Hyponatremia ( Low Sodium )

Hyponatraemia –Defined as serum sodium ( Na ) concentration of < 135 meq/l

Most common electrolyte disorder in clinical practice Seen in 15-30 % of patients in hospital setting ( particularly ICU ) Incidence and prevalence differs- based largely on study population and clinical setting Heterogenous disorder – often poses diagnostic and therapeutic challenge ( numerous pathophysiological mechanisms and multiple underlying pathological conditions ) Associated with ↑↑ mortality in hospital patients ( independent risk fx )

Mild 130-135
 Moderate- 125-129
 Severe 
< 125. Acute < 48 hrs
 Chronic > 48 hrs

Based on time of onset cutoff 48 hrs. Symptomatic versus asymptomatic
 Hypotonic , isotonic or hypertonic 
( based on serum osmolality )

Most common is hypotonic hyponatraemia
 Hypovolemic , euvolemic or hypervolemic 
( volume status )

Pseudohyponatraemia -a laboratory artefact that may occur with high conc of triglycerides , cholesterol or protein leading to nonhypotonic hyponatraemia

Risk factors- Old age
- degenerate physiology
- multiple co-morbidities
- polypharmacy Hospitalization or nursing home status
seen in almost 1/2 of acute geriatric admissions Drugs as
SSRIs , diuretics Underlying medical conditions as CCF , cirrhosis , AKI/CKD , hypothyroidism , adrenal insufficiency, malignancy

Often multifactorial European and US guidelines- help as evidence base for management
is still limited Most common causes of hyponatraemia are
○ SIADH- syndrome of inappropriate antidiuresis 
○ diuretic use
○ polydipsia
○ adrenal insufficiency
○ hypovolemia
○ heart failure
○ liver cirrhosis Management of hypotonic and non-hypotonic hyponatraemia is different US guideline divides hypotonic
hyponatremia 
further into
○ hypovolemic
○ euvolemic
○ hypervolemic

most commonly used approach differentiation between euvolemic and hypovolemic HN is notoriously difficult hypervolemic -relatively easier (edema or ascites

Often an incidental finding Symptoms are related to 
○ underlying cause
○ if associated with fluid loss or dehydration
○ severity of hyponatraemia
○ rate at which it develops Most people with mild hyponatraemia ( 130-135 ) are asymptomatic particularly if it has developed slowly 
Brain adapts by generating idiogenic osmoles Symptoms if present predominantly reflect CNS disturbance due to cerebral edema induced by water movement into the brain Symptoms may develop once level reaches 115 or earlier if fall is rapid)

Acute- CNS disturbance Nausea ,Vomiting , drowsiness Headache , confusion , seizures
hyponatremic encephalopathy Coma , cardiorespiratory arrest and death due to cerebral oedema and ↑↑ ICP. Features can be non specific Frequent falls Gait disturbance Concentration and cognitive deficits ↑↑ osteoporosis and fractures

Volume status
pulse rate
postural changes in BP
JVP
oedema , ascites ( overload )
Signs of dehydration eg skin turgor , dry mucous membranes Auscultate chest – rales or crackles ( vol overload ) Neurological status – r/o signs and symptoms of cerebral oedema R/O any acute illness as pneumonia , gastroenteritis GI symptoms eg nausea and vomiting ( ↑↑ in acute ) Low urine output ( fluid intake / loss , thirst ) Weight changes Consider known conditions that may have caused ↓ Na as CCF , 
renal or liver disease Consider underlying neoplasia

Serum sodium conc Electrolytes , urea , creatinine and glucose TFT , LFT , Lipids Serum osmolality 
( helps differentiate hypotonic from hypertonic hyponatraemia )
< 275 mmol/ kg is hypotonic
> 295 mmol/ kg is hypertonic
Normal is isotonic Urine osmolality Serum cortisol or ACTH hormone test – consider in euvolemic patients ( may exclude adrenal insufficiency ) Immunoglobulins Imaging – eg CT brain , chest etc 
( look for cause of SIADH ). Three essential tests + History + Physical examination in evaluation- Urine osmolality helps identify conditions associated with impaired free-water excretion and primary polydipsia ie helps evaluate causes of euvolaemic hyponatraemia- Serum osmolality helps readily differentiate between true hyponatraemia and psuedohyponatraemia- Urinary sodium conc helps differentiate between hyponatraemia 2ary to hypovolemia and SIADH ie helps confirm the presence of hypovolemia or euvolemia

