Hyponatraemia
Hyponatraemia - Summary
Hyponatraemia is defined as a serum sodium concentration of less than 135 mmol/L. It is the most common electrolyte disorder encountered in clinical practice.
The severity of hyponatraemia can be classified by the serum sodium concentration.
Mild hyponatraemia when the serum sodium concentration is 125–134 mmol/L.
Moderate hyponatraemia when the serum sodium concentration is 115–124 mmol/L.
Severe hyponatraemia when the serum sodium concentration is less than 115 mmol/L.
Volume status can be used to classify hyponatraemia:
Hypovolaemic hyponatraemia — decreased total body water and greatly decreased total body sodium.
Hypervolaemic hyponatraemia — increased total body water and increased total body sodium.
Euvolaemic hyponatraemia — slightly increased total body water and normal total body sodium.
The rate of onset of hyponatraemia can also be used for classification. However, in practice, most people present with hyponatraemia of an undetermined duration.
Acute hyponatraemia is defined as having had a duration of less than 48 hours.
Chronic hyponatraemia is defined as having a duration of 48 hours or more.
The cause of hyponatraemia is often multifactorial. Common causes include:
Drugs (for example, thiazide diuretics).
Syndrome of inappropriate antidiuretic hormone secretion.
Heart failure.
Hyponatraemia is usually an incidental finding on routine blood tests. Most people with hyponatraemia are asymptomatic, particularly if hyponatraemia is mild and has developed slowly. When symptoms are present, they are often non-specific and are related to both the severity of the hyponatraemia and its rate of onset.
Early symptoms include:
Anorexia.
Nausea.
Lethargy and apathy (associated with slow-onset hyponatraemia).
Late symptoms (associated with severe or rapid-onset hyponatraemia).
Disorientation.
Agitation.
Seizures.
Coma.
If not already measured, or when hyponatraemia is an incidental finding on a routine blood test, blood should be taken to measure the serum sodium concentration and plasma osmolality to confirm the diagnosis of hyponatraemia. Confirming hyponatraemia is important as borderline serum sodium concentrations may simply reflect a variation in laboratory measures.
If the plasma osmolality is normal (285–295 mOsmol/Kg) or high (greater than 295 mOsmol/Kg), blood should be taken to measure serum lipid, glucose, and protein concentrations to exclude fictitious and redistributive hyponatraemia.
If hyponatraemia is severe or significantly symptomatic, admission to hospital for urgent treatment should be arranged.
Advice from an endocrinologist is required if the person has asymptomatic, moderate hyponatraemia.
A cause of hyponatraemia should be sought in a person with asymptomatic, mild hyponatraemia.
In all people, the serum sodium measurement should be repeated after 1 week, to exclude a rapidly decreasing serum sodium concentration that will require admission to hospital.
If the person has an acute illness that may be contributing to the hyponatraemia, the underlying problem should be treated and the serum sodium concentration rechecked after 2 weeks.
Drugs that may be contributing to the hyponatraemia should be stopped if appropriate, and the serum sodium concentration rechecked after 2 weeks.
Have I got the right topic?
This CKS topic covers the diagnosis of hyponatraemia, how to determine the underlying cause, and the management of hyponatraemia in primary care; it briefly describes the secondary care management of hyponatraemia.
The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary health care.
How up-to-date is this topic?
How up-to-date is this topic?
Changes
October 2010 to January 2011 — this is a new CKS topic. The evidence-base has been reviewed in detail, and recommendations are clearly justified and transparently linked to the supporting evidence.
Update
New evidence
Evidence-based guidelines
No new evidence-based guidelines since 1 November 2010.
HTAs (Health Technology Assessments)
No new HTAs since 1 November 2010.
Economic appraisals
No new economic appraisals relevant to England since 1 November 2010.
Systematic reviews and meta-analyses
Systematic reviews published since the last revision of this topic:
Jaber, B.L., Almarzougi, L., Borgi, L., et al. (2011) Short-term efficacy and safety of vasopressin receptor antagonists for treatment of hyponatremia. American Journal of Medicine 124(10), 997.e1-997.e9. [Abstract] [Free Full-text]
Primary evidence
No new randomized controlled trials published in the major journals since 1 November 2010.
New policies
No new national policies or guidelines since 1 November 2010.
New safety alerts
No new safety alerts since 1 November 2010.
Changes in product availability
No changes in product availability since 1 November 2010.
Goals and outcome measures
Goals
To support primary health care professionals to:
Detect and diagnose hyponatraemia
Determine the likely underlying cause, if possible and appropriate
Offer appropriate management to people with hyponatraemia depending on the likely underlying cause
Admit the person to hospital for immediate treatment and investigation when appropriate
Refer the person to a specialist for further investigation and management depending on the likely underlying cause
Background information
Definition
What is it?
Hyponatraemia is defined as a serum sodium concentration of less than 135 mmol/L [Smellie et al, 2007; GAIN, 2010].
The severity of hyponatraemia can be classified by the serum sodium concentration [Reynolds and Seckl, 2005; Smellie et al, 2007].
Mild hyponatraemia when the serum sodium concentration is 125–134 mmol/L.
Moderate hyponatraemia when the serum sodium concentration is 115–124 mmol/L.
Severe hyponatraemia when the serum sodium concentration is less than 115 mmol/L.
Volume status can be used to classify hyponatraemia [Reynolds and Seckl, 2005].
Hypovolaemic hyponatraemia — decreased total body water and greatly decreased total body sodium.
Hypervolaemic hyponatraemia — increased total body water and increased total body sodium.
Euvolaemic hyponatraemia — slightly increased total body water and normal total body sodium.
The rate of onset of hyponatraemia can also be used for classification [Reynolds et al, 2006]. (However, in practice, most people present with hyponatraemia of an undetermined duration.)
Acute hyponatraemia is defined as having had a duration of less than 48 hours.
Chronic hyponatraemia is defined as having a duration of 48 hours or more.
Pathophysiology
What is the pathophysiology of hyponatraemia?
Hyponatraemia results from a relative excess of body water to sodium.
The pathophysiology is almost always due to failed suppression of antidiuretic hormone (ADH), by physiological (for example hypovolaemia), pathological (for example heart failure), or iatrogenic (for example drugs) mechanisms.
Serum sodium concentrations are determined by the amount of serum water.
Serum water is controlled by urinary dilution. Urinary dilution is regulated mainly by ADH, which produces concentrated urine by increasing water reabsorption across the renal collecting ducts.
In a healthy individual, consumed water is rapidly excreted in dilute urine as the lower plasma osmolality suppresses the release of ADH.
In nearly all causes of hyponatraemia, there is an inability to suppress ADH. However, in rare causes of hyponatraemia, ADH is suppressed but there is either excess water intake (primary polydipsia) or a reduced threshold for the release of ADH (reset osmostat syndrome) which makes it difficult for the kidneys to excrete excess water.
[Milionis et al, 2002; Reynolds and Seckl, 2005; Reynolds et al, 2006; Achinger and Ayus, 2010]
Causes
What causes it?
The cause of hyponatraemia is often multifactorial [Reynolds et al, 2006; GAIN, 2010].
Common causes include [Reynolds et al, 2006; Bissram et al, 2007; GAIN, 2010]:
Drugs (for example, thiazide diuretics).
Syndrome of inappropriate antidiuretic hormone secretion.
Causes are related to a person's volume status [Reynolds and Seckl, 2005].
