MANAGEMENT OF ASPHYXIA

1. MANAGEMENT OF
ASPHYXIA
BY
DR OSEZELE OKOENE
SUPERVISED BY DR ALIKA

2. OUTLINE
INTRODUCTION
CLINICAL FEATURES
INVESTIGATIONS
TREATMENT
PROGNOSIS
PREVENTION
CONCLUSION
REFERENCES

3. INTRODUCTION
Anoxia:
- indicates a complete lack of oxygen.
Hypoxia:
- refers to decreased oxygenation to cells or organs.

4. Hypoxaemia:
- Refers to decreased arterial concentration of oxygen
Ischaemia:
 Refers to blood flow to cells or organs that is insufficient
to maintain their normal function.

5. Perinatal asphyxia is a condition of impaired blood gas
exchange that if persistent leads to progressive
hypoxaemia and hypercapnia.

6. Hypoxic–ischemic encephalopathy (HIE) is an important
cause of permanent damage to CNS tissues that may
result in neonatal death or manifest later as cerebral
palsy or developmental delay.

7. Being called to attend the emergent delivery of a term
infant in distress is something many pediatricians or
other medical personal will be required to do.

8. Once an infant is born and resuscitated,‭ often the next
question is ‘‘will the baby be all right’’?‭ It is important
for us as paediatricians to be knowledgeable about and
begin to determine if an infant may have birth asphyxia.

9. Because of uterine contraction during the normal birth
process,‭ all fetuses experience some asphyxia.
It is those fetuses who experience a significant asphyxial
episode that are at risk of developing hypoxic-ischemic
encephalopathy or other end-organ sequelae.

10. The American Academy of Paediatrics (AAP) and the
American College of Obstetrics and Gynaecology
(ACOG) set up guidelines in 1996 to define perinatal
asphyxia severe enough to result in acute neurological
injury.
Four criteria must be met before an infant is said to
have birth asphyxia.

11. 1. Profound metabolic or mixed acidemia (pH < 7) in an
umbilical artery blood sample.
2. Persistence of an Apgar score of 0-3 for longer than 5
minutes.
3. Neonatal neurologic sequelae (e.g. seizures,‭ coma,‭
hypotonia).
4. Multiple organ dysfunction (e.g. kidney,‭ lungs,‭ liver,‭
heart,‭ intestines)

12. However,‭ infants may have experienced asphyxia or
brain hypoxia remote from the time of delivery and may
have exhibited the signs and symptoms of hypoxic
encephalopathy prior to the time of birth and,‭
therefore,‭ may not meet all of the criteria set forth by
the AAP and ACOG.

13. CLINICAL
FEATURES

14. Birth asphyxia can result in CNS injury alone (16% of
cases),‭ CNS and other end-organ damage (46%),‭ isolated
non-CNS organ injury (16%),‭ or no end-organ damage
(22%).

15. FETAL
Intrauterine growth restriction with increased vascular
resistance may be the first indication of fetal hypoxia.
During labor,‭ the fetal heart rate slows and beat-to-beat
variability declines. Continuous heart rate recording
may reveal a variable or late deceleration pattern.

16. Patterns of fetal heart rate
deceleration
The diagram shows early deceleration occurring during the
peak of uterine contractions as a result of pressure on the
fetal head

17. Patterns of fetal heart rate
deceleration
Late deceleration caused by uteroplacental insufficiency

18. Patterns of fetal heart rate
deceleration
Variable deceleration as a result of umbilical cord compression

19. AT DELIVERY AND BIRTH
The presence of meconium-stained amniotic fluid
indicates that fetal distress may have occurred.
Affected infants may be depressed and may fail to
breathe spontaneously.

20. CNS Manifestations
Clinical manifestations and course vary depending on
hypoxic-ischemic encephalopathy severity.

21. Mild hypoxic-ischemic
encephalopathy
Muscle tone is usually normal with brisk deep tendon
reflexes during the first few days.
Transient behavioral abnormalities,‭ such as poor
feeding,‭ irritability,‭ or excessive crying or sleepiness,‭
may be observed.
Typically resolves in less than 24h

22. Moderate hypoxic-ischemic
encephalopathy
The infant is lethargic,‭ with significant hypotonia and
diminished deep tendon reflexes.
The grasping,‭ Moro,‭ and sucking reflexes may be
sluggish or absent.
The infant may experience occasional periods of apnea.

