Emerging Cellular-Based Therapies in Carbon Monoxide Poisoning

2021 ◽  
Author(s):  
David H. Jang ◽  
Sarah Piel ◽  
John C. Greenwood ◽  
Johannes K. Ehinger ◽  
Todd J. Kilbaugh
Keyword(s):  
Carbon Monoxide ◽  
Hydrogen Sulfide ◽  
Active Site ◽  
Carbon Monoxide Poisoning ◽  
Co Poisoning ◽  
Multiple Sources ◽  
Engine Exhaust ◽  
Neurological Sequelae ◽  
Carbon Compounds ◽  
House Fires

Carbon monoxide (CO) is an odorless and colorless gas has multiple sources that include engine exhaust, faulty furnaces and other sources of incomplete combustion of carbon compounds such as house fires. The most serious complications for survivors of consequential CO exposure is persistent neurological sequelae occurring in up to 50% of patients. CO inhibits mitochondrial respiration by specifically binding to the heme a3 in the active site of CIV like hydrogen sulfide, cyanide and phosphides. While hyperbaric oxygen remains the cornerstone for treatment, it has variable efficacy requiring new approaches to treatment. There are a paucity of cellular-based therapies in the area of CO poisoning, there have been recent advancements that include antioxidants and a mitochondrial substrate prodrug. The succinate prodrugs derived from chemical modification of succinate are endeavored to enhance delivery of succinate to cells, increasing uptake of succinate into the mitochondria, and providing metabolic support for cells. The therapeutic intervention of succinate prodrugs is thus potentially applicable to patients with CO poisoning via metabolic support for fuel oxidation and possibly improving efficacy of HBO therapy.

Current and research therapies for the prevention and treatment of delayed neurological syndrome associated with carbon monoxide poisoning: A narrative review

2020 ◽  
Vol 39 (6) ◽  
pp. 765-772
Author(s):  
B del Moral-Barbudo ◽  
R Blancas ◽  
D Ballesteros-Ortega ◽  
M Quintana-Díaz ◽  
Ó Martínez-González
Keyword(s):  
Carbon Monoxide ◽  
Hyperbaric Oxygen ◽  
Carbon Monoxide Poisoning ◽  
Narrative Review ◽  
Co Poisoning ◽  
Common Environment ◽  
Neurological Sequelae ◽  
Neurological Syndrome ◽  
Oxygen Administration ◽  
Prevention And Treatment

Severe carbon monoxide (CO) poisoning causes fulminant deaths in common environment as well as neurological sequelae to survivors. Prevention of delayed neurological syndrome (DNS) after exposure to CO, the most important sequela, is based up to date on hyperbaric oxygen administration. Nevertheless, its use remains controversial due to the lack of evidence regarding its efficacy. The aim of this review is to report therapies under investigation for preventing or improving DNS, some of them with promising results in humans.

Myositis associated with carbon monoxide poisoning

2019 ◽  
pp. 63-67
Author(s):  
Lindell K. Weaver ◽  
◽  
L. Christine Oliver ◽  
Kayla Deru ◽  
Anat O. Stemmer-Rachamimov ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Clinical Investigation ◽  
Carbon Monoxide Poisoning ◽  
Inflammatory Myopathy ◽  
Acute Poisoning ◽  
Thigh Muscle ◽  
Co Poisoning ◽  
Engine Exhaust ◽  
Reactive Protein ◽  
Occult Malignancy

Introduction: Carbon monoxide (CO) poisoning causes hypoxia and inflammation, which could adversely affect muscle. We could find no published information about CO poisoning causing myositis. Case report: A 53-year-old previously healthy female semi-truck driver had CO poisoning from a faulty diesel engine exhaust intermittently over three months, culminating in an episode of acute CO poisoning, with syncope after exiting the truck at the end of the three-month period. Neuropsychological symptoms immediately after the acute poisoning event were followed by the development of fatigue, weakness and myalgias within two months and a diagnosis of “polymyositis” within four months. C-reactive protein and creatine kinase were elevated. Electromyogram showed pure myopathy without sensory abnormalities. Occult malignancy was ruled out. Thigh muscle biopsy revealed severe inflammatory myopathy and myonecrosis. Muscle specialist pathologists interpreted the biopsy as toxic or viral inflammatory myopathy, not polymyositis, with CO poisoning as the likely etiology. She received steroids and mycophenolate. Nineteen months later, a repeat biopsy was negative for inflammation or myopathic process. Alternative diagnoses were ruled out by clinical investigation and her course over the next five years. Conclusions: This patient’s presentation and clinical course support a diagnosis of myositis from CO poisoning, although it is possible that the myositis was either idiopathic or post-viral (without evidence of a causative virus).

