DÄ internationalArchive51-52/2018The Diagnosis and Treatment of Carbon Monoxide Poisoning

Review article

The Diagnosis and Treatment of Carbon Monoxide Poisoning

Dtsch Arztebl Int 2018; 115: 863-70. DOI: 10.3238/arztebl.2018.0863

Eichhorn, L; Thudium, M; Jüttner, B

Background: The symptoms of carbon monoxide (CO) poisoning are nonspecific, ranging from dizziness and headache to unconsciousness and death. A German national guideline on the diagnosis and treatment of this condition is lacking at present.

Method: This review is based on a selective literature search in the PubMed and Cochrane databases, as well as on existing guidelines from abroad and expert recommendations on diagnosis and treatment.

Results: The initiation of 100% oxygen breathing as early as possible is the most important treatment for carbon monoxide poisoning. In case of CO poisoning, the reduced oxygen-carrying capacity of the blood, impairment of the cellular respiratory chain, and immune-modulating processes can lead to tissue injury in the myocardium and brain even after lowering of the carboxyhemoglobin (COHb) concentration. In patients with severe carbon monoxide poisoning, an ECG should be obtained and biomarkers for cardiac ischemia should be measured. Hyperbaric oxygen therapy (HBOT) should be critically considered and initiated within six hours in patients with neurologic deficits, unconsciousness, cardiac ischemia, pregnancy, and/or a very high COHb concentration. At present, there is no general recommendation for HBOT, in view of the heterogeneous state of the evidence from multiple trials. Therapeutic decision-making is directed toward the avoidance of sequelae such as cognitive dysfunction and cardiac complications, and the reduction of mortality. Smoke intoxication must be considered in the differential diagnosis. The state of the evidence on the diagnosis and treatment of this condition is not entirely clear. Alternative or supplementary pharmacological treatments now exist only on an experimental basis.

Conclusion: High-quality, prospective, randomized trials that would enable a definitive judgment of the efficacy of HBOT are currently lacking.

LNSLNS

Carbon monoxide (CO) at low concentrations is an odorless and colorless gas with a molecular weight that is similar to that of air. It develops in incomplete combustion processes of substances containing carbon (e1). In addition to fires, defect gas boilers, or wood pellet storage facilities, the risk of poisoning as a result of smoking hookah has become a focus in recent years (1, e2). Relevant alerting key words and the use of portable CO meters are intended to raise awareness in rescue personnel.

In the USA, 20 000–50 000 cases of carbon monoxide poisoning occur every year (2). Treatment for accidental carbon monoxide poisoning costs the US healthcare system some $1.3 billion every year (e3). For Germany, the only available data are those from the German Federal Statistical Office, for inpatients and deaths with a diagnosis of CO intoxication (T58 in ICD-10) (e4). In the USA, the total number of deaths due to CO poisoning fell between 1999 and 2014 (from 1967 cases to 1319 cases) (e5), whereas in Germany, numbers have steadily risen in recent years. In 2015, 648 patients died as a result of CO poisoning (0.8 deaths/100 000 population) (eTable). Fatality depends on exposure times to CO and its concentrations and is crucially affected by the toxicity of further gases involved (comparative case series [3]).

Cases of carbon monoxide poisoning in Germany (ICD 10: T58, inpatients) (e63)
Cases of carbon monoxide poisoning in Germany (ICD 10: T58, inpatients) (e63)
eTable
Cases of carbon monoxide poisoning in Germany (ICD 10: T58, inpatients) (e63)

Pathophysiology

Carbon monoxide diffuses rapidly through the alveolar membrane and binds with an affinity that is 230–300 times that of oxygen, preferably to the iron ion in heme. Conformation changes lead to a leftward shift in the position of the oxyhemoglobin dissociation curve, to reduced oxygen transport capacity, and to reduced oxygen release into the peripheral tissue (2). Within tissue, CO also binds to other heme-containing proteins, such as skeletal and myocardial myoglobin. Since elimination times in tissue and blood differ (e7), tissue injury can also develop with a delay.

At the cellular level, carbon monoxide leads—among others—to an activation of neutrophils, to a proliferation of lymphocytes, to mitochondrial dysfunction, and to lipid peroxidation (2, 4). The development of oxygen radicals, oxidative stress, inflammation, and apoptosis is comparable to a reperfusion injury and constitutes a substantial damage mechanism (2, 5, 6).

Clinical symptoms and long-term sequelae

The clinical symptoms of acute carbon monoxide intoxication range from headache and dizziness to loss of orientation, symptoms of cardiac angina, loss of consciousness, and death. They depend on the concentration and duration of exposure (7, 8). Detecting chronic poisoning with mild symptoms is often problematic (e8, e9), since the symptoms resemble those of influenza (e10).

In the long term, neurological injuries will manifest—for example, ataxias, dementia, concentration deficits, or abnormal behavior (2, 911, e11). Changes in subcortical structures and the pallidum, as well as hippocampal atrophy, have been observed (e12e14). The severity of the initial intoxication did not necessarily correspond with the development of neuronal long term damage (e15, e16). Since long-term damage can manifest after an initially symptom-free interval ranging from days to weeks (9, 12) after the initial intoxication, a high estimated number of unreported cases has to be assumed (e17).

Patients with pre-existing coronary heart disease are exposed to a greater risk for myocardial infarction and arrhythmias (e18). A retrospective study including 230 patients with CO poisoning described in 37% of cases raised cardiac biomarkers or changes on the electrocardiogram (13). In the prospective study of the same collective, 32 out of these 85 patients with myocardial involvement died during the median follow-up period of 7.6 years, whereas in the group without myocardial involvement only 22 of 145 patients died (adjusted hazard ratio 2.1; 95% CI [1.2; 3.7]; P=0.009). Age at the time of intoxication was an independent predictor of long-term mortality (AHR 1.2 for every additional five years in age; 95% CI [1.1; 1.3]; P<0.001) (14). Additional retrospective cohort studies showed an association between CO poisoning and the occurrence of severe cardiovascular events (AHR 2.00; 95% CI [1.83; 2.18]; or AHR 1.83; 95% CI [1.43; 2.33]) (15, 16). In case of comorbidities (diabetes mellitus, hypertension, hyperlipoproteinemia), the risk increased by a factor of 14.7 (95% CI [10.9; 19.9]) (16). Table 1 shows a summarized overview of the studies.

Selection of larger studies of the effects of carbon monoxide on the health of patients
Selection of larger studies of the effects of carbon monoxide on the health of patients
Table 1
Selection of larger studies of the effects of carbon monoxide on the health of patients

Method

For this review article, we conducted a search according to existing guidelines in the guideline databases AWMF [Association of the Scientific Medical Societies in Germany] (e19), NCG [National Guideline Clearinghouse] (e20), and GIN [Guidelines International Network] (e21).

For an evidence-based assessment we conducted a selective literature search in the databases Medline (accessed via PubMed [e22]) and the Cochrane Database (e23) (eBox).

Search strategy
Search strategy
eBox
Search strategy

Diagnosis and therapy

Therapeutic recommendations as per the included reference guidelines

The description of the therapeutic recommendations in patients with CO poisoning was undertaken in accordance with the German Instrument for Methodological Guideline Appraisal [Deutsches Leitlinien-Bewertungsinstrument, DELBI] (e24). We checked for methodological quality, level of evidence, and grade of recommendation (e25). We based our appraisal of the evidence of the Oxford scheme (e26) (Table 2).

Contents and levels of evidence of identified recommendations and guidelines
Contents and levels of evidence of identified recommendations and guidelines
Table 2
Contents and levels of evidence of identified recommendations and guidelines

Preclinical phase

Administration of 100% oxygen as early as possible is recommended for all patients with a relevant suspected diagnosis (in alert patients, for example, by means of non-invasive continuous airway pressure (CPAP), or respiration using a mask with a demand valve, or administration of 15 L/min O2 through a reservoir mask) (20, 2124). In suspected CO poisoning, an early diagnosis has a crucial role in initiating targeted and timely treatment. In principle, the diagnosis of CO poisoning is based on clinical symptoms and suspected or confirmed exposure (25). For the purposes of verification, carboxyhemoglobin (COHb) should be measured in a blood gas analysis (BGA) (20). Preclinically, a validated spectral photometric method of BGA is mostly not available. Normal pulse oximeters are not suitable for distinguishing between COHb and oxyhemoglobin (e27, e28), whereas 8-wave pulse oximeters enable detection (e29, e30). However, precision has been reported to be poor (e31), and no recommendation for their standard use has been issued by the American College of Emergency Physicians (20). Since the COHb measurement is only one concern when assessing the overall clinical symptoms, the authors still deem pulse oximetry to be a useful—and low-cost (e32)—orientation tool in the emergency rescue setting.

