The Efficacy of N-Butylphthalide and Dexamethasone Combined with Hyperbaric Oxygen on Delayed Encephalopathy After Acute Carbon Monoxide Poisoning.

BACKGROUND: Carbon monoxide (CO) poisoning is a common health problem among people in many countries, primarily because of its severe clinical effects and high toxicological morbidity and mortality. Acute brain injury and delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) are the most common neurological complications. This study was performed to assess the efficacy of N-butylphthalide (NBP) and dexamethasone (DXM) combined with hyperbaric oxygen (HBO) in patients with DEACMP. PATIENTS AND METHODS: A total of 171 patients with DEACMP were recruited and assigned to the combined therapy group (receiving NBP and DXM 5 mg/day plus HBO therapy) or the control group (HBO therapy as monotherapy). Conventional treatments were provided for all patients. The cognition and movement changes in patients were evaluated by the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA) scale and the Barthel index of activities of daily living (ADL) before and after the treatment at 1 month, 3 months, and 1 year, respectively. RESULTS: At 1 month, 3 months, and 1 year after the treatment, the MMSE, MoCA and ADL scores were all significantly higher in the combined therapy group than those in the control group. There were no significant alterations in blood glucose, blood lipids, or liver and kidney function during the whole treatment session. Some patients experienced loss of appetite, mild headache and minor skin irritations. However, these patients recovered by themselves and needed no additional medications or special treatment. CONCLUSION: These results indicated that NBP and DXM combined with HBO for the treatment of DEACMP can significantly improve the cognitive and motor functions of patients and is very safe.

Fasudil alleviates brain damage in rats after carbon monoxide poisoning through regulating neurite outgrowth inhibitor/oligodendrocytemyelin glycoprotein signalling pathway.

Carbon monoxide (CO) poisoning can lead to many serious neurological symptoms. Currently, there are no effective therapies for CO poisoning. In this study, rats exposed to CO received hyperbaric oxygen therapy, and those in the Fasudil group were given additional Fasudil injection once daily. We found that the escape latency in CO poisoning group (CO group) was significantly prolonged, the T1 /Ttotal was obviously decreased, and the mean escape time and the active escape latency were notably extended compared with those in normal control group (NC group, P < 0.05). After administration of Fasudil, the escape latency was significantly shortened, T1 /Ttotal was gradually increased as compared with CO group (>1 week, P < 0.05). Ultrastructural damage of neurons and blood-brain barrier of rats was serious in CO group, while the structural and functional integrity of neuron and mitochondria maintained relatively well in Fasudil group. Moreover, we also noted that the expressions of neurite outgrowth inhibitor (Nogo), oligodendrocyte-myelin glycoprotein (OMgp) and Rock in brain tissue were significantly increased in CO group, and the elevated levels of the three proteins were still observed at 2 months after CO poisoning. Fasudil markedly reduced their expressions compared with those of CO group (P < 0.05). In summary, the activation of Nogo-OMgp/Rho signalling pathway is associated with brain injury in rats with CO poisoning. Fasudil can efficiently down-regulate the expressions of Nogo, OMgp and Rock proteins, paving a way for the treatment of acute brain damage after CO poisoning.

Evaluation of changes in magnetic resonance diffusion tensor imaging after treatment of delayed encephalopathy due to carbon monoxide poisoning.

Diffusion tensor imaging of the brain tissue microstructure was performed to predict or diagnose the pathophysiological mechanism underlying delayed encephalopathy after carbon monoxide poisoning and the treatment effect was analyzed. The changes in the diffusion parameters (average diffusion coefficient and fractional anisotropy) in adult patients after hyperbaric oxygen therapy of delayed encephalopathy after carbon monoxide poisoning were not significant differences of the two lateral ventricles or anterior or posterior limb of the internal capsule. In the group exposed to hyperbaric oxygen therapy, the fractional anisotropy values of the white matter in the ventricles of the brain and anterior and posterior limbs of the internal capsule were higher than those recorded before therapy, while the average diffusion coefficient values were significantly lower. These finding provide important monitoring indicators for clinicians.

Carbon Monoxide Poisoning: Pathogenesis, Management, and Future Directions of Therapy.

