Therapeutic Advances in Drug Safety Review

Ther Adv Drug Saf

Management of hyponatraemia in older (2011) 2(1) 9—17
DOI: 10.1177/
people: old threats and new opportunities 2042098610394233
! The Author(s), 2011.
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Roy L. Soiza and Hannah S.C. Talbot http://www.sagepub.co.uk/
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Abstract: Hyponatraemia is the commonest electrolyte abnormality seen in clinical practice,

and is especially prevalent in frail, older people. However, the serious implications of hypo-
natraemia in this age group are seldom recognized by clinicians. Hyponatraemia is associated
with osteoporosis, impaired balance, falls, hip fractures and cognitive dysfunction. Even mild,
apparently asymptomatic hyponatraemia is associated with prolonged stays in hospital, insti-
tutionalization and increased risk of death. Emerging evidence of the potential benefits of
improved treatment of hyponatraemia is slowly generating renewed clinical interest in this
area. The development of specific vasopressin-2 receptor antagonists (vaptans) has the
potential to revolutionize the management of hyponatraemia, in particular for the syndrome of
inappropriate antidiuretic hormone. However, challenges remain for the attending physician.
Diagnosing the cause or causes of hyponatraemia in older people is difficult, and incorrect
diagnosis can lead to treatment that worsens the electrolyte imbalance. Established treat-
ments are often poorly tolerated and patient outcomes remain poor, and the role of vaptans in
the treatment of older people is unclear. This review summarizes the existing evidence base
and highlights areas of controversy. It includes practical guidance for overcoming some
common pitfalls in the management of the elderly patient with hyponatraemia.

Keywords: arginine vasopressin, elderly, hyponatraemia, syndrome of inappropriate antidi-

uretic hormone, tolvaptan, vasopressin receptor antagonist

Introduction caused chiefly by excessive entry of water into Correspondence to:

Hyponatraemia is the commonest electrolyte
abnormality seen in clinical practice. It is recog-
nized that severe hyponatraemia can be symp-
tomatic and life threatening. However, there is
comparatively little awareness of the growing evi-
dence that even a mild degree of chronic hypona-
traemia can have serious clinical consequences.
Similarly, the importance of the speed of onset
of hyponatraemia as a prognostic marker is not
always appreciated. This review highlights his-
toric difficulties and important new insights and
developments in the management of hyponatrae-
mia in older people.
Presentation
Hyponatraemia is often discovered incidentally
on routine blood testing. It is classically divided
into mild (130—134 mmol/l), moderate
(125—129 mmol/l) and severe (<125 mmol/l).
Symptoms attributable to hyponatraemia are
Dr Roy L. Soiza, MB, ChB,
brain cells and include malaise, headache, MRCP(UK)
nausea and confusion. Since brain cells can Department of Medicine
for the Elderly, Woodend
adapt to changes in plasma tonicity over time, Hospital, Eday Road,
more severe symptoms such as seizures, coma Aberdeen AB15 6XS, UK
roy.soiza@nhs.net
or even death occur mainly in rapid-onset hypo-
Hannah S.C. Talbot, BA
natraemia. However, in older people, hypona- School of Medicine and
traemia may be an important contributor to the Dentistry, University of
Aberdeen, Aberdeen, UK
major geriatric syndromes such as immobility
and falls [Renneboog et al. 2006], bone deminer-
alization [Verbalis et al. 2009], hip fractures
[Gankam Kegne et al. 2008] and cognitive
impairment [Miller, 2006].
Prevalence
Hyponatraemia complicates a wide range of clin-
ical entities but is especially prevalent in older
people. The overall prevalence in the hospital
population is about 15% [Upadhyay et al. 2006]
but is much higher in certain vulnerable popula-
tions, such as admissions to acute geriatric

