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Synonyms and Keywords: Hyponatraemia
The electrolyte disturbance hyponatremia exists in humans when the sodium (Natrium in Latin) concentration in the plasma falls below 130 mmol/L. At lower levels water intoxication may result, an urgently dangerous condition. Hyponatremia is an abnormality that can occur in isolation or, as most often is the case, as a complication of other medical illnesses.
Certain conditions that interfere with laboratory tests of serum sodium concentration (such as extraordinarily high blood levels of lipid or protein) may lead to an erroneously low measurement of sodium. This is called pseudohyponatremia, and can occur when laboratories use the flame-photometric and indirect (but not direct) ion-selective electrode assays. This is distinct from a true dilutional hyponatremia that can be caused by an osmotic shift of water from cells to the bloodstream after large infusions on mannitol or intravenous immunoglobulin.
When the plasma osmolarity is low, the extracellular fluid volume status may be in one of three states:
- Low volume. Loss of water is accompanied by loss of sodium.
Treat underlying cause and give IV isotonic saline. It is important to note that sudden restoration of blood volume to normal will turn off the stimulus for continued ADH secretion. Hence, a prompt water diuresis will occur. This can cause a sudden and dramatic increase the serum sodium concentration and place the patient at risk for so-called "central pontine myelinolysis" (CPM). That disorder is characterized by major neurologic damage, often of a permanent nature.
Because of the risk of CPM, patients with low volume hyponatremia may eventually require water infusion as well as volume replacement. Doing so lessens the chance of a too rapid increase of the serum sodium level as blood volume rises and ADH levels fall.
- Normal volume.
The cornerstone of therapy for SIADH is reduction of water intake. If hyponatremia persists, then demeclocycline (an antibiotic with the side effect of inhibiting ADH) can be used. SIADH can also be treated with specific antagonists of the ADH receptors, such as conivaptan or tolvaptan.
- High volume. There is retention of water.
Placing the patient on water restriction can also help in these cases.
Severe hyponatremia may result from a few hours of heavy exercise in high temperature conditions, such as hiking in desert areas, or from endurance athletic events when electrolytes are not supplied. (Such an incident notably happened to long-distance athlete Craig Barrett in 1998).
Natural History, Complications and Prognosis
Chronic hyponatremia can lead to such complications as neurological impairments. These neurological impairments most often affect gait and attention and can lead to falls, osteoporosis, and increased reaction time.
Complications for chronic hyponatremia are most dangerous for geriatric patients. Falls are the leading cause of deaths related to injury among people 65 years or older. In a recent study the incidence of hyponatremia in elderly patients with large-bone fractures was more than double that of non-fracture patients. Recent work by Verbalis et al. suggests that hyponatremia induces osteoporosis and found the adjusted odds ratio for developing osteoporosis to be 2.87 times higher among adults with mild hyponatremia compared to those without.
Acute hyponatremia can lead to much more serious complications including brain disease, brain herniation, cardiopulmonary arrest, cerebral edema, seizures, coma, and death.
- Serum osmolality
- Blood urea nitrogen (BUN)/creatinine
- Urine sodium
- Thyroid stimulating hormone (TSH)
- Serum glucose
- Hyponatremia is due to an excess of free water in the body, not due to a deficiency of sodium.
- The treatment of hyponatremia is therefore free water restriction.
- In patients who are receiving intravenous therapy, you should make sure that D5W is not infusing, and that drug infusions are mixed in normal saline, and not D5W.
- The patients access to water and juice should be restricted.
- In some refractory cases, the water to the room must be turned off.
The treatment of hyponatremia will depend on the underlying cause and whether the patient's volume status is hypervolemic, euvolemic, or hypovolemic. In the setting of hypovolemia, intravenous administration of normal saline may be effective, but caution must be exercised not to raise the serum sodium level too quickly (see below). Euvolemic hyponatremia is usually managed by fluid restriction and treatment to abolish any stimuli for ADH secretion such as nausea. Likewise, drugs causing SIADH should be discontinued if possible. Patients with euvolemic hyponatremia that persists despite those measures may be candidates for a so-called vaptan drug as discussed below. Hypervolemic hyponatremia should be treated by treating the underlying cause (e.g. heart failure, cirrhosis). In practice, it may not be possible to do so, in which case the treatment of the hyponatremia becomes the same as that for euvolemic hyponatremia (i.e. fluid restriction and/or use of a vaptan drug).
