Methylthioninium chlorid

C8H12N2 99-98-9) see Methylthioninium chloride 4-ainino-l,3-dimethylbenzene (CgH N 95-6S-7) see Picotamide (5K,6S)-6-aniino-2,2-dimethyl-l,3-dioxepan-5-ol acetate (salt)... 

Two patients who were taking lithium carbonate for mood disorders and who underwent coronary artery bypass grafting developed refractory hypotension during cardiac surgery, which responded to methylthioninium chloride (116). The authors suspected that chronic lithium therapy had caused cardiac embarrassment and recommended that lithium be withdrawn before cardiac surgery. 

DL-methionine. methylthioninium chloride (methylene blue) naloxone penicillamine potassium ferric hexacyanoferrate(II). 2Hj O (Prussian blue)... 

Several other cases of methemoglobinemia after the administration of topical benzocaine formulations have been reported (14—19). All recovered completely without sequelae after the intravenous administration of methylthioninium chloride 1-2 mg/kg. 

An elderly man received benzocaine 20% spray to the throat in preparation for transesophageal echocardiography. He became unwell 1 hour later, with lethargy, central cyanosis, hypoxia, dyspnea, tachypnea, and tachycardia (23). His arterial blood was burgundy-colored and the methemoglobin concentration was 41%. He was treated with two doses of methylthioninium chloride 2mg/kg and was weaned from oxygen within 10 hours. 

A 57-year-old man developed severe methemoglobme-mia after receiving topical benzocaine spray and lidocaine jelly during awake fiberoptic intubation (25). After intubation, his oxygen saturation fell to 65% on 100% oxygen. He was cyanosed and had dark arterial blood sample with normal gas tensions. His methemoglobin concentration was 60% and treatment with methylthioninium chloride was successful. 

Flutamide can cause methemoglobinemia (6-8) or sulfhemoglobinemia (5). The latter occurred in a 70-year-old man who had taken flutamide 150 mg tds for 1 month and developed cyanosis and anemia that was not responsive to methylthioninium chloride (methylene blue). 

Gentamicin is synergistic with methylthioninium chloride (methylene blue) in vitro against P. aeruginosa (70). 

In 12 of 52 patients treated with ifosfamide there was neurocortical toxicity greater than grade 2 (6). They were successfully treated with intravenous methylthioninium chloride (methylene blue) 50 mg 3-hourly, which was also prophylactic in three patients. 

There have again been several reports of methemoglobinemia following topical anesthesia (26,27). Most have been associated with topical benzocaine, and the patients recovered fully after the administration of methylthioninium chloride. 

A 27-year-old woman with diabetes mellitus, complicated by diabetic retinopathy and chronic renal insufficiency with anemia, developed methemoglobinemia (11%) after peribulbar blockade with prilocaine 80 mg, bupivacaine 30 mg, hyaluronidase, and napha-zoline (325). She recovered uneventfully after methylthioninium chloride 1.5 mg/kg. 

Severe hemolytic reactions have been attributed to methylthioninium chloride (4). 

Methylthioninium chloride marking of a colonic polyp resulted in an inflammatory mass with small arteries showing both segmental and circumferential fibrinoid necrosis with thrombosis (5). 

Significant neonatal morbidity can occur after transabdominal infusion of methylthioninium chloride to diagnose premature rupture of fetal membranes, to stain the amniotic fluid in twin pregnancies, or after postpartum administration of methylthioninium chloride. Toxic manifestations include hyperbilirubinemia, Heinz body hemolytic anemia, and possible desquamation of the skin. In most cases it appears that toxicity was the result of an overdose of methylthioninium chloride (6-9). 

Multiple ileal occlusions have been reported in babies born to mothers who had twin pregnancies and who had received methylthioninium chloride administered during amniocentesis (10-12). In a number of cases it was found that methylthioninium chloride had been injected into the amniotic sac of the affected twins. 

Methylthioninium chloride phototoxicity may also be related to the high prenatal dose of the dye relative to patient s small size and young gestational age (13). 

Methylthioninium chloride is sometimes given intra-thecally to track the source of a cerebrospinal fluid leak. This procedure involves considerable risk of spinal cord damage, with its attendant neurological consequences (15-17). 

A 59-year-old man had 6 ml of unbuffered methylthioninium chloride injected into the lumbar theca in an attempt to localize the source of cerebrospinal fluid rhinorrhea (18). After injection of the dye he became shocked, and within the next few days developed a mild paraparesis, which subsequently progressed to total paraplegia. 

Overdosage of methylthioninium chloride given intravenously, which has happened inadvertently during urinary tract surgery, can cause shock and pseudocyanosis. The latter is due to the blue tinge of methylthioninium... 

Methylthioninium chloride is somewhat irritating, and topical anesthesia is recommended before its use prolonged systemic exposure can cause the fundus to turn visibly blue (8). 

In a 6-year-old boy, 10 ml of a 2% solution given for bilateral percutaneous nephrostomy produced a degree of cyanosis that demanded methylthioninium chloride treatment (13). 

A 7-month-old girl was ventilated with inhaled nitric oxide 40 ppm and developed methemoglobinemia after the application of Emla to an 8 cm area of skin for 5 hours (17). Shortly after removal she developed cyanosis, with a methemoglobin concentration of 16%, which resolved with two doses of methylthioninium chloride. 

The precise mechanisms that explain protamine-mediated systemic hypotension are unknown, but there is evidence that it may be mediated by the endothelium and dependent on nitric oxide/cyclic guanosine monophosphate it has been suggested that methylthioninium chloride (methylene blue) may be of use in treating hemodynamic complications caused by the use of protamine after cardiopulmonary bypass (4). 

Cetacaine spray used to anesthetize the oropharynx before endoscopy led to dyspnea, central cyanosis, and an oxygen saturation of 80% methemoglobinemia was diagnosed, and the patient recovered rapidly with methylthioninium chloride 1 mg/kg over 5 minutes. 

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