by Rebecca Gagne-Henderson PhD ACHPN APRN
This blog is written for both clinicians and interested human beings. It describes what happens physiologically if we are allowed to die naturally. A caveat is that for the healthy living individual “it ain’t pretty”, but for the dying individual, it is an incredibly beautiful and mysterious mechanism. Again, to the living watching as our loved ones are dehydrated, with their eyes sunken in, Cheyne Stokes respiration, death rattle and peculiar smells it would be logical to believe that suffering is laying before us crying for help. That belief belies what we can’t see. This blog will explain that which we cannot see.
It contains scientific jargon, but everything is also explained in a simple and understandable manner for the non-scientist. Even if you think you know what happens, you just may not, as I had to complete a rigorous literature review to understand.
The discussion surrounding the withholding and withdrawal of Artificial Nutrition and Hydration (ANH) weaves sociocultural, religious, ethical, legal and political concerns into a complex web (1-4). What a mess. Discussions tend to polarize, making reasoned debate challenging, and indulging in emotional diatribes tempting for many. Unfortunately, this debate neglects biology. We all pride ourselves on our allegiance to science, but in these cases, emotion is paramount.
What I will discuss in this blog is something that few know. I once taught this to a group of Yale primary care residents. I told them that what I was about to teach them is something that they don’t learn in medical school. After my presentation, you could have heard a pin drop…no questions, no comments…they filed out of the room, except for one resident. She approached me and said, “You are right Rebecca; they don’t teach this in medical school”. What I taught them I will share with you now and is based a great deal on a chapter I wrote several years ago (5).
I became interested in this topic during the Terry Schiavo trial (1). There was a great deal of controversy. Many people I respected were delivering “misinformation”. They were saying that the withdrawal of Artificial Nutrition and Hydration” would cause suffering and starvation. This presumption is understandable. After all, it is the most natural thing in the world for all of us—families and clinicians alike—to want to feed and hydrate a fellow human being. Food and water hold a great deal of meaning in all cultures. The meaning of food includes nurturing, love, fun, sustenance, and life itself. To withhold nutrition feels counterintuitive to the way we as humans understand caring. However, even those who are not medical professionals need to understand the sometimes-difficult reality of how our bodies die and specifically how food and water can actually cause harm at the end of life.
I became obsessed with learning what happens as we die without a feeding tube. I even bought a two-volume set describing the history and results of human starvation (6). They sit in my strange library alongside my books on euthanasia, my collection of the works of Eric Cassell (7-10), Nicholas Christakis (11) and, of course, Kevin Toolis (12, 13); my favorites. In my opinion, they are all required reading. In addition, I scoured the stacks and libraries to find as much information as I could. Much of the data is not recent. I believe this is because it is a difficult phenomenon to study after the introduction of research ethics. Much of my more recent citations are from animal studies for obvious reasons.
The Dying Process and Feeding tubes.
There has been a great deal of controversy regarding the “starvation” of patients who do not receive ANH (14, 15). The most commonly offered family and patient information is regarding “fluid overload”. That refers to a phenomenon when we provide AHN to a patient who is dying and whose renal function is failing. This causes the unprocessed fluid to go to the patients’ lungs, and into the tissues causing swelling. Sometimes this can progress to the point when fluid “weeps” through the tissues in the arms and legs causing copious drainage. In those with advanced dementia, there is a loss of the ability to absorb nutrients. This is now common knowledge amongst palliative providers (16, 17). Whilst this is true, there is a more exact, wonderful and less graphic description of the dying process when ANH is withheld. We can offer this information to family members, that not only educates but also comforts us.
