*This is an article from the Summer 2022 issue of Contentment Magazine.
By Lewis Coleman, MD, FAIS
Madness is rare in individuals – but in groups, parties, nations, and ages it is the rule. – Friedrich Nietzsche
Of all the ignorance and superstition that bedevils human existence, the notion that carbon dioxide is toxic and dangerous is arguably the most outrageous. The widely ballyhooed notion that carbon dioxide is a “greenhouse gas” that threatens to melt the polar ice and drown civilization seems silly considering that CO2 is a “trace gas” that exists in atmospheric concentrations of 0.03% that fluctuates slowly over geologic time. Episodes of “global warming” occur every few hundred years despite negligible change in atmospheric CO2 concentrations. For example, an episode of “global warming” in the early 1400’s enabled a fleet of gigantic Chinese junks to explore and map the world and document an ice-free passage around the North Pole that has recently re-appeared, so that commercial shipping now enjoys an alternative to the Panama Canal. The panic that followed the Apollo 13 explosion offers perhaps the most dramatic contemporary example of the ignorant fear of CO2 that permeates science and society. The supposedly sophisticated astronaut support team assumed that exhaled CO2 might kill the astronauts within the few days before they returned to earth, and their construction of a makeshift CO2 absorption contraption was hailed as a triumph of American ingenuity. But the danger was imaginary, because weeks would have been required weeks for the CO2 concentration to approach dangerous levels, and the CO2 could have been flushed from the spacecraft using abundant remaining oxygen reserves.1How did this fear of CO2 arise and become so pervasive?
Every cell in the body produces CO2 continuously as a by-product of metabolism. The adult male body contains about 1.8 L/kg—up to 126 L of carbon dioxide.2 Most of it combines with calcium and collagen to form bone. About 20 Liters exists as free gas in the lung or is dissolved in body fluids and tissues, as compared to 1 L of oxygen and 1 L of nitrogen.3 If it were toxic, we would all be dead. If it were narcotic, we would all be drunk. Instead, CO2 is benign, beneficial, and essential for life. Oxygen is useless without it, because it enables all elements of oxygen capture from the atmosphere and its transport and delivery to cells deep within the body. Furthermore, it provides the most potent, practical, affordable, and safe medical treatments yet discovered, and it can help us reverse the ravages of stress. But CO2 treatments, which were commonplace 100 years ago, have been hidden and forgotten in our era of supposedly advanced medicine, and this ignorance has caused countless unnecessary deaths.4,5 How can patients trust doctors who are ignorant of such fundamental facts? This essay will review the chemistry, pathophysiology, and therapeutic properties of carbon dioxide, and explain the mechanism of oxygen transport and delivery, in hopes of counteracting ignorance.
CO2 Chemistry and Pathophysiology
Carbon dioxide differs from the other gases in several ways that explain how it facilitates oxygen transport and delivery, and how it mimics general anesthesia and toxicity:
- It is odorless at normal atmospheric concentrations of 0.03% but it causes a painful sense of suffocation when it is inhaled in concentrations above 1%. This is sometimes mistaken as toxicity, but CO2 is benign and inert, and cannot damage tissues.
- It has refrigerant properties. When compressed it releases heat and converts from gas to liquid. When released from a pressurized container it absorbs heat.
- It is theoretically preferable to commercial refrigerants because it is cheap, chemically inert, and devoid of toxicity.
- It is more readily isolated from the atmosphere by compression and cooling than other atmospheric gases. This explains why it was the first gas to be isolated from the atmosphere.
- Although it mixes uniformly with other gases in the atmosphere, it has a slightly greater molecular weight than the other gases, so that most atmospheric CO2 hovers near the earth’s surface.
- When released from a pressurized container it forms a cool, invisible, colorless cloud that is temporarily affected by gravity so that it pours like water and collects in dependent spaces until it absorbs enough heat to mix with surrounding gases.
- It inhibits the binding of oxygen to hemoglobin molecules in red blood cells. Breathing lowers the concentration of carbon dioxide in the lungs to 5% to optimize the saturation of hemoglobin with oxygen. Higher partial pressures of CO2 in organs and peripheral tissues release oxygen from blood into organs and tissues.
