Hrev_master [page 56] [Emergency Care Journal 2021; 17:9677] Emergency Care Journal 2021; volume 17:9677 Abstract If acute carbon monoxide poisoning is a well-known emer- gency situation, this is not the case for chronic poisoning. The missed diagnosis of acute CO poisoning is a well-known problem but the identification of a chronic poisoning is very challenging. Knowledge and awareness of chronic poisoning is less defined and probably there is a great number of patients with undiagnosed chronic CO poisoning. It is possible that in case of missed diagno- sis because of non-specific symptoms, chronic CO poisoning could be responsible for significant morbidity. We describe the case of a married couple who were rescued almost simultaneously, to show this clinical condition. Introduction If acute carbon monoxide poisoning is a well-known emer- gency situation,1,2 this is not the case for chronic poisoning.3 The latter has a very variable spectrum of symptoms, often less overt and consequently more difficult to report, because they are not always recognizable.3-5 It is likely that chronic carbon monoxide intoxication is much more frequent than one might imagine, and that it can sometimes escape even the most experienced clinicians. Here we describe the case of a married couple who were rescued almost simultaneously. They suffered from different symptoms, which could have deceived a doctor and delayed the diagnosis. Case Report The first patient was a 44-years-old man, with a silent history, taken to our Emergency Department at night because of diarrhoea, fatigue, and mildly diffused chest pain. He was alert, without fever and he had normal vital signs (150/80 mmHg arterial pressure, 90 bpm, 99% arterial saturation) and a normal ECG (Figure 1a). His neurological physical assessment was normal and the only impor- tant objective element was his skin, which appeared to be exten- sively reddened (particularly his face, chest and both hands). Along with this patient, we evaluated his wife, a 40-years-old woman without a significant past medical history: she referred recent onset of toothache, diffuse arthralgia, non-specific chest pain. Also, her vital parameters were normal (120/60 mmHg arte- rial pressure, 98 bpm, 99% arterial saturation), but she appeared confused even in the absence of signs of neurological deficit, fever and other objectives signs. Her ECG was also normal (Figure1b). In both cases the triage nurses were alerted by the smell of burnt wood, and decided to perform a venous blood gas examina- tion: in the man, the carbon monoxide level resulted normal (3.3%), while in his wife we detected a slight but significant increase (8.8%, in no smoker woman). The other parameters were normal. In fact, they lived in an unattended country house, and used an unspecified wood stove for heating, so despite not particularly high carbon monoxide values, chronic exposure seemed plausible. They were both immediately treated with 100% O2 non-rebreathing masks. Blood tests were normal except for a high level of cardiac Troponin I: 987 ng/mL in the man, and 1087 in the woman. Cardiac ultrasound, carried out following the discovery of elevated troponin values, showed no abnormalities in cardiac contractility or morphology. After a consultation with the specialist of the bariatric center of the referring hospital, considering the cardiac and neurological involvements, both patients were transferred to start hyperbaric treatment. They were treated for five days, with a progressive resolution of their clinical conditions, and then discharged to their home. An inspection from fire workers in their home found an irregular indoor home heating system with CO leak. Discussion CO is a colorless, odorless, non-irritating gas produced by incomplete combustion of any fuel, due to poor oxygenation of fire.1,2 The pathophysiology of carbon monoxide poisoning is com- plex and not completely known, in particular in chronic, occult Correspondence: Alessandro Riccardi, Emergency Room and Emergency Medicine, Ospedale San Paolo, Savona (SV), Italy. E-mail: dottriccardi@gmail.com Key words: Carbon monoxide poisoning; acute myocardial infarction; acute