Confirmation of COHb does not differ to a clinically relevant degree in arterial and venous specimens (e33, e34). In order to evaluate the acid-base status, however, arterial measurement should be the method of choice. Hampson et al. showed on the basis of a database analysis of 1505 patients that with an initial pH value <7.2, mortality increased by up to 50%, independently of COHb (26). If concomitant cardiac symptoms occur, a 12-lead ECG should be conducted and cardiological biomarkers determined (20). Generally, the type of exposure to CO (e35), as well as exposure time and exposure level (7), will affect the severity of clinical symptoms. The mere CO measurement correlates poorly with the severity of the clinical manifestation (8, 26). What is important is therefore the overall clinical picture, not the individual measurement. An exact history should consist of type and duration of exposure, initial main symptoms (syncope, confusion, hypoxia, chest tightness, arrhythmias), more unspecific neurological symptoms (headache, nausea, impaired vigilance), and a possible pregnancy should be checked for.

Elimination

The supreme objective is the elimination of carbon monoxide from the organism, in order to avert acute and long-term sequelae. The treatment should be continued until the COHb measurement has dropped to normal values (<3%) and the patient is free from symptoms (25). After exposure to fumes, and in addition to CO, additive cyanide poisoning should also be considered, whose effects will develop within minutes (4, 22, e36). Poison information centers in Germany therefore recommend that in case of severe intoxication owing to smoke inhalation, combined intoxication with CO and cyanides should be considered and a cyanide antidote should be given that has few adverse effects—such as hydroxocobalamin (e37). Administration of hydroxocobalamin can, however, seriously hamper the precision of a blood gas analysis for CO (e38e41). By contrast to the cyanide antidote, no established pharmacological concept exists for CO, even though some animal studies have shown promising approaches (2, e42e46).

The higher the provided partial pressure of oxygen (pO2), the quicker the CO will be eliminated. The elimination half life of CO after respiration of indoor air is about 320 minutes and can be reduced to 74 ± 25 minutes by treating patients with 100% oxygen (e47). Treatment with hyperbaric oxygen (pO2 = 2.5bar) lowered the half life to about 20 minutes (e48, e49). The fivefold half life that is required for complete elimination is about 370 minutes for treatment with normobaric 100% oxygen (Figure). Some animal studies have shown that using hyperbaric oxygen restricts inflammatory processes, mitochondrial dysfunction, and lipid peroxidation (e50e56). Recent clinical studies (Table 2) have also focused on late sequelae of CO intoxication, such as dementia, diabetes mellitus, cardiovascular events, and raised long-term mortality (11, 1315, 19). Being older than 36 years (odds ratio [OR]: 2.6; 95% CI [1.3; 4.9]) and an exposure period of longer than 24 hours (OR: 2.0; 95% CI [1.0; 3.8]; P=0.046) are considered risk factors for developing neuronal late sequelae (27).

Decrease in carboxyhemoglobin (COHb) under different therapeutic conditions (2).
Decrease in carboxyhemoglobin (COHb) under different therapeutic conditions (2).
Figure
Decrease in carboxyhemoglobin (COHb) under different therapeutic conditions (2).

Because the studies available so far are subject to great heterogeneity, no clear, generally accepted recommendation exists for what should be done (Table 3). No controlled randomized multicenter study with defined exclusion and inclusion criteria, defined treatment algorithms, and an adequate follow-up protocol has been conducted so far (20).

Assessment of hyperbaric oxygen therapy versus normobaric oxygen therapy

The intracellular and extracellular effects of carbon monoxide poisoning affect in particular the organs without oxygen reserves (heart, brain). Toxicologically, the quickest possible elimination of the poison is the most sensible way to prevent further injury. The higher the partial pressure of oxygen provided, the shorter the elimination period—which would in theory support hyperbaric oxygen therapy (HBOT). In practice, however, HBOT is the subject of controversial discussion (20, 21). Critics point out the great logistical challenges and lacking evidence. In actual fact, the heterogeneity of the studies to date (in terms of study design, kind of exposure, severity of intoxication, delay in treatment, treatment pressures applied, and follow-up period) barely allows for any evidence-based recommendation regarding the type and extent of HBOT (25). What adds to the dilemma is the fact that the HBOT therapy schemes applied vary widely across Europe (e57), which imposes limitations on future meta-analyses and their validity too.

The study evidence for the benefit of HBOT in adults with regard to neurological sequelae subsequent to CO poisoning is inconclusive. An older randomized study found no benefit for HBOT after one month in 629 patients with acute CO intoxication (2 standard atmospheres [atm]) (28). A randomized controlled double blinded trial (31) including 191 patients showed no difference after one month, irrespective of the selected treatment pattern (2.8 atm versus NBOT). What is of note, however, is the fact that the proportion of patients seen at follow-up was low, at 46%. Annane et al. (32) randomized 385 patients to two study arms. HBOT (2 atm) was not found to confer any benefit in terms of cognitive performance compared with NBOT; rather, repeated HBOT tendentially yielded worse outcomes. These three studies included patients whose therapy was started within 12 hours of CO exposure.

In contrast, a non-blinded prospective randomized trial reported by Thom et al. found fewer delayed neurological symptoms after HBOT, independently of the initial extent and clinical symptoms of the intoxication. Neurological testing also yielded better results for the HBOT group after one month (36). Weaver et al. evaluated in a prospective randomized double blinded study the long term course after HBOT (3 atm). They found a benefit for HBOT in cognitive outcomes after six and 12 months (10). However, Weaver et al. named as their study objective the target parameter of delayed neurological deficit, yet what they actually showed was rates of persistent neurological deficit (10). Furthermore, the study was stopped early when a benefit advantage emerged for HBOT (e58).

A 2011 Cochrane review critically discussed the studies available up to that date. The authors concluded in their meta-analysis that the benefit of HBOT versus normobaric oxygen treatment is not confirmed (OR 0.78; 95% CI [0.54; 1.12]). However, the conclusion is qualified by the heterogeneity of the available studies (21). No further larger prospective studies have been published since then.

Recent retrospective database analyses have shown the importance of HBOT in particular with regard to preventing long-term sequelae. A study by Rose et al. showed that using HBOT reduced acute case fatality as well as case fatality after one year (36). Huang et al. in a retrospective analysis of more than 25 000 cases of CO poisoning also showed a benefit for HBOT in terms of mortality at four years (34). However, the treatment was not found to have any effect on late neurological sequelae.

In these analyses, confounding variables with a risk of bias are especially the heterogeneous therapeutic schemes for HBOT and the fact that the study by Huang et al. does not provide any information of the severity of the intoxication. It is possible that the most severely intoxicated patients were not given HBOT. Still, the large number of cases of CO poisoning underlines the importance of such patients in clinical practice. The large amount of late sequelae and raised long-term mortality also give cause for alarm (11, 1315, 17, 19) (Table 1). It remains to be seen whether prospective studies will in future allow for a profound reassessment of HBOT. A recent prospective study is about to conclude (ClinicalTrials.gov, registration number NCT00465855).

Pregnant women and children

No randomized trials in pregnant women exist; recommendations are based on theoretical studies (e59), animal experiments (e60), and analyses from trauma care (e61). It seems that in the fetal system, saturation as well as elimination occur slower than in the maternal system. Especially in case of longer exposures, fetal COHb measurements may even exceed maternal levels (e62). A case report showed a COHb measurement of 61% at fetal autopsy, although the mother had a measurement of 7% after just an hour’s O2 treatment. For this reason, some authors regard pregnancy as a strict indication for HBOT (23), especially in the presence of neurological symptoms, signs of fetal stress, occurrence of syncope, or high COHb levels (4).

Because of small case numbers, assessing and making recommendations for hyperbaric oxygen therapy in children is possible to a limited degree only in the studies published to date. In the studies reported by Meert et al. (0.1–14.9 years, median 3.5 years) (37) and Chou et al. (0–18 years, median 7.2 years) (38), smoke inhalation often resulted in circulatory arrest; this was barely seen in pure CO intoxication. Neither of the two studies showed a benefit for HBOT versus NBOT. In a retrospective analysis by Chang et al. (33), fire fumes were excluded as a potential confounder (0.1–12.2 years, median 6.2 years); no benefit advantage was found for HBOT in terms of preventing neurological deficits. However, it should be borne in mind that the initial COHb was significantly higher in the HBOT group (27.4±7.3 versus 17.6±6.3). These negative results are contrasted by a recently published, large retrospective cohort analysis, which showed reduced fatality after HBOT especially in patients younger than 20 years (34) (Table 3). In parallel to adults, children (0–18 years, median 11 years) with severe CO poisoning also had raised troponin T concentrations (39).

