|Year : 2020 | Volume
| Issue : 1 | Page : 30-36
Neurocognitive sequelae after carbon monoxide poisoning and hyperbaric oxygen therapy
Ke Ning1, Yan-Yan Zhou2, Ning Zhang1, Xue-Jun Sun1, Wen-Wu Liu3, Cui-Hong Han4
1 Department of Navy Aviation Medicine, Faculty of Naval Medicine, Naval Medical University, Shanghai, China
2 Department of Orthopedic Surgery, Changzheng Hospital, Naval Medical University, Shanghai, China
3 Department of Diving and Hyperbaric Medicine, Naval Medical University, Shanghai, China
4 Department of Pathology, the Affiliated No 1 People's Hospital of Jining City, Jining Medical University, Jining, Shandong Province, China
|Date of Submission||04-May-2019|
|Date of Decision||16-May-2019|
|Date of Acceptance||08-Sep-2019|
|Date of Web Publication||13-Mar-2020|
MD Cui-Hong Han
Department of Pathology, the Affiliated No 1 People's Hospital of Jining City, Jining Medical University, Jining, Shandong Province
Source of Support: None, Conflict of Interest: None
Carbon monoxide (CO) has been the leading cause of poisoning mortality in many countries and hyperbaric oxygen (HBO) is a widely accepted treatment for CO poisoning. However, some patients with CO poisoning will still develop neurocognitive sequelae regardless of HBO therapy, which can persist since CO poisoning or be present days to weeks after a recovery from CO poisoning. HBO has been used in the prevention and treatment of neurocognitive sequelae after CO poisoning, and some mechanisms are also proposed for the potential neuroprotective effects of HBO on the neurocognitive impairment after CO poisoning, but there is still controversy on the effectiveness of HBO on neurocognitive sequelae after CO poisoning. In this paper, we briefly introduce the neurocognitive sequelae after CO poisoning, summarize the potential predictive factors of neurocognitive sequelae, and discuss the use of HBO in the treatment and prevention of neurocognitive sequelae after CO poisoning.
Keywords: carbon monoxide; poisoning; neurocognitive sequelae; persistent neurological sequelae; delayed neurological sequelae; predictors; hypoxia; hyperbaric oxygen; normobaric oxygen; prevention
|How to cite this article:|
Ning K, Zhou YY, Zhang N, Sun XJ, Liu WW, Han CH. Neurocognitive sequelae after carbon monoxide poisoning and hyperbaric oxygen therapy. Med Gas Res 2020;10:30-6
|How to cite this URL:|
Ning K, Zhou YY, Zhang N, Sun XJ, Liu WW, Han CH. Neurocognitive sequelae after carbon monoxide poisoning and hyperbaric oxygen therapy. Med Gas Res [serial online] 2020 [cited 2020 Jul 7];10:30-6. Available from: http://www.medgasres.com/text.asp?2020/10/1/30/279981
| Introduction|| |
Carbon monoxide (CO) is an odorless, colorless, and tasteless gas, and thus it is highly difficult to detect when escaping. CO at a concentration higher than 35 ppm is toxic to humans. CO is the leading cause of poisoning mortality in many countries and may be responsible for more than half of all fatal poisonings worldwide. Although patients can improve over many months, and even up to 1 year, at 6 years after CO poisoning, survivors of CO poisoning usually suffer from long term neurocognitive sequelae related to brain injury., The neurological or cognitive sequelae can occur immediately and persist over time, or the onset can be delayed, and the persistent neurological sequelae (PNS) and delayed neurological sequelae (DNS) are common following acute CO poisoning. It seems that DNS patients have more severe symptoms and worse clinical outcomes than the PNS patients, and the DNS patients had more significant progress on general cognitive function, psychomotor speed, and visual-spatial ability than did the acute group after continuous hyperbaric oxygen (HBO) therapy. The symptoms of DNS typically develop after an interval of 2–40 days. The symptoms of neurocognitive sequelae related to brain injury after CO poisoning include impaired memory, cognitive dysfunction, depression, anxiety, and/or vestibular and motor deficits, and these deficits are evident by 6 weeks. Mimura et al. reported 68.6% of patients had intellectual disturbances and 48.7% had neurologic symptoms at 33 years after CO poisoning, which seems to illustrate the irreversible nature of these deficits. In a study involving 25,912 patients with CO poisoning, Huang et al. found the prevalence rate of neurological sequelae after CO poisoning was 9.1% in total, and the rate was 2.3% in the first 2 weeks and 6.2% at the end of the first year. In a more recent study, Huang et al. found he incidence rates of degenerative diseases of the central nervous system, psychiatric diseases, and other diseases of the nervous system were 23.2, 87.8, and 57.6 per 1000 person-years in patients receiving HBO therapy and 14.9, 59.3, and 34.9 per 1000 person-years in patients without HBO therapy, respectively. In addition, there is evidence showing that the incidences of cognitive deficits and neurologic deficits are 19% and 37% after CO poisoning, respectively. The reported incidence of DNS varies from 0.06% to 40% with the onset 2 to 40 days after CO poisoning,, but the information regarding the prevalence of PNS is limited. In a prospective study, Weaver et al. reported 37% of the participants (n = 238) had cognitive sequelae at 6 weeks, of which 59% had PNS and 28% had DNS, a ratio of 2:1 (PNS: initial cognitive dysfunction persists to 6 weeks after CO poisoning; DNS: a decline of at least 1 standard deviation on a neuropsychological subtest score from a prior score). In the current review, we briefly summarized the predictive factors, mechanisms and HBO treatment of neurocognitive sequelae following CO poisoning by searching the PubMed.
