RESUMO
BACKGROUND AND OBJECTIVES: Approximately 50,000 emergency department visits per year due to carbon monoxide (CO) poisoning occur in the United States alone. Tissue hypoxia can occur at very low CO concentration exposures because CO binds with a 250-fold higher affinity than oxygen to hemoglobin. The most effective therapy is 100% hyperbaric oxygen (HBO) respiration. However, there are only a limited number of cases with ready accessibility to the specialized HBO chambers. In previous studies, we developed an extracorporeal veno-venous membrane oxygenator that facilitates exposure of blood to an external visible light source to photo-dissociate carboxyhemoglobin (COHb) and significantly increase CO removal from CO-poisoned blood (photo-extracorporeal veno-venous membrane oxygenator [p-ECMO]). One objective of this study was to describe in vitro experiments with different laser wavelength sources to compare CO elimination rates in a small unit-cell ECMO device integrated with a light-diffusing optical fiber. A second objective was to develop a mathematical model that predicts CO elimination rates in the unit-cell p-ECMO device design upon which larger devices can be based. STUDY DESIGN/MATERIAL AND METHODS: Two small unit-cell p-ECMO devices consisted of a plastic capillary with a length and inside diameter of 10 cm and 1.15 mm, respectively. Either five (4-1 device) or seven (6-1 device) gas exchange tubes were placed in the plastic capillary and a light-diffusing fiber was inserted into one of the gas exchange tubes. Light from lasers emitting either 635 nm or 465 nm wavelengths was coupled into the light-diffusing fiber as oxygen flowed through the gas exchange membranes. To assess the ability of the device to remove CO from blood in vitro, the percent COHb reduction in a single pass through the device was assessed with and without light. The Navier Stokes equations, Carreau-Yesuda model, Boltzman equation for light distribution, and hemoglobin kinetic rate equations, including photo-dissociation, were combined in a mathematical model to predict COHb elimination in the experiments. RESULTS: For the unit-cell devices, the COHb removal rate increases with increased 635 nm laser power, increased blood time in the device, and greater gas exchange membrane surface-to-blood volume ratio. The 6-1 device COHb half-life versus that of the 4-1 device with 4 W at 635 nm light was 1.5 min versus 4.25 min, respectively. At 1 W laser power, 635 nm and 465 nm exhibited similar CO removal rates. The COHb half-life times of the 6-1 device were 1.25, 2.67, and 8.5 min at 635 nm (4 W), 465 nm (1 W), and 100% oxygen only, respectively. The mathematical model predicted the experimental results. An analysis of the in vivo COHb half-life of oxygen respiration therapy versus an adjunct therapy with a p-ECMO device and oxygen respiration shows a reduction from 90 min to as low as 10 min, depending on the device design. CONCLUSION: In this study, we experimentally studied and developed a mathematical model of a small unit-cell ECMO device integrated with a light-diffusing fiber illuminated with laser light. The unit-cell device forms the basis for a larger device and, in an adjunct therapy with oxygen respiration, has the potential to remove COHb at much higher rates than oxygen therapy alone. The mathematical model can be used to optimize the design in practical implementations to quickly and efficiently remove CO from CO-poisoned blood.
