Hyponatremia

by Vigor Arva and Gregor Prosen

Case Presentation

A 72-year-old man was brought to the emergency department (ED) by his daughter. She reported that he had nausea, vomiting, and confusion and had been unwell for the last few days. He had hypertension and heart failure for the previous ten years and was on ACE-inhibitor, beta-blocker and thiazide diuretic.

At triage, the patient’s vital signs were usual: BP 110/70 mmHg, HR 95/min, RR 15/min, temperature 36.1°C and SpO2 100% on room air. He appeared lethargic and walked with an unsteady gait. He had no focal neurological deficit. He had a normal skin turgor and no edema. Postural BP revealed mild orthostatic hypotension. The lab results showed a serum sodium concentration of 115 mEq/L.

Critical Bedside Actions and General Approach

Hyponatremia is the most frequent electrolyte disturbance and refers to when the serum Na is <135mEq/L. The management principles are as follow:

  1. Assess severity and acuity
  2. Determine type (based on plasma osmolarity and volume status)
  3. Identify and treat the underlying cause
  4. Prevent complications

Hyponatremia can be classified as

  • mild (125-134 mEq/L),
  • moderate (120-124 mEq/L)
  • severe (<120 mEq/L)

The physician should carefully evaluate the underlying cause before attributing the symptoms to hyponatremia alone as mild and moderate hyponatremia are often asymptomatic. Determining the rate of change is important since rapid changes of sodium concentration usually present more dramatically with more neurologic involvement. The management differs based on the rate of change.

Differential Diagnoses

The type of hyponatremia has to be determined to narrow down the differential diagnoses. Based on serum osmolality, we distinguish between hypertonic, isotonic, and hypotonic hyponatremia.

  1. Hypertonic hyponatremia (osmotic pressure > 295 mOsm/L) occurs when a large concentration of osmotically active substances pull additional water and dilute sodium concentration.
    • Hyperglycemia (for each 1mmol/L rise in blood glucose, the serum sodium decreases by 0.3mmol/L)
    • Administration of osmotic agents, such as mannitol, glycerol, sorbitol, and radiocontrast infusion
  2. Isotonic hyponatremia (osmotic pressure 275-295 mOsm/L) (Also known as pseudo-hyponatremia) occurs with high levels of osmotically inactive substances.
    • Hyperlipidemia
    • Hyperproteinemia (multiple myeloma etc.)
  3. Hypotonic hyponatremia (osmotic pressure < 275 mOsm/L) is subdivided based on clinical evaluation of volume status and urine sodium concentration.
    1. Hypovolemic
      • Urinary sodium > 20mEq/L: renal losses (diuretics, salt-wasting nephropathy, mineralocorticoid deficiency)
      • Urinary sodium <20mEq/L: extrarenal (hypotonic fluids, GI, and third space loss, sweating in CF patients)
    2. Euvolemic
      • Syndrome of inappropriate ADH secretion (SIADH)
      • Drugs
      • Hypothyroidism
      • Pain, stress, nausea, psychosis, water intoxication
    3. Hypervolemic
      • Urinary sodium > 20 mEq/L: renal failure
      • Urinary sodium < 20 mEq/L: CHF, nephrotic syndrome, liver cirrhosis

If SIADH is suspected, evaluate for its cause. The acronym MADCHOP lists the causes of SIADH:

  • Malignancy
  • ADH secretion (ectopic)
  • Drugs (e.g., SSRIs, ecstasy)
  • CNS disease
  • Hormone deficiency (hypothyroidism, adrenal insufficiency)
  • Others
  • Pulmonary

Drugs that commonly cause hyponatremia include ADH, nicotine, MDMA, SSRI, sulfonylureas, opioids, barbiturates, NSAIDs, paracetamol, carbamazepine, phenothiazine, TCA, colchicine, cyclophosphamide, and MAOI.

History and Physical Examination Hints

The signs and symptoms of hyponatremia are usually vague and nonspecific. Patients may present with nausea, vomiting, anorexia and general malaise. Pay attention to neurologic signs including a headache, confusion, lethargy, seizures, and coma. Hyponatremia can also manifest as muscle cramps, ataxia, hemiparesis, and focal weaknesses. Symptoms may develop acutely (<24h) or may develop gradually and subtly over days.

Ask patients about their fluid intake (polydipsia) and losses, comorbidities (e.g., heart and renal diseases, malignancies), medications (e.g., thiazide diuretics) and any recent illness (gastrointestinal diseases with vomiting or diarrhea), or use of recreational drugs.

During the physical examination, attention should be focused on neurological examination and volume status. The latter can be assessed by checking skin turgor, capillary refill, and whether pitting edema, raised jugular venous pressure, and orthostatic hypotension are present. The signs of the common causes of hyponatremia, such as cirrhosis and heart failure, should be carefully elicited.

Emergency Diagnostic Tests and Interpretation

If hyponatremia is suspected, check the serum sodium level (Normal reference: 135-145 mEq/L) and serum osmolality (Normal reference: 275-295 mOsm/L), preferably at the bedside if available. Serum osmolality can also be calculated by using the following formula:

Osmolality (in mmol/L) = 2 Na + Glucose + Urea

After the type of hyponatremia, Checking the urine sodium and osmolality to evaluate the etiology further. Note to monitor these values after treatment for hyponatremia is initiated.

If pseudohyponatremia is suspected, verify if the serum sodium measure is affected by protein and lipid concentration. If this is the case, add serum protein and lipid levels to exclude pseudohyponatremia.

Exclude other electrolytes abnormalities, especially potassium. These disorders often co-exist in conditions such as adrenal insufficiency.

Point of care ultrasound can be used to evaluate volume status. Nerve sheath diameter can be measured using ocular ultrasound if cerebral edema is suspected.

