Definition:Umbilical artery PH<75min apgar <3Multiple organ dysfunctionHypoxic ischemic encephalopathy

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Asphyxia(Hypoxia-Ischemia)

Fetal hypoxiaFetal hypoxia

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may be caused by various disorders in the mother, may be caused by various disorders in the mother, including including

(1) (1) inadequate oxygenation of maternal blood inadequate oxygenation of maternal blood from from hypoventilation during anesthesia, cyanotic heart hypoventilation during anesthesia, cyanotic heart disease, respiratory failure, or carbon monoxide disease, respiratory failure, or carbon monoxide poisoning;poisoning;

(2) (2) low maternal blood pressure low maternal blood pressure from acute blood loss, from acute blood loss, spinal anesthesia, or compression of the vena cava and spinal anesthesia, or compression of the vena cava and aorta by the gravid uterus;aorta by the gravid uterus;

(3) (3) inadequate relaxation of the uterus inadequate relaxation of the uterus to permit to permit placental filling asplacental filling as

a result of uterine tetany caused by the administration of a result of uterine tetany caused by the administration of excessiveexcessive

oxytocin;oxytocin; (4) (4) premature separation of the placentapremature separation of the placenta;; ((5)impedance to the circulation of blood through 5)impedance to the circulation of blood through

the umbilical cordthe umbilical cordas a result of compression or knotting of the cord; and as a result of compression or knotting of the cord; and (6) (6) Placental insufficiency Placental insufficiency from toxemia or postmaturity.from toxemia or postmaturity.

Co gas intoxicationCo gas intoxication

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Spinal anesthesiaSpinal anesthesia

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preeclampsiapreeclampsia

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HypoventilationHypoventilation in general in general anesthesiaanesthesia

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Abruptio placentaAbruptio placenta

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Cord compressionCord compression

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umbilical cord knotumbilical cord knot

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Spinal anesthesiaSpinal anesthesia

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Maternal hypotensionMaternal hypotension

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Umbilical cord knotUmbilical cord knot

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Nuchal cordNuchal cord

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After birthAfter birth

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hypoxia may be caused by (1)failure of oxygenation (severe forms of CHD

or severe pulmonary disease)(2) anemia severe enough to lower the oxygen

content of the blood (severe hemorrhage, hemolytic disease);

(3) shock severe enough to interfere with the transport of oxygen to vital organs (from overwhelming sepsis,

massive blood loss, and intracranial or adrenal hemorrhage.)

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factor stage1 stage2 stage3

pupils mydriasis myosis Unequal, poor light reflex

consciousness hyperalert lethargic Stuporous, coma

DTR/ clonus Hyperactive hyperactive absent

myoclonus present present absent

EEG normal Low voltage changing to seizure activity

Burst suppresion to isoelectric

posture Normal flexion decerebrate

Muscle tone Normal Hypotonic flaccid

Moro reflex Strong Weak absent

seizure None common decerebration

duration <24hr 24hr to-14days Days to weeks

outcome Good Variable Death, severe deficit

Burst suppressionBurst suppression

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Organ injury during asphyxia

Central nervous system: hypoxic ischemic encephalopathy, infarction, ICH, seizure, cerebral edema, hypertonia, hypotonia.

Cardiovascular system: myocardial ischemia, poor contractility, cardiac stun, tricuspid insufficiency, hypotension.

Respiratory system: pulmonary hypertension, pulmonary hemorrhage, respiratory distress syndrome.

Gastrointestinal system: ulceration with hemorrhage, necrosis, perforation.

Adrenal: adrenal hemorrhage

Kidney: acute tubular or cortical necrosis

Skin: subcutaneous fat necrosis

Metabolic : SIADH, hyponatremia, hypo/hyperglycemia, hypocalcemia, myoglobinuria, hyperammonemia, hyperuricemia,

hyperkalemia, elevated liver enzyme

Hematology : disseminated intravascular coagulation – transient left shift (NRBC)

Intracranial hemorrhageIntracranial hemorrhage

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NECNEC

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Adrenal hemorrhageAdrenal hemorrhage

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Subcutaneous fat Subcutaneous fat necrosisnecrosis

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RDSRDS

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Subcutaneous fat Subcutaneous fat necrosisnecrosis

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Subcutaneous fat Subcutaneous fat necrosisnecrosis

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PATHOPHYSIOLOGYPATHOPHYSIOLOGYAnimal studies suggest that hypoxia will not cause lethal brain injury without ischemia. The topography of injury typically correlates to areas of decreased cerebral blood flow. After an episode of hypoxia and ischemia, anaerobic metabolism occurs, which generates increased amounts of lactate and inorganic phosphates. Excitatory and toxic amino acids, particularly glutamate, accumulate in the damaged tissue. Increased amounts of intracellular Na+ and Ca++ may result in tissue swelling and cerebral edema. There is also increased production of free radicals and nitric oxide and free iron in these tissues.

