Correspondence

The Syndrome of Inappropriate Antidiuresis

N Engl J Med 2007; 357:941-942August 30, 2007

Article

To the Editor:

In the article on the syndrome of inappropriate antidiuresis (SIAD), by Ellison and Berl (May 17 issue),1 I disagree with the statement, in the discussion of areas of uncertainty, that “SIAD is characterized by a water excess, rather than a sodium deficit.” In fact, salt depletion occurs, as shown in elegant observations made by William B. Schwartz between 1950 and 1970. If one continuously administers vasopressin in dogs maintained on zero salt and normal water intake, volume expansion with urinary salt loss occurs initially. This period is followed by an “escape” water diuresis, resulting in a reduction of total body water but not enough to allow for total correction of the serum sodium concentration. If the vasopressin is discontinued or if water is withheld without the administration of salt, additional volume contraction occurs, and the sodium concentration may or may not be totally corrected. Both volume-contraction–stimulated vasopressin release and inappropriate vasopressin release (or exogenously administered vasopressin) are salt-deficient states and should be recognized as such.2

David C. Lowance, M.D.
LifeLink of Georgia, Norcross, GA 30071
dlowa80715@aol.com

2 References

1. 1

   Ellison DH, Berl T. The syndrome of inappropriate antidiuresis. N Engl J Med 2007;356:2064-2072
   Full Text | Web of Science | Medline

2. 2

   Lowance DC, Garfinkle HB, Mattern WD, Schwartz WB. The effect of chronic hyponatremic volume expansion on the renal regulation of acid base equilibrium. J Clin Invest 1972;51:2928-2940
   CrossRef | Web of Science | Medline

To the Editor:

In Ellison and Berl's discussion of the diagnosis and management of hyponatremia, a point that we would further emphasize is prevention. The authors note our recommendation of 0.9% sodium chloride in the perioperative period, but we have recommended using 0.9% sodium chloride for the prevention of hyponatremia in all states of excess arginine vasopressin,1 especially after the perioperative period, when arginine vasopressin can be elevated for up to 72 hours.2 The avoidance of hypotonic fluids is the single most important factor for the prevention of hospital-acquired hyponatremia. Table 1 of the article by Ellison and Berl supports our point that virtually every hospitalized patient is at risk for the syndrome of inappropriate secretion of antidiuretic hormone. Although Holliday et al. now accept our recommendation of 0.9% sodium chloride in the perioperative period, they still oppose its use beyond the perioperative setting and for other states of excess arginine vasopressin.3,4 Hospital-acquired hyponatremia is a largely preventable condition, and neurologic morbidity could be virtually eliminated by administering 0.9% sodium chloride as part of maintenance parenteral fluids in patients at risk for excess arginine vasopressin.

Michael L. Moritz, M.D.
Children's Hospital of Pittsburgh, Pittsburgh, PA 15213
michael.moritz@chp.edu

Juan C. Ayus, M.D.
Renal Consultants of Houston, Houston, TX 77019

4 References

1. 1

   Moritz ML, Ayus JC. Prevention of hospital-acquired hyponatremia: a case for using isotonic saline. Pediatrics 2003;111:227-230
   CrossRef | Web of Science | Medline

2. 2

   Ayus JC, Wheeler JM, Arieff AI. Postoperative hyponatremic encephalopathy in menstruant women. Ann Intern Med 1992;117:891-897
   Web of Science | Medline

3. 3

   Holliday MA, Friedman AL, Segar WE, Chesney R, Finberg L. Acute hospital-induced hyponatremia in children: a physiologic approach. J Pediatr 2004;145:584-587
   CrossRef | Web of Science | Medline

4. 4

   Moritz ML, Ayus JC. Hospital-induced hyponatremia. J Pediatr 2005;147:273-274
   Web of Science | Medline

Author/Editor Response

Lowance objects to our statement that SIAD is characterized by an excess of water rather than a salt deficit. We agree that salt losses, together with water excess, contribute to hyponatremia in SIAD.1 Yet salt losses in this setting are secondary to excess arginine vasopressin; they are not the cause of that excess. Treatment of SIAD with 0.9% saline alone is often ineffective and, in some patients, can be detrimental, as we discuss in our article. In contrast, when hyponatremia results from depletion of extracellular fluid, salt replacement (usually with 0.9% saline alone) is essential. Thus, therapeutic errors may result if both states are defined the same way, as “salt deficient.”

We agree with Moritz and Ayus, who recommend 0.9% saline as the preferred intravenous fluid for hospitalized patients in all states of excess arginine vasopressin. Although the authors of a 2003 analysis have questioned assumptions that underlie earlier recommendations to administer hypotonic fluid as maintenance therapy,2 others continue to disagree.3 This remains an area of uncertainty in which evidence from trials is lacking.

David H. Ellison, M.D.
Oregon Health and Science University, Portland, OR 97239
ellisond@ohsu.edu

Tomas Berl, M.D.
University of Colorado Health Sciences Center, Denver, CO 80262

3 References

1. 1

   Verbalis JG. Whole-body volume regulation and escape from antidiuresis. Am J Med 2006;119:Suppl 1:S21-S29
   CrossRef | Web of Science | Medline

2. 2

   Shafiee MAS, Bohn D, Hoorn EJ, Halperin ML. How to select optimal maintenance intravenous fluid therapy. QJM 2003;96:601-610
   CrossRef | Medline

3. 3

   Holliday MA, Friedman AL, Segar WE, Chesney R, Finberg L. Acute hospital-induced hyponatremia in children: a physiologic approach. J Pediatr 2004;145:584-587
   CrossRef | Web of Science | Medline

Citing Articles (1)

Citing Articles

1. 1

   G. Lindner, C. Schwarz, N. Kneidinger, L. Kramer, R. Oberbauer, W. Druml. (2008) Can we really predict the change in serum sodium levels? An analysis of currently proposed formulae in hypernatraemic patients. Nephrology Dialysis Transplantation 23:11, 3501-3508
   CrossRef