Article, Hyperbaric Medicine

Factors affecting the prognosis of patients with delayed encephalopathy after acute carbon monoxide poisoning

Original Contribution

Factors affecting the prognosis of patients with Delayed encephalopathy after acute carbon monoxide poisoning

Huijun Hu MD a, Xiaowen Pan MD a,?, Yi Wan MD b, Qi Zhang MD a, Wenbin Liang MD c

aHyperbaric oxygen Center of CPLA, Navy General Hospital, Beijing 100048, China

bDepartment of medical statistics, The Fourth Military Medical University, Xi’an 710032, China

cDepartment of Physiology, Division of Cardiology, University Health Network, University of Toronto, Toronto, Ontario, Canada M5S 1A1

Received 3 April 2009; revised 24 September 2009; accepted 25 September 2009

Abstract

Objective: Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is a disease with poor prognosis. The present study was conducted to determine the factors that affect the prognosis of DEACMP patients.

Methods: In a retrospective study, 46 DEACMP patients were chosen by the following criteria: (1) a clear history of acute carbon monoxide poisoning, a distinct “lucid interval,” and neuropsychologic symptoms; (2) first-time admittance to a hospital (within 1 week of onset of disease); and (3) completion of standard treatment period in our hospital. All patients received hyperbaric oxygen (HBO2) treatments. Results: Fifty percent (23 of 46) of the DEACMP patients showed improvements after HBO2 treatments. Age, lucid interval, danger-activities of daily living scores (assessed at worst conditions), and complications were related (P b .05) to the prognosis of DEACMP patients, whereas sex, fundamental diseases, HBO2 treatment in Acute stage, intoxication time, unconsciousness duration, and GM1 ganglioside administration were not (P N .05) related to prognosis.

Conclusion: Hyperbaric Oxygen treatment appears useful in treating DEACMP patients; and patients with greater age and more complications, but shorter lucid interval and less danger-activities of daily living scores, are more likely to have poor prognosis.

(C) 2011

Introduction

Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is a group of neuropsychologic disorders that occur days or weeks later after the disappear- ance of the symptoms of Acute carbon monoxide poisoning [1-3]. Carbon monoxide poisoning is common, and the incidence of DEACMP, although not yet fully known [3], is relatively high. Risk factors for DEACMP in acute CO

* Corresponding author. Tel.: +86 10 66958246.

E-mail address: [email protected] (X. Pan).

poisoning patients include an age more than 35 years and a CO exposure duration of more than 24 hours [3,4]. No specific treatment is available [3] for DEACMP, and poor prognosis is a characteristic of the disease. Hyperbaric oxygen (HBO2) treatment has been suggested to reduce incidence of DEACMP when used at acute CO poisoning phase [5-8], but it remains unclear if HBO2 is useful in treating DEACMP when used at a late phase after the development of DEACMP. The present study was, therefore, carried out to assess the effectiveness of HBO2 on DEACMP patients and to study the relationships between the clinical characteristics and the prognosis of DEACMP patients with the hope of identifying factors that have a major impact on

0735-6757/$ – see front matter (C) 2011 doi:10.1016/j.ajem.2009.09.030

262 H. Hu et al.

the prognosis of DEACMP patients in order that better treatment strategies may be made.

Methods

The study was approved by the institutional review board, and signed consent forms were obtained from all patients or their family members.

Subjects

The present retrospective study included 46 DEACMP patients (male, 28; female, 18; age 20~84 years; average age, 54.1 +- 13.4) who were admitted to and treated in our hospital from 2005 to 2008. Patients were diagnosed as DEACMP and

included in study based on the following criteria: (1) patients have a clear history of Acute CO poisoning, a distinct “lucid interval,” and neuropsychologic symptoms, such as dementia;

(2) first-time admittance to a hospital (within 1 week of onset of disease); and (3) at least a standard treatment period was completed in our hospital. All the 46 DEACMP patients underwent CO poisoning due to incorrect use of furnace at their homes. The patients were hospitalized for 28 to 95 days (62 +- 8 days). When admitted to the hospital, 27 of the patients had high-degree dementia; disabilities of oral communication, walking, and eating; aconuresis; and encopresis. Eleven of the patients had moderate-degree dementia and difficulty of oral communication, but could walk and eat. Six of the patients had reduced response, slow body movements, and reduced memory, but are able to orally communicate and had no aconuresis and encopresis. Two of the patients mainly presented jelling, crying, and depression. All patients had an activity of daily living (ADL, see below) score of less than 60 when admitted.

