Methylene Blue Administration Research Articles

Targeting mitochondrial dysfunction using methylene blue or mitoquinone to improve skeletal aging.

Methylene blue (MB) is a well-established antioxidant that has been shown to improve mitochondrial function in both in vitro and in vivo settings. Mitoquinone (MitoQ) is a selective antioxidant that specifically targets mitochondria and effectively reduces the accumulation of reactive oxygen species. To investigate the effect of long-term administration of MB on skeletal morphology, we administered MB to aged (18 months old) female C57BL/J6 mice, as well as to adult male and female mice with a genetically diverse background (UM-HET3). Additionally, we used MitoQ as an alternative approach to target mitochondrial oxidative stress during aging in adult female and male UM-HET3 mice. Although we observed some beneficial effects of MB and MitoQ in vitro, the administration of these compounds in vivo did not alter the progression of age-induced bone loss. Specifically, treating 18-month-old female mice with MB for 6 or 12 months did not have an effect on age-related bone loss. Similarly, long-term treatment with MB from 7 to 22 months or with MitoQ from 4 to 22 months of age did not affect the morphology of cortical bone at the mid-diaphysis of the femur, trabecular bone at the distal-metaphysis of the femur, or trabecular bone at the lumbar vertebra-5 in UM-HET3 mice. Based on our findings, it appears that long-term treatment with MB or MitoQ alone, as a means to reduce skeletal oxidative stress, is insufficient to inhibit age-associated bone loss. This supports the notion that interventions solely with antioxidants may not provide adequate protection against skeletal aging.

The use of methylene blue to control the tumor oxygenation level

BackgroundHypoxia is a characteristic feature of many tumors. It promotes tumor proliferation, metastasis, and invasion and can reduce the effectiveness of many types of cancer treatment. ObjectiveThe aim of this study was to investigate the pharmacokinetics of methylene blue (MB) and its impact on the tumor oxygenation level at mouse Lewis lung carcinoma (LLC) model using spectroscopic methods. ApproachThe pharmacokinetics of MB were studied qualitatively and quantitatively using video fluorescence imaging and fluorescence spectroscopy. The degree of hemoglobin oxygenation in vivo was examined by calculating hemoglobin optical absorption from the measured diffuse reflectance spectra. The distribution of MB fluorescence and the lifetime of NADH were analyzed using laser scanning microscopy and fluorescence lifetime imaging microscopy (FLIM) to assess cellular metabolism. ResultsAfter intravenous administration of MB at 10–20 mg/kg, it quickly transitioned in the tumor to a colorless leucomethylene blue, with maximum accumulation in the tumor occurring after 5–10 min. A concentration of 10 mg/kg resulted in a relative increase of the tumor oxygenation level for small tumors (volume 50–75 mm3) and normal tissue 120 min after the introduction of MB. A shift in tumor metabolism towards oxidative phosphorylation (according to the lifetime of the NADH coenzyme) was measured using FLIM method after intravenous administration of 10 mg/kg of MB. Intravenous administration of MB at 20 mg/kg results in a long-term decrease in oxygenation, which persisted for at least 120 min after the administration and did not return to its initial level. ConclusionsAdministration of MB at 10 mg/kg shown to increase tumor oxygenation level, potentially leading to more effective antitumor therapy. However, at higher doses (20 mg/kg), MB may cause long-term decrease in oxygenation.

Methylene Blue in Metformin Intoxication: Not Just Rescue But Also Initial Treatment.

Metformin (MTF) is a widely used oral antidiabetic medication. Regardless the reason, high doses of MTF cause lactic acidosis as a result of its effects on mitochondrial ATP production and no-mediated vascular smooth muscle relaxation. Metformin-associated lactic acidosis can be life-threatening despite all treatments. Methylene blue (MB) has the potential to reverse the toxic effects of MTF through its effects on both the mitochondrial respiratory chain and nitric oxide production. The use of MB in MTF intoxication has only been reported in a limited number of cases. Herein, we present a 16-year-old female patient who attempted suicide by ingesting high doses of MTF. Supportive treatments, such as vasopressor, inotropic treatments, and sodium bicarbonate, were started in the patient who developed fluid-resistant hypotension after pediatric intensive care unit admission. Because of rising lactate levels, Continuous renal replacement therapy (CRRT) was started immediately. Despite all treatments, hypotension and hyperlactatemia persisted; MB was given as a rescue therapy. Noticeable hemodynamic improvement was observed within 30 minutes of initiating MB infusion, allowing a gradual decrease in the doses of inotropic infusions within the first hour of therapy. Patient's cardiovascular support was discontinued on the second day, and she was discharged on the fifth day. We speculate that, considering the mechanisms of MTF toxicity and the mechanisms of action of MB, it is suggested that early administration of MB, not only as a rescue treatment but as the initial approach to MTF poisoning in combination with other treatments, may result in improved outcomes.

