Perinatal Asphyxia Perinatal Asphyxia Etiology of Perinatal by mikeholy

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									                                                                                                Perinatal Asphyxia
              Perinatal Asphyxia
                                                                                        P. Asphyxia
                                                                                           – Impaired gas exchange leading to hypoxemia,
                                                                                             hypercapnia, and acidosis in fetus or neonate
                                                                                        Neonatal depression
                                                                                           – Prolonged transition (from intrauterine to
                                                                                             extrauterine)
                                                                                           – Have low 1-5 minutes Apgars
                                                                                           – No neurobehavioral changes
                                                                                        Hypoxic – Ischaemic Encephalopathy
                                                                                           – Abnormal neurobehavioral status
                                                                                              • Due to impaired cerebral blood flow
           Manjeet Kaur, MD, DCH, FAAP, FRCP                                               – Decreased level of consciousness
         Lancaster General Women & Babies Hospital




      Etiology of Perinatal Asphyxia                                                            Cord PH and Acidemia

Incidence – 1 to1.5% live births                                                        • Traditionally asphyxia was defined as cord
Risk Factors:                                                                             umbilical artery PH<7.2 (5-20%) del)
   – Maternal factors
       • Hypertension, infection, diabetes, vascular, pulmonary, cardiac disease etc.   • Evidence suggests risk of neurologic sequaelae
   – Placental Factors                                                                    increased when cord umbilical artery PH <7.0
       • Abruption
   – Cord Accidents
                                                                                          (3% del)
       • Compression, prolapse, entanglement                                            • In a study – (Pearlman) 8/47 (17%) with PH
   – Fetal factors
       • Anemia, hydrops, infection
                                                                                          <7.0 developed neurologic sequaelae
   – Neonatal                                                                           • In another study base deficit in term infants >14
       • CHD, PPHN, Cardiomyopathy
                                                                                          – moderate to severe neurologic sequaelae
* 90% asphyxia events occur in antepartum or intrapartum period




                                                                                                             Systemic Organ Involvement Following

                      Pathophysiology

    • ↓ Blood flow to placenta
    • ↓ Oxygen delivery to fetus
    • ↑ O2 consumption by mother/fetus
    Brief Asphyxia
    • Transient ↑ and then ↓HR
    • Mild ↑ blood pressure
    • ↑ Central venous pressure
    • No change in cardiac output
    • Diving reflex - ↑ proportion to brain, heart, adrenals
      (50 – 500%)




                                                                                                                                                    1
      Sequence of Events in Prolonged Asphxia                                         Factors Impairing Autoregulation of CBF

     Asphyxia                                      Decreased CO/Decreased BP
                                                                                                    Hypercarbia → Vasodilation → increased CBF
(↓PaO2, ↑ PaCO2, ↓pH)        ↓ CBF (loss of cerebral autoreg)                      1. CO2           Hypocarbia → Vasoconstriction → decreased CBF
                                    Anaerobic metabolism
                                    ↑ Lactic acid (acidosis)                                        Hypoxia → Neuronal damage
                            ↓ Glucose + ATP (cellular energy failure)
                                                                                   2. Oxygen        Hyperoxia → Vasoconstriction → decreased CBF

                            Failure of intracellular ion pumps
                                                                                                    Vasoparalysis → pressure passive system for CBF results in
                                       ↑ Na, Cl, Ca, H20                           3. HIE           hyperemia and congestion
                             ↑ Na = cell swelling (cytotoxic edema)
                           ↑ Ca = ↑ neuronal transmitters- glutamate,                               Hypoglycemia → increased CBF
                                            ↑ free radicals                        4. Glucose       *hyperglycemia → increased lactates → aggravate neuronal injury
                          Free fatty acid release and lipid peroxidation
                                                                                                    → increased CBF, increased oxygen free radicals and excitatory
                         Disrupt cell membrane and metabolism                      5. Hyperthemia   amino acids
                               Irreversible neuronal injury
                          Apoptosis = delayed cell death – 8-72 hours              6. Seizures      Vasodilation → increased CBF
  *Immature neurons and white matter is very vulnerable




                            Pathophysiology                                                      Basal Nuclei (Ganglia)

