Therapeutic hypothermia can save lives, provide interstellar travel, and expand consciousness

“Some of them, pale and emaciated by hunger, fainted and died stretching out on the snow. They were seen going without feelings, not knowing where they were going. When they could no longer continue walking, losing the strength of their bodies and their strength of spirit, they fell to their knees. Their pulse was rare and imperceptible; for some, breathing was rare and weakly noticeable; for others, it broke out in the form of complaints and groans. Sometimes the eyes were open, immobile, empty, wild, and the brain covered silent nonsense. ”



This presentation belongs to the French doctor Pierre Jean Morisheau-Beaupré, who wrote The Treatise on the Effects and Properties of Cold in 1826, is one of the most complete first descriptions of hypothermia, a condition in which the body temperature drops to dangerously low below 35 ° C. He wrote about his experience of Napoleon's retreat from Russia in 1812, almost 80 years before this medical term appeared.



The name hypothermia comes from the Greek ὑπο, “from below, under” and θέρμη, “warm.” Its symptoms depend on the degree of temperature drop, but initially they include shivering, poor coordination, difficulty in movement, and disorientation. In extreme cases, heart rate slows down a lot, retrograde amnesia and confusion set in. With the further fall of the victim may make irrational decisions, their speech may be disturbed. There are cases when for not very understandable reasons they begin to take off their clothes and seek refuge in confined spaces before death occurs.



However, today this intolerable condition is specifically caused by doctors in order to slow down the metabolism and allow patients to survive. After decades of scientific controversy, hypothermia helps stop hostile phenomena leading to death. Its therapeutic value is the ability to slow down the physiological needs of the cells; if the frozen cells do not need a lot of oxygen and other nutrients during or after an injury or cardiac arrest, when the blood flow stops, it will take them much longer to collapse and die. The link between hypothermia and anabiosis , a state with termination of vital functions, which many hope will help us stay alive in space for years on the way to Mars and Earth-2, is not accidental. Although the exact mechanisms of its occurrence are complex, hypothermia slows down the metabolism, postpones the destructive effects of oxygen deficiency until normal blood circulation returns.



A new area of ​​therapeutic hypothermia even begins to redefine the boundaries of life. In the past, the Rubicon between life and death was the absence of a heartbeat. Later we learned that the brain in the absence of a pulse can survive for a while, and people who have experienced cardiac arrest were pulled out while their brains remained intact. But without circulation, the brain cannot live for very long.



In recent years, advanced methods of hypothermic cooling cope with slowing brain activity to a minimum, and push the boundaries of death far beyond the point at which the heart stops. Among other benefits, these breakthroughs have allowed researchers to expand their study of experiences associated with short-term death based on reports from people who have experienced long periods of cardiac arrest and have returned. They also breathed new life into the study of hibernation of a person in order to use hypothermic cooling for astronauts going to interstellar space.



Cold therapy was first used as a local therapy. The earliest documented uses include references found in Edwin Smith papyrus . It is the oldest known medical text dating from 3500 BC, named after its owner, who bought it from a seller in Luxor in 1862. He describes how the Egyptians used the cold to treat abscesses. Later, in the IV-V centuries BC in the Greek medical school of Hippocrates, it was proposed to place patients in the snow to stop bleeding, apparently, through the narrowing of blood vessels. But it was not until the end of the 18th century that James Curie , a doctor from Liverpool, conducted the earliest known experiments related to hypothermia of the whole body. He immersed healthy volunteers, apparently selflessly committed, into the water at a temperature of 6.5 ° C for up to 45 minutes in an attempt to find a way to help sailors who suffered from cold water during shipwrecks. His research was greatly helped by improvements in the accuracy of thermometers.



After the dawn of modern medicine, when trained doctors began to make diagnoses and treat diseases based on scientific evidence, everything changed. Start research put the experiments of the American neurosurgeon Temple Fay. When he was a medical student in the 1920s, he was asked why cancer with metastasis rarely appears in the limbs. Then he had no answer, but he noted that the temperature of a person’s limbs is relatively low. He ingeniously linked this fact with the discovery made by him on his farm in Maryland - that lowering the temperature inhibits the growth of chick embryos. He hypothesized that cold can be used to treat and prevent the growth of cancer. It was a moment of insight. By 1929, he received a professorship in neurosurgery at Temple University in Philadelphia. Soon he began to use basic methods of cooling the entire body, putting ice on patients, for example, and developing various methods of local cooling — including coarse and large-sized devices that are inserted into the skull by today's standards.



