Methemoglobin Levels Research Articles

Периоперационное кондиционирование оксидом азота для предотвращения острого почечного повреждения при кардиохирургических вмешательствах у пациентов с хронической болезнью почек: промежуточные результаты рандомизированного контролируемого исследования DEF

INTRODUCTION: Acute kidney injury (AKI) is a common and serious complication after cardiac surgery performed under cardiopulmonary bypass (CPB). Patients with chronic kidney disease (CKD) are particularly vulnerable to cardiac surgery-associated AKI. Nitric oxide (NO) has great potential for implementing multi-organ protection in cardiac surgery. OBJECTIVES: To test the hypothesis that perioperative nitric oxide conditioning has a good safety profile and reduces the incidence of acute kidney injury during cardiac surgery under cardiopulmonary bypass in patients with chronic kidney disease. MATERIAL AND METHODS: An interim analysis of the results of the single-center prospective randomized controlled trial DEFENDER was conducted. Currently, the study included 96 patients with CKD who underwent cardiac surgery under CPB. Patients was randomized into 2 equal groups consisting of 48 people each. In the experimental group, during the operation and 6 hours after it, 80 ppm NO was delivered through the ventilator and CPB circuits. In the control group, during the operation and 6 hours after it, a standard oxygen-air mixture without NO was delivered through the ventilator and CPB circuits. The end points of the study were: the difference between groups in the incidence of AKI, the incidence of postoperative complications, outcomes and the safety profile of NO therapy. RESULTS: In the experimental group, the incidence of AKI was significantly lower compared to the control group (16,7 и 35,4 %, p = 0.036). In the experimental group, nitrogen dioxide concentration in the gas-air mixture and methemoglobin level were not above the reference range. The groups did not differ in the frequency of blood transfusions, the amount of postoperative bleeding, or the number of platelets on the first day after surgery. CONCLUSIONS: Perioperative nitric oxide conditioning has a good safety profile and reduces the incidence of acute kidney injury during cardiac surgery with CPB in patients with chronic kidney disease.

Impact of met-haemoglobin and oxidative stress on endothelial function in patients with transfusion dependent β-thalassemia

Transfusion dependent β-thalassemia is a genetic blood disorder characterized by chronic anaemia. Blood transfusion is lifesaving but comes at a cost. Iron overload emerges as a prime culprit as a free radicals damage endothelial cells. Chronic anaemia further disrupts oxygen delivery, exacerbating the oxidative stress. Increased levels of met-haemoglobin and malondialdehyde compromise endothelial function. This research sheds light on the impact of met-haemoglobin and oxidative stress on endothelial function in 50 patients with transfusion dependent β-thalassemia major compared to 50 healthy individuals as control. Blood samples were collected & subjected to CBC, biochemical analysis including creatinine, ferritin, CRP, LDH, and HCV antibodies. Oxidative stress was assessed using met-haemoglobin & malondialdehyde. Endothelial dysfunction was evaluated by endothelial activation and stress index (EASIX). EASIX, met-haemoglobin and malondialdehyde were significantly increased in patients (1.44 ± 0.75, 2.07 ± 0.2, 4.8 ± 0.63; respectively) compared to the control (0.52 ± 0.24,0.88 ± 0.34,0.8 ± 0.34; respectively). Significant strong positive correlation was found between EASIX and met-haemoglobin, malondialdehyde, serum ferritin and CRP (P = 0.00, r = 0.904, P = 0.00, r = 0.948, P = 0.00, r = 0.772, P = 0.00, r = 0.971; respectively. Met-haemoglobin as well as EASIX should be routinely estimated to assess endothelial function especially before the decision of splenectomy. Antioxidant drugs should be supplemented.