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PATHOPHYSIOLOGYPATHOPHYSIOLOGYThe initial circulatory response of the fetus is increased shunting through the ductus venosus, ductus arteriosus, and foramen ovale, with transient maintenance of perfusion of the brain, heart, and adrenals in preference to the lungs, liver, kidneys, and intestine) Diving reflex).

*During prolonged partial asphyxia this redistribution of available cardiac output to more vital organs happens. (Michigan manual of NICU)

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PATHOLOGYPATHOLOGY

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The pathology of hypoxia-ischemia is dependent on the affected organ and the severity of the injury. Early congestion, fluid leak from increased capillary permeability, and endothelial cell swelling may then lead to signs of coagulation necrosis and cell death. Congestion and petechiae are seen in the pericardium, pleura, thymus, heart, adrenals, and meninges. Prolonged intrauterine hypoxia may result in inadequate perfusion of the peri ventricular white matter, resulting, in turn, in PVL.

Pulmonary arteriole smooth muscle hyperplasia may develop, which predisposes the infant to pulmonary hypertension .

If fetal distress produces gasping, the amniotic fluid contents (meconium, squames, lanugo) are aspirated into the trachea or lungs.

The combination of chronic fetal hypoxia and acute hypoxic ischemic injury after birth results in gestational age-specific neuropathology .

NEUROPATHOLOGYNEUROPATHOLOGY

Preterm infantsPreterm infants Term infantsTerm infants

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PVL (later, spastic diplegia),

status marmoratus of the basal ganglia,

and IVH.

neuronal necrosis of the cortex

→cortical atrophyand parasagittal

ischemic injury.Proximal limb

weakness Upper extremities

affected more than lower extremities.

IUGRIUGR with increased vascular resistance may be the

1st indication of fetal hypoxia. During labor,

the fetal heart rate slowsthe fetal heart rate slows,, and

beat-to-beatbeat-to-beat variability variability declines.declines.

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Clinical manifestations Clinical manifestations before birthbefore birth

preventionprevention

Particularly in infants near term, these signs should lead to the administration of high concentrations of oxygen to the mother and immediate delivery to avoid fetal death or CNS damage.

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1-the presence of yellow, meconium-stained amniotic fluid is evidence that fetal distress

has occurred. 2-these infants are frequently depressed and

fail to breathe spontaneously. (Delayed crying).

3-During the ensuing hours, they may remain hypotonic or change from hypotonic to

hypertonic, or their tone may appear normal .4- low Apgar score and need for CPR at birth.

5- pale – cyanotic 6- seizure during the first 24-48 hr of birth.

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Clinical manifestations at Clinical manifestations at birthbirth

Symptoms developSymptoms develop over a series of days, over a series of days, making it important to perform making it important to perform serial neurological examinations.

During the initial hoursDuring the initial hours after an insult, infants after an insult, infants have a depressed level of consciousness.have a depressed level of consciousness. Periodic breathing with apnea or bradycardia is Periodic breathing with apnea or bradycardia is present, butpresent, but cranial nerve functions are often cranial nerve functions are often spared with intact pupillaryspared with intact pupillary responses and responses and spontaneous eye movement. Seizures are spontaneous eye movement. Seizures are commoncommon with extensive injury. Hypotonia is also with extensive injury. Hypotonia is also common as an earlycommon as an early manifestation.manifestation.

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SeizureSeizure

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phenobarbital the drug of choice, is given with an intravenous loading dose (20 mg/kg); additional doses of 5-10 mg/kg (up to 40-50 mg/kg total) may be needed.

Phenytoin (20 mg/kg loading dose) or lorazepam (0.1 mg/kg) may be needed for refractory seizures.

Phenobarbital levels should be monitored 24 hr after the loading dose and maintenance therapy (5 mg/kg/24 hr) are begun.

Therapeutic phenobarbital levels are 20-40 μg/ mL .

Other organs:Other organs:

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heart failure and cardiogenic shock,

persistent pulmonary hypertension,

respiratory distress syndrome, gastrointestinal perforation, hematuria, and Acute tubular necrosis

IMAGINGIMAGING

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Ultrasound Ultrasound has limited utility in evaluation of hypoxic

injury in the term infant; it is the preferred modality in evaluation of the preterm infant.

CT scansCT scans are helpful in identification of focal

hemorrhagic lesions, diffuse cortical injury, and damage to the basal ganglia; CT has limited ability to identify cortical injury within the 1st few days of life.

Diffusion-weighedDiffusion-weighed MRIMRI is the preferred imaging modality because of

its increased sensitivity and specificity early in the process and its ability to outline the topography of the lesion.

