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What are the neurological, physical, etc. differences between someone who is in a coma (one that is not medically-induced) and someone who is colloquially deemed "brain dead" (being physically kept alive by machines)? Is there a certain minimal brain activity that is present in a comatosed state that is not present in brain death?
I found a decent definition here which defines the difference as:
- Brain death: Irreversible cessation of all functions of the entire brain, including the brain stem. A person who is brain dead is dead, with no chance of revival
- Coma: A state of profound unresponsiveness as a result of severe illness or brain injury
I can find other similar, vague definitions in a few other places.
I am wondering what is different about the neuronal structures or electrical activity between brain death and coma. Is there simply no (zero) neural/electrical activity with brain death, whereas there is with coma? What would be physiologically different with brain death that would prohibit such neuro-electrical activity?
I'd recommend reading a review paper on disorders of consciousness, which cover the spectrum of minimally conscious states, vegetative states, and coma. Brain death is outside the context of disorders of consciousness, but is often discussed for comparison. Nico Schiff is one expert in the area; I've attached a reference to a review he coauthored at the bottom and I'll draw mostly from that review in this answer.
Schiff and Fins write, with some bolded emphasis by me:
At present, brain death is diagnosed if clinical evidence of the complete loss of brainstem function is present at the bedside and the patient demonstrates a failure of ventilatory drive in the setting of documented hypercapnia (significant elevation of blood partial pressure of carbon dioxide over a chosen threshold) - the 'apnea test'. Fulfillment of these criteria should invariably associate with an 'empty skull': no sign of any metabolic activity or blood flow measured by positron emission tomography, a ground truth linking the biological model to the clinical assessments
The first two statements are most relevant clinically; PET is not commonly used except in research and rare cases of uncertainty. Biologically, brain death is when the brain is… dead. There is no recoverable neural function. The signs are a lack of any brainstem reflexes, including lack of respiratory drive. Additionally, other potential causes of these symptoms (such as pharmacological causes) must be ruled out.
Coma is a state of unconsciousness, but some brain functions are preserved. Again from Schiff and Fins:
Both comatose and vegetative state patients are unresponsive to environmental stimuli, although reflex movements may be present; in neither condition are goal-directed behaviors initiated. Comatose patients lack state variations and typically remain in a closed-eyes state that is unchanging even when presented with the most vigorous stimulation.
Comatose patients do not meet the criteria for brain death described above, but do have a complete inability to respond to stimuli and do not make purposeful movements besides reflexes. Schiff and Fins (and others) compare this state to deep anesthesia. Though your question posits that there should be some distinction between medically-induced and one that is not, there is really no functional difference. The possibility of recovery is tricky to assess, but generally patients who spend a long time in coma have a worse prognosis than those that do.
The clinical approach is different. A brain dead patient is dead. Nothing can be done to recover function; potential for organ donation can be considered, but there is nothing medically to do for the individual. For a comatose patient, it's more complex, and decisions need to be made regarding the level of medical support to provide given expected prognosis in both probability and extent of recovery.
In brain death, the neurons are dead. The lack of electrical activity is not because they are in some quiescent state, it's because they are dead. With coma, it's less clear except that there are signs that some neural function remains. Coma is really a clinical state, not a biological one. It's not always possible to determine the level of irreversible damage in a comatose patient, nor the extent of possible recovery.
Schiff, N. D., & Fins, J. J. (2016). Brain death and disorders of consciousness. Current biology, 26(13), R572-R576.
How Can We Tell If a Comatose Patient Is Conscious?
Steven Laureys greets me with a smile as I enter his office overlooking the hills of Liège. Although his phone rings constantly, he takes the time to talk to me about the fine points of what consciousness is and how to identify it in patients who seem to lack it.
Doctors from all over Europe send their apparently unconscious patients to Laureys&mdasha clinician and researcher at the University of Liège&mdashfor comprehensive testing. To provide proper care, physicians and family members need to know whether patients have some degree of awareness. At the same time, these patients add to Laureys&rsquo understanding. The interview has been edited for clarity.
What is consciousness?
It is difficult enough to define &ldquolife,&rdquo even more so to define &ldquoconscious&rdquo life. There is no single definition. But of course, in clinical practice we need unambiguous criteria. In that setting, everyone needs to know what we mean by an &ldquounconscious&rdquo patient. Consciousness is not &ldquoall or nothing.&rdquo We can be more or less awake, more or less conscious. Consciousness is often underestimated much more is going on in the brains of newborns, animals and coma patients than we think.
So how is it possible to study something as complex as consciousness?
There are a number of ways to go about it, and the technology we have at our disposal is crucial in this regard. For example, without brain scanners we would know much, much less than we now do. We study the damaged brains of people who have at least partially lost consciousness. We examine what happens during deep sleep, when people temporarily lose consciousness. We&rsquove also been working with Buddhist monks because we know that meditation can trigger alterations in the brain connections that are important in the networks involved in consciousness show changes in activity. Hypnosis and anesthesia can also teach us a great deal about consciousness. In Liège, surgeons routinely operate on patients under hypnosis (including Queen Fabiola of Belgium). Just as under anesthesia, the connections between certain brain areas are less active under hypnosis. And finally, we are curious to understand what near-death experiences can tell us about consciousness. What does it mean that some people feel they are leaving their bodies, whereas others suddenly feel elated?
What processes in the brain create consciousness?
Two different networks seem to play a role: the external, or sensory, network and the internal self-consciousness network. The former is important for the perception of all sensory stimuli. To hear, we need not only ears and the auditory cortex but also this external network, which probably exists in each hemisphere of the brain&mdashin the outermost layer of the prefrontal cortex as well as farther back, in the parietal-temporal lobes. Our internal consciousness network, on the other hand, has to do with our imagination&mdashthat is, our internal voice. This network is located deep within the cingulate cortex and in the precuneus. For us to be conscious of our thoughts, this network must exchange information with the thalamus.
What happens in a comatose person?
The brain is so heavily damaged that neither of the networks functions correctly anymore. This malfunction can occur as a result of serious injury, a brain hemorrhage, cardiac arrest or a heart attack. At most, a coma lasts for a few days or weeks. As soon as patients open their eyes, they are said to &ldquoawaken&rdquo from the coma. This does not, however, mean that a person is conscious. Most patients who awaken from a coma soon recuperate. But a minority will succumb to brain death a brain that is dead is completely destroyed and cannot recover. But some patients who are not brain-dead will never recover either.
How do we know whether a coma patient who has awakened is conscious?
For that we use the Glasgow Coma Scale. The physician says, &ldquoSqueeze my hand.&rdquo Or we observe whether the patient responds to sounds or touch. If patients do not respond, the condition used to be called &ldquovegetative&rdquo they appear to be unconscious. If a patient responds but is unable to communicate, we categorize the consciousness as &ldquominimal.&rdquo Such patients may, for example, follow a person with their eyes or answer simple questions. If we pinch their hand, they will move it away. But these signs of consciousness are not always evident, nor do we see them in every patient. A patient who awakens from a coma may also develop a so-called locked-in syndrome, being completely conscious but paralyzed and unable to communicate, except through eye blinks.
So the difference between unresponsiveness, minimal consciousness and locked-in would seem to be hard to determine.
That&rsquos right. If there is no response to commands, sounds or pain stimuli, this does not necessarily mean that the patient is unconscious. It may be that the patient does not want to respond to a command or that the regions of the brain that process language are so damaged that the person simply doesn&rsquot understand me. Then there are cases in which the brain says, &ldquoMove!&rdquo but the motor neural pathways have been severed. Family members are often quicker than physicians to recognize whether a patient exhibits consciousness. They may perceive subtle changes in facial expression or notice slight movements that escape the physician&rsquos attention.
Patients are brought to Liège from all over Europe to undergo testing. How do you determine whether they are conscious?
Well, of course, the physician will say, &ldquoSqueeze my hand&rdquo&mdashbut this time while the patient is in a brain scanner. If the motor cortex is activated, we know that the patient heard and understood and therefore is conscious. We also want to determine the chances of recovery and what the physician or the patient&rsquos family can do. With different brain scanners, I can find out where brain damage is located and which connections are still intact. This information tells family members what the chances of recovery are. If the results show that there is no hope whatsoever, we then discuss difficult topics with the family, such as end-of-life options. Occasionally we see much more brain activity than anticipated, and then we can initiate treatment aimed at rehabilitation.
One well-known case was that of Rom Houben.
That&rsquos right. He was a very important patient for us: as far as anyone could tell, he had been left completely unresponsive for 23 years after a car accident. But in the mid-2000s we placed him in a brain scanner and saw clear signs of consciousness. It is possible that he experienced emotions over all those years. He was the first of our patients who was given a different diagnosis after such a long time. We subsequently conducted a study in several Belgian rehab centers and found that 30 to 40 percent of unresponsive patients may exhibit signs of consciousness.
I&rsquove heard that Houben was eventually able to type words with the help of his communication facilitator.