A Case for Co-oximetry: Methemoglobinemia secondary to a Rare Hemoglobin Variant

Abstract Introduction/Objective The presence of dyshemoglobins and some inherited hemoglobin (Hb) variants can cause over or underestimation of oxygen saturation (O2sat) when using a pulse oximeter (ox). These noninvasive medical devices rely on two wavelengths, a pulsing arterial bed, and light absorption properties of Hb to measure the difference between deoxy- and oxy-Hb. In contrast, a co-oximeter (co-ox) requires arterial blood. By using at least four wavelengths, co-ox measures the functional and fractional O2sat to detect all forms of Hb, including those that do not bind oxygen (O2), such as methemoglobin (metHb). Methemoglobinemia may be congenital or acquired, resulting from exposure to certain toxins, metabolic disorders, enzymatic deficiencies such as cytochrome b5 reductase deficiency, or hemoglobinopathies. Methods/Case Report A healthy, adolescent male undergoing a sports physical at his pediatrician’s office was hypoxic by pulse ox and sent to the emergency department (ED) for evaluation. On exam, he had cold, blue tinged fingertips and lips but was otherwise asymptomatic. His O2sat was 88-90% on room air with minimal improvement with 6L of supplemental O2. Co-ox revealed a metHb level > 20%. The father also mentioned that the mother had frequent ED visits for hypoxia. Capillary Hb electrophoresis showed peaks in the HbA, HbF, and HbA2 zones of 78.3%, 17.9%, and 3.6%, respectively. All CBC parameters were within the reference intervals. The large peak in the HbF zone would suggest hereditary persistence of fetal hemoglobin (HPFH); however, the clinical picture was not consistent. Further reference laboratory investigation determined that the patient was heterozygous for Hb Tübingen (HbTüb), a beta globin chain variant resulting from a point mutation at position 106. By mass spectrometry, the variant quantified as 38% of the total hemoglobin, indicating underestimation by electrophoretic techniques. Results (if a Case Study enter NA) NA Conclusion This case presents an essentially asymptomatic patient with hypoxia and elevated methemoglobin levels. Electrophoretic hemoglobinopathy and CBC workup were clinically inconsistent with HPFH and the presence of an aberrant hemoglobin migrating in the HbF must be considered in the differential diagnosis. The manifestation of HbTüb as methemoglobinemia in this context adds complexity to the diagnostic puzzle. Further laboratory exploration into the underlying mechanisms driving this unique presentation is crucial for a comprehensive understanding and tailored management approach.

Methaemoglobin as a surrogate marker of primaquine antihypnozoite activity in Plasmodium vivax malaria: A systematic review and individual patient data meta-analysis.

The 8-aminoquinolines, primaquine and tafenoquine, are the only available drugs for the radical cure of Plasmodium vivax hypnozoites. Previous evidence suggests that there is dose-dependent 8-aminoquinoline induced methaemoglobinaemia and that higher methaemoglobin concentrations are associated with a lower risk of P. vivax recurrence. We undertook a systematic review and individual patient data meta-analysis to examine the utility of methaemoglobin as a population-level surrogate endpoint for 8-aminoquinoline antihypnozoite activity to prevent P. vivax recurrence. We conducted a systematic search of Medline, Embase, Web of Science, and the Cochrane Library, from 1 January 2000 to 29 September 2022, inclusive, of prospective clinical efficacy studies of acute, uncomplicated P. vivax malaria mono-infections treated with radical curative doses of primaquine. The day 7 methaemoglobin concentration was the primary surrogate outcome of interest. The primary clinical outcome was the time to first P. vivax recurrence between day 7 and day 120 after enrolment. We used multivariable Cox proportional-hazards regression with site random-effects to characterise the time to first recurrence as a function of the day 7 methaemoglobin percentage (log base 2 transformed), adjusted for the partner schizonticidal drug, the primaquine regimen duration as a proxy for the total primaquine dose (mg base/kg), the daily primaquine dose (mg/kg), and other factors. The systematic review protocol was registered with PROSPERO (CRD42023345956). We identified 219 P. vivax efficacy studies, of which 8 provided relevant individual-level data from patients treated with primaquine; all were randomised, parallel arm clinical trials assessed as having low or moderate risk of bias. In the primary analysis data set, there were 1,747 patients with normal glucose-6-phosphate dehydrogenase (G6PD) activity enrolled from 24 study sites across 8 different countries (Indonesia, Brazil, Vietnam, Thailand, Peru, Colombia, Ethiopia, and India). We observed an increasing dose-response relationship between the daily weight-adjusted primaquine dose and day 7 methaemoglobin level. For a given primaquine dose regimen, an observed doubling in day 7 methaemoglobin percentage was associated with an estimated 30% reduction in the risk of P. vivax recurrence (adjusted hazard ratio = 0.70; 95% confidence interval [CI] [0.57, 0.86]; p = 0.0005). These pooled estimates were largely consistent across the study sites. Using day 7 methaemoglobin as a surrogate endpoint for recurrence would reduce required sample sizes by approximately 40%. Study limitations include the inability to distinguish between recrudescence, reinfection, and relapse in P. vivax recurrences. For a given primaquine regimen, higher methaemoglobin on day 7 was associated with a reduced risk of P. vivax recurrence. Under our proposed causal model, this justifies the use of methaemoglobin as a population-level surrogate endpoint for primaquine antihypnozoite activity in patients with P. vivax malaria who have normal G6PD activity.

