Michael Nurock
The idea of putting incurably ill patients into the deep freeze with the hope that a remedy will be discovered some time in the future is not new. But until recently it has been more the domain of science fiction than academically recognised medical inquiry.
This is all set to change. The doyens of international resuscitation research are intent on making a concept they call “suspended animation” a reality.
The past 100 years are witness to a previously unfathomable mastery of human life. Techniques such as cardio- pulmonary and circulatory resuscitation, combined with the rapid deployment of emergency services, mean that civilians involved in accidents stand a better chance than ever of surviving physical trauma.
This is not true for soldiers, however. Dr Ronald Bellamy, writing in Critical Care Medicine, says that roughly half of all fatally injured soldiers die of internal haemorrhage. The problem is that these major trauma patients require urgent surgery – usually to stop internal bleeding. Unlike cardiac arrest, which can be treated at the scene with equipment and drugs, major trauma requires a well-stocked operating room with experienced medical personnel.
This led Bellamy and Dr Peter Safar to agree that “the mortally wounded person, with a potentially salvageable brain and ultimately repairable injuries, would have a chance to survive only after a completely new resuscitative approach”.
In the same Critical Care Medicine issue, Safar defines this approach as “suspended animation” – the protection and preservation of the whole organism during prolonged clinical death, for transport and repair (resuscitative surgery) without pulse (no heart beat), followed by delayed resuscitation to complete recovery. Patients would need to be put into suspended animation within ten minutes of injury, and the state would need to be maintainable for one to two hours, but Bellamy notes that even 30 minutes would be clinically useful.
So how to do it? The biggest problem is that when the heart stops beating, the body is deprived of oxygen-laden blood – a state called ischaemia. Humans can tolerate ischaemia for a few minutes, but beyond this a series of events are triggered including the depletion of vital energy stores, increased levels of acid in the tissues, various electrolyte disturbances, and the production of toxic cellular by- products. This culminates with damage to DNA and irreversible cell death.
There are a similar range of complications that occur when a tissue’s oxygen supply is temporarily cut off and then later restored. This “reperfusion injury” is caused by the circulation of various products that build up as a result of the initial period of ischaemia.
Researchers have proposed interventions for each of the above problems, and they do so based on currently existing knowledge. Interestingly, the science- fiction stories aren’t far off. Hypothermia – or cooling the body – plays a major role. It has been shown to prolong survival in bleeding animals and those whose hearts have stopped. Additionally, giving such hypothermic animals special solutions intravenously seems to improve the outcome for certain organs and may help prevent the build-up of toxic products during periods of ischaemia.
In humans, cardiac surgeons have used the benefits of hypothermia and a stopped heart since the Fifties. Hearts destined for transplant are regularly maintained for up to six hours in special cooled solutions. It is thought that cooled tissue has a much lower requirement for oxygen and may produce fewer toxic by-products even when ischaemic.
But the idea of hypothermia leaves many unresolved questions. The most important being how far the human body can be cooled without producing irreversible effects due to the cooling process itself. When human tissue is cooled to freezing, the physical structure changes, making it incompatible with life even after being thawed. Other questions include how to achieve the state of hypothermia, how quickly, and once achieved – how to reverse it?
To address these problems, researchers are looking at hibernation, a state not too different to that envisaged for suspended animation. Hibernating animals radically reduce their body temperature – sometimes as low as 1C. Scientists have identified a hibernation induction trigger (Hit) that permits animals to achieve this state. Interestingly, the Hit molecule is thought to be opioid or morphine-like in structure. Researchers feel that Hits may help protect an organism from the harmful effects of ischaemia.
But animals also deal with ischaemia in other ways. The most impressive may be the aquatic turtle which dives into lake mud to avoid the winter water freeze, and holds its breath for six months!
Researchers note that such animals are metabolically very choosy about their energy sources, using as much carbohydrate for fuel as possible. They also severely restrict their energy utilisation during such periods, as well as producing complicated defence mechanisms against ischaemic injuries.
Finally, they are able to change their heart rates, and blood flow – sending blood to the areas that most need it, and in some cases releasing stored oxygen sources from the spleen.
All of these effects are achieved through the internal manufacture of chemicals which regulate the above processes, and protect the organism from the negative effects of ischaemia. Scientists are gathering more and more clues to the identity and function of these substances.
Many studies have added to such understanding but doctors are still a long way off, defying Shakespeare when he wrote: “A man can die but once.”