Yes, but his facilitator was the only person who seemed able to understand and translate his minimal hand signals. She probably typed words of her own unconsciously. This form of communication doesn&rsquot generally work, and our team was wrongly connected with it. It is a complex case that the media has failed to report adequately. They were more interested in telling sensational, simplistic human-interest stories. Nonetheless, it&rsquos a good example of why we must be extraordinarily careful in diagnosing this condition.
How can minimal consciousness be distinguished from locked-in syndrome?
Minimally conscious patients can barely move and are not completely aware of their surroundings. In other words, their motor and mental abilities are limited. Locked-in patients can&rsquot move either, but they are completely conscious. They have suffered a particular type of injury to the brain stem. Their cerebral cortex is intact but is disconnected from their body. All they can move is their eyes&mdashsomething that neither the patient nor the physician is aware of at the beginning. This is why diagnosis is so difficult. Just because patients cannot move does not mean they are unconscious. This is a classic fallacy consciousness does not reside in our muscles but in our brains.
How can a person who cannot move manage to communicate?
To communicate with a minimally conscious patient for the first time here in Liège, we placed him in a scanner. Of course, the scanner cannot tell us directly whether someone is saying yes or no. But there are a couple of tricks. For example, we can tell the patient, &ldquoIf you want to say yes, imagine that you are playing tennis. If you intend to say no, make a mental trip from your front door to your bedroom.&rdquo &ldquoYes&rdquo answers activate the motor cortex &ldquo no&rdquo answers engage the hippocampus, which plays a role in spatial memory. Because these two regions of the brain are located far apart from each other, it is pretty easy to tell the difference between yes and no. From that point on, we can ask the patient pertinent questions.
What other potential techniques do you have in the pipeline?
In the future, it may be possible to read brain signals using scalp electrodes and a brain-computer interface. This would make communication much quicker and less costly than with a brain scanner. We have also found that it is possible to examine a person&rsquos pupils: we ask patients to multiply 23 by 17 if they intend to say yes. This difficult problem causes the patients to concentrate, and their pupils will dilate slightly as a result. If we direct a camera at their eyes and a computer analyzes the signals, we can determine quite quickly whether the intended answer is positive or negative.
Think of the movie The Diving Bell and the Butterfly about Jean-Dominique Bauby, the editor of the French fashion magazine Elle. He suffered a stroke that left him with locked-in syndrome. He wrote an entire book&mdashon which the movie was based&mdashby blinking his one remaining functional eye. We are now able to place an infrared camera over patients&rsquo eyes, which enables them to chat or write relatively easily.
Can consciousness be stimulated?
Yes, by transcranial direct-current stimulation. Using scalp electrodes, we can stimulate particular regions of the brain. By careful placement, we can select the region responsible for speech, which is connected with consciousness. If I stimulate this region of the brain, the patient may hear and understand what I say. In some cases, a patient has been able to communicate transiently for the first time after a 20-minute stimulation&mdashby, for example, making a simple movement in response to a question. Other patients have been able to follow a person with their eyes. Although consciousness does not reside in our muscles, stimulating patients may enable them to move muscles consciously.
This technique works in about half of patients with minimal consciousness. In my opinion, this represents the future of treatment, even though we do not yet know precisely which regions of the brain are the most responsive to stimulation or whether they should be stimulated on a daily basis. But I don&rsquot want to give people false hope. We are still faced with the question of the minimum acceptable quality of life. This is a major philosophical and ethical problem that will be answered differently by different people. I would recommend that everyone discuss these issues in advance with a trusted person. Then you will know that, if you are ever in that position, your desires and values will be taken into account.
Do you think that consciousness can be reduced to the brain alone?
We already know quite a bit about the brain processes that underlie attention, perception and emotions. There is no point in throwing this knowledge out the window. As a neurologist, I see the consequences of brain damage every day. It remains to be discovered whether the brain is the entire story. Scientific research has to be conducted with an open mind. The topic of consciousness is rife with philosophical implications and questions. As a physician, it is my aim to translate this knowledge into practice. It may be frustrating that we currently lack the tools to measure the hundreds of billions of synapses with their tangled mass of neurotransmitters. Nonetheless, I think it is a mistake to infer from this that we can never understand consciousness.
ABOUT THE AUTHOR(S)
Anouk Bercht is a science writer based in the Netherlands. She writes frequently about psychology.
Steven Laureys is a professor of neurology at the University of Liège and leads the Coma Science Group at Liège University Hospital Center. He has received numerous awards, among them the 2017 Francqui Prize, the most important Belgian science award.
Nobody Declared Brain Dead Ever Wakes Up Feeling Pretty Good
A day rarely goes by that I don't read a few sensational headlines: "Man Declared Dead Feels 'Pretty Good'" or "Husband Celebrates Miracle as 'Brain Dead' Wife Wakes Up in Hospital." I recently read an article that seemed to describe a man on death row in Huntsville, Texas. It attempted to shock its readers with the claim that a college student had been declared brain dead and "just hours before he was slated to be killed and his organs given to another patient," he miraculously recovered. That's right, they said "killed."
As a neurologist who specializes in brain injury, I have cared for many brain-injured patients and there were times when they did better than I anticipated, but sensational articles like these only confuse the public. During the health care legislation debates, the mere mention of insurance coverage for consultation on end-of-life decisions brought forth hysterical cries of "death panels" from people like Sarah Palin who exhorted that "my parents or my baby with Down's Syndrome will have to stand in front of Obama's 'death panel'. " But if the headlines are fiction, what is the truth?
HOW OUR BRAIN ACTUALLY WORKS
Brains are far more complex machines than even the most sophisticated computer. We turn on our computer with a simple switch. The screen entertains us as it boots up and we start to check our email, linger on Facebook to catch up with friends, or read the latest headlines. Have you ever wondered what your brain is doing in the early morning as you awaken to your automatic coffeemaker brewing that first cup of joe?
The main part of our brain, the cerebrum, sits inside our skull and is attached to our spinal cord by the small, but critical, brain stem. Inside the brain stem is a small, but critical, group of nerve cells known as the Reticular Activating System (RAS) that send messages up into the brain, not only to wake us up, but also to keep us alert. We call this process arousal -- no, not that tingling that you get when you kiss the man or woman of your dreams, but stimulation that keeps you awake. But just being awake isn't enough.
We need an intact upper brain to be aware of ourselves and our surrounding environment. Awareness is a higher-level function that requires areas of the cerebrum to process the information we see and hear. A patient may have their eyes open and look like they're awake, but if the brain is severely damaged they may have no awareness of their surroundings. We call this a vegetative state.
On the other hand, people who are in a coma are not awake and have no awareness of themselves or their environment. You can talk to them, pinch them, show them pictures of their family -- they will not respond. However, these patients are not brain dead. This is the source of the confusion that leads to the sensational headlines and stories.
In 1976, Karen Ann Quinlan was in a vegetative state, but lived for nine more years after her ventilator was discontinued. Theresa Schiavo had been in a vegetative state for 15 years. After a protracted legal battle her husband was granted permission to withdraw her nutritional support and she died. Both young women, like the people in the headlines, were not brain dead. People in a vegetative state usually have extensive brain damage, but may blink their eyes and look around, breathe on their own, yawn, chew, and even withdraw their arms or legs to painful stimulation. They are not brain dead, and no one is going to take their organs.
WHAT, EXACTLY, IS BRAIN DEATH?
What is the difference between someone in a coma, who may or may not improve, and someone who is truly brain dead and may be a candidate to donate their organs? Brain death is the irreversible cessation of all functions of the entire brain, including the all-important brain stem that houses the RAS and the mechanism that controls our breathing. Dead is dead. Brain death isn't a different type of death, and patients who meet the criteria of brain death are legally dead.
There are strict criteria for brain death and these criteria (PDF) are carefully followed before a patient becomes an organ donor or their ventilator is unplugged. They must be in a coma with no brain stem or pupillary reflexes. They do not breathe on their own when taken off their ventilator, and an electroencephalogram (EEG) records a complete absence of brain activity. Although most states only require the diagnosis of one physician, the patient's family can always ask for a second opinion.
The sensational headlines hinder our efforts as physicians to educate the public about organ donation and cause unnecessary anxiety for families who are considering donating their loved one's organs. No one who has met the criteria for brain death has ever survived -- no one. It can be difficult to predict a person's outcome after a severe brain injury, but it can be said with certainty that a brain dead individual is dead, the same as if their heart was not beating.
In most hopeless situations, our society's current default is to continue all medical measures unless otherwise clearly stated. At the same time, there is a move afoot in state capitols to pass legislation that would make the withdrawal of nutrition and hydration impossible unless it is specifically stated prior to injury. As of 2007, only 41 percent of people had a living will and both living wills and advanced directives tend to be very general. Now is the time to sit down with your family and discuss what you want done if you were in a hopeless situation or brain dead. There is still a critical shortage of organs available for donation. If the concept of brain death is keeping you from becoming a donor, you can check that off your list and sign up now.