One of the natural signs of impending death is the loss of the ability to swallow and eat. Prior to what is known as “actively dying”, patients with end-stage dementia, or sometimes the old and/or those with other illnesses (e.g., chronic obstructive pulmonary disease [COPD], heart disease, or cancer), become very weak and unable to eat (18, 19). This usually indicates that the person is nearing death. In such circumstances the feeding tube will not change the disease outcome and offers no meaningful contribution to comfort (20) For patients who are alert and able to participate in regular activities but have lost the ability to swallow and eat, a feeding tube may be a helpful way for them to continue to be nourished. Patients who fall into this category include those with ALS (Lou Gehrig’s disease), multiple sclerosis, and some kinds of cancer. While these diseases may eventually result in the patient’s loss of life, a feeding tube may extend the time a patient has some quality of life.
It is widely believed by families and, even now, by some doctors that these tubes can prevent pneumonia. However, this belief is false. Rather, patients with feeding tubes have no decreased risk of pneumonia and may even be at increased risk (21, 22). In addition, the tube can foster other problems such as bleeding at the tube site in the abdomen, infection at the site, oozing and leakage, diarrhea, abdominal pain, vomiting, and nausea (23).
The Physiology of Dehydration and Starvation
It is the most natural thing in the world for all of us—families and clinicians alike—to want to feed and hydrate the patient. Food and water hold a great deal of meaning in all cultures. The meaning of food includes nurturing, love, fun, sustenance, and life itself. To withhold nutrition feels counterintuitive to the way we as humans understand caring for those we love or who are in our charge. However, even those who are not medical professionals need to understand the sometimes-difficult reality of how our bodies die and specifically how food and water can actually cause harm at the end of life. With such knowledge, we can come alongside the dying so that we not only intend to care but also actually cooperate with bodily processes as much as possible to offer comfort and healing at the end of life. I once had a well-meaning physician tell me that we would starve the patient should we discontinue ANH, and rather we should decrease the rate of administration as this patient was not “tolerating” the feeding. I had to explain that this plan, with certitude, would cause the patient to starve.
Hydration – Calorie intake = Starvation – a very simple calculation.
THE PHYSIOLOGY OF STARVATION
Starvation is a long physiological course that can take up to three months to occur in the healthy individual (6, 24). For those with end-stage cancer and other terminal illnesses, starvation may already be occurring by the time ANH becomes a concern due to the natural course of the disease (25).
Now for the pedantic piece. This is written for both clinicians and lay people. Understanding starvation and its relationship to hydration help us know how to care for patients and accurately assess how our actions regarding ANH affect a dying patient. Starvation occurs in three stages.
After not consuming nutrition for a day or two, our liver begins to release stored glycogen to sustain us, as this is then readily converted to glucose (a form of nutrition). The liver has a limited supply of glycogen, lasting only a couple of days. As the stores of glycogen are depleted, a process known as gluconeogenesis concurrently begins (26). This stage occurs in the 3–5 days after the last consumption of nutrition (27). Once the liver is completely depleted of glycogen, the body continues in the post-absorptive stage by converting fat and protein to glycerol and producing ketones as a byproduct. Ketones sustain our brain and, very interestingly, also give us a sense of satiation (27).
This period occurs for up to 5–7 weeks after ceasing nutrition intake and is marked by the onset of gluconeogenesis. Gluconeogenesis is a remarkably complex process in which the kidneys and liver utilize protein and fat broken down from the muscle and organs that are catabolized to be used as energy to continue nourishing the body.
Prolonged and terminal starvation
During this period gluconeogenesis slows and the body is left to sustain itself solely on ketones. Death occurs as late as 3 months after the complete absence of nutrition (6, 25, 26).
Ketones provide the sensation of satiation. It is heartening to know that as ketones are produced, simultaneously dynorphins are produced through the breakdown of proteins. These dynorphins are a type of endogenous opiate that is 6–10 times more potent than morphine and also provides an analgesic and anesthetic action (they are known as kappa agonists) (28). An anesthetic effect is different from an analgesic effect (pain relief). Anesthesia blunts feeling and causes drowsiness and apathy. This drowsiness and apathy allow for relaxation and an indifference to what is happening (28, 29). To a healthy person, this is distressing to imagine, but it comforts an individual at the end of the long process of starvation. When we withdraw or withhold ANH from a patient, the starvation process does not cause the patient’s death unless he is already near starvation due to being in the late stages of the disease process (i.e.; Cancer with cachexia).