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Therapeutic Advances in Drug Safety 2 (1)

medicine, where hyponatraemia is observed in to improvements in mortality, though there is

almost half of all cases [Hoyle et al. 2006].
Chronic hyponatraemia is present in 18% of
nursing home residents [Miller et al. 1995]. The
reasons for the higher prevalence in old age relate
to increased prevalence of comorbidity, high rates
of prescribing of drugs known to cause hypona-
traemia and ageing-related changes to homeo-
static mechanisms (see Table 1) [Soiza et al.
2008].
Prognosis
Mortality depends on the severity of hyponatrae-
mia and can approach 50% when severe [Clayton
et al. 2006]. However, there is often a mismatch
between the severity of the symptoms and the
degree of hyponatraemia [Arieff et al. 1976].
This is partly because the speed of onset of hypo-
natraemia is of greater prognostic significance
than the degree of hyponatraemia itself. Two
groups have independently shown that the drop
in hyponatraemia had a greater effect than sever-
ity of hyponatraemia on key clinical outcomes,
such as length of stay in hospital, mortality and
institutionalization [Chua et al. 2007; Gill et al.
2006]. Nevertheless, a large prospective study of
around 98,000 admissions to hospital showed
even mild hyponatraemia is associated with
increased mortality [Walkar et al. 2009]. There
is still some debate over how much of the
increased risk of death is directly attributable to
hyponatraemia, and how much is due to under-
lying disease. Consequently, it remains unclear if
better management of hyponatraemia itself leads
growing evidence that it might [Walkar et al.
2009; Clayton et al. 2006; Hoorn et al. 2006].
Moreover, the finding that the drop in serum
sodium during hospital admission is strongly
associated with adverse outcome in older people
[Chua et al. 2007] also suggests that active strat-
egies to prevent or minimize hyponatraemia in
hospital will improve outcomes. However, evi-
dence of improvement in clinically meaningful
outcomes with better management of hypona-
traemia remains very limited and equivocal.
Underlying causes
Although hyponatraemia has many potential
causes, the commonest cause is believed to be
the syndrome of inappropriate antidiuretic hor-
mone (SIADH) [Hannon and Thompson, 2010;
Huda et al. 2006]. Given the high prevalence of
hyponatraemia in older people, SIADH should
also be highly prevalent in this population.
However, the causes of hyponatraemia in older
people have rarely been specifically studied, and
older people are notoriously underrepresented in
the medical literature. A very recent Israeli study
made the important finding that hyponatraemia
in older people is often multifactorial rather than
attributable to a single entity [Shapiro et al.
2010]. The authors diagnosed SIADH in 39
out of 86 (45%) elderly individuals, making it
the commonest cause. However, the reliability
of these data has been challenged [Soiza and
Hoyle, 2010] because the diagnosis of
SIADH depends crucially on patients being in

Table 1. Reasons for increased prevalence of hyponatraemia in old age.

High prevalence of conditions known to cause hyponatraemia
 Chronic congestive cardiac failure
 Chronic kidney disease
 Dehydration
 Bronchopneumonia
 Neurological disease, including stroke
 Malignancy
Frequently prescribed drugs causing hyponatraemia
 Thiazide diuretics
 Selective serotonin reuptake inhibitors
 Neuroleptic medications
 Carbamazepine.
Age-related changes in homeostatic mechanisms that contribute to hyponatraemia
 Decreased glomerular filtration rate
 Decreased urinary concentrating ability
 Decreased aldosterone levels
 Increased levels of arginine vasopressin
 Increased levels of atrial natriuretic peptide
 Lower sensitivity of thirst mechanisms
 Difficulty imbibing fluids (e.g. because of physical or cognitive impairment)