Hyponatremia must be corrected slowly in order to lessen the chance of the development of central pontine myelinolysis (CPM), a severe neurological disease. In fact, overly rapid correction of hyponatremia is the most common cause of that potentially devastating disorder. During treatment of hyponatremia, the serum sodium should not be allowed to rise by more than 8 mmol/l over 24 hours (i.e. 0.33 mmol/l/h rate of rise). In practice, too rapid correction of hyponatremia and thence CPM is most likely to occur during the treatment of hypovolemic hyponatremia. In particular, once the hypovolemic state has been corrected, the signal for ADH release disappears. At that point, there will be an abrupt water diuresis (since there is no longer any ADH acting to retain the water). A rapid and profound rise in serum sodium can then occur. Should the rate of rise of serum sodium exceed 0.33 mmol/l/h over several hours, vasopressin may be administered to prevent ongoing rapid water diuresis.
Pharmaceutically, vasopressin receptor antagonists can be used in the treatment of hyponatremia, especially in patients with SIADH, congestive heart failure or liver cirrhosis. A vasopressin receptor antagonist is an agent that interferes with the action at the vasopressin receptors. A new class of medication, the "vaptan" drugs has been specifically developed to inhibit the action of vasopressin on its receptors (V1A, V1B, and V2). These receptors have a variety of functions, with the V1A and V2 receptors are expressed peripherally and involved in the modulation of blood pressure and kidney function respectively, while the V1A and V1B receptors are expressed in the central nervous system. V1A is expressed in many regions of the brain, and has been linked to a variety of social behaviors in humans and animals.
The “vaptan” class of drugs contains a number of compounds with varying selectivity, several of which are either already in clinical use or in clinical trials as of 2010.
Unselective (mixed V1A, V2)
The V2-receptor antagonists tolvaptan and conivaptan allow excretion of electrolyte free water and are effective in increasing serum sodium in euvolemic and hypervolemic hyponatremia.
Rate of Na Correction
The rate of correction of hyponatremia should be 0.5-1.0meq/L/hr, with not more than a 12 meq/l correction in 24 hrs. If the patient has ongoing seizures (or [Na+]<115 meq/li), correction can be attempted at up to 2 meq/L/hr, but only while seizure activity lasts and the [Na+] exceeds 125-130 meq/Li.
- Weisberg LS. (1989) Pseudohyponatremia: a reappraisal. Am J Med, 86(3):315-8. PMID 2645773
- Nguyen MK et al. (2007) A new method for determining plasma water content: application in pseudohyponatremia. Am J Phys - Renal, 292(5):F1652-6. PMID 17299138
- Harminder, S. Sandhu et al. "Hyponatremia associated with large-bone fracture in elderly patients." Int Urol Nephrol (2009) 41:733-737.
- Ayus, Juan Carlos and Michael L. Moritz. "Bone Disease as a New Complication of Hyponatremia: Moving Beyond Brain Injury". CJASN ePress. Jan 14, 2010. 10.2215/CJN.09281209.
- Bernsen HJ, Prick MJ (1999). "Improvement of central pontine myelinolysis as demonstrated by repeated magnetic resonance imaging in a patient without evidence of hyponatremia". Acta Neurol Belg. 99 (3): 189–93. PMID 10544728. Unknown parameter
- Horacio J. Adrogué, M.D. and Nicolaos E. Madias, M.D (2000-05-25). "Hyponatremia". N Engl J Med 2000; 342:1581-1589. The New England Journal of Medicine.
- Robert D. Zenenberg,Do, et. al (2010-04-27). "Hyponatremia: Evaluation and Management". Hospital Practice. 38 (1): 89–96. doi:10.3810/hp.2010.02.283. PMID 20469629. Unknown parameter