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BioMed Research International

Volume 2014, Article ID 814736, 5 pages
http://dx.doi.org/10.1155/2014/814736

Research Article
A Positive Babinski Reflex Predicts Delayed Neuropsychiatric
Sequelae in Chinese Patients with Carbon Monoxide Poisoning

Jian-Fang Zou,1 Qiming Guo,1 Hua Shao,1 Bin Li,2 Yuxiu Du,3 Maofeng Liu,4
Fengling Liu,4 Lixin Dai,5 Min-Hsien Chung,6,7 Hung-Jung Lin,6,8,9 How-Ran Guo,10,11
Tzu-Meng Yang,6 Chien-Cheng Huang,6,12 and Chien-Chin Hsu6,8
1
Clinical Division of Occupational Medicine, Institute of Occupational Health and Occupational Medicine,
Academy of Medical Science, Shandong Province 250000, China
2
Division of Toxicology, National Institute of Occupational Health and Poison Control, Beijing 100050, China
3
Department of Medicine, Second People’s Hospital of Dongying, Shandong Province 250000, China
4
Department of Medicine, Qilu Petrochemical Corporation Hospital, Shandong Province 250000, China
5
Department of Medicine, Second People’s Hospital of Kenli, Shandong Province 250000, China
6
Department of Emergency Medicine, Chi-Mei Medical Center, Tainan 710, Taiwan
7
Department of Emergency Medicine, Chi-Mei Medical Center, Liouying, Tainan 710, Taiwan
8
Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan 710, Taiwan
9
Department of Emergency Medicine, Taipei Medical University, Taipei 110, Taiwan
10
Department of Environmental and Occupational Health, Medical College, National Cheng Kung University, Tainan 701, Taiwan
11
Department of Occupational and Environmental Medicine, National Cheng Kung University Hospital, Tainan 701, Taiwan
12
Department of Child Care and Education, Southern Taiwan University of Science and Technology, Tainan 710, Taiwan

Correspondence should be addressed to Chien-Cheng Huang; [email protected]

and Chien-Chin Hsu; [email protected]

Received 19 February 2014; Revised 11 April 2014; Accepted 15 April 2014; Published 15 May 2014

Academic Editor: Shih-Bin Su

Copyright © 2014 Jian-Fang Zou et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

As the human population increased in China, the carbon monoxide is a serious environmental toxin in public health. However,
predicting the delayed neuropsychiatric sequelae (DNS) of carbon monoxide poisoning (COP) has not been well studied. We
investigated the independent predictors of DNS in patients with COP. This study was conducted at four hospitals in China. Data were
retrospectively collected from 258 patients with COP between November 1990 and October 2011. DNS was the primary endpoint.
A positive Babinski reflex was the independent predictor for DNS: sensitivity = 53.8% (95% confidence interval [CI]: 26.1–79.6),
specificity = 88.6% (95% CI: 83.7–92.1), positive predictive value (PPV) = 20.0% (95% CI: 9.1–37.5), and negative predictive value
(NPV) = 97.3% (95% CI: 94.0–98.9). The area under the receiver operating characteristic curve = 0.712 (95% CI: 0.544–0.880). A
positive Babinski reflex was very memorable, immediately available, and applicable in clinical practice. Even when the sensitivity
and PPV of a positive Babinski reflex were unsatisfactory, it had a good specificity and NPV for excluding the risk of DNS. In
patients without a positive Babinski reflex, the risk for DNS was only 2.7%. This finding may help physicians make decisions about
dispositions for patients with COP.

