Neonatal Therapeutic Hypothermia (Therapeutic Hypothermia)

Overview of Neonatal Therapeutic Hypothermia

Hypoxic-ischemic encephalopathy (HIE) is a serious condition that occurs in newborns who don’t get enough oxygen during birth. This lack of oxygen can lead to high rates of death in the infant or long-term developmental issues. This condition is quite common, with up to 1.5 new cases for every 1000 babies born in advanced countries. It’s even more common in developing countries, where it can affect up to 30 in every 1000 newborns.

Babies with HIE can face many challenges. The death rate for this condition varies widely, somewhere between 10% and 60%. Many of the babies who survive can have long-term developmental issues.

There is a treatment for HIE known as therapeutic hypothermia, which involves cooling the baby’s body to reduce damage. A big review of many studies has shown this treatment to be helpful.

However, it’s important to remember that not all babies are helped by therapeutic hypothermia. In some situations, the evidence is not clear or it might not be beneficial.

Let’s take a closer look at these cases:

1. In low-income and middle-income countries: Some studies suggest therapeutic hypothermia might not help to reduce death or severe disability in these settings. Also, this treatment might even cause increased bleeding and low blood platelet count (thrombocytopenia). However, this is not agreed upon by everyone, and many experts believe we should continue using this treatment in these situations.

2. In premature babies under 35 weeks of pregnancy: For babies born prematurely, the use of therapeutic hypothermia is not clear-cut. Some studies suggest it might cause complications. A major study is currently being conducted to help us understand this better. As of now, this treatment is not standard care for premature babies.

3. When the HIE is mild: There’s evidence that even mild HIE can harm a baby’s cognitive function. However, it’s not clear if therapeutic hypothermia helps these babies. More research is needed to better understand the risks and benefits for this group.

4. For late start of therapeutic hypothermia: Sometimes, it is not possible to start therapeutic hypothermia within the usual 6-hour time frame. A recent study suggests starting the treatment later might still be helpful, but this is not agreed upon by all experts. Most medical centers do not use late cooling as a standard treatment.

5. For longer or deeper therapeutic hypothermia: A study has shown that using therapeutic hypothermia for more extended periods or cooling the body at a lower temperature did not improve the outcomes for babies at 18 months of age.

In summary, while therapeutic hypothermia can be beneficial for many babies with HIE, it isn’t for everyone, and more research is needed.

Anatomy and Physiology of Neonatal Therapeutic Hypothermia

The process of getting injured involves several stages, beginning with the initial damage, and then progressing through a few phases – each getting gradually worse. The first phase, or latent phase, lasts about 30 minutes to 6 hours. This is then followed by the secondary phase that lasts from about 6 hours to 3 days, and finally, the tertiary phase that can last for several months.

Right at the start, if the injury is severe, it can disrupt the normal flow of glucose–which is a type of sugar your body uses for energy–to your brain. This means that your brain cells can’t make as much ATP, a molecule that serves as your body’s main energy source. As a result, your brain cells might die. For less serious injuries, your body will try to direct blood flow to the most crucial parts of your brain, like the brainstem. However, this comes at the cost of other parts of the brain, like the cerebral cortex and cerebral hemispheres, which can be negatively impacted.

The latent phase starts about an hour after the injury, as long as your body has been able to restore the oxygen supply. This phase lasts about 6 to 12 hours, during which there can be some recovery within your cells. However, this phase also sees increased inflammation and possible further nerve cell death due to a series of reactions in your cells known as apoptotic cascades. This is also the phase during which therapeutic hypothermia, a treatment that cools your body down to slow your metabolism and reduce inflammation, is typically given.

The secondary phase starts after the latent phase. This phase is usually defined by injury from free radicals (harmful molecules), failure of the mitochondria (the energy-producing parts of your cells), cell death, and potential worsened symptoms, which often lead to seizures.

