Cool It - Induced Hypothermia Targets Brain Injury

Cool It - Induced Hypothermia Targets Brain Injury

Hypothermia can kill. It most often afflicts people who have been shipwrecked or lost in the woods. It isn’t a treatment you would expect to receive in hospital. It is, however, becoming a common and useful method to prevent severe brain damage in patients that have suffered unconsciousness due a lack of oxygenated blood—such as those who have suffered a sudden cardiac arrest.

This article shall explore the what, when, why and how, of this (relatively) new therapy.

What

The term is not that common, but usually understood by the general public. It comes from hypo - meaning below, and the Greek thermē - for heat. It describes a normally dangerous situation where the body temperature is lower than normal. (There is also another very similar word hyperthermia, which has the same origins, except hyper means beyond, and describes higher than normal body temperature.)

So why is induced hypothermia (or therapeutic cooling) now being used by EMTs and hospital ERs? And how can it help prevent brain damage? To answer these questions we need to go back in time, and also understand what happens inside the cells of our bodies. Quite simply, the cold slows down the bodily functions and thus “preserves” the brain cells. This has been known for some time, and even seems a little obvious. Freezing things stops them from decaying. We all know that. But we are not talking about freezing (cryogenics) because unfreezing living tissue has not been very successful (yet?). Instead we are talking about cooling the whole body rapidly, and slowly bringing it back to normal temperature. I’m sure you have used a cool pack to relive muscle pain or the discomfort of a sprain. The application of cold, however, does more than just numb the nerves.

Many centuries ago, the ancient Greek physician, Hippocrates, advocated packing wounded soldiers in ice. During the Napoleonic wars, battlefield surgeons noticed that injured Generals, sitting by the fire, fared worse than the soldiers left out in the cold. Jumping to the 1950’s we see hypothermia being utilized to reduce blood flow during cerebral aneurysm surgery. It has also been standard practice during bypass surgery for many years. And, now in the 21st century we are identifying the therapeutic mechanisms, with a view to recommending mild hypothermia for many neurologic emergencies. In 2002, the International Liaison Committee on Resuscitation (ILCOR) published an advisory statement supporting the use of induced hypothermia for SCA victims, which the American Heart Association (AHA) has endorsed. Further studies are warranted, to establish a more accurate understanding of the beneficial results and mechanisms, as well as precise definition of the ideal temperatures and duration of cooling.

Why

So, what is the current theory on why cooling the brain prevents further injury? At the cellular level, oxygen is used to manufacture energy for the cell to perform its function. When cells are deprived of oxygen, a series of chemical reactions begin to protect that cell from further damage. If the oxygen supply is restored within seconds, there is minimal cell damage. If oxygen levels are low for several minutes or more, and then restored to normal the damaged cells respond much differently. The prolonged disruption of the cell's oxygen supply leads to the cells attempting to commit suicide in a process called cellular apoptosis or programmed cell death. Hypothermia can reduce the production of the signals that lead cells to attempt to kill themselves and it therefore encourages more brain cells to live.

In an interesting twist to this story, the resumption of blood flow (reperfusion) can actually make the whole situation worse! Once an SCA victim is resuscitated—the measure is usually “return of spontaneous circulation” (ROSC)— the white blood cells carried to the area by the newly returning blood, release a host of inflammatory factors (a normal immune response) leading to increased intracranial pressure, which in turn leads to further cell injury..

When

Induced hypothermia therapy is more effective if it is applied soon after injury. This inhibits the previously described, complex cascade of processes that occurs after a period of restricted blood flow. The recommendation for cardiac arrest patients is as follows: Unconscious adult patients with spontaneous circulation after out-of-hospital cardiac arrest should be cooled to 32-34°C for 12-24 hours, when the initial rhythm was VF.