Assuntos
Intoxicação por Monóxido de Carbono , Humanos , Intoxicação por Monóxido de Carbono/terapia , Oxigenadores de Membrana , Hemoglobinas/análise , Hemoglobinas/metabolismo , Carboxihemoglobina/análise , Carboxihemoglobina/metabolismo , Oxigênio , Modelos TeóricosRESUMO
BACKGROUND AND OBJECTIVES: Carbon monoxide (CO) inhalation is the leading cause of poison-related deaths in the United States. CO binds to hemoglobin (Hb), displaces oxygen, and reduces oxygen delivery to tissues. The optimal treatment for CO poisoning in patients with normal lung function is the administration of hyperbaric oxygen (HBO). However, hyperbaric chambers are only available in medical centers with specialized equipment, resulting in delayed therapy. Visible light dissociates CO from Hb with minimal effect on oxygen binding. In a previous study, we combined a membrane oxygenator with phototherapy at 623 nm to produce a "mini" photo-ECMO (extracorporeal membrane oxygenation) device, which improved CO elimination and survival in CO-poisoned rats. The objective of this study was to develop a larger photo-ECMO device ("maxi" photo-ECMO) and to test its ability to remove CO from a porcine model of CO poisoning. STUDY DESIGN/MATERIALS AND METHODS: The "maxi" photo-ECMO device and the photo-ECMO system (six maxi photo-ECMO devices assembled in parallel), were tested in an in vitro circuit of CO poisoning. To assess the ability of the photo-ECMO device and the photo-ECMO system to remove CO from CO-poisoned blood in vitro, the half-life of COHb (COHb-t1/2 ), as well as the percent COHb reduction in a single blood pass through the device, were assessed. In the in vivo studies, we assessed the COHb-t1/2 in a CO-poisoned pig under three conditions: (1) While the pig breathed 100% oxygen through the endotracheal tube; (2) while the pig was connected to the photo-ECMO system with no light exposure; and (3) while the pig was connected to the photo-ECMO system, which was exposed to red light. RESULTS: The photo-ECMO device was able to fully oxygenate the blood after a single pass through the device. Compared to ventilation with 100% oxygen alone, illumination with red light together with 100% oxygen was twice as efficient in removing CO from blood. Changes in gas flow rates did not alter CO elimination in one pass through the device. Increases in irradiance up to 214 mW/cm2 were associated with an increased rate of CO elimination. The photo-ECMO device was effective over a range of blood flow rates and with higher blood flow rates, more CO was eliminated. A photo-ECMO system composed of six photo-ECMO devices removed CO faster from CO-poisoned blood than a single photo-ECMO device. In a CO-poisoned pig, the photo-ECMO system increased the rate of CO elimination without significantly increasing the animal's body temperature or causing hemodynamic instability. CONCLUSION: In this study, we developed a photo-ECMO system and demonstrated its ability to remove CO from CO-poisoned 45-kg pigs. Technical modifications of the photo-ECMO system, including the development of a compact, portable device, will permit treatment of patients with CO poisoning at the scene of their poisoning, during transit to a local emergency room, and in hospitals that lack HBO facilities.
Assuntos
Intoxicação por Monóxido de Carbono , Venenos , Animais , Monóxido de Carbono , Intoxicação por Monóxido de Carbono/terapia , Carboxihemoglobina/metabolismo , Humanos , Fototerapia/métodos , Ratos , SuínosAssuntos
Intoxicação por Monóxido de Carbono/fisiopatologia , Escala de Coma de Glasgow , Exame Neurológico , Adulto , Intoxicação por Monóxido de Carbono/metabolismo , Intoxicação por Monóxido de Carbono/terapia , Carboxihemoglobina/metabolismo , China , Progressão da Doença , Feminino , Humanos , Oxigenoterapia Hiperbárica , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto JovemRESUMO
AIM: Carbon monoxide (CO) is a colorless, odorless gas and tasteless. CO poisoning (COP) is one of the most frequently encountered inhalation poisonings. The most common cause of morbidity in COP is delayed neurological sequelae (DNS). DNS is the occurrence of neuropsychiatric findings within 2-240â¯days after discharge of patients with COP and there are no definitive diagnostic criteria. The aim of our study is; to determine the risk factors and incidence of DNS. METHOD: Our study is a retrospective, observational study. Patients with the diagnosis of COP in the emergency department between 2015 and 2016 were included in the study. Patients age, gender, findings in the initial physical examination (PE) and neurological examination (NE), blood carboxyhemoglobin (COHb) level, relation between hyperbaric oxygen (HBO) treatment and DNS were assessed. RESULTS: Total of 72 patients were included in the study. Mean age was 33.43⯱â¯20.89. It was determined that pathological findings in the initial NE are a significant predictive factor for DNS (Odds ratio 18.600, p:0.004). Significant relation between NE and HBO treatment was present (p:00.1). There was no statistically significant relationship between initial COHb level and receiving HBO treatment (p:0.9). Median COHb level of patients with DNS was 30 (min:10, max: 43), median COHb level of patients without DNS was 25 (min:10, max:44) and there was no statistically significant relationship between the two groups according to COHb levels (p:0.7). CONCLUSION: Pathological findings in the initial neurological examination had a predictive value for delayed neurological sequelae in patients with carbon monoxide poisoning.
