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1.
Am J Med Sci ; 360(4): 329-337, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32631574

RESUMO

Methylene blue (MB) is considered to be the first synthetic medication ever used in humans. There are many indications for MB, including vasoplegic shock. Nitric oxide (NO), the central mediator of sepsis, promotes vasoplegia by enhancing the guanylate cyclase cyclic guanosine monophosphate second messenger system, the effect of which is attenuated by MB. Therefore, the use of MB represents a unique pharmacologic approach towards treating the underlying pathophysiology of vasoplegia in sepsis. There are numerous reports of the successful use of MB in refractory shock in the literature. This manuscript describes the historical aspects of the identification of NO as the endothelial derived relaxation factor and its role in the pathogenesis of vasoplegia in septic shock. An analysis of the existing evidence for the use of MB as an inhibitor of NO in vasodilatory shock is provided. The adverse effects associated with the use of MB and an approach to optimal dosing in septic shock are also addressed.


Assuntos
Azul de Metileno/uso terapêutico , Óxido Nítrico/antagonistas & inibidores , Choque Séptico/tratamento farmacológico , Vasoplegia/tratamento farmacológico , Humanos , Azul de Metileno/administração & dosagem , Azul de Metileno/efeitos adversos , Choque Séptico/complicações , Choque Séptico/metabolismo , Vasodilatação/efeitos dos fármacos , Vasoplegia/etiologia , Vasoplegia/metabolismo
3.
Expert Opin Pharmacother ; 21(6): 619-627, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32037892

RESUMO

INTRODUCTION: Alzheimer's disease (AD) is a major cause of morbidity worldwide and its prevalence is expected to rise. Previous studies involving compounds that target the accumulation of amyloid ß protein have been unsuccessful, renewing interest in therapies directed against intracellular deposits of tau proteins. Derived from methylene blue, hydromethylthionine is a tau aggregation inhibitor that recently emerged as a promising disease-modifying treatment for AD. AREAS COVERED: Herein, the authors cover the chemistry, pharmacodynamics and pharmacokinetics of hydromethylthionine and its oxidized form methylthionine chloride (MTC) that was first studied, as well as clinical efficacy and safety of hydromethylthionine in the treatment of mild to moderate AD. EXPERT OPINION: Randomized clinical trials with hydromethylthionine failed to show any impact of the doses used on the disease course. Data analysis from a non-randomized cohort showed that a smaller dose of the drug previously thought to be ineffective and used as placebo, prescribed as monotherapy rather than as add-on to AD approved symptomatic therapies may slow cognitive decline. This finding was further confirmed by a pharmacokinetic analysis study showing a dose/response relationship with doses around 16 mg daily. Future trials need to study the pharmacological properties of hydromethylthionine and ascertain the optimal safe and effective dose to be used.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Disfunção Cognitiva/prevenção & controle , Azul de Metileno/análogos & derivados , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Estudos de Coortes , Progressão da Doença , Relação Dose-Resposta a Droga , Humanos , Azul de Metileno/efeitos adversos , Azul de Metileno/farmacocinética , Azul de Metileno/uso terapêutico , Agregados Proteicos/efeitos dos fármacos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Proteínas tau/metabolismo
4.
Int J Gynaecol Obstet ; 148(2): 157-161, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31628667

RESUMO

OBJECTIVE: To investigate the safety and efficacy of mixed methylene blue (MB) compound injection for treatment of vulvar non-neoplastic epithelial disorders (NNEDs). METHODS: A prospective observational study among 118 women with vulvar NNEDs treated with intradermal injection of mixed MB compound at a hospital in Wuhan, China, between 2013 and 2016. Itching score, skin hypopigmentation area percentage (SHAP), and recurrence were assessed by interview and physical examination before and after treatment. Adverse effects were recorded. RESULTS: Before treatment, mean ± SD itching score was 7.78 ± 1.59. It decreased rapidly immediately after treatment and remained low thereafter (1.82 ± 2.31, 1.69 ± 2.39, 1.97 ± 2.73, 2.05 ± 2.72, and 2.19 ± 2.86 at 1, 3, 6, 12, and 24 months, respectively). Before treatment, mean ± SD SHAP was 28.01% ± 18.28%. SHAP decreased gradually and remained stably low 6 months later (26.28% ± 17.95%, 21.19% ± 18.42%, 19.19% ± 18.67%, 18.68% ± 18.91%, and 18.65% ± 19.20% at 1, 3, 6, 12, and 24 months, respectively). The recurrence rate in 2 years was 21.2% (25/118) with no major complications. CONCLUSIONS: Intradermal injection of mixed MB compound was found to be an effective and safe treatment for vulvar NNEDs. ClinicalTrials.gov: NCT03200808.