- It directly stimulates respiratory chemoreceptors to enable breathing.
- It counteracts the respiratory depression caused by narcotics.
- It accelerates narcotic metabolism and clearance.
- It directly releases nitric oxide from capillaries, and thereby reduces microvascular flow resistance via the mechanism of “nitrergic neurogenic vasodilation.” This increases cardiac output and accelerates oxygen transport to cells.
- Breathing gas mixtures supplemented with CO2, or absorbing CO2 through the skin, can improve both tissue perfusion and tissue oxygenation, and thereby counteract the effects of disease more effectively than conventional medications.
- When mixed with atmospheric air in concentrations up to 10%, CO2 enhances the release of oxygen from hemoglobin and improves tissue oxygenation. Higher concentrations of CO2 in atmospheric air disrupt hemoglobin loading with oxygen in the lung and threaten asphyxiation. This mimics general anesthesia because it disrupts consciousness but is readily reversed by restoration of oxygen to the brain. This was a common trick produced by “shills” in circus side shows at the turn of the previous century.
- When mixed with oxygen in concentrations of 2% to 30%, CO2 enhances tissue and organ oxygenation by optimizing the release of oxygen from hemoglobin. CO2 concentrations greater than 30% cause asphyxiation regardless of oxygen supplementation.
In the spring issue of Contentment magazine, I mentioned the mechanism of oxygen transport and delivery, which captures oxygen from the atmosphere and delivers it to cells deep within the body. This important mechanism was understood by the turn of the previous century, but is inexplicably absent from modern medical publications. Carbon dioxide enables all aspects of this mechanism, and is therefore as essential to vertebrate life as oxygen. It activates respiratory chemoreceptors to stimulate breathing, reduces microvascular flow resistance to speed the transport of oxygenated arterial blood to peripheral tissues, and releases oxygen from red cells into organs and tissues.
Cellular metabolism continuously releases carbon dioxide. It readily dissolves in body fluids and tissues, and slowly leaks through the skin and equilibrates with the ambient atmosphere. Respiratory chemoreceptors adapt to this equilibrium and seek to maintain it. Almost all oxygen in the body is bound tightly to hemoglobin in red cells, and hemoglobin is normally 100% saturated with oxygen as blood transits the lung. The oxygen is quickly consumed by cells when it is released from hemoglobin into tissues. Therefore, there is little “oxygen reserve” in the body, and oxygen transport and delivery must be continuous to maintain cellular oxygenation. If a heart attack, drowning, or airway obstruction disrupts oxygen transport and delivery, the available oxygen in blood will be consumed within minutes, followed by brain cell oxygen starvation and death.
Inhaling atmospheric air supplemented with small amounts of carbon dioxide beneficially enhances the release of oxygen from hemoglobin into tissues, and counteracts the cellular hypoxia caused by of disease and disability. In contrast, CO2 depletion disrupts oxygen transport and delivery by reducing cardiac output and tissue perfusion, and by inhibiting the release of oxygen from hemoglobin into tissues.
CO2 is a “trace gas” that constitutes only 0.03% of atmospheric air at sea level; most CO2 hovers near the surface of the earth and is nearly absent at high altitudes such as the top of mountains. This explains “mountain sickness” and the “death zone” phenomenon that occurs near the peak of Mt. Everest. Persons breathing CO2 deficient air at extreme altitudes suffer brain hypoxia that sometimes causes unpredictable and catastrophic loss of consciousness, and repeated exposure to such circumstances causes the brain damage. Breathing CO2 is the most effective treatment.6
Unlike CO2, oxygen is toxic. Breathing pure oxygen for more than 24 hours causes lethal lung inflammation, and invites oxygen fueled fires. Furthermore, it doesn’t improve tissue oxygenation in most circumstances, because hemoglobin is normally 100% saturated with oxygen as it transits the lung even without oxygen supplementation. Nevertheless, patients are routinely flooded with 100% oxygen, and the need for carbon dioxide is ignored.
Oxygen Transport and Delivery
The mechanism of oxygen transport and delivery occurs in a sequence of steps, as follows:
- Carbon dioxide stimulates respiratory chemoreceptors, which activates breathing.
