Hypokalaemia can be life-threatening, depending on its severity and the underlying cause.
Even when not too serious it can make patients feel acutely or chronically ill, and this group presents more frequently in primary care. As ever, the most important step is to recognise that hypokalaemia is present and not dismiss it as a laboratory artefact.
Artefactual hypokalaemia, unlike artefactual hyperkalaemia, is very rare.
Indeed, delayed separation of serum or plasma from whole blood may obscure true hypokalaemia, because potassium leaks from the red cells.
There is little consensus on what level of hypokalaemia is clinically significant, but a serum level of less than 3.0mmol/l is a cause for concern.
If analytical factors can usually be ignored, what are the main causes?
Instead of a long list, it is helpful to separate the causes into those that trigger potassium to move out of the plasma and into cells (transcellular shift) and those in which the patient is depleted of total body potassium.
Electrical excitability of the cell
A misconception is that since most potassium is intracellular, the plasma level is not so important.
However, the electrical excitability of the cell depends on the ratio of the potassium level outside and inside the cell. So a change in extracellular potassium from, say, 5.0 to 2.5mmol/l is a large change in the ratio, but not necessarily of the amount in the body.
It is the effect of hypokalaemia on cellular excitability, particularly the heart and skeletal muscle, that is key to understanding its clinical effects. If digoxin or anti-arrhythmic drugs are being taken, hypokalaemia is a particular concern.
Many of the investigations are more easily done in secondary care but the key is recognising there is hypokalaemia sufficient to cause concern.
Causes of hypokalaemia
- Drugs: beta-2 agonists, risperidone, quetiapine.
- Rarities including thyrotoxicosis.
- Artefactual hypokalaemia is occasionally seen in leukaemias if separation of serum or plasma from whole blood is delayed.
- Usually renal but sometimes gastrointestinal losses and, rarely, decreased intake (such as elderly patients on a 'tea and toast' diet).
- Mineralocorticoid excess in Conn's and Cushing's syndromes or iatrogenic.
- Drugs: loop and thiazide diuretics, particularly in the elderly; steroids.
- Diarrhoea, including laxative abuse.
- Many rarities including Bartter's and Gitelman's syndromes and renal tubular acidosis.
Most diagnoses of hypokalaemia need the involvement of secondary care, although initially this may entail no more than a phone call. Clearly, hypokalaemia that is more severe -say a serum potassium of less than 2.5mmol/l - is a medical emergency demanding urgent referral.
Key points in the history are: easy fatiguability, particularly on exercise, muscle weakness, drugs, family history and gastrointestinal symptoms.
Measuring the blood pressure, ideally more than once, is vital. The ECG classically shows small T waves and the appearance of U waves but these are relatively uncommon signs seen in severe hypokalaemia.
The combination of hypertension and hypokalaemia should always raise the possibility of excess mineralocorticoid activity. This may be iatrogenic or due to adrenal overproduction in Conn's and Cushing's syndromes - although hypokalaemia may well be absent in both these syndromes.
The secondary hyperaldosteronism of renal artery stenosis or liver cirrhosis can also cause hypokalaemia.
Laboratory investigations are numerous, and several are more easily done in secondary care. However, two important initial investigations may help confirm a diagnosis from the history: measurement of serum bicarbonate and 24-hour urine potassium.
Samples for bicarbonate measurement must reach the laboratory within a few hours. Patients must be given a clear explanation, with a written copy to take home, of how to collect a 24-hour urine sample properly.
Interpretation of a 24-hour urine result may not be straightforward and often needs the help of a general or renal physician.
A high serum bicarbonate level may be part of a metabolic alkalosis causing hypokalaemia and it may also be an effect of total body loss of potassium.
This two-way process needs to be recognised.
- Serum bicarbonate and creatinine, magnesium, 24-hour urine for potassium, chloride and calcium.
- Renin and aldosterone.
- Urinary free cortisol and dexamethasone suppression test.
- Urine pH.
- Screening for laxative and purgative abuse.
(Second-line investigations are more easily done in a hospital setting)
Oral potassium is, where possible, always preferred and is relatively safe provided renal function is normal. Severe hypokalaemia needs urgent hospital referral and may require cautious treatment with intravenous potassium.
If abnormal losses such as severe diarrhoea have been identified, these underlying causes need prompt treatment in their own right. If referral is required to make the diagnosis - and this is usually the case - initial therapy should be discussed with an appropriate physician before the first outpatient appointment.
Replacement MIMS lists several forms of potassium supplement in both tablet and syrup formulation and patients may show a marked preference for one or the other.
The box lists those in common use. The need to take multiple doses during the day can be difficult and causes non-concordance.
The recommended oral intake is 25- 50mmol daily for prevention of hypokalaemia in patients on a normal diet. If there is already potassium depletion, larger doses may be needed.
Target serum level
Finding the right dosage depends on factors such as treatment of an underlying cause, other medication and what the therapeutic target is. Many would accept a target serum level of 3.5mmol/l but depending on the aetiology even that may be difficult.
If there is coexisting renal impairment, it can be helpful if correction of hypokalaemia is closely monitored by secondary care as well. Caution is necessary if a potassium-sparing diuretic, ACE inhibitor or angiotensin-II receptor blocker is being taken concurrently. Combination with potassium supplements potentiates increases in serum potassium.
There is no simple rule for the frequency of serum potassium measurement but the more severe the initial abnormality and the higher the dose of potassium supplement the more frequent measurement needs to be.
Of course, long-term potassium supplementation should never be a substitute for making the diagnosis.
Sando-K: effervescent potassium bicarbonate and chloride, containing 12mmol potassium and 8mmol chloride per tablet.
Kloref: effervescent betaine hydrochloride, potassium benzoate, bicarbonate and chloride equivalent to 6.7mmol each of potassium and chloride per tablet.
Slow-K: slow-release potassium chloride 600mg per tablet.
Kay-Cee-L: sugar-free syrup containing 1mmol/ml potassium and chloride.
Dr Anthony Norden, consultant chemical pathologist and affiliated lecturer, Cambridge University Hospitals NHS Foundation Trust.