Sodium

Question 1

Describe the classes of hyponatraemia based on serum sodium classification

Answer 1

mild is 130-135 mmol/L;
moderate is 125-129 mmol/L;
profound is <125 mmol/L

Question 2

Describe the classes of hyponatraemia as based on neurological symptoms

Answer 2

Moderately severe: nausea without vomiting, confusion, headache.
Severe: vomiting, cardiorespiratory distress, abnormal and deep somnolence, seizures, coma.

Question 3

How are acute and chronic hyponatraemia differentiated?

Answer 3

Acute develops in under 48 hours, chronic develops over a time period over 48 hours.

Question 4

what is the primary risk of rapid correction of chronic hyponatraemia?

Answer 4

osmotic demyelination syndrome

Question 5

When do signs of osmotic demyelination develop?

Answer 5

3-4 days after treatment

Question 6

what are the signs/consequences of osmotic demyelination syndrome?

Answer 6

dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma, death.

Question 7

what is the general target for rise in serum sodium concentration for any treatment for hyponatraemia?

Answer 7

target is 5 mmol/L rise in serum sodium concernration but no more than 10mmol/L rise in first 24 hours of treatment and 8 mmol/L for every 24 hours therafter (until reach a serum sodium of 130mmol/L).

Question 8

What must be considered if sodium rises by more than 10mmol/L in the first 24 hours or by more than 8 mmol/L every 24 hours thereafter in the course of treating hyponatraemia?

Answer 8

Should consider corrective action by re-lowering the sodium concentration.

Question 9

What are the three measurements that should be taken into account to assess a patient’s volume status?

Answer 9

blood pressure, heart rate, urea

Question 10

In a patient with what volume status should hypertonic saline not be used to correct hyponatraemia?

Answer 10

hypovolaemic patient who is likely to be hyponatraemic due to volume depletion should not receive hypertonic sodium chloride.

Question 11

What confirms hypotonic hyponatraemia?

Answer 11

plasma osmolality <275 mOsm/kg (>275 mOsm/kg should spark consideration of non-hypotonic hyponatraemia causes)

Question 12

what are four differentials for non-hypotonic hyponatraemia?

Answer 12

hyperglycaemia;
ethanol;
pseudohyponatraemia: due to paraproteinaemia or hypertriglyceridaemia

Question 13

In the case of hypotonic hyponatraemia with urine osmolality <100 mOsm/kg, what are 4 likely causes?

Answer 13

primary polydipsia;
inappropriate IV fluids;
low oral sodium intake;
beer potomania

Question 14

if a patient has hypotonic hyponatraemia and urine osmolality is >= 100 mOsm/kg what should you next measure to narrow the differential?

Answer 14

measure urine sodium (to see whether above or below 30 mmol/L)

Question 15

if a patient with hypotonic hyponatraemia has a urine osmolality >= 100 mOsm/L and urine sodium < 30 mmol/L, is their effective arterial volume high or low?

Answer 15

low

Question 16

List 6 differentials for a patient with hypotonic hyponatraemia with urine osmolality >=100 mOsm/L and urine sodium <30 mmol/L

Answer 16

If clinically hypervolaemic (ECF expanded):
heart failure; liver failure; nephrotic syndrome.

If clinically hypovolaemic (ECF contracted):
GI loss; 3rd space loss; previous diuretic loss.

Question 17

what intervention may affect urine sodium levels so should be considered when interpreting the result?

Answer 17

administration of IV sodium chloride 0.9% prior to measurement

Question 18

if a patient has hypotonic hyponatraemia and a urine osmolality >= 100 mOsm/kg and urine sodium >= 30 mmol/L what are 9 differentials for the cause?

Answer 18

If patient is on diuretics:

• diuretics;
• kidney disease;

If patient is clinically hypovolaemic (ECF contracted):

• vomiting;
• primary adrenal failure;
• renal salt wasting;
• CSWS (cerebral salt wasting syndrome);

If patient is clinically euvolaemic (ECF normal):

• SIADH;
• secondary adrenal insufficiency;
• hypothyroidism (context of myxoedema).