States of Disordered Consciousness
In the first scenario below, we consider Matt’s condition in the days, weeks, and months after his accident and describe his states of consciousness, along with what was known about his prognosis. Patients with severe brain injury and coma who recover may, depending on the severity of the brain injury, progress through several levels of consciousness, from coma, to vegetative state, to minimally conscious state, to consciousness, with varying degrees of motor, cognitive, and affective impairment. The range of potential outcomes is wide.
Coma—Neither Awake nor Aware
Two days after the accident, Matt did not open his eyes, make any purposeful spontaneous movements, or respond to Dr. Robert’s commands or to any other stimuli, including painful stimuli. Dr. Roberts concluded that the RAS was not working, and she described Matt as being in coma—he was neither awake nor aware. She had good reason to believe that Matt was not simply in the locked-in state, which is the state of being conscious but unable to move. This happens rarely after certain types of stroke (which would have been seen on his brain scan), or in the late stages of some neuromuscular diseases.
The presence of coma early after an injury does not predict a patient’s outcome. Patients with widespread injury to the brain are more likely to have severe neurologic deficits and are at a higher risk of prolonged unconsciousness. Patients with more focal injuries (for example, only a brainstem injury) may have less severe neurologic impairment and are more likely to have temporary coma. The nature of the neurologic impairments depends on the areas of the brain that have been injured, and Matt’s injuries were uncertain. Although his brain CT scan did not reveal major structural injuries, he may have suffered (1) widespread injury to the neurons of the cortex and thalamus because he was deprived of oxygen and (2) injury to the white matter because of the physical forces of the traumatic brain injury.
Although the RAS was not functioning normally, Dr. Roberts found that other important brainstem areas were still functioning. Matt’s pupils responded to light, his eyes blinked when his eyelashes were touched, he gagged when a suction catheter was passed through the endotracheal tube to his lungs, and he was initiating breaths on his own, even though he required support from the ventilator. The presence of these brainstem functions was favorable but did not indicate whether he would eventually recover consciousness. Although he had spontaneous breathing, he could not swallow safely or protect his airway from aspiration (sucking liquids into the lung), which would cause pneumonia therefore, he needed the endotracheal tube. He also required a nasogastric tube into the stomach to receive a feeding solution for adequate nutrition.
Coma usually lasts for no more than two to three weeks. In most instances, coma evolves to the next level of consciousness, known as the vegetative state.
Vegetative State—Awake but Unaware
Unless the RAS is severely injured, its function returns in two to three weeks. Ten days after Matt’s accident, his eyes began to open in response to painful stimuli, which implied the presence of wakefulness and that spontaneous eye opening would eventually occur. However, despite the fact that his eyes were open, when Dr. Roberts called his name or placed her face close to his, Matt did not look at her, which indicated that even though he was awake, he was not aware of her or of his surroundings—i.e., he was still unconscious. Similarly, his motor responses to pain consisted only of reflexes and not purposeful movements. Note that although patients in vegetative state have reflex responses to pain, because they are not conscious, they cannot experience either pain or suffering. Therefore, Matt’s condition was defined as the vegetative state, a condition that may either be a temporary stage in recovery from coma or may be more longstanding if the brain injuries are severe and irreversible.
Endotracheal and nasogastric tubes that are placed when patients emergently enter the hospital can remain in the body for only a limited period of time because they may cause injury to the larynx or stomach over an extended period of time. However, patients in vegetative state, like Matt, are incapable of protecting their airways or of taking oral nutrition and hydration. Therefore, a more permanent breathing tube, called a tracheostomy, is surgically inserted through the front of the neck directly into the trachea, and a semi-permanent tube, known as gastrostomy tube, is inserted directly through the abdominal wall into the stomach so that the patient can receive nutrition and hydration.
Two weeks after his brain injury, Matt’s prognosis was still uncertain. Dr. Roberts told Matt’s parents that in the best case, he would regain consciousness but would likely have severe, permanent physical and cognitive limitations. In the worst case, he would never regain consciousness. Matt’s parents, not wanting to give up prematurely and hoping that he would eventually “wake up,” elected to have the tracheostomy and gastrostomy tubes placed.
Persistent Vegetative State
Six weeks after Matt’s accident, he was breathing through the tracheostomy without the support of a ventilator however, he still required the gastrostomy tube for nutrition and hydration. He was transferred to a rehabilitation hospital, where Dr. Roberts examined him again and found that he was still vegetative—awake but unaware. By convention, after one month, the vegetative state is described as the persistent vegetative state (PVS). Dr. Roberts explained to Matt’s parents that the term “PVS” does not stand for “ permanent vegetative state” and that Matt’s long-term prognosis was still uncertain. Because patients may emerge from PVS, usually within 3–12 months, clarifying the distinction between persistent vegetative state and permanent vegetative state was important.
Matt’s parents asked Dr. Roberts about Matt’s odds of recovering consciousness. The most important factor influencing the likelihood of recovery is the type of brain injury a patient has suffered. Patients in the PVS after a traumatic brain injury can regain awareness as late as 12 months after the injury however, after that, the likelihood of recovery is very slim. The prognosis with brain injury caused by hypoxic-ischemic injury (lack of blood flow and oxygen) is worse than that with injury caused by trauma. Common causes of hypoxic-ischemic injury are cardiac arrest and drowning. Patients with hypoxic-ischemic brain damage are very unlikely to recover any awareness after only three months in the vegetative state and among those who do, a good neurologic recovery is very rare. Age is also an important factor. Younger patients have a higher probability of recovering consciousness early on but after 3–12 months (depending on type of injury), even children are extremely likely to remain in a vegetative state.
Matt’s brain injury was a combination of traumatic and hypoxic-ischemic injury because he was not breathing immediately after the accident. As a result, at six weeks after injury, the odds of Matt recovering some consciousness were small but not impossible. However, if Matt remained in the PVS at three months, his odds of recovering consciousness would be extremely poor, and Dr. Roberts would be able to say with a high degree of certainty that Matt would not have a good cognitive or functional recovery.
The Minimally Conscious State
Nine weeks after the accident, Matt started responding—just a tiny bit—to examiners and his environment. His caregivers noticed that if his eyes were open and someone called to him, his eyes would often, but not consistently, look in the direction of the voice. Sometimes, if his blood was being drawn, he would moan or grimace or weakly pull away from the pain, in a purposeful nonreflexive way. His parents had also seen him attempt to mouth words, but he did not do so on a consistent basis.
Matt was showing possible signs of consciousness, but his degree of neurologic functioning was not sufficient for him to communicate his needs or to care for himself. His condition had progressed to the minimally conscious state (MCS), which is characterized by either minimal or fleeting and inconsistent responses that nonetheless are consciously driven and represent more than the reflex responses seen in coma and the PVS. Some patients in the MCS progress to have consistent awareness, whereas others continue to fluctuate between the PVS and the MCS. In some sense, the MCS is better than PVS because it suggests that some parts of the cortex, thalami, and white matter are working in a coordinated fashion. However, in the MCS, Matt was able to perceive his pain and his circumstances but was unable to communicate to others about his experience or his own perception of his condition. Because his MCS was the result of such a severe and widespread brain injury, Matt still needed the feeding tube for nutrition and hydration, and meticulous nursing care for all of his physical needs.
After Matt emerged into the MCS, his parents were hopeful that he would continue to improve. Sadly, after three more months, he had not. He continued to fluctuate between the PVS and the MCS. Dr. Roberts informed Matt’s parents that the likelihood of a good recovery—meaning that Matt could communicate his needs and make useful movements with his hands and arms—was exceedingly low. Although she could not rule out the possibility of minimal improvement over months or years, she could say that he would never be able to care for himself or engage in complex social interactions.
Matt’s parents considered whether Matt would want them to continue tube feedings in his current condition without a reasonable chance of a recovery that he would think was meaningful. After many discussions with their family, friends, social workers, and clinicians, Matt’s parents concluded that he would not have wanted to continue treatment, and they asked that the tube feedings be stopped. This request was honored, and nine days later, Matt passed away without evidence of pain or discomfort.
In the previous scenario, Matt progressed from coma to the vegetative state to the MCS. However, rather than improve, some patients in coma worsen. In the following alternate scenario, Matt’s brain injuries were much worse than described above, and the clinical course differed significantly.
Two days after his accident, Matt was comatose and had no brainstem reflexes. His pupils did not respond to light, his eyelids did not blink when his eye was touched with sterile cotton, he did not have a gag or cough reflex in response to tracheal suction, and he did not initiate any breaths on his own—all breathing was provided by the ventilator. Dr. Roberts concluded that Matt had suffered severe and potentially irreversible injury to all of the neurons in his brainstem, cortex, and thalami and that his condition was probably worsening toward brain death, a term that refers to irreversible loss of all clinical brain functions, including all brainstem reflexes and the drive to breathe.
