Keeping a Cooled Baby Comfortable: A Gentler Sedative Shows Promise During Treatment for Birth-Related Brain Injury

A plain-language look at a 2025 research review of dexmedetomidine, the medicine used to soothe newborns during three days of cooling therapy

When a baby is born deprived of oxygen and develops a brain injury called hypoxic-ischemic encephalopathy, the standard treatment is to cool the baby's body for three days to protect the brain. During those three days the baby needs medicine to stay calm and comfortable, and for years that medicine has usually been an opioid such as morphine. A 2025 research review that combined seven earlier studies of 609 babies found that a different, gentler sedative — dexmedetomidine — kept babies just as comfortable, appeared just as safe, and was linked to fewer seizures, all while letting babies breathe more on their own. The findings are encouraging but come from studies that were not the strongest kind of experiment, so researchers say a proper trial is still needed before dexmedetomidine can be called clearly better.

Why This Question Matters

To understand why the choice of a calming medicine matters so much, it helps to understand the treatment it supports. Around the time of birth, some babies briefly lose their supply of oxygen and blood flow to the brain. This can cause a serious injury known as hypoxic-ischemic encephalopathy, or HIE, which is one of the leading causes of newborn death and long-term disabilities such as cerebral palsy [1][2]. Doctors discovered that carefully lowering the baby's body temperature for about 72 hours — a treatment called therapeutic hypothermia, or simply "cooling" — can reduce this damage by slowing down the harmful chemical reactions that follow the injury. Cooling is now the standard of care, and it genuinely helps.

But cooling is not comfortable. A cooled baby can shiver and feel stressed, and that stress raises the body's energy use in a way that can work against the very protection cooling is meant to provide. So keeping the baby calm and free of pain is not a luxury — it is part of the treatment itself. The 2025 review by a team led by Enrico Cocchi set out to ask a simple but surprisingly unsettled question: which calming medicine is the best one to use [1]?

How Babies Used to Be — and Still Often Are — Sedated

For most of the time doctors have been cooling babies, the calming medicine has been an opioid — morphine or fentanyl — sometimes combined with another sedative. This became the routine largely out of habit and familiarity rather than because anyone had proven it was the best option. In fact, when researchers surveyed hospitals around the world, they found wide differences in what units actually use, and that a newer medicine, dexmedetomidine, has already become the first choice in about a third of hospitals in the United States [3]. A careful review by the respected Cochrane organization went further and concluded there was simply not enough good evidence to say which sedation approach is best during cooling [4].

The older opioid medicines have some real drawbacks in these fragile babies. Because cooling slows down how quickly the body breaks down drugs, opioids can build up. They can also slow a baby's breathing, which sometimes means a baby who might have breathed on their own needs to be placed on a ventilator. Dexmedetomidine works differently: it calms babies while largely leaving their natural breathing intact, and it does not interfere with the brain-wave monitor doctors use to watch for silent seizures. Those qualities are what made researchers curious enough to study it seriously.

What the Researchers Did

The Cocchi team did not run a new experiment on babies. Instead they performed what is called a systematic review and meta-analysis — a careful method of gathering every qualifying study already published on a topic and, where the numbers allow, combining them into one larger and more reliable picture. They searched the major medical databases for studies published between 2014 and 2024 and found seven that fit, together involving 609 babies who were cooled for HIE [1].

Four of these studies compared babies given dexmedetomidine against babies given the traditional opioids, and their results could be pooled together; in total 152 babies received dexmedetomidine and 334 received opioid-based sedation. These included a study by Naveed comparing dexmedetomidine with fentanyl [5], one by Cosnahan comparing it with morphine [6], and a larger study by Surkov [7]. The remaining three were smaller reports describing only babies who received dexmedetomidine [8]. It is worth being honest about one limitation from the start: none of these were randomized controlled trials, the gold-standard type of study in which babies are assigned to treatments purely by chance. That matters for how confident we can be, a point we return to below.

What They Found

The first and most basic question was whether the gentler medicine actually keeps babies calm enough. It did. Using a standard comfort score, babies on dexmedetomidine were rated essentially the same as babies on opioids, and they did not need extra rescue doses more often [1]. In other words, switching to the newer drug did not leave babies under-treated.

The next questions were about safety, because dexmedetomidine's known side effects are a slower heart rate and, sometimes, lower blood pressure. Here the pooled results were reassuring. Low blood pressure occurred about equally often in both groups, and in one study most of the low-blood-pressure episodes were actually happening before the dexmedetomidine was even started — a sign they came from the underlying birth injury rather than the medicine [9]. Heart rates did tend to run a little lower on dexmedetomidine, which is expected, but no study found a dangerous excess of very slow heart rates. Importantly, the number of babies who died did not differ between the two approaches [1].

Two findings stood out as especially hopeful. First, babies given dexmedetomidine had far fewer seizures during cooling — about 7% compared with about 48% in the comparison group — and needed less anti-seizure medication [1]. Seizures are common and worrying in these babies, so a medicine that might reduce them is genuinely exciting. Second, there were encouraging trends toward getting babies off the breathing machine sooner and to full milk feeds sooner, fitting with dexmedetomidine's gentler effect on breathing and the gut. These last trends were not strong enough to be certain, but they point in a welcome direction [7].

