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ELECTROLYTE SOLUTION APPROXIMATING PLASMA CONCENTRATIONS: Title and subTitle BreakWITH INCREASED POTASSIUM FOR ROUTINE FLUID AND ELECTROLYTE REPLACEMENT FREE

Charles L. Fox, Jr., M.D.; James M. Winfield, M.D.; Lawrence B. Slobody, M.D.; Charles M. Swindler, M.D.; John K. Lattimer, M.D.
[+] Author Affiliations

Aided in part by a grant from the Division of Research Grants and Fellowships, National Institutes of Health.

The balanced electrolyte solution was prepared by the Research Division of the Cutter Laboratories (Dr. Walter E. Ward, Medical Director) in accordance with our formula for experimental study and clinical trials.


JAMA. 1952;148(10):827-833. doi:10.1001/jama.1952.02930100045010
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Published online

Recent studies have emphasized the desirability of maintaining normal levels of electrolytes and water in plasma and tissue cells. This is difficult to accomplish because the electrolyte composition of the primary replacement solutions generally available for parenteral therapy is significantly different from normal plasma. For example, 0.9% sodium chloride solution contains too much chloride but no bicarbonate and no potassium.

Attempts were made, therefore, to devise a water solution of plasma electrolytes to correct most anomalies. Animal experiments were conducted to obtain the first approximations, and then the proposed solution was subjected to clinical trial. The results to date have been sufficiently encouraging to warrant this report of our observations.

ANIMAL EXPERIMENTS  Hemorrhage was investigated first because of its ubiquity and importance in medicine and surgery and its reproducibility in dogs. Massive volumes of blood were removed from unanesthetized dogs and concurrently replaced with an electrolyte solution.1 During and after the

REFERENCES

Fox, C. L., Jr., and Freeman, B. B.:  Electrolyte, Nitrogen and Protein Changes That Follow Massive Removal of Red Cells and Plasma Protein , Federation Proc. 8:49-50 ( (March) ) 1949;.
Fox, C. L., Jr.:  Stable Internal Standard Flame Photometer for Potassium and Sodium Analyses , Anal. Chem. 23: 137 [ (Jan.) ] 1951;
Van Slyke, K. K., and Evans, E. I.: Unpublished data cited by Van Slyke.28
Rosenthal, S. M., and Tabor, H.:  Electrolyte Changes and Chemotherapy in Experimental Burn and Traumatic Shock and Hemorrhage , Arch. Surg. 51:244-252 ( (Nov.) -Dec.) 1945;.
Rosenthal, S. M.:  Experimental Chemotherapy of Burns and Shock: IV. Production of Traumatic Shock in Mice; V. Therapy with Mouse Serum and Sodium Salts , Pub. Health Rep. 58: 1429-1436 ( (Sept. 24) ) 1943;.
Tabor, H., and Rosenthal, S. M.:  Experimental Chemotherapy of Burns and Shock: Electrolyte Changes in Tourniquet Shock , Pub. Heal h Rep. 60:401-419 ( (April 13) ) 1945;.
Gamble, J. L.: Chemical Anatomy, Physiology and Pathology of Extracellular Fluid: A Lecture Syllabus , ed. 5, Cambridge, Mass., Harvard University Press, 1947;.
Hartmann, A. F., and Senn, M. J. E.:  Studies in Metabolism of Sodium r-Lactate: Response of Normal Human Subjects to Intravenous Injection of Sodium r-Lactate , J. Clin. Invest. 11:327-335 ( (March) ) 1932;
 Studies in Metabolism of Sodium r-Lactate: Response of Human Subjects with Acidosis to Intravenous Injection of Sodium r-Lactate , SennJ. Clin. Invest. 11: 337-344 ( (March) ) 1932;
 Studies in Metabolism of Sodium r-Lactate: Response of Human Subjects with Liver Damage, Disturbed Water and Mineral Balance, and Renal Insufficiency to Intravenous Injection of Sodium r-Lactate , SennJ. Clin. Invest. 11:345-355 ( (March) ) 1932;.
