Therapeutic hypothermia, or targeted temperature management, involves reducing an infant's core body temperature to 33-34°C for 72 hours after birth to reduce the risk of brain injury from hypoxic-ischemic encephalopathy (HIE). Cooling should begin as soon as possible after birth and within 6 hours to be effective. It reduces mortality and neurodevelopmental disabilities at 18 months according to clinical trials. Eligible infants have gestational age ≥34 weeks, signs of encephalopathy, and evidence of perinatal asphyxia. Cooling must be performed carefully by lowering the temperature 0.5°C per hour and avoiding overcooling or rewarming too quickly.

1. Neonatal
Therapeutic
Hypothermia
(Targeted Temperature Management)
Dr CSN Vittal

2. Definition
• Deliberate reduction of the core body
temperature, typically to a range of about
33° to 34° C for 72 hours in newborns who
are likely to develop HIE

3. Neonatal Therapeutic
Hypothermia
Neonatal therapeutic hypothermia is a
relatively new treatment option in
which an infant’s total body (TOBY)
temperature is reduced shortly after
birth in order to reduce the chances
of severe brain damage and slow
down disease progression

4. What is the evidence?
From animal models –
Moderate Hypothermia
• cerebral metabolic O2 rate
• suppress chemical reactions associated
with reperfusion injury
A Cochrane review (8 RCTs; 638 term infants with moderate/ severe
encephalopathy and evidence of intrapartum asphyxia) showed that TH reduced
combined outcome of mortality or major neurodevelopmental disability by 24% to 18
months of age.

5. RECOMMENDATIONS OF THE NEONATAL
ENCEPHALOPATHY TASK FORCE
Screening Criteria
• Neonates ≥ 34 weeks gestational age &
• Concern for encephalopathy or seizure event
• Any one of the following:
• sentinel event prior to delivery such as uterine rupture, profound
bradycardia, or cord prolapse
• low Apgar scores ➔ ≤ 5 at 10 minutes of life
• prolonged resuscitation at birth ➔ chest compressions, and/or
intubation, and/or mask ventilation at 10 minutes
• acidosis ➔ pH < 7.1 from cord or patient blood gas within 60
minutes of birth
• abnormal base excess ➔ ≤ -10 mEq/L from cord gas or patient
blood gas within 60 minutes of birt
The Neonatal Encephalopathy Task Force Recommendations on Therapeutic
Hypothermia were developed under the auspices of the Academic Medical Center
Patient Safety Organization (AMC PSO) Neonatal Encephalopathy Task Force.

6. Hypoxic Ischemic Encephalopathy
• Neonatal encephalopathy is a clinical syndrome of
disturbed neurological function that presents early in
life, with an incidence of approximately 1/1000 to
6/1000 live births.
• Hypoxic-ischemic encephalopathy (HIE) accounts for
a significant proportion of encephalopathic newborns.
Ferriero DM. Neonatal brain injury. N Engl J Med 2004;351(19):1985–95.

7. HIE - Indicators
• hyperalertness
• irritability
• lethargy or obtundation
• coma
• decreased spontaneous activity
• hypotonicity or flaccidity
• decerebrate posturing
• absent or weak suck
• abnormal pupillary reflex
• abnormal Moro reflex
• persistent bradycardia
• periodic breathing or apnea

8. EXCLUSION CRITERIA FOR THERAPEUTIC
HYPOTHERMIA
Absolute Exclusion Criteria
• gestational age < 34 weeks
Relative Exclusion Criteria
(at the discretion of the accepting attending physician at the
Level III facility)
• IUGR < 1,750 grams
• severe congenital anomalies/genetic
syndromes/ established metabolic disorders
• major intracranial hemorrhage
• overwhelming septicemia
• uncorrectable, clinically relevant coagulopathy

9. When to start cooling?
• Cooling should be started as soon as
possible after resuscitation is
completed. Current evidence
suggests that cooling is unlikely to be
beneficial if started more than six to
eight hours after birth.

10. ELIGIBILITY CRITERIA - I
• Must fulfil all three criteria.
• Additional, separate, written parental consent is not legally
required.
AND
1 Neonates ≥ 36 weeks gestational age and
less than 6 hours of age
Therapeutic Hypothermia - Is Indicated
+

11. AND
2
Any one of the following
• sentinel event prior to delivery, such as uterine
rupture, profound fetal bradycardia, or cord
prolapse
• low Apgar scores ➔ ≤ 5 at 10 minutes of life
• prolonged resuscitation at birth ➔ chest
compressions and/or intubation and/or mask
ventilation at 10 minutes
• severe acidosis ➔ pH < 7.0 from cord or
neonate blood gas within 60 minutes of birth
• abnormal base excess ➔ ≤ -16 mEq/L from
cord gas or neonate blood gas within 60 minutes
of birth
ELIGIBILITY CRITERIA - I
Therapeutic Hypothermia - Is Indicated
+