But his crude methods caused criticism and anarchy at the hospital. He used giant ice baths - up to 70 kg in one - in operating theaters for periods up to 48 hours. Melting led to constant flooding that needed to be absorbed by something. The rooms were cooled through the opening of windows, which is why not only patients, but also employees were exposed to local icy winds. In addition, at that time it was quite difficult to accurately measure the patient's body temperature without appropriate (usually rectal) thermometers designed specifically for this purpose. The then thermometers were not calibrated to measure temperatures below 34 ° C. Because of this, Fay was extremely unpopular with the medical staff, and the staff once even rebelled against his "people cooling service."



However, Fay was a genius. In one of his earlier reports, he cited mortality in 11.2% of cases and success in 95.7% of cases in the area of ​​pain relief through cooling therapy. What is important, these experiments showed not only that people can remain in a hypothermic state, cooled to 32 ° C for several days, but also that they can be removed from it with a significant improvement in their condition.



Unfortunately, the events turned so suddenly and regrettably that his early reports fell into the hands of the Nazis, and knowledge was used in hundreds of cruel experiments conducted during the Second World War. The prisoners were forced to dive into ice-water tanks, and the experiments used the “wait and see what happens” approach. This data has been declared unscientific. The association with torture slowed down subsequent research for decades. At that time there was such a thing as “temperature barrier”, according to which lowering of body temperature was necessary to be avoided by all means.



Only in the mid-1980s, the pioneer of anesthesiology, Peter Safar, born in 1924 in Vienna, ventured to conduct research on therapeutic hypothermia, despite its poor reputation. He worked at the University of Pittsburgh with dogs, and confirmed that after cardiac arrest, small brain hypothermia (33-36 ° C) significantly improved the neurobiological outcome of treatment and prevented brain damage. Safar successfully resumed research on hypothermia. The treatment invented by him was called "a slowdown in vital activity for the purpose of delayed resuscitation."



The science of therapeutic hypothermia was motivated by exceptional histories of patients who survived after drowning in cold water. Take, for example, medical intern Anna Bagenholm, who experienced cardiac arrest after an accident while skiing in northern Norway in 1999. She survived by being in ice water under a crust of ice for 80 minutes, and spent several hours without a pulse before her heartbeat returned.



After the onset of the new millennium, Joseph Varon, today - the head of the intensive care unit in the hospital system at Central University of Houston, sent therapeutic hypothermia to new heights. In 2005, a man who was on vacation, was taken by plane from Mexico to Houston after he drowned. Varon told me: “I flew with him to Houston. The guy was dead for a couple of hours. They restored the work of the heart, and as a result we were able to cool it and not just bring the brain back to life - it also recovered. ” This case was told in the journal Resuscitation. "When Pope John Paul II experienced a cardiac arrest that year, I was asked to fly to the Vatican and cool it."



Varon, among his best known as “Dr. Frost,” as well as Fay, initially experienced skepticism on the part of the medical staff. “When I started doing this in Houston, I used a lot of ice. The temperature in the room fell extremely hard, ”he said. Soon he was using hypothermia to protect patients from brain damage as a result of various injuries, including cardiac arrest, heart attack and liver failure. His patients are regularly cooled to low temperatures, up to 32 ° C - and for up to 11 days. In 2014, he used hypothermia to save himself after a heart attack. “The first thing that came to my mind was: cool me down!” Varon told me.



Over time, his technique has improved. Today, Varon uses a variety of different devices to apply both local hypothermia and whole body cooling, usually to lower the patient's temperature to 32 ° C during recovery from cardiac arrest after their heart has started up again. This technology uses hydrogel-pillow machines with cold water circulating in them to cool patients, biofeedback mechanisms for temperature control, a computerized catheter inserted into the leg and allowing the patient to cool and remain conscious - a key point for an accurate assessment of neurobiological parameters.



Moreover, in some cases involving serious injuries, emergency clinical trials are waiting for patients from, say, firearms or cold arms. They are cooled to 10 ° C, often when they no longer have a pulse or breathing. Yes, it turns out that doctors cool the "dead" in order to save their lives.



Cooling may extend the time period, which is extremely short in other cases, during which the necessary surgical assistance can be provided to victims, especially in order to prevent blood loss. Notable trials called Emergency Preservation and Resuscitation (EPR) are held in Pittsburgh and Baltimore in those places where there is the greatest number of injuries from firearms and cold arms. EPR is used as a last resort, when standard resuscitation methods do not work, and the victim has a 5% chance of survival. The procedure includes replacing the patient's blood with a cooling saline circulating through the body, which prevents the oxygen starvation of cells and tissues. When used in patients, the heart can become clogged again after no pulse, up to one hour. The goal of the experiment is to compare 10 patients who underwent EPR with 10 who did not pass it, and see if it affects survival. Official results have not been disclosed.



