QLI Anoxic-Hypoxic Brain Injury Webinar

In this informative webinar, Dr. Snell, QLI Director of Psychology and Neuropsychology, discusses the role of oxygen within the body, particularly within the brain, and why our brains are so sensitive to a lack of oxygen. The goal is to better understand the nature of Anoxic-Hypoxic brain injuries and to be aware of some of the things that you can anticipate and therefore be a little bit better prepared for within this type of injury.

Speakers: Tim Benak, Dr. Jeff Snell

Video Transcription

Introduction

Tim:
All right. Good morning, everyone. Welcome to another Webinar Wednesday here at QLI. I’m in studio Q by myself today. Dr. Snell bailed on me, but I guess when you’re the popular guy and you’ve been doing virtual conferences and webinars throughout the last year, you kind of build yourself a little studio in your own office over there, Jeff.

Dr. Snell:
I didn’t know what kind of a shot you were going to take at me when I wasn’t going to be with you this morning, but I’m glad to see that’s the direction that we’re going. So, okay. Yeah, we can play that game.

Tim:
On a positive note here this morning though. No, we appreciate you being here with us. We’ve got Dr. Snell, a familiar voice for probably quite a few of you on our webinars. If you’ve attended in the past, you’ve definitely probably heard one from him. And today he’s going to be going over anoxic-hypoxic brain injuries. So a requested presentation, he kind of goes a little bit deeper into a very specific diagnosis of a brain injury. You know, we cover brain injury, 101, we do CBT. We do a lot of other things, and this one goes a little bit deeper, and we know our audience appreciates that. So Dr. Snell, as always, I figure we should talk about you for a second. I know you don’t like that too much.

Dr. Snell:
Yeah, let’s keep it brief.

Tim:
But if you can give everyone just a quick little overview of your career here at QLI in about a sentence or two, and then we’ll go ahead and launch into the webinar.

Dr. Snell:
Couple of sentences. I am the director of the psychology and neuropsychology department here at QLI, and I have been at QLI coming up on 23 years. I’ve spent a career here at QLI. Lovely place to work, fantastic coworkers, very creative and dynamic clinical team. I would not want to go anywhere else.

Tim:
Absolutely. I would second all of those things. And you’re definitely an expert. When you say 23 years, you’ve been around the block. You know what you’re talking about. I know I made a shot at you, but you definitely… you are requested and you speak nationally. And so we are very lucky as an organization to have you here at our disposal to do our webinars and far more things than just that. So a little bit of housekeeping just before we launch. As always, there will be a poll question. If you’re wanting to receive a CEU certificate for attending today, please make sure that you answer that at the end of the presentation, and we want this to be conversational. So if you have questions, something pops into your brain while Dr. Snell’s talking, I will be monitoring the chat and the question and answer. And so if appropriate, I will interrupt Jeff. And if not, we’ll save things to the end.

Dr. Snell:
I’ve got the chat window open as well, Tim, so I can see it as folks type stuff in.

Tim:
All right. Sounds good.

Dr. Snell:
You’re going to have a full question at the end as well? Yes.

Tim:
Yes. Yep.

Dr. Snell:
Okay.

Tim:
And then we may also ping you throughout the conversation. We want to have a little bit of an interactive conversation through the chat, so be on the lookout for that. If I hear Dr. Snell say something interesting, I may ping the audience to talk about it a little bit. So with that, Jeff, I’ll go ahead and turn the mic over to you.

Dr. Snell:
All right. Well, if I do say anything interesting, make sure you make a note of it. So thanks, Tim. So within this presentation, we’re going to talk about the role of oxygen within the body, particularly within the brain, and why our brains are so sensitive to a lack of oxygen. To get to that, we’re going to really get into the weeds and talk about oxygen. I think we’re going to start out at an atomic level. So sub weed level. We’ll move up to a cellular level and detail the role of oxygen in sustaining life. And we’re going to move out to a broader level and talk about the vulnerabilities within the human brain to decreased or absent availability of oxygen. And we’ll talk about the various conditions that can result in an injury to the brain secondary to that lack of oxygen. From there, we’re going to move out broader still to talk about the issues that can result from this particular type of brain injury, as well as secondary conditions associated with this unique mechanism of neurological insult. So there will be aspects of this presentation that are highly technical and others that are grossly oversimplified. But my goal here is for you to better understand the nature of this particular kind of brain injury, and to be aware of some of the things that you can anticipate and therefore be a little bit better prepared for within this type of injury.

The Basics of Oxygen

Dr. Snell – [00:04:26]
Dry air contains by volume about 78% nitrogen, 21% oxygen, and then the remaining 1% is a variety of little trace gases. Nitrogen, which makes up the vast majority of our atmosphere, has no effect on our body. Our bodies don’t utilize nitrogen in any appreciable way. And the scientific explanation for that is that nitrogen has a triple covalent bond. It’s a very stable molecule. It’s reluctant to react with anything. It takes extreme conditions for nitrogen to react spontaneously. You’re talking about arcing or lightning, heat because of that atomic structure.

Oxygen, on the other hand, forms covalent bonds. Covalent is much more inclined to react, to bond or to break bonds and interact with other elements at standard conditions, those at which life exists. Now, when we talk about oxygen in our atmosphere, or O2, oxygen that we talk about is really a molecule of two oxygen atoms.

Dr. Snell:
If you look at a table of elements, oxygen is one of those elements. But oxygen that we breathe is two oxygen atoms bound together. The formal name of that is diatomic oxygen or molecular oxygen. Throughout this talk, I’m going to use the term oxygen to primarily refer to that O2 molecule rather than the atomic element. So around 21% when you inhale of what you breathe in is oxygen. So the air that you breathe in is about 21% oxygen. The air that you breathe out contains around 16% oxygen and about 5% CO2. Now that’s why you can perform rescue breathing. You can actually benefit someone by exhaling into their lungs because there’s sufficient oxygen in your exhaled breath to support life. Oxygen has the molecular capability of oxidation and electron transfer, which is crucial to using substances at a cellular level to create energy.And that’s what we are going to talk about within the cells of our brain. CO2, on the other hand, is a waste product that cells produce as they use oxygen as a catalyst for creating energy.

