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Cyanide 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. After 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. In 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. Our 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. • Hydroxocobalamin is a common antidote for suspected inhalation injury in burn patients. • Hydroxocobalamin does not lead to methemoglobinemia or increased mortality. • Hydroxocobalamin does not lead to significant changes in outcomes for burn patients. [ABSTRACT FROM AUTHOR]

Abstract Methionine synthase reductase deficiency (cblE) is a rare autosomal recessive inborn error of cobalamin metabolism caused by pathogenic variants in the methionine synthase reductase gene (MTRR). Patients usually exhibit early‐onset bone marrow failure with pancytopenia including megaloblastic anemia. The latter can remain isolated or patients may present developmental delay and rarely macular dysfunction. Treatment mostly includes parenteral hydroxocobalamin to maximize the residual enzyme function and betaine to increase methionine concentrations and decrease homocysteine accumulation. We report herein 2 cblE siblings diagnosed in the neonatal period with isolated pancytopenia who, despite treatment, exhibited in adulthood hemolytic anemia (LDH >11 000 U/L, undetectable haptoglobin, elevated unconjugated bilirubin) which could finally be successfully treated by hydroxocobalamin dose escalation. There was no obvious trigger apart from a parvovirus B19 infection in one of the patients. This is the first report of such complications in adulthood. The use of LDH for disease monitoring could possibly be an additional useful biomarker to adjust hydroxocobalamin dosage. Bone marrow infection with parvovirus B19 can complicate this genetic disease with erythroblastopenia even in the absence of an immunocompromised status, as in other congenital hemolytic anemias. The observation of novel hemolytic features in this rare disease should raise awareness about specific complications in remethylation disorders and plea for hydroxocobalamin dose escalation.

Background/Objective : Hydroxocobalamin is indicated for cyanide poisoning and its package insert states it should be given "without delay". We sought to evaluate time to administration and clinical characteristics when hydroxocobalamin was administered in a quaternary care academic medical center. Methods : All hydroxocobalamin administrations from January 1, 2007 to December 31, 2018 were analyzed. Data points recorded were: carboxyhemoglobin, cyanide and methemoglobin levels, hospital time and course, time and dose of hydroxocobalamin administration, lactate and bicarbonate levels, initial and nadir pH, initial heart rate, and initial and lowest systolic blood pressure. Results : Fifty-six cases were identified. One case was excluded as hydroxocobalamin was administered for nitroprusside toxicity. Among 55 cases analyzed, 93% (n = 51) were adults. Median hospital length of stay was 4.3 days (IQR 2.5 to 12). Burn, inhalation injury, and smoke inhalation were 80% of admitting diagnoses. Median time to hydroxocobalamin administration was 208 minutes (IQR 62.5 to 330). Eleven of 55 cases died. Hydroxocobalamin was given within 60 minutes of arrival in 12 cases, of which 3 died. All adults received 5 g of hydroxocobalamin. Time to hydroxocobalamin administration was longer in death cases [median: 221 minutes (IQR 119 to 594)] vs survivors [median: 184.5 minutes (IQR 62.8 to 315)]. Seventeen cases had cyanide levels drawn, with 9 being measurable, but none were toxic. Conclusions : Significant delay in hydroxocobalamin administration was seen in this study. Cases that resulted in death had significantly longer times to hydroxocobalamin administration. Further studies are warranted to identify reasons for delays in hydroxocobalamin administration. [ABSTRACT FROM AUTHOR]

Transcobalamin II (TC) promotes the cellular uptake of cobalamin (Cbl) through receptor-mediated endocytosis of the TC-cbl complex in peripheral tissues. TC deficiency is a rare disorder that causes intracellular Cbl depletion. It presents in early infancy with a failure to thrive, diarrhea, anemia, agammaglobulinemia, and pancytopenia. Data from five TC-deficient patients including clinical, biochemical, and molecular findings, as well as long-term outcomes, were collected. Mutation analysis revealed one unreported pathogenic variant in the TCN2 gene. One patient had exocrine pancreatic insufficiency. We conducted a retrospective analysis of C3 and C3/C2 from dried blood samples, as this is implemented for newborn screening (NBS). We detected a marked increase in the C3/C2 ratio in two samples. Treatment was based on parenteral Cbl. Three patients treated before six months of age had an initial favorable outcome, whereas the two treated later or inadequately had neurological impairment. This is the first report of Argentinean patients with TC deficiency that detected a new variant in TCN2. NBS may be a tool for the early detection of TC deficiency. This data emphasizes that TC deficiency is a severe disorder that requires early detection and long-term, aggressive therapy. Accurate diagnosis is imperative, because early detection and treatment can be life-saving. [ABSTRACT FROM AUTHOR]

