Diagnostics: Dysnatremias

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Sodium is a major cation in the extracellular space and therefore the most important osmotically active particle. It is closely linked to the body’s fluid balance, so decreased or defective sodium excretion leads to an expansion of the extracellular volume, and intravascular volume, promoting increased in blood pressure. [1] Since the bulk of sodium output/excretion occurs through the urine and is the responsibility of the kidney (most important determinant of Na balance). The daily body requirement of sodium is 500mg aka 120mg NaCl aka <0.25 tsp. The average intake is 3600mg aka 9500mg NaCl. [2] Given this, it is no surprise that we see irregularities in Na frequently as a vast number of patients have underlying comorbidities such has HTN, CKD, and obesity due to poor diet. The important thing for us to figure out is when “dysnatremia” is the cause behind the patient’s presentation and how we are to manage it in the Emergency Department.

Hyponatremia

SeveritySymptoms
Mild (130-135 mEq/L)Acute: asymptomatic, malaise, fatigue, muscle cramping / weakness Chronic: falls, unsteadiness, attention deficits
Moderate (125-129 mEq/L)Nausea Confusion Headaches Gait disturbances
Severe (<125 mEq/L)Vomiting Cardiorespiratory distress Abnormal and deep somnolence Seizures Coma0

Eunatremia or normal serum Na concentration is 135-145 mEq/L. Hyponatremia is the state of decreased serum sodium concentrations, <135 mEq/L. It is primarily a disorder of water balance. This is the more common sodium irregularity to present in the ED, both as a true cause of the presentation or incidentally. Its severity is classified based off the following numerical values: mild (130-135 mEq/L), moderate (125-129 mEq/L), or severe (<125 mEq/L). Symptoms are typically neurological and unfortunately largely non-specific such as headaches, nausea, or confusion (see table 1 for symptoms). Causes are multifactorial and the onset can be acute (<48 hours) or chronic (≥ 48 hours or duration unknown). [3] Consideration of a patient’s volume status and renal ability to retain / excrete sodium is important when investigating the cause of hyponatremia as they affect the management and treatment. One must also take into consideration conditions that cause pseudohyponatremia such as high protein states (ex. multiple myeloma) or elevated glucose levels (ex. HHS, DKA). Table 2 breaks down the various types of hyponatremia in relation to their volume status along with corresponding causes.

Basic workup for hyponatremia, regardless of patient presentation or hypothesized cause, includes FSBG, BMP, and serum osmolality. [4] These labs can quickly help distinguish between the various causes. A clinical examination of the volume status of that patient can also be useful (ex. dehydration vs peripheral edema). After this point, the workup is dependent on the form of hyponatremia. That being said, obtaining urine studies is strongly recommended in all patients with hyponatremia as that can be useful to our medicine colleagues to tease out the cause. All of the above is only if a patient is stable; if a patient presents with severe symptoms and a Na < 125, patient should immediately start receiving treatment.

Hypotonic HypovolemicHypotonic EuvolemicHypotonic HypervolemicIsotonicHypertonic
Serum Osm<280 mOsm/kg H2O<280 mOsm/kg H2O<280 mOsm/kg H2O280 – 295 mOsm/kg H2O>295 mOsm/kg H2O
Extracellular Fluid VolumeLow extracellular fluid volumeNormal extracellular fluid volumeIncreased extracellular fluid volumeNormal extracellular fluid volumevariable
Renal Causes Acute or chronic renal failure w/ polyuria  Diuretics  Mineralocorticoid deficiency  Cerebral salt wasting Acute or chronic renal failure  SIADH  Exercise-associated  Glucocorticoid deficiency  Severe hypothyroidism  Acute or chronic renal failure w/ oliguria
Extrarenal Causes GI loss - Diarrhea - Vomiting  Dermal fluid loss - Burns - Excessive Sweating  Third spacing fluid loss  Bleeding Decreased Na intake aka tea and toast diet  Water intoxication - Hypotonic IVF - Primary polydipsia - Beer potomania  CHF  Cirrhosis  Hypoproteinemia aka nephrotic syndrome  Hyperlipidemia  Hyperparaprotinemia  Hyperglycemia  IV mannitol  IV contrast

+ Hypovolemic

  • Most frequent electrolyte disorder [5]

  • Definition: Low serum Na and low serum osmolality (<280 data-preserve-html-node="true" mOsm/kg H2O) with decreased in extracellular fluid volume

  • Pathophysiology: relative excess of H20 compared to Na extracellularly, either due to dilution or depletion

    • Varies depending on the cause

  • Most commonly seen in the Emergency Department:

    • Diuretic Use

      • Pathophysiology [6]

      • Thiazide diuretics block Na-K-Cl cotransporter in distal convoluting tubule -> more Na in collecting duct -> more Na lost (taking H2O with it) -> depletional hyponatremia, Occurring after Loop of Henle