Dr. Snell
Our red blood cells are responsible for oxygen transport throughout the body. And all of our cells are dependent upon oxygen as an ingredient for the manufacturing of energy. As we’ll discuss and of primary importance to our topic, the brain requires an uninterrupted supply of oxygen to carry out its role in the human body. And brain tissue is exquisitely sensitive to any variation of that oxygen supply. The necessity of oxygen in any given tissue in the body is a factor of the ability of that tissue to store oxygen and then how rapidly that tissue uses oxygen. If you think of it in terms of fuel, it relates to how much fuel a given tissue can store, and then how fast it uses that fuel. As we’ll talk about shortly, brain tissue has extremely limited oxygen storage ability, and therefore it requires a constant supply of fresh oxygenated blood to function.

Dr. Snell:
Now, as an adult human, you have approximately 20 to 30 trillion red blood cells at any given time. It comprises approximately a quarter of the total human body cell count. Even more if you live at a high altitude. These cells develop in the bone marrow and they circulate for about 100 to 121 days in the body before they’re programmed to die. They break down and their components are recycled. I want to stick a little red flag on that: programmed cell death. That’s important and it’s going to come up again a couple of times later in this talk. Now when red blood cells age out, they are removed by microphages within the liver and within the spleen. There are hormones in your body that regulate the production of red blood cells on the basis of oxygen levels. Again, if you live at a higher altitude where there’s a little bit less oxygen within the atmosphere, your body produces more red blood cells so that you can carry in an adequate amount of oxygen to your cells.The primary hormone is erythropoietin and erythropoietin is made in the kidneys. So kidney damage or removal of a kidney can result in anemia due to a lack of the hormone that’s needed for red blood cell production.

How Oxygen Works in Our Body

Dr. Snell – [00:08:47]
Now oxygen is taken up in the lungs and approximately 97% is taken up via hemoglobin, which is a protein in red blood cells. The other 3% is simply dissolved within the blood plasma. Now at an atomic level, each molecule of hemoglobin contains four iron atoms. Now this is why blood has a red color because of those iron atoms. Each of the iron atoms combined with one molecule of oxygen. And because oxygen is made up of two oxygen atoms, that means that one molecule of hemoglobin with its four iron atoms can bond with a total of eight oxygen atoms. And that’s the transport system that carries oxygen throughout our body.

Dr. Snell:
Once the oxygen is taken up by the lungs in that hemoglobin, it’s distributed throughout the body to supply all of the cells within our body with the oxygen that they need to live and to function. It is released from the hemoglobin as the red blood cells squeeze through the body’s capillaries. At the same time, those iron atoms bind with carbon dioxide, and they carry that back to the lungs where the red blood cells get squeezed again and release the CO2 to diffuse into the lungs and be exhaled. The graphic that you see on the screen right now represents the circulation cycle of a single red blood cell from the lungs to the heart, then out to a given point in the body, back to the heart where it’s sent to the lungs reoxygenated and the whole cycle starts again. The circulation of a single red blood cell takes approximately 20 seconds to get from point to point within the body.

Dr. Snell:
The neuron represented here is a nervous system cell, and that neuron… Something just lost… There we go. That neuron has various aspects that I want you to pay attention to. The cell body, deep within the cell body, has mitochondria, which are the manufacturers of the energy that the cell needs as well as a myelin sheath that covers the axon where the signal is sent out to the synapse. Within our central nervous system, cells in textbooks are often represented by a single cell body like you see here, that large yellow blob in the middle, connected to other single neurons. And in fact, within the central nervous system, neurons typically connect to between 1,000 and 10,000 neighboring cells. So it’s an extremely rich interconnection. In some parts of the brain, it’s up to 200,000 neighboring cells. In the artificially colored image that you see on the screen, the numerous little bright spots that you see along the branches, the dendrites, of the central cell body that represent synapse points, these are places where other cells are interacting with this particular cell.Amazingly complex inputs for the ultimate purpose of determining whether or not this cell fires off a signal to the next cell or cells downstream.

Dr. Snell:
Cells are packed together within the outer layers of the cortex, which makes that wrinkled walnut looking surface that you typically view and think of when you talk about a representation of the human brain. All of these rich interconnections involve electrochemical impulses. The neurotransmitters are released in the presence of the activation of the synapse. That requires an action potential to be propagated from the cell body down the axon, and then it releases chemicals. That process in and of itself takes energy, and resetting the cell to its pre depolarized state also takes energy. Throughout the whole of the brain, that energy is derived in part from the presence of oxygen. Without oxygen, the energy levels needed for functioning are simply not present.

Dr. Snell:
The brain does not have the capacity to store oxygen, so it needs a very rich network of blood supply throughout. What you see on this page and the next page is a good representation of the complexity of the routes throughout which blood travels within the brain to keep the cells supplied with the oxygen that they need to function. And you have to remember that these images, these representations, really only show you the surface level and the major divisions of the arterial branches. Throughout the whole of your brain and your entire body, there’s an amazingly rich interconnection of arteries, capillaries through which that oxygen exchange occurs, and then veins to route the blood back to the heart and lungs for reoxygenation. It’s even more rich within your brain, even more delicate within your brain as well because again, the brain doesn’t have the capacity to store oxygen. Every one of the approximately 87 billion neurons contained within your brain is directly connected to this complex distribution network.

Dr. Snell:
Now, your brain uses a lot of oxygen, more than other organs. Depending on the source you look at, your brain uses on average around 20 to 25% of the total amount of oxygen in your bloodstream. And since it uses a lot of fuel that it cannot store, it has to have a continual flow to provide it. If that supply gets cut off, well, bad things happen, and they happen really quickly.