The impact of hyperthermia after acute carbon monoxide poisoning on neurological sequelae

2018 ◽  
Vol 38 (4) ◽  
pp. 455-465 ◽  
Author(s):  
JM Moon ◽  
BJ Chun ◽  
SD Lee ◽  
MH Shin
Keyword(s):  
Carbon Monoxide ◽  
Carbon Monoxide Poisoning ◽  
Early Period ◽  
Maximum Temperature ◽  
Co Poisoning ◽  
Neurological Sequelae ◽  
Neurological Outcomes ◽  
Significant Difference ◽  
The Impact

This study investigated whether hyperthermia within the first 24 h after presentation was associated with long-term neurological outcomes after acute carbon monoxide (CO) poisoning. This retrospective study included 200 patients with acute severe CO poisoning. Hyperthermia (≥ 37.5°C) developed during the first 24 h after presentation in 55 (27.5%) patients, and poor long-term neurological sequelae assessed at 23 months after acute CO poisoning developed in 19.5% of the patients. The incidence of poor long-term neurological outcomes was significantly higher in the hyperthermia group than in the normothermia group. Patients with poor long-term neurological outcomes had higher maximum temperatures than patients with good outcomes. No significant difference was found in the time of hyperthermia onset within the first day according to the neurological outcomes. Hyperthermia (adjusted odds ratio (aOR) 5.009 (95% confidence interval (CI) 1.556–16.126)) and maximum temperature (aOR 2.581 (95% CI 1.098–6.063)) within the first 24 h after presentation to the emergency department were independently associated with poor long-term neurological outcomes. Body temperature measurements, which are easily and noninvasively recorded at the bedside in any facility, help to predict the risk for poor long-term neurological outcomes. This study carefully emphasizes fastidious control of pyrexia, particularly during the early period after acute CO poisoning.

scholarly journals Cerebral White Matter Lesions on Diffusion-Weighted Images and Delayed Neurological Sequelae after Carbon Monoxide Poisoning: A Prospective Observational Study

Diagnostics ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 698
Author(s):  
Sangun Nah ◽  
Sungwoo Choi ◽  
Han Bit Kim ◽  
Jungbin Lee ◽  
Sun-Uk Lee ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
White Matter ◽  
Carbon Monoxide Poisoning ◽  
Subsequent Development ◽  
Brain Lesions ◽  
University Hospital ◽  
Co Poisoning ◽  
Neurological Sequelae ◽  
Diffusion Weighted Images ◽  
Diffusion Weighted

Introduction: Carbon monoxide (CO) poisoning can result in delayed neurological sequelae (DNS). Factors predicting DNS are still controversial. This study aims to determine whether acute brain lesions observed using diffusion-weighted magnetic resonance imaging (MRI) following acute CO poisoning are related to the subsequent development of DNS. Methods: This prospective study was conducted on patients with CO poisoning treated at a university hospital in Bucheon, Korea. From August 2016 to July 2019, a total of 283 patients visited the hospital because of CO poisoning. Exclusion criteria included age under 18 years, refusing hyperbaric oxygen therapy, refusing MRI, being discharged against medical advice, being lost to follow-up, having persistent neurological symptoms at discharge, and being transferred from another hospital 24 h after exposure. Results: Of the 154 patients included in the final study, acute brain lesions on MRI (ABLM) were observed in 49 patients (31.8%) and DNS occurred in 30 patients (19.5%). In a logistic regression analysis, lower Glasgow coma scale score and higher exposure time were associated with DNS, and the presence of ABLM in white matter was significantly associated with DNS (OR 6.741; 95% CI, 1.843–24.660; p = 0.004). Conclusion: The presence of ABLM in white matter was significantly related to the occurrence of DNS. Early prediction of the risk of developing DNS through MRI may be helpful in treating patients with CO poisoning.

scholarly journals Variability in Treatment for Carbon Monoxide Poisoning in Japan: A Multicenter Retrospective Survey

2018 ◽  
Vol 2018 ◽  
pp. 1-5
Author(s):  
Motoki Fujita ◽  
Yasutaka Oda ◽  
Kotaro Kaneda ◽  
Yoshikatsu Kawamura ◽  
Takashi Nakahara ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Observational Study ◽  
Online Survey ◽  
Prospective Observational Study ◽  
Carbon Monoxide Poisoning ◽  
Co Poisoning ◽  
Neurological Sequelae ◽  
Retrospective Survey ◽  
Consciousness Disturbance ◽  
Long Time

