Electrolytes in cardiology

How potassium, magnesium, sodium and calcium imbalances can lead to serious heart complications.

Potassium, magnesium, sodium and calcium imbalances can lead to serious heart complications

In this article you will learn:

  • The standard serum concentrations of key electrolytes
  • Common medicines that can affect electrolyte concentrations
  • How to manage increases and decreases in electrolytes affecting the heart

The electrolytes potassium, magnesium, sodium and calcium play a crucial role in the function of the myocardium, the muscular tissue of the heart. Movement of these ions across the semi-permeable myocardial cell membrane causes the voltage across the membrane to exceed a threshold and generate an action potential, resulting in muscle contraction. Electrolytes carry electrical charge and are maintained to tight physiological concentrations through various mechanisms to ensure appropriate heart function (see ‘Standard serum concentrations’).

An imbalance of these electrolytes can have detrimental effects on the heart, causing or contributing to arrhythmia and cardiac arrest[1]
. Life-threatening arrhythmias are commonly associated with potassium disorders, particularly hyperkalaemia in which the potassium level is elevated, and less commonly with disorders of serum calcium and magnesium. Electrolyte imbalances also have wider effects in the body, although these are largely outside the scope of this article.


Standard serum concentrations




 *Reference ranges for electrolyte levels vary depending on individual laboratories and institutional defined ranges; this table is a guide only.

Electrolyte

Standard range*

Potassium

3.5–5.0 mmol/l

Magnesium

0.7–1.1 mmol/l

Sodium

135–146 mmol/l

Calcium

2.20–2.67 mmol/l

Renal excretion plays a major role in maintaining electrolyte balance in the body, so changes to renal function can affect electrolyte concentrations in the heart.

Kidney disease, hypoaldosteronism and adrenal insufficiency can all impair the balance of electrolytes, particularly potassium.

In addition to the role of renal function in maintaining electrolyte balance, some drugs can cause significant deviations in serum electrolyte concentration through various mechanisms (see ‘Common medicines that can cause electrolyte disturbances’)[2]
.


Common medicines that can cause electrolyte disturbances

Electrolyte

Drug class causing serum deviation

Potassium

 

Hypokalaemia

 

  • Thiazide and related diuretics (e.g. bendroflumethiazide)
  • Loop diuretics (e.g. furosemide)
  • Beta2 agonists (e.g. salbutamol)
  • Insulin
  • Aminoglycosides (e.g. gentamicin)

 

Hyperkalaemia

  • Potassium-sparing diuretics (e.g. amiloride)
  • Aldosterone antagonists (e.g. spironolactone)
  • Angiontensin converting enzyme inhibitors (e.g. ramipril)
  • Angiotensin-II receptor antagonists (e.g. losartan)
  • Non-steroidal anti-inflammatory drugs (e.g. ibuprofen)
  • Heparin

Magnesium

 

Hypomagnesaemia

  • Thiazide and related diuretics (e.g. bendroflumethiazide)
  • Loop diuretics (e.g. furosemide)
  • Digoxin
  • Aminoglycosides (e.g. gentamicin)

Hypermagnesaemia

  • Antacids (e.g. magnesium trisilicate)
  • Magnesium supplements

Sodium

 

Hyponatraemia

  • Thiazide and related diuretics (e.g. bendroflumethiazide)
  • Loop diuretics (e.g. furosemide)
  • Vasopressin
  • Selective serotonin reuptake inhibitors (e.g. fluoxetine)

Hypernatraemia

  • Sodium supplements (e.g. hypertonic saline)
  • Lithium
  • Tetracyclines (e.g. demeclocycline)
  • Amphotericin
  • Caution with drugs that contain a high content of sodium, e.g. effervescent formulations and intravenous drugs such as benzylpenicillin and aciclovir

Calcium

 

Hypocalcaemia

  • Calcitonin
  • Bisphosphonates (e.g. alendronic acid)

Hypercalcaemia

 

  • Thiazide and related diuretics (e.g. bendroflumethiazide)
  • Vitamin D analogues
  • Lithium (chronic use)
  • Vitamin A

Treatment of minor, asymptomatic electrolyte disturbance can often be achieved by the resolution of modifiable causes, including drug-induced causes or a patient’s diet (for example, drinking excessive amounts of coconut water can cause hyperkalaemia[2]
).




