Management of hyponatraemia

Dr. Shiva Mongolu

Consultant Endocrinologist

Hull & East Yorkshire Hospitals NHS Trust

Honorary Senior Lecturer HYMS

Aims

• Understand the physiology of Na

• How to approach hyponatraemia

• Identify cause

• SIADH treatment options

Background

• Hyponatremia is the most common endocrine

abnormality

• Incidence 15-30% of hospitalised patients

[Na<135]

• Increased mortality [RR 1.95]

• Gait instability and falls – mild hyponatremia

Physiology

Sodium is therefore regulated by 3 mechanisms: 1) RAAS 2) ADH release 3) Thirst mechanism

Volume regulation vs osmoregulation

How to approach

• How is the patient?

• Is it acute or chronic?

• Is it SIADH or volume depletion?

• Do I need to intervene?

Case 1

45 yr old male, h/o ETOH excess, found collapsed on

street

On arrival to ED, GCS 13, confused and disorientated,

no focal CNS signs

Meds: Vit B co-strong, Thiamine

Collateral Hx: No D+V/fluid loss

Na 109 K 3.2 Ur 1.5 Cr 45

Has seizures in ED, generalised tonic-clonic lasting 2

mins

GCS dropped to 9

What would you do?

1. Arrange tests (serum/urine osm/urine Na) and

wait for results

2. Give 0.9% Saline

3. Give 1.8% Saline on the ward

4. Contact ICU for 3% saline Rx

Correct answer 4

What happens in acute hyponatraemia?

Acute vs Chronic

• > 48 hrs duration chronic

• Assume chronic unless evidence to contrary

• Danger of rapid correction

• Central pontine Myelinolysis (Osmotic Demyelination syndrome)

• Suggested rate of correction

• No more than 0.5-1 mmol/L every hr

• Less than 8-10 mmol/L in 24 hrs

• Less than 18 mmol/L in 48 hrs

Do I need to intervene ?

Rx Rapid correction Risk of ODS

No Rx Cerebral edema Seizures Death

ACUTE HYPONATRAEMIA brain edema marked, minimal brain volume regulation

CHRONIC ASYMPTOMATIC HYPONATRAEMIA complete brain volume regulation minimal brain edema

CHRONIC SYMPTOMATIC HYPONATRAEMIA some brain edema, partial brain volume regulation

Case 2

62 yr old lady referred with acute confusion,

unsteadiness, falls; preceeded by vomiting &

diarrhoea a week before

On Bendrofluazide for HTN

Clinically euvolemic, GCS 14, AMT 8/10

Na 103 K 4.5 Cortisol 982 TFT normal

Serum Osm 230 Urine Osm 630 Urine Na 18

What is the likely cause?

1. Volume depletion

2. Drug induced

3. SIADH

4. 1 & 2

5. All of the above

Stepwise Approach

• Establish hypotonicity [Glu, Lipids,

paraproteins]

• Measure urine osmolality

• Measure urine Sodium

Correction for hyperglycaemia 1.6 mmol Na for every 5 mmol increase in glucose. E.g. Patient with Na of 127, Glucose of 30mmol/L. After correction –> Na = 135

Hypotonic hyponatraemia

• Hypovolemic • Solute loss

• Cerebral salt wasting

• Salt wasting nephropathy

• diuretics

• Hypervolemic • Liver cirrhosis, heart failure, nephrotic syndrome

• Euvolemic hyponatraemia (SIADH)

Hypovolemic hyponatraemia vs SIADH

In SIADH – urine Na is usually > 30 mEq/L (20-40) In Hypovolemia – urine Na < 25 mEq/L (15-20) * Assuming not on diuretics, normal dietary salt intake

Hypovolemic hyponatraemia vs SIADH

• Urine osmolality > 100 indicates impaired ability to dilute urine

• Usually secondary to raised ADH level

• Note – raised ADH can be both appropriate or inappropriate

• If in doubt, treat with 0.9% Saline 1000 mls over 8-10 hours

• If Na improves, it indicates hypovolemia. If doesn’t change/falls, it is SIADH

What is the likely cause?

1. Volume depletion

2. Drug induced

3. SIADH

4. 1 & 2

5. All of the above

Correct answer 4

Sodium 103

Serum osmo 230

Urine osmo 630

Urine Sodium 18

What is the treatment?

1. Fluid restrict to 1L

2. Slow Sodium tablets

3. 0.9% Saline

4. 1.8% Saline

5. Demeclocycline

6. Tolvaptan

Correct answer 3

Case 2

0.9% Saline 8-12 hrly + Slow Sodium tablets

Na improved to 109 in 24 hrs, 118 in 48 hrs

Saline and Slow Na stopped

Na continued to improve and was 126 on day3

Discharged with OP fu

Case 2 – follow-up

• Represented 1 week later with agitation, emotional lability, unable to care for herself and her husband

• Quite tearful, drooling of saliva, slow speech and agitation

• Na 135

• MRI Brain

‘Increased signal in basal ganglia bilaterally, including head of caudate nuclei and the putamina as well as pons consistent with central pontine myelinolysis’

Risk factors for ODS

Serum Sodium at presentation

Duration of hyponatremia

Rate of correction

More common in : Alcoholism Malnutrition Advanced liver disease

Case 3

76 yr old male

4 day history of confusion and falls

Fit and well

Started on Citalopram and Zopiclone 2 weeks ago due to low mood and memory problems

Examination unremarkable

Na 112 K 3.2 normal renal function

Serum osmo 230 Urine osm 283 urine Na 31

TSH 1.3 SST normal

CT Head – no acute infarction/haemorrage

What is the likely Diagnosis?

