Fever after central nervous system insult may exacerbates brain injury and worsens outcome. Therapeutic hypothermia (TH) acts as a neuroprotectant to minimize neuronal loss or damage, with an aim to improve patient outcome. In the case of acute brain injury including traumatic brain injury, cardiac arrest or status epilepticus, numerous animal experimental trials have produced positive results of TH, but translating results to human studies with reliable guidelines has proved more challenging.
While TH is an e?ective neuroprotective therapy for newborn with hypoxic ischemic encephalopathy, where it has been shown to improve both survival and neurodevelopmental outcome; the use of TH as neuroprotective measure in other pediatric populations still a matter of debate.
TH is not without its own adverse effects. These include arrhythmia, electrolyte imbalance, infection, coagulopathy, and hypotension with rewarming.
We aimed to conduct a comprehensive review for the current indications and the benefits of hypothermia therapy in acute brain injury the pediatric population (beyond the neonatal period) by analyzing neurologic outcomes, mortality, and adverse effects.

Also add pharmacokinetics of medications and TH++++
Pathophysiology
Current indications
1. Cardiac arrest
The benefits of TH are enhanced in animal models when cooling begins during cardiac arrest or soon thereafter. Experimental studies have shown that TH can protect the heart against the ischemic processes occurring after cardiac arrest and reduce the neuronal injury secondary to global ischemia.
In humans, the e?ect of TH on overall neurologic outcome has been studied in many patient populations, with varying results. While use of TH in adult cardiac arrest patients showed bene?t in both survival and neurologic outcome in early studies, more recent data has shown no difference in outcome for targeted temperature control at 36°C compared with TH at 33°C 20–22. Studies of pediatric patients (non-newborns) with cardiac arrest have not demonstrated e?cacy of TH. Most notably, the therapeutic hypothermia after pediatric cardiac arrest #THAPCA# group tested TH (33°C) versus targeted normothermia (36.8°C) after both out-of-hospital and in-hospital arrests in pediatric patients 8,9. In both cases, there was no di?erence in survival or good functional outcome between the groups, although patients selected for these trials were severely ill, as eligibility criteria required dependence on mechanical ventilation with Glasgow Coma Scale