Sodium

Summary:

• Acute hyponatraemia post-op in general surgical patients would mostly be extra-renal fluid losses (hypovolaemic), SIADH/physiological stress (euvolaemic) or renal/liver/heart failure (hypervolaemic)
  • Sodium 126-130: monitor daily electrolytes and review medications if chronic.
  • Sodium 120-125: send urine and serum osmolality and sodium levels, and fluid restrict to 500mL less than daily urine output. Identify cause.
  • Sodium <120 or any symptoms: refer ICU for consideration of monitoring and hypertonic saline.
• Acute hypernatraemia in surgical patients is usually due to dehydration from loss of hypotonic body fluids
  • Sodium 145-150: volume resuscitate with crystalloid and PO water; identify and fix fluid loss
  • Sodium >150: review aetiology, consider medical referral

Pathophysiology

• The underlying problem is a change in cell volume, but it presents as a change in the plasma sodium concentration (hypernatraemia or hyponatraemia)
• They should be approached in terms of a single variable: the extracellular volume (which consists of both extravascular (interstitial) fluid and intravascular (plasma) fluid compartments).
  • Note that plasma volume is about 25% of interstitial fluid volume
  • Sodium itself equilibrates through both interstitial fluid and plasma
  • 75% of infused saline solutions will distribute in the interstitial fluid, and 25% in plasma
• Osmotic activity
  • The property that determines movement of water between fluid compartments, and is a reflection of the number of solute particles per unit volume of solvent. Osmotic activity depends only on the NUMBER of solute particles in a fluid, and not the electrical charge/size/chemical behaviour of solutes.
  • The unit of measurement for osmotic activity is the osmole (osm), which is defined as one gram molecular weight (one mole) of a non-dissociable substance, and is equivalent to Avogadro's number. It can be expressed in two different ways:
    • Osmotic activity per volume of solution - osmolarity mOsm/L
    • Osmotic activity per volume of water - osmolality mOsm/kg H2O
  • Plasma is mostly (93%) water, so the osmotic activity of plasma solutes is typically expressed as osmolality. For ECF in general, either osmolality or osmolarity can be used, as they will be almost identical (unless a toxin has accumulated to increase the 'osmolal gap', which is the difference between measured and calculated osmolality).
    • Plasma osmolality can be either calculated or measured. Note that sodium accounts for 98% of effective osmotic activity of ECF - sodium concentration in ECF is the principal determinant of the distribution of total body water in the intracellular and extracellular fluid compartments.

• 'Effective plasma osmolality' will be almost identical to 'total plasma osmolality', and you can just omit the urea

• Water and solutes will rearrange themselves between fluid compartments to reach equilibrium: osmotic activity, based on osmotic pressure. The fluid with the higher osmotic activity is called hypertonic, and the fluid with the lower osmotic activity is called hypotonic.

• Impact of osmotic activity
  • A change in the relative osmotic activity of ECF produces a transcellular water shift
  • When the ECF is hypertonic, water moves out of cells
  • When the ECF is hypotonic, water moves into cells
• Anti-diuretic hormone (ADH)
  • Released by the posterior pituitary in response to an increase in the osmolality of ECF, promoting water reabsorption in the distal renal tubules
  • Normally suppressed at plasma sodium < 135
  • Also released in response to non-osmotic factors - hypotension (via baroreceptors), physiological stress (along with ACTH release from anterior pituitary)
  • SIADH occurs when these non-osmotic release triggers persist despite a sodium level < 135, and is an important factor in the development of severe and sustained hyponatraemia. The hallmarks are euvolaemia, hypotonic plasma, inappropriately concentrated urine (urine osmolality >100mosm/kg H2O), and a high urine sodium level.

Hypernatraemia

• Definition
  • Plasma sodium concentration >145mEq/L
• Aetiology (see algorithm below)
  • Loss of sodium and water, with water loss > sodium loss (hypotonic fluid loss)
    • The most common cause of community-acquired hypernatraemia
    • Pretty much any body fluid loss is hypotonic, and will lead to hypernatraemia if lost excessively and not replaced
    • This should normally be managed by thirst response, so if this has not taken place it is an indicator of significant pathology
    • Plasma volume is often maintained due to colloid osmotic pressure drawing fluid from interstitial compartment into plasma
  • Free water loss
    • Common in ICU patients with hypernatraemia, and usually occurs when sodium losses are replaced, leaving a net free water deficit
    • Diabetes insipidus - loss of urine that is largely devoid of solute
      • Central DI (failure of ADH release from posterior pituitary) - traumatic brain injury, anoxic encephalopathy, meningitis, brain death.
      • Nephrogenic DI (impaired end-organ responsiveness to ADH) - amphotericin, aminoglycosides, radiocontrast dyes, dopamine, lithium, hypokalaemia, and the recovery (polyuric) phase of ATN. Usually less severe than central DI.
      • The hallmark is dilute urine in the face of hypertonic plasma. <200mosm/L in central DI and 200-500mosm/L in nephrogenic DI. Failure of the urine osmolarity to increase in the first few hours of fluid restriction is diagnostic of DI.
      • Response to vasopressin will differentiate central from nephrogenic DI.
  • Gain of sodium and free water, with sodium gain > free water gain (gain of hypertonic fluid)
    • Uncommon, usually the result of sodium bicarbonate infusions for metabolic acidosis, or aggressive use of hypertonic saline to treat increased ICP
    • Excessive ingestion of table salt in patients with psychiatric disorders
• Consequences
  • Hypertonicity moves fluid out of cells, which is most evident in the CNS
  • Hypernatraemic encephalopathy - ranges from agitation and lethargy to coma and seizures
• Approach
• Hypovolaemic hypernatraemia
  • Correct the two consequences of hypotonic fluid loss:
    1. Sodium has been lost, which reduces ECV -> volume resuscitation with isotonic saline if any evidence of low-flow state. Does not usually lead to hypovolaemic shock.
    2. Free water deficit (water has been lost in excess of sodium) -> correct with some sort of water or hypotonic fluid slowly. Aim to replace about half the free water deficit in the first 12-24 hours. There are some complicated calculators for ICU to play with.
• Hypernatraemia without hypovolaemia
  • DI - replace free water deficits and correct sodium slowly
  • Vasopressin is required in central DI to prevent ongoing free water losses.
• Hypertonic hypernatraemia
  • Excess sodium and water are excreted rapidly if renal function is normal
  • If renal function is impaired, diuretics may be necessary