| Predictive Factors|| |
Some studies have been conducted to investigate the factors predicting the neurocognitive sequelae following CO poisoning. The available factors can be classified as the demographics, clinical characteristics, blood biochemical parameters, imaging findings and treatments.
Age and sex are two important factors affecting the outcomes of acute CO poisoning. There is evidence showing that old age, male sex and comorbidities were found to be independent predictors for neurocognitive sequelae after CO poisoning. However, the age and sex as predictors of neurocognitive sequelae after CO poisoning is controversial. The study of Pepe et al. revealed the DNS had no relationship with age and sex.
The clinical characteristics (especially symptoms and signs) may reflect the severity of CO poisoning, and thus it is reasonable that they can be employed for the prediction of neurocognitive sequelae after CO poisoning. Studies have indicated that a longer duration of admission, CO exposure duration > 6 hours, systolic blood pressure < 90 mmHg, Glasgow Coma Scale score < 9, Mini-Mental State Examination score, a lack of pupil reflex and a positive Babinski reflex were associated with the development of DNS or neurological sequelae,,,, but voluntary exposure, headache and transient loss of consciousness failed to predict neurocognitive sequelae. Of note, a loss of consciousness was found to be related to the development of neurological sequelae in other studies.,
A variety of studies have investigated the blood parameters as the predictors of neurocognitive sequelae after CO poisoning. Available studies have indicated plasma copeptin, serum S-100B protein,,, neuron-specific enolase, serum lactate level,, serum N-terminal pro-B-type natriuretic peptide, troponin, creatine kinase,, creatine kinase-MB, lactate dehydrogenase, serum anion gap, serum ubiquitin C-terminal hydrolase-L1, and creatine phosphokinase and leukocytosis are related to the neurocognitive sequelae after CO poisoning, and this risk increases with the number of independent predictors. In addition, neuron-specific enolase could improve the prediction accuracy of initial Glasgow Coma Scale. It has been hypothesized that CO poisoning maybe also causes the formation of myelin basic protein (MBP) and DNS occurs due to extensive myelin and neuronal loss. Study also shows cerebrospinal fluid-MBP can serve as a sensitive predictor of both the development and outcomes of DNS. As mentioned above, serum N-terminal pro-B-type natriuretic peptide, troponin, creatine kinase and creatine kinase-MB are possible prognostic factors for the development of neurocognitive sequelae after CO poisoning, and all these parameters are related to myocardial injury. This is supported by more recent findings that patients having myocardial injury had elevated risk for both PNS and DNS and QTc prolongation within 6 hours after CO exposure was a predictor of DNS However, the application of these parameters in clinical practice warrants more clinical studies, and there is still controversy on several blood parameters (such as lactate level). Thom et al. used Luminex-based technology to determine the concentration of 180 proteins in 63 suspected CO poisoning patients, and they concluded that the CO pathophysiology was complex and this technique had insufficient power to identify reliable plasma predictors of neurological sequelae although their findings support a view that CO exposure caused acute inflammatory events in humans. Of note, some studies fail to found the relationship between carboxyhemoglobin and neurocognitive sequelae after CO poisoning although carboxyhemoglobin is a common blood parameter that is detected on admission and used to diagnose CO poisoning and assess the severity of CO poisoning.,
Several studies have also investigated the relationships of treatments after CO poisoning with neurocognitive sequelae. In the study of Lin et al., use of tranquilizer and treatment in intensive care unit increased the risk for PNS. Chang et al. found treatment in the intensive care unit because of prolonged loss of consciousness was the independent risk factor for DNS and rescue by a ventilator was independently associated with PNS. The intubation requirement was also found to be a possible prognostic factor for development of DNS after CO poisoning. A treatment for CO poisoning is HBO therapy, studies also assess the relationship between HBO therapy and neurocognitive sequelae after CO poisoning, but there is still controversy on this issue. Chang et al. found HBO therapy did not affect the incidence of both DNS and PNS. In addition, there is evidence showing that more sessions of HBO therapy was associated with the development of DNS and HBO therapy seemed to increase the risk for neurocognitive sequelae. However, in a study with small sample size, Chan et al. found a 100% protective effect of HBO therapy against development of DNS in patients with severe CO poisoning (24 patients receiving HBO therapy did not develop DNS).