10 http://taw.sagepub.com

a euvolaemic state, and there is no reliable bio-
marker of volaemic status in older people [Hoyle
et al. 2010]. Further research is required to better
delineate the common causes of hyponatraemia
in older people and a reliable biomarker of volae-
mic status needs to be developed.
Management
Management of hyponatraemia is notoriously
challenging and evidence suggests it is often
poorly managed [Thompson, 2010; Huda et al.
2006; Baron and Hutchinson, 2005]. The key to
successful treatment is accurate diagnosis of the
underlying causes. Diagnostic algorithms have
been developed to help with this, with determi-
nation of volaemic status a key step in guiding
further management [Verbalis et al. 2007].
However, because of the multiple pathologies
underlying hyponatraemia in older people
[Shapiro et al. 2010], coupled with discrepancies
in clinical assessment [Hoyle et al. 2010], the
result is often an unclear diagnosis and incorrect
treatment. Owing to poorer compensation mech-
anisms, the frail older person with concomitant
disease has little room for treatment error, so safe
and effective initial therapeutic management is
essential for optimal outcomes. However, estab-
lished treatments such as saline infusions, fluid
restriction, demeclocycline, loop diuretics, urea
and lithium are often unpredictable, with variable
efficacy and toxicity [Cawley, 2007].
Correction of hyponatraemia itself probably
improves outcomes [Verbalis et al. 2007;
Clayton et al. 2006]. When hyponatraemia is of
rapid onset (<48 h) and associated with severe
neurological symptoms, a rapid but modest cor-
rection (2—4 mmol/l over 1 h) is recommended
with a bolus infusion of 100 ml of 3% saline
[Verbalis et al. 2007]. In this situation, even
a small decrease in cerebral oedema can have
a major effect on raised intracranial pressure
[Battison et al. 2005]. Failure to correct hypona-
traemia by more than 4 mmol/l in 24 h is associ-
ated with poor outcome [Nzerue et al. 2003].
However, if correction of serum sodium is too
rapid (>12 mmol/l in 24 h) this can result in
potentially fatal osmotic demyelination syn-
drome. The challenge for clinicians is to provide
therapy that keeps the patient safe from serious
complications of hyponatraemia while avoiding
correction rates that risk iatrogenic injury
[Sterns et al. 2009]. An important expert consen-
sus guideline developed in 2007 noted the ‘sub-
stantial morbidity and mortality’ of severe
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RL Soiza and HSC Talbot
hyponatraemia observing that ‘optimal treatment
strategies (in severe hyponatraemia) are not
established’ [Verbalis et al. 2007]. Much ambigu-
ity remains with conventional treatment for
osmotic demyelination syndrome since it is diffi-
cult to determine hyponatraemic aetiology and
duration, while consensus on the rate of correc-
tion remains elusive [Snell and Bartley, 2008].
Nevertheless, most experts agree that correction
should never exceed 10 mmol/l in 24 h or
18 mmol/l in 48 h [Verbalis et al. 2007].
Treatment of chronic hyponatraemia has often
been neglected by clinicians, probably because
it is incorrectly perceived to be benign or because
it is challenging to diagnose and treat.
Nevertheless, correction of chronic hyponatrae-
mia has the potential to deliver significant indi-
vidual and public health benefits. A number of
therapeutic strategies are available, and the devel-
opment of oral vasopressin receptor antagonists
has the potential to revolutionize this area of
practice.
Established therapies
Isotonic saline (0.9%) infusion
Intravenous isotonic saline is used to treat acute
hypovolaemic hyponatraemia. Especially in the
elderly population, immobility, reduced cognitive
function, comorbidities and malnutrition are the
main compounding factors that may lead to
dehydration. Treatment is dependent on accurate
assessment of a patient’s volaemic state, which
includes assessing skin turgor, jugular venous
pressure, postural changes in blood pressure
and pulse, buccal mucous membranes, degree
of thirst and presence of oedema. Clinical assess-
ment is often incorrect, resulting in older people
with fluid depletion being wrongly treated with
