Anticholinergic Toxidrome as a Possible Explanation for Methylene Blue Toxicity

BACKGROUND Methylene blue has multiple uses in medicine. It is generally used to treat refractory vasoplegia and methemoglobin toxicity, and can be used as a dye to localize the parathyroid glands intra-operatively. In refractory vasoplegia, methylene blue inhibits endothelial nitric oxide and guanylate cyclase, causing vasoconstriction and potentially stabilizing blood pressure. Multiple complications have been associated with the use of methylene blue. These are related to either the sole effect of methylene blue or the combined effect of methylene blue and certain antidepressants, such as selective serotonin reuptake inhibitors (SSRIs). To the best of our knowledge, in the setting of post-cardiac surgery vasoplegia, there have been no reports of the neurological toxicity of methylene blue in the absence of SSRI use. In this case report, we describe the anticholinergic manifestations associated with the use of methylene blue in post-cardiac surgery vasoplegia. CASE REPORT A male patient in his mid-sixties with severe mitral regurgitation underwent elective mitral valve replacement. Postoperatively, he was hypotensive and required a high dose of vasopressors. Methylene blue was administered to treat refractory vasoplegia. The patient became anuric and febrile, with bilateral mydriasis. Internal cooling and continuous renal replacement therapy were initiated, and symptoms rapidly resolved. The patient was discharged after prolonged hospitalization with a permanent catheter for hemodialysis. CONCLUSIONS Anticholinergic toxidrome may explain the neurological adverse effects associated with high doses of methylene blue. Physicians should be cautious when using methylene blue in combination with other anticholinergic drugs and in conditions of renal failure. The development of methylene blue toxicity warrants the urgent discontinuation of the agent and early drug elimination.