         A.       Profound Asphyxia:
              •      eg placental abruption, cord prolapse, uterine rupture
              •      Neurons – mature and functional – more vulnerable
              •      Mature neurons in central gray matter of basal ganglia
                     (putamen, globus, pallidum, caudate, thalamus, brainstem
                     and pre & post cerebral or Rolandic gyri – motor strip of
                     brain
                  Acute Profound Injury:
              •      Seen as edema
              •      24 hours after the event - peak at 72 hours resolved by the
                     end of day 5
              •      Edema resolves – damaged tissue left → mineralization →
                     increased density




                    Cerebrum: Lateral Views                                                         Acute Profound Injury
                                                                                                          MRI –T2 Imaging




                                                                                       3 Day Old




                                                                                                                                                                      2
                       Partial Prolonged Asphyxia                                                                                  Partial Prolonged Asphyxia
(nuchal cord, cord compression, placental insufficiency, difficult resuscitation, pneumothorax, apnea & bradycardia )




                                                                                                                            • Seen in 24 hrs as watershed infarction
         • Gradual decrease CBF & Oxygen                                                                                    • Cortex hypodense with edema of white matter
         • Shift of blood – protection of mature                                                                            • Seen in parasaggital areas; frontal & parietal lobes
                                                                                                                               –   (unilat or bilat inspite of global hypoxia)
           neurons                                                                                                          • Increased edema post injury – peak at 72 hours may
                                                                                                                              obliterate most of lat ventricles – resolves by 96 hours
         • Burden on supratentorial distal parts of                                                                         • Seen as mass effect by 6 - 7 days
           cortex “watershed zones” between ant &                                                                           • Injured cortex atrophies – loss of cortex, shrinkage, and
                                                                                                                              calcification, and cystic changes
           middle cerebral artery (CA), (frontal &                                                                          • MRI – DWI most sensitive
           parietal lobe) + between post and middle                                                                            – T2 Loss of signals- brighter due to edema
                                                                                                                               – Left ventricles compressed due to edema
           cerebral artery (parietal & occipital)                                                                              – Later cystic encephalomalacia




                       Partial Prolonged Asphyxia                                                                       Chronic Changes: Partial Prolonged Asphyxia


                                                                                                                        1 Month Old           Axial T1-                              Axial T2-
                                                                                                                                              weighted                               weighted
                             CT                                                        Axial T2-
                                                                                                                                               image                                  image
                                                                                       weighted
                                                                                        image
2 Day Old



                                                                                                                                                  Axial T1-
                                                                                                                                                  weighted
                                                                                                                        4-6 year old               image




      Chronic Injury Following Profound Asphyxia                                                                          Chronic Injury Following Profound Asphyxia
                   T2 Weighted MRI                                                                                                          CT Scan




3 – 7 Year Old                                                                                                               18 Month Old




                                                                                                                                                                                                 3
      Clinical Effects of Asphyxia                                                Clinical Measures of Asphyxia

 • Central Nervous System                                                    1.       FHR Monitoring
                                                                                  –      since 1970’s
     – Sarnat stages of HIE – Stage I to Stage III                                –      Long term sequaelae unaffected
     – Diagnosis – requires abnormal neuro exam on day                       2.       Meconuim Stained Amniotic Fluid (MSAF)
       of birth                                                                   –      10-20% deliveries
     – Other suspicious criteria                                                  –      Most MSAF infants do not have CP
         • Apgars score <3 at >5 min                                         3.       Apgar Score
         • FHR < 60 BPM                                                           –      Persistent low apgar score at 5,10, 20 min
         • Seizures in first 24-48hrs                                                    (despite intense resuscitation) ---- increased morbidity &
                                                                                         mortality
             – 50% seizures not due to asphyxia
                                                                                  –      Low apgar & fetal acidemia ---- increased risk of
         • Antenatal acidosis                                                            encephelopathy
         • Need for PPV > 1 min or first cry after > 5 mins                  4.       Resuscitation
         • EEG – burst suppression, low voltage                                   –      Need for CPR in DR increased abnormal neuro outcome