Hypovolaemia
Renal losses — Kidney disease, diuretics, salt-wasting nephropathy, cerebral salt-wasting, and mineralocorticoid deficiency (for example, Addison's disease).
Non-renal losses — skin losses (burns, sweating), gastrointestinal losses (diarrhoea, vomiting), and third-space losses (pancreatitis).
Hypervolaemia
Nephrotic syndrome.
Chronic renal failure.
Euvolaemia
Syndrome of inappropriate antidiuretic hormone secretion.
Water intoxication (primary polydipsia, excess intravenous hypotonic fluids).
Low dietary intake of sodium.
Exercise-associated hyponatraemia.
[Goh, 2004; Reynolds et al, 2006; Smellie et al, 2007]
Drugs
Drugs
Medication that causes hyponatraemia does so by increasing the action of antidiuretic hormone (ADH) [Chan, 1997; Reynolds et al, 2006]. See Pathophysiology.
The most common drugs that cause hyponatraemia include:
Diuretics. Diuretics increase the release of ADH and cause hyponatraemia in around 20% of people taking them [Clayton et al, 2006].
Severe hyponatraemia is nearly always seen with thiazide diuretics rather than loop diuretics [Chow et al, 2003].
A combination of hyponatraemia plus hypokalaemia is suggestive of diuretic-induced hyponatraemia [Janicic and Verbalis, 2003].
Selective serotonin reuptake inhibitors. These drugs increase the release of ADH and cause hyponatraemia in around 0.5–32% of people taking them (especially in the elderly). Hyponatraemia also appeared to develop within the first few weeks of treatment and resolved 2 weeks after stopping the medication [Jacob and Spinler, 2006].
Antipsychotics. Antipsychotics may only be part of the mechanism behind hyponatraemia in people with psychotic illness. Other factors to consider include psychogenic polydipsia, physiological increases in ADH with psychotic episodes, increasing thirst with anticholinergic properties of drugs [Chan, 1997]. For example, a systematic review (search date: April 2010) found that a history of polydipsia was seen in 67% of people taking antipsychotic medication [Meulendijks et al, 2010].
Nonsteroidal anti-inflammatory drugs potentiate the renal action of ADH and reduce prostaglandin synthesis, causing an increase in water retention by increasing the water permeability across the renal collecting ducts [Chan, 1997].
Carbamazepine [van Amelsvoort et al, 1994].
Drugs that less commonly cause hyponatraemia include sulphonylureas, tricyclic antidepressants, dopamine agonists, opiates, oxytocin, theophylline, chlorpropamide, clofibrate, angiotensin-converting enzyme inhibitors, angiotensin-II receptor antagonists, melphalan, proton pump inhibitors, and amiodarone [Reynolds and Seckl, 2005; Reynolds et al, 2006].
Syndrome of inappropriate antidiuretic hormone secretion
Syndrome of inappropriate antidiuretic hormone secretion
Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most frequent cause of hyponatraemia in hospitalized people [Hannon and Thompson, 2010].
Syndrome of inappropriate antidiuretic hormone secretion occurs when the body's control of ADH secretion is lost and ADH is secreted independently of the body's need.
Syndrome of inappropriate antidiuretic hormone secretion is a diagnosis of exclusion and is caused by a wide range of disorders [Hannon and Thompson, 2010].
Drugs (for example selective serotonin reuptake inhibitors). See Drugs.
Cerebral disorders (for example meningitis, encephalitis, head injury, brain tumour or abscess, cerebrovascular disease, multiple sclerosis).
Chest disorders (for example bacterial pneumonia, chronic obstructive pulmonary disease, empyema, tuberculosis, pneumothorax).
Cancer (for example small cell lung cancer, mesothelioma, stomach cancer, pancreatic cancer, lymphoma, leukaemia, thymoma).
Others (for example hereditary SIADH [Feldman et al, 2005], idiopathic SIADH, acute intermittent porphyria, multiple sclerosis, and Guillain–Barré syndrome).
[Goh, 2004; Reynolds and Seckl, 2005; Hannon and Thompson, 2010]
Heart failure
Heart failure (with oedema)
Hyponatraemia is thought to occur in around 20% of people with heart failure [Upadhyay et al, 2006]; the severity of hyponatraemia is directly related to the severity of cardiac dysfunction [De Luca et al, 2005].
Hyponatraemia is primarily caused by a low cardiac output [Leier et al, 1994].
Although people with oedema and heart failure have an increase in plasma volume, they are effectively volume depleted which stimulates sodium and water retention by the release of three hormones, namely antidiuretic hormone, renin (subsequently leading to increases in angiotensin II), and norepinephrine.
Cerebral salt wasting
Cerebral salt-wasting
Cerebral salt-wasting (CSW) has been reported in people with intracranial disease (for example subarachnoid haemorrhage, traumatic brain injury, or intracranial surgery). Cerebral salt-wasting:
Is thought to be the result of elevated levels of atrial and/or brain natriuretic peptide, which causes an increase in sodium and water excretion [Lien and Shapiro, 2007].
Was thought to be related to the syndrome of inappropriate antidiuretic hormone secretion (SIADH), but is now considered to be a separate clinical entity. However, it may coexist with SIADH.
People with CSW meet some of the diagnostic criteria for SIADH.
Distinguishing CSW from SIADH can be difficult. However, it is important to distinguish between the two disorders as people need opposite treatments for the two conditions (for example fluid repletion versus fluid restriction).
In CSW people usually have hypovolaemia; this is unlike people with SIADH who have a normal plasma volume.
Endocrine
Endocrine
Endocrine disorders are an uncommon cause of hyponatraemia [Goh, 2004].
Glucocorticoid insufficiency (Addison's disease and hypopituitarism)
Glucocorticoid deficiency is thought to be due to an increased release of antidiuretic hormone (ADH).
In Addison's disease, hyponatraemia is also partly explained by the absence of aldosterone, which results in renal sodium wasting [Schrier, 2006]. A combination of hyponatraemia plus hyperkalaemia is suggestive of Addison's disease.
Hypopituitarism and adrenocorticotropic hormone deficiency is a less common cause of hyponatraemia as there is preservation of aldosterone release [Olchovsky et al, 2005].
Hypothyroidism
Hyponatraemia is reported in up to 10% of people with hypothyroidism, although it is usually mild and asymptomatic [Montenegro et al, 1996].
Hypothyroidism is thought to cause hyponatraemia by an increase in the release of ADH due to a reduced cardiac output, volume depletion, and inappropriate secretion of ADH [Schmitz et al, 2001].
Exercise-associated hyponatraemia
Hyponatraemia - exercise-associated hyponatraemia
Exercise-associated hyponatraemia is hyponatraemia occurring during, or up to 24 hours after, prolonged physical exertion (for example running a marathon).
The primary cause is excess fluid intake beyond that required to replace insensible losses. However, in addition, there seems to be inappropriate release of antidiuretic hormone which causes water retention. See Pathophysiology.
Risk factors include female sex, low body weight, and the concomitant use of nonsteroidal anti-inflammatory drugs.
Kidney disease
Kidney disease
Conditions causing chronic kidney disease (for example polycystic kidney disease, chronic pyelonephritis) result in a sodium-losing nephropathy state [Goh, 2004]. See the CKS topic on Chronic kidney disease - not diabetic.
