This presentation provides rationale , feasibility and methods of providing cooling during retrieval , in hypoxic ischemic encephalopathy

1. Dr.Gopakumar Hariharan

2.  Introduction
 Mechanism of benefit –
Pathophysiology
 Relevant researches
 Why , who , when and how
to cool
 Discussion

3.  Pregnancy at term
 Mum presented to ED with severe abdominal
pain and bleeding pervaginum .
 Emergency LSCS –Heart rate – 10 / min , no
respiratory effort , hypotonic and pale
 Required prolonged respiration – lasted for
more than 10 minutes for adequate heart rate
to ensue
 Cord PH – 6.9 , BE – 18
 ???? Cooling ???

4.  Perinatal asphyxia is an insult to the fetus or
the newborn due to lack of oxygen (hypoxia)
and/or a lack of perfusion (ischemia) to
various organs.
 Hypoxia ischaemia remains a significant
cause of neonatal mortality and morbidity
and adverse neurodevelopmental outcome
 Therapeutic cooling – found to improve
neurodevelopmental outcome in asphyxiated
babies

5.  1960’s versus 1980’s
 Hypothermia in cardiac arrest and traumatic
brain injury in adults – probable benefit in
neurological outcome
 Mariane Thorensen (Researcher on Cerebral
perfusion ) - Intrigued by stories of children
who fell through norwegian ice and suffered
prolonged drowning in iced water - emerged
with preserved cerebral function
 Data from animal studies – beneficial effect

6. Pathophysiology

7.  Result of decreased cerebral blood flow and
oxygen delivery - failure of aerobic metabolism
 Anaerobic glycolysis - excessive production of
lactic acid, as well as tissue acidosis, depletion of
the high energy phosphate compounds ATP and
phosphocreatine, and inability to maintain cell
membrane function.

8.  Results in loss of electrolyte gradients, with cell
swelling and necrosis.
 Damage during this period occurs prior to
hypothermia therapy and will not be affected by
treatment

9.  Follows reperfusion of the brain - Accounts for the
major neuronal cellular loss
 The decline in phosphocreatine and ATP is not
accompanied by brain acidosis, but it results in
apoptosis, or programmed cell death.

10.  Hyperaemia, cytotoxic oedema, mitochondrial
failure, accumulation of excitotoxins, apoptosis NO
synthesis and activation of microglia
 Degree of energy failure and apoptosis -
proportional to the severity of adverse
neurodevelopmental outcomes

11.  Increased seizure activity - may further
deplete energy reserves.
 Magnetic resonance spectroscopy studies in
infants with moderate to severe HIE have
confirmed normal cerebral oxidative
metabolism shortly after birth followed by
evidence of secondary energy failure.

12. Therapeutic ‘window of
opportunity’
Interval following
resuscitation of the
asphyxiated newborn,
before the secondary
phase of impaired energy
metabolism and injury is
fully established.

14. Why cooling ??

15.  Reduced loss of high energy phosphates during
ischaemia
 Attenuates bloodbrain barrier damage and
neuronal apoptosis
 Reduced release of excitatory tranmitters and free
radical production
 Decreased cerebral metabolic rate for glucose and
oxygen
 Prevents or ameliorates secondary cerebral energy
failure.

16. The time factor
Time critical
Hypothermia to between
33oC and 34oC initiated
as soon as possible
after delivery reduces
Sheep brain mortality and disability
EEG and in babies with HIE(Level
Histological 1a evidence)

17.  Shows the statistically significant (p =0.0006)
therapeutic benefit of hypothermia after HIE
on death and neurodevelopmental disability
with a relative risk of 0.76 (95%CI, 0.65 -
0.89).
 ICE trial based in Australia and the TOBY trial
based in the UK ceased recruitment during
2007 ( categorical benefit noted )

18. Cool cap trial
NICHD trial
TOBY trial
ICE trial

19.  Cooling for 72 hours
started within 6 hours of
delivery – based on
auckland pilot studies
arbitrary based on
animal studies
 Whole body temperature
- 34. 5 degrees
Result – Nonsignificant trend towards improvement in
the primary outcome of death or disability at 18
months overall

21. TOBY trial unequavocally demonstrated that
cooling increases an infants chance of
surviving without neurological deficits at 18
months and reduces neurodevelopmental
impairment in survival

22.  Reduction of systemic temperature necessary
to achieve deep brain cooling
 Head cooling equipment expensive
 Delays the cooling process in case of retrieval

23. When to cool??

24. All the 4 criteria should be met
1) More than or equal to 35 weeks of gestation
2) Less than 6 hours post birth
3) Evidence of asphyxia
4) The presence of moderate / severe HIE

25. Apgar less than 6 at 10 minutes or continued need for
resuscitation with PPV with or without chest compressions at
10 minutes
Any acute perinatal event that may result in HIE ( ie abruptio
placentae , cord prolapse , severe FHR abnormality etc )
Cord PH less than 7 or BE of -12 mmol / L or less
If cord PH not available , arterial PH less than 7 or BE less
than -12 mmol / L within 60 minutes of birth

26. Category Moderate Severe Encephalopathy
encephalopathy
Level of consiousness Lethargy Stupor / coma
Spontaneous activity Decreased activity No activity
Posture Decorticate Decerebrate
Tone Hypotonia Flaccid
Primitive reflexes Weak suck,Incomplete Absent suck,absent
moro moro
Autonomic system ( any one of these )
Pupils Constricted Dilated / Non reactive
Heart rate Bradycardia Variable heart rate
Respirations Periodic breathing Apnea