A new approach to detect the imbalance of hemoglobin and methemoglobin levels in human plasma based on a fluorescent modified nanocellulose chemosensor

This work has developed a new, rapid, highly sensitive, and precise approach to identify the imbalance levels of hemoglobin and methemoglobin through fluorescence emission spectroscopy. A study on a new Schiff base-modified nanocellulose (PY-PDA-DANC) applied as a fluorescent chemosensor is reported. To prepare the chemosensor, nanocellulose (NC) was first converted into 2,3-dialdehyde nanocellulose (DANC), and then modified by grafting o-phenylenediamine (PDA), followed by 1-pyrenecarboxaldehyde giving rise to the new blue-fluorescent complex PY-PDA-DANC. All the synthesized products were characterized using FTIR, 1H NMR, XRD, EDX and UV–vis spectroscopy. The fluorescence response of PY-PDA-DANC against various metal ions (Co2+, Cr3+, Cu2+, Fe2+, Fe3+, Hg2+, K+, Mg2+, Mn2+, Na+, Ni2+, Pb2+ and Zn2+) in DMSO/H2O media was evaluated using PL spectroscopy. The fluorescent sensor showed high and selective quenching response to both Fe2+ and Fe3+ ions with low limit of detection (LOD). PY-PDA-DANC was also successfully applied for sensing of heme–iron coordinated to hemoglobin (HB) and methemoglobin (MHB), displaying a LOD of 28.45 nM and 65.36 nM, respectively. Subsequently, it was applied for the analysis of [Fe2+@HB] and [Fe3+@MHB] in human plasma sample with good recoveries.

A novel stoploss mutation CYB5R3 c.906A>G(p.*302Trpext*42) involved in the pathogenesis of hereditary methemoglobinemia

Recessive congenital methemoglobinemia (RCM) is a hereditary autosomal disorder with an extremely low incidence rate. Here, we report a case of methemoglobinemia type I in a patient with congenital persistent cyanosis. The condition was attributed to a novel compound heterozygous mutation in CYB5R3, characterized by elevated methemoglobin levels (13.4 % of total hemoglobin) and undetectable NADH cytochrome b5 reductase (CYB5R3) activity. Whole-exome sequencing (WES) revealed two heterozygous mutations in CYB5R3: a previously reported pathogenic missense mutation c.611G>A(p.Cys204Tyr) inherited from the father, and a novel stop codon mutation c.906A>G(p.*302Trpext*42) from the mother, the latter mutation assessed as likely pathogenic according to ACMG guidelines. In cells overexpressing the CYB5R3 c.906A>G mutant construct, the CYB5R3 mRNA level was significantly lower than in cells overexpressing the wild-type (WT) CYB5R3 construct. However, there was no significant difference in protein expression levels between the mutant and WT constructs. Notably, an additional protein band of approximately 55 kDa was detected in the mutant cells. Immunofluorescence localization showed that, compared to wild-type CYB5R3, the subcellular localization of the CYB5R3 p.*302Trpext*42 mutant protein did not show significant changes and remained distributed in the endoplasmic reticulum and mitochondria. However, the c.906A>G(p.*302Trpext*42) mutation resulted in increased intracellular reactive oxygen species (ROS) levels and decreased NAD+/NADH ratio, suggesting impaired CYB5R3 function and implicating this novel mutation as likely pathogenic.

