A cool treatment saves the brain

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Are you a shiverer? Then you cope better with the cold. But without protective mechanisms, the body’s core temperature quickly drops and there is a risk of frostbite. At the same time, a body that is cooled down copes better without oxygen, something researchers can utilise to save lives.

It is below freezing in the room. A man wearing only swimming trunks, shoes and mittens is sitting on a chair. In another room there is a bath filled with water at a temperature of 15 degrees. Does it sound nice?

“No, it is clearly uncomfortable. Our research subjects are thus often people who are themselves very interested in what happens to the body in extreme conditions,” says Ola Eiken, Professor of Environmental Physiology at KTH Royal Institute of Technology in Stockholm and docent in Physiology at Karolinska Institutet.

He has himself participated in some of the experiments conducted at his workplace, where their investigations include looking at how the body reacts to high and low temperatures. This largely involves basic research in which the goal is to find markers indicating which individuals run an increased risk of local cold injuries, in the worst case frostbite. The fact is that this is rather unknown today. 

Cold can damage us in two ways; either through local frostbite in a body part, or through hypothermia, where the core temperature of the body drops. And people with a strong defence against cooling down  appear to have an increased risk of local cold injuries. 

When exposed to cold, their vessels contract, so that blood flow to primarily the fingers and toes decreases. Then, from time to time, the body releases the blood flow again so that a surge of warm blood reaches the extremities, possibly a physical defence against local frostbite. The disadvantage is that the blood then cools down, which reduces the body’s core temperature. How often and for how long the body releases the blood flow in this way is individual. 

A limited reinstatement of flow to the extremities leads to greater risk of frostbite, but reduces the risk of cooling down, and vice versa. The body’s main defence against cooling down is shivering, and how effectively we shiver is also individual. Some of the research subjects who bathe in the 15-degree water shiver violently. This causes the muscles to release energy, providing warmth and keeping the body temperature up. But others do not shiver at all and are unprotected against the cold. Their body temperature falls quickly. After 20–25 minutes, it can be as low as 35 degrees. Violent – or effective – shiverers can remain in the 15-degree water for longer, some of them for more than an hour and a half, while fundamentally maintaining their body temperature. 

“This is something of a mystery today. The research subjects who are perceived as homogeneous differ greatly on this point and we don’t know why,” says Ola Eiken.

But which group feels that they are freezing the most – the shiverers or those whose body temperature decreases? 

“It has not been possible to confirm any patterns there either,” says Ola Eiken. Studies show that well-trained people who shiver can increase their metabolism by a factor of six and generate a lot of heat. But this is tiring work. Energy stores are depleted and the body becomes exhausted. The defence against the cold is temporary and in order to survive, you need to find external heat sources. Every year, 30–45 Swedes die in accidents where they have been cooled down. In many of these accidents, the victims have consumed alcohol or drugs, which reduces the body’s ability to shiver and constrict the blood vessels. People with mental disorders or dementia and those involved in recreational activities who are taken by surprise by cold weather are among those more likely to die from hypothermia. And it is probable that the statistics don´t show all the deaths – for example, some of those who are found drowned with a life jacket have actually died of hypothermia.

When it comes to local frostbite injuries, some occupations are more exposed, such as reindeer herders, sailors, fishermen and farmers. People involved in recreational activities also belong to those ulnerable, with mountaineers and snow mobile drivers found among those affected. 

Frostbite also occurs among the homeless and some people with mental illness. The experiment Ola Eiken leads is always called to a halt when the body temperature of a research subjects falls to 35 degrees. Such a small drop is actually completely harmless. But major changes take place at lower body temperatures (see the graphic on age 44. Despite this, seriously hypothermic people can survive and escape with no injuries whatsoever. The Swede Anna Bågenholm survived an accident in which she remained under ice for 80 minutes. Her body temperature decreased to 13.7 degrees and she had a cardiac arrest that lasted for over two minutes. Anna Bågenholm survived without serious injury, but was forced to change her job from surgery to radiology due to impairment of the fine motor control in her fingers. That the body is able to withstand such an event is due to the decreasing metabolism. The lower the body temperature, the lower the metabolism. This means among other things that the organs use less oxygen.

