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    HYPERKALAEMIA

    DEFINITION

    A serum potassium concentration greater than 5.5 mmol/L (mEq/L).  A
    concentration above 6.5 is considered critical.

    TOXIC CAUSES

    Secondary to excessive potassium intake

         High-dose potassium penicillin salts
         Large ingestions of potassium salts 
              Salt substitutes 
              Slow-release potassium chloride tablets
         Rapid or excessive administration of intravenous potassium

    Secondary to impaired renal potassium excretion
         Angiotensin-converting enzyme (ACE) inhibitors
         Non-steroidal anti-inflammatory drugs (NSAIDs)
         Potassium-sparing diuretics

    Secondary to shift of potassium from cells to serum
         Inhibition of Na+/K+ ATPase activity
              Digitalis glycosides
              Digoxin
              Digitoxin
              Oleander  (Nerium oleander)
         Intracellular leakage/transfer
              Arginine
              Hydrogen fluoride and fluoride salts
              Hypertonic solutions
         Succinylcholine (in patients with myopathy, recent burns, spinal
           cord injury)
         Toxic rhabdomyolysis
         Toxic haemolysis

    Other/Unknown
         Alpha-adrenoreceptor agonists
         Beta-adrenergic blocking agents
         Heparin 

    Note: Severe hyperkalaemia is rarely a direct complication of acute
    poisoning. Most commonly it develops secondary to complications of the
    poisoning especially rhabdomyolysis, acute renal failure and metabolic
    acidosis.

    NON-TOXIC CAUSES

    Acidosis
    Acute renal failure 
    Acute tumour lysis syndrome after chemotherapy
    Hypoaldosteronism
         Primary (Addison's disease)
         Secondary
    Rapid transfusion of aged blood
    Tissue damage (crush injury, burns, infections)

    DIFFERENTIAL DIAGNOSIS

    Pseudohyperkalaemia
    Haemolysis of blood sample
    Leukocytosis
    Prolonged tight application of tourniquet while drawing blood sample
    Thrombocytosis

    CLINICAL FEATURES

    The important clinical manifestations of hyperkalaemia reflect
    membrane depolarisation with decreased conduction velocity and a
    faster rate of membrane repolarisation.

    The effects of hyperkalaemia on the cardiac conduction system are
    initially reflected by electrocardiographic changes which include tall
    peaked T waves and ST segment depression.  As conduction becomes
    further delayed, there is prolongation of the PR interval with
    decreased amplitude and disappearance of the P wave and widening QRS
    complex with blending of the QRS complex and T wave ("sine wave"). 
    Ventricular tachycardia, ventricular fibrillation or asystole may
    ensue.

    Neuromuscular features include muscular weakness.  A flaccid paralysis
    affecting the extremities may occur in severe cases and rarely extends
    to involve the trunk and respiratory muscles.

    Gastrointestinal effects include abdominal pain (intermittent
    intestinal colic), diarrhoea and nausea.

    RELEVANT INVESTIGATIONS

    Serum potassium 
    Serum sodium, chloride, and bicarbonate 
    Renal function tests (urea, creatinine)
    ECG (peaked T waves, PR prolongation, QRS widening, bradycardia, 
      AV block)
    Blood glucose
    Creatine kinase
    Urinalysis (dipstick test for hemoglobinuria/myoglobinuria)
    Arterial blood gas analysis
    Serum digoxin 

    TREATMENT

    Hyperkalaemia with ECG manifestations and/or a serum potassium
    concentration of greater than 6.5 mmol/L is a medical emergency and
    requires immediate treatment, starting with establishment of
    continuous cardiac monitoring and intravenous access.

    Although the underlying causes of hyperkalaemia must be appropriately
    managed, life-threatening hyperkalaemia must be urgently treated on
    its own merits.  Methods available include: 

     Antagonism of membrane effects of hyperkalaemia

          Calcium salts -- either  10% Calcium gluconate or  10% 
          Calcium chloride (100 mg/mL) is suitable. 

