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Therapeutic hypothermia – catching your death of warm

Ben Wicks

Previous employee

It’s February, it’s snowing and 56 year old Steve Grinstan has collapsed outside the delicatessen on the corner of 7th and 55th in New York suffering from a heart attack. The attending paramedics re-establish his normal heart rhythm within a few minutes, but Steve remains lying on the ground looking very cold. Next, the paramedics start infusing him with ice cold saline before putting him in the ambulance. The small group of bystanders stamp their feet in the cold and wander off discussing whether the unfortunate man may survive the heart attack, only to die of cold.

Strange as it may seem, the cold may actually help Steve make a full recovery. Over the last few years the deliberate use of therapeutic hypothermia in the treatment of heart attack and several other acute conditions has become more and more widespread, and is now almost routine.

The use of hypothermia in medicine isn’t a new idea. In the 4th Century BC Hippocrates described putting snow on an injured person, and the benefits of chilling patients was also tried during the Napoleonic wars. However, medical science embraced some fairly crazy ideas back then so it isn’t surprising that proper investigation of therapeutic hypothermia didn’t begin in earnest until the second half of the 20th century. Even then there were some fatalities because the clinicians got carried away and cooled people too much – only in the 1980s did clinicians begin to realise that cooling a patient by just a few degrees could have a significant benefit.

 
How can cold be good?

Most of your body is designed to work optimally at 37°C. All of your cells and enzymes are geared up to do their work at this temperature. If your core temperature drops below 37°C then your physiology begins to slow down, your cells work more slowly, consume less energy and need less oxygen. This fact has been exploited for several decades to help protect the brain during heart transplant or cardiopulmonary bypass (CPB) surgery when blood flow to the brain is slowed and sometimes briefly stopped.

In 2002, two landmark clinical studies reported that mild hypothermia (cooling to 32-34°C) could improve the neurological outcomes of heart attack patients. Since then a great deal more clinical investigation has been carried out, and whilst there have been differences in the clinical protocols and measured outcomes, a picture is emerging which unequivocally shows that therapeutic hypothermia can improve survival and neurological function of heart attack patients. Direct brain injury can also be treated with therapeutic hypothermia, with several studies also strongly suggesting that cooling the brain can help prevent damage following traumatic brain injury. Interestingly, it’s not just the brain which may benefit from being cooled. Preliminary evidence also suggests that cooling may even help protect the heart muscle itself which is starved of oxygen during a heart attack.

 
What does cooling actually do?

The influence of cooling on cellular and biochemical mechanisms within the brain is fairly complex.

All cells are normally regulated by a complex series of biochemical feedback systems which keep everything in balance within the cell (homeostasis). Damage caused by lack of oxygen can upset these mechanisms and can cause cells to spiral out of control and even push cells into a programmed self-destruct mode (known as apoptosis). Cooling helps to dampen the severity of these swings and reduces the risk of a cascade resulting in cell damage or death.

Nerve cells constantly send signals to one another by producing special chemicals known as neurotransmitters. When nerve cells are damaged they can give out toxic levels of these chemicals which can kill the transmitting cells and their neighbours; hypothermia helps reduce this level of neurotransmitter release.

 
How much chilling is helpful?

The clinical community is working hard to determine the optimum way to use therapeutic hypothermia, but as the process of clinical trialling is time consuming and difficult, there are as yet few hard and fast rules.
 

The first question is ‘how quickly should cooling be initiated after the injury’?

This subject is hotly debated (sorry) but most people agree that cooling should start as early as possible after a heart attack or brain injury, and there is evidence that shows that it may still be worthwhile cooling a patient up to 12 hours after the injury or event.

 
The second question is ‘how cold’?

Whilst cardiopulmonary bypass patients are sometimes cooled to temperatures as low as 15°C, it appears that cooling by only 3-5°C is probably sufficient for treatment after heart attack or brain injury. Even a few degrees of cooling has a significant effect, as brain metabolism decreases by around six percent for every one degree decrease in temperature below 37°C.

 
The last question is ‘how long’?

Cooling is normally applied for 24 hours, sometimes longer. The process of rewarming the patient is usually controlled to make sure that it occurs gradually over a period of several hours, typically at 0.25 – 0.5°C per hour. Most of the cooling systems and devices on the market can be used to help rewarm the patient.