fluid restriction, ultimately worsening the hypo-
natraemia. Furthermore, no clinical sign or col-
lective set of signs has proven reliability in older
people with hyponatraemia [Hoyle et al. 2010],
for example, about a fifth of healthy, community-
dwelling people aged 65 or over have postural
hypotension, an otherwise good marker of hypo-
volaemia in younger people [Rutan et al. 1992].
Measurement of urinary sodium and osmolality
is helpful in diagnosing the cause of hyponatrae-
mia [Soiza et al. 2008], but does not normally
help distinguish hypovolaemia from SIADH. To
deal with this uncertainty, we recommend seek-
ing expert advice and considering a trial of 1 l
intravenous isotonic saline infusion over 2 h in
11
Therapeutic Advances in Drug Safety 2 (1)
symptomatic patients with severe hyponatraemia
when there is doubt if they are hypovolaemic or
euvolaemic. Serum sodium and evidence of
hypervolaemia should be checked thoroughly as
there is a theoretical possibility of pulmonary
oedema and overly rapid correction of hypona-
traemia, particularly in older people, so expert
clinical supervision is recommended. A good
response in serum sodium immediately after the
infusion would be most consistent with hypovo-
laemia, while hyponatraemia in SIADH does not
respond to 0.9% saline [Verbalis et al. 2007].
Consideration could be given to a further and
final 500 ml trial over 2 h if the results and clinical
progression are equivocal and there is no suspi-
cion of hypervolaemia. It is important to note
that this method has not been evaluated in any
scientific study so its sensitivity and specificity is
unknown, but may be much better tolerated and
give faster results than a trial of enforced fluid
restriction. Ultimately, clinicians should always
be prepared to revise their diagnosis and thera-
peutic strategy if there is no improvement in
hyponatraemia.
Discontinuation of drugs
Eliminating possible causes of hyponatraemia is
an essential part of treatment. A medication
review of the patient should be carried out and
careful consideration should be given to
substituting, reducing the dose or stopping med-
ications associated with low sodium. The poten-
tial conflict between the need to treat
hyponatraemia and the underlying indication
for the responsible medication must be acknowl-
edged and may need discussion and expert advice
(e.g. from a geriatrician, endocrinologist or psy-
chiatrist, depending on the situation).
Polypharmacy is commonly encountered in
older people. In particular, diuretics and selective
serotonin reuptake inhibitors are frequently pre-
scribed, both of which can lead to low serum
sodium. Prescribed medications are a contribut-
ing factor in the development of severe hypona-
traemia in almost half of all cases seen in older
people in hospital [Shapiro et al. 2010].
Hyponatraemia as a result of drug—drug interac-
tions is also an important consideration. Thiazide
diuretics and nonsteroidal anti-inflammatory
drugs increase the risk of developing hyponatrae-
mia in older people [Aaseth et al. 2001].
Discontinuation of drugs can be combined with
an isotonic saline infusion with careful monitor-
ing of the clinical and biochemical response.
12
Fluid restriction
Fluid restriction, to around 800 ml/day is used
when a patient presents with euvolaemic hypona-
traemia such as in SIADH [Kumar and Berl,
1998]. This form of treatment for hyponatraemia
is often slow and can be difficult for patients to
maintain in the long term because of hidden liq-
uids in foods and discomfort with thirst [Zieste
et al. 2009; Adrogue and Madias, 2000].
Unfortunately, thirst remains a prominent fea-
ture in SIADH because of downward resetting
of the thirst ‘osmostat’ [Smith et al. 2004], that
is, thirst is induced at a lower plasma osmolality
than is normal.
Demeclocycline
Demeclocycline is a longer-term treatment
option used in euvolaemic patients with
SIADH, in particular secondary to a malignancy.
It is often reserved for cases in which fluid restric-
tion has failed. At the level of the kidneys, deme-
clocycline works by achieving a nephrogenic
diabetes insipidus effect through an unknown
mechanism in around 60—70% of cases [Zieste
et al. 2007], but is ineffective in the remainder.