23. Seizures typically occur early within the first 24 hours
after birth.
Full recovery within 1-2 weeks is possible and is
associated with a better long-term outcome.

24. Severe hypoxic-ischemic
encephalopathy
Stupor or coma is typical. The infant may not respond to
any physical stimulus.
Breathing may be irregular,‭ and the infant often
requires ventilatory support.
Generalized hypotonia and depressed deep tendon
reflexes are common.

25. Neonatal reflexes (e.g. sucking,‭ swallowing,‭ grasping,‭
Moro) are absent.
Pupils may be dilated,‭ fixed,‭ or poorly reactive to light.
Irregularities of heart rate and blood pressure (BP) are
common during the period of reperfusion injury,‭ as is
death from cardiorespiratory failure.

27. Non-CNS multi-organ dysfunction
can present as follows
1. Renal. Acute tubular necrosis can present with
haematuria or renal insufficiency or failure.
2. Pulmonary. Respiratory failure or pulmonary
hypertension may result.
3. Cardiac. Reduced cardiac contractility, severe
hypotension and tricuspid regurgitation may occur.

28. 4. Hepatic. Abnormal liver enzymes, elevated serum
bilirubin and decreased coagulation factors secondary
to hepatic dysfunction.
5. Haematologic. Thrombocytopenia due to bone marrow
suppression and decreased platelet survival add to the
coagulopathy.
6. Gastrointestinal. Paralytic ileus or necrotizing
enterocolitis (NEC) are due to decreased end-organ
perfusion.

29. 7. Metabolic. Acidosis (elevated lactate), hypoglycaemia
(hyperinsulinism), hypocalcaemia (increased phosphate
load, correction of metabolic acidosis), and
hyponatraemia/syndrome of inappropriate antidiuretic
secretion (SIADH).

30. INVESTIGATIONS

31. MAGNETIC RESONANCE IMAGING
Diffusion-weighted MRI is the preferred imaging
modality in neonates with HIE because of its increased
sensitivity and specificity early in the process and its
ability to outline the topography of the lesion.

32. Several patterns of brain injury seen in term and late
preterm infants are considered to be typical of hypoxic-
ischemic brain injury. These include the watershed
predominant pattern and the basal ganglia/thalamus
predominant pattern.

33. MRI is also a useful tool in the determination of
prognosis. Studies indicate that infants with
predominant injuries to the basal ganglia or thalamus
(BGT) have an unfavorable neurological outcome when
compared with infants with a white matter predominant
pattern of injury.

34. COMPUTED TOMOGRAPHY
CT scans are helpful in identifying focal hemorrhagic
lesions, diffuse cortical injury, and damage to the basal
ganglia.
CT has limited ability to identify cortical injury during
the 1st few days of life.
The high water content of the brain and the high
protein content of the CSF make result in poor
parenchymal contrast resolution.
Also evidence suggests that even a single CT scan
exposes children to potentially harmful radiation.

35. CRANIAL ULTRASONOGRAPHY
Cranial ultrasonography has the advantage of being
noninvasive and portable.
It can be used for locating haemorrhages, defining
ventricular size and detecting severe cerebral edema.
It has limitations though as it does not adequately
image the outer limits of the cerebral cortex nor is
cranial sonography a sensitive tool for identifying milder
white matter abnormalities that can be appreciated on
head MRI.

36. ELECTROENCEPHALOGRAM
An electroencephalogram (EEG) can help to distinguish
neonatal seizures from other phenomena, and can also
identify subclinical seizures.
They can provide evidence for the presence and severity
of encephalopathy, as well as provide prognostic
information.
At any time, a burst-suppression or an isoelectric
pattern is associated with poor outcome.
A normal EEG at 7 days predicts normal outcome.

37. Two types used: conventional (cEEG) and amplitude-
integrated EEG (aEEG).
Amplitude-integrated electroencephalography (aEEG)
may help to determine which infants are at highest risk
for long-term brain injury.

38. RETINAL AND OPHTHALMIC
EXAMINATION
This examination may be valuable, particularly as part
of an evaluation for developmental abnormalities of the
brain.