Hyponatraemia

• Definition
  • Plasma sodium concentration < 135mEq/L
  • Typically a hypotonic condition, but there are instances of isotonic hyponatraemia and hypertonic hyponatraemia
• Aetiology
  • Isotonic
    • Pseudohyponatraemia - difference between the measured and actual concentration of sodium. Marked increases in plasma lipids or proteins. Needs to have lipids >1500mg/dL or protein > 12-15 g/dL.
  • Hypotonic
    • Hypovolaemic hyponatraemia - sodium loss with excess free water retention.
      • Sodium loss decreases ECV, which triggers baroreceptor-mediated ADH release, and excess free water retention then decreases the extracellular sodium concentration
      • Free water intake worsens the problem
      • Causes:
        • Renal loss - thiazide diuretics, cerebral salt wasting (TBI, neurosurgery, subarachnoid haemorrhage), primary adrenal insufficiency
        • Extra-renal loss - GIT losses
      • The source of sodium loss is usually apparent, but can be elicited with urine sodium concentration
    • Euvolaemic hyponatraemia - excess water intake or excess water retention from non-osmotic ADH release.
      • ADH-related - SIADH (see above under pathophysiology), physiological stress (post-op patients), severe hypothyroidism
      • SIADH - CNS disturbance, malignancies especially SCLC, drugs (see list at bottom of page), surgery, pulmonary disease, hormone deficiencies or administration, HIV infection, or hereditary SIADH
      • Not ADH-related - primary polydipsia in schizophrenics
      • Differentiate between the two groups with urine osmolality
    • Hypervolaemic hyponatraemia - sodium and water retention, with water retention exceeding sodium retention.
      • Cirrhosis, heart failure, renal failure (eGFR <15)
      • Differentiate with urine osmolality, but diuretic therapy can increase the osmolality of urine
  • Hypertonic
• Clinical features
  • Severe hypotonic hyponatraemia causes a life-threatening encephalopathy - cerebral oedema, increased ICP, risk of brain herniation. Symptoms start as headache, nausea and vomiting, and confusion, and finish with seizures, coma and death. Much higher risk with <48 hour course of acute hyponatraemia.
  • Symptomatic hyponatraemia usually occurs with a sodium of <120
• Approach
  • Low ECV
    • Isotonic saline to restore euvolaemia
    • If symptomatic, hypertonic saline could be used
  • Normal ECV
    • Furosemide could be used in symptomatic hyponatraemia if there is a concern for fluid overload, like in patients with heart failure, could give 20-40mg IV
    • If fluid restriction is intolerable or ineffective, consider drug therapies
  • High ECV
    • ICU-level decision
    • Hypertonic saline could be used for severely symptomatic patients
    • Otherwise, fluid restrict and furosemide diurese
• Infusion rate
  • Infusion rate of hypertonic saline = body weight * desired rate of increase in sodium
  • This gives the infusion rate in mL/hr of 3% hypertonic saline.
  • Needs to be corrected at a similar rate to that which it developed to avoid cerebral fluid shifts and osmotic demyelinating syndrome (central pontine myelinolysis) - dysarthria, quadriparesis, and loss of consciousness.
    • For chronic - raise sodium by 0.5 per hour, and stop rapid correction when you get to 120
    • For acute - raise sodium by 4-6 in the first 1-2 hours, and stop rapid correction when you get to 120
  • 3% saline can be safely administered in a peripheral vein according to UTD. If central access is needed, establishing it shouldn't delay starting therapy.
• Pharmacotherapy
  • Vasopressin antagonists - vaptans - alternative to fluid restriction in patients with euvolaemic or hypervolaemic hyponatraemia, except renal failure
  • Demelocycline - tetracycline derivative that blocks ADH in renal tubules

Non-ketotic hyperglycaemia (Hyperosomlar Hyperglycaemic State - HHS)

• See separate topic under 'peri-op diabetes'

Drugs causing SIADH:

Antidepressants

SSRIs

Tricyclic

MAOI

Venlafaxine

Antiseizure medications

Carbamazepine

Sodium valproate

Lamotrigine

Antipsychotics

Phenothiazines

Butyrophenones

Anticancer drugs

Vinca alkaloids

Platinum compounds

Ifosfamide

Melphalan

Cyclophosphamide

Methotrexate

Pentostatin

Antidiabetic drugs

Chlorpropamide

Tolbutamide

Vasopressin analogues

Desmopressin

Oxytocin

Terlipressin

Vasopressin

Miscellaneous

Opiates

MDMA (ecstasy)

Levamisole

Interferon

NSAIDs

Clofibrate

Nicotine

Amiodarone

Proton pump inhibitors

Monoclonal antibodies

Linezolid