    Clinical Measures of Asphyxia                                                           Sarnat Stages of HIE
                                                                                                    I Mild                II Moderate                    III Severe
                                                              1. Consciousness                       Irritable           Lethargic/obtunded               Comatosed
                                                              2. Neuromuscular                     Overactive          Decreased Spontaneous            Decreased/Absent
                                                                                                                            Movements                Spontaneous Movements
                  Conclusion                                  3. Tone                                Normal                 Mild hypotonia               Flaccid/ absent
                                                              4. Myoclonus                           Present                    Present                      Absent
 • Constellation of three markers of far                      5. Suck                                 Weak                      Weak                         Absent

   greater value in identifying risk of brain                 6. Moro
                                                              7. ANS
                                                                                               Strong/low Threshold
                                                                                                 Gen. sympathetic
                                                                                                                                Weak
                                                                                                                            Gen. parasymp
                                                                                                                                                             Absent
                                                                                                                                                     Mid often unequal Poor
   injury (340 fold)                                                                                Mydriasis                  Miosis                     Light Reflex
                                                              8. Resp                              Spontaneous            Occasional Apnea               Periodic Apnea
                – 5 minute apgar score of < 5                 9. HR                                Tachycardia               Bradycardia                  Bradycardia
                                                              10. Seizures                            None            Common: Focal/Multifocal            Uncommon
               – Need for DR intubation/CPR                                                                              (6-24hrs of age)                Decerebration

                – Umbilical arterial PH <7.0                  11. EEG                                Normal              Low voltage (early)
                                                                                                                      •Focal/multifocal (later) sz
                                                                                                                                                           Ispotential

                                                                                                                           •Spike & wave
                                                              12. Duration                          < 24 hours                2-14 days                 Hours to weeks
                                                              13. Outcome                         100% normal               80% Normal                      50% die
                                                                                                                       (abnormal if symptoms          50% severe sequealae
                                                                                                                             >5-7 days)




   Other Neurologic Criteria (HIE)                                        Multiorgan Dysfunction - Hypoxia

 Increased Intracranial pressure (>10mm of Hg)                         • Diving reflex – blood to brain, heart & adrenals
  cerebral edema
                                                                        • Seen in 60-80% of term asphyxiated infants
    Peaks at 36-72 hours
    Often represents extensive necrosis                                     – Kidney
                                                                                  • Most common organ effected
 Seizures
                                                                                  • Prox tubule – Acute tubular necrosis
    20-50% (at 6-24 hrs)
                                                                                  • Oliguria, azotemia (transient)
    Seen in Sarnat II, rarely in III
    Subtle tonic, multifocal, clonic, rarely generalized                    – Cardiac
    May present as abrupt change in HR/Resp or BP                                • Transient myocardial ischemic
                                                                                         – EKG - ST depression and T- waves changes
    Seizures –Increased cerebral metabolic rate
      Increased injury                                                                  – ECHO
      May compromise ventilation                                                            » Decreased left ventricle contractibility
                                                                                             » Increased ventricular and diastolic pressure




                                                                                                                                                                              4
             Multiorgan Dysfunction (cont’d)                                                                                                     Lab Evaluation

     • GIT                                                                                                          1.        Renal
           – Increased risk of bowel ischemia and necrotizing enterocolitis
                                                                                                                          –       BUN, Creatinine increase 2-4 days after insult
     • Liver                                                                                                        2.        Liver
           – Increased hepatocellular enzymes due to damage
                                                                                                                          –       LFTS – increased AST, ALT, PT, PTT, Albumin, Bilirubin,
           – DIC                                                                                                                  Ammonia
           – Inadequate glycogen stores - hypoglycemia
                                                                                                                    3.        Cardiac
     • Pulmonary                                                                                                          –       Cardiac enzymes –Increased cardiac Troponin (CTN1)
           – Increased pulmonary vascular resistance                                                                                         »    (In neonates normal 0-0.9)
                 • PPHN, pulmonary hemorrhage, pulmonary edema                                                                   •      Increased serum creatinine kinase
                 • RDS due to surfactant production failure                                                                      •      CKMB > 5% myocardial injury
     • Endocrine                                                                                                    4.        Brain Injury
           – Suppression of parathyroid – hypocalcemia & hypomagnesemia                                                   –       Serum creatinine kinase BB
                                                                                                                                 •      Increased at 12 hrs




                                    Lab Evaluation                                                                                                  Treatment