PROGNOSISPROGNOSIS

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The outcome of HIE correlates to the timing andThe outcome of HIE correlates to the timing and severity of the insult and ranges from complete severity of the insult and ranges from complete recovery to death.recovery to death. The prognosis varies The prognosis varies depending on whether the metabolic anddepending on whether the metabolic and cardiopulmonary complications (hypoxia, cardiopulmonary complications (hypoxia, hypoglycemia, shock)hypoglycemia, shock) are treated, the infant's are treated, the infant's gestational age gestational age (outcome is poorest if the(outcome is poorest if the infant infant is preterm),is preterm), and the severity of the and the severity of the encephalopathy.encephalopathy.

SevereSevere encephalopathy, characterized by flaccid encephalopathy, characterized by flaccid coma,coma, apnea, absent oculocephalic reflexes, and apnea, absent oculocephalic reflexes, and refractory seizures, isrefractory seizures, is associated with a poor associated with a poor prognosis. A low Apgar score at 20 min,prognosis. A low Apgar score at 20 min, absence absence of spontaneous respirations at 20 min of age, and of spontaneous respirations at 20 min of age, and persistencepersistence of abnormal neurologic signs at 2 wk of abnormal neurologic signs at 2 wk of age also predictof age also predict death or severe cognitive and death or severe cognitive and motor deficits. motor deficits.

PROGNOSISPROGNOSIS

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The combined use of an early electroencephalogram (EEG) and MRI is useful in predicting outcome in term infants with HIE.

Normal MRI and EEG findings are associated with a good recovery, whereas severe MRI and EEG abnormalities predict a poor outcome. Infants with stage 2 and 3 encephalopathy are at the highest risk for adverse outcome.

Microcephaly and poor head growth Microcephaly and poor head growth during the 1st year of life also correlate with injury to the basal ganglia and white matter and adverse developmental outcome at 12 mo.

All survivors of moderate to severe encephalopathy require comprehensive high-risk medical and developmental follow-up ) including BAEPs )Early identification of neurodevelopmental problems allows prompt referral for developmental, rehabilitative, neurologic care, and early intervention services so that the best possible outcome can be achieved.

PrognosisPrognosis

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The degree of maturity at birth is an important predictor of mortality in infants asphyxiated at birth.

Metabolic acidosis is a bad prognostic factor as compared with respiratory acidosis.

Extended Apgar score is a reliable predictor of ultimate neurologic morbidity, especially when very low scores are obtained at 20 minutes.

The time from birth until onset of spontaneous, sustained respirations is correlated with long term neurologic function. data suggests that a prolonged delay in the initiation of spontaneous respirations is a reasonable indicator of irreversible brain damage.

For infants with severe HIE the outcome is far worse, varying from a 50% to 100% mortality rate to severe disability with an average incidence of 65% to 75%.

PrognosisPrognosis

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Infants may be at higher risk for Infants may be at higher risk for neurodevelopmental sequelae if:neurodevelopmental sequelae if:

1-apgar score ≤3 at≥ 20 minutes2- seizures are difficult to control3-EEG shows burst suppression pattern4-severe, protracted oliguria or renal

failure is seen5-the infant has an abnormal neurologic

examination at≥5days postnatal age( term infants)

(Michigan manual of NICU)(Michigan manual of NICU)

Brain deathBrain death

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after neonatal HIE is diagnosed by the clinical findings of coma unresponsive to pain, auditory, or visual stimulation; apnea with PC02 rising from 40 to over 60 mm Hg without ventilatory support; and absent brainstem reflexes (pupil, oculocephalic, oculovestibular, corneal, gag, sucking).These findings must occur in the absence of hypothermia, hypotension, and elevated levels of depressant drugs (phenobarbital).

An absence of cerebral blood flow on radionuclide scans and no electrical activity on EEG (electrocerebral silence) is inconsistently observed in clinically brain-dead neonatal infants.

Persistence of the clinical criteria for 2 days in term and 3 days in preterm infants predicts brain death in most asphyxiated newborns.

Nonetheless, no universal agreement has been reached regarding the definition of neonatal brain death. Consideration of withdrawal of life support should include discussions with the family, the health care team, and, if there is disagreement, an ethics committee.

medical orders for asphyxiamedical orders for asphyxia

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1- NPO (risk of NEC)2- Restriction of intravenous fluid3- CBC – Retic – NRBC – Na – K – BUN – Cr – Bs –

Ca – P – uric acid – ABG – PT – NH3 – SGOT – SGPT – Alb – Total protein – LP→ (L/P ratio)*

4- Brain sonography – CT scan – MRI5- EEG / a EEG6- Local cranial hypothermia – allopurinol -

nicardipine – Phenobarbital7- control for seizure8- control I/O9- daily weight10- control brain edema* lactate/ pyruvate

Local cranial hypothermiaLocal cranial hypothermia a EEGa EEG

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