- Breathing replenishes oxygen in the lung, and lowers carbon dioxide concentrations in the lung to 5%, which optimizes the loading of oxygen onto the hemoglobin molecules in red blood cells transiting the lung, causing oxygenated arterial blood to turn bright red.
- The heart pumps oxygenated arterial blood from the lungs to capillary beds in organs and tissues.
- Carbon dioxide releases nitric oxide (NO) from capillary walls to open the “capillary gate” via the mechanism of “nitrergic neurogenic vasodilation.” This reduces microvascular flow resistance, which increases cardiac output, and speeds the delivery of oxygenated blood to oxygen-starved tissues. For example, exercising muscle cells increase their CO2 production, causing localized CO2 elevations that reduce microvascular resistance and speed delivery of oxygenated blood to the active muscle tissues. CO2 is thus the primary regulator of blood flow and distribution.
- Elevated CO2 partial pressures release oxygen from hemoglobin molecules into organs and tissues to satisfy cellular oxygen demand.
- Hemoglobin turns blue after releasing its oxygen into tissues.
- Oxygen depleted venous blood returns to the lungs to be re-oxygenated.
Hyperventilation versus Hypoventilation
Because of the Leake/Waters hoax (explained below), anesthesiologists are traditionally trained to use mechanical hyperventilation to eliminate the supposedly toxic and narcotic effects of carbon dioxide. Hyperventilation is inherently harmful and confers no benefits.7 This is counterintuitive, because breathing is obviously essential for life, so that it seems reasonable that more breathing is better, but such is not the case. Hemoglobin is normally 100% saturated with oxygen as blood transits the lung, so that hyperventilation cannot improve “oxygen reserve” or tissue oxygenation. Instead, hyperventilation dangerously depletes CO2 tissue reserves, which disrupts oxygen transport and delivery, causes oxygen starvation in organs and tissues, and unpredictably undermines postoperative respiratory drive.8-10 Even brief voluntary hyperventilation causes cerebral oxygen starvation that manifests as dizziness and disorientation. This is especially problematic in geriatric patients with low metabolic rates who cannot readily replenish depleted CO2 tissue reserves.
The following examples illustrate the dangers of hyperventilation:
- Shallow Water Blackout Syndrome: Healthy young swimmers lose consciousness and drown after voluntarily hyperventilating in the mistaken belief that this will increase their oxygen reserves and enable them to swim longer under water. Instead, the hyperventilation depletes CO2 tissue reserves, which paralyzes respiratory chemoreceptors and dangerously abolishes the urge to breathe. The swimmer thus exhausts the supply of oxygen in blood and suffers painless brain hypoxia that undermines judgment, so that he loses consciousness and drowns.
- The “death zone” on Mt. Everest: Spontaneous hyperventilation and CO2 depletion due to low concentrations of oxygen and carbon dioxide at high altitudes causes mountain climbers to unexpectedly faint and fall to their deaths. More than 400 Darwin Award winners reside permanently at the peak of Mt. Everest.
- Guides who routinely expose themselves to the extreme conditions of Mt. Everest often suffer hypoxic brain damage.
- Hyperventilated patients unexpectedly fall asleep, stop breathing, and die while recovering from uneventful surgery because the hyperventilation depletes CO2 tissue reserves, paralyzes respiratory chemoreceptors, and renders respiratory drive unstable until metabolic activity replenishes CO2 tissue reserves. In geriatric patients, this can sometimes require several hours, as in the mysterious death of Andy Warhol.8
- Hyperventilation during surgery depletes carbon dioxide body reserves and prevents the release of oxygen from the hemoglobin molecule.9 This causes harmful tissue and organ oxygen starvation that manifests as postoperative delirium and dementia, especially in geriatric patients.
- Newborn respiratory arrest after Cesarean section: Hyperventilation depletes the CO2 tissue reserves of the fetus as well as the mother, and newborn babies are more vulnerable to CO2 depletion than their mothers.
- Prolonged postoperative respiratory depression after cardiac bypass, because bypass technicians, like anesthesiologists, believe that CO2 is “toxic waste, like urine” that must be “rid from the body.”