Where deranged electrolyte levels have led to clinical manifestations and patients present with symptoms (and/or ECG abnormalities) as described above, prompt treatment to correct the electrolyte levels is often required.

Potassium

Potassium is the most abundant intracellular cation (positively charged ion) in the body. The intracellular concentration is around 20 times greater than in the extracellular fluid, resulting in a large concentration gradient. This maintains the excitability of nerve and muscle cells.

Potassium levels are predominantly regulated by the hormone aldosterone (via renal excretion), catecholamines, insulin and levels of bicarbonate. Potassium concentrations are also affected by pH. As serum pH decreases (acidaemia), serum potassium levels rise as potassium shifts from the cellular to the vascular space; conversely, when pH increases (alkaemia), serum potassium levels decrease as potassium moves into cells.

Hyperkalaemia and hypokalaemia lead to significant abnormalities in cardiac conduction. There is no standard definition for the severity of potassium level changes; instead, they are thought of as a continuum, with severity graded by the accompanying clinical symptoms.

Hyperkalaemia results in progressive conduction problems, which if left untreated can result in cardiac arrest and death. Patients often present with weakness, which progresses to flaccid paralysis or deep tendon reflexes, and cardiac arrest.

Hyperkalaemia can cause suppressed conduction, resulting in tall, peaked T waves (at serum levels around 5.5–6.0 mmol/l), or a prolonged PR interval and a widened QRS interval (at 6.0–7.0 mmol/l). Cardiac arrest from complete heart block occurs at serum potassium levels greater than 8.0 mmol/l[3]
.

There are three key components for treating hyperkalaemia: removing potassium from the body; cardiac protection; and shifting potassium into cells.

In mild hyperkalaemia, polystyrene sulphonate resins (such as calcium resonium) can be given to gradually reduce levels by preventing further potassium absorption from the gastrointestinal tract. The dose varies depending on the preparation used, and may be given orally or rectally. They are contraindicated in patients with obstructive bowel disease.

Polystyrene sulphonate resins have a peak effect at around six hours and, owing to this extended effect and risk of subsequent hypokalaemia, treatment should stop when the patient’s serum potassium level reaches 5.0 mmol/l or lower. It is common practice to measure serum levels daily, although depending on clinical severity, more frequent levels may need to be taken[4]
.

Moderate hyperkalaemia (6.0–6.4 mmol/l) may require a more rapid shift in extracellular potassium, and patients may require an intravenous injection of soluble insulin (5–10 units) and 50 ml glucose 50% given over 5 to 15 minutes as per local protocols.

This can be repeated in cases of resistant hyperkalaemia with close monitoring of blood glucose.
This treatment has a rapid onset and offset of action, and a polystyrene sulphonate resin is often co-administered to ensure that hyperkalaemia does not recu
r
[4]
.

Patients with severe hyperkalaemia (>6.5 mmol/l) require both treatments outlined above, in addition to further interventions, such as intravenous sodium bicarbonate and/or high-dose nebulised beta2 agonists (salbutamol), which will be administered as per local policy as both treatment options are off-label (e.g. salbutamol 10 mg nebulised as required).

Patients with severe hyperkalaemia, or those who exhibit ECG changes associated with hyperkalaemia, should be treated with 10–20 ml calcium gluconate 10% by slow intravenous injection. This does not reduce potassium levels but reduces the risk of pulseless ventricular tachycardia or ventricular fibrillation by increasing the threshold potential of myocytes. During hyperkalaemia, the resting membrane potential is raised, and increasing the threshold potential will normalise this gradient.

Rapid administration of calcium in those taking digoxin should be avoided owing to the risk of arrhythmias; however, calcium may still be used in the treatment of life-threatening hyperkalaemia if the patient is monitored closely. If the patient is also receiving sodium bicarbonate, this should be through a different line to the calcium salts, as the combination causes precipitates[4]
.

Hypokalaemia (serum potassium levels <3.5 mmol/l) can affect the conduction of an action potential, which at its extreme can cause ventricular tachycardia[3]
. It can be caused by pH changes and medicines such as insulin, dopamine and beta2 agonists, which can cause increased cellular uptake of potassium.

Hypokalaemia can also be due to increased loss of potassium through renal excretion, which may be caused by diabetes insipidus, hypercalcaemia, hyperaldosteronism, excessive fluid replacement therapy and diarrhoea.