Liver failure
Liver failure
Hyponatraemia is thought to occur in around 30% of people admitted to hospital with advanced liver cirrhosis. In an outpatient setting, the prevalence is suggested to be around 15% [Upadhyay et al, 2006].
Hyponatraemia develops due to systemic vasodilation, which stimulates water and sodium retention by the release of three hormones, namely antidiuretic hormone, renin (subsequently increasing angiotensin-II concentrations), and norepinephrine.
Primary polydipsia
Primary polydipsia
Primary polydipsia (excess water consumption) is seen in around 7% of people with a psychotic illness [Jose and Perez-Cruet, 1979].
Primary polydipsia is thought to be caused by a central defect in thirst regulation. The osmotic threshold for thirst is reduced below the threshold for the release of ADH, encouraging people with primary polydipsia to continue to drink despite a low plasma osmolality [Schrier, 2006].
Reset osmostat syndrome
Reset osmostat syndrome
Reset osmostat syndrome has been identified as a cause of chronic hyponatraemia in pregnancy, quadriplegia, psychosis [Siegel, 2008], and other chronic debilitating disorders such as tuberculosis, encephalitis, malnutrition, and malignancy [Elisaf et al, 1996]. Reset osmostat syndrome:
Is due to the secretion of antidiuretic hormone at a lower plasma osmolality. Consequently, the corrective mechanism to re-establish normal serum sodium concentration occurs at a lower threshold, resulting in a persistent and stable low serum sodium concentration.
Is thought to be a variant of syndrome of Syndrome of inappropriate antidiuretic hormone secretion (SIADH), and is found in about a third of people with SIADH.
Incidence and prevelance
How common is it?
Hyponatraemia is the most common electrolyte disorder encountered in clinical practice [Reynolds et al, 2006; Upadhyay et al, 2006].
Hyponatraemia is more common in women, the elderly, and in people who are hospitalized [Schrier, 2010].
The incidence and prevalence of hyponatraemia depend largely on the patient population and the clinical setting [Upadhyay et al, 2006].
Mild hyponatraemia in hospitalized people is reported to be around 15–20% [Asadollahi et al, 2006], with 3–5% of hospitalized people having a serum sodium concentration of less than 130 mmol/L [Reynolds and Seckl, 2005].
An American hospital-based study found the prevalence of hyponatraemia to be around 14% in people attending the outpatient department. The study was a retrospective evaluation of 27,496 patient notes. The results showed that 14% of people has a serum sodium concentration of less than 134 mmol/L, and of these, 4% had a concentration of less than 130 mmol/L [Bissram et al, 2007].
A retrospective evaluation of 119 people in an American nursing home found a prevalence of hyponatraemia of 18% in residents compared with a prevalence of 8% in a similarly-aged ambulatory group of people. In addition, 53% of the nursing home residents had had at least one episode of hyponatraemia in the previous 12 months [Miller et al, 1995].
Risk factors
What are the risk factors?
The most significant risk factor is age [Chan, 1997; Miller, 1998].
Hyponatraemia is common among the elderly, and may be caused by physiological changes, disease processes, or drugs.
Physiological changes in the elderly, such as a reduced renal diluting capacity, increased release of antidiuretic hormone at baseline, and increased circulating levels of atrial natriuretic peptide, all lead to an increased risk of hyponatraemia.
About half of elderly people with hyponatraemia have features typical of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). See Causes.
Thiazide diuretics are more likely to cause hyponatraemia in elderly people with a low body mass index.
A Hong Kong hospital-based, retrospective, case-control study evaluated 439 people admitted to hospital for symptomatic hyponatraemia. It found that each 10-year increment of age was associated with a two-fold increase in the risk of hyponatraemia (hazard ratio 2.14, 95% CI 1.59 to 2.88); and for a 5 kg increase in body mass, there was a 27% decrease in the risk of hyponatraemia (odds ratio 0.77, 95% CI 0.68 to 0.87) [Chow et al, 2003].
Prognosis
What is the prognosis?
Hospitalized people with hyponatraemia are associated with an increased mortality and are more vulnerable to longer hospital stays compared with people with normal serum sodium concentrations [Gill et al, 2006].
A UK prospective, case-controlled, hospital-based study evaluated the outcome of hyponatraemia (serum sodium concentration of less than 125 mmol/L) in 208 people admitted to hospital.
The study found that the overall mortality was 27% in people with a low serum sodium concentration compared with 9% in the control group (p = 0.009).
The length of hospital admission was also greater by 2–3 days (p < 0.005) in people with hyponatraemia compared with controls.
In particular, people who had a decrease in serum sodium concentration after admission were at the highest risk of death. The authors concluded this finding may represent a 'sicker' group of patients who require increased monitoring.
An analysis of the literature on hyponatraemia supported the association of increased mortality in people with hyponatraemia compared with people with a normal serum sodium concentration [Asadollahi et al, 2006].
The review highlighted that many of the studies predicting mortality were small, and did not include control groups.
Therefore, although there seems to be an increased mortality with hyponatraemia, it is uncertain whether this is a direct adverse effect, or simply a marker of a 'sicker' patient.
Hyponatraemia is potentially life threatening, particularly when it is severe (serum sodium concentration less than 115 mmol/L) and of acute onset (over a period of less than 48 hours), owing to the effects of hyponatraemia on the brain (for example seizures).
Diagnosis and assessment
Diagnosis and assessment of hyponatraemia
Clinical features
What are the clinical features of hyponatraemia?
Hyponatraemia is usually an incidental finding on routine blood tests.
Most people with hyponatraemia are asymptomatic, particularly if hyponatraemia is mild (serum sodium concentration of 130–135 mmol/L) and has developed slowly.
When symptoms of hyponatraemia are present, they are often non-specific and are related to both the severity of the hyponatraemia and its rate of onset.
Early symptoms
Anorexia.
Nausea.
Lethargy and apathy (associated with slow-onset hyponatraemia).
Late symptoms (associated with severe or rapid-onset hyponatraemia).
Disorientation.
Agitation.
Seizures.
Coma.
Basis for recommendation
Basis for recommendation
Most people are asymptomatic
The information that most people with mild hyponatraemia are asymptomatic is from expert opinion in review articles [Goh, 2004; Reynolds et al, 2006; Smellie et al, 2007].
Symptoms are often non-specific
This information is from expert opinion in a review article [Goh, 2004], and the guideline Hyponatraemia in adults (on or after 16th birthday), published by the Guideline and Audit Implementation Network (GAIN) for the Northern Ireland Department of Health [GAIN, 2010].
The extent that symptoms are related to severity and rate of onset
This information is derived from narrative reviews [Goh, 2004; Reynolds et al, 2006], and the guideline Hyponatraemia in adults (on or after 16th birthday) published by the GAIN for the Northern Ireland Department of Health [GAIN, 2010].
In primary care, most people present with hyponatraemia of an undetermined duration [Verbalis et al, 2007]. Therefore, for practical reasons, CKS have used the term 'developed slowly' rather than the recognized 'acute' or 'chronic' classification.
Clinical features
The clinical features of hyponatraemia are derived from expert opinion from a narrative review [Kumar and Berl, 1998] and the guideline Hyponatraemia in adults (on or after 16th birthday), published by the GAIN for the Northern Ireland Department of Health [GAIN, 2010].
Advanced symptoms associated with severe hyponatraemia is described in two expert reviews [Goh, 2004; Reynolds et al, 2006].
