BMJ 2015;351:h4762 doi: 10.1136/bmj.

h4762 (Published 20 October 2015)

Page 1 of 6

Practice

PRACTICE
RATIONAL TESTING

Investigating hyperkalaemia in adults

12

Timothy J McDonald principal clinical scientist and honorary clinical senior lecturer , Richard A
23
4
Oram specialist registrar , Bijay Vaidya consultant endocrinologist and honorary associate professor
Department of Blood Sciences, Royal Devon and Exeter Hospital, Exeter EX2 5DW, UK; 2NIHR Exeter Clinical Research Facility, University of
Exeter Medical School, Exeter; 3Department of Renal Medicine, Royal Devon and Exeter Hospital, Exeter; 4Department of Endocrinology, Royal
Devon and Exeter Hospital and University of Exeter Medical School, Exeter
1

This series of occasional articles provides an update on the best use

of key diagnostic tests in the initial investigation of common or important
clinical presentations. The series advisers are Steve Atkin, professor
of medicine, Weill Cornell Medical College Qatar; and Eric Kilpatrick,
Division Chief, Clinical Chemistry, Sidra Medical and Research Center,
Qatar; honorary professor, department of clinical biochemistry, Hull
Royal Infirmary, Hull York Medical School. To suggest a topic for this
series, please email us at practice@bmj.com.

A 42 year old woman was admitted to hospital after a blood test

performed by her general practitioner for investigation of
intermittent abdominal pain showed a high serum potassium
level of 6.6 mmol/L (reference range 3.5-5.3 mmol/L).1 She
was otherwise well and not taking any medications. When she
arrived in the emergency medical unit, her blood pressure was
140/70 mmHg, and other physical examination showed no
significant abnormalities. Her electrocardiographic (ECG) results
were normal.

What is the next investigation?

Background

Hyperkalaemia is defined as serum potassium concentration

>5.3 mmol/L and is commonly graded as mild (5.4-6.0 mmol/L),
moderate (6.1-6.5 mmol/L) or severe (>6.5 mmol/L).2 It is
reported in 1-2.5% of hospitalised patients,3 and in 0.2-0.7% of
a population based cohort of people aged 55 years.4 It is most
often associated with renal failure and drugs that cause
hyperkalaemia.3
Most potassium (98%) in the body is intracellular, with a small
proportion in the extracellular compartment.5 This
intracellular-extracellular potassium gradient is essential for
normal nerve and muscle function. Small increases in
extracellular potassium can have adverse effects on the heart
and skeletal muscles. Mild hyperkalaemia is often asymptomatic,
but severe hyperkalaemia is associated with life threatening
arrhythmias and sudden cardiac death. A retrospective analysis
of >240 000 people showed that, in people with mild
hyperkalaemia, the risk of all-cause mortality within 24 hours

of testing was10-fold higher than background rates, and in

moderate to severe hyperkalaemia (>6 mmol/L) the odds
increased up to 30-fold.6

Is the patient safe?

Check first if the patient is in immediate danger (fig 1), as
hyperkalaemia can cause life threatening arrhythmias. If serum
potassium is very high (>6.5 mmol/L), the potassium has risen
rapidly, or there are clinical manifestations of hyperkalaemia
(such as muscle weakness, paraesthesia, and arrhythmias)
rapidly assess the patient in an acute facility with cardiac
monitoring. In cases of severe hyperkalaemia, implementation
of treatment (with intravenous calcium gluconate, insulin and
dextrose infusion, salbutamol nebuliser, or dialysis) takes
precedence over diagnosing the aetiology.8

For moderate to severe hyperkalaemia (>6.0 mmol/L), undertake

an ECG test, which may show bradycardia, tall and narrow T
waves (>10 mm high in precordial leads or >5 mm in limb
leads), a prolonged PR interval, loss of P waves, and broadening
of QRS complexes (fig 2). Eventually T waves can merge with
QRS complexes and degenerate into ventricular fibrillation.9

History
As this usually elucidates the cause of hyperkalaemia, consider
the following:
MedicationsHyperkalaemia is most commonly associated
with drugs, particularly in association with heart failure,
hypertension, and acute kidney injury or chronic kidney
disease.7 10 Box 1 lists common drugs involved, including
those that limit renal potassium excretion, nephrotoxic
drugs, and drugs containing potassium.