      • Loop diuretics block Na-K-Cl cotransporter in thick ascending limb -> more Na in collecting duct -> more Na lost (taking H2O with it) -> depletional hyponatremia. Less likely as it blocks resorption of ions (prevents countercurrent gradient) -> decreased osmolality of medulla -> decreased H2O reabsorption

    • Management:

      • Cease diuretic use
      • Fluid restriction and NPO
      • Trend BMPs

    • GI loss (diarrhea, vomiting)

    • Pathophysiology

      • Increased H2O loss -> increased serum osmolality -> increased in ADH -> increased H2O resorption in collecting ducts -> increased H2O in serum -> dilutional hyponatremia

    • Management:

      • Treat underlying cause
      • Symptoms management
      • Keep NPO
      • Small fluid boluses (250-500cc of LR or Plasmalyte/Normosol) [7]
      • Trend BMPs

+ Euvolemic

  • Definition: Low serum Na and low serum osmolality (<280 data-preserve-html-node="true" mOsm/kg H2O) with normal extracellular fluid volume

    • Pathophysiology: relative excess of H20 compared to Na extracellularly, either due to dilution or depletion

      • Varies depending on the cause

      • Most common cause is SIADH [8] (Syndrome of Inappropriate Secretion of Antidiuretic Hormone)

      • Etiologies: CNS disturbances, malignancies, drugs, pulmonary disease, HIV, hereditary

      • Drugs: antidepressants, anticonvulsants, antipsychotics, antidiabetics, anti-cancer meds, vasopressin analogues, opioids, NSAIDs, amiodarone, ciprofloxacin, PPI, ecstasy, etc

      • Unregulated release of ADH (regardless of plasma osmolality) -> increased H2O resorption in collecting ducts -> increased urine osmolality and Na -> dilutional hyponatremia

    • Diagnosis of exclusion and therefore essential criteria need to be meet after excluding other possible causes such as adrenal, thyroid, pituitary, or renal insufficiency

    • Management:

      • Stop offending agent if medication induced

      • Treat underlying cause if not medication induced

      • Fluid restriction and NPO
      • Trend BMPs
      • Consider the following controversial medications
        • Demeclocycline (US guidelines recommend, EU against due to side effects) [3]
        • Consider Tolvaptan (V2 receptor antagonist) [9]
        • Do not use in patients with hepatic impairment as it can worsen liver function

+ Hypervolemic

  • Most commonly CHF (Congestive Heart Failure)

    • 20-30% of CHF NYHA class III and IV have hyponatremia [10]
    • Associated with increased risk of death, independent of other comorbidities

  • Pathophysiology

    • Fall in MAP (perceived hypovolemia in vasculature due to third spacing) -> baroregulated vasopressin secretion stimulated + activation of RAAS -> increased H2O retention
  • Management:
    • Fluid restriction and NPO
    • Trend BMPs
    • Loop diuretics in acute heart failure has shown to be well tolerated [11], [12]
    • ACEi have been shown to increased serum Na levels in patients with heart failure in small studies [12], [13]
    • Vaptans have not shown significant improvement in patient outcomes [12], [14]

Treatment of hyponatremia is very dependent on the pathophysiology of the disease process, as seen above. Most importantly, cell swelling is imperative to keep in mind when managing as the brain is confined by the skull. With acute hyponatremia (<48 hours), the brain is not able to adapt to the swelling of the cells, and therefore patient can present with alarming neurologic symptoms and may die from brain herniation. With chronic hyponatremia (≥ 48 hours or duration unknown), the brain cells can compensate by extruding organic solutes from their cytoplasm, allowing for intracellular osmolality to equal plasma osmolality, therefore minimizing shift of water inside cells. [4] Therefore, management of acute and chronic hyponatremia should differ within the ED.  

Recently, numerous guidelines to manage hyponatremia has emerged. Specifically, a 2014 guideline was created to provide instructions on the diagnosis and treatment for adults with hypotonic hyponatremia. This paper reviewed the Cochrane Database, DARE, CENTRAL, and MEDLINE to aid with diagnosis and treatment recommendations. Barring the discussion below about severe hyponatremia with CNS dysfunction, the guidelines were clear about standard treatment. For patients with mild hyponatremia, the guidelines encouraged fluid restriction and rapid diagnosis. Treatment of the cause and inpatient sodium monitoring was considered gold standard. For patients with moderate hyponatremia, the guidelines suggested adding on a single IV infusion of 150mL of 3% hypertonic saline with goal of 5 mEq/L increased in serum Na concertation per 24hrs. [15]  

Clinical pearl: If you are at a site that does not have access to hypertonic saline, an ampule of bicarbonate can be used as a substitute.  

