What is the immediate management and treatment approach for neonates experiencing seizures?

Immediate Management and Treatment of Neonatal Seizures

Phenobarbital remains the first-line antiseizure medication for neonatal seizures, with levetiracetam or phenytoin as second-line options, and all antiseizure medications should be discontinued before discharge home if seizures were acute provoked without evidence of neonatal-onset epilepsy. 1

Initial Stabilization and Assessment

Airway, Breathing, and Circulation Management:

• Position the neonate in a "sniffing" position to maintain airway patency 2
• Administer high-flow oxygen immediately to prevent hypoxia 2
• Establish vascular or intraosseous access without delay 2
• Have airway equipment and mechanical ventilation immediately available, as respiratory depression is the most important risk with antiseizure medications 3
• Maintain normal body temperature using radiant heat sources, avoiding both hypothermia and hyperthermia 2

Urgent Diagnostic Workup:

• Check blood glucose level immediately to rule out hypoglycemia as a correctable cause 2, 3
• Obtain serum calcium, magnesium, sodium, complete blood count, and blood culture if infection is suspected 2
• Perform neurological evaluation assessing level of consciousness, pupillary responses, and abnormal movements 2
• Consider etiologies including hypoxic-ischemic encephalopathy (most common cause), intracranial hemorrhage, stroke, infection, and metabolic disorders 2, 4, 5

First-Line Antiseizure Medication

Phenobarbital Administration:

• Administer phenobarbital 20 mg/kg IV as the first-line treatment for neonatal seizures regardless of etiology 1
• Phenobarbital is probably more effective than levetiracetam in achieving seizure control after first loading dose (RR 2.32,95% CI 1.63 to 3.30) and after maximal loading dose (RR 2.83,95% CI 1.78 to 4.50) 6
• Phenobarbital achieves therapeutic plasma levels (15-30 mcg/mL) within minutes, with 77% of neonatal seizures responding at doses up to 40 mcg/mL serum concentration 2
• Premature infants (<32 weeks) respond significantly better to phenobarbital than term infants 2

Exception for Suspected Channelopathy:

• If family history suggests channelopathy as the cause, use phenytoin or carbamazepine instead of phenobarbital 1

Second-Line Treatment for Refractory Seizures

When First-Line Fails:

• If seizures persist after phenobarbital loading, administer one of the following second-line agents: phenytoin, levetiracetam, midazolam, or lidocaine 1
• Seizures are refractory to initial loading doses in >50% of cases 4
• In neonates with cardiac disorders, levetiracetam may be the preferred second-line agent 1

Specific Second-Line Dosing (from related guidelines):

• Levetiracetam 40 mg/kg IV bolus (maximum 2,500 mg) given as slow infusion over 5-10 minutes 2
• Phenytoin 15-20 mg/kg IV loading dose 2
• Lorazepam 0.1 mg/kg IV/IO for active seizures if benzodiazepine approach is used 2

Role of EEG Monitoring

Continuous EEG is Essential:

• Clinical identification of neonatal seizures is unreliable since seizures often lack apparent clinical correlates 4
• Electroencephalography should be used to accurately diagnose and manage neonatal seizures 4
• Treating both clinical and electrographic seizures (including electrographic-only seizures) to achieve lower seizure burden may be associated with improved outcomes 1
• Consider enhanced EEG monitoring in at-risk populations including neonates with stroke and those with unexplained reduced consciousness 7

Special Considerations for Hypoxic-Ischemic Encephalopathy

Therapeutic Hypothermia:

• Therapeutic hypothermia may reduce seizure burden in neonates with hypoxic-ischemic encephalopathy 1
• Hypoxic-ischemic encephalopathy is the most common cause of neonatal seizures 4, 5

Pyridoxine Trial for Refractory Cases

Vitamin B6-Dependent Epilepsy:

• Attempt a trial of pyridoxine in neonates presenting with clinical features of vitamin B6-dependent epilepsy and seizures unresponsive to second-line antiseizure medications 1

Discontinuation of Antiseizure Medications

Critical Practice Point:

• Following cessation of acute provoked seizures without evidence of neonatal-onset epilepsy, discontinue all antiseizure medications before discharge home, regardless of MRI or EEG findings 1
• This applies to all neonates who achieve seizure control and do not have evidence of ongoing epilepsy 1
• Maintenance therapy with antiseizure medications compared to no maintenance therapy may have little or no effect on mortality before discharge (RR 0.69,95% CI 0.39 to 1.22), mortality at 18-24 months (RR 0.94,95% CI 0.34 to 2.61), or neurodevelopmental disability at 18-24 months (RR 0.89,95% CI 0.13 to 6.12) 6

Monitoring During Treatment

Vital Parameters:

• Monitor oxygen saturation continuously 2
• Monitor for respiratory depression, especially with benzodiazepines and phenobarbital 2, 3
• Monitor pupillary size and reaction, as unilateral sluggish or absent responses indicate raised intracranial pressure 2
• For patients with Glasgow coma score ≤8 who remain unconscious, consider elective intubation and ventilation 2

Common Pitfalls to Avoid

Critical Errors:

• Do not use prophylactic antiseizure medications in neonates without seizures, as this is not associated with improved long-term outcomes and may harm neurological recovery 7, 1
• Do not restrain the infant during seizures or place anything in the mouth 2
• Do not continue maintenance antiseizure medications at discharge for acute provoked seizures without evidence of neonatal-onset epilepsy 1
• Do not delay establishing vascular access or having airway equipment ready before administering antiseizure medications 2, 3

Team Communication and Consultation

Coordinated Care:

• Clearly assign roles to team members during resuscitation 2
• Designate a team leader to coordinate care 2
• Use closed-loop communication to prevent errors 2
• Consider early consultation with pediatric neurology if available 2
• Inform parents/guardians about the diagnosis of seizures and initial treatment options 1