The symptom of lethargy related to slow-onset hyponatraemia is described in an expert review [Kugler and Hustead, 2000].
Confirming a diagnosis
How should I confirm a diagnosis of hyponatraemia?
If not already measured, or when hyponatraemia is an incidental finding on a routine blood test, take blood to measure the serum sodium concentration and plasma osmolality, to confirm the diagnosis of hyponatraemia. Confirming hyponatraemia is important as borderline serum sodium concentrations may simply reflect a variation in laboratory measures.
If the plasma osmolality is normal (285–295 mOsmol/Kg) or high (greater than 295 mOsmol/Kg), take blood to measure serum lipid, glucose, and protein concentrations to exclude fictitious and redistributive hyponatraemia.
If the plasma osmolality is low (less than 280 mOsmol/Kg), diagnose:
Mild hyponatraemia — when the serum sodium concentration is 125–134 mmol/L.
Moderate hyponatraemia — when the serum sodium concentration is 115–124 mmol/L.
Severe hyponatraemia — when the serum sodium concentration is less than 115 mmol/L.
Fictitious and redistributive hyponatraemia
In fictitious hyponatraemia, normal plasma osmolality (285–295 mOsmol/kg) is associated with very high levels of serum lipids and proteins. The actual serum sodium concentration is normal (pseudo-hyponatraemia) but presents as low owing to the measurement technique used by the laboratory.
Newer methods of measuring serum sodium concentration make pseudo-hyponatraemia very unlikely nowadays.
A high plasma osmolality (greater than 295 mOsmol/kg) is associated with very high levels of blood glucose. This type of hyponatraemia is called 'redistributive hyponatraemia' and is of no physiological importance.
However, a person with a high blood glucose level will require investigation for underlying diabetes and correction of their high blood glucose level. The serum sodium concentration will correct as the blood glucose level decreases. See the CKS topic on Diabetes - type 2.
Basis for recommendation
Basis for recommendation
Measurement of serum sodium concentration and plasma osmolality
This recommendation is based on expert opinion from the guideline Hyponatraemia in adults (on or after 16th birthday) published by the Guideline and Audit Implementation Network for the Northern Ireland Department of Health [GAIN, 2010] and a review article, Best practice in primary care pathology [Smellie et al, 2007].
Mild, moderate, or severe hyponatraemia
Diagnosis of hyponatraemia as mild, moderate, or severe is based on expert opinion from a review article [Reynolds and Seckl, 2005].
Normal or high plasma osmolality.
Nowadays, most laboratories will use ion-selective electrodes to measure serum electrolytes. These newer methods avoid the risk of falsely low serum sodium readings related to high levels of lipids and proteins [Nguyen et al, 2007].
A low serum sodium concentration can also occur in severe hyperglycaemia as the high levels of glucose draw intracellular water into the extracellular space diluting the serum sodium concentration [Goh, 2004]. This hypertonic hyponatraemia has no physiological importance, and the serum sodium concentration will correct itself as a normal blood glucose level is re-established [Goh, 2004].
Identifying a cause
How should I identify an underlying cause of hyponatraemia?
Do not routinely look for a cause of hyponatraemia in primary care if the person has hyponatraemia that is severe (serum sodium concentration of less than 115 mmol/L) or significantly symptomatic. These people should be admitted to hospital for urgent treatment. See Secondary care management.
Seek advice from an endocrinologist if the person has asymptomatic, moderate hyponatraemia (serum sodium concentration of 115–124 mmol/L).
Look for a cause of hyponatraemia in a person with asymptomatic, mild hyponatraemia (serum sodium concentration greater than 125 mmol/L).
Repeat the serum sodium measurement and check for previously low serum sodium concentrations. This will help determine whether the hyponatraemia is sudden and requires hospital admission. These people are at greatest risk of neurological complications.
Assess volume status (check for postural changes in blood pressure, jugular venous pressure, and presence or absence of oedema or clinical signs of dehydration). Determining volume status can help identify the causes of hyponatraemia, however changes may be subtle and difficult to interpret.
Determine whether the person is taking any drugs that can cause hyponatraemia (for example diuretics).
Ask about fluid intake and nocturnal polyuria (suggesting a possible diagnosis of primary polydipsia).
Check for disorders that cause hyponatraemia. If clinically indicated, do the appropriate tests:
Intercurrent illness (such as gastroenteritis, or pneumonia) or chronic illness (such as anorexia nervosa).
Renal disease — urinalysis for urine protein. See the CKS topic on Chronic kidney disease - not diabetic.
Hypothyroidism — thyroid function tests. See the CKS topic on Hypothyroidism.
Addison's disease — serum cortisol (morning sample, at 8–9 a.m.). See the CKS topic on Addison's disease.
Heart failure and liver disease. See the CKS topic on Heart failure - chronic.
Myeloma — serum and urine protein electrophoresis, including Bence–Jones proteins.
Cancer (especially lung and upper gastrointestinal cancers).
If no apparent cause can be identified clinically, send a spot urine to measure urinary sodium concentration and urinary osmolality together with a blood sample to measure serum sodium concentration and plasma osmolality.
Measurement of urinary osmolality and urinary sodium concentration may help to determine an underlying cause of hyponatraemia. See Interpreting urinary sodium and urinary osmolality.
Basis for recommendation
Basis for recommendation
Admission for severe or symptomatic hyponatraemia
The recommendation to admit people with severe or symptomatic hyponatraemia is based on expert opinion from a review article, Best practice in primary care pathology [Smellie et al, 2007].
Severe hyponatraemia (sodium concentration less than 115 mmol/L), particularly if of rapid onset, is associated with substantial morbidity and can be life threatening [Asadollahi et al, 2006].
A prospective, randomized controlled trial investigating 204 hospitalized people with severe hyponatraemia found that a serum sodium concentration of less than 125 mmol/L was associated with a statistically significant prolonged admission and increased mortality compared with a normal serum sodium concentration. The authors concluded that these people may represent a 'sicker' group, and need increased monitoring and surveillance [Gill et al, 2006].
Investigation of asymptomatic mild hyponatraemia
The recommendation to investigate asymptomatic mild or moderate hyponatraemia in primary care is based on a narrative review, Best practice in primary care pathology [Smellie et al, 2007].
Repeating serum sodium concentration measurement
The recommendation to repeat the serum sodium concentration measurement to confirm hyponatraemia is based on expert opinion from a review article, Best practice in primary care pathology [Smellie et al, 2007].
The review suggested that a persistent and stable serum sodium concentration of 132–135 mmol/L, in a clinically well person, may represent a statistical population outlier and may not require investigation unless there has been a recent large fall in the serum sodium concentration.
Assessment of fluid status
The recommendation to assess fluid status is based on expert opinion from the guideline Hyponatraemia in adults (on or after 16th birthday) published by the Guideline and Audit Implementation Network (GAIN) for the Northern Ireland Department of Health [GAIN, 2010], and a several expert reviews [Goh, 2004; Reynolds et al, 2006; Smellie et al, 2007].
Differentiating clinically between euvolaemia and hypovolaemia can be difficult, especially if the classic features of volume depletion (such as tachycardia and low blood pressure) are not present [McGee et al, 1999].
Further investigations
The recommendation to consider further investigations is based on expert opinion from the guideline Hyponatraemia in adults (on or after 16th birthday) published by the GAIN for the Northern Ireland Department of Health [GAIN, 2010] and on expert opinion in narrative reviews [Goh, 2004; Reynolds et al, 2006; Smellie et al, 2007].