                                                                                                           •    Neonate
1.     Cranial Sonogram - less useful in assessing edema,                                                      1.    Ventilation
       midline shift, cortical watershed areas and ventricular                                                       1.       Maintain CO2 – Normal Range
       compression.                                                                                                                  Hypercapnia – Cerebral vasodilation + acidosis – uneven/increased CBF
                                                                                                                                     Hypocapnia PCO2 < 25 ---- decreased CBF
2.     CT - useful in determining extent of edema (D2-4)                                                             2.       Maintain Oxygen Levels in Normal Range
3.     MRI - T1&T2 weighted – Best modality for neonatal brain                                                                       Hypoxemia – cell damage
      1.     Diffusion weighted images abnormal within hours – (imp for prognosis)                                                   Hyperoxia – vasoconst ----decreased CBF
                                                                                                                                     ….Increased free oxygen radical damage
      2.     Can not differentiate edema from cell death
                                                                                                               2.    Temperature
4.     MRS – Magnetic Resonance Spectroscopy                                                                                  Maintain normal range – Avoid hyperthermia
      1.     Measure increased lactate (following neonatal hypoxia)                                            3.    Perfusion
      2.     Measures choline and aspartate                                                                                   Maintain adequate BP & adequate cerebral perfusion
5.     EEG – Evaluate seizure activity                                                                         4.    Maintain Metabolic Normalcy
                                                                                                                              Hypocalcemia – decrease cardiac contractility
      1.     Background abnormal activity                                                                                     Hypoglycemia – detrimental to neurons
            1.    Burst suppression                                                                                           Hyperglycemia – increases brain lactate
            2.    Low voltage                                                                                                     1. Cell damage
            3.    Isoelectric                                                                                                     2. Increased edema




                                           Treatment                                                                      Management of Target Organs

      5.     Judicious Fluid Management                                                                             Cardiac
            1.    Avoid overload                                                                                          – Correlation of hypoxemia, acidosis, hypoglycemia
            2.    Inappropriate antidiuretic hormone (SIADH) often seen 3-4days after hypoxic insult
                  1.   Hyponatremia & hypoosmolarity with concentrated urine ( increased S.G., increased
                                                                                                                          – Avoid volume overload
                       osmolarity)                                                                                        – May require inotropes such as dopamine and may need
            3.    Fluid restriction – aids in decreasing cerebral edema                                                     afterload reduction with peripheral B antagonists
      6.     Treat Seizures                                                                                                 (isoproteranol) to maintain BP & perfusion
            1.    Difficult to control                                                                                    – Maintain normal arterial blood pressure
            2.    Controversial use in absence of EEG seizures
                  1.   Phenobarbital – 20mg/kg load IV, if Sz continue additional load of 10-20mg/kg IV.
                                                                                                                          – Monitor CVP – adequate preload, not hypovolemia (Normal:
                        Maintenance: 3-5 mg/kg/d                                                                            5-8 term)
                  2.
                        Therapeutic Levels: 20-40
                       Phenytoin – Added if not controlled - 15 - 20 mg/kg IV.
                                                                                                                    Renal
                        Maintenance:4-8 mg/kg/d                                                                           – Measure urine output, urine SG, Lytes, osmolarity
                        Therapeutic Levels: 15-20                                                                         – Oliguria/anuria – avoid fluid overload –IVF 60 ml/k/d –
                  3.   Benzodiazepine – Lorazepam 0.05 - 0.1 mg/kg/dose                                                     consider low dose dopamine
            3.    Wean anti convulsants –when no Sz clinically and by EEG
                  1.   Phenobarb is tapered over several weeks                                                            – No urine – 10-20ml/kg fluid challenge and furosemide x1
                  2.   If EEG abnormal – continue Phenobarb for 3-6 months




                                                                                                                                                                                                             5
 Management of Target Organs                                       Neuroprotective Strategies

GIT                                                       1. Antagonists of excitatory neurotransmitters:
   – Withhold feeds till good bowel sounds and stools         eg.ketomine
     are heme-negative                                       1. Free Radical Scavengers: Superoxide,
Liver Function Tests                                             dismutase, Vit E
   – Monitor ALT, AST, clotting (PT, PTT & fibrinogen),      2. Calcium Channel Blockers: magnesium
     albumin, bilirubin & ammonia levels                         sulphate nicardipine
Hematologic                                                  3. Cycloxigenase inhibitors: Indomethacin
   – PT, PPT, fibrinogen, platelets                              (not much human newborn data)
   – Abnormalities may need cryoprecipitates/platelets    2. Induced Hypothermia: cold cap/total body
                                                              cooling (ongoing trials)




   Outcome: Perinatal Asphyxia                                   Outcome: Perinatal Asphyxia