The tertiary phase is the last stage and can last months. This phase involves the restructuring and further late cell death. The period between the initial cell death and secondary cell death is about 6 hours. This time period is also a key opportunity to start therapeutic hypothermia, which is believed to help by slowing down your brain’s metabolism, reducing inflammation, minimizing cell death and suppressing abnormal receptor activity.

Why do People Need Neonatal Therapeutic Hypothermia

Therapeutic hypothermia is a medical treatment for infants experiencing certain health problems. It essentially involves cooling the baby’s body below normal body temperature for a specific period of time. This approach can be beneficial in helping the brain recover from lack of oxygen or injury. A study conducted by The New England Journal of Medicine showed that this treatment is beneficial for babies with moderate to severe brain damage (encephalopathy).

If your baby is being considered for this treatment, they would need to meet three sets of qualification rules. Let’s simplify these:

First, they have to meet specific demographic criteria. This means:

• The baby should be at least 36 weeks old in terms of gestational age.
• The baby’s weight at birth should be 1800 grams or more.
• The baby should be up to 6 hours old.

The second qualification set is based on certain measurements in the baby’s blood. For instance:

• If a blood test conducted within the first hour after birth shows a certain level of acid (pH of 7.0 or lower) or the base deficit is 16 mmol/L or above, the baby is considered to meet the biochemical criteria.
• If the pH is more than 7.0 but not above 7.15 or the base deficit is below 16 but above 10 mmol/L, or if a blood gas test isn’t available within the hour, there are additional conditions needed. These are related to childbirth complications that may have harmed the baby, indicated by issues like a low APGAR score (which assesses a baby’s health) at 10 minutes or the need for assisted breathing for 10 minutes+. Only if these additional criteria are met does the baby qualify under the biochemical criteria.

The third qualification set is done through a physical exam conducted by the doctor. They will look for signs of moderate to severe encephalopathy or brain damage in the baby. To meet the examination criteria, the baby has to show at least three of six specific symptoms. These include reduced consciousness (from lethargic to coma-like states), reduced or no activity, changes in posture, weakened or absent reflex responses, and signs of impaired autonomic nervous system (which controls bodily functions such as heart rate and breathing). If the baby is having seizures, they automatically qualify under this set of criteria.

If your baby meets all of these conditions – demographic, biochemical, and examination – they could qualify for therapeutic hypothermia treatment. This decision should always be discussed with the parents, and if agreed, the cooling treatment should begin immediately.

When a Person Should Avoid Neonatal Therapeutic Hypothermia

There are several instances where therapeutic hypothermia, a treatment often used to improve survival and brain function, cannot be used:

• If a baby is born earlier than 36 weeks into the pregnancy.
• If a newborn baby weighs less than 1800 grams.
• If the baby is more than six hours old when the treatment is planned to start, although some doctors do consider the treatment for up to a day after birth.
• If a baby is born with a major birth defect.
• If it seems that the baby is unlikely to survive.
• If the child has severe bleeding that is life-threatening (known as life-threatening coagulopathy). However, babies with less dangerous bleeding can still benefit from therapeutic hypothermia. This is because asphyxia and cold can typically make babies bleed a little more

Therapeutic hypothermia should not be done if the infant has significant head trauma or a skull fracture that causes heavy bleeding inside the skull. Minor bleeding under the scalp, known as subgaleal bleeding, can also make the treatment risky. However, cooling the entire body (called whole-body cooling) could be an option after the baby’s initial state is stabilized.

If the baby has a birth defect called an imperforate anus, where the anus is blocked or missing, selective head cooling should not be done. This is because the rectal temperature, which is needed to guide the treatment, cannot be correctly measured. However, whole-body cooling could still be considered along with a different method for measuring temperature – such as using an esophageal probe.

Equipment used for Neonatal Therapeutic Hypothermia

The necessary tools for a procedure known as therapeutic hypothermia (a treatment that lowers the body’s temperature) include:

• A cooling device: This machine is used to decrease the body’s temperature.
• A single-use esophageal probe or rectal temperature probe: These tools are used to accurately measure the body’s temperature.
• An overhead warming bed with an skin temperature probe: This is used to monitor and control the skin temperature.
• A cardiorespiratory monitor: This device tracks heart and lung function.
• An amplitude-integrated electroencephalogram (EEG) or similar tool: This is used to monitor brain activity. It should be available in the hospital (but it can be activated after the cooling process has started).
• A gel pad for the head (needed for a specific procedure known as SHC).