But Samuel Tisherman, the test leader, is extremely optimistic. He has long been trying to go beyond the limits of the possible, and worked with Safar on anabiosis in the 1980s, when he was in medical school. Now his test subjects are regularly cooled from a normal temperature of 37 ° C to a staggering 10 ° C for 20 minutes. Tisherman explains: “We need to do this quickly, because the person’s pulse has already disappeared; the idea itself is to reduce the body's need for oxygen. " In particular, it is necessary to cool the heart and brain, since these organs are more susceptible to oxygen starvation. After cooling, the patient without a pulse and blood pressure is transferred to the operating room. Finally, in such extreme conditions, the surgeon tries to eliminate the sources of blood loss and fix other injuries. After that, the patient is slowly heated. “We hope that after heating, their heart will start beating,” said Tisherman.



When asked about the current progress in experiments related to such problems, Tisherman thought, and then said with a soft laugh: “We are doing this. This is progress! ”It will be necessary to wait for the formal results of clinical trials, but it seems that the critical milestone is near.



Hypothermia, in addition to medical care for the terminally ill, will someday be able to be used for what most of us met in science fiction literature - for anabiosis. The idea received an impetus in the 1960s, during the space race between the USSR and the USA, and was recently resurrected in a form known today as a torpor [numbness characteristic of hibernating animals]. trans.]. Torpor offers many advantages for long-term space travel. It can prevent medical problems, including muscle atrophy and bone loss, which are known to occur during a prolonged stay in zero gravity. In addition to such preventive measures, it can be used for psychological purposes. Loss of consciousness prevents unnecessary stress and excessive boredom, which can come along with months of space travel in an enclosed space, not to mention interpersonal conflicts that will most likely arise in a small team over such a long period.



Businesses like SpaceWorks from Atlanta are getting new funding from agencies like NASA for programs like “Innovative Advanced Concepts” that explore human anabiosis. SpaceWorks innovative approach rests on huge savings in food, waste processing, storage and space requirements, which in other cases will have a huge impact on the weight of the vessel and the cost of the mission. “We presented them with a realistic idea and showed monetary advantages and all the math,” said Douglas Tolk, director of the department of surgical services at the naval base in Limur, pc. California. He has been working on this project for SpaceWorks since 2013. He told me: "I am a doctor, and a huge fan of NF - and this is the perfect union for these worlds!"



The current SpaceWorks plan includes a short-term torpor period, in which space travelers enter with a period of two weeks, with a decrease in metabolism by 7% for every degree Celsius. “We know that many mammals are capable of hibernation, so we don’t have a question,“ can mammals hibernate? ”Said Talk. - We have a question: Can we call it in people, and how? We know that we are capable of this in the short term, and we even have studies showing that we can extend it for two weeks. ” Sense speaks of a case that occurred in China in 2008, when a woman in a coma after aneurysm was cooled for 14 consecutive days to prevent further brain damage and speed recovery. Surprisingly, she fully recovered.



There is a clear concept of the path from our current knowledge of hypothermic stasis while traveling to Mars. The expert said that this journey should begin at the lunar station, where "the astronauts will go to get closer to the torpor and learn what to expect from falling into hibernation and leaving it." SpaceWorks plans to support the life of astronauts with the help of a surgically implanted intravenous device, a “mediport,” similar to what is used today for chemotherapy in patients with cancer. They will also have esophageal tubes that go straight to the stomach for feeding. “These devices have a very small degree of side effects. When the team passes all the checks, it will go to the module for stasis, go to bed and connect its monitoring and feeding systems. And then we reduce the temperature in the room. To initiate a torpor we will not, as they do in hospitals, with the help of sedatives. We will use pharmaceuticals that lower body temperature to 32 ° C and slow down metabolism. ”



The creation of such tools is the main goal of Tolk and his colleagues. They have already achieved success with pigs, which, he said, was key, since "for the first time, something like hibernation was obtained using pharmacology in mammals that are not susceptible to it." After a workout on the moon, team members will enter and exit stasis in turn, so that someone will always be awake and watch the safety of the others.



Changing the nature of sleep in space and time can change human nature. The emergence of the possibility of including "hibernation on demand" may mean that we have outgrown our internal circadian rhythms, tied to such elements of the cosmos as day and night. Our genetic bases dictate biology tied to the rhythms of the Earth’s rotation. This setting is necessary to regulate sleep schedules, eating, hormone release, blood pressure and body temperature. These rhythms are one of the main parts of our humanity. If hypothermic hibernation slows down metabolic processes and suppresses our rhythmic biological needs, can it, for example, delay the effects of aging? Will travelers on Mars be able to make up for the time spent on hibernation on long voyages back and forth? Or, if we imagine a distant future, can star researchers return to Earth hundreds and thousands of years after leaving it?



