Transcript Hypothermia for Hypoxic Ischemic Encephalopathy

Hypothermia for Hypoxic
Ischemic Encephalopathy
Mitchell Imm, M.D.
What now?
• Meta-analysis (3 randomized clinical trials) shows that
mild hypothermia is associated with a significant
reduction in death or severe disability
Edwards and Azzopardi. “Therapeutic Hypothermia Following Perinatal Asphyxia.” Archives of Disease
in Childhood: Fetal and Neonatal ed. 2006.
• What form: Selective head cooling vs. Whole Body
cooling?
• What degree of hypothermia provide the most
neuroprotection?
• What is the optimum duration of hypothermia?
• Is it effective outside of 6 hours?
• Is it protective for infants with severe HIE?
• Will the benefits endure when the child reaches school
age?
Hypoxic Ischemic Encephalopathy
• Caused by impaired cerebral blood flow
• Moderate to severe HIE occurs 2-4/1000 live
births
• 10% mortality rate for newborns with moderate
HIE
• 60% mortality rate for newborns with severe
HIE.
• 25-30% survivors with moderate HIE have long
term disabilities
• Nearly 90% survivors with severe HIE have long
term disabilities
Pathogenesis of HIE
Hypoxic-ischemic insult
Primary energy failure
Latent phase
Secondary energy failure
Hypoxic Ischemic Insult
• Usually cause by interruption in placental
blood flow
• Subsequent interruption of cerebral blood
flow
• fetal response
– Cerebral vasodilatation
– Redistribution of organ blood flow
– Loss of cerebral autoregulation
Birth Asphyxia
• Condition of impaired gas exchange that leads to hypoxemia and
hypercapnia
• Fetal acidosis: umbilical arterial pH <7.0 and base deficit >=12
• Early onset of moderate-severe encephalopathy
• Spastic quadriplegic or dyskinetic CP
• Exclusion of other identifiable etiologies
• Other nonspecific criteria
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Sentinel hypoxic event before or during labor
Sustained fetal bradycardia or other signs of non-reassuring fetal status
APGAR 0-3 beyond 5 minutes
Multi-organ failure within 72 hours
Early imaging studies showing acute, non-focal cerebral abnormality
»
From ACOG Task Force in Neonatal Encephalopathy and Cerebral Palsy, 2003
Risk Factors
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Severe preecclampsia
Placental abruption
Multiples
Antepartum hemorrhage
IUGR
Malpresentation
Cord prolapse
Stat C-section
Maternal fever
Pathogenesis of HIE
Hypoxic-ischemic insult
Primary energy failure
Latent phase
Secondary energy failure
Primary Energy Failure
• Decreased high energy phosphate
compounds, e.g. phosphocreatine and
ATP
• Failure of ion pumps leading to Na, K, Ca
ionic gradient disturbances
• Mitochondrial dysfunction
• Glutamate release
• NMDA receptor overstimulation
Pathogenesis of HIE
Hypoxic-ischemic insult
Primary energy failure
Reperfusion
Latent phase
Secondary energy failure
Reperfusion
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Return of cerebral blood flow
Normal blood pressure
Normal intracellular pH
Transient improvement of cytotoxic edema
No seizures
Latent Phase
• Depressed EEG activity
• Recovery of the mitochondria
Pathogenesis of HIE
Hypoxic-ischemic insult
Primary energy failure
Reperfusion
Latent phase
Secondary energy failure
Secondary Energy Failure
• 6-24 hours after insult
• Decreased high energy phosphates
• Similar pathways as Primary Energy
failure
• Seizures
• Cytotoxic edema
• Excitotoxins
• Cell death
Secondary Energy Failure
“The severity of secondary phase energy
failure is strongly correlated with adverse
neurodevelopmental outcomes at 1 and 4
years of age.”
RA Polin, TM Randis, R Sahni. “Systemic Hypothermia to Decrease
Morbidity of Hypoxic-ischemic Brain Injury.” Journal of Perinatology. 2007
Mechanisms of Cell Injury
• Failure of ion pumps
• Influx of Na, Ca, and water
• Glutamate release and subsequent activation of NMDA
glutamate receptors
• Further increase in intracellular Ca
• Activation of lipases, proteases, endonulceases,
phospholipases
• NO synthesis
• Oxygen free radical synthesis
• Free fatty acid peroxidation
• Inflammatory mediators
Cell Death
• Necrosis
– organelle disruption
– plasma membrane disruption and rupture
– cell swelling
• Apoptosis
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programmed cell death
cell shrinkage
nuclear pyknosis
chromatin condensation
genomic fragmentation
Apoptosis
• Caspase activation
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cysteine proteases
cleavage of inhibitor of caspase-activated DNase
Inactivates DNA repair enzyme
activation of caspase-activated DNase
DNA fragmentation and chromatin condensation
• Apoptosis inducible factor
– independent of caspase
– translocates to the nucleus
– leads to DNA fragmentation and chromatin
condensation
Patterns of Brain Injury
• Most common area of injury occurs in
parasagittal cortex (watershed areas) and basal
ganglia and thalamus.
