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Hyponatraemia
GIM SpR Training Day
September 2016
Jenny Clayton
Consultant Diabetes and Endocrinology
Nottingham University Hospitals
Plan of action- hyponatraemia
• Why is it important?
• Classification of hyponatraemia
• Case history
• Diagnostic work up
• Emergency treatment acute severe hyponatraemia
• Treatment non severe hyponatraemia
Hyponatraemia guideline
Why is it important?
• Common – present in 15-20% emergency admissions to
hospital.
• Spectrum mild/subtle symptoms to severe/life-threatening
symptoms.
• Associated increased mortality and morbidity.
• Associated increased length of stay.
• Presents to all specialities: medical, oncology, intensivists,
surgeons, neurosurgeons.
• Potential to do harm- risk of osmotic demyelination.
How can it be classified?
• Symptoms?
– Mild/asymptomatic
– Moderate
– Severe
• Sodium concentration?
– Mild
– Moderate
– Severe
• Onset?
– Acute
– Chronic
• Volume status?
– Hypovolaemic
– Euvolaemic
– Hypervolaemic
• Aetiology?
– Usually multifactorial in
medical in-patients (75%)
• Symptoms relate to the sodium concentration and
time scale of the drop (acute vs chronic).
0 24 48 72 96 120 144 168120
125
130
135
140
145
Patient 2
Patient 1
Time (hours)
So
diu
m c
on
cen
trati
on
(mM
ol/
l).
• Causes according to volume status.
• Accurate diagnosis essential to guide appropriate treatment.
Hypovolaemic Euvolaemic Hypervolaemic
Renal sodium loss Thiazide diuretics CCF
Osmotic diuresis Hypothyroidism Cirrhosis
Diuretic agents 2º Adrenal insufficiency Nephrotic syndrome
1º Adrenal insufficiency SIADH Renal failure
Salt-wasting nephropathy CNS disorders Pregnancy
Cerebral salt wasting Cancer
Extrarenal sodium loss Drugs
D & V Pulmonary disease
Blood loss Miscellaneous e.g.post op
Fluid sequestration (3rd space) Decreased solute intake
Excess sweating
Case History
Case History – day 1, admission 1
• 39 year old male.
• MOPED accident 16/3/16, alcohol related.
• Admission under trauma team
• Subdural haematoma
• Pneumocephalus
• Basal skull fracture
• Complex facial fracture
• Sesamoid fracture left thumb
• CT CAP: adrenal incidentaloma
Na 138
K 4.1
Urea 4.1
Creatinine 77
LFTs normal
Case history- day 2, admission 1
• Discharged home
• FU orthopaedic hand clinic
• FU ENT
• FU ophthalmology
• Endocrine referral re adrenal incidentaloma.
Bloods that day
• Na 126
• Random cortisol 619
Case history – 4 days later…
• Seen at orthopaedic pre-op clinic
• Feeling unwell, nauseus
• Na 116
• K 4.7
• Urea 2.5
• Creat 54
Emergency admission to medical ward arranged
Case history- day 1, admission 2
• Further history?
• Further assessment?
• Investigations?
Results
• Na 116
• K 4.7
• Urea 2.5
• Creat 54
• Random cortisol 407
• Calcium 2.23
• TSH 3.8
• Serum osmolality 236
• Urine osmolality 634
• Urine Na 138
• Urine K 62
• CXR Right basal atelectesis
Diagnosis- cause of hyponatraemia?
Management?
Fluid restriction?
Frequency of electrolyte checks?
Sodium rise targets?
Case history - progress
• Fluid restriction 1.5 L • Day 1: sodium 116 mmol/l
• Day 2: sodium 117 mmol/l
• Day 3: sodium 120 mmol/l
• Day 4: sodium 118 mmol/l
• Day 5: sodium 118 mmol/l
• Day 6: sodium 118 mmol/l
• Day 7: sodium 121 mmol/l
• Day 8: sodium 122 mmol/l
• Day 9: sodium 131 mmol/l �discharged
• 2 weeks later @ GPs: sodium 136 mmol/l
Was the fluid restriction
effective?
Alternative management
strategies?
What is the latest guidance for the work up
and management of hyponatraemia?
Management of hyponatraemia
• Joint guidance European
endocrine society, European
Renal society, European
Society Intensive care.