Magnetic resonance imaging (MRI) and computed tomography (CT) are the common tools used in the assessment of brain injury.,, It has been confirmed that CO poisoning may result in focal and generalized neuroanatomical abnormalities observed on MRI and CT. Imaging examinations can not only be used for the assessment of early neurological lesions after CO poisoning, but also be employed to aid the diagnosis of neurocognitive sequelae. The imaging findings of the brain after CO poisoning and those in patients with neurocognitive sequelae have been described elsewhere., Here, we only discuss the predictive value of imaging findings of the brain. Several studies have shown that the presence of acute brain lesions on MRI was significantly associated with the development of DNS, and fractional anisotropy value of white matter on diffusion tensor imaging is also predictive for DNS., Head CT findings indicating hypoxic encephalopathy and regional cerebral blood flow are also predictive for the development of DNS., Proton magnetic resonance spectroscopy can monitor the neurochemical disturbances to assess the pathophysiology of CO poisoning. It was reported that the presence of a lactate peak was a predictor for a poor long-term outcome, and proton magnetic resonance spectroscopy within 1 week after CO poisoning could be employed to predict DNS development. The striatal dopamine transporter binding measured by single photon emission CT withmTc-TRODAT could help to predict the development of DNS. However, Ozcan et al. found the white matter lesions which progress to demyelination and end up in neuropsychological sequelae could not always be diagnosed by early CT and MRI in CO poisoning.
Several investigators also investigate the predictive value of polymorphism for neurocognitive sequelae in patients after CO poising. Liang et al. investigated the PARK2 polymorphism and clinical outcome in patients following CO poisoning and found the allelic variant of rs1784594 was a risk factor for DNS. In the study of Li et al., results showed variants at NRXN3 was associated with DNS after acute CO poisoning. Hopkins et al. investigated the APOE genotypes in 86 of 152 CO-poisoned patients and their results showed HBO therapy reduces cognitive sequelae after CO poisoning in the absence of the epsilon4 allele.
| Mechanisms|| |
The pathogenesis of neurocognitive sequelae is still poorly understood, and several mechanisms have been proposed: (1) hypoxia: It is well known that the affinity of CO to hemoglobin is 300 times higher than that of oxygen, and the release of CO from carboxyhemoglobin is 3600 times slower than that of oxygen, which may cause hypoxia following CO poisoning, which was proposed as a factor related to neurocognitive sequelae. The termination of CO exposure or treatment for CO poisoning seems to be an oxygenation, which mimics the ischemia/reperfusion injury to the brain. In addition, CO may also bind to the mitochondrial cytochrome oxidase to inhibit mitochondrial respiration, which reduces ATP production, directly or indirectly causing damage to cells; the extended and generalized inhibition of cytochrome oxidase could explain the persistence of different symptoms after the normalization of carboxyhemoglobin levels. Although CO induced hypoxia plays a role in the pathogenesis of CO poisoning, its contribution is likely much less than previously suspected since many of the second order effects described are not completely explained by hypoxemic hypoxia. (2) Immune-mediated injury: CO poisoning may also causes adduct formation between MBP and malonylaldehyde, resulting in an immunological cascade. Cerebrospinal fluid-MBP can serve as a sensitive predictor of both the development and outcomes of DNS. (3) Metabolic dysfunction: CO poisoning may cause metabolic dysfunction in the brain, affecting the neurological dysfunction., (4) Cytotoxicity of neurotransmitter: it has been found that glutamate increases significantly after CO poisoning and glutamate activates N-methyl-D-aspartate receptors, enhancing cellular dysfunction and apoptosis., (5) Reactive oxygen species: CO poisoning may significantly increase the reactive oxygen species production in the brain and weaken antioxidant systems, and lipid peroxidation was found to be involved in the memory impairment of CO-induced delayed neuron damage. In addition, anti-oxidative strategies have also employed for the treatment of acute CO poisoning and its neurocognitive sequelae, and Mannaioni et al. proposed the addition of free radical scavengers (such as glutathione, acetylcysteine, and tempol) to the standardized treatment of acute CO poisoning. (6) Cell death: CO poisoning may cause cell death via different ways (apoptosis and autophagy), predisposing brain injury.,,, (7) Others: CO may also induce neuronal ion channel dysfunction and inflammation,, which also contribute to the pathogenesis of neurocognitive sequelae. In addition, the nicotinic cholinergic system is also related to DNS.
| Effects of Hyperbaric Oxygen Therapy|| |
HBO therapy refers to an intervention in which an individual breathes near 100% oxygen while inside a hyperbaric chamber that is pressurized to greater than sea level pressure (1 atmosphere absolute [ATA]). Although CO poisoning is an indication to HBO therapy and there is evidence showing HBO therapy is associated with lower mortality,, the effects of HBO therapy on the development of neurocognitive sequelae remain controversial., In the following section, we summarized the use of HBO in the therapy and the prevention of neurocognitive sequelae.
