Review article
Hyponatremia in acute brain disease: the cerebral salt wasting syndrome

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Abstract

Hyponatremia in acute brain disease is a common occurrence, especially after an aneurysmal subarachnoid hemorrhage. Originally, excessive natriuresis, called cerebral salt wasting, and later the syndrome of inappropriate antidiuretic hormone secretion (SIADH), were considered to be the causes of hyponatremia. In recent years, it has become clear that most of these patients are volume-depleted and have a negative sodium balance, consistent with the original description of cerebral salt wasting. Elevated plasma concentrations of atrial or brain natriuretic peptide have been identified as the putative natriuretic factor. Hyponatremia and volume depletion may aggravate neurological symptoms, and timely treatment with adequate replacement of water and NaCl is essential. The use of fludrocortisone to increase sodium reabsorption by the renal tubules may be an alternative approach.

Introduction

Hyponatremia is a common finding in acute brain disease. In neurosurgical patients with a subarachnoid hemorrhage (SAH), it is observed in ∼30% of the cases studied [1], [2], [3]. The hyponatremia is usually mild to moderate with a plasma sodium concentration between 120 and 130 mmol/l, but it may occasionally be severe [4]. The falling sodium level can progressively lead to neurological problems like confusion, lethargy, seizures and, finally, coma [5], [6]. Concurrent hyponatremia in subarachnoid hemorrhage may increase the severity of neurological symptoms because of the increased risk of cerebral edema and ischemia [1], [7], [8]. Early diagnosis and treatment are, therefore, essential.

Hyponatremia was reported in the 1950s in a number of patients with various causes of brain disease. As excessive natriuresis was observed, the term ‘cerebral salt wasting’ (CSW) was coined for this syndrome [9], [10], [11]. The proposed natriuretic factor was not identified, and after the discovery of antidiuretic hormone (ADH), the syndrome of inappropriate ADH secretion (SIADH) was favored as the causal mechanism [12], [13], [14]. CSW is now seldom, if ever, mentioned in the standard textbooks of internal medicine or of electrolyte physiology. However, in recent years, the cause of hyponatremia in neurosurgical patients has been the subject of considerable debate. Evidence has accumulated implicating CSW as the most common cause of hyponatremia in acute brain disease. This has important implications for treatment since fluid restriction, which is appropriate for SIADH treatment, may actually further aggravate volume depletion and cerebral ischemia [8].

Section snippets

Definition of CSW and how it differs from SIADH

CSW may be defined as ongoing excessive natriuresis in patients with intracranial disease, causing volume depletion and hyponatremia. In SIADH, levels of ADH are inappropriately high with respect to serum osmolality and volume status, leading to renal water retention and dilutional hyponatremia. CSW is difficult to distinguish from SIADH when the diagnosis of SIADH is based on the commonly used criteria of: (i) hyponatremia with low plasma osmolality, (ii) urine sodium excretion over 30 mmol/l,

CSW or SIADH?

CSW is now seen as the cause of hyponatremia after SAH and most likely also as the cause of this condition in other intracranial diseases. However, SIADH should still be considered in the differential diagnosis of hyponatremia in patients with intracranial disease [37]. A minority of patients have shown no evidence of volume depletion as measured by PV, TBV, or central venous pressure measurements, which is compatible with SIADH [17], [18], [19], [38]. Also, several case reports have clearly

Pathogenesis and natriuretic factors

Excessive urinary sodium loss occurs in the presence of a high urine osmolality and a urinary sodium concentration that frequently exceeds the plasma sodium concentration [7], [17], [26]. In addition, normokalemia and sometimes hyperkalemia are present in CSW. These findings indicate that the sodium resorption in CSW is primarily disturbed in the medullary collecting duct [45].

Natriuretic peptides have been studied in hyponatremia during acute brain disease, and it follows from their actions

Digoxin-like substances and hyponatremia in acute brain disease

A potassium/sodium shift has been proposed to account for the decrease in plasma sodium concentration in patients with acute brain disease [43]. If such a shift were, in fact, to occur, it could be due to endogenous inhibitors of the Na+/K+-ATPase pump, such as endogenous digoxin-like substances (DLS) [59], [60], [61], [62]. DLS could also contribute to natriuresis by acting on the Na+/K+-ATPase pump in the renal tubules. DLS can be readily measured in the hypothalamus and in the plasma and

Diagnosis and treatment of hyponatremia in acute brain disease

Volume status is the crucial aspect that distinguishes CSW from SIADH. Data obtained from physical examination, clinical parameters, and laboratory values (Table 1) should be considered together when judging the volume status of the patient with hyponatremia.

Measurement of the extracellular volume is not standard practice, as it is elaborate and costly. Plasma renin activity, ADH, and ANP/BNP measurements are not readily available and do not usually differentiate between SIADH and CSW. Any of a

Conclusion

Hyponatremia is a common occurrence during acute brain disease. Although the criteria for SIADH are usually met, the most common pathogenesis involves excessive natriuresis and concomitant diuresis, leading to a negative sodium balance and volume depletion. This is known as the cerebral salt wasting syndrome, and it appears to be mediated, at least in part, by increased plasma concentrations of atrial and brain natriuretic factors. The diagnosis of CSW can be ascertained by showing a decrease

Acknowledgements

The author wishes to thank Professor R. Krediet, Professor L. Arisz, and Dr R. Koopman for their critical reading of the manuscript.

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