Plasma sodium concentration is the main determinant of plasma osmolality and as such, it is maintained within a narrow physiological range by hypothalamic osmoregulation. Hypernatremia is defined as a plasma sodium concentration greater than 145 mmol/l, often classified as mild (plasma sodium 145–150 mmol/l), moderate (plasma sodium 151–155 mmol/l) and severe (plasma sodium >155 mmol/l) [1]. The reported prevalence of hypernatremia varies depending on the clinical setting with retrospective analyses identifying a prevalence of 0.5–1 % in the community but up to 10 % in intensive care units [2], [3]. Usually, excessive water losses alone do not result in hypernatremia as increased plasma osmolality stimulates hypothalamic osmoregulation: secretion of arginine vasopressin (AVP) and thirst [4] (Fig. 1). Hypernatremia occurs when water losses are inadequately replaced which is often the case when patients cannot access free water [5]. Consequently, the elderly, infants and young children, hospitalised patients and any patient with reduced consciousness or reduced cognition is at high risk of developing hypernatremia. Patients with hypernatremia invariably have dysfunctional salt and water homeostasis as a result of either impaired access to free water, impaired thirst response or impaired ability to concentrate urine. Inpatient hypernatremia is most often seen in old, frail, bed bound patients who have appropriate physiological AVP secretion to concentrate urine but inadequate thirst or access to water. Notably, nursing home residents exhibit a ten-fold higher prevalence of hypernatremia compared to community dwelling elderly patients due to cognitive and physical barriers impairing access to free water [6]. Elderly patients have a reduced thirst appreciation [7] and often have iatrogenic precipitants of hypernatremia such as diuretic therapy or intentional fluid restriction in the setting of congestive cardiac failure [8]. Moreover, evidence suggests poor recognition and suboptimal management of hypernatremia in elderly patients resulting in increased morbidity and mortality [6], [9], *[10]. Disorders of AVP, such as AVP deficiency or AVP resistance are rare.

Under normal circumstances, hypothalamic osmoreceptors expressed in the subfornical organ (SFO) and the organum vasculosum of the lamina terminalus (OVLT) are activated in response to an elevation in plasma osmolality stimulating the synthesis and release of AVP. Additionally, in hypotensive states, AVP is released in response to stimulation of baroreceptors in the carotid sinus, aortic arch, cardiac atria and pulmonary venous system [11], [12]. When plasma osmolality rises above ∼285mosmol/kg (known as the osmotic threshold for AVP synthesis and secretion), specialized neurons of the SFO and OVLT depolarize and stimulate the synthesis of AVP in the magnocellular neurons of the supraoptic and paraventricular nuclei of the hypothalamus. AVP is transported as a prohormone coupled with copeptin and neurophysin II, via neurosecretory granules to the posterior pituitary, where it is stored in nerve termini. Following osmoreceptor stimulation AVP is cleaved from it’s prohormone and released into systemic circulation where it binds to vasopressin receptors including vasopressin 2 (V2) receptors on the basolateral membrane of renal collecting duct principal cells [4]. An intracellular cascade ensues, increasing intracellular cyclic adenosine monophosphate (cAMP) which promotes protein kinase A-mediated translocation of aquaporin 2 (AQ2) water channels from intracellular vesicles to the luminal membrane of the collecting duct. AQ2 water channels at the luminal membrane allow reabsorption of water from urine into blood along osmotic gradients. The SFO and OVLT also stimulate the thirst centre in the cerebral cortex at a slightly higher osmotic threshold than AVP, promoting free water intake [13]. The net result of urinary concentration and free water intake normalizes plasma osmolality and sodium concentration (Fig. 1). At plasma osmolalities below the osmotic thresholds both AVP release and thirst are inhibited, allowing hypotonic diuresis.

Total body water (TBW) consists of two compartments, extracellular fluid (ECF) and intracellular fluid (ICF), and is estimated to be approximately 60 % of body weight in men and 50 % in women [14]. Normally, ECF and ICF account for 40 and 60 % of TBW, respectively [5]. Osmolalities in the ECF and ICF must be equal to allow free movement of water across cell membranes. When hypernatremia occurs, there is increased osmolality of the ECF compartment. To overcome the osmotic gradient between the ECF and ICF, water moves from the intracellular space resulting in cellular shrinkage and, at the level of the brain, reduced brain volume [15]. The brain undergoes adaptive processes to normalize brain volume involving rapid cellular uptake of inorganic ions (sodium, potassium and chloride) followed by a more delayed accumulation of organic osmolytes (myo-inositol, amino acids) [5]. Acute hypernatremia (<48 h) is often accompanied with significant neurological symptoms (lethargy, weakness, seizures or even coma) due to these changes in brain volume and should be immediately corrected. Where the sodium trajectory is unknown or elevated for more than 48 h (chronic hypernatremia) osmotic brain adaptation has occurred, less symptoms are evident, and expert opinion favours a slower rate of correction of no more than 0.5 ml/l per hour and an maximal absolute change of 10 mmol/l per day [5]. Most of the evidence for slow correction in hypernatremia is founded in cases of paediatric hypernatremia [16], [17], [18]. The maximum safe rate of correction in adults has not been established. Reassuringly, there have been no reports of cerebral oedema due to rapid correction of hypernatremia in adults. In fact, a large retrospective analysis of 4265 patients identified longer hospital stay and higher mortality with slow correction of hypernatremia [19]. A reasonable approach, given the theoretical risk, is to aim for correction of approximately 10 mmol/l per day, however, if this maximal target is inadvertently exceeded, plasma sodium does not need to be therapeutically raised again [20]. Results are awaited of a randomized clinical trial comparing the efficacy and safety of rapid intermittent bolus compared to slow infusion of electrolyte-free solution in management of severe hypernatremia [21].

Mortality associated with hypernatremia varies from 20 % to 60 % depending on severity of hypernatremia, comorbidities and associated illnesses [3], *[15], [22], [23]. Hypernatremia is also associated with prolonged length of stay and increased perioperative morbidity including perioperative coronary events, pneumonia and venous thromboembolism [3], [24]. In traumatic brain injury, severe hypernatremia confers an eight-fold increased risk of mortality [25], often heralding the onset of rising intracranial pressure, progressing to tonsillar herniation and death [26]. Delayed correction of hypernatremia, irrespective of severity of hypernatremia, results in increased in-hospital and 30-day mortality *[19], [27]. Despite this, there are numerous reports of suboptimal management and assessment of inpatient hypernatremia [9], [27], [28].