39. SPECIAL SENSORY EVALUATION
A full-scale hearing test should be carried out and is
now mandatory in some countries.

40. LABORATORY TESTS
A number of laboratory tests should be conducted at the
time of admission and monitored serially as indicated.
Many of the tests are performed to assess the severity
of brain injury and to monitor the functional status of
systemic organs

41. Electrolytes urea and creatinine to rule out SIADH
secretion and acute tubular damage.
Cardiac and liver enzymes. These tests may show the
degree of HIE injury to these organs and provide some
insight into injuries to other organs.
Blood gas monitoring is used to assess acid-base status
and to avoid hyperoxia and hypoxia as well as
hypercapnia and hypocapnia.
Coagulation profile.

42. MANAGEMENT

43. Principles of Management
Supportive therapy
Anticonvulsants
Neuroprotective interventions
Monitoring

44. RESUSCITATION
For resuscitation to be effective, there must be
availability of well trained personnel, good
communication between paediatricians and
obstetricians for early identification of high risk babies
and readiness for resuscitation as the need arises.

45. The ABCD of resuscitation is :
 Establish patent airway
 Initiate breathing
 Maintain circulation
 Drugs

46. ESTABLISHMENT OF A PATENT
AIRWAY
The first and most important step in resuscitation of the
asphyxiated newborns is good ventilation of the lungs.
 This can only be accomplished by positioning the head
to establish the airway and clearing it subsequently by
suctioning.
The head must not be hyperextended or flexed
otherwise airflow will be restricted.

48. INITIATION OF BREATHING
With failure of the newborn to initiate breathing despite
physical stimulation or with the heart rate <100 bpm,
artificial ventilation should be initiated usually by
positive pressure ventilation with a well fitted facial
mask and supplemental oxygen.

50. The newborn is ventilated at a rate of 40-60 breaths per
minute with a pressure of 20-30 cm of H20.
Initial inflating pressure may be as high as 40 cm of H20
for effective aeration of the gasless lung.
Watch chest movements and ensure the lungs are
adequately aerated.

51. MAINTAIN CIRCULATION
If the heart rate continues to be <60 bpm in spite of 30
seconds of positive pressure ventilation, chest
compression should be initiated.
The thumbs are placed on the lower third of the
sternum, between the xiphoid and the line drawn
between the nipples.

53. The sternum is compressed a third of the
anteroposterior diameter of the chest at a regular rate
of 90 compressions/minute while ventilating the infant
at 30 breaths/minute, synchronized such that every 3
compressions are followed by 1 breath.
The heart rate should be checked periodically and chest
compressions discontinued when the heart rate is >60
bpm.

54. If these maneuvers fail to initiate spontaneous and
regular breathing with increase in heart rate after 30
seconds, then proceed to endotracheal intubation.
Babies who are born limp, apneic and pulseless should
be promptly intubated after birth.

56. The laryngoscope blade is advanced to lift the
epiglottis, as shown, and the laryngoscope is then
lifted upwards. Gentle pressure on the trachea with
the little finger or by an assistant helps bring the
vocal cords into view.

57. The endotracheal tube is then advanced below the vocal
cords.

58. Multiple unsuccessful attempts at intubation by
inexperienced persons may make a difficult situation
worse.
In these cases it may be best to continue mask
ventilation until experienced help arrives.

59. DRUGS USED IN RESUSCITATION
Drugs are recommended if the heart rate remains <60
beats/min despite adequate ventilation and chest
compressions for a minimum of 30 s.

60. Epinephrine may be necessary during resuscitation
when adequate ventilation, oxygenation, and chest
compression have failed and the heart rate is still <60
beats/min.
This drug causes peripheral vasoconstriction, enhances
cardiac contractility, and increases heart rate.

61. Volume expanders are indicated in the hypovolemic
infant.
They include ringers lactate, normal saline and O
negative whole blood.

62. Naloxone hydrochloride. Naloxone (Narcan) is a
narcotic antagonist and should be administered to an
infant with respiratory depression unresponsive to
ventilatory assistance whose mother has received
narcotics within 4 hours before delivery.

63. Dopamine is indicated in neonates with hypotension
secondary to myocardial depression.

64. Resuscitation should be stopped after 15 minutes if
there are no respiratory efforts or cardiac activity in the
presence of adequate ventilation, cardiac massage and
appropriate medication.