neurological syndromes. Conflict of interests: None. This work was not supported by any grant. Contributions: All authors endorse this paper. RL wrote the introduc- tion, MM and PB wrote the case report, AR wrote the discussion sec- tion, all authors reviewed the references. Availability of data and material: any material or data about these case reports all avaible. Ethics approval and consent to participate: Informed consent from both patients was obtained for publication of this case report. Received for publication: 12 February 2021. Revision received: 13 April 2021. Accepted for publication: 20 April 2021. This work is licensed under a Creative Commons Attribution 4.0 License (by-nc 4.0). ©Copyright: the Author(s), 2021 Licensee PAGEPress, Italy Emergency Care Journal 2021; 17:9677 doi:10.4081/ecj.2021.9677 Chronic carbon monoxide poisoning. A report of two cases Alessandro Riccardi, Paolo Bientinesi, Marta Monteverdi, Roberto Lerza Emergency Room and Emergency Medicine, Ospedale San Paolo, Savona, Italy Non -co mmerc ial us e o nly poisoning.3 We can consider different pathophysiological aspects: i) the high affinity of carbon monoxide to haemoglobin (up to 300 times than oxygen), and its stability, lead to peripheral tissue hypoxia in the whole body;1,2 ii) the carbon monoxide can bind any kind of heme-containing proteins, like cytochromes, myoglobin, and guanylyl cyclase: CO can reduce cellular activity in different ways, and can induce direct myocardial toxicity;6-11 iii) there are increasing suggestions of an important role of nitric oxide: NO level increases in CO exposure in animal model, with a reduction in brain flow and systemic hypotension;12-14 The missed diagnosis of acute CO poisoning is a well-known problem:15 some retrospective analysis in acute coronary syndrome or ischemic stroke showed a prevalence of undiagnosed CO poi- soning in up to 30% patients,11,16 and a strategy to identify any sus- pected case in the ED is mandatory;1,3,15 but the identification of a chronic poisoning is very challenging:3,15 knowledge and aware- ness of chronic poisoning is less defined and probably there is a great number of patients with undiagnosed chronic CO poisoning. It is possible that chronic CO poisoning is responsible for signifi- cant morbidity, especially if diagnosis is not reached because of non-specific symptoms, and some particular issues.17,18 First of all, there is few evidence in literature, and there is no defined role in CO levels in blood sample:1 in our patients, only the female had a slight increase in CO levels, similar to a level consid- ered normal for smoker. The male had a normal level of CO, and he had no marked neurological complaints. There is no agreement about the exact pathophysiology in chronic, occult poisoning: probably, a continuous, submaximal exposure could lead to cellu- lar bindings, with severe neurological and cardiac toxicity.2-5,10,11 For both patients, we excluded other causes that could lead to their symptom through a careful evaluation. Surely the alteration in both spouses of troponin levels could suggest the diagnosis of Takotsubo syndrome, but we underline that the chest pain was undefined and not typical in both, electrocardiograms were inex- pressive and cardiac ultrasound did not show the typical pattern. Moreover, their histories did not show a possible stressful event as Case Report Figure 1. The EKG of our patients: a) the male patient, b) the female patient. [Emergency Care Journal 2021; 17:9677] [page 57] Non -co mmerc ial us e o nly it is often described in Takotsubo syndrome. The hyperbaric treat- ment was immediately started and showed a progressive and dra- matic improvement in neurological symptoms and reduction of troponin levels. This further supports the diagnosis of chronic CO poisoning. But how is it possible to suspect a CO poisoning in patients with normal CO levels? A high index of suspicion is very important.1,3 First of all, a cluster of patients living together sharing the same neurological or cardiological symptoms, must lead to a suspected CO poisoning. Secondarily, if present, the typical skin coloration (see Figure 2, as in our male patient) is