Assuntos
Intoxicação por Monóxido de Carbono/fisiopatologia , Carboxihemoglobina/metabolismo , Doenças do Sistema Nervoso/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Atenção , Intoxicação por Monóxido de Carbono/metabolismo , Intoxicação por Monóxido de Carbono/psicologia , Intoxicação por Monóxido de Carbono/terapia , Criança , Pré-Escolar , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/psicologia , Confusão/epidemiologia , Confusão/etiologia , Confusão/fisiopatologia , Confusão/psicologia , Feminino , Hospitalização , Humanos , Oxigenoterapia Hiperbárica/estatística & dados numéricos , Hiperfagia/epidemiologia , Hiperfagia/etiologia , Hiperfagia/fisiopatologia , Hiperfagia/psicologia , Lactente , Tempo de Internação , Masculino , Transtornos da Memória/epidemiologia , Transtornos da Memória/etiologia , Transtornos da Memória/fisiopatologia , Transtornos da Memória/psicologia , Pessoa de Meia-Idade , Rigidez Muscular/epidemiologia , Rigidez Muscular/etiologia , Rigidez Muscular/fisiopatologia , Rigidez Muscular/psicologia , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/fisiopatologia , Doenças do Sistema Nervoso/psicologia , Exame Neurológico , Exame Físico , Equilíbrio Postural , Fatores de Risco , Transtornos de Sensação/epidemiologia , Transtornos de Sensação/etiologia , Transtornos de Sensação/fisiopatologia , Transtornos de Sensação/psicologia , Fatores de TempoRESUMO
Objective: Preterm infants are prone to increased bilirubin burden and display adverse outcomes if left unmonitored; therefore, predicting an increased bilirubin production is of paramount importance.Methods: We aimed to evaluate carboxyhemoglobin (COHb) levels in moderate (GA: 320/7-336/7) and late preterm (GA: 340/7-366/7) infants to assess whether this molecule could be used as an early predictor of phototherapy requirement.Results: A total of 221 infants were enrolled in the study. On admission, carboxyhemoglobin levels of infants who received phototherapy were significantly higher than that of infants who did not require this treatment, and this difference persisted in the consecutive hours (median (min-max): 1.2% (0.3-1.7) versus 0.8% (0.4-1.1); p < .001). The initial and consecutive COHb levels showed positive correlation (r = 0.77, p < .001). In the post-hoc analysis, direct antiglobulin test positivity significantly affected phototherapy requirement (p < .001). Receiver operating characteristics analysis showed that a COHb level of ≥0.95% was found to have a sensitivity of 90% and a specificity of 88%. Multinomial logistic regression analysis demonstrated that high COHb levels on admission significantly increased the likelihood of phototherapy requirement when adjusted for covariants (adjusted odds ratio: 2.2; 95% confidence interval: 1.4-3.5; p < .001).Conclusion: Carboxyhemoglobin measurement can be simply used to predict preterm infants who will require phototherapy.
Assuntos
Carboxihemoglobina/metabolismo , Hiperbilirrubinemia/diagnóstico , Bilirrubina/sangue , Estudos de Casos e Controles , Feminino , Idade Gestacional , Humanos , Hiperbilirrubinemia/sangue , Hiperbilirrubinemia/terapia , Recém-Nascido , Recém-Nascido Prematuro/sangue , Masculino , Fototerapia , Gravidez , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
Aims: We investigated the relationship between total serum bilirubin (TSB) and carboxyhemoglobin (COHb) in term neonates with detected and treated hemolysis within a particular time frame with the aim of augmenting the case for early diagnosis and prevention of morbidity in hemolysis. Materials and Methods: The study group comprised term newborns who were above the 95th percentile for TSB, underwent intravenous immunoglobulin (IVIG) or applied total exchange transfusion due to hemolysis. Newborns without hemolysis who were above the 95th TSB percentile and required phototherapy comprised the control group. Results: At a cutoff COHb value of 2.2%, 80.8% sensitivity, 95.5% specificity, 18.1 likelihood ratio, positive predictive value of 94.7%, and negative predictive value of 83.2% were identified. Conclusion: We found that COHb is a sensitive and specific method for detecting hemolysis, and it can be used in the early diagnosis of hemolytic diseases causing early and severe hyperbilirubinemia.
