...POISON in small doses can be MEDICINE. Proper dose, route and slow administration of drugs cannot only prevent adverse effects, can also turn poison into medicine!
P.S. CARBON MONOXIDE (CO) can be therapeutically used very much; as thalidomide, despite having gone into disrepute in the 60s, is being used for cancer like multiple myeloma; and leprosy.
There is potential therapeutic role of inhaled CO (100 - 500 ppm), which is in excess of CO inspired during routine low flow anaesthesia with Amsorb, a new carbon dioxide absorbent (which produces CO, 1- 3 ppm), though traditional dehydrated soda lime forms more (< 630 ppm) with Desflurane.
Amsorb consists of calcium hydroxide and calcium chloride (a compatible humectant - moisture retainer) but no sodium or potassium hydroxide (identified to form CO). Also, it includes two setting agents (calcium sulphate and polyvinylpyrrolidine) to improve hardness and porosity.
Also, with Sevoflurane, Amsorb forms much less compound A (<3.3 ppm) compared to traditional absorbents (>32 ppm).
Low flow anaesthesia implies fresh gas flow lower than that required to prevent rebreathing in a circuit, which is about 6 L/min for Bain circuit (1.5 - 2.0 times minute volume), for efficient controlled ventilation and for Magill's efficient spontaneous breathing 70 - 85 ml/kg/min (5 - 6 L/min in an adult). Therefore, fresh gas flow below 6 L/min is low flow, which is possible in a closed circuit or circle system!
Besides, prevention of early drying of sodalime and CO formation, low flow anaesthesia has several advantages: economical, improved dynamics of inhaled gases, mucocilliary clearance; reduces water vapour loss and maintains temperature; and prevents ozone depletion and heat trapping greenhouse effect. High 2-6 L/min, Low 1 L/min, Minimal 0.5 L/min and Metabolic flow 0.35 L/min.
Endogenously produced CO has beneficial effect in terms of cytoprotection in many different tissues and organ systems. Exogenous CO, in low dose, when inhaled, may prove to be clinically useful to Anaethesiologists in the future.
It has been already tested in humans, in chronic obstructive pulmonary disease (COPD) to be producing anti-inflammatory effects, when CO inhaled 100-125 ppm for 2 hours a day for 4 days in a row. It helped reduce eosinophils in sputum and interleukin - 5 in bronchoalveolar lavage and improved Airway responsiveness to Methacholine. It also reduces airway reactivity in asthma (CO inhaled 250 ppm) through cGMP dependent pathway.
In animal models, CO inhalation has shown beneficial effect in hyperoxia induced lung injury, ventilator-induced lung injury by reducing tumor necrosis factor-α (TNF- α). Also, mechanically ventilated pneumococcal pneumonia, acute lung injury. In aspiration, inhalation of 500 ppm CO for 6 hours protects the lungs following ischemia and reperfusion by preventing apoptosis. These pro-survival effects have been observed in lung transplantation, coronary artery occlusion, cardiopulmonary bypass (CPB).
The mechanisms of such cytoprotection involve the p38 MAPK pathway, the phosphatidylinositol 3-kinase/Akt pathway, and Egr-1 expression.
Hypoxia induced pulmonary arterial hypertension is relieved by chronic exposure to 50 ppm via activation of calcium-activated potassium channels within pulmonary artery smooth muscle cells.
Inhaled CO also protects the heart, suppresses graft rejection; inhibits platelet aggregation, thrombosis, myocardial infarction, and cardiomyocyte apoptosis.
Brain protection during cardiac and neurosurgery is possible by preconditioning with low dose inhaled CO 250 ppm for 3 hours, a day prior to surgery, which completely prevented cell death in the neocortex and hippocampus following deep hypothermic circulatory arrest.
The beneficial effect of inhaled CO in mechanically ventilated patients in Intensive Care Unit and Operation Theatre might lead to incorporation of CO as a gaseous agent in the future. It can help recovery from various disease processes, can prevent perioperative injury, and can enhance anaesthetic outcome and survival.
Amsorb: a new carbon dioxide absorbent for use in anesthetic breathing systems:
https://www.ncbi.nlm.nih.gov/m/pubmed/10551585/
Comparison of Amsorb, sodalime, and Baralyme degradation of volatile anesthetics and formation of carbon monoxide and compound a in swine in vivo:
https://www.ncbi.nlm.nih.gov/m/pubmed/11753018/
Inhalational anaesthesia with low fresh gas flow:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3800325/
Anesthesia-related Carbon Monoxide Exposure: Toxicity and Potential Therapy:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5021316/
Mapleson's Breathing Systems:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3821268/
P.S. CARBON MONOXIDE (CO) can be therapeutically used very much; as thalidomide, despite having gone into disrepute in the 60s, is being used for cancer like multiple myeloma; and leprosy.
