Hypoxic-Ischemic Encephalopathy Medication

  • Author: Santina A Zanelli, MD; Chief Editor: Ted Rosenkrantz, MD   more...
 
Updated: Dec 15, 2011
 

Medication Summary

Providing standard intensive care support, correcting metabolic acidosis, close monitoring of the fluid status, and seizure control are the main elements of treatment in patients with hypoxic-ischemic encephalopathy (HIE). Anticonvulsants are the only specific drugs used often in this condition.

Treat seizures early and control them as fully as possible. Even asymptomatic seizures (ie, seen only on EEG) may continue to injure the brain.

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Anticonvulsants

Class Summary

These agents are used to control seizures.

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Phenobarbital (Luminal)

 

DOC when clinical or EEG seizures are noted; is continued on the basis of both EEG findings and clinical status. In most cases, can be weaned and stopped during the first month of life; however, treatment is continued for several months to 1 year in infants with persistent neurological abnormalities and clinical or EEG evidence of seizures; EEG and clinical status should guide decision. In high doses, has been used prophylactically by a few researchers, but its efficacy has not been established. In infants who are heavily sedated or paralyzed, phenobarbital may be used prophylactically at standard dose.

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Phenytoin (Dilantin)

 

Usually the third DOC in neonatal seizures; may be used in patients with seizures that do not respond to phenobarbital or lorazepam. Oral absorption is negligible for the first several months of life.

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Lorazepam (Ativan)

 

Second DOC for acute control of seizures refractory to phenobarbital.

By increasing the action of GABA, which is a major inhibitory neurotransmitter in the brain, may depress all levels of CNS, including limbic and reticular formation.

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Cardiovascular (Inotropic) Agents

Class Summary

These agents increase blood pressure (BP) and combat shock. Drugs in this category act primarily by increasing systemic vascular resistance, cardiac contractility, and stroke volume, thus increasing cardiac output.

Most inotropic agents also have dose and gestational age-dependent effects on vessels, particularly those of the renal and GI systems. For the most part, these effects are beneficial but, at higher doses, the systemic side effects may be unpredictable.

In experimental animals, cerebral blood flow (CBF) is unaffected by these drugs when used in recommended therapeutic doses. However, no clear information is available on the effects of these drugs on CBF in neonates.

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Dopamine (Intropin)

 

Stimulates both adrenergic and dopaminergic receptors. Hemodynamic effect is dependent on the dose. Lower doses predominantly stimulate dopaminergic receptors that in turn produce renal and mesenteric vasodilation. Cardiac stimulation and renal vasodilation produced by higher doses.

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Dobutamine (Dobutrex)

 

Second inotropic DOC, preferred by some as first choice in severe cardiogenic shock.

Produces vasodilation and increases inotropic state. At higher dosages may cause increased heart rate, exacerbating myocardial ischemia.

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Contributor Information and Disclosures
Author

Santina A Zanelli, MD  Assistant Professor, Department of Pediatrics, Division of Neonatology, University of Virginia Health System

Santina A Zanelli, MD is a member of the following medical societies: American Academy of Pediatrics, Society for Neuroscience, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Coauthor(s)

Dirk P Stanley, MD  Resident Physician, Department of Pathology, University of Virginia Health System

Disclosure: Nothing to disclose.

David A Kaufman  MD, Associate Professor of Pediatrics, Division of Neonatology, University of Virginia Health System

David A Kaufman is a member of the following medical societies: American Academy of Pediatrics, European Society for Paediatric Infectious Diseases, Medical Society of Virginia, Pediatric Infectious Diseases Society, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Specialty Editor Board

Ted Rosenkrantz, MD  Professor, Departments of Pediatrics and Obstetrics/Gynecology, Division of Neonatal-Perinatal Medicine, University of Connecticut School of Medicine

Ted Rosenkrantz, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Pediatric Society, Connecticut State Medical Society, Eastern Society for Pediatric Research, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Brian S Carter, MD, FAAP  Professor of Pediatrics (Neonatology), Vanderbilt University School of Medicine; Director, Neonatal Follow-up Program, Monroe Carell Jr Children's Hospital at Vanderbilt

Brian S Carter, MD, FAAP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Hospice and Palliative Medicine, American Academy of Pediatrics, American Society for Bioethics and Humanities, American Society of Law, Medicine & Ethics, National Hospice and Palliative Care Organization, Society for Pediatric Research, and Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Carol L Wagner, MD  Professor of Pediatrics, Medical University of South Carolina

Carol L Wagner, MD is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American Medical Women's Association, American Public Health Association, American Society for Bone and Mineral Research, American Society for Clinical Nutrition, Massachusetts Medical Society, National Perinatal Association, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Chief Editor

Ted Rosenkrantz, MD  Professor, Departments of Pediatrics and Obstetrics/Gynecology, Division of Neonatal-Perinatal Medicine, University of Connecticut School of Medicine

Ted Rosenkrantz, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Pediatric Society, Connecticut State Medical Society, Eastern Society for Pediatric Research, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Tonse NK Raju, MD, to the development and writing of this article.

