Hyponatremia (Practical Approach) - Dr. Gawad

Hyponatremia
Practical Approach
Mohammed Abdel Gawad
Nephrology Consultant - Alexandria - Egypt
MD Nephrology - Mansoura University
European Specialty Examination in Nephrology (ESENeph)
NephroTube Founder/Admin
Member of ISN education SoMe team
Co-chair of AFRAN Web & Media Committee
drgawad@gmail.com
@Gawad_Nephro
NephroTube Webinar, 01-July-2021

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Normal serum sodium
135-145 mEq/L (mmol/L)
Hyponatremia serum sodium
< 135 mEq/L (mmol/L)
the most common disorder of body fluid and
electrolyte balance encountered in clinical practice
• Beukhof CM, Hoorn EJ, Lindemans J, Zietse R. Clinical Endocrinology 2007 66 367–372
• Upadhyay A, Jaber BL, Madias NE. Seminars in Nephrology 2009 29 227–238

Fluid Compartments
POTASSIUM SODIUM

Goce Spasovski et al, Nephrol Dial Transplant (2014) 29 (Suppl. 2): ii1–ii39
Hyponatremia is primarily a
disorder of water balance
Relative excess of body water compared to
total body sodium and potassium content
H2O > Na

Talk Outline
• Presentation
• Diagnosis
• Management:
–General rules
–Stepwise approach
–Overcorrection
–Dialysis of Hyponatremic Patient

Hyponatremia
Clinical Presentation
The presence of these symptoms and their severity depend
on both the MAGNITUDE of the hyponatremia and the
RATE at which the hyponatremia developed

Hyponatremia
Pathogenesis of Central Effect
M.Gawad www.nephrotubecne.com
Normally: ICF Osmolality = ECF Osmolality
Intracellular Extracellular

Hyponatremia
Hyponatremia: ICF Osmolality > ECF Osmolality
Intracellular Extracellular
Intracellular
swelling &
edema
H2O
M.Gawad www.nephrotubecne.com

Hyponatremia
Hyponatremia: ICF Osmolality > ECF Osmolality

Hyponatremia
How brain adapt hyponatremia ??
(especially chronic cases)

Hyponatremia
How brain adapt hyponatremia ??
(especially chronic cases)
Maximal compensation for a
decrease in plasma osmolality
typically requires up to
48 hours.
Adrogue HJ & Madias NE. Hyponatremia. NEJM 2000 342 1581–1589.
Avoid rapid correction of
hyponatremia

Repeat serum Na
The level should be repeated to rule out:
– Lab error.
– blood-drawing error.
Precautions of sample taking:
– the blood should be drawn through the
skin (not from an IV line).
– the blood should be drawn from a vein that
does not have IV fluids flowing through it.

What is the next step?
What is the relation between
Na and Plasma Osmolality?
Normally ranges between 275 and 295 mmol/L

Rose BD, Post TW. Clinical Physiology of Acid-Base and Electrolyte Disorders,
5th ed, McGraw-Hill, New York 2001. p.699.
Translocational

Rose BD, Post TW. Clinical Physiology of Acid-Base and Electrolyte Disorders,
5th ed, McGraw-Hill, New York 2001. p.699.
Exclude Pseudo &
Translocational Hyponatremia
Translocational

True vs Pseudo - Hyponatremia
Turchin A, Seifter JL, Seely EW. New England Journal of Medicine 2003 349 1465–1469

In which compartment of the following we are
measuring sodium concentration ??
Blood
5 liters
Plasma
55%, 3 liters
Water 90%
Lipids, proteins &
other inorganic
substances
Cellular
elements
45%, 2 liters
RBCs WBCs Platelets
Pseudohyponatremia
(Normal Plasma Osmolality)
Introduction

TAKE CARE it is:
Na CONCENTRATION, Not Na LEVEL
Pseudohyponatremia
Introduction

Hyperlipidemia &
Hyperproteinemia
True vs Pseudo - Hyponatremia

Pseudohyponatremia
Hyperlipidemia & Hyperproteinemia
Na is here
Flame
photometry
measure Na in
relation to all
compartments