Introduction: For patients with catecholamine‐resistant vasoplegic syndrome (VS) during liver transplantation (LT), treatment with methylene blue (MB) and/or hydroxocobalamin (B12) has been an acceptable therapy. However, data on the effectiveness of B12 is limited to case reports and case series. Methods: We retrospectively reviewed records of patients undergoing LT from January 2016 through March 2022. We identified patients with VS treated with vasopressors and MB, and abstracted hemodynamic parameters, vasopressor requirements, and B12 administration from the records. The primary aim was to describe the treatment efficacy of B12 for VS refractory to vasopressors and MB, measured as no vasopressor requirement at the conclusion of the surgery. Results: One hundred one patients received intraoperative VS treatment. For the 35 (34.7%) patients with successful VS treatment, 14 received MB only and 21 received both MB and B12. Of the 21 patients with VS resolution after receiving both MB and B12, 17 (89.5%) showed immediate, but transient, hemodynamic improvements at the time of MB administration and later showed sustained response to B12. Conclusion: Immediate but transient hemodynamic response to MB in VS patients during LT supports the diagnosis of VS and should prompt B12 administration for sustained treatment response. [ABSTRACT FROM AUTHOR]

Cyanide poisoning frequently complicates major burn injuries with inhalation syndrome. The established treatment protocol recommends a standard dose of 70 mg/kg of hydroxocobalamin for adults, with the option to administer a second dose, not exceeding a maximum of 140 mg/kg. Our objective is to chronicle the case of a patient for whom an escalated dosage, exceeding the approved limit, was imperative to reverse the intoxication. The unconventional decision to administer such high doses proved life-saving, albeit not conforming to the medication’s technical specifications. Notably, side effects observed were not markedly worse than those associated with the standard dose, except for the occurrence of moderate kidney failure. It is worth noting that this renal complication is also documented with standard doses and did not necessitate renal replacement therapy. [ABSTRACT FROM AUTHOR]

Hydroxocobalamin is used for cyanide toxicity after smoke inhalation, but diagnosis is challenging. Retrospective studies have associated hydroxocobalamin with acute kidney injury (AKI). This is a retrospective analysis of patients receiving hydroxocobalamin for suspected cyanide toxicity. The primary outcome was the proportion of patients meeting predefined appropriate use criteria defined as ≥1 of the following: serum lactate ≥8 mmol/L, systolic blood pressure (SBP) <90 mmHg, new-onset seizure, cardiac arrest, or respiratory arrest. Secondary outcomes included incidence of AKI, pneumonia, resolution of initial neurologic symptoms, and in-hospital mortality. Forty-six patients were included; 35 (76%) met the primary outcome. All met appropriate use criteria due to respiratory arrest, 15 (43%) for lactate, 14 (40%) for SBP, 12 (34%) for cardiac arrest. AKI, pneumonia, and resolution of neurologic symptoms occurred in 30%, 21%, and 49% of patients, respectively. In-hospital mortality was higher in patients meeting criteria, 49% vs. 9% (95% CI 0.16, 0.64). When appropriate use criteria were modified to exclude respiratory arrest in a post-hoc analysis, differences were maintained, suggesting respiratory arrest alone is not a critical component to determine hydroxocobalamin administration. Predefined appropriate use criteria identify severely ill smoke inhalation victims and provides hydroxocobalamin treatment guidance. • Clinical use criteria may identify appropriate candidates for hydroxocobalamin treatment. • Criteria applied: hypotension, cardiac or respiratory arrest, seizure, or elevated lactate. • Respiratory arrest alone may not be an indicator for hydroxocobalamin treatment. • Time to treatment should be optimized at institutions using hydroxocobalamin. • Emerging associations of hydroxocobalamin with kidney injury require further study. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to assess the impact of hydroxocobalamin (OHCbl) infusion on arterial blood gas and oximetry values in patients with vasoplegic syndrome. Methods Blood samples collected from 95 patients receiving OHCbl infusion were assayed using the ABL90 FLEX Plus blood gas analyzer for the concentration of methemoglobin (MetHb), total hemoglobin (tHb), carboxyhemoglobin (COHb), arterial oxygen saturation (SaO2), arterial oxygen partial pressure (PaO2), and arterial carbon dioxide partial pressure (PaCO2). Interference of OHCbl on these variables was evaluated using the measured difference between the preinfusion and postinfusion samples. Results Blood MetHb (%) measured after the infusion of OHCbl (5g) were significantly higher than the baseline levels, with a median of 4.8 (IQR, 3.0−6.5) versus 1.0 (IQR, 1.0−1.2) (P <.001). Blood COHb (%) increased from a median of 1.3 (IQR, 1.0−1.8) to 1.7 (IQR, 1.3−2.2) (P <.001) following the OHCbl infusion. No differences were seen in median levels of tHb, PaO2, PaCO2, and SaO2 between pre- and post-OHCbl treatment. Conclusion The presence of OHCbl in blood clearly interfered with the oximetry measurements of the hemoglobin component fractions by falsely increasing the levels of MetHb and COHb. Blood levels of MetHb and COHb cannot be reliably determined by the co-oximetry when OHCbl is known or suspected. [ABSTRACT FROM AUTHOR]