It is this mechanism that is now being deliberately used in several ways in healthcare. For over ten years, it has been customary to use cold treatment to prevent brain injury following cardiac arrests that take place outside of hospital. This is rarely required for cardiac arrests in hospitals as patients who are resuscitated quickly suffer less oxygen deprivation and injuries. 

Cold treatment normally begins with the patient being injected with cold fluids. This rapidly cools the patient’s body temperature down to about 33 degrees. The low temperature is then maintained for 24 hours using cooling blankets that use circulating cold fluids or with other, more advanced methods. The patient is given muscle relaxant drugs in order to prevent any resulting shivering. The patient is also kept under general anaesthetic, which further reduces their metabolism.

However, in most cases cooling is only begun several hours after the cardiac arrest, following transport to hospital in an ambulance, investigations and admission to the intensive care unit. This is something that Per Nordbergcardiologist and PhD student at the Department of Clinical Research and Education at Stockholm South General Hospital, Karolinska Institutet, wants to change. He is researching a new method for cold treatment that the paramedics can begin while they are administering cardiopulmonary resuscitation. The patient is equipped with a nasal catheter similar to those used to provide oxygen, a hose with two prongs that are inserted into the nostril. This delivers chilled gas to the patient, lowering the temperature locally in the brain. The rest of the body is cooled down later in the hospital.

“By beginning cold treatment early, we think that there is potential to save the nerve cells that die as a result of oxygen deficiency during a cardiac arrest. We also believe that we can limit the second wave of cell death that follows a cardiac arrest,” says Per Nordberg.

The brain is stressed as a result of the oxygen deficiency during cardiac arrest and a cascade of biochemical processes begins. For example, the nerve cells begin uncontrolled release of the signalling substance glutamate, something which ultimately results in an excess of calcium – leading to the death of the nerve cell. Slowing down the brain’s metabolism by early cooling may be one way to counteract these negative processes. 

However, this idea is not new. An American study was published at the end of 2013 in which cardiac arrest patients had been randomly chosen to receive cooling in the hospital as normal or in the ambulance. But the study showed there was no benefit to fast cooling. Many patients had another cardiac arrest before they arrived at the hospital. This may be because the quick cooling in the ambulance was performed by injecting large quantities of cold fluids, up to two litres, immediately after the heart was restarted.

According to Per Nordberg “it is probably too great a load for the newly started heart to pump such a large volume of fluid around the body. I was not completely surprised by the study’s results.” Thus, the study is not entirely dismissive of quick cooling, rather of how this is done, he believes. He is now leading a large study in which the patients are randomly selected for cooling in accordance with current procedures or while they are in the ambulance – except that cooling is done via the nose. A total of 500 patients will be included in the study and it is hoped that it will be completed in 2015. The hypothesis is that early cooling will lead to fewer brain injuries among the patients, so that they end up with fewer problems in terms of impaired memory or physical disabilities.

Per Nordberg believes that cooling to protect the brain can help more patient groups than it is currently being used for, such as stroke patients. As opposed to cardiac arrest patients, however, these people are often conscious, and the use of cooling via the nose requires the patient to be unconscious or anaesthetised. 

“We have tested the spray on healthy test subjects when they were awake, but they became very stressed due tothe discomfort caused by having your nostrils cooled. Their blood pressure and heart rate rose, which is counterproductive in this context,” says Per Nordberg. 

He also believes that cooling treatment can be refined further in the long-term, with better data concerning which body temperature is actually optimal and how long the cooling should last. 

“I wouldn’t be surprised if future studies indicate that the body temperature should be reduced even further and that it should be kept at a low for longer, perhaps 72 hours.” 

Cooling treatment for 72 hours is customary in another area of healthcare, namely neonatal care. Sweden was one of the first countries in the world to introduce cooling treatment for children with acute oxygen deficiency, born at 36 weeks or earlier. 

