BRIDGET HARRIS lies on a hospital bed with a nylon hood covering her head. As cold air streams from the hood and over her scalp, her lips gradually turn blue and her speech slows. Within an hour, her core body temperature has dropped by 0.5 °C, but she remains comfortable. "The airflow is almost relaxing," she says. "It sounds like white noise."
Harris, a PhD student at the University of Edinburgh, UK, is testing her own invention: a cooling helmet designed to induce mild hypothermia.
We all know that a cool cloth applied to the forehead can ease a headache, but now researchers like Harris are investigating whether technologies that cool the brain itself could prevent brain damage following a stroke or cardiac arrest. Similar techniques could also protect the heart and kidneys from damage during surgery.
For some time, doctors have observed that cooling patients following a heart attack can reduce brain damage. Although they are not yet sure of the mechanism behind this effect, researchers suspect that cooling the brain by 4 °C, to around 33 °C, reduces the metabolism of brain cells, reducing their hunger for oxygen for the crucial moments during which blood is in short supply. Damage seems to be reduced even if the brain is only cooled once the heart has been restarted, suggesting that cooling may also slow the release of toxic chemicals from neurons and glial cells - a process called the ischaemic cascade, which triggers further brain-cell death up to 24 hours after a cardiac arrest or stroke.
Previously, doctors have induced "therapeutic hypothermia" by applying ice packs or cooling blankets to the whole body, or injecting cold saline solution into the veins. However, cooling the whole body can increase the risk of infection and pneumonia, so researchers are now building targeted devices that chill the brain directly.
Harris's hood, for example - developed with her supervisor Peter Andrews and medical technology company KCI of San Antonio, Texas - exploits the dense network of blood vessels on the scalp that carries blood to the brain. The device consists of two nylon sheets that fit around the head, one on top of the other, with small perforations in the layer closest to the skin. When cold air is blown between the two sheets, these perforations allow it to penetrate to the skin at regular intervals across the scalp, cooling the blood vessels. "It's a bit like a hairdryer hood - it doesn't cover the face and one lies with one's head inside it," says Harris.
In tests on volunteers, the hood was able to cool the brain by almost 1 °C per hour - a similar rate to whole-body cooling methods (British Journal of Anaesthesia, DOI: 10.1093/bja/aem405).
To produce an even more rapid change in brain temperature, though, other researchers are developing techniques to cool the brain from within the body, by chilling the blood before it reaches the brain.
The nose provides an ideal route for this, since it evolved partly for heat exchange, says Allan Rozenberg of BeneChill in San Diego, California. "The nasal cavity is filled with a mass of blood vessels that warm incoming air," he says. "Arteries carrying blood to the brain pass in close proximity to this mesh of capillaries, so cooling the nasal cavity also cools the blood that reaches the brain."
So BeneChill has developed a system called RhinoChill, which sprays a fine mist of perfluorocarbon droplets deep within the nasal cavity via two tubes inserted through the nostrils. Perfluorocarbon was chosen because it evaporates rapidly, cooling the walls of the nasal cavity, and a steady stream of oxygen further accelerates the evaporation. "If you touch washing that's drying in the breeze, it feels cold because of the rapid evaporation. This has a similar effect," says Rozenberg.
Studies on animals suggest the device can cool the brain by as much as 2.4 °C an hour. Two clinical trials on cardiac arrest and stroke victims are under way, but healthy volunteers who tested early prototypes that used chilled saline solution responded positively, says Rozenberg: "At very cold temperatures some people got 'ice cream headaches'," but with a solution at about 10 °C, the recipients found it "refreshing".
Cooling blood from the lungs could also be used to chill the brain, since the carotid arteries lead directly from the chest to the head. A team from the Argonne National Laboratory in Illinois are attempting to achieve this by squirting a small amount of icy slurry into the entrance to the lungs via a narrow tube passed down the windpipe. Once the brain has cooled to a suitable temperature, the melted ice is simply sucked back out again using the same tube - the same process used to remove water from the lungs of someone who has nearly drowned.
The difficulty, according to team member Ken Kasza, was ensuring the icy particles didn't start to snowball within the narrow tube used to deliver the slurry, making it stick like a thick milkshake in a straw. To prevent this, the team mixed the ice particles in a slightly saline solution that melted their rough edges until they were smooth and round. "The particles just slip by one another and don't form an entangled mass," says Kasza.
The ice slurry can cool the brain by 4 °C - the safe limit before damage is risked - in less than 15 minutes, says Kasza, who has so far tested the technique on pigs. His team is investigating whether their icy slurry could also be applied to the kidneys (see picture) and the heart during invasive surgery, to prevent damage to the organs when blood flow is suspended for the operation.
One of the main advantages of all the new techniques is that they are simple enough to apply before or immediately after resuscitation following a heart attack - minimising the delay between the heart malfunction and cooling the brain. "A paramedic could deliver the slurry," says Kasza.
What's more, a recent study in pigs suggests that immediate cooling with the RhinoChill device, besides reducing brain damage, could also improve the chances of success of the resuscitation itself, although it is not yet certain why this is. Sixteen pigs were given a heart attack, and then left for 15 minutes before CPR was applied to start their hearts again. Of the eight pigs cooled using the RhinoChill system during CPR, six survived, compared with just two of the eight who were left unchilled (Resuscitation, DOI: 10.1016/j.resuscitation.2008.03.087).
Rapid application of such techniques could be particularly good news for stroke victims. "Clot-busting drugs can only be administered after diagnosis and brain scans in the hospital," says Andrews. "But applying therapeutic cooling at the scene of the stroke could lengthen the time window in which the drugs are effective - before too much damage has occurred," he says.
Richard Lyon from the Royal Infirmary of Edinburgh, who is investigating the mechanisms behind therapeutic hypothermia, says it is not yet certain that immediate cooling at the scene of the cardiac arrest does significantly reduce brain damage compared with cooling applied hours later, since there have been conflicting studies. But in any case, he says, more widespread use of therapeutic cooling within hospitals should radically improve patient outcomes.
The use of therapeutic cooling in hospitals should radically improve patient outcomes
"Current research shows that therapeutic cooling saves a life for every seven people it is applied to, and prevents significant brain damage in one person in every six," he says. "This could be a real revolution in resuscitative care."
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