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HEME : Health and Medical Journal pISSN : 2685 Ae 2772 eISSN : 2685 Ae 404x Available Online at : https://jurnal.
id/index.
php/heme/issue/view/80 Therapeutic Hypothermia in Severe Neonatal Hypoxic-Ischemic Encephalopathy: A Case Report and Literature Review Eny Yantri1,2.
Zulfahmi1,2 Department of Child Health.
Faculty of Medicine.
Universitas Andalas.
Padang.
West Sumatera.
Indonesia Department of Maternal and Child.
Dr.
Djamil Hospital.
Padang.
West Sumatera.
Indonesia Abstract Hypoxic-ischemic encephalopathy (HIE) remains a leading cause of neonatal mortality and long-term neurodevelopmental disability worldwide, with therapeutic hypothermia emerging as the standard neuroprotective intervention for eligible neonates with moderate to severe HIE.
We report a case of a late preterm female neonate .
-37 weeks gestatio.
born via emergency cesarean section due to severe maternal preeclampsia with respiratory failure, who presented with severe birth asphyxia (APGAR scores 1/.
, profound metabolic acidosis .
mbilical cord pH 6.
7, base excess -20 mmol/L), and severe encephalopathy (Thompson score .
Therapeutic hypothermia was initiated within 6 hours of birth and continued for 72 hours, followed by controlled rewarming, with the patient requiring mechanical ventilation for 10 days and hospitalization for 17 days total.
The patient demonstrated progressive neurological improvement with Thompson scores decreasing from 15 to 3 over the first four days of treatment, while cerebral regional oxygen saturation remained within normal limits throughout cooling therapy.
The infant was successfully weaned from mechanical ventilation, achieved full enteral feeding, and was discharged home without apparent neurological sequelae.
This case demonstrates the successful implementation of evidence-based therapeutic hypothermia protocols in severe HIE management, emphasizing that early recognition, appropriate patient selection, precise temperature control, and comprehensive supportive care are critical for optimal outcomes, while long-term neurodevelopmental followup remains essential for all HIE survivors.
KeywordsAi hypoxic-ischemic encephalopathy, therapeutic hypothermia, neonatal asphyxia Abstrak Ensefalopati hipoksik-iskemik (HIE) tetap menjadi penyebab utama kematian neonatal dan disabilitas perkembangan saraf jangka panjang di seluruh dunia, dengan hipotermia terapeutik muncul sebagai intervensi neuroprotektif standar untuk neonatus yang memenuhi syarat dengan HIE sedang hingga berat.
Kami melaporkan kasus neonatus perempuan prematur akhir .
sia kehamilan 36-37 mingg.
yang lahir melalui operasi caesar darurat karena preeklampsia berat pada ibu dengan gagal napas, yang menunjukkan asfiksia berat saat lahir .
kor APGAR 1/.
, asidosis metabolik berat .
H tali pusat 6,7, kelebihan basa -20 mmol/L), dan ensefalopati berat .
kor Thompson .
Hipotermia terapeutik dimulai dalam 6 jam setelah kelahiran dan dilanjutkan selama 72 jam, diikuti dengan penghangatan kembali terkontrol, dengan pasien membutuhkan ventilasi mekanik selama 10 hari dan rawat inap selama total 17 hari.
Pasien menunjukkan perbaikan neurologis progresif dengan skor Thompson menurun dari 15 menjadi 3 selama empat hari pertama pengobatan, sementara saturasi oksigen regional serebral tetap dalam batas normal selama terapi Bayi tersebut berhasil disapih dari ventilasi mekanik, mencapai pemberian makan enteral penuh.
Health and Medical Journal HEME.
Vol Vi No 1 January 2026 dan dipulangkan ke rumah tanpa gejala sisa neurologis yang jelas.
Kasus ini menunjukkan keberhasilan penerapan protokol hipotermia terapeutik berbasis bukti dalam penanganan HIE berat, menekankan bahwa pengenalan dini, pemilihan pasien yang tepat, kontrol suhu yang akurat, dan perawatan suportif komprehensif sangat penting untuk hasil yang optimal, sementara tindak lanjut perkembangan neurologis jangka panjang tetap penting bagi semua penyintas HIE.
Kata kunciAi ensefalopati hipoksik-iskemik, hipotermia terapeutik, asfiksia neonatal Email : heme@unbrah.