THE PHYSIOLOGY OF DEHYDRATION
Again, the patient who has ANH withheld or withdrawn will die not of starvation but rather usually of dehydration. Difficulties arise when well-meaning clinicians recommend ANH to the dying patient or the family but do so without a full understanding of the physiology of dehydration. The failure to appropriately recognize and diagnose the patient as dying obviously contributes to this difficulty (AH HA, a topic for a future blog).
This proves much easier in a patient’s home or in a clinic, but it is less clear and sometimes confounded in a hospital setting in which the “curative” model prevails (18). As with the accusation that we are starving a dying patient if we withdraw or withhold ANH, another common misunderstanding is that such a patient will be thirsty and experience pain during the dehydration process. This is a biologically complex process and will be simplified here for our purposes, as the intricacies of dehydration go beyond the scope of this offering. When we are no longer able to swallow and do not consume food or fluids, our kidneys continue to function and produce urine—a process that requires enough blood volume to create pressure against the kidneys to filter waste from our blood. When the kidneys continue to produce urine without fluid replacement, the blood volume decreases and thus our blood pressure decreases (30). At this point, the compensatory mechanisms of dehydration begin. With the depletion of blood volume, baroreceptors (receptors that detect when blood pressure is low) recognize the need to increase the pressure. They signal the brain to release vasopressin, a hormone that causes the blood vessels to constrict and thus works to increase our blood pressure. As vasopressin is released from the pituitary gland, endorphin is also released from the pituitary (30). Endorphins are similar to dynorphins as endogenous opiates. As our body attempts to regulate its homeostasis, these endorphins provide analgesia and euphoria; when vasopressin is released, a related hormone known as oxytocin is co-expressed from the pituitary. As dehydration progresses, our body increases the release of these three hormones. Meanwhile, the kidneys begin a process leading to the release of a stronger vasopressor known as angiotensin II (30). The additional angiotensin II causes increased release of vasopressin, endorphins and oxytocin (31). As this process continues and one’s blood pressure decreases, compensatory mechanisms begin to fail and the heart and respiratory rates increase, which increases CO2 levels (30, 32). These CO2 levels further promote release of endorphins. Inexorably, the respiratory rate slows and the heart stops, resulting in death (33, 34). Like the more commonly known depressive effect of morphine upon respiration, the release of endorphins and dynorphins correlates with the decrease in respiratory rate (33, 35). This is what I call an endorphin burst. All three of the substances—endorphins, oxytocin, and vasopressin—arise from the hypothalamus and are released from the pituitary (30).
We have already discussed the comforting actions of endorphins, but what about oxytocin? Oxytocin is sometimes referred to as the “love hormone,” or the “hug drug” and it is released in numerous situations, such as during labor and immediately following childbirth. When a woman breastfeeds, her body releases oxytocin, which provides a feeling of love and well-being to the mother, but it is also passed through the milk to the baby and promotes bonding.
Our bodies also release oxytocin at orgasm, and it is responsible for what is colloquially known in the human context as the “afterglow” (36). It can also be released when we have a good, cathartic cry (37), sometimes resulting in what we know as “crying ourselves to sleep.” And this hormone is released at the hour of our death.
An important sidebar is that dynorphins during starvation block the release of oxytocin. Starvation is not a completely uncomfortable death, but dehydration, on the other hand, has the wonderful aspect of the “hug drug”, oxytocin.
I know that was a lot, but it is such important information. It is part of wearing the armour of truth as we advocate for our patients and loved ones. I believe it will also give solace to families making difficult decisions. My next blog will be an exploration of the existential dimensions of this mechanism. Ciao for now.
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