Measuring urinary sodium concentration and urinary osmolality
This recommendation is based on expert opinion from a review article, Best practice in primary care pathology [Smellie et al, 2007].
Some reviews suggest that a urinary osmolality should not be requested as it can be misleading, and urinary sodium concentration can be difficult to interpret in clinical practice [Reynolds et al, 2006]. However, CKS believes that these tests are easy to request and can support a specialist in determining an underlying cause for hyponatraemia.
Interpreting urinary sodium and urinary osmolality
How should I interpret urinary sodium concentration and urinary osmolality?
Urinary results should always be interpreted in the clinical context. For example, diuretic medication can cause a low or a high urinary sodium concentration, depending on the timing of the last dose.
Urinary sodium concentration reflects renal perfusion and the person's effective circulating plasma volume.
Urinary sodium concentration of less than 20–30 mmol/L suggests:
Non-renal losses (for example gastrointestinal [diarrhoea], skin [sweating and burns], and third-space losses [pancreatitis]).
Diuretics (early recovery phase of diuretic use).
Liver cirrhosis with ascites, nephrotic syndrome, congestive cardiac failure.
Over-hydration with hypotonic fluids (usually parental administration in hospital).
Low dietary salt intake (for example in alcoholism).
A urinary sodium concentration of greater than 20–30 mmol/L suggests:
Renal losses (for example diuretics, aldosterone deficiency, cerebral wasting, salt-loosing nephropathy, chronic renal failure).
Syndrome of inappropriate antidiuretic hormone secretion (SIADH). See Suspecting a diagnosis of SIADH.
Reset osmostat syndrome.
Endocrine disorders (for example hypothyroidism, hypopituitarism, Addison's disease).
Primary polydipsia.
Urinary osmolality reflects the kidney's ability to concentrate urine.
Urinary osmolality greater than 100 mOsmol/kg is seen in all causes of hyponatraemia, except in primary polydipsia, reset osmostat syndrome, or when a person has a low dietary salt intake (such as in alcoholism).
Basis for recommendation
Basis for recommendation
Urinary sodium concentration
Owing to the inconsistency in the medical literature regarding the urinary sodium concentration to distinguish between causes of hyponatraemia, the recommendation to use a urinary sodium concentration of 20–30 mmol/L is based on expert opinion from several reviews [Goh, 2004; Reynolds et al, 2006; Smellie et al, 2007] and the Oxford textbook of medicine [Achinger and Ayus, 2010].
The expert review Best practice in primary care pathology [Smellie et al, 2007] used a urinary sodium concentration of 20 mmol/L as the lower cut off value.
Another review also used a urinary sodium concentration of 20 mmol/L as the lower cut off value, but considered 40 mmol/L to be the upper cut off value [Milionis et al, 2002].
The guideline Hyponatraemia in adults (on or after 16th birthday), published by the Guideline and Audit Implementation Network (GAIN) for the Northern Ireland Department of Health, suggested urinary sodium concentrations of 15 mmol/L as the lower cut off value [GAIN, 2010].
Urinary osmolality
The recommendation to use a urinary osmolality of 100 mOsmol/kg as a cut off to distinguish between primary polydipsia and reset osmostat syndrome from all other causes of hyponatraemia is based on expert opinion from several review articles [Kugler and Hustead, 2000; Milionis et al, 2002; Reynolds et al, 2006; Smellie et al, 2007], the guideline Hyponatraemia in adults (on or after 16th birthday) published by GAIN for the Northern Ireland Department of Health [GAIN, 2010], and an American guideline, Hyponatraemia treatment guideline 2007: expert panel recommendations [Verbalis et al, 2007].
Suspecting a diagnosis of SIADH
When should I suspect a diagnosis of syndrome of inappropriate antidiuretic hormone secretion (SIADH)?
The diagnosis of syndrome of inappropriate antidiuretic hormone secretion (SIADH) is usually confirmed in secondary care.
The diagnosis of SIADH will often require specialist procedures (for example a measurement of the person's fractional excretion of urate). See Managing hyponatraemia in primary care.
Syndrome of inappropriate antidiuretic hormone secretion is a diagnosis of exclusion. Specialist investigations are required to determine an underlying cause of SIADH.
Suspect SIADH if all of the following diagnostic criteria are met:
Hyponatraemia (serum sodium concentration less than 135 mmol/L).
Decreased plasma osmolality (less than 280 mOsmol/kg).
Increased urine osmolality (greater than 100 mOsmol/kg).
Increased urinary sodium concentration (greater than 30mmol/L).
No clinical or biochemical features of adrenal and thyroid dysfunction.
No dehydration on clinical examination.
No use or recent use of diuretic medication.
Basis for recommendation
Basis for recommendation
Diagnosis of exclusion
This recommendation is based on expert opinion from review articles [Milionis et al, 2002; Goh, 2004; Reynolds et al, 2006; Smellie et al, 2007; Hannon and Thompson, 2010].
The diagnosis of syndrome of inappropriate antidiuretic hormone secretion (SIADH) may require specialist tests
This recommendation is based on expert opinion from reviews [Milionis et al, 2002; Goh, 2004; Reynolds et al, 2006; Smellie et al, 2007; Hannon and Thompson, 2010], and what CKS considers to be best practice due to the complicated process of diagnosing SIADH and managing the disorder.
Measuring fractional excretion of urate in SIADH has been derived from a narrative review [Fenske et al, 2008].
Diagnostic criteria
This information has been derived from expert review articles [Milionis et al, 2002; Goh, 2004; Reynolds et al, 2006; Smellie et al, 2007; Decaux and Musch, 2008; Hannon and Thompson, 2010] and the original criteria described [Verbalis, 1989].
Management
Management
Scenario : Management: covers referral criteria, the management of hyponatraemia in primary care, and the initial management of hyponatraemia in secondary care.
Scenario : Management
Scenario : Management of hyponatraemia
Admission to hospital
When should I admit a person with hyponatraemia to hospital?
Admit the person with hyponatraemia to hospital immediately for urgent treatment with intravenous fluids if they:
Have a serum sodium concentration of less than 115 mmol/L (severe hyponatraemia).
Are symptomatic.
Have signs of hypovolaemia.
Seek advice from an endocrinologist, nephrologist, or clinical pathologist regarding admission to hospital or an urgent referral.
If the person has asymptomatic, moderate hyponatraemia (serum sodium concentration of 115–124 mmol/L).
Basis for recommendation
Basis for recommendation
Admit if the person has hyponatraemia that is severe or symptomatic, or if they have signs of hypovolaemia
This recommendation is based on expert opinion from several narrative reviews [Goh, 2004; Reynolds et al, 2006; Smellie et al, 2007], the American guideline Hyponatraemia treatment guidelines 2007: Expert panel recommendations [Verbalis et al, 2007], and the guideline Hyponatraemia in adults (on or after 16th birthday) published by the Guideline and Audit Implementation Network (GAIN) for the Northern Ireland Department of Health [GAIN, 2010].
If the person has hyponatraemia that is severe, or if they are significantly symptomatic (such as suffering from confusion), or have signs of hypovolaemia, they are at risk of cerebral oedema and require urgent intervention with intravenous fluids under specialist care.