One issue is the unpredictability of its effect,
occurring any time from two to several days
after initiation, and caution must be taken to
avoid overly rapid correction and even develop-
ment of hypernatraemia. Demeclocycline is
sometimes tolerated poorly by patients because
it can cause nausea and skin photosensitivity, as
well as being associated with nephrotoxicity
[Curtis et al. 2002].
Hypertonic saline (3% or 5%)
Hypertonic saline is very rarely indicated, and
few experts recommend its use, but it can be
given as an infusion or in a bolus of either 3%
or 5% solution. The 5% solution is not recom-
mended to avoid confusion with 5% dextrose
solution. Hypertonic saline is only used in the
treatment of acute symptomatic hyponatraemia
characterized by severe symptoms, such as loss
of consciousness and seizures [Gross et al.
1998]. Treatment difficulty lies in getting an opti-
mum balance, as too slow a correction or over-
correction of hyponatraemia can lead to further
complications [Sterns et al. 1994].
Overcorrection leading to hypernatraemia as a
result of treatment may require supplementation
with hypotonic fluids [Soupart and Decaux,
1996]. These problems can be minimized with
checks every 2 h of serum sodium so that the
treatment is tailored to the individual patient
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[Moritz and Ayus, 2010]. Provision of such
intensive monitoring and the risks of complica-
tions restrict usage of hypertonic saline to
patients in intensive care or high-dependency
units under specialist supervision.
Salt tablets
The concept of treating low serum sodium with
sodium supplements has intuitive appeal.
However, sodium chloride tablets are seldom
helpful in treatment because hyponatraemia usu-
ally reflects an imbalance in total body water,
rather than sodium depletion. Even in conditions
associated with high sodium losses, daily dietary
sodium intake is almost always adequate to main-
tain normal sodium concentration [Hew-Butler
et al. 2006]. Cases with poor oral intake are nor-
mally best treated with intravenous supplementa-
tion. Salt tablets should be avoided in most
patients with euvolaemic and hypervolaemic
hyponatraemia because the resulting thirst and
increased water intake and retention can worsen
hyponatraemia.
Diuretics
Loop diuretics such as furosemide are indicated
in all forms of hypervolaemic hyponatraemia
[Verbalis et al. 2007]. Loop diuretics can help
to correct hyponatraemia in SIADH [Hantman
et al. 1973], but they can also worsen hyponatrae-
mia by increasing urinary sodium excretion
[Gross, 2008]. Therefore, they are not recom-
mended for use in euvolaemic hyponatraemia.
There are no studies of diuretic therapy in the
context of SIADH in older people specifically.
Thiazide diuretics have no therapeutic role and
are frequently implicated in the aetiology of
hyponatraemia in older people [Shapiro et al.
2010].
Other potentially therapeutic agents that are
not recommended
Lithium reduces the maximum concentrating
ability of the kidney, helping to minimize
sodium loss and water retention [Waller et al.
1988]. Lithium induces a nephrogenic diabetes
insipidus effect in a third of cases [Baylis and
Heath, 1978] by downregulating vasopressin-sti-
mulated aquaporin-2 expression [Nielsen et al.
2008]. However, expert consensus is that lithium
is less desirable than alternatives due to its incon-
sistent results and significant adverse effects and
toxicities [Sherlock and Thompson, 2010;
Verbalis et al. 2007]. Urea, given orally or as an
infusion, has been suggested as an option for
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RL Soiza and HSC Talbot
euvolaemic hyponatraemia, particularly SIADH.
Urea can produce a rapid correction of hypona-
traemic brain oedema while being associated with
a reduced risk of myelinolysis [Sterns et al. 1994].
The benefits of oral urea in SIADH are that it
allows a less rigorous fluid restriction, although
difficulties include lack of availability in some
countries, bad taste and development of azotemia
[Verbalis et al. 2007]. Consequently, lithium and
urea are seldom used in the treatment of hypona-
traemia in older people.
Vasopressin receptor antagonists
Owing to the high prevalence of SIADH, the