Assuntos
Inibidores Enzimáticos/administração & dosagem , Hiperplasia/tratamento farmacológico , Azul de Metileno/administração & dosagem , Líquen Escleroso Vulvar/tratamento farmacológico , Adulto , China , Inibidores Enzimáticos/efeitos adversos , Feminino , Humanos , Hiperplasia/complicações , Injeções , Azul de Metileno/efeitos adversos , Pessoa de Meia-Idade , Estudos Prospectivos , Prurido/tratamento farmacológico , Prurido/etiologia , Vulva/efeitos dos fármacos , Líquen Escleroso Vulvar/complicações
5.
Intensive Care Med ; 45(11): 1503-1517, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31646370

RESUMO

BACKGROUND: Vasopressors are administered to critically ill patients with vasodilatory shock not responsive to volume resuscitation, and less often in cardiogenic shock, and hypovolemic shock. OBJECTIVES: The objectives are to review safety and efficacy of vasopressors, pathophysiology, agents that decrease vasopressor dose, predictive biomarkers, ß1-blockers, and directions for research. METHODS: The quality of evidence was evaluated using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). RESULTS: Vasopressors bind adrenergic: α1, α2, ß1, ß2; vasopressin: AVPR1a, AVPR1B, AVPR2; angiotensin II: AG1, AG2; and dopamine: DA1, DA2 receptors inducing vasoconstriction. Vasopressor choice and dose vary because of patients and physician practice. Adverse effects include excessive vasoconstriction, organ ischemia, hyperglycemia, hyperlactatemia, tachycardia, and tachyarrhythmias. No randomized controlled trials of vasopressors showed a significant difference in 28-day mortality rate. Norepinephrine is the first-choice vasopressor in vasodilatory shock after adequate volume resuscitation. Some strategies that decrease norepinephrine dose (vasopressin, angiotensin II) have not decreased 28-day mortality while corticosteroids have decreased 28-day mortality significantly in some (two large trials) but not all trials. In norepinephrine-refractory patients, vasopressin or epinephrine may be added. A new vasopressor, angiotensin II, may be useful in profoundly hypotensive patients. Dobutamine may be added because vasopressors may decrease ventricular contractility. Dopamine is recommended only in bradycardic patients. There are potent vasopressors with limited evidence (e.g. methylene blue, metaraminol) and novel vasopressors in development (selepressin). CONCLUSIONS: Norepinephrine is first choice followed by vasopressin or epinephrine. Angiotensin II and dopamine have limited indications. In future, predictive biomarkers may guide vasopressor selection and novel vasopressors may emerge.


Assuntos
Choque/tratamento farmacológico , Vasoconstritores/farmacologia , Angiotensina II/efeitos adversos , Angiotensina II/farmacologia , Angiotensina II/uso terapêutico , Estado Terminal/terapia , Dopamina/efeitos adversos , Dopamina/farmacologia , Dopamina/uso terapêutico , Epinefrina/efeitos adversos , Epinefrina/farmacologia , Epinefrina/uso terapêutico , Humanos , Azul de Metileno/efeitos adversos , Azul de Metileno/farmacologia , Azul de Metileno/uso terapêutico , Norepinefrina/efeitos adversos , Norepinefrina/farmacologia , Norepinefrina/uso terapêutico , Fenilefrina/efeitos adversos , Fenilefrina/farmacologia , Fenilefrina/uso terapêutico , Choque/fisiopatologia , Terlipressina/efeitos adversos , Terlipressina/farmacologia , Terlipressina/uso terapêutico , Vasoconstritores/efeitos adversos , Vasoconstritores/uso terapêutico , Vasopressinas/efeitos adversos , Vasopressinas/farmacologia , Vasopressinas/uso terapêutico
6.
AANA J ; 87(1): 26-28, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31587740

RESUMO

A change in urine color is an unusual intraoperative occurrence, which can be distressing for the anesthesia provider. Abnormal changes in color are generally benign effects of medications and foods; however, a change in urine color may be a sign of an underlying pathologic condition. Methylene blue, a nonpathogenic, water-soluble, commonly used dye for diagnostic tests, has on rare occasions, been reported to discolor urine green intraoperatively or postoperatively. We report on a patient who produced green discoloration of urine intraoperatively after methylene blue administration, which was benign and resolved spontaneously.


