Use of methylene blue in hepatic arterial infusion pump resulting in serotonin syndrome.

Introduction

Methylene blue is a phenothiazine derivative commonly used in medicine for staining and therapeutic purposes. It is a potent monoamine oxidase (MAO) inhibitor but is considered a relatively safe drug with few adverse effects and is often used during surgical procedures to assist with identification of structures such as nerves, tissues, and endocrine glands. Methylene blue also has therapeutic indication in the treatment of methemoglobinemia, vasoplegic shock, Alzheimer’s disease, and paediatric Malaria. Dosing regimen varies depending on indication for use and route of administration.

The most common side effect of methylene blue is an abnormal urine or stool color. Less common side effects include but are not limited to mild bladder irritation, frequent urination, dizziness, nausea and vomiting, abdominal pain, diarrhea, headaches, and increased sweating (rxlist.com). An uncommon, albeit potentially catastrophic, side effect of methylene blue administration is serotonin syndrome. Administration of methylene blue on its own however, has not been known to cause serotonin toxicity.

Case Report

A 35 year old female with past medical history significant for anxiety, hypertension, and colorectal carcinoma presented for exploratory laparotomy and placement hepatic arterial infusion pump for treatment of disease recurrence with metastases to liver and lung. Because of aberrant hepatic vasculature requiring extended dissection time and intraoperative vascular surgery consultation, the total operating time was a protracted 8 h. Methylene blue was injected by the surgeon directly into the liver to delineate hepatic vasculature and help in confirming hepatic pump placement. A total of 85 mL of 0.5% methylene blue was administered by the surgeon. Methylene blue vials were ordered and dispensed from pharmacy with dose recommendation of up to 7 mg/Kg or 560 mg (112 mL of 0.5% methylene blue) . The surgeon documented that patient was receiving SSRI preoperatively, but it is unclear if surgeon was aware of the dangers of concomitant administration of methylene blue and SSRI. In addition, fentanyl was administered intraoperatively, and serotonin toxicity has also been described with concurrent use of MAO-inhibitors and phenylpiperidine series opioids. Because the patient had also been on SSRIs and received an extremely high dose of methylene blue during surgery, she was monitored closely in the PACU postoperatively for symptoms of serotonin syndrome. While her recovery was initially uneventful, on postop day 1, she became increasingly lethargic with tachypnea, tachycardia, hyperreflexia, and myoclonus was elicited. Due to the severity and progression of symptoms, care was escalated and the patient was evaluated by the critical care service and psychiatry. Cyproheptadine was started and all serotonergic agents were discontinued. While a rare occurrence, cyproheptadine causing hepatitis and acute liver failure has been reported .Hence, liver function tests were monitored during her treatment with cyproheptadine. The patient’s symptoms improved over the next couple of days and she was restarted on SSRI and discharged home uneventfully on postoperative day 7.

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Anesthesiology Case Reports