Hypoxic-ischaemic encephalopathy and therapeutic hypothermia — formative SAQs

SAQ 1 — The eligible term infant and the cooling decision (20 marks, ~15 minutes)

A term infant (39 weeks, birthweight 3400 g) is born after an emergency caesarean for placental abruption. Cord blood pH is 6.88, base deficit 14 mmol/L. Apgar scores are 1, 3, and 5 at 1, 5, and 10 minutes, with ongoing mask ventilation at 10 minutes. At 2 hours of age the infant is lethargic, with generalised hypotonia and depressed Moro and suck reflexes, and is not seizing. [1]

Questions

1. Define the clinical syndrome, grade the encephalopathy using the Sarnat criteria, and state whether this infant meets the cooling eligibility criteria. (5 marks) [1]
2. Outline the immediate bedside management before and during the cooling assessment, naming the first bedside test and the principle of temperature management. (5 marks) [4]
3. Describe the cooling protocol in full — target temperature, duration, window for initiation, and rewarming rate. State the evidence that supports it. (6 marks) [4]
4. Describe the supportive neurocare that must be maintained during the 72 hours of cooling, and name two complications of hypothermia. (4 marks) [10]

Model answer (must-hit)

1. The infant has moderate hypoxic-ischaemic encephalopathy (Sarnat stage 2 — lethargy, hypotonia, depressed primitive reflexes) with biochemical evidence of perinatal asphyxia (cord pH under 7.0, base deficit at least 12 mmol/L, Apgar 5 at 10 minutes, ongoing resuscitation). Moderate HIE is cooling-eligible. [1]
2. Stabilise airway, breathing, circulation. Check the blood glucose immediately (the first bedside test); treat hypoglycaemia with 10% dextrose 2 mL/kg IV. Keep the infant normothermic (36.5–37.5 °C) — never actively warm an asphyxiated infant, and avoid hyperthermia, which worsens outcome. Send a septic screen and start antibiotics. Assess Sarnat stage and activate cooling within 6 hours of life. [4]
3. Therapeutic hypothermia: target core 33.5 to 34.5 °C for 72 hours, started within 6 hours of life, using a servo-controlled whole-body or selective-head device; rewarm at 0.5 °C per hour. Supported by the CoolCap (Gluckman 2005), NICHD (Shankaran 2005) and TOBY (Azzopardi 2009) trials and the Jacobs 2013 Cochrane meta-analysis, which collectively show cooling reduces death and major disability by roughly a quarter. [3] [4] [5]
4. Maintain normoglycaemia, normoxia, normocapnia and normotension — each secondary insult extends the brain injury cooling is trying to prevent. Treat seizures to an electrographic endpoint with phenobarbital 20 mg/kg IV first-line. Monitor and correct coagulopathy and thrombocytopenia. Two complications: sinus bradycardia (common, benign, not an indication to rewarm) and coagulopathy or thrombocytopenia. Others include pulmonary hypertension and subcutaneous fat necrosis with late hypercalcaemia. [10]

SAQ 2 — The late-presenting infant and the boundary of the evidence (20 marks, ~15 minutes)

A term infant is transferred to the tertiary NICU at 10 hours of age with lethargy, hypotonia and a history of perinatal asphyxia (cord pH 6.9, Apgar 4 at 10 minutes). The referring registrar asks whether therapeutic hypothermia is still indicated. [8]

Questions

1. State the standard position on therapeutic hypothermia initiated after 6 hours of age, and cite the trial that defines the boundary. (5 marks) [8]
2. Explain the pathophysiological reason why cooling loses its benefit beyond the 6-hour window, naming the phase of injury that is the cooling target. (5 marks) [10]
3. Outline how you would counsel the team about the options and the principle that should govern the decision. (5 marks) [8]
4. State the role (if any) of adjuvant neuroprotective therapies such as erythropoietin, and cite the relevant trial. (5 marks) [8]

Model answer (must-hit)

1. Cooling initiated between 6 and 24 hours of age is not standard practice. The Laptook 2017 randomised trial (the late-hypothermia study) tested cooling started at 6 to 24 hours of life and found no significant reduction in death or moderate-to-severe disability at 18 to 22 months. The proven neuroprotective benefit is confined to cooling started within 6 hours of life. [8]
2. The cooling target is the latent phase — the window of partial metabolic recovery (roughly 6 to 48 hours) between the primary insult and the secondary energy failure. Cooling works by slowing cerebral metabolism and interrupting the excitotoxic and inflammatory cascade before secondary neuronal death is established. Once secondary energy failure has taken hold, the cascade has run, and cooling can no longer intercept it — which is why the 6-hour boundary exists. [10]
3. Counsel that the evidence does not support routine cooling beyond 6 hours, but that individual centres may weigh the equipoise against the absence of an alternative neuroprotective option, particularly for an infant close to the 6-hour mark. The governing principle is evidence-based practice: the family should be informed of the uncertainty, and any cooling outside the standard criteria should follow specialist consultation and local protocol. [8]
4. Adjuvant therapies have so far been disappointing. The Wu 2022 trial of high-dose erythropoietin added to cooling found it did not improve outcomes and may have harmed, tempering enthusiasm for adjuvant drug therapy. Other candidates (xenon, melatonin, stem cells) remain investigational. Cooling remains the only proven neuroprotective intervention. [8]