Use of hydroxocobalamin to treat intraoperative vasoplegic syndrome refractory to vasopressors and methylene blue during liver transplantation.

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. 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. 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. 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.

Linfonodo ilíaco medial como alvo de metástase em cadelas com neoplasmas mamários malignos

ABSTRACT: The regional lymphatic connections of the mammary glands in canines are poorly investigated, both in healthy animals and in those with mammary neoplasms. The objective was to establish the occurrence of metastases in the medial iliac lymph nodes (MILN) in bitches with mammary neoplasm, in addition to evaluating the effectiveness of the technique of lymphatic labeling of the MILN, administering methylene blue (MB) dye intrauterinely or intradermally. Thirty-two bitches with tumors in different mammary glands were included in the study. In 13 bitches (GU group), the MILNs were stained with intrauterine MB, followed by unilateral lymphadenectomy, ovariohysterectomy (OVH) and unilateral mastectomy. Nineteen bitches (GI group) underwent OVH, followed by MILN staining with intradermal MB, lymphadenectomy, and unilateral mastectomy. In GU, 11 bitches (84.62%) exhibited MB-stained MILNs, but staining was not observed in two (15.38%). Metastasis to MILNs was observed in three bitches (9.38%) from the GI and two (6.25%) from the GU. Intrauterine and intradermal staining of MILNs in bitches with mammary tumors was efficient, but intradermal administration of MB produced better results. Given metastatic spread to MILNs in approximately 15.63% of patients, we recommend that screening for MILNs should be considered as part of the staging of animals with malignant mammary neoplasms.

Exploring Methylene Blue and Its Derivatives in Alzheimer's Treatment: A Comprehensive Review of Randomized Control Trials.

Methylene blue (MB) and its compounds are investigated for their potential benefits in the management of Alzheimer's disease (AD). ADis a widely seen neuropathological disorder characterized by the gradual decline of cognitive abilities, ultimately leading to the development of severe dementia. It is anticipated that there will be a significant increase in the prevalence of ADdue to the agingpopulation. Histopathologically, AD is distinguished by the presence of intracellular tangles of neurofibrillary tissues (NFTs) and extracellular amyloid plaques within the brain. MB is a thiophenazine dye with FDA approval for treating several illnesses. Its ease in crossing the blood-brain barrier and potential therapeutic use in central nervous system diseases have increased interest in its application for treating AD. The literature review includes randomized clinical trials investigating MB's potential benefits in treating AD. The findings of the studies indicate that the administration of MB has demonstrated enhancements in cognitive function, reductions in the accumulation of plaques containing beta-amyloid, improvements in memory and cognitive function in animal subjects, and possesses antioxidant properties that can mitigate oxidative stress and inflammation within the brain. Thisreview evaluates the modern and latest research on the application of MB for treating AD.

Hydroxocobalamin Versus Methylene Blue for the Treatment of Vasoplegic Shock Associated With Cardiopulmonary Bypass

To compare changes in vasopressor requirements and hemodynamic responses after hydroxocobalamin or methylene blue administration for vasoplegic shock (VS). Retrospective cohort analysis. Single-center, academic medical center. Cardiothoracic surgery adult patients. Hydroxocobalamin or methylene blue. The primary outcome was a change in vasopressor requirements over the first 24 hours (1, 3, 6, 12, and 24 hours) after hydroxocobalamin or methylene blue initiation. Secondary outcomes included changes in mean arterial pressure (MAP), systemic vascular resistance, and lactate. A total of 120 adult patients who received hydroxocobalamin (n=77) or methylene blue (n=43) were included. Vasopressor requirements at baseline were 0.34 µg/kg/min (95% CI 0.28-0.4) norepinephrine equivalent (NEE) in the hydroxocobalamin group, and 0.59 µg/kg/min (95% CI 0.52-0.66) NEE in the methylene blue group; p < 0.001. Vasopressor requirements decreased significantly at each time point within each group (hour 1 mean [95% CI] NEE, hydroxocobalamin 0.27 µg/kg/min [0.21-0.33]; methylene blue 0.44 µg/kg/min [0.38-0.51]; p < 0.001). The mean MAP at baseline was 65 mmHg (95% CI 63-67) in the hydroxocobalamin group, and 57 mmHg (95% CI 54-59) in the methylene blue group; p < 0.001. The mean MAP increased significantly from baseline at each time point within each group (hour 1 mean [95% CI] hydroxocobalamin 73 mmHg [71-75]; methylene blue 67 mmHg [65-70]; p < 0.001). After adjusting for baseline characteristics, a significantly greater reduction in vasopressor requirements and an increase in MAP were noted in the hydroxocobalamin group compared with the methylene blue group. Hydroxocobalamin was associated with a greater reduction in vasopressor requirements than methylene blue in treating VS associated with cardiopulmonary bypass.