Aerobic Respiration in Cells

Dr. Snell – [00:14:20]
This graphic represents a gross oversimplification of aerobic respiration in a cell. Basically you have energy factories in every cell: mitochondria. These organelles inside of the cell utilize glucose and lipids, and they combine with oxygen to manufacture ATP. Adenosine triphosphate is the cell’s energy source.

Dr. Snell:
The cells can continue to produce energy even in the absence of oxygen, but only for a very short time and using something called anaerobic respiration. And in doing so, less energy is produced, it’s a temporary fix, and it produces toxic byproducts from that anaerobic energy production process.

Dr. Snell:
Not all the cells in your brain need as much energy and use oxygen at the same rate. As neurons fire they use energy. And they’re constantly resupplying that energy by utilizing oxygen of the mitochondria in the cell producing ATP. That energy substance that makes things happen. If a single cell or group of cells run out of ATP, then the neuron doesn’t have the energy needed to open and close ion channels. The cells can no longer fire. In other words, they can no longer send a signal.

Dr. Snell:
Now, like an engine in your car, provided the engine’s in good working condition, it needs a steady supply of fuel to keep running. Some areas in your brain are only active in firing when they are called on, a physical action, a cognitive action that causes those cells to light up, to fire. The part of our brain that activates when you do a certain task, like standing up reading a page of text, those are highly localized nodes within the brain that are only active in sending a signal when that action needs to occur. Now, interestingly enough, when you think about an action, there is an activation that a cellular level of the cells needed to plan and initiate that action. That happens at a cortical level. But at the same time, if you don’t intend on carrying out the action, there are gating nodes downstream of that action generation that prevent that from being physically carried out. So when you think about throwing a ball, there’s a part of your brain that would be necessary to make that happen that actually starts that process, but that process then gets interrupted before it gets to moving your arm if you don’t really intend to throw a ball at that moment. So our brains are really complex and interesting in how they work.

Dr. Snell:
Other areas of the brain are always working hard. In other words, like an engine, they’re always revving. Things of which you’re not consciously aware. There are things within your brain that you don’t necessarily want to have conscious control over, or have to pay attention to. Simple physiological aspects, like making your heart beat, keeping you breathing, but also regions of the brain responsible for things like memory functioning. The hippocampus, as we will talk about a little bit more, it is a structure deep within your mid-brain that is critical for getting information from your conscious attention into your short and long-term memory. It works even while you are asleep. In the motor analogy, this is an engine that’s always revving. It’s always using more fuel.

Dr. Snell:
So what happens when you have two engines sitting side by side. One of them is at idle and the other is revving. And they both have their fuel supply interrupted at the same time. Well, they’re both going to stop eventually, but the revving engine runs out of fuel first because it’s using more fuel faster. The cells that aren’t being taxed at the moment when the interruption of oxygen occurs is going to have fuel ready for action until they’re called upon. But the cells that are always working, they’re going to run out sooner. When a cell runs out of fuel, the first impact is that it doesn’t have the energy needed to regenerate from a deep polarized state and then subsequently fire and send another signal. In the absence of blood flow, the cells in your brain that are firing really only have about 10 to 15 seconds of available energy. And then they can no longer generate enough energy to send signals.

Dr. Snell:
This is one of the many ways in which Hollywood gets it wrong when it comes to the brain. The hero is getting choked out, and he manages to fight, struggle, kick for a minute, two minutes. Well, if somebody wraps their arm around your neck and shuts off your oxygen supply to your brain, you’ve got about 10 to 15 seconds of consciousness. Now that doesn’t make for a very durable hero, but it is a much more realistic depiction of what happens when you lose oxygen to the brain. If the cells cannot send a signal, then you are going to lose the function of those cells and some of those cells are involved in maintaining our consciousness. So that shuts down pretty early.

Dr. Snell:
In an airplane when they tell you if the masks drop down, put your mask on first before you help somebody else. That’s because they’re telling you’ve got about 10 or 15 seconds to do something in that situation when you’re at high altitude. Because in 10 or 15 seconds, you’re going to lose consciousness and no longer be able to be a help. Any energy generation that occurs after that lack of oxygen, that interruption occurs, again, starts to build up toxic byproducts. If blood flow is not restored within about four to six minutes, active cells begin a process that will ultimately result in cellular death and decomposition if not interrupted by restoration of energy stores. That’s the programmed cell death that I mentioned earlier and I will mention again.

Mechanisms of Injury

Dr. Snell – [00:20:19]
From the standpoint of damage that occurs to the brain in the absence of oxygen, there are some primary classifications or types of insults each of which have the potential to globally affect brain tissue. Now there are overlaps here with the damage that occurs as a result of stroke, but a stroke is a very localized loss of blood flow and the resulting damage to the cells secondary to that loss of oxygen. Now, with a stroke, it can be anywhere from a pinpoint tiny artery that you don’t even notice to a major blood supply that involves close to a quarter of the brain’s volume. Either can be impacted by that loss of blood flow. We call the area compromised by that loss of oxygen and infarction. That is an area which is compromised secondary to a loss of oxygen because of a blockage or leak of blood flow. Now there are also overlaps with traumatic brain injury, particularly severe traumatic brain injury.

Dr. Snell:
During the acute phase of TBI, for example, the metabolic demands of the brain increase, but oxygen delivery to the brain decreases due to reductions in cerebral blood flow, as well as even barriers to oxygen diffusion caused by edema swelling within the endothelial level of the capillaries, which blocks blood flow. It’s further worsened by a neuroinflammatory response to the trauma itself and can result in capillary collapse and increased intercranial pressures. So immediately after a TBI, a time when the brain needs more oxygen, it’s typically getting less, causing further damage.

Dr. Snell:
Now, when I mention stroke, that localized loss of a blood flow, the tissue that is impacted is supplied by a specific artery that is blocked or broken. The mechanisms of injury in the case of anoxic or hypoxic injury represents a global threat to the brain. The brain as a whole is exposed to decreased levels of oxygenation. And the severity of the effects reflect the amount of tissue exposed to the loss and the amount of time that the cells go without this needed oxygen supply.

