Serotonin SyndromeGabriel Tsao, MS3

Ben Berk, MS4

Gabriel Tsao, MS3

Stanford University

School of Medicine

Left Brain vs Right Brain

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

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

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

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

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.

Serotonin In the CNS

Modulates attention, behavior and thermoregulation

In the Periphery Vascular tone and

gastric motility

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

Features of Serotonin Syndrome

Classic clinical triad: Mental status

changes Autonomic

hyperactivity Neuromuscular

abnormalities Wide ranging

symptoms

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

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

Associated Drugs MR meds

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

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

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