NoBlood

The Art of Maximizing Limited Resources

In the worst crisis, there is a need to manage a patient who has lost a large amount of blood. It may reach a point where the hemoglobin count has dropped to levels below 3 g/dl or more. The bleeding has been stopped and every effort is being put forth to increase the red cell production. But, there are signs that oxygen delivery is not sufficient. What can be done at this point?

Dynamics of Cellular Oxygen Utilization

Oxygen is a key component for the production of energy in the body. It operates as part of the aerobic metabolism. This form of energy production is similar to that of a fire. Wood may provide the combustible material, which is combined with oxygen to produce carbon dioxide (CO2), heat, and water. The body uses a similar process though without the heat. The main transport agent of this cold energy production is ATP. ATP, or Adenosine Triphosphate is an adenosine-derived nucleotide, C10H16N5O13P3, that supplies large amounts of energy to cells for various biochemical processes, including muscle contraction and sugar metabolism, through its hydrolysis to ADP. Without the activity of ATP and ADP in the cell’s mitochondria it would die.

Hemoglobin is the primary carrier of oxygen in the bloodstream with a small amount being carried by the watery part of blood, the plasma. The circulatory system has a reserve capacity to carry oxygen. This is easy to understand when you realize that an office worker and a professional athlete have the same average hemoglobin concentration in the blood stream. But how can a marathoner run 26 miles and an office worker becomes winded after one flight of stairs?

There are several processes by which the body increases its delivery potential of oxygen. The first involves the hemoglobin itself. Hemoglobin has a natural affinity for oxygen. In essence, it grabs onto oxygen tightly and it does not want to let it go. To make it easier for oxygen to be released from hemoglobin the red blood cell produces an enzyme known as 2,3 DPG, or diphosphoglycerate. Without this enzyme hemoglobin would not release its oxygen. This is the condition that occurs when blood is transfused that is 24 hours old, the standard transfused. Such blood carries oxygen, but it does not release it to the cells and can even scavange it from the few cells that are releasing their oxygen to cells. One can get a false sense of security because of a better hemoglobin concentration and a pink skin tone, but for up to 24 hours, it is not improving cellular oxygenation. In extreme or long term anemia the 2,3 DPG levels increase to much higher levels. This has allowed some individuals to live normal lives with hemoglobins as low as 5 g/dl, much lower than normal. However, this increase in 2,3 DPG takes time and there is no way at present to increase it medically.

The oxyhemoglobin dissociation curve is a graphical method to display how hemoglobin responds to its environment in relationship to its transport potential for oxygen. Some forces may shift it to the left like an increase in pH or a decrease in temperature and 2,3-DPG, which makes hemoglobin have a greater affinity to oxygen. Other agents, such as a decrease in pH or an increase in temperature and 2,3-DPG concentration may cause a shift to the right of this curve. Thus, these agents can be considered variables that to some degree can be manipulated during therapy of extreme anemia.

The last aspect of increasing oxygen delivery is related to the compensatory mechanisms of the heart. Oxygen delivery to the body is a function of how much the heart can pump per minute. At rest, the heart beats slower and not as deep as in heavy exercise. These two main functions, heart rate and stroke volume, are important determinants of oxygen delivery. As a patient’s hemoglobin decreases the heart begins to compensate by beating faster and harder, thereby sending the remaining hemoglobin around the body more efficiently.

With this basic understanding of oxygen mechanics in the body it is easier to comprehend how to augment oxygen delivery and consumption in the body. Such understanding may help in a crisis situation.

Life Without Oxygen

There are two main pathways to energy production in the body. We have discussed thoroughly the aerobic metabolism. Aerobic means with oxygen. However, there is an anaerobic metabolism that supports life for very short periods of time. Anaerobic means without oxygen. How can this be so?

In the initial phase of the metabolism of glucose there is a release of energy without the presence of oxygen. However, as a waste product this reaction produces lactic acid. As the process of anaerobic metabolism continues, the concentration of lactic acid continues to increase until it becomes impossible for the cell to function. Therefore, this anaerobic metabolism cannot be expected to provide a long-term solution for oxygen management, but it can play a significant part.