In as early as 1985, Myers and colleagues68 reported 12.1% neurological sequelae in a series of 82 patients treated with normobaric oxygen. Ten patients returned with headaches, irritability, personality changes, confusion, and loss of memory. These recurring symptoms resolved rapidly with HBO therapy. They recommend that HBO be used whenever CO symptoms recur. Thereafter, increasing institutes employ HBO for the treatment of neurocognitive sequelae after CO poisoning, and some case reports, clinical studies and animal studies published confirm the neuroprotective effects of HBO on them.,, Chang et al. conducted HBO therapy in a series of patients with DNS and found 8–40 sessions of HBO therapy was able to decrease the severity of impairment in DNS patients. After reviewing literature, Lee et al. concluded that HBO may be effective in treating DNS after CO poisoning. Spagnolo et al. even reported the delayed HBO therapy improved the DNS in a 62-year-old man suffering from CO poisoning who did not receive HBO therapy at baseline. Another advantage of HBO therapy is that it is relatively safe for pregnant women and children, and it can also be used during mechanical ventilation.
Of note, there is limited evidence of the efficacy of HBO treatment, and supportive and symptomatic treatment is recommended for patients diagnosed with neurocognitive sequelae after CO poisoning. Some investigators attempt to use HBO therapy in combination with other strategies in the treatment of neurocognitive sequelae after CO exposure. There is evidence showing that N-butylphthalide is protective on CO poisoning in animals and Xiang et al. found combined application of N-butylphthalide and HBO could significantly improve the cognitive dysfunction of patients with DNS and have great clinical efficacy. In addition, HBO therapy combined with risperidone, acupuncture, high dose ganglioside, edaravone, dexamethasone85 and hypothermia is also found to improve the neuropsychological functions of patients after CO poisoning.
Prevention with HBO
As above mentioned, several factors are closely related to the development of neurocognitive sequelae after CO poisoning, in which HBO therapy is an important one. Based on the findings from a clinical study, Thom et al. recommended HBO treatment in acute CO poisoning to decrease the incidence of DNS after CO poisoning. They further investigated the potential mechanism and found the prophylactic effect of HBO therapy on DNS was related to the inhibition of MBP induced lymphocyte activation after CO poisoning. Early HBO therapy is employed to prevent the development of neurocognitive sequelae. Weaver et al. proposed emergent HBO therapy within 24 hours appeared to reduce the risk of cognitive sequelae after acute CO poisoning. For children with CO poisoning, HBO therapy affected the neuropsychological symptoms88 and Gozubuyuk et al. proposed HBO therapy should be performed within first 6 hours of poisoning if possible, and HBO therapy should be repeated within 6 to 8 hours if loss of consciousness persists after HBO therapy, which may improve the prognosis. After literature reviewing, Lee et al. also concluded immediate administration of HBO during acute CO intoxication may prevent neuropsychiatric sequelae.
Although the effects of HBO vs normobaric oxygen therapy on long-term neurocognitive outcomes after CO poisoning remain unclear, the 2017 American College of Emergency Physicians (ACEP) Clinical Policy on CO Poisoning provides level B recommendations that HBO or high-flow normobaric oxygen therapy should be used for acute CO-poisoned patients. In addition, some investigators also investigate the role of oxygen partial pressure in the therapeutic effects of oxygen. In an in vitro study, Jurič et al. compared the effectiveness of normobaric oxygen vs. HBO in the treatment of CO poisoning, and their results showed oxygen therapy (1 hour) disclosed pressure- and time-dependent efficacy in restoring astrocytic mitochondrial function and the prevention of apoptosis. In the study of Thom et al., 7 of 30 patients (23%) developed DNS after treatment with ambient-pressure oxygen (DNS occurred 6 ± 1 days after poisoning), but none developed sequelae in 30 patients after HBO treatment. Lin et al. conducted a systematic review and meta-analysis of randomized controlled trials to investigate the therapeutic efficacy of normobaric and HBO on neuropsychometric dysfunction after CO poisoning. They conclude that patients receiving HBO treatment had a lower incidence of neuropsychological sequelae (including headache, memory impairment, difficulty concentrating, disturbed sleep, and DNS) as compared to those treated with normobraic oxygen. Hampson et al compared two hyperbaric treatment protocols for CO poisoning (2.4 ATA, 100% oxygen, 90 minutes vs. US Air Force CO protocol [3.0 ATA maximum pressure]) and results showed there was no significant difference in the proportion of patients with abnormal neurological testing at 14–21 days (4/18 vs. 2/12; P = 0.71). In addition, the effect on headache after CO poisoning was also similar between HBO therapy and normobaric oxygen therapy.