Summary: Reducing agents and oxidizing agents have been identified as contributors to vitamin B12 losses associated with food processing and/or storage. We evaluated the effects of redox active agents on cyanocobalamin stability in heat‐treated non‐fat milk and neutral pH buffers. The largest average cyanocobalamin losses occurred in the presence of an added thiol (glutathione, cysteine, dithiothreitol and the thiamine decomposition product 2‐methyl‐3‐furanthiol) or dithionite, whereas cyanocobalamin recoveries generally increased in the presence of an added oxidizing agent. Cyanocobalamin instability in the heat‐treated, non‐fat milk (~40% loss after 90 min at 100 °C) was attributed to a combination of heat, cystine/cysteine, oxygen and a low‐level presence of transition metals, a combination also found in many other foods for which B12 instability has been reported. The proposed cyanocobalamin decomposition pathway – complexation with heat‐exposed cysteine thiolate, cobalt reduction, hydrolysis of the complex, conversion to hydroxocobalamin and irreversible oxidation – follows the sequence described by others. [ABSTRACT FROM AUTHOR]

Abstract—Vitamin B12, or cobalamin, is essential for normal body function and is used in the therapies of different diseases. Vitamin B12 has anti-inflammatory and antioxidant properties that can play an important role in the prevention of some diseases. On the other hand, it has been reported that vitamin B12 in combination with such reducing agents as ascorbate (vitamin C) and thiols showed prooxidant activity. This review provides information on the roles of vitamin B12 in diseases accompanied by inflammation and oxidative stress and the effects of vitamin B12 administrated alone and in combinations with different reducing agents such as ascorbate and thiols on oxidative stress. In addition, the mechanisms of prooxidant actions of combinations of vitamin B12 with these reducing agents depending on the form of vitamin B12 (hydroxocobalamin and cyanocobalamin) are discussed. Understanding the mechanisms of prooxidant action of vitamin B12 is necessary for developing strategies for therapeutic administration of vitamin B12. [ABSTRACT FROM AUTHOR]

Methylmalonic acidemia(MMA) is one of the common diseases in hereditary organic acid metabolism disorder. The disorder is mainly treated by using vitamin B12 which comes in various forms.The use of the methylcobalamin and adenosylcobalamin in China cannot meet the needs of children with MMA. Parenteral use of hydroxocobalamin of high concentration has significant advantages in the treatment of MMA. But, the accessibility to hydroxocobalamin is challenging now.Through the supervision and adjustment of hydroxocobalamin, we explored the strategy of using the drugs. Meanwhile, we are considering the oral use of the hydroxocobalamin as supplement to treatment. Solving the challenges of the hydrococobalamin is helpful to meet the treatment of MMA and to provide a new possibility for the use of medication for rare diseases. The improvement in policy and supervision measures will facilitate the development, involvement, and production of hydroxocobalamin, so that the patients will have a good chance of access to the treatment.