Conclusion

In sum, on the basis of the randomized controlled trials published to date, no superiority can be confirmed for HBOT over normobaric oxygen therapy. The latest publications were of retrospective database evaluations that showed greater benefits for HBOT in terms of neurological outcomes and long-term survival. A guideline for the treatment of CO intoxication is currently in development (AWMF registration number 040–012) and aims to standardize relevant healthcare in Germany. On this background, HBOT should be the method of choice in adult patients with neurological deficits, cardiac ischemias, loss of consciousness, metabolic acidosis, and COHb values >25%. Regardless of these inclusion criteria, any decision to treat is always an individual decision. Every patient with clinical symptoms of CO intoxication should be treated with high oxygen partial pressures until the COHb concentration has dropped to ≤ 3% or clinical symptoms have resolved completely (25).

Conflict of interest statement
Dr Eichhorn and Prof Jüttner are board members of the German Diving and Hyperbaric Medical Society.

Prof Jüttner is the spokesperson of the section for hyperbaric medicine of the German Interdisciplinary Association of Intensive Care and Emergency Medicine (DIVI).

Dr Thudium declares that no conflict of interest exists.

Manuscript received on 4 June 2018, revised version accepted on
24 September 2018.

Translated from the original German by Birte Twisselmann, PhD.

Corresponding author
Dr. med. Lars Eichhorn

Universitätsklinikum Bonn

Klinik und Poliklinik für Anästhesiologie und
Operative Intensivmedizin

Sigmund-Freud-Straße 25, 53105 Bonn

lars.eichhorn@ukbonn.de

Supplementary material

For eReferences please refer to:
www.aerzteblatt-international.de/ref5118

eTable, eBox:
www.aerzteblatt-international.de/18m0863

1.
Eichhorn L, Michaelis D, Kemmerer M, Jüttner B, Tetzlaff K: Carbon monoxide poisoning from waterpipe smoking: a retrospective cohort study. Clin Toxicol Phila Pa 2018; 56: 264–72 CrossRef MEDLINE
2.
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 CrossRef MEDLINE PubMed Central
3.
Committee on Acute Exposure Guideline Levels; Committee on Toxicology; National Research Council. Acute exposure guideline levels for selected airborne chemicals: volume 8. www.epa.gov/sites/production/files/2014-11/documents/carbon_monoxide_final_volume8_2010.pdf (last accessed on 21 September 2018).
4.
Culnan DM, Craft-Coffman B, Bitz GH, et al.: Carbon monoxide and cyanide poisoning in the burned pregnant patient: an indication for hyperbaric oxygen therapy. Ann Plast Surg 2018; 80(3 Suppl 2): 106–12 CrossRef
5.
Chiew AL, Buckley NA: Carbon monoxide poisoning in the 21st century. Crit Care 2014; 18: 221 CrossRef PubMed Central
6.
Roderique JD, Josef CS, Feldman MJ, Spiess BD: A modern literature review of carbon monoxide poisoning theories, therapies, and potential targets for therapy advancement. Toxicology 2015; 334: 45–58 CrossRef MEDLINE
7.
Weaver LK: Carbon monoxide poisoning. N Engl J Med 2009; 360: 1217–25 CrossRef MEDLINE
8.
Hampson NB, Dunn SL, UHMCS/CDC CO Poisoning Surveillance Group: Symptoms of carbon monoxide poisoning do not correlate with the initial carboxyhemoglobin level. Undersea Hyperb Med 2012; 39: 657–65 MEDLINE
9.
Pepe G, Castelli M, Nazerian P, et al.: Delayed neuropsychological sequelae after carbon monoxide poisoning: predictive risk factors in the emergency department. A retrospective study. Scand J Trauma Resusc Emerg Med 2011; 19: 16 CrossRef MEDLINE PubMed Central
10.
Weaver LK, Hopkins RO, Chan KJ, et al.: Hyperbaric oxygen for acute carbon monoxide poisoning. N Engl J Med 2002; 347: 1057–67 CrossRef MEDLINE
11.
Wong CS, Lin YC, Hong LY, et al.: Increased long-term risk of dementia in patients with carbon monoxide poisoning. Medicine (Baltimore) 2016; 95: e2549 CrossRef MEDLINE PubMed Central
12.
Lettow I, Hoffmann A, Burmeister HP, Toepper R: [Delayed neuropsychological sequelae after carbon monoxide poisoning]. Fortschr Neurol Psychiatr 2018; 86: 342–7 CrossRef CrossRef MEDLINE
13.
Satran D, Henry CR, Adkinson C, Nicholson CI, Bracha Y, Henry TD: Cardiovascular manifestations of moderate to severe carbon monoxide poisoning. J Am Coll Cardiol 2005; 45: 1513–6 CrossRef MEDLINE
14.
Henry CR, Satran D, Lindgren B, Adkinson C, Nicholson CI, Henry TD: Myocardial injury and long-term mortality following moderate to severe carbon monoxide poisoning. JAMA 2006; 295: 398–402 CrossRef MEDLINE
15.
Wong CS, Lin YC, Sung LC, et al.: Increased long-term risk of major adverse cardiovascular events in patients with carbon monoxide poisoning: a population-based study in Taiwan. PLoS ONE 2017; 12: e0176465 CrossRef MEDLINE PubMed Central
16.
Lee FY, Chen WK, Lin CL, Kao CH: Carbon monoxide poisoning and subsequent cardiovascular disease risk. Medicine (Baltimore) 2015; 94: e624 CrossRef MEDLINE PubMed Central
17.
Huang CC, Chung MH, Weng SF, et al.: Long-term prognosis of patients with carbon monoxide poisoning: a nationwide cohort study. PLoS ONE 2014; 9: e105503 CrossRef MEDLINE PubMed Central
18.
Kaya H, Coşkun A, Beton O, et al.: COHgb levels predict the long-term development of acute myocardial infarction in CO poisoning. Am J Emerg Med 2016; 34: 840–4 CrossRef MEDLINE
19.
Huang CC, Ho CH, Chen YC, et al.: Increased risk for diabetes mellitus in patients with carbon monoxide poisoning. Oncotarget 2017; 8: 63680–90 CrossRef
20.
Wolf SJ, Maloney GE, Shih RD, Shy BD, Brown MD: Clinical policy: critical issues in the evaluation and management of adult patients presenting to the emergency department with acute carbon monoxide poisoning. Ann Emerg Med 2017; 69: 98–107 CrossRef MEDLINE
21.
Buckley NA, Juurlink DN, Isbister G, Bennett MH, Lavonas EJ: Hyperbaric oxygen for carbon monoxide poisoning. Cochrane Database Syst Rev 2011; 4: CD002041 CrossRef
22.
Mintegi S, Clerigue N, Tipo V, et al.: Pediatric cyanide poisoning by fire smoke inhalation: a European expert consensus. Pediatr Emerg Care 2013; 29: 1234–40 CrossRef MEDLINE
23.
Truhlář A, Deakin CD, Soar J, et al.: Kreislaufstillstand in besonderen Situationen. Notf Rettungsmedizin 2015; 18: 833–903 CrossRef
24.
Mathieu D, Marroni A, Kot J: Tenth European consensus conference on hyperbaric medicine: recommendations for accepted and non-accepted clinical indications and practice of hyperbaric oxygen treatment. Diving Hyperb Med 2017; 47: 24–32 CrossRef MEDLINE
25.
Hampson NB, Piantadosi CA, Thom SR, Weaver LK: Practice recommendations in the diagnosis, management, and prevention of carbon monoxide poisoning. Am J Respir Crit Care Med 2012; 186: 1095–101 CrossRef MEDLINE
26.
Hampson NB, Hauff NM: Risk factors for short-term mortality from carbon monoxide poisoning treated with hyperbaric oxygen. Crit Care Med 2008; 36: 2523–7 CrossRef MEDLINE