To confirm brain death, Dr. Roberts performed a series of formal tests known as the brain death examination, which is recommended by the American Academy of Neurology to look for any brain function. This examination confirmed that Matt was comatose and that he lacked all brainstem reflexes, including respiratory drive. When the ventilator was temporarily disconnected from the endotracheal tube while his vital signs were being carefully monitored, Matt made no effort to breathe–even when the carbon dioxide level in the bloodstream reached levels that normally elicit gasping and breathing. Following her hospital’s protocol, six hours later, Dr. Roberts performed a second brain death examination, which elicited the same findings.
As is the practice in the U.S. and many other nations, Dr. Roberts pronounced Matt dead on the basis of brain-death criteria. She explained how she made this determination to Matt’s parents and told them that the ventilator and any fluids or medications would soon be stopped, once they had had a chance to say goodbye.
In accordance with hospital protocol and national standards of practice, Matt’s parents were told about the possibility of organ donation. Patients pronounced dead by brain-death criteria have the opportunity to donate all of their major organs (kidneys, liver, pancreas, intestines, heart, and lungs) and tissues (cornea, skin, bone) because the organs and tissues can remain viable for transplantation until the ventilator is stopped. Matt’s parents believed Matt would want to donate his organs, and after discussion with the regional Organ Procurement Organization, they agreed to the donation.
A Brain Dead Little Girl Raises Some Big Questions
Starting a couple of weeks before Christmas, tragic news about Jahi McMath hit the media, and has scarcely abated since. Jahi is a 13-year-old girl who suffered a cardiac arrest and massive brain bleed following a routine tonsillectomy. She was declared whole brain dead on December 13 at Children’s Hospital and Research Center in Oakland, California. Her parents have been fighting ever since to prevent withdrawal of the ventilator and other interventions that have been sustaining her body, and succeeded in getting a series of court injunctions to prevent Children’s Hospital from removing “life support.”
As of this writing (January 22), Jahi is still on the machines and has been transferred to an undisclosed facility for continued care, despite the indisputable fact that a person who has suffered whole brain death is legally dead in all 50 states.
Predictably, bioethicists have been interviewed to offer their opinions about the case, and those opinions have been uncompromising—Jahi is not just brain dead, she is plain dead. Since there is no obligation to provide “life” support or any other medical treatment to a dead person, Children’s Hospital would have been fully within its rights to withdraw that treatment once Jahi was declared dead.
Laurence McCullough, bioethicist at Baylor College of Medicine, is quoted as saying that “There are no ethical issues in the care of someone who is brain-dead, because the patient is now a corpse . . . orders should have been immediately written to discontinue all life support. . . . The family should have been allowed to spend some time with the body if they wished. And then her body should have been sent to the morgue. That is straightforward. There is no ethical debate about that.”
Echoing similar comments imputed to Arthur Caplan (NYU Langone Medical Center) in the same article, McCullough is reputed to have said that “‘brain death’ is no different than any other sort of death: A brain-dead person is no longer alive. The term simply describes how the death was determined.”
McCullough and Caplan are right about the law. There is no difference between a person who is declared dead because his brain will no longer work, and a person declared dead because his heart and lungs have irreversibly stopped working. They are equally “dead,” legally speaking.
But in other respects brain death is different than other sorts of death. To begin with, brain-dead is not stone cold dead. When the whole brain has died, including the brain stem, the most important vital function that’s lost is the signal to breathe. But a ventilator can fill the lungs with air, providing oxygen to the rest of the body, even if the patient can no longer breathe on her own. Since the heart can operate relatively independently of the brain, a brain-dead person on a ventilator can have a heartbeat, might be warm and soft to the touch, and might have normal color. Brain-dead patients on ventilators don’t look like corpses. And, depending on a variety of factors, a brain-dead body might be successfully maintained for months—even enough time to bring a fetus to term—a factor in the case of another brain dead patient in Texas.
Given what they are probably seeing and feeling, then, it is completely understandable why Jahi’s parents believe their eyes rather than the doctors. From their perspective, the ventilator is keeping their daughter alive, not preserving a corpse. It wouldn’t be surprising if their discussions with the medical staff encouraged that idea. The very term “life support” creates a cognitive dissonance when applied to the brain dead patient who is allegedly dead. Encouraging the parents to agree to withdrawal of the ventilator because “The machine is the only thing keeping her alive” sends a similar mixed message. Even something like “Her condition is hopeless there is nothing more we can do” suggests the ventilator is a kind of treatment that’s not going to prevent the patient’s death. The question whether it can prevent something presumes it hasn’t yet occurred.
In a study I did many years ago, experienced ICU physicians and nurses, who all understood the concept of brain death, and believed that brain-dead patients were legally dead, commonly used these sorts of expressions (Tomlinson, 1990). I suspect they are still commonly used, because a conversation about withdrawing hopeless treatment is much simpler and more familiar to all involved than an explanation of why a patient with a beating heart is dead.
So how can a person with a beating heart be dead? The answer is anything but straightforward.
Should we say—as many have about Jahi—that sooner or later her body will begin to deteriorate and her heart will stop? This is true enough, but all it really proves is that brain death is invariably terminal on anyone’s understanding of “dead.”
Should we say that if it weren’t for the ventilator, Jahi’s breathing and heartbeat would have stopped once her brain died? Yes, this is true. With the death of the brain, spontaneous respiration stops, and the heart stops very soon thereafter. The brain orchestrates the vital functions, and so the death of the brain spells the permanent loss of the vital functions. But this is not quite accurate. The death of the brain spells the end of the spontaneous vital functions. Why can’t we say that the ventilator is substituting for the function previously performed by the brain stem, and so keeping the patient alive by artificial means?
Enough already! Shouldn’t we just say that death is not really about the loss of the vital biological functions, or about the brain’s role in supporting them. It’s about the death of the person. The death of Jahi’s brain is the absolutely 100% accurate sign that she—the conscious person—will never return. Whether her heart keeps beating doesn’t matter. She’s gone.
This is a very attractive idea. After all, what does death mean to me, from the personal point of view, if not the end of my human experience? Whatever may continue after that doesn’t affect me in the least. If we accept this view, however, we will have to struggle with what to think about those persons whose brains still support respiration and heartbeats, but not conscious awareness. Was Terri Schiavo dead for the 14 years she was in a persistent vegetative state, with no awareness of herself or her environment, according to the neurologists who examined her? Just as dead as Jahi McMath is now?
“Dead” was a pretty simple notion once upon a time. Jahi McMath should remind us—bioethicists included—that it’s a lot more complicated now.
Tom Tomlinson, Ph.D., is the Director of the Center for Ethics and Humanities in the Life Sciences and a Professor in the Department of Philosophy at Michigan State University.
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DEATH: Natural or assisted? A guide to medical end-of-life issues
Here is an explanation of common terms used during end-of-life discussions.
What is withdrawal of nutrition or hydration?
What is the persistent vegetative state (PVS) or minimally conscious state (MCS)?
What is a ventilator-dependent patient?
What is a do-not-resuscitate order?
What is an advance directive?
(* terms with an asterisk in the text are defined below)
What is Euthanasia?
Euthanasia is the intentional causing or hastening of death in a person with a medical condition that is judged to be serious. The patient may either be (a) alert and (b) aware and (c) competent to make their own decisions and (d) able to communicate or the patient may have (a) decreased alertness (due to encephalopathy* or coma*), (b) diminished awareness (learning disability*, dementia*,vegetative state*) and (c) be incompetent to make their own decisions or (d) be unable to communicate due to aphasia*, or inability to speak. Euthanasia is voluntary, when an alert, aware, competent patient agrees to it being performed, and euthanasia is involuntary when it is performed on a patient without the patient's clear understanding and agreement. Euthanasia may be an obvious, clear-cut act acknowledged as such by both the medical staff and patient or may be an action or series of actions that are put forward as being "standard" medical treatment. An example of a clear act is when a patient is given a lethal intravenous dose of potassium or insulin or an oral fatal dose of sedatives. However, a patient may be given gradually escalating doses of morphine, benzodiazepines or other narcotics for sedation or analgesia, in the knowledge that the medication will hasten death. If morphine is being used primarily to treat severe pain not responsive to other analgesics, in a painful terminal condition, (such as advanced widespread cancer), it may be given in the knowledge that a side-effect of the treatment may be a hastening of death (so-called principle of double effect). This cannot be considered euthanasia. However, if excessive and repeated doses of morphine or sedatives are given to a sick patient who is not in pain, for the purpose of "comforting the patient" or to "relieve air hunger" or to relieve "laboured breathing" this may really be euthanasia under the guise of "standard" medical treatment.