1. Introduction important. Carbon monoxide poisoning (COP) is common

in modern society, resulting in significant morbidity and
As society changes due to the challenge of sustainable devel- is one of the leading causes of poisoning death [1]. In
opment in the face of increased human population especially the country of East Asia such as Taiwan, COP caused 526
in the East Asia region, the role of toxicology in enlightened emergency department visits and 55 deaths during 2009–2013
public health and public policy will become even more [2]. In People’s Republic of China, a 1.35 billion population
2 BioMed Research International

(59 times than Taiwan and 4.3 times than United States), 2. Materials and Methods
the number of COP is even harder to estimate. However,
because COP is commonly misdiagnosed, the true numbers 2.1. Study Design, Setting, Population, and Selection of Partici-
are likely much higher [3]. Acute COP may induce hypoxic pants. Between November 1990 and October 2011, data were
encephalopathy with variable degrees of brain damage, rang- retrospectively collected from patients with COP at four hos-
ing from confusion to deep coma [4]. Approximately one- pitals in Shandong Province, People’s Republic of China: the
third of the patients succumb during acute intoxication, and Institute of Occupational Health and Occupational Medicine,
most of the remaining patients recover completely from the Second People’s Hospital of Dongying, Qilu Petrochemical
first episode [4]. However, 0.2–40% of the survivors develop Corporation Hospital, and Second People’s Hospital of Kenli.
delayed neuropsychiatric sequelae (DNS) within 2–4 weeks Patients were enrolled if they had documented exposure to
after this pseudo recovery [4, 5]. The main reasons for such carbon monoxide (elevated carbon monoxide hemoglobin
a large variation might be different population and variabil- (COHb) level or ambient carbon monoxide concentration)
ity in choosing patients. The common clinical features of or obvious exposure to carbon monoxide, and if they had any
DNS are cognitive changes, sphincter incontinence, akinetic of the following symptoms: loss of consciousness, confusion,
mutism, Parkinsonism, and dystonia [4]. Most patients show headache, malaise, fatigue, forgetfulness, dizziness, visual dis-
prominent improvement in all clinical features, particularly turbances, nausea, vomiting, cardiac ischemia, or metabolic
in sphincter incontinence and akinetic mutism [4]. Some acidosis (a calculated base excess lower than −2.0 mmol per
sequelae, such as dystonia and cognitive impairments, may liter or a lactate concentration higher than 2.5 mmol per liter).
persist [4]. If the COHb level was below 10 percent, the patient was
The recommended treatment for acute COP is 100 per- eligible only if COP was the only plausible diagnosis. Patients
cent normobaric oxygen, commonly delivered from a were excluded if they had a history of neurological disease or
reservoir through a facemask that prevents rebreathing psychiatric disorders.
[6]. Hyperbaric-oxygen therapy is often recommended for
patients with acute COP, especially if they have lost con- 2.2. Data Collection and Definition of Variables. All the
sciousness or have severe poisoning [6]. A double-blind patients were given 100% oxygen at the time that COP was
randomized study [6] reported that CO-poisoned patients suspected. The studied hospitals’ Human Investigation Com-
given three hyperbaric oxygen treatments within 24 hours of mittee approved the protocol. The reviewers were blinded to
presentation manifest approximately one-half the rate of neu- the patients’ hospital course and outcomes. Information for
ropsychiatric sequelae at 6 weeks, 6 months, and 12 months a number of variables for each patient was recorded. Any
after treatment than do those treated with normobaric oxy- variable not present or equivocal in the patient’s medical
gen. Another study found that hyperbaric oxygen treatment history or physical exam was considered absent.
was associated with a significant reduction in the incidence Elderly was defined as ≥65 years. We defined an age
of DNS; however, the success of hyperbaric oxygen treatment variable of “>35 years” based on a study [10] which reported
may require that it be used within 6 hours after COP [7]. The that being >35 years old was a risk factor for neuropsychiatric
risk of DNS may also be substantially lowered by prescribing sequelae. Altered mental status was defined as any state
that the patient has at least 12 hours of daily bed rest, of awareness that differs from the normal awareness of a
not do any stressful physical activity, and not be subjected conscious person at admission. Loss of consciousness was
to stressful medical procedures [8]. However, hyperbaric defined as a transient loss of consciousness [3]. The lack
oxygen has many limitations, such as relative inconvenience, of a pupil reflex was defined as a lack of response to light
high cost, and the complications of hyperoxic seizures, aural stimulation in one eye. A positive Babinski sign was defined
barotrauma, anxiety, and oxidative stress [6]. Identifying as an upturning or extensor plantar response elicited when
patients with a high risk for DNS but who really need hyper- the sole of the foot was stimulated with a blunt instrument.
baric oxygen treatment is the most important. In addition, The enrolled patients were divided into two groups: (i)
recognizing the independent predictors of a high risk for without DNS (DNS− ) and (ii) with DNS (DNS+ ). All the
DNS in patients with COP should help physicians predict study variables were used for comparisons between groups.
the prognosis. Until now, however, the results of predicting
the DNS of COP are sparse and inconsistent; thus, prediction
seems impractical. One study [9] proposed that elderly 2.3. Definition of Endpoint. We used DNS as the primary
patients with more comorbidities, but shorter lucid intervals endpoint. Patients who had a recurrence of original symp-
and fewer dangerous activities of daily living, are more likely toms or developed new symptoms (headache, difficulty con-
to have a poor prognosis. However, “more complications, centrating, lethargy, emotional lability, amnestic syndromes,
lucid intervals, and dangerous activities of daily living” are dementia, psychosis, Parkinsonism, chorea, apraxia, agnosia,
difficult to define. Another study [5] showed that decreased peripheral neuropathy, urinary incontinence, etc.) [9] after
Glasgow Coma Scales level and methemoglobin levels were COP were considered DNS+ for this analysis.
independent risk factors associated with DNS. However, this
study enrolled only pediatric patients, which cannot give us 2.4. Data Analysis. All analyses were done using SPSS 16.0 for
a complete picture of DNS. To clarify this issue, we explored Windows (SPSS Inc., Chicago, IL, USA). Continuous data are
independent mortality predictors in patients with COP in our means ± standard deviation (SD). Comparisons between two
clinical setting. groups were made using either an independent-samples t-test
BioMed Research International 3