Assuntos
Anestesiologia , Neoplasias da Mama/cirurgia , Complicações Intraoperatórias/diagnóstico , Azul de Metileno/efeitos adversos , Urina , Adulto , Cor , Feminino , Humanos , Complicações Intraoperatórias/enfermagem , Mastectomia , Enfermeiras Anestesistas , Biópsia de Linfonodo Sentinela
10.
Eur J Obstet Gynecol Reprod Biol ; 238: 58-62, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31112852

RESUMO

Methylene blue is commonly used as a tracer in sentinel lymph node mapping for many malignant diseases or chromopertubation during gynecologic laparoscopy. In contrast with other blue dyes such as patent blue V or isosulfan blue, methylene blue rarely causes an allergy-like reaction in patients undergoing sentinel lymph node mapping. However, in chromopertubation, some cases of allergy-like reaction to methylene blue have been reported; these comprise two types: an allergic reaction and methemoglobinemia. In this study, a systematic literature review of allergy-like reactions caused by methylene blue dye following laparoscopic chromopertubation was conducted. A search was conducted in PUBMED, Web of Science, and Scopus from inception until June 2018, using the terms: "methylene blue", "complication", "allergic", "hypersensitive", "lung/pulmonary edema"," methemoglobinemia", "anaphylactic shock", "chromopertubation", "pertubation", "laparoscopic", and "laparoscopy". Ultimately, the eligibility criteria were fulfilled by only 12 case reports. Among 13 cases including our case of severe anaphylactic shock after chromopertubation, allergic reactions were diagnosed in four cases, methemoglobinemia in six, and there was no confirmed diagnosis in three cases; the clinical course consisted of skin changes, blue discoloration of body fluids, respiratory failure, and hemodynamic failure, regardless of the underlying diagnoses. Regarding diagnosis, methemoglobinemia was confirmed with co-oximetry (spectrophotometry). First-line therapy included supportive care for both cases of allergic reactions and methemoglobinemia.


Assuntos
Anafilaxia/induzido quimicamente , Inibidores Enzimáticos/efeitos adversos , Azul de Metileno/efeitos adversos , Adulto , Feminino , Humanos , Laparoscopia
11.
J Allergy Clin Immunol Pract ; 7(7): 2194-2204.e7, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30857939

RESUMO

BACKGROUND: Despite numerous efforts to describe the clinical manifestations and the epidemiology of perioperative hypersensitivity (POH), there remains room to increase awareness among anesthetists and immunologists/allergists. OBJECTIVE: To report the findings of a 17-year survey of suspected POH in Antwerp, Belgium. METHODS: We analyzed clinical and diagnostic data from 715 patients referred because of a suspected POH reaction, between January 1, 2001, and May 31, 2018. A total of 456 patients demonstrating a POH could be queried about subsequent anesthesia. RESULTS: A total of 608 cases formed the final dataset; 208 had a non-life-threatening reaction and 400 a life-threatening reaction. In life-threatening reactions, hypotension was predominating. In the non-life-threatening reactions, 83.9% of the patients displayed cutaneous manifestations. In life-threatening reactions, intravenous adrenaline and fluids were administered in 75.7% and 31%, respectively, and 41.3% had their intervention abandoned. Mast cell activation (MCA) was mainly, but not exclusively, observed in severe grades but did not predict the mechanistic process nor the culprit. A cause was identified in 77.8% of severe and 48.6% of milder cases. Main culprits were neuromuscular blocking agents, latex, cefazolin, and dyes. A total of 156 cases had uneventful anesthesia, except 1 patient who was inadvertently re-exposed to hidden chlorhexidine. CONCLUSIONS: This study highlights that there is room for an improved acute management and an optimized diagnostic workup that should not be restricted to patients with severe reactions and/or showing MCA.