There is potential therapeutic role of inhaled CO (100 - 500 ppm), which is in excess of CO inspired during routine low flow anaesthesia with Amsorb, a new carbon dioxide absorbent (which produces CO, 1- 3 ppm), though traditional dehydrated soda lime forms more (< 630 ppm) with Desflurane.
Amsorb consists of calcium hydroxide and calcium chloride (a compatible humectant - moisture retainer) but no sodium or potassium hydroxide (identified to form CO). Also, it includes two setting agents (calcium sulphate and polyvinylpyrrolidine) to improve hardness and porosity.
Also, with Sevoflurane, Amsorb forms much less compound A (<3.3 ppm) compared to traditional absorbents (>32 ppm).
Low flow anaesthesia implies fresh gas flow lower than that required to prevent rebreathing in a circuit, which is about 6 L/min for Bain circuit (1.5 - 2.0 times minute volume), for efficient controlled ventilation and for Magill's efficient spontaneous breathing 70 - 85 ml/kg/min (5 - 6 L/min in an adult). Therefore, fresh gas flow below 6 L/min is low flow, which is possible in a closed circuit or circle system!
Besides, prevention of early drying of sodalime and CO formation, low flow anaesthesia has several advantages: economical, improved dynamics of inhaled gases, mucocilliary clearance; reduces water vapour loss and maintains temperature; and prevents ozone depletion and heat trapping greenhouse effect. High 2-6 L/min, Low 1 L/min, Minimal 0.5 L/min and Metabolic flow 0.35 L/min.
Endogenously produced CO has beneficial effect in terms of cytoprotection in many different tissues and organ systems. Exogenous CO, in low dose, when inhaled, may prove to be clinically useful to Anaethesiologists in the future.
It has been already tested in humans, in chronic obstructive pulmonary disease (COPD) to be producing anti-inflammatory effects, when CO inhaled 100-125 ppm for 2 hours a day for 4 days in a row. It helped reduce eosinophils in sputum and interleukin - 5 in bronchoalveolar lavage and improved Airway responsiveness to Methacholine. It also reduces airway reactivity in asthma (CO inhaled 250 ppm) through cGMP dependent pathway.
In animal models, CO inhalation has shown beneficial effect in hyperoxia induced lung injury, ventilator-induced lung injury by reducing tumor necrosis factor-α (TNF- α). Also, mechanically ventilated pneumococcal pneumonia, acute lung injury. In aspiration, inhalation of 500 ppm CO for 6 hours protects the lungs following ischemia and reperfusion by preventing apoptosis. These pro-survival effects have been observed in lung transplantation, coronary artery occlusion, cardiopulmonary bypass (CPB).
The mechanisms of such cytoprotection involve the p38 MAPK pathway, the phosphatidylinositol 3-kinase/Akt pathway, and Egr-1 expression.
Hypoxia induced pulmonary arterial hypertension is relieved by chronic exposure to 50 ppm via activation of calcium-activated potassium channels within pulmonary artery smooth muscle cells.
Inhaled CO also protects the heart, suppresses graft rejection; inhibits platelet aggregation, thrombosis, myocardial infarction, and cardiomyocyte apoptosis.
Brain protection during cardiac and neurosurgery is possible by preconditioning with low dose inhaled CO 250 ppm for 3 hours, a day prior to surgery, which completely prevented cell death in the neocortex and hippocampus following deep hypothermic circulatory arrest.
The beneficial effect of inhaled CO in mechanically ventilated patients in Intensive Care Unit and Operation Theatre might lead to incorporation of CO as a gaseous agent in the future. It can help recovery from various disease processes, can prevent perioperative injury, and can enhance anaesthetic outcome and survival.
Amsorb: a new carbon dioxide absorbent for use in anesthetic breathing systems:
https://www.ncbi.nlm.nih.gov/m/pubmed/10551585/
Comparison of Amsorb, sodalime, and Baralyme degradation of volatile anesthetics and formation of carbon monoxide and compound a in swine in vivo:
https://www.ncbi.nlm.nih.gov/m/pubmed/11753018/
Inhalational anaesthesia with low fresh gas flow:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3800325/
Anesthesia-related Carbon Monoxide Exposure: Toxicity and Potential Therapy:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5021316/
Mapleson's Breathing Systems:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3821268/
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