It has already applied the principles of 'permissive hypercapnia' during mechanical ventilation in several clinics at ARDS of COVID-19 patients, which is likely to save lives. Nevertheless, treating ARDS with mechanical ventilation is not a 21st-century solution[2]. I had stated that hypocapnia could cause vicious circles and death at critically ill patients[1]. Several vicious circles have also been identified in ARDS, and hypocapnia may also play a role in them, for example, enhances pulmonary hypertension[3] and decreases surfactant formation[4]. Does the question arise, whether the vicious circles can be stopped even before ARDS develops? Surprisingly few works of literature are known to use a mixture of carbon dioxide and oxygen therapeutically at any disorders. Administration of 5% carboxygene in animal experiments reversed the process of surfactant depletion.
Article Hypocapnia and mental stress can trigger vicious circles in ...
@Giannoni et al. successfully influenced pCO2 levels during Cheyne-Stokes respiration: "dynamic CO2 administration, delivered at an appropriate time during periodic breathing, can almost eliminate oscillations in end-tidal CO2 and ventilation.” During the procedure, the average pCO2 level increased, and there was a moderate increase in respiratory volume. The introduction of the method in the early stage of ARDS may be beneficial, as the increase in metabolism in hyperventilation is mostly due to the decreased pCO2 levels.
@Khambatta HJ and Sullivan SF (1974) mechanically hyperventilated dogs for several hours. Energy expenditure increased significantly, which could not originate from the 'work of breathing' because the hyperventilation was passive during the study. In summary, it is in principle possible to reduce the increased metabolism caused by hyperventilation.
https://journals.physiology.org/doi/pdf/10.1152/jappl.1974.37.5.665
Thank you for sharing this information. Carbon dioxide supplementation therapy is not a medicament. It is pathophysiology.
https://thorax.bmj.com/content/74/3/219
it is well documented that the increase in dead space and ventilatory ratio, both highly Dependent on the body’s production of CO2, correlate with mortality in ARDs more reliably than p/f ratio (ie hypoxemia despite o2 delivery). As such, I think the solution is to reduce the amt of CO2, not add to it... permissive hypercapnia works not because it increases body CO2 but bc it prevents further baro and volutrauma.
The permissive hypercapnia is already widely accepted. (See Hamilton Medical's protocol (attached) This is only another method. Combined with mechanical ventilation is a safe mode to try it. I have discussed it with @John Laffey (who is one of the inventors of permissive hypercapnia). He has found the idea to be inventive and distinct. He maybe applies it.
We allow permissive hypercapnia for those patients on APRV. Our general protocol is to keep the pH 7.25 or greater as long as the patient is not exhibit hypotension. i have not used carbogen therapy for many years. Use to use it for Neuro patients to regulate cerebral blood flow.
Thank you for your answer. I have been looking for the effects of CO2 on biological systems. I hope that ARDS could be prevented at an early stage. It can be reversing the vicious circles by administering carbogen. I know that CO2 administration can cause a massive increase in respiratory volume, which is undesirable. I hope that the concomitant administration of bicarbonate will prevent a significant volume increase in breathing. It would compensate for the hypercapnia. It is probable that the protective effects of permissive hypercapnia depend on pCO2 levels and not pH, because intracellular pH correlates with pCO2 during acute hypercapnia. I should like to study the relevant literature. And why is all this? COVID-19 comes to poor African and Asian countries who have no ventilator machines ... You should help developing countries with working out new, cheaper methods.
The method of permissive hypercapnia is now widely accepted in treating ARDS during mechanical ventilation as opposed to the traditional one, although there is still no agreement on the standards. Several doctors consider the possibility of a decrease in pH and an increase in pCO2 to be almost limitless. @Josh Farkas would draw the boundaries for both 'permissive pH' and 'permissive pCO2' []. According to him, one of the studies about permissive hypercapnia performed one of the best results because the Na-bicarbonate infusion was allowed [].
https://emcrit.org/pulmcrit/hypercapnia/
COVID viral pneumonia, and other forms of viral and bacterial pneumonia can be quickly controlled and cured if their underlying cause is understood.
The lung is a "target organ" for stress because it is chock full of tissue factor, which activates factor VII to initiate tissue repair. Normally tissue factor in extravascular tissues is isolated from factor VII in flowing blood by the vascular endothelium, a delicate, selectively permeable single layer of cells that lines the inner surface of all blood vessels and is the sole constituent of capillaries. The coronavirus, the flu virus, and other viruses that cause the "common cold" all exert their pathological effects by disrupting the vascular endothelium and exaggerating contact between tissue factor and factor VII. Factor VII activation acts as a "trigger" for the enzymatic interaction of factors VII, VIII, IX and X that generates thrombin, soluble fibrin, and insoluble fibrin to maintain and repair tissues. The virus thus causes excessive activation of factor VII, which results in excessive production of thrombin, soluble fibrin, and insoluble fibrin. Thrombin energizes inflammation. Soluble fibrin exudates flood the alveoli and disrupt gas exchange. In addition, the glycoprotein/soluble fibrin exudates promote collagen generation that causes pulmonary sclerosis and permanent lung damage if the pneumonia is not promptly controlled.
The lung is intensely innervated with autonomic nerve endings that exaggerate sympathetic nervous activity in the presence of pulmonary inflammation caused by thrombin. The sympathetic nervous activity releases von Willebrand Factor from the vascular endothelium, which binds to and stabilizes hepatic enzyme factor VIIIC to for "coagulation" factor VIII, which accelerates thrombin generation to energize its conversion of soluble fibrin to insoluble fibrin.