Assuntos
Carboxihemoglobina/metabolismo , Hemólise/fisiologia , Hiperbilirrubinemia/diagnóstico , Sensibilidade e Especificidade , Sistema ABO de Grupos Sanguíneos/metabolismo , Feminino , Humanos , Hiperbilirrubinemia/metabolismo , Recém-Nascido , Icterícia Neonatal/diagnóstico , Icterícia Neonatal/metabolismo , MasculinoRESUMO
BACKGROUND: Carbon monoxide (CO) poisoning may result in acute neurological sequelae, cognitive sequelae, and delay neurological sequelae. The administration of hyperbaric oxygen (HBO) to prevent the development of delayed neurological sequelae in CO poisoning have extensively investigated but conflicting results have been reported. We performed a systematic literature review and meta-analysis of randomized controlled trials (RCTs) evaluating HBO treatment and its effect on neuropsychometric dysfunction after CO poisoning. METHODS: We searched Medline, Embase, Pubmed, and the Cochrane Register of Controlled Trials from inception to December 2017. Eligible studies compared HBO therapy with normobaric oxygen (NBO) in patients with CO poisoning. RESULTS: Six studies compared HBO with NBO in CO poisoning patients. Compared with patients treated with NBO, a lower percentage of patients treated with HBO reported headache (16.2% vs 16.5%, relative risk [RR]â=â0.83, 95% CIâ=â0.38-1.80), memory impairment (18.2% vs 23.8%, RRâ=â0.80, 95% CIâ=â0.43-1.49), difficulty concentrating (15.0% vs 18.4%, RRâ=â0.86, 95% CIâ=â0.55-1.34), and disturbed sleep (14.7% vs 16.2%, RRâ=â0.91, 95% CIâ=â0.59-1.39). Two sessions of HBO treatment exhibited no advantage over one session. CONCLUSIONS: The meta-analysis indicated that compared with CO poisoning patients treated with NBO, HBO treated patients have a lower incidence of neuropsychological sequelae, including headache, memory impairment, difficulty concentrating, disturbed sleep, and delayed neurological sequelae. Taking into consideration the cost-effectiveness of one session of HBO, one session of HBO treatment could be an economical option for patients with CO poisoning with high severity.
Assuntos
Intoxicação por Monóxido de Carbono/complicações , Oxigenoterapia Hiperbárica/efeitos adversos , Transtornos da Memória/prevenção & controle , Doenças do Sistema Nervoso/prevenção & controle , Transtornos do Sono-Vigília/prevenção & controle , Intoxicação por Monóxido de Carbono/terapia , Carboxihemoglobina/metabolismo , Progressão da Doença , Humanos , Oxigenoterapia Hiperbárica/economia , Oxigenoterapia Hiperbárica/métodos , Transtornos da Memória/etiologia , Transtornos da Memória/terapia , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/terapia , Avaliação de Resultados em Cuidados de Saúde , Oxigenoterapia/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Transtornos do Sono-Vigília/etiologia , Transtornos do Sono-Vigília/terapia , Resultado do TratamentoRESUMO
BACKGROUND: African-American (AA) infants are known to have, overall, lower bilirubin levels than infants of other ethnicities during their birth hospitalization. However, they are known to have a higher incidence of severe hyperbilirubinemia and are over represented in the US Kernicterus Registry. Heme oxygenase-1 (HO) is the rate limiting enzyme in heme metabolism leading to the equimolar production of bilirubin, carbon monoxide (CO) and free iron (Fe). Short (S) (GT)n repeats (<25) in the promoter region of the gene encoding the inducible HO-1 isozyme augment its expression, while long (L) repeats (>33) lead to an attenuation, modulating the production of bilirubin and CO. The impact of HO-1 promoter polymorphisms on bilirubin levels has not been well studied in (AA) infants. OBJECTIVE: The objectives of this study were to compare the distribution of (GT)n repeat lengths in the HO-1 promoter region in a cohort of AA infants to those found in other ethnicities and to evaluate the contribution of this polymorphism to the degree of hyperbilirubinemia and the level of COHbc in this cohort. METHODS: We prospectively studied a cohort of term AA infants with O+ mothers. Per hospital routine, infants' blood type, Rh status, direct antiglobulin test (DAT), and total bilirubin (TB) levels were checked prior to discharge. After parental consent, blood was collected for DNA extraction and carboxyhemoglobin (COHbc) measurements at the same time as the infants' newborn screen. An infant's TB percentile risk based on the Bhutani nomogram was used to determine need for phototherapy or follow-up. (GT)n repeat length in the HO-1 promoter was determined for each allele using PCR after DNA extraction from dried bloodspots. Size of allele lengths were typed as short (S, <25), medium (M, 25-33) or long (L, >33). RESULTS: One hundred eighty infants were studied for a total of 360 separate alleles. 12.2% (44/360) of alleles were S which was significantly less than all other ethnicities reviewed. Carboxyhemoglobin (COHbc) levels and bilirubin percentiles were higher among infants who had at least one S allele when compared to those who had at least one L allele in the cohort as a whole: COHbc 0.92 ± 0.35 vs. 0.85 ± 0.37; p = 0.28 and Bilirubin percentile 48.6 ± 34.0 vs. 44.9 ± 31.6; p = 0.51. This relationship remained when only those infants who were DAT neg were examined: COHbc 0.81 ± 0.26 vs. 0.74 ± 0.21; p = 0.11 and Bilirubin percentile 43.6 ± 29.9 vs. 37.5 ± 28.7; p = 0.28. CONCLUSIONS: The presence of L alleles of this variant is significantly greater among infants who are either African or of African descent. There was a trend toward lower COHbc levels among infants with at least one L allele as opposed to at least one S allele, although this did not have a statistically significant impact on TB risk percentile.