27.
Weaver LK, Valentine KJ, Hopkins RO: Carbon monoxide poisoning: risk factors for cognitive sequelae and the role of hyperbaric oxygen. Am J Respir Crit Care Med 2007; 176: 491–7 CrossRef MEDLINE
28.
Raphael JC, Elkharrat D, Jars-Guincestre MC, et al.: Trial of normobaric and hyperbaric oxygen for acute carbon monoxide intoxication. Lancet Lond Engl 1989; 2: 414–9 CrossRef
29.
Ducassé JL, Celsis P, Marc-Vergnes JP: Non-comatose patients with acute carbon monoxide poisoning: hyperbaric or normobaric oxygenation? Undersea Hyperb Med 1995; 22: 9–15 MEDLINE
30.
Thom SR: Oxidative stress is fundamental to hyperbaric oxygen therapy. J Appl Physiol (1985) 2009; 106: 988–95 CrossRef MEDLINE PubMed Central
31.
Scheinkestel CD, Bailey M, Myles PS, et al.: Hyperbaric or 337 normobaric oxygen for acute carbon monoxide poisoning: a randomised controlled clinical trial. Med J Aust 1999; 170: 203–10 MEDLINE
32.
Annane D, Chadda K, Gajdos P, Jars-Guincestre MC, Chevret S, Raphael JC: Hyperbaric oxygen therapy for acute domestic carbon monoxide poisoning: two randomized controlled trials. Intensive Care Med 2011; 37: 486–92 CrossRef MEDLINE
33.
Chang YC, Lee HY, Huang JL, Chiu CH, Chen CL, Wu CT: Risk factors and outcome analysis in children with carbon monoxide poisoning. Pediatr Neonatol 2017; 58: 171–7 CrossRef MEDLINE
34.
Huang CC, Ho CH, Chen YC, et al.: Hyperbaric oxygen therapy is associated with lower short and long-term mortality in patients with carbon monoxide poisoning. Chest 2017; 152: 943–53 CrossRef MEDLINE
35.
Rose JJ, Nouraie M, Gauthier MC, et al.: Clinical outcomes and mortality impact of hyperbaric oxygen therapy in patients with carbon monoxide poisoning. Crit Care Med 2018; 46: e649–55 CrossRef MEDLINE
36.
Thom SR, Taber RL, Mendiguren II, Clark JM, Hardy KR, Fisher AB: Delayed neuropsychologic sequelae after carbon monoxide poisoning: prevention by treatment with hyperbaric oxygen. Ann Emerg Med 1995; 25: 474–80 CrossRef
37.
Meert KL, Heidemann SM, Sarnaik AP: Outcome of children with carbon monoxide poisoning treated with normobaric oxygen. J Trauma 1998; 44: 149–54 CrossRef
38.
Chou KJ, Fisher JL, Silver EJ: Characteristics and outcome of children with carbon monoxide poisoning with and without smoke exposure referred for hyperbaric oxygen therapy. Pediatr Emerg Care 2000; 16: 151–5 CrossRef
39.
Akcan Yildiz L, Gultekingil A, Kesici S, Bayrakci B, Teksam O: Predictors of severe clinical course in children with carbon monoxide poisoning. Pediatr Emerg Care 2018 (Epub ahead of print: doi: 10.1097/PEC.0000000000001580 CrossRef
40.
Rodkey FL, O’Neal JD, Collison HA, Uddin DE: Relative affinity of hemoglobin S and hemoglobin A for carbon monoxide and oxygen. Clin Chem 1974; 20: 83–4 MEDLINE
e1.
Penney D, Benignus V, Kephalopoulos S, Kotzias D, Kleinman M, Verrier A: WHO guidelines for indoor air quality: selected pollutants. Carbon monoxide. World Health Organization 2010. www.ncbi.nlm.nih.gov/books/NBK138710/ (last accessed on 21 September 2018).
e2.
von Rappard J, Schönenberger M, Bärlocher L: Carbon monoxide poisoning following use of a water pipe/hookah. Dtsch Arztebl Int 2014; 111: 674–9 VOLLTEXT
e3.
Hampson NB: Cost of accidental carbon monoxide poisoning: a preventable expense. Prev Med Rep 2016; 3: 21–4 CrossRef MEDLINE PubMed Central
e4.
Gesundheitsberichterstattung des Bundes – gemeinsam getragen von RKI und Destatis. Diagnose T58 (ICD). Tabelle: Diagnosedaten der Krankenhäuser Deutschland. www.gbe-bund.de/ (last accessed on 21 September 2018).
e5.
Hampson NB: U.S. mortality due to carbon monoxide poisoning, 1999–2014. Accidental and intentional deaths. Ann Am Thorac Soc 2016; 13: 1768–74.
e6.
Joels N, Pugh LG: The carbon monoxide dissociation curve of human blood. J Physiol 1958; 142: 63–77 CrossRef
e7.
Bruce EN, Bruce MC, Erupaka K: Prediction of the rate of uptake of carbon monoxide from blood by extravascular tissues. Respir Physiol Neurobiol 2008; 161: 142–59 CrossRef MEDLINE PubMed Central
e8.
Kao LW, Nañagas KA: Carbon monoxide poisoning. Emerg Med Clin North Am 2004; 22: 985–1018 CrossRef MEDLINE
e9.
Harper A, Croft-Baker J: Carbon monoxide poisoning: undetected by both patients and their doctors. Age Ageing 2004; 33: 105–9 CrossRef MEDLINE
e10.
Tomaszewski C: Carbon monoxide poisoning. Early awareness and intervention can save lives. Postgrad Med 1999; 105: 39–40, 43–48, 50.
e11.
Kwon OY, Chung SP, Ha YR, Yoo IS, Kim SW: Delayed postanoxic encephalopathy after carbon monoxide poisoning. Emerg Med J 2004; 21: 250–1 CrossRef PubMed Central
e12.
Hsiao CL, Kuo HC, Huang CC: Delayed encephalopathy after carbon monoxide intoxication—long-term prognosis and correlation of clinical manifestations and neuroimages. Acta Neurol Taiwanica 2004; 13: 64–70.
e13.
Parkinson RB, Hopkins RO, Cleavinger HB, et al.: White matter hyperintensities and neuropsychological outcome following carbon monoxide poisoning. Neurology 2002; 58: 1525–32 CrossRef MEDLINE
e14.
Lim PJ, Shikhare SN, Peh WCG: Clinics in diagnostic imaging (154). Carbon monoxide (CO) poisoning. Singapore Med J 2014; 55: 405–10 CrossRef MEDLINE PubMed Central
e15.
Chambers CA, Hopkins RO, Weaver LK, Key C: Cognitive and affective outcomes of more severe compared to less severe carbon monoxide poisoning. Brain Inj 2008; 22: 387–95 CrossRef MEDLINE
e16.
Kim DM, Lee IH, Park JY, Hwang SB, Yoo DS, Song CJ: Acute carbon monoxide poisoning: MR imaging findings with clinical correlation. Diagn Interv Imaging 2017; 98: 299–306 CrossRef MEDLINE
e17.
Keleş A, Demircan A, Kurtoğlu G: Carbon monoxide poisoning: how many patients do we miss? Eur J Emerg Med 2008; 15: 154–7.
e18.
Lippi G, Rastelli G, Meschi T, Borghi L, Cervellin G: Pathophysiology, clinics, diagnosis and treatment of heart involvement in carbon monoxide poisoning. Clin Biochem 2012; 45: 1278–85 CrossRef MEDLINE
e19.
Leitlinien: Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF e. V.). www.awmf.org (last accessed on 21 September 2018).
e20.
National Guideline Clearinghouse, Agency for Healthcare Research and Quality, Maryland, USA. www.guidelines.gov/ (last accessed on 21 September 2018).
e21.
International Guideline Library: The Guidelines International Network. Perthshire, Scotland. www.g-i-n.net/ (last accessed on 21 September 2018).
e22.
PubMed—National Library of Medicine. www.ncbi.nlm.nih.gov/pubmed/ (last accessed on 21 September 2018).
e23.
Cochrane Library. www.cochranelibrary.com (last accessed on 21 September 2018).
e24.
Deutsche Leitlinien-Bewertungsinstrument (DELBI). www.leitlinien.de/leitlinien-grundlagen/leitlinienbewertung/delbi (last accessed on 21 September 2018).
e25.
Semlitsch T, Blank WA, Kopp IB, Siering U, Siebenhofer A: Evaluating guidelines: a review of key quality criteria. Dtsch Arztebl Int 2015; 112: 471–8 VOLLTEXT
e26.