- Prolonged depression of respiratory drive after mechanical hyperventilation during surgery.
- “Opioid hypersensitivity” for hours after surgery, because narcotics and CO2 depletion synergistically depress respiratory chemoreceptor function.
- Increased ECMO (extra-corporeal membrane oxygenation) morbidity and mortality.
- Exaggerated morbidity and mortality in the presence of Obstructive Sleep Apnea (OSA).
- Intra-operative infarction (heart attacks and strokes) due to oxygen starvation in heart muscle.
- Increased morbidity and mortality due to cancer, heart disease, and chronic illnesses in the distant aftermath of seemingly successful surgery due to inadequate narcotic analgesia during surgery.11
- Retrolental fibroplasia due to hyperventilation with 100% oxygen in premature babies, because CO2 depletion prevents the release of oxygen into immature retinal cells.
These examples of CO2 pathophysiology are discussed in detail in my previously mentioned paper called “Four Forgotten Giants of Anesthesia History” that can be downloaded from its publisher or from my website, www.stressmechanism.com, along with copies of all my published papers. They are also explained in my book “50 Years Lost in Medical Advance: The Discovery of Hans Selye’s Stress Mechanism” that is published by the AIS via Amazon.com.
The Shortcomings of Pulse Oximetry
Few nurses, doctors, and even anesthesiologists appreciate the complicated characteristics and deceptive shortcomings of pulse oximetry, which is the most common means to monitor oxygen in hospitals and clinics. It does not measure the partial pressure of oxygen in tissues, which is the critical measure of cellular oxygenation. Instead, it determines blood oxygen saturation using an algorithm that assesses light frequencies reflected from oxygen in blood. Unfortunately, it cannot distinguish between oxygen bound to hemoglobin and oxygen saturated in plasma, and it can be “fooled” by numerous circumstances. For example, it cannot detect hypoventilation when patients are breathing 100% oxygen, and it cannot detect cellular oxygen starvation caused by mechanical hyperventilation that depletes carbon dioxide and disrupts the release of oxygen from hemoglobin into tissues. This happens routinely when patients are hyperventilated during surgery, based on the false belief that carbon dioxide is a “waste gas” that must be removed from the body.
The Forgotten Therapeutic Benefits of CO2
The approaching apocalypse of WWI inspired medical research that clarified the mechanism of oxygen transport and delivery. Friedrich Miescher (1844–1895), the Swiss physician who discovered DNA, demonstrated that carbon dioxide regulates breathing.12,13 Christian Bohr (1855-1911), a Danish researcher, discovered that carbon dioxide inhibits the affinity of hemoglobin for oxygen.14 Physicians of that era were astonished by the therapeutic properties of carbon dioxide.15 Yandell Henderson, a famous American researcher, demonstrated that CO2 optimizes cardiorespiratory function and prevents unexpected postoperative respiratory arrest.10,16 American nurse-anesthetists embraced carbon dioxide supplementation to deter ether explosions, optimize cardiorespiratory function, and prevent postoperative asthma, atelectasis, pneumonia, nausea, and unpredictable respiratory arrest. Their successes inspired widespread utilization of Carbogen, a mixture of oxygen and carbon dioxide in pressurized tanks, to treat medical emergencies including drowning, smoke inhalation, asthma, pneumonia, heart attacks, strokes, alcohol inebriation, narcotic overdose, sepsis, infections, and newborn babies with breathing problems. Carbogen became standard equipment on fire trucks in major cities and saved numerous lives.7
Carbon Dioxide Treatments
Disease is harmful stress mechanism hyperactivity that wastes its substrates and produces excessive and defective versions of its products that damage tissues and disrupt cellular oxygenation. Tissue hypoxia induces abnormal fibroblast collagen production, which causes tissue sclerosis that progressively disrupts tissue and organ function and undermines longevity. CO2 therapy counteracts cellular hypoxia by opening the capillary gate, inducing angiogenesis (capillary proliferation), and promoting oxygen release from hemoglobin into tissues. Thus, CO2 can palliate disease, promote cure, and improve outcome in nearly all forms of disease. For example, “facultative anaerobes” cause most stubborn and dangerous bacterial infections, including osteomyelitis, Lyme disease, gas gangrene, MRSA (methicillin-resistant staphylococcus aureus), and stasis ulcers. These microbes are poisoned by oxygen and thrive in its absence, but can tolerate low oxygen levels, so that they thrive in poorly perfused and oxygenated bones, ligaments, and prostate. Carbon dioxide promotes antibiotic penetration by improving tissue perfusion, and it promotes antibiotic potency by poisoning facultative anaerobes with oxygen.