What It Means for Families

If your baby is being cooled and the care team mentions dexmedetomidine, this research is the reason it is increasingly on the table. It offers a way to keep a baby comfortable during a stressful treatment while allowing more natural breathing and possibly reducing seizures. Some hospitals have moved toward using it as their main sedative and have been able to cut opioid use dramatically while keeping babies calm [10]. For a baby with a milder injury who might otherwise avoid a ventilator, that respiratory advantage can be especially meaningful.

At the same time, families deserve a balanced picture. Dexmedetomidine is used "off-label" in newborns, meaning it was not originally approved specifically for them, and the evidence so far, while promising, comes from studies that cannot fully rule out other explanations for the good results. The researchers were careful to say this is a safe and promising option that deserves a proper trial — not a proven winner. One thing the review made very clear is that hospitals have used widely different doses, so careful, standardized dosing and close monitoring of heart rate and blood pressure are essential [11].

What Researchers Are Working On Next

The honest bottom line is that this review turns a promising hunch into a well-documented case for the next step: a proper randomized trial, which the authors note is already underway. Such a trial would assign babies to dexmedetomidine or a traditional sedative by chance, removing the biases that observational studies cannot escape, and would ideally follow the children for two years to see how they develop. Researchers also want to agree on a standard dose so that every hospital is using the medicine the same way. Until those answers arrive, the take-home message for families is cautiously positive: a gentler sedative is showing real promise for keeping cooled babies comfortable, and the science to confirm it is actively being done.

A note on the science: this article discusses sedation during treatment for a serious newborn brain injury. If your family is facing this situation, your baby's care team is the best source of guidance for your individual circumstances.

References

  1. Cocchi E, Shabani J, Aceti A, Ancora G, Corvaglia L, Marchetti F. Dexmedetomidine as a Promising Neuroprotective Sedoanalgesic in Neonatal Therapeutic Hypothermia: A Systematic Review and Meta-Analysis. Neonatology. 2025;122(4):495–504. doi:10.1159/000546017 ↩
  2. Sánchez-Rodríguez EC, López VJ. Hypoxic ischemic encephalopathy (HIE). Front Neurol. 2024;15:1389703. doi:10.3389/fneur.2024.1389703 ↩
  3. Lee K-S, Massaro A, Wintermark P, Soul J, Natarajan G, Dizon MLV, et al. Practice variations for therapeutic hypothermia in neonates with hypoxic-ischemic encephalopathy: an international survey. J Pediatr. 2024;274:114181. doi:10.1016/j.jpeds.2024.114181 ↩
  4. Bäcke P, Bruschettini M, Sibrecht G, Thernström Blomqvist Y, Olsson E. Pharmacological interventions for pain and sedation management in newborn infants undergoing therapeutic hypothermia. Cochrane Database Syst Rev. 2022;11:CD015023. doi:10.1002/14651858.CD015023.pub2 ↩
  5. Naveed M, Bondi DS, Shah PA. Dexmedetomidine versus fentanyl for neonates with hypoxic ischemic encephalopathy undergoing therapeutic hypothermia. J Pediatr Pharmacol Ther. 2022;27(4):352–357. doi:10.5863/1551-6776-27.4.352 ↩
  6. Cosnahan AS, Angert RM, Jano E, Wachtel EV. Dexmedetomidine versus intermittent morphine for sedation of neonates with encephalopathy undergoing therapeutic hypothermia. J Perinatol. 2021;41(9):2284–2291. doi:10.1038/s41372-021-00998-8 ↩
  7. Surkov D. Using of dexmedetomidine in term neonates with hypoxic-ischemic encephalopathy. Medicni Perspektivi. 2019;24(2):24–33. doi:10.26641/2307-0404.2019.2.170123 ↩
  8. O'Mara K, Weiss MD. Dexmedetomidine for sedation of neonates with HIE undergoing therapeutic hypothermia: a single-center experience. AJP Rep. 2018;8(3):e168–e173. doi:10.1055/s-0038-1669938 ↩
  9. Acun C, Ali M, Liu W, Karnati S, Fink K, Aly H. Effectiveness and safety of dexmedetomidine in neonates with hypoxic ischemic encephalopathy undergoing therapeutic hypothermia. J Pediatr Pharmacol Ther. 2024;29(3):232–240. doi:10.5863/1551-6776-29.3.232 ↩
  10. Elliott M, Fairchild K, Zanelli S, McPherson C, Vesoulis Z. Dexmedetomidine During Therapeutic Hypothermia: A Multicenter Quality Initiative. Hosp Pediatr. 2024;14(1):30–36. doi:10.1542/hpeds.2023-007403 ↩
  11. Mantecón-Fernández L, Lareu-Vidal S, González-López C, Solís-Sánchez G, Suárez-Rodríguez M. Dexmedetomidine: an alternative to pain treatment in neonatology. Children (Basel). 2023;10(3):454. doi:10.3390/children10030454 ↩