Water +
Na
Proteins,
Lipids
Cells
Na conc to
water = 50%
Na conc to
plasma =
35% Water +
Na
Proteins,
Lipids
Cells
Na conc to
water = 50%
Na conc to
plasma =
15%
The above numbers are not true values, they are only for demonstration
Pseudohyponatremia
M.Gawad www.nephrotube.com

The traditional method of measuring the
sodium concentration in plasma flame
photometry uses the entire volume of the
sample, which includes both the aqueous
and nonaqueous phases of plasma.
Pseudohyponatremia

Therefore, for patients with marked
elevations in plasma lipids or plasma
proteins, ask the hospital laboratory to use
an ion-specific electrode to measure the
plasma sodium concentration.
Pseudohyponatremia
Pseudohyponatraemia still occurs despite
the use of ion-selective electrodes

Serum Na x 93
99 – 1.03 (triglyceride gm/L) – 0.73 (protein gm/L)
Corrected Na =
Pseudohyponatremia
Stephen Sigworth, MD, MSHA. Sodium Disorders

Translocational- Hyponatremia
(High Plasma Osmolality)
High Serum Glucose or
Hypertonic Infusions
•Carlotti AP et al. Intensive Care Medicine 2001 27 921–924
•Oster JR et al. Archives of Internal Medicine 1999 159 333–336
•Hillier TA et al. American Journal of Medicine 1999 106 399–403
Translocational

Translocational Hyponatremia
(High Plasma Osmolality)
Here Na is truly low
(i.e. not lab error),
but
plasma osmolality is high
Handbook of Critical Care Nephrology. Chapter 19. 2021
Carlotti AP et al. Intensive Care Medicine 2001 27 921–924
Hypertonic
Infusions
Adjusted sodium = Na + 1.6 × (glucose/100)

How to differentiate between 3 types
of hyponatremia?
Logic = Measure Plasma Osmolality
Translocational

Serum Cholesterol,
TG,
Total proteins
History,
Blood glucose
Translocational

Repeat serum Na
Exclude Drugs
5

Repeat serum Na
Exclude Drugs
4
5

H2O > Na
True Hyponatremia Cause?
Adrogue HJ, Madias NE. Clinical Endocrinology 2000 52 667–678
5

Hoorn EJ et al. QJM: Monthly Journal of the Association of Physicians 2005 98 529–540
5

Clinical assessment of volume status ?!
Generally not very accurate
Likely to lead to misclassification of hyponatraemia
Low sensitivity (0.5–0.8) and specificity (0.3–0.5)
Algorithms that start with a clinical
assessment of volume status are not accurate
Hoorn EJ et al. QJM: Monthly Journal of the Association of Physicians 2005 98 529–540
5

Start with urine osmolality
and sodium concentration
(best determined in the same urine
sample)
Use the terms:
a- Effective circulating volume
b- Extracellular fluid volume
Instead of hyper, hypo,
euo - volumic

This diagnostic tree is a simplification and
does not guarantee completeness in each
individual
5

5

SIAD is a diagnosis of exclusion
Janicic N et al. Endocrinology and Metabolism Clinics of North America 2003 32 459–481

SIAD is a diagnosis of exclusion

https://emedicine.medscape.com
/article/919609-overview
May 13, 2020
Kidney International (2009) 76, 934–938

The overwhelming majority of patients in the neurosurgical setting with
hyponatremia after subarachnoid hemorrhage, trauma, or surgery have
SIADH, not CSW

Patients who develop hemodynamic instability and frank volume depletion
in response to fluid restriction have CSW, and patients whose urine volume
decreases and sodium improves with fluid restriction have SIADH

occasional increase in FEphosphate >20% in RSW
FEphosphate should be
determined before administering saline

SIADH RSW/CSW
Volume before treatment Euvolemia Hypovolemia
(orthostatic hypotension)
FEphosphate before
administering saline
Normal ± >20%
hemodynamic instability
and frank volume
depletion with fluid
restriction
No Yes
After correction of
hyponatremia