Oxford Centre for Evidence-based Medicine—levels of evidence (March 2009). www.cebm.net/2009/06/oxford-centre-evidence-based-medicine-levels-evidence-march-2009/ (last accessed on 21 September 2018).
e27.
Barker SJ, Tremper KK: The effect of carbon monoxide inhalation on pulse oximetry and transcutaneous PO2. Anesthesiology 1987; 66: 677–9 CrossRef
e28.
Bozeman WP, Myers RA, Barish RA: Confirmation of the pulse oximetry gap in carbon monoxide poisoning. Ann Emerg Med 1997; 30: 608–11 CrossRef
e29.
Barker SJ, Curry J, Redford D, Morgan S: Measurement of carboxyhemoglobin and methemoglobin by pulse oximetry: a human volunteer study. Anesthesiology 2006; 105: 892–7 CrossRef
e30.
Roth D, Herkner H, Schreiber W, et al.: Accuracy of noninvasive multiwave pulse oximetry compared with carboxyhemoglobin from blood gas analysis in unselected emergency department patients. Ann Emerg Med 2011; 58: 74–9 CrossRef MEDLINE
e31.
Touger M, Birnbaum A, Wang J, Chou K, Pearson D, Bijur P: Performance of the RAD-57 pulse CO-oximeter compared with standard laboratory carboxyhemoglobin measurement. Ann Emerg Med 2010; 56: 382–8 CrossRef MEDLINE
e32.
Bickler MP, Rhodes LJ: Accuracy of detection of carboxyhemoglobin and methemoglobin in human and bovine blood with an inexpensive, pocket-size infrared scanner. PLOS ONE 2018; 13: e0193891 CrossRef MEDLINE PubMed Central
e33.
Touger M, Gallagher EJ, Tyrell J: Relationship between venous and arterial carboxyhemoglobin levels in patients with suspected carbon monoxide poisoning. Ann Emerg Med 1995; 25: 481–3 CrossRef
e34.
Lopez DM, Weingarten-Arams JS, Singer LP, Conway EE: Relationship between arterial, mixed venous, and internal jugular carboxyhemoglobin concentrations at low, medium, and high concentrations in a piglet model of carbon monoxide toxicity. Crit Care Med 2000; 28: 1998–2001 CrossRef
e35.
Goldbaum LR, Orellano T, Dergal E: Mechanism of the toxic action of carbon monoxide. Ann Clin Lab Sci 1976; 6: 372–6 MEDLINE
e36.
Baud FJ: Akute Vergiftungen mit Kohlenmonoxid und Zyaniden. Ther Umsch 2009; 66: 387–97 CrossRef MEDLINE
e37.
Kaiser G, Schaper A: Akute Kohlenmonoxidvergiftung. Notf Rettungsmedizin 2012; 15: 429–35.
e38.
Pace R, Bon Homme M, Hoffman RS, Lugassy D: Effects of hydroxocobalamin on carboxyhemoglobin measured under physiologic and pathologic conditions. Clin Toxicol Phila Pa 2014; 52: 647–50 CrossRef MEDLINE
e39.
Baud F: Clarifications regarding interference of hydroxocobalamin with carboxyhemoglobin measurements in victims of smoke inhalation. Ann Emerg Med 2007; 50: 625–6; author reply 626 CrossRef MEDLINE
e40.
Lee J, Mukai D, Kreuter K, Mahon S, Tromberg B, Brenner M: Potential interference by hydroxocobalamin on cooximetry hemoglobin measurements during cyanide and smoke inhalation treatments. Ann Emerg Med 2007; 49: 802–5 CrossRef MEDLINE
e41.
Livshits Z, Lugassy DM, Shawn LK, Hoffman RS: Falsely low carboxyhemoglobin level after hydroxocobalamin therapy. N Engl J Med 2012; 367: 1270–1 CrossRef MEDLINE
e42.
Roderique JD, Josef CS, Newcomb AH, Reynolds PS, Somera LG, Spiess BD: Preclinical evaluation of injectable reduced hydroxocobalamin as an antidote to acute carbon monoxide poisoning. J Trauma Acute Care Surg 2015; 79(4 Suppl 2): S116–20 MEDLINE PubMed Central
e43.
Moallem SA, Mohamadpour AH, Abnous K, et al.: Erythropoietin in the treatment of carbon monoxide neurotoxicity in rat. Food Chem Toxicol 2015; 86: 56–64 CrossRef MEDLINE
e44.
Rezaee MA, Mohammadpour AH, Imenshahidi M, et al.: Protective effect of erythropoietin on myocardial apoptosis in rats exposed to carbon monoxide. Life Sci 2016; 148: 118–24 CrossRef MEDLINE
e45.
Hashemzaei M, Barani AK, Iranshahi M, et al.: Effects of resveratrol on carbon monoxide-induced cardiotoxicity in rats. Environ Toxicol Pharmacol 2016; 46: 110–5 CrossRef MEDLINE
e46.
Azarov I, Wang L, Rose JJ, et al.: Five-coordinate H64Q neuroglobin as a ligand-trap antidote for carbon monoxide poisoning. Sci Transl Med 2016; 8: 368ra173.
e47.
Weaver LK, Howe S, Hopkins R, Chan KJ: Carboxyhemoglobin half-life in carbon monoxide-poisoned patients treated with 100% oxygen at atmospheric pressure. Chest 2000; 117: 801–8 CrossRef
e48.
Pace N, Strajman E, Walker EL: Acceleration of carbon monoxide elimination in man by high pressure oxygen. Science 1950; 111: 652–4 CrossRef
e49.
Prockop LD, Chichkova RI: Carbon monoxide intoxication: an updated review. J Neurol Sci 2007; 262: 122–30 CrossRef MEDLINE
e50.
Thom SR: Antagonism of carbon monoxide-mediated brain lipid peroxidation by hyperbaric oxygen. Toxicol Appl Pharmacol 1990; 105: 340–4 CrossRef
e51.
Jurič DM, Šuput D, Brvar M: Hyperbaric oxygen preserves neurotrophic activity of carbon monoxide-exposed astrocytes. Toxicol Lett 2016; 253: 1–6 CrossRef MEDLINE
e52.
Thom SR, Bhopale VM, Fisher D: Hyperbaric oxygen reduces delayed immune-mediated neuropathology in experimental carbon monoxide toxicity. Toxicol Appl Pharmacol 2006; 213: 152–9 CrossRef MEDLINE
e53.
Garrabou G, Inoriza JM, Morén C, et al.: Mitochondrial injury in human acute carbon monoxide poisoning: the effect of oxygen treatment. J Environ Sci Health Part C Environ Carcinog Ecotoxicol Rev 2011; 29: 32–51 CrossRef MEDLINE
e54.
Meirovithz E, Sonn J, Mayevsky A: Effect of hyperbaric oxygenation on brain hemodynamics, hemoglobin oxygenation and mitochondrial NADH. Brain Res Rev 2007; 54: 294–304 CrossRef MEDLINE
e55.
Liu WC, Yang SN, Wu CWJ, Chen LW, Chan JYH: Hyperbaric oxygen therapy alleviates carbon monoxide poisoning-induced delayed memory impairment by preserving brain-derived neurotrophic factor-dependent hippocampal neurogenesis. Crit Care Med 2016; 44: e25–39 CrossRef MEDLINE
e56.
Xue L, Wang WL, Li Y, et al.: Effects of hyperbaric oxygen on hippocampal neuronal apoptosis in rats with acute carbon monoxide poisoning. Undersea Hyperb Med 2017; 44: 121–31 CrossRef MEDLINE
e57.
Mutluoglu M, Metin S, Arziman I, Uzun G, Yildiz S: The use of hyperbaric oxygen therapy for carbon monoxide poisoning in Europe. Undersea Hyperb Med 2016; 43: 49–56 MEDLINE
e58.
Bassler D, Briel M, Montori VM, et al.: Stopping randomized trials early for benefit and estimation of treatment effects: Systematic review and meta-regression analysis. JAMA 2010; 303: 1180–7 CrossRef MEDLINE
e59.
Hill EP, Hill JR, Power GG, Longo LD: Carbon monoxide exchanges between the human fetus and mother: a mathematical model. Am J Physiol 1977; 232: H311–23 MEDLINE
e60.
Longo LD, Hill EP: Carbon monoxide uptake and elimination in fetal and maternal sheep. Am J Physiol 1977; 232: H324–30 MEDLINE
e61.
Smith KA, Bryce S: Trauma in the pregnant patient: an evidence-based approach to management. Emerg Med Pract 2013; 15: 1–18.
e62.
Roderique EJD, Gebre-Giorgis AA, Stewart DH, Feldman MJ, Pozez AL: Smoke inhalation injury in a pregnant patient. A literature review of the evidence and current best practices in the setting of a classic case. J Burn Care Res 2012; 33: 624–33 CrossRef MEDLINE