However, there is still controversy about the efficacy of HBO on development of neurocognitive sequelae after CO poisoning. In patients with initial impairment of consciousness after CO poisoning who received 4-hour normobaric oxygen treatment, HBO therapy seemed to have no influence on the development of neuropsychiatric sequelae. On the basis of six randomized controlled trials, Buckley et al. speculated that the efficacy of HBO for the prevention of neurological sequelae was still uncertain, which might be ascribed to the significant methodologic and statistical heterogeneity. Gilmer et al. also found HBO was not effective in preventing neurologic sequelae in mice and there was no benefit of HBO over normobaric oxygen following severe CO poisoning. Scheinkestel et al. also compared HBO with normobaric oxygen in patients with CO poisoning, and found more patients receiving HBO required additional treatments; more HBO treated patients had a worse outcome in the learning test and a greater number of abnormal test results at completion of treatment; DNS was restricted to HBO treated patients (P = 0.03), but no outcome measure was worse in normobaric oxygen group. Two randomized controlled trials also failed to show the evidence of superiority of HBO over normobaric oxygen in patients with transient loss of consciousness, and two HBO sessions were associated with worse outcomes than one HBO session in comatose patients. In a population-based cohort study involving 24,046 patients with CO poisoning, Huang et al. found the risk for neurologic sequelae was higher in patients with CO poisoning who received HBO therapy than in those who did not after adjusting for age, sex, and other confounding factors, and similar findings were observed after stratifying the patients by age, sex, underlying comorbidities, and monthly income. Moreover, they found the increased risk was most prominent in the first 2 weeks and remained significant up to 6 months later. In addition, the effectiveness of HBO therapy still remains unclear in preventing dementia.
| Conclusions|| |
CO has been the leading cause of poisoning mortality in many countries. Although great progress has been achieved in the treatment of CO poisoning, some patients will still develop neurocognitive sequelae after CO poisoning, which can persist since CO poisoning or be present days to weeks after a recovery from CO poisoning. Administration of supplemental oxygen is the primary treatment for CO poisoning, but the delivery of supplemental oxygen via HBO remains inconclusive as a primary treatment strategy. Moreover, the effectiveness of HBO in the prevention and treatment of neurocognitive sequelae is still controversial. A recent study with large sample size brings promise to the use of HBO in the therapy of CO poisoning, but this study remains distant from the ideal of a large blinded multicenter randomized controlled trial. As shown by Cowl, “it is time to justify HBO delivery for CO poisoning.”
Study design: CHH, WWL, YYZ; data search and manuscript drafting: KN, CHH; manuscript revising: YYZ, NZ, XJS. All authors approved the final version of the manuscript for publication.
Conflicts of interest
The authors have no conflicts of interests to declare.
Copyright license agreement
The Copyright License Agreement has been signed by all authors before publication.
Checked twice by iThenticate.
Externally peer reviewed.
Open access statement
This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
| References|| |
Raub JA, Mathieu-Nolf M, Hampson NB, Thom SR. Carbon monoxide poisoning--a public health perspective. Toxicology
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
Hopkins RO, Weaver LK, Valentine KJ, Mower C, Churchill S, Carlquist J. Apolipoprotein E genotype and response of carbon monoxide poisoning to hyperbaric oxygen treatment. Am J Respir Crit Care Med
Tsai CF, Yip PK, Chen SY, et al. The impacts of acute carbon monoxide poisoning on the brain: Longitudinal clinical and 99mTc ethyl cysteinate brain SPECT characterization of patients with persistent and delayed neurological sequelae. Clin Neurol Neurosurg
Yeh ZT, Tsai CF, Yip PK, et al. Neuropsychological performance in patients with carbon monoxide poisoning. Appl Neuropsychol Adult
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
Mimura K, Harada M, Sumiyoshi S, et al. Long-term follow-up study on sequelae of carbon monoxide poisoning; serial investigation 33 years after poisoning. Seishin Shinkeigaku Zasshi
Huang CC, Ho CH, Chen YC, et al. Demographic and clinical characteristics of carbon monoxide poisoning: nationwide data between 1999 and 2012 in Taiwan. Scand J Trauma Resusc Emerg Med