                                                            • School
• Sarnat Stage I (Mild)                                         – All Stage I –expected grades at 8 years
                                                                – 65-80% Stage II – expected grades at 8 years
   – 98-100% normal neurological outcome                    • Other Parameters –
                                                                – Apgars < 4 – significant risk with:
• Sarnat Stage II (Moderate)                                         • Math & reading x 3-7 higher risk
                                                                     • Attention deficit disorder x14 higher risk
   – 20-40% die/abnormal neuro outcome                          – Presence of seizures
                                                                     • Seizures for 1day – CP 7%
   – Signs >7 days have poorer outcome                               • Seizures more than 3 day – CP 40%
                                                                – On EEG – extreme persistent burst suppression
• Sarnat Stage III (Severe)                                          • 90-100% poor outcome – death or severe sequelae
                                                            • MRI – Diffuse weighted images (DWI MRI) bet 2-18 days
   – 50-90% die – All survivors have major                      – Normal neuromotor outcome
                                                                – Abnormality of gray matter – worse motor/cognitive outcome
     neurodevelopmental impairment                              – Abnormal basal ganglia - 93% risk of abnormal neurodevelopmental
                                                                  outcome




                                                                                Neonatal Seizures
          Neonatal Seizures
                                                            Seizures
                                                                – Paroxysmal alterations of neurologic function including
                                                                  motor, behavioral, and/or autonomic changes

                                                            Incidence
                                                                – 3 in 1000 term infants
                                                                – 60 in 1000 preterm infants

                                                            Neonatal Brain
                                                                – Immature with transient over expression of excitatory
                                                                  neurotransmitters i.e. glutamate receptors
                                                                – Inhibitory gamma-aminobutyric acid (GABA) ion channels
                                                                  are under expressed
        Manjeet Kaur, MD, DCH, FAAP, FRCP
      Lancaster General Women & Babies Hospital




                                                                                                                                     6
                             Etiology of Seizures                                                                 Etiology of Seizures

Etiology                                                  Incidence (%)
                                                                                          Perinatal hypoxia – Umbilical artery pH <7.0 Base deficit >12
1.Cerebral hypoxia-ischemia                                         -
   a. Global (e.g., perinatal asphyxia)                            40
                                                                                             - Apgar score <5 at 5 mins.
   b. Focal infarction (arterial or venous)                        15                        - MRI studies
2. Intracranial hemorrhage                                         15
3. CNS infection                                                    5
                                                                                             - Most postasphyxial seizures occur in first 24hrs – 50% within first 12hrs
4. Metabolic disease                                                -
   a. Transient                                                     5
   b. Inborn errors of metabolism                                   1                     Focal ischemic injury – Strokes 1 in 4000 live births
5. Cerebral dysgenesis                                              5
6. Neonatal epileptic syndrome                                      1                        - Seizures without known risk factors
7. Neonatal abstinence syndrome                                     1                        - Mostly left middle cerebral artery (MCA)
8. Idiopathic                                                      10
                                                                                             - Thus – right-sided clonic seizures


                                                                                          Cerebral vein thrombosis – more encephalopathic, depressed
                                                                                            mentation prior to seizures




                             Etiology of Seizures                                                                 Etiology of Seizures

                                                                                            CNS Infection
                                                                                                - CMV & Toxoplasmosis – seizure within first 3 days of life
          Intracranial hemorrhage                                                               - Viral - include HSV - seizures within first 3 days of life
          Term – primary subarachnoid hemorrhage or                                             - Bacterial meningitis (GBS & E coli) – seizures in latter part of first week
            subdural hemorrhage (SDH)
                  SDH – large babies, breech, instrumentation – due to                      Metabolic disturbances
                  sheering forces, tears of the tentorium or cortical veins                     - Hypoglycemia – transient i.e. IDM, IUGR, asphyxia
                                                                                                - Inborn errors – hyperinsulinism (Beckwith-Wiedeman Syndrome)
                                                                                                     - galactosemia, glycogen storage
          Premature – seizure within first 3 days in sick
            newborns with IVH                                                                   - Hypocalcemia – 3% of seizures – hypoxia / hypoparathyroidism
                                                                                                     - DeGeorge syndrome (deletion of chromosome 22)
                                                                                                - Hyponatremia – SIADH (inappropriate antidiuretic hormone) / hypoxia
              Seizures after 3 days – periventricular
              hemorrhagic infarction