Ascorbic Acid for Methemoglobinemia Treatment: A Case Report and Literature Review

Purpose: Ascorbic acid has been proposed as an alternative treatment for methemoglobinemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. However, its efficacy has never been compared to that of methylene blue given the inability of patients with G6PD deficiency to receive methylene blue. We present a case of methemoglobinemia treated with ascorbic acid in a patient without G6PD deficiency who had previously received methylene blue. Summary: A 66-year-old male was treated for methemoglobinemia deemed to be secondary to benzocaine throat spray. He received intravenous (IV) methylene blue but had a severe reaction: diaphoresis, lightheadedness, and hypotension. The infusion was stopped prior to completion. Approximately 6 days later he presented with methemoglobinemia following an additional overconsumption of benzocaine and was treated with ascorbic acid. In both instances his methemoglobin levels were >30% on arterial blood gas on admission and decreased to 6.5% and 7.8%, respectively, after administration of methylene blue and ascorbic acid. Conclusion: Ascorbic acid had a similar effect on decreasing the concentration of methemoglobin compared to methylene blue. Further research into use of ascorbic acid as a recommended agent for treatment of methemoglobinemia is warranted.

Relationship between contrast-induced nephropathy and blood methemoglobin levels in acute coronary syndrome patients

Relationship between contrast-induced nephropathy and blood methemoglobin levels in acute coronary syndrome patients

Dapsone Induced Methemoglobinemia: The Importance of Early Diagnosis

We present a case of a 65-year-old male with lower respiratory tract infection who developed methemoglobinemia after starting dapsone therapy. The patient presented with cyanosis and dyspnea, and arterial blood gas analysis revealed a methemoglobin level of 14%. Dapsone was discontinued, and the patient was treated with methylene blue and Vitamin C IV infusion, which resulted in rapid improvement of symptoms and normalisation of methemoglobin levels. This case highlights the importance of recognizing dapsone-induced methemoglobinemia early and promptly initiating appropriate treatment to prevent complications.

Novaluron and indoxacarb induced methemoglobinemia – unveiling a rare poisoning

Introduction and aim. In India, the utilization of agricultural pesticides for intentional self-poisoning is a prevalent method, and it is associated with substantially higher fatality rates compared to other self-poisoning approaches. Plethora, an agricultural insecticide containing novaluron (5.25%) and indoxacarb (4.5%), has recently been introduced and widely used in India and various other regions for its broad-spectrum lepidopteran control. While there have been documented cases of isolated self-poisoning involving indoxacarb, there is currently no literature reporting incidents of human poisoning specifically related to novaluron. Description of the case. An 83-Year-old male was presented to the emergency department (ED) with a history of consumption of 50 mL of an insecticide suspension concentrate called ‘PLETHORA’ to commit suicide. He had one episode of vomiting and dizziness after the ingestion. There was associated cyanosis, and the patient was put on high-flow oxygen at 10 L/min through a face mask. The patient was diagnosed to have methemoglobinemia and was successfully treated with methylene blue and ascorbic acid. One hour post methylene blue injection showed a methemoglobin level of 1%, and the patient gradually improved. Patients presenting with novaluron and indoxacarb poisoning require supportive treatment as there is no specific antidote. There should be a high index of suspicion for methemoglobinemia in such patients, and timely management is necessary to prevent further complications. The patient was successfully managed and discharged after the 3rd day of admission. Conclusion. The management of patients with novaluron and indoxacarb poisoning primarily involves supportive care, as there is currently no specific antidote available for these substances. Maintaining a high suspicion index for the development of methemoglobinemia and timely management of other complications is crucial for the best possible patient outcomes.

Modulation of the Human Erythrocyte Antioxidant System by the 5- and 6-Membered Heterocycle-Based Nitroxides.

Nitroxides are stable radicals consisting of a nitroxyl group, >N-O•, which carries an unpaired electron. This group is responsible for the paramagnetic and antioxidant properties of these compounds. A recent study evaluated the effects of pyrrolidine and pyrroline derivatives of nitroxides on the antioxidant system of human red blood cells (RBCs). It showed that nitroxides caused an increase in the activity of superoxide dismutase (SOD) and the level of methemoglobin (MetHb) in cells (in pyrroline derivatives) but had no effect on the activity of catalase and lactate dehydrogenase. Nitroxides also reduced the concentration of ascorbic acid (AA) in cells but did not cause any oxidation of proteins or lipids. Interestingly, nitroxides initiated an increase in thiols in the plasma membranes and hemolysate. However, the study also revealed that nitroxides may have pro-oxidant properties. The drop in the AA concentration and the increase in the MetHb level and in SOD activity may indicate the pro-oxidant properties of nitroxides in red blood cells.

Effect of nitric oxide delivery via cardiopulmonary bypass circuit on postoperative oxygenation in adults undergoing cardiac surgery (NOCARD trial): a randomised controlled trial.