• Parasagittal injury caused by prolonged or
partial asphyxia and causes cognitive
impairments
• Basal ganglia/thalamus injury caused by acute,
near total asphyxia and presents with more
seizure activity. Long term sequelae are
cognitive defects, rigidity, seizures, motor
speech impairment
Modified Sarnat Staging of HIE
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Level of consciousness
Activity
Neuromuscular control
Complex/primitive reflexes
Autonomic function
Seizures
Sarnat Stage 1 (mild)
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Hyper-alert
Active
Normal muscle tone
Mild distal flexion
Overactive stretch reflexes
Weak suck
Strong Moro
Slight tonic neck
Mydriasis
Tachycardia
No seizures
Neuro exam usually normalizes by 3-4 days
No long term sequelae
Sarnat Stage 2 (moderate)
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Lethargic or obtunded
Decreased activity
Mild hypotonia
Strong distal flexion
Overactive stretch reflexes
Weak or absent suck
Weak or incomplete Moro
Strong tonic neck
Miosis
Bradycardia
Focal or multi-focal seizures
Sarnat Stage 3 (severe)
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Stupor or coma
No activity
Flaccid muscle tone
Intermittent decerebration
Decreased or absent stretch reflexes
Absent suck
Absent Moro
Absent tonic neck
Variable pupils; fixed, deviated, non-reactive, and dilated
Variable heart rate
Uncommon seizures
Other Studied Treatments
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Mannitol
Glucocoticoids
Phenobarbital
Calcium Channel Blockers
Magnesium Sulfate
Allopurinol
Resuscitating with FiO2 0.21 instead of 1.0
Superoxide dismutase
Hypothermia for HIE
• Miller et al. “Hypothermia in the Treatment of
Asphyxia Neonatorum.” 1964
• Gluckman et al. “Selective Head Cooling with
Mild Systemic Hypothermia after Neonatal
Encephalopathy Multicenter Randomized Trial.”
Lancet. 2005
• Shankaran et al. “Whole Body Hypothermia for
Neonates with Hypoxic-Ischemic
Encephalopathy.” New England Journal of
Medicine. 2005.
Hypothermia for HIE
• in animal models temperature reductions
of 2-5 degrees C provided neuroprotection
• Impacts multiple pathways to brain injury
• Affecting excitatory amino acids, brain
metabolism, cerebral blood flow, nitric
oxide production, apoptosis
Selective Head Cooling
• N=234 randomized. 218 subjects were
evaluated at 18 months
• 07/1999 to 01/2002
• Cool cap placed within 6 hours (avg. 4.3 hours
of life)
• Used the Cool Cap from Natus Medical
Incorporated. http://www.natus.com
• Infants randomized to normothermic control
group (rectal temp 37 degrees Celsius) or
hypothermic treatment group (rectal temp 34
degrees Celsius) for 72 hours
Selective Head Cooling
Selective Head Cooling
Selective Head Cooling
• Follow up @ 18 months for a
neurodevelopmental exam; height, weight, head
circumference measurements; Bayley-II
psychometric testing; audiology assessment;
vision assessment
• Primary Outcome measures: Mortality and
Severe Neurodevelopmental Disability (Gross
Motor Function impairment level 3-5, Bayley
mental scale<70, bilateral cortical visual
impairment)
Selective Head Cooling
• entry criteria
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At least 36 weeks gestation
APGAR <5 @ 10 min, or
Continued resuscitation, or
Severe acidosis ph<7, base deficit >= 16 on an
umbilical cord blood sample or ABG/VBG done within
60 minutes of birth
– Then, assessed for moderate or severe
encephalopathy using the modified Sarnat
– Then, aEEG showing moderate or severe background
activity and/or seizures
Normal aEEG
Upper margin of
band of aEEG
activity above 10
uV and lower
margin of band of
aEEG activity
above 5 uV
Moderately abnormal aEEG
Upper margin of
band of aEEG
activity above 10
uV and lower
margin below 5
uV.
