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  • 0.4 case per 1000 patient-months for patients who were taking nefazodone
  • Mild cases, afebrile by tachycardia
  • Clonus and hyperreflexia most important
  • Compared to gold standard of medical toxicologist
  • Reflexes,
  • SerSyndrome

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