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Cerebral Salt Wasting Versus SIADH: What

Richard H. Sterns and Stephen M. Silver
Rochester General Hospital, Rochester, University of Rochester School of Medicine and Dentistry, Rochester,
New York

ABSTRACT that era (Donald Seldin, personal tele-

The term cerebral salt wasting (CSW) was introduced before the syndrome of phone communication, October 2007).
inappropriate antidiuretic hormone secretion was described in 1957. Subse- In 1936, McCance defined the conse-
quently, CSW virtually vanished, only to reappear a quarter century later in the quences of salt depletion in normal
neurosurgical literature. A valid diagnosis of CSW requires evidence of inappro- man.1 Patients with extrarenal salt losses
priate urinary salt losses and reduced “effective arterial blood volume.” With no complicated by hyponatremia were
gold standard, the reported measures of volume depletion do not stand scrutiny. found to be commonplace, and consis-
We cannot tell the difference between CSW and the syndrome of inappropriate tent with McCance’s description, they
antidiuretic hormone secretion. Furthermore, the distinction does not make a excreted urine virtually free of sodium.
difference; regardless of volume status, hyponatremia complicating intracranial In 1950, Peters et al.2 reported three
disease should be treated with hypertonic saline. patients seen at Yale New Haven Hospi-
tal with hyponatremia and diseases of the
J Am Soc Nephrol 19: 194 –196, 2008. doi: 10.1681/ASN.2007101118
central nervous system. In each patient,
urine sodium losses persisted despite hy-
ponatremia and a high-salt diet. Al-
though two of the patients were severely
Last year, a visitor from Addis Ababa, tently high urine osmolality, we gave him
hypertensive, they were described as ex-
Ethiopia, was admitted to our hospital hypertonic saline.
hibiting “clinical signs of dehydration.”
with tuberculous meningitis, hyponatre- We had trouble telling the difference
Two years later, Cort3 described another
mia, atrial flutter, hypotension, and a he- between CSW and the syndrome of inap-
similar patient seen at Yale, and he
matocrit of 64%. Hemoconcentration propriate antidiuretic hormone secre-
named the syndrome CSW. On a se-
and a urine sodium of 196 mmol/L, ob- tion (SIADH), and the distinction did
verely sodium-restricted diet, his patient
tained after saline, suggested renal salt not alter our approach to his manage-
continued to excrete sodium in her
wasting. Once Addison disease was ex- ment. Was our experience typical? Is
urine; however, despite negative sodium
cluded, we wondered whether the patient there a difference between CSW and
balance, she remained normotensive.3,4
had cerebral salt wasting (CSW). After car- SIADH? And if so, what difference does it
In 1953, Leaf et al.5 demonstrated that
dioversion, and without additional saline, make? The ambiguity of our case is
exogenous administration of the antidi-
his weight stabilized and blood pressure rather typical of most of the literature on
uretic hormone vasopressin resulted in
(BP) normalized without orthostatic the subject of CSW. A historical overview
hyponatremia and a natriuresis depen-
change. Blood urea nitrogen (BUN) and may help us better understand why we
dent on water retention and weight gain.
uric acid remained low, urine sodium fell ask, is this CSW or SIADH?
This was not “salt wasting”; it was a phys-
to 71 mmol/L, and urine osmolality was Shortly after World War II, the avail-
iologic response to an expanded intra-
473 mOsm/kg despite persistent hypona- ability of the flame photometer made
tremia. His hematocrit settled in the mid- clinical determinations of the serum so-
50s. A medical student of Ethiopian heri- dium concentration possible. Yale was Published online ahead of print. Publication date
available at
tage reminded us that residents of Addis one of the first medical centers to have
Ababa have high hematocrits because of the new device, and some of the first Correspondence: Richard H. Sterns, 1425 Portland
Avenue, Rochester, NY 14621. Phone: 585-922-
the altitude. While wondering what to call published observations about hypona- 4242; Fax: 585-922-4440; E-mail: Richard.Sterns@
his disease, we turned our attention to tremia came from Yale. The role that salt
therapy. Because of neurologic symptoms depletion played in the etiology of hypo- Copyright © 2008 by the American Society of
with refractory hyponatremia and a persis- natremia was well known to clinicians of Nephrology