Causes of Injury

Stagnant Anoxia

Dr. Snell – [00:22:30]
Stagnant anoxia, also called ischemic anoxia, or another term is hypoxic ischemic injury. This involves an interruption of the blood flow through the tissues that allow for exchange of oxygen. So according to a 1989 study, at that time anesthesia accidents and cardiovascular disease each accounted for just under one third of all cardiac arrests. In other words, many individuals sustained anoxia secondary to surgical complications as did secondary to cardiac events associated with disease processes. Other causes of cardiac arrest can also be associated with asphyxia, most often due to suicide attempts or by near dry drowning incidents or even choking. So if we break it down by percentages, cardio disease accounts for of the different types of stagnant anoxia about 30%. Anesthesia accidents also close to 30%. Asphyxia is around 16%. Chest trauma, so crush injuries or penetrating injuries to the chest that interfere with respiration, around 10%. And electrocution, which also interrupts cardiac functioning, around 6.5%.

Respiratory Suppression/Arrest

Dr. Snell:
Now there are a couple of others here to make up the remaining 6% that are more respiratory suppression issues, one being barbiturate poisoning, opiates most commonly nowadays, and severe bronchial asthma incidents. They don’t necessarily interrupt oxygen exchange in the lungs, and they don’t exactly fit into the stagnant category, but they also don’t fit as well into other categories.So we go ahead and lump them in here.

Dr. Snell:
Respiratory depression means that a person’s rate and depth of breathing are lower than normal, interrupted by something blocking or usually a secondary process that refers to the secession of breathing or suppression. This results in low oxygen levels and high carbon dioxide levels within the blood. The severity of potential damage is dependent upon the degree of suppression, or in the case of an arrest, the amount of time of the interruption of breathing. Now, just suppression typically doesn’t result in brain changes, except in more severe cases or the cumulative effect of repeated interruptions or suppression. The long standing case such as might be encountered in sleep apnea, those repeated hypoxic episodes can actually have a cumulative effect. In doing evaluations, for example, for individuals who have memory difficulties, oftentimes you’re looking for signs and symptoms of dementia, but you also have to rule out physiological issues like sleep apnea that can potentially cause memory suppression simply as a repeated cumulative effect of those apneic episodes.Even relatively mild suppressions of oxygen in the blood, which might be encountered in cases of sleep apnea, you can have that memory loss and decreased attention. So these repeated instances are things that you need to rule out when someone comes in for an evaluation saying, “I’ve got problems with my memory.”

Anoxic Anoxia

Dr. Snell:
Now another type of mechanism of injury is an anoxic anoxia or hypoxic hypoxia. And one aspect that many people have been exposed to at one time or another with this is high altitude environments to which you are unacclimatized. Going up into the mountains when your body is not used to such an elevation and the reduced oxygen available at high altitudes can result in hypoxic alterations to both physiological and psychological functioning within a relatively short period of time. Immediately upon ascent to a high altitude there’s a reduction in blood oxygenation, which in turn reduces the amount of oxygen available to the brain and to the body. And it’s even more pronounced if you engage in activity at high altitude because that increases the oxygen demands within your body.

Dr. Snell:
Now I had an experience that I still remember as a kid when we, my family, went to Colorado and went up the Cog Railway and went up the top of Pikes Peak. Now in Louisiana, the highest point in Louisiana is about 535 feet. It’s called Driskill Mountain, even though you wouldn’t really call a 535 foot elevation a mountain. But that’s as high as you can get in Louisiana. When we went up to top of Pikes Peak, which is just over 14,000 feet, there is a greatly reduced amount of oxygen at that altitude. Now we went there and, of course, had really never seen much in the way of snow. There’s a lot of snow on top of Pikes Peak. We go outside, we play in the snow, we throw snowballs at each other. My dad’s running around having a blast. And inside about 10 minutes, he’s back inside the visitor area sitting down and then eventually laying down because he was feeling dizzy and nauseous. And it was basically a situation of oxygen deprivation. So the combination of reduced oxygen at that level combined with the amount of physical activity that we engaged in means that his brain was not getting the amount of oxygen that it needed for just the normal demands of maintaining being able to engage in such activity.

Tim:
Just fantastic family memories there, right?

Dr. Snell:
Oh yeah, absolutely. We never stopped giving him crap about that either because the rest of us apparently went through that without any problems whatsoever.

Tim:
I was about to say, does age have a factor in that, Jeff?

Dr. Snell:
That I don’t know. I think the more… the degree to which your body is acclimatized probably has a bigger issue with that. And if you are older, certainly if you have spent your entire life as he had at that point at lower elevations, then that would be a bigger issue. Yes.

Tim:
Somebody said there’s a new visitor center, it’s opening up this summer, and how hydrated you are really affects how the oxygen impacts you up there.

Dr. Snell:
Yep. And from that standpoint, the hydration is basically the fluid within your body that carries the blood, carries the red blood cell, so your blood plasma. If the hydration level of your blood plasma, if it becomes more concentrated, is thicker, than you don’t get as much circulation efficiency. And so that’s the direct relationship between hydration and being able to deal with the lowered oxygen level. You know, within pilot training, they refer to this condition as oxygen starvation, and you have to with pilots, particularly those in the military, they have to be trained to recognize the initial symptoms associated with that. Glider pilots sometimes encounter this as well. If they get picked up by a thermal and taken into a higher altitude, that oxygen starvation can cause the brain as well as other vital organs to become impaired.

Dr. Snell:
One particularly noteworthy attribute associated with hypoxia is the fact that some of the initial symptoms involve kind of a euphoria, kind of a carefree feeling, which is really dangerous if you don’t recognize that that is a symptom of reduced oxygen availability. With that increased oxygen starvation, your extremities become less responsive, your movements become less coordinated, you demonstrate poor judgment, decreased reaction time. All things that if you are operating something as complex as a fighter jet, you need to recognize and be able to react to. So as hypoxia worsens, your field of vision begins to narrow. It’s kind of a graying out. You start to lose peripheral vision. So you have to recognize these signs and symptoms and be able to react to them appropriately. So again, at high altitude the air itself just doesn’t have the amount of oxygen that you need.