History of chronic kidney disease and risk factors for acute

kidney injury, such as diarrhoea and vomiting, drugs (such
as non-steroidal anti-inflammatory agents), and
sepsisAngiotensin converting enzyme inhibitors and

Correspondence to: B Vaidya b.vaidya@exeter.ac.uk

For personal use only: See rights and reprints http://www.bmj.com/permissions

Subscribe: http://www.bmj.com/subscribe

BMJ 2015;351:h4762 doi: 10.1136/bmj.h4762 (Published 20 October 2015)

Page 2 of 6

PRACTICE

The bottom line

The cause of hyperkalaemia in adults is usually obvious from the patients history: the commonest causes are acute kidney injury,
chronic kidney disease, and drugs
Spurious hyperkalaemia is a common cause of raised serum potassium levels and must be excluded when investigating hyperkalaemia
of uncertain aetiology
Severe hyperkalaemia (>6.5 mmol/L) is associated with life threatening arrhythmias and should be treated in an acute facility with
electrocardiographic monitoring
If hyperkalaemia is moderate or severe, or its cause unclear, initial investigations are electrocardiography, renal function, glucose,
full blood count, and assessment of acid-base balance
Refer patients with no obvious explanation for their hyperkalaemia for endocrine or renal assessment

angiotensin II receptor blockers can often precipitate

hyperkalaemia in presence of volume depletion.

Excessive dietary intakeThis can cause hyperkalaemia,

but only in patients with renal impairment. Foods high in
potassium include white beans, dark leafy greens (such as
spinach), many fresh fruits, dried fruit (such as apricots),
baked potatoes, yoghurt, fish, avocados, and mushrooms
(www.kidney.org/atoz/content/potassium).

History of diabetesHyperkalaemia is common in diabetic

ketoacidosis before initiation of treatment. Diabetes can
also cause type 4 renal tubular acidosis, which is associated
with hyperkalaemia.
History of treatment for malignancyConsider tumour
lysis syndrome.

History of crush injury, extreme physical exercise, or

hypothermiaConsider rhabdomyolysis; patients may
present with muscle pain and weakness or dark red urine,
or both.
Massive volumes of blood transfusionLarge potassium
loads from this can occasionally lead to transient
hyperkalaemia.
Hypotension, particularly with fatigue, anorexia, weight
loss, or skin pigmentationConsider Addisons disease
(primary adrenal insufficiency).

Extreme muscle weakness in a young personConsider

hyperkalaemic periodic paralysis, a rare autosomal
dominant condition characterised by episodes of
hyperkalaemia and muscle weakness that can be
precipitated by potassium-rich foods, exercise, stress,
fatigue, weather changes, certain pollutants (such as
cigarette smoke), and fasting.11

Physical examination
The physical signs of hyperkalaemia are often present only in
severe cases12 and can also be masked by the associated illnesses
that have caused the hyperkalaemia. Check for flaccid muscle
weakness, depressed deep tendon reflexes, and signs of cardiac
arrhythmias. The absence of clinical signs does not exclude life
threatening hyperkalaemia and advanced ECG changes. The
presence of hyperpigmented skin and low blood pressure with
a postural drop should suggest Addisons disease as the cause
of hyperkalaemia.

Laboratory investigations
In mild hyperkalaemia with an obvious cause, laboratory
investigations will be limited to monitoring serum potassium
concentrations. However, if hyperkalaemia is moderate to severe
or the cause of hyperkalaemia is unclear, initial basic
investigations should include a full blood count (to assess blood
dyscrasia causing spurious hyperkalaemia), creatinine and urea
For personal use only: See rights and reprints http://www.bmj.com/permissions

(renal function), bicarbonate (acid-base disturbance), and

glucose (diabetes) (fig 1).