 
The science of cooling

We live in an age of amazing medical technology where we can see inside the brain using MRI, or visualise the beating heart of a baby in its mother’s womb using ultrasound. The challenge of rapidly cooling a person by a few degrees therefore seems trivial – surely you’d think there was some kind of wireless technology which could be applied? Disappointingly, the physics of cooling is rather mundane and clunky, and you can’t avoid the need to create a close physical coupling between the cooling system and the warm inside of the patient. You’ve just got to get the cold in and the heat out, and there’s a lot of heat to get out. Cooling someone by 5°C requires the same dissipation of heat as cooling three kettles full of boiling water down to room temperature (~1700kJ or ~half a kilowatt hour).

One of the quickest and easiest ways of chilling someone is to infuse them with several litres of ice cold saline. This only cools the body by around half a degree, but it can be done quickly and is a good start. Many health providers are already advocating this intervention for heart attack treatment since it can be administered easily and requires little additional infrastructure, just a fridge in the ambulance.

 
Chilling out

Although you might think that it’s very easy to get cold, the human body is amazingly good at keeping itself warm. A series of physiological systems make sure your core temperature doesn’t vary significantly – shivering is an obvious example – and so it is quite difficult to quickly get someone cold. Despite its relative infancy, there are already therapeutic hypothermia products on the market and the medical device industry has come up with some quite creative, and at times bizarre, methods to induce and maintain hypothermia.

 
Therapeutic hypothermia systems fall into three main categories:

  • Extracorporeal (which cool the outside of the body)
  • Natural orifice (yes, you’ve guessed it!)
  • Intravascular (which cool from within the bloodstream)

Extracorporeal systems are the simplest, cheapest and most widespread. The normal format uses cold pads which are placed onto the patient’s skin, and a refrigeration unit circulates cold water through the pads, with the most efficient pads having a gel coating to ensure maximal thermal conductivity between the coolant circuit and the skin.

The major disadvantages of extracorporeal systems are their limited cooling rate of ~1.5°C per hour, and the fact that a relatively large area of skin needs to be covered with the pads. The skin is quite a good insulation layer and vasoconstriction limits the amount of core blood which circulates near the skin.

Natural orifice systems, as the name suggests, use the body’s orifices as a cooling interface (you’re probably wincing as you read this). Theoretically, cooling should be quicker and more efficient since mucus membranes are thinner and less insulating than normal skin. Whilst almost all the imaginable orifices have been tried, the ‘RhinoChill Intranasal Cooling System’ deserves particular mention. Designed for out-of-hospital use on heart attack patients, the product squirts a rapidly evaporating coolant into the nasal cavity of the patient, cooling the blood and the nearby brain. If you get a headache eating ice-cream too quickly then you can imagine what the RhinoChill feels like! The product FAQ includes the incongruous question “What should be done if the patient’s nose turns white?” As you might expect, there are practical issues with almost all natural orifice systems and they are unlikely to capture much of the market without significant advances in usability and performance.

Whatever happens, the future for therapeutic hypothermia within emergency medicine and critical care seems fairly assured

Intravascular systems use specially designed large-bore catheters which are inserted into the femoral vein. Cold saline is constantly circulated through the hollow catheter which, in turn, cools the blood. The catheter is sealed at one end so no coolant comes into contact with blood. The advantage of systems such as the Zoll Thermogard XP and Philips’ InnerCool RTx is that they can achieve very high cooling rates in excess of 2°C per hour. The downside is that the procedure to insert a catheter is fairly invasive, carries some risks, requires a well-qualified clinician and in practice, the fast cooling rate may be offset by the time required to place the catheter.

Surface cooling, extracorporeal products seem likely to become the widely used technology but no one type of cooling technology is likely to dominate the entire market, and all three main types of cooling products are likely to find their own particular niche. There seems little chance that a pharmaceutical approach (a ‘chill pill’) will ever be found which has the ability to influence the myriad of complex intracellular and extracellular mechanisms which can be dampened by simple cooling.

 

What’s the future?

Expect to see more novel cooling products and technologies emerging in the next few years, particularly for the out-of-hospital / emergency care setting. Cold, breathable gas mixtures may have some potential in this regard. Mixtures of oxygen and inert gases with a higher thermal capacity than air have been explored for some time but some new approaches, including frozen mists, might make this approach feasible.

Whatever happens, the future for therapeutic hypothermia within emergency medicine and critical care seems fairly assured. The growing body of clinical evidence means that it will become adopted as standard for the treatment of heart attack and traumatic brain injury.

This article was taken from issue 3 of Insight magazine. Get your free copy of the latest issue here.

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