194 ISSN : 1046-6673/1902-194 J Am Soc Nephrol 19: 194–196, 2008 CLINICAL COMMENTARY

vascular volume. Four years later, The diagnosis of CSW is often based bral injury. So-called brain natriuretic
Schwartz et al.6 published their landmark on negative sodium balance. However, peptide is usually of cardiac origin; jug-
paper on SIADH. A subsequent paper patients with SIADH also develop nega- ular venous sampling in suspected
from the group at Yale attributed hypo- tive sodium balance.5,6,16 –18 Sodium lost CSW did not support cerebral release
natremia in neurologic disease to in response to water retention or to cat- of the peptide.22
SIADH.7 For over 20 yr, the term CSW echolamine-induced vasoconstriction In many reports of CSW, correction
virtually vanished from the literature. and hypertension is a physiologic natri- of hyponatremia with salt is cited as ev-
In 1981, Nelson et al.8 studied hypo- uresis rather than “salt wasting.”4 Bal- idence of sodium depletion. However,
natremia in neurosurgical patients, pri- ance studies should include data from any maneuver increasing the ratio of
marily subarachnoid hemorrhage, and the first contact with medical or para- body electrolyte to body water corrects
found that isotopically measured blood medical personnel; one such analysis hyponatremia, regardless of the cause.
volumes were contracted; he attributed showed that over 90% of patients with What is missing is the demonstration
this finding to CSW. Other authors asso- subarachnoid hemorrhage were in posi- that volume expansion provoked a wa-
ciated hyponatremia in subarachnoid tive sodium balance on their arrival to ter diuresis (reflecting the loss of a vol-
hemorrhage with increased levels of na- the intensive care unit and subsequent ume stimulus for vasopressin). On the
triuretic peptides, negative sodium bal- “negative sodium balance,” therefore an contrary, patients with purported CSW
ance,9,10 and low central venous pres- appropriate physiologic response to a continue to excrete concentrated urine
sure.11 A MEDLINE search between 1981 surfeit of sodium.4 Patients with sub- despite large volumes of isotonic sa-
and the present, using the keyword CSW, arachnoid hemorrhage are treated with line. A prospective study of patients
yielded 119 articles, with only 3 articles extremely large volumes of isotonic sa- with subarachnoid hemorrhage
before that. CSW is back in fashion. line to maintain cerebral perfusion. De- showed that isotonic saline prevented
A valid diagnosis of “salt wasting” re- creasing the infusion rate could lead to a volume contraction but did not pre-
quires evidence of inappropriate urinary brief “overshoot” natriuresis because of vent hyponatremia.23
salt losses and a reduced “effective arte- adaptive internalization of the compo- Traditional markers of volume deple-
rial blood volume.” Unfortunately, there nents of sodium reabsorption in the tion are not helpful. Renin and aldoste-
is no gold standard to define inappropri- proximal tubule in response to sustained rone levels are typically suppressed, but
ate urinary sodium excretion. “Effective volume expansion.4,19 these findings have been ascribed to a re-
arterial blood volume” is a concept, not a Like the Peters et al.2 first report of the duction in sympathetic tone and/or sup-
measurable variable; in fact, we often de- syndrome, many articles on CSW rely on pressed secretion by natriuretic pep-
fine it clinically by looking at urine so- clinical impressions of volume depletion. tides.24 Therefore, low levels of these
dium excretion.12 Nephrologists know what a difficult de- hormones are said to be the cause of salt
The literature on CSW relies on sev- termination this can be. Few published wasting rather than the response to vol-
eral criteria for volume depletion: direct reports detail the clinical findings sup- ume expansion. Uric acid levels are low
determinations of blood and plasma vol- porting a diagnosis of hypovolemia. BP in both SIADH and CSW.15 In SIADH, a
ume, negative sodium balance, clinical values are rarely included. Central ve- low serum uric acid level is ascribed to
impressions, plasma levels of arginine nous pressure measurements have be- volume expansion. In CSW, the same
vasopressin and natriuretic peptides, and come the gold standard in the neurosur- finding is ascribed to impaired sodium
responses to therapy.4,13–15 None of these gical literature; a central venous pressure reabsorption by the proximal tubule.
measures is up to the task. less than 5 cm H2O is said to be inconsis- One group has proposed that the re-
Some reports of CSW have used a low tent with SIADH and diagnostic of sponse of uric acid clearance to correc-
red cell mass to define hypovolemia. CSW.11 However, the central venous tion of hyponatremia be used as a diag-
However, salt wasting should leave red pressure is rarely measured in SIADH nostic test,15,25 but without a gold
cell mass constant, lowering plasma vol- without neurologic disease, and the cen- standard to define volume depletion, we
ume and raising the hematocrit. Plasma tral venous pressure has been shown to have difficulty accepting this surrogate
volume measurements are at least di- be a poor marker of cardiac filling pres- marker.
rected at the correct variable, but they sure.20 Our neurosurgical colleagues are likely
cannot answer the question either. Most Plasma levels of arginine vasopres- to continue to ascribe hyponatremia to
of the plasma volume resides in venous sin and natriuretic peptides offer little CSW. Neurointensivists routinely infuse
capacitance vessels. Sympathetically me- help. Both CSW and SIADH are asso- large volumes of saline to their patients,
diated venoconstriction can reduce ciated with the nonosmotic release of and for good reason. Vasospasm and cere-
plasma volume without causing true hy- vasopressin. In SIADH, natriuretic bral infarction are serious concerns in sub-
povolemia.4 Negative fluid balance peptide levels increase in response to arachnoid hemorrhage; hyponatremia,
should cause hemoconcentration. Sur- overfilling of the arterial circulation with its attendant cerebral edema, in-
prisingly, the hematocrit is rarely re- with water,21 a response indistinguish- creases the risk of this complication.26
ported in cases of purported CSW.14 able from secretion provoked by cere- Because isotonic saline neither prevents

