Correspondence

Intravenous Immune Globulin and Pseudohyponatremia

N Engl J Med 1998; 339:632August 27, 1998

Article

To the Editor:

A 49-year-old woman admitted with typical Guillain–Barré syndrome was treated with intravenous immune globulin (Gamimune N 10%, Bayer, Elkhart, Ind.), at a dose of 45 g per day (0.4 g per kilogram of body weight) for five days.

The sodium concentration, measured with the use of an ion-selective electrode in diluted serum specimens (“indirect potentiometry”), decreased from 143 mmol per liter on day 1 to 127 mmol per liter on day 4. On day 5, when the serum sodium concentration was 122 mmol per liter, urine osmolality was 474 mOsm per liter, the urinary sodium concentration was 45 mmol per liter, and the serum protein value was elevated (10 g per deciliter), but serum glucose and lipid concentrations and thyroid function were normal. Plasma exchange was started on day 6 because of progression and complete flaccid quadriplegia; the serum sodium and protein concentrations promptly returned to normal.

Hyponatremia occurs in up to 26 percent of patients with the Guillain–Barré syndrome, usually because of inappropriate antidiuretic hormone secretion.1 Pseudohyponatremia is a laboratory artifact due to hyperlipidemia or hyperproteinemia.2 Intravenous infusion of immune globulin increases the protein-containing nonaqueous phase of plasma, with a consequent relative decrease in plasma water volume. Since sodium is present only in the aqueous phase, each unit volume of plasma measured has less sodium-containing water, and this is interpreted as hyponatremia. The automated method of measurement used by most laboratories involves the use of an ion-selective electrode with prediluted serum or plasma specimens. This method measures the sodium concentration per liter of serum but does not correct for elevated protein or lipid concentrations. Ion-selective–electrode systems are available that analyze whole-blood specimens with no dilution required. These systems are not affected by the concentrations of protein or lipids in solution.

Pseudohyponatremia has been reported after the administration of intravenous immune globulin in patients with other neurologic diseases, but it has not been as pronounced as in this case.3 True hyponatremia with normal or hypertonic plasma may be seen in association with hyperglycemia as a result of the movement of water from cells into the extracellular fluid space.

The recognition that hyponatremia during intravenous infusion of immune globulin may be an artifact may prevent changes in management that could have deleterious effects. Unnecessary fluid restriction may lead to dehydration, which may impair renal function or exacerbate the effects of dysautonomia.

Nicholas Lawn, M.D.
Eelco F.M. Wijdicks, M.D.
Mary F. Burritt, Ph.D.
Mayo Clinic, Rochester, MN 55905

3 References

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Citing Articles (12)

Citing Articles

1. 1

   Goce Dimeski, Tony Badrick, Andrew St John. (2010) Ion Selective Electrodes (ISEs) and interferences—A review. Clinica Chimica Acta 411:5-6, 309-317
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2. 2

   Eugene Daphnis, Kostas Stylianou, Michael Alexandrakis, Irene Xylouri, Eleftheria Vardaki, Spyros Stratigis, John Kyriazis. (2007) Acute Renal Failure, Translocational Hyponatremia and Hyperkalemia following Intravenous Immunoglobulin Therapy. Nephron Clinical Practice 106:4, c143-c148
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3. 3

   Matthias Wittstock, Uwe K. Zettl. (2006) Adverse effects of treatment with intravenous immunoglobulins for neurological diseases. Journal of Neurology 253:S5, v75-v79
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4. 4

   Minhtri K. Nguyen, Anjay Rastogi, Ira Kurtz. (2006) True hyponatremia secondary to intravenous immunoglobulin. Clinical and Experimental Nephrology 10:2, 124-126
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5. 5

   2006. Immunoglobulins. , 1719-1730.
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6. 6

   Gheun-Ho Kim. (2006) Pseudohyponatremia: Does It Matter in Current Clinical Practice?. Electrolyte & Blood Pressure 4:2, 77
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7. 7

   David Berlana, Antonio Vidaller, Ramón Jódar, Eduard Fort, Alicia Domingo, Lourdes Pastó. (2005) Changes in biochemical, hematological and immunological profiles after low-dose intravenous immunoglobulin administration in patients with hypogammaglobulinemia. Transfusion Clinique et Biologique 12:6, 433-440
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8. 8

   Irina Knezevic-Maramica, Margot S. Kruskall. (2003) Intravenous immune globulins: an update for clinicians. Transfusion 43:10, 1460-1480
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9. 9

   Beth A. Steinberger, Stephen M. Ford, Teresa A. Coleman. (2003) Intravenous immunoglobulin therapy results in post-infusional hyperproteinemia, increased serum viscosity, and pseudohyponatremia. American Journal of Hematology 73:2, 97-100
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10. 10

    B. M. Colls. (2003) Guillain-Barre syndrome and hyponatraemia. Internal Medicine Journal 33:1-2, 5-9
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11. 11

    K. S. R. Sivasai, T. Mohanakumar, D. Phelan, S. Martin, M. E. Anstey, D. C. Brennan. (2000) Cytomegalovirus immune globulin intravenous (human) administration modulates immune response to alloantigens in sensitized renal transplant candidates. Clinical and Experimental Immunology 119:3, 559-565
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12. 12

    &NA;. (1998) Immunoglobulins. Reactions Weekly &NA;:719, 8
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