M. Prodanchuk1, H. Balan1, P. Zhminko1, A. Stroii1, M. Kalysh2, V. Chernenko1
1L.I. Medved’s Research Center of Preventive Toxicology, Food and Chemical Safety, Ministry of Health, Ukraine (State Enterprise), Kyiv, Ukraine
2Kyiv City Clinical Hospital of Emergency Medical Care, Kyiv, Ukraine.
ABSTRACT. Acute carbon monoxide poisoning is the most prevalent form of toxic gas intoxication, ranking second only to injuries among domestic causes of death and disability. The ongoing hostilities in Ukraine have resulted in a substantial escalation in the number of fires and acute carbon monoxide (CO) poisonings. In light of these developments, there is an imperative to synthesize the extant knowledge concerning the mechanisms of CO toxicity. A comprehensive understanding of these mechanisms is pivotal in elucidating the clinical manifestations of acute poisoning, delayed pathology, and justifying the contemporary treatment strategy.
Aim. To summarise the current ideas about the mechanisms of toxic action of carbon monoxide (CO), the clinical manifestations of acute poisoning, delayed pathology, treatment strategies, and the features of the course of CO poisoning in wartime.
Materials and Methods. Open sources of public information and scientific literature data on the topic of the study were analysed. An analytical review of modern publications of scientific online libraries PubMed, MedLine, Elsevier on the mechanisms of toxic action, features of the clinical course of acute CO poisoning, delayed pathology and treatment strategies was conducted.
Results. To date, the mechanism of toxic action of CO has not been sufficiently elucidated. It is known that it is almost 300–400 times more related to erythrocyte heme than oxygen (O2), and is also characterized by increased affinity for cytochrome oxidase (CcO), myoglobin, neuroglobin and other tissue haemoproteins. It has been established that this is associated with the redistribution of electron localization at the O2 site in the porphyrin ring of heme and the formation of HbCO, which disrupts the supply of O2 to tissues, contributes to the formation of vascular and tissue hypoxia with the development of mitochondrial dysfunction and energy deficiency, as well as activation of lipid peroxidation, inflammatory processes, immunological shifts and the development of delayed multi-organ pathology of the brain, heart, muscles, kidneys, liver and skin. There are still no specific antidotes for the treatment of CO poisoning. Modern treatment strategies for patients with acute CO poisoning include optimization of gas exchange and pharmacological mitigation of pathophysiological damage. Depending on the severity of hypoxia, oxygen inhalation, hyperbaric oxygenation, extracorporeal membrane oxygenation and photohaemotherapy are used to normalize gas exchange. Recently, the use of a number of drugs based on CO high-affinity molecules (scavengers) based on haemoproteins has been proposed: a constructed recombinant variant of human neuroglobin (Ngb-H64Q-CCC), modified human erythrocyte haemoglobins (S-Hb and NEM-Hb), low-molecular-weight scavengers based on water-soluble porphyrins that absorb CO and can be used as antidotes.
Conclusions. CO poisoning prevails among toxic gas intoxications, especially in war conditions due to the destruction and fires at residential and industrial buildings, energy supply systems as well as a significant increase in the number of fires. The toxic effect of CO is attributable to its high affinity not only to erythrocyte heme and CcO, but also to other tissue-specific haemoproteins, which disrupts the supply of O2 to tissues and contributes to the formation of vascular and tissue hypoxia with a CO reservoir and the development of both acute intoxication and delayed pathology.
The use of oxygen inhalation alone does not solve the issue of effective treatment and prevention of the development of delayed multiorgan pathology in patients with acute CO poisoning. The use of effective agents using CO scavengers, which accelerate the dissociation of HbCO in the blood and tissues and reduce the concentration of CO, is considered promising.
Keywords: CO, toxicity, mechanism of action, acute poisoning, delayed pathology, treatment strategy, CO scavengers.
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The article was received by the editors on September 16, 2024.