Question 19

what test is necessary to exclude a key differential in a patient with hypotonic hyponatraemia, urine osmolality >= mOsm/kg and urine sodium >= 30 mmol/L ?

Answer 19

short synacthen test to exclude adrenal insufficiency

Question 20

who should be asked for advice and or review before administration and prescription of hypertonic sodium chloride for treatment of hyponatraemia?

Answer 20

specialist endocrine or renal senior

Question 21

in patients with hypovolaemic hyponatraemia, what is the priority for treatment?

Answer 21

fluid replacement/resuscitation (still important not to correct sodium at more than 10 mmol/L in first 24 hours)

Question 22

how is hypovolaemia diagnosed and how is success of reuscitation measured in the context of hypovolaemic hyponatraemia?

Answer 22

clinical diagnosis and same parameters for judgement of success of resuscitation: tachycardia/ supine hypotension/ absent JVP/ postural hypotension)

Question 23

what fluids can be considered for fluid resuscitation in hypovolaemia hyponatraemia?

Answer 23

something relatively isotonic eg. Plasmalyte 148 or Hartmann’s or normal saline (aka sodium chloride 0.9%). (DO NOT use hypotonic fluids as this will worsen the hyponatraemia).

Question 24

how often should serum sodium be re-checked during resuscitation of hypovolaemic hyponatraemia?

Answer 24

at least every 4 hours

Question 25

When treating hypovolaemic hyponatraemia, what should be strictly monitored (in addition to serum sodium)? why?

Answer 25

hourly input/output because patient may become polyuric once they become euvolaemic and the non-osmotic stimulus for ADH production will drop: their sodium may begin to correct too quickly.

Question 26

what is the hypertonic solution and regimen (including how often to check the serum sodium) recommended for use in acute hyponatraemia?

Answer 26

single aliquot of 300mls of sodium chloride 1.8% over 30 minutes then check serum sodium after infusion (tell lab it's urgent) and at least every 4 hours afterwards until serum sodium >125 mmol/L and then at least every 6hours until serum sodium >= 130mmol/L. May need to give more infusions of hypertonic sodium chloride 1.8% but only after post-infusion serum sodium level known and have more specialist/renal advice, aiming for 5 mmol/L increase in serum sodium, no more than 10mmol/L increase in first 24 hours and no more than 8 mmol/L increase every 24 hours after that.

Question 27

for what route of administration is hypertonic sodium chloride 1.8% licensed?

Answer 27

central line (however if balance of risk/urgency requires peripheral cannula use a large one: minimum 18G [green venflon] in a large vein eg antecubital fossa, though this is an unlicensed use and site needs to be monitored closely for signsof extravasation injury and necrosis)

Question 28

what is the key to distinguishing between CSWS and SIADH?

Answer 28

patient's fluid status: CSWS causes hypovolaemia due to natriuresis whereas SIADH is euvolaemic.

Question 29

what is natriuresis?

Answer 29

excretion of sodium in urine

Question 30

what pathology is often described in patients with CSWS?

Answer 30

subarachnoid haemorrhage (but actually because patients with SAH usually receive isotonic sodium chloride as par of their treatment, if somebody becomes hyponatraemic after SAH it is more likely to be due to SIADH than CSWS as CSWS is still rare)

Question 31

what is used to treat CSWS?

Answer 31

IV sodium chloride 0.9% (though it usually resolves spontaneously within 2 to 3 weeks of cerebral insults)

Question 32

what is the initial treatment for SIADH?

Answer 32

fluid restriction

Question 33

blood urea in CSWS vs SIADH?

Answer 33

blood urea raised in CSWS, low or normal in SIADH

Question 34

blood pressure in CSWS vs SIADH?

Answer 34

low BP or postural hypotension in CSWS vs normal BP in SIADH

Question 35

central venous pressure in CSWS vs SIADH?

Answer 35

low in CSWS vs normal in SIADH

Question 36

urine sodium in CSWS vs SIADH?

