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DR MOHD MAGHAYREH PRTH
Definition : The World Health Organization has defined
birth asphyxia as “failure to initiate and sustain breathing at birth” and based on Apgar score as an Apgar score of <7 at one minute of life.
1 -1.5% of live births It is inversely related to gestational age and birth weight It occur in (o.5%(of live born infants with gestational age >36wk It account for 20% of perinatal deaths
Ante partum events (20%)
– – – –
cardiac problem, hemorrhage, diabetes pre eclamptic toxemia,
fetal: IUGR, congenital anomalies
Intrapartum events (35%)
birth trauma, abruption, uterine rupture, uteroplacental insufficiency
Ante partum and Intrapartum (35%) Postpartum events (10%)
1. 2. 3. 4. 5.
apnea, bradycardia, septic shock, pulmonary disease, some CHD (LVOT obstr), PDA (premie
Mechanisms of asphyxia during labor, delivery, and the immediate postpartum period
Interruption of the umbilical circulation (cord compression). Inadequate perfusion of the maternal side of the placenta (maternal hypotension, hypertension, abnormal uterine contractions). Impaired maternal oxygenation (cardiopulmonary disease, anemia). Altered placental gas exchange (placental abruption, previa, insufficiency). Failure of the neonate to accomplish lung inflation and successful transition from fetal to neonatal cardiopulmonary circulation
The essential criteria for diagnosing perinatal asphyxia as outlined by ACOG & AAP are
2. 3. 4.
Prolonged metabolic or mixed acidemia (pH < 7.00) on an umbilical cord arterial blood sample Persistence of an Apgar score of 0-3 for > 5 minutes Clinical neurological manifestations e.g. seizure, hypotonia, coma or hypoxic-ischaemic encephalopathy in the immediate neonatal period Evidence of multiorgan system dysfunction in the immediate neonatal periods
Perinatal asphyxia PATHOPHYSIOLOGY
Insult to the fetus / newborn
Lack of oxygen - hypoxia &/or Lack of perfusion – ischemia
2. Effect of ischemia & hypoxia contribute to tissue injury.
CARDIOVASCULAR RESPONSES TO ASPHYXIA
ASPHYXIA (↓PaO2 ,↑PaCO2, ↓(pH Redistribution of Cardiac Output ↓Renal, Intestinal Blood Flow ↑Cerebral, Coronary, Adrenal Blood Flow
Ongoing Asphyxia ↓Cerebral Blood Flow
)Asphyxia ( continues
Shunting within the brain
Anterior Circulation Suffers
Posterior Circulation Maintained
CEREBRAL CORTICAL LESIONS
Target organs of perinatal asphyxia
Kidneys Brain Heart Lung
50% 28 % 25% 23% < 5%
Liver, Bowel, Bone marrow
ISCHEMIA AND REPERFUSION INJURY
Calcium influx Phospholipase activation Arachidonic acid release
Prostaglandins Vasodilation Reperfusion
At cellular level
Cerebral O2 ↓ Substrate supply ↓ Synaptic inactivation (Reversible) Energy failure Memb. pump failure
Major circulatory changesduring )asphyxia )summary
1. Loss of cerebrovascular autoregulation under conditions of
Hypercapnia, Hypoxemia, Acidosis
2.Cerebral blood flow (CBF) becomes "pressure passive," leaving the infant at risk for 1. cerebral ischemia with systemic hypotension 2. cerebral hemorrhage with systemic hypertension
3. Increase in CBF secondary to
Redistribution of cardiac output. Initial systemic hypertension. Loss of cerebrovascular auto regulation, Focal accumulation of vasodilator factors )H+, K+, adenosine, and prostaglandins).
4. With prolonged asphyxia, there is a
Decrease in cardiac output. Hypotension. Fall in CBF..