Ringer, S.:  Concerning Influence Exerted by Each of Constituents of Blood on Contraction of Ventricle , J. Physiol. 3:380-393, 1880;-82
 Third Contribution Regarding Influence of Inorganic Constituents of Blood on Ventricular Contraction , RingerJ. Physiol. 4:222-225, 1883;
 Further Contribution Regarding Influence of Different Constituents of Blood on Contraction of Heart , RingerJ. Physiol. 4:29-42, 1883;.
Hartmann, A. F.:  Theory and Practice of Parenteral Fluid Administration , J. A. M. A. 103: 1349-1354 ( (Nov. 3) ) 1934;.
Govan, C. D., Jr., and Darrow, D. C.:  Use of Potassium Chloride in Treatment of Dehydration of Diarrhea in Infants , J. Pediat. 28: 541-549 ( (May) ) 1946;.
Randall, H. T.; Habif, D. V.; Lockwood, J. S., and Werner, S. C.:  Potassium Deficiency in Surgical Patients , Surgery 26:341-363 ( (Sept.) ) 1949;.
Randall, H. T.; Habif, D. V., and Lockwood, J. S.:  Sodium Deficiency in Surgical Patients and Failure of Urine Chloride as Guide to Parenteral Therapy , Surgery 28:182-208 ( (Aug.) ) 1950;.
Mudge, G. H.; Manning, J. A., and Gilman, A.:  Sodium Acetate as a Source of Fixed Base , Proc. Soc. Exper. Biol. & Med. 71: 136-138 ( (May) ) 1949;.
Cori, C. F., and Cori, G. T.:  Glycogen Formation in Liver from d- and l- Lactic Acid , J. Biol. Chem. 81: 389-403 ( (Feb.) ) 1929;.
Hartmann, A. F.; Perley, A. M.; Basman, J.; Nelson, M. V., and Asher, C.:  Further Observations on Metabolism and Clinical Uses of Sodium -Lactate , J. Pediat. 13: 692-723 ( (Nov.) ) 1938;.
Engel, F. L.; Martin, S. P., and Taylor, H.:  On Relation of Potassium to Neurological Manifestations of Hypocalcemic Tetany , Bull. Johns Hopkins Hosp. 84:285-301 ( (April) ) 1949;.
Sherry, S.; Eichna, L. W., and Earle, D. P., Jr.:  Low Potassium Syndrome in Chronic Nephritis , J. Clin. Invest. 27:556 ( (July) ) 1948;.
Hirschfelder, A. D., and Haury, V. D.:  Clinical Manifestations of High and Low Plasma Magnesium: Dangers of Epsom Salt Purgation in Nephritis , J. A. M. A. 102: 1138-1141 ( (April 7) ) 1934;.
Pfeiffer, C.; Roby, C., and Smith, R. B.:  Diuretic Effect of Potassium, Calcium and Magnesium Given Orally in Salt Solution , Am. J. Physiol. 134:729-732 ( (Nov.) ) 1941;.
McCance, R. A., and Widdowson, E. M.:  Fate of Calcium and Magnesium After Intravenous Administration to Normal Persons , Biochem. J. 33:523-529 ( (April) ) 1939;.
Holler, J. W.:  Potassium Deficiency Occurring During Treatment of Diabetic Acidosis , J. A. M. A. 131: 1186-1189 ( (Aug. 10) ) 1946;.
Danowski, T. S.:  Newer Concepts of Role of Potassium in Disease , Am. J. Med. 7:525-531 ( (Oct.) ) 1949;.
Wilkinson, A. W.; Billing, B. H.; Nagy, G., and Stewart, C. P.:  Excretion of Potassium After Partial Gastrectomy , Lancet 2:135-137 ( (July 22) ) 1950;.
Winfield, J. M.; Fox, C. L., Jr., and Mersheimer, W. L.:  Etiological Factors in Postoperative Salt Retention and Its Prevention , Ann. Surg. 134:626-635 ( (Oct.) ) 1951;.
