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

• 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 ?

No Rx Cerebral edema Rx Seizures Rapid correction Death Risk of ODS ACUTE HYPONATRAEMIA brain edema marked, minimal brain volume regulation

CHRONIC SYMPTOMATIC HYPONATRAEMIA some brain edema, partial brain volume regulation

CHRONIC ASYMPTOMATIC HYPONATRAEMIA complete brain volume regulation minimal brain edema Case 2

 62 yr old lady referred with acute confusion, unsteadiness, falls; preceeded by & 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,

Correction for hyperglycaemia

paraproteins] 1.6 mmol Na for every 5 mmol increase in glucose.

E.g. Patient with Na of 127, Glucose of • Measure urine osmolality 30mmol/L. After correction –> Na = 135 • Measure urine Sodium Hypotonic hyponatraemia

• Hypovolemic • Solute loss • Cerebral salt wasting • Salt wasting nephropathy • • Hypervolemic • Liver , , • 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 Sodium 103 2. Drug induced Serum osmo 230 3. SIADH Urine osmo 630 4. 1 & 2 Urine Sodium 18 5. All of the above

Correct answer 4

What is the treatment?

1. Fluid restrict to 1L 2. Slow Sodium tablets 3. 0.9% Saline 4. 1.8% Saline 5. 6.

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 soluteload  Urine volume = urineosm =160/400 = 0.4L = 400ml  Excess water excretion = 400 mls (160 mmol of solute diluted in 400 ml of water gives osmolality of 400)

Effect of Saline in SIADH soluteload • Urine volume = urineosm • 1 litre of 0.9% Saline contains = 300 mosm (154 Na + 154 Cl) and 1000 ml of H2O 300 • Urine volume = 600 = 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! 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?