development of specific antidiuretic hormone
(arginine vasopressin) receptor blockers was
long awaited. These agents are theoretically supe-
rior to the alternatives above in the treatment of
SIADH as they target the underlying pathological
mechanism specifically. Their potent diuretic
effect means they may also have a role in hyper-
volaemic hyponatraemia [Shoaf et al. 2007].
Their effect in this regard is often termed ‘aqua-
retic’ because they promote excretion of solute-
free water, as opposed to the natriuresis seen with
conventional diuretic drugs. The relevant recep-
tor is the V2 receptor found on the basolateral
membrane of the cells in the distal convoluted
tubules and the collecting ducts of the kidney,
as well as the vascular endothelium. There are
two other vasopressin receptors (V1a and V1b)
whose activation causes several effects, including
vasoconstriction, platelet aggregation, inotropic
stimulation (V1a) and pituitary adrenocorticotro-
pic hormone secretion (V1b) [Thibonnier et al.
1998].
The first vasopressin receptor antagonist (vaptan)
to be developed was conivaptan, which acts on
both V1a and V2 receptors [Decaux, 2001].
Conivaptan has been licensed in the USA for
the treatment of euvolaemic or hypervolaemic
hyponatraemia for about 5 years. Fears about
the potential for drug interactions resulted in
US Food and Drug Administration approval for
use in hospital for a maximum of 4 days and in
intravenous form only, despite being potentially
suitable for oral administration [Ghali et al.
2006]. Interest in this group of drugs has been
reinvigorated with the more widespread availabil-
ity of the first oral vaptan approved for long-term
use, tolvaptan. In the USA, tolvaptan has a
license for the treatment of both hypervolaemic
hyponatraemia and SIADH, but in the UK it
is currently restricted to the SIADH only.
13
Therapeutic Advances in Drug Safety 2 (1)
All vaptans are inhibitors of the cytochrome P450
3A4 system, with conivaptan displaying particu-
lar potency in this regard, hence the limitations
on its license. Tolvaptan also differs from coni-
vaptan in being a selective V2 receptor antagonist.
Other selective V2 receptor antagonists include
mozavaptan [Saito et al. 1997], lixivaptan
[Wong et al. 2003] and satavaptan [Soupart
et al. 2006], but these are not available to pre-
scribing clinicians at the time of writing.
Safety and adverse effects
In two randomized controlled trials that included
patients with hyponatraemic SIADH (n ¼ 91),
heart failure (n ¼ 71) or cirrhosis (n ¼ 63) aged
up to 100 years (SALT-1 and SALT-2), the prev-
alence of serious adverse effects after treatment
with tolvaptan was similar to that seen with pla-
cebo [Schrier et al. 2006]. Common adverse
effects in the first month of therapy included
thirst (14%), dry mouth (13%), weakness (9%),
constipation (9%) and nausea (8%). Tolvaptan
also demonstrated a good safety profile after a
median 9.9 months of treatment in a large trial
of patients with heart failure [Konstam et al.
2007], but only 10% of patients had hyponatrae-
mia. The long-term safety profile of tolvaptan in
the setting of hyponatraemia was assessed in an
open-label extension of the SALT trials called
SALTWATER [Berl et al. 2010]. According to
the authors, six of 111 patients in the study had
to discontinue treatment because of probable
adverse drug reactions (each for a different
reason: ventricular tachycardia, irritability,
hypernatraemia, anorexia, renal failure, pruri-
tus). Pollakiuria, polydipsia and polyuria were
also seen, but in only 10% or less of patients.
This reassuring adverse-effect profile is perhaps
surprising given the extreme diuresis observed in
early studies, typically averaging over 5 l of urine
excretion per day [Shoaf et al. 2007].
It is uncertain whether tolvaptan would be as well
tolerated in frail, older people. Despite the inclu-
sion of some extremely elderly people in trials of
tolvaptan, the mean age of participants was just
60 years in SALT-1, 62 years in SALT-2 and 65
years in SALTWATER. The tolerability in the
age group with arguably the most to gain from
this treatment is therefore still unclear and it
seems reasonable to postulate that some frailer
patients would require urinary catheterization
