What are the potential adverse effects of administering intravenous (IV) phenytoin to a newborn suspected of having convulsions if the diagnosis is later found to be incorrect?

Potential Adverse Effects of IV Phenytoin in a 3-Day-Old Newborn

The administration of 60 mg IV phenytoin to this 3-day-old newborn carries significant risk of adverse effects even if convulsions were not present, primarily because neonates have markedly increased toxicity risk due to decreased protein binding, altered pharmacokinetics, and heightened cardiovascular sensitivity. 1, 2

Critical Safety Concerns in Neonates

Cardiovascular Toxicity

• Hypotension and cardiac arrhythmias are the most serious immediate risks, occurring even at recommended doses and infusion rates in pediatric patients. 2
• Cardiac complications can include bradycardia, heart block, ventricular tachycardia, ventricular fibrillation, asystole, and cardiac arrest—events that have been reported in children without underlying cardiac disease. 2
• The 30-minute infusion time used (60 mg over 30 minutes = 2 mg/min) may have exceeded safe rates depending on the infant's weight, as the maximum rate should not exceed 1-3 mg/kg/min in pediatric patients. 2

Neonatal-Specific Pharmacokinetic Risks

• Neonates have significantly decreased protein binding of phenytoin, leading to higher free (unbound) phenytoin levels and increased toxicity risk—this is why phenobarbital is preferred over phenytoin in this age group. 1, 3
• The altered pharmacokinetics in newborns result in unpredictable drug levels and prolonged elimination, with difficulty achieving stable therapeutic concentrations. 4
• A case report documented a one-month-old infant with phenytoin toxicity showing extremely slow elimination reflecting zero-order kinetics, with levels remaining elevated for over 160 hours. 5

Neurological Adverse Effects

• Phenytoin encephalopathy can develop, manifesting as cognitive impairment, lethargy, decreased level of consciousness, and cerebellar dysfunction. 6, 5
• A newborn with phenytoin toxicity presented with progressive lethargy, diminished activity, poor responsiveness, and dysconjugate gaze. 5
• These neurological effects are particularly concerning in neonates who are already vulnerable to developmental complications. 6

Additional Adverse Effects Regardless of Seizure Presence

Gastrointestinal Complications

• Ileus and abdominal distension have been reported as presenting symptoms in children with toxic phenytoin levels. 5
• Hypothermia, poor feeding, and hypoactive bowel sounds may develop. 5

Local Tissue Toxicity

• Local irritation at the IV site occurred in 15% of patients receiving IV phenytoin in one study. 1
• Soft tissue irritation, inflammation, edema, and discoloration can occur with or without extravasation. 2
• "Purple glove syndrome" with pain distal to injection site has been reported, though less commonly in pediatric patients. 2, 7
• Extravasation was documented in 27% of pediatric patients in one prospective study. 7

Hematologic and Metabolic Effects

• Hematopoietic complications including thrombocytopenia, leukopenia, and agranulocytosis have been reported, some fatal. 2
• Hyperglycemia may occur due to inhibition of insulin release. 2

Monitoring and Management Recommendations

Immediate Monitoring Required

• Continuous cardiac and respiratory monitoring should be maintained for at least 4 hours after phenytoin administration, as adverse cardiovascular reactions can occur during and after infusion. 2
• Blood pressure monitoring is essential, with readiness to reduce infusion rate or discontinue if hypotension develops. 3, 2
• Observe for signs of local tissue toxicity at the IV site and distally. 2

Laboratory Monitoring

• Phenytoin levels should be checked within 2-4 hours after completion of infusion to assess for supratherapeutic levels. 8
• In neonates with altered protein binding, monitoring of unbound (free) phenytoin concentrations is more clinically relevant than total levels. 2
• Therapeutic total phenytoin levels are 10-20 mcg/mL, but neonates may develop toxicity at lower total levels due to increased free fraction. 2

Clinical Assessment

• Monitor for neurological signs of toxicity: lethargy, poor feeding, decreased responsiveness, nystagmus, ataxia (if developmentally assessable), and any change in mental status. 2, 6, 5
• Assess for gastrointestinal symptoms including abdominal distension and feeding intolerance. 5
• Check vital signs including temperature, as hypothermia has been reported. 5

Key Clinical Pitfalls

• The most critical error was choosing phenytoin over phenobarbital as first-line therapy in a neonate, as phenobarbital is strongly preferred due to phenytoin's increased toxicity risk in this age group. 1, 3
• Infusing phenytoin too rapidly increases cardiovascular complications—the rate should never exceed 1 mg/kg/min in neonates. 1, 2
• Using glucose-containing solutions for dilution causes precipitation and should be avoided; only normal saline should be used. 1, 3, 2
• Failure to prepare for respiratory support is dangerous, especially if benzodiazepines were also administered. 1, 3

Bottom Line on Risk Assessment

Even if this infant did not have true seizures, the phenytoin administration itself poses independent risks that require vigilant monitoring. The adverse effects are not contingent on whether seizures were present—they stem from the drug's inherent toxicity profile, which is amplified in neonates. 2, 4 Recovery from adverse effects is typically spontaneous and complete if recognized early and managed appropriately, but serious complications including cardiac arrest have been reported. 2, 7