a possible indicator, although is emerged in post-mortem cases. Further, an evaluation of the type of domestic heating is important, although not always clear. In our cases, the evaluation of both patients, with acute cardiac injury in both of them led us to the correct diagnosis. But what would happened if the patients had been evaluated at different times and by different physicians? The cluster of symptoms in correlated patients or sharing the same for living space is mandatory: but in case of single patients, diagnosis could be missed.3 Conclusions Is it possible to think of CO poisoning for all patients with an acute ischemic complaint evaluated in an ED? All authors agree that venous CO levels are as diagnostic as arterial ones,1 but this could lead to an increase in sanitary costs without a real impact on health results. Probably the use of oxygen and carbon monoxide oximeter could make diagnosis of ED poisoning19,20 easier, but this is useless in case of chronic, severe exposure with normal or quite to normal CO blood levels. References 1. Locatelli C. Intossicazione acuta da monossido di carbonio: il punto di vista del tossicologo. Medicina Subacquea e Iperbarica 2009;2:19-23. 2. Kao LW, Nañagas KA. Carbon monoxide poisoning. Med Clin North Am 2005;89:1161-94. 3. Wright J. Chronic and occult carbon monoxide poisoning: we don't know what we're missing. Emerg Med J 2002;19:386-90. 4. Heckerling PS. Occult carbon monoxide poisoning: a cause of winter headache. Am J Emerg Med 1987;5:201–4. 5. Dolan MC, Haltom TL, Barrows GH, Short CS, Ferriell KM. Carboxyhemoglobin levels in patients with flu-like symptoms. Ann Emerg Med 1987;16:782-6. 6. Hardy KR, Thom SR. Pathophysiology and treatment of car- bon monoxide poisoning. J Toxicol Clin Toxicol 1994;32:613- 29. 7. Zhang J, Piantadosi CA. Mitochondrial oxidative stress after carbon monoxide hypoxia in the rat brain. J Clin Invest 1992;90:1193-9. 8. Wittenberg BA, Wittenberg JB. Effects of carbon monoxide on isolated heart muscle cells. Res Rep Health Eff Inst 1993;(62):1-12; discussion 13-21. 9. Radi R, Rodriguez M, Castro L, Telleri R. Inhibition of mito- chondrial electron transport by peroxynitrite. Arch Biochem Biophys 1994;308:89-95. 10. Rastelli G, Callegari S, Locatelli C, Vezzani G. Il danno mio- cardico indotto dall'intossicazione acuta da monossido di car- bonio [Myocardial injury in carbon monoxide poisoning]. G Ital Cardiol 2009;10:227-33. 11. Balzan MV, Cacciottolo JM, Mifsud S. Unstable angina and exposure to carbon monoxide. Postgrad Med J 1994;70:699– 702. 12. Ischiropoulos H, Beers MF, Ohnishi ST, et al. Nitric oxide pro- duction and perivascular nitration in brain after carbon monox- ide poisoning in the rat. J Clin Invest 1996;97:2260-7. 13. Thom SR, Fisher D, Manevich Y. Roles for platelet-activating factor and *NO-derived oxidants causing neutrophil adherence after CO poisoning. Am J Physiol Heart Circ Physiol 2001;281:H923-30. 14. Hartsfield CL. Cross talk between carbon monoxide and nitric oxide. Antioxid Redox Signal 2002;4:301-7. 15. Heckerling PS, Leikin JB, Maturen A. Occult carbon monox- ide poisoning: validation of a prediction model. Am J Med 1988;84:251-6. 16. Heckerling PS, Leikin JB, Terzian CG, et al. Occult carbon monoxide poisoning in patients with acute neurological illness. Clin Toxicol 1990;28:29–44. 17. Sadovnikoff N, Varon J, Sternbach GL. Carbon monoxide poi- soning. An occult epidemic. Postgrad Med. 1992;92:86-8, 92- 6. 18. Zorbalar N, Yesilaras M, Aksay E. Carbon monoxide poison- ing in patients presenting to the emergency department with a headache in winter months. Emerg Med J 2014;31:e66-70. 19. Rose JJ, Wang L, Xu Q, et al. Carbon monoxide poisoning: pathogenesis, management, and future directions of therapy. Am J Respir Crit Care Med 2017;195:596-606. Erratum in: Am J Respir Crit Care Med 2017;196:398-399. 20. Koyuncu S, Bol O, Ertan T, et al. The detection of occult CO poisoning through noninvasive measurement of carboxyhemo- globin: A cross-sectional study. Am J Emerg Med 2020;38: 1110-4. Case Report [page 58] [Emergency Care Journal 2021; 17:9677] Figure 2. Skin coloration of male patient. Non -co mmerc ial us e o nly