A Systematic Approach to the Treatment of Hyponatraemia.

The work in this thesis was designed to develop an evidence base for the mainstays of treatment of acute and chronic hyponatraemia, and to contribute to our understanding of the morbidity and mortality associated with hyponatraemia. The work provides the first head to head comparison of bolus and slow infusion of 3% saline in acute syndrome of inappropriate antidiuresis (SIAD), and demonstrates bolus administration of 3% saline is associated with faster initial elevation of plasma sodium concentration and improvement in GCS, thus supporting the switch to bolus treatment of symptomatic acute SIAD. We present the first prospective randomised controlled trial data for fluid restriction in chronic SIAD, using prospective data in a well-defined cohort of patients. The results highlight the suboptimal efficacy of fluid restriction in a significant proportion of patients with chronic SIAD. The thesis also illustrates how improvements in the management approach to hyponatraemia in our hospital have led to a reduction in mortality in patients with severe hyponatraemia over time. While hyponatraemia-treatment rates are higher in elderly patients than their younger counterparts with hyponatraemia, plasma sodium is more often uncorrected at discharge. Hyponatraemia in both age groups is associated with increased mortality compared with eunatraemic controls, but the impact is greater in younger patients. The data produced from these studies emphasise the clinical need for other treatment strategies for chronic SIAD, particularly if a clinically significant reduction in morbidity is to be targeted, both in clinical practice and in future research studies.