Hyponatremia

Introduction

Alterations of sodium reflect disturbances of the body water. Hyponatremia occurs in 15 to 20 % of hospitalized patients. This condition poses a challenge for diagnosis and treatment. The terminology and definitions of hyponatremia are often inconsistent and confusing. This checklist is based on a European guideline from 2014, with some additional context from UpToDate.

Measuring sodium

You measure sodium via photometric or ion selective electrodes. Photometric measurements can be affected by the osmolality. Therefore, it’s a good idea to confirm your measurement with a second sample and different methodology. Ion selective electrodes can be found in blood gas analyzers and are readily available as point of care devices. Always confirm that your results are plausible and eliminate potential errors. When monitoring your therapy, don’t compare different methodologies, i.e., don’t compare blood gases with serum measurements.

Terminology

You can classify hyponatremia first by osmolality into hypotonic or non-hypotonic hyponatremia. The guidelines only cover hypotonic hyponatremia, this is the first diagnostic step. The feared cerebral edema is a classic complication of hypotonic hyponatremia. After confirming a hypotonic hyponatremia, you can then distinguish between a hypovolemic, euvolemic and hypervolemic form. It is not standardized, whether this refers to total body water, extracellular volume, or effective blood volume. The European guideline emphasizes that clinical evaluation of volume status is a difficult task, therefore giving relevance to the volume status only late in the evaluation. The severity of hyponatremia is defined as

• Mild: 130 to 135 mmol/l
• Moderate: 125 to 129 mmol/l
• Severe: below 125 mmol/l

Depending on the time of development two further forms also exist:

• Acute hyponatremia with a documented duration of under 48 hours
• Chronic hyponatremia with a documented duration of over 48 hours.
• If you can’t classify a hyponatremia with certainty as acute, it is a chronic hyponatremia.

Depending on symptoms (nausea, confusion, vomiting, dizziness, seizures) you can divide into

• Symptomatic hyponatremia
• Asymptomatic hyponatremia

Diagnosis

It is essential to take your samples early on (before giving fluids, for example) to have a chance of correctly diagnosing the cause of hyponatremia. While one often wants to find a singular disease as trigger for hyponatremia, in multimorbid patients it is often a result of mixed etiologies. In severe or symptomatic hyponatremia the diagnostic must not delay the treatment, as early and deceisive correction is essential for a good outcome for your patient.

You should always try to acquire:

• Serum electrolytes (Na, K, Ca, Mg, phosphate), glucose, calculated osmolality, measured osmolality if available, cortisol, and further blood work depending on differential diagnosis.
• Urine: sodium (in spot urine), osmolality. You might need more urine than for a standard urinalysis, so contact your lab if unsure how much urine is needed.

For further subdivision on the cause of hyponatremia you might need the volume status (extracellular volume). Look for edema during your exam and use point of care ultrasound if available.

Evaluation etiology

The European guidelines provide a short, but practical approach to diagnosis. UpToDate features a much more refined approach, which is often helpful during difficult/more advanced diagnosis.

1. Confirm a hypotonic hyponatremia by calculating or measuring osmolality. It has to be below 275 mOsm/kg to qualify for this approach.
2. Urine osmolality equal or less than 100 mOsm/kg
   • The kidney is producing “diluted urine” in case of increase intake of water (e.g. polydipsia) or reduced intake of osmoles (malnutrition, alcoholism).
   • You patient has received volume before samples were taken.
   • This means:
     • Secretion of (relative) large amounts of water in relation to osmoles will cause a rise in serum sodium.
     • If your patient pees a lot, they are about to have a fast rise in serum sodium!
3. Urine osmolality greater than 100 mOsm/kg
   • This means:
     • The kidneys are retaining water, the patient will not correct their serum sodium.
     • Isotonic volume can aggravate the hyponatremia, due to the kidneys losing sodium while retaining water.
   • In itself unspecific, to further evaluate you need urine sodium and volume status (extracellular fluid = ecf):
   • Urine sodium less/equal to 30 mmol/l
     • increased ecf: heart failure, liver cirrhosis, nephrotic syndrome
     • decreased ecf: diarrhea/vomiting = extrarenal loss, diuretic medication
   • Urine sodium greater than 30 mmol/l
     • Loss due to diuretic medication or renal failure – check history and lab work
     • Low ecf: vomiting, cerebral salt wasting, (primary) adrenal insufficiency
     • Normal ecf: SIADH, (secondary) adrenal insufficiency, hypothyroidism

Further diagnosis

Depending on the suspected cause, you need further evaluation of adrenal or thyroid function. The SIADH is a diagnosis of exclusion, and the guideline emphasizes that it has to be distinguished from cerebral salt wasting. The following table is from the guidelines and gives an overview of the typical findings:

Therapy

Therapy is based on severity, symptoms and duration of hyponatremia. You should monitor your patients’ sodium levels as needed with the same measurement method (i.e. blood gas analyzer) every 4 to 6 hours.

