Serotonin Syndrome

Question 1

The classical triad of serotonin syndrome consists of:

Answer 1

mental status changes, autonomic hyperactivity, neuromuscular abnormalities

Question 2

DDx of serotonin syndrome should include:

Answer 2

Neuroleptic malignant syndrome, Anticholinergic toxicity, Malignant hyperthermia, Sympathomimetic toxicity, Meningitis, Encephalitis

Question 3

A pt has been determined to have serotonin syndrome. What (3) immediate treatments do you want to initiate?

Answer 3

1) Discontinue serotonergic agents
2) Sedate using benzodiazepines (eg, lorazepam 1 to 2 mg IV per dose; 0.02 to 0.04 mg/kg/dose in children): goal is to eliminate agitation, neuromuscular abnormalities (eg, tremor, clonus), and elevations in heart rate and blood pressure; titrate dose to effect
3) Provide: oxygen (maintain SpO2 ≥94); IV fluids; continuous cardiac monitoring

Question 4

A pt with serotonin syndrome has a temp of 41.2 C (106.2 F!). What do you want to do?

Answer 4

Treat patients with temperature >41.1°C with immediate sedation, paralysis, and endotracheal intubation; treat hyperthermia with standard measures; avoid antipyretics such as acetaminophen

Question 5

Benzos have been given to your pt with SS, but the pt is still agitated, has tremors, and clonus. Now what?

Answer 5

If benzodiazepines and supportive care fail to improve agitation and abnormal vital signs, give cyproheptadine (12 mg orally or by orogastric tube for initial adult dose;

Question 6

SS can precipitate due to a variety of reasons, whether it be 2 serotonergic drugs, and increase of a serotonergic drug, or a combination of serotonergic agents and other medications. Which drug class do you want to be especially mindful of (caution!!) when mixing with serotonergic agents?

Answer 6

MAOIs. Episodes of serotonin syndrome involving a monoamine oxidase inhibitor may be more severe and more often lead to adverse outcomes, including death

Question 7

What are the most common mental status changes in a pt with SS?

Answer 7

Mental status changes can include anxiety, agitated delirium, restlessness, and disorientation [12]. Patients may startle easily.

Question 8

What are typical ‘autonomic hyperactivity’ symptoms in SS?

Answer 8

Autonomic manifestations can include diaphoresis, tachycardia, hyperthermia, hypertension, vomiting, and diarrhea

Question 9

Examples of typical findings consistent with ‘neuromuscular abnormalities’ in SS include:

Answer 9

Neuromuscular hyperactivity can manifest as tremor, muscle rigidity, myoclonus, hyperreflexia, and bilateral Babinski sign. Hyperreflexia and clonus are particularly common; these findings, as well as rigidity, are more often pronounced in the lower extremities

Question 10

An individual treated for major depression with a serotonergic agent may develop mild tremor and hyperreflexia. Is this serotonin syndrome?

Answer 10

Yes! Although technically meeting the diagnostic criteria for serotonin syndrome, the patient may benefit more (ie, be significantly less depressed) with continued administration of the agent, even though it produces obvious but tolerable signs of serotonergic excess. However, clinicians should be extremely careful not to add other serotonergic drugs to the regimen of such a patient, and must remain vigilant for any worsening in condition

Question 11

You are adding a second serotonergic drug to a pts med list. You want to be vigilant of a possible SS. When would you most expect to see S/Sx of serotonergic syndrome?

Answer 11

The majority of cases of serotonin syndrome present within 24 hours, and most within six hours, of a change in dose or initiation of a drug

Question 12

Typical changes in VS in a pt with SS?

Answer 12

Typical vital sign abnormalities include tachycardia and hypertension, but severe cases may develop hyperthermia and dramatic swings in pulse and blood pressure

Question 13

What is something unique about the neuromuscular findings in a pt with SS?

Answer 13

Neuromuscular findings are typically more pronounced in the lower extremities

Question 14

To confirm the diagnosis, a serotonin level may be drawn. T/F

Answer 14

False. Serotonin syndrome is a clinical diagnosis; serum serotonin concentrations do not correlate with clinical findings, and no laboratory test confirms the diagnosis

Question 15

What are some lab findings that you could see in SS?

Answer 15

some nonspecific laboratory findings may develop, including an elevated white blood cell count, elevated creatine phosphokinase, and decreased serum bicarbonate concentration

Question 16

SS is diagnosed based on clinical findings. The Hunter Toxicity Criteria. What is this?

Answer 16

To fulfill the Hunter Criteria, a patient must have taken a serotonergic agent and meet ONE of the following conditions:

Spontaneous clonus
Inducible clonus PLUS agitation or diaphoresis
Ocular clonus PLUS agitation or diaphoresis
Tremor PLUS hyperreflexia
Hypertonia PLUS temperature above 38ºC PLUS ocular clonus or inducible clonus

Question 17

How can you differentiate SS from NMS?

Answer 17

Serotonin syndrome is often misdiagnosed as NMS, but the two can readily be distinguished on the basis of history, examination findings, and clinical course. NMS develops over days to weeks, whereas serotonin syndrome develops over 24 hours. Serotonin syndrome is characterized by neuromuscular hyperreactivity (tremor, hyperreflexia, myoclonus), while NMS involves sluggish neuromuscular responses (rigidity, bradyreflexia). Hyperreflexia and myoclonus are rare in NMS. In addition, resolution of NMS typically requires an average of nine days, compared with less than 24 hours (usually) for resolution of serotonin syndrome. Hyperthermia, altered mental status, muscle rigidity, leukocytosis, elevated creatine phosphokinase, elevated hepatic transaminases, and metabolic acidosis are seen in severe cases of both conditions, which highlight the necessity of a thorough history and physical examination.

Question 18

How can you differentiate SS from anticholinergic toxicity?

Answer 18

Anticholinergic toxicity classically presents with hyperthermia, agitation, altered mental status, mydriasis, dry mucous membranes, urinary retention, and decreased bowel sounds after the use of an anticholinergic agent. In contrast with serotonin syndrome, muscular tone and reflexes are normal in anticholinergic poisoning

Question 19

How can you differentiate SS from other causes of agitated delirium?

Answer 19

Serotonin syndrome may be distinguished from other causes of agitated delirium on the basis of neuromuscular findings. Whereas patients with serotonin syndrome show signs of neuromuscular activation (eg, tremor, hyperreflexia and clonus that are greater in the lower extremities, ocular clonus, and increased muscle tone), patients with sympathomimetic toxicity or infections of the central nervous system lack these findings

Question 20

An essential call that must be made when a pt is suspected of having SS is to whom?

Answer 20

As with any toxic exposure, consultation with a medical toxicologist, clinical pharmacologist, or poison control center can provide valuable assistance with clinical decision-making.