Severely Abnormal aEEG
Upper and
lower margin
of band of
aEEG activity
below 10 uV
Seizures on aEEG
sudden
increase in
voltage
accompanied by
narrowing of the
band of aEEG
activity and
followed by a
brief period of
suppression
Selective Head Cooling
• Adverse Events
– Overall there was no statistically significant difference
between the treatment and control groups, except for:
– Minor cardiac arrhythmia
• 9% vs. 1%
• Mild sinus bradycardia
– Scalp edema
• 21% of treatment subjects
• Resolved without any intervention after Cool Cap removed
Results
• Treatment group
• Control group
– 108 subjects
– 45% (49) favorable
outcome
– 55% (59) unfavorable
outcome
– 110 subjects
– 34% (37) favorable
outcome
– 66% (73) unfavorable
outcome
• Death 33%
• Severe motor disability
19%
• Death 38%
• Severe motor disability
31%
No significant difference in rates of death or
severe disability at 18 months (p=0.10)
Results
• Infants with moderate aEEG abnormalities
(N=172) there was a significant reduction
in death or severe disability @ 18 months
(48% vs. 66%, p=0.02)
• Infants with severe aEEG abnormalities
(N=46) there was no significant difference
(68% vs. 79%, p=0.5)
Conclusions
“Although induced head cooling is not
protective in a mixed population of
infants with neonatal encephalopathy, it
could safely improve survival without
severe neurodevelopmental disability in
infants with less severe aEEG changes.”
Whole Body Hypothermia
• N=208 (239 eligible)
• 07/2000 to 05/2003
• Patients enrolled by 6 hours of life (avg. 5
hours 2 min of life)
• Subject randomized to hypothermic
treatment group (esophageal temp 33.5
degrees C) for 72 hours vs. normothermic
control group
Methods
• Treatment group placed on infant blanket cooled
to 5 degrees C. Esophageal temperatures were
monitored and set to 33.5 degrees C by the
servomechanism. Abdominal wall temperatures
monitored.
• Esophageal and abdominal wall temp monitored
every 15 min for 4 hours, every hour for 8 hours,
then every 4 hours
• Rewarming 0.5 degrees C every hour till infant’s
temp was 36.5 degrees C after 72 hours of
hypothermia
Whole Body Hypothermia
Follow up
• Primary outcome: death or disability (moderate
or severe)
• Evaluated at 18-22 months for neuromotor
disability, Bayley II, growth, vision assessment,
hearing assessment
• Severe disability defined as Bayley Mental
Development Index<70, GMFCS grade 3-5,
hearing impairment requiring hearing aids,
blindness
• Moderate disability Bayley MDI 70-84 plus 1 of
the following: GMFCS grade 2, epilepsy, hearing
impairment without amplification
Entry Criteria
• At least 36 weeks gestation
• Acidosis pH<7, base deficit >=16 on an umbilical
cord blood sample or 1 hour blood gas, or
• If pH 7.01-7.15, base deficit 10-15.9, and blood
gas unavailable, there must be acute perinatal
event and 10 min APGAR <= 5 or assisted
ventilation for >= 10 min
• Then, neurological examination to determine
severity of encephalopathy using the modified
Sarnat
Sarnat Stage 2 (moderate)
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Lethargic or obtunded
Decreased activity
Mild hypotonia
Strong distal flexion
Overactive stretch reflexes
Weak or absent suck
Weak or incomplete Moro
Strong tonic neck
Miosis
Bradycardia
Focal or multi-focal seizures
Sarnat Stage 3 (severe)
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Stupor or coma
No activity
Flaccid muscle tone
Intermittent decerebration
Decreased or absent stretch reflexes
Absent suck
Absent Moro
Absent tonic neck
Variable pupils; fixed, deviated, non-reactive, and dilated
Variable heart rate
Uncommon seizures
Exclusion Criteria
• Unable to enroll by 6 hours of age
• Major congenital anomalies
• Severe growth restriction (BW<1800
grams)
• Refusal of consent
• Moribund infants for whom no further
treatment was planned
Adverse Events
• no significant difference between
treatment and control groups, except for
sinus bradycardia and skin changes
• Mean HR 109 for treatment group vs. 140
for control group
• Skin changes include erythema, sclerema,
cyanosis, subcutaneous fat necrosis
(4/102 infants)
Results
• Treatment group
– 102 subjects
– 56% (57) favorable
outcome
– 44% (45) unfavorable
outcome
• Death 24% (24)
• Control group
– 103 subjects
– 38% (39) favorable
outcome
– 62% (64) unfavorable
outcome
• Death 37% (38)
Significant difference in rates of death or moderate to
severe disability at 18-22 months (p=0.01).
