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.