Answer 36

may be very raised in CSWS, raised in SIADH

Question 37

urine volume in CSWS vs SIADH?

Answer 37

high urine volume in CSWS vs low in SIADH

Question 38

thirst in CSWS vs SIADH?

Answer 38

increased thirst in CSWS, normal in SIADH

Question 39

What are the criteria for diagnosis of SIADH? (6 points)

Answer 39

Diagnosis of exclusion. 1. hypo-osmolality: plasma osmolality <275 mOSm/kg or plasma sodium <135 mmol/L; 2. inappropriate urinary concentration (Uosm >100mOsm/kg) for hyponatraemia; 3. patient clinically euvolaemic; 4. Elevated urinary sodium (>30mmol/L) with normal dietary salt and water intake; 5. Exclusion of hypothyroidism, glucocorticoid deficiency (MUST do a short synacthen test), or diuretic use; 6. normal renal and cardiac function.

Question 40

list at least a couple drugs that stimulate release of ADH and so should be in your differential for SIADH cause?

Answer 40

``` nicotine; phenothiazines; tricyclic antidepressants; vinca alkaloids; cyclophosphamide; dopamine agonists; selective serotonin receptor inhinbitors; opiates; thioxanthenes; haloperidol; oxytocin; MDMA (ecstasy) ```

Question 41

name at least a couple of drugs that potentiate the action of ADH or have direct renal effects so should be in your differential for what caused SIADH?

Answer 41

``` desmopressin (DDAVP); cyclophosphamide; prostaglandin synthesis inhibitors; NSAIDS; paracetamol; carbamazepine ```

Question 42

name at lease two types of drugs that have mixed or uncertain actions on ADH that may make them a cause of SIADH?

Answer 42

ACE inhibitors; PPIs/omeprazole; melphalan.

Question 43

name 4 pulmonary infections that can cause SIADH?

Answer 43

TB; pneumonia; aspergillosis; empyema

Question 44

list three non-infective pulmonary causes of SIADH?

Answer 44

adult respiratory distress syndrome; COPD; positive-pressure ventilation

Question 45

name 7 tumour locations that may cause of SIADH

Answer 45

``` pulmonary/mediastinal; duodenal; pancreatic; ureteral/prostate; uterine; nasopharyngeal; leukaemia ```

Question 46

what is the "triple phase response" after transspenoidal adenomectomy?

Answer 46

initial cranial diabetes insipidus then 4-8 days later a transient remission or SIAD occurs for 2-8 days then a recurrence of permanent diabetes insipidus

Question 47

name a few CNS-related causes of SIADH

Answer 47

``` mass lesions; inflammatory diseases; degenerative/demyelinating diseases; SAH; head trauma; pituitary stalk section; acute psychosis; delirium tremens; hydrocephalus; transspenoidal adenomectomy. ```

Question 48

What is Type A SIADH and what is usually the underlying cause?

Answer 48

random hypersecretion of ADH: plasma ADH levels remain inappropriately elevated and don't lower when plasma osmolality lowers so usually severe hyponatraemia occurs. Usually small cell carcinomas of lung.

Question 49

what is Type B SIADH?

Answer 49

elevated basal secretion of ADH despite normal regulation by osmolality

Question 50

what is Type C SIADH?

Answer 50

inappropriate release of ADHat abnormally low threshold of plasma osmolality (there's a definable osmotic threshold for ADH release and lowering plasma osmolality below this level stops ADH secretion, preventing severe hyponatraemia) : many cases of chronic hyponatraemia especially in the elderly, are type C.

Question 51

What is Type D SIADH?

