Hyponatremia– Causes, Symptoms, Diagnosis, Treatment and Ongoing care

Basics

Description

  • Hyponatremia is a plasma sodium concentration of <135 mEq/L.
  • System(s) affected: Endocrine/Metabolic

Epidemiology

Incidence

  • Most common electrolyte disorder seen in general hospital population (1)
  • Predominant age: All ages
  • Predominant sex: Male = Female.

Prevalence

2.5% of hospitalized patients (1)

Risk Factors

Genetics

  • Polymorphisms have been demonstrated.
  • Mutations have been associated with nephrogenic syndrome of inappropriate antidiuresis (NSIAD).

General Prevention

Depends on underlying condition

Pathophysiology

  • Hypovolemic hyponatremia: Decrease in total body water and greater decrease in total body sodium; decreased extracellular fluid volume; orthostatic hypotension and other changes consistent with hypovolemia are present.
  • Euvolemic hyponatremia: Increase in total body water with normal total body sodium; extracellular fluid volume is minimally to moderately increased but with no edema.
  • Hypervolemic hyponatremia: Increase in total body sodium and greater increase in total body water; extracellular fluid increased markedly; edema present
  • Redistributive hyponatremia: Shift of water from intracellular compartment to extracellular compartment with resulting dilution of sodium; total body water and total body sodium unchanged; occurs with hyperglycemia.
  • Pseudohyponatremia: Dilution of aqueous phase by excessive proteins, glucose, or lipids; total body water and total body sodium unchanged; occurs in hypertriglyceridemia or multiple myeloma.
  • Low sodium creates an osmotic gradient between plasma and cells, and fluid shifts into cells, causing edema and increased intracranial pressure (ICP).

Etiology

  • Hypovolemic hyponatremia: Extrarenal loss of sodium (urine Na <30 mmol/L):
    • GI loss: Vomiting, diarrhea
    • Third spacing: Peritonitis, pancreatitis, burns, rhabdomyolysis
    • Skin loss: Burns, sweating, cystic fibrosis
    • Heat-related illnesses
  • Hypovolemic hyponatremia: Renal loss of sodium (urine Na >30 mmol/L):
    • Cerebral Salt Wasting Syndrome (CSWS)
    • Adrenal pathology (e.g., Addison disease, hemorrhage, tuberculosis)
    • Diuretics
    • Osmotic diuresis
  • Euvolemic hyponatremia (urine Na >30 mmol/L):
    • Hypothyroidism
    • Hypopituitarism or other cause of glucocorticoid deficiency
    • Medications (e.g., carbamazepine, clofibrate, cyclosporine, levetiracetam, opiates, oxcarbazepine, phenothiazines, tricyclic antidepressants, vincristine) (2,3,4)
    • Primary polydipsia
    • Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
    • Iatrogenic (e.g., excess hypotonic IV fluids)
  • Hypervolemic hyponatremia (urine Na <30 mmol/L, except chronic renal failure):
    • Nephrotic syndrome
    • Cirrhosis
    • Congestive heart failure (CHF)
    • Chronic renal failure
  • Redistributive hyponatremia:
    • Hyperglycemia
    • Mannitol infusion
    • Hypertriglyceridemia
  • Multiple myeloma

Commonly Associated Conditions

  • Hypothyroidism
  • Hypopituitarism
  • Adrenocortical hormone deficiency
  • HIV patients
  • SIADH associated with cancers, pneumonia, tuberculosis, encephalitis, meningitis, head trauma, cerebrovascular accident (CVA), HIV infection (5)[B],(6)
  • Acute neurological patients, brain injury (7,8,9)
  • Marathon runners in hot environment

Heart failure, electrolyte disorder, hypovolemic hyponatremia, low sodium, body water, skin loss, hypotension, multiple myeloma,

Diagnosis

  • Symptoms related to the rate of fall in serum sodium and the degree of hyponatremia (10,11)
  • Mild (130–135 mEq/L): Usually asymptomatic
  • Moderate (120–130 mEq/L): Nausea, vomiting, malaise
  • Severe: (115–120 mEq/L): Headache, lethargy, restlessness, disorientation
  • With severe/rapid decreases, can cause seizure, coma, and respiratory arrest and may be fatal
  • Other signs and symptoms: Weakness, muscle cramps, anorexia, hiccups, depressed deep tendon reflexes, hypothermia, positive Babinski responses, cranial nerve palsies, orthostatic hypotension

Physical Exam

  • Volume status: Skin turgor, jugular venous pressure, heart rate, orthostatic BP
  • Exam for underlying illness: Signs of CHF, cirrhosis, hypothyroidism

