#479: Serotonin Syndrome - Signs, Symptoms & Nursing Interventions

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You take a look at her medical history and see that she takes Certraline for depression and Tramadol for pain. Is something going on here? The short answer is yes, and the long answer is what we're going to talk about in this episode. And essentially, what is going on here is serotonin syndrome. This is a condition that occurs when there is an overabundance of serotonergic activity in the central nervous system.

Serotonin syndrome can range from mild, where the person doesn't even seek medical treatment, to severe and if left untreated, can be fatal. So let's do a quick review of serotonin and what it is. It is a neurotransmitter that plays a really important role in mood, attention, behavior, and temperature regulation. Well, we tend to think of antidepressants when we look at sources of exogenous serotonin, exogenous meaning it's something that we take in, the body's not producing it.

Though the body does obviously produce its own serotonin, we're talking about sources of exogenous serotonin. Key thing is the antidepressants that I just mentioned, supplements, illicit drugs, and then a few other medications as well. We'll talk about those in just a moment.

Additionally, serotonin syndrome can occur due to drug reactions between specific medications. So when does serotonin syndrome occur? So typically it's going to manifest within 24 hours of the impending event. So a lot of times this is a dose adjustment of a serotonergic medication, maybe adding a new medication.

a drug interaction because maybe the patient's been taking a an antidepressant, an SSRI, and now they get added another drug that causes an interaction and excess serotonin. It could be from supplements, It can be from illicit drug use. So again, about less than 24 hours, maybe just a few hours for the symptoms to manifest. So what medications and supplements increase serotonergic activity? When are we going to be looking at our patient with a heightened suspicion that this could happen.

Here are the medications that can impact serotonin. And these are the most likely ones to trigger serotonin syndrome. So these include SSRIs, which are Selective serotonin reuptake inhibitors. Examples include Certralein or Zoloft and Eschatalipram or Lexapro. These are medications used to treat depression. Closely related are the SNRIs. These are serotonin and norepinephrine reuptake inhibitors.

And examples include venlofaxine, which is effectsor, and duloxetine, which is symbolta. Again, used for depression. I believe I've seen it used for maybe anxiety disorders, maybe some O C D. things like that. So mental health conditions. We also have TCA's tricyclic antidepressants such as amitryptaline. And MAOIs. These are monoamine oxidase inhibitors and include medications such as phenylzine or nardis.

and these MAOIs pose the highest risk for serotonin syndrome. And then other antidepressants like bupropion or wellbutrin, Trazodone, which is often prescribed as a sleep aid, and Mirtazepine, which is sometimes prescribed as an appetite stimulant. Honestly. I don't know a hundred percent if it's used as an epite stimulant in humans. I'm assuming so, but I can tell you with 100% certainty it is used in cats because my dearly departed Oliver was on martazepine in his final months.

You're taking sertraline for depression. You're not going to be wanting to take dextromethorphan on top of it because it could cause serotonin syndrome. Another one are migraine medications like Tegritol. which is really hard to say. Tegritol, carbamazepine is the generic name, and Sumatriptan, which is Imotrex. And there are others, but those are some common ones.

And then pain medications can also increase serotonergic activity like codeine, fentanyl, hydrocodone, oxycodone, myperidine, and tramadol. Maybe not on their own with regular, you know, moderated prescribed use, but in conjunction with, say, an SSRI or something like that, you're definitely looking at potential serotonin syndrome.

Also anti nausea medications like metaclopromide and onansitron, and then The antibiotic that I mentioned earlier, Lanezolid, which goes by the brand name Xyvox, this is an antibiotic used for bacterial infections like community and hospital-acquired pneumonia and also skin infections. Lithium is another one. Supplements like ginseng, nutmeg, and a big one is Saint John's Wort.

And then of course illicit drugs, which I've mentioned a couple of times. Examples include cocaine, amphetamines, LSD, and MDMA or ecstasy. Now it's important to note that polypharmacy. Being prescribed multiple drugs is a significant risk factor for serotonin syndrome. For example, let's say you've got a patient who's taking therapeutic doses, so nothing out of the ordinary. of say surtraline, no adverse effects. They're doing just fine.