Consider spurious hyperkalaemia

(pseudohyperkalaemia)

Spurious hyperkalaemia (pseudohyperkalaemia) is common

and in extreme cases reported to account for up to 20% of
elevated potassium results.13 Contamination of serum collection
tubes with the anticoagulant ethylenediamine tetra-acetic acid
(EDTA), which has high a concentration of potassium salt, is
a widely reported problem.14 Other causes include difficult
venepuncture, prolonged tourniquet time,15 16 long transit times
to laboratory (compounded by cold storage),17 in vitro
haemolysis, and thrombocytosis or lymphocytosis.18 Rarely,
spurious hyperkalaemia can be familial (a red cell membrane
defect allowing increased leakage of potassium from red cells
when blood cools to room temperature).19
If spurious hyperkalaemia is suspected then a second blood
sample, ideally collected in a lithium heparin tube and taken
without a tourniquet, should be transported immediately to the
laboratory for analysis. If familial pseudohyperkalaemia is
suspected, sequentially measure potassium levels on a lithium
heparin blood sample stored at room temperature; in familial
pseudohyperkalaemia, potassium levels will rise in vitro with
increasing storage time.20

Renal function

Hyperkalaemia in the context of renal impairment will normally

be associated with the other typical biochemical abnormalities
such as elevated urea and creatinine levels and metabolic
acidosis.

Acid-base balance

Metabolic acidosis is often associated with hyperkalaemia

through mechanisms including potassium retention in the renal
tubules and shift of potassium from the intracellular to the
extracellular compartment. Metabolic acidosis with a reduced
blood pH or reduced serum bicarbonate can be assessed by
measuring either arterial blood gas or venous serum
bicarbonate.21

Common causes of metabolic acidosis with hyperkalaemia

include
Renal impairmentEither chronic kidney disease or acute
kidney injury (the most common cause).
Type 4 renal tubular acidosisThis group of conditions
is associated with relative deficiency of mineralocorticoids
or insensitivity to mineralocorticoid action on renal tubules;
it can be caused by diabetes, drugs (non-steroidal
anti-inflammatory drugs, trimethoprim, heparin, and
calcineurin inhibitors), obstructive uropathy, chronic
tubulointerstitial disease, as well as rare hereditary forms.
Subscribe: http://www.bmj.com/subscribe

BMJ 2015;351:h4762 doi: 10.1136/bmj.h4762 (Published 20 October 2015)

Page 3 of 6

PRACTICE

Box 1: Important drugs associated with hyperkalaemia

Decreased renal potassium excretion
Angiotensin converting enzyme inhibitors
Angiotensin II receptor blockers
Spironolactone
Amiloride
Renin inhibitors
blockers*
Trimethoprim*
Calcineurin inhibitors (such as ciclosporin and tacrolimus)*
Pentamidine*
Heparins*

Nephrotoxic drugs
Non-steroidal anti-inflammatory drugs*

Trans-cellular shift
Glucose infusions or insulin deficiency
Digoxin poisoning

Drugs containing potassium

Potassium supplement
Laxatives such as Movicol, Klean Prep, and Fybogel
Penicillin

*Can also cause hyperkalaemia secondary to type 4 renal tubular acidosis

Diabetic ketoacidosisHyperkalaemia may occur with

metabolic acidosis at presentation. Check blood glucose
and blood or urinary ketones if you suspect this condition.
Serum potassium rapidly falls after initiation of treatment
with intravenous insulin and fluids.

Tissue ischaemia and necrosisThis may cause both lactic

acidosis and the leak of potassium into the extracellular
space, with resultant hyperkalaemia, particularly if renal
impairment is present.

When to refer?
Severe hyperkalaemia or moderate hyperkalaemia with
symptoms warrants referral to an acute hospital by ambulance.
Patients with ongoing unexplained hyperkalaemia, even if mild,
warrant referral for specialist endocrine or renal assessment as
appropriate.

