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Pharmacologic Management of Neonatal Seizures Brandy Zeller, Pharmd Jeanne Giebe, MSN, NNP-BC, RN

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Pharmacologic Management of Neonatal Seizures Brandy Zeller, Pharmd Jeanne Giebe, MSN, NNP-BC, RN Pointers in Practical Pharmacology Pharmacologic Management of Neonatal Seizures Brandy Zeller, PharmD Jeanne Giebe, MSN, NNP-BC, RN Continuing Nursing Education ABSTRACT (CNE) Credit Seizures are most often the only sign of a central nervous dysfunction in the neonate. Neonatal seizures A total of 3.0 contact hours may be earned as CNE credit are a symptom of a specific disease entity. The search for a cause of neonatal seizures should focus on for reading the articles in this issue perinatal history or acute metabolic changes in the neonate. There are four classifications of neonatal identified as CNE and for completing seizures: clonic, tonic, myoclonic, and subtle. Simultaneous electroencephalogram and video recording an online posttest and evaluation. To be successful the learner must are tools to assist the practitioner in the evaluation of difficult-to-assess subtle behaviors. Although obtain a grade of at least 80% on many seizures may be prevented by careful attention to metabolic changes and the neonate’s overall the test. Test expires three (3) years from publication date. Disclosure: condition, those that cannot be prevented may require pharmacologic treatment. First-generation The authors/planning committee antiepileptic drugs such as phenobarbital and phenytoin are still the first and second lines of therapy, have no relevant financial interest even as questions concerning their limited clinical effectiveness and concern for potential neurotoxicity or affiliations with any commercial interests related to the subjects continue. discussed within this article. No commercial support or sponsorship Keywords: neonatal; seizures; antiepileptic; phenobarbital; phenytoin; midazolam; lidocaine; was provided for this educational activity. ANN/ANCC does not levetiracetam endorse any commercial products discussed/displayed in conjunction with this educational activity. The Academy of Neonatal Nursing is accredited as a provider of continuing nursing education by the American EIZURES ARE OFTEN THE ONLY SIGN OF 1 Nurses Credentialing Center’s chronic stresses on the brain. General causes Commission on Accreditation. a central nervous dysfunction in the of neonatal seizures are included in Table 1. S 1 Provider, Academy of Neonatal neonate. Seizures require prompt medical Primary intracranial conditions that may Nursing, approved by the California attention and raise concerns about the cause cause neonatal seizures include meningitis, Board of Registered Nursing, Provider #CEP 6261; and Florida and clinical condition of the neonate as well as intracranial hemorrhage, encephalitis, and Board of Nursing, Provider #FBN effects on the developing brain from seizure tumor, whereas secondary processes include 3218, content code 2505. activity and the use of anticonvulsants.1–2 hypoglycemia, hypoxic-ischemia, hypocalce- The purpose of this article is to review the etiology and pharmacologic Identifying an exact incidence in neonatal mia, hypomagnesemia, hyponatremia, and management of neonatal seizures. seizures is difficult. It is estimated that the drug withdrawal.1,10,12 There has also been a incidence of clinical seizures in the newborn link identified between intrapartum fever and is 1–3 per 1,000 live births. Seizures occur unexplained neonatal seizure activity, increasing more frequently in the preterm newborn the risk of these seizures by fourfold even when especially in lower gestational ages and birth the presence of infections was not found.13 weights. Various reports identify rates of 2–3 Clinical symptoms may or may not be per 1,000 live births in the general popu- associated with surface electroencephalo- lation and term babies, 4.4 per 1,000 live gram (EEG) changes. Seizures in the neo- births between 1,500 and 2,500 g, 55–130 natal period are considerably different as per 1,000 live births ,1,500 g, and up to compared with seizures in older children and 64 per 1,000 live births in infants ,1,000 g adults, which are well organized. Seizure birth weight.1–9 activity is less organized in the preterm infant Neonatal seizures are a symptom of a spe- as compared with a term infant because of cific disease entity.10 Seizures may be associ- incomplete neurophysiologic development. ated with any disorder directly or indirectly This makes detecting seizure activity in any affecting the central nervous system (CNS) neonate considerably more difficult, and it and may be caused by various acute and may oftentimes go unnoticed.1 Accepted for publication March 2015. N EONATAL N ETWORK VOL. 34, NO. 4, JULY/AUGUST 2015 © 2015 Springer Publishing Company 239 http://dx.doi.org/10.1891/0730-0832.34.4.239 