Diagnostic Tests & Interpretation

Lab

  • Serum sodium <135 mmol/L
  • Plasma osmolality
  • Urine sodium and osmolality
  • Renal function
  • Hepatic function
  • Thyroid function
  • Serum glucose, lipids
  • Hypovolemic hyponatremia:
    • Plasma osmolality low
    • Blood urea nitrogen (BUN): creatinine ratio >20:1
    • Urine sodium >20 mEq/L (>20 mmol/L): Renal loss
    • Urine sodium <10 mEq/L (<10 mmol/L): Extrarenal loss
    • Serum potassium >5.0 mEq/L (>5 mmol/L): Consider mineralocorticoid deficiency.
  • Euvolemic hyponatremia:
    • Plasma osmolality low
    • BUN: creatinine ratio <20:1
    • Urine sodium >20 mEq/L (>20 mmol/L)
    • Thyroid-stimulating hormone (TSH) test to rule out hypothyroidism
    • 1-h cosyntropin-stimulation test to rule out adrenal insufficiency
  • Hypervolemic hyponatremia:
    • Plasma osmolality low
    • Urine sodium <10 mEq/L (<10 mmol/L) in nephrotic syndrome, CHF, cirrhosis
    • Urine sodium >20 mEq/L (>20 mmol/L) in acute and chronic renal failure
  • Redistributive hyponatremia:
    • Plasma osmolality normal or high
    • Glucose or mannitol levels elevated
  • Pseudohyponatremia:
    • Plasma osmolality normal
    • Triglyceride, glucose, or protein levels elevated

Imaging

  • CT scan of head if pituitary problem suspected or if SIADH from CNS problem suspected
  • CXR to rule out pulmonary pathology if SIADH diagnosed

Differential Diagnosis

See Etiology.

Treatment

Medication

  • Treatment tailored to clinical situation: Degree and rate of hyponatremia and whether or not the patient is symptomatic; some general principles apply (10).
  • Asymptomatic, euvolemic patients can be treated with fluid restriction plus addressing the underlying cause.
  • For severely hyponatremic/symptomatic patients, generally considered safe to increase the serum Na by 0.6–2.0 mEq/L each hour, not to exceed 8 mEq/24 h.
  • Treatment of underlying condition: Heart failure, cirrhosis, etc., essential
  • In patients with euvolemic or hypervolemic hyponatremia, tolvaptan, an oral vasopressin V2-receptor antagonist, was effective in increasing serum sodium concentrations (12).
  • Rapid correction of severe symptomatic hyponatremia has been associated with central pontine myelinolysis, a neurologic disorder that induces loss of myelin and supportive structures in pons and occasionally in other areas of the brain. This results in irreversible injury. Symptoms are apparent 2–6 days after injury and include seizure, coma, spastic paraparesis, dysarthria, and dysphagia.
  • Use of hypertonic saline (3% NaCl) has only a slight evidence base; consider consulting with specialist before undertaking this treatment (5).
  • Chronic hyponatremia owing to SIADH: Demeclocycline (inhibits ADH action at the collecting duct) if fluid restriction alone is not effective:
    • Contraindication: Can cause nephrotoxicity in patients with liver disease
    • In doses of 600–1,200 mg/d, drug produces a nephrogenic diabetes insipidus.
    • Significant possible interactions: Oral anticoagulants, oral contraceptives, penicillin

Additional Treatment

General Measures

  • Inpatient treatment mandatory if acute hyponatremia or symptomatic; acute (developing over <48 h) hyponatremia carries the risk of cerebral edema.
  • Inpatient treatment is advised if asymptomatic and serum sodium <125 mEq/dL.
  • Assess all medications patient is taking.
  • Institute seizure precautions.

In-Patient Considerations

Admission Criteria

  • Admission mandatory if acute hyponatremia or symptomatic; acute (developing over <48 h) hyponatremia carries the risk of cerebral edema.
  • Admission is advised if patient is asymptomatic and has a serum sodium <125 mEq/dL.

Ongoing Care

Diet

  • Euvolemic hyponatremia: Water restriction to 1 L/d
  • Hypervolemic hyponatremia: Water and sodium restriction

Prognosis

  • In hospitalized patients, hyponatremia is associated with elevated risk of adverse clinical outcomes and higher mortality (13,14).
  • Recently, in community-dwelling middle-aged and elderly adults, mild hyponatremia has been shown to be an independent predictor of death.
  • Associated with poor prognosis in patients with acute pulmonary embolism (15)
  • Associated with poor prognosis in liver cirrhosis and in patients waiting for liver transplant and is associated with significant post-operative risk and short-term graft lost (14,16)

Complications

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  • Occult tumor may present with SIADH.
  • Hypervolemia if saline used
  • Central pontine myelinolysis (see above) (17)
  • Hyponatremia is cause in 30% new-onset seizures in ICU.
  • Chronic hyponatremia is associated with an increased odds of osteoporosis (18).