Treatments

The HBO2 treatment was given to all patients. Patients were placed in a multiplace chamber pressurized with Compressed air; treating pressure was 0.2 MPa (2 ATA) with 100% O2 through a face mask for 60 minutes (which is defined as 1 HBO2 session), once a day. A consecutive treatment for 10 days was defined as a period of treatment, with a 2- to 3-day internal between each period of treatment. The total numbers of HBO2 sessions received by the patients were 24 to 82 (49.2 +- 25.5 sessions). Monosialoteterahexosyl ganglioside treatment (GM1 ganglioside, 100 mg/d intrave- nously, 10 days for a period of treatment) was given to 12 of the patients, with 4 finishing 1 period of treatment and 8 finishing 2 periods of treatment.

Clinical assessment indices

The following 10 factors, which may affect the prognosis of DEACMP patients, were selected for statistical analysis before

the onset of the study based on previous reports [2,4,9] and our own previous clinical experience: age, sex, fundamental diseases, HBO2 treatment in acute stage, intoxication time, unconsciousness duration, lucid interval, danger-ADL scores, complications, and GM1 ganglioside administration. Funda- mental diseases referred to hypertension, diabetes, coronary heart disease, or stroke; intoxication time referred to duration of acute CO intoxication; and complications referred to aspirated pneumonia or hypostatic pneumonia that happened after DEACMP onset. The ADL scoring is composed of physical ADL and instrumental ADL, including the following items: use of toilet, eating, dressing, walking, bathing, making phone call, shopping, doing housework, laundry, use of traffic vehicles, and taking medicine, etc. The scores are as follows: 5 points = can complete by himself/herself, 3 points = with some difficult, 2 points = need help, and 0 point = cannot complete. The ADL scoring was assessed as follows (total score = 100 points): a score higher than 60 points indicates good status (no help is needed for daily life), a score between 60 and 40 points indicates moderate disability (help is needed for daily life), a score between 40 and 20 points indicates severe disability (help is heavily needed for daily life), and a score less than 20 points indicates complete disability (total dependence of daily life). Danger-ADL score referred to the scoring made when patients were in the most Serious conditions in the DEACMP stages, which were usually 2 to 3 weeks after onset of the disease.

Assessment of treatment

The treatment effects of the 46 patients were assessed approximately 2 months after the onset of DEACMP. Patients were divided into improvement group and non- improvement group based on their conditions at assessment. The patients who fell into the improvement group had an ADL score higher than 60 points and were capable of simple verbal communication, independent eating, walking, and using toilet with independent daily life. The patients who fell into the nonimprovement group had an ADL score less than 40 points and were incapable of verbal communication with completely dependent daily life.

Statistics

Data were presented as mean +- standard deviation. Comparison of measurement data between 2 groups was made with t test. Comparison of categorical data between 2 groups was made by ?2 test. Multiple-factor analysis was conducted with logistic regression. A P value b .05 was considered significant.

Results

Twenty-three of the 46 DEACMP patients showed improvements (ADL score N60) after the treatments in our

Prognosis of patients with delayed encephalopathy 263

hospital; the other 23 patients did not show much improvement (ADL score b40). Therefore, the effectiveness ratio was 50%.

Statistical analyses of the 10 selected factors are shown in Table 1. These results showed that age, lucid interval, danger-ADL scores, and complications are related (P b .05, n = 46) to the prognosis of DEACMP patients. In contrast, sex, fundamental diseases, HBO2 treatment in acute stage, intoxication time, unconsciousness duration, and GM1 ganglioside administration are not related (P N .05, n = 46) to the prognosis of the patients. Multiple-factor logistic analysis of the 4 factors selected in single-factor analysis (Table 2) showed that age and danger-ADL score were more important factors affecting prognosis of DEACMP patients, whereas lucid interval and complications were less important factors.

Limitations

Three major limitations of this study require acknowl- edgments. First, the number of patients (46) in the study is relatively small because of the short period (3 years) of the study. Second, the study did not include a control group of DEACMP patients that did not receive HBO2 treatment. Third, assessment of treatment effects of DEACMP patients was made 2 months after the start of treatment, which is not the best time because a longer term may be more preferable. In our studies, we have been able to collect long-term follow- up data from only 15 of these DEACMP patients. These 15 patients included 4 patients from the improvement group (as assessed at 2 months) and 11 patients from the nonimprove- ment group. All the 4 patients who had an ADL score higher

Table 1 Comparison of multiple factors between the nonimprovement and improvement groups of DEACMP patients

Table 2 Multifactor logistic analysis of factors affecting prognosis of DEACMP patients

Factors

Age

B

SE Wald P value Exp (B)

-0.085 0.033

.598 .010

Danger-ADL score 0.067 0.019 12.875 .000

0.919

1.069

than 60 at 2 months still showed an ADL score of higher than 60 after 4 to 20 months, suggesting that the effects of HBO2 treatment observed at 2 months are likely sustainable. Seven of the 11 patients in the “nonimprovement group” (as assessed at 2 months) still had a low ADL (b60) when assessed at a later time point. However, 4 of the 11 patients in the nonimprovement group showed improvement (ADL N60) after 5 to 18 months, suggesting that the effects of HBO2 may be underestimated if assessed only at 2 months.

