HYPOKALAEMIA

    DEFINITION

    A serum potassium concentration less than 3.5 mmol/L (mEq/L).

    A serum potassium concentration of less than 2 mmol/L is regarded as
    severe hypokalaemia.

    TOXIC CAUSES

    Hypokalaemia in acute poisonings a consequence of one the following
    mechanisms:

    Secondary to shift of potassium from extracellular to intracellular
    space
         Competitive blockade of K+ channels
              Barium
              Chloroquine
         Increased Na+/K+ ATPase activity
              Beta 2 agonists (e.g. albuterol/salbutamol, terbutaline,
                epinephrine)
              Caffeine 
              Insulin 
              Theophylline, 
         Toxic metabolic alkalosis or respiratory alkalosis

    Secondary to increased renal losses of potassium
         Chronic glucocorticoid administration
         Chronic toluene abuse
         Liquorice and carbenoxolone
         Potassium-losing diuretics

    Secondary to increased gastrointestinal losses of potassium
         Any acute poisoning associated with protracted vomiting or
           diarrhoea.

    Secondary to increased potassium loss in sweat
         Cholinergic syndrome with severe sweating

    NON-TOXIC CASES

    Secondary to shift of potassium from extracellular to intracellular
      space
         Insulinoma
         Metabolic or respiratory alkalosis
         Total parenteral nutrition

    Secondary to increased gastrointestinal losses of potassium
         Anorexia nervosa/bulimia
         Diarrhoea
         Prolonged gastric suction
         Toxic megacolon 

         Villous adenoma of colon
         Vomiting, protracted
         Zollinger-Ellison syndrome

    Secondary to increased renal losses of potassium
         Cushing's syndrome 
         Hyperaldosteronism, primary or secondary
         Increased urinary flow (postobstructive diuresis, large 
           IV infusions)
         Magnesium deficiency
         Renal tubular acidosis

    Inadequate dietary intake of potassium
         Alcoholism
         Anorexia nervosa
         Intravenous infusion of potassium-free fluid 
         Malnutrition

    CLINICAL FEATURES

    At serum potassium concentrations between 2.5 and 3.5 mmol/L the
    patient may be asymptomatic or experience mild symptoms, including
    weakness and muscle fatigue.  As serum potassium concentration falls
    below 2.5 mmol/L, clinical manifestations may progress to include
    severe muscle weakness, ileus, respiratory paralysis and atrial and
    ventricular arrhythmias.  The patient with severe hypokalaemia is at
    risk of sudden death from respiratory or cardiac arrest (ventricular
    tachycardia).

    Hypokalaemia alters the resting membrane potential and slows
    repolarisation.  These changes are reflected in the electrocardiogram
    by depression of ST segments, flattening of the T wave, and prominence
    of the U wave (rarely).  The absence of a visible T wave and the
    presence of a U wave may mimic QT prolongation. 

    DIFFERENTIAL DIAGNOSIS

    Arrhythmias:  Hypoxia, use of digitalis or other drugs, myocardial
    injury, and other electrolyte disturbances (hypomagnesaemia).
    Muscle weakness: Myasthenia gravis, botulism, and central or
    peripheral neurological disease.

    RELEVANT INVESTIGATIONS

    Serum potassium
    Serum sodium, chloride, and bicarbonate
    Renal function tests (urea, creatinine)
    ECG
    Arterial blood gas analysis
    Urine potassium concentration (24 hour collection)

    TREATMENT

    Treatment is determined by the acuity and mechanism of the
    intoxication, as well as the serum potassium, the severity of
    symptoms, and the presence or absence of ECG abnormalities.  For
    patients with hypokalaemia due to chronic diuretic use or prolonged
    severe gastrointestinal or renal potassium losses, the total body
    potassium deficit may be as large as 300 to 500 mEq. On the other
    hand, hypokalaemia due to intracellular shift of potassium is
    associated with relatively small total body potassium deficit and may
    not warrant aggressive replacement.

    Mild hypokalaemia can usually be managed with oral potassium
    supplements.  Moderate-to-severely symptomatic patients require, in
    addition to management of the underlying condition, continuous cardiac
    monitoring and intravenous potassium supplementation.  Specific
    management of acute complications such as cardiorespiratory arrest,
    ventricular arrhythmias, respiratory failure and rhabdomyolyis is also
    indicated.

     Mild hypokalaemia (3 to 3.5 mmol/L)
         Oral potassium supplementation of 30 to 100 mmols/day is
         adequate.
         Elixir: 10% elixir provides 20 mmols/tablespoon; 2 to 3
         tablespoons/day is usually sufficient. Best tolerated when
         diluted with juice and taken with meals.
         Tablets: Wax matrix tablets contain 6 to 8 mmols/tablet and may
         be better tolerated than the liquid form.

     Moderate hypokalaemia (2.5 to 3 mmol/L)
         Oral potassium replacement as for mild hypokalaemia, if
         tolerated.  In symptomatic patients, and those unable to take
         oral potassium, administer up to 10 mmol of potassium per hour
         intravenously, with continuous cardiac monitoring and frequent
         monitoring (e.g. every 4 hours) of the serum potassium
         concentration.

     Moderately severe hypokalaemia (2 to 2.5 mmol/L)
         Oral potassium replacement as for mild hypokalaemia, if
         tolerated. In addition, administer up to 15 mmol of potassium per
         hour intravenously, with continuous cardiac monitoring and
         frequent monitoring (e.g. every 4 hours) of the serum potassium
         concentration.

     Severe hypokalaemia (<2 mmol/L)
         Oral potassium replacement as for mild hypokalaemia, if
         tolerated. In addition, administer up to 20 mmol of potassium per
         hour intravenously, with continuous cardiac monitoring and
         frequent monitoring (e.g. every 4 hours) of the serum potassium
         concentration.  In very severe cases, infusion rates as high as
         30 mmol/hour have been used, but caution should be exercised
         because of the potential for cardiotoxicity, especially if the
         potassium is administered via a central catheter.

     Pediatric dosing of potassium is based on the body weight, duration
    and mechanism of hypokalaemia, and the potassium level. In general,
    dosing should not exceed 0.25 mmol/kg per hour.

     Hypokalaemia associated with beta-2 adrenergic stimulation may be
    treated with beta-adrenergic blockers (eg, propranolol, esmolol).
    Caution should be used if the patient has a history of asthma. 

    CLINICAL COURSE AND MONITORING

    Continuous monitoring of cardiac rhythm together with careful
    monitoring of serum potassium and other electrolyte concentrations,
    acid-base status, and renal function is indicated until severe
    hypokalaemia and the underlying cause are controlled.

    Over-zealous infusion of potassium in the acute phase of hypokalaemia
    secondary to potassium channel blockade or beta-2-adrenergic
    stimulation may result in rebound hyperkalaemia during recovery.

    LONG-TERM COMPLICATIONS

    Hypoxic brain and other organ injury may occur as a result of cardiac
    or respiratory arrest secondary to hypokalaemia. 

    Acute renal failure may be associated with rhabdomyolysis secondary to
    hypokalaemia.

    AUTHOR(S)/REVIEWERS:

    Author:        Dr Barbara Groszek
                   Department of Clinical Toxicology, Jagiellonian
                   University
                   31-826 Kraków, Os. Zlota Jesien 1
                   Poland

    Reviewers:     Birmingham 3/99: B Groszek, H Kupferschmidt,
                   N Langford, K Olson, J Pronczuk.