Hypoxia-Ischaemia Of The Newborn (Perinatal Hypoxia/Hypoxic-Ischaemic Encephalopathy (HIE))
Description Diagnostic criteria General and supportive measures Medicine treatment Referral ICD-10 code: P21.9 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 rhyt
Description
Diagnostic criteria
General and supportive measures
Medicine treatment
Referral
ICD-10 code: P21.9
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 preterm or term).
- Evidence of intrapartum asphyxia or hypoxia:
- Apgar < 5 at 5 and 10 minutes OR
- pH < 7.0 and BD ⩾ 12 mmol/l OR
- Ongoing resuscitation for more than 10 minutes.
- Evidence of encephalopathy:
- Clinical examination using the modified Sarnat staging.
OR - Abnormal aEEG.
- Clinical examination using the modified Sarnat staging.
Modified Sarnat staging
- Encephalopathy defined as the presence of one or more signs in at least 3 of the 6 categories:
| Moderate encephalopathy | Severe encephalopathy | ||
| 1. | Level of consciousness | Lethargic | Stupor/coma |
| 2. | Spontaneous activity | Decreased activity | No activity |
| 3. | Posture | Distal flexion/complete extension | Decerebrate |
| 4. | Tone | Hypotonia | Flaccid |
| 5. |
Primitive reflexes - Suck |
Weak |
Absent |
| 6. |
Autonomic nervous system - Pupils |
Constricted |
Deviated, dilated or non-reactive to light |
Thompson Score (Long-term prognostication)
| Score | 1 | 2 | 3 |
| Limb tone | Generally hypertonic | Generally hypotonic | Flaccid |
| LOC | Hyperalert, hyperreactive or staring | Lethargic/ Obtunded | Comatose/ Stuporous |
| Visible fits | Infrequent (< 3/day) | Frequent (> 2/day) | |
| Posture | Fisting and/or cycling | Strong distal flexion | Decerebrate |
| Moro | Partial | Absent | |
| Grasp | Poor | Absent | |
| Suck | Poor | Absent and/or bites | |
| Resp. effort | Hyperventilation | Brief apnoea | Apnoea (IPPV) |
| Fontanelle | Full, not tense | Tense |
Thompson, et al. The value of a scoring system for hypoxic ischaemic encephalopathy in predicting neurodevelopmental outcome. Acta Paediatr. 1997;86:757-761.
GENERAL AND SUPPORTIVE MEASURES
- Resuscitate
- Avoid hyperthermia.
- Admit to a neonatal high care or intensive care facility.
- Mild HIE: ambient temperature at the lower range of a neutral thermal environment.
- Infants ≥ 36 weeks gestation with moderate HIE (stage 2): whole body or head cooling if appropriate monitoring is available.
- Initiate within 6 hours of birth to maintain rectal (core) temperature at 33.5– 34.5ºC (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 at 36.5–36.8ºC.
|
Neonates not eligible for cooling:
|
- Ventilatory support if PaO2 < 60 mmHg (8 kPa) and/or PaCO2 > 55 mmHg (7.3 kPa) in newborns with moderate HIE (stage 2) or severe HIE (stage 3), depending on available resources.
- 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 40 mL/kg in the first 24–48 hours to avoid cerebral oedema.
- Use dextrose water 10% or a neonatal maintenance solution, potassiumfree, 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 breast milk) 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 (8 and 10.5 kPa) and saturation 90–95% (normal range):
- Oxygen.
See: Respiratory Distress in the Newborn for figure 1: Blood cell transfusion thresholds for preterm neonates. If anaemia is present according to thresholds in figure 1
- Packed red cells, IV, 10–20 mL/kg (consider pack size) over 3 – 4 hours in haemodynamically stable patients. More rapid transfusions may be appropriate in bleeding and haemodynamically unstable patients.
If infection is suspected or confirmed:
Treat as follows (if no renal dysfunction is present):
- Ampicillin, IV, 100 mg/kg/dose. Decrease the dose to 50 mg/kg/dose once meningitis has been excluded.
| Gestational Age | Postnatal Age | Dose |
| ≤ 34 weeks | ≤ 7 days | 50 mg/kg/dose every 12 hours |
| 8 to 28 days | 75 mg/kg/dose every 12 hours | |
| >34 weeks | ≤ 28 days | 50mg/kg/dose every 8 hours |
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 μg/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:
- Midazolam, IV.
- Loading dose: 0.05 mg/kg IV over 10 minutes.
- Followed by a continuous infusion of 0.03-0.3 mg/kg/hour.
OR
- Lidocaine (lignocaine), IV.
- Loading dose: 2 mg/kg over 10 minutes.
- Follow with a continuous infusion of:
6 mg/kg/hour for 6 hours, then
4mg/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:
- Midazolam, IV.
- Loading dose: 0.05 mg/kg over 10 minutes.
- Followed by a continuous infusion of 0.03–0.3 mg/kg/hour.
OR
A safe dose of lidocaine (lignocaine) in preterm neonates has not been established but the following dosing schedule has been used.
- Lidocaine (lignocaine), 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 the next 2 days.
CAUTION
Do not use lidocaine (lignocaine) if phenytoin was given. Do not use lidocaine (lignocaine) for seizures in newborns with congenital heart disease, dysrhythmias, acute heart failure and shock.
|
- A safe lidocaine (lignocaine) dosing regimen for term infants undergoing hypothermia treatment for HIE has not been established; recommended to use half infusion dosages. - Clearance of lidocaine (lignocaine) is slower in hypothermic preterm infants and neonates and there is a risk of accumulation. - Start tapering earlier than 3 days if seizures are well controlled. - Continuous monitoring of ECG, heart rate and blood pressure is mandatory if lidocaine (lignocaine) is used. - Main adverse effects of lidocaine (lignocaine): dysrhythmias and bradycardia. - Life threatening dysrhythmias may indicate lidocaine (lignocaine) toxicity. Treat with: |
Cardiac failure
Restrict fluid.
- Furosemide, IV/oral/nasogastric tube, 1 mg/kg/24 hours as a single daily dose.
- Dobutamine IV, 5–15 μg/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.
Syndrome of inappropriate ADH
Moderate fluid restriction of 40 mL/kg/24 hours 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 (4.5 kPa), 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 (lignocaine) toxicity.
Standard Treatment Guidelines And Essential Medicines List For South Africa, Hospital Level, Paediatrics, 2023 Edition
Chapter 19: Prematurity And Neonatal Conditions, 19.6 Neurological, 19.6.1 Hypoxia-ischaemia Of The Newborn (Perinatal Hypoxia/Hypoxic-Ischaemic Encephalopathy (HIE))