              Adult dose: 5 to 10 mL (500 to 1 000 mg) IV over 1 to 
              5 min., may repeat every 5 to 10 minutes up to two times as
              required.

              Paediatric dose: 0.2 to 0.3 mL/kg (20 to 30 mg/kg) per
              dose up to maximum single dose of 5 ml (500 mg) IV over 5 to
              10 min., repeated up to four times.

              Onset of action: 1 to 5 minutes.

              Duration of action: approximately 1 hour.

              Notes:    (i) Calcium should not be administered to patients
                        with suspected digoxin toxicity.
                        (ii) Calcium salts should not be given through the
                        same line with sodium bicarbonate, as a
                        precipitate of calcium carbonate may form.

     Promotion of shift of potassium to the intracellular space.

          Glucose and Insulin 

              Adult dose: 25 g (250 mL of a 10% solution)  dextrose IV
              over 30 minutes followed by continued infusion at a slower
              rate. Five units of regular insulin per 25 g glucose are
              added to the infusion.  Alternatively, 50 mL of a 50%
              dextrose solution with 5 units of regular insulin may be
              administered IV over 5 minutes.

              Paediatric dose: 0.5 to 1 g/kg of dextrose followed by
              1 unit of regular insulin IV for every 5 g of glucose
              infused.  This dose may be repeated every 10 to 30 min.

              Onset of action: 30 to 60 minutes.  

              Duration of action: 4 to 6 hours or while infusion
              continues.

          Sodium bicarbonate --  8.4% Sodium bicarbonate solution (1 mL =
         1 mmol = 1 mEq)

              Adult dose: 50 mL IV over 5 minutes, repeated at 20 to 30
              minute intervals.

              Paediatric dose: 1 to 2 mL/kg/dose IV every 2 to 4 hours
              or as required by pH.

              Onset of action: 10 to 15 minutes.

              Duration of action: 1 to 2 hours.

     Removal of Potassium from the body.

          Cation-exchange resins.  These orally or rectally adminstered
         agents exchange K+ for Na+ or Ca++.  Suitable agents
         include  Sodium Polystyrene Sulfonate (Kayexalate(R) , Resonium
         ţA(R)) and  Calcium Polystyrene Sulfonate (Calcium Resonium(R),
         Resonium Calcium(R)).

              Adult dose: Oral: 60 mL of suspension (15 g of resin) 1 to
              4 times per day as needed.

              Rectal: 30 to 50 g of resin as a retention enema following a
              cleansing enema. Dilute with sorbitol or 20% dextrose in
              water. Enema must be retained for 30 to 45 minutes.

              Paediatric dose: Approximately 1 g of the resin/kg/dose
              given orally every 6 hours or rectally every 2 to 6 hours.

              Note: Do not use Calcium Polystyrene Sulfonate in digoxin
              poisoning.

          Dialysis.  Peritoneal and haemodialysis are effective methods
         for removing potassium. Haemodialysis is indicated in patients
         who cannot tolerate fluids or have kidney dysfunction.

          Intravenous diuretics (thiazides, loop diuretics).  The dose
         required depends on renal function.

     Specific antidotal measures

          Digoxin specific antibody fragments are effective in lowering
         the potassium in patients with acute cardiac glycoside
         intoxication.

    CLINICAL COURSE AND MONITORING

    If hyperkalaemia occurs in intoxicated patients as a secondary
    complication (e.g. rhabdomyolysis, acute renal failure and/or systemic
    acidosis), the clinical course is usually determined by the nature and
    severity of the underlying poisoning and its complications.

    The treatments described above are most likely to be required in cases
    of poisoning which involve an increase in the total body potassium
    load, such as the ingestion of a large amount of a potassium salt. In
    poisoning by digoxin or other cardiac glycosides, normal potassium
    homeostasis is usually restored once Na+/K+ ATPase activity is
    reactivated by appropriate antidote administration.

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

    LONG-TERM COMPLICATIONS

    Brain or other organ injury may occur as a result of cardiac arrest
    secondary to hyperkalaemia. 

    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.