Contact an endocrinologist if the person has asymptomatic, moderate hyponatraemia
This recommendation is based on expert opinion from reviews [Goh, 2004; Smellie et al, 2007] and the American guideline Hyponatraemia treatment guidelines 2007: Expert panel recommendations [Verbalis et al, 2007].
The American guideline recommends advice from secondary care if the person's serum sodium concentration is less than 125 mmol/L.
Referral to a specialist
When should I refer a person with hyponatraemia?
Refer to an endocrinologist, nephrologist, or chemical pathologist:
If the cause of hyponatraemia is not clear.
If an endocrine disorder is suspected. Admission to hospital or urgent referral may be required if Addison's disease is suspected. See the CKS topic on Addison's disease.
If syndrome of inappropriate antidiuretic hormone secretion (SIADH) is suspected. Specialist advice is needed to confirm a diagnosis, determine an underlying cause, and initiate management.
If cancer is suspected as an underlying cause of SIADH, refer urgently (to be seen within 2 weeks) to the appropriate specialist. See the CKS topics in the clinical speciality Cancer - suspected (NICE referral advice).
If primary polydipsia is suspected.
If reset osmostat syndrome or cerebral salt-wasting is suspected. Specialist advice is needed to confirm the diagnoses and initiate appropriate treatment.
Refer to the appropriate specialist, to discuss management options.
If the person has hyponatraemia thought to be caused by heart failure, renal failure, or liver failure. See the CKS topics on Heart failure - chronic and Chronic kidney disease - not diabetic.
Basis for recommendation
Basis for recommendation
Refer to an endocrinologist if the cause of hyponatraemia is not clear
This recommendation is based on what CKS considers to be best practice. In most people, hyponatraemia is multifactorial, and interpretation of urinary sodium concentration and urinary osmolality can be difficult and unreliable [Reynolds et al, 2006; Chubb, 2009]. Therefore, specialist advice is appropriate if hyponatraemia is persistent and no cause can be identified in primary care.
Refer to an endocrinologist if syndrome of inappropriate antidiuretic hormone secretion is suspected
This recommendation is based on expert opinion from a review article, Best practice in primary care pathology [Smellie et al, 2007].
Refer to an endocrinologist if endocrine disease is suspected
This recommendation is based on expert opinion from a review article, Best practice in primary care pathology [Smellie et al, 2007] and what CKS considers to be best practice.
Hyponatraemia related to an endocrine disorder is uncommon, and will require specialist input to confirm the diagnosis and initiate treatment.
Refer to an endocrinologist if reset osmostat syndrome or cerebral salt-wasting is suspected
This recommendation is extrapolated from expert opinion from a review [Milionis et al, 2002].
Distinguishing SIADH from reset osmostat syndrome and cerebral salt-wasting can be difficult, and requires specialist interventions such as a fluid challenge or monitoring of renal uric acid handling. See Cerebral salt-wasting and Reset osmostat syndrome.
Refer to the appropriate specialist if heart failure, renal failure, or liver failure is contributing to hyponatraemia
This recommendation is based on expert opinion from several reviews [Goh, 2004; Reynolds et al, 2006; Smellie et al, 2007], the American guideline Hyponatraemia treatment guidelines 2007: Expert panel recommendations [Verbalis et al, 2007], and the guideline Hyponatraemia in adults (on or after 16th birthday) published by the Guideline and Audit Implementation Network (GAIN) for the Northern Ireland Department of Health [GAIN, 2010].
There are no published guidelines on how to treat hyponatraemia in people with heart failure, renal failure, or liver failure. It is uncertain whether hyponatraemia is a marker of disease severity or an actual contributor to poor outcome in these disorders. Therefore, specialist advice is necessary before initiating any changes to management such as water and dietary salt restriction [Verbalis et al, 2007].
Managing hyponatraemia in primary care
How should I manage a person with hyponatraemia not needing hospital admission or a referral to a specialist?
People with asymptomatic, mild hyponatraemia (serum sodium concentration of 125 mmol/L or greater) not needing admission to hospital or referral to a specialist may be managed in primary care.
In all people, repeat the serum sodium measurement after 1 week, to exclude a rapidly decreasing serum sodium concentration that will require admission to hospital.
If the person has an acute illness that may be contributing to the hyponatraemia, treat the underlying problem and recheck the serum sodium concentration after 2 weeks.
If the person is taking drugs that may be contributing to the hyponatraemia, stop them if appropriate, and recheck the serum sodium concentration after 2 weeks.
If the person is taking a drug that cannot be stopped (for example an antipsychotic drug), contact their appropriate specialist to discuss whether to stop the drug, monitor the serum sodium concentration, or refer to an endocrinologist, nephrologist, or clinical pathologist. See Referral to a specialist.
If the serum sodium concentration remains low after discontinuation of the drug, look for another underlying cause, or refer the person to an endocrinologist.
Basis for recommendation
Basis for recommendation
Investigating a person with asymptomatic, mild hyponatraemia
This recommendation is based on expert opinion from a review, Best practice in primary care pathology [Smellie et al, 2007]. The review states that chronic (duration greater than 48 hours), mild hyponatraemia can often be managed at home.
Repeat serum sodium measurement after 1 week
This recommendation is practical advice extrapolated from reviews [Goh, 2004; Smellie et al, 2007] and the American guideline Hyponatraemia treatment guidelines 2007: Expert panel recommendations [Verbalis et al, 2007].
The literature suggests admitting people with rapidly decreasing serum sodium concentrations. These people are at high risk of cerebral oedema and death. Repeating the serum sodium measurement after one week will help detect vulnerable people needing admission.
Treat an acute illness that may be contributing to hyponatraemia
This recommendation is based on expert opinion from a narrative review, Best practice in primary care pathology [Smellie et al, 2007].
The review states that elderly people are vulnerable to hyponatraemia during an acute diarrhoeal illness. Treatment (such as oral rehydration) of the acute problem, may resolve the hyponatraemia without further investigation or intervention.
Stop any drugs contributing to hyponatraemia if appropriate and recheck serum sodium concentration
This recommendation is based on expert opinion from several reviews [Goh, 2004; Reynolds et al, 2006; Smellie et al, 2007], the American guideline Hyponatraemia treatment guidelines 2007: Expert panel recommendations [Verbalis et al, 2007], and the guideline Hyponatraemia in adults (on or after 16th birthday) published by the Guideline and Audit Implementation Network (GAIN) for the Northern Ireland Department of Health [GAIN, 2010].
Drug-induced hyponatraemia usually results from syndrome of inappropriate antidiuretic hormone secretion (SIADH), and will resolve following cessation of the offending drug [Chan, 1997].
In a systematic (search date: December 2005) review to evaluate the role of selective serotonin reuptake inhibitors (SSRIs) in hyponatraemia, after discontinuation of SSRIs, most serum sodium concentrations returned to normal in 2 weeks [Jacob and Spinler, 2006].
The recommendation to look for another underlying cause or refer the person to an endocrinologist if their serum sodium concentration remains low after discontinuation of the drug, is based on what CKS considers to be good clinical practice, and evidence from review articles state that hyponatraemia is often multifactorial.
Secondary care management
How is hyponatraemia managed in secondary care?
In secondary care, the overall management is aimed at determining and treating the underlying cause of hyponatraemia. Treatment will usually be based on the presence or absence of symptoms, the rate of onset of hyponatraemia, and the person's volume status. The person presenting in secondary care with:
Symptomatic hyponatraemia (usually of rapid onset, less than 48 hours) may be given hypertonic saline (3%) to restore their serum sodium concentration to a safe level (usually greater than 120 mmol/L).
