Predictors for Delayed Encephalopathy Following Acute Carbon Monoxide Poisoning

Kaoru Kudo; Kotaro Otsuka; Junko Yagi; Katsumi Sanjo; Noritaka Koizumi; Atsuhiko Koeda; Miki Yokota Umetsu; Yasuhito Yoshioka; Ayumi Mizugai; Toshinari Mita; Yu Shiga; Fumito Koizumi; Hikaru Nakamura; Akio Sakai


BMC Emerg Med. 2014;14(3) 

In This Article


Patients' Background and Circumstances

It has been reported that aging promotes DNS as a complication of CO poisoning,[8] and that no DNS-developing cases were seen in patients younger than 30 years of age.[10] Based on these reports, we initially expected that increased general fragility caused by aging may lead to the development of DNS. However, in the present study the youngest DNS case was 23 years old and, although the mean age tended to be higher in the DNS-developing group, there was no significant difference in mean age between the DNS-developing and non-DNS-developing groups.

The location of exposure was generally classified as in a room at home and in a car. Pavese, et al. and O'Donnell, et al. state that CO gas concentration at the scene multiplied by duration of exposure is an important determinant of the severity of acute CO poisoning.[24,25] While CO gas concentration is likely to be affected by the size of the space and the time to filling the space with CO, no significant difference was observed in place of exposure or estimated duration of exposure.

Results regarding estimated duration of exposure may be affected by the fact that duration of exposure was known only for half of all cases. Specific circumstances of exposure were varied, such as a case who had prolonged exposure to CO by burning briquettes in a car and frequently getting in and out of the car to vomit outside, and another who had prolonged exposure in a well-ventilated wooden shed. While the product of CO gas concentration and duration of exposure cannot properly be calculated without collecting detailed information on individual circumstances, there is a limit to information available for collection in acute clinical settings. It is therefore considered that the wide variety of circumstantial factors involved in space and duration of exposure prevented any significant difference in these factors from being detected with respect to the development of DNS.

Physical Findings and Laboratory Results at First Consultation

The results show that more severe consciousness disturbance at the time of first hospital consultation is associated with higher likelihood of developing DNS. There have been sporadic reports that consciousness disturbance[26] and prolonged loss of consciousness[10] involved in acute CO poisoning are risk factors for developing DNS. Acute CO poisoning resulting from attempted suicide is often combined with other means of suicide attempt, such as alcohol use or drug abuse, and these multiple factors may result in aggravation or prolongation of consciousness disturbance.

In the present study, all cases underwent head CT on the day of admission. Cases with low-density area in the globus pallidus were significantly more likely to develop DNS. CO produces parenchymal necrosis in fragile areas in the cerebral gray matter, particularly bilateral symmetric necrosis of the globus pallidus, which has been reported to be characteristic of CO poisoning.[8] Other areas often affected include the hippocampus, cerebellum and substantia nigra, where affected parts appear as low-density areas on CT. While CO gas concentration multiplied by duration of exposure is considered an important determinant of the severity of acute CO poisoning as mentioned above, in clinical settings it is often difficult to accurately find out how long the unconscious patient has been exposed to CO. However, a report has proposed a cut-off value of 570 min as a duration of exposure above which abnormal CT/MRI findings are predicted to be observed at the initial stage.[27] Using this threshold, it should be possible to estimate, from head CT findings at emergency admission, whether or not the patient has had prolonged exposure. A number of reports have identified abnormal CT/MRI findings[26] as a risk factor for developing DNS, which is also the case with this study. On the other hand, 20% of the cases with no abnormal CT findings did develop DNS, suggesting that even cases without abnormal findings require attention to the clinical course.

Hematology results show that abnormally high CK, CK-MB and LDH levels are significantly associated with the development of DNS. In acute CO poisoning cases, hypoxia and impaired cellular respiration caused by CO induce damage to multiple organs. These high CK levels are caused by damage to skeletal muscles. In this regard, the effect of pressure ulcer formation, which was seen in a number of cases due to prolonged immobility in the same position, should also be taken into account. LDH is an enzyme found in almost all cells and is released into the bloodstream when cells are damaged. As such, it is used as an indicator for assessing the severity of general condition.[28] The high LDH and CK-MB levels are considered to have been caused by myocardial injury. While these high levels have both been caused by prolonged exposure to CO, the hematological changes observed are regarded as nonspecific and not characteristic of CO poisoning.[11]

The CO -Hb level only indicates the binding ratio between CO and Hb. As such, it decreases with time once CO inhalation is stopped, and decreases more efficiently as a result of oxygen administration in the ambulance. For this reason, CO-Hb levels following emergency admission are not directly associated with the degree of systemic tissue damage, as seen in the results of this study, which failed to show a significant association between CO-Hb levels and the development of DNS. In fact, the non-DNS-developing group had a higher mean CO-Hb level. However, a high CO-Hb level at admission indicates that the patient has been exposed to correspondingly high levels of CO, a fact which should be borne in mind in taking measures in the clinical setting.

Overall, F3 was the most common psychiatric main diagnosis according to ICD-10. In the psychiatric assessments of severity, no significant difference was observed between the DNS-developing and non-DNS-developing groups in BPRS score, which assesses the severity of psychiatric symptoms only, or in LCU score, which assesses the intensity of life events. However, the GAS score was significantly lower in the DNS-developing group. The GAS is a comprehensive functional assessment scale covering psychological, social and occupational functions, with lower GAS scores indicating more severe conditions. Assessment was conducted by a psychiatrist who collected, immediately after admission, information on the immediately preceding circumstances from the patient's family, etc. In the DNS-developing group, patients' overall function was significantly poorer. Clinically, the GAS score was independent of the development of DNS, and a lower GAS score was not considered to be a predictor for development of DNS. However, individuals with a lower GAS score may be profiled as individuals with worsening psychiatric symptoms to the extent that they affect physical and social functioning. These individuals may carefully plan to commit suicide by actions such as selecting a location away from public view, sealing up a car or room, and combining multiple methods of suicide. These actions would result in exposure to CO sufficient to subsequently cause DNS.

Clinical Course After Hospitalization

Given that the maxim period before the onset of intermittent CO poisoning was 35 days in this study, at least 5 weeks' follow-up is believed necessary. Length of hospital stay was inevitably longer in the DNS-developing group, since patients in this group needed time to recover from DNS. Similarly, the number of HBO therapy sessions was larger in the DNS-developing group, since approximately 60 HBO sessions are required once DNS develops.

On the other hand, 62% of all cases and 77% of the cases in the DNS-developing group received HBO therapy on the day of emergency admission. This suggests that, despite its efficacy in acute CO poisoning and DNS cases, HBO therapy may not be able to completely prevent the development of DNS even if administered during the initial stage of treatment.