CO2 treatments can be made even more effective using modern medical machines, monitors, and medications. For example, hyperbaric oxygen treatment could be improved by the addition of carbon dioxide to the inhaled gas mixture. With modern capnography, patients with chronic illnesses could safely sleep in tents with air enriched with carbon dioxide to counteract the symptoms of their illnesses. Carbon dioxide can also be safely absorbed through the skin to improve the management of numerous medical conditions.13
The Hoax that Halted Medical Advance
Dr. George Washington Crile founded the nurse anesthesia profession after WWI, when physicians were in short supply.16 Crile was famous in his own time and should be remembered as the father of anesthesia, but his achievements have been relegated to obscurity. He invented cardiopulmonary resuscitation, performed the first successful blood transfusion, proved that narcotics can cure lethal infections, and that preoperative sedation and narcotic supplementation of general anesthesia optimizes surgical outcome. The nurses combined ether anesthesia with Crile’s narcotic principles and the equally famous CO2 research of Dr. Yandell Henderson.7
Their success inspired widespread use of Carbogen (a synergistic mixture of 5% CO2 with 95% oxygen) to treat asthma, atelectasis, pneumonia, alcohol inebriation, smoke inhalation, heart attacks, strokes, morphine overdose, and breathing problems in newborn babies. It saved countless lives. Their growing fame caused consternation among physicians, who coveted their practice.17 Drs. Chauncey Leake and Ralph Waters (who famously founded the anesthesiology profession) conspired to vilify the nurses’ reputation by concocting specious scientific experiments and fictitious medical accounts that characterized carbon dioxide as “toxic waste, like urine, that must be rid from the body” using mechanical hyperventilation during surgery.
Seldom have so few civilians caused so much harm to so many. They perpetrated a devastating hoax that has persisted to the present and killed countless patients, even though it flies in the very face of science.7 The hoax was so effective that Carbogen and carbon dioxide, which are perhaps the most potent and practical medical treatments yet discovered, were frightened from medical knowledge and practice. The hoax discourages treatments with beneficial narcotics because they are incompatible with mechanical hyperventilation.18 It has escaped the bounds of anesthesia. It has even been embraced by animal researchers, who illogically use carbon dioxide for both anesthesia and euthanasia without considering its inhumane consequences.19-22 It persists despite recent research that has re-discovered the therapeutic benefits of narcotics and hypercarbia. Its persistence can only be explained by covert corporate influence that profits at the price of public health. The evidence is reviewed in my book, “The Great Medical Hoax of the 20th Century.”17
My question is: why have these scientific and medical triumphs been abandoned and forgotten, and how has this hoax persisted in the presence of science? Could it be that powerful chemical corporations are threatened by the prospect of cheap, non-toxic CO2 replacing their profitable refrigerants? Could it be that powerful medical corporations promote hyperventilation that is incompatible with safe narcotic use in order to promote their toxic NSAID analgesics and otherwise undermine public health for the sake of profits?
Too many patients have died on account of the destructive CO2 hoax. What is exciting is that carbon dioxide therapy represents but one of a set of simple, safe, powerful, and predictable treatments guided by stress theory that can optimize cardiorespiratory function, minimize stress mechanism hyperactivity, restore organ function, cure disease, and save lives. Furthermore, stress theory paves the path to profitable pharmaceutical development that promises to eradicate disease altogether. I will explore these prospects in future issues of Contentment Magazine.
For those interested, the following sources illustrate the extensive therapeutic uses of carbon dioxide that were employed in the forgotten past:
1 Eisele, J. H., Eger, E. I., 2nd & Muallem, M. Narcotic properties of carbon dioxide in the dog. Anesthesiology 28, 856-865 (1967).
