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Abstract

Introduction: Case Presentation: A 69 year-old woman with a history of depression on paclitaxel and chondrosarcoma underwent left proximal femur resection and replacement in our hospital. Post-operatively, she was noted to have some "shivering" movements and was given fentanyl for pain as well as a dose of meperidine and was admitted to the ward for care. At 4am the following morning, the patient was found to be poorly responsive with a MAP (mean arterial pressure) around 40 mmHg. She then became hypertensive with SBPs in the 200s and MAPs > 100, for which she received 10mg of IV metoprolol and a nicardipine drip was initiated as the patient was transferred to the ICU, where her blood pressure again dropped to MAPs in the 40s and her heart rate slowed to the 50s; nicardipine was stopped, and epinephrine and levophed drips were initiated. Her temperature increased to 38.4°C. The patient had a waxing and waning mental status and bizarre, pressured speech. She also had bilateral myoclonic motions as well as clonus in her lower extremities. The patient was diagnosed with serotonin syndrome by fulfilling Hunter Toxicity Criteria. She received care with withdrawal of paclitaxel, benzodiazepines, and a dose of cyproheptadine with normalization of her blood pressure, mental status, and neurological exam within 24 hours. She has not been restarted on an SSRI (selective serotonin reuptake inhibitor). Discussion: This case provides an opportunity to review the pharmacology, differential diagnosis, clinical spectrum, and management of serotonin syndrome. Our patient met Hunter Toxicity Criteria for the serotonin syndrome by her use of an SSRI as well as one of the following: 1) Spontaneous clonus 2) Inducible clonus plus agitation or diaphoresis, 3) Ocular clonus plus agitation or diaphoresis, 4) tremor plus hyperreflexia, or 5) hypertonism plus temperature > 38 °C (100 °F) plus ocular clonus or inducible clonus. She met multiple criteria. In 2004, there were 48,204 SSRI exposures resulting in an adverse outcome, including over 100 deaths. Several experts argue that "serotonin toxicity" is a more appropriate term than serotonin syndrome, since the clinical spectrum is a predictable consequence of high levels of serotonin rather than an idiosyncratic reaction, such as neuroleptic malignant syndrome. The clinical presentation can run the spectrum from mild tremor to severe autonomic instability, fever and altered mental status. Many medications result in increases in serotonin by a variety of pathways or direct agonism of the serotonin receptor. Common classes that include multiple offending agents include: antidepressants, opiates, anti-emetics, atypical antipsychotics and illicit drugs such as MDMA (Ecstasy). Both fentanyl and meperidine have serotonergic properties, and this patient classically showed symptoms within 24 hours of the additional serotonergic agents. She received supportive care with removal of the agent, which is essential, as well as with short-acting vasoactive medications and benzodiazepines. Antipyretics such as acetaminophen are not advised for serotonin-syndrome related pyrexia. She also received a dose of cyproheptadine, a histamine-1 receptor antagonist with nonspecific 5-HT1A and 5-HT2A antagonism, which can be used in patients who are still having agitation or unstable vital signs despite supportive care. Conclusion: Serotonin syndrome has significant prevalence in the increasing population of patients on chronic SSRI therapy, and its presence is frequently under recognized by physicians as it has a varied clinical presentation. There are many medications that have serotonergic properties and can precipitate serotonin toxicity. It is essential for clinicians to maintain a high suspicion for this disorder to avoid the potentially severe and lethal complication of missing it. It may also be more appropriate to refer to this disease as serotonin toxicity, as it is a predictable consequence of excess serotonin.