• First published consensus
guideline on management.
• Published 2014, European
Journal of Endocrinology, 47
pages long!
UK
Work up/investigations
Careful history/drug history
Assessment of volume status/examination
Drug category Examples
Anticancer agents Vinca alkaloids (vincristine, vinblastine)
Platinum compounds (cisplatin, carboplatin)
Alkylating agents (IV cyclophosphamide, melphalan)
Antidepressants SSRI, Tricyclics, MAOIs
Anti-epileptic drugs Carbamazepine, Oxycarbazepine, Sodium valproate
Anti-hypertensive agents ACE inhibitors
Diuretics Thiazides, Indapamide, Amiloride, Loop diuretics
Antipsychotic drugs Phenothiazines, Butyrophenones (haloperidol)
Proton pump inhibitors Omeprazole
Work up/investigations
Careful history/drug history
Assessment of volume status
Screening blood/urine panel
• U&Es
• Glucose
• Lipids
• Thyroid function
• Liver function
• Cortisol
• Plasma osmolality
• Urine osmolality
• Urine sodium
• Urine potassium
Is it hypotonic hyponatraemia?Could it be pseudo hyponatraemia?
Is the patient hyperglycaemic?Could it be a drip arm sample?
Work up/investigations
Careful history/drug history
Assessment of volume status
Further investigations
• CXR
• CT head
• Short synacthen test
• CT CAP
Screening blood/urine panel
• U&Es
• Glucose
• Lipids
• Thyroid function
• Liver function
• Cortisol
• Plasma osmolality
• Urine osmolality
• Urine sodium
• Urine potassium
Aetiology according to volume status and
urinary sodium
HYPOVOLAEMICHYPOVOLAEMICHYPOVOLAEMICHYPOVOLAEMIC EUVOLAEMICEUVOLAEMICEUVOLAEMICEUVOLAEMIC HYPERVOLAEMICHYPERVOLAEMICHYPERVOLAEMICHYPERVOLAEMICUrinary Na >20mmol/L
Urinary Na <20mmol/L
Urinary Na>20mmol/L
Urinary Na >20mmol/L
Urinary Na <20mmol/L
Renal losses• Osmotic diuresis• Diuretic therapy• Addison’s disease• Salt-losing nephropathy•Cerebral salt wasting
Extra-renal losses• Diarrhoea• Vomiting• Burns• Fistulae• Pancreatitis
• SIADH• Glucocorticoiddeficiency• Hypothyroidism• Diuretic therapy• Drugs
• Acute or chronic renal failure• Diuretic therapy
• Nephroticsyndrome• Cirrhosis• Cardiac failure
Management of hyponatraemia
Balance of risk
• Risk of cerebral oedema greatest if drop in sodium is severe and
acute (<48hrs).
• Risk of osmotic demyelination is greater with more chronic
hyponatraemia (>48hrs), severe hyponatraemia and rapid
correction.
Untreated severe hyponatraemia.
Risk of neurological sequelae from cerebral oedema
Treatment of severe hyponatraemia.
Risk of neurological sequelae from osmotic demyelination syndrome
Osmotic demyelination
• Develops one to several days after treatment of hyponatraemia.
• Demyelination of pontine and extrapontine (thalamus, basal
nuclei, cerebellum) neurons.
• Flaccid quadriplegia, pseudobulbar palsy, seizures, coma, death.
• At risk groups: elderly, children, malnourished, alcoholics, CNS
disease, hypoxaemia.
MRI appearances:T2 images show hyperintense areas of demyelination.
Management of severe hyponatraemia
Guidance same in European and UK papers.
* If low body weight give 3% saline at 2mls/kg body weight over 20 minutes
Previous approach: Adrogue
Formula
Change in serum Na
= Infusate Na (513)-serum Na
Total body water+1
Total body water = Body weight x 0.6/0.5/0.45
(young male/young female,old male/old female)
Hyponatraemia with severe symptoms(somnolence, seizures, coma)
First hour management
• 150 mls 3% (hypertonic)
saline over 20 mins*.
• Check sodium
concentration.
• Further 150 mls 3% saline
and repeat until sodium
risen by 5 mmol/L.
• Manage in level 2/3 bed.
Hyponatraemia with severe symptoms(Vomiting, somnolence, seizures, coma)
First hour management
• 150 mls 3% (hypertonic)
saline over 20 mins*.