References

1. Upadhyay A, Jaber BL, Madias NE. Epidemiology of hyponatremia. Semin Nephrol. 2009;29:227–38.

2. Ben Salem C, Hmouda H, Bouraoui K. Drug-induced hyponatremia: adding to the list. Am J Kidney Dis. 2008;52:1025–6; author reply 1027.

3. Meulendijks D, Mannesse CK, Jansen PA et al. Antipsychotic-induced hyponatraemia: a systematic review of the published evidence. Drug Saf. 2010;33:101–14.

4. Jacob S, Spinler SA et al. Hyponatremia associated with selective serotonin-reuptake inhibitors in older adults. Ann Pharmacother. 2006;40:1618–22.

5. Yeates KE, Singer M, Morton AR. Salt and water: a simple approach to hyponatremia. CMAJ. 2004;170:365–9.

6. Lim YJ, Park EK, Koh HC et al. Syndrome of inappropriate secretion of antidiuretic hormone as a leading cause of hyponatremia in children who underwent chemotherapy or stem cell transplantation.Pediatr Blood Cancer. 2010;54:734–7.

7. Brimioulle S, Orellana-Jimenez C, Aminian A et al. Hyponatremia in neurological patients: cerebral salt wasting versus inappropriate antidiuretic hormone secretion. Intensive Care Med. 2008;34:125–31.

8. Costa KN, Nakamura HM, da Cruz LR et al. Hyponatremia and brain injury: absence of alterations of serum brain natriuretic peptide and vasopressin. Arq Neuropsiquiatr. 2009;67:1037–44.

9. Chang CH, Liao JJ, Chuang CH et al. Recurrent hyponatremia after traumatic brain injury. Am J Med. Sci. 2008;335:390–3.

10. Ellison DH, Berl T. Clinical practice. The syndrome of inappropriate antidiuresis. N Engl J Med. 2007;356:2064–72.

11. Duracher C, Baugnon T, Blanot S, et al. Intraoperative hyponatremia: is it related to surgical procedure or fluid maintenance? Paediatr Anaesth. 2009;19:711–2.

12. Rozen-Zvi B, Yahav D, Gheorghiade M, Korzets A, Leibovici L, Gafter U et al. Vasopressin receptor antagonists for the treatment of hyponatremia: systematic review and meta-analysis. Am J Kidney Dis.2010;56:325–37.

13. Kugler JP, Hustead T. Hyponatremia and hypernatremia in the elderly. Am Fam Physician. 2000;61:3623–30.

14. Cárdenas A, Ginès P. Predicting mortality in cirrhosis–serum sodium helps. N Engl J Med. 2008;359:1060–2.

15. Scherz N, Labarère J, Méan M et al. Prognostic Importance of Hyponatremia in Patients with Acute Pulmonary Embolism. American journal of respiratory and critical care medicine. 2010

16. Fukuhara T, Ikegami T, Morita K et al. Impact of preoperative serum sodium concentration in living donor liver transplantation. J Gastroenterol Hepatol. 2010;25:978–84.

17. Fleming JD, Babu S. Images in clinical medicine. Central pontine myelinolysis. N Engl J Med. 2008 Dec 4;359(23):e29.

18. Verbalis JG, Barsony J, Sugimura Y et al. Hyponatremia-induced osteoporosis. J Bone Miner Res. 2010;25:554–63.

Additional Reading

Callahan MA, Do HT, Caplan DW, et al. Economic impact of hyponatremia in hospitalized patients: a retrospective cohort study. Postgrad Med. 2009;121:186–91.

20. Cowtan T et al. Thiazide diuretics. N Engl J Med. 2010;362:659–660

21. Ernst ME, Moser M et al. Use of diuretics in patients with hypertension. N Engl J Med. 2009;361:2153–64.

See Also (Topic, Algorithm, Electronic Media Element)

Algorithm: Hyponatremia

Codes

ICD9

276.1 Hyposmolality and/or hyponatremia

Snomed

89627008 hyponatremia (disorder)

Clinical Pearls

  • Alcohol-dependent individuals with vitamin deficiencies, elderly women taking thiazide diuretics, and people with hypokalemia or burns are at increased risk of central pontine myelinolysis. A longer duration of hyponatremia is also a risk factor.
  • Elderly people have lower total body water, decreased thirst mechanism, decreased urinary concentrating ability, kidneys are less responsive to ADH, and individuals show decreased renal mass, renal blood flow, and glomerular filtration rate.
  • Bronchogenic carcinoma, pancreas, duodenal, prostate, thymoma, lymphoma, and mesothelioma are neoplastic diseases associated with SIADH.
  • MDMA (ecstasy) is an illicit drug that causes hyponatremia (5)[B].

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