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Serotonin SyndromeGabriel Tsao, MS3
Ben Berk, MS4
Gabriel Tsao, MS3
Stanford University
School of Medicine
Left Brain vs Right Brain
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Case ID/CC: 45 yo w/ h/o bipolar disorder s/p sigmoid
colectomy for adeno CA. Prior outpatient meds: Lexapro 10, Seroquel 800 qhs,
Keppra 500/1000, Xanax >4mg qd, Ambien 10 qhs Hospital course: acutely psychotic post-op Max Inpatient Meds: Lexapro 10, Seroquel 800 qhs,
Keppra 500 q8, Valproic Acid 750/1000, Versed gtt 6, clonidine patch, Ativan 3/3/3/5, Fentanyl gtt 200, Haldol 4/4/4/10, donepazil 10, zofran 8, and olanzapine 5mg q8h PRN
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Physical exam Hyperthermia ~40º, tremor, agitation,
diarrhea, diaphoretic, HTN Psych recommended discontinuing all
psychiatric medications, only on valium and fentanyl.
Within 48 hrs, pt dramatically recovered
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Serotonin Syndrome Libby Zion (1984)
An 18 yo college student who presented to the hospital with a fever of 103.5, agitation, confusion, “jerking motions.”
Had been taking an antidepressent, phenelzine. Given meperidine in the hospital Increasingly agitated, restrained Six hours later, temp 107, cardiac arrest
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Public Outrage Ms. Zion was seen only be an intern and R2
The R2 had 40+ other patients to cover 36 hour shift
Father was a writer for NY Times Story featured in NY Times, Newsweek, Washington Post,
60 Minutes 1986 DA convened Grand Jury 1989 NY State adopted 80 hr resident work week
restriction w/ supervision guidelines 2003 ACGME adopts similar standards
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Incidence of Serotonin Syndrome Observed in all age groups Increasing incidence thought to be associated with
increased use of serotonergic agents 2004: Toxic Exposure Surveillance System
48,204 exposures to SSRIs that resulted in moderate or major outcomes in 8187 pts and 103 deaths.
Occurs in 14-16% of persons who overdose SSRIs Incidence difficult to assess
85% of physicians in 1999 were unaware of serotonin syndrome as a clinical diagnosis
Mackay FJ, et al. Antidepressants and the serotonin syndrome in general practice. Br J Gen Pract 1999; 49:871-9.
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Serotonin In the CNS
Modulates attention, behavior and thermoregulation
In the Periphery Vascular tone and
gastric motility
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Serotonin Syndrome Stimulation of postsynaptic 5HT1A and
5HT1B receptors implicated No one receptor solely responsible
Any combination of drugs that has net effect increased serotonin neurotransmission Classically two simultaneously, but can be with
initiation of a single drug or increasing dose in a sensitive individual
Seen in intentional overdoses
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Features of Serotonin Syndrome
Classic clinical triad: Mental status
changes Autonomic
hyperactivity Neuromuscular
abnormalities Wide ranging
symptoms
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Diagnosis Hunter Criteria: (84% sensitive, 97% specific)
Must have taken a serotonergic agent Plus one of following
Spontaneous clonus Inducible clonus plus agitation or diaphoresis Ocular clonus plus agitation or diaphoresis Tremor and hyper-reflexia Hypertonia Temperature above 38 plus ocular or inducible clonus
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Serotonin Syndrome vs NMS Development
SS develops over 24 hrs, often 6 hrs NMS develops over days to weeks
Neuromuscular responses SS characterized by hyperreactivity
Tremor, hyperreflexia, myoclonus NMS involves sluggish responses
Rigidity, bradyreflexia
Resolution SS usually resolves within 24 hrs NMS requires an average of 9 days
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Associated Drugs MR meds
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Management Removal of precipitating drugs
Most cases typically resolve within 24 hrs of removal Administration of 5HT antagonists
Cyproheptadine: 12 mg initial dose, 2 mg q1h Control of agitation
Benzodiazepines regardless of symptom severity Physical restraints alone ill-advised (lactic acidosis, temp)
Control of hyperthermia (>41.1) Sedation, neuromuscular paralysis, orotracheal intubation
Control of autonomic instability
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Pitfalls Misdiagnosis of serotonin syndrome
Failure to comprehend rapidity of progression Failure to comprehend adverse pharm effects Muscle rigidity can mask clonus and hyperreflexia
If serotonin syndrome not obvious: Withhold 5HT antagonist therapy Provide all other therapy Anticipate need for aggressive therapy
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Thanks Dr. Purtill Dr. Spain Dr. Patterson Team
Dr. Garland, Amy, Sarah, Geoff and Geoff, Ron, Rich, Rebecca, Ngoc, Ben
Our twins in the ICU