(assuming normal distribution) or Mann-Whitney-Wilcoxon ROC curve

1.0
tests (assuming non-normality) for the continuous variables.
Either a 𝜒2 test or a Fisher’s exact test was used for categorical
variables. The significant level was set at 𝑃 < 0.05 (two tailed) 0.8
in all analyses, but in choosing variables to be included in the
multiple logistic regression analysis, a cutoff of 0.1 was applied
0.6

Sensitivity
in order to include more potential covariates. The area under
the receiver operating characteristic (ROC) curves was used
to compare a predictor’s specification. 0.4

3. Results 0.2

The final study cohort consisted of 258 patients (123 men

[48%] and 135 women [52%]) after patients who had a neu- 0.0
0.0 0.2 0.4 0.6 0.8 1.0
rological or psychiatric history had been excluded (Table 1).
1 − specificity
Their ages ranged from 6 to 97 years (mean age: 54.9 ±
22.4; median, 59). Thirteen patients (5.03%) had DNS. Two Figure 1: The area under the ROC curve for a positive Babinski
hundred patients (77.5%) had undergone hyperbaric oxygen reflex.
therapy.
Univariate analysis showed that patients with the follow-
ing variables had a higher risk for DNS (𝑃 < 0.05): ischemic
that has damaged the corticospinal tract. Occasionally, a
stroke history and a positive Babinski reflex (Table 1). Other
pathological Babinski reflex is the first (and only) indication
variables were not significantly different between groups.
of a serious disease process, and a clearly abnormal Babinski
Multiple logistic regression modeling, using the univariate
reflex often prompts detailed neurological investigations of
comparison with significance set at 𝑃 < 0.1 (Table 1), showed
the brain or the spine [13].
that the only presenting variable independently associated
Acute brain injury in patients who have been exposed to
with DNS was a positive Babinski reflex (Table 2).
carbon monoxide appears to arise largely from hypoxia. Stud-
The presence of a positive Babinski reflex had a sensitivity
ies with mice [14], however, have shown that cerebral blood
of 53.8% (95% confidence interval [CI]: 26.1–79.6), specificity
flow initially increases within minutes of carbon monoxide
of 88.6% (95% CI: 83.7–92.1), positive predictive value (PPV)
exposure. Blood flow remains elevated until the mouse loses
of 20.0% (95% CI: 9.1–37.5), and negative predictive value
consciousness, when transient cardiac compromise causes
(NPV) of 97.3% (95% CI: 94.0–98.9) for DNS. Two hundred
its blood pressure to decrease [14]. Because of this, autoreg-
and seventeen patients in 223 patients without a positive
ulation until cardiovascular homeostasis is exhausted and
Babinski sign did not have DNS; therefore, the NPV is 97.3%.
asphyxia or apnea begins Neurons are the central nervous
In other words, only 2.7% patients (6/223) without a positive
system cells most vulnerable to hypoxic-ischemic insult, and
Babinski sign had DNS. The area under the ROC curve for
they have the highest oxygen and glucose demands [14].
a positive Babinski reflex was 0.712 (95% CI: 0.544–0.880),
Acute and intense COP can lead directly to diffuse hypoxic-
which showed good diagnostic accuracy (Figure 1).
ischemic encephalopathy and predominantly involve the gray
matter [14]. The globus pallidus is the most common site
4. Discussion of involvement in COP. Occasionally, the caudate nucleus,
putamen, and thalamus are involved in COP, but less so than
