Overview
Definition:
Therapeutic hypothermia (TH), also known as therapeutic cooling, involves selectively lowering the core body temperature of term and near-term newborns diagnosed with moderate to severe hypoxic-ischemic encephalopathy (HIE)
The goal is to reduce the metabolic rate, inflammation, and excitotoxicity, thereby limiting secondary brain injury and improving neurological outcomes.
Epidemiology:
HIE occurs in approximately 1-8 per 1000 live births in developed countries, with higher rates in low- and middle-income countries
Among affected infants, moderate to severe HIE is associated with significant mortality and long-term neurodevelopmental disability, making early intervention crucial.
Clinical Significance:
HIE is a leading cause of preventable brain injury in neonates
TH has been demonstrated in multiple randomized controlled trials to significantly reduce mortality and severe disability in survivors, making it a cornerstone of neonatal resuscitation and neuroprotection
Understanding strict inclusion criteria is vital for maximizing benefits and avoiding unnecessary interventions.
Inclusion Criteria
Gestational Age:
Infants born at ≥ 36 weeks of gestation.
Timing Of Onset:
Therapy should be initiated within 6 hours of birth, ideally as soon as possible after the insult is recognized.
Signs Of HIE:
Evidence of moderate to severe encephalopathy, typically characterized by the presence of at least one of the following: abnormal neurological status (e.g., altered consciousness, hypotonia, seizures), abnormal neuroimaging (e.g., MRI showing evidence of hypoxic-ischemic injury), or abnormal amplitude-integrated electroencephalography (aEEG).
Confirmation Of Perinatal Asphyxia:
Clinical evidence of a significant perinatal event, such as: Apgar score < 5 at 5 minutes of age
Umbilical cord arterial pH < 7.0 or base deficit ≥ 12 mmol/L within 60 minutes of birth
Need for resuscitation at birth (e.g., positive pressure ventilation for > 1 minute, chest compressions)
Suspicion of intrapartum asphyxia based on maternal or fetal risk factors.
Exclusion Criteria:
Major congenital anomalies incompatible with life or survival
Known severe coagulopathy or bleeding diathesis that cannot be corrected
Prematurity < 36 weeks gestation (unless specific institutional protocols are in place for carefully selected preterm infants).
Diagnostic Approach
History Taking:
Detailed history of labor and delivery, including antenatal complications, fetal monitoring, Apgar scores, cord blood gas analysis, and immediate postnatal interventions
Assess for any events suggesting perinatal asphyxia.
Physical Examination:
Comprehensive neurological examination to assess the degree of encephalopathy: level of consciousness (alert, lethargic, stuporous, comatose), tone (normal, hypotonic, hypertonic), posture, reflexes, and presence of seizures
Assess vital signs and signs of organ system dysfunction (e.g., cardiovascular, respiratory, renal).
Investigations:
Umbilical cord blood gas analysis (pH, base deficit)
Complete blood count, electrolytes, glucose, calcium, lactate, liver function tests, and renal function tests to assess for organ dysfunction
Electroencephalography (EEG) or amplitude-integrated EEG (aEEG) to objectively assess brain electrical activity and detect seizures
Neuroimaging (cranial ultrasound, MRI brain) to evaluate the extent and pattern of hypoxic-ischemic injury
Specific patterns on MRI (e.g., involvement of basal ganglia, thalamus, parasagittal cerebral cortex) are highly suggestive of HIE.
Differential Diagnosis:
Other causes of neonatal encephalopathy should be considered and ruled out, including sepsis, intracranial hemorrhage, metabolic disorders (e.g., hypoglycemia, inborn errors of metabolism), genetic disorders, congenital brain malformations, and drug withdrawal
Careful correlation of clinical findings, timing of events, and investigations is crucial.
Management Principles Of Cooling
Target Temperature:
Controlled whole-body cooling to a rectal temperature of 32-34°C for 72 hours, or selective head cooling to a cranial temperature of 33-34°C while maintaining systemic temperature between 36-37°C.
Re Warming:
Gradual re-warming over 4-8 hours to a target systemic temperature of 36.5-37.5°C
Monitor for shivering during re-warming.
Monitoring:
Continuous rectal or esophageal temperature monitoring
Frequent neurological assessments
Continuous EEG/aEEG monitoring to detect seizures
Monitoring of vital signs, blood pressure, and peripheral perfusion
Routine laboratory monitoring for electrolytes, glucose, calcium, and organ function.
Complications Of Hypothermia
Early Complications:
Bradycardia, hypotension, arrhythmias
Increased risk of bleeding (due to impaired platelet function and coagulation)
Electrolyte imbalances (e.g., hypokalemia, hypomagnesemia)
Hyperglycemia or hypoglycemia
Renal dysfunction
Pulmonary hypertension.
Late Complications:
Infection (due to immunosuppression)
Prolonged QT interval
Potential for impaired cardiac function
Potential for bone abnormalities (rare).
Management Of Complications:
Careful fluid and electrolyte management
Blood product transfusions if bleeding occurs
Management of arrhythmias and hypotension
Close monitoring for signs of infection
Cardiovascular monitoring
Gradual re-warming with close observation.
Prognosis
Factors Affecting Prognosis:
Severity of encephalopathy at diagnosis
Apgar score and cord pH values
Presence and pattern of injury on neuroimaging (especially MRI)
Seizure activity
Response to cooling therapy
Presence of multi-organ dysfunction.
Outcomes:
Infants with mild HIE often have good outcomes
Those with moderate to severe HIE treated with TH have improved outcomes compared to historical controls, with significantly reduced rates of mortality and severe neurodevelopmental disability
However, a significant proportion still experience long-term sequelae.
Follow Up:
Long-term neurodevelopmental follow-up is essential, typically including developmental assessments at 18-24 months corrected age, assessment of motor function, cognitive abilities, and sensory impairments
Ongoing monitoring may include audiology and ophthalmology evaluations.
Key Points
Exam Focus:
Strict adherence to inclusion criteria is paramount for effective and safe therapeutic hypothermia in neonatal HIE
Recall gestational age (≥ 36 weeks), timing (< 6 hours), and objective evidence of moderate-to-severe encephalopathy or confirmed asphyxia.
Clinical Pearls:
Always consider other causes of encephalopathy in the differential diagnosis
Initiate cooling as early as possible once criteria are met
Continuous multidisciplinary monitoring is critical during hypothermia and re-warming.
Common Mistakes:
Delaying initiation of cooling beyond the critical 6-hour window
Treating infants who do not clearly meet encephalopathy or asphyxia criteria
Inadequate monitoring of temperature, neurological status, and potential complications.