Treatments for Hypoxic-Ischemic Encephalopathy (HIE)

There are certain circumstances under which a baby with HIE may not be eligible for therapeutic hypothermia, such as extreme prematurity or a birth weight under 1,750 grams. Read about cooling treatment and the eligibility criteria here.

The oxygen-depriving insult that causes a baby’s HIE is not the only injury; rather, it sets off a chain reaction: rippling outward from the initial injury site, cells become injured, die, and release certain substances that are toxic to other cells. Therapeutic hypothermia slows down this injury process, allowing the baby’s brain to heal and minimizing the spread of damage (3). This treatment involves cooling the baby for three days and then slowly warming them back up (1).

In addition to providing therapeutic hypothermia, medical professionals should very closely monitor babies with HIE for abnormalities in heart rate, breathing patterns, temperature, etc. They should also be on the lookout for frequently-associated conditions such as seizures, infections, and persistent pulmonary hypertension (among many other possible issues). Often, a newborn with HIE will require medical interventions to support their basic biological functions and prevent or manage dangerous complications. The following treatments are frequently indicated for infants with HIE.

Babies with HIE often have respiratory problems, and may require help with breathing in order to prevent additional brain damage from oxygen deprivation. Some babies require resuscitation after birth. Others need more ongoing assistance, such as high-frequency ventilation, inhaled nitric oxide, and extracorporeal life support (ECMO) (4, 5).

Infant seizures can be difficult to recognize, so it important that doctors provide EEG monitoring for high-risk babies. Neonatal seizures must be treated promptly because seizure activity can lead to additional brain damage, including an increased risk of epilepsy (3). Phenobarbital is often used as the first line of treatment, although other drugs and interventions may be needed depending on individual circumstances. It is also very important to treat any underlying causes of seizures (6).

Often, fluid restriction is recommended for infants with HIE until their renal function and urine output are evaluated, but this guideline is not based on evidence from randomized clinical trials. Therefore, decisions about fluid and electrolyte management should be individualized. It is very important to avoid hypoglycemia (low blood sugar) and hyperglycemia (high blood sugar), both of which can increase brain damage (3).

If an infant is ineligible for therapeutic hypothermia, it is still very important to closely monitor their core body temperature and avoid hyperthermia (5). In neonates with HIE, hyperthermia has been associated with an increased risk of negative outcomes such as death or moderate-to-severe disability (3).

There are a variety of possible treatments for HIE that are still in the experimental phase (some are undergoing clinical trials, while others are still being tested on animals). The following are just a few examples of promising treatments.

Erythropoietin is a hormone produced by the kidneys. It instructs stem cells in bone marrow to make more red blood cells (7), and serves a variety of neuroprotective functions. Clinical trials on infants with HIE have shown a reduced risk of death and improved neurological outcomes in infants receiving erythropoietin (8). It may also provide added benefit when used in combination with therapeutic hypothermia.

Phenobarbital is part of a class of medications called barbiturates, which slow activity in the brain. It can help to treat seizures and manage anxiety, among other uses (9). There is also some evidence that phenobarbital can benefit babies with severe HIE when given prophylactically (as a preventative measure).

In a small randomized trial, babies who received phenobarbital had fewer seizures, and also had better neurological outcomes at age three. However, it is important to know that a study on another type of barbiturate (thiopental) showed an increased risk of hypotension, and did not appear to improve seizure rates or neurological outcomes. Therefore, further research is needed on the safety and efficacy of barbiturates for treating HIE (3).

The use of stem cells to treat HIE and related conditions (such as cerebral palsy) is currently under extensive study. Transplantation of stem cells has the potential to promote cell regeneration, prevent inflammation, and improve cell survival rates.

Studies on animal models with HIE have shown that stem cells can migrate to the area of injury. However, the effectiveness of stem cell therapy is likely dependent on a variety of factors, including timing and duration of the therapy, type of cells used, and dose given. Much more research is needed before this becomes an available treatment for babies with HIE (3, 10).

Allopurinol is an antioxidant that inhibits free radical formation (free radicals contribute to cellular damage associated with HIE). Although research on rats with HIE has indicated that allopurinol can decrease the severity of lasting brain damage, human clinical trials have been less conclusive (10,  11).

Additional research is needed, but early studies indicate that it may be most beneficial when administered prenatally to a pregnancy complicated by fetal hypoxia (10).

Magnesium sulfate is often given prenatally to women at risk of premature delivery. It has been shown to improve neurological outcomes and reduce rates of brain injuries such as cerebral palsy (click here to learn more) (CP). It has also been studied as a postnatal treatment for babies with HIE, but so far results have been inconclusive with regard to safety and efficacy (10, 12).

Xenon is a noble gas that may benefit babies with HIE when used in combination with therapeutic hypothermia. The first study on human neonates found a significant benefit of administering xenon along with therapeutic hypothermia, but a larger cohort study did not find significant results (possibly because they used this treatment beyond the first six hours after birth).

Further evidence is needed on the effectiveness of xenon, as well as optimal timing, duration, and concentration (13).

NOS is an enzyme that is upregulated after a hypoxic event; certain isoforms of NOS then contribute to neuronal loss. Some researchers have suggested that inhibiting NOS could prevent further brain injury in babies with HIE; this has shown promise in animal models.

A recent publication suggests that the most promising strategy for clinical trials in human infants is selective inhibition of both neuronal NOS and inducible NOS, but that inhibition of endothelial NOS should be avoided because it is actually very important in maintaining pulmonary blood flow and preventing pulmonary hypertension. Inhibitors that are non-selective could also target eNOS, which may counteract the benefits of inhibiting nNOS and iNOS (14).

HIE is a birth injury that often results from medical malpractice during or around the time of delivery (for more information, please see our page on causes of HIE). It is also malpractice if a medical professional or organization fails to provide appropriate treatment to a newborn with HIE (such as therapeutic hypothermia), missing a critical window of time to prevent additional brain damage.

Sometimes, parents choose to sue if their child’s HIE was caused by negligent medical care, or if their child did not receive appropriate treatment in the immediate aftermath of a hypoxic-ischemic injury.

If you are interested in learning more about whether you have a case, please reach out to our team at ABC Law Centers: Birth Injury Lawyers today for a free case review. In fact, you would pay nothing throughout the entire legal process unless we win or favorably settle your case.

Our firm focuses exclusively on HIE and other birth injuries, so we have the legal and medical expertise needed to successfully advocate for your family.

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11. Annink, K. V., Franz, A. R., Derks, J. B., Rudiger, M., Bel, F. V., & Benders, M. J. (2017). Allopurinol: Old Drug, New Indication in Neonates?. Current pharmaceutical design, 23(38), 5935-5942.
12. Anabrees, J. (2013). Magnesium sulphate for newborns with HIE; synopsis of evidence from a systematic review. Journal of clinical neonatology, 2(3), 114.
13. Amer, A. R., & Oorschot, D. E. (2018). Xenon Combined With Hypothermia in Perinatal Hypoxic-Ischemic Encephalopathy: A Noble Gas, a Noble Mission. Pediatric neurology.
14. Favié, L., Cox, A. R., van den Hoogen, A., Nijboer, C. H., Peeters-Scholte, C. M., van Bel, F., … & Groenendaal, F. (2018). nitric Oxide Synthase inhibition as a neuroprotective Strategy Following Hypoxic–ischemic encephalopathy: evidence From Animal Studies. Frontiers in neurology, 9, 258.