J Am Soc Nephrol 19: 194 –196, 2008 CSW Versus SIADH 195

nor cures hyponatremia, infusion of FC: A syndrome of renal sodium loss and Marsh DJ, Holstein-Rathlou NH, McDon-
hyponatremia probably resulting from inap- ough AA: Rapid redistribution and inhibition
hypertonic saline has become routine.27 propriate secretion of antidiuretic hormone. of renal sodium transporters during acute
Nephrologists may be more comfort- Am J Med 23: 529 –542, 1957 pressure natriuresis. Am J Physiol 270:
able with a diagnosis of SIADH. But how 7. Carter NW, Rector FC Jr, Seldin DW: Hypo- F1004 –F1014, 1996
should we treat SIADH associated with natremia in cerebral disease resulting from 20. Kumar A, Anel R, Bunnell E, Habet K, Zanotti
intracerebral pathology? We believe that the inappropriate secretion of antidiuretic S, Marshall S, Neumann A, Ali A, Cheang M,
hormone. N Engl J Med 264: 67–72, 1961 Kavinsky C, Parrillo JE: Pulmonary artery oc-
any degree of hyponatremia in a patient 8. Nelson PB, Seif SM, Maroon JC, Robinson clusion pressure and central venous pres-
with an intracranial mass lesion or hem- AG: Hyponatremia in intracranial disease: sure fail to predict ventricular filling volume,
orrhage, head trauma, recent stroke, or perhaps not the syndrome of inappropriate cardiac performance, or the response to vol-
brain surgery should mandate treatment secretion of antidiuretic hormone (SIADH). ume infusion in normal subjects. Crit Care
with hypertonic saline. The risk of neu- J Neurosurg 55: 938 –941, 1981 Med 32: 691– 699, 2004
9. Wijdicks EF, Vermeulen M, ten Haaf JA, Hi- 21. Cogan E, Debieve MF, Pepersack T,
rologic deterioration or herniation in jdra A, Bakker WH, van Gijn J: Volume de- Abramow M: Natriuresis and atrial natri-
such patients is too great, water restric- pletion and natriuresis in patients with a rup- uretic factor secretion during inappropri-
tion is too slow, and isotonic saline can tured intracranial aneurysm. Ann Neurol 18: ate antidiuresis. Am J Med 84: 409 – 418,
worsen hyponatremia in SIADH.28 211–216, 1985 1988
Is there a difference between CSW 10. Wijdicks EF, Ropper AH, Hunnicutt EJ, Rich- 22. Powner DJ, Hergenroeder GW, Awili M, Atik
ardson GS, Nathanson JA: Atrial natriuretic MA, Robertson C: Hyponatremia and com-
and SIADH? We doubt that one can be factor and salt wasting after aneurysmal sub- parison of NT-pro-BNP concentrations in
proven. And if they are different, what arachnoid hemorrhage. Stroke 22: blood samples from jugular bulb and arterial
difference does it make? Probably none; 1519 –1524, 1991 sites after traumatic brain injury in adults: a
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196 Journal of the American Society of Nephrology J Am Soc Nephrol 19: 194 –196, 2008