1. Asphyxia (Hypoxia-Ischemia)
Definition:
Umbilical artery PH<7
5min apgar <3
Multiple organ dysfunction
Hypoxic ischemic encephalopathy

2. Fetal hypoxia
may be caused by various disorders in the mother, including
(1) inadequate oxygenation of maternal blood from hypoventilation during anesthesia, cyanotic heart disease, respiratory failure, or carbon monoxide poisoning;
(2) low maternal blood pressure from acute blood loss, spinal anesthesia, or compression of the vena cava and aorta by the gravid uterus;
(3) inadequate relaxation of the uterus to permit placental filling as
a result of uterine tetany caused by the administration of excessive
oxytocin;
(4) premature separation of the placenta;
(5)impedance to the circulation of blood through the umbilical cord
as a result of compression or knotting of the cord; and
(6) Placental insufficiency from toxemia or postmaturity.

3. Co gas intoxication

4. Spinal anesthesia

5. preeclampsia

6. Hypoventilation in general anesthesia

7. Abruptio placenta

8. Cord compression

9. umbilical cord knot

10. Spinal anesthesia

11. Maternal hypotension

12. Umbilical cord knot

13. Nuchal cord

14. After birth 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.)

15. Unequal, poor light reflex
factor
stage1
stage2
stage3
pupils
mydriasis
myosis
Unequal, poor light reflex
consciousness
hyperalert
lethargic
Stuporous, coma
DTR/ clonus
Hyperactive
hyperactive
absent
myoclonus
present
EEG
normal
Low voltage changing to seizure activity
Burst suppresion to isoelectric
posture
Normal
flexion
decerebrate
Muscle tone
Hypotonic
flaccid
Moro reflex
Strong
Weak
seizure
None
common
decerebration
duration
<24hr
24hr to-14days
Days to weeks
outcome
Good
Variable
Death, severe deficit

16. Burst suppression

17. 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)

18. Intracranial hemorrhage

19. NEC

20. Adrenal hemorrhage

21. Subcutaneous fat necrosis

22. RDS

23. Subcutaneous fat necrosis

24. Subcutaneous fat necrosis

25. PATHOPHYSIOLOGY
Animal 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.

26. PATHOPHYSIOLOGY
The 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)

27. PATHOLOGY
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 .

28. NEUROPATHOLOGY PVL (later, spastic diplegia),
Preterm infants
Term infants
PVL (later, spastic diplegia),
status marmoratus of the basal ganglia,
and
IVH.
neuronal necrosis of the cortex
→cortical atrophy
and
parasagittal ischemic injury.
Proximal limb weakness
Upper extremities affected more than lower extremities.

29. Clinical manifestations before birth
IUGR
with increased vascular resistance may be the 1st indication of fetal hypoxia.
During labor,
the fetal heart rate slows,
and
beat-to-beat variability declines.

30. prevention
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.

31. Clinical manifestations at birth
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 hr of birth.

32. Symptoms develop over a series of days, making it important to perform serial neurological examinations.
During the initial hours after an insult, infants have a depressed level of consciousness. Periodic breathing with apnea or bradycardia is present, but cranial nerve functions are often spared with intact pupillary responses and spontaneous eye movement. Seizures are common with extensive injury. Hypotonia is also common as an early manifestation.

33. Seizure
phenobarbital the drug of choice, is given with an intravenous loading dose (20 mg/kg); additional doses of 5-10 mg/kg (up to 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 μg/ mL .

34. Other organs:
heart failure and cardiogenic shock,
persistent pulmonary hypertension,
respiratory distress syndrome,
gastrointestinal perforation,
hematuria, and
Acute tubular necrosis

35. IMAGING
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 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-weighed MRI
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.

36. PROGNOSIS
The outcome of HIE correlates to the timing and severity of the insult and ranges from complete recovery to death. The prognosis varies depending on whether the metabolic and cardiopulmonary complications (hypoxia, hypoglycemia, shock) are treated, the infant's gestational age (outcome is poorest if the infant is preterm), and the severity of the encephalopathy.
Severe encephalopathy, characterized by flaccid coma, apnea, absent oculocephalic reflexes, and refractory seizures, is associated with a poor prognosis. A low Apgar score at 20 min, absence of spontaneous respirations at 20 min of age, and persistence of abnormal neurologic signs at 2 wk of age also predict death or severe cognitive and motor deficits.

37. PROGNOSIS
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 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.

38. Prognosis
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%.

39. Prognosis
Infants may be at higher risk for neurodevelopmental sequelae if:
1-apgar score ≤3 at≥ 20 minutes
2- seizures are difficult to control
3-EEG shows burst suppression pattern
4-severe, protracted oliguria or renal failure is seen
5-the infant has an abnormal neurologic examination at≥5days postnatal age( term infants)
(Michigan manual of NICU)

40. Brain death
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.

41. medical orders for asphyxia
1- NPO (risk of NEC)
2- Restriction of intravenous fluid
3- 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 – MRI
5- EEG / a EEG
6- Local cranial hypothermia – allopurinol - nicardipine – Phenobarbital
7- control for seizure
8- control I/O
9- daily weight
10- control brain edema
* lactate/ pyruvate

42. Local cranial hypothermia
a EEG