Dr. Snell:
Question popped up there. “How does this affect a healthy body like NBA players’ playing in Denver time for the body to adjust?” You know, oftentimes there is some degree if, for example, professional basketball players are playing across the country, they’re going to be exposed to multiple different environments, including those at high altitude where there is that decreased amount of oxygen available. So that acclimatization actually occurs to some degree the more that you’re exposed to it. So if an NBA player had absolutely never been at higher altitude and then went to Denver, they would probably spend a lot of time on the bench sucking oxygen because their body simply would not be able to meet those needs. But most individuals playing at that level play in various levels across the country, and they do develop a little bit more of acclimatization to those altitudes. They are at a disadvantage if that is not the major area in which they play.

Dr. Snell:
It’s also why I think a lot of the Olympic training center. That area is in Colorado so that wherever somebody goes in the world they’ve already got that advantage. If you acclimatized to a higher level, your body actually becomes much more efficient at utilizing the oxygen that’s available so that when you then compete at a lower level, closer to sea level, your body is going to be hyper efficient when it comes to the amount of oxygen that your body can carry. So some of those training centers are specifically located at high altitude because of that. Thank you for that question, Ellie.

Histotoxic Anoxia

Dr. Snell:
Another type of injury involves histotoxic anoxia. In other words, oxygen is available in the environment and it is getting to your brain, but the oxygen can’t be metabolized within the tissue. So in other words, something is interrupting that. Cyanide, for example, makes it so the cells of an organism are unable to use oxygen through inhibition of a particularly cytochrome oxidase that is necessary for that oxygen transfer. One that is probably more common is carbon monoxide, a single molecule of carbon bonded to an oxygen atom. When present in the lungs, it binds preferentially with the hemoglobin. In other words, the hemoglobin is much more attractive to that particular molecule and it effectively takes up those iron binding points. It blocks oxygen molecules from being able to attach to the red blood cell. Now, carbon monoxide poisoning. Often we think of this as, for example, a suicide attempt by running a car in an enclosed garage, but carbon monoxide poisoning is the leading cause of accidental poisoning deaths in America. Actually, there are around 430 deaths and 50,000 ER visits associated with accidental CO2 poisoning in America every year. Household furnaces that aren’t adequately ventilated, gas heater systems, hot water heaters, these are things that if their exhaust system is leaking, you can then get carbon monoxide being released into that environment. That risk increases in colder months and in colder climates.

Dr. Snell:
Now, again, we are much more less likely to have the doors and windows open airing out the house when it’s single digits outside. So we stay buttoned up, and if we’ve got a leaky furnace exhaust, then that becomes a problem. The rate of injury and death in the recent severe cold experience in Texas, for example, resulted from several such issues where people were trying to stay warm in a case where their electricity was interrupted, and in doing so, there were several cases of both death, as well as a number of cases of injury associated with accidental poisoning from carbon monoxide. Symptoms from carbon monoxide poisoning include headaches, nausea, and fatigue. Those symptoms are often mistaken for flu. They’re very similar to flu-like symptoms. That’s why there have been a lot of public service announcements over the years encouraging people to be aware of the risk and to have carbon monoxide detectors in their homes.

Dr. Snell:
Technology has also created new risks associated with carbon monoxide poisoning. A lot of people now have keyless vehicles. So in other words, you just have to have the key in your pocket for the car to start and run, or you can auto start your car just by pushing a button and warm it up. Now, there are numerous documented instances in which somebody with a vehicle where you only have to have the key in your pocket forgets to physically shut the car off after coming home from a shopping trip. They leave the car running and they shut the garage door and walk in the house. Or somebody who uses a remote starter thinking that the car is parked outside the garage when actually it’s inside. So before that technology existed, those were not risks that existed, but they are things that now can and have occurred.

Anemic Anoxia

Dr. Snell:
In anemic anoxia, the blood can’t carry sufficient oxygen to the brain because of the blood itself, and this can be from a variety of different factors. The first one is just a loss of blood. If you don’t have the normal amount of blood in your body, stab wound affecting a major artery, for example, then that causes a decreased amount of oxygen being available because of the lack of red blood cells, the lack of blood. Anemia can also be a secondary process from a lack of red blood cell production. Remember I talked about hormone issues secondary to kidney damage. If you don’t have enough red blood cells within your circulatory system, that can cause something that would be diagnosed as anemia and affect your functioning. Something like sickle cell anemia. This is an inherited red blood cell disorder where the shape of the red blood cells impact their ability to flow efficiently through the smallest blood vessels in the circulatory system. That can result in reduced oxygen transport because of a reduced or blocked red blood cells. There are various lung diseases that interfere with the lung’s ability to oxygenate the blood. And so if that oxygen exchange is interfered with, again, you have the consequences of reduced availability of oxygen in a system that requires a constant supply.

Mechanisms of Injury/Symptoms

Dr. Snell – [00:37:50]
Okay. Here’s one of those really complicated things that I wanted to toss up, but I put it up there just to talk about not the whole life and energy cycle of a human cell, but the kind of about the seven o’clock position within that diagram, something called apoptosis. That apoptosis is the process of programmed cell death. It’s different than necrosis, which is a cellular death secondary to infections or toxins or trauma. But apoptosis occurs in a natural and orderly fashion. It’s the process of disposal of cellular debris handled effectively so that no harm is done. And it’s essential.

Dr. Snell:
In fact, this process continues on a daily basis. An adult human loses about 50 to 70 billion cells per day secondary to apoptosis. In a year that amounts to a proliferation and destruction of a mass of cells that is roughly equivalent to between 75 to 100% of your body weight. So this is the process by which cells are replaced. They die off and are replaced. It maintains a homeostasis. It replaces what goes away and it replenishes our body. When it occurs in a large and disorderly fashion, the breakdown of cells becomes toxic to the cells around them. This is a process called necrosis. If a neuron cell function shuts down relatively quickly, that four to six minutes that I talked about earlier at room temperature, then you can have necrosis, particularly if you have a large amount of those cells that are affected.

