Hypokalaemia

• Severity
  • • Mild 3-3.5
    • Moderate 2.5-3
    • Severe < 2.5
• Symptoms
  • • As serum potassium concentration decreases, the nerves and muscles are predominantly affected causing fatigue, weakness, leg cramps, constipation
    • Arrhythmias
    • In severe cases – rhabdomyolysis, ascending paralysis and respiratory difficulties may occur
• ECG changes
  • • Decreased T wave amplitude, or inversion
    • Prominent U Waves (best seen in V2–V3). When the U-wave becomes taller than the T-wave, potassium is usually under 3. Can cause pseudo-long QT if they fuse with the t waves
    • ST depression
    • Peaked P waves and PR-interval prolongation
    • Arrhythmias (especially if patient is taking digoxin) such as torsades, but also AF, VT and VF
    • Arrest
• Risk factors for arrythmia in hypokalaemia
  • • QT prolongation
    • Digoxin treatment
    • Acute MI
    • Severe hypomagnesaemia
    • Very low K+ or ongoing fall in K+ likely (eg. DKA, refeeding syndrome)
• The relationship between total body K+ and serum K+ is exponential
  • • Therefore small drop in serum K+ can represent a larger drop in total body K+
    • This varies with acid/base balance, and the deficit will be even larger in DKA
• Daily requirement in health is 1 mmol/kg, so 70 mmol for an average man required if they are nil-by-mouth
• 2 tablets three time daily of sando K = 72 mmol (12 mmol per tablet)
• Suitable target might be 5-5.3 for DKA, > 4 for cardiac patients, >3 for oliguric renal failure

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Causes

• Gastrointestinal loss – diarrhoea, vomiting (low urinary K+)
• Drugs (probably the commonest cause)
  • • Diuretics (especially indapamide)
    • Laxatives
    • Steroids
    • Beta-agonists and theophylline
    • Penicillins (high dose – especially flucloxacillin)
    • Insulin
    • Others – ARVs, chemotherapy (cisplatin), NSAIDs, lithium
• Renal losses
  • • Renal tubular disorders (RTA type 1 and 2, non-anion gap metabolic acidosis)
    • Other tubular syndromes (Barters, Liddle’s, Gitelman’s, hypokalaemic periodic paralysis)
    • AVP deficiency
    • Dialysis
• Endocrine disorders (often also hypertension)
  • • Cushing’s Syndrome
    • Hyperaldosteronism/Conns (but most have normal K+)
• Other
  • • Metabolic alkalosis
      • • Can cause hypokalaemia or result from it
        • K+ usually severely low to be the main cause of an alkalosis eg milk-alkali syndrome, bicarbonate use
    • Magnesium depletion
    • Poor dietary intake – ETOH dependence, anorexia
    • Refeeding syndrome
    • Hypothermia
    • Liquorice ingestion – especially Scandinavians! (of note the likes of Basset Allsorts have barely any proper liquorice in them)
    • Hypokalaemia occurs commonly at the end of a haemodialysis session or during treatment with peritoneal dialysis

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Investigation

• Check the blood pressure – helps differentiate uncommon causes
• Bloods – check cortisol, bone profile, Mg2+, VBG with attention to pH, glucose, chloride and HCO3
• Consider checking renin & aldosterone (though often not helpful)
  • • Ideally should be checked once K+ corrected as hypokalaemia will suppress aldosterone level
    • A hypokalaemic metabolic alkalosis is the metabolic fingerprint of aldosterone
    • If hypertensive and low renin – consider Conn’s, Cushing’s and Liddle’s
    • If hypertensive and high renin – consider RAS, diuretics
• Consider checking urinary K+
  • • Hypokalaemia with low urinary K+
      • • Low K+ intake
        • Losses eg diarrhoea
        • PHP
        • Insulin and beta agonists
    • Hypokalaemia with high urinary K+ (>15) ie. K+ wasting / Renal losses
      • • DKA
        • Low Mg2+
        • Drugs eg diuretics
        • Renal causes
• Can check a spot urinary chloride if there’s a metabolic alkalosis – can be useful in determining the cause of hypokalaemia
  • • <20mmol is ‘chloride responsive’ – vomiting, NG suction, CF
    • >20mmol is ‘chloride resistant’ – diuretics, severe K+ depletion, exogenous alkali, magnesium deficiency, tubular/endocrine disorders

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Management

• Continuous ECG monitor – mandated if K+ <3
• Potassium replacement
  • • The maximum recommended IV dose of potassium is 20 mmol/hr.
    • More rapid infusion (e.g. 2 mmol / min for 10 min, followed by 10 mmol over 5– 10 min) is indicated for unstable arrhythmias when cardiac arrest is imminent
• Also give magnesium – this has the advantage that it can be given fast
• Consider PPI if vomiting – loss of gastric acid causes metabolic alkalosis causes hypokalaemia. PPI can therefore help
• Consider K+ sparing diuretic if severe volume overload, or persistent renal K+ wasting despite oral supplements. Spironolactone takes 1-2 days to work, but amiloride works faster

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Uncommon causes

• See also renal tubular disorders
• Bartter’s syndrome
  • • Resembles treatment with high dose loop diuretic
    • Low K+, low Na+, elevated urinary K+ and Na+, elevated bicarbonate, elevated renin and aldosterone, metabolic alkylosis, normotensive.
    • May also be a learning disability/short stature. Presents young.
    • Hard to get the K+ up
• Gitelman’s syndrome
  • • Resembles treatment with high dose thiazide diuretic
    • More benign than Barters
    • Inherited AR
    • Salt wasting/craving
    • Polyuria, hypotension or normal BP, fatigue, muscle cramps
    • Hypokalaemic metabolic alkylosis (due to hyperaldosteronism)
    • Hypomagnesaemia
    • Reduced urinary calcium
• Renal Tubular Acidosis (types 1-3) – normotensive, low bicarbonate
• Liddle’s syndrome
  • • May be biochemically identical to Conns
    • Hypertension
    • Hypokalaemic metabolic alkylosis
    • Low or normal renin and aldosterone
• EAST/SeSAME syndrome
• Periodic paralysis
  • • Severely low K+ with rapid onset lower limb weakness, spreading to upper limbs and can affect respiratory muscles
    • AD with variable penetrance
    • Different phenotypes (high K+, or low K+)
    • Treat by avoiding triggers and oral K+ if hypokalaemic
    • Thyrotoxic periodic paralysis is a subset
      • • Occurs in Asian males and there is less likely to be a family history
        • Night-time paralysis precipitated by insulin, ETOH, meals, anxiety, exercise
        • Once hyperthyroid, a genetic mutation in the electrolyte ion transport is triggered causing hypokalaemia
        • Total body K+ not low – therefore replace, but cautiously
        • Propranolol and carbimazole if hyperthyroid