Cardiac surgery involving cardiopulmonary bypass induces a significant systemic inflammatory response, contributing to various postoperative complications, including pulmonary dysfunction, myocardial and kidney injuries. To investigate the effect of Nitric Oxide delivery via the cardiopulmonary bypass circuit on various postoperative outcomes. A prospective, single-centre, double-blinded, randomised controlled trial. Rabin Medical Centre, Beilinson Hospital, Israel. Adult patients scheduled for elective cardiac surgery were randomly allocated to one of the study groups. For the treatment group, 40 ppm of nitric oxide was delivered via the cardiopulmonary bypass circuit. For the control group, nitric oxide was not delivered. The primary outcome was the incidence of hypoxaemia, defined as a p a O2 /FiO 2 ratio less than 300 within 24 h postoperatively. The secondary outcomes were the incidences of low cardiac output syndrome and acute kidney injury within 72 h postoperatively. Ninety-eight patients were included in the final analysis, with 47 patients allocated to the control group and 51 to the Nitric Oxide group. The Nitric Oxide group exhibited significantly lower hypoxaemia rates at admission to the cardiothoracic intensive care unit (47.1 vs. 68.1%), P = 0.043. This effect, however, varied in patients with or without baseline hypoxaemia. Patients with baseline hypoxaemia who received nitric oxide exhibited significantly lower hypoxaemia rates (61.1 vs. 93.8%), P = 0.042, and higher p a O2 /FiO 2 ratios at all time points, F (1,30) = 6.08, P = 0.019. Conversely, this benefit was not observed in patients without baseline hypoxaemia. No significant differences were observed in the incidence of low cardiac output syndrome or acute kidney injury. No substantial safety concerns were noted, and toxic methaemoglobin levels were not observed. Patients with baseline hypoxaemia undergoing cardiac surgery and receiving nitric oxide exhibited lower hypoxaemia rates and higher p a O2 /FiO 2 ratios. No significant differences were found regarding postoperative pulmonary complications and overall outcomes. NCT04807413.

Population pharmacokinetics of primaquine and its metabolites in African males

BackgroundPrimaquine (PQ) is the prototype 8-aminoquinoline drug, a class which targets gametocytes and hypnozoites. The World Health Organization (WHO) recommends adding a single low dose of primaquine to the standard artemisinin-based combination therapy (ACT) in order to block malaria transmission in regions with low malaria transmission. However, the haemolytic toxicity is a major adverse outcome of primaquine in glucose-6-phosphate dehydrogenase (G6PD)-deficient subjects. This study aimed to characterize the pharmacokinetic properties of primaquine and its major metabolites in G6PD-deficient subjects.MethodsA single low-dose of primaquine (0.4–0.5 mg/kg) was administered in twenty-eight African males. Venous and capillary plasma were sampled up to 24 h after the drug administration. Haemoglobin levels were observed up to 28 days after drug administration. Only PQ, carboxy-primaquine (CPQ), and primaquine carbamoyl-glucuronide (PQCG) were present in plasma samples and measured using liquid chromatography mass spectrometry. Drug and metabolites’ pharmacokinetic properties were investigated using nonlinear mixed-effects modelling.ResultsPopulation pharmacokinetic properties of PQ, CPQ, and PQCG can be described by one-compartment disposition kinetics with a transit-absorption model. Body weight was implemented as an allometric function on the clearance and volume parameters for all compounds. None of the covariates significantly affected the pharmacokinetic parameters. No significant correlations were detected between the exposures of the measured compounds and the change in haemoglobin or methaemoglobin levels. There was no significant haemoglobin drop in the G6PD-deficient patients after administration of a single low dose of PQ.ConclusionsA single low-dose of PQ was haematologically safe in this population of G6PD-normal and G6PD-deficient African males without malaria.Trial registration NCT02535767

Comparison of the effects of gasoline burn and chromic acid burn on different internal organs and immune functions in rats.