Dr. Snell:
Reperfusion injury can also occur when a blood supply returns to tissue after a period of ischemia. Remember I said earlier that you build up those toxic byproducts in anaerobic respiration and that those toxic byproducts, when blood flow is restored, can cause inflammation and oxidative damage throughout the induction of oxidative stress. Leukocytes, they’re sent to the affected area. They can build up in the capillaries and obstruct them. The chemical process associated with ATP metabolism creates highly reactive radicals, and they can react with the returning oxygen by forming very aggressive and damaging compounds that then in turn damage cell membranes, they damage proteins, and cause further damage systemically. This is like throwing gas on a fire. So even that restoration in a relatively short span of time can cause as many problems as it otherwise tries to avoid.

Dr. Snell:
The signaling for cell death can be a direct consequence from a neurological insult, or it can be a secondary process associated with all the factors that we’ve talked about above. There are areas within the brain that demonstrate a heightened reactivity to the loss of oxygen. The process of cellular death releases glutamate and free radicals, which are cytotoxic. And it further exacerbates the neurological insult. That secondary phase of death can occur hours or even days later. So there’s a slower wave of damage, a cascade of damage that can occur to the support cells, as well as the neurons around an area secondary to that diffuse hemispheric diffuse hemispheric demyelinisation. This delayed wave of damage is typically not manifested, because it’s associated with secondary cells, until several days or even weeks after the initial neurological insult. So when somebody has a severe anoxic injury, they go to the hospital and then they look pretty good immediately after they get back home. You can have a second wave of damage that then represents all of that demyelinisation within the internal pathways that transmit signals throughout the brain, which results functionally in a radical decline in a person’s ability after their injury.

Symptoms Associated with ABI

Dr. Snell – [00:41:52]
So with anoxia, you have multiple different levels of injury that are affected. Though that’s why we call this a cascade of symptoms. It’s kind of like once the first domino gets kicked over this cascade occurs, and in some cases is very difficult to interrupt. The process and progression of symptoms with the global effects of anoxia, it has a rapid onset and rapid, severe consequences. Like I said, if neurons within your brain are completely deprived of oxygen for four to six minutes, they will begin to die. And large areas of the brain can then result in something that is incompatible with life, or it can radically interfere with the brain’s function. One of the more severe initial presentations is that of a coma followed by an unresponsive wakefulness syndrome.

Dr. Snell:
This particular term unresponsive wakefulness syndrome has begun to replace what is considered a more pejorative term, which used to be within the medical community, persistent vegetative state. That unresponsive wakefulness syndrome describes a progression beyond coma, but a state in which there’s wakefulness, but an apparent loss of awareness, typically reflected by ambiguous or absent signs of consciousness or command following in a bedside examination. It’s also defined by severely altered consciousness. That minimally conscious state is another level of altered consciousness, but with minimal to definite behavioral evidence of either self-awareness or environmental awareness. It can be objectively demonstrated at bedside evaluation. May not be consistent, but there are times in which definite evidence of awareness are present.

Dr. Snell:
In addition to that initial neurological insult, I talked a minute ago about that secondary wave. The medical term for that is delayed post-hypoxic leukoencephalopathy. It’s a demyelinating syndrome characterized by acute onset of neuropsychiatric symptoms days to weeks following an apparent recovery from coma after prolonged cerebral hypo-oxygenation. It’s diagnosed after excluding other potential causes of delirium. But with a clinical history of, for example, carbon monoxide poisoning, narcotic overdose, myocardial infarction, or any other kind of global cerebral event, this can occur. This diagnosis can be supported by neuroimaging that shows diffuse hemispheric demyelinisation, typically sparing cerebellar and brain stem tracks.

Dr. Snell:
It can also be detected by elevated cerebral spinal fluid myelin basic proteins. Basically the lack of oxygen impacts the support cells, and then that impact is manifested more slowly over time.

Recovery after anoxic or hypoxic brain injury, like other aspects of brain injury, results in changes to an individual’s functional abilities that can either be transitory or long lasting in nature.

Prognosis and Treatment

Dr. Snell – [00:45:00]
The amount of brain tissue that’s injured and the mechanism by which that injury occurs, that makes prognosis difficult after an injury. Like all brain injury, the effects can be mild, even transient in nature. They can be moderate or they can be more severe. So for example, somebody choking on a hot dog. They have oxygen deprived to their body. They’re reacting to that physically. If you do the Heimlich maneuver and you clear that choking hazard, it’s a transient issue. It’s resolved with no injury. And without intervention, that can lead to a cascade of events that can cause injury or even death in relatively short order.

Dr. Snell:
If on the other hand, the anoxic insult is secondary to an overdose. Detoxification using medications that work against that particular compound is going to be helpful. So with the effects of opioids, for example, you have probably seen at some point someone be administered Narcan, the commercial name for naloxone. That compound binds with the opiate receptors without activating them. And it is dramatic. You can see someone that is in a completely unresponsive state from an opioid overdose administered Narcan, and within a matter of minutes that individual is pretty much back to baseline. They are walking, talking, and able to interact. That is a phenomenal and fast change as a result of that particular compound. Resuscitation efforts are an immediate response as well. Optimizing blood pressure, maintaining systemic perfusion. These are all critical components for emergent treatment. Clinical management is then focused on supportive care, treatment of the underlying cause of the hypoxia if it can be treated, and prevention to the degree that you can for any ongoing brain injury.

Dr. Snell:
Okay. Question there. “What is the long term impact of the use of Narcan to bring someone back?” Because it is such a short acting compound, I am not aware of any long-term negative effects of utilizing Narcan to basically knock somebody out of an overdose state. But if you know of something that I don’t, I would love for you to pitch that in and I’ll reflect it out to the entire group.