Results
• There was no significant difference between
treatment and control groups when basing it on
the degree of encephalopathy (moderate 32%
vs. 48%, p=0.09; severe 72% vs. 85%, p=0.24)
• There was no significant difference when
comparing the incidence of disabling CP,
blindness, severe hearing impairment, Bayley
Mental Development Index, Bayley Psychomotor
Development Index
Conclusion
“As compared with the usual care, whole-body
cooling to an esophageal temperature 33.5
degrees C initiated within the 1st 6 hours after
birth and continued for 72 hours reduced the
rate of death or moderate or severe disability
in term newborns with encephalopathy in this
study.”
HYPOTHERMIA FOR HYPOXIC ISCHEMIC ENCEPHALOPATHY
EFFECT ON OVERALL MORTALITY
STUDY
Risk Difference
( 95% CI )
GUNN 1998
-0.06 (-0.35, 0.22)
SHANKARAN 2002
-0.08 (-0.47, 0.32)
EICHER 2005
-0.11 (-0.34, 0.12)
GLUCKMAN 2005
-0.05 (-0.18, 0.08)
SHANKARAN 2005
-0.12 (-0.25, 0.00)
SHAO
-0.11 (-0.24, 0.02)
TYPICAL ESTIMATE
-0.09 (-0.16,-0.02)
SOLL 2006
Decreased
Risk
Increased
0.2
0.5
1.0
2.0
0.2
0.5
1.0
2.0
Relative Risk and 95% CI
HYPOTHERMIA FOR HYPOXIC ISCHEMIC ENCEPHALOPATHY
EFFECT ON DISABILITY OR DEATH
STUDY
Risk Difference
( 95% CI )
GUNN 1998
0.08 (-0.26, 0.42)
GLUCKMAN 2005
-0.12 (-0.25, 0.01)
SHANKARAN 2005
-0.16 (-0.30,-0.03)
TYPICAL ESTIMATE
-0.12 (-0.21,-0.04)
SOLL 2006
Decreased
Risk
Increased
0.2
0.5
1.0
2.0
0.2
0.5
1.0
2.0
Relative Risk and 95% CI
What now?
• Meta-analysis (3 randomized clinical trials) shows that
mild hypothermia is associated with a significant
reduction in death or severe disability
Edwards and Azzopardi. “Therapeutic Hypothermia Following Perinatal Asphyxia.” Archives of Disease
in Childhood: Fetal and Neonatal ed. 2006.
• What form: Selective head cooling vs. Whole Body
cooling?
• What degree of hypothermia provide the most
neuroprotection?
• What is the optimum duration of hypothermia?
• Is it effective outside of 6 hours?
• Is it protective for infants with severe HIE?
• Will the benefits endure when the child reaches school
age?
HYPOTHERMIA FOR THE TREATMENT OF
HYPOXIC ISCHEMIC ENCEPHALOPATHY
From the NICHD Hypothermia Workshop
Implications for clinical practice:
“Based on the available evidence and the known gaps in knowledge, at
the current time, therapeutic hypothermia should be deemed as an
evolving therapy the long-term safety and efficacy of which need to be
established.”
“…The known heterogeneity in neuropathological changes after
perinatal HIE combined with potential regional heterogeneity of
treatment effects will lead to marked differential effects on outcomes
among survivors of HIE (e.g. physical disability versus cognitive
deficits). This underscores the need for longer term follow up of all HIE
infants undergoing any treatment.”
HYPOTHERMIA FOR THE TREATMENT OF
HYPOXIC ISCHEMIC ENCEPHALOPATHY
Implications for clinical practice (cont):
“Therapeutic hypothermia, if offered, should be used only under
published protocols as used in the Cool Cap (selective hypothermia) and
NICHD trials (whole body hypothermia), or as part of ongoing controlled
trial(s) of induced hypothermia for HIE, with appropriate follow up
mechanisms…..”
NICHD Hypothermia Workshop
HYPOTHERMIA FOR THE TREATMENT OF
HYPOXIC ISCHEMIC ENCEPHALOPATHY
Implications for clinical practice:
“The ongoing TOBY, ICE, and other hypothermia trials need to be completed to
enhance our understanding of the role of hypothermia in perinatal asphyxia. Scientists
planning future trials may wish to consider protocol designs similar to the ones already
implemented so that specific questions can be answered and the results can
systematically compared to the existing experience.”