Footnote 12. Danowski.20b
Elman, R.; Lemmer, R. A.; Weichselbaum, T. E.; Owen, J. G., and Yore, R. W.:  Minimum Postoperative Maintenance Requirements for Parenteral Water, Sodium, Potassium, Chloride and Glucose , Ann. Surg. 130:703-722 ( (Oct.) ) 1949;.
Sterile 10 cc. ampules containing 5 mEq. per cubic centimeter of potassium acetate were supplied by the Cutter Laboratories; addition of 5 cc. to 1 liter of balanced electrolyte solution raises the concentration of potassium to 35 mEq. per liter.
Gamble, J. L., and others:  Effects of Large Loads of Electrolytes , Pediatrics 7:305 [ (March) ] 1951;
Ariel, I. M., and Kremen, A. J.:  Compartmental Distribution of Sodium Chloride in Surgical Patients Pre- and Postoperatively , Ann. Surg. 132:1009-1026 ( (Dec.) ) 1950;.
Hartmann, A. F.:  Treatment of Severe Diabetic Acidosis: Comparison of Methods, with Particular Reference to Use of Racemic Sodium Lactate , Arch. Int. Med. 56:413-434 ( (Sept.) ) 1935;.
Van Slyke, D. D.:  Effects of Shock on Kidney , Ann. Int. Med 28:701-722 ( (April) ) 1948;.
Wilde, W. S.:  Chloride Equilibrium in Muscle , Am. J. Physiol 143:666-676 ( (May) ) 1945;.
Coller, F. A.; Campbell, K. N.; Vaughan, H. H.; Iob, L. V., and Moyer, Carl A.:  Postoperative Salt Intolerance , Ann. Surg. 119: 533-542 ( (April) ) 1944;.
Coller, F. A.; Vaughan, H. H.; Kalder, N. B., and Moyer, C. A.:  Translocation of Fluid Produced by Intravenous Administration of Isotonic Salt Solutions in Man Postoperatively , Ann. Surg. 122: 663-677 ( (Oct.) ) 1945;.
Johnson, H. T.; Conn, J. W.; Iob, L. V., and Coller, F. A.:  Postoperative Salt Retention and Its Relation to Increased Adrenal Cortical Function , Ann. Surg. 132:374-385 ( (Sept.) ) 1950;.
Fox, C. L., Jr., and Slobody, L. B.:  Tissue Changes in Nephrotic Syndrome: Demonstration of Potassium Depletion , Pediatrics 7:186-192 ( (Feb.) ) 1951;.
Mudge, G. H., and Taggart, J. V.:  Effect of Acetate on Renal Excretion of p-Aminohippurate in Dog , Am. J. Physiol. 161:191-197 ( (April) ) 1950;.
Pitts, R. F.:  Acid-Base Regulation by Kidneys , Am. J. Med. 9: 356-372 ( (Sept.) ) 1950;.
Wolf, A. V.: The Urinary Function of the Kidney , New York, Grune & Stratton, 1950;.
Danowski, T. S.; Peters, J. H.; Rathbun, J. C.; Quashnock, J. M., and Greenman, L.:  Studies in Diabetic Acidosis and Coma, with Particular Emphasis on Retention of Administered Potassium , J. Clin. Invest. 28: 1-9 ( (Jan.) ) 1949;.
Darrow, D. C.:  Retention of Electrolytes During Recovery from Severe Dehydration Due to Diarrhea , J. Pediat. 28:515-540 ( (May) ) 1946;.
Govan, C. D., Jr., and Weiseth, W. M.:  Potassium Intoxication: Report of Infant Surviving Serum Potassium Level of 12.27 Millimoles per Liter , J. Pediat. 28: 550-553 ( (May) ) 1946;.
Darrow, D. C.:  Disturbances in Electrolyte Metabolism in Man and Their Management , Bull. New York Acad. Med. 24:147-165 ( (March) ) 1948;.
Currens, J. H., and Crawford, J. D.:  Electrocardiogram and Disturbance of Potassium Metabolism , New England J. Med. 243:843-850 ( (Nov. 30) ) 1950;.
Darrow, D. C., and Pratt, E. L.:  Fluid Therapy: Relation to Tissue Composition and Expenditure of Water and Electrolyte , J. A. M. A. 143: 365-373 ( (May 27) ); 432-439 (June 3) 1950;.
