Saline Towards Failing: Preventing Overcorrection of Hyponatremia in the ED

CASE

A 64 yo woman with past medical history of chronic hyponatremia due to psychogenic polydipsia, hypertension, and bipolar disorder was brought in by EMS following a syncopal event at home.

She had several days of NBNB emesis and diarrhea at home.
She had increased her water intake because she was concerned about her fluid loss.
She had been feeling very weak and lightheaded for the past several days, leading up to her syncopal event.

On exam:

Vitals: Temp 36.2, BP 171/98, P 80, RR 17, O2 Sat 94% on RA
Physical exam notable for somnolence, confusion, flat affect, and the presence of bilateral lower extremity edema
Initial labs notable for Na 116, K 3.5, Ca 9.0, Mg 1.8, glucose 55, Cr 0.81. Trop, lactate, CBC, VBG wnl
CT Head/C-spine showed no acute or subacute pathology
EKG showing normal sinus rhythm, QTc interval 500ms, non-specific T wave changes with T wave inversion in V1 and T wave flattening in V2-V3

Common Symptoms in Patients with Profound Hyponatremia (Na <125)

Prevalence of symptoms in 298 patients with profound hyponatremia, defined as serum Na <125 mmol/L, who presented consecutively to two Swiss academic medical centers between 2011 and 2013, adapted from Nigro et al, 2015.

Summary of Evidence:

Although hyponatremia is the most common electrolyte disorder encountered in clinical practice [1],management of hyponatremia continues to vex even the most experienced clinicians.[2-6]

Since the 1980s, clinicians have recognized neurologic sequelae resulting from both under and over correction of serum sodium levels.[7]

1. Acute hyponatremia (hyponatremia developing in <48 hours) leads to cerebral edema and potential brain herniation, a clinical emergency resulting in significant morbidity and mortality if untreated.[2-4]

2. Overly rapid correction of chronic hyponatremia (hyponatremia present >48 hours) can result in osmotic demyelination syndrome (ODS), with resultant neurologic sequelae presenting up to a week after treatment.[2-4]

Historically, guidance for management of hyponatremia has differentiated between acute and chronic hyponatremia.[3]

1. For acute hyponatremia:

Correction of 4 to 6 mmol Na/L in the first 4-6 hours is adequate to prevent against brain herniation and improve clinical status of patients.[5]
This recommendation is based on a review of case reports and thus relatively small sample size.[5]

2. For chronic hyponatremia:

The rate of sodium correction should be limited to avoid ODS.[2-6]
There are a few documented cases of ODS occurring after correction of 10 mmol Na/L in 24 hours.[3]
Recommendations for correction limit are based on case reports of ODS and retrospective single-center studies with small sample sizes. [3]
Other risk factors for ODS include alcohol abuse, liver disease, medications including thiazide diuretics, and the degree/duration of the osmotic demyelination syndrome.[2,6]

Clinicians, particularly in the emergency room, often have limited available information on the duration of hyponatremia and must incorporate current clinical status in determining management strategy for hyponatremic patients.[2,3]

A management framework for all patients with severe hyponatremia should thus incorporate:

1. The necessary correction rate to avoid brain herniation in acute hyponatremia as the therapeutic goal.[2-6]

2. The minimum correction rate known to result in ODS as the therapeutic limit.[2-6]

RECOMMENDATIONS

Two expert panels, one European5 and one American6, recently published recommendations for treatment of hyponatremia, with general agreement over the basic approach to hyponatremic patients.[3]

To treat severe hyponatremia:

Infuse boluses of 3% hypertonic saline to initially correct the sodium level by 4-6 mmol/L.[5,6]
Disagreement exists over the exact regimen of bolus infusion (initial bolus of 100 mL vs 150 mL) and definition of severe symptoms (whether nausea/vomiting is a severe symptom).[3,5,6]

To avoid overcorrection:

Limit daily increase in serum sodium to 10 mmol/L in the first 24 hours5,6; consider a limit of 8 mmol/L if the risk of ODS is high.[6]
Consideration: Clinicians may replace water losses or administer desmopressin after achieving the desired correction level to prevent accidental overcorrection of sodium through aquaresis.[4,6]

To treat overcorrection:

Consider therapeutic re-lowering of sodium level to a value below the therapeutic limit if the daily correction limit is exceeded.[3,5,6]
This recommendation is based on animal studies and does not have a good body of clinical evidence to support it.[3,5,6]
Clinicians should consult nephrology for input on management following sodium overcorrection.[5]

For patients with mild symptoms or chronic hyponatremia:

Consider fluid restriction, use of vasopressin antagonists, and treatment of underlying cause.[2,3,6]

REFERENCES

1) Upadhay A, Jaber BL, Madias NE. Epidemiology of hyponatremia. Semin Nephrol. 2009; 29:227-238. DOI: 10.1016/j.semnephrol.2009.03.004

2) Adrogue HJ, Madias NE. The challenge of hyponatremia. J Am Soc Nephrol. 2012; 23: 1140-1148. DOI: 10.1681/ASN.2012020128

3) Sterns RH. Treatment of severe hyponatremia. Clin J Am Soc Nephrol. 2018; 13: 641-649. DOI: 10.2215/CJN.10440917

4) Sterns RH, Nigwekar SU, Hix JH. The treatment of hyponatremia. Semin Nephrol. 2009; 29: 282-299. DOI: 10.1016/j.semnephrol.2009.03.002

5) Spasovski G, Vanholder R, Allolio B, Annane D, Ball S, Bichet D, Decaux G, Fenske W, hoorn EJ, Ichai C, Joannidis M, Soupart A, Zietse R, Haller M, van der Veer S, van Biesen W, Nagler E. Clinical practice guideline on diagnosis and treatment of hyponatremia. Nephrol Dial Transplant. 2013; 29: ii1-ii39. DOI: 10.1093/ndt/gfu040

6) 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; 126: S1-S42. DOI: 10.1016/j.amjmed.2013.07.006

7) Berl T. Treating hyponatremia: damned if we do and damned if we don’t. Kidney International. 1990; 37: 1006-1018. DOI: 10.1038/ki.1990.78

8) Nigro N, Winzeler B, Suter-Widmer I, Schuetz P, Arici B, Bally M, Blum C, Bingisser R, Bock A, Huber A, Muller B, Nickel CH, Christ-Crain M. Symptoms and characteristics of individuals with profound hyponatremia: a prospective multicenter observational study. J Am Geriatr Soc. 2015; 63: 470-475. DOI: 10.1111/jgs.13325