Huang CC, Ho CH, Chen YC, et al. Impact of hyperbaric oxygen therapy on subsequent neurological sequelae following carbon monoxide poisoning. J Clin Med
Rose JJ, Wang L, Xu Q, et al. Carbon monoxide poisoning: pathogenesis, management, and future directions of therapy. Am J Respir Crit Care Med
Myers RA, DeFazio A, Kelly MP. Chronic carbon monoxide exposure: a clinical syndrome detected by neuropsychological tests. J Clin Psychol
Kitamoto T, Tsuda M, Kato M, Saito F, Kamijo Y, Kinoshita T. Risk factors for the delayed onset of neuropsychologic sequelae following carbon monoxide poisoning. Acute Med Surg
Weaver LK, Hopkins RO, Chan KJ, et al. Hyperbaric oxygen for acute carbon monoxide poisoning. N Engl J Med
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
Ku HL, Yang KC, Lee YC, Lee MB, Chou YH. Predictors of carbon monoxide poisoning-induced delayed neuropsychological sequelae. Gen Hosp Psychiatry
Zou JF, Guo Q, Shao H, et al. Lack of pupil reflex and loss of consciousness predict 30-day neurological sequelae in patients with carbon monoxide poisoning. PLoS One
Zou JF, Guo Q, Shao H, et al. A positive Babinski reflex predicts delayed neuropsychiatric sequelae in Chinese patients with carbon monoxide poisoning. Biomed Res Int
Chan MY, Au TTs, Leung KS, Yan WW. Acute carbon monoxide poisoning in a regional hospital in Hong Kong: historical cohort study. Hong Kong Med J
Pang L, Wang HL, Wang ZH, et al. Plasma copeptin as a predictor of intoxication severity and delayed neurological sequelae in acute carbon monoxide poisoning. Peptides
Brvar M, Mozina H, Osredkar J, Mozina M, Brucan A, Bunc M. The potential value of the protein S-100B level as a criterion for hyperbaric oxygen treatment and prognostic marker in carbon monoxide poisoned patients. Resuscitation
Park E, Ahn J, Min YG, et al. The usefulness of the serum s100b protein for predicting delayed neurological sequelae in acute carbon monoxide poisoning. Clin Toxicol (Phila)
Kim H, Choi S, Park E, Yoon E, Min Y, Lampotang S. Serum markers and development of delayed neuropsychological sequelae after acute carbon monoxide poisoning: anion gap, lactate, osmolarity, S100B protein, and interleukin-6. Clin Exp Emerg Med
Cha YS, Kim H, Do HH, et al. Serum neuron-specific enolase as an early predictor of delayed neuropsychiatric sequelae in patients with acute carbon monoxide poisoning. Hum Exp Toxicol
Jung JW, Lee JH. Serum lactate as a predictor of neurologic outcome in ED patients with acute carbon monoxide poisoning. Am J Emerg Med
Moon JM, Chun BJ, Shin MH, Lee SD. Serum N-terminal proBNP, not troponin I, at presentation predicts long-term neurologic outcome in acute charcoal-burning carbon monoxide intoxication. Clin Toxicol (Phila)
Kudo K, Otsuka K, Yagi J, et al. Predictors for delayed encephalopathy following acute carbon monoxide poisoning. BMC Emerg Med
Pang L, Wu Y, Dong N, et al. Elevated serum ubiquitin C-terminal hydrolase-L1 levels in patients with carbon monoxide poisoning. Clin Biochem
Thom SR, Bhopale VM, Fisher D, Zhang J, Gimotty P. Delayed neuropathology after carbon monoxide poisoning is immune-mediated. Proc Natl Acad Sci U S A
Kuroda H, Fujihara K, Kushimoto S, Aoki M. Novel clinical grading of delayed neurologic sequelae after carbon monoxide poisoning and factors associated with outcome. Neurotoxicology
Lin MS, Lin CC, Yang CC, et al. Myocardial injury was associated with neurological sequelae of acute carbon monoxide poisoning in Taiwan. J Chin Med Assoc
Liao SC, Mao YC, Hung YM, Lee CH, Yang CC. Predictive role of QTc prolongation in carbon monoxide poisoning-related delayed neuropsychiatric sequelae. Biomed Res Int
Thom SR, Bhopale VM, Milovanova TM, et al. Plasma biomarkers in carbon monoxide poisoning. Clin Toxicol (Phila)
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
Guo D, Wilkinson DA, Thompson BG, et al. MRI characterization in the acute phase of experimental subarachnoid hemorrhage. Transl Stroke Res
Pang J, Chen Y, Kuai L, et al. Inhibition of blood-brain barrier disruption by an apolipoprotein E-mimetic peptide ameliorates early brain injury in experimental subarachnoid hemorrhage. Transl Stroke Res
Bahjat FR, Alexander West G, Kohama SG, et al. Preclinical development of a prophylactic neuroprotective therapy for the preventive treatment of anticipated ischemia-reperfusion injury. Transl Stroke Res
Hopkins RO, Woon FL. Neuroimaging, cognitive, and neurobehavioral outcomes following carbon monoxide poisoning. Behav Cogn Neurosci Rev
Otubo S, Shirakawa Y, Aibiki M, et al. Magnetic resonance imaging could predict delayed encephalopathy after acute carbon monoxide intoxication. Chudoku Kenkyu