Fox, C. L., Jr.:  Oral Sodium Lactate in Treatment of Burn Shock , J. A. M. A. 124:207-212 ( (Jan. 22) ) 1944;.
Harkins, H. N.; Cope, O.; Evans, E. I.; Phillips, R. A., and Richards, D. W.:  Fluid and Nutritional Therapy of Burns , J. A. M. A. 128:475-479 ( (June 16) ) 1945;.
 Saline Solution in Treatment of Burn Shock , Pub. Health Rep. 65: 1317-1320 ( (Oct. 13) ) 1950;.
MacFee, W. F., and Baldridge, R. R.:  Post-Operative Shock and Shock-Like Conditions: Treatment by Infusion in Large Volume , Ann. Surg. 91:329-341 ( (March) ) 1930;.

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Fox, C. L., Jr., and Freeman, B. B.:  Electrolyte, Nitrogen and Protein Changes That Follow Massive Removal of Red Cells and Plasma Protein , Federation Proc. 8:49-50 ( (March) ) 1949;.
Fox, C. L., Jr.:  Stable Internal Standard Flame Photometer for Potassium and Sodium Analyses , Anal. Chem. 23: 137 [ (Jan.) ] 1951;
Van Slyke, K. K., and Evans, E. I.: Unpublished data cited by Van Slyke.28
Rosenthal, S. M., and Tabor, H.:  Electrolyte Changes and Chemotherapy in Experimental Burn and Traumatic Shock and Hemorrhage , Arch. Surg. 51:244-252 ( (Nov.) -Dec.) 1945;.
Rosenthal, S. M.:  Experimental Chemotherapy of Burns and Shock: IV. Production of Traumatic Shock in Mice; V. Therapy with Mouse Serum and Sodium Salts , Pub. Health Rep. 58: 1429-1436 ( (Sept. 24) ) 1943;.
Tabor, H., and Rosenthal, S. M.:  Experimental Chemotherapy of Burns and Shock: Electrolyte Changes in Tourniquet Shock , Pub. Heal h Rep. 60:401-419 ( (April 13) ) 1945;.
Gamble, J. L.: Chemical Anatomy, Physiology and Pathology of Extracellular Fluid: A Lecture Syllabus , ed. 5, Cambridge, Mass., Harvard University Press, 1947;.
Hartmann, A. F., and Senn, M. J. E.:  Studies in Metabolism of Sodium r-Lactate: Response of Normal Human Subjects to Intravenous Injection of Sodium r-Lactate , J. Clin. Invest. 11:327-335 ( (March) ) 1932;
 Studies in Metabolism of Sodium r-Lactate: Response of Human Subjects with Acidosis to Intravenous Injection of Sodium r-Lactate , SennJ. Clin. Invest. 11: 337-344 ( (March) ) 1932;
 Studies in Metabolism of Sodium r-Lactate: Response of Human Subjects with Liver Damage, Disturbed Water and Mineral Balance, and Renal Insufficiency to Intravenous Injection of Sodium r-Lactate , SennJ. Clin. Invest. 11:345-355 ( (March) ) 1932;.
Ringer, S.:  Concerning Influence Exerted by Each of Constituents of Blood on Contraction of Ventricle , J. Physiol. 3:380-393, 1880;-82
 Third Contribution Regarding Influence of Inorganic Constituents of Blood on Ventricular Contraction , RingerJ. Physiol. 4:222-225, 1883;
 Further Contribution Regarding Influence of Different Constituents of Blood on Contraction of Heart , RingerJ. Physiol. 4:29-42, 1883;.
Hartmann, A. F.:  Theory and Practice of Parenteral Fluid Administration , J. A. M. A. 103: 1349-1354 ( (Nov. 3) ) 1934;.
Govan, C. D., Jr., and Darrow, D. C.:  Use of Potassium Chloride in Treatment of Dehydration of Diarrhea in Infants , J. Pediat. 28: 541-549 ( (May) ) 1946;.