Assuntos
Negro ou Afro-Americano/genética , Heme Oxigenase-1/genética , Hiperbilirrubinemia Neonatal/genética , Polimorfismo Genético , Regiões Promotoras Genéticas , Alelos , Bilirrubina/sangue , Biomarcadores/sangue , Carboxihemoglobina/metabolismo , Feminino , Predisposição Genética para Doença , Humanos , Hiperbilirrubinemia Neonatal/sangue , Hiperbilirrubinemia Neonatal/etnologia , Recém-Nascido , Masculino , Estudos ProspectivosRESUMO
INTRODUCTION: The carboxyhemoglobin half-life (COHb t1/2) during hyperbaric oxygen (HBO2) is often quoted as 23 minutes, derived from the average of two adult male volunteers breathing HBO2 at 3 atmospheres absolute (ATA). However, the mean COHb t1/2 of 12 male volunteer smokers was 26.3 minutes at 1.58 ATA and in 12 non-intubated carbon monoxide (CO) poisoned patients treated at 3 ATA, was 43 minutes. CASE REPORT: An 81-year old male, poisoned by an improperly ventilated natural gas heater, was intubated for coma, then treated with HBO2. His PaO2/FiO2 = 283 from aspiration. His initial COHb was 34.4%, and 18 minutes before HBO2, 5.9%. After a compression interval of 17 minutes, the COHb measured after 22 minutes at 3 ATA was 3.3%. RESULTS: By exponential decay, his COHb t1/2 before HBO2 was 95 minutes. We estimate the range for COHb t1/2 during compression as 62-81 minutes and for the 3-ATA interval, 58 to 49 minutes, respectively. The mid-point estimate of COHb t1/2 at 3 ATA was 53 minutes. CONCLUSIONS: The COHb t1/2 we calculated is greater than previously reported, but longer in our patient possibly because of concomitant respiratory failure, lung dysfunction, and mechanical ventilation. The often-cited COHb t1/2 of 23 minutes, likely underestimates the actual COHb t1/2 in CO-poisoned patients, especially those with cardiopulmonary dysfunction.
Assuntos
Intoxicação por Monóxido de Carbono/metabolismo , Intoxicação por Monóxido de Carbono/terapia , Carboxihemoglobina/metabolismo , Oxigenoterapia Hiperbárica , Idoso de 80 Anos ou mais , Meia-Vida , Humanos , Masculino , Resultado do TratamentoRESUMO
Throughout the world both intentional and inadvertent exposure to carbon monoxide (CO) remains an important public health issue. While CO poisoning can be lethal, the morbidity is predominantly due to nervous system injury. A previously healthy 22-year-old woman was found unconscious at home by her sister. Her parents were found dead in the house with a recent history of a dysfunctional furnace. She was presumed to have CO poisoning despite an initial carboxyhaemoglobin level of 2.5%. Patient had both clinical and radiological evidence of neurological damage. However, with multiple sessions of hyperbaric oxygen (HBO) therapy she recovered to a near normal functional status. There is no consensus that exists among treating physicians about the role of hyperbaric oxygen in management of neurological injury. The case described here has significant neurological damage related to CO exposure but improved after HBO therapy.