Who is needed to perform Neonatal Therapeutic Hypothermia?

The staff required for carrying out a procedure called therapeutic hypothermia includes certain specialized personnel. These include a neonatologist or pediatrician, who are doctors with special training in caring for newborn or extremely ill babies. There also needs to be a registered nurse who helps manage the overall care. Finally, a pediatric neurologist may be involved. This is a doctor who specializes in the brain and nervous system diseases in children. They would be responsible for interpreting an EEG (a test that checks for problems with the electricity in the brain) and may follow up with the child after he or she has left the hospital.

Preparing for Neonatal Therapeutic Hypothermia

Before starting a treatment called therapeutic hypothermia for a newborn, there needs to be a way for doctors to deliver fluids or treatments directly into the blood, this is known as vascular access. The best way to do this is usually through the umbilical cord. If doctors are unable to use the umbilical cord, they may use a peripheral intravenous line (a small tube inserted into a vein, often in the hand or arm) and if possible, a peripheral arterial line (a small tube inserted into an artery, often in the wrist or ankle), to keep track of the baby’s blood pressure. It’s also needed to connect the baby to a pulse oximeter, a device that measures the level of oxygen in their blood, and a cardiorespiratory monitor, a machine that monitors heart rate and breathing.

Doctors will first assess and record the baby’s health status including physical and brain functions. This record will include the reasons why they believe the baby needs therapeutic hypothermia. It’s also suggested that initial lab tests are completed on the baby. This may include a complete blood count (this measures the cells that make up the blood), coagulation profile (this checks how well the baby’s blood clots), a complete metabolic panel (this measures the chemicals in the baby’s blood), an arterial blood gas (this measures the levels of oxygen and carbon dioxide in the baby’s blood), and testing for a protein called troponin that can assess the health of the baby’s heart. These tests should be repeated regularly as needed during the cooling process, with the electrolytes (salts and minerals in the body that control body fluids and transmit nerve impulses) being checked at least daily.

How is Neonatal Therapeutic Hypothermia performed

Let’s explain therapeutic hypothermia in simpler terms. This is a treatment technique where a baby’s body temperature is decreased slightly to help their body heal. There are two ways this can be done: selective head cooling (SHC) or whole-body cooling (WBC).

1. Selective head cooling (SHC) involves placing a special cap on the baby’s head. This cap circulates cold water to reduce the baby’s core temperature. We aim to get the temperature around the head and brain cooler than the rest of the body – ideally between 34 to 35 °C. Every 12 hours, we remove the cooling cap to check if the baby’s scalp is irritated from wearing the cap.

2. Whole-body cooling (WBC) uses a special blanket that circulates water which can be made cooler or warmer. WBC cools down the entire body at the same pace. The target temperature for WBC is slightly lower, between 33 to 34 °C.

These cooling devices have a monitoring probe to measure the baby’s temperature and keep it within the target range by changing the water temperature in the cap or blanket. This treatment lasts for about 72 hours, after which we gently raise their temperature at a rate of 0.5 °C per hour. This process, called rewarming, takes around 4 hours with SHC and around 6 hours with WBC.

To compare, whole-body cooling cools down all parts of the brain uniformly, whereas selective head cooling cools down the brain’s outer layer more than its inner parts. Both offer protection to the baby’s brain, as shown through brain scan results (EEG and MRI) of infants who have received the treatment. Both methods are also similarly safe and effective with similar side effects. In the United States, most centers prefer whole-body cooling because it’s easier to apply and it makes monitoring the baby’s brain easier.