Randall, H. T.; Habif, D. V.; Lockwood, J. S., and Werner, S. C.:  Potassium Deficiency in Surgical Patients , Surgery 26:341-363 ( (Sept.) ) 1949;.
Randall, H. T.; Habif, D. V., and Lockwood, J. S.:  Sodium Deficiency in Surgical Patients and Failure of Urine Chloride as Guide to Parenteral Therapy , Surgery 28:182-208 ( (Aug.) ) 1950;.
Mudge, G. H.; Manning, J. A., and Gilman, A.:  Sodium Acetate as a Source of Fixed Base , Proc. Soc. Exper. Biol. & Med. 71: 136-138 ( (May) ) 1949;.
Cori, C. F., and Cori, G. T.:  Glycogen Formation in Liver from d- and l- Lactic Acid , J. Biol. Chem. 81: 389-403 ( (Feb.) ) 1929;.
Hartmann, A. F.; Perley, A. M.; Basman, J.; Nelson, M. V., and Asher, C.:  Further Observations on Metabolism and Clinical Uses of Sodium -Lactate , J. Pediat. 13: 692-723 ( (Nov.) ) 1938;.
Engel, F. L.; Martin, S. P., and Taylor, H.:  On Relation of Potassium to Neurological Manifestations of Hypocalcemic Tetany , Bull. Johns Hopkins Hosp. 84:285-301 ( (April) ) 1949;.
Sherry, S.; Eichna, L. W., and Earle, D. P., Jr.:  Low Potassium Syndrome in Chronic Nephritis , J. Clin. Invest. 27:556 ( (July) ) 1948;.
Hirschfelder, A. D., and Haury, V. D.:  Clinical Manifestations of High and Low Plasma Magnesium: Dangers of Epsom Salt Purgation in Nephritis , J. A. M. A. 102: 1138-1141 ( (April 7) ) 1934;.
Pfeiffer, C.; Roby, C., and Smith, R. B.:  Diuretic Effect of Potassium, Calcium and Magnesium Given Orally in Salt Solution , Am. J. Physiol. 134:729-732 ( (Nov.) ) 1941;.
McCance, R. A., and Widdowson, E. M.:  Fate of Calcium and Magnesium After Intravenous Administration to Normal Persons , Biochem. J. 33:523-529 ( (April) ) 1939;.
Holler, J. W.:  Potassium Deficiency Occurring During Treatment of Diabetic Acidosis , J. A. M. A. 131: 1186-1189 ( (Aug. 10) ) 1946;.
Danowski, T. S.:  Newer Concepts of Role of Potassium in Disease , Am. J. Med. 7:525-531 ( (Oct.) ) 1949;.
Wilkinson, A. W.; Billing, B. H.; Nagy, G., and Stewart, C. P.:  Excretion of Potassium After Partial Gastrectomy , Lancet 2:135-137 ( (July 22) ) 1950;.
Winfield, J. M.; Fox, C. L., Jr., and Mersheimer, W. L.:  Etiological Factors in Postoperative Salt Retention and Its Prevention , Ann. Surg. 134:626-635 ( (Oct.) ) 1951;.
Footnote 12. Danowski.20b
Elman, R.; Lemmer, R. A.; Weichselbaum, T. E.; Owen, J. G., and Yore, R. W.:  Minimum Postoperative Maintenance Requirements for Parenteral Water, Sodium, Potassium, Chloride and Glucose , Ann. Surg. 130:703-722 ( (Oct.) ) 1949;.
Sterile 10 cc. ampules containing 5 mEq. per cubic centimeter of potassium acetate were supplied by the Cutter Laboratories; addition of 5 cc. to 1 liter of balanced electrolyte solution raises the concentration of potassium to 35 mEq. per liter.
Gamble, J. L., and others:  Effects of Large Loads of Electrolytes , Pediatrics 7:305 [ (March) ] 1951;
Ariel, I. M., and Kremen, A. J.:  Compartmental Distribution of Sodium Chloride in Surgical Patients Pre- and Postoperatively , Ann. Surg. 132:1009-1026 ( (Dec.) ) 1950;.