“There is an urgent need for national and international registries to enable ongoing
data collection of data on perinatal encephalopathy, its treatments, and long-term
outcomes.”
“Institutions offering hypothermia in non-research settings also need to document
clinical data in a systematic way, and ensure long-term follow-up of treated infants
using standardized follow-up protocols developed by centers conducting hypothermia
trials and preferably submit information to such registries.”
NICHD Hypothermia Workshop
Pending Studies
• TOBY (Total Body Cooling Trial): N=325.
Submitted for publication in 2009
• ICE (Infant Cooling Evaluation): N=204.
Study stopped due to lack of equipoise.
• Neo nEuro Network: N=121. Study
stopped due to lack of equipoise.
“even if the three trials named
previously with 650 infants did not
show any positive effect the RR
would still have a CI less than 1.0
and the NNT would increase to 15.”
Dr. Marianne Thoresen
Total Body Cooling Protocol
Inclusion Criteria
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≥ 36 weeks gestation
≥ 1800 grams
≤ 6 hours old
pH ≤ 7 or base deficit ≥ 16
Seizures
History of acute perinatal event
APGAR ≤ 5 at 10 minutes or Continued
ventilation for ≥ 10 minutes
• Abnormal neurological exam
NO
36 weeks gestation, ≥ 1800 grams, ≤ 6 hours old
Blood gas pH of 7.0 or less
- cord gas (venous/arterial), OR
- any postnatal blood gas within the
first hour of life (ABG/CBG/VBG)
OR
Base deficit of 16 mEq/L or more
Cord gas or any postnatal blood gas in the
first hour of life
NOT ELIGIBLE
pH of 7.01 to 7.15
or
Base Deficit of 10 to 15.9 mEq/L
NO
YES
NO
NO
History of an Acute Perinatal Event
Examples: abruptio placenta, cord prolapse, variable or late decelerations
And either:
YES
YES
SEIZURES?
10 minute
APGAR
Score of ≤ 5
or
Ventilation initiated
at birth and continued
for at least 10 minutes
YES
NO
NEURO EXAM
ELIGIBLE FOR COOLING
YES
NO
At least one sign in any 3 of 6 categories
Category
Moderate Encephalopathy
1. Level of consciousness
Lethargic
2. Spontaneous activity
Decreased activity
3. Posture
Distal flexion
Full extension
4. Tone
Hypotonia (focal/general)
5. Primitive reflexes
Suck
Weak
Moro
Incomplete
6. Autonomic system
Pupils
Constricted
Heart Rate
Respirations
Bradycardia
Periodic breathing
Severe Encephalopathy
Stupor/coma
No activity
Decerebrate
Flaccid
Absent
Absent
Skew dev, dilated
Non-reactive
Variable HR
Apnea
Exclusion Criteria
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> 6 hours old
Major congenital abnormality
Known chromosomal abnormality
Severe growth restriction (weight < 1800
grams)
• Moribund infants
Target Vital Signs
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Temperature 33.5°C ± 0.5°C
MABP 45-65 mmHg
O2 Sat 93-98%
PCO2 45-58 mmHg (analyzed at 37°C,
true value is lower by 0.83)
• PO2 60-100 mmHg
Equipment
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Blanketrol III
Pediatric cooling blanket and hoses
7 L sterile water
Esophageal and rectal temperature probes
BRAINZ aEEG monitor
aEEG low impedence needle leads
aEEG hydrogel lead
Pre-cooling Phase
• AVOID HYPERTHERMIA. Keep
temperature 36-37°C
• Foley
• aEEG leads placement
• Arterial access
• Venous access
• Do not let these steps delay initiation of
hypothermia
Cooling Phase
• Place esophageal and rectal temperature
probe. CXR to confirm proper placement
of esophageal probe
• Place infant on cooling blanket
• Set target temperature on Blanketrol III to
33.5°C
• Push Set Gradient Variable ± 10°C
• Cool for 72 hours
Vital Sign Monitoring
• Vital signs every 15 min till set
temperature is reached
• Time 0 begins once patient’s temperature
is 33.5°C
• Hours 0-2: vital signs every 15 min
• Hours 2-4: vital signs every 30 min
• Hours 4 to 72: vital signs every hour
Skin Integrity Checks
• Skin assessed every hour
• Sclerema Neonatorum: generalized hardening of the
skin and soft tissue
• Scalp swelling
• Erythema
• Cyanosis