The Liverpool Care Pathway (LCP) started in the United Kingdom in the 1990s with the stated aim of “driving up the quality of care for the dying”. The LCP had a central flaw that patients were put on it when they were determined to be “imminently dying” although it is not possible to make this “diagnosis”. Patients who were labelled as “dying” were given combinations of morphine, midazolam (a benzodiazepine tranquilliser) and glycopyrrolate (a medication that dries respiratory secretions) intravenously in increasing doses through a battery-powered syringe driver. Fluids were discontinued in most cases and patients died in a mean time of 33 hours. This uniform very short time to death shows that the LCP was effectively a form of euthanasia. The LCP was discontinued by the Neuberger Report in 2014. It was replaced by guidelines delineated in the National Institute for Clinical Excellence (NICE) in 2015 which still contain the central flaw of the “diagnosis” of imminent death and these new guidelines are if anything worse than the LCP. Despite this they are still in use throughout the NHS in the UK. It should be noted that the combination of dehydration and sedation, as used in the LCP, is particularly lethal. Dehydration in the elderly rapidly leads toencephalopathy* and renders the patient unable to take oral fluids and removes the patient’s capacity to be involved in their care decisions.
Another form of euthanasia that is frequently practised is to switch off a ventilator (mechanical respirator) that is assisting breathing in a patient who is unable to breathe on their own. Some patients are put on a ventilator because they have lung disease and need the extra oxygen- these patients may be alert and be able to communicate. Some patients cannot breathe on their own because of brain disease. This may be reversible as in encephalopathy*, or may be severe and irreversible such as in the persistent vegetative state*. It is frequently difficult to determine early in the course of an illness whether the condition is reversible or not and this usually only becomes clear with passage of time. Patients on ventilators are frequently in a deep coma and they may deteriorate and die. It is often difficult to know without a full neurological examination whether a patient is in deep coma or if they are dead. A series of tests has been drawn up to determine the presence of brain death (see section 5: How is death determined*) and these are usually administered by a neurologist or neurosurgeon. If these tests determine that brain death has occurred, it is legitimate to switch off a ventilator even though the heart may still be beating, because in this situation the ventilator is not keeping the patient alive. There is however, an increasing tendency in intensive care units to discontinue ventilator support in patients who have either severe irreversible brain damage who are not dead (see persistent vegetative state*), or in patients with potentially reversibleencephalopathy*. The stated reason for discontinuing ventilator support is often because the patient's prognosis for recovery to their previous state of functioning is judged to be poor. There is also an increasing tendency to discontinue ventilator support in patients with severe respiratory disease when it is judged that they have become ventilator-dependent* and might need to have ventilator support for the rest of their lives. Mechanical ventilation is clearly an artificial method of life support. Ventilation can be life-saving in an acute illness and patients are usually put on a ventilator as a temporary measure. Difficulty breathing is part of the terminal stages of several illnesses such as large strokes or severe long-standing lung disease. Mechanical ventilation is not part of the recommended treatment of such illnesses because there is little chance that it will help and a high chance the patient will die despite being put on a ventilator or that they will become ventilator-dependent*. When a poor outcome to ventilation is predicted, patients or relatives are usually advised to sign a do-not-resuscitate (DNR) order* This will ensure that a ventilator will not be used as part of the patient’s treatment and the difficult situation of ventilator-dependency will not arise. Clearly, there is a big difference between a person dying because a ventilator was not used for an inappropriate indication and a patient dying because a ventilator that was keeping a patient alive, was switched off. If a patient needs a ventilator to survive, death is a direct consequence of switching off the machine and this makes this a form of euthanasia.
What is Physician-Assisted Suicide?
Physician assisted suicide is when a physician assists a person to commit suicide by providing them with the means to kill themselves. This may be by prescribing a lethal dose of oral medications for a person which the patient then takes at some later time. Alternatively the physician may play a more active role by providing a person with a machine that once set in action, automatically delivers a large intravenous dose of a sedative, such as a barbiturate, followed by a drug such as a large dose of potassium, that stops the heart or a paralysing agent that stops breathing. The first drug puts the person to sleep, the second kills them. The physician is more directly involved in this type of assisted suicide because apart from prescribing lethal drugs, he/she provides the machine and presumably must also set up the intravenous infusion for the person. A physician may also assist suicide by withdrawing food and water from a patient at the patient's request. The law in many countries does not interfere if a person stops taking food and water of their own volition, but if this occurs in a hospital, the physician in charge, by acquiescing, assists in the suicide.
What is withdrawal of nutrition or hydration (food or water)?
Discontinuation of food and water is a form of euthanasia that is increasingly practised. The most frequent targets are patients who are unable to swallow, have encephalopathy* or are in coma*, or patients with advanced dementia*who cannot feed themselves. These patients have to be temporarily fed by a feeding tube through the nose or permanently fed by a tube inserted into the stomach through the skin. Most patients in whom withdrawal of food and water is considered are not competent to be involved in the immediate decision to discontinue food or water but may have made an advance directive* that they do not want life support measures taken if they become terminally ill. Many physicians who withdraw food and water in response to advance directives state that a feeding tube is a form of artificial life support that is similar to a ventilator. Withdrawal of hydration was a central feature of the LCP and continues to be practised in the sick elderly who are determined to be “imminently dying”.
Provision of food and water is however, the most fundamental of nursing duties. Food and water are necessary to maintain life and their withdrawal with the intent to hasten death is euthanasia. There is much misinformation about provision of hydration, especially in those patients determined to be “dying”.
It is said that when a person is near death the body “shuts down” and no longer needs nutrition and hydration. There are no reliable studies that support this claim and discontinuation of fluids and hydration are likely to hasten or cause death. Clinical signs of dehydration (especially the skin ridging sign) should be looked for daily in the elderly or sick. Inadequate oral intake should lead to giving of intravenous fluids. A person needs 1.5 to 2.5 litres of fluid a day or 1.5ml/kg/hr. Giving fluids subcutaneously is not a reliable means of delivering fluid as fluids tend to pool under the skin or leak. Leaving a patient without fluids for more than 24 hrs should be a reportable clinical incident.
It is also said that intravenous fluids are potentially dangerous so the risk has to be balanced against the benefit. This has been very overstated however since the risk of giving fluid is small but the withholding of fluid is rapidly fatal. Too much intravenous fluid in the elderly can lead to fluid overload, but this is easily diagnosed and treated by slowing the infusion or by giving diuretics. The risk of not giving fluids is that the patient is thirsty, (and severe thirst is extremely distressing) that the patient develops encephalopathy* or that death is hastened or caused.
If a patient is unable to swallow they should be given feeds by nasogastric tube. Nasogastric tubes tend to annoy patients if kept in for long and are often become displaced but they can be “bridled” with a thin tape to hold the tube into the back of the nose. If it seems likely that oral feeding will not be resumed within a week or so, Percutaneous Endoscopic Gastrostomy (PEG) tube feeding should be considered. PEG tubes are very well tolerated by patients and in stroke patients who cannot swallow it has been shown that they recover better if PEG tube is instituted early. A PEG tube can always be removed when it is no longer needed.
There has been a major tendency to delay nasogastric or PEG feeding in UK hospitals nowadays but patients feel better and recover better if fed adequately and starvation can hasten or cause death. Relatives should insist on adequate fluids and nutrition being given at all times.
What is unassisted death?
To die naturally a patient should die from the consequences of old age or disease. The patient's death may be at least partly due to surgery, to a treatment or to a medication (or to their complications), that is given in an appropriate dose and for an appropriate indication, with the intent of treating a disease or relieving pain. When giving a potentially lethal medication, there must be no intent to hasten death. Treatment may be withdrawn from a patient and this may indirectly result in their death. Patients do not have any obligation to use medical treatments and may opt to allow a disease condition to take its natural course. This becomes morally questionable when the patient is young and the treatment is easy and life-saving, such as a blood transfusion for a sudden severe loss of blood. A physician is under an obligation to use available treatments to attempt to prolong life or relieve suffering. If treatments to prolong life are likely to result in suffering a physician may, in consultation with patients or relatives, decide to withhold treatment. Treatment that has already been instituted may also be withdrawn if the prolongation of life they result in causes suffering, in a patient who is terminally ill. If withdrawal of a treatment has a high likelihood of directly resulting in the death of a patient, the doctor has a moral obligation not to withdraw it, even if the patient or relatives request it, because this constitutes an intent to cause or hasten death. (For example switching off a ventilator in a patient unable to breathe will result in immediate death).
How is death determined?