                                                                                                 Modes of Delivery & Clinical Features
                            Etiology of Seizures
                                                                                             Associated with Neonatal Epidural Hemorrhage
    Pyridoxine Dependency
        Pyridoxine binds to enzyme glutamic acid decarboxylase
        (GAD)
            responsible for conversion of neurotransmitter, glutamate
        to inhibitor – neurotransmitter GABA – In CSF ↓GABA +
            ↑glutamate
               • Impaired GAD--- increase in excitatory activity (increased glutomate –
                 detrimental to neurons)
               • EEG monitoring and i/v pyridoxine administration
    Glycine Encephalopathy (Nonketotic Hyperglycinemia) (AR)
         – High level of glycine in brain CSF
         – Excitatory in brain – myoclonic seizures
         – Inhibitory in brain stem and spinal cord – respiratory disturbances ,
           stupor & hypotonia
         – Die by 1 year of age




                                                                                                                                                                                7
MRI- Term Infant Temporal Lobe Injury at Birth
             (secondary to forceps delivery)
                                                                       Etiology of Seizures

                                                          Folic Acid- Responsive Seizures
                                                             – Questionable etiology – Initially seizures respond to
                                                               phenobarb or pyridoxine and subsequently recur and warrant a
                                                               24-48 hour trial of folic acid
                                                          Cerebral Dysgenesis
                                                             – Lissencephaly (disorder of neuronal migration)
                                                             – Agenesis of the corpus callosum
                                                             – Holoprosencephaly
                                                          Epileptic Syndromes of Newborn
                                                             –   Benign familial neonatal seizures: AD
                                                             –   Onset DOL 2-3 – may recur for days to weeks
                                                             –   Most normal neurodevelopment outcome
                                                             –   10% develop epilepsy




             Etiology of Seizures                                      Etiology of Seizures

  Benign Idiopathic Seizures                              Neonatal Myoclonic Encephalopathy
     – 5% of seizures in term infants – Onset DOL 5          – Partial seizures and massive myoclonus
     – Normal pregnancy and delivery – Apgars >8             – Start as focal motor seizures and progress to
     – Neurological status normal                              infantile spasms
     – Seizures - clonic (never tonic) / apneic              – EEG bursts coincide with massive myoclonus
     – Ictal EEG 1-3 minute seizure                          – Long term outcome poor
     – Questionable transient zinc deficiency (CSF           – High mortality in first year
       zinc level decreased)                                 – Severe mental retardation in survivors
     – Seizures seldom persist >2 weeks                      – Questionably related to nonketotic
     – No development of epilepsy                              hyperglycinemia




               Clinical Diagnosis                                       Clinical Diagnosis

  Subtle Seizures – ½ of all seizures in term             Clonic Seizures
     & preterm                                               – Repetitive fast contraction and slow
     – Tonic eye deviation: roving, nystagmoid                 relaxation
       eye movements, sudden eye opening                     – Unifocal, multifocal or generalized
     – Oro-buccal: sucking, chewing, lip                     – Unifocal clonic – often due to stroke/trauma
       smacking, associated with drooling
                                                             – Multifocal rarely follow a sequential march
     – Epileptic Apnea: bradycardia with initial
       tachycardia                                           – Due to immature brain – unable to propagate
         •   Felt to be nonepileptic “brainstem release        synchronized discharges
             phenomena”




                                                                                                                              8
            Clinical Diagnosis                                         Clinical Diagnosis

                                                         Myclonic Seizures
  Tonic Seizures
                                                           – Lightening fast contractions
    – Sustained muscle contractions without
      repetitive features (generalized/focal)              – Nonrhythmic, multifocal or generalized
    – Generalized may mimic                                – EEG – single high voltage or burst supression
      decerebrate/decorticate posturing (premature           and then slow wave complex later
      with IVH)                                              hypsarrhythmia
    – EEG – no seizure pattern, multifocal or              – Diffuse serious brain dysfunction
      generalized voltage depression very
      abnormal bursts suppressions                         – Poor prognosis
    – Prognosis is poor                                  Seizure Mimics
                                                           – Jitterness, immature, non-nutritive sucking




