What can be done to reduce pain during IV phenytoin infusion?

Managing Pain During IV Phenytoin Infusion

The most effective strategy to reduce pain during IV phenytoin infusion is to slow the infusion rate to 25 mg/min or less, ensure administration through a large-bore peripheral or central venous catheter, dilute appropriately in normal saline, and flush before and after administration—or preferably, switch to fosphenytoin which causes significantly less local irritation. 1, 2, 3

Understanding Why Phenytoin Causes Pain

• IV phenytoin contains propylene glycol (40%) and ethanol (10%) with a highly alkaline pH of 12, which directly causes the venous irritation and pain your patient is experiencing 1
• This chemical composition is responsible for soft tissue irritation, phlebitis, and potentially severe complications including purple glove syndrome and tissue necrosis 2

Immediate Interventions to Reduce Pain

Slow the Infusion Rate

• Reduce the infusion rate to 25 mg/min or slower rather than the maximum 50 mg/min rate 4, 5
• Studies demonstrate that slowing from 40 mg/min to 20 mg/min significantly reduces burning and discomfort at the IV site 4
• In one case report, dividing a loading dose into two separate infusions at 25 mg/min eliminated adverse effects entirely 5

Optimize IV Access and Administration Technique

• Administer through a large-gauge catheter into a large peripheral or central vein to minimize local concentration and irritation 2
• Verify catheter patency with a sterile saline flush before starting phenytoin 2
• Flush the line with sterile saline immediately after phenytoin administration to clear residual alkaline solution from the vein 2
• Dilute phenytoin in normal saline to a final concentration of ≥5 mg/mL (never use dextrose solutions as this causes precipitation) 6

The Superior Alternative: Fosphenytoin

• Fosphenytoin is strongly preferred over phenytoin for IV administration as it causes significantly fewer local adverse reactions 1, 3
• Fosphenytoin can be administered at 150 PE/min (three times faster than phenytoin) with minimal pain or tissue irritation 1, 3
• The water-soluble formulation of fosphenytoin eliminates the propylene glycol and ethanol that cause phenytoin's local toxicity 3
• Therapeutic phenytoin levels are achieved at comparable times to IV phenytoin despite the 7-15 minute conversion time 3

Important Caveat with Fosphenytoin

• Rapid fosphenytoin infusion (>150 PE/min) can cause transient paresthesias and pruritus, though these are systemic rather than local effects and resolve quickly 3

Critical Safety Monitoring During Administration

• Monitor ECG continuously for bradycardia, arrhythmias, and heart block 6, 2
• Check blood pressure frequently as hypotension can occur even at recommended infusion rates 6, 2
• Reduce infusion rate or stop if heart rate decreases by 10 beats/min 1, 6
• Watch for neurological side effects including ataxia, nystagmus, tremor, and somnolence 1

What NOT to Do

• Never administer phenytoin intramuscularly—this causes severe pain, necrosis, and abscess formation 2
• Never exceed 50 mg/min infusion rate in adults as this dramatically increases cardiovascular toxicity risk 2
• Never mix phenytoin with dextrose-containing solutions 6
• Do not ignore early signs of extravasation or local irritation, as purple glove syndrome can develop days later and may require fasciotomy or even amputation in severe cases 2