Death is normally determined by the cessation of the pulse and breathing. Determination of death in a patient who is connected to a ventilator is more difficult, because the heart often continues to beat after death of the brain. The main problem in the determination of death is that the ventilator continues to breathe for the patient, and it is not possible to test whether the patient is able to breathe without the machine unless it is switched off. Switching off the ventilator however, may result in brain injury if the patient is not dead. It is generally accepted (including by Pope John Paul II) that if there is irreversible complete loss of function of the brainstem (the part of the brain in charge of consciousness, breathing and regulation of the heart) this means death of the whole brain and that this is equivalent to death of the person even though some organs may continue to function for a period of time. A series of tests has been drawn up to determine the presence of brainstem death and these are usually administered by a neurologist or neurosurgeon. The tests performed are: a) looking for eye movements in response to turning the patient's head, or in response to putting cold water in the ears, b) looking for an eyeblink in response to touching the eye, c) looking for any movement in response to a mechanical stimulus to the head or limbs, d) looking for a constriction of the pupils in response to a light e) checking to see if the patients gags with stimulation of the throat. f) to ascertain the absence of all brain activity two electroencephalograms (brain wave tests) at least six hours apart can be performed. If all these tests are negative and certain baseline conditions such as adequate body temperature and lack of recent sedative drug ingestion, the physician will perform a breathing test. This is the final crucial test and it is done under carefully controlled conditions. The patient may have to remain off the ventilator for several minutes to allow carbon-dioxide to accumulate in the blood, because this is a strong stimulus for breathing. There is a risk that the high levels of carbon-dioxide may affect the heart and the heart may stop beating during this test. If the patient is not seen to breathe over a period of observation of about three minutes without the breathing machine but with 100% oxygen, then the patient is determined to be brain dead. The patient is usually temporarily put back on the machine and it may be necessary to repeat all the tests again after a few hours. When brain death has been ascertained the breathing machine can be switched off. It is well known that the heart may continue to beat after brain death, even for several months. There have been cases where a pregnant brain dead patient has been kept on a ventilator and this has allowed a healthy infant to be born.
What are "persistent vegetative state (PVS)" and “minimally conscious state (MCS)”?
PVS and MCS are conditions in which severe brain damage causes the patient to have reduced awareness and ability to respond meaningfully to the environment. The patient with PVS is typically one who suffers a severe head injury, a prolonged cardiac arrest or multiple strokes. The patient with PVS is able to open their eyes and may have normal sleep/wake cycles. With PVS they may look like they are awake, but seem to be totally unresponsive to their surroundings. The patient may be able to breathe on their own or need a ventilator. The patient is usually unable to swallow and needs a feeding tube. It has been found that patients with PVS may have cognitive activity without showing it and specialised centres recommend functional magnetic resonance imaging (MRI) while calling their name, as one way of determining this. (see reference Di et al below). Over weeks or months the PVS patient may start to focus on faces or even track movements. They may respond to sounds or turn to them or show other meaningful responses indicating they are now in the MCS. Treatment with galvanic vestibular stimulation is showing early promise of improving level of awareness in the MCS. (see Vanzan et al below) The diagnosis of PVS becomes more definite if there is no improvement over time, and recovery is said to be unlikely 12 months after a traumatic injury and 3 months after non-traumatic injury. Occasional patients who have appeared to have persistent vegetative state* have started to communicate in a limited, but conscious and meaningful manner after a period of years. (see Childs et al below).
What is a "ventilator-dependent" patient?
Patients are not normally put on a ventilator unless there is a strong chance that they will get better and be able to breathe again without the machine. Patients with acute reversible respiratory or brain or neuromuscular conditions (e.g. myasthaenia gravis) are most likely to benefit from a ventilator. Often a ventilator is the only treatment that will save a patient’s life and there is pressure from relatives to use this treatment. Patients with long standing or with severe irreversible brain or lung disease are however unlikely to benefit from a ventilator. The severe brain or lung disease is not cured by the machine but the patient may be kept alive by being on the machine but not be able to breathe sufficiently by themselves to be taken off the ventilator. This is called being ventilator-dependent. A patient can breathe using a ventilator for an unlimited period of time, and there are many portable types of ventilator and many people live at home with the aid of a ventilator. The cost of being maintained on a ventilator in an intensive care unit is high and this is one reason that there is increasing pressure to switch off the ventilator if a patient is unable to breathe without it after a trial of several days. This is clearly a form of euthanasia since the action of switching off the ventilator directly results in the death of the patient. Not all cases are clear-cut however, some patients are able to breathe on their own for a period of a few hours, when the ventilator is first disconnected but then they get tired and breathing deteriorates and the patient dies if not put back on the ventilator. Is it ever morally justifiable to permanently discontinue ventilator support in this situation? If there is a reasonable chance that the patient may be able to breathe on their own, and they are in fact able to so for at least a couple of hours, it is probably reasonable to discontinue the ventilator if the patient or surrogate* know and accept the risk of death. If the patient subsequently dies, death can reasonably be ascribed to the underlying disease rather than to the discontinuation of the ventilator. This is an area fraught with dangers because a surrogate may not always act in the patient's interest. The patient must be given every chance for their lung function to return to baseline before an attempt is made to discontinue the ventilator. Premature withdrawal of ventilation is likely to fail. If, on discontinuing the ventilator, it is immediately clear that the patient is unable to breathe sufficiently, the ventilator should be re-instituted. Once the patient is removed from a ventilator, narcotics should only be given, if after a period of time the patient starts to be unduly distressed and it becomes obvious that they are not going to survive. Excessive haste in removing ventilator support or in giving narcotics with the intent to hasten death is euthanasia. Despite this, in some intensive care units the most frequent mode of dying is by switching off of the ventilator. Patient who are perceived to be recovering from coma too slowly or to have irreversible brain injury are often switched off. This is despite the fact that judging prognosis of cognitive outcome is extremely difficult even for experts.
This area has been compounded in recent years for the need for transplantation organs. Patients whose ventilators are switched off “become potential donors”. Current “dead-donor rules” state that the heart must stop beating before organs can be taken, but the time interval has gradually been reduced from 10 minutes to even 75 seconds by some recommendations. The National Academy of Medicine in the USA requires a five minute cessation of heart beat but does not require brain death criteria to be fulfilled before switching off. The moral issue is however that unless brain stem death has been tested for and established, then switching off of the ventilator is a form of euthanasia. If the brain death test is not performed it is not possible to be sure that the person’s brain is irreversibly damaged. The strong push for organs for transplantation starts to become a justification for switching off ventilators without establishing brain death criteria - which is not acceptable.
What is a do-not-resuscitate order?
A do-not-resuscitate (DNR) order is an order placed in a patient's hospital chart telling the doctor not to attempt to resuscitate a patient if the patient is in imminent danger of death. When signing a DNR order a patient is usually concerned about being connected to a ventilator. The decision to sign a DNR order usually means that the patient or surrogate* has decided that resuscitation would cause the patient unnecessary suffering and would not alleviate the underlying illness. DNR orders are important for protecting a patient against excessive medical interventions which often cause needless suffering in the terminally sick and elderly. Institution of a DNR order should not be a pretext for reducing the level of nursing and medical care a patient gets.
What is an advance directive?
An advance directive is a legal document drawn up by a person stipulating their preferences with regard to end-of-life care should they become sick and unable to express these preferences themselves. The advance directive usually states that if the person has a terminal illness that they do not wish extraordinary resuscitative measures to be taken. The problem is that it is difficult for an advance directive to cover all the possible situations that may occur and there is a wide range of interpretation left up to the surrogate*. Individuals may take "resuscitative measures" to mean either mechanical ventilation or even just placing a feeding tube or intravenous infusion. Also a severe disabling stroke may be interpreted as "fatal" illness. An advance directive may in this way be used by a surrogate* as a reason for not giving food and water to a patient with a severe but non-fatal medical condition.
What is palliative care?
Palliative care refers to the treatment of patient with a terminal condition such as cancer with a therapy that will not cure the patient but will make what remains of their life easier. Palliative care is very important in the management of any incurable illness, particularly if the patient is distressed or in pain. Physicians have realized that they have to be very aggressive in treating pain and suffering in these patients. Relief from psychological and financial stresses are also important but often harder to achieve. The commitment of physicians to palliative care is undergoing renewed scrutiny in the light of the rise of assisted suicide and euthanasia, and some feel that current interest in euthanasia and assisted suicide is the result of inadequate palliative care. Unfortunately, since the goal of palliative care is primarily to "reduce suffering" many people now consider palliative care to include the hastening of death in order to reduce suffering. Withdrawal of nutrition and hydration are considered by some to be part of palliative care. In addition, the use of strong narcotics which was once restricted to pain management, is becoming accepted for a range of indications such as anxiety, shortness of breath and to suppress feelings of hunger when feeding is withdrawn. In this way palliative care is quickly becoming a euphemism for euthanasia.
Aphasia. This is loss of the ability to speak due to inability to formulate language in the brain.
Coma.This is the name for a severe degree of loss of alertness and the patient looks like someone in a deep sleep that cannot be aroused. Coma may be due to severe encephalopathy (in which case the patient may recover) or due to brain injury (in which case recovery may be limited). Any brain injury may cause coma but the most frequent are traumatic injuries and injury due loss of blood supply (strokes) or cardiac arrest.
Dementia. A permanent deficit in multiple areas of brain cognitive function that arises during life. The most frequent cause is Alzheimer's disease. Patients with advanced Alzheimer's disease may be incontinent and need total nursing care and tube feeding. Dementia is increasingly wrongly used for any loss of brain function in the elderly such as poor memory, confusion or personality change whether reversible or not. Worsening of memory is very common with increasing age and should not be classed as dementia. Unfortunately patients with a label of dementia are at greater risk of poor care or even euthanasia.