Methylene blue reduces the serum levels of interleukin-6 and inhibits STAT3 activation in the brain and the skin of lipopolysaccharide-administered mice.

It is valuable to search for novel and economical agents for inhibiting STAT3 activation and blocking increases in IL-6 levels, due to the important roles of STAT3 and IL-6 in inflammation. Since Methylene Blue (MB) has shown therapeutical potential for multiple diseases, it has become increasingly important to investigate the mechanisms underlying the effects of MB on inflammation. Using a mouse model of lipopolysaccharide (LPS)-induced inflammation, we investigated the mechanisms underlying the effects of MB on inflammation, obtaining the following findings: First, MB administration attenuated the LPS-induced increases in the serum levels of IL-6; second, MB administration attenuated LPS-induced STAT3 activation of the brain; and third, MB administration attenuated LPS-induced STAT3 activation of the skin. Collectively, our study has suggested that MB administration can decrease the levels of IL-6 and STAT3 activation - two important factors in inflammation. Since MB is a clinically used and relatively economical drug, our findings have suggested therapeutic potential of MB for multiple inflammation-associated diseases due to its effects on STAT3 activation and IL-6 levels.

Nonconvulsive Status Epilepticus and Encephalopathy Related to Ifosfamide – A Case Report

Introduction: Ifosfamide (IFX) is an alkylating drug used for chemotherapy to manage a wide range of malignancies including testicular, ovarian, head-and-neck cancers, lymphomas, and sarcomas. Central nervous system (CNS) toxicity is known to occur in 10%–40% of patients who are administered high doses of IFX. CNS toxicity includes an encephalopathy with underlying nonconvulsive status epilepticus manifesting with altered sensorium, mental confusion, seizures, ataxia, visual hallucinations, akinetic mute state extrapyramidal features, or coma. Case Report: We describe the case of a 65-year-old woman with a rapidly evolving confusional state and progressive decline in the fluency of speech progressing to mutism immediately after IFX chemotherapy. Results: Electroencephalogram (EEG) revealed evidence of nonconvulsive status epilepticus. The patient was managed with anticonvulsants, discontinuing IFX, and intravenous methylene blue infusion. Subsequently, the patient had significant improvement to an alert state with normalization of EEG abnormality. Conclusion: CNS toxicity following IFX usually manifests within 24 h of the drug administration, although clinical manifestations of toxicity may occur up to 4–6 days and a significant number of these patients may have a nonconvulsive status as the cause of the encephalopathy. Patients with encephalopathy following IFX should be evaluated with early EEG to assess for the presence or absence of a nonconvulsive status. Patients with a positive EEG would benefit from prompt and aggressive anticonvulsant therapy along with cessation of IFX therapy with or without intravenous methylene blue administration.

Spectroscopic study of methylene blue in vivo: effects on tissue oxygenation and tumor metabolism

Methylene blue (MB) is a promising photosensitizer (PS) for the treatment of pathological neoplasms, since it has both photodynamic activity (under laser irradiation) and redox and catalytic properties (in the absence of light). In the framework of this work, using spectroscopic methods, the effect of intravenous administration of MB on tissue oxygenation of hemoglobin in small animals in vivo in tumor and normal tissues was analyzed. The influence of MB on cell metabolism was analyzed. It has been shown that the use of MB promotes an increase in oxygen consumption by the tumor, and also leads to a shift in metabolism towards oxidative phosphorylation. It was shown that the use of MB contributes to an increase in oxygen consumption by the tumor, and also leads to a shift in metabolism towards oxidative phosphorylation.