e63.
Gesundheitsberichterstattung des Bundes – gemeinsam getragen von RKI und Destatis. Diagnose T58 (ICD). Tabelle: Sterbefälle. www.gbe-bund.de/ (last accessed on 21 September 2018).
Department of Anaesthesiology and Intensive Care University Hospital Bonn (UKB), Bonn:
Dr. med. Lars Eichhorn, Dr. med. Marcus Thudium
Clinic for Anesthesiology and Intensive Care Medicine, Hannover Medical School:
Prof. Dr. med. Björn Jüttner
Treating carbon monoxide poisoning
Treating carbon monoxide poisoning
Box 1
Treating carbon monoxide poisoning
Decrease in carboxyhemoglobin (COHb) under different therapeutic conditions (2).
Decrease in carboxyhemoglobin (COHb) under different therapeutic conditions (2).
Figure
Decrease in carboxyhemoglobin (COHb) under different therapeutic conditions (2).
Key messages
Selection of larger studies of the effects of carbon monoxide on the health of patients
Selection of larger studies of the effects of carbon monoxide on the health of patients
Table 1
Selection of larger studies of the effects of carbon monoxide on the health of patients
Contents and levels of evidence of identified recommendations and guidelines
Contents and levels of evidence of identified recommendations and guidelines
Table 2
Contents and levels of evidence of identified recommendations and guidelines
Search strategy
Search strategy
eBox
Search strategy
Cases of carbon monoxide poisoning in Germany (ICD 10: T58, inpatients) (e63)
Cases of carbon monoxide poisoning in Germany (ICD 10: T58, inpatients) (e63)
eTable
Cases of carbon monoxide poisoning in Germany (ICD 10: T58, inpatients) (e63)
1.Eichhorn L, Michaelis D, Kemmerer M, Jüttner B, Tetzlaff K: Carbon monoxide poisoning from waterpipe smoking: a retrospective cohort study. Clin Toxicol Phila Pa 2018; 56: 264–72 CrossRef MEDLINE
2.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 CrossRef MEDLINE PubMed Central
3.Committee on Acute Exposure Guideline Levels; Committee on Toxicology; National Research Council. Acute exposure guideline levels for selected airborne chemicals: volume 8. www.epa.gov/sites/production/files/2014-11/documents/carbon_monoxide_final_volume8_2010.pdf (last accessed on 21 September 2018).
4.Culnan DM, Craft-Coffman B, Bitz GH, et al.: Carbon monoxide and cyanide poisoning in the burned pregnant patient: an indication for hyperbaric oxygen therapy. Ann Plast Surg 2018; 80(3 Suppl 2): 106–12 CrossRef
5.Chiew AL, Buckley NA: Carbon monoxide poisoning in the 21st century. Crit Care 2014; 18: 221 CrossRef PubMed Central
6.Roderique JD, Josef CS, Feldman MJ, Spiess BD: A modern literature review of carbon monoxide poisoning theories, therapies, and potential targets for therapy advancement. Toxicology 2015; 334: 45–58 CrossRef MEDLINE
7.Weaver LK: Carbon monoxide poisoning. N Engl J Med 2009; 360: 1217–25 CrossRef MEDLINE
8.Hampson NB, Dunn SL, UHMCS/CDC CO Poisoning Surveillance Group: Symptoms of carbon monoxide poisoning do not correlate with the initial carboxyhemoglobin level. Undersea Hyperb Med 2012; 39: 657–65 MEDLINE
9.Pepe G, Castelli M, Nazerian P, et al.: Delayed neuropsychological sequelae after carbon monoxide poisoning: predictive risk factors in the emergency department. A retrospective study. Scand J Trauma Resusc Emerg Med 2011; 19: 16 CrossRef MEDLINE PubMed Central
10.Weaver LK, Hopkins RO, Chan KJ, et al.: Hyperbaric oxygen for acute carbon monoxide poisoning. N Engl J Med 2002; 347: 1057–67 CrossRef MEDLINE
11.Wong CS, Lin YC, Hong LY, et al.: Increased long-term risk of dementia in patients with carbon monoxide poisoning. Medicine (Baltimore) 2016; 95: e2549 CrossRef MEDLINE PubMed Central
12.Lettow I, Hoffmann A, Burmeister HP, Toepper R: [Delayed neuropsychological sequelae after carbon monoxide poisoning]. Fortschr Neurol Psychiatr 2018; 86: 342–7 CrossRef CrossRef MEDLINE
13.Satran D, Henry CR, Adkinson C, Nicholson CI, Bracha Y, Henry TD: Cardiovascular manifestations of moderate to severe carbon monoxide poisoning. J Am Coll Cardiol 2005; 45: 1513–6 CrossRef MEDLINE
14.Henry CR, Satran D, Lindgren B, Adkinson C, Nicholson CI, Henry TD: Myocardial injury and long-term mortality following moderate to severe carbon monoxide poisoning. JAMA 2006; 295: 398–402 CrossRef MEDLINE
15.Wong CS, Lin YC, Sung LC, et al.: Increased long-term risk of major adverse cardiovascular events in patients with carbon monoxide poisoning: a population-based study in Taiwan. PLoS ONE 2017; 12: e0176465 CrossRef MEDLINE PubMed Central
16.Lee FY, Chen WK, Lin CL, Kao CH: Carbon monoxide poisoning and subsequent cardiovascular disease risk. Medicine (Baltimore) 2015; 94: e624 CrossRef MEDLINE PubMed Central
17.Huang CC, Chung MH, Weng SF, et al.: Long-term prognosis of patients with carbon monoxide poisoning: a nationwide cohort study. PLoS ONE 2014; 9: e105503 CrossRef MEDLINE PubMed Central
18.Kaya H, Coşkun A, Beton O, et al.: COHgb levels predict the long-term development of acute myocardial infarction in CO poisoning. Am J Emerg Med 2016; 34: 840–4 CrossRef MEDLINE
19.Huang CC, Ho CH, Chen YC, et al.: Increased risk for diabetes mellitus in patients with carbon monoxide poisoning. Oncotarget 2017; 8: 63680–90 CrossRef
20.Wolf SJ, Maloney GE, Shih RD, Shy BD, Brown MD: Clinical policy: critical issues in the evaluation and management of adult patients presenting to the emergency department with acute carbon monoxide poisoning. Ann Emerg Med 2017; 69: 98–107 CrossRef MEDLINE
21.Buckley NA, Juurlink DN, Isbister G, Bennett MH, Lavonas EJ: Hyperbaric oxygen for carbon monoxide poisoning. Cochrane Database Syst Rev 2011; 4: CD002041 CrossRef
22.Mintegi S, Clerigue N, Tipo V, et al.: Pediatric cyanide poisoning by fire smoke inhalation: a European expert consensus. Pediatr Emerg Care 2013; 29: 1234–40 CrossRef MEDLINE
23.Truhlář A, Deakin CD, Soar J, et al.: Kreislaufstillstand in besonderen Situationen. Notf Rettungsmedizin 2015; 18: 833–903 CrossRef
24.Mathieu D, Marroni A, Kot J: Tenth European consensus conference on hyperbaric medicine: recommendations for accepted and non-accepted clinical indications and practice of hyperbaric oxygen treatment. Diving Hyperb Med 2017; 47: 24–32 CrossRef MEDLINE
25.Hampson NB, Piantadosi CA, Thom SR, Weaver LK: Practice recommendations in the diagnosis, management, and prevention of carbon monoxide poisoning. Am J Respir Crit Care Med 2012; 186: 1095–101 CrossRef MEDLINE
26.Hampson NB, Hauff NM: Risk factors for short-term mortality from carbon monoxide poisoning treated with hyperbaric oxygen. Crit Care Med 2008; 36: 2523–7 CrossRef MEDLINE
27.Weaver LK, Valentine KJ, Hopkins RO: Carbon monoxide poisoning: risk factors for cognitive sequelae and the role of hyperbaric oxygen. Am J Respir Crit Care Med 2007; 176: 491–7 CrossRef MEDLINE