Jeon SB, Sohn CH, Seo DW, et al. Acute brain lesions on magnetic resonance imaging and delayed neurological sequelae in carbon monoxide poisoning. JAMA Neurol
Kim YS, Cha YS, Kim MS, et al. The usefulness of diffusion-weighted magnetic resonance imaging performed in the acute phase as an early predictor of delayed neuropsychiatric sequelae in acute carbon monoxide poisoning. Hum Exp Toxicol
Hou X, Ma L, Wu L, et al. Diffusion tensor imaging for predicting the clinical outcome of delayed encephalopathy of acute carbon monoxide poisoning. Eur Neurol
Chang CC, Lee YC, Chang WN, et al. Damage of white matter tract correlated with neuropsychological deficits in carbon monoxide intoxication after hyperbaric oxygen therapy. J Neurotrauma
Sesay M, Bidabé AM, Guyot M, Bédry R, Caillé JM, Maurette P. Regional cerebral blood flow measurements with Xenon-CT in the prediction of delayed encephalopathy after carbon monoxide intoxication. Acta Neurol Scand Suppl
Kuroda H, Fujihara K, Mugikura S, Takahashi S, Kushimoto S, Aoki M. Altered white matter metabolism in delayed neurologic sequelae after carbon monoxide poisoning: A proton magnetic resonance spectroscopic study. J Neurol Sci
Yang KC, Ku HL, Wu CL, et al. Striatal dopamine transporter binding for predicting the development of delayed neuropsychological sequelae in suicide attempters by carbon monoxide poisoning: A SPECT study. Psychiatry Res
Ozcan N, Ozcam G, Kosar P, Ozcan A, Basar H, Kaymak C. Correlation of computed tomography, magnetic resonance imaging and clinical outcome in acute carbon monoxide poisoning. Braz J Anesthesiol
Liang F, Li W, Zhang P, et al. A PARK2 polymorphism associated with delayed neuropsychological sequelae after carbon monoxide poisoning. BMC Med Genet
Li W, Zhang Y, Gu R, et al. DNA pooling base genome-wide association study identifies variants at NRXN3 associated with delayed encephalopathy after acute carbon monoxide poisoning. PLoS One
Miró O, Casademont J, Barrientos A, Urbano-Márquez A, Cardellach F. Mitochondrial cytochrome c oxidase inhibition during acute carbon monoxide poisoning. Pharmacol Toxicol
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
Omaye ST. Metabolic modulation of carbon monoxide toxicity. Toxicology
Ishimaru H, Katoh A, Suzuki H, Fukuta T, Kameyama T, Nabeshima T. Effects of N-methyl-D-aspartate receptor antagonists on carbon monoxide-induced brain damage in mice. J Pharmacol Exp Ther
Thom SR, Fisher D, Zhang J, Bhopale VM, Cameron B, Buerk DG. Neuronal nitric oxide synthase and N-methyl-D-aspartate neurons in experimental carbon monoxide poisoning. Toxicol Appl Pharmacol
Akyol S, Erdogan S, Idiz N, et al. The role of reactive oxygen species and oxidative stress in carbon monoxide toxicity: an in-depth analysis. Redox Rep
Wang P, Zeng T, Zhang CL, et al. Lipid peroxidation was involved in the memory impairment of carbon monoxide-induced delayed neuron damage. Neurochem Res
Bi M, Li Q, Guo D, et al. Sulphoraphane improves neuronal mitochondrial function in brain tissue in acute carbon monoxide poisoning rats. Basic Clin Pharmacol Toxicol
Sun Q, Cai J, Zhou J, et al. Hydrogen-rich saline reduces delayed neurologic sequelae in experimental carbon monoxide toxicity. Crit Care Med
Mannaioni PF, Vannacci A, Masini E. Carbon monoxide: the bad and the good side of the coin, from neuronal death to anti-inflammatory activity. Inflamm Res
Tofighi R, Tillmark N, Dare E, Aberg AM, Larsson JE, Ceccatelli S. Hypoxia-independent apoptosis in neural cells exposed to carbon monoxide in vitro. Brain Res
Wang W, Tian L, Li Y, et al. Effects of hydrogen-rich saline on rats with acute carbon monoxide poisoning. J Emerg Med
Piantadosi CA, Zhang J, Levin ED, Folz RJ, Schmechel DE. Apoptosis and delayed neuronal damage after carbon monoxide poisoning in the rat. Exp Neurol
Dallas ML, Boyle JP, Milligan CJ, et al. Carbon monoxide protects against oxidant-induced apoptosis via inhibition of Kv2.1. FASEB J
Thom SR, Bhopale VM, Han ST, Clark JM, Hardy KR. Intravascular neutrophil activation due to carbon monoxide poisoning. Am J Respir Crit Care Med
Xiang WP, Xue H, Wang BJ. Delayed encephalopathy of acute carbon monoxide intoxication in rats: potential mechanism and intervention of dexamethasone. Pak J Pharm Sci
Ochi S, Abe M, Li C, et al. The nicotinic cholinergic system is affected in rats with delayed carbon monoxide encephalopathy. Neurosci Lett
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
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
Myers RA, Snyder SK, Emhoff TA. Subacute sequelae of carbon monoxide poisoning. Ann Emerg Med
Adir Y, Bentur Y, Melamed Y. Hyperbaric oxygen for neuropsychiatric sequelae of carbon monoxide poisoning. Harefuah
. 1992;122:562-563, 616.