Background. The aim of this study was to identify practice differences in the treatment of carbon monoxide (CO) poisoning with or without hyperbaric oxygen (HBO2) therapy in Japan. Materials and Methods. Using an online survey website (Google form), we created a questionnaire and invited interested institutions to join the COP-J Study, a prospective observational study of CO poisoning in Japan. Results. Forty-eight (63%) of 76 institutions replied to the questionnaire. Thirty-three institutions (69%) administered HBO2 therapy to patients with CO poisoning, and 15 institutions (31%) did not. Consciousness disturbance on arrival, exposure to CO for a long time, and elevation of arterial carboxyhemoglobin (CO-Hb) were the major indications for HBO2 therapy. The maximum therapeutic pressures were 2.0, 2.5, and 2.8 atmospheres absolute (ATA) at 19 (58%), 6 (18%), and 8 (24%) institutions, respectively. The number of HBO2 sessions on the first day was 1–3, and 1–7 sessions were administered on days 2–7. Seventeen (35%) institutions treated patients with delayed neurological sequelae (DNS) and 15 of them used HBO2 therapy for DNS. Conclusions. This survey indicates that HBO2 therapy for CO poisoning was varied in both the indications and practice regimens used in Japan.

scholarly journals Use of hyperbaric oxygen therapy for preventing delayed neurological sequelae in patients with carbon monoxide poisoning: A multicenter, prospective, observational study in Japan

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253602
Author(s):  
Motoki Fujita ◽  
Masaki Todani ◽  
Kotaro Kaneda ◽  
Shinya Suzuki ◽  
Shinjiro Wakai ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Observational Study ◽  
Hyperbaric Oxygen ◽  
Prospective Observational Study ◽  
Carbon Monoxide Poisoning ◽  
Clinical Treatment ◽  
Co Poisoning ◽  
Neurological Sequelae ◽  
Factors Associated ◽  
Multicenter Prospective Observational Study

Background The purpose of this study was to clarify the practical clinical treatment for acute carbon monoxide (CO) poisoning in Japan and to investigate the efficacy of hyperbaric oxygen (HBO2) therapy in preventing delayed neurological sequelae (DNS) in the acute phase of CO poisoning. Methods We conducted a multicenter, prospective, observational study of acute CO poisoning in Japan. Patients with acute CO poisoning were enrolled and their treatment details were recorded. The primary endpoint was the onset of DNS within 2 months of CO exposure. Factors associated with DNS were assessed with logistic regression analysis. Results A total of 311 patients from 57 institutions were registered and 255 were analyzed: 171 received HBO2 therapy (HBO2 group) and 84 did not (normobaric oxygen [NBO2] group). HBO2 therapy was performed zero, once, twice, or three times within the first 24 h in 1.8%, 55.9%, 30.9%, and 11.3% of the HBO2 group, respectively. The treatment pressure in the first HBO2 session was 2.8 ATA (47.9% of the HBO2 group), 2.0 ATA (41.8%), 2.5 ATA (7.9%), or another pressure (2.4%). The incidence of DNS was 13/171 (7.6%) in the HBO2 group and 3/84 (3.6%) in the NBO2 group (P = 0.212). The number of HBO2 sessions in the first 24 h was one of the factors associated with the incidence of DNS (odds ratio, 2.082; 95% confidence interval, 1.101–3.937; P = 0.024). Conclusions The practical clinical treatment for acute CO poisoning, including HBO2 therapy, varied among the institutions participating in Japan. HBO2 therapy with inconsistent protocols showed no advantage over NBO2 therapy in preventing DNS. Multiple HBO2 sessions was associated with the incidence of DNS.

scholarly journals Predictive Role of QTc Prolongation in Carbon Monoxide Poisoning-Related Delayed Neuropsychiatric Sequelae

2018 ◽  
Vol 2018 ◽  
pp. 1-8
Author(s):  
Shu-Chen Liao ◽  
Yan-Chiao Mao ◽  
Yao-Min Hung ◽  
Ching-Hsing Lee ◽  
Chen-Chang Yang
Keyword(s):  
Carbon Monoxide ◽  
Roc Curve ◽  
Carbon Monoxide Poisoning ◽  
Chang Gung Memorial Hospital ◽  
Qtc Interval ◽  
Continuous Variables ◽  
Co Poisoning ◽  
Qtc Prolongation ◽  
Roc Curve Analysis ◽  
Delayed Neuropsychiatric Sequelae