But if trazodone is added as a sleep aid, and they also take a cough syrup containing dextromethorphan, now we're looking at potentially developing serotonin syndrome. This is why patient education is a really critical component when starting a new medication or increasing the dose of a medication. And one of the key things to teach your patient

are to recognize the signs and symptoms of serotonin syndrome so that they know when it's occurring so that they can seek help. We'll get into that next.

as we go through the straighty nursing latte method. So let's dive into that now. The first letter in the latte method is an L and that stands for how does the patient look? Basically, what are the signs and symptoms? So there's a classic triad of symptoms for serotonin syndrome, and that is. Mental status changes, autonomic instability, and neuromuscular abnormality. So looking at mental status changes, we have things like agitation, confusion, anxiety, and restlessness.

Autonomic instability, this leads to things like hypertension, tachycardia, hyperthermia. Diaphoresis, diarrhea, and nausea, and also possibly vomiting with that as well. And then neuromuscular abnormalities. These include tremor, hyperreflexia, clonus, especially on the lower extremities, specifically at the ankle, muscle rigidity, lack of coordination, or ataxia.

and ocular clonus. So an easy way to trigger your memory for these is M-A-N or MAN, mental status changes, autonomic instability, and neuromuscular abnormalities. So another important thing to be aware of is that symptoms can range from mild, and you know, sometimes you'll see mild symptoms listed as diarrhea, nausea. and maybe some tremor or shivering to severe, which would be fever, muscle rigidity, and seizures.

Left untreated, serotonin syndrome can lead to rhabdomyelysis due to extreme muscle rigidity, that activity of the muscles. Can lead to metabolic acidosis, renal failure, myoglobin urea, disseminated intravascular coagulation, or DIC, and acute respiratory distress syndrome, or ARD. And of course, it can be fatal. It's really, really vital to notice the condition early and intervene quickly. So those are the key signs and symptoms of serotonin syndrome.

The next letter in the latte method is an A, and this stands for assessment. So what are the key assessments we're going to do for this patient? First off, we're going to monitor and trend their vital signs. A rising heart rate, a rising blood pressure, and a rising temperature are all cause for concern.

And note that the hyperthermia with serotonin syndrome can be pretty significant with temperatures that can get up to 106 degrees Fahrenheit, even higher. So you're definitely keeping a close eye on the vital signs. Neurologically, we're assessing level of consciousness, level of agitation, we're assessing for anxiety, orientation, all of those things. And then neuromuscular. We're observing for tremors, ocular clonus, ataxia, which is that uncoordinated movement, and muscle rigidity.

And then for the GI system, assessing the bowel sounds likely to be hyperactive with that. diarrhea, that nausea, that vomiting that can occur, and then cardiac. We want to put this patient on a cardiac monitor. Really essential because of that autonomic instability associated with serotonin syndrome. And then medications. We're doing a full med reconciliation, looking at all of the patients' medications. This includes their scheduled meds, their PRN meds.

They're herbal supplements if they take any, any over-the-counter medications they utilize, and illicit drugs as well. So those are the key things that we're going to be assessing with our patient with serotonin syndrome. Again, we're looking at vital signs, neurostatus, neuromuscular status, the GI tract, the heart, and their medication.

So the next letter in the latte method is a T and that stands for tests. So what tests are utilized? to monitor or evaluate this patient. So there's no single lab test to confirm serotonin syndrome. And the diagnosis is primarily achieved through clinical examination of the patient. But labs definitely may be ordered to identify complications and monitor them and also to rule out possible other causes. So some labs that you may see ordered include a white blood cell count.

Oftentimes white blood cells are increased in serotonin syndrome. electrolytes. So electrolyte imbalances can mimic some of the signs of serotonin syndrome, but they can also occur in serotonin syndrome when things get severe and we're getting into things like rebdomyysis and all of that. So we're definitely looking at electrolyte levels. Creatmin and B UN assess renal function and monitor for acute kidney injury, which can occur.