Hyperbaric Oxygen

Hyperbaric Oxygen therapy, or HBO, is a treatment where the body of the individual is placed in a self contained chamber and exposed to higher than normal air pressure. This pressure is measured in atmospheres above normal. At the same time, the patient also receives increased amounts of oxygen. This combination allows the remaining hemoglobin to carry more oxygen. Under these conditions, it is possible to force enough oxygen to dissolve in the watery part of blood to significantly improve the patient. In fact, in one article, is has been stated, "HBO treatment could and has sustained life without hemoglobin." 1 However, one cannot be kept in such a chamber continuously. How can HBO thus be effective?

As oxygen delivery to the tissue drops, it reaches a point where anaerobic metabolism increases. This is typically seen by a rise in serum lactate levels, a binding compound used by the body to neutralize the acid. Once oxygen delivery increases, the lactic acid is further metabolized and removed. This scenario is played daily in athletes. As they vigorously use their muscles there is a buildup of lactate acid and later, during rest, the body removes this acid. Such causes the familiar aching muscles experienced by the weekend warrior.

In this fashion, the human body can act as a rechargeable battery for oxygen storage. This helps to understand the principle of total body oxygen debt. As the hemoglobin drops, there is an increase in lactic acid production. If this cannot be controlled, it can lead to a number of medical problems. This is where HBO comes into play.

During the time of HBO therapy, the body recharges itself of oxygen, or pays off some of its oxygen debt. For that time, the body’s lactate level improves. While the patient is outside the HBO chamber there is a consumption of the oxygen gains made while in the chamber. Thus, with this charging and discharging of the oxygen debt the doctor is able to keep the patient sustained long enough until the enhanced red blood cell production produces significant results.

Keeping it Cold

While camping outside on a cold night, you start a fire to keep warm. As we are warm-blooded we do a similar thing internally to regulate our body temperature. Humans consume fuel and oxygen in making the heat to warm their bodies as the campfire mentioned above. With a decreased oxygen carrying capacity, it becomes important to limit ways in which oxygen is being consumed. One area is the maintaining the body temperature. This is where a technique known as hypothermia becomes effective.

Hypothermia means below normal temperature and describes a technique used by doctors to lower the body temperature. At times this is done for reasons involving surgery. If the body temperature is lowered and the ability of the body to produce heat (this is done typically by rapid vibrations of muscle contractions or shivering) is blocked, then the body’s rate of oxygen consumption decreases. Muscle relaxants or even paralyzing agents are used to keep the skeletal muscles from making heat for the body. As the temperature drops, the rates of chemical activity decreases and the body goes into a form of artificially induced hibernation.

Though this technique can be used successfully for short periods of time, it is one that is not good for extended lengths. The human body was not designed to ‘hibernate’ like a bear. As the body temperature drops certain metabolic activities vital to life become sluggish. For instance, the clotting system is quite dependent on a variety of chemical reactions occurring between a many chemical agents. Thus, as the body temperature drops the ability of the blood to adequately clot decreases. Therefore, you would not want to use hypothermia in a patient who is actively bleeding. There is less ability for the body to digest food. Cellular metabolism, such as that used by the bone marrow to make red blood cells can be slower. There are some questions about the effectiveness of the white blood cells to mount a credible defense against certain infectious agents that thrive in cold conditions. Caution would be needed in using hypothermia in a patient with a known infection.

In a pinch, hypothermia can be a great aid in decreasing oxygen consumption. The clinician must be careful, though, in watching the patient carefully for other complications occurring.

The Fear of Infection

Oxygen is a key component in fighting the infections that we are afflicted with. How so? It may help to understand if one remembers how hydrogen peroxide or H2O2 is used to clean a wound. When you pour this on an open sore it immediately foams up. Why? The hydrogen peroxide molecule is not the most stable since it is an unbalanced form of water, or H2O. This second oxygen molecule can be easily released. When this is done in the presence of bacteria it literally ‘burns’ up the bacteria in a form of chemical fire. The white blood cells of the body use a similar action.

As white blood cell flow through the circulation and encounter bacteria or other foreign matter, they engulf such like a form of digestion. Once this object is encapsulated within the white blood cell it is bathed in superoxidase compounds and destroyed or ‘burned’ up with cold fire. Without this, the white blood cells, though effectively attacking the bacterial agents, are not able to break down and destroy the bacteria. But where does the white blood cell get the components to make the superoxidase compounds?