2 Cherniack, N. S. & Longobardo, G. S. Oxygen and carbon dioxide gas stores of the body. Physiological reviews 50, 196-243, doi:10.1152/physrev.19184.108.40.206 (1970).
3 Campbell, A. & Poulton, E. P. Oxygen and carbon dioxide therapy. (Oxford University Press, H. Milford, 1934).
4 Overdyk, F. J. postoperative Opioids Need System-Wide Overhaul. Anesthesia Patient Safety Foundation Newsletter (2010).
5 Overdyk, F. J. Postoperative opioids remain a serious patient safety threat. Anesthesiology 113, 259-260; author reply 260-251, doi:10.1097/ALN.0b013e3181e2c1d9
00000542-201007000-00041 [pii] (2010).
6 Harvey, T. C. et al. Effect of carbon dioxide in acute mountain sickness: a rediscovery. Lancet 2, 639-641, doi:10.1016/s0140-6736(88)90465-5 (1988).
7 Coleman, L. S. Four Forgotten Giants of Anesthesia History. Journal of Anesthesia and Surgery 3, 1-17, doi:10.15436/2377-1364.16.468 (2015).
8 Coleman, L. S. in apsf Newsletter Vol. Winter 2009-2020 (Anesthesia Patient Safety Foundation, Administrator, Deanna Walker Anesthesia Patient Safety Foundation Building One, Suite Two 8007 South Meridian Street Indianapolis, IN 46217-2922 e-mail address: [email protected] FAX: (317) 888-1482, 2010).
9 Coleman, L. S. A call for standards on perioperative CO(2) regulation. Can J Anaesth, doi:10.1007/s12630-011-9469-7 (2011).
10 Henderson, Y. Resuscitation with Carbon Dioxide. Science 83, 399-402, doi:10.1126/science.83.2157.399 (1936).
11 Monk, T. G., Saini, V., Weldon, B. C. & Sigl, J. C. Anesthetic management and one-year mortality after noncardiac surgery. Anesth Analg 100, 4-10 (2005).
12 Dahm, R. Friedrich Miescher and the discovery of DNA. Dev Biol 278, 274-288, doi:10.1016/j.ydbio.2004.11.028 (2005).
13 Buess, H. Joh. Friedrich Miescher and the contribution of Basle physicians to the biology of the nineteenth century. Yale J Biol Med 25, 250-261 (1953).
14 Chr. Bohr, K. H., and August Krogh. Concerning a Biologically Important Relationship -The Influence of the Carbon Dioxide Content of Blood on its Oxygen Binding. Skand. Arch. Physiol. 16, 401-412 (1904).
15 Rose, A. Carbonic Acid In Medicine/Carbon Dioxide in Medicine. (Funk & Wagnalls Company, 1905).
16 Henderson, Y. in Cyclopedia of Medicine (1940).
17 Coleman, L. S. 170 (American Institute of Stress/Amazon.com, California, 2022).
18 Ainslie, S. G., Eisele, J. H., Jr. & Corkill, G. Fentanyl concentrations in brain and serum during respiratory acid–base changes in the dog. Anesthesiology 51, 293-297 (1979).
19 Conlee, K. M., Stephens, M. L., Rowan, A. N. & King, L. A. Carbon dioxide for euthanasia: concerns regarding pain and distress, with special reference to mice and rats. Lab Anim 39, 137-161, doi:10.1258/0023677053739747 (2005).
20 Danneman, P. J., Stein, S. & Walshaw, S. O. Humane and practical implications of using carbon dioxide mixed with oxygen for anesthesia or euthanasia of rats. Lab Anim Sci 47, 376-385 (1997).
21 Hawkins, P. et al. A Good Death? Report of the Second Newcastle Meeting on Laboratory Animal Euthanasia. Animals (Basel) 6, doi:10.3390/ani6090050 (2016).
22 Makowska, J., Golledge, H., Marquardt, N. & Weary, D. M. Sedation or inhalant anesthesia before euthanasia with CO2 does not reduce behavioral or physiologic signs of pain and stress in mice. J Am Assoc Lab Anim Sci 51, 396-397; author reply 397-399 (2012).
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