• Check sodium concentration.
• Further 150 mls 3% saline
and repeat until sodium risen
by 5 mmol/L.
• Manage in level 2/3 bed.
Subsequent management
• Stop hypertonic saline.
• Slow infusion 0.9% saline.
• Diagnosis specific treatment.
• Limit rise in sodium in first 24
hours to ≤ 10mmol/l and
8mmol/l each following 24
hours.
• Check sodium at least 6
hourly.
– If sodium rise is excessive then IV dextrose or
desmopressin may be required.
– Small increase in sodium often gives major clinical
improvements.
Hyponatraemia with moderately severe
symptoms (nausea, confusion, headache)
• Cause specific treatment.
• Stop contributing/provoking
medications if possible.
• Immediate treatment with single
infusion of 150 mls 3% hypertonic
saline over 20 minutes.
• Aim 5 mmol/l increase in 24 hours.
• Limit sodium rise to ≤ 10mmol/l in first
24 hrs and 8mmol/l in each following
24 hours.
• Check sodium at 1,6 & 12 hours.
Alarm bells………
European
guideline
Management of non severe hyponatraemia
General hyponatraemia management
• Stop non-essential fluids, medications that can
contribute/provoke.
• Cause specific treatment.
• Avoid increase in sodium concentration >10mmol/l in first 24
hours and >8 mmol/l in each subsequent 24 hours.
Hyponatraemia with hypovolaemia*
• Restore extracellular volume with IV 0.9% saline or a balanced
crystalloid solution at 0.5-1 ml/kg/hour.
• If haemodynamic compromise the need for rapid fluid
resuscitation overrides the risk of an overly rapid increase in
sodium.
• Close biochemical and clinical monitoring, may need level 2
bed.
* If unclear if hypovolaemic or euvolaemic can give 1 litre 0.9% saline over
12 hours and review response at 6 and 12 hours.
Hyponatraemia with hypervolaemia
• Treat underlying condition.
• Fluid restriction to prevent further fluid overload.
• OK to use loop diuretics (fluid loss>urine sodium losses)
Euvolaemic hyponatraemia
• Confirm it is hypotonic
hyponatraemia
– Plasma osmolality <275
mOsm/kg.
• Check urine osmolality
– Urine osmolality
<100mOsm/Kg suggests
primary polydipsia or
beer potomania.
• Confirm diagnosis of SIADH
– Hypotonic plasma (<270
mOsm/kg).
– Inappropriate urine
osmolality (>100 mOsm/kg);
usually > plasma osmolality.
– Excessive renal sodium loss
(>20mmol/l).
– Normal renal, adrenal and
thyroid function.
– Interpret with caution if
patient on diuretics.
Treatment of SIADH
• Treat underlying cause
• Fluid restriction
– Use estimate of
electrolyte-free water
clearance to predict
response
– Furst formula:
urine/plasma
electrolyte ratio (U/P)
Furst formula
U/P electrolyte ratio=
Urine [Na] +Urine [K] mmol/l
Serum [Na] mmol/l
U/P < 0.5 :Fluid restrict to 1000mls
U/P 0.5-1.0 :Fluid restrict to 500mls
U/P >1.0 : Fluid restriction unlikely to
be beneficial
Treatment of SIADH
UK consensus
• Fluid restrict as first line:
Furst formula (24-48 hours)
• Second line (consult
endocrinologist)
– Demeclocycline 150-
300mg tds
– Tolvaptan 15mg OD: 6
hourly Na checks.
Prescribe as single doses.
Allow free fluids.
European guide
• Fluid restrict as first line:
Furst formula
• Second line
– Increased solute with 0.25-
0.5g/kg per day of urea or
– Low dose loop diuretic and
oral sodium chloride
• Vasopressin receptor
antagonists are not
recommended.
• Demeclocycline or lithium is
not recommended.
Black triangle
alerts for
tolvaptan
Use with caution
and very careful
monitoring
UK consensus
algorithm
Summary
• Hyponatraemia is very common. Careful clinical
assessment, investigation and interpretation of the
biochemistry essential.
• Severe hyponatraemia is a medical emergency and
needs cautious management. Primum non nocere.
• New algorithms offer practical guidance.
Thank you!