Indoxacarb poisoning induced methemoglobinemia-a rare presentation in paediatric age group

Indoxacarb, an oxadiazine insecticide, has high insecticidal and low mammalian toxicity. The insecticidal activity of indoxacarb is attributed to its ability to block sodium channels in the insect nervous system. Several cases of indoxacarb-induced methemoglobinemia have been reported in adults, but presentation in paediatric age group is rare. Methaemoglobinaemia occurs after indoxacarb ingestion because its aromatic metabolites are biotransformed to active intermediates that produce methaemoglobin. The case involved is an adolescent girl who presented to the PICU 3 hours after suicidal ingestion of 10-15 ml of indoxacarb. After 15 min of consumption of poison she developed pain abdomen and vomiting. At PICU, she complained of nausea, vomiting and dizziness. Her vital signs were heart rate 96/min, BP 110/80 mmHg, oxygen saturation 78% on room air and GCS 15/15. Despite receiving 10L/ min of oxygen via NRBM mask. Her ECG showed normal sinus rhythm without ischaemic change, and CXR showed no specific abnormality. Initial arterial blood gas analysis revealed pH-7.413, pO2-123.6 mmHg, pCO2-37.7 mmHg, HCO3 23.5 mmol/L. Other laboratory results were normal. Methaemoglobinemia is a rare clinical presentation of indoxacarb poisoning. The treatment plan includes timely administration of injection methylene blue.

The effects of acute Methylene Blue administration on cerebral blood flow and metabolism in humans and rats.

Methylene Blue (MB) is a brain-penetrating drug with putative neuroprotective, antioxidant and metabolic enhancing effects. In vitro studies suggest that MB enhances mitochondrial complexes activity. However, no study has directly assessed the metabolic effects of MB in the human brain. We used in vivo neuroimaging to measure the effect of MB on cerebral blood flow (CBF) and brain metabolism in humans and in rats. Two doses of MB (0.5 and 1 mg/kg in humans; 2 and 4 mg/kg in rats; iv) induced reductions in global cerebral blood flow (CBF) in humans (F(1.74, 12.17)5.82, p = 0.02) and rats (F(1,5)26.04, p = 0.0038). Human cerebral metabolic rate of oxygen (CMRO2) was also significantly reduced (F(1.26, 8.84)8.01, p = 0.016), as was the rat cerebral metabolic rate of glucose (CMRglu) (t = 2.6(16) p = 0.018). This was contrary to our hypothesis that MB will increase CBF and energy metrics. Nevertheless, our results were reproducible across species and dose dependent. One possible explanation is that the concentrations used, although clinically relevant, reflect MB's hormetic effects, i.e., higher concentrations produce inhibitory rather than augmentation effects on metabolism. Additionally, here we used healthy volunteers and healthy rats with normal cerebral metabolism where MB's ability to enhance cerebral metabolism might be limited.

SIRT5-related desuccinylation modification of AIFM1 protects against compression-induced intervertebral disc degeneration by regulating mitochondrial homeostasis

Mitochondrial dysfunction plays a major role in the development of intervertebral disc degeneration (IDD). Sirtuin 5 (SIRT5) participates in the maintenance of mitochondrial homeostasis through its desuccinylase activity. However, it is still unclear whether succinylation or SIRT5 is involved in the impairment of mitochondria and development of IDD induced by excessive mechanical stress. Our 4D label-free quantitative proteomic results showed decreased expression of the desuccinylase SIRT5 in rat nucleus pulposus (NP) tissues under mechanical loading. Overexpression of Sirt5 effectively alleviated, whereas knockdown of Sirt5 aggravated, the apoptosis and dysfunction of NP cells under mechanical stress, consistent with the more severe IDD phenotype of Sirt5 KO mice than wild-type mice that underwent lumbar spine instability (LSI) surgery. Moreover, immunoprecipitation-coupled mass spectrometry (IP-MS) results suggested that AIFM1 was a downstream target of SIRT5, which was verified by a Co-IP assay. We further demonstrated that reduced SIRT5 expression resulted in the increased succinylation of AIFM1, which in turn abolished the interaction between AIFM1 and CHCHD4 and thus led to the reduced electron transfer chain (ETC) complex subunits in NP cells. Reduced ETC complex subunits resulted in mitochondrial dysfunction and the subsequent occurrence of IDD under mechanical stress. Finally, we validated the efficacy of treatments targeting disrupted mitochondrial protein importation by upregulating SIRT5 expression or methylene blue (MB) administration in the compression-induced rat IDD model. In conclusion, our study provides new insights into the occurrence and development of IDD and offers promising therapeutic approaches for IDD.