Burn as physical injury ranks as the fourth most prevalent trauma across the world. In this study, we aimed to compare the impact of gasoline burn and chromic acid burn on the internal organs and immune functions in rats. The results showed that the levels of methemoglobin (MHb) to total hemoglobin (Hb) as well as the Cr6+ content showed significant elevation in the chromic acid burn group relative to the gasoline burn group. HE staining was used to evaluate the histological changes in the injured tissues as well as the tissues excised from internal organs. We found that chromic acid burn-induced more severe damage to rat tissues. Gasoline burn showed no significant impact on the intestinal tissues of rats, while the chromic acid burn-induced increased cell death in rat intestines. Moreover, the results of HE staining also revealed that gasoline burn and chromic acid burn showed no evident impact on rat hearts. Gasoline burn also showed no significant effects on the liver, lungs and kidneys of rats, while the chromic acid burn caused injuries to such internal organs in comparison with the control and gasoline burn groups. In addition, the MPO activity was higher in the liver, intestine, lungs and kidneys of rats with chromic acid burn. Furthermore, the expression of inflammation response cytokines was examined in the serum of rats. The results demonstrated that the levels of IL-6, IL-1β and TNF-α showed a significant increase in both the gasoline burn and chromic acid burn groups of rats relative to the control, and the levels were higher in the chromic acid burn group in comparison with the gasoline burn group. In conclusion, the chromic acid burn-induced more severe organ injury, inflammation and immune response compared with the gasoline burn, which may provide reference data for the clinical treatment of patients with different burn injuries.

704 Hydroxocobalamin Is Not Associated with Methemoglobinemia in Patients with Inhalation Injury and Suspected Cyanide Toxicity

Abstract Introduction Cyanide poisoning is a serious threat to burn patients, especially those exposed to smoke from fires, often leading to cyanide toxicity and cardiovascular collapse. Cyanokit, a widely used hydroxocobalamin product able to convert cyanide molecules into safe compounds, is known for its potential to avoid methemoglobinemia, a side effect of other treatments. Concerns about cyanokit's safety, especially in burn patients, have arisen due to recent cases with elevated methemoglobin levels. This study investigates methemoglobin levels in burn patients treated with Cyanokit, aiming to enhance our understanding of cyanide antidote therapy complexities, ultimately leading to safer treatment strategies. Methods A retrospective study was conducted of burn patients admitted to a single institution from 2013-2023 with inhalation injury treated with cyanokit for suspected cyanide toxicity. We also analyzed a control cohort of similar patients with inhalation injury not treated with cyanokit. We analyzed changes and peaks in methemoglobin, lactate levels, kidney function tests, ventilator days, % total body surface area (TBSA), medications and dressings, and mortality. Results In the study, 36 patients with suspected inhalation injury were treated with cyanokit, compared to 32 patients with inhalation injury who weren't treated with cyanokit. Baseline characteristics showed no statistically significant differences between the groups, including age, gender, BMI, and %TBSA. No significant differences were found in initial, final, peak, or change in methemoglobin levels, initial lactate levels, mortality, Baux score, kidney function tests, ventilator days, surgeries, or use of medications/treatments (e.g., Silvadene dressings, Vitamin C) between the two groups (Table 1). When controlling for covariates, multiple linear regression analysis (age, gender, and %TBSA) indicated that cyanokit administration was not significantly associated with changes in methemoglobin or mortality. Conclusions Contrary to our initial hypothesis, our study did not find significant harm or benefit of cyanokit in burn patients during the acute phase. Methemoglobin, lactate levels, mortality, and kidney function remained largely unchanged. This study's limitations, particularly the rarity of inhalation injury cases with concern for cyanide toxicity, warrant consideration. Further research is required to comprehensively elucidate the impact of cyanokit administration on burn patients' outcomes. Applicability of Research to Practice Given the high stakes involved in treating cyanide poisoning promptly, our study holds significance for refining treatment strategies and enhancing patient safety. This insight is vital for medical practitioners making critical decisions in managing cyanide poisoning in burn patients, while also underlining the need for further research to fully understand the broader impact of cyanokit administration in this context.

Hydroxocobalamin is not associated with methemoglobinemia in patients with inhalation injury and suspected cyanide toxicity and a proposed algorithm for hydroxocobalamin administration