28.Raphael JC, Elkharrat D, Jars-Guincestre MC, et al.: Trial of normobaric and hyperbaric oxygen for acute carbon monoxide intoxication. Lancet Lond Engl 1989; 2: 414–9 CrossRef
29.Ducassé JL, Celsis P, Marc-Vergnes JP: Non-comatose patients with acute carbon monoxide poisoning: hyperbaric or normobaric oxygenation? Undersea Hyperb Med 1995; 22: 9–15 MEDLINE
30.Thom SR: Oxidative stress is fundamental to hyperbaric oxygen therapy. J Appl Physiol (1985) 2009; 106: 988–95 CrossRef MEDLINE PubMed Central
31.Scheinkestel CD, Bailey M, Myles PS, et al.: Hyperbaric or 337 normobaric oxygen for acute carbon monoxide poisoning: a randomised controlled clinical trial. Med J Aust 1999; 170: 203–10 MEDLINE
32.Annane D, Chadda K, Gajdos P, Jars-Guincestre MC, Chevret S, Raphael JC: Hyperbaric oxygen therapy for acute domestic carbon monoxide poisoning: two randomized controlled trials. Intensive Care Med 2011; 37: 486–92 CrossRef MEDLINE
33.Chang YC, Lee HY, Huang JL, Chiu CH, Chen CL, Wu CT: Risk factors and outcome analysis in children with carbon monoxide poisoning. Pediatr Neonatol 2017; 58: 171–7 CrossRef MEDLINE
34.Huang CC, Ho CH, Chen YC, et al.: Hyperbaric oxygen therapy is associated with lower short and long-term mortality in patients with carbon monoxide poisoning. Chest 2017; 152: 943–53 CrossRef MEDLINE
35.Rose JJ, Nouraie M, Gauthier MC, et al.: Clinical outcomes and mortality impact of hyperbaric oxygen therapy in patients with carbon monoxide poisoning. Crit Care Med 2018; 46: e649–55 CrossRef MEDLINE
36.Thom SR, Taber RL, Mendiguren II, Clark JM, Hardy KR, Fisher AB: Delayed neuropsychologic sequelae after carbon monoxide poisoning: prevention by treatment with hyperbaric oxygen. Ann Emerg Med 1995; 25: 474–80 CrossRef
37.Meert KL, Heidemann SM, Sarnaik AP: Outcome of children with carbon monoxide poisoning treated with normobaric oxygen. J Trauma 1998; 44: 149–54 CrossRef
38.Chou KJ, Fisher JL, Silver EJ: Characteristics and outcome of children with carbon monoxide poisoning with and without smoke exposure referred for hyperbaric oxygen therapy. Pediatr Emerg Care 2000; 16: 151–5 CrossRef
39.Akcan Yildiz L, Gultekingil A, Kesici S, Bayrakci B, Teksam O: Predictors of severe clinical course in children with carbon monoxide poisoning. Pediatr Emerg Care 2018 (Epub ahead of print: doi: 10.1097/PEC.0000000000001580 CrossRef
40.Rodkey FL, O’Neal JD, Collison HA, Uddin DE: Relative affinity of hemoglobin S and hemoglobin A for carbon monoxide and oxygen. Clin Chem 1974; 20: 83–4 MEDLINE
e1.Penney D, Benignus V, Kephalopoulos S, Kotzias D, Kleinman M, Verrier A: WHO guidelines for indoor air quality: selected pollutants. Carbon monoxide. World Health Organization 2010. www.ncbi.nlm.nih.gov/books/NBK138710/ (last accessed on 21 September 2018).
e2.von Rappard J, Schönenberger M, Bärlocher L: Carbon monoxide poisoning following use of a water pipe/hookah. Dtsch Arztebl Int 2014; 111: 674–9 VOLLTEXT
e3.Hampson NB: Cost of accidental carbon monoxide poisoning: a preventable expense. Prev Med Rep 2016; 3: 21–4 CrossRef MEDLINE PubMed Central
e4.Gesundheitsberichterstattung des Bundes – gemeinsam getragen von RKI und Destatis. Diagnose T58 (ICD). Tabelle: Diagnosedaten der Krankenhäuser Deutschland. www.gbe-bund.de/ (last accessed on 21 September 2018).
e5.Hampson NB: U.S. mortality due to carbon monoxide poisoning, 1999–2014. Accidental and intentional deaths. Ann Am Thorac Soc 2016; 13: 1768–74.
e6.Joels N, Pugh LG: The carbon monoxide dissociation curve of human blood. J Physiol 1958; 142: 63–77 CrossRef
e7.Bruce EN, Bruce MC, Erupaka K: Prediction of the rate of uptake of carbon monoxide from blood by extravascular tissues. Respir Physiol Neurobiol 2008; 161: 142–59 CrossRef MEDLINE PubMed Central
e8.Kao LW, Nañagas KA: Carbon monoxide poisoning. Emerg Med Clin North Am 2004; 22: 985–1018 CrossRef MEDLINE
e9.Harper A, Croft-Baker J: Carbon monoxide poisoning: undetected by both patients and their doctors. Age Ageing 2004; 33: 105–9 CrossRef MEDLINE
e10.Tomaszewski C: Carbon monoxide poisoning. Early awareness and intervention can save lives. Postgrad Med 1999; 105: 39–40, 43–48, 50.
e11.Kwon OY, Chung SP, Ha YR, Yoo IS, Kim SW: Delayed postanoxic encephalopathy after carbon monoxide poisoning. Emerg Med J 2004; 21: 250–1 CrossRef PubMed Central
e12.Hsiao CL, Kuo HC, Huang CC: Delayed encephalopathy after carbon monoxide intoxication—long-term prognosis and correlation of clinical manifestations and neuroimages. Acta Neurol Taiwanica 2004; 13: 64–70.
e13.Parkinson RB, Hopkins RO, Cleavinger HB, et al.: White matter hyperintensities and neuropsychological outcome following carbon monoxide poisoning. Neurology 2002; 58: 1525–32 CrossRef MEDLINE
e14.Lim PJ, Shikhare SN, Peh WCG: Clinics in diagnostic imaging (154). Carbon monoxide (CO) poisoning. Singapore Med J 2014; 55: 405–10 CrossRef MEDLINE PubMed Central
e15.Chambers CA, Hopkins RO, Weaver LK, Key C: Cognitive and affective outcomes of more severe compared to less severe carbon monoxide poisoning. Brain Inj 2008; 22: 387–95 CrossRef MEDLINE
e16.Kim DM, Lee IH, Park JY, Hwang SB, Yoo DS, Song CJ: Acute carbon monoxide poisoning: MR imaging findings with clinical correlation. Diagn Interv Imaging 2017; 98: 299–306 CrossRef MEDLINE
e17.Keleş A, Demircan A, Kurtoğlu G: Carbon monoxide poisoning: how many patients do we miss? Eur J Emerg Med 2008; 15: 154–7.
e18.Lippi G, Rastelli G, Meschi T, Borghi L, Cervellin G: Pathophysiology, clinics, diagnosis and treatment of heart involvement in carbon monoxide poisoning. Clin Biochem 2012; 45: 1278–85 CrossRef MEDLINE
e19.Leitlinien: Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF e. V.). www.awmf.org (last accessed on 21 September 2018).
e20.National Guideline Clearinghouse, Agency for Healthcare Research and Quality, Maryland, USA. www.guidelines.gov/ (last accessed on 21 September 2018).
e21. International Guideline Library: The Guidelines International Network. Perthshire, Scotland. www.g-i-n.net/ (last accessed on 21 September 2018).
e22.PubMed—National Library of Medicine. www.ncbi.nlm.nih.gov/pubmed/ (last accessed on 21 September 2018).
e23.Cochrane Library. www.cochranelibrary.com (last accessed on 21 September 2018).
e24.Deutsche Leitlinien-Bewertungsinstrument (DELBI). www.leitlinien.de/leitlinien-grundlagen/leitlinienbewertung/delbi (last accessed on 21 September 2018).
e25.Semlitsch T, Blank WA, Kopp IB, Siering U, Siebenhofer A: Evaluating guidelines: a review of key quality criteria. Dtsch Arztebl Int 2015; 112: 471–8 VOLLTEXT
e26.Oxford Centre for Evidence-based Medicine—levels of evidence (March 2009). www.cebm.net/2009/06/oxford-centre-evidence-based-medicine-levels-evidence-march-2009/ (last accessed on 21 September 2018).