Heme.
Vol Vi No 1
January 2026
INTRODUCTION
Hypoxic-ischemic encephalopathy represents one of the most devastating neurological conditions affecting newborns worldwide, occurring in approximately 1.
5 per 1,000 live births in developed countries.
This condition results from inadequate oxygen delivery and reduced cerebral blood flow during the perinatal period, leading to complex pathophysiological cascades that can result in permanent neurological disability or death.
Despite significant advances in obstetric and neonatal care over the past decades.
HIE continues to be responsible for approximately 23% of all neonatal deaths globally, representing approximately 840,000 deaths The introduction of therapeutic hypothermia as a neuroprotective intervention has HIE management, representing the first evidencebased treatment to demonstrate significant neurodevelopmental outcomes.
Multiple randomized controlled trials and subsequent meta-analyses demonstrated that cooling therapy reduces the combined outcome of death or major neurodevelopmental disability at 18-24 months by approximately 25%.
The pathophysiology of HIE involves a complex cascade of cellular and molecular events that unfold in distinct phases following the initial hypoxic-ischemic insult.
The primary injury phase results in immediate cellular energy failure due to impaired oxidative metabolism, leading to ATP depletion and failure of energydependent cellular processes.
This initial phase is followed by a secondary energy failure phase that typically occurs 6-48 hours after the insult, characterized by oxidative stress, inflammation, excitotoxicity, and Therapeutic secondary injury phase, explaining why early initiation within six hours of birth is crucial for optimal neuroprotective effects.
We present a detailed case report of a late preterm infant who developed severe HIE following birth asphyxia in the context of maternal severe preeclampia.
This case provides an opportunity to examine contemporary evidence-based management strategies, the critical role of therapeutic hypothermia in neuroprotection, and the importance of comprehensive supportive care in achieving optimal outcomes.
II.
CASE PRESENTATION
PATIENT DEMOGRAPHICS AND BIRTH
HISTORY
A female neonate was born at 36-37 weeks gestational age via emergency cesarean section at our tertiary care facility.
The mother was a 37-year-old G3P1A1 who had received regular antenatal care from a beginning in the seventh month of An ultrasound examination during this period revealed no fetal abnormalities and normal amniotic fluid however, the mother was diagnosed with gestational hypertension at that time.
The delivery was precipitated by severe respiratory failure and pulmonary edema, requiring maternal intubation and mechanical The mother received multiple sedative agents including fentanyl, ketamine, and midazolam, while the cesarean section was performed under general anesthesia.
Laboratory .
,650/mmA) and anemia .
g/dL), while platelet count was elevated at 498,000/mmA.
Both HIV and hepatitis B surface antigen tests were negative.
The infant's birth weight was 3,200 grams, body length 49 cm, placing her in the appropriate-for-gestational-age according to Fenton growth curves.
The Health and Medical Journal HEME.
Vol Vi No 1 January 2026 Ballard score confirmed gestational age at 36-37 weeks.
However, the delivery circumstances resulted in severe birth asphyxia, evidenced by profoundly low APGAR scores of 1 at one minute and 3 at five minutes.
and chloride 102 mmol/L.
Renal function studies demonstrated blood urea nitrogen 28 mg/dL and creatinine 1.
0 mg/dL.
Random blood glucose was 95 mg/dL.
Chest radiography performed on admission revealed bilateral lung field opacity consistent with neonatal pneumonia and The infant presented with absence of possible respiratory distress syndrome, spontaneous respiratory effort, weak muscle requiring ongoing respiratory support and tone, and peripheral cyanosis.
Immediate antibiotic therapy.
resuscitation efforts included positioning, drying, and tactile stimulation.
Positive The initial neurological examination revealed pressure ventilation was initiated with peak evidence of severe encephalopathy.
The inspiratory pressure of 25 cmHCCO, positive infant demonstrated hypotonia, lethargy end-expiratory pressure of 5 cmHCCO, and progressing to coma, absent primitive fraction of inspired oxygen at 30%.
Initial reflexes including Moro and grasp reflexes, heart rate was under 100 beats per minute poor sucking reflex, and requirement for and oxygen saturation remained critically mechanical ventilation due to inadequate low at 61% in the first minute.
By the third respiratory effort.