12. 3
Any one of the following
• Clinical event, like seizure
• Neonatal encephalopathy
•Altered state of consciousness (reduced
or absent response to stimulation)
AND
•Abnormal tone (focal or general hypotonia
or flaccid) AND
•Abnormal primitive reflexes (weak or
absent suck or Moro).
ELIGIBILITY CRITERIA - I
Therapeutic Hypothermia - Is Indicated

13. Encephalopathy score (Thompson Score)
recorded when cooling in commenced and then daily
for the first four days after birth
Tone normal hyper hypo flaccid
LOC normal hyperalert, stare lethargic comatose
Fits none < 3 per day > 2 per day
Posture normal fisting, cylcing strong distal flexion decerebrate
Moro normal partial absent
Grasp normal poor absent
Suck normal poor absent ± bites
Respir normal hyperventilation brief apnea IPPV (apnea)
Fontanell normal full, not tense tense
Sign 0 1 2 3
A score ≥12 is associated with adverse outcomes
(death before discharge and development of severe epilepsy)

14. ELIGIBILITY CRITERIA - II
• Must fulfil all three criteria.
• Additional, separate, written parental consent is not legally
required.
AND
1
Neonates ≥ 34 weeks gestational age and
less than 12 hours of age
Therapeutic Hypothermia - Should be Considered
+

15. ELIGIBILITY CRITERIA - II
AND
2
Therapeutic Hypothermia - Should be Considered
Any one of the following
• sentinel event prior to delivery, such as uterine
rupture, profound fetal bradycardia, or cord prolapse
• low Apgar scores ➔ ≤ 5 at 10 minutes of life
• prolonged resuscitation at birth ➔ chest
compressions and/or intubation and/or mask
ventilation at 10 minutes
• severe acidosis ➔ pH < 7.0 from cord or
neonate blood gas within 60 minutes of birth
• abnormal base excess ➔ ≤ -10 mEq/L from
cord gas or neonate blood gas within 60 minutes of
birth
• post-natal collapse resulting in hypoxic-
ischemic injury (i.e., near-SIDS type event)
+

16. ELIGIBILITY CRITERIA - II
3
Therapeutic Hypothermia - Should be Considered
Any one of the following
• clinical event concerning for seizure
• neonatal encephalopathy
• Neonatal Task Force recommends that institutions
adopt a standardized, mutually agreeable assessment
tool to diagnose encephalopathy.
• If exam is unreliable, an EEG may be a useful
adjunct tool for assessing and qualifying neonatal
encephalopathy.

17. Initial Stabilization and
Management
in the Community Setting
Passive Cooling
• Passive cooling should be initiated as soon as
a potentially eligible neonate is identified,
ideally in the delivery room
(core temperature should be monitored).
– Turn off radiant warmers or isolette heaters
(including transport isolette).

18. Initial Stabilization and
Management
in the Community Setting
• Target core temperature (rectal or esophageal) for
therapeutic cooling is 33.5 °C ± 1 °C.
- Do not use skin thermometers.
- Core temperature should be monitored every 5–15 minutes.
- Slowly titrate heat source as needed to achieve target
temperature.
Note: If neonate has never been warmed, they are easily
over-cooled, even passively.
• Once core temperature falls to 34 °C, have external heat
source available set at 33.5 °C
• If core temp raises above 34 °C try opening isolatte ports
or unwrap neonate
•If cord gases are not obtained or there are ongoing concerns,
neonatal blood gases should be sent within the first hour of birth.

19. Initial Stabilization and
Management
in the Community Setting
• Blood Gases
• There should be a low threshold for
obtaining cord gases or early neonate
blood gases.
• If cord gases are not obtained or there
are ongoing concerns, neonatal blood
gases should be sent within the first hour
of birth. Repeat as appropriate.

20. Initial Management
at Level II Or III center
Access : UVC or Peripheral IV lines
Labs : CBC, Electrolytes, Bl culture, ABG, LFTs,
Coagulation studies
Respiratory : Target SpO2 94-99%;
Target pCO2 4—50 mm Hg
CVS : Maintain BP, and heart rate
Infections : Evaluate sepsis and treat
Sedation : modest sedation improves neonatal outcome
•If cord gases are not obtained or there are
ongoing concerns, neonatal blood gases
should be sent within the first hour of birth.