A. Cortical changes. Cortical edema, with flattening of cerebral convolutions cortical necrosis cortical atrophy microcephaly. B. Selective neuronal necrosis is the most common type of injury observed in neonatal HIE. C. Other findings seen in term infants include : 1-status marmoratus of the basal ganglia and thalamus 2-parasagittal cerebral injury
D-Periventricular leukomalacia (PVL)
It is hypoxic-ischemic necrosis of peri ventricular white matter resulting from cerebral hypo perfusion and the vulnerability of the oligodendrocyte within th white matter to free radicals, excitotoxin neurotransmitters, and cytokines It is the most significant problem contributing to long-term neurologic deficit in the premature infant, although it does occur in sick full-term infants as well. The incidence of PVL increases with the length of survival and the severity of postnatal cardiorespiratory disturbances
- involving the pyramidal tracts usually results in spastic diplegic or quadriplegic CP. Visuoperception deficits may result from involvement of the optic radiation
E. Porencephaly, hydrocephalus,
hydranencephaly, and multicystic encephalomalacia may follow focal and multifocal ischemic cortical necrosis, PVL, or intraparenchymal hemorrhage. F. Brainstem damage is seen in the most severe cases of hypoxic-ischemic brain injury and results in permanent respiratory impairment
Clinical consequences of perinatal asphyxia
Brain ( Hypoxic Ischemic Encephalopathy, HIE ) Altered sensorium Irritability, lethargy, deeply comatose Tone disturbances :hypotonia of proximal girdle muscles )lack of head control & weakness of shoulder muscle in term infants )
consequences of perinatal ).asphyxia )cont
Brain ( Hypoxic Ischemic
Encephalopathy,HIE ) Autonomic disturbances eg. hypotension, increase salivation, abnormal pupillary reflex Altered neonatal reflexes -Moro’s, sucking , swallowing Seizures
Fetal and neonatal assessment
Fetal Heart rate monitoring
fetal bradycardia repetitive late decelerations of the fetal heart rate, low fetal scalp or cord pH
Passage of Meconium Failure to establish spontaneous
respiration low Apgar Scores
Hypoxic - Ischemic Encephalopathy Multi organ Involvement
Principles of management
Prevent further organ damage
Maintain oxygenation, ventilation & perfusion Correct & maintain normal metabolic & acid base milieu Prompt management of complications
Sarnat staging of hypoxic-ischemic encephalopathy.
Grade 1 (mild) Grade2 (moderate) Grade 3 (severe)
Level of consciousness
Normal or hypertonia
Depressed or absent
Seizures Complex reflexes
High mortality and neurologicl disability
According to Sarnat classification of severity
stage 1 stage 2 stage 3
100 % normal 80 % normal 50 % death 50 % major sequalae
Admit in nursery,if -Apgar score <3 at 1 minute -Babies requiring intubation chest
compressions or medications Nurse in thermo-neutral temperature to maintain skin temperature at 36.5oC Secure IV line , fluids 2/3 rd of maintenance Fluid bolus if CRT > 3 secs or blood pressure low Inj vit k Stomach wash
HR, RR, colour, CRT, O2 saturation, BP & temperature Assessment of neurologic status
Tone, seizures, consciousness, pupillary size & reaction, sucking, swallowing
Abdominal circumference Urine output
Blood gases & pH Bedside blood sugar by Dextrostix Hematocrit S. electrolytes ( Na, K) S. calcium BUN, creatinine
Sepsis screen & blood culture to exclude in-
utero or acquired infection during resuscitation X-ray chest to look for pneumothorax, malformations, cardiac enlargement
Computed tomography )CT) scan
First week after an insult : 2. Cortical neuronal injury 3. Edema The value of CT several weeks after severe asphyxial insults: The assessment of diffuse cortical neuronal injury identification of focal and multiple ischemic brain injury.
Ultrasonography is the method of choice for routine .screening of the premature brain
1-intraventricular hemorrhage 2- necrosis of basal ganglia and thalamus. 3- It is superior to CT in identifying both the acute and subacute-chronic manifestations of periventricular white matter injury.
Ultrasonography limitations in the first weeks
of life include its inability to
Reliably identify mild injury 3. Lesions that are peripherally located 4. Distinguish between hemorrhagic and ischemic lesions in the cerebral parenchyma.
Magnetic resonance imaging )MRI)
the technique of choice for evaluation of hypoxic ischemic cerebral injury in term and premature newborns
The advantages of MRI include the following:
It does not expose the neonate to radiation. better anatomic imaging detail and resolution. It clearly demonstrates the myelinization delay that almost invariably accompanies asphyxial brain injury. MRI may provide insight into the timing and duration of the asphyxial injury..
Magnetic resonance imaging )MRI)
4. MRI is probably the best method available
to diagnose hypoxic brain injuries in mildly to moderately affected patients and to detect discrete lesions of the cerebellum and brainstem. 5. It may provide clues to other disorders (eg, metabolic or neurodegenerative disorders) that may also present as obtundation or coma in the newborn period.
Magnetic resonance imaging )MRI)
6. Ischemic lesions can be identified as early as 24 h after the insult. 7. MRI can help differentiate between partial asphyxia and anoxia 8. MRI demonstrates the structural sequelae of asphyxial injury on follow-up and has prognostic value. Repeat MRI at 3 months of age will usually show the full extent of brain injury.
Evoked electrical potentials
(auditory, visual, or somatosensory) performed within the first hours of life may help to select infants for treatment with neuroprotective agents. They also have prognostic value in defining areas of CNS damage Persistence of deficits beyond the neonatal period correlates with persistence of other signs of brain injury.
