EBM: Severely Symptomatic Hyponatremia: What to do with it in the Emergency Department?

For adult patients presenting to the ED with labs and severe symptoms indicative of hyponatremia, for whom do we need to intervene, what are those interventions and what are the outcomes of those interventions?


Etiology 

  • Meds:  thiazides SSRIs, chronic steroids (adrenal insufficiency)

  • Hx: SIADH (cancer, meds), CHF, renal failure, liver failure, hyperK, potomania

 

Physiology Pearls

  • Going down! The brain has an extraordinary ability to adapt to osmotic disturbance. Brain cells shed organic osmolytes in response to hyponatremia, permitting osmotic equality between intracellular and extracellular fluids without an increase in cell water. This adaptation made the patient vulnerable to iatrogenic injury from aggressive efforts to correct his electrolyte disturbance. 

  • Going up! Spotaneous water diuresis could lead to a dangerous and rapid increase in serum sodium levels - it’s not the water coming in that’s going to kill your patient, it’s the coming out. This is a recurrent theme in the treatment of hypoNa, so consider both desmopressin (DDAVP) and 3% hypertonic saline solution.



Workup

  • Glucose (significant hyperglycemia can cause pseudohyponatremia —> sodium correction rate for hyperglycemia: 1.6 mmol/L for every 100 mg/dL increase)

  • Serum osmolality — if elevated, it can indicate pseudohyponatremia from extreme hypertriglyceridemia or hyperproteinemia

  • Metabolic panel

  • Urine osmolality, urine sodium

  • Can consider thyroid studies, BNP, CT head if etiology is unclear


Management

Remember, give hypertonics only for severely symptomatic patients e.g. coma, seizure, respiratory distress, profoundly AMS. 

  • 150 cc of 3% Hypertonic saline over 20 minutes

    • 100 ml of 3% NaCl = 50 ml of 8.4% bicarbonate (one ampule). It’s about 2x strength - 51 mEq of sodium in 100 ccs of 3%.  So, can give 1.5 amps of NaHCO3. Repeat up to 3x every 20 minutes until symptoms resolve.

  • Correction Goals: Aim for 6 mEq/L for the first 6 hours in the ED.

    • Medical literature recommendations vary between 8 and 12 mmol/L per 24 h correction. Inconsistencies exist in the recommended dose of NaCl, its initial infusion speed, and which second line interventions to consider. 

  • STOP all isotonic or hypotonic fluids and restrict!

    • Free water can kill. But remember, it’s not the water in, it’s the water out that’s going to kill your patient.

    • Consider vasoactive medications in patients with shock, especially if non-fluid-responsive

  • Place a foley. Consider DDAVP.

    • If urine output  > 100cc/hr and urine osm < 100 mosm/L, consider DDAVP to prevent free water excretion from kidneys..

    • DDAVP plus unrestricted fluid intake can worsen the patient's hyponatremia. 

Recent Medical Literature: Don’t underdo it, but don’t overdo it either.

In their 100-mL group, 41% of the patients received a second bolus of hypertonic saline (median time 3 hours) that still failed to raise sNa properly in 58% of the cases

Initial treatment of severe hypotonic hyponatremia is more effective with a NaCl 3% bolus of 250 mL than of 100 mL and does not increase the risk of overcorrection

This RCT found that rapid intermittent bolus and slow continuous infusion are both safe and effective.  Study resulted in more overcorrection than expected for both groups, but the bolus group was found to have a lower incidence of relowering therapy and an increased achieved target correction rate within 1 hour. 

The frontier: Very recent study that suggests fixed dosing  in folks of low and high body weight to more overcorrection and undercorrection, respectively. Prospective studies are needed to develop and validate individualized dosing models.

The Bottom Line

  • 6-mmol/L increase appears to be sufficient for patients with the most severe manifestations of hyponatremia. The first day's increase can be accomplished during the first 6 hours of therapy, with subsequent increases postponed until the next day.

  • Be more careful in those at risk for osmotic demyelination (i.e. central pontine myelinolysis): serum Na ≤120 mmol/L for greater than 48 hours duration, patients with alcohol use disorder, malnutrition, end stage liver disease, Na < 105. Consider DDAVP in these patients.

Calculate sodium correction rate

POST BY: DR. MIKE FELLENBAUM, PGY3

FACULTY EDITING BY: NIK SEKOULOPOULOS, MD

References

  • Adrogué HJ, Tucker BM, Madias NE. Diagnosis and Management of Hyponatremia: A Review. JAMA. 2022;328(3):280–291.

  • Baek SH, Jo YH, Ahn S, et al.. Risk of Overcorrection in Rapid Intermittent Bolus vs Slow Continuous Infusion Therapies of Hypertonic Saline for Patients With Symptomatic Hyponatremia: The SALSA Randomized Clinical Trial. JAMA Intern Med. 2021;181(1):81-92.

  • Farkas J. Hyponatremia. IBCC, EmCrit. June 25, 2021. Accessed June 2023. <https://emcrit.org/ibcc/hyponatremia/>

  • Massop K, Haverkort DA, Bech AP, de Boer H. NaCl 3% bolus therapy as emergency treatment for severe hyponatremia: Comparison of 100 ml versus 250 ml. J Clin Endocrinol Metab. 2023; 108(8):e521-e526.

  • Nagler EV, Vanmassenhove J, van der Veer SN, Nistor I, Van Biesen W, Webster AC, Vanholder R. Diagnosis and treatment of hyponatremia: a systematic review of clinical practice guidelines and consensus statements. BMC Med. 2014;12:1.

  • Pelouto A, Refardt JC, Christ-Crain M, Zandbergen AAM, Hoorn EJ. Overcorrection and undercorrection with fixed dosing of bolus hypertonic saline for symptomatic hyponatremia. Eur J Endocrinol. 2023; 188: 322–330

  • Spasovski G, Vanholder R, Allolio B, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Eur J Endocrinol. 2014;170(3):G1-47.

  • Sterns RH. Hix JK. Silver S. Treating profound hyponatremia: a strategy for controlled correction. Am J Kidney Dis. 2010; 56: 774-779.

  • Verbalis JG, Goldsmith SR, Greenberg A, et al. Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations. Am J Med. 2013;126(10):S1-42.

  • https://www.mdcalc.com/calc/480/sodium-correction-rate-hyponatremia-hypernatremia

EBMLauren McCafferty