Hyponatremia
Initial workup checklist:
Serum sodium, Serum osmolality, protein, lipid, sugar
Urine sodium, Urine osmolality
An indirect ion-selective electrode (ISE) dilutes a patient’s serum with a buffer in a ratio ranging from 1:16 to 1:34 before measuring the concentration of electrolytes. The results obtained from the indirect ISE depend on the solid content in the sample due to this dilution step. When the volume of plasma solids increases, it can lead to inaccurately low indirect ISE values for serum electrolytes.
Low serum osmolality (Hypo-tonic): Less than 275-280 mOsm/kg True hyponatremia:
Normal serum osmolality (Iso-tonic): 280-290 mOsm/kg Hyperglycemia, Hyperlipidemia, hyperproteinemia
High serum osmolality (Hypertonic): >290 mOsm/kg Severe hyperglycemia, Mannitol
Corrected sodium (Hyperglycemia)
*Corrected sodium = Measured sodium + 0.024 x (serum glucose - 100) =
Corrected sodium = Measured sodium + 0.016 x (serum glucose - 100) =
UOsm >100 mmol/L
UOsm <100 mmol/L
Psychogenic polydipsia
Reset osmostat
Beer potomania
UNa <20 mmol/L
UNa >20 mmol/L
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Etiologies and treatment
Hyperglycemia: Insulin, isotonic saline
Hyperlipidemia: Statin
Hyperproteinemia, e.g. multiple myeloma: chemotherapy
Hypovolemic hyponatremia
Cerebral salt wasting: Isotonic or hypertonic saline
Diuretic use: Stop diuretic therapy
GI loss (e.g., diarrhea, vomiting): intravenous fluids
Mineralocorticoid deficiency: Steroid replacement therapy
Osmotic diuresis: Correct gludose level, stop mannitol use
Salt-wasting nephropathy: Correct underlying cause
Third spacing (e.g., bowel obstruction, burns): intravenous fluids, relieve obstruction
Euvolemic hyponatremia
Beer potomania syndrome: decrease alcohol use, increase protein intake
Exercise-associated hyponatremia: Isotonic or hypertonic saline
Hypothyroidism: Thyroid replacement therapy
Low solute intake: Increase sodium intake
Nephrogenic SIADH: Fluid restriction, loop diuretics
Psychogenic polydipsia: Psychiatric therapy
Reset osmostat: Treat underlying cause
SIADH: Fluid restriction, consider vaptans
Drug induce SIADH (barbuturates, carbamazepine, chlopropamide, diuretics, opoids, SSRI, tolbutamide, vincristine): stop the drug
Water intoxication: diuresis
Hypervolemic hyponatremia
Heart failure: Diuretics
Hepatic failure/cirrhosis: Furosemide, spironolactone, transplant
Nephrotic syndrome: treat the cause
Renal failure (acute or chronic): Correct underlying disease
Drugs and conditions associated with acute hyponatraemia (<48 h).
Postoperative phase
Post-resection of the prostate, post-resection of endoscopic uterine surgery
Polydipsia
Exercise
Recent thiazides prescription
3,4-Methylenedioxymethamphetamine (MDMA, XTC)
Colonoscopy preparation
Cyclophosphamide (i.v.)
Oxytocin Recently started desmopressin therapy
Recently started terlipressin, vasopressin
The correction rate does not need to be limited in patients with true acute hyponatremia, and it is not necessary to re-lower excessive corrections. However, if there is any doubt about whether the hyponatremia is acute or chronic, the guidelines for correcting chronic hyponatremia should be adhered to.
Treatment of chronic severe symptomatic hyponatremia
Serum sodium <125 mmol/L with severe symptoms (e.g. seizures, metal status changes)
For moderate symptom
Infuse 3% saline (0.5 to 2 ml per kg per hour) to increase serum sodium level by 6 to 8 mmol per L (not to exceed 10 to 12 mmol per L in the first 24 hours or 18 mmol per L in 48 hours).
Consider desmopressin, 1 to 2 mcg every 4-6 hours
For severe symptom
Give single intravenous bolus of 100 to 150 ml 3% saline over 10 minutes with goal of increasing serum sodium level by 2 to 3 mmol per L; check sodium level every 20 minutes until symptom resolve; may repeat bolus twice if symptom do not resolve.
Symptom resolution
Check sodium levels every two hours; adjust infusion and switch to isotonic saline.
Determine the cause of hyponatremia
Risk of developing ODS
Target Serum sodium correction
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Prevention overcorrection
- Saline or vaptan therapy should be temporarily withheld once the targeted daily increase has been achieved.