These tests may not be always easily available / ordered in general practice making the evaluation of hyponatraemia challenging . Interpretation is not always straightforward- keep a low threshold in seeking help by e-mail/ph as necessary

If testing – remember that they need to be done on 
the same day ( paired testing )

Repeat Na level based on 
clinical judgement and obtain 
background clinical hx- R/O pseudohyponatraemia (due to high serum protein or lipid levels or hyper osmolar due to severe hyperglycaemia )
 Assess the trend 
( acute of chronic )

Hypervolemia- ↑ in total body Na with greater ↑ in TBW*- Liver cirrhosis CCF Renal failure Nephotic syndrome

can manifest as oedema or ascites-Euvolemia- normal body Na with ↑ in TBW-SIADH Secondary adrenal insufficiency Hypothyroidism
( rare ) Excess drinking Hyperglycaemia Drugs-Hypovolemia- dec in TBW with greater decrease in total body Na-Renal loss eg
Thiazide 
Addisons
Salt wasting nephropathy Extra-renal loss
diarrhoea , vomitting , ↑↑ sweating Third space loss
Sm bowel obst
Pancreatitis , burns

Medication review-Usually develops within the first few weeks of Rx If offending medication stopped check Na in 1-2 weeks. Seek advice from prescribing specialist if the medication cannot be stopped readily. Diuretics – thiazides , Indapamide , Amiloride , loop diuretics
Responsible in about 20 % of people who take them- more severe cases almost always with thiazide than loop SSRIs – cause ↓ Na in about 1/3rd of people who take them Antipsyhotics – cause ↑↑ thirst ( polydipsia )
eg haloperidol and phenothiazines via SAIDH NSAIDs ( rare ) – cause water retention by increasing water permeability across the renal collecting ducts Carbamazepine -↑ ADH release and more frequent in elderly
 Other medications include tricyclic antodepressants , ACEi , ARBs , PPIs , sulphonylureas , dopamine agonists , opiates , amiodarone , some chemotherapy medications

Underlying cause- Intercurrent illnesses ( eg chest infections , GI disease or UTIs ) Renal disease Hypothyroidism Addisons disease CCF , liver disease or fluid overload Myeloma Cancers. Diagnosis of exclusion Several criteria exist for diagnosis for 
eg Barrter and Schwartz ( 1967 ) Be wary of diagnosing SIADH in the community as 
○ several conditions can cause SIADH
○ wide differential diagnosis
○ may need extensive investigations particularly to r/o cancer before establishing a diagnosis Given the complexities CKS recommends that an urgent 2 week referral should be made if SIADH is suspected

Admit- Acute onset or severe hyponatraemia
( CKS – severe is < 125 mmol / L ) Patient is symptomatic Rapid fall – considered as fall of
 > 10 mmol /L in 48 hrs Signs of hypovolemia Suspected Addisons disease. Refer- Cause not clear SIADH suspected or cancer is suspected as cause of SIADH ( 2 wk ) Primary polydipsia ↓↓ Na persists after stopping a suspected offending medication

Summary- Hyponatraemia is seen frequently and is associated with significant morbidity and mortality Can happen with volume depletion , overload or euvolemia Cerebral oedema is a medical emergency- occurs more frequently when HN develops rapidly over 
< than 48 hrs

References- References
 Diagnosis and Treatment of Hyponatraemia : Compilation of the Guidelines Ewout J Hoorn and Robert Zietse J Am Soc Nephrol 28 ;1340-1349 , 2017 Hyponatraemia CKS NHS – last revised March 2015 Hyponatraemia : A Practical approach Manisha Sahay , Rakesh Sahay Indian Journal of Endocrinology and Metabolism Nov-Dec 2014 Vol 18 Issue 6 Intensive care – Tutorial 134 Hyponatraemia by Dr Peter Allan and Dr Saibal Ganguly from ATOTW tutorials www.afsahq.org BMJ Best Practice Hyponatreamia Hyponatraemia : Special Considerations in Older Patients J Clin Med 2014 , 3, 944-958 Hyponatraemia e-Medicine Medscape Eric E Simon et al Jan 2018 Investigating hyponatraemia BMJ 2011 ; 342 : d 1118 The Pharmaceutical Journal – How to manage adults with hyponatraemia Clinical Pharmacist Jan 2012 Hyponatraemia ( Adults ) in Primary Care North Bristol NHS Trust guidance


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