Carbon Monoxide is a poisonous gas, tasteless, odorless.

Common sources of carbon monoxide include vehicle exhaust fumes,  poorly ventilated fires, malfunctioning heaters, and smoking.

Carbon monoxide causes not only acute fatal poisoning but also may cause a delayed neurologic syndrome called delayed encephalopathy, which occasionally occurs after an interval of several days to several weeks post-exposure (1).

Possible care

Delayed neuropsychiatric sequelae (DNS) are serious complications of carbon monoxide poisoning; neuropsychiatric disorders can occur within a few days of recovery from acute poisoning. Hyperbaric oxygen therapy (HBOT) has been the main treatment of carbon monoxide (CO) poisoning and was recommended as the treatment choice for CO poisoning by the American Undersea and Hyperbaric Medical Society and the Tenth European Consensus Conference on Hyperbaric Medicine of the European Underwater and Baromedical Society. However, the optimal timing for commencing HBOT in patients with CO poisoning remains unknown. We therefore conducted a retrospective study in an attempt to target the optimal time of HBOT for DNS prevention. We identified several potential predictors of DNS in patients with CO poisoning who received HBOT. Multivariable logistic regressions further revealed that longer duration from CO exposure to HBOT, loss of consciousness, and the presence of multiple victims were independent predictors of DNS development. HBOT should be performed as early as possible and preferably within 22.5 h after CO poisoning (2).

Carbon monoxide (CO) has been shown to induce several cardiovascular abnormalities, as well as necrosis, apoptosis and oxidative stress in the brain. Magnesium sulfate (MS) has been shown to have beneficial activities against hypoxia in the brain. In the present study, the possible protective effects of MS against CO‑induced cerebral ischemia were investigated. Histopathological evaluation revealed that MS reduced the number and intensity of necrotic insults. The Bax/Bcl2 ratio and malondialdehyde (MDA) levels were significantly decreased in a dose‑dependent manner in the MS‑treated rats compared to the positive control group, while a significant dose‑dependent increase in Akt expression, a pro‑survival protein, was observed. In addition, MS administration reduced pro‑apoptotic indice levels, ameliorated histological insults, favorably modulated oxidative status and increased Akt expression levels, indicating a possible neuroprotective effect in the case of CO poisoning. On the whole, the findings of this study indicate that MS may prove to be useful in protecting against CO‑induced cerebral injury (3).

Beneficial effects

Inhalation of high concentrations of carbon monoxide (CO) is known to lead to serious systemic complications and neuronal disturbances. However, it has been found that not only is CO produced endogenously, but also that low concentrations can bestow beneficial effects which may be of interest in biology and medicine. As translocation of CO through the human organism is difficult, small molecules known as CO-releasing molecules (CORMs) deliver controlled amounts of CO to biological systems, and these are of great interest from a medical point of view. These actions may prevent vascular dysfunction, regulate blood pressure, inhibit blood platelet aggregation or have anti-inflammatory effects. This review summarizes the functions of various CO-releasing molecules in biology and medicine (4).

Acute respiratory distress syndrome (ARDS) is a prevalent disease with significant mortality for which no effective pharmacologic therapy exists. Low-dose inhaled carbon monoxide (iCO) confers cytoprotection in preclinical models of sepsis and ARDS. Precise administration of low-dose iCO is feasible, well-tolerated, and appears to be safe in patients with sepsis-induced ARDS. Excellent agreement between predicted and observed COHb should ensure that COHb levels remain in the target range during future efficacy trials (5).

Snake venom contains a myriad of classes of enzyme which have been investigated for medicinal and toxinological purposes, including phospholipase A2 (PLA2), which is responsible for anticoagulant, myotoxic and neurotoxic effects. Given the importance of PLA2, the purposes of the present investigation were to characterize the coagulation kinetic behavior of a PLA2 purified from Crotalus adamanteus venom (Ca-PLA2) in human plasma with thrombelastography and determine if carbon monoxide could inhibit its activity. Carbon monoxide inhibited Ca-PLA2 activity in a concentration dependent fashion, with loss of detectable activity at 100 µM of carbon monoxide releasing molecule-2. These findings, while preliminary, open the possibility that other PLA2 contained in snake venom with multiple toxicities (e.g., myotoxin, neurotoxin) may be heme bearing and CO-inhibitable, which have profound potential basic and clinical science implications (6)