The above recommendation differs slightly from the 2013 guidelines [4] that are widely followed and regarded:

  • ↑ Serum sodium of 1–2 mEq/L/hour until an increase of 4–6 mEq/L has been reached within six hours

  • Serum sodium level not be increased by more than 10-12 mEq/L in any 24-hour period and/or 18 mEq/L in any 48-hour period

Severe Hyponatremia w/ CNS Dysfunction [15]

  • Chronicity does not matter in this scenario

    • First hour:

      • 150mL IV 3% hypertonic saline over 20 mins

      • Check Na

      • Repeat 150mL IV 3% hypertonic saline over 20 mins

    • Continue steps 1-3 until target of 5 mEq/L increase in Na concentration

      • If improved with above:

        • Stop hypertonic infusion

        • KVO IVFs

        • Diagnosis specific treatment

        • Limit serum Na concentration increase to 10 mEq/L during first 24 hours

        • Limit serum Na concentration increase to 8 mEq/L during every 24 hours thereafter

        • Stop treatment once Na = 130 mEq/L

      • If NOT improved with above:

        • Continue IV 3% hypertonic saline w/ goal 1 mEq/L/hr

        • Q4h Na checks

    • Stop infusion once:

      • Symptoms improve, OR

      • Serum Na concentration increased 10 mEq/L in total, OR

      • Serum Na concentration = 130 mEq/L

    • Consider adding desmopressin to prevent overcorrection in patients with sodium < 120 mEq/L [16]

    • Desmopressin leads to renal water retention and therefore iatrogenic hyponatremia.

  • The study was unable to definitely prove if addition helped but the study did not show any adverse effects associated with therapy and therefore the strategy appeared to be valid.

Chronic Hyponatremia

Rapid correction should be avoided as it can lead to osmotic demyelination syndrome (ODS)

  • Highly unlikely to occur in patients who have been hyponatremic for <24 hours or in patients with initial Na ≥ 120 mEq/L

  • If overcorrection does happen, limit free water excretion: [17]

    • IV D5 @ 3-6 mL/kg over 1-2 hours and free water flushes

    • Desmopressin (vasopressin) @ 1-2mcg q8h

    • Can be given concurrently with hypertonic to prevent rapid rise or as a rescue medication

Hypernatremia

SeveritySymptoms
Mild (145-150 mEq/L)Signs of dehydration: decreased salivation, dry mucous membranes and skin
Moderate (150-160 mEq/L)Confusion, Irritability, Restlessness, Lethargy, Muscle weakness, Hyperreflexia
Severe (>160 mEq/L)Focal neurological deficits, Seizures, Altered mental status, Stupor, Coma

Hypernatremia is the states of elevated serum concentrations, typically exceeding 145 mEq/L. This is the less common sodium irregularity to present in the ED, either as the initial complaint or incidental finding. It is primarily seen in infants and the elderly, and very commonly seen in the ICU setting. An increased the serum Na concentration is most often due to free water deficit but can occasionally be due to high sodium intake or reabsorption. For this reason, unlike hyponatremia, hypernatremia is always a hypertonic state (serum osmolality > 280 mOsm/kg). Symptoms are predominantly neurological and non-specific in nature (see table 3), similar to hyponatremia. However, these symptoms are typically accompanied by signs of clinical dehydration therefore assessing for a patient’s volume status on physical exam is useful. Causes are multifactorial and the onset can be acute (<48 hours) or chronic (≥ 48 hours or duration unknown). Chronic hypernatremia tends to be asymptomatic but can present with irritability, anorexia, nausea, weakness, dehydration, and AMS. [18]

As with hyponatremia, basic workup for hypernatremia, regardless of patient presentation or hypothesized cause, includes BMP, serum osmolality, and urine studies. [19] As there are a multitude of causes of hypernatremia, the focus will be on the common causes / presentations to the Emergency Department.

HypovolemicEuvolemicHypervolemic
Extracellular Fluid Volume↓ extracellular fluid volume due to hypotonic fluid lossnormal extracellular fluid volume due to pure water deficit ↑ extracellular fluid volume due to intake of hypertonic water or retention of sodium in excess of water
Renal Causes Diuretics  Osmotic diuresis - Hyperglycemia (ex. DKA, HHS) - Mannitol - Uremia - High-protein tube feeds - Osmotic diuretics Diabetes insipidus - Central - Nephrogenic  Primary hyperaldosteronism  Cushings syndrome
Extra-renal Causes GI loss - Diarrhea - Vomiting - Fistula  Dermal fluid loss - Burns - Excessive Sweating  Third-spacing Mechanical ventilation  Primary hypodipsia  Lack of access to water - AMS - Immobilization - Physically restrained - Quadriparesis Iatrogenic - Excessive NaCl infusion - Excessive NaHCO3 - Excessive hypertonic saline - Hemodialysis  Seawater consumption