Hartmann, A. F.:  Treatment of Severe Diabetic Acidosis: Comparison of Methods, with Particular Reference to Use of Racemic Sodium Lactate , Arch. Int. Med. 56:413-434 ( (Sept.) ) 1935;.
Van Slyke, D. D.:  Effects of Shock on Kidney , Ann. Int. Med 28:701-722 ( (April) ) 1948;.
Wilde, W. S.:  Chloride Equilibrium in Muscle , Am. J. Physiol 143:666-676 ( (May) ) 1945;.
Coller, F. A.; Campbell, K. N.; Vaughan, H. H.; Iob, L. V., and Moyer, Carl A.:  Postoperative Salt Intolerance , Ann. Surg. 119: 533-542 ( (April) ) 1944;.
Coller, F. A.; Vaughan, H. H.; Kalder, N. B., and Moyer, C. A.:  Translocation of Fluid Produced by Intravenous Administration of Isotonic Salt Solutions in Man Postoperatively , Ann. Surg. 122: 663-677 ( (Oct.) ) 1945;.
Johnson, H. T.; Conn, J. W.; Iob, L. V., and Coller, F. A.:  Postoperative Salt Retention and Its Relation to Increased Adrenal Cortical Function , Ann. Surg. 132:374-385 ( (Sept.) ) 1950;.
Fox, C. L., Jr., and Slobody, L. B.:  Tissue Changes in Nephrotic Syndrome: Demonstration of Potassium Depletion , Pediatrics 7:186-192 ( (Feb.) ) 1951;.
Mudge, G. H., and Taggart, J. V.:  Effect of Acetate on Renal Excretion of p-Aminohippurate in Dog , Am. J. Physiol. 161:191-197 ( (April) ) 1950;.
Pitts, R. F.:  Acid-Base Regulation by Kidneys , Am. J. Med. 9: 356-372 ( (Sept.) ) 1950;.
Wolf, A. V.: The Urinary Function of the Kidney , New York, Grune & Stratton, 1950;.
Danowski, T. S.; Peters, J. H.; Rathbun, J. C.; Quashnock, J. M., and Greenman, L.:  Studies in Diabetic Acidosis and Coma, with Particular Emphasis on Retention of Administered Potassium , J. Clin. Invest. 28: 1-9 ( (Jan.) ) 1949;.
Darrow, D. C.:  Retention of Electrolytes During Recovery from Severe Dehydration Due to Diarrhea , J. Pediat. 28:515-540 ( (May) ) 1946;.
Govan, C. D., Jr., and Weiseth, W. M.:  Potassium Intoxication: Report of Infant Surviving Serum Potassium Level of 12.27 Millimoles per Liter , J. Pediat. 28: 550-553 ( (May) ) 1946;.
Darrow, D. C.:  Disturbances in Electrolyte Metabolism in Man and Their Management , Bull. New York Acad. Med. 24:147-165 ( (March) ) 1948;.
Currens, J. H., and Crawford, J. D.:  Electrocardiogram and Disturbance of Potassium Metabolism , New England J. Med. 243:843-850 ( (Nov. 30) ) 1950;.
Darrow, D. C., and Pratt, E. L.:  Fluid Therapy: Relation to Tissue Composition and Expenditure of Water and Electrolyte , J. A. M. A. 143: 365-373 ( (May 27) ); 432-439 (June 3) 1950;.
Fox, C. L., Jr.:  Oral Sodium Lactate in Treatment of Burn Shock , J. A. M. A. 124:207-212 ( (Jan. 22) ) 1944;.
Harkins, H. N.; Cope, O.; Evans, E. I.; Phillips, R. A., and Richards, D. W.:  Fluid and Nutritional Therapy of Burns , J. A. M. A. 128:475-479 ( (June 16) ) 1945;.
 Saline Solution in Treatment of Burn Shock , Pub. Health Rep. 65: 1317-1320 ( (Oct. 13) ) 1950;.
MacFee, W. F., and Baldridge, R. R.:  Post-Operative Shock and Shock-Like Conditions: Treatment by Infusion in Large Volume , Ann. Surg. 91:329-341 ( (March) ) 1930;.
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