General rules – 0.9% or 3% NaCl infusion
Maximum correction limit (i.e. Stop infusion when)
10 mmol/l in the
first 24 h
8 mmol/l during
every 24 h
thereafter
130 mmol/l is
reached or
serum sodium
concentration
increases
10 mmol/l in
total
symptoms
improved

General rules – 0.9% or 3% NaCl infusion
Maximum correction limit (i.e. Stop infusion when)
10 mmol/l in the
first 24 h
8 mmol/l during
every 24 h
thereafter
130 mmol/l is
reached or
serum sodium
concentration
increases
10 mmol/l in
total
symptoms
improved
If the symptoms still have not improved, it is unlikely that
the symptoms are due to the hyponatremia and
alternative explanations should be sought

Adrogué–Madias Formula
Adrogue HJ, Madias NE. New England Journal of Medicine 2000 342 1581–1589

Total Body Water Assessment (TBW)
men <70 years old 0.6 × body weight
men ≥70 years old
women <70 years old
0.5 × body weight
women ≥70 years old 0.45 × body weight

Keep in mind that if hypokalaemia is
present, correction of the hypokalaemia
will contribute to an increase in serum
sodium concentration.
Kamel KS, Bear RA. Am J Kidney Dis. 1993;21(4):439.

Keep in mind that if hypokalaemia is
present, correction of the hypokalaemia
will contribute to an increase in serum
sodium concentration.
Kamel KS, Bear RA. Am J Kidney Dis. 1993;21(4):439.
Case Rep Nephrol. 2017; 2017: 4521319

Anesthesiology Clin N Am 20 (2002) 329–346

Symptomatic?
Yes
Severe
Moderately
severe
No
Acute Chronic
Circulating volume
Reduced
Circulating volume
Not Reduced
ECF
expanded
ECF not
expanded
Management - Algorithm

Management – Severe Symptoms
IV infusion of 150
ml 3% hypertonic
(2 ml/kg) in case
of obviously
deviant body
composition
20 min
check
serum Na
Maximum:
Repeat twice
Maximum:
5 mmol/l
increase
A. Improvement of
symptoms
→ Stop 3% infusion
B. No improvement
of symptoms
→ continue infusion
targeting general
rules of raising
serum Na
keep the i.v. line
open by infusing the
smallest feasible
volume of 0.9%
saline until cause-
specific treatment is
started
First-hour management:

Management – Moderate Symptoms
IV infusion of 150
ml 3% hypertonic
(2 ml/kg) in case
of obviously
deviant body
composition
20 min
check
serum Na
A. Improvement of
symptoms
→ Stop 3% infusion
B. No improvement
of symptoms
→ continue infusion
targeting general
rules of raising
serum Na
keep the i.v. line
open by infusing the
smallest feasible
volume of 0.9%
saline until cause-
specific treatment is
started

Management – Acute presentation
IV infusion of 150
ml 3% hypertonic
(2 ml/kg) in case
of obviously
deviant body
composition
20 min
check
serum Na
If the acute decrease in serum sodium concentration exceeds 10 mmol/l

Management – Chronic presentation
Reduced Circulating volume
targeting general
rules of raising
serum Na

Circulating volume Expanded
ECF Expanded
JAMA. 2007;297(12):1319-1331

• Increased number of deaths in those patients treated with
vasopressin receptor antagonists in comparison with those treated
with placebo.
• Vasopressin receptor antagonists may actually worsen outcomes.
• Rozen-Zvi B et al. American Journal of Kidney Diseases 2010 56 325–337
• Jaber BL et al. American Journal of Medicine 2011 124 971–979
ECF Expanded
JAMA. 2007;297(12):1319-1331

• Increased number of deaths in those patients treated with
vasopressin receptor antagonists in comparison with those treated
with placebo.
• Vasopressin receptor antagonists may actually worsen outcomes.
• Rozen-Zvi B et al. American Journal of Kidney Diseases 2010 56 325–337
• Jaber BL et al. American Journal of Medicine 2011 124 971–979
ECF Expanded
Heart Faliure: ADH receptor antagonists, either intravenous (IV) conivaptan
or oral tolvaptan, would be appropriate agents to increase serum sodium
although they have not been shown to improve heart failure outcomes
JAMA. 2007;297(12):1319-1331