Sense was not sure whether human hibernation would turn the circadian needs upside down, but said that it is possible to find a fundamental, genetic switch to hibernation in humans. “Advanced research suggests the presence of such a switch as HIT (hibernation-inducing trigger),” he said. - This is a kind of chemical that prepares the body and includes hibernation along with the ability to endure this state. I think that somewhere in our DNA there is the ability to turn on hibernation, and that this possibility has been lost in the process of evolution. ”



Another challenge to our identity can come from expanding the boundaries of life. Once death was determined by cardiac arrest. When the heart stopped, the man was no more. Then we expanded the concept to "brain death" - the absence of brain waves means the point of no return. Now hypothermic patients demonstrate simultaneously the death of the heart and brain, but they are reanimated, which again expands the boundaries of life.



Take the Norwegian hospital where Bagenholm was treated after her ski accident in 1999. Prior to her admission, all patients with hypothermia and no pulse died; the survival rate was zero. However, when the hospital realized that patients could have brain activity for hours, and perhaps even days after the cardiac arrest, they began to apply more aggressive resuscitation attempts, and increased their survival rate to 38%.



Emergency cases of patients admitted in a frozen state have changed our approach to death. In 2011, a 55-year-old man with cardiac arrest was brought to Emory Hospital in Atlanta, and brought to a hypothermic state to protect the brain. After a neurological examination, the doctors announced the death of his brain, and after 24 hours he was brought to the operating room to remove organs. However, according to a report in the journal Critical Care Medicine, the doctors then recorded corneal and cough reflexes and spontaneous breathing. Although there was no hope for his resuscitation, and it was not possible to revive him, such cases cast a shadow of doubt on the long-established neurological tests, which are still used to determine the time of death.



Even more unusual perspectives are drawn by patients who are brought back to life with the help of new techniques. One of the most amazing cases was described by Sam Parnia, director of resuscitation research at Langon Medical School in New York. Parnia investigated resuscitation through hypothermia, not only to save patients, but also to look for answers to deep questions: when is death final and irrevocable? What do we feel on that side of death? When does the work of consciousness stop? His latest work suggests that consciousness lives for many minutes after a cardiac arrest — and it can be delayed by cooling the brain, slowing down cell death and giving doctors a chance to reverse the process and pull the patient back. Parnie's studies, many of which were improved by hypothermia, show that the dying brain is in a “calm,peaceful state "; According to reports collected over the years, many patients describe the feeling of a friendly, bright light.



Breakthroughs in the field of hypothermia alarm the public, and because of this they serve as a stumbling block. Some of the people who resist them are pragmatic: therapeutic hypothermia increases the risk of lowering blood clotting and tissue damage from lack of oxygen, which has led to the death of many victims of unintentional hypothermia. These symptoms are known as the "death triad." Therefore, there is no agreement on how to work with this technique, Varon says. “Disputes about temperature and duration will continue. Every person is special, so you cannot find any recipe suitable for everyone, ”he said.



From the very beginning of his EPR experiments, Tisherman has been struggling with persistent criticism from medical professionals. Especially his colleagues are concerned about the impossibility of blood coagulating in such extremely cold conditions, and this problem for patients who are at risk of dying from injuries and blood loss is difficult to overestimate. Yet Tisherman objects that his patients are already at high risk of dying. “Their chance of survival is 5%,” he says, “so why not try something new?”



Another criticism is associated with neurological consequences. What if a patient survives a gunshot or stab wound with an EPR but suffers irreversible brain damage due to a prolonged lack of oxygen? “Such a problem is present at any cardiac arrest, whether there is an injury there or not,” says Tisherman. - If your heart stops, then it does not matter if you are participating in EPR tests or not - there is a chance that you will survive, but you will receive significant brain damage, and this risk is regardless of cooling. We do not yet know whether this risk increases or decreases what we are doing. ” He describes this problem as a matter of survival. “Often, resuscitation patients wake up and live, and everything is fine with them, or they simply do not live. We do not know. Yes, there is a risk. They are dying, and we need to work to ensure that they survive and wake up. "



Work goes fast. Advances in hypothermia raise the question of determining the nature of man, pushing the boundaries of consciousness and death, and can bring us closer to our visit to other worlds. On a winding road, then entering a difficult place, then returning to the plain, hypothermia constantly opens and develops new therapeutic advantages. Morisho-Bupre would be delighted.