Assuntos
Intoxicação por Monóxido de Carbono/terapia , Monóxido de Carbono/efeitos adversos , Carboxihemoglobina/metabolismo , Oxigenoterapia Hiperbárica , Oxigênio/uso terapêutico , Adulto , Intoxicação por Monóxido de Carbono/sangue , Intoxicação por Monóxido de Carbono/complicações , Feminino , Humanos , Doenças do Sistema Nervoso/etiologia , Adulto JovemRESUMO
BACKGROUND: Neonatal hyperbilirubinemia is influenced by a wide variety of factors, one of which is hemolysis. Serious hyperbilirubinemia may lead to a kernicterus with detrimental neurologic sequelae. Patients suffering from hemolytic disease have a higher risk of developing kernicterus. Carbon monoxide (CO), a byproduct of hemolysis or heme degradation, was described by Sjöstrand in the 1960s. It is transported as carboxyhemoglobin (COHb) and exhaled through the lungs. We were interested in a potential correlation between COHb and total serum bilirubin (TSB) and the time course of both parameters. MATERIALS AND METHODS: We used a point of care (POC) blood gas analyzer and did a retrospective analysis of bilirubin and COHb data collected over a 60-day period. RESULTS: An arbitrary cut-off point set at 2% COHb identified four patients with hemolytic disease of different origins who required phototherapy. In one patient with atypical hemolytic uremic syndrome (aHUS), COHb preceded the rise in bilirubin by about 2 days. Despite this displacement, there was a moderately good correlation of COHb with TSB levels <15 mg/dL (257 µmol/L) (r2: 0.80) and direct bilirubin (r2: 0.78) in the first patient. For all the four patients and all time points the correlation was slightly lower (r2: 0.59). CONCLUSIONS: COHb might be useful as a marker for high hemoglobin turnover to allow an earlier identification of newborns at risk to a rapid rise in bilirubin.
Assuntos
Bilirrubina/metabolismo , Carboxihemoglobina/metabolismo , Hiperbilirrubinemia/sangue , Biomarcadores/sangue , Humanos , Recém-Nascido , Estudos RetrospectivosRESUMO
OBJECTIVES: To evaluate carboxyhemoglobin (COHb) values measured with a CO-oximeter (Roche-cobas b 221) in jaundiced newborns with or without hemolysis and healthy controls in order to assess whether COHb measurement determined with a CO-oximeter could be used as an indicator of hemolysis in newborns with ABO alloimmunization. METHODS: A total of 86 term newborn infants were prospectively studied. The study cohort consisted of three subgroups: 18 infants with ABO HDN, 21 infants with hyperbilirubinemia without hemolytic disease who required phototherapy, and 47 healthy controls. The COHb, bilirubin, and Hb levels were measured. RESULTS: The three subgroups did not differ significantly with respect to birth weight, gestational age, gender, Apgar score, or mode of delivery. The ABO HDN infants had significantly higher COHb values than the healthy controls (median 2.4% versus 1.3%, p < 0.0005) and the group with hyperbilirubinemia without hemolytic disease (median 2.4% versus 1.3%, p < 0.0005), although the infants with hyperbilirubinemia without hemolytic disease did not have significantly higher COHb values compared with the healthy controls. The cut-off value of 1.7% COHb had 72% sensitivity and 97% specificity for confirming hemolysis in ABO alloimmunization. CONCLUSIONS: Our data show that COHb values determined with CO-oximeters are higher in newborns with hemolysis than in those without hemolysis. COHb measured with CO-oximeters could be used to confirm hemolysis in infants with ABO alloimmunization.