Red blood cells are carrying under normal circumstances more than enough oxygen to fuel the body cells with extra left over. If a passing white blood cell needs oxygen, a major component of a superoxidase compound, it is able to pull such from a passing red blood cell. This is a very efficient and effective method. However, if there is extreme anemia, then there may not be red blood cells present for white blood cells to extract oxygen to fight infection. In essence you have plenty of soldiers (white blood cells) but these have no bullets (superoxidase compound) to destroy the enemy.

In this condition there is an increased possibility for infection to rapidly grow and overwhelm the body. If severe, it can lead to sepsis. Sepsis itself can further release hormones and other reactionary chemicals into the body that can lead to further problems with oxygen delivery, blood flow, and can result in shock. In an extremely anemic patient, the most deadly of conditions is sepsis, and such has been blamed for many deaths. Thus, it becomes paramount to help the immune system to fight bacterial infections early on before than can become rampant. How?

There are no simple solutions. Isolation techniques are a plus. Avoidance of visitors who have signs of infections is important. Prophylactic antibiotics have been used by some to decrease the likelihood of common infectious agents from starting to multiply. Antibiotic coated catheters are also a plus as well as careful handwashing and sterilization of all equipment used will help as well.

Avoiding Vampires

Diagnostic tests are mainstay for providing needed health care to a patient. Such tests can help the doctor determine much about a patient’s condition. Based on these test the therapy can be modified appropriately. A major source of product to be tested comes from blood. Why? Can this be bad for the patient? If so, what can be done instead.

The technique of withdrawing blood from the body is known as phlebotomy. If a doctor needs blood for a particular diagnostic test he orders blood to be drawn and sent to the lab. A common system employs a type of tube called a Vacutainer. These tubes are sealed with rubber on one end and a vacuum is placed on them. When the vein is accessed and these tubes connected, they ‘suck’ up a prescribed amount of blood into the tube. But is this dangerous? It may.

The typical volume used for most tests for adults is 10-15 cc’s (ml) of blood. Each test may require its own tube of blood. Also, many tests are done serially, or regularly, each day. If easy access lines are connected to the patient it becomes even easier to withdraw blood for tests. Though each tube by itself represents a small amount, the great number of tests and tubes can easily begin to add up. Therefore, doctors use the phrase iatrogenic anemia to describe patients who have been ‘sucked dry’ for laboratory tests. But what can be done?

There are many tests that a doctor can request these days. Also, fear of litigation causes some doctors to order extra tests for fear of future reprisal. Other tests are ‘standing’ orders on the doctor’s chart for all of their patients. In extreme cases of anemia it behooves the doctor to carefully review each of the tests being ordered. Can two or more tests be taken from one tube of blood? Is the test absolutely necessary or can I tell by clinical experience that all is well. If extremely anemic, what difference does it make to know how low a patient is if all is being done that is possible.

There are newer techniques of testing blood with lesser amounts be drawn out. For instance, pediatric tubes are typically only 5 cc’s (ml) in size, or one half to one third an adult tube. Even newer techniques of microsampling devices allow for tests to be done on 1-2 cc’s of blood and now ultramicrosampling devices have lowered this to 1-2 drops (one-tenth of a cc) blood.

Hurry and Wait

That the bleeding has been stopped, as much as possible has been returned, and the body is being stimulated to make more red blood cells. You have started HBO, volume expanders, hypothermia and more. What is left? The waiting game. As the red cell count nears its nadir the doctors much carefully monitor the patient’s condition. Once the lowest count is reached is a matter of time as the red cell count now begin its climb upward. Soon active young red blood cells, with plenty of mitochondrial activity and flexibility will be rushing oxygen to the cells of the body. Lactic acid will be processed away and other harmful toxins will be removed and the body will again be refreshed.

This is the most difficult of times for both the clinician and the patient. But, with careful application of technical skills and modern medicine, the patient will begin to improve. All the time with the clear feeling of not having to worry about any hidden surprise that may await them in the future from blood use. They will not be saved now, only to die a few years latter from an unknown infectious agent received.

1. Grim PS, "Hyperbaric Oxygen Therapy," JAMA, 1990, April 25, Vol. 263, No. 16