Further specialised investigations

These investigations are guided by the clinical presentation and
physical findings.
Short ACTH stimulation testHyperkalaemia in
association with signs and symptoms of adrenal
insufficiency, hyponatraemia, or the presence of other
autoimmune disease should prompt investigation for
primary adrenal insufficiency or Addisons disease. A short
ACTH (adrenocorticotrophic hormone) stimulation test is
the investigation of choice to diagnose or exclude this. If
the patient is very sick, in the acute setting, then a random
cortisol test could be useful to identify hypoadrenalism
rapidly; however, a normal result does not rule out
hypoadrenalism and should not stop treatment if clinical
suspicion is high.
Plasma renin and aldosteroneThese measurements can
help to identify deficiency or insensitivity of
mineralocorticoid as the cause of hyperkalaemia. Low
aldosterone with high renin indicates primary
mineralocorticoid deficiency, such as Addisons disease.

For personal use only: See rights and reprints http://www.bmj.com/permissions

Low aldosterone with low renin suggests type 4 renal

tubular acidosis. However, high aldosterone and high renin
suggests mineralocorticoid insensitivity (also known as
pseudohypoaldosteronism), which may be seen in some
forms of type 4 renal tubular acidosis.

Serum creatinine kinase and urine myoglobinThese may

confirm rhabdomyolysis if clinical presentation is
suggestive.

Outcome
An urgent blood test in the hospital showed normal full blood
count, renal function, bicarbonate, and electrolytes, including
normal serum potassium at 4.1 mmol/L. This suggested that the
patients previously raised potassium was due to spurious
hyperkalaemia. We analysed serum potassium levels after
keeping her blood sample following venesection at room
temperature for 6 hours.19 This showed serum potassium readings
of 4.5, 5.3, 5.6, and 6.7 mmol/L at 0, 2, 4, and 6 hours,
respectively. These results are consistent with spurious
hyperkalaemia resulting from intracellular potassium leakage.
We discharged her home with reassurance.
We thank Hannah Oram (general practitioner), Junaid Zaman
(cardiologist), and Soroush Shojai (renal physician) for their helpful
comments on the manuscript.
Contributors: TJMcD and RAO wrote the first draft of the manuscript.
All authors revised the manuscript and approved the final version. BV
is guarantor.
Competing interests: We have read and understood the BMJ policy on
declaration of interests and have no relevant interests to declare.
Patient consent not required (patient anonymised, dead, or hypothetical).
Provenance and peer review: Commissioned; externally peer reviewed.
1
2

Pathology-Harmony-Group. Harmonisation of reference intervals (www.pathologyharmony.

co.uk/graphics/Pathology%20Harmony%20II%20%20for%20web.pdf), 2011.
Soar J, Perkins GD, Abbas G, Alfonzo A, Barelli A, Bierens JJ, et al. European
Resuscitation Council Guidelines for Resuscitation 2010 Section 8. Cardiac arrest in
special circumstances: electrolyte abnormalities, poisoning, drowning, accidental

Subscribe: http://www.bmj.com/subscribe

BMJ 2015;351:h4762 doi: 10.1136/bmj.h4762 (Published 20 October 2015)

Page 4 of 6

PRACTICE

How patients were involved in the creation of this article

At the planning stage of this article, we consulted a patient who had an emergency admission with a high serum potassium level. She also
reviewed and commented on the article before submission, which helped to improve clarity of the article.