Where hypothermia decreases energy requirements, enzyme function and free radical production; hyperthermia increases these activities in ischemic cells. It is important to note that fever is a common complication in patients with brain injury. And fever is defined as an elevation in thermoregulatory set-point—in order to neutralize a perceived threat inside the body, such as invasion by bacteria or virus. Unfortunately, brain temperatures frequently exceed core temperatures by as much as two degrees, possibly caused by cerebral thermopooling—problems in getting rid of the excess heat due to local swelling. So the body’s natural response to injury—fever and swelling—is actually capable of damaging the brain cells. Hence the need for cooling.

How

Now that we have determined the benefit, and the science behind the therapy, we need to understand the methods and of course the side-effects. There are a number of techniques to achieve induced hypothermia in the hospital; ice and water blankets; non-invasive heat-conducting pads applied to the skin; and catheters inserted into large blood vessels to circulate ice-cold fluids. All three can cool the body; the easiest to use is the non-invasive pads, but the invasive catheters cool the fastest.

It is imperative to a successful outcome that the cooling be restricted to the ideal temperature range. Outside the hospital the choices are limited, but often EMTs will use chilled saline solution to bring down a patient’s temperature. Unfortunately, there is a limit to how much additional intravenous fluid the body can tolerate (around 2 quarts).

The most well understood technique is of course that ancient method; applying ice or a water blanket. It is simple in concept, but can be slow to cool, hard to control accurately, and sometimes lead to cooling lower than the AHA recommended 32-34 degrees C (89.6-93.2 F). Ice and water blankets are, however, the easiest to deploy.

Catheterization is the most effective at cooling the blood, and thus cools the body fastest. The temperature can also be controlled most accurately. It is also inherently more risky, because it involves inserting a large bore catheter into the femoral vein all the way to the vena cava, deep inside the torso, and left there for the duration of the therapy. There is always the risk of infection and damage to blood vessels or tissue whenever a foreign body is introduced. In addition, a trained physician is required to monitor the placement of the endovascular catheter, making it an expensive treatment.

Combining both these positive attributes—the non-invasive nature of water blankets with the precision and speed of catheters— with the added important ability to re-warm patients, is the non-invasive heat-conducting pads. There are a number of devices available, but several of the SCA Foundation survivors have received treatment with an Arctic Sun Temperature Management System. This advanced device is designed to simulate water immersion, and incorporated a thin pad design, which is more comfortable for the patient and less cumbersome for nurses to administer patient care. The single use, radiolucent, hydrogel pads adhere to the abdomen, back and thighs covering approximately 40% of the patient's body surface area. The system uses water pulled under negative pressure (which prevents water leakage) at a high velocity for rapid heat exchange. The system reacts to patient temperature and automatically adjusts the circulating pad water temperature to achieve a preset patient target temperature, for both cooling and re-warming.

These machines typically cost tens of thousands of dollars, with a useful life of seven years or more. The pads are single use, and with a total cost of around $1000 per treatment the therapy is highly cost effective in reducing prolonged stays in ICU and neurological rehabilitation.

Whichever cooling method is used, one major obstacle needs to be overcome—shivering. Patients will begin to shiver at around 36 °C (96.8 °F), and shivering leads to warming in addition to increasing overall oxygen consumption. It is the body’s natural mechanism to control temperature, and must be suspended during hypothermia therapy, typically through mild sedation. Often unconscious, unresponsive patients are intubated, in which case they are sedated anyway.

An unexpected consequence of induced hypothermia therapy is the image of it being a “miracle worker”. When family members are told of the treatment—hard to avoid as the patient is really quite cold to the touch—they immediately assume the patient can recover full brain function. In addition, some of the publicity has prompted requests to use this “new technique” in patients where it may not be beneficial. Therefore strict criteria for cooling therapy is warranted, the best results are obtained when the physicians follow the recommended guidelines—Unconscious adult patients with spontaneous circulation after out-of-hospital cardiac arrest, when the initial rhythm was VF.

- Jeremy Whitehead

Further information:
The Lancet; Vol 371 June 7, 2008 - "Induced Hypothermia and Fever Control for Prevention and Treatment of Neurological Injuries."
ILCOR Advisory Statement October 2002:" (Circulation. 2003;108:118.)

 

 

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