and even intravenous saline infusion to protect
against incontinence and excessive sodium and
water loss.
14
Efficacy and effectiveness
Results from SALT-1 and SALT-2 showed con-
vincingly that tolvaptan was superior to placebo
at increasing serum sodium concentration within
24 h and up to 30 days after dose administration
[Schrier et al. 2006]. The improvement in sodium
was accompanied by a significant improvement in
symptom score using the Mental Component of
the Medical Outcomes Study 12-item Short-
Form General Health Survey [Ware et al. 1995].
Tolvaptan was also more effective than fluid
restriction at normalizing serum sodium in one
small, randomized trial [Gheorghiade et al.
2006]. However, serum sodium concentration
was found to fall again within a week of disconti-
nuing the drug [Schrier et al. 2006]. Indeed, 85%
of patients who went on to participate in the
open-label SALTWATER trial were hyponatrae-
mic again at entry [Berl et al. 2010], suggesting
that chronic treatment with tolvaptan would be
required to maintain normonatraemia. Given the
high cost of the drug (currently priced in the UK
at approximately £75 (E86/US$119) per day of
treatment [British National Formulary]) it
remains unclear what its role in clinical practice
will be.
Tolvaptan was not significantly better than pla-
cebo at improving mortality in the EVEREST
study of patients with chronic heart failure
[Konstram et al. 2007], although a subgroup
analysis of patients with hyponatraemia has not
yet been published. While there remains a lack of
convincing evidence on ‘hard’ endpoints, such as
improved quality of life, decreased mortality,
reduction in length of stay in hospital or evidence
of cost effectiveness, it is unlikely to become a
commonly used therapy in clinical practice. It
may nevertheless find niche roles for short-term
use in relatively acute, severe euvolaemic hypona-
traemia (e.g. after chemotherapy in patients with
cancer), or in symptomatic, chronic hyponatrae-
mia secondary to SIADH when fluid restriction
has failed and commissioners or insurers are gen-
erous enough to cover the cost of the drug.
Although these findings may initially suggest an
extremely limited role for the potential use of
vaptans in very elderly people, this may prove to
be their most lucrative market for the following
reasons: hyponatraemia is more common in this
increasingly prevalent age group; the clinical
implications of any improvements in balance
and cognition will be much greater than in a
younger population; the economic burden of
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falls [Heinrich et al. 2010] and cognitive impair-
ment [Luengo-Fernandez et al. 2010] is huge;
and the shortened life expectancy of older
people with hyponatraemia may make the pros-
pect of potentially lifelong treatment more palat-
able to healthcare funders.
Conclusions
Hyponatraemia in older people remains a
common yet neglected area of clinical practice.
Recent advances in the understanding of the
pathological associations of even apparently
asymptomatic chronic hyponatraemia, and the
development of new therapeutic options have
created renewed interest in this condition.
Improved treatment of hyponatraemia could deli-
ver significant health and economic benefits in
the form of fewer falls and hip fractures,
improved cognition, and reductions in hospital
stay and institutionalization. However, evidence
of these benefits with improved management
remains scant and clinicians still face the chal-
lenge of appropriate diagnosis and cost-effective
selection of therapeutic options. Future work
should focus on improving current diagnostic
tools or algorithms. In particular, a valid bio-
marker of volaemic status in older people with
hyponatraemia is especially desirable. New and
emerging therapies should focus on gathering evi-
dence of their safety and benefits in terms of
‘hard’ clinical outcomes and cost effectiveness.
Funding
This research received no specific grant from any
funding agency in the public, commercial, or not-
for-profit sectors.
Conflict of interest statement
Dr Soiza is a member of an Otsuka
Pharmaceuticals (UK) advisory board.
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