65. FLUID AND ELECTROLYTE
MANAGEMENT
Initial fluid restriction is recommended as HIE infants
are predisposed to a fluid overload state from renal
failure secondary to acute tubular necrosis (ATN) and
syndrome of inappropriate ADH secretion (SIADH).
The avoidance of volume overload helps avert cerebral
edema.

66. A single dose of theophylline (8mg/kg) may be
considered within the first hour to increase glomerular
filtration by blocking adenosine mediated renal
vasoconstriction.

67. BLOOD GLUCOSE
Timely and frequent monitoring of blood glucose levels
is essential.
Avoid hypoglycemia and hyperglycemia because both
may accentuate brain damage.
Initial hypoglycaemia (<40mg/dL) amplifies the risk of
progression from moderate to severe encepalopathy.

68. TREATMENT OF SEIZURES
Aggressive treatment of seizures is critical and may
necessitate continuous EEG monitoring.
Phenobarbital, the drug of choice for seizures, is given
with an intravenous loading dose (20 mg/kg) and
maintenance therapy is instituted (5 mg/kg/24hr).
 Phenytoin (20 mg/kg loading dose) or lorazepam
(0.1 mg/kg) may be needed for refractory seizures.”

69. Studies suggest that seizures, including asymptomatic
electrographic seizures, may contribute to brain injury
and increase the risk of subsequent epilepsy.

70. Keep in mind that seizures may be caused by
hypoglycaemia or hypocalcaemia.

71. NEUROPROTECTIVE
INTERVENTIONS

72. HYPOTHERMIA
Therapeutic hypothermia attenuates secondary energy
failure by decreasing the following:

Cerebral metabolism.

Inflammation.

Excitotoxicity.

Oxidative damage.

Cellular apoptosis.

73. 1. Hypothermia
Reduced Oxygen Supply
Cellular Hypoxia
Primary Energy Failure Primary Neuronal Death
Resuscitation
Pseudo-normal period
Secondary Energy Failure
Encephalopathy
Delayed Neuronal Death
Seizures

74. Moderate induced hypothermia (cooling) to a rectal
temperature of 33-340
C improves survival and
neurological outcomes to 18 months of age in infants
with moderate to severe perinatal aphyxia
encephalopathy.

75. Two methods have been used in
clinical trials for brain cooling.
In selective head cooling, a cap
(CoolCap) is used.
The other method is to provide
whole body hypothermia (whole
body cooling). The infant is placed
over a commercially available
cooling blanket.

76. In selective head cooling, a cap (CoolCap) with channels
for circulating cold water is placed over the infant's
head, and a pumping device facilitates continuous
circulation of cold water.

77. In whole body hypothermia, the infant is placed on a
commercially available cooling blanket, through which
circulating cold water flows, so that the desired level of
hypothermia is reached quickly and maintained for 72
hours.

78. CLINICAL/ELIGIBILITY CRITERIA
FOR HYPOTHERMIA
1. Age: 6 hours or less.
2. Gestational age at birth: 36 weeks or more.
3. Evidence of fetal acidaemia.
a) Apgar score 5 or less at 10 minutes after birth
b) Blood gas: < 7.0 with a base deficit of 16 or greater.
c) Continuous need for active resuscitation at 10 minutes of
age and/or need for external cardiac massage or
adrenaline during resuscitation.

79. 4. Evidence of moderate to severe encephalopathy based
on clinical features
a. Altered state of consciousness.
b. Abnormal tone.
c. Abnormal primitive reflexes.

80. CONTRAINDICATIONS TO COOLING
TREATMENT
Life limiting congenital abnormality or abnormalities
indicative of a poor long term outcome.
Moribund infant with persisting severe encephalopathy
such that further treatment is likely to be futile.
Infants requiring imminent or immediate surgical
treatment during the first 3 days of life.

81. REWARMING
The rectal temperature should be allowed to rise by no
more than 0.2-0.30
C per hour to 37 (+/- 0.2 0C).
The infant’s temperature must be monitored for 24
hours after normothermia has been achieved to prevent
rebound hyperthermia that might be detrimental.

82. Complications of induced hypothermia include
thrombocytopenia (usually without bleeding), reduced
heart rate, and subcutaneous fat necrosis (associated
with hypercalcemia in some) and the potential for
overcooling and the cold injury syndrome.