Carbon monoxide (CO) poisoning affects 50,000 people a year in the United States. The clinical presentation runs a spectrum, ranging from headache and dizziness to coma and death, with a mortality rate ranging from 1 to 3%. A significant number of patients who survive CO poisoning suffer from long-term neurological and affective sequelae. The neurologic deficits do not necessarily correlate with blood CO levels but likely result from the pleiotropic effects of CO on cellular mitochondrial respiration, cellular energy utilization, inflammation, and free radical generation, especially in the brain and heart. Long-term neurocognitive deficits occur in 15-40% of patients, whereas approximately one-third of moderate to severely poisoned patients exhibit cardiac dysfunction, including arrhythmia, left ventricular systolic dysfunction, and myocardial infarction. Imaging studies reveal cerebral white matter hyperintensities, with delayed posthypoxic leukoencephalopathy or diffuse brain atrophy. Management of these patients requires the identification of accompanying drug ingestions, especially in the setting of intentional poisoning, fire-related toxic gas exposures, and inhalational injuries. Conventional therapy is limited to normobaric and hyperbaric oxygen, with no available antidotal therapy. Although hyperbaric oxygen significantly reduces the permanent neurological and affective effects of CO poisoning, a portion of survivors still have substantial morbidity. There has been some early success in therapies targeting the downstream inflammatory and oxidative effects of CO poisoning. New methods to directly target the toxic effect of CO, such as CO scavenging agents, are currently under development.

Carbon monoxide poisoning in our homes - report of two survivors from North India.

Carbon monoxide poisoning can result from, e.g., the use of unvented coal-burning heaters, indoor barbecues, or inhalation of exhaust of vehicles. The latter is sometimes used to commit suicide. The most common presentation of carbon monoxide poisoning is cerebral hypoxia. Despite frequent use of indoor coal-burning heaters and stoves during winter months in the northern part of India, carbon monoxide poisoning has been infrequently reported. We describe two cases of carbon monoxide poisoning who reported to the Emergency Department in the early morning of a winter season with un-witnessed, unexplained development of altered level of consciousness.

Delayed leukoencephalopathy after acute carbon monoxide intoxication.

Delayed leukoencephalopathy is an uncommon complication of hypoxic-ischemic events of different etiologies, including carbon monoxide intoxication. We present a case of a 40-year-old male patient who was admitted with rapidly progressive neurocognitive and behavioral deficits. There was a history of accidental carbon monoxide intoxication one month before, presenting with loss of consciousness and short hospitalization, followed by a complete clinical recovery. The imaging studies in the delayed phase depicted confluent, symmetric supra-tentorial white matter lesions in keeping with diffuse demyelinization. Restricted diffusion and metabolite abnormalities in magnetic resonance proton spectroscopy were also seen. The diagnosis of CO-mediated delayed post-hypoxic leukoencephalopathy was assumed after exclusion of other mimickers. Hyperbaric oxygen therapy was tentatively performed and the patient had a favorable clinical and radiological evolution.

The relationship between blood lactate, carboxy-hemoglobin and clinical status in CO poisoning.

AIM: We aimed to determine the relationship between blood lactate, carboxy-hemoglobin (COHb) levels and the severity of clinical findings in patients with CO poisoning. MATERIALS AND METHODS: Patients over 18 years old and of both gender who were admitted to Emergency Department with the diagnosis of CO poisoning between 10.02.2008 and 17.03.20011 were enrolled in this study. Detailed physical examination of each patient was performed, patients and their relatives were informed about the study and written consents were noted. The levels of consciousness, physical examination findings, electrocardiographic findings, Glasgow Coma Scale (GCS) scores, laboratory results (lactate, COHb, CK-MB, Troponin-I levels) and applied treatments [normobaric oxygen therapy (NBOT), hyperbaric oxygen therapy (HBOT)] were recorded to standart data entry form for each patient. "SPSS for Windows version 18″ package program was used for statistical analysis of the data. RESULTS: Total 201 patients were included in this study. Thirty five patients (17.4%) received HBOT and lactate, COHb, CKMB, Troponin-I levels of this group were higher than the other patients. Lactate and COHb levels were statistically significantly higher in patients with GCS < 15 than the ones with GCS = 15 (p < 0.01). The patients whose both Troponin-I and CK-MB levels increased have higher lactate levels (p = 0.038), but COHb levels of these patients did not change (p = 0.495). CONCLUSIONS: According to our study, blood lactate and COHb levels were both correlated with the changes of consciousness in CO poisoning. Blood lactate levels together with COHb in defining indications for HBO treatment might be suggested.

Initial blood lactate correlates with carboxyhemoglobin and clinical severity in carbon monoxide poisoned patients.