Answer 51

there doesn't seem to be a defect in osmoregulation of ADH, instead maybe there's an activating mutation of the V2 receptor or abnormal control of aquaporin-2 water channels in renal collecting tubules, or some other antidiuretic is being produced other than ADH (so actually this is SIAD- syndrome of inappropriate anti-diuresis)

Question 52

describe the management of chronic hyponatraemia due to SIADH

Answer 52

1. withold meds that may be causing/exacerbating; 2. identify/treat cause; 3. CXR in all pts with SIADH; 4. if new (within 12 months) and unexplained hyponatraemia, consider CT chest even if normal CXR to exclude bronchogenic carcinoma! (hypo-osmolality/hyponatraemia may pre-date radiographic changes by 3-12 months); 5. strict fluid restriction of 800-1000ml per day (start with 1000ml per day restriction); 6. if fluid restriction doesn't begin to resolve the hyponatraemia within 3-4 days, can try oral demeclocycline 600-1200 mg per day in divided doses (usually takes 3-4 days and restores Na+ levels within 5-14 days) while continuing fluid restriction; monitor renal function every day on demeclocycline and stop immediately if any sign of renal dysfunction; 7. as alternative to demeclocycline, may try combo of loop diuretic and oral sodium chloride (Slow-sodium (TM) tables or if NG/PEG tub then sodium chloride 1 mmol/ml oral solution [unlicensed]): this approach is more likely to work at urine osmolalities over 350 mOsm/kg because it induces increased renal free water clearance).

Question 53

what is Tolvaptan/ mechanism of action?

Answer 53

a V2 receptor antagonist: selectively antagonises antidiuretic effect of ADH by binding to V2 receptrs in kidney, increasing water loss without loss of electrolytes so will reduce total body water while raising plasma [sodium].

Question 54

what is Tolvaptan licensed for?

Answer 54

euvolaemic and hypervolaemic hyponatraemia (do NOT use in hypovolaemic hyponatraemia) -- not a formulary medicine in NHS Scotland however can obtain via IPTR in NHS Lothian by application by responsible consultant: usually in case of hyponatraemia due to SIADH secondary to underlying malignancy

Question 55

when is Tolvaptan most useful?

Answer 55

chronic biochemically severe euvolaemic or hypervolaemic hyponatraemia with mild to moderate symptoms (in acute severe symptomatic hyponatraemia, hypertonic sodium chloride is a better choice)

Question 56

what is the recommended starting dose of Tolvaptan?

Answer 56

7.5mg (half of the licensed dose, to avoid rapid rise in Na) -- review daily, and initially check sodium 4-6 hourly until determine correct dose for the patient!

Question 57

what are 4 patient groups in which Tolvaptan is contraindicated?

Answer 57

patient unable to sense/appropriate respond to thirst; liver disease; renal failure; anuric patients

Question 58

if a patient has a limited ability to drink eg due to oral or GI disease, what may require prescription alongside Tolvaptan?

Answer 58

glucose 5% (especially on day one of tolvaptan therapy when there's the most aquaresis)

Question 59

what antibiotic should be discontinued while on tolvaptan?

Answer 59

demeclocycline

Question 60

should fluid restriction and or hypertonic sodium chloride 1.8% be used alongside tolvaptan?

Answer 60

No. Discontinue fluid restriction. Don't use with hypertonic sodium chloride 1.8%.

Question 61

what pathway metabolises tolvaptan? relevance?

Answer 61

cytochrome p450 (so, avoid or cautiously use enzyme inducers/inhibitors)

Question 62

what organ function should be monitored during tolvaptan therapy?

Answer 62

LFTs (increased risk of liver injury, immediately discontinue tolvaptan if LFT derangement and monitor for liver failure features)

Question 63

when should tolvaptan therapy be discontinued?

Answer 63

upon resolution of symptoms and/or normalisation of serum sodium: BUT, sudden discontinuation may cause relapse of hyponatraemia so may need to slowly taper down dose and fluid restrict: especially if underlying cause of SIADH, eg malignancy, hasn't resolved. Check serum Na+ daily after discontinuation until Na+ levels stabilise.

Question 64

what should the approach be if hyponatraemia is corrected too rapidly?

Answer 64

discontinue whatever the active treatment for hyponatraemia is, consult renal/endocrine team: may consider sodium-free IV infusion, eg glucose 5% and may be need to add some IV desmopressin...