Methylene blue toxicity following infusion to localize parathyroid adenoma

Abstract

The parathyroid glands are small, inconspicuous, and variable in number, colour and position. Their identification is vital for excision of hyper-functioning glands and for preservation of normally functioning ones in patients undergoing thyroidectomy. Intravenous infusion of methylene blue at a dose of 7.5 mg/kg is commonly used to aid visualization of the parathyroid glands intra-operatively. Methylene blue is generally considered benign, and there are only two cases published in the literature reporting toxicity following intravenous infusion--such toxicity is a diagnosis of exclusion. We report a case of methylene blue toxicity resulting in expressive aphasia, confusion and disinhibition following infusion for parathyroid adenoma localization. The patient made a complete recovery over 48 hours. Methaemoglobinaemia was excluded as a cause. We suggest that the mechanism of toxicity was a direct effect of methylene blue, although an adverse interaction with serotonin re-uptake inhibitors could not be excluded. In keeping with the UK National Poisons Information Service recommendations, we have altered our practice and now use methylene blue at a dose not exceeding 4 mg/kg. This has not affected our success rate for identification of parathyroid glands. We report this case to highlight the rare occurrence of methylene blue toxicity when used at a dose of 7.5 mg/kg.

Serotonin syndrome following methylene blue infusion during parathyroidectomy: A case report and literature review

“…All of the patients experienced symptoms consistent with serotonin syndrome (or serotonin toxicity), including agitation, confusion, hypertonicity and clonus. [1][2][3][4][5][6][7] The most significant common feature of these cases is that five patients were concurrently taking a selective serotonin reuptake inhibitor (SSRI), or a serotonin norepinephrine reuptake inhibitor. One patient was receiving clomipramine, a tricyclic antidepressant with high serotonergic activity.…”

“…One patient was receiving clomipramine, a tricyclic antidepressant with high serotonergic activity. 8 Despite this, four of the previous published cases did not consider the possibility of serotonin syndrome, two simply mentioned the possibility of an unspecified 'drug interaction' between methylene blue and SSRIs, 3,6 and only one report specifically mentioned serotonin syndrome but dismissed it as 'unlikely'. 7 We present an additional, similar case, and consider the evidence for a diagnosis of serotonin syndrome.…”

Effects of methylene blue on propofol requirement during anaesthesia induction and surgery

“…cases of transient neurological complications in relation to MB infusion have recently been reported in the medical literature [10][11][12][13][14][15][16][17][18]. Of note, no sensorimotor deficits have been reported and brain computed tomography (CT) scans were all unremarkable.…”

“…Although considered to be safe, numerous adverse effects including nausea and vomiting, chest pain, hypertension or hypotension, dyspnoea, haemolysis and neuropsychological disturbances have been described after intravenous administration of MB in the dose range of 1-10 mg.kg )1 [1,7]. Following parathyroidectomy, 22cases of transient neurological complications in relation to MB infusion have recently been reported in the medical literature [10][11][12][13][14][15][16][17][18]. Of note, no sensorimotor deficits have been reported and brain computed tomography (CT) scans were all unremarkable.…”

Assessment of Utility of Staining in the Intraoperative Localization of Parathyroid Glands

“…Methylene blue (MB), a thiazide staining agent, was initially used in the treatment of intoxications with methemoglobin-generating agents, because of its ability to cumulate in endocrine gland tissues, was used for the first time by Dudle in 1971 to stain parathyroid glands. Since this time there were reports positively assessing this method in patients with both primary and secondary hyperparathyroidism (12,13). Selective venous catheterization (SVC) is an invasive procedure used to determine PTH level in the venous blood taken from mediastinal veins (inferior thyroid veins).…”