Hypovolemic Hypernatremia

  • Dermal Fluid Loss

    • Presentations

      • ICU patient with insensible loss

      • Elderly patient with history of dementia and inability to complete ADLs

      • Hikers lost in hot climate for days

      • Burn victims

    • Pathophysiology

      • Loss of free water (not Na) through insensible losses -> decreased in extracellular fluid volume -> concentration of solutes -> increased serum Na concentration

    • Management [18], [20]

      • Oral / enteral hydration is superior to IV hydration (1/2 NS or 5% D5W)

      • Calculate free water deficit to determine the amount of repletion a patient will require

        • FWD = TBW x {(serum [Na] / 140) – 1}

      • For patients with severe hypernatremia with signs of shock, start with immediate management with isotonic fluids to correct extracellular fluid depletion

        • Acute Hypernatremia: replete entire water deficit within 24 hours (brain has not adapted therefore no risk of cerebral edema)

          • IV D5W @ 3-6 mL/kg/hr (max 666 mL/hr)

          • Trend BMPs and glucose

          • Na <145 mEq/L -> infusion rate 1 mL/kg/hr

          • Na ≤140 mEq/L -> discontinue infusion

          • Goal: reduce serum Na concentration by 1 mEq/L/hr 

Chronic Hypernatremia

  • Most commonly presentation of hypernatremia, mostly presenting with altered mental status

  • Reduce serum Na concentration by 0.5 mEq/L/hr, with no more than 10 mEq/L over 24 hours

  • Regimen

    • IV D5W @ 1.35 mL/kg/hr (max 150 mL/hr)

    • Trend BMPs and glucose

  • Overcorrecting can cause cerebral edema however, this is most commonly seen in a younger patient population. There has been no solid evidence in adults over 40 that rapid correction of sodium can cause harm. [21] In fact, studies show that under correction causes more harm than rapid correction, with difficulty achieving eunatremia. [22] 

Post by Raveena Chhabria, MD

Dr. Chhabria is a PGY-1 in Emergency Medicine at the University of Cincinnati

Editing by Ryan LaFollette, MD

Dr. LaFollette is co-editor of TamingtheSRU.com and an Associate Professor of Emergency Medicine at the University of Cincinnati.

References

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  3. Hoorn, Ewout J., and Robert Zietse. "Diagnosis and treatment of hyponatremia: compilation of the guidelines." Journal of the American Society of Nephrology 28.5 (2017): 1340-1349.

  4. Verbalis, Joseph G., et al. "Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations." The American journal of medicine 126.10 (2013): S1-S42.

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  9. Schrier, Robert W., et al. "Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia." New England Journal of Medicine 355.20 (2006): 2099-2112.

  10. Gheorghiade, Mihai, et al. "Relationship between admission serum sodium concentration and clinical outcomes in patients hospitalized for heart failure: an analysis from the OPTIMIZE-HF registry." European heart journal 28.8 (2007): 980-988.

  11. Filippatos, Theodosios D., and Moses S. Elisaf. "Hyponatremia in patients with heart failure." World journal of cardiology 5.9 (2013): 317.

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  13. Oster, J R, and B J Materson. “Renal and electrolyte complications of congestive heart failure and effects of therapy with angiotensin-converting enzyme inhibitors.” Archives of internal medicine vol. 152,4 (1992): 704-10.

  14. Gheorghiade, Mihai et al. “Vasopressin v(2) receptor blockade with tolvaptan versus fluid restriction in the treatment of hyponatremia.” The American journal of cardiology vol. 97,7 (2006): 1064-7. doi:10.1016/j.amjcard.2005.10.050

  15. Spasovski, Goce, et al. "Clinical practice guideline on diagnosis and treatment of hyponatraemia." Nephrology Dialysis Transplantation 29.suppl_2 (2014): i1-i39.

  16. Sood, Lonika, et al. "Hypertonic saline and desmopressin: a simple strategy for safe correction of severe hyponatremia." American Journal of Kidney Diseases 61.4 (2013): 571-578.

  17. Ward, Frank L et al. “The Role of Desmopressin in the Management of Severe, Hypovolemic Hyponatremia: A Single-Center, Comparative Analysis.” Canadian journal of kidney health and disease vol. 5 2054358118761051. 21 Mar. 2018, doi:10.1177/2054358118761051

  18. Braun, Michael M., Craig Barstow, and Natasha Pyzocha. "Diagnosis and management of sodium disorders: hyponatremia and hypernatremia." American family physician 91.5 (2015): 299-307.

  19. “EM@3AM: Hypernatremia.” EmDOCs.net - Emergency Medicine Education, 14 July 2018, http://www.emdocs.net/em3am-hypernatremia/.

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  22. Bataille, Stanislas, et al. "Undercorrection of hypernatremia is frequent and associated with mortality." BMC nephrology 15.1 (2014): 1-9.