Disorders of Newborn , Pediat Clin N Amer 11:363-400 ( (May) ) 1964;.
Roberts, M., and Linn, S.:  Acute and Subchronic Toxicity of 2-amino-2-hydroxymethyl-1, 3-propanediol , Ann NY Acad Sci 92:724-734 ( (June) ) 1961;.
Brinkman, G.L., et al:  Treatment of Respiratory Acidosis With THAM , Amer J Med Sci 239:341-346 ( (March) ) 1960;.
Nahas, G.G.:  Pharmacology of Tris (hydroxymethyl) aminomethane (THAM) , Pharmacol Rev 14:447-472 ( (Sept) ) 1962;.
Tarail, R., and Bennett, T.E.:  Hypoglycemic Activity of Tris-Buffer in Man and Dog , Proc Soc Exp Biol Med 102:208-209 ( (Oct) ) 1959;.
Parker, R.C.: Methods of Tissue Culture , ed 3, New York: Harper & Row, Publishers, Inc., 1961;.
Martin, G.M.:  Use of Tris (hydroxymethyl) aminomethane Buffers in Cultures of Diploid Human Fibroblasts ; Proc Soc Exp Biol Med 116:167-171 ( (May) ) 1964;.
Bras, G., and McLean, E.:  Toxic Factors in Veno-occlusive Disease , Ann NY Acad Sci 111:392-398 ( (Dec) ) 1963;.
McLean, E.; Bras, G.; and György, P.:  Veno-occlusive Lesions in Livers of Rats Fed Crotalaria fulva, Brit J Exp Path 45:242-247 ( (June) ) 1964;.
McLean, E.; Bras, G.; and McLean, A.E.M.:  Venous Occlusions in the Liver Following Dimethylnitrosamine , Brit J Exp Path 46:367-369 ( (Aug) ) 1965;.

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Bleich, H.L., and Schwartz, W.B.:  Tris-Buffer (THAM): An Appraisal of Its Physiologic Effects and Clinical Usefulness , New Eng J Med 274:782-786 ( (April 7) ) 1966;.
Kaplan, S.A.:  Tris (Hydroxymethyl) Aminomethane (THAM)—A New Buffer for Therapeutic Use , Amer J Dis Child 103:1-3 ( (Jan) ) 1962;.
Nahas, G.G.:  Clinical Pharmacology of THAM [tris (hydroxymethyl) aminomethane] , Clin Pharmacol Ther 4:785-803 ( (Nov) -Dec) 1963;.
Moore, D., and Bernhard, W.F.:  Method for Control of Severe Alterations in Acid-Base Equilibrium , Circulation 27: 665-669 ( (April) ) 1963;.
Selmonosky, C.A.; Goetz, R.H.; and State, D.:  The Role of Acidosis in the Irreversibility of Experimental Hemorrhagic Shock , J Surg Res 3:491-496 ( (Dec) ) 1963;.
Cosby, R.S., et al:  Respiratory Effects of Tris (THAM) in Acidosis and Alkalosis , Clin Pharmacol Ther 5:185-192 ( (March) -April) 1964;.
Nahas, G.G.:  Use of Organic Carbon Dioxide Buffer in vivo , Science 129:782 ( (March 20) ) 1959;.
Kaplan, S.; Fox, R.P.; and Clark, L.C., Jr.:  Amine Buffers in the Management of Acidosis: Study of Respiratory and Mixed Acidosis , Amer J Dis Child 103:4-9 ( (Jan) ) 1962;.
Brinkman, G.L.; Brunswick, W.L.; and Whitehouse, F.W.:  Use of 2-amino-2-hydroxymethyl-1, 3-propanediol in Correction of Metabolic and Respiratory Acidosis , Ann NY Acad Sci 92: 735-742 ( (June) ) 1961;.
Hinshaw, J.R.; Cramer, L.M.; and Miller, H.C.:  Tris-Buffer in Treatment of Severely Burned Patients , Surgery 56:505-508 ( (Sept) ) 1964;.
Israels, S., in discussion, Strauss, J., et al:  Effects of 2-amino-2-hydroxymethyl-1, 3-propanediol on Renal Function in Reference to Salicylate and Glucose , Ann NY Acad Sci 92:579-595 ( (June) ) 1961;.
Peirce, E.C., II:  Correction of Acidosis With Tris (hydroxymethyl) aminomethane , Arch Surg 80:693-697 ( (April) ) 1960;.
Stahlman, M.:  Treatment of Cardiovascular Disorders of Newborn , Pediat Clin N Amer 11:363-400 ( (May) ) 1964;.
Roberts, M., and Linn, S.:  Acute and Subchronic Toxicity of 2-amino-2-hydroxymethyl-1, 3-propanediol , Ann NY Acad Sci 92:724-734 ( (June) ) 1961;.
Brinkman, G.L., et al:  Treatment of Respiratory Acidosis With THAM , Amer J Med Sci 239:341-346 ( (March) ) 1960;.
Nahas, G.G.:  Pharmacology of Tris (hydroxymethyl) aminomethane (THAM) , Pharmacol Rev 14:447-472 ( (Sept) ) 1962;.
Tarail, R., and Bennett, T.E.:  Hypoglycemic Activity of Tris-Buffer in Man and Dog , Proc Soc Exp Biol Med 102:208-209 ( (Oct) ) 1959;.
Parker, R.C.: Methods of Tissue Culture , ed 3, New York: Harper & Row, Publishers, Inc., 1961;.
Martin, G.M.:  Use of Tris (hydroxymethyl) aminomethane Buffers in Cultures of Diploid Human Fibroblasts ; Proc Soc Exp Biol Med 116:167-171 ( (May) ) 1964;.
Bras, G., and McLean, E.:  Toxic Factors in Veno-occlusive Disease , Ann NY Acad Sci 111:392-398 ( (Dec) ) 1963;.
McLean, E.; Bras, G.; and György, P.:  Veno-occlusive Lesions in Livers of Rats Fed Crotalaria fulva, Brit J Exp Path 45:242-247 ( (June) ) 1964;.
McLean, E.; Bras, G.; and McLean, A.E.M.:  Venous Occlusions in the Liver Following Dimethylnitrosamine , Brit J Exp Path 46:367-369 ( (Aug) ) 1965;.
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