Not your typical epileptic

[harold1981]

We were called to a homeless shelter at the end of our evening shift the other day for a 41yo male with seizures. Upon arrival we find the man under his blankets. He is alert, oriented and agitated. His skin is flushed, warm and diaphoretic, he is drooling. He is complaining of palpitations and 'not feeling well'. The 'seizure activity' observed by the personnel of the shelter is more of a trembling over his whole body, that came up suddenly three hours ago. The man is restless and vague in his answers. He denies substance use, although he admits to being an ex-heroin user. Our findings are a respiratory rate of 30, clear lung sounds, sats of 99%, sinustachycardia of 120, BP of 170/110. Bloodglucose of 5.2 mmol/L, temperature of 39.1 degrees Celsius, he has no other complaints that can lead to one of his body systems. His EKG is normal. He has no allergies, in his medical history he is being treated for his heroin addiction with Methadon via an outpatient center, and Quetiapine for ocassional psychotic complaints. He has been clean from drug use since two years. Since a week he's been using a food supplement, St. John's Wort, for his depressed mood.
We provide him with an IV, monitoring, and 1000mg IV paracetamol as an antipyretic. Upon transfering him to the stretcher he vomits, so we give him 4mg of ondansetron as well. His condition remains unchanged during the trip to hospital.

At the ED he is later diagnosed with serotonin syndrome, exacerbated by the combination of Quetiapine and St. John's Wort. He is admitted to the ICU. The emergency physician tells us that knowing this, we could have given him Midazolam at the scene for symptom relief, but this condition was completely new for me.

 

[chaz90]

I've heard of it, but there's not a chance I would have picked up on it during the call. Interesting case!

 

[Gurby]

According to my internet researching, serotonin syndrome is usually rapid onset after medication administration. It also usually requires at least 2 drugs with different mechanisms. I wonder if these symptoms came on shortly after medication administration or after taking St John's Wort?

Also not a chance I would have picked this up during the call... But maybe now if I see it in the future I will!

 

[medicsb]

This is the sort of patient that is ripe for a publishable case study for EMS, EM, and toxicology. It take some effort to do, but this is potentially great teaching case.

 

[Akulahawk]

According to my internet researching, serotonin syndrome is usually rapid onset after medication administration. It also usually requires at least 2 drugs with different mechanisms. I wonder if these symptoms came on shortly after medication administration or after taking St John's Wort?

Also not a chance I would have picked this up during the call... But maybe now if I see it in the future I will!

This is why we need to be aware of what medications and ask about herbal supplements the patient takes. If a patient is taking St. John's Wort, always have Serotonin Syndrome in mind. Almost as soon as I read Quetiapine and St. John's Wort, I started considering that those two may be the cause of the symptoms the patient was experiencing. Here's a list of symptoms that are pretty common:

Symptoms occur within minutes to hours, and may include:

• Agitation or restlessness
• Diarrhea
• Fast heartbeat and high blood pressure
• Hallucinations
• Increased body temperature
• Loss of coordination
• Nausea
• Overactive reflexes
• Rapid changes in blood pressure
• Vomiting

If you look at the symptoms the patient experienced and compare it to the list above, you might see some of them match pretty well.

 

[wilderness911]

Ondansetron is a 5-HT3 receptor antagonist, wouldn't that be contraindicated in a patient suffering from serotonin toxicity? Not trying to armchair QB this call, just thinking out loud for future cases. Thanks for writing up your experience with this patient and sharing it. Great teaching tool and a good reminder that St. John's wort should be looked at as any other SSRI from a prehospital standpoint.

 

[Gurby]

Ondansetron is a 5-HT3 receptor antagonist, wouldn't that be contraindicated in a patient suffering from serotonin toxicity? Not trying to armchair QB this call, just thinking out loud for future cases. Thanks for writing up your experience with this patient and sharing it. Great teaching tool and a good reminder that St. John's wort should be looked at as any other SSRI from a prehospital standpoint.

I'm so confused...

Zofran is a 5-HT antagonist. According to wikipedia, "agonists at 5-HT would increase the severity of certain symptoms associated with serotonin syndrome" ( https://en.wikipedia.org/wiki/Serotonin_syndrome#Pathophysiology ).

And yet, sources seem to say that zofran is associated with serotonin syndrome: "The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists." (http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm418818.htm).

What is the mechanism? Agonists and antagonists are both associated with serotonin syndrome...?

Is it the fact that zofran is specific for 5-HT3? Does it maybe block certain serotonin receptors, causing increased stimulation of other (more important?) ones via Le Chatelier's principle?

 

[wilderness911]

I'm so confused...

Zofran is a 5-HT antagonist. According to wikipedia, "agonists at 5-HT would increase the severity of certain symptoms associated with serotonin syndrome" ( https://en.wikipedia.org/wiki/Serotonin_syndrome#Pathophysiology ).

And yet, sources seem to say that zofran is associated with serotonin syndrome: "The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists." (http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm418818.htm).

What is the mechanism? Agonists and antagonists are both associated with serotonin syndrome...?

Is it the fact that zofran is specific for 5-HT3? Does it maybe block certain serotonin receptors, causing increased stimulation of other (more important?) ones via Le Chatelier's principle?

I believe that it inhibits serotonin reuptake at the synapses, thereby increasing overall concentration of serotonin at the synaptic cleft. Could be wrong though, anyone able to confirm?

 

[harold1981]

I think it works like this:
Serotonin is involved in a number of physiological functions in the body. But first it needs to connect with a serotonin receptor.
There are a number of different serotonin receptors, each triggering a different physiological reaction.
One of those receptors is 5HT3, which activates the vomit center in the brain, and therefore the vomit reflex.
Ondansetron blocks those 5HT3 receptors, therefore preventing the dopamine of binding with them, but leaving the dopamine molecules free to bind with other type of serotinon receptors.
With this in mind, I don't think that Ondansetron will increase serotonin levels or make a serotonin syndrome worse. It will only prevent the already high serotonin levels of being used to vomit.

 

[Doczilla]

80% of our seretonin is found in the gut. Zofran is so popular because it antagonizes those peripheral seretonin receptors, which in turn prevents vagus nerve stimulation. As a contrast, drugs like Phenergan work peripherally in the gut as well as centrally in the CTZ.

As far as I'm aware, Zofran has predominantly peripheral action; and in a case like SS where the treatment is primarily supportive, stopping the vomiting is probably more important. They need fluids, benzos, and active cooling. Maybe a tube if they're obtunded.