Dr. Snell:
Severe anoxic injury can result in death. It can result in persistent coma only to an unresponsive wakefulness syndrome. In that case expected recovery might be minimal if a person maintains that status for an extended period of time. In an unresponsive wakefulness syndrome, a person is awake but unaware. They have sleep-wake  cycles and their eyes can be open for prolonged periods, but there’s no evidence of consciousness on a physical examination. It’s considered persistent or permanent at about three months post injury for an anoxic injury. When it comes to traumatic brain injury, however, that’s not considered a persistent or permanent state until around 12 months post injury. Meaningful recovery after such a time is relatively rare.

Dr. Snell:
On the other hand, minimally conscious state involves a severely altered consciousness in which minimal but definitely sustained or reproducible behavioral evidence is present. This can be a stage of recovery again, or it can also be a more permanent state. Our brain cells are so exquisitely sensitive to a lack of oxygen, and permanent cellular loss of an area of the brain certainly reduces the chances of functional recovery of the ability supported by that region of the brain. In other words, if the nodes associated with certain aspects of functioning are that severely compromised, the chances of getting that particular function back can take years, months, or it may never fully resolve. Protection of brain tissue has involved things like cooling the brain via the bloodstream, administering steroids to reduce brain swelling and inflammation, barbiturates to reduce brain activity and thus reduce the metabolic or catalytic demand for oxygen within the tissues, or proactively treating things like seizure risk.

Dr. Snell:
And then the process of rehabilitation involves all of the speech therapy, PTOT, all the different things that are needed for the specific symptoms with which that particular patient presents. As we talked about, some symptoms are more common with individuals who’ve sustained such an injury, and you can anticipate that those therapeutic needs are more likely to exist.

Dr. Snell:
Various acute treatments might be involved after an anoxic insult. So we’ve talked about how the brain uses energy and how that runs out when the fuel is not there. An induced coma or significantly lowering the brain’s temperature, both of these things are aimed at reducing the cerebral metabolic rate, dialing down the energy demand, and therefore preserving more tissue that would otherwise progress into that cascade of chemical events that results in cellular death. Therapeutic hypothermia is one way to try and attenuate that cascade by lowering  the body temperature.

Dr. Snell:
Another is hyperbaric oxygen treatment. In a randomized controlled study, many studies actually, they’ve shown that this can be highly effective in the first two weeks post injury. Now again, past that phase, results have been much less consistent. So in the chronic phase there is not as much evidence for consistent efficacy of hyperbaric oxygen treatment. And there are potential adverse risks that you have to consider. I’ve spoken with folks who said, “No, this is a miracle. This worked for me.” Other folks who have done this, and it did not substantially change. But in the acute phase it is shown to be an effective means. The value of these approaches though have been questioned in meta-analytic studies, probably because, again, brain injury is not a homogeneous diagnosis. It covers a lot of ground because it’s not a unitary construct. Studies that look at that as a diagnosis tend to be pretty wide.

Common Deficits

Cognitive Deficits

Dr. Snell – [00:51:30]
I’m going to jump through a couple of things here, just major things, symptoms that are common. One being memory. Disruption of memory function is extremely common with significant anoxic/hypoxic events, including, as I mentioned before, the cumulative effect of repeated hypoxic events. With memory deficits and anoxia, the disruption tends to be for new information. We’re talking about memory, but not lifelong memory. Long-term memories of self or personal experience, those tend to be intact and readily available. But if there’s compromise of memory, it’s almost always frontal organizational aspect for somebody that has those more longer term in memories that are being impacted. It’s not really a true loss of information, and it tends to improve over time with subsequent recall of that past or learned information. So what you’ve learned throughout your life, your life you’ve lived, who you’re married to, all those kind of things. That information typically does not cause problem. That information tends to recover. I’m talking about memory though in terms of acquisition, storage, and retrieval of new information. So in a neuropsychological assessment I read you a list of words and I ask you to read it back to me. I ask you to recall it later. I ask you to recognize that information from a list. All of these are different aspects of memory that we want to look at what stage of memory is being interrupted.

Physical Deficits

Dr. Snell:
The next slide has to do with common deficits associated with physical functioning, and that primary symptom would be ataxia, a discoordination. Jerky motions, uncoordinated fine motor, or even gross motor. The movement disorders associated with anoxia appear to be very cerebellar in presentation, although it’s not clear to the degree to which this reflects actual cerebellar damage or disruption. It is likely more within the internal capsule, those pathways and tracks within the center of the brain, the white matter pathways that send information back and forth. Those myelinated pathways, again, can be damaged or interrupted by that secondary process that I talked about earlier, and as a result have these motor difficulties. These include spasticity, rigidity, spasms. Quadriparesis is usually present, so a weakness in all of the limbs. Since anoxic/hypoxic injury is global in nature, that disruption tends to be present throughout. It can also affect other aspects of functioning that require fine neuromuscular coordination control like speech, like vision. With regard to vision, even if all the components of vision are intact, a discoordination of the muscles that control the eyes can interfere with visual perception.

Psychological

Dr. Snell:
From a psychological aspect, depression is very common following almost any type of brain injury, but same for anoxic injury. This can be secondary to changes in the balance or the production or the utilization of neurotransmitters, disruption of nodes within the brain that are associated with management of our mood and emotions, and then of course, life adjustment issues associated with awareness for those individuals who demonstrate that level of awareness of their own deficits following a severe injury. Personality changes usually reflect frontal executive dysfunction. So a loss of emotional or behavioral regulation. And with severe enough injury, you can get symptoms that appear psychotic in nature. But these are related to neurological changes in the brain, loss of the neural nodes associated with vision, perception, or conscious processing of information. There’s lots of overlap here as well with medications that individuals might be on after a significant medical injury. So you have to be cautious and rule out medication side effects before you jump into treating psychotic symptoms that could be present after an injury.