Hypotonic hyponatremia

1. SIADH (drug induced)

2. ? Volume depletion

What treatment?

Given 0.9% Saline slowly

Repeat Na 109

Diagnosis?

SIADH

No improvement with fluid restriction 800mls/24hr

Confusion worsening , GCS 14/15

What next?

Tolvaptan vs 1.8% Saline vs 3% Saline

Treated with 1.8% Saline 500 mls 50ml/hr

Na gradually improved to 124 and 132 at discharge

Fluid restrict or Saline?

• Volume status unclear from clinical assessment

1000mls of 0.9% saline over 10hrs, measure urine and serum sodium pre / post

• Dual diagnosis

i.e. SIADH + depleted intravascular volume, e.g. in septic shock, high-volume diarrhoea

Initial treatment with 0.9% saline, may require intermittent hypertonic saline (1.8%) if large volumes of IV fluids required

Does Fluid restriction work?

General guidelines:

restrict all intake consumed by drinking,not just water

aim for fluid restriction that is 500ml/d below the 24-hr urine output

do not restrict sodium intake

Does Fluid restriction work?

Predictors of failure of fluid restriction*

high urine osmolality (>500 mOsm/kg H2O) urine Na+K greater than serum [Na] 24 hr urine output < 1500 ml/day Increase in serum[Na] < 2mmol/day

*The urine/plasma electrolyte ratio: a predictive guide to water restriction. Furst H et al; Am J Med Sci 2000

What about slow sodium tablets?

• SIADH vs salt wasting? • Oral sodium tablets favored in neurosurgical units

• Role in transient aldosterone resistance?

• Does it help in SIADH? • Excess sodium excreted in urine together with water

• Effect can be estimated from urine osmolality

• May be effective in mild SIADH (Na > 125, urine osmolality < 500)

• Is not practical in patients with moderate to severe SIADH as amount of oral sodium required is excessive

Effect of Slow Na in SIADH

Eg : patient with a urine osmolality of 400, taking 2 tablets QDS

1 tablet of slow Na contains = 20 mmol solute (10mmol Na + 10mmol Cl)

8 tablets = 160 mmol

Urine volume = =160/400 = 0.4L = 400ml

Excess water excretion = 400 mls (160 mmol of solute diluted in 400 ml of water gives osmolality of 400)

urineosmsoluteload

Effect of Saline in SIADH

• Urine volume =

• 1 litre of 0.9% Saline contains = 300 mosm (154 Na +

154 Cl) and 1000 ml of H2O

• Urine volume = = 0.5L = 500 ml

• Input = 1000 ml H2O + 300 solute

• Output = 500 ml H2O + 300 solute

• Net water gain = 500 ml H2O (causes further drop in Na)

• 0.9% Saline therefore does not work in pure SIADH!

urineosm

soluteload

600

300

When to use Demeclocycline?

• Induces reversible nephrogenic diabetes insipidus

• Doses used in studies 600-1200mg daily

• Effect takes atleast 72 hrs

• Significant rise in 5-7 days

• Risk of hypernatraemia and renal impairment

• Can be used in chronic SIADH

What about Tolvaptan? Confirmed SIADH, alternative diagnosis excluded

AND

Symptomatic Hyponatremia with Na < 125 not responding to fluid restriction (1000mls/24h)

OR

Na <125 despite fluid restriction (1000mls/24h) and discharge would be expedited with correction of hyponatremia

OR

Definite acute onset significant hyponatremia with acute symptoms ( may consider direct treatment with tolvaptan rather than fluid restriction in select cases ) with history and findings in keeping with SIADH

Hypertonic Saline

• Indicated in patients where there is :-

• EITHER urgent need to correct symptomatic hyponatraemia

• OR other measures unavailable/have failed

• OR dual diagnosis (hypovolaemia + SIADH) requiring high volume / continuous IV fluid replacement therapy

• Will correct hyponatraemia regardless of underlying aetiology!

Hypertonic Saline Option of 1.8% saline and 3% saline 1.8% saline (308mmol of Na/L) 500ml bags readily available

(ITU/NeuroITU/pharmacy if not kept on ward)

Can be safely given via peripheral cannula on ward (only via slow infusion through a pump)

For treatment on ward - 500mls at 50mls/hr with repeat measurement of Na at the end of infusion to assess response in serum Na.

Summary In severe hyponatraemia (Na<110mmol/L) or neurological

compromise, urgent correction with 3% Saline (irrespective of the cause) in ITU setting

Two main causes of hypotonic hyponatraemia in

inpatients are : hypovolemia and SIADH

Assume hyponatraemia chronic unless there is clear evidence

When treating hyponatraemia, consider the risks of cerebral edema vs risks of rapid Rx

Contact Local Endocrine team for advice

Thank you

Questions?