BackgroundCyanide poisoning poses a significant threat to burn patients exposed to smoke in residential or workplace fires, leading to central nervous system dysfunction, hemodynamic instability, cardiovascular collapse, and death. Prompt administration of an effective antidote is critical. Hydroxocobalamin, a form of vitamin B12, is the gold standard treatment for cyanide toxicity, by binding to cyanide molecules and converting them into non-toxic cyanocobalamin that is eliminated by the kidneys. This mechanism is distinct from previous cyanide antidotes, which induce the formation of methemoglobin to bind to cyanide. Recent case studies have reported elevated methemoglobin levels after hydroxocobalamin administration, raising concerns regarding its safety. The current study investigates smoke inhalation patients treated with hydroxocobalamin at a single institution Burn Unit in hopes of enhancing our understanding of the complexities surrounding cyanide antidote therapy. MethodsAfter Institutional Board Approval, a retrospective cohort study was conducted. Our sample comprised burn patients with inhalation injury admitted to a single institution from 2013 to 2023 and treated with hydroxocobalamin for suspected cyanide toxicity. We also analyzed a matched control cohort of similar patients with inhalation injury not treated with hydroxocobalamin. We analyzed changes and peaks in methemoglobin levels, lactate levels, blood urea nitrogen (BUN) and creatinine, ventilator days, % total body surface area (TBSA), various types of medications and dressings, and mortality. Statistical analyses included t-tests, chi-square, linear and logistic regressions, and correlation analysis. ResultsIn the study, 36 patients with suspected inhalation injury were treated with hydroxocobalamin at the Los Angeles General (LAG) Burn Unit from 2013 to 2023, who were matched to 32 control patients with inhalation injury who were not treated with hydroxocobalamin. Demographic and baseline characteristics showed no statistically significant differences between the groups, including age, gender, BMI, and %TBSA. No significant differences were found in initial, final, peak, or change in methemoglobin levels. The study also revealed no significant disparities in initial lactate levels, mortality, kidney function tests, ventilator days, surgeries, or use of medications/treatments (e.g., Silvadene dressings, Vitamin C) between the two groups. When controlling for covariates, multiple linear regression analysis (age, gender, and %TBSA) indicated that hydroxocobalamin administration was not significantly associated with changes in methemoglobin or mortality. Increased %TBSA, however, was linked to elevated lactate levels. ConclusionsOur investigation sought to assess the potential risks associated with hydroxocobalamin administration in burn patients with concomitant inhalation injury. Contrary to our initial hypothesis, we found no statistically significant differences in methemoglobinemia, lactate levels, mortality, or kidney function. The influence of other factors, such as methemoglobinemia-inducing drugs or hydroxocobalamin's interference with co-oximetry, adds complexity. Although elevated methemoglobin levels were observed in some cases, their clinical significance was limited. However, this study's limitations, particularly the rarity of inhalation injury cases with concern for cyanide toxicity, warrant consideration. Further research is required to comprehensively elucidate the impact of hydroxocobalamin administration on burn patients' outcomes.

Indoxacarb poisoning causing methemoglobinemia treated with parenteral vitamin C: a case report

IntroductionThis case study reports on a suicide attempt involving indoxacarb and vitamin C. Indoxacarb is a neurotoxic insecticide used in agriculture and as a flea controller in pets. Cotton, vegetables, and fruits are treated with indoxacarb, an insecticide that can be applied both indoors and outdoors. It causes skin allergies, methemoglobinemia, and hemolytic anemia. It is also attributed to allergic reactions through ingestion, inhalation, physical contact, and translaminar action. This case report highlights use of vitamin C in methemoglobinemia caused by indoxacarb poisoning. Indoxacarb poisoning has the potential to be extremely serious and even lethal. In this instance, the patient initially had no symptoms after ingesting a substance containing indoxacarb in an attempt at suicide. However, further tests revealed methemoglobinemia and low oxygen levels.Case presentationA 28-year-old south-east Asian female patient ingested an insecticide containing 5.25% novaluron, 4.5% indoxacarb, and 25% thiamethoxam, and reported that she noticed muddy brown urine but presented with no active signs or symptoms of poisoning. Upon examination, the patient was fully conscious, alert, and hemodynamically stable, but had an oxygen saturation of 84%. Gastric lavage was performed, and blood investigations revealed a muddy-brown-colored blood sample and methemoglobin levels of 12%. The patient was treated with high-dose vitamin C and showed significant improvement, with a drop in methemoglobin levels to 1.2% and an increase in oxygen saturation to 97%.DiscussionIndoxacarb poisoning can cause severe methemoglobinemia. Vitamin C may be a useful treatment option for methemoglobinemia caused by indoxacarb, particularly in cases in which traditional treatment with methylene blue is contraindicated or not tolerated. Hence high doses of ascorbic acid, that is, vitamin C, were administered to the patient, which lowered their methemoglobin levels and improved oxygen levels without much safety concerns.ConclusionThis example emphasizes the significance of early indoxacarb poisoning detection and treatment as well as the possible advantages of utilizing ascorbic acid in the management of methemoglobinemia, and highlights the use of vitamin C in the treatment of methemoglobinemia caused by indoxacarb poisoning. Therefore, it is important for healthcare professionals to be aware of the potential for indoxacarb to cause methemoglobinemia and to consider vitamin C as a treatment option.

