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Serotonin syndrome, characterized by a triad of mental status changes, autonomic hyperactivity, and neuromuscular abnormalities, portends poor prognosis. We report a case of serotonin syndrome induced by the concomitant administration of linezolid and venlafaxine in a lung transplant patient on tacrolimus that was successfully treated with renal replacement therapy.
The patient was a 35 year old female with a history of depression on venlafaxine and cystic fibrosis who was admitted to the intensive care unit with acute respiratory distress syndrome following recent lung transplant. Anti-rejection medications included tacrolimus, mycophenolate mofetil and prednisone. Her course was complicated by multi-organism pneumonia and sepsis requiring broad spectrum antibiotics including linezolid which was started 20 days prior to this presentation. On hospital day 35, she had rapid decompensation characterized by severe hypertension, diaphoresis, muscle rigidity, severe lactic acidosis, oliguric acute kidney injury, and hyperkalemia. Pertinent laboratories showed creatinine 2.1 mg/dL, blood urea nitrogen 76.1 mg/dL, potassium 6.1 mEq/L, bicarbonate 15 mEq/L, and creatinine kinase 323 U/L. White blood cell 20.8x10^3 cells/uL and hemoglobin 7.4 g/dL. Continuous renal replacement therapy (CRRT) was initiated initially due to severe lactic acidosis and hyperkalemia. Despite CRRT, lactic acid continued to rise to the level >20 mmol/L. We suspected serotonin syndrome was the culprit of progressive lactic acidosis rather than severe sepsis, so the decision was made to switch to hemodialysis in hope to rapidly clear the potential culprit agent, linezolid. Her lactic acidosis improved and normalized at 15 hours post hemodialysis. Her neurological symptoms also gradually improved and muscle rigidity improved within 1 day.
To our knowledge, this case is the first to describe serotonin syndrome in the setting of tacrolimus, linezolid, and venlafaxine that was successfully treated with dialysis. The patient was on venlafaxine pre-transplant and was started on tacrolimus for anti-rejection. Subsequently, linezolid was added for infection while she developed acute kidney injury. This setting significantly increased risk of serotonin syndrome due to reduced renal clearance leading to drug accumulation. While tacrolimus and venlafaxine are poorly dialyzable agents, linezolid is removed by dialysis due to its size (molecular weight of 337 Dalton). The rapid improvement in her clinical course is likely attributed to linezolid removal.
This case raises an awareness of serotonin syndrome in patients with severe lactic acidosis. Patients often develop hypertension and muscle rigidity rather than hypotension in typical sepsis patients. Physicians need to be cautious when prescribing multiple pro-serotonergic drugs especially in the setting of renal impairment. Hemodialysis for rapid drug clearance may avert the course and improve survival in serotonin syndrome.