NN34-4_Final_A6_239-244.indd 239 6/17/15 1:48 PM TABLE 1 n Common Causes of Neonatal Seizures Classification Causes Acute metabolic conditions (pH, HCO3, Na, K, Ca, Mg, glucose, blood urea Hypocalcemia nitrogen) Hypoglycemia; hyperglycemia Hypomagnesemia Pyridoxine dependency or deficiency Hyponatremia; hypernatremia Inherited metabolic conditions (acidosis is common; assess urine amino acids, Maple syrup urine disease organic acids, NH3, galactose) Nonketotic hyperglycemia Hyperprolinemia Hyperglycinemia Galactosemia Urea cycle abnormalities Organic acidemias Infections (12% of cases; assess cerebrospinal fluid [CSF]; culture blood, CSF; Viral encephalitis; herpes or enterovirus infection polymerase chain reaction assay in CSF; imaging) Congenital infections Bacterial meningitis Sepsis Brain abscess Septic venous thrombosis Intracranial hemorrhage (15% of cases; imaging; CSF examination) Subdural hematoma Cerebral contusion Subarachnoid hemorrhage Epidural hemorrhage Intraventricular hemorrhage (premature) Hypoxic ischemia (0–3 days) most common (60%) Congenital malformations Neonatal drug withdrawal (e.g., opiates) Local anesthetic intoxication Kernicterus Specific nongenetic syndromes Benign familial neonatal seizures Idiopathic (in only 10%, no cause is found) From Gardner SL, Carter MS, Enzman-Hines M, et al. Merenstein and Gardner’s Handbook of Neonatal Intensive Care. 7th ed. St. Louis, MO: Mosby Elsevier; 2011. Reprinted with permission. The search for a cause for neonatal seizures should be protein.1,14 Cranial ultrasounds are particularly helpful in focused on known history of perinatal problems or acute met- identifying and following intraventricular bleeding or hydro- abolic changes to narrow the differential diagnoses. Blood cephalus. Computed tomography (CT) scan or magnetic res- glucose should be checked at the bedside and confirmed in onance imaging (MRI) may also be indicated as a follow-up the laboratory. Lumbar puncture is another critical procedure to the original cranial ultrasound.1 to do as soon as the neonate is clinically stable in order to Neonatal seizures are classified into four types: clonic, rule out meningitis. Both hypoglycemia and meningitis are tonic, myoclonic, and subtle (more common in the prema- dangerous but very treatable causes of neonatal seizures.1,12 ture neonate; Table 2). Volpe notes that “a seizure is defined Sepsis should never be overlooked as a cause of neonatal clinically as a paroxysmal alteration in neurologic function, seizures. Systemic infections can cause seizures because of that is behavioral, motor or autonomic function” and is a man- the complications of shock, coagulopathy, hypoxia, and mul- ifestation of an underlying disorder rather than being an iso- tisystem organ failure. Appropriate cultures to be obtained lated disorder.1(p211) Simultaneous EEG and video recording include blood, urine, cerebrospinal fluid (CSF), and tracheal allows the practitioner to evaluate difficult-to-assess subtle aspirate. CSF should be examined for red blood cells and behaviors, apnea, bradycardia, jerks, and twitches commonly white blood cells, organisms by Gram stain, glucose, and seen in the preterm neonate who has seizures.1 N EONATAL N ETWORK 240 JULY/AUGUST 2015, VOL. 34, NO. 4 NN34-4_Final_A6_239-244.indd 240 6/17/15 1:48 PM TABLE 2 n Traditional Categorization of Neonatal Seizures Classification/Types Clinical Manifestations Definition/Description Clonic Rhythmic jerks (1–3/s) Focal: well localized to a body part Focal clonic Rate slows during seizure Multifocal: several body parts jerking Multifocal clonic 1 Electroencephalogram (EEG) seizure activity simultaneously or in migrating order Tonic Characterized by posturing Focal: continued posturing of limb or a Focal tonic Focal: 1 EEG seizure activity posturing (asymmetric) of trunk or neck Generalized tonic Generalized: usually no EEG seizure activity Generalized: extension of lower limbs with either upper limb extension (looks like decerebrate posturing) or upper limb flexion (looks like decorticate posturing) Myoclonic Faster jerking than in clonic seizures Focal: flexor jerking of upper limbs Focal myoclonic Flexor muscles (limbs) involved Generalized: bilateral jerking of upper Generalized myoclonic Focal: usually no EEG seizure activity extremities; sometimes lower limbs are involved; often single or irregular jerks Generalized: 1 EEG seizure activity Subtle (more common in the premature infant) Abnormal behavioral, autonomic, or motor Ocular: nystagmus, horizontal or vertical activities that do not result from the other deviation of eyes, staring episodes, eyelid three seizure classifications flutter or blinking 1 EEG seizure activity with only some of the Facial: repetitive sucking, mouth movements, seizure activities tongue protrusion, chewing, drooling Limb: bicycling, swimming movements, “boxing” or “hooking” motions, stepping
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