Every year, between 100 and 200 such children are born in Sweden. About one quarter can be kept alive or saved from severe brain injury by cooling. Despite this, not all children receive the treatment they need – at least in 2011, according to a review conducted by the Swedish Brain Foundation and researchers from Karolinska Institutet. One reason is that the treatment must be initiated within six hours of  birth.

Because the majority of hospitals cannot offer cooling, the frail, newborn babies must be immediately transferred; requiring a quick decision by a skilled paediatrician. During the transfer, the child is often placed in a normal transport incubator or in a type of cooling suit, which requires a special ambulance. 

“There are examples where the body temperature has decreased too much during the transfer, as low as to 28 degrees. This is not good and can affect the outcome of the cooling treatment. There is a need for simpler and safer transfers of children who need cooling treatment. It would also be good if it could be initiated earlier,” says Linus Olson, PhD, civil engineer and researcher at the Department of Women’s and Children’s Health. 

He has produced a cooling mattress that works without either electricity or water, which means it can be used in all ambulances and hospitals. It consists of a plastic cover filled with a so called phase-change material, which can transform from a solid to a liquid phase, using the child’s body heat as a source of energy in the process. After about half an hour on the cooling mattress, the child reaches a temperature of about 33.5 degrees.

“A big plus is that the mattress then maintains this temperature in a very stable way. It is also very much cheaper than the equipment that is currently used for cooling treatment. In addition to the opportunity to improve transfers in Sweden, we see the potential for improved neonatal care in developing countries,” says Linus Olson. 

We are speaking over a somewhat crackly Skype link from Vietnam, where Linus Olson is involved in a research study testing the mattress on newborn children with acute oxygen deficiency. Cooling treatment is currently only available at a couple of hospitals in Vietnam, which has a population of 90 million. In this study, the mattress will be used to allow cooling treatment already during transport to and at additional hospitals. 

“The goal is to save lives and reduce brain injuries among children with acute oxygen deficiency. If the study confirms that the mattress is effective in these contexts, there are plans to introduce it more permanently in neonatal care in Vietnam. In the long-term, other countries with less developed neonatal care will be of interest,” says Linus Olson.

The cooling mattress is also being tested in a study in Sweden. In the first stage, newborns with oxygen deficiency will be randomly selected to be transferred by air, either in a normal transport incubator or on the cooling mattress. The next stage will involve the same thing, but with normal ambulance transfers. The outcome being studied is how many children in each group dies or have serious brain injuries by the age of six; the study’s results are thus a long way off. 

“If it turns out that transfers with the cooling mattress are better than using the transport incubator, there is good reason to consider a change to current procedures.” 


Facts: Three ways to survive the cold

  • Newborn infants cannot shiver. Instead they are born with large quantities of brown body fat, an energy store that can be turned into heat when required. Animals that hibernate also keep warm partly  with the help of brown fat.
  • Frogs and reptiles are cold-blooded, which means that they cannot warm themselves with their own body heat. They survive winter by finding a place that the cold does not really reach. 
  • Some frogs and reptiles can counteract ice forming in their bodies – they can partly freeze, yet survive. When the temperature drops, frogs increase the amount of the sugar glucose they produce in their body fluids. Glucose reduces the freezing point and this protects their cells from freezing and being destroyed.


Nine degrees below freezing

Below 37 degrees
The body begins to shiver and the teeth chatter. Peripheral blood vessels contract.

Below 35 degrees
Metabolism drops and the body begins to go into energy-saving mode. Energy-intensive but protective shivering normally stops. The nervous system is affected and movements, speech and cognitive ability become worse. It becomes hard to grasp and swim, which naturally is deadly for those who are in the water or far from shelter

28 degrees
Most people fall unconscious. The heart beats slowly and there is a clear risk of cardiac rhythm disturbances or cardiac arrest. The muscles become stiff. 

Below 28 degrees
It is often difficult to tell whether someone is alive or dead. The body appears to be in rigor mortis, breathing is shallow and so slow that it is hard to notice. There can be up to one minute between weak heartbeats.

Published in Medical Science 2015

Text: Annika Lund