• Exaggerated acrocyanosis
• Waffling
• Shift baby’s position slightly on the blanket to prevent
severe waffling. If baby is too unstable, simply emptying
and refilling the cooling blanket may suffice
Baseline Lab Schedule
• Admission: CBC, CMP, Coags, Mg, Phosphorus,
Direct Bilirubin, GGT, Blood gas
• Hour 12: blood gas, iCa, glucose
• Hour 24: blood gas, iCa, CMP, Mg,
Phosphorous, Coags, CBC
• Hour 36: blood gas, iCa, glucose
• Hour 48: blood gas, iCa, glucose, BMP, Mg,
Phosphorus, CBC
• Hour 60: blood gas, iCa, glucose
• Hour 72: blood gas, iCa, glucose, RT K+, CMP,
Phosphorus, Mg, Coags
Alterations during Hypothermia
• Sinus Bradycardia: HR reduced by 14 bpm
per 1°C drop in temp
• Diuresis due to mitigation of ADH
• Decrease platelet count 10-39%
• Prolonged coagulation studies, which may
be a physiologic response to slower,
stickier blood flow
• Shivering
Alterations during Hypothermia
• Hypokalemia: This is NOT a true loss in
total body K+ but rather an intra-cellular
shift of K+. K+ will shift extra-cellularly upon
rewarming.
• Hyperglycemia: due to decreased insulin
release and decreased glucose utilization
• Hypomagnesemia
• Hypophosphatemia
• Hypocalcemia
Alterations during Hypothermia
• Drug metabolism decreased, especially
drugs metabolized by liver, eg.
phenobarbital, vecuronium, morphine
• Shivering
• Hypocapnia: 4% reduction in pCO2 per
1°C drop in temp
• Thicker respiratory secretions requiring
more frequent suctioning and may
increase risk of pulmonary infection
Rewarming
• Gradually raise baby’s temperature 0.5°C per hour
• Place a pillow under the baby’s head
• Each hour increase the Set Point Temp on the Blanketrol
III by 0.5°C till 36.5°C is reached
• Turn off Blanketrol III. Remove esophageal probe
• Turn on radiant warmer and set servo temperature to
36.5°C
• Keep baby’s temperature 36 to 36.5°C for the next 24
hours
• Babies can easily become hot after hypothermia
Vital Signs and Labwork
• Vital signs checked every 30 minutes till target
temperature reached
• Hour 1: Blood gas, iCa, glucose, RT K+
• Then blood gas, iCa, glucose, RT K+ every 2
hours
• When 36.5°C is reached, check blood gas, iCa,
glucose, BMP, Mg, phosphorus, CBC, Coags
• 24 hours after completion of rewarming, check
blood gas, iCa, glucose, CMP, Mg, phosphorus,
Direct bilirubin, GGT
Changes with Rewarming
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Seizures
Hypotension: usually secondary to hypovolemia
Hyopglycemia
Watch for Hyperkalemia
Drug metabolism improves. Dosages may need
to be increased to pre-cooling levels
• Stools may be fatty
• Apnea
Quality Assurance
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Patient’s temperature range
Onset of hypothermia
Mortality
18 month neurodevelopmental outcome
– f/u with Dr. Del Angel
• Infection
• Skin Integrity
Transport
• Criteria for referring hospitals
– APGAR ≤ 5 at 10 minutes
– Need for continued assisted ventilation past 10
minutes
– Acidosis in the 1st hour of life (pH ≤ 7 or base deficit ≥
16)
– Seizures
• Avoid hyperthermia. Monitor temperatures
every 30 minutes. Keep temperature between
36-37°C (96.8 to 98.6°F)
• Can we get the patient hypothermic before 6
hours of life?
Late Onset Hypothermia Trials
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University of Texas Southwestern Medical Center at Dallas
Contact: Pablo J. Sanchez, MD 214-648-3753
Contact: Nancy A. Miller, RN 214-648-3780
Principal Investigator: Pablo J. Sanchez, MD
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University of Texas Health Science Center at Houston
Contact: Kathleen A. Kennedy, MD MPH 713-500-6708
Contact: Georgia E. McDavid, RN 713-500-5734
Principal Investigator: Kathleen A. Kennedy, MD MPH
Principal Investigator: Jon E. Tyson, MD MPH
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http://clinicaltrials.gov/show/NCT00614744
Entry Criteria: age 6 to 24 hours old
Exclusion Criteria: any infant with a core temp < 34°C for >1 hour