Asphyxia HypoxiaIschemia Definition Umbilical artery PH7 5 min

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

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. 2

Co gas intoxication 3

Spinal anesthesia 4

preeclampsia 5

Hypoventilation in general anesthesia 6

Abruptio placenta 7

Cord compression 8

umbilical cord knot 9

Spinal anesthesia 10

Maternal hypotension 11

Umbilical cord knot 12

Nuchal cord 13

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. ) 14

factor stage 1 stage 2 stage 3 pupils mydriasis myosis Unequal, poor light reflex consciousness hyperalert lethargic Stuporous, coma DTR/ clonus Hyperactive hyperactive absent myoclonus 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 <24 hr to-14 days Days to weeks outcome 15 Good Variable Death, severe deficit

Burst suppression 16

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 17 enzyme

Intracranial hemorrhage 18

NEC 19

Adrenal hemorrhage 20

Subcutaneous fat necrosis 21

RDS 22

Subcutaneous fat necrosis 23

Subcutaneous fat necrosis 24

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. 25

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) 26

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. 27

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

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

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. 30

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 24 -48 hr of birth. 31

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.

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 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/ m. L. 33

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

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 1 st 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. 35

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. 36

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 1 st 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. 37

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%. 38

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≥ 5 days postnatal age( term infants) (Michigan manual of NICU) 39

Brain death after neonatal HIE is diagnosed by the clinical findings of coma unresponsive to pain, auditory, or visual stimulation; apnea with PC 02 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. 40

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 – NH 3 – 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 41

Local cranial hypothermia 42 a EEG