The Thompson score, a minute, the infant remained apneic with validated assessment tool for HIE severity, inadequate respiratory effort, demonstrating was calculated at 15 points, indicating severe nasal flaring and severe chest retractions, encephalopathy and meeting criteria for with oxygen saturation improving only to therapeutic hypothermia eligibility.
5 The Endotracheal intubation was performed Thompson score evaluation revealed using a 3.
5 mm endotracheal tube placed at 9 maximum scores in multiple categories: tone cm depth, followed by continued positive .
- flacci.
, level of consciousness .
pressure ventilation with increased oxygen comatos.
Moro reflex .
- absen.
, grasp concentration to 50%.
By the fifth minute, reflex .
- absen.
, suck reflex .
- absen.
, oxygen saturation reached 92%, chest and respiration .
- requiring mechanical expansion became adequate and symmetrical, ventilatio.
The fontanelle was not tense, peripheral cyanosis resolved, and chest and no seizures were observed during the retractions diminished significantly.
initial assessment period.
LABORATORY AND DIAGNOSTIC FINDINGS
Blood gas analysis from umbilical cord blood revealed profound mixed respiratory and metabolic acidosis with pH 6.
7, pCOCC 117 mmHg, pOCC 9 mmHg, bicarbonate 15.
mmol/L, and base excess -20 mmol/L.
Arterial blood gas analysis confirmed severe metabolic acidosis with pH 7.
12, pCOCC 39 mmHg, pOCC 28 mmHg, bicarbonate 15.
mmol/L, and base excess -21 mmol/L.
Initial laboratory investigations revealed a complete blood count with hemoglobin 17.
1 g/dL, hematocrit 48%, white blood cell count 20,210/mmA, 205,000/mmA.
Electrolyte panel showed sodium 138 mmol/L, potassium 3.
6 mmol/L.
Email : heme@unbrah.
THERAPEUTIC HYPOTHERMIA PROTOCOL
IMPLEMENTATION
Based on the clinical presentation meeting established criteria for moderate to severe HIE, therapeutic hypothermia was initiated within 6 hours of birth6.
The patient met gestational age Ou36 weeks, evidence of perinatal hypoxia-ischemia .
ow APGAR scores, need for resuscitation, severe acidosi.
, and clinical evidence of severe encephalopathy (Thompson score >.
Whole-body therapeutic hypothermia was implemented using passive controlled cooling method with continuous core Heme.
Vol Vi No 1 January 2026 temperature monitoring via rectal probe.
The target temperature range was maintained between 33AC and 34AC for a total duration of 72 hours7.
Temperature was monitored continuously, and cooling was adjusted to maintain precise temperature control within the therapeutic range.
During the cooling period, comprehensive monitoring included hourly vital sign assessment, continuous pulse oximetry, and cerebral regional oxygen saturation .
rSOCC) monitoring using nearinfrared spectroscopy (NIRS).
The crSOCC values remained within normal range .
4%) throughout the cooling period, suggesting adequate cerebral perfusion during treatment.
REWARMING AND RECOVERY PHASE
After completing 72 hours of therapeutic hypothermia, controlled rewarming was initiated at a rate of 0.
5AC per hour to reach target normothermia of 36.
5AC over approximately 7 hours7.
During the rewarming phase, intensive monitoring continued with hourly vital signs, crSOCC monitoring, neurological assessment, and blood glucose monitoring to detect any signs of clinical deterioration.
The Thompson score showed progressive improvement over the treatment course, decreasing from the initial score of 15 to 6 on day 2, then to 3 on days 3 and 4, indicating significant neurological This improvement was reflected in enhanced muscle tone, improved level of CLINICAL COURSE AND MANAGEMENT consciousness, and gradual return of The patient required mechanical ventilation primitive reflexes.
pressure-controlled intermittent mandatory ventilation with By day 5, the patient was successfully volume guarantee (PC-SIMV VG) mode.
weaned from mechanical ventilation and Initial ventilator settings included positive transitioned to continuous positive airway end-expiratory pressure of 6 cmHCCO, tidal pressure (CPAP) with positive end-expiratory volume of 12.
8 mL .
mL/k.
, respiratory pressure of 6 cmHCCO and fraction of inspired rate of 50 breaths per minute, and fraction of oxygen of 30%.
Enteral feeding was initiated inspired oxygen of 40%.