21. Preparation for sending to
Cooling Center
• 1 hour of age – Passive cooling commenced
• Cooling centre contacted. NTS contacted
• Changed from axillary to rectal temperature monitoring
• 2 hours of age – rectal temp 35.1
• 3 hours of age – rectal temp 36.3
• 3 hours 40 mins – Transport team commenced active
cooling using cold water gloves
• 7 hours of age – target rectal temp of 33-340C achieved
• 8 hours of age – arrived at Cooling Centre – active
cooling using cooling mattress commenced

23. 30.5
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temperature
Hours from start of cooling
Temperature chart for Registered cooled baby
Recorded rectal temperatures for baby 2087
Target Low
Target High
•

24. NlCU Management
(Cooling Center)
• The target core temperature for therapeutic cooling is
33.5 °C ± 1 °C.
• Secure vascular access:
– Establish venous access, as soon as possible. Scalp IV
is not ideal and may need to be removed for EEG lead
placement.
– Establish umbilical venous access (UVC)—double
lumen—if possible.
– Do not delay the commencement of therapeutic
hypothermia to place umbilical lines.
– Arterial line, if indicated.
Cooling should not be delayed for the neurology service
review,

25. MiraCradle prototoype

27. Neuro consult..
• Obtain head ultrasound (HUS) as soon as possible to evaluate
for intracranial hemorrhage as a potential contraindication to
continued cooling.
• Obtain an EEG/aEEG to assess for encephalopathy and
seizures
• Seizure control:
– First choice agent for treating seizures: phenobarbital.
– Continue video EEG recording for 24 hours or longer if
seizures are detected.
• MR imaging:
– In consultation with neurology, determine optimal timing of
MRI.

28. Laboratory monitoring…
• Blood cultures should be obtained, as indicated.
• Other labs should be monitored per institutional protocol.
• Platelets:
– Thrombocytopenia is common in hypothermia.
– Due to the ongoing risk of cerebral hemorrhage,
consider transfusing at a threshold platelet count of 50k
• PT/PTT/INR -- as soon as possible.
• AST and ALT.
• Serum lactate, ideally from blood gas.
• Anti-epileptic levels, if indicated.
• Monitor for fat necrosis and associated risk of hypercalcemia.

29. Fluid and Electrolytes
• NPO during hypothermia.
• IV fluids should be restricted to avoid cerebral
and pulmonary edema. avoiding over-hydration
• start at 60 mL/kg/24 hours and adjust based on
strict ins/outs.
• Maintain glucose and electrolytes within normal
limits.
Management of Acidosis:
• NaHCO3 should be avoided
• Add acetate, as needed, to the TPN for
correction of acidosis.
•

30. Respiratory
• Maintain arterial blood gas pCO2 in range of
40–50 mmHg to optimize cerebral perfusion.
• If on supplemental oxygen, avoid hyperoxia.
- Target SaO2 94–99%.
- Arterial PaO2 should not exceed 100 mmHg.
Suspected or proven pulmonary hypertension is not
a contraindication to cooling and is not an indication
for early rewarming.

32. Rewarming
• Begin after 72 hours of cooling.
• Rewarming should be done slowly. Increase
core temperature 0.2–0.5 °C per hour until core
temperature reaches 36.5 °C.
• There is an increased risk of seizures during
rewarming. Consider EEG monitoring.

33. Subsequent progress
• Day 2 - Hypotension resolved
• Day 3 - Extubated – self ventilating in air
Cooling continued for 72 hours then slow
rewarming (0.50C per hour)
• Day 4 – weak gag reflex present – started NG
feeds
• Day 5 – gag reflex improved – started breast
feeds
• Day 7 – full sucking feeds achieved
- MRI scan normal
• Day 8 – discharged home

34. Adverse effects of Hypothermia
• Sinus bradycardia
• Hypotension – needing inotropes
• Mild thrombocytopenia
• Persistent pulm hypertension with impaired
oxygenation
• Prolonged bleeding time
• Rarely – subcutaneous fat necrosis with or
without hypercalcemia

35. Selective Head Cooling
• Cooling caps fitted around an infant’s
head, with the aim of maintaining
fontanelle temperature below 30°C.
• A rectal temperature of 34°C ± 0.5°C is
maintained using a servo-controlled
radiant heater.
• Expensive
• May cause scalp edema or skin breakdown
• Difficult to maintain rectal temp
• Limited access for EEG monitoring

36. TOBY Trial
• Randomised to Intensive Care alone or Intensive
care plus Total body cooling to 33-340C for 72 hours
then slow rewarming by 0.50C per hour
• Continuous rectal temperature monitoring
• Primary outcome: Combined death & severe
neurodevelopmental disability at 18 months
• Secondary outcomes

37. TOBY Trial
Outcome Hypothermia
(%)
Normothermia
(%)
P value
Primary outcome:
Combined death & severe
neurodisability
45 53
(Note: predicted 70)
0.17
Secondary outcomes
(significant)
Survival without neurologic
abnormality
44 28 0.003
Cerebral palsy 28 41 0.03
Trial on 767 infants confirm that 72 hours of cooling to a core temperature
of 33-34o C started within six hours of birth reduces death and disability at
18 months of age and improves a range of neurodevelopmental outcomes
in survivors

38. Reference
• The Neonatal Encephalopathy Task Force Recommendations on
Therapeutic Hypothermia were developed under the auspices of
the Academic Medical Center Patient Safety Organization (AMC
PSO) Neonatal Encephalopathy Task Force.

39. • Dr.C.S.N.Vittal