Encephalopathy.This is a disorder of brain function affecting the whole brain diffusely. An example is the confused drowsy state caused by severe alcohol overdose. The patient is drowsy, unable to focus on what is said and cannot make sensible conversation. If severe the patient goes into a coma. There are many causes including drug overdose, epileptic seizures and severe heart, lung, liver or kidney disease. Dehydration in an elderly person can cause encephalopathy. Encephalopathy implies absence of permanent brain injury and is often reversible.
Learning disability.A permanent deficit in brain cognitive function present from birth. May be caused by cerebral palsy.
Persistent Vegetative State.This is a condition in which severe brain damage causes the patient to have reduced awareness and an inability to respond meaningfully to the environment.
Surrogate.A person legally empowered to take end-of-life decisions for a patient if the patient is unable to do so. Usually the next of kin (wife, oldest child) or a person legally specified by the patient.
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Profound, prolonged hypoglycemia can cause brain death. In studies of insulin-induced hypoglycemia in monkeys, 5𠄶 hours of blood glucose concentrations of less than 1.1 mmol/l (20 mg/dl) were required for the regular production of neurological damage (12) the average blood glucose level was 0.7 mmol/l (13 mg/dl). Fortunately, hypoglycemia of that magnitude and duration occurs rarely in people with diabetes.
The mechanisms of the common, hypoglycemia-induced functional brain failure and of the rare, hypoglycemia-induced brain death that occurs at very low, and at least in primates prolonged, plasma glucose concentrations (Figure (Figure1) 1 ) differ. The former is the result of brain fuel deprivation per se, but the latter is not. As summarized by Suh and colleagues in their study reported in this issue of the JCI (13), a variety of mechanisms are thought to be involved in the pathogenesis of hypoglycemic neuronal death. These include glutamate release and activation of neuronal glutamate receptors, production of reactive oxygen species, neuronal zinc release, activation of poly(ADP-ribose) polymerase, and mitochondrial permeability transition.
In their current report, Suh and colleagues (13) describe additional studies of the mechanisms of hypoglycemia-induced neuronal necrosis. Based on systematic cell culture and in vivo rodent studies of glucose deprivation followed by glucose provision, they provide evidence that hypoglycemic superoxide production and neuronal death are increased by NADPH oxidase activation during glucose reperfusion. These effects were reduced by an inhibitor of NADPH oxidase, deficiency of a subunit of the enzyme, and blockade of NADPH regeneration, among other findings. Notably, superoxide formation and neuronal death increased with increasing glucose concentrations during the posthypoglycemic reperfusion period. That finding is generally consistent with earlier findings by these investigators (14) and by others (15).
In order to reproducibly cause the study endpoints, including neuronal death, these studies (13) were generally performed at glucose concentration extremes. In the cell culture studies, glucose deprivation conditions were established by the use of a medium containing no glucose, while conditions of glucose provision were established by adding glucose to the medium at 10.0 mmol/l (180 mg/dl), several-fold greater than normal brain extracellular fluid glucose concentrations. In the in vivo studies, blood glucose concentrations averaged 0.4 mmol/l (7 mg/dl), causing an isoelectric EEG, during hypoglycemia and approximately 7.5 mmol/l (135 mg/dl) during glucose reperfusion that was documented to cause detrimental effects. Superoxide production, and presumably neuronal death, occurred as a result of hypoglycemia, but these occurred to a greater extent with glucose reperfusion, less so when posthypoglycemic blood glucose concentrations were raised to the range of 1.0𠄲.0 mmol/l (18 mg/dl) than when they were raised to the range of 5.0.0 mmol/l (90 mg/dl). Studies involving less profound hypoglycemia were not reported.
The distinction between the common hypoglycemia-induced functional brain failure and the rare hypoglycemia-induced brain death drawn here is admittedly arbitrary. Plasma glucose concentrations of less than 1.0 mmol/l (18 mg/dl) occur occasionally in people with diabetes (9), and dying brain cells, presumably neurons, have been reported following episodes of hypoglycemia at plasma glucose levels of 1.7𠄱.9 mmol/l (30 mg/dl) — but not following episodes of hypoglycemia at plasma glucose levels of 2.5 mmol/l (45 mg/dl) — in rats (16). Thus, it could be reasoned that these categories are not binary and that there is a continuous spectrum with increasing risk of neuronal death at progressively lower plasma glucose concentrations. Nonetheless, seemingly complete recovery follows the vast majority of episodes of clinical hypoglycemia.
The appropriate clinical extrapolation of these data is not entirely clear. As the authors point out (13), plasma glucose concentrations must be raised in hypoglycemic patients. In the common clinical setting of hypoglycemia-induced functional brain failure, plasma glucose levels should be raised into the physiological range promptly with the expectation that recovery of brain function will follow. At this point there is no clear evidence that posttreatment hyperglycemia is detrimental to recovery, but there is no reason to think it is beneficial in that setting. On the other hand, undertreatment will delay recovery. In the rare clinical setting of profound, prolonged hypoglycemia, where the risk of neuronal death is higher, the data suggest that plasma glucose levels should be raised cautiously with avoidance of hyperglycemia (13). Nonetheless, it would seem reasonable to raise the plasma glucose level into the physiological range (e.g., ϣ.9 mmol/l [70 mg/dl]) promptly. Clearly, additional studies of this important issue are needed.
Death and Cessation of Circulation
While doctors have been declaring death for centuries criteria for death determination after cardiac arrest were rarely formalized, and ranged from absence of movement, breathing, heart sounds, pulse or ECG activity. Current practices remain highly variable and inconsistent (11).
The ability to restore circulation with cardiopulmonary resuscitation, and even more so with extracorporeal support or reanimate heart function with ex-situ support, defies historical concepts of death determination based on the simple detection of heart and circulatory cessation. Effectively, modern in-hospital death after cardiac arrest is contingent on the consideration of CPR and ECMO to circulate oxygen – indications for use, availability and decisions at the end-of-life. In advanced health care systems, death can only occur after CPR and/or ECMO is either discontinued or not provided.
These realities are germane to criticisms of death determination in DCD. Here the complexities of science and philosophy entangle within debates around the minimal period of observation before death can be declared (see the below section on auto-resuscitation), whether loss of circulatory function is not “irreversible” within the time limits proposed and whether death is related to arrest of heart function or arrest of circulation. Given the ability to reanimate the heart by ex-situ oxygenated circulation this infers that the heart is not ”, but it is unable to sustain circulation in the body of origin. It is therefore not the arrest of heart function, but the absence of circulation (intrinsic or extrinsic) that determines death after cardiac arrest. The debate between defining the term irreversible as meaning “cannot be reversed under any circumstances” versus permanent where circulation “will not reverse under existing circumstances” (12, 13) is generally confined to academia. Most clinicians responsible for the declaration of death appear to accept in practice the permanence standard (14). The Institute of Medicine (15) and the ethics committee of the American College of Critical Care Medicine (16) take a similar pragmatic view to the ambiguity surrounding the term “irreversible”. Fundamentally, and most relevant to DCD, is not whether the body or brain circulation and function can be resumed (because it can), but rather, whether it will be. This is contingent on the preceding CPR and ECMO decisions.
Incoherence between Tests and Concept
The standard diagnostic tests for brain death consist of demonstrating coma, absence of a handful of brain-stem reflexes, and apnea. None of these has any bearing on the integrative unity of the organism. Even if the clinical tests are understood as a proxy for postulated nontestable integrative brain-stem functions, that assumes, first, that there is a set of unstated brain-stem functions that determine the difference between a living and a dead organism, and second, that the triad of coma, absence of several brain-stem reflexes, and apnea necessarily implies absence of those hypothesized functions. Neither of those assumptions has ever been established nor is plausible.
I know a case of a teenage girl with end-stage glioblastoma multiforme that had invaded the brain stem. At one point, she fulfilled all criteria for brain death (including an apnea test with final pCO2 89 mm Hg) except for a right corneal reflex and a weak cough to tracheal suctioning. Forty-eight days later, she fulfilled all criteria and was declared brain-dead. Is it coherent that, in the context of perfect functioning of all nonbrain organs, a right corneal reflex and a weak cough should determine the boundary between life and death? What if the tumor infiltration had eliminated the cough but not the corneal reflex? Would it have made any sense that a right corneal reflex should be the sole discriminator between life and death?
Reversing brain death: Far-fetched or feasible?
From gene editing to human head transplantation, the limits of medical science are being pushed further than ever. And now, researchers have turned their attention to another extraordinary mission: reversing brain death.
Share on Pinterest A controversial phase I trial will aim to restore life to 20 people who have been declared brain dead.
Though it sounds similar to the makings of fiction, scientists have received approval for the first ever trial that aims to restore neuronal activity in humans who have been declared brain dead.
