What cardiac side effects can phenytoin cause, especially with intravenous or high‑dose administration, and how should they be monitored and managed?

Cardiac Side Effects of Phenytoin

Intravenous phenytoin causes hypotension and cardiac arrhythmias (including bradycardia, heart block, ventricular tachycardia, ventricular fibrillation, asystole, and cardiac arrest) especially with rapid infusion, and requires continuous cardiac monitoring during and after administration. 1

Primary Cardiovascular Toxicities

Hypotension is the most common cardiac side effect:

• Occurs in approximately 5% of patients receiving IV phenytoin 2
• Can be severe and life-threatening, particularly in critically ill, elderly, or hemodynamically unstable patients 1
• May occur even at recommended infusion rates and doses 1

Cardiac arrhythmias include the full spectrum of conduction abnormalities:

• Bradycardia and heart block (including junctional bradycardia) 3, 1, 4
• Ventricular tachycardia and ventricular fibrillation 1
• Asystole and cardiac arrest resulting in death 1
• These complications have been reported in both adults and children, even without underlying cardiac disease 1

Critical Administration Parameters

Maximum infusion rates must be strictly observed:

• Adults: Do not exceed 50 mg/minute 1
• Pediatric patients: Do not exceed 1-3 mg/kg/min OR 50 mg/minute, whichever is slower 3, 1
• Reduce infusion rate if heart rate decreases by 10 beats per minute 3, 5

The formulation itself contributes to toxicity:

• IV phenytoin contains 40% propylene glycol and 10% ethanol with pH of 12 5
• These excipients contribute significantly to cardiovascular adverse effects 5
• Must be diluted only in normal saline; incompatible with glucose-containing solutions 3

Monitoring Requirements

Continuous cardiac and respiratory monitoring is mandatory:

• ECG monitoring during and after infusion 5, 1
• Blood pressure monitoring throughout administration 5, 1
• Vital signs should be monitored closely, with particular attention to heart rate changes 5

High-risk populations require extra vigilance:

• Critically ill patients 1
• Elderly patients 1
• Patients with hypotension or severe myocardial insufficiency 1
• Patients with abnormal neurological signs at presentation (20% incidence of hypotension versus 3.5% when absent) 2

Oral Phenytoin Cardiac Toxicity

Chronic oral overdose can cause severe cardiotoxicity, though this is rare:

• Life-threatening junctional bradycardia has been reported with serum levels reaching 91 mcg/mL 4
• May require temporary pacemaker implantation for severe bradycardia and hypotension 4
• Consider phenytoin toxicity in patients presenting with dysrhythmias and cardiovascular collapse who have hyperbilirubinemia, hypoalbuminemia, or severe electrolyte imbalance 4
• Cardiac complications from oral ingestion alone are extremely rare; no cardiovascular adverse effects reported in oral overdoses except in cases with very high serum levels and hypoalbuminemia 6

Safer Alternative: Fosphenytoin

Fosphenytoin is strongly preferred when available:

• Can be administered at 150 PE/min (versus 50 mg/min for phenytoin) 5
• Has fewer adverse cardiovascular events compared to IV phenytoin 3, 5
• Does not contain propylene glycol or ethanol 7
• Compatible with dextrose solutions unlike phenytoin 7
• The American Academy of Pediatrics states "If available, fosphenytoin is preferred, because it has a lower risk of adverse cardiac effects" 3

Management of Cardiovascular Toxicity

Immediate interventions when toxicity occurs:

• Reduce infusion rate or discontinue phenytoin immediately 1
• Provide supportive care focused on maintaining vital functions 8
• No specific antidote exists for phenytoin cardiotoxicity 8
• Temporary pacemaker may be required for severe bradycardia 4

Additional Complications

Local tissue toxicity is also a concern:

• Purple glove syndrome, tissue necrosis, and phlebitis can occur 5
• Extravascular administration can result in severe skin injury 3

Key Clinical Pitfall

The most critical error is rapid infusion: While cardiovascular toxicity increases with infusion rates above recommendations, these events have been reported even at or below recommended rates 1. A 2016 systematic review found that rapid infusion rate (>50 mg/min) was the major cause of increased mortality in case reports, while no serious cardiovascular adverse effects leading to death occurred in clinical trials using recommended rates 6. Therefore, never exceed maximum infusion rates, and consider even slower rates in high-risk patients.