Assuntos
Sistema ABO de Grupos Sanguíneos , Incompatibilidade de Grupos Sanguíneos/sangue , Carboxihemoglobina/metabolismo , Hemólise , Feminino , Humanos , Recém-Nascido , Masculino , Oximetria , Estudos ProspectivosRESUMO
The physiological gaseous molecule, carbon monoxide (CO) becomes a subject of extensive investigation due to its vasoactive activity throughout the body but its role in gastroprotection has been little investigated. We determined the mechanism of CO released from its donor tricarbonyldichlororuthenium (II) dimer (CORM-2) in protection of gastric mucosa against 75% ethanol-induced injury. Rats were pretreated with CORM-2 30 min prior to 75% ethanol with or without 1) non-selective (indomethacin) or selective cyclooxygenase (COX)-1 (SC-560) and COX-2 (celecoxib) inhibitors, 2) nitric oxide (NO) synthase inhibitor L-NNA, 3) ODQ, a soluble guanylyl cyclase (sGC) inhibitor, hemin, a heme oxygenase (HO)-1 inductor or zinc protoporphyrin IX (ZnPPIX), an inhibitor of HO-1 activity. The CO content in gastric mucosa and carboxyhemoglobin (COHb) level in blood was analyzed by gas chromatography. The gastric mucosal mRNA expression for HO-1, COX-1, COX-2, iNOS, IL-4, IL-1ß was analyzed by real-time PCR while HO-1, HO-2 and Nrf2 protein expression was determined by Western Blot. Pretreatment with CORM-2 (0.5-10 mg/kg) dose-dependently attenuated ethanol-induced lesions and raised gastric blood flow (GBF) but large dose of 100 mg/kg was ineffective. CORM-2 (5 mg/kg and 50 mg/kg i.g.) significantly increased gastric mucosal CO content and whole blood COHb level. CORM-2-induced protection was reversed by indomethacin, SC-560 and significantly attenuated by celecoxib, ODQ and L-NNA. Hemin significantly reduced ethanol damage and raised GBF while ZnPPIX which exacerbated ethanol-induced injury inhibited CORM-2- and hemin-induced gastroprotection and the accompanying rise in GBF. CORM-2 significantly increased gastric mucosal HO-1 mRNA expression and decreased mRNA expression for iNOS, IL-1ß, COX-1 and COX-2 but failed to affect HO-1 and Nrf2 protein expression decreased by ethanol. We conclude that CORM-2 released CO exerts gastroprotection against ethanol-induced gastric lesions involving an increase in gastric microcirculation mediated by sGC/cGMP, prostaglandins derived from COX-1, NO-NOS system and its anti-inflammatory properties.
Assuntos
Monóxido de Carbono/metabolismo , Compostos Organometálicos/farmacologia , Substâncias Protetoras/farmacologia , Estômago/patologia , Animais , Carboxihemoglobina/metabolismo , Cromatografia Gasosa , Ciclo-Oxigenase 2/metabolismo , Etanol , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Heme Oxigenase (Desciclizante)/metabolismo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Protoporfirinas/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Wistar , Fluxo Sanguíneo Regional , Estômago/irrigação sanguínea , Estômago/efeitos dos fármacos , Estômago/enzimologiaRESUMO
RATIONALE: Carbon monoxide (CO) exposure is a leading cause of poison-related mortality. CO binds to Hb, forming carboxyhemoglobin (COHb), and produces tissue damage. Treatment of CO poisoning requires rapid removal of CO and restoration of oxygen delivery. Visible light is known to effectively dissociate CO from Hb, with a single photon dissociating one CO molecule. OBJECTIVES: To determine whether illumination of the lungs of CO-poisoned mice causes dissociation of COHb from blood transiting the lungs, releasing CO into alveoli and thereby enhancing the rate of CO elimination. METHODS: We developed a model of CO poisoning in anesthetized and mechanically ventilated mice to assess the effects of direct lung illumination (phototherapy) on the CO elimination rate. Light at wavelengths between 532 and 690 nm was tested. The effect of lung phototherapy administered during CO poisoning was also studied. To avoid a thoracotomy, we assessed the effect of lung phototherapy delivered to murine lungs via an optical fiber placed in the esophagus. MEASUREMENTS AND MAIN RESULTS: In CO-poisoned mice, phototherapy of exposed lungs at 532, 570, 592, and 628 nm dissociated CO from Hb and doubled the CO elimination rate. Phototherapy administered during severe CO poisoning limited the blood COHb increase and improved the survival rate. Noninvasive transesophageal phototherapy delivered to murine lungs via an optical fiber increased the rate of CO elimination while avoiding a thoracotomy. CONCLUSIONS: Future development and scaling up of lung phototherapy for patients with CO exposure may provide a significant advance for treating and preventing CO poisoning.
Assuntos
Intoxicação por Monóxido de Carbono/terapia , Carboxihemoglobina/metabolismo , Fototerapia/métodos , Animais , Intoxicação por Monóxido de Carbono/sangue , Carboxihemoglobina/análise , Modelos Animais de Doenças , Taxa de Depuração Metabólica/fisiologia , CamundongosRESUMO
The first descriptions of carbon monoxide (CO) and its toxic nature appeared in the literature over 100 years ago in separate publications by Drs. Douglas and Haldane. Both men ascribed the deleterious effects of this newly discovered gas to its strong interaction with hemoglobin. Since then the adverse sequelae of CO poisoning has been almost universally attributed to hypoxic injury secondary to CO occupation of oxygen binding sites on hemoglobin. Despite a mounting body of literature suggesting other mechanisms of injury, this pathophysiology and its associated oxygen centric therapies persists. This review attempts to elucidate the remarkably complex nature of CO as a gasotransmitter. While CO's affinity for hemoglobin remains undisputed, new research suggests that its role in nitric oxide release, reactive oxygen species formation, and its direct action on ion channels is much more significant. In the course of understanding the multifaceted character of this simple molecule it becomes apparent that current oxygen based therapies meant to displace CO from hemoglobin may be insufficient and possibly harmful. Approaching CO as a complex gasotransmitter will help guide understanding of the complex and poorly understood sequelae and illuminate potentials for new treatment modalities.