OBJECTIVE: The aim of this study was to assess the role of blood lactate levels at admission in carbon monoxide (CO)-poisoned patients for establishing severity of poisoning and short term prognosis. METHOD: All cases of CO poisoning visited in the emergency department during the years 2012 and 2013 were retrieved from the hospital database. The concentration of COHb and lactate was assessed in arterial blood in all patients with suspected CO poisoning, along with the plasma concentration of troponin I (TnI). The control population for TnI results consisted in 125 blood donors. RESULTS: Twenty three (61%) out of 38 CO-poisoned patients underwent hyperbaric oxygen (HBO) treatment, and 10 (26%) were admitted to a hospital ward. A significant correlation was found between lactate and COHb (r=0.54; p<0.001), and between lactate and TnI (r=0.44; p=0.001). A significant correlation was also found between COHb and TnI (r=0.38; p=0.020). Blood lactate levels were higher in patients treated with HBO and hospital admission. In multivariate analysis, none of the parameters was associated with HBO treatment, whereas increased value of blood lactate (p=0.036) was the only significant predictor of hospital admission. Twenty five (66%) patients had detectable TnI levels compared to 13% controls (p<0.001), whereas 16% CO-poisoned patients had TnI levels >99th percentile compared to 2% controls (p=0.003). The odds ratio for detectable TnI and TnI >99th percentile in CO-poisoned patients were 13.1 (p<0.001) and 7.6 (p=0.006), respectively. CONCLUSION: Initial blood lactate level may be useful for risk stratification of CO-poisoned patients, especially for predicting hospitalization.

[Case of carbon monoxide poisoning with delayed encephalopathy assessed by magnetic resonance imaging].

A 21-year-old man attempted suicide by burning charcoal in a car for more than one day and was admitted to a regional hospital. On admission, his blood carboxyhemoglobin concentration was 4.4%. The patient was transferred to our emergency department because of suspected carbon monoxide poisoning. Hyperbaric oxygen therapy (HBO) was performed 5 times over 3 days. Fluid-attenuation inversion recovery (FLAIR) and diffusion-weighted (DWI) magnetic resonance imaging (MRI) performed on day 3 showed high signal-intensity lesions in the cerebral white matter. Additional HBO was performed once per day until day 16. Wecheler Memory Scale-Reviced (WMS-R) and Mini-Mental State Examination (MMSE) performed on day 17 showed his cognitive impairment. He gradually recovered the cognitive function and was discharged from the hospital without neurological sequelae on day 49. Delayed encephalopathy after acute carbon monoxide poisoning with dementia, mental impairment, and psychosis is a serious complication. Hyperintensity in FLAIR and DWI MRI predicts delayed encephalopathy and indicates cellular edema and demyelination of the white matter. One of the risk factors is prolonged carbon monoxide exposure. This case suggests that the patient, who was exposed to carbon monoxide for many hours, was at a high risk of delayed encephalopathy despite the low blood carboxyhemoglobin concentration and therefore must be monitored using MRI.

An autopsy case of acute carbon monoxide poisoning after a long-term vegetative state.

A 23-year-old woman was rescued from an accidental fire in a state of cardiopulmonary arrest. Based on the diagnosis of carbon monoxide (CO) poisoning, she received hyperbaric oxygen therapy and survived in a vegetative state. After 1 and a half years, she died without recovering from the vegetative state. At autopsy, the brain was observed to be moderately softened with a severely atrophied appearance and ventricular enlargement. In addition, a characteristic damage of hypoxic-ischemic leukoencephalopathy was also observed clearly in both the bilateral globus pallidus and cerebral white matter, which are typical findings of past acute CO poisoning. A long-term vegetative state causes the brain to soften and liquefy because of reactive gliosis and autolytic change. The cause of death becomes difficult to diagnose only from the autopsy findings in general. This case is rare in that the past acute CO poisoning could be diagnosed from the remaining typical cerebral findings even after a long-term vegetative state.

Rapid elimination of CO through the lungs: coming full circle 100 years on.

At the start of the 20th century, CO poisoning was treated by administering a combination of CO(2) and O(2) (carbogen) to stimulate ventilation. This treatment was reported to be highly effective, even reversing the deep coma of severe CO poisoning before patients arrived at the hospital. The efficacy of carbogen in treating CO poisoning was initially attributed to the absorption of CO(2); however, it was eventually realized that the increase in pulmonary ventilation was the predominant factor accelerating clearance of CO from the blood. The inhaled CO(2) in the carbogen stimulated ventilation but prevented hypocapnia and the resulting reductions in cerebral blood flow. By then, however, carbogen treatment for CO poisoning had been abandoned in favour of hyperbaric O(2). Now, a half-century later, there is accumulating evidence that hyperbaric O(2) is not efficacious, most probably because of delays in initiating treatment. We now also know that increases in pulmonary ventilation with O(2)-enriched gas can clear CO from the blood as fast, or very nearly as fast, as hyperbaric O(2). Compared with hyperbaric O(2), the technology for accelerating pulmonary clearance of CO with hyperoxic gas is not only portable and inexpensive, but also may be far more effective because treatment can be initiated sooner. In addition, the technology can be distributed more widely, especially in developing countries where the prevalence of CO poisoning is highest. Finally, early pulmonary CO clearance does not delay or preclude any other treatment, including subsequent treatment with hyperbaric O(2).

