THERAPEUTIC RECOMMENDATIONS FOR MANAGEMENT OF SEVERE HYPONATREMIA - CURRENT CONCEPTS ON PATHOGENESIS AND PREVENTION OF NEUROLOGIC COMPLICATIONS

Patients with hyponatremia are exposed to major neurological complicat ions. On the one hand hyponatremia itself produces brain edema, increa sed intracranial pressure which potentially leads to subsequent neurop athological sequelae or death. On the other hand excessive correction could be followed by development of brain demyelinating lesions (centr al pontine or extrapontine myelinolysis) with major disability or fata l outcome. Understanding of brain adaptative mechanisms to changes in osmolality largely contributes to explain these neurological events. W hen serum sodium decreases, the brain prevents swelling by extruding e lectrolytes and organic osmolytes, a process almost fully achieved aft er 48 h. Conversely, during subsequent increase in serum sodium, reest ablishment of intracerebral osmolytes occurs but their reuptake is mor e delayed (+/- 5 days). In both circumstances, these mechanisms can be overwhelmed, leading to brain damage. Acute hyponatremia (< 48 h) is generally hospital-acquired, mainly in the postoperative state and/or after excessive fluid administration. After abrupt fall in serum sodiu m, seizure, respiratory arrest and coma may develop and these manifest ations are sometimes explosive in nature. Recognition of even minor sy mptoms is crucial and implies prompt correction. There is generally no risk of brain myelinolysis in acute hyponatremia. Some factors are su spected to aggravate the prognosis of hyponatremic encephalopathy, inc luding female gender (menstruant women), hypoxia and young age. Chroni c hyponatremia (> 48 h) usually develops outside the hospital and is g enerally better tolerated. The risks of brain myelinolysis can be larg ely reduced by limiting the correction level to less than or equal to 15 mEq/l/24 h. However, if necessary, the initial rate of correction c an be rapid provided that the final correction remains < 15 mEq/l/24 h . However, when other recognized risk factors for myelinolysis (hypoka lemia, liver disease, poor nutritional state, bums) are present, corre ction should not exceed 10 mEq/l/24 h. Demyelinization is also observe d in hypernatremia but it follows greater (50%) increase in serum sodi um than from hyponatremic baseline. For symptomatic hyponatremia, rapi d correction is usually obtained by hypertonic saline (3%) infusion. A nother option consists in administration of intravenous or oral urea. Urea allows a rapid reduction of brain edema and intracranial pressure which is followed by subsequent correction of hyponatremia. Experimen tal data also suggest that treatment of hyponatremia with urea is asso ciated with a lower incidence of myelinolysis. In hyponatremic patient s without symptoms, there is no need for rapid correction and the trea tment should be more conservative. Close monitoring of the serum sodiu m is indicated initially and if necessary, correction must be stopped and diuresis interrupted with dDAVP. Given recent experimental data, i n patients overly corrected (Delta SNa > 15 mEq/l/24 h), the risk of m yelinolysis could be greatly reduced by rapidly decreasing the serum s odium through hypotonic fluids administration and dDAVP.