Discussion

The major findings of the study are that (1) HBO2 treatment is useful in treating DEACMP and (2) age, lucid interval, danger-ADL scores, and complications are impor- tant factors affecting the prognosis of DEACMP patients. The results show that patients with greater age and less danger-ADL scores are more likely to have a bad prognosis. It has been unclear if HBO2 is effective for DEACMP. Although one earlier report [8] suggested that HBO2 improves the neuropsychologic symptoms of CO poisoning sequelae, HBO2 is generally not used at more than 24 hours after the acute CO poisoning [10]. In the present study,

Factors

Nonimprovement group

Improvement group

Value of

?2 or

t

P value

Age (y)

59.5 +- 12.9

48.7 +- 11.7

2.980

.005

Sex

Male

17

11

3.286

.070

Female

6

12

Fundamental diseases

No

14

17

0.890

.345

Yes

9

6

Intoxication time (h)

13.7 +- 6.1

13.0 +- 3.4

0.477

.636

HBO2 treatment in acute stage

No

8

5

0.965

.326

Yes

15

18

Unconsciousness duration (h)

14.7 +- 18.6

19.1 +- 36.6

-0.518

.607

Lucid interval (d)

17.6 +- 7.7

25.9 +- 6.5

-3.949

.000

Danger-ADL scores (points)

4.1 +- 7.2

41.1 +- 25.6

-6.660

.000

Complications

No

12

22

11.275

.001

Yes

11

1

Use of GM1

No

17

17

0.0

1.0

Yes

6

6

264 H. Hu et al.

significant improvements have been observed in 50% of the DEACMP patients that received HBO2, suggesting that HBO2 may be useful in treating these patients. However, the present study did not provide information on how HBO2 improves DEACMP, which patients should receive HBO2, or what is the optimal protocol of HBO2 treatments for DEACMP. Accordingly, further studies are needed to answer these questions.

In the present study, the DEACMP patients had an average age of 54 years, which is consistent with previous reports that older age (N35 years) is a risk factor for developing DEACMP in patients with acute CO poisoning [4]. Our data suggested that older people, in addition to their higher risk of DEACMP after acute CO poisoning, tend to have a worse prognosis when they develop DEACMP compared with younger DEACMP patients.

Danger-ADL score is determined when patients have the worst conditions. A negative relationship between danger- ADL score and the prognosis of DEACMP patients is indicated by the present study. A lower danger-ADL score indicates more serious conditions of the patients, which may contribute to a worse prognosis. Furthermore, patients with lower danger-ADL scores have significant difficulty in walking, eating, and verbal communication, which usually forces them to long-term bed rest and insufficient nutrition intake that, in turn, put them to higher risk of developing complications, such as lung infection and thrombus formation in deep veins of lower extremities.

Lucid interval refers to the interval between the recovery of patients from acute CO intoxication and the appearance of DEACMP symptoms (such as dementia). The present study indicates that a shorter lucid interval is related to worse prognosis of the DEACMP patients. A shorter lucid interval reflects more severe damage of tissues during acute CO intoxication and rapid progress of the disease, which may contribute to the worse prognosis.

Currently, no specific drug is available for treatment of DEACMP. GM1 ganglioside is a new drug that improves nutrition of brain cells. GM1 ganglioside has been shown to promote growth of axon and synapse and to repair the injured

myelin sheath. Although it has been used for more than 10 years, there has been no systemic report on the effectiveness of GM1 ganglioside on DEACMP patients. The present study suggests that GM1 ganglioside use is not likely to affect the prognosis of DEACMP patients. However, given the small sample number (only 12 patients used GM1 ganglioside) of the study, a conclusion cannot be drawn; and it remains to be determined.

In summary, this study suggests that HBO2 is useful for treating DEACMP; and patients with greater age and more complications, but shorter lucid interval and less danger-ADL scores are more likely to have bad prognosis. More efforts should be made to treat patients with such characteristics.

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