Severe carbon monoxide poisoning complicated by hypothermia: a case report.

It is proposed that the significant elevation of interleukin-6 (>400 pg/mL) in cerebrospinal fluid during the early phase of carbon monoxide poisoning may be a predictive biomarker for the development of delayed encephalopathy. A 52-year-old man presented to the emergency department with severe carbon monoxide poisoning. On arrival, the patient was comatose with decorticate rigidity (Glasgow Coma Scale, E1V1M3). His core body temperature, measured in the urinary bladder, was 32.4°C. Laboratory blood analysis revealed elevated CO-Hb (36.0%) and metabolic acidosis with elevated lactate (pH 7.081; base excess [BE], -19.2 mmol/L; HCO3, -9.8 mmol/L; lactate, 168.8 mg/dL). After treatment with hyperbaric oxygen and several different rewarming techniques, he became alert and his core body temperature increased to normal. Interleukin-6 in cerebrospinal fluid at 5.5 hours after his last exposure to carbon monoxide was significantly elevated (752 pg/mL). However, he did not develop delayed encephalopathy. In this case, hypothermia in the range of therapeutic hypothermia (32°C to 34°C) may have suppressed formation of reactive oxygen species and subsequent lipid peroxydation, preventing the development of delayed encephalopathy. Therapeutic hypothermia initiated soon after the last exposure to carbon monoxide may be an effective prophylactic method for preventing the development of delayed encephalopathy.

The time-dependent protective effect of hyperbaric oxygen on neuronal cell apoptosis in carbon monoxide poisoning.

INTRODUCTION: The progressive clinical course with delayed neurological damage in carbon monoxide (CO) poisoning may be due to neuron apoptosis. The usefulness of hyperbaric oxygen (HBO) in different time periods after CO exposure in neuronal cell apoptosis reduction has not been evaluated thus far. The aim was to evaluate HBO efficacy in reducing neuronal apoptosis in different time periods after CO exposure. METHODS: Wistar rats were exposed to 3000 ppm CO in air for 60 min and 100% oxygen at a pressure of three bar for 30 min 0-12 h after CO exposure. The apoptosis was evaluated by immunohistochemical analysis with antibodies against activated caspase-3 and the percentage of caspase-3 positive hippocampal ganglionic cells was reported. RESULTS: It was shown that CO poisoning results in ganglionic cell apoptosis. The percentage of apoptotic cells in rats exposed to CO was the highest (32%), whereas the percentage of apoptotic cells in rats exposed to HBO 0 and 1 h after CO was similar with a lower percentage than rats exposed to CO. The percentage of apoptotic cells in rats exposed to HBO 3 and 5 h after CO was similar with a lower percentage than rats exposed to HBO 0 and 1 h after CO. The percentage of apoptotic cells in rats exposed to HBO 7-12 h after CO was similar with a higher percentage than rats exposed to HBO 5 h after CO. CONCLUSION: HBO has a time-dependent protective effect on CO-induced neuron apoptosis with the highest efficiency at 3 and 5 h after CO poisoning.

Damage of white matter tract correlated with neuropsychological deficits in carbon monoxide intoxication after hyperbaric oxygen therapy.

Carbon monoxide (CO) intoxication can result in cognitive deficits and demyelinating changes of the white matter (WM), for which hyperbaric-oxygen (HBO) treatment is considered effective in reducing neuropsychiatric symptoms. This study aimed to analyze cognitive functions and WM diffusion properties in CO intoxication after standard HBO treatment. Seventeen CO intoxicated patients were evaluated 4-6 months after HBO treatment. They also underwent diffusion tensor imaging (DTI) and cognitive assessment, and the results were compared with those from 34 age-matched controls. DTI was transformed into fractional anisotropy (FA) and mean diffusivity (MD) and assessed at every voxel level with tract-based spatial statistics across the brain. Correlation between reduced FA and increased MD with neuropsychological deficits were performed. Cognitive results showed that impairment in executive function, as well as verbal and visual memories, were most prominent. There were extensive areas of increased MD and decreased FA. Correlation analyses showed that memory retrieval, judgment, and verbal generation tasks were related to FA of the frontotemporal WM. MD showed weaker correlation with cognitive deficits. These data suggest that neurologic deficits and WM changes are detectable 4-6 months after HBO therapy. The correlation of WM diffusion with cognitive deficits also suggests that reduced connectivity between different cortical regions is a pathophysiologic mechanism.