e27.Barker SJ, Tremper KK: The effect of carbon monoxide inhalation on pulse oximetry and transcutaneous PO2. Anesthesiology 1987; 66: 677–9 CrossRef
e28.Bozeman WP, Myers RA, Barish RA: Confirmation of the pulse oximetry gap in carbon monoxide poisoning. Ann Emerg Med 1997; 30: 608–11 CrossRef
e29.Barker SJ, Curry J, Redford D, Morgan S: Measurement of carboxyhemoglobin and methemoglobin by pulse oximetry: a human volunteer study. Anesthesiology 2006; 105: 892–7 CrossRef
e30.Roth D, Herkner H, Schreiber W, et al.: Accuracy of noninvasive multiwave pulse oximetry compared with carboxyhemoglobin from blood gas analysis in unselected emergency department patients. Ann Emerg Med 2011; 58: 74–9 CrossRef MEDLINE
e31.Touger M, Birnbaum A, Wang J, Chou K, Pearson D, Bijur P: Performance of the RAD-57 pulse CO-oximeter compared with standard laboratory carboxyhemoglobin measurement. Ann Emerg Med 2010; 56: 382–8 CrossRef MEDLINE
e32.Bickler MP, Rhodes LJ: Accuracy of detection of carboxyhemoglobin and methemoglobin in human and bovine blood with an inexpensive, pocket-size infrared scanner. PLOS ONE 2018; 13: e0193891 CrossRef MEDLINE PubMed Central
e33.Touger M, Gallagher EJ, Tyrell J: Relationship between venous and arterial carboxyhemoglobin levels in patients with suspected carbon monoxide poisoning. Ann Emerg Med 1995; 25: 481–3 CrossRef
e34.Lopez DM, Weingarten-Arams JS, Singer LP, Conway EE: Relationship between arterial, mixed venous, and internal jugular carboxyhemoglobin concentrations at low, medium, and high concentrations in a piglet model of carbon monoxide toxicity. Crit Care Med 2000; 28: 1998–2001 CrossRef
e35.Goldbaum LR, Orellano T, Dergal E: Mechanism of the toxic action of carbon monoxide. Ann Clin Lab Sci 1976; 6: 372–6 MEDLINE
e36.Baud FJ: Akute Vergiftungen mit Kohlenmonoxid und Zyaniden. Ther Umsch 2009; 66: 387–97 CrossRef MEDLINE
e37.Kaiser G, Schaper A: Akute Kohlenmonoxidvergiftung. Notf Rettungsmedizin 2012; 15: 429–35.
e38.Pace R, Bon Homme M, Hoffman RS, Lugassy D: Effects of hydroxocobalamin on carboxyhemoglobin measured under physiologic and pathologic conditions. Clin Toxicol Phila Pa 2014; 52: 647–50 CrossRef MEDLINE
e39.Baud F: Clarifications regarding interference of hydroxocobalamin with carboxyhemoglobin measurements in victims of smoke inhalation. Ann Emerg Med 2007; 50: 625–6; author reply 626 CrossRef MEDLINE
e40.Lee J, Mukai D, Kreuter K, Mahon S, Tromberg B, Brenner M: Potential interference by hydroxocobalamin on cooximetry hemoglobin measurements during cyanide and smoke inhalation treatments. Ann Emerg Med 2007; 49: 802–5 CrossRef MEDLINE
e41. Livshits Z, Lugassy DM, Shawn LK, Hoffman RS: Falsely low carboxyhemoglobin level after hydroxocobalamin therapy. N Engl J Med 2012; 367: 1270–1 CrossRef MEDLINE
e42.Roderique JD, Josef CS, Newcomb AH, Reynolds PS, Somera LG, Spiess BD: Preclinical evaluation of injectable reduced hydroxocobalamin as an antidote to acute carbon monoxide poisoning. J Trauma Acute Care Surg 2015; 79(4 Suppl 2): S116–20 MEDLINE PubMed Central
e43.Moallem SA, Mohamadpour AH, Abnous K, et al.: Erythropoietin in the treatment of carbon monoxide neurotoxicity in rat. Food Chem Toxicol 2015; 86: 56–64 CrossRef MEDLINE
e44.Rezaee MA, Mohammadpour AH, Imenshahidi M, et al.: Protective effect of erythropoietin on myocardial apoptosis in rats exposed to carbon monoxide. Life Sci 2016; 148: 118–24 CrossRef MEDLINE
e45.Hashemzaei M, Barani AK, Iranshahi M, et al.: Effects of resveratrol on carbon monoxide-induced cardiotoxicity in rats. Environ Toxicol Pharmacol 2016; 46: 110–5 CrossRef MEDLINE
e46.Azarov I, Wang L, Rose JJ, et al.: Five-coordinate H64Q neuroglobin as a ligand-trap antidote for carbon monoxide poisoning. Sci Transl Med 2016; 8: 368ra173.
e47.Weaver LK, Howe S, Hopkins R, Chan KJ: Carboxyhemoglobin half-life in carbon monoxide-poisoned patients treated with 100% oxygen at atmospheric pressure. Chest 2000; 117: 801–8 CrossRef
e48.Pace N, Strajman E, Walker EL: Acceleration of carbon monoxide elimination in man by high pressure oxygen. Science 1950; 111: 652–4 CrossRef
e49.Prockop LD, Chichkova RI: Carbon monoxide intoxication: an updated review. J Neurol Sci 2007; 262: 122–30 CrossRef MEDLINE
e50.Thom SR: Antagonism of carbon monoxide-mediated brain lipid peroxidation by hyperbaric oxygen. Toxicol Appl Pharmacol 1990; 105: 340–4 CrossRef
e51. Jurič DM, Šuput D, Brvar M: Hyperbaric oxygen preserves neurotrophic activity of carbon monoxide-exposed astrocytes. Toxicol Lett 2016; 253: 1–6 CrossRef MEDLINE
e52.Thom SR, Bhopale VM, Fisher D: Hyperbaric oxygen reduces delayed immune-mediated neuropathology in experimental carbon monoxide toxicity. Toxicol Appl Pharmacol 2006; 213: 152–9 CrossRef MEDLINE
e53.Garrabou G, Inoriza JM, Morén C, et al.: Mitochondrial injury in human acute carbon monoxide poisoning: the effect of oxygen treatment. J Environ Sci Health Part C Environ Carcinog Ecotoxicol Rev 2011; 29: 32–51 CrossRef MEDLINE
e54.Meirovithz E, Sonn J, Mayevsky A: Effect of hyperbaric oxygenation on brain hemodynamics, hemoglobin oxygenation and mitochondrial NADH. Brain Res Rev 2007; 54: 294–304 CrossRef MEDLINE
e55.Liu WC, Yang SN, Wu CWJ, Chen LW, Chan JYH: Hyperbaric oxygen therapy alleviates carbon monoxide poisoning-induced delayed memory impairment by preserving brain-derived neurotrophic factor-dependent hippocampal neurogenesis. Crit Care Med 2016; 44: e25–39 CrossRef MEDLINE
e56.Xue L, Wang WL, Li Y, et al.: Effects of hyperbaric oxygen on hippocampal neuronal apoptosis in rats with acute carbon monoxide poisoning. Undersea Hyperb Med 2017; 44: 121–31 CrossRef MEDLINE
e57.Mutluoglu M, Metin S, Arziman I, Uzun G, Yildiz S: The use of hyperbaric oxygen therapy for carbon monoxide poisoning in Europe. Undersea Hyperb Med 2016; 43: 49–56 MEDLINE
e58. Bassler D, Briel M, Montori VM, et al.: Stopping randomized trials early for benefit and estimation of treatment effects: Systematic review and meta-regression analysis. JAMA 2010; 303: 1180–7 CrossRef MEDLINE
e59.Hill EP, Hill JR, Power GG, Longo LD: Carbon monoxide exchanges between the human fetus and mother: a mathematical model. Am J Physiol 1977; 232: H311–23 MEDLINE
e60.Longo LD, Hill EP: Carbon monoxide uptake and elimination in fetal and maternal sheep. Am J Physiol 1977; 232: H324–30 MEDLINE
e61.Smith KA, Bryce S: Trauma in the pregnant patient: an evidence-based approach to management. Emerg Med Pract 2013; 15: 1–18.
e62.Roderique EJD, Gebre-Giorgis AA, Stewart DH, Feldman MJ, Pozez AL: Smoke inhalation injury in a pregnant patient. A literature review of the evidence and current best practices in the setting of a classic case. J Burn Care Res 2012; 33: 624–33 CrossRef MEDLINE
e63.Gesundheitsberichterstattung des Bundes – gemeinsam getragen von RKI und Destatis. Diagnose T58 (ICD). Tabelle: Sterbefälle. www.gbe-bund.de/ (last accessed on 21 September 2018).