Assuntos
Antídotos/uso terapêutico , Dióxido de Carbono/toxicidade , Intoxicação por Monóxido de Carbono/terapia , Oxigenoterapia Hiperbárica , Animais , Dióxido de Carbono/sangue , Intoxicação por Monóxido de Carbono/sangue , Intoxicação por Monóxido de Carbono/fisiopatologia , Carboxihemoglobina/metabolismo , Gases , Humanos , Canais Iônicos/efeitos dos fármacos , Canais Iônicos/metabolismo , Terapia de Alvo Molecular , Óxido Nítrico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Resultado do TratamentoRESUMO
Carbon monoxide poisoning is both an ancient and current cause of inadvertent (accidental) death and more recently has emerged as a cause of suicide worldwide. This article describes the pathophysiology and epidemiology of this most toxic and frequently occult poison.
Assuntos
Intoxicação por Monóxido de Carbono/terapia , Eritropoetina/uso terapêutico , Hematínicos/uso terapêutico , Oxigenoterapia Hiperbárica/métodos , Acidentes/estatística & dados numéricos , Intoxicação por Monóxido de Carbono/epidemiologia , Intoxicação por Monóxido de Carbono/metabolismo , Carboxihemoglobina/metabolismo , Hemoglobinas/metabolismo , Humanos , Tentativa de Suicídio/estatística & dados numéricos , Reino Unido/epidemiologiaRESUMO
Diathermy is known to produce a mixture of waste products including carbon monoxide. During transcervical hysteroscopic surgery, carbon monoxide might enter the circulation leading to the formation of carboxyhaemoglobin. In 20 patients scheduled for transcervical hysteroscopic resection of myoma or endometrium, carboxyhaemoglobin was measured before and at the end of the surgical procedure, and compared with levels measured in 20 patients during transurethral prostatectomy, and in 20 patients during tonsillectomy. Haemodynamic data, including ST-segment changes, were recorded. Levels of carboxyhaemoglobin increased significantly during hysteroscopic surgery from median (IQR [range]) 1.0% (0.7-1.4 [0.5-4.9])% to 3.5% (2.0-6.1 [1.3-10.3]%, p < 0.001), compared with levels during prostatectomy or tonsillectomy. Significant ST-segment changes were observed in 50% of the patients during hysteroscopic surgery. Significant correlations were observed between the increase in carboxyhaemoglobin and the maximum ST-segment change (ρ = -0.707, p < 0.01), between the increase in carboxyhaemoglobin and intravasation (ρ = 0.625; p < 0.01), and between intravasation and the maximum ST-segment change (ρ = -0.761; p < 0.01). The increased carboxyhaemoglobin levels during hysteroscopic surgery appear to be related to the amount of intravasation and this could potentially be a contributing factor to the observed ST-segment changes.
Assuntos
Carboxihemoglobina/metabolismo , Diatermia/métodos , Eletrocardiografia/métodos , Histeroscopia/métodos , Tonsilectomia/métodos , Ressecção Transuretral da Próstata/métodos , Adulto , Idoso , Análise de Variância , Biomarcadores/sangue , Estudos de Coortes , Feminino , Hemodinâmica/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
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 18â³ 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.
Assuntos
Intoxicação por Monóxido de Carbono/sangue , Intoxicação por Monóxido de Carbono/patologia , Carboxihemoglobina/metabolismo , Lactatos/sangue , Adulto , Monóxido de Carbono/sangue , Intoxicação por Monóxido de Carbono/terapia , Creatina Quinase Forma MB/sangue , Feminino , Escala de Coma de Glasgow , Hemoglobinas , Humanos , Oxigenoterapia Hiperbárica , Masculino , Oxigenoterapia , Estudos Prospectivos , Troponina I/sangueRESUMO
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.