Predicting acute brain lesions on magnetic resonance imaging in acute carbon monoxide poisoning: a multicenter prospective observational study

In this study, 21.2% of patients with acute CO poisoning developed ABLs on MRI. High levels of TnI and WBC, present of LOC, GCS score < 9 at presentation, longer CO exposure duration, and older age were independently associated with ABLs on brain MRI.

Previous studies on the factors predicting the development of ABLs on MRI in patients with acute CO poisoning were performed in single institutions and had small sample sizes^22,23,24. Our study was conducted at two institutions and included a relatively larger number of patients compared to previous studies. Although the registry was not purposely established for studying the development of ABLs on MRI, the strength of this study lies in its inclusion of prospective registry data with sufficient information on the general characteristics and prognostic variables of patients with acute CO poisoning. Moreover, we utilized data that had been minimized for missing values (Appendix Table 6). In the HBOT protocol, Asan Medical Center had a 30-min maintenance time and Hanyang University Hospital had a 1-h maintenance time, but other variables in the registry remained the same, indicating low heterogeneity. The schedule of MRI scans, which could potentially affect the diagnosis of ABLs on MRI, exhibited similar practice in both hospitals, with scans performed within the period of 24 to 48 h after initial CO exposure.

Reactive oxygen species produced as a result of acute CO poisoning have been found to cause damage to the endothelium of the coronary artery by affecting platelet aggregation^25,26. Additionally, hypoxia caused by COHb impairs myocardial cell respiration, leading to direct damage to cardiac muscle²⁷. TnI levels in the blood are used as an indicator of myocardial damage; an increase in TnI levels in patients with acute CO poisoning is associated with an increased risk of DNS²⁵. Kim et al. reported that the initial TnI level at ED (aOR 13.66, 95% CI: 1.42–141.83) was an independent predictor for ABLs. The AUC for initial TnI at ED was 0.761 (95% CI: 0.64–0.88) and the optimal cut-off value was 0.105 ng/mL, with a sensitivity of 70.4% and a specificity of 79.2%²³. Similarly, in our study, TnI independently predicted the occurrence of ABLs on MRI, with an AUC of 0.853. MRI timing was relatively late in the previous study, which included patients who underwent MRI within 240 h of CO exposure with a median (IQR) time of 53.21 h (39.50–67.45), whereas our study conducted MRIs 24–48 h after CO exposure and had a larger sample size (1034 patients versus 103 patients). Hence, it is probable that the differences in methodology contributed to some discrepancy in the results.

Kim et al. reported that CO exposure duration > 5 h was a predictor of ABLs in CO poisoning patients with altered mental status (aOR 7.08, 95% CI: 3.46–15.51), with an AUC of 0.815, and sensitivity and specificity of 79.1% and 69.9%, respectively²⁴. In line with previous research, our study showed that a longer duration of CO exposure was found to be an independent predictor of ABLs on MRI among patients exposed to CO poisoning. Notably, our results align with previous study, further supporting the established threshold of more than 5 h as the optimal cut-off point²⁴. Moreover, the findings indicated that exposure to CO for more than 5 h posed a risk for occurrence of ABLs in all patients affected by CO poisoning, regardless of their mental state.

CO poisoning leads to COHb-induced hypoxia, dysfunction of mitochondria, and increased platelet activation. Activated platelets can stimulate neutrophils to degranulate and release myeloperoxidase, thereby exacerbating the inflammatory cascade^13,28. An increase in WBC count is a cardinal sign of the presence of acute inflammation²⁹. The experimental study showed that CO-mediated DNS is linked to an adaptive immunological response³⁰. Pepe et al. reported that leukocytosis (aOR 3.31; CI 95%: 1.02–10.71) is independent prognostic factor in CO poisoning patients³¹. A recent study showed that abnormal WBC count (aOR 2.57, 95% CI: 1.19–5.70) is predictor of ABL in CO poisoning patients with an altered mental status²⁴. Similarly, results of this study demonstrated that an elevated WBC count is predictor of ABL in CO poisoning patients.

Previous studies have suggested an association between a GCS score < 9 and the development of DNS and/or ABLs^22,23,32. Results from our study were comparable. A GCS score < 9 is clinically useful not only as a predictor of DNS, but also as a predictor of ABLs. LOC has been reported as a predictive factor for DNS, but not as an independent predictor of ABLs^22,23,24,33. However, our study showed that LOC was a statistically significant independent predictor of ABL. O’Donnell et al. evaluated 19 patients who had suffered from CO poisoning and subsequently experienced LOC and found that 68% (13 out of 19) showed abnormalities in their brain MRI scans³⁴. Among the 13 patients who exhibited abnormalities on brain MRI, it was observed that 23% (3 out of 13) had a GCS score > 9 ³⁴. Changes in the mental status of patients with CO poisoning, which is often transient in nature, suggests that the presence of a LOC can serve as a useful clinical indicator for predicting the development of both DNS and ABL.

HBOT rapidly eliminates CO from circulatory system and results in beneficial outcomes on CO-induced brain injury. These benefits include reducing lipid peroxidation and decreasing the migration of endothelial leukocytes³⁵. Consequently, HBOT is thought to be beneficial for preventing DNS in patients with CO poisoning which is suggested to be an important part of early intervention^33,35,36. However, the optimal number of HBOT sessions for patients with CO poisoning remains controversial³⁷. A previous nationwide cohort study reported that patients who received two or more sessions of HBOT showed better clinical outcomes in comparison to those who received a singular session of therapy³⁸. Moreover, a case report has been showed that CO poisoning patient who recovered from the paroxysmal sympathetic hyperactivity after receiving repetitive HBOT³⁹. Therefore, the administration of multiple sessions of HBOT may be helpful for patients with severe carbon monoxide poisoning. The presence of ABL is a strong prognostic indicator for patients with CO poisoning, and predicting its occurrence can help decisions regarding therapeutic interventions¹⁵. Unfortunately, our data did not include information on the occurrence of DNS, so we could not analyze the association between HBOT and the occurrence of DNS.

This study had several limitations. First, although the study was conducted using prospectively collected data from two tertiary hospitals, it is difficult to generalize the results of our study to all CO poisoning patients. Second, since not all CO poisoning patients underwent a brain MRI, there is a potential risk of selection bias. It is difficult to establish that the findings of this study adequately reflected the general characteristics of all acute CO poisoning patients because approximately one-third (530 out of 1603) of the enrolled patients were excluded because brain MRI was not performed. The recommendation for a brain MRI scan among patients enrolled in registry was not conducted selectively. Instead, all patients were recommended to receive an MRI. The majority of patients who declined the MRI scan cited financial concerns. Third, the possible effects of co-ingestion of alcohol or drugs were not considered. In the case of CO poisoning as a suicide method, patients often consume alcohol or drugs⁴⁰, which may concurrently have an effect on the patient’s altered state of consciousness. Due to the effect of co-ingested alcohol or drugs, the initial GCS score upon presentation to the ED may have been overestimated. Nevertheless, the levels of TnI and WBC are unaffected by alcohol and drug use and can be used as predictors of ABLs on MRI.

In summary, it may be useful to predict the occurrence of ABLs on brain MRI using TnI, GCS score, LOC, CO exposure duration, and WBC count in patients with acute CO poisoning. Moreover, it may help clinicians to decide if a patient should be transferred to an institution with MRI or HBOT capability. However, patients who did not undergo MRI were excluded from the analysis. Therefore, well-designed, large-scale studies are needed for more conclusive results.