Prevention

Dr. Snell:
Now, because this is an unplanned and unintended injury, prevention tends to be broad and aimed at education of those primary risks to which all of us are exposed to minimize the likelihood of being injured in the first place. So again, chew your food slowly, cut your food up, learn CPR, learn the Heimlich maneuver, be able to be able to be of assistance if someone else is experiencing that. Have carbon monoxide detectors in your home so that you can be aware of those increased levels before they get to the level of actually causing you damage. And when it comes to opiates, again, you get respiratory suppression at higher levels or also  interactions with alcohol. So being aware of the potential interactions, there are a lot of medications that your doctor might give you, then they tell you do not drink while you’re taking this medication. The reason being of that interaction effect, a heightened effect of that particular drug, which can cause respiratory suppression. Alcohol in and of itself in sufficient quantity can also cause respiratory suppression, so that is heightened by certain things as well. And then also just maintaining a general healthy lifestyle, engaging in cardiovascular exercise, monitoring your health. Those are things that you should do on a regular basis to maintain your health in the first place.

Dr. Snell:
References are within here as well. And here is my contact information, my direct office number, and my email. And I welcome any questions that you have. I did see one here. “Is it possible to reoxygenate too quickly? And if so, what problems are associated with this?” The one risk associated with reoxygenation, again, it can have to do with some aspects… Well, reoxygenation, one is going to redistribute all those free radicals that have occurred as a result of anaerobic respiration. The alternative, however, is to allow those cells to die. So there are some issues that are associated with reoxygenation. Basically though, if you are suffering from a lack of oxygen, you want to get as much oxygen into the bloodstream as you can. That’s why, again, that reoxygenation associated with hyperbaric oxygen treatment in the acute phase can be helpful because all the other things that are working against getting oxygen to the brain, swelling,  that cerebral vascular swelling, endothelial swelling in the capillaries, you want to get as much oxygen in as you can so that you can then restore function, and then try and chemically, to the degree you can, treat some of the issues that are associated with all of the inflammation that is then secondary to those free radicals getting loose within the brain.

Conclusion

Tim – [00:58:57]
And then real quick, Jeff. I just want to–

Dr. Snell:
Oh yeah, sorry.

Tim:
No, you’re good. I did launch the poll question. So if you’re looking to receive your CEU certificate following this presentation, please make sure you do answer that. If you don’t see that on your screen right now, it may be an issue with a popup blocker or something that you have going on on your end. So reach out to us at qliwebinars@qliomaha.com if you cannot see that, and we’ll make sure to get you marked down to make sure that you do receive the evaluation to fill out. And then once you fill out that evaluation, you’ll receive your certificate.  I do want to before people peel off, I know it’s 9:59 here, if you ever… If you have anyone, any patients or any claims that you have questions on, Jeff did put his contact information there. Or if you want to learn more about QLI, you can reach out directly to me at tim.benak@qliomaha.com, or just use the qliwebinars@qliomaha.com and I will get in contact with you. Jeff, we did have a few questions here. I want to make sure we get to those. We have some time here with Jeff. If you do have questions, please put those in. And if we don’t get to them live, I will make sure that they get over to Jeff post webinar, so.

Dr. Snell:
I think we hit the majority of them.

Tim:
We did. We had one that came in early.

Dr. Snell:
Oh, okay.

Tim:
From Shelly. “Is there a significant incidence of tramadol overdose? Is it prescribed so frequently… It is prescribed so frequently we tend to think of it as a safe drug.” I think this was talking about… I don’t remember what part of the presentation. But have you seen any tramadol overdose?

Dr. Snell:
Yeah. Slightly different mechanism than the opiate overdoses, but yes. Anything that has the potential at higher levels to result in respiratory suppression, anything that would be abused in that way certainly has the potential for that. I don’t know any statistics quite frankly on specific drug overdoses. Opiates in general certainly gets a lot of attention these days and continues to be a major issue. But as far as tramadol goes as a specific drug, I don’t have any off the cuff information on that.

Tim:
Okay. We had a few other ones. Let’s see here. A question about the poll. Yes, there was just one question, so if you received that and answered it, you are good. Jeff, we also had like 355 people on today, which it’s not quite a record for you, but you still tend to be setting the… I think you’re maybe in first, second, third, fourth, and fifth for the highest attended webinars that we’ve hosted, so.

Dr. Snell:
Well, I guess that means I still get free coffee, right?

Tim:
Yeah. Ah… maybe. Yeah, I think so. I’ll talk to Pat.

Dr. Snell:
Only if I make it myself.

Tim:
Yeah. That’s right. Yeah. People asking you about an email to contact us at. qliwebinars@qliomaha.com. It’s the one that you should receive your invites to the webinars from, so. And then next month be on the lookout for that invite. We will have our PM&R doc, Dr. Jim Colt talking about spasticity. So he’s going to be in studio Q for the first time with us for a QLI Webinar Wednesday, so we’re excited about that.

Dr. Snell:
We have a couple of questions on how folks can obtain credit for this course.

Tim:
Yep, so–

Dr. Snell:
Can you say that again?

Tim:
Yep, I will. There was a poll question. And if you were not able to answer that, reach out to us. We do offer CCMC credit for these. So reach out to at qliwebinars@qliomaha.com. If you did answer the poll question, you will automatically receive a follow up email that’ll contain an evaluation, make sure you fill out that evaluation and then it’s through Jotform. Jotform will automatically send you a copy of the slides as well as your certificate will be attached to that PDF, so.

Dr. Snell:
Thank you for all the kind words. And I guess at this point we will wrap it up.

Tim:
Yep, exactly. Again, we appreciate you being here and we look forward to having you join next month’s presentation. If you have any questions, want to learn more about QLI, just want to give some kudos to Jeff. Reach out to him. His contact information is there. He loves when people, just send him nice messages. Right, Jeff? No. He won’t comment on that. He doesn’t like that. Everyone have a fantastic day. Happy St. Patrick’s Day. Be safe out there. And we look forward to having another one, have you joining us next month. Take care.

Categories: Brain Injury, Uncategorized