Heated tobacco products

Heated tobacco products (HTPs) are new tech devices that release nicotine and other volatile compounds into an inhalable aerosol by heating the tobacco. At their operating temperatures, tobacco combustion is unlikely.The aim of this randomized cross-over study was to measure the exposure levels of the combustion marker, carbon monoxide in the exhaled breath (eCO) of subjects after use of two HTPs and to compare these levels with participants' own brand of cigarettes.A total of 12 healthy smokers who reported smoking ≥10 conventional cigarettes per day for at least 5 years took part in the study. Product administration consisted of a first round of 10 puffs, which was followed by an identical second round after a 5 min pause in between rounds. After obtaining a baseline eCO value, this measure was recorded at 5, 10, 15, 30, and 45 min after the first puff of the first round. In contrast to combustible cigarettes, no eCO elevations were observed in the exhaled breath after use of the HTPs under investigation in any of the study participants (7).

Molecular Formula : CO

Molecular Weight : 28,01

CAS : 630-08-0

Bibliografia__________________

(1) Carbon monoxide poisoning-induced delayed encephalopathy accompanies decreased in microglial cell numbers: distinctive pathophysiological features from hypoxemia-induced brain damage.

Sekiya K, Nishihara T, Abe N, Konishi A, Nandate H, Hamada T, Ikemune K, Takasaki Y, Tanaka J, Asano M, Yorozuya T.

Brain Res. 2018 Dec 19. pii: S0006-8993(18)30645-0. doi: 10.1016/j.brainres.2018.12.027.

(2) Targeting optimal time for hyperbaric oxygen therapy following carbon monoxide poisoning for prevention of delayed neuropsychiatric sequelae: A retrospective study.

Liao SC, Mao YC, Yang KJ, Wang KC, Wu LY, Yang CC.

J Neurol Sci. 2019 Jan 15;396:187-192. doi: 10.1016/j.jns.2018.11.025. Epub 2018 Nov 22

(3) Magnesium sulfate ameliorates carbon monoxide‑induced cerebral injury in male rats.

Bagheri G, Rezaee R, Tsarouhas K, Docea AO, Shahraki J, Shahriari M, Wilks MF, Jahantigh H, Tabrizian K, Moghadam AA, Bagheri S, Spandidos DA, Tsatsakis A, Hashemzaei M.

Mol Med Rep. 2018 Dec 17. doi: 10.3892/mmr.2018.9771.

(4) Carbon monoxide and its donors - their implications for medicine.

Adach W, Olas B.

Future Med Chem. 2019 Jan;11(1):61-73. doi: 10.4155/fmc-2018-0215. Epub 2018 Dec 11.
Mol Med Rep. 2018 Dec 17. doi: 10.3892/mmr.2018.9771

(5) A phase I trial of low-dose inhaled carbon monoxide in sepsis-induced ARDS.

Fredenburgh LE, Perrella MA, Barragan-Bradford D, Hess DR, Peters E, Welty-Wolf KE, Kraft BD, Harris RS, Maurer R, Nakahira K, Oromendia C, Davies JD, Higuera A, Schiffer KT, Englert JA, Dieffenbach PB, Berlin DA, Lagambina S, Bouthot M, Sullivan AI, Nuccio PF, Kone MT, Malik MJ, Porras MAP, Finkelsztein E, Winkler T, Hurwitz S, Serhan CN, Piantadosi CA, Baron RM, Thompson BT, Choi AM.

JCI Insight. 2018 Dec 6;3(23). pii: 124039. doi: 10.1172/jci.insight.124039

(6) Carbon monoxide inhibits the anticoagulant activity of phospholipase A2 purified from Crotalus adamanteus venom.

Nielsen VG.

J Thromb Thrombolysis. 2018 Oct 29. doi: 10.1007/s11239-018-1763-6

(7) Carbon monoxide levels after inhalation from new generation heated tobacco products.

Caponnetto P, Maglia M, Prosperini G, Busà B, Polosa R.

Respir Res. 2018 Aug 31;19(1):164. doi: 10.1186/s12931-018-0867-z.