Serotonin Syndrome

Question 1

What is serotonin syndrome?

Answer 1

Serotonin syndrome is a potentially life-threatening drug reaction that is associated with increased levels of serotonin.

Question 2

What are the clinical features of serotonin syndrome?

Answer 2

1. Triad of neuroexcitatory features:
   neuromuscular - tremor, clonus, myoclonus, hyper-reflexia, pyramidal rigidity
   autonomic - diaphoresis, fever, tachycardia, tachypnea, diarrhea/hyperactive bowel sounds, shock
   altered mental status - agitation, excitement, confusion

Question 3

What drugs or combinations of drugs increase serum serotonin levels?

Answer 3

SSRIs (sertraline, paroxetine)
MAOIs (phenelzine)
Other antidepressants (trazodone, buspirone)
Antiemetics (ondansetron, metoclopramide)
MDMA
Amphetamines
Cocaine
Phenylpiperidine opioids: meperidine, fentanyl, sufentanil, alfentanil, remifentanil, dextromethorphan

Question 4

Name the phenylpiperidine opioids.

Answer 4

Meperidine
Fentanyl
Sufentanil
Alfentanil
Remifentanil
Dextromethorphan

Question 5

What is the differential diagnosis for suspected serotonin syndrome?

Answer 5

1. Malignant hyperthermia
   - increased EtCO2
   - temporal relationship to inhalational agents or succinylcholine
   - rigor-mortis like rigidity
   - hyporeflexia
2. Neuroleptic malignant syndrome
   - idiopathic reaction to dopamine antagonists evolving over several days
   - lead-pipe rigidity
   - bradykinesia
3. Anticholinergic syndrome
   - normal reflexes
   - mydriasis, delirium, dry mouth, hot skin, urinary retention, absent bowel sounds

Question 6

What is the management of serotonin syndrome?

Answer 6

1. Stop the offending drug
2. Supportive care (IV fluids, direct acting vasopressors, short-acting beta-blockers, dilating agents
3. Benzodiazepines to treat agitation and blunt hyperadrenergic component.
4. Give 5-HT 2A antagonists: cyproheptadine 12mg PO/NG, then 2mg q2hr if symptoms continue. Daily dose 24 to 32 mg.
5. Control hyperthermia
   - surface cooling
   - if severely ill with temperature 41.1 C, patient should be paralyzed, sedated, and intubated (do not use succinylcholine)
   - no role for antipyretics as hyperthermia is due to muscle activity and not alteration in hypothalamic set point

Question 7

What is the role of physical restraints in serotonin syndrome?

Answer 7

The altered mental status may appear to warrant restraints but their use may increase mortality by increasing isometric contraction resulting in lactic acidosis and hyperthermia.

Question 8

What medications can be used to treat serotonin syndrome?

Answer 8

5-HT 2A antagonists, specifically cyproheptadine 12mg PO/NG, then 2mg q2hr if symptoms continue. Daily dose 24 to 32 mg.

Question 9

What is the dosing of cyproheptadine for serotonin syndrome?

Answer 9

12mg PO/NG, then 2mg q2hr if symptoms continue. Daily dose 24 to 32 mg.

Question 10

What antipyretics are effective in serotonin syndrome?

Answer 10

None. Hyperthermia is due to muscle activity, not alteration in hypothalamic set point.