A typical ECG for a patient with hypokalaemia will show flattened T waves, U waves (waves following a T wave, not typically seen on standard ECG traces), depressed ST segments or premature ventricular or atrial complexes that may signal worsening conduction blockade; at the extreme it can indicate impending ventricular tachycardia.

Mild hypokalaemia should be treated conservatively by correction of the cause (if possible) with or without oral supplementation. Patients with more severe hypokalaemia with related symptoms and ECG abnormalities should be treated with intravenous potassium.

The dose used and rate of infusion is dependent on the severity and clinical presentation; ECG monitoring is required if the rate of infusion is more than 20 mmol/hour or if the concentration is more than 80 mmol/l. Concentrations of more than 40 mmol/l potassium should preferably be given by a central line, or via a large peripheral vein[5]
. Patients receiving high-dose intravenous potassium require regular monitoring of serum potassium levels (ranging from every 30 minutes to hourly) and continuous ECG monitoring.

Many patients who are potassium deficient are also deficient in magnesium. Magnesium is important for potassium uptake and for the maintenance of intracellular potassium levels, particularly in the myocardium. Magnesium supplementation will facilitate more rapid correction of hypokalaemia and is recommended in severe cases of hypokalaemia[6]
.

Magnesium

Magnesium is the second most abundant intracellular cation. The interaction with magnesium and the enzyme sodium–potassium ATPase (which acts to pump potassium into cells in exchange for sodium) plays a crucial part in regulating cellular concentration gradients[3]
.

Hypermagnesaemia is rare in patients without significantly impaired renal function; magnesium is mainly excreted by the kidneys, which have the capacity to secrete large quantities. Elevated magnesium levels can be seen following extensive soft-tissue injury or necrosis (e.g. trauma, burns or following cardiac arrest) as magnesium is mobilised from within cells[7]
.

Patients with serum magnesium levels of 1.0–2.0 mmol/l are generally asymptomatic, although those taking digoxin may be at increased risk of digoxin toxicity. Volume expansion is common in patients with serum magnesium levels of more than 2.0 mmol/l, which can lead to a reduction in cardiac output.

Patients with serum magnesium levels of more than 4.0 mmol/l may experience nausea, lethargy and weakness, which can lead to respiratory failure, paralysis and coma. Prolongation of the cardiac action potential and conduction can occur at serum magnesium levels of more than 10.0 mmol/l, resulting in asystole (flatline).

Common ECG changes associated with hypermagnesaemia include a prolonged PR and QT interval, T wave peaking, and atrioventricular block (AV block, or complete heart block). Where these are noted, continuous ECG monitoring is recommended until magnesium levels reduce and ECG changes resolve[3]
.

Treatment of hypermagnesaemia is based on the patient’s fluid and kidney function. Patients with hypovolaemia and normal renal function can be treated with aggressive intravenous hydration therapy, which will rebalance serum ion concentrations. Patients with significant renal impairment may require dialysis[3]
.

Magnesium acts as a calcium channel blocker, and at high concentrations this can give rise to electrical conduction abnormalities and require intravenous calcium administration; this usually occurs when serum calcium levels are low.

Hypomagnesaemia can occur in chronic or acute asthma. This may be due to genetic factors, low magnesium intake in asthmatics or the side effects of beta2-agonists, corticosteroids or theophylline increasing urinary loss of magnesium[4]
. It can also be due to conditions that affect absorption from the gastrointestinal tract, such as diarrhoea or alcohol misuse.

Signs and symptoms of hypomagnesaemia include neuromuscular manifestations such as tetany (involuntary contraction of muscles), tremors, seizures, delirium and psychosis.

Severe hypomagnesaemia can cause prolonged PR and QT intervals (which can be seen on an ECG), which can lead to increased QRS duration and development of torsades de pointes[6]
.

Patients with diuretic-induced hypomagnesaemia should either discontinue treatment (following consultation with a doctor) or, if this is not possible, be prescribed a potassium-sparing diuretic, which will increase magnesium reabsorption in the collecting duct (see ‘Diuretic therapy explained’)[3]
.

Significant hypomagnesaemia should be treated with intravenous magnesium, particularly if ECG changes are observed or when the patient is hypokalaemic. Intravenous magnesium is given as an 8–20 mmol bolus dose in an emergency or, more usually, as an infusion over 6 hours.