- For the rest of the day, further correction from urinary-free water losses should be prevented either by replacing losses with 5% dextrose in water or oral water or by terminating further urinary losses by administering 2-4 mg of desmopressin parenterally
- In high-risk patients for osmotic demyelination syndrome (ODS), consider a preemptive strategy using desmopressin (DDAVP) every 6-8 hours alongside a 3% hypertonic saline infusion titrated to achieve a 6-mmol/L/d. This method, known as a "DDAVP clamp," induces iatrogenic SIADH, preventing rapid correction of sodium levels and allowing for a gradual rise in sodium.
Re-lowering
- Withhold the next vaptan dose if sodium correction exceeds 8 mmol/L.
- Consider high-dose glucocorticoids (e.g., dexamethasone, 4 mg every 6 hours) for 24-48 hours after excessive correction.
- Administer desmopressin: 2-4 mg every 8 hours, parenterally.
- Replace water orally or with 5% dextrose in water IV at 3 mL/kg/h.
- Recheck serum sodium levels hourly and continue therapy until the target is reached.
Treatment of chronic severe symptomatic hyponatremia
Serum sodium <125 mmol/L per L with severe symptoms (e.g. seizures, metal status changes)
For moderate symptom
immediate treatment with a single i.v. infusion of 150 ml 3% hypertonic saline or equivalent over 20 min
For severe symptom
Infuse 150 ml of 3% hypertonic saline over 20 minutes and recheck serum sodium concentration after this initial infusion.
Repeat the infusion of 150 ml of 3% hypertonic saline for another 20 minutes.
Monitoring the serum sodium levels at 1, 6, and 12 hours.
Assessing the to treat the patient for severely symptomatic hyponatremia if the serum sodium concentration continues to drop despite addressing the underlying condition.
Symptom resolution
i.v. line open by infusing the smallest feasible volume of 0.9% saline until cause-specific treatment is started
Determine the cause of hyponatremia
Checking the serum sodium concentration after 6 and 12 h and daily afterwards until the serum sodium concentration has stabilised under stable treatment
Symptom not improved
Intravenous 3% hypertonic saline infusion targets a 1 mmol/L increase in serum sodium per hour.
Stop the infusion of 3% hypertonic saline or an equivalent when:
1) symptoms improve,
2) serum sodium increases by 10 mmol/L, or
3) serum sodium reaches 130 mmol/L—whichever comes first.
Monitor serum sodium concentration every 4 hours during continuous i.v. infusion of 3% hypertonic saline or equivalent.
For chronic hyponatremia without severe or moderately severe symptom
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cause-specific treatment
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In cases of moderate or profound hyponatremia, avoid increasing the serum sodium concentration by more than 10 mmol/l in the first 24 hours and by more than 8 mmol/l during each subsequent 24-hour period.
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checking the serum sodium concentration every 6 h until the serum sodium concentration has stabilised under stable treatment
SIAD
Fluid restriction is necessary to prevent further fluid overload
Consider equal second-line treatments: increasing solute intake with 0.25–0.50 g/kg per day of urea, or a combination of low-dose loop diuretics and oral sodium chloride.
The use of a vasopressin receptor antagonist is not recommended.
Patients with expanded extracellular fluid
Fluid restriction is essential to prevent additional fluid overload
The use of a vasopressin receptor antagonist is not recommended.
Patients with reduced circulating volume
restore extracellular volume, administer an intravenous infusion of 0.9% saline or a balanced crystalloid solution at a rate of 0.5 to 1.0 ml/kg per h
If there is hemodynamic instability, the requirement for rapid fluid resuscitation takes priority over the risk of a too-rapid increase in serum sodium concentration.
Target Serum sodium correction
Limiting the increase in serum sodium concentration to a total of 10 mmol/l during the first 24 h and an additional 8 mmol/l during every 24 h thereafter until the serum sodium concentration reaches 130 mmol/l
Re-lowering
Consult an expert to determine whether it is appropriate to administer a one-hour infusion of 10 ml/kg body weight of electrolyte-free water (such as glucose solutions) while strictly monitoring urine output and fluid balance.
Additionally, consult an expert to assess the appropriateness of adding 2 mg of intravenous desmopressin, keeping in mind that this should not be repeated more frequently than every 8 hours.
References
Verbalis JG, Goldsmith SR, Greenberg A, Korzelius C, Schrier RW, Sterns RH, Thompson CJ. Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations. Am J Med. 2013 Oct;126(10 Suppl 1):S1-42.
Spasovski G, Vanholder R, Allolio B, Annane D, Ball S, Bichet D, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemiaThe guidelines were peer reviewed by the owner societies and by external referees prior to publication. European Journal of Endocrinology. 2014 Mar 1;170(3):G1–47.