3
4
5
6
7
8
9
10
11

hypothermia, hyperthermia, asthma, anaphylaxis, cardiac surgery, trauma, pregnancy,

electrocution. Resuscitation 2010;81:1400-33.
Paice B, Gray JM, McBride D, Donnelly T, Lawson DH. Hyperkalaemia in patients in
hospital. BMJ 1983;286:1189-92.
Liamis G, Rodenburg EM, Hofman A, Zietse R, Stricker BH, Hoorn EJ. Electrolyte disorders
in community subjects: prevalence and risk factors. Am J Med 2013;126:256-63.
Halperin ML, Kamel KS. Potassium. Lancet 1998;352:135-40.
Einhorn LM, Zhan M, Hsu VD, Walker LD, Moen MF, Seliger SL, et al. The frequency of
hyperkalemia and its significance in chronic kidney disease. Arch Intern Med
2009;169:1156-62.
Acker CG, Johnson JP, Palevsky PM, Greenberg A. Hyperkalemia in hospitalized patients:
causes, adequacy of treatment, and results of an attempt to improve physician compliance
with published therapy guidelines. Arch Intern Med 1998;158:917-24.
UK Renal Association. Clinical practice guidelines: treatment of acute hyperkalaemia in
adults. 2014. www.renal.org/docs/default-source/guidelines-resources/joint-guidelines/
treatment-of-acute-hyperkalaemia-in-adults/hyperkalaemia-guideline---march-2014.pdf.
Slovis C, Jenkins R. ABC of clinical electrocardiography: Conditions not primarily affecting
the heart. BMJ 2002;324:1320-3.
Perazella MA. Drug-induced hyperkalemia: old culprits and new offenders. Am J Med
2000;109:307-14.
Egan TJ, Klein R. Hyperkalemic familial periodic paralysis. Pediatrics 1959;24:761-73.

12
13
14
15
16
17
18
19
20
21

Freeman SJ, Fale AD. Muscular paralysis and ventilatory failure caused by hyperkalaemia.
Br J Anaesth 1993;70:226-7.
Moore ML, Bailey RR. Hyperkalaemia in patients in hospital. N Z Med J 1989;102:557-8.
Cornes MP, Ford C, Gama R. Spurious hyperkalaemia due to EDTA contamination:
common and not always easy to identify. Ann Clin Biochem 2008;45:601-3.
Wiederkehr MR, Moe OW. Factitious hyperkalemia. Am J Kidney Dis 2000;36:1049-53.
Don BR, Sebastian A, Cheitlin M, Christiansen M, Schambelan M. Pseudohyperkalemia
caused by fist clenching during phlebotomy. N Engl J Med 1990;322:1290-2.
Verresen L, Lins RL, Neels H, De Broe ME. Effects of needle size and storage temperature
on measurements of serum potassium. Clin Chem 1986;32:698-9.
Sevastos N, Theodossiades G, Efstathiou S, Papatheodoridis GV, Manesis E,
Archimandritis AJ. Pseudohyperkalemia in serum: the phenomenon and its clinical
magnitude. J Lab Clin Med 2006;147:139-44.
Vaidya B, Chan K, Drury J, Connolly V. A race to the lab. Lancet 2002;359:848.
Stewart GW, Turner EJ. The hereditary stomatocytoses and allied disorders: congenital
disorders of erythrocyte membrane permeability to Na and K. Baillieres Best Pract Res
Clin Haematol 1999;12:707-27.
Cowley NJ, Owen A, Bion JF. Interpreting arterial blood gas results. BMJ 2013;346:f16.

Cite this as: BMJ 2015;351:h4762

BMJ Publishing Group Ltd 2015

For personal use only: See rights and reprints http://www.bmj.com/permissions

Subscribe: http://www.bmj.com/subscribe

BMJ 2015;351:h4762 doi: 10.1136/bmj.h4762 (Published 20 October 2015)

Page 5 of 6

PRACTICE

Figures

Fig 1 Algorithm for investigation and management of hyperkalaemia in adults

For personal use only: See rights and reprints http://www.bmj.com/permissions

Subscribe: http://www.bmj.com/subscribe

BMJ 2015;351:h4762 doi: 10.1136/bmj.h4762 (Published 20 October 2015)

Page 6 of 6

PRACTICE

Fig 2 Electrocardiographic changes associated with hyperkalaemia (reproduced with permission from Slovis et al9)

For personal use only: See rights and reprints http://www.bmj.com/permissions

Subscribe: http://www.bmj.com/subscribe