Objective. Delayed neuropsychiatric sequelae (DNS) are serious complications of carbon monoxide (CO) poisoning that adversely affect poisoned patients’ quality of life as well as socioeconomic status. This study aimed to determine clinical predictors of DNS in patients with CO poisoning. Methods. This retrospective study included all CO-poisoned patients admitted to the emergency department (ED) of Linkou Chang Gung Memorial Hospital in Taiwan from 1 January 2009 to 31 December 2015. The medical records of all patients with CO poisoning were carefully reviewed, and relevant data were abstracted into a standardised form. Univariate and multivariate logistic regression models were used to identify predictors of DNS after CO poisoning. Receiver operating characteristic (ROC) curve analysis was used to determine the ideal cut-off value for continuous variables that predict the development of DNS. Results. A total of 760 patients with CO poisoning were identified during the study period. Among them, 466 were eligible for the analysis of predictors of DNS. In multivariate analysis, Glasgow Coma Scale <9 (odds ratio [OR], 2.74; 95% confidence interval [CI], 1.21–6.21), transient loss of consciousness (OR, 3.59; 95% CI, 1.31–9.79), longer duration from CO exposure to ED presentation (OR, 1.05; 95% CI, 1.03–1.08), and corrected QT (QTc) prolongation (OR, 2.61; 95% CI, 1.21–5.61) were found to be associated with a higher risk of DNS. The area under the ROC curve (AUC) for QTc interval measured within 6 h after exposure best predicted the development of DNS, with a result of 0.729 (95% CI 0.660–0.791). Moreover, the best cut-off value of the QTc interval was 471 ms, with a sensitivity of 53.3% and a specificity of 85.1%. Conclusions. We identified several potential predictors of DNS following CO poisoning. Among them, QTc prolongation found within 6 h after exposure is a novel predictor of DNS, which may be helpful in the future care of patients with CO poisoning.

scholarly journals Delayed Neurological Sequelae Following Carbon Monoxide Poisoning and Skin Graft: A Case Report

2020 ◽  
Vol 5 (4) ◽  
pp. 164-167
Author(s):  
Reza Bidaki ◽  
Azadeh Rahavi ◽  
Farzaneh Dehghani ◽  
Mohamad Ebrahim Ghanei ◽  
Najmeh Zaer-Alhosseini ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Case Report ◽  
Skin Graft ◽  
Carbon Monoxide Poisoning ◽  
Neurological Sequelae

Brain stem and spinal cord demyelination due to acute carbon monoxide poisoning

2021 ◽  
pp. 247-253
Author(s):  
Yan Lv ◽  
Yv Zhang ◽  
Shuyi Pam ◽  
Keyword(s):  
Spinal Cord ◽  
Carbon Monoxide ◽  
Brain Stem ◽  
Carbon Monoxide Poisoning ◽  
Recovery Period ◽  
Extended Period ◽  
Severe Case ◽  
Co Poisoning ◽  
Secondary Demyelination ◽  
The Brain

Demyelination throughout the brain stem and spinal cord caused by acute carbon monoxide (CO) poisoning has not been previously reported. Magnetic resonance imaging (MRI) has revealed that acute CO poisoning primarily affects the subcortical white matter of the bilateral cerebral hemispheres and basal ganglia. Here we report the case of a patient with delayed neuropsychological sequelae (DNS) due to acute CO poisoning. A 28-year-old man was admitted to our department following a suicide attempt by acute CO poisoning. After a six-month pseudo-recovery period, he was diagnosed with DNS, with MRI evidence of demyelinating change of the bilateral cerebral peduncles. Demyelination was identified throughout the brain stem, expanding from the bilateral cerebral peduncles to the medulla oblongata, occurring approximately six months after poisoning. One and a half years after acute CO poisoning, demyelination of the cervical and thoracic spine was observed, most notable in the lateral and posterior cords. It is evident that previously published research on this topic is extremely limited. Perhaps in severe cases of acute CO poisoning the fatality rate is higher, leading to fewer surviving cases for possible study. This may be because a more severe case of acute CO poisoning would result in the higher likelihood of secondary demyelination. This research indicates that clinicians should be aware of the risk of secondary demyelination and take increased precautions such as vitamin B supplementation and administration of low-dose corticosteroids for an extended period of time in order to reduce the extent and severity of demyelination.

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