Assuntos
Anafilaxia/terapia , Hipersensibilidade a Drogas/terapia , Hipersensibilidade ao Látex/terapia , Período Perioperatório , Adulto , Anafilaxia/induzido quimicamente , Anafilaxia/diagnóstico , Anafilaxia/fisiopatologia , Angioedema/fisiopatologia , Angioedema/terapia , Antibacterianos/efeitos adversos , Anti-Infecciosos Locais/efeitos adversos , Teste de Degranulação Basófila , Bélgica , Espasmo Brônquico/fisiopatologia , Espasmo Brônquico/terapia , Reanimação Cardiopulmonar , Cefazolina/efeitos adversos , Criança , Clorexidina/efeitos adversos , Corantes/efeitos adversos , Erupção por Droga/etiologia , Erupção por Droga/fisiopatologia , Erupção por Droga/terapia , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/etiologia , Hipersensibilidade a Drogas/fisiopatologia , Epinefrina , Hidratação , Gelatina/efeitos adversos , Humanos , Hipotensão/fisiopatologia , Hipotensão/terapia , Imunoglobulina E/metabolismo , Testes Intradérmicos , Hipersensibilidade ao Látex/diagnóstico , Hipersensibilidade ao Látex/etiologia , Hipersensibilidade ao Látex/metabolismo , Mastócitos , Azul de Metileno/efeitos adversos , Bloqueadores Neuromusculares/efeitos adversos , Corantes de Rosanilina/efeitos adversos , Índice de Gravidade de Doença , Testes Cutâneos , Simpatomiméticos/uso terapêutico , Triptases/metabolismo
13.
Wien Med Wochenschr ; 169(1-2): 41-43, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30349973

RESUMO

Methemoglobinemia is characterized by an increased level of methemoglobin (MetHb) in the peripheral blood. MetHb levels increase after tumescent anesthesia and need to be monitored. If a patient becomes symptomatic and/or the MetHb levels increase >10%, intravenous injection of an antidote is recommended. Toluidine blue is twice as effective as methylene blue in this respect.A 27-year-old woman with advanced lipedema underwent her third liposuction under tumescent anesthesia. After surgery, her MetHb levels increased and needed injection of toluidine blue. She developed an acute and painful edema after extravasation of some toluidine blue due to a bursting vein. This is the first report in the recent medical literature. Clinical presentation, course, and treatment are described.


Assuntos
Edema/induzido quimicamente , Lipectomia , Metemoglobinemia , Azul de Metileno/efeitos adversos , Adulto , Feminino , Humanos , Cloreto de Tolônio
14.
A A Pract ; 12(9): 321-324, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30431442

RESUMO

We report the perioperative course of a 75-year-old woman undergoing robotic-assisted laparoscopic hysterectomy and tumor debulking. The patient developed severe, persistent hypertension after intraoperative methylene blue administration requiring a Surgical Intensive Care Unit admission with further investigative evaluation revealing a previously undiagnosed pheochromocytoma. Our discussion focuses on the differential diagnoses for her perioperative hypertension. We evaluate whether methylene blue triggered a pheochromocytoma crisis in our patient and emphasize the caution and critical thinking we all should demonstrate while providing anesthetic care.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Hipertensão/etiologia , Azul de Metileno/efeitos adversos , Feocromocitoma/diagnóstico , Adenocarcinoma/cirurgia , Neoplasias das Glândulas Suprarrenais/cirurgia , Idoso , Procedimentos Cirúrgicos de Citorredução , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Histerectomia/efeitos adversos , Achados Incidentais , Laparoscopia/efeitos adversos , Feocromocitoma/cirurgia , Procedimentos Cirúrgicos Robóticos/efeitos adversos
16.
Psychosomatics ; 59(6): 539-546, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30104021

RESUMO

BACKGROUND: Serotonin syndrome (SS) is a potentially serious side effect of serotonergic drugs. Cases of SS have been reported from the administration of methylene blue (MB), an agent with monoamine oxidase inhibiting properties. To date, the reported cases of MB-induced SS have all been with MB given parenterally. We report a case induced by the initiation of a MB-containing oral agent. METHODS: A case of SS felt to be induced by the initiation of an MB-containing orally-administered urinary analgesic, started in a patient concurrently treated with multiple serotonergic drugs, is presented. A systematic literature review of MB-induced SS follows. The review consisted of searches in MEDLINE databases using the key terms "methylene blue" and "serotonin syndrome". The authors read all abstracts, and articles related to MB and serotonin toxicity; non-associated articles were discarded. Results are summarized. RESULTS: 23 manuscripts were identified, resulting in 50 unique cases of MB-induced SS. The majority of cases were related to peri-operative use of MB in parathyroidectomies or for the treatment of vasoplegic shock. All cases were associated with MB given parenterally. Concurrent treatment with serotonergic antidepressants was described in all 50 cases. Symptoms of SS ranged from mild to severe. One fatality was reported. CONCLUSIONS: Methylene blue can induce SS, felt to be secondary to MAOI properties. Although previous reports have exclusively been associated with MB given via parental administration, our case suggests that SS can be induced by oral administration of MB-containing agents.