Passive cooling is another option if the neonatal unit doesn’t have a cooling facility. This involves turning off any warming device, removing clothes, and not using a blanket so that the baby can naturally cool down. We would check the baby’s temperature at least every 15 to 30 minutes. Passive cooling is often used as a temporary solution until the baby can be transferred to a medical facility equipped with cooling devices.

Possible Complications of Neonatal Therapeutic Hypothermia

Therapeutic hypothermia is a treatment that doctors use to cool the body’s temperature. Although this treatment is generally safe, there can be a few, short-term side effects.

1. Heart-related problems
* Bradycardia: This is when your heart rate slows down significantly, by around 15 beats per minute for every degree in temperature change. Even though newborn babies can handle slower heart rates if their blood pressure is still okay, a very slow heart rate (below 60 beats per minute) can be cause for concern. In this case, the doctor might need to run a full EKG, a test that checks how your heart is working.
* Hypotension: This is another word for low blood pressure. Cooling down the body can lower your heart’s output and cause your blood vessels to squeeze shut, both of which can lead to low blood pressure. If blood pressure goes too low, doctors might need to do an echocardiogram, a type of ultrasound, to check your heart’s health. They might then give you IV fluids, medicines, or steroids to help raise your blood pressure back up.
* Prolonged QT interval and problems with the heart’s rhythm: Lower body temperatures can cause changes to the electrical activity inside the heart, leading to irregular, and sometimes dangerous, heart rhythms.

2. Lung-related problems
Therapeutic hypothermia can affect your lungs too. It can cause the body to make less surfactant, a substance that keeps the tiny air sacs in the lungs from collapsing. It can also make the blood vessels in the lungs squeeze shut, leading to high blood pressure in these vessels. This can worsen oxygen levels in the body, but luckily, it usually gets better once the body is warmed up again.

The treatment can also cause problems with the body’s electrolytes (chemicals that help the body function properly), like low levels of potassium, sodium, magnesium, and phosphate. This can affect different parts of the body in different ways.

Cooling the body can also slow down the blood’s ability to clot, potentially lead to an increased risk of infections, delay the stomach from emptying (which can affect how well the body absorbs food), and alter how pain and sedation medications work in the body.

When doctors bring the body’s temperature back up (called rewarming), there can be a few complications as well, like seizures, periods where you stop breathing for a short time (called apnea), and a higher risk of low blood pressure.

What Else Should I Know About Neonatal Therapeutic Hypothermia?

Several clinical trials have been investigating a treatment technique called therapeutic hypothermia for newborns who have suffered from hypoxic-ischemic encephalopathy (HIE), a type of brain damage caused by a lack of oxygen and blood flow.

One of these trials, named the “Cool Cap” study, looked at 234 newborns with moderate to severe HIE. The researchers divided these into two groups: one that received head cooling treatment (116 newborns) and another that received conventional care (118 newborns). After 18 months, they found that the number of newborns who either passed away or suffered severe disability was lower in the group that received head cooling (55%) compared to those who had conventional care (66%). However, they found that head cooling was more beneficial for newborns with less severe HIE.

The Total Body Hypothermia (TOBY) trial involved 325 newborns with moderate to severe HIE. They were also divided into two groups: one group underwent whole-body cooling, and the other group received conventional care. After 18 months, fewer babies in the cooling group (45%) suffered severe disability or death compared to the conventional care group (53%). Importantly, the babies who underwent cooling had a higher survival rate without any neurological issues.

The NICHD Neonatal Research Network (NRN) trial also studied whole-body cooling in newborns with HIE. They found that cooling decreased the number of infants who died or developed disabilities compared to infants who received standard care.

Lastly, the most recent study, the Infant Cooling Evaluation (ICE) trial, discovered that the cooling group had a lower death rate and higher survival rate without disabilities compared to the control group.

Overall, a review of 11 clinical trials revealed that therapeutic hypothermia appears to benefit newborns with moderate to severe HIE by lowering their mortality and disability rates. The advantages of this treatment, which helps improve the chances of survival and good neurological outcomes, appear to outweigh any potential short-term side effects.