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.