Drug-induced prolonged QT and arrhythmias
Overview
Drug-induced QT prolongation occurs when drugs block the hERG (IKr) potassium channel, slowing phase 3 repolarisation. This prolongs the action potential, predisposes to early afterdepolarisations (EADs), and can trigger torsades de pointes (TdP) - a polymorphic VT that may degenerate into VF.
•QTc calculated using Bazett formula: QTc = QT / √RR
•Prolonged QTc: >440 ms (males), >460 ms (females); QTc >500 ms = high-risk threshold
Risk factors
Risk factors for drug-induced QT prolongation
Female sex
Advanced age
Pre-existing cardiac disease / heart failure
Congenital long QT syndrome (even subclinical)
Hypokalaemia
Hypomagnesaemia
Hypocalcaemia
Bradycardia
Polypharmacy with multiple QT-prolonging drugs
CYP3A4 inhibitors raising drug plasma levels
IV route of administration
High doses
Presentation
•Palpitations - often first symptom; self-terminating TdP episode
•Pre-syncope / syncope - sudden onset, rapid recovery if TdP self-terminates
•Cardiac arrest - TdP degenerating to VF; may be first presentation
•Incidental ECG finding - QTc prolongation on routine monitoring
Investigations
🥇 First-line
•12-lead ECG - measure QTc in leads II, V5, or V6; identify TdP if present
•Serum electrolytes (U&Es, magnesium, calcium) - correct hypokalaemia, hypomagnesaemia, hypocalcaemia
•Full drug history - identify all QT-prolonging agents and CYP3A4 interactions
•Continuous cardiac monitoring / telemetry - if QTc >500 ms or symptomatic
🥈 Second-line
•Holter monitoring - paroxysmal TdP in unexplained syncope on QT-prolonging drugs
•Genetic testing for congenital long QT syndrome - if strong family history, recurrent TdP, or disproportionate QT prolongation
Management
Step 1 · Acute TdP
- 1Withdraw causative drug immediately
- 2IV magnesium sulphate 2 g over 10-15 min - first-line for TdP even if magnesium is normal
- 3Correct hypokalaemia - target K⁺ >4.0 mmol/L with IV potassium
- 4Continuous cardiac monitoring
- 5Cardiology review
TdP self-terminates
Continue monitoring; correct electrolytes; identify and remove all QT-prolonging drugs; QTc typically normalises within 24-72 hours
TdP degenerates to VF / haemodynamic compromise
Immediate DC cardioversion / defibrillation per ALS protocol; consider overdrive pacing to shorten QT
Step 2 · QTc prolongation found incidentally (no TdP)
- 1Withdraw or reduce dose of causative drug
- 2Correct electrolyte disturbances
- 3Review all co-prescribed QT-prolonging agents
- 4Repeat ECG after correction
Step 3 · Long-term follow-up
- 1Cardiac follow-up to exclude congenital long QT syndrome
- 2Add clear medication alert to patient records
- 3Inform future prescribers
Causative drug classes
•Macrolide antibiotics - erythromycin, clarithromycin
•Antiemetics - domperidone, ondansetron (dose-dependent; avoid IV where oral suffices)
•Antipsychotics - haloperidol, amisulpride, pimozide
•Antiarrhythmics - class Ia (quinidine, procainamide), class III (amiodarone, sotalol)
•Antihistamines - mizolastine
•Antimalarials - chloroquine, quinine
•Other - ivabradine, tolterodine, some antifungals and antivirals
Prevention and contraindicated combinations
•Check full drug history before prescribing - avoid two or more QT-prolonging drugs concurrently
•Check and correct electrolytes before starting high-risk agents
•Baseline ECG in high-risk patients (cardiac disease, known electrolyte disturbances, IV QT-prolonging drugs)
•Use lowest effective dose and shortest course; prefer oral over IV where possible
•Do not prescribe macrolides to patients with prior QT prolongation, prior TdP, or significant electrolyte disturbances