Potentially useful techniques
1. Magnetic resonance spectroscopy (MRS) provides a measure of "energy reserve."
Using phosphorus-/(31P) MRS It has been shown that asphyxiated newborns tend to have lower phosphocreatine/inorganic phosphate ratios (impaired brain oxidative phosphorylation) lower ATP/total phosphorus ratios than normal patients. 2. Proton MRS allows noninvasive observations to be made of the derangement of cerebral metabolites (N-acetylaspartate (NAA) and lactic acid) when oxidative phosphorylation is impaired. The normalization of phosphorous metabolite ratios with time may reflect loss of severely affected neurons. Neuronal loss, gliosis, and delay in myelination would be reflected by a relative loss of NAA. 3. Near-infrared spectroscopy on the first day after injury may demonstrate increased cerebral venous oxygen saturation and decreased cerebral oxygen extraction, despite increased cerebral oxygen delivery, suggestive of a postasphyxial decrease in oxygen utilization
1. Evolution of EEG changes may provide
information on the severity of the asphyxial injury, 2. The type of EEG abnormality may be indicative of a specific pathologic variety. 3. Identification of EEG abnormalities within the first hours after delivery may be helpful in selecting infants for treatment with neuroprotective agents
Aims of specific management
Maintain temperature, perfusion, oxygenation,
ventilation & normal metabolic state
Temperature Perfusion: BP CRT Oxygen PaO2 saturation CO2 Glucose Calcium
36.5° C – 37.5° C
Mean 40-60 mm Hg ( Term) maintain < 3 sec 60-80mmHg 90-93 % 35-45 mm of Hg 70-110 mg/dl 9-11 mg/dl
Maintain perfusion Normal blood pressure CRT < 3 secs Normal urine output ( >1ml/kg/hr) Absence of metabolic acidosis
Maintain mean arterial pressure and CRT by giving slow bolus of crystalloid 10 ml/kg over 20 minutes. Repeat one more time , if still does not improve Use vasopressors Dopamine and /or Dobutamine to increase BP Sodium bicarbonate 1-2 ml/kg diluted in 5 % dextrose can be used for babies with documented acidosis after establishing respiration
Oxygenation & ventilation Adequate perfusion Normal glucose & calcium Normal hematocrit Treat seizure
TREATMENT OF SEIZURES
Correction of hypoglycemia, hypocalcemia &
Prophylactic Phenobarbitone ? Therapeutic Phenobarbitone
20 mg / kg (loading), 5 mg / kg / d (maintenance)
Lorazepam – 0.05 – 0.1 mg / kg Diazepam to be avoided
Phenobarbital is the drug of choice. continued until the EEG is normal and there are no clinical seizures for ³2 months. The benefit of prophylactic therapy remains controversial.
Potential new therapies should aim at preventing delayed neuronal death
once an asphyxial insult has occurred.
It is estimated that there is
opportunity after acute asphyxia whereby administration of a
neuroprotective agent could reduce or prevent brain damage.
a 6- to 12-h window of
1. Magnesium has an inhibitory effect on excitation of the N-methyl-D- aspartate type of glutamate receptors competitively blocks Ca2+ entry through voltage-dependent Ca2+ channels during hypoxia SIDE EFFECT Apnea may occur, and Higher doses carry a significant risk of hypotension. Use of magnesium sulfate (MgSO4) remains controversial.
Prevention of free radical formation ))CONTINUE
– – –
. Xanthine oxidase inhibitor. In a pilot study (Van Bel et al, 1998), allopurinol
reduced free radical formation and enhanced electrical brain activity in severely asphyxiated newborns.
addition, allopurinol reduced nonprotein iron ( prooxidant)
Resuscitation with room air. In the Resair 2 trial (Saugstad 2001), room air-resuscitated 1. infants recovered more quickly as assessed by time to first cry, 5-min Apgar score, and sustained pattern of respiration. 2. Neonates resuscitated with 100% oxygen manifest biochemical changes indicative of prolonged oxidative stress at 4 weeks of age (Vento et al, 2001
Potential new therapies should aim at )preventing delayed neuronal death )CONTINUE
3. Excitatory amino acid antagonists. 4. Calcium channel blockers. 5. Inhibition of nitric oxide production. Increased
plasma nitric oxide levels has been shown as a marker for severity of brain injury and poor neurologic outcome )Shi et al, 2000). 6. Selective head cooling. Hypothermia is thought to protect the brain from injury by preventing the decline in high-energy phosphates. Phosphocreatine and adenosine triphosphate are maintained
Predictors of poor neurodevelopmental outcome
Failure to establish resp. by 5 minutes Apgar score of 3 or less at 5 minutes Onset of seizures with in 12 hours Abnormal EEG & failure to normalise by 7
days of life Refractory seizures Stage III HIE Inability to establish oral feeds by 1 wk Abnormal neuro-imaging
Regular antenatal check ups High risk approach Anticipation of complications during labour Timely intervention ( eg. LSCS)
Timely referral Management of maternal complications
There is always more to come!