83. FUTURE NEUROPROTECTIVE
AGENTS
Other potential neuroprotective agents are currently
being investigated. They include:
Free radical inhibitors such as allopurinol. Three small
randomised controlled trials that examined whether giving
allopurinol to newborn infants following perinatal asphyxia
affected their outcomes were identified. None of these
trials provided any evidence of benefit. Larger trials are
needed to exclude important effects on survival and
disability.

84. Prophylactic use of calcium channel blockers has been
beneficial in animal studies with the theory being that
neuronal death occurs through elevated cytosolic
calcium. Their use in neonates is currently
contraindicated due to adverse cardiovascular effects.

85. Magnesium an N-methyl-D-aspartate (NMDA) glutamate
receptor antagonist may have a beneficial effect on
preventing cerebral palsy based on retrospective clinical
data but it may have similar cardiovascular risks and
trials have been inadequate.

86. Erythropoietin has been shown some evidence of
improved outcomes for term infants with mild to
moderate HIE by modulating neuronal injury and
promoting neuronal regeneration.
However the evidence is not sufficient enough to
support the use of erythropoietin in infants with HIE.
There are several on-going trials that will provide much
needed data regarding the safety and efficacy of this
potential new therapy.

87. There is some clinical evidence that high-dose
prophylactic phenobarbital may decrease
neurodevelopmental impairment in infants with HIE but
it’s role remains unclear.

88. PROGNOSIS

89. PREDICTORS OF POOR
NEURODEVELOPMENTAL OUTCOME
Infants with initial cord or initial blood pH of<6.7.
Infants with Apgar scores of 0-3 at 5 min.
A low Apgar score at 20 min.
High base deficit (>20-25 mmol/L).

90. Decerebrate posture
Severe basal ganglia-thalamic lesions.
Persistence of severe HIE at 72 hours.
Lack of spontaneous activity.

91. Absence of spontaneous respirations at 20 min of age.
 Persistence of abnormal neurologic signs at 2 weeks of
age.

92. All survivors of moderate to severe encephalopathy
require comprehensive high-risk medical and
developmental follow-up.

93. MORBIDITY AND MORTALITY
Moderate HIE
 Infants with moderate encephalopathy have a 20 to 35%
risk of later sequelae from the insult.
Severe HIE
 Infants with severe encephalopathy have a 75% risk of
dying in the neonatal period, and among survivors, an
almost universal risk of sequelae exists.

94. LONG TERM HANDICAPS
Developmental delay.
Cerebral palsy.
Microcephaly.
Seizures.
Blindness.
Deafness.
Problems with cognition, memory, fine motor skills, and
behaviour.

95. PREVENTION
Recognition of high risk pregnancies.
Adequate antenatal monitoring during pregnancy and
labour (CT, fetal scalp pH).
Good communication between the Obstetrician and
Paediatrician at the peripartum period.
Efficient resuscitation at birth.
Institution of therapeutic hypothermia within 6 hours of
birth.

96. REFERENCES
Robert M. Kliegman, Bonita M.D. Stanton, Joseph St. Geme &
Nina F Schor. Nelson Textbook of Pediatrics 20th
ed. Page
5899,6092-6114.
[Guideline] Committee on fetus and newborn, American
Academy of Pediatrics and Committee on obstetric practice,
American College of Obstetrics and Gynecology. Use and
abuse of the APGAR score. Pediatr. 1996.
Tricia Lacy Gomella with M.Douglas Cunningham and Fabien
G.Eyal, Neonatology , Management, Procedures, On-call
Problems, Diseases and Drugs, 7th
Edition, Pages 807-812
Miller SP, Weiss J, Barnwell A, et al. Seizure-associated brain
injury in term newborns with perinatal asphyxia. Neurology.
2002 Feb 26

97. Krishna M Goel, Devendra K Gupta; Hutchison’s
Paediatrics 2nd
Edition, Pages 31.
Chaudhari T, McGuire W, Allopurinol for preventing
mortality and morbidity in newborn infants with HIE,
Cochrane 2012.
Gonzalez FF, Erythropoietin: a novel therapy for
hypoxic-ischaemic encephalopathy? Dev Med Child
Neurol. 2015

98. THANKS FOR
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