Hyperkalaemia

Hyperkalaemia is defined as plasma potassium in excess of 5.3mEq/L.

Potassium is the most abundant intracellular cation. Hyperkalaemia has 3 basic causes:

• Increased intake of potassium per se is an unlikely cause.
• Decreased excretion, especially with renal failure or due to drugs.
• A rapid shift from the intracellular to the extracellular space.

The time of greatest risk is at the extremes of life. In patients in hospital, drugs are implicated in about 75% of cases. Men are more likely than women to get hyperkalaemia whilst women are more likely to experience hypokalaemia.

• Normally all potassium that is ingested is absorbed and excretion is 90% renal and 10% alimentary. Most excretion by the gut is via the colon and in chronic renal failure this can maintain a fairly normal blood level of potassium. It seems likely that the elevated K⁺ levels in chronic renal failure trigger the excretion of potassium via the colon.¹ Patients with chronic renal failure must be careful of food rich in potassium such as oranges and chocolate but there is plenty of potassium in meats, beans, fruits, and potatoes.
• Massive tissue damage leads to loss of potassium into the circulation. In crush syndrome this may be accompanied by renal impairment. Massive haemolysis also releases vast amounts of potassium. Fresh water drowning is more swiftly fatal than salt water drowning because the fresh water enters the circulation from the lungs and osmotic pressure causes erythrocytes to swell and burst. The sudden release of potassium can stop the heart. Massive tumour lysis² can also raise potassium.
• Drugs than inhibit the renal excretion of potassium can cause hyperkalaemia but they are most dangerous if used in combination or if renal function declines. They include potassium sparing diuretics, ACE inhibitors,³ AT2 antagonists and spironolactone. ACE and AT2 inhibitors may be used together in refractory microalbuminuria. Either of these with spironolactone may be used in congestive heart failure. Diarrhoea and vomiting can then lead to dehydration, reduced renal output and a dangerous increase in potassium levels. NSAIDs can also impair K⁺ excretion. Diabetics may have impaired renal function, be on ACE inhibitors⁴ and a healthy diet for diabetics tends to be low in sodium and high in potassium. Managing patients with diabetes and congestive heart failure is a difficult balance but the heart failure must be treated aggressively with ACE inhibitors and the new beta blockers.⁵
• Potassium is often raised in diabetic ketoacidosis. Insulin pushes both glucose and potassium into cells and potassium levels must be monitored during treatment. Glucagon impairs the intracellular shift of potassium.
• Deficiency of steroid hormones and mineralocorticoids may lead to hyperkalaemia.
• Even in sickle cell trait, strenuous exertion, especially in the unfit and dehydrated, can precipitate sickling, haemolysis and sudden death from hyperkalaemia.⁶

The following drugs have also been implicated in raising potassium levels:

• Ciclosporin and tacrolimus
• Pentamidine
• Co-trimoxazole
• Heparin
• Ketoconazole
• Metyrapone
• Also ask about herbal remedies⁷

Symptoms

Symptoms are nonspecific and include weakness and fatigue. Occasionally, a patient presents with muscular paralysis or shortness of breath. They also may complain of palpitations or chest pain.

Signs

• There is little abnormality except occasional bradycardia due to heart block or tachypnoea from respiratory muscle weakness.
• Muscle weakness and flaccid paralysis
• Depressed or absent tendon reflexes
• Physical examination is unlikely to suggest the diagnosis, except if severe bradycardia is present or if muscles are tender as well as weak, suggesting rhabdomyolysis.

• Any unexpected result should be repeated. If blood has been left standing a long time or shaken vigorously, damage to erythrocytes will result in K⁺ loss from cells and a spurious result. Check U&E and creatinine too.
• Check 24 hours urine volume and electrolytes.
• A normocytic, normochromic anaemia may suggest acute haemolysis. (Macrocytosis from folate deficiency develops only later).
• Blood glucose
• Serum potassium will monitor the extracellular concentration but the best way to assess the intracellular situation is an ECG and in severe cases continuous monitoring is required. There is poor correlation between intracellular and extracellular problems.⁸ 98% of body potassium in intracellular.
• If the patient takes digoxin, check blood levels.

ECG

In hyperkalaemia the ECG may show:

• Peaked T waves
• Prolongation of the PR interval
• Widening of the QRS
• Loss of the P wave
• Sine wave pattern
• Sinus arrest
• In patients with heart disease and abnormal baseline ECG, bradycardia may be the only new ECG abnormality.

Hyperkalaemia is uncommon but serious. The diagnosis is based on a laboratory report and, especially if the result is unexpected, before initiating treatment it is necessary to consider the possibility that the result may be spurious. There are a number of possible explanations for unexpectedly high results:^9,10

• There may have been difficulty collecting the sample.
• The fist may have been clenched.
• The blood may have been squirted through a needle into the bottle causing haemolysis.
• After collection the sample should be gently rocked to mix the anticoagulant. Shaking will cause haemolysis.
• Use of the wrong anticoagulant, especially potassium EDTA
• Length of storage of the specimen
• Excessive cooling of specimen (in cold winter months, K⁺ in specimens from GP surgeries tends to be higher than in the summer¹⁰).
• Thrombocytosis
• Severe leucocytosis can cause elevated or depressed K⁺.
• Red cell disorders may cause haemolysis.

If there is doubt about the validity of the result, repeat it.

The aggression of treatment will depend upon the level of potassium, the rate of rise and ECG abnormalities.

The aims are:

• Decrease K⁺ absorption.
• Increase K⁺ uptake into cells.
• Increase K⁺ excretion.
• Determine the cause to prevent recurrence or identify toxicities such as drugs, to help reverse the situation.

Non-Drug

• Decrease high intake of K⁺ in the diet

Drugs

• Stop any K⁺ supplements or drugs that conserve K⁺
• Give intravenous calcium if there is cardiotoxicity
• Glucose and insulin IV can push K⁺ into the cells
• Sodium bicarbonate to correct any acidosis although it is generally avoided in diabetic ketoacidosis
• Beta agonists including salbutamol have been used but are controversial because of side-effects
• Fluid replacement plus loop diuretic
• Cation exchange resins¹¹ can be given orally or per rectum

Invasive Procedures

• Dialysis may be required

In a study of patients in hospital¹² hyperkalaemia was an independent risk factor for death. 1.4% of 29,000 patients developed hyperkalemia with an overall mortality of 14.3%. The risk increased as potassium levels rose. 28% with serum potassium level above 7 mEq/L died, compared with 9% of those with a level less than 6.5 mEq/L. In 7 of 58 deaths, it was directly attributed to hyperkalemia. Most fatal cases were complicated by renal failure but patients who died of hyperkalemia had normal potassium levels within 36 hours before death.

Much dangerous hyperkalaemia is iatrogenic. If patients take 2 drugs that reduce K⁺ excretion, check U&E if they develop diarrhoea or vomiting. Beware of NSAIDs with these drugs. In patients with renal impairment, the ACE inhibitor and AT2 antagonists are very effective and reduce blood pressure and possible albumin loss but they must be used with care to prevent hyperkalaemia. Whether the newer AT2 antagonists are any safer than the ACE inhibitors is still unknown.¹³