27. Moderate or severe asphyxia - defined as
seizures OR presence of signs in atleast 3 of
the 6 categories
If the neonate meets elibility criteria 1 , 3 and 4 , but is 6 – 12
hours of age , delayed initiation of cooling may be considered at
the discretion of the attending neonatologist

28. How to cool
??

29.  Switch off warmer in case of radiant warmer
 Switch of incubator , open port holes
 Nurse baby naked
 Keep nappy undone
 Temperature monitoring
 Consider reducing environmental temp by
adding fan ( ? A/C )

30. Arch Dis Child Fetal Neonatal Ed 2010;95:F408–F412.

31.  4 cold packs in fridge temperature ( 10
degrees )
 2 frozen cold packs
 Disposible rectal probes
 Cable for connecting rectal probes
 Cotton covers for cold packs
 Cardiopulmonary monitoring
Neonatology clinical guidelines
KEM & Princes Margeret Hospitals
Perth

32. Temp ranges No of cool packs Areas to be applied
applied
> 37 degrees 4 Head , Shoulders , neck , trunk
36.1 - 37.0 3 Shoulders , neck , trunk
35.1 – 36.0 2 Shoulders , trunk
34.1 – 35.0 1 Trunk
33 . 0 – 34.0 0 Nil
Watch temp range more closily in infants treated with anticonvulsants or
muscle relaxants ( tend to cool rapidly )
Keep cold packs in cotton bags

33.  Commercially available water bottles filled
with water ( 25 degrees )
 Phase changing mattress with a melting point
of 32 degrees ( acts as heat buffers and
stabilizes temp of objects with which it
comes in contact )

34.  Passive heating and cooling substances ,
usually made of a salt hydride , fatty acid and
ester or paraffin such as octadene .
 PCMs are solid at room temperature , but
when in contact with warmer objects they
liquify and absorb and store heat
 Liquid PCMs can solidify and give off heat
 Temp monitoring required – additional
blankets if low temp , or additional PCMs if
temp high outside therapeutic range

35.  S Iwata,O Iwata,L Olson,A Kapetanakis,T
Kato,S Evans,Y ArakiT Kakuma,T
Matsuishi, F Setterwall,H Lagercrantz,N J
Robertson. Therapeutic hypothermia can
be induced andmaintained using either
commercial water bottles ora ‘‘phase
changing material’’ mattress in a newborn
piglet model . Arch Dis Child
2009;94:387–391.

36.  Criticool
 Hypothermia achieved by adjusting
temperature of water pumped through the
cooling mattress using feedback from
patients core ( rectal ) and surface
temperature
 Disadv – weighs 35 kg ( not including 1 to 4 L
of water ) & must be secured well

38.  Alternative – weighs
only 7 kg
 Both Requires AC
power . No battery
back up
 Not certified for air
transfer
 Used in TOBY trial

39.  Advise the peripheral hospital , prior to
arrival of Medstar team
 Full blood examination , Platelet count
 Urea and electrolytes
 S.Electrolytes , S . Calcium
 PT , APTT
 Blood glucose
 ABG / CBG
 LFT
 Neurological assessment + Sarnat staging

41. Passive cooling

42. Comparison
Median 33.3
35.2 29.8-36.3
( 31.5-36.60
Median Median
N=19
N=10
N=17
StMichaels Hospital
Bristol

43. Comparison of
Temp maintanance

44. Servo –controlled
N =9
Johnston ED, Becher J-C, Mitchell AP, et al. Arch Dis Child Fetal Neonatal Ed
(2011).

45. Median time for achieving target- 45 min
Temp increased due to CVS instability
Johnston ED, Becher J-C, Mitchell AP, et al. Arch Dis Child Fetal Neonatal Ed
(2011).

46. Chance of overcooling with active cooling with
adjuncts would be decreased as experience improves (
Fairchild et al,2010 )

47.  Long term neurological outcome – 18 months
early to diagnose CP and cognitive deficits
 Best way of assessing core temperature
 Does temperature fluctuations cause any
adverse outcome
 How best is brain cooled with reduction in
rectal temperature

48. 1) Feasible method - Active
vs passive cooling
2) Best method of
temperature monitoring –
Rectal versus esophageal
3) Equipments and packs
4) Education of Peripheral
centres

49.  Sinus bradycardia, increased blood pressure and increased
oxygen requirement - transient and reversible with
rewarming
 Thrombocytopenia
 Arrhythmias – Long QT
 Less likely to occur when the rectal temperature remained
within 33.0oC- 34.0oC.
Adverse effects of hypothermia are physiological, transient and reverse with
rewarming ( Level 1a evidence )

50.  End point was composite – death or severe
disability . Statistically robust but doubtful clinical
utility
 No blinding – not possible given the patient
population . But introduces unquantifiable bias
 Disability assessed at 18 months of gestation . Not
possible to rule out possibility of cerebral palsy in
evolution
 Remains to see whether the benefit retained
through out childhood and beyond ( cognitive
defects )

51.  Neonatal cooling initiated during retrieval
definitely provides benefit for asphyxiated babies
 Active cooling ( with adjuncts or custom made )
gives better temperature control than passive
cooling . Regardless attempts at any form of
cooling is good enough
 Close core temperature monitoring with rectal
probe allows to maintain temp in therapeutic
range
 No major adverse events noted in neonates