We found that a positive Babinski reflex was an independent the globus pallidus [14]. Involvement of the brainstem may
predictor for DNS in Chinese patients with COP. In addition, be a reflection of more severe poisoning because its posterior
a positive Babinski reflex was very memorable, immediately structures are more resistant to hypoxia [14]. In the DNS
available, and applicable in clinical practice. Even when the after COP, the characteristic findings of brain MRI were small
sensitivity and PPV of a positive Babinski reflex were unsat- necrotic foci and demyelinating changes in the cerebral white
isfactory, it had a good specificity and NPV for excluding the matter and globus pallidus [4]. Demyelination with relative
risk of DNS. In patients without a positive Babinski reflex, the preservation of the axons was prominent in the frontal lobes
risk for DNS was only 2.7%. This finding may help physicians of patients with DNS [4]. The pathophysiology of DNS may
make decisions about dispositions for patients with COP. In be due to direct myelinotoxic effect of carbon monoxide [8].
patients with a higher risk for DNS, earlier treatment and This investigation has several limitations. First, we did
more appropriate utilization of health care services, including not include the level of COHb and exposure duration for
hyperbaric oxygen and close followup, should be considered. analysis because these data were unavailable for all but a
There are no published reports that a Babinski reflex is few patients. However, the diagnosis of COP cannot depend
associated with the prognosis of COP. Only some studies solely depended on the level of COHb, because COHb
[11, 12] have proposed that a positive Babinski reflex is one of testing is not available in every hospital. Moreover, many
the neurologic manifestations of COP in children. A positive patients were delayed before being sent to the hospital,
Babinski reflex might indicate an upper motor neuron lesion which resulted in a poor correlation between the COHb
4 BioMed Research International

Table 1: Univariate analysis of variables of 258 patients of COP with delayed neuropsychiatric sequelae (DNS).

DNS− DNS+ All

Variable 𝑃 value
(𝑛 = 245) (𝑛 = 13) (𝑛 = 258)
Age (mean ± SD) 54.4 ± 22.4 63.6 ± 22.3 54.9 ± 22.4 0.184
Age > 35 years (%) 71.2 84.6 79.5 1.000
Elderly (Age ≥ 65 years) (%) 32.7 53.8 33.7 0.136
Gender: male (%) 47.2 61.5 48.0 0.397
Systolic blood pressure (mean ± SD) 129.5 ± 22.1 136.7 ± 23.1 129.9 ± 22.1 0.293
Heart rate (mean ± SD) 87.1 ± 17.0 88.5 ± 13.7 87.2 ± 16.9 0.767
Respiratory rate (mean ± SD) 20.3 ± 2.3 21.0 ± 3.3 20.3 ± 2.4 0.287
Body temperature (mean ± SD) 36.6 ± 0.5 36.7 ± 0.9 36.6 ± 0.6 0.758
Occupational exposure (%) 12.7 23.1 13.2 0.389
Current smoker (%) 12.2 23.1 12.8 0.223
Hypertension history (%) 18.8 38.5 19.8 0.143
Diabetes history (%) 4.1 7.7 4.3 0.440
Ischemic stroke history (%) 5.7 23.1 6.6 0.045
Altered mental status (%) 33.8 61.5 35.3 0.069
Loss of consciousness (%) 61.2 84.6 62.4 0.140
Headache (%) 41.2 30.8 40.7 0.569
Dizziness (%) 57.6 30.8 56.2 0.083
Nausea or vomiting (%) 36.7 46.2 37.2 0.561
Lack of pupil reflex (%) 10.2 7.7 10.1 >0.95
Positive Babinski reflex (%) 11.4 53.8 13.6 <0.001
Incontinence (%) 23.7 38.5 24.4 0.316
Hyperbaric oxygen therapy (%) 79.3 69.2 78.7 0.483
COP: carbon monoxide poisoning; SD: standard deviation.