COVID viral pneumonia---indeed, all forms of pneumonia----should be treated as follows:
1. elective intubation to support ventilation as needed and isolate the contagion from health care workers
2. Permissive hypercarbia in the range of 50-100 torr to optimize cardiorespiratory function. CO2 is benign, beneficial, therapeutic, and essential for life. It is devoid of toxicity or narcotic effects. It enhances oxygen transport and deivery. It is the primary regulator of the capillary gate, so that hypercarbia reduces microvascular flow resistance and enhances cardiac output, tissue perfusion, and tissue oxygenation. The depletion of CO2 tissue reserves via mechanical hyperventilation amounts to criminal stupidity. It offers no benefits and is inherently harmful. This has been understood for more than 100 years.
3. generous narcotic dosage to inhibit harmful nociception and sympathetic nervous activity
4. Intravenous treatment with one of the following chemicals: magnesium sulphate, EDTA, or trisodium citrate. All of these chemicals have considerable practical experience in clinical use. All three exert their benefits by binding to Ca+, which inhibits thrombin generation that causes inflammation.
5. antibiotics in the event that viral pneumonia is complicated by bacterial pneumonia.
These combined measures will quickly restore homeostasis, whereupon the body will quickly and effectively rid itself of the offending viruses and/or bacteria. Prompt, effective treatment will cure the illness, salvage lives, and prevent permanent lung damage caused by collagen generation that produces pulmonary sclerosis.
Thank you for your valuable answer. You mentioned 'increased sympathetic activity' plays a significant role in COVID-ARDS.
It can be presented that hypocapnia and the vicious circle maintained by hypocapnia play a critical role in the perpetually increasing sympathetic activity. (See my article).
I accept that ‘permissive hypercapnia’ has a colossal regulator to cool down this increased sympathetic activity and that it can be sustained for days without tissue damage. It is an (almost) physiological process. I would like to point out that you should attempt to interrupt the vicious circles of sympathetic activity maintained by hyperventilation/ hypocapnia in the 'pre-ARDS' phase by co-administration of carboxygen and Na-bicarbonate - without mechanical ventilation. On the one hand, there is no ventilator machine for everyone and everywhere (think about Africa). On the other hand, mechanical ventilation is not physiological either, and it would be better to prevent trouble, not to cure it when it is already advanced.
Article Hypocapnia and mental stress can trigger vicious circles in ...
The therapeutic benefits of dioxide were understood 100 years ago. Anyone interested in this subject might be interested in my review of this history called "Four Forgotten Giants of Anesthesia History" https://www.ommegaonline.org/article-details/Four-Forgotten-Giants-of-Anesthesia-History/468
Research Proposal Can hypocapnia trigger ARDS and kill coronavirus diseased patients?
Where is the literature source for the finding " Administration of 5% carboxygene in animal experiments reversed the process of surfactant depletion" ?
Several works of literature demonstrate that hypocapnia (and not metabolic alkalosis!) plays a significant role in the inhibition of surfactant formation.
https://www.atsjournals.org/doi/full/10.1164/rccm.200408-998OC
Today, it also seems to be proven that this is caused by an increase in mitochondrial Ca2+ levels, which means ATP-energy insufficiency.
https://thorax.bmj.com/content/74/3/219
We do not know how reversible this process is. Ventilator-induced ‘permissive hypercapnia’ already works well, but it’s a little too late for many.
https://www.nejm.org/doi/full/10.1056/nejmra012457
THEREFORE, the lack of surfactant and the development of ARDS should be prevented by raising pCO2 level in anyhow (not with respiratory machinery!). Maybe it's not that hard? At an early stage, perhaps the administration of a small dose of iv. Na-bicarbonate would be sufficient (monitored), taking care not to develop metabolic alkalosis, as well. Therefore, it may still need to be co-administered with carbogen and/or intracellular pCO2-boosting medicine (acetazolamide?).
https://www.karger.com/Article/Abstract/194878
https://www.nature.com/articles/cddis2017403
Research Features British magazine presents one of my articles and highlights the role of acute hypocapnia in diseases. Hypocapnia can trigger vicious circles which may lead to a fatal outcome if the body has no energy reserves and is unable to meet the challenge posed by hypocapnia.
https://researchfeatures.com/challenge-meeting-energy-demands-acute-hypocapnia/
Mixtures of CO2 and oxygen in a pressurized tank are called "Carbogen." It's one of the most powerful medical treatments known, and this was widely understood for about 30 years at the beginning of the previous century after Yandell Henderson, who was director of the human physiology lab at Yale, performed animal experiments that proved the therapeutic properties of CO2. It's one of the great crimes of corporate America that this knowledge has been concealed from public awareness. It's even been removed from medical textbooks. For treatment of COVID the Carbogen should be combined with endotracheal intubation, generous narcotics, and sedation to minimize the body's reaction to the virus. The patients should recover much more quickly with this treatment. Check my published paper called "Four Forgotten Giants of Anesthesia History."
Thank you, Lewis, for your answer. I have read it. We are rowing in the same boat. We need to gather believers. What do you think of my article published in the Research Features?
Dear Lewis,
Please attach your opinion to my article in the Research Features Magazine
I update my question:
Research Proposal Sodium bicarbonate as (also) medicine for COVID-19 infection
Dear Andreas,
I believe that hypercarbia would be helpful in treating COVID, but only if it were combined with 1/2 MAC general anesthesia (or some other form of sedation) to prevent anxiety and fear, plus generous narcotic dosage to minimize harmful sympathetic nervous activity, plus magnesium sulphate to inhibit thrombin activity. The combined effects of these treatments should prevent inflammation and excessive exudate production, and restore the ability of the body to destroy and expel the virus.