The side effects reported for demeclocycline and lithium were
such that we recommend not using them for any degree of
hyponatraemia.
ECF Expanded

ECF Expanded
consider furosemide

Rapid Correction of Hyponatremia
Bad Effect
Rare but dramatic complication
Osmotic demyelination syndrome
Rapid correction of Na
=
Rapid increase in plasma
osmolality
Rapid shift of
water form
intracellular
space

Consideration should be given to correcting the sodium even
slower

Consideration should be given to correcting the sodium even
slower
In some situations, specific treatments of hyponatremia are so
effective that patients will autocorrect their hyponatremia faster
than 8 mmol/L/d
• psychogenic polydipsia
• tea and toast syndrome
• volume depletion
• thiazide-induced hyponatremia
• adrenal insufficiency

Cases of ODS despite guideline-based
correction speeds have been reported
Eur J Endocrinol. 2014;170(3):G1-G47.
Cureus. 2020;12(1):e6547.

Bad Effect
Rare but dramatic complication
Osmotic demyelination syndrome
Diagnosis:
The lesions are detectable by both CT scan and MRI. MRI is
more sensitive (because it is better able to visualize the brain
stem and is more sensitive to changes in the white matter).
Timing is critical in diagnostic studies because lesions do not
become apparent for up to four weeks. Because of this delay,
an initially negative study does not rule out.
Harring TR, Deal NS, Kuo DC. Emerg Med Clin North Am. 2014 May;32(2):379-401.

What to do?
If increases >10 mmol/l during the first 24 h or >8 mmol/l in
any 24 h thereafter
Discontinuing the ongoing
active treatment (1D).
Consulting an expert to
discuss if it is appropriate to
start an infusion of 10 ml/kg
body weight of electrolyte-
free water (e.g. glucose
solutions) over 1 h under
strict monitoring of urine
output and fluid balance (1D).
Consulting an expert to
discuss if it is appropriate to
add i.v. desmopressin 2 μg,
with the understanding that
this should not be repeated
more frequently than every
8h (1D).

A more proactive approach is to start DDAVP at the outset of the
treatment of hyponatremia; this is called a DDAVP clamp
How to avoid?

Hyponatremia in a Patient on Hemodialysis
How to Manage?
Plasma Na level
of the patient
Daugirdas, JT, Ross, et al. Acute hemodialysis Prescription. In:
Handbook of Dialysis, Philadelphia 2007
Dialysate sodium
concentration
Maximum difference
15-20 mEq

How to Manage?
Concurrent infusions
of 5 % dextrose
(D5W)
Every 1L of D5W will
decrease serum
sodium concentration
by 3.5 mEq / L
Adrogue HJ, Madias NE. Hypernatremia. N Engl J Med 2000; 342(20):1493-1499.

CRRT may also be used to safely correct hyponatremia.
CRRT is less efficient in the rate at which serum sodium is
changed and results in a more gradual correction over a
longer time span
Am J Kidney Dis. 2014;64:305.
How to Manage?

Uremia may provide some protection against
osmotic demyelination
Rapid correction of Na
=
Rapid increase in plasma
osmolality
High
intracellular
urea level

The presence of symptoms and their severity depend on
both the MAGNITUDE of the hyponatremia and the
RATE at which the hyponatremia developed
Home Messages

Normal Maximal compensation for a decrease in plasma
osmolality typically requires up to 48 hours.
Avoid rapid correction of hyponatremia
Home Messages

3% NaCl infusion is mandatory in:
- Severe symptoms
- Moderate symptoms
- Acute presentation
Home Messages

Uremia may provide some protection against
osmotic demyelination
Home Messages

Hyponatremia (Practical Approach) - Dr. Gawad

Hyponatremia (Practical Approach) - Dr. Gawad

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