Table 2: Multivariate logistic regression modeling using univariate 5. Conclusion

comparison 𝑃 < 0.1 of 258 patients of COP with delayed neuropsy-
chiatric sequelae. We conceived a retrospective study to investigate the inde-
pendent predictor of DNS in Chinese patients with COP. A
Odds ratio (95% positive Babinski reflex was the independent predictor with a
Variable confidence interval) 𝑃 value good specificity of 88.6% and NPV of 97.3% for excluding the
Full model Final model risk of DNS. In patients without a positive Babinski reflex, the
Dizziness 0.6 (0.2–2.0) NA risk for DNS was only 2.7%. This finding may help physicians
Altered mental status 1.1 (0.2–4.6) NA make decisions about dispositions for patients with COP.
Ischemic stroke history 2.1 (0.4–9.9) NA
Positive Babinski reflex 6.2 (1.7–22.7) 9.0 (2.8–28.8) <0.001
COP: carbon monoxide poisoning; NA: not available; variable not included
Conflict of Interests
in the final model.
The authors declare that there is no conflict of interests
regarding the publication of this paper.
and the patient’s prognosis. In addition, many studies [1, 6,
9, 15] also report that the COHb level was not a predictor
for neurologic sequelae. The length of time that a patient Authors’ Contribution
was exposed to carbon monoxide is usually unavailable and
incorrect because the victim may be confused or may have Jian-Fang Zou, Tzu-Meng Yang, Chien-Cheng Huang, and
lost consciousness. In addition, there are no witnesses in Chien-Chin Hsu conceived the study concept and design, did
most circumstances of COP. Second, data were collected from statistical analysis, analyzed and interpreted the data, wrote
a retrospective chart review. These clinical presentations or the paper, and reviewed and edited the paper. Jian-Fang Zou,
records may not have been completely documented. Third, Qiming Guo, Hua Shao, Bin Li, Yuxiu Du, Maofeng Liu,
the number of patients might have been too small to generate Fengling Liu, and Lixin Dai acquired, analyzed, and inter-
sufficient statistical power and the degree and characteristics preted data. Min-Hsien Chung, Hung-Jung Lin, and How-
of DNS were not classified in detail. Therefore, future studies Ran Guo did statistical analysis, analyzed and interpreted
with larger study populations and more detailed evaluations data, and reviewed and edited the paper. Jian-Fang Zou takes
of DNS are warranted. responsibility for the paper as a whole. All authors have read
BioMed Research International 5

and approved the final paper. Jian-Fang Zou and Tzu-Meng The American Journal of Roentgenology, vol. 189, no. 4, pp.
Yang contributed equally to this work as first authors. W205–W211, 2007.
[15] L. K. Weaver, R. O. Hopkins, K. J. Chan et al., “Hyperbaric oxy-
gen for acute carbon monoxide poisoning,” The New England
Acknowledgments Journal of Medicine, vol. 347, no. 14, pp. 1057–1067, 2002.
This study was supported by Grant CMFHR10252 from the
Chi-Mei Medical Center. The authors thank Bill Franke for
his invaluable advice and editorial assistance.

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