Emergency Treatment Options

Initiate therapy with 100 mL of 3% NaCl over 10-15 minutes in patients with severe acute hyponatremia (sodium < 120 mEq/L) and neurological symptoms, such as seizures, confusion or coma. At this point, recheck the serum sodium. Give a second dose of 3% NaCl if hyponatremia is still severe and the patient still symptomatic. Additional doses are not advised given the risk of overcorrection. If 3% NaCl is not available, consider using NaHCO3 solution.

If the patient is stable, evaluate the patient’s volume status to determine the management strategy.

Hypovolemic patients benefit more from increasing volume rather than sodium correction per se. If the patient’s serum sodium is <130 mEq/L, Ringer’s lactate solution (sodium concentration = 130mEq/L) may be used. It has the advantage of treating concurrent hypokalemia if present – correcting this often improves serum sodium. Otherwise, use Normal Saline (sodium concentration = 154 mmol/L) for volume correction.

Sodium concentration in different solutions

0.9% NaCl: 154 mmol/L
Ringer’s Lactate: 130 mmol/L
0.45% NaCl: 77 mmol/L
5% Dextrose in water (D5W): 0 mmol/L

In general, patients with euvolemic and hypervolemic hyponatremia should be fluid restricted. For patients with SIADH and congestive heart failure, consider adding loop diuretics. For those with glucocorticoid deficiency, hydrocortisone should be administered. In these three conditions, a vasopressin receptor antagonist may be considered in consultation with the inpatient specialists if the hyponatremia is refractory.

The amount and speed at which sodium is corrected must be determined before initiating replacement therapy. This can be calculated manually or via several online calculators, such as Medcalc.

The rules of 6s and 100s can be used to avoid over-correction.

  • Rule of 6s:
    • “Six in six hours for severe symptoms, then stop.” If symptoms are not severe, then “six a day makes sense for safety.” In other words, for patients with severe symptoms, raise the sodium level by a maximum of 6 mEq/L over 6 hours. For those without severe symptoms, the maximum is 6 mEq/L over 24 hours.
  • Rule of 100s:
    • If the output is more than 100 mL/hr, and the osmolality is less than 100 mosm/kg H2O, consider administering IV DDAVP 1 microgram to slow down the correction rate.

Rapid overcorrection is a risk factor for osmotic demyelination syndrome. As it has a predilection for the pons, it is also previously known as central pontine myelinolysis. Diagnosis is initially clinical, but later changes can be seen on the MRI. Clinical presentation can take place after 2-6 days and may be irreversible. Symptoms range from ataxia and paresis to the “locked-in syndrome.” As the prognosis is poor, care should be taken to avoid this complication in the first place when correcting hyponatremia.

Figure 1. Treatment algorithm for hyponatremia (Conceived by Dr. Edward Etchells). Please read the whole article for more information (link).

Pediatric, Geriatric, Pregnant Patient, and Other Considerations

The most common cause of hyponatremia in the pediatric population is the gastrointestinal fluid loss (emesis or diarrhea) and inappropriate rehydration with a hypotonic solution. Ingestion of overly diluted formula and excessive water are other causes. Diagnosis and treatment are as described above.

Exercise-induced hyponatremia, a form of dilutional hyponatremia, may happen when patients consume excessive water or hypotonic liquids during exercise. Endurance sports and training, such as ultra-marathons, Ironman triathlons, and intensive military training deserve particular attention. Ironically, the patient may wrongly attribute the symptoms of lethargy (caused by hyponatremia) to dehydration, prompting further fluid intake. The management of these patients should follow the schema given above.

If hyponatremia is an incidental finding in an otherwise asymptomatic patient, water restriction can be advised until voiding occurs, to avoid development of symptomatic hyponatremia5

Disposition Decisions

Patients with neurologic symptoms should be admitted to the ward or the ICU. Patients requiring excessive sodium correction should be placed under close monitoring.

Asymptomatic patients with mild hyponatremia from benign causes can be discharged with advice. They should be followed up by their primary physicians or referred to a specialist.

References and Further Reading

  • Helman A. Episode 60: Emergency Management of Hyponatremia. Interview with Dr. Melanie Baimel and Dr. Edward Etchells [Internet]; 2015. Podcast. Available from: http://emergencymedicinecases.com/episode-60-emergency-management-hyponatremia/
  • Tintinalli JE, Stapczynski JS. Tintinalli’s emergency medicine : a comprehensive study guide. 7th ed. New York: McGraw-Hill Medical; 2011.
  • Marx JA, Hockberger RS, Walls RM, Adams J, Rosen P. Rosen’s emergency medicine : concepts and clinical practice. 7th ed. Philadelphia: Mosby/Elsevier; 2010.
  • Nickson C. Hyponatremia. Life in the Fastlane 2015; http://lifeinthefastlane.com/ccc/hyponatraemia/. Accessed 29.04, 2016.
  • Hew-Butler T, Rosner MH, Fowkes-Godek S, et al. Statement of the Third International Exercise-Associated Hyponatremia Consensus Development Conference, Carlsbad, California, 2015. Clin J Sport Med. 2015;25(4):303-320.

Links To More Information

  • Emergency Medicine Cases – Baimel M, Etchells E. Hyponatremia.  – Link
  • Seheult R. Hyponatremia Explained Clearly. MEDCRAMvideos. Available on youtube: https://www.youtube.com/watch?v=0a3gt6UQgeM
    Accessed April 29th 2016.
  • Farkas J. Taking control of severe hyponatremia with DDAVP. PulmCrit on EMCrit. http://emcrit.org/pulmcrit/taking-control-of-severe-hyponatremia-with-ddavp/
    Accessed April 29th 2016.