Hypoxia ischaemia of the newborn (perinatal hypoxia hypoxic-ischaemic encephalopathy (hie))

P21.9

• Description
• Diagnostic criteria
• General and supportive measures
• Medicine treatment
• Referral

DESCRIPTION

Ischaemia and decreased oxygen delivery to the foetus/baby during the prepartum, intrapartum or immediate postpartum period, with hypoxic-ischaemic damage to the central nervous system and to other body systems.

Complications include:

• Cardiovascular: heart rate and rhythm disturbances, heart failure and hypotension.
• Pulmonary: respiratory distress/respiratory failure, pulmonary hypertension and pulmonary haemorrhage.
• Renal: renal failure, acute tubular/cortical necrosis and urinary retention.
• Gastrointestinal tract: ileus and necrotising enterocolitis.
• Central nervous system: increased intracranial pressure, cerebral oedema, encephalopathy, seizures, inappropriate antidiuretic hormone (ADH) secretion, hypotonia and apnoea.
• Metabolic: hypoglycaemia, hyperglycaemia, hypocalcaemia, hypomagnesaemia and metabolic acidosis.
• Body temperature: abnormal.
• Other: disseminated intravascular coagulation.

DIAGNOSTIC CRITERIA

To make the diagnosis of HIE, all of the following are required:

• Gestation ≥ 36 weeks (i.e. late premature or term).
• Evidence of intrapartum asphyxia or hypoxia.
• Evidence of encephalopathy.

Other criteria to consider:

• History of foetal distress and/or meconium stained amniotic fluid.
• Apgar scores:
  • one-minute Apgar score ≤ 3,
  • five-minute Apgar score of ≤ 6,
• Arterial blood lactate > 5 mmol/L.
• Severe mixed acidosis:
  • pH < 7.2,
  • base excess > –10,
  • PaCO₂ > 55 mmHg.
• Haematuria.
• Troponin T increased.
• Prolonged resuscitation (>10 min).

Stages of hypoxic-ischaemic encephalopathy (HIE) – Sarnet and Sarnet

GENERAL AND SUPPORTIVE MEASURES

• Resuscitate.
• Avoid hyperthermia.
• Admit to neonatal high care or intensive care facility, if available.
• Mild HIE: ambient temperature at lower range of neutral thermal environment.
• Infants ≥ 36 weeks gestation with moderate HIE (stage 2): whole body or head cooling.
  • Initiate within 6 hours of birth to maintain rectal (core) temperature at 33–34ºC (whole body cryotherapy) or 34-35ºC (head cooling) for 72 hours.
  • Slowly rewarm at a rate of 0.5ºC/hour until core temperature 36.5-37.0ºC, then maintain axillary or skin temperature is at 36.5–36.8ºC.

• Ventilatory support if PaO₂ < 60 mmHg and/or PaCO₂ > 55 mmHg in newborns with moderate HIE (stage 2).
• Maintain:
  • Blood glucose at 2.6–6 mmol/L.
  • Haematocrit at ≥ 40%.
  • Blood pressure at 70/35 mmHg in a term infant and 50/35 mmHg in a preterm infant. Mean blood pressure at least 5–10 mmHg more than the gestational age.
• IV fluids
  • Frequent assessment of fluid balance, i.e. intake and output.
  • Restrict fluids to 50–60 mL/kg in the first 24–48 hours.
  • Use dextrose water 10% or a neonatal maintenance solution potassium-free until the possibility of renal failure has been excluded.
• Maintain serum electrolytes, calcium, magnesium and acid-base status within normal physiological range.
• Nutrition:
  • No enteral feeds for at least the first 12–24 hours.
  • Enteral milk feeds (preferably breastmilk) only after ileus has been excluded.
  • Consider IV alimentation if enteral feeds are not possible after 24 hours.
• Monitor:
  • neurological status,
  • fluid balance,
  • vital signs,
  • temperature,
  • acid-base status,
  • blood glucose,
  • blood gases,
  • electrolytes,
  • SaO₂,
  • calcium, magnesium,
  • blood pressure,
  • renal function, and
  • brain function (aEEG), where available.
• Brain imaging – at least one cranial US during admission if available.
• Follow up for assessment of neurodevelopment, hearing and vision.