Oxygen saturation with breast milk at 20 mL/kg/day via was maintained between 92-95% throughout orogastric tube, with gradual advancement by the treatment period.
20-30 mL/kg/day while monitoring feeding Fluid management during the cooling period included temporary fasting with total COMPLICATIONS
AND
SECONDARY
parenteral nutrition providing 60 mL/kg/day MANAGEMENT on day 1, progressively increasing to 80-100 The clinical course was complicated by mL/kg/day by days 2-3.
The nutrition several issues requiring active management.
regimen included dextrose infusion at Around day 10-12, the patient experienced glucose infusion rate of 7.
2 mg/kg/minute, respiratory protein at 2 g/kg/day, and lipid at 1 g/kg/day reinstitution of CPAP support, along with which will be increased gradually every day intermittent fever reaching 38.
7AC and according to age.
Antibiotic therapy was feeding intolerance manifested by vomiting initiated empirically with ampicillin- 2-3 times daily.
Laboratory investigations sulbactam 100 mg/kg/day divided into two during this period revealed anemia with doses and gentamicin 5 mg/kg/dose hemoglobin 9.
8 g/dL, requiring careful administered every 36 hours, adjusted for monitoring but not transfusion.
Blood gestational age.
Metabolic acidosis was cultures were obtained and remained bicarbonate negative for bacterial growth.
Chest correction to prevent rapid pH changes that radiography showed persistent bilateral could exacerbate neurological injury.
Antibiotic therapy was escalated Health and Medical Journal HEME.
Vol Vi No 1 January 2026 second-line cefoperazone-sulbactam 200 mg three times daily and amikacin 25 mg three times daily.
Enteral feeding was temporarily reduced to 80-100 mL/kg/day to improve tolerance, with gradual re-advancement as tolerated.
The patient demonstrated gradual clinical improvement over the following days, with successful weaning from CPAP by day 13, resolution of fever, and improvement in feeding tolerance.
By day 15, the patient was maintaining adequate oxygenation on room air and had achieved full enteral feeding at 150 mL/kg/day with good tolerance.
DISCHARGE AND FOLLOW-UP PLANNING
The patient was discharged home on the 17th day of hospitalization in stable condition.
discharge, the infant was breathing spontaneously on room air with oxygen saturations >95%, maintaining normal vital signs, and demonstrating age-appropriate neurological examination findings.
Feeding was well established with breast milk at 150 mL/kg/day with normal sucking reflex and no signs of feeding difficulties.
management of severe neonatal HIE.
The patient presented with multiple high-risk factors including late preterm birth, severe maternal preeclampsia, profound birth asphyxia, and severe encephalopathy, all of which historically would have predicted poor outcomes in the pre-hypothermia era.
The severe metabolic acidosis documented in this case .
mbilical cord pH 6.
7, base excess -20 mmol/L) provides objective evidence of significant tissue hypoxia and impaired cellular metabolism during the perinatal These laboratory findings, combined with the clinical presentation of severe encephalopathy (Thompson score .
, indicate substantial disruption of normal cerebral energy metabolism and activation of secondary injury cascades.
The maternal complications, particularly severe preeclampsia with respiratory failure, created a complex clinical scenario affecting placental perfusion and fetal oxygenation.
Preeclampsia is associated with placental insufficiency and altered uteroplacental blood flow, representing one of the most significant maternal risk factors for HIE development.
The requirement for maternal intubation and high-dose sedation further complicated fetal well-being, although the clear amniotic fluid and absence of chorioamnionitis suggested that the primary pathophysiology was related to placental insufficiency rather than infectious complications10.
The late preterm gestational age .
-37 week.
represents an additional risk factor for HIE development, as these infants demonstrate increased vulnerability to hypoxic-ischemic injury compared to term infants due to incomplete brain maturation and reduced cerebral autoregulation capacity.
Comprehensive discharge planning included detailed education for the family regarding signs and symptoms requiring immediate medical attention, proper feeding techniques, and importance of regular follow-up care.
The family was instructed to monitor weight gain, feeding patterns, and developmental milestones at home.
Follow-up arrangements included a scheduled visit to the neonatology outpatient clinic one week after discharge, with subsequent regular developmental assessments scheduled at 3, 6, 12, and 24 months of age to monitor for any signs of complications related to the HIE diagnosis.
The therapeutic hypothermia protocol implemented in this case adhered closely to i.
DISCUSSION