            Clinical Diagnosis                               Diagnosis – Neonatal Seizures

Seizures
  – Rarely stimulus – sensitive                            EEG
  – Cannot be abolished by passive restraint                 – Repetitive electrical discharges
  – Often associated with autonomic/ocular                   – Record EEG immediately after seizure
    phenomena                                                – If changes captured
  – EEG changes – unless brain stem reflex release               • Continuous video
    phenomena                                                    • EEG monitoring 24-48 hours after last seizure
                                                                 • Repeat EEG in 1 week prognostic and guide for
Epileptic Apnea                                                    discontinuation of meds
  – Rarely last >10-20 seconds                               – Blood glucose , lytes, calcium, magnesium
  – Initial tachycardia common and then bradycardia          – Urine & meconium , drug screen
  – EEG discharges                                           – Imaging: US, CT & MRI




   Treatment of Neonatal Seizures                           Treatment of Neonatal Seizures

  Why Treat Seizures?                                      Reversible Causes
    – Hemodynamic and respiratory disturbances               – Treat hypoglycemia
    – Disrupt cerebral autoregulation –fluctuations in           • Target glucose 70-120 mg/dL
                                                                 • Continuous infusion of up to 8 mg/kg/minute
      BP
                                                                 • Glucagon or hydrocortisone
    – Massive energy consumption
                                                             – Treat hypocalcemia
    – Rapid fall of cerebral glucose, increased brain            • IV 5% calcium gluconate at 2 mL/kg under cardiac
      lactate                                                      monitoring
    – Increased extracellular glutamate (toxic levels)       – Treat hypomagnesemia
    – Disrupt protein & lipid metabolism of                      • IM 50% magnesium sulfate at 0.2mL/kg
      immature neurons                                       – Calcium increases renal magnesium excretion, so Mg
                                                               may be needed in hypocalcemia




                                                                                                                      9
   Treatment of Neonatal Seizures                                    Treatment of Neonatal Seizures

Specific Anticonvulsants                                        Specific Anticonvulsants
  – Phenobarbital                                                  – Benzodiazepines –Lorazepam/Diazepam
     • 20 mg/kg load over 10-15 minutes if seizure persists –          • Diazepam 0.1 mg/kg increase slowly to 0.3 mg/kg IV
       boluses of 5 mg/kg to a total of 40 mg/kg (Th level
                                                                         until seizure stops
       20-40) maintenance dose 12 hours after loading dose
       of 5 mg/kg/d                                                    • Lorazepam –Advantages over Diazepam
                                                                           – 0.05 mg/kg I/V
  – Phenytoin
                                                                           – Onset in 2-3 minutes last 6-24 hours (diazepam lasts minutes,
     • 20 mg/kg slow I/V 1 mg/kg/minute (therapeutic level                   lesser resp. depression)
       15-20)
                                                                           – May repeat dose after several minutes to a total of 0.10 mg/kg
     • Given in normal saline
                                                                       • Midazolam (newest Benzodiazepines)
     • Fosphenytoin prodrug preferred, soluble in dextrose,
                                                                           – I/V 0.02-0.1 mg/kg followed by continuous infusion of 0.01
       safer, faster rate                                                    to 0.06 mg/kg/hr
     • Phenonbarbital and Dilantin control 85% seizures




   Treatment of Neonatal Seizures                               Prognosis of Neonatal Seizures by Etiology

                                                                Etiology                         Normal Outcome (%)
     Pryidoxine
        – I/V 50-100mg – EEG seizures cease                     Hypoxia-ischemia                                 50
          within minutes                                        Meningitis                                       50
        – Maintenance of 10-100 mg/day orally                   Hypoglycemia                                     50
     Folinic Acid                                               Subarachnoid hemorhage                           90
                                                                Early hypocalcemia                              50
        – If fail anticonvulsants & pyridoxine
                                                                Late hypocalcemia                               100
        – Folinic acid 2.5 mg/kg enterally twice
                                                                Intraventricular                                10
          daily x 24-48 hrs                                     hemorrhage
                                                                Cerebral Dysgenesis                               0
                                                                Unknown                                          75




Prognosis of Neonatal Seizures by Etiology

  Prognosis
    – By EEG
        • Severe EEG abnormality, burst supression,
                                                                               Questions??????
          marked voltage supression, adverse neuro
          outcome – 90%
        • Longer seizures on EEG >30 minutes worse
          prognosis
    – By Gestation
        • Seizures <32 week have 80% mortality
        • Significantly compromised neurologic outcome




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