MEDICINE TREATMENT

To keep PaO₂ between 60 and 80 mmHg and saturation 90-94% (normal range):

• Oxygen.

Haematocrit <40%:

• Packed red cells, IV, 10 – 20 mL/kg (consider pack size).

If infection is suspected or confirmed:
Treat as follows (if no renal dysfunction is present):

• Ampicillin, IV, 50 mg/kg/dose.
  • If age < 7 days: 50 mg/kg 12 hourly.
  • If 7 days – 3 weeks of age: 50 mg/kg 8 hourly.
  • If > 3 weeks of age: 50 mg/kg 6 hourly.

PLUS

• Gentamicin, IV, 5 mg/kg once daily.

Where available, gentamicin doses should be adjusted on the basis of therapeutic drug levels.

• Trough levels (taken immediately prior to next dose), target plasma level < 1 mg/L.
• Peak levels (measured 1 hour after commencement of IV infusion or IM/IV bolus dose), target plasma level > 8 mg/L.

Hypotension

• Sodium chloride 0.9%, IV, 20 mL/kg over 1 hour.
  AND
• Dopamine, IV, 5–15 mcg/kg/minute.
  AND/OR
• Dobutamine, IV, 5–15 mcg/kg/minute if cardiac dysfunction or failure is present.
  • Continue with blood pressure support until blood pressure is stabilised.

Seizure Control

Administer anticonvulsants with monitoring of cardiorespiratory function.

• Phenobarbitone, IV:
  • Loading dose: 20 mg/kg over 10 minutes.
  • Refractory seizures: Additional 10 mg/kg up to 40 mg/kg.

Maintenance:

• Phenobarbitone, IV or oral:
  • 4 mg/kg/day beginning 12–24 hours after the loading dose.

Admit neonates with seizures refractory to phenobarbitone to a high or intensive care unit.
Cardiorespiratory support is usually required in this category of infants.
For term normothermic neonates:

• Lignocaine (lidocaine), IV.
  • Loading dose: 2 mg/kg over 10 minutes.
  • Follow with a continuous infusion of:
    6 mg/kg/hour for 6 hours, then
    4 mg/kg/hour for 12 hours, followed by
    2 mg/kg/hour for 12 hours.
  • If seizures are well controlled, taper slowly over 12 hours.

For preterm neonates:
A safe dose of lidocaine in preterm neonates has not been established but the following dosing schedule has been used.

• Lignocaine (lidocaine), IV.
  • Loading dose: 2 mg/kg over 10 minutes.
  • Follow with a continuous infusion of 3 mg/kg/hour for 3 days.
  • Taper dose gradually over next 2 days.

Cardiac failure

Restrict fluid.

• Furosemide, IV/oral/nasogastric tube, 1 mg/kg/24 hours as a single daily dose.
• Dobutamine IV, 5–15 mcg/kg/minute.

Hypocalcaemia

Serum total calcium < 1.8 mmol/L or ionised calcium < 0.7 mmol/L.

• Calcium gluconate 10%, slow IV, 1–2 mL/kg over 15 minutes under ECG monitoring.

Hypomagnesaemia

Serum magnesium < 0.6 mmol/L:

• Magnesium sulphate 50%, IV, 0.2 mL/kg as a single dose.

Hypoglycaemia

Blood glucose < 2.6 mmol/L:

• Dextrose 10%, bolus IV, 2.5–5 mL/kg (250–500 mg/kg).
  Dextrose 10% = 10 g dextrose in 100 mL.
  Do not repeat dextrose bolus; titrate the glucose concentration of the IV fluid to increase glucose delivery.

Inappropriate ADH:

Moderate fluid restriction of 50–60 mL/kg/24hours for the first 24–48 hours.
Raise head of cot by 10–15 cm.

Cerebral oedema/raised intracranial pressure

Moderate hyperventilation to lower PaCO₂ to 35 mmHg, if ventilation facilities are available.

REFERRAL

• Neurological assessment of survivors at 3 months.
• Moderate HIE (gestational age ≥ 36 weeks) to reach referral hospital before 6 hours post birth.
• Lidocaine toxicity.