Lin YT, Chen SY, Lo CP, et al. Utilizing cerebral perfusion scan and diffusion-tensor MR imaging to evaluate the effect of hyperbaric oxygen therapy in carbon monoxide-induced delayed neuropsychiatric seqeulae- a case report and literature review. Acta Neurol Taiwan
Liu WC, Yang SN, Wu CW, Chen LW, Chan JY. Hyperbaric oxygen therapy alleviates carbon monoxide poisoning-induced delayed memory impairment by preserving brain-derived neurotrophic factor-dependent hippocampal neurogenesis. Crit Care Med
Chang DC, Lee JT, Lo CP, et al. Hyperbaric oxygen ameliorates delayed neuropsychiatric syndrome of carbon monoxide poisoning. Undersea Hyperb Med
Lee HF, Mak SC, Chi CS, Hung DZ. Hyperbaric oxygen for carbon monoxide poisoning-induced delayed neuropsychiatric sequelae. Zhonghua Yi Xue Za Zhi (Taipei)
Spagnolo F, Costa M, Impellizzeri M, et al. Delayed hyperbaric oxygen treatment after acute carbon monoxide poisoning. J Neurol
Brown DB, Mueller GL, Golich FC. Hyperbaric oxygen treatment for carbon monoxide poisoning in pregnancy: a case report. Aviat Space Environ Med
Gozubuyuk AA, Dag H, Kacar A, Karakurt Y, Arica V. Epidemiology, pathophysiology, clinical evaluation, and treatment of carbon monoxide poisoning in child, infant, and fetus. Northern clinics of Istanbul
Bessereau J, Aboab J, Hullin T, et al. Safety of hyperbaric oxygen therapy in mechanically ventilated patients. Int Marit Health
Geraldo AF, Silva C, Neutel D, Neto LL, Albuquerque L. Delayed leukoencephalopathy after acute carbon monoxide intoxication. J Radiol Case Rep
Li Q, Cheng Y, Bi MJ, et al. Effects of N-Butylphthalide on the expressions of Nogo/NgR in rat brain tissue after carbon monoxide poisoning. Environ Toxicol Pharmacol
Xiang W, Xue H, Wang B, et al. Efficacy of N-butylphthalide and hyperbaric oxygen therapy on cognitive dysfunction in patients with delayed encephalopathy after acute carbon monoxide poisoning. Med Sci Monit
Huarcaya-Victoria J, Podestá-Ampuero A, Ledesma-Gastañadui M, Reinoso-Santa Cruz C. Treatment of delayed post-hypoxic leukoencephalopathy as a complication of carbon monoxide poisoning with risperidone and hyperbaric oxygen therapy. Actas Esp Psiquiatr
Mao M, Rao P, Mou X, Guo L, Zhang L. Clinical observation on delayed encephalopathy after carbon monoxide poisoning treated with acupuncture to restore consciousness combined with hyperbaric oxygen treatment. Zhongguo Zhen Jiu
Zhao ZR, Zhang JD, Wu AP, Wang R, Li Z. Clinical effects of ganglioside on delayed encephalopathy after acute carbon monoxide poisoning. Zhongguo Zonghe Linchuang
Zhou QA, XU JY, Hu AP, et al. Observation on recover of cerebral infraction patients by Taijiquan training. Zhongguo Shiyong Shenjing Jibing Zazhi
Xiang W, Xue H, Wang B, et al. Combined application of dexamethasone and hyperbaric oxygen therapy yields better efficacy for patients with delayed encephalopathy after acute carbon monoxide poisoning. Drug Des Devel Ther
Feldman J, Renda N, Markovitz GH, Chin W, Sprau SE. Treatment of carbon monoxide poisoning with hyperbaric oxygen and therapeutic hypothermia. Undersea Hyperb Med
Thom SR, Bhopale VM, Fisher D. Hyperbaric oxygen reduces delayed immune-mediated neuropathology in experimental carbon monoxide toxicity. Toxicol Appl Pharmacol
Karaman D, Metin S, Kara K, et al. Neuropsychological evaluation of children and adolescents with acute carbon monoxide poisoning. Pediatr Emerg Care
American College of Emergency Physicians Clinical Policies Subcommittee (Writing Committee) on Carbon Monoxide Poisoning, 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
Jurič DM, Finderle Ž, Šuput D, Brvar M. The effectiveness of oxygen therapy in carbon monoxide poisoning is pressure- and time-dependent: a study on cultured astrocytes. Toxicol Lett
Lin CH, Su WH, Chen YC, et al. Treatment with normobaric or hyperbaric oxygen and its effect on neuropsychometric dysfunction after carbon monoxide poisoning: a systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore)
Hampson NB, Dunford RG, Ross DE, Wreford-Brown CE. A prospective, randomized clinical trial comparing two hyperbaric treatment protocols for carbon monoxide poisoning. Undersea Hyperb Med
Hampson NB, Ocak T. Comparison of normobaric vs. hyperbaric oxygen in the relief of carbon monoxide headache pain. Undersea Hyperb Med
Raphael JC, Elkharrat D, Jars-Guincestre MC, et al. Trial of normobaric and hyperbaric oxygen for acute carbon monoxide intoxication. Lancet
Buckley NA, Juurlink DN, Isbister G, Bennett MH, Lavonas EJ. Hyperbaric oxygen for carbon monoxide poisoning. Cochrane Database Syst Rev
Gilmer B, Kilkenny J, Tomaszewski C, Watts JA. Hyperbaric oxygen does not prevent neurologic sequelae after carbon monoxide poisoning. Acad Emerg Med
Scheinkestel CD, Bailey M, Myles PS, et al. Hyperbaric or normobaric oxygen for acute carbon monoxide poisoning: a randomised controlled clinical trial. Med J Aust
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
Lai CY, Huang YW, Tseng CH, Lin CL, Sung FC, Kao CH. Patients with carbon monoxide poisoning and subsequent dementia: a population-based cohort study. Medicine (Baltimore)
Cowl CT. Justifying Hyperbaric oxygen delivery for carbon monoxide poisoning: time to respond to pressure with a large-scale randomized controlled trial. Chest