Methylene blue dosing strategies in critically ill adults with shock-A retrospective cohort study.

Shock increases mortality in the critically ill and the mainstay of therapy is the administration of vasopressor agents to achieve hemodynamic targets. In the past, studies have found that the NO-pathway antagonist methylene blue improves hemodynamics. However, the optimal dosing strategy remains elusive. Therefore, we investigated the hemodynamic and ICU outcome parameters of three different dosing strategies for methylene blue. We performed a retrospective cohort study of patients in shock treated with methylene blue. Shock was defined as norepinephrine dose >0.1 μg/kg/min and serum lactate level >2 mmol/l at the start of methylene blue administration. Different demographic variables, ICU treatment, and outcome parameters were evaluated. To compare the differences in the administration of vasopressors or inotropes, the vasoactive inotropic score (VIS) was calculated at different time points after starting the administration of methylene blue. Response to methylene blue or mortality at 28 days were assessed. 262 patients from July 2014 to October 2019 received methylene blue. 209 patients met the inclusion criteria. Three different dosing strategies were identified: bolus injection followed by continuous infusion (n = 111), bolus injection only (no continuous infusion; n = 59) or continuous infusion only (no bolus prior; n = 39). The groups did not differ in demographics, ICU scoring system, or comorbidities. In all groups, VIS decreased over time, indicating improved hemodynamics. Cardiogenic shock and higher doses of norepinephrine increased the chance of responding to methylene blue, while bolus only decreased the chance of responding to methylene blue treatment. 28-day mortality increased with higher SAPSII scores and higher serum lactate levels, while bolus injection followed by continuous infusion decreased 28-day mortality. No severe side effects were noted. In this cohort, methylene blue as a bolus injection followed by continuous infusion was associated with a reduced 28-day mortality in patients with shock. Prospective studies are needed to systematically evaluate the role of methylene blue in the treatment of shock.

Methemoglobinemia.

The targeted audience for this simulation are emergency medicine providers, including residents as well as advanced practice providers, to properly educate on recognizing, diagnosing, and managing methemoglobinemia. Methemoglobinemia is a blood disorder characterized by the presence of ferric form of hemoglobin in the blood. This form of hemoglobin can carry oxygen but is unable to release it effectively causing a range of symptoms including headache, dizziness, nausea, and cyanosis. It is rarely congenital and mostly caused by the exposure to oxidizing agents, such as local anesthetics and quinolones.1 Normally, oxygen can bind to hemoglobin while it is in the ferrous state (Fe2+). In cases of methemoglobinemia, the heme iron configuration is converted from ferrous (Fe2+) to ferric (Fe3+), making it unable to bind to oxygen. As a result, normal ferrous hemes experience an increased affinity for oxygen causing a leftward shift in the oxygen dissociation curve. This in turn causes functional anemia due to reduced oxygen carrying capacity.1 Methemoglobinemia can result from exposure to different medications as well as environmental factors and presents like other disease processes including chronic obstructive pulmonary disease exacerbations. Congenital methemoglobinemia due to cytochrome b5 reductase deficiency is very rare, but the actual incidence is not known. Increased frequency of disease has been found in Siberian Yakuts, Athabaskans, Eskimos, and Navajo.2 Although it is also an unusual occurrence, acquired methemoglobinemia is much more frequently encountered than the congenital form.1In a 10-year retrospective study looking at the incidence rate of topical anesthetic-induced methemoglobinemia, it was found that the overall prevalence was 0.035%. A major risk factor was hospitalization at the time of a procedure being performed. An increased risk was also seen with benzocaine-based anesthetics.3. At the end of this simulation case, participants should be able to: 1) recognize shortness of breath, cyanosis and respiratory distress, and the difference between all of them based on the clinical presentation 2) identify the underlying cause of the condition by conducting a thorough history and physical 3) know how to identify and treat methemoglobinemia by ordering necessary labs and interventions and understand the pathophysiology leading to methemoglobinemia 4) recognize patient's response to treatment and continue to reassess. This is a high-fidelity simulation case that allows participants to evaluate and treat methemoglobinemia in a safe environment. The case is followed by a debriefing and small group discussion to review patient care skills, medical knowledge, interpersonal communication, practice-based learning, and improvement. The educational content and efficacy were evaluated by oral feedback and a debriefing session immediately after completion of the simulation. A 5-point Likert scale was sent out to participants pre-simulation and post-simulation. Questions on the survey included whether they felt confident in their ability to recognize methemoglobinemia, understood the physiology and causes of methemoglobinemia, and felt confident in their ability to treat methemoglobinemia. Sixteen learners responded to the survey, consisting of EM residents and medical students. Post simulation, approximately 92% of EM residents answered agree or strongly agree in their ability to recognize and treat methemoglobinemia compared to pre-sim survey of about 62.5%. Post-simulation feedback also resulted in positive reception, and learners found it useful to run through an uncommonly seen case in the hospital. Results showed overall improvement in recognition and treatment of methemoglobinemia among residents and medical students. This simulation improved recognition of methemoglobinemia including signs and symptoms associated with it. Proper management and treatment options were included such as administration of methylene blue. Overall, this simulation was helpful in teaching EM residents how to recognize, manage, and treat methemoglobinemia. In addition, post-simulation debriefing allowed further discussion among residents, which they found valuable. Methemoglobinemia, shortness of breath, cyanosis, respiratory distress, anemia, methemoglobin, oxygen dissociation curve, emergency medicine simulation.