Preparing a 3% NaCl solution from 10 %

If you don’t have 3 % NaCl solutions readily available: Mix 30 ml NaCl 10 % with 70 ml Aqua

Symptomatic hyponatremia

• Symptoms: Seizures, confusion, headache, nausea and vomiting, reduced level of consciousness
• Use the same approach when you fear that a worsening severe hyponatremia might cause a risk of death
• Admit to intensive care
• Therapy
  1. 150 ml 3% NaCl over 20 minutes i.v., in case of overweight or underweight use 2 ml/kg body weight. This is safe to give with a peripheral line!
  2. Check sodium and compare with initial sodium:
     • Rise below 4 to 5 mmol/l: repeat step 1.
     • Rise of 5 mmol/l:
       • If no clinical improvement is seen, the symptoms are likely caused by something else. Recheck your diagnosis! You can continue giving 3% NaCl with a rise of serum sodium of 1 mmol/l. Limit your total rise to 10 mmol/l above initial sodium levels in the first 24 hours and to a maximum of 130 mmol/l.
       • If clinical improvement is seen: Limit correction to 10 mmol/l in the first 24 hours, and then to 8 mmol/24 hours thereafter with a maximum of 130 mmol
       • Your initial rise is included, for example if you raise a sodium of 110 mmol/l to 114 mmol/l after 150 ml NaCl 3%. You can then target a max. sodium of 120 mmol/l after 24 hours - so you still have 6 mmol/l “left”.

Acute hyponatremia, asymptomatic

• Make sure the same measurement method has been used for the compared values
• Treat underlying cause
• In case of drop > 10 mmol/l
  • Give 150 ml 3% NaCl i.v. over 20 minutes.

Chronic hyponatremia

• Restrict fluid intake, check medication
• Treat underlying cause
• Mild hyponatremia: Don’t treat based on lab values, fluid restriction can decrease quality of life without improving morbidity or mortality
• Moderate or severe hyponatremia: Limit increase to 10 mmol/l in the first 24 hours, then to 8 mmol/l/24 hours thereafter.

Special considerations

• In increased extracellular fluid, restrict fluid intake in symptomatic hyponatremia only
• SIADH (only in moderate or severe hyponatremia):
  • Restrict fluid intake or
  • 0.25 to 0.5 mg/kg body weight urea per day or
  • Give loop diuretic + oral NaCl (monitor electrolytes + volume status)
• Reduced volume:
  • Give balanced electrolyte solution at 0.5 to 1 ml/kg body weight/hour
  • If patient is unstable: stabilizing circulation is more important than rate of sodium correction.

Handle overcorrection

If urine output increases to more than 100 ml/h, there is a risk of sodium overcorrection. This can happen when hypovolemia is treated, which reduces vasopressin activity and leads to more free water clearance. In this situation, monitor the patient’s sodium levels closely. Osmotic demyelination is a serious complication that depends more on the initial osmolality than on the sodium levels alone. Even if the patient has no symptoms, demyelination can occur later. Therefore, it is important to adjust the sodium levels to the planned target (i.e. to “ping-pong” back down if they rise too quickly)

Overcorrection occurs when sodium is rising over 10 mmol/l in the first 24 hours, or over 8 mmol/l every 24 hours thereafter. In this case:

1. Stop current therapy
2. You can consider giving 10ml/kg body weight of 5% Glucose over one hour, thereby introducing free water. Limiting factors can be fluid balance or electrolyte disturbances (mainly low potassium)
3. You can give 2 µg desmopressin (=DDAVP) every 8 hours to reduce water elimination.

You can combine therapies: If you want to lower sodium, the combination of Desmopressin and 5% Glucose is sensible, if you want to limit the raise (but still raise it) you can also give Desmopressin and 3% NaCl. To stabilize sodium, Desmopressin alone is possible.

Non-hypotonic hyponatremia

Non-hypotonic hyponatremia occurs due to osmoles, that “draw” water into the extracellular space. Examples include glucose in case of hyperglycemia or in hyperosmolar hyperglycemic state. Alcohol or hyperuricemia can cause a normotonic hyponatremia. Exogenous i.v. IgG or resorption of large amounts of surgical irrigation fluid during a procedure can also cause a hyponatremia. In these cases, a more rapid correction is possible.

Further reading

• The IBBC chapter on hyponatremia
• The European guideline on hyponatremia
• UpToDate chapters on diagnostic evaluation and treatment of hyponatremia

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