Urgent treatment is needed to reduce neurological symptoms and avoid worsening complications (such as coma).
Asymptomatic (or mild symptoms), hypovolaemic hyponatraemia will be given intravenous normal saline (0.9%), which will be continued until the person's blood pressure is restored.
The correction of serum sodium concentration should be limited to 8 mmol/L to 12 mmol/L in the first 24 hours or 18 mmol/L over a period of 48 hours, especially if the duration of hyponatraemia is undetermined.
A more rapid correction of serum sodium concentration may cause central pontine myelinolysis. In central pontine myelinolysis, the brain cells shrink, causing irreversible neurological complications (usually a few days after the serum sodium concentration is corrected).
Asymptomatic (or mild symptoms), euvolaemic hyponatraemia will usually be fluid restricted.
Fluid intake must be restricted to around 500–1000 mL per day.
Dietary salt is not restricted. These people will have a normal or low total body sodium level.
Several days of fluid restriction is required before the serum sodium will start to rise.
Asymptomatic (or mild symptoms), hypervolaemic hyponatraemia will have treatment focused on optimizing their underlying disorder (for example liver failure).
Treatment usually involves fluid restriction and dietary salt restriction, with or without diuretic medication.
Refractory hyponatraemia will have the underlying cause(s) of hyponatraemia reconsidered.
In people with euvolaemic hyponatraemia, the specialist may give an intravenous fluid challenge to determine whether the person has clinically unapparent hypovolaemia. If the person is hypovolaemic, their serum sodium concentration will begin to rise when they are given intravenous fluids.
In people with hyponatraemia associated with syndrome of inappropriate secretion of antidiuretic hormone (SIADH), liver cirrhosis, or heart failure, the specialist may use medication that blocks the action of ADH. For example, demeclocycline or a vasopressin antagonist (such as tolvaptan). These drugs promote water excretion. See the section on Pathophysiology.
Basis for recommendation
Basis for recommendation
Management of hyponatraemia in secondary care
This information is derived from several reviews [Goh, 2004; Reynolds et al, 2006; Smellie et al, 2007], the American guideline Hyponatraemia treatment guidelines 2007: Expert panel recommendations [Verbalis et al, 2007], and the guideline Hyponatraemia in adults (on or after 16th birthday) published by the Guideline and Audit Implementation Network (GAIN) for the Northern Ireland Department of Health [GAIN, 2010].
The strength of evidence on fluid repletion or fluid restriction for managing hyponatraemia is, at best, the outcome of retrospective analyses, or what experts consider to be logical and best practice [Reynolds and Seckl, 2005].
Evidence
Evidence
Supporting evidence
There is no supporting evidence section on interventions for hyponatraemia or its underlying causes, because treatments are usually delivered in secondary care.
Search strategy
Scope of search
A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on the primary care management of hyponatraemia.
Search dates
January 2000 – November 2010
Key search terms
Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline and these were adapted for other databases. Further details are available on request.
exp Hyponatremia/, Hyponatremia.tw, Hyponatraemia.tw
exp Addison Disease/ exp Diarrhea/, exp Vomiting/, exp Diuretics/, exp Inappropriate ADH Syndrome/
Table 1. Key to search terms.| Search commands | Explanation |
|---|---|
| / | indicates a MeSh subject heading with all subheadings selected |
| .tw | indicates a search for a term in the title or abstract |
| exp | indicates that the MeSH subject heading was exploded to include the narrower, more specific terms beneath it in the MeSH tree |
| $ | indicates that the search term was truncated (e.g. wart$ searches for wart and warts) |
Sources of guidelines
National Institute for Health and Clinical Excellence (NICE)
Scottish Intercollegiate Guidelines Network (SIGN)
National Guidelines Clearinghouse
British Columbia Medical Association
Institute for Clinical Systems Improvement
Guidelines International Network
National Library of Guidelines
National Health and Medical Research Council (Australia)
University of Michigan Medical School
Michigan Quality Improvement Consortium
Royal Australian College of General Practitioners
National Resource for Infection Control
NHS Scotland National Patient Pathways
Agency for Healthcare Research and Quality
UK Ambulance Service Clinical Practice Guidelines
RefHELP NHS Lothian Referral Guidelines
Medline (with guideline filter)
Driver and Vehicle Licensing Agency
NHS Plus (occupational health practice)
Sources of systematic reviews and meta-analyses
Systematic reviews
Protocols
Database of Abstracts of Reviews of Effects
Medline (with systematic review filter)
EMBASE (with systematic review filter)
Sources of health technology assessments and economic appraisals
NIHR Health Technology Assessment programme
NHS Economic Evaluations
Health Technology Assessments
Canadian Agency for Drugs and Technologies in Health
International Network of Agencies for Health Technology Assessment
Sources of randomized controlled trials
Central Register of Controlled Trials
Medline (with randomized controlled trial filter)
EMBASE (with randomized controlled trial filter)
Sources of evidence based reviews and evidence summaries
DynaMed
Central Services Agency COMPASS Therapeutic Notes
Sources of national policy
Health Management Information Consortium (HMIC)
Sources of medicines information
The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.
British National Formulary (BNF)
electronic Medicines Compendium (eMC)
European Medicines Agency (EMEA)
References
Achinger, S.G. and Ayus, J.C. (2010)
Asadollahi, K., Beeching, N. and Gill, G. (2006) Hyponatraemia as a risk factor for hospital mortality. QJM 99(12), 877-880. [Abstract] [Free Full-text]
Bissram, M., Scott, F.D., Liu, L. and Rosner, M.H. (2007) Risk factors for symptomatic hyponatraemia: the role of pre-existing asymptomatic hyponatraemia. Internal Medicine Journal 37(3), 149-155. [Abstract]
Chan, T.Y. (1997) Drug-induced syndrome of inappropriate antidiuretic hormone secretion. Causes, diagnosis and management. Drugs & Aging 11(1), 27-44. [Abstract]
Chow, K.M., Szeto, C.C., Wong, T.Y. et al. (2003) Risk factors for thiazide-induced hyponatraemia. QJM 96(12), 911-917. [Abstract] [Free Full-text]
Chubb, S.A. (2009) Hyponatremia treatment guidelines 2007: expert panel recommendations. Clinical Biochemist. Reviews 30(1), 35-38. [Free Full-text]
Clayton, J.A., Rodgers, S., Blakey, J. et al. (2006) Thiazide diuretic prescription and electrolyte abnormalities in primary care. British Journal of Clinical Pharmacology 61(1), 87-95. [Abstract] [Free Full-text]
Decaux, G. and Musch, W. (2008) Clinical laboratory evaluation of the syndrome of inappropriate secretion of antidiuretic hormone. Clinical Journal of The American Society of Nephrology 3(4), 1175-1184. [Abstract] [Free Full-text]
De Luca, L., Klein, L., Udelson, J.E. et al. (2005) Hyponatremia in patients with heart failure. American Journal of Cardiology 96(12A), 19L-23L. [Abstract]
Elisaf, M.S., Konstantinides, A. and Siamopoulos, K.C. (1996) Chronic hyponatremia due to reset osmostat in a patient with colon cancer. American Journal of Nephrology 16(4), 349-351. [Abstract]
Feldman, B.J., Rosenthal, S.M., Vargas, G.A. et al. (2005) Nephrogenic syndrome of inappropriate antidiuresis. New England Journal of Medicine 352(18), 1884-1890. [Abstract] [Free Full-text]
Fenske, W., Stork, S., Koschker, A.C. et al. (2008) Value of fractional uric acid excretion in differential diagnosis of hyponatremic patients on diuretics. Journal of Clinical Endocrinology and Metabolism 93(8), 2991-2997. [Abstract] [Free Full-text]
GAIN (2010) Hyponatraemia in adults (on or after 16th birthday). ..Guidelines and Audit Implementation Network.www.gain-ni.org
Gill, G., Huda, B., Boyd, A. et al. (2006) Characteristics and mortality of severe hyponatraemia - a hospital-based study. Clinical Endocrinology 65(2), 246-249. [Abstract]
Goh, K.P. (2004) Management of hyponatremia. American Family Physician 69(10), 2387-2394. [Abstract] [Free Full-text]
Hannon, M.J. and Thompson, C.J. (2010) The syndrome of inappropriate antidiuretic hormone: prevalence, causes and consequences. European Journal of Endocrinology 162(Suppl 1), S5-S12. [Abstract] [Free Full-text]
Henriksen, J.H., Bendtsen, F., Gerbes, A.L. et al. (1992) Estimated central blood volume in cirrhosis: relationship to sympathetic nervous activity, beta-adrenergic blockade and atrial natriuretic factor. Hepatology 16(5), 1163-1170. [Abstract]
Jacob, S. and Spinler, S.A. (2006) Hyponatremia associated with selective serotonin-reuptake inhibitors in older adults. Annals of Pharmacotherapy 40(9), 1618-1622. [Abstract]
Janicic, N. and Verbalis, J.G. (2003) Evaluation and management of hypo-osmolality in hospitalized patients. Endocrinology and Metabolism Clinics of North America 32(2), 459-481. [Abstract]
Jose, C.J. and Perez-Cruet, J. (1979) Incidence and morbidity of self-induced water intoxication in state mental hospital patients. American Journal of Psychiatry 136(2), 221-222.