Dramatic destruction of methicillin-resistant Staphylococcus aureus infections with a simple combination of amoxicillin and light-activated methylene blue.

Staphylococcus aureus is and continues to be a leading cause of bacterial infections throughout the world. Given the global dissemination of multi-drug resistant (MDR) S. aureus, particularly methicillin-resistant S. aureus (MRSA), novel solutions against S. aureus infections are urgently needed. In our study on the interactions between commonly used photosensitizers and antibiotics in the clinic, we discovered that MRSA can be dramatically destroyed by a simple combination of amoxicillin and light-activated methylene blue (MB). To guide the clinical application of this combination therapy, we quantitatively assessed the interaction between light-activated MB and amoxicillin against S. aureus and its treatment order, dosage, and time length dependence. Furthermore, we evaluated the efficacy of this combination therapy in treating and halting the progression of MRSA infections with the catheter biofilm infection model and the pig skin burn infection model. In the end, we disclosed the antimicrobial mechanisms of this combination therapy to further facilitate its clinical translation. Amoxicillin and light-activated MB can mutually boost each other's uptake in S. aureus, producing up to 8 logs of reduction of MRSA infections when they are co-administrated. Such an anti-S. aureus synergy could be triggered with the currently used MB and amoxicillin clinical administration regimens. It is effective against S. aureus pathogens regardless of their antibiotic resistance backgrounds and does not create significant bacterial resistance with five days of continuous applications. It can lead to more than 99% of reduction of S. aureus infections established not only on the medical devices but also on the body surfaces. Possessing a fusion of effectiveness, safety, sustainability, and broad applicability, this simple combination of light-activated MB and amoxicillin can ultimately reform our treatment against MDR S. aureus pathogens including MRSA, significantly alleviating the health and economic burden of S. aureus infections across the world.

Metolachlor Poisoning with Lactic Acidosis Improved by Thiamine Administration: A Case Report

BACKGROUND Metolachlor is a chloroacetamide herbicide that is extensively used worldwide. Ingestion of metolachlor causes acute toxicity via the generation of methemoglobin. Elevated levels of methemoglobin inhibit the transport of oxygen to tissue, causing hypoxia and lactic acidosis. A common treatment approach has been to reduce methemoglobin by administration of methylene blue. Herein, we present a case of metolachlor poisoning causing lactic acidosis that was treatable by thiamine administration, in which the methemoglobin level was not elevated. CASE REPORT A 61-year-old man was admitted to the emergency room with seizures and impaired consciousness after the ingestion of metolachlor (250 mL, 83%) with the intent to commit suicide. The patient's methemoglobin and lactate levels on admission were 0.9% and 11.8 mmol/L, respectively. After admission, the levels of lactate decreased gradually; however, they increased 13 h after admission. There was no evidence of heavy alcohol consumption, hyponutrition, or chronic thiamine deficiency. We initially administered a thiamine bolus (100 mg), which immediately improved his consciousness, followed by continuous administration of the same substance (1500 mg/day). The patient's consciousness improved, and was discharged from the intensive care unit on day 4. CONCLUSIONS Metolachlor can cause metabolic dysfunction and lactic acidosis without an increase in methemoglobin. Moreover, thiamine administration may be beneficial for patients with metolachlor intoxication exhibiting symptoms of elevated lactate levels, impaired consciousness, and lack of elevated methemoglobin levels.