1H MR spectroscopy of gray and white matter in carbon monoxide poisoning.

Carbon monoxide (CO) intoxication leads to acute and chronic neurological deficits, but little is known about the specific noxious mechanisms. (1)H magnetic resonance spectroscopy (MRS) may allow insight into the pathophysiology of CO poisoning by monitoring neurochemical disturbances, yet only limited information is available to date on the use of this protocol in determining the neurological effects of CO poisoning. To further examine the short-term and long-term effects of CO on the central nervous system, we have studied seven patients with CO poisoning assessed by gray and white matter MRS, magnetic resonance imaging (MRI) and neuropsychological testing. Five patients suffered from acute high-dose CO intoxication and were in coma for 1-6 days. In these patients, MRI revealed hyperintensities of the white matter and globus pallidus and also showed increased choline (Cho) and decreased N-acetyl aspartate (NAA) ratios to creatine (Cr), predominantly in the white matter. Lactate peaks were detected in two patients during the early phase of high-dose CO poisoning. Two patients with chronic low-dose CO exposure and without loss of consciousness had normal MRI and MRS scans. On follow-up. five of our seven patients had long-lasting intellectual impairment, including one individual with low-dose CO exposure. The MRS results showed persisting biochemical alterations despite the MRI scan showing normalization of morphological changes. In conclusion, the MRS was normal in patients suffering from chronic low-dose CO exposure; in contrast, patients with high-dose exposure showed abnormal gray and white matter levels of NAA/Cr, Cho/Cr and lactate, as detected by (1)H MRS, suggesting disturbances of neuronal function, membrane metabolism and anaerobic energy metabolism, respectively. Early increases in Cho/Cr and decreases of NAA/Cr may be related to a poor long-term outcome, but confirmation by future studies is needed.

Formic acid: a rare but deadly source of carbon monoxide poisoning.

INTRODUCTION: Formic acid decomposes upon contact with strong acids producing carbon monoxide. Carbon monoxide poisoning from such a source, however, is extremely rare. CASE REPORT: A 26-year-old man committed suicide by mixing 2.5 L of formic acid and 2.5 L of sulfuric acid in three beakers and staying in a closed room. The 53-year-old father performed cardiopulmonary resuscitation on his son but soon lost consciousness. In hospital, he initially manifested coma, hypoxemia, metabolic acidosis, and a carboxyhemoglobin level of 45.8%. He was treated with hyperbaric oxygen but developed acute respiratory distress syndrome on day four despite an early improvement. He was successfully weaned from the ventilator on day 8. The 53-year-old mother felt dizziness, headache and had a carboxyhemoglobin level of 23.0%. Her symptoms improved after oxygen therapy. DISCUSSION AND CONCLUSIONS: Formic acid is a highly fatal source of carbon monoxide poisoning when mixed with sulfuric acid. In addition to the toxicities of carbon monoxide, concomitant inhalation of formic acid fumes can cause severe lung injury, which may complicate the management of carbon monoxide poisoning.

Diffusion-tensor MR imaging for evaluation of the efficacy of hyperbaric oxygen therapy in patients with delayed neuropsychiatric syndrome caused by carbon monoxide inhalation.

The purpose of this study is to assess the efficacy of hyperbaric oxygen therapy (HBOT) in patients with delayed neuropsychiatric syndrome (DNS) caused by carbon monoxide (CO) inhalation using diffusion tensor magnetic resonance (MR) imaging and neuropsychological test. Conventional and diffusion tensor brain MR imaging exams were performed in six patients with DNS immediately before and 3 months after the HBOT to obtain fractional anisotropy (FA) values. Six age- and sex-matched normal control subjects also received MR exams for comparison. Mini-Mental State Examination (MMSE) was also performed in patients immediately before and 3 months after the HBOT. A significantly higher mean FA value was found in control subjects as compared with the patients both before and 3 months after the HBOT (P < 0.001). The mean FA value 3 months after the HBOT was also significantly higher than that before the HBOT in the patient group (P < 0.001). All of the patients regained full scores in the MMSE 3 months after the HBOT. Diffusion tensor MR imaging can be a quantitative method for the assessment of the white matter change and monitor the treatment response in patients of CO-induced DNS with a good clinical correlation. HBO may be an effective therapy for DNS.