Kugler, J.P. and Hustead, T. (2000) Hyponatremia and hypernatremia in the elderly. American Family Physician 61(12), 3623-3630. [Abstract] [Free Full-text]
Kumar, S. and Berl, T. (1998) Sodium. Lancet 352(9123), 220-228. [Abstract]
Leier, C.V., Dei Cas, L. and Metra, M. (1994) Clinical relevance and management of the major electrolyte abnormalities in congestive heart failure: hyponatremia, hypokalemia, and hypomagnesemia. American Heart Journal 128(3), 564-574. [Abstract]
Lien, Y.H. and Shapiro, J.I. (2007) Hyponatremia: clinical diagnosis and management. American Journal of Medicine 120(8), 653-658. [Abstract]
McGee, S., Abernethy, W.B., III and Simel, D.L. (1999) The rational clinical examination. Is this patient hypovolemic? Journal of the American Medical Association 281(11), 1022-1029. [Abstract]
Meulendijks, D., Mannesse, C.K., Jansen, P.A. et al. (2010) Antipsychotic-induced hyponatraemia: a systematic review of the published evidence. Drug Safety 33(2), 101-114. [Abstract]
Milionis, H.J., Liamis, G.L. and Elisaf, M.S. (2002) The hyponatremic patient: a systematic approach to laboratory diagnosis. Canadian Medical Association Journal 166(168), 1056-1062. [Abstract] [Free Full-text]
Miller, M. (1998) Hyponatremia: age-related risk factors and therapy decisions. Geriatrics 53(7), 32-38. [Abstract]
Miller, M., Morley, J.E. and Rubenstein, L.Z. (1995) Hyponatremia in a nursing home population. Journal of The American Geriatrics Society 43(12), 1410-1413. [Abstract]
Montenegro, J., Gonzalez, O., Saracho, R. et al. (1996) Changes in renal function in primary hypothyroidism. American Journal of Kidney Diseases 27(2), 195-198. [Abstract]
Nguyen, M.K., Ornekian, V., Butch, A.W. and Kurtz, I. (2007) A new method for determining plasma water content: application in pseudohyponatremia. American Journal of Physiology Renal Physiology 292(5), F1652-F1656. [Abstract] [Free Full-text]
Olchovsky, D., Ezra, D., Vered, I. et al. (2005) Symptomatic hyponatremia as a presenting sign of hypothalamic-pituitary disease: a syndrome of inappropriate secretion of antidiuretic hormone (SIADH)-like glucocorticosteroid responsive condition. Journal of Endocrinological Investigation 28(2), 151-156. [Abstract]
Oren, R.M. (2005) Hyponatremia in congestive heart failure. American Journal of Cardiology 95(9A), 2B-7B. [Abstract]
Reynolds, R.M. and Seckl, J.R. (2005) Hyponatraemia for the clinical endocrinologist. Clinical Endocrinology 63(4), 366-374. [Free Full-text]
Reynolds, R.M., Padfield, P.L. and Seckl, J.R. (2006) Disorders of sodium balance. BMJ 332(7543), 702-705. [Free Full-text]
Rogers, I.R. and Hew-Butler, T. (2009) Exercise-associated hyponatremia: overzealous fluid consumption. Wilderness & Environmental Medicine 20(2), 139-143. [Abstract]
Rosner, M.H. (2009) Hyponatremia in heart failure: the role of arginine vasopressin and diuretics. Cardiovascular Drugs and Therapy 23(4), 307-315. [Abstract]
Schmitz, P.H., de, M.eijer, P.H. and Meinders, A.E. (2001) Hyponatremia due to hypothyroidism: a pure renal mechanism. Netherlands Journal of Medicine 58(3), 143-149. [Abstract]
Schrier, R.W. (2006) Body water homeostasis: clinical disorders of urinary dilution and concentration. Journal of The American Society of Nephrology 17(7), 1820-1832. [Free Full-text]
Schrier, R.W. (2010) Does 'asymptomatic hyponatremia' exist? Nature reviews. Nephrology 6(4), 185.
Siegel, A.J. (2008) Hyponatremia in psychiatric patients: update on evaluation and management. Harvard Review of Psychiatry 16(1), 13-24. [Abstract]
Smellie, W.S., Hampton, K.K., Bowley, R. et al. (2007) Best practice in primary care pathology: review 8. Journal of Clinical Pathology 60(7), 740-748. [Abstract] [Free Full-text]
Stuempfle, K.J (2010) Exercise-associated hyponatremia during winter sports. Physician and Sportsmedicine 38(1), 101-106. [Abstract]
Upadhyay, A., Jaber, B.L. and Madias, N.E. (2006) Incidence and prevalence of hyponatremia. American Journal of Medicine 119(7 Suppl 1), S30-S35. [Abstract]
van Amelsvoort, T., Bakshi, R., Devaux, C.B. and Schwabe, S. (1994) Hyponatremia associated with carbamazepine and oxcarbazepine therapy: a review. Epilepsia 35(1), 181-188. [Abstract]
Verbalis, J.G. (1989) Hyponatraemia. Baillieres Clinical Endocrinology & Metabolism 3(2), 499-530.
Verbalis, J.G., Goldsmith, S.R., Greenberg, A. et al. (2007) Hyponatremia treatment guidelines 2007: expert panel recommendations. American Journal of Medicine 120(11 Suppl 1), S1-S21. [Abstract]