Methylene blue: a controversial diagnostic acid and medication?

A narrative review of the literature was conducted to determine if the administration of methylene blue (MB) in humans has potential risks. Studies were identified from MEDLINE, Web of Science, Scopus, and Cochrane. MB is a diagnostic substance used during some diagnostic procedures and also a part of the treatment of several diseases including methemoglobinemia, vasoplegic syndrome, fosfamide-induced encephalopathy, and cyanide intoxication, and the detection of leaks or position of parathyroid corpuscles during surgery. Although the use of MB is historically justified, and it ought to be safe, because it originated as a diagnostic material, the basic toxicological characteristics of this substance are unknown. Despite reports of severe adverse effects of MB, which could significantly exceed any possible benefits evaluated for the given indication. Therefore, the clinical use of MB currently represents a controversial problem given the heterogeneity of available data and the lack of preclinical data. This is in conflict with standards of safe use of such substances in human medicinal practice. The toxic effects of the application of MB are dose-dependent and include serious symptoms such as hemolysis, methemoglobinemia, nausea and vomitus, chest pain, dyspnoea, and hypertension. Some countries regard MB as harmful because of the resulting skin irritation and triggering of an adverse inflammatory response. MB induced serotoninergic toxicity clinically manifests as neuromuscular hyperactivity. This review aims to summarize the current understanding concerning the indications for MB administration and define the potential adverse effects of MB.

Two Cases of Methemoglobinemia Caused by Prilocaine, A Local Anesthetic

In situations of methemoglobinemia, elevated amounts of methemoglobin decrease hemoglobin's ability to bind oxygen. Cases of methemoglobinemia may appear with a mild or severe presentation at emergency departments. This disorder can be inherited or acquired. In the initial phase of treatment, intravenous administration of methylene blue is preferable. This methemoglobinemia may be caused by prilocaine, one of the local anesthetics used for surgical procedures. This paper attempts to describe the examination, diagnostic, and treatment processes of two patients who presented to the emergency room with cyanosis and shortness of breath following the administration of local anesthetic. We aimed to contribute to the literature by explaining the importance of differential diagnosis, clinical findings, and treatment in methemoglobinemia.

Methylene blue for vasodilatory shock in the intensive care unit: a retrospective, observational study

BackgroundRefractory vasodilatory shock is a state of uncontrolled vasodilation associated with underlying inflammation and endothelial dysregulation. Rescue therapy for vasoplegia refractory to catecholamines includes methylene blue (MB) which restores vascular tone. We hypothesized that (1) at least 40% of critically ill patients would respond positively to MB administration and (2) that those who responded to MB would have a survival benefit.MethodsThis study was a retrospective review that included all adult patients admitted to an intensive care unit treated with MB for the indication of refractory vasodilatory shock. Responders to MB were identified as those with a ≥ 10% increase in mean arterial pressure (MAP) within the first 1-2 hours after administration. We examined the association of mortality to the groups of responders versus non-responders to MB. A subgroup analysis in patients undergoing continuous renal replacement therapy (CRRT) was also performed.Statistical calculations were performed in Microsoft Excel® (Redmond, WA, USA). Where appropriate, the comparison of averages and standard deviations of demographics, dosing, MAP, and reductions in vasopressor dosing were performed via Chi squared, Fisher's exact test, or two-tailed t-test with a p-value < 0.05 being considered as statistically significant. After using the F-test to assess for differences in variance, the proper two tailed t-test was used to compare SOFA scores among responders versus non-responders.ResultsA total of 223 patients were included in the responder analysis; 88 (39.5%) had a ≥ 10% increase in MAP post-MB administration that was not associated with a significant change in norepinephrine requirements between responders versus non-responders (p=0.41). There was a non-statistically significant trend (21.6% vs 14.8%, p=0.19) toward improved survival to hospital discharge in the MB responder group compared to the non-responder group. In 70 patients undergoing CRRT, there were 33 responders who were more likely to survive than those who were not (p = 0.0111).ConclusionsIn patients with refractory shock receiving MB, there is a non-statistically significant trend toward improved outcomes in responders based on a MAP increase >10%. Patients supported with CRRT who were identified as responders had decreased ICU mortality compared to non-responders.