Sodium

Sodium is the main extracellular cation in the body and has significant effects on serum osmolality. Together with potassium it has a large role in controlling membrane potentials in the myocardium, and therefore a significant role in governing cardiac action potentials. However, unlike potassium, fluctuations in serum sodium levels rarely cause significant cardiac problems until severe variation from normal physiological values has occurred[5]
.

Symptoms of sodium deviations are rarely cardiac specific and usually include nausea, vomiting, weakness and confusion, which can result in seizures or coma if left untreated. Consistent ECG changes are not common[2]
.

Excess total body water in relation to sodium is often seen in patients with severe cardiac failure, whereby compensatory mechanisms for sodium regulation are compromised (resulting in hypervolaemic hyponatraemia). Patients should be placed on fluid restriction and treated with a diuretic, which will reduce water levels and gradually correct serum sodium levels.

Calcium

Calcium has a significant effect on cells in the myocardium, affecting conduction, intracellular signalling and contraction of muscle fibres. In particular, calcium levels can alter the duration of the plateau phase (phase 2) of the myocardial action potential and affect heart conduction.

Excessive calcium levels can lead to short QT interval, and calcium deficiency can result in a prolonged QT interval. At further extremes, conduction abnormalities can lead to cardiac arrest[8]
.

Hypercalcaemia can lead to shortened QT intervals, which, if left untreated, can result in AV block. In addition, hypercalcaemia affects smooth muscle fibres, causing muscle weakness[6]
.

High levels of calcium (>2.67 mmol/l) require urgent treatment in patients who have a shortened QT interval on ECG. Hypercalcaemia can be managed initially with aggressive fluid administration, such as sodium chloride 0.9% to encourage renal excretion, and patients with prolonged QRS intervals (as shown on ECG) should be treated with loop diuretics (not thiazides and related diuretics as these promote hypercalcaemia) to force further calcium excretion. If unsuccessful, intravenous bisphosphonates can be used to slow the rate of bone turnover and reduce serum calcium levels, which is commonly undertaken in those with concomitant malignancy[8]
.

Hypocalcaemia will lengthen the QT interval, which can lead to AV block and cardiac arrest. Symptoms of hypocalcaemia include cramps and tetany.

Patients with serum calcium levels <2.1 mmol/l who present with these symptoms require rapid intravenous treatment with intravenous calcium.

Reversible causes of hypocalcaemia, including drug-induced hypocalcaemia, should be corrected if possible. Patients treated for hypocalcaemia should also be given intravenous magnesium to aid correction of serum calcium levels[8]
.

Sadeer Fhadil MRPharmS, 
is Highly Specialist Cardiac Pharmacist and 
Paul Wright, MFRPSII MRPharmS, MSc, IPresc is L
ea
d Ca
rdiac Pharmacist, both at the Heart Hospital, University College London Hospitals NHS Foundation Trust.

References

[1] Fisch C. Relation of electrolyte disturbances to cardiac arrhythmias. Circulation 1973: 47; 408–419.

[2] Rees R, Barnett J, Marks D & George M Coconut water-induced hyperkalaemia. Br J Hosp Med. 2012; 73(9): 534.

[3] Elgart H. Assessment of fluids and electrolytes. AACN Clin. Issues 2004;15(4):607–621.

[4] Das SK, Haldar AK, Ghosh I et al. Serum magnesium and stable asthma: Is there a link? Lung India 2010:27(4): 205–208.

[5] Potassium chloride. UCL Hospitals Injectable Medicines Administration Guide: Third Edition. London:Blackwell Publishing 2010.

[6] Soar J, Perkins GD, Abbas G et al. European Resuscitation Council guidelines for resuscitation 2010 section 8. Cardiac arrest in special circumstances: electrolyte abnormalities, poisoning, drowning, accidental hypothermia, hyperthermia, asthma, anaphylaxis, cardiac surgery, trauma, pregnancy, electrocution. Resuscitation. 2010: 82; 1400–1433.

[7] Bringhurst FR, Demay MB, Krane SM et al. Bone and mineral metabolism in health and disease. In: Kasper DL, Braunwald E, Fauci AS et al, eds. Harrison’s Principles of Internal Medicine. 16th ed. New York, NY: McGraw-Hill; 2005.

[8] Marks AR. Calcium and the heart: a question of life and death. J Clin Inv 2003: 111; 597–600.

Last updated
Citation
The Pharmaceutical Journal, PJ, 14 February 2015, Vol 294, No 7849;294(7849):DOI:10.1211/PJ.2015.20067712