Assuntos
Analgésicos/administração & dosagem , Inibidores Enzimáticos/efeitos adversos , Azul de Metileno/efeitos adversos , Síndrome da Serotonina/induzido quimicamente , Neoplasias da Bexiga Urinária/cirurgia , Idoso , Humanos , Masculino
17.
Endoscopy ; 50(10): 1027-1032, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29906809

RESUMO

BACKGROUND: An oral formulation of methylene blue with colonic delivery (MB-MMX) has been developed to increase detection of colorectal polys during colonoscopy. Traditionally, there have been safety concerns regarding DNA damage when methylene blue is exposed to white light. The aim of this study was to evaluate DNA damage in colonic mucosa after MB-MMX chromoendoscopy. METHODS: This was an open-label phase II safety study to assess for genotoxicity on colorectal biopsies of patients undergoing two sequential colonoscopies before and after an oral dose of 200 mg MB-MMX added to their bowel prep. Analysis of a biomarker of double-stranded DNA breaks, γH2AX, was performed on biopsy specimens. RESULTS: Ten patients were included in the study. The mean expression of γH2AX ± 95 % confidence intervals of the 50 biopsies before and after MB-MMX administration were 0.58 ± 0.08 and 0.62 ± 0.09, respectively (P = 0.24). None of the analyzed samples showed excess positive γH2AX expression, confirming the absence of DNA damage on biopsies after methylene blue exposure. No deaths or serious adverse events occurred. CONCLUSIONS: An oral dose of 200 mg of MB-MMX did not result in any detectable DNA damage.


Assuntos
Corantes/efeitos adversos , Dano ao DNA , Histonas/genética , Mucosa Intestinal , Azul de Metileno/efeitos adversos , Administração Oral , Biópsia , Colo/patologia , Colonoscopia , Corantes/administração & dosagem , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Mucosa Intestinal/patologia , Masculino , Azul de Metileno/administração & dosagem , Pessoa de Meia-Idade
18.
Contemp Clin Trials ; 71: 96-102, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29864547

RESUMO

Methylene blue-MMX® tablets are proposed as an aid for detection and visualisation of adenomas and carcinomas in patients undergoing colonoscopy, by improving their detection rate and highlighting the presence of the intestinal dysplastic lesions. Single total doses of 100 and 200 mg were administered to healthy volunteers undergoing a bowel cleansing preparation and a full colonoscopy to investigate the colonic staining. The pharmacokinetics of methylene blue and the safety after exposure to the tablets were also investigated. With 200 mg, the best staining, assessed as the sum of acceptable and good staining, was achieved in the ascending colon and rectosigmoid (75% subjects each), the transverse and the descending colon (approximately 63% each). Absence of staining or overstaining were reported for no colonic region of interest in any subject. Similar results were observed in the 100 mg dose group. Methylene blue blood concentrations reached a peak (Cmax) in a median time (Tmax) of 12 h with 100 mg and 16 h with 200 mg. AUC0-t was 10.7 ±â€¯6.7 µg/mLxh after 100 mg and 25.2 ±â€¯7.4 µg/mLxh after 200 mg. Half-life ranged between 9 and 22 h after the lower dose and between 6 and 26 h after the higher dose. The cumulative urinary excretion was about 28% after 100 mg and about 39% after 200 mg up to 60 h post-dose. The overall frequency of adverse events after single dose of the test product administered along with a bowel cleansing preparation was 39%, but only one was related to the test product: abnormal transaminases. The most frequent adverse event was a transient polyuria (17%). One serious adverse event (gastrointestinal haemorrhage) led the subject to study discontinuation and hospitalisation and another subject withdrew the study due to one adverse event (haematemesis). Either event was not related to methylene blue.


Assuntos
Colo , Colonoscopia/métodos , Azul de Metileno , Coloração e Rotulagem , Administração Oral , Adulto , Disponibilidade Biológica , Catárticos/uso terapêutico , Colo/diagnóstico por imagem , Colo/patologia , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/patologia , Corantes/administração & dosagem , Corantes/efeitos adversos , Corantes/farmacocinética , Relação Dose-Resposta a Droga , Voluntários Saudáveis , Humanos , Aumento da Imagem/métodos , Aumento da Imagem/normas , Masculino , Azul de Metileno/administração & dosagem , Azul de Metileno/efeitos adversos , Azul de Metileno/farmacocinética , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Melhoria de Qualidade , Eliminação Renal , Coloração e Rotulagem/métodos , Coloração e Rotulagem/normas
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