The proof-of-concept study – which forms a part of the Reanima Project – is the brainchild of two life sciences companies: Bioquark, Inc., based in the United States, and Revita Life Sciences, based in India.
Due to begin later this year, the trial will recruit 20 individuals who have suffered brain death as a result of traumatic brain injury (TBI), but whose bodies are biologically alive as a result of cardiopulmonary and trophic support – a model referred to as a “living cadaver.”
To participate in the trial, each subject must be aged between 15 and 65 years, be unwilling for organ donation, and have written consent from a legally acceptable representative.
Researchers – including Bioquark CEO Ira Pastor – will test a variety of techniques that previous studies have demonstrated to possess neuroregenerative properties, and these will be combined with devices that have been shown to stimulate the central nervous system of coma patients.
Using this “combinatorial approach,” the researchers hope to move subjects from a brain dead state into a coma state, effectively bringing them back to life.
Unsurprisingly, the proposal has been met with much criticism. Last year, an article published in the journal Critical Care – penned by researchers Ariane Lewis and Arthur Caplan of the New York University Langone Medical Center in New York City – claimed that the trial has “no scientific foundation” and “borders on quackery.”
Pastor’s response to such criticism? “A hundred years ago they said the same things about cardiopulmonary resuscitation and organ transplantation – now look how far we’ve come.”
We take a closer look at the science behind Pastor and team’s project and ask, “Is it really feasible to bring someone back from the dead?”
Defined as the “irreversible loss of all functions of the brain, including the brainstem,” brain death occurs as a result of brain injury. This may occur through TBI, stroke, or the loss of blood flow or oxygen to the brain.
Share on Pinterest Brain death is defined as the complete, irreversible loss of all brain function.
Brain death is a legal definition of death once brain function ceases, the body is no longer able to perform activities that are crucial for our survival, such as breathing, regulation of heartbeat, and swallowing.
To declare a person as brain dead, a physician must confirm a complete absence of brain reflexes – such as pupillary response to light and facial muscle movement – and the inability to breathe without ventilatory support. Other tests may also be required to confirm brain death.
Brain death should not be confused with coma. While a person in a coma is unconscious, parts of their brain are still functioning, and there is a possibility that their condition may improve.
Patients who are brain dead, however, are considered to have a complete loss of brain function, and there is no way to overturn this – yet.
Pastor and team believe that their controversial trial represents the first step toward the regeneration of neurons and the restoration of neuronal functioning in humans. In essence, they believe that they could one day achieve what most people perceive to be unachievable: restoring life to the clinically dead.
The clinical trial will involve a four-step approach. The spinal cords of the brain dead subjects will be injected with stem cells, which are cells that have the ability to differentiate into other cell types, including neurons.
“The stem cells – minimally manipulated, autologous, adult stem cells derived and expanded from patient fat and/or peripheral blood – will serve as some new ‘bricks’ in the regenerative process,” Pastor explained to Medical News Today.
Subjects will also be injected with a peptide called BQ-A – derived from ooplasms, the cytoplasm of an egg, or oocyte – which Pastor told us will act as the “blue print” and “mortar” in the regenerative process.
As well as aiding neuronal growth, Pastor explained that the peptides will help to reprogram and recondition the surrounding tissue at the location where stem cells are injected, and they will also help to target and destroy components of dead tissue.
Once these steps are complete, median nerve stimulation techniques and transcranial laser therapy will be applied to each subject for 15 days, with the aim of spurring connections between the newly formed neurons.
“In short, it is our contention that there will be no ‘single magic bullet’ for success and any traditional single drug approach would be fairly futile. Hence why we are employing this type of ‘combinatorial’ approach,” Pastor told MNT.
After the procedure, each subject will be continuously monitored in the intensive care unit. In particular, the researchers will monitor the patients’ brain activity, pulse, blood pressure, respiration changes, and oxygen saturation.
“Our main hope is that this trial will show us that the ‘gray zone’ between deep coma and irreversible coma is indeed just that – ‘gray,’ and that, with the tools of 21st century regenerative medicine, that there are possibilities to push that transition in the opposite direction to save lives, as well as begin a new chapter in the treatment of the wide range of consciousness disorders – coma, persistent vegetative state, locked-in syndrome, etc.,” said Pastor.
“Secondarily,” he added, “we hope the trial will answer certain ‘deeper’ issues about the human mind.”
Individually, each of the four techniques that Pastor and team plan to use in their trial have shown promise for improving brain functioning. Research indicates that stem cell therapy and transcranial laser therapy may help to repair brain damage .
Furthermore, studies have shown that median nerve stimulation can help to awaken comatose patients , while transcranial laser therapy has been found to improve recovery from neurodegenerative disease .
But are such studies enough to suggest that, when combined, these techniques can revive patients who have been declared brain dead? Some researchers have their doubts.
“By definition, DNC [death by neurological criteria] requires irreversible cessation of all functions of the entire brain, including the brainstem. As such, the proposal that DNC could be reversible is self-contradictory,” Caplan and Lewis wrote in their article last year.
Echoing Caplan and Lewis’s comments, Dr. Dean Burnett, a neuroscientist at the Centre for Medical Education at Cardiff University in the United Kingdom, told The Telegraph, “While there have been numerous demonstrations in recent years that the human brain and nervous system may not be as fixed and irreparable as is typically assumed, the idea that brain death could be easily reversed seems very far-fetched, given our current abilities and understanding of neuroscience.”
Responding to such denunciation, Pastor told MNT that there have been numerous reports of spontaneous brain death reversal in scientific literature in recent years. He pointed us toward the case of a 10-month-old boy who, after being declared clinically brain dead, began breathing 15 hours later.
“Although controversial, hotly debated, and resulting in poor prognoses, we believe such cases highlight that things are not always black or white in this area of severe disorders of consciousness, and provide important clues for further investigation,” said Pastor.
Pastor and team are far from surprised by the criticism their project has received. “[…] being something that has never been attempted and at the very far end of the disorders of consciousness spectrum, it seems a ‘very far-fetched’ project to many – although not to all – and this is indeed true.”
“However, the ‘very far-fetched’ criticism is one we have anticipated from the neuroscience community, and frankly it has been quite fun when we sit down to explain our ideas and convert these folks to the ‘Wow. That is still far-fetched but you may be on the right path to get it done, eventually.'”
Other concerns that researchers have raised about the trial are of an ethical nature. Following on from their comments that brain death reversal has “no scientific foundation,” Lewis and Caplan wrote, “The suggestion that DNC could be reversed provides families of brain dead patients a cruel, false hope for recovery. This is especially so for families that believe in reincarnation.”
Pastor strongly refutes this claim and says that it could be argued that even approved medications are offering “false hope.”
“Why? Because we know that based on the inclusion/exclusion criteria of our registrational clinical trials – combined with the fact that, in 2017, we incorporate next to zero pharmacogenomic or, more importantly, toxicogenomic information in our study designs – that all of the ‘disease output-targeted’ drugs that eventually make it to the market will only work in a small percentage of their target population,” Pastor told MNT.
“This is a widely acknowledged, but largely unspoken truth from the pharmaceutical industry – we are not offering false hope – it is just hope.”
Another ethical concern involves the neurological state of trial subjects. The aim of the trial is to shift patients from a brain dead state into a state of minimal consciousness, or a coma. Some critics claim that reverting a patient to such a state is immoral.
“Aside from being in a sense a bit flattering, [this] translates to that we may succeed in transitioning a brain dead subject into a coma subject and, in doing so, we will have a) given the subject a poor quality of life, and b) added new costs to the healthcare system,” Pastor told MNT.
“We find this critique ludicrous – […] you can debate forever whether a dead person has a better quality of life than a coma patient – but to think that if we succeed at such a monumental scientific transition, that we would actually then stop, and not try to continue on with patients through the disorders of consciousness spectrum to an eventual state of wakefulness, is just silly,” he added.
“And in a system that spends $7 trillion annually, we think that a few coma patients would not add significantly to additional burden.”
There is no doubt that Pastor and team’s proposal is eccentric in these modern times, when we have yet to find a cure for cancer, reversing brain death seems an impossible feat.
But Pastor strongly believes that such an achievement may not be as far away as many people believe. Talking to MNT, he noted that cancer and many other diseases are often caused by “multiple biological processes that interact in complex networks.”
“Brain death – not to simplify it by any means – by comparison has only one ultimate, quite well defined end regulatory state, making it much easier for us to develop, target, or modify our methods towards a successful outcome,” he said.
“ Let’s just say we believe that this first ‘level’ of brain death […] will be solved long before cancer ever is.”
If this first phase of the Reanima Project is successful, Pastor said that the team will then attempt to restore independent breathing and heartbeat to each patient. “Yielding a subject that is no longer technically dead anymore, the next step is continue on with patients through the disorders of consciousness spectrum, to an eventual state of wakefulness,” he added.
Pastor and team hope that by this time next year, they will have conquered the first step toward making a seemingly impossible feat possible: bringing the dead back to life.