Extracorporeal cardio-pulmonary resuscitation in a patient with missed diagnosis of sodium nitrite intoxication.

Critical poisoning with sodium nitrite (NaNO2) can present challenges in promptly identifying and managing acute methemoglobinemia. We report the case of an overt self-intoxication by an initially unknown agent, leading to cardiac arrest. Despite prodromal signs of cyanosis, coma, desaturation, and hypotension, methemoglobinemia went unrecognized during extracorporeal cardiopulmonary resuscitation (ECPR) as the point-of-care test failed to provide methemoglobin levels, leading to untreated methemoglobinemia. The blood flowing through the oxygenator notably maintained the same brown colour. Return of spontaneous circulation was never achieved, and the patient was declared dead after 60min of unsuccessful resuscitation. Cause of death by means of NaNO2 voluntary ingestion was later clarified and confirmed by postmortem finding of elevated nitrite and nitrate concentration. This case highlights the risk of failure of ECPR in the context of cardiac arrest due to methemoglobinemia, emphasizing the critical need for prompt recognition of the causative agent and early administration of antidotes.

Metahemoglobinemia inducida por dapsona: reporte de un caso en el servicio de urgencia

Methemoglobinemia is a low prevalence but potentially severe condition in the Emergency Department. One of its leading causes is drug induction, dapsone being one of them. Dapsone is a synthetic sulfone with antimicrobial properties, often prescribed for prophylaxis against Pneumocystis jiroveci infection and other implications. This report presents the case of a 39-year-old male recently diagnosed with HIV on antiretroviral therapy along with prophylactic dapsone, who sought medical attention in the emergency room due to symptoms of cough, dyspnea, and fever. On admission, the patient exhibited a state of tachypnea and an oxygen saturation of 78% in room air, which is partially corrected with supplemental oxygen at an inspired oxygen fraction of 50%, achieving oxygen saturation of 90% by pulse oximetry. Chest X-ray revealed no abnormalities, and arterial blood gas analysis showed a partial pressure of oxygen of 380 mmHg with oxygen saturation of 100%. Given the disparity between pulse oximetry, arterial blood gas results, and the normal chest X-ray, a co-oximetry was conducted, revealing a methemoglobin level of 10.4% The patient was admitted to the ICU and continued receiving oxygen therapy. Dapsone was discontinued and the patient’s condition improved. without the need for methylene blue administration or alternative therapies.

Methemoglobinemia in a child with congenital epidermolysis bullosa

Introduction . Methemoglobinemia is a rather rare cause of hypoxemia and hypoxia, however, with a severe course of the disease and an increase in the concentration of methemoglobin in the blood of more than 20 %, this can cause the development of multi-organ dysfunction and death.The objective was to descript the case of methemoglobinemia in a child with congenital epidermolysis bullosa with the use of a combined drug containing benzocaine.Materials and methods. Newborn premature baby boy, from the first pregnancy, gestation period 36 weeks, suffering from congenital epidermolysis. Birth weight 2850 g, height 47 cm. Apgar score in the first minute – seven, on the fifth – eight points. As a local treatment, an aerosol for external use «Olazol» was prescribed. At the age of 56 hours from the moment of birth, a sharp deterioration in the child’s condition was noted in the form of a decrease in SpO2 to 72–76 %, pronounced tachycardia, an increase in methemoglobin concentration in the blood (53.7 %).Results. A distinctive feature of this case was the presence of severe methemoglobinemia, which led to severe metabolic acidosis, venous hypoxemia and tissue hypoxia. Timely diagnosis and adequate therapy in the early stages of the pathological process contributed to the complete stabilization of the child’s condition and the normalization of the blood gas composition fifteen hours after the start of therapy.Conclusion. The use of drugs containing benzocaine in the early neonatal period is a risk factor for the development of methemoglobinemia, which requires a dynamic assessment of the level of methemoglobin in the blood in order to prevent tissue hypoxia.