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Fetal response to asphyxia illustrating the initial redistribution of blood flow to vital organs. With prolonged asphyxial insult and failure of compensatory mechanisms, cerebral blood flow falls, leading to ischemic brain injury.
Pathophysiology of hypoxic-ischemic brain injury in the developing brain. During the initial phase of energy failure, glutamate mediated excitotoxicity and Na+/K+ ATPase failure lead to necrotic cell death. After transient recovery of cerebral energy metabolism, a secondary phase of apoptotic neuronal death occurs. ROS = Reactive oxygen species.
Risk factors for neonatal encephalopathy.
Severe acute hypoxic-ischemic neuronal change in the basal ganglia is noted. Histologic examination reveals severe hypoxic-ischemic neuronal change, characterized by the presence of pyknotic and hyperchromatic nuclei, the loss of cytoplasmic Nissl substance, and neuronal shrinkage and angulation (arrow). These alterations begin to appear approximately 6 hours following hypoxic-ischemic insult. Reactive astrocytosis is evident approximately 24-48 hours after the primary hypoxic-ischemic event.
Significant astrocytosis in the basal ganglia following hypoxic-ischemic insult is observed. An immunohistochemical stain for glial fibrillary acidic protein (GFAP) was performed on the same tissue shown in the previous image to demonstrate the prominent gliosis secondary to the hypoxic-ischemic event. GFAP is a useful marker to study astrocytic response to injury. This gliosis of the basal ganglia, along with subsequent hypermyelination, is responsible for the evolution of status marmoratus over months to years.
Bilateral acute infarctions of the frontal lobe are shown. The infarctions depicted in the figure (arrows) are consistent with watershed infarctions secondary to global hypoperfusion. The lesions depicted in the image are consistent with an acute ischemic event, occurring within 24 hours of death. The regions most susceptible to hypoperfusion include the end-artery zones between the anterior, middle, and posterior cerebral arteries.
A prior hypoxic-ischemic event involving the occipital lobe has resulted in a chronic lesion marked by dyslamination, neuronal loss, and disorganized arrangements of myelinated white matter fibers. Grossly, the lesion was marked by preserved gyral crests and involved sulci, resulting in prominent, mushroom-shaped gyri.
A Luxol-Fast Blue stain was performed on the same tissue shown in the previous image to demonstrate the haphazard arrangement of myelinated white matter fibers projecting into the gray matter of the occipital cortex.
Randomized controlled trials of therapeutic hypothermia for moderate-to-severe hypoxic-ischemic encephalopathy (HIE).
Periventricular leukomalacia is depicted. This cystic lesion, present in the cingulate cortex, is consistent with periventricular leukomalacia. Note the extensive hemorrhage within the cystic space as well as the hemosiderin-laden macrophages around the lesional rim.
Periventricular leukomalacia is depicted. This figure depicts the lesion seen in the previous image at higher magnification. Extensive hemosiderin and reactive astrocytosis is present surrounding the lesion (center of field). Note the proximity of the lesion to the ependymal lining of the lateral ventricle (far right).
Summary of potential neuroprotective strategies.
Table. Sarnat Clinical Stages of Perinatal Hypoxic Ischemic Brain Injury[28]
State 1Stage 2Stage 3
Level of ConsciousnessHyperalertLethargic or obtundedStuporous
Neuromuscular Control
Muscle toneNormalMild hypotoniaFlaccid
PostureMild distal flexionStrong distal flexionIntermittent decerebration
Stretch reflexesOveractiveOveractiveDecreased or absent
Segmental myoclonusPresentPresentAbsent
Complex Reflexes
SuckWeakWeak or absentAbsent
MoroStrong; low thresholdWeak; incomplete; high thresholdAbsent
OculovestibularNormalOveractiveWeak or absent
Tonic neckSlightStrongAbsent
Autonomic FunctionGeneralized sympatheticGeneralized parasympatheticBoth systems depressed
PupilsMydriasisMiosisVariable; often unequal; poor light reflex
Heart RateTachycardiaBradycardiaVariable
Bronchial and Salivary SecretionsSparseProfuseVariable
GI MotilityNormal or decreasedIncreased; diarrheaVariable
SeizuresNoneCommon; focal or multifocalUncommon (excluding decerebration)
EEG FindingsNormal (awake)Early: low-voltage continuous delta and theta



Later: periodic pattern (awake)



Seizures: focal 1-to 1-Hz spike-and-wave



Early: periodic pattern with Isopotential phases



Later: totally isopotential



Duration1-3 days2-14Hours to weeks
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