Fatal Methaemoglobin Intoxication Following Ketamine Infusion in a Depressed MELAS Patient: A Possible Association?

Methemoglobinemia is defined as an increase in methemoglobin of > 2% of hemoglobin. Ketamine is increasingly used for severe depression. To our knowledge, a patient with mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) who died suddenly and unexpectedly 1-12 h after ketamine infusion with high postmortem methemoglobin has not yet been reported. The patient was a 32-year-old woman with MELAS, manifesting as migraine, deafness, diabetes, bloating, and a seizure, due to the mtDNA variant m.3243A>G who received a single infusion of ketamine for the treatment of depression and posttraumatic stress disorder. Presumably, 1-12 h later, the patient died in her apartment, initially with no apparent cause for her demise. The autopsy revealed a methemoglobin level of 71% (normal: 0-2%). Whether ketamine was responsible for the death remains speculative, but ketamine has a mitochondrial toxic effect by reducing ATP production and impairing methemoglobin reductase, which may have led to methemoglobinemia. In conclusion, ketamine should be administered with caution in MELAS patients, particularly those with a history of seizures, and if unavoidable, these patients should be carefully monitored during and after ketamine infusion.