Sodium bicarbonate likely to be decreased because of the acidotic state. And then CPK is often increased due to that constant muscle rigidity and the damage that causes the muscle. Liver function tests is another one because liver injury can occur. These labs would help you evaluate the severity of liver injury, and also looking at coagulation studies.

Earlier, I mentioned DIC or disseminated intravascular coagulation as a potential complication. So if we think the patient's going into DIC, we want to look at those coagulations. Urine studies can reveal blood in the urine, which is a red flag for rhabdomylysis, and a TOX panel could identify substances that could contribute to serotonin syndrome as well. Serum lactate could be elevated in metabolic acidosis associated with severe toxicity. So we'd probably want to be looking at that.

And then blood cultures, probably most likely using blood cultures to rule out infection or sepsis as a cause for the patient's change in status. And then an ABG could be done. In severe cases, again, that patient will be acidotic. And an ABG can help us determine the level of the acidosis. And if respiratory function is affected and the patient is getting into maybe acute respiratory distress syndrome, very, very severe case, then an ABG would show the level of hypoxemia.

And then obviously specific labs to rule out other causes. So other conditions that have assessment findings that. could kind of muddy the waters a little bit when you're looking at serotonin syndrome include anticholinergic toxicity, malignant hyperthermia. neuroleptic malignant syndrome. Acute dystonic reactions, meningitis,

substance withdrawal and thyroid storm. So various tests may be utilized to rule these out as causes for the patient's signs and symptoms. For example, with you know meningitis. then they would do a lumbar puncture and look at the CSF. So just an example of other labs that might be used. And then another key component is clinical evaluation of the patient. And the physician may use a tool such as the Hunter Serotonin Toxicity Criteria.

as they're making the diagnosis. And it is used to diagnose serotonin syndrome when a causative agent is in use and the patient has at least one of the following manifestations. So either Spontaneous clonus. or inducible clonus along with agitation or diaphoresis, or ocular clonus with agitation and diaphoresis. Another option is tremor and hyperreflexia. And then the final option that would qualify them as having serotonin syndrome is hypertonia plus a temperature above 38 degrees.

Celsius, which is 100.4 degrees Fahrenheit, along with ocular or inducible clouds. So if you're asking what is Clonus Nurse Mo, it is a series of involuntary rhythmic and rapid muscle contractions and relaxations. Cumally, this looks like shaky, pulsating motions, particularly in the ankles, wrists, or the knees. And in the case of serotonin syndrome, the clonus is very specific to the ankle. Next, we'll get into treatments and patient education, but before that, a quick little break.

Note that symptoms can persist though for several days, especially when the patient is taking a medication with a long half-life, such as fluoxetine. Now, I'm not saying the patient's gonna be just fine a okay. Because if they had severe symptoms, they could already be having some complication like rhabdomylysis. That rhabdomylysis is not going to resolve just because you've stopped the serotonergic medication.

What we're talking about when we say symptoms resolve is that let's say the patient has mild symptoms. We take away the serotonergic agent, their symptoms resolve. But if they do have a complication, that is going to persist, and that would have to be treated separately. So I just wanted to be very clear about that.

So in addition to discontinuing those medications, supportive care is utilized to bring the body back into balance. And also again, we're addressing complications. So some things that you might see. is hydration with IV fluids. So hyperthermia can cause fluid losses. So we want the patient to stay hydrated. We're aiming for that urine output greater than or equal to Zero point five mils per kilogram per hour. That's a basic rule of thumb.

And then additionally, let's say the patient has rhabdomylysis. IV fluids, pretty aggressive IV fluids, are critical in rhdomylysis in order to protect the kidneys from going into renal failure. So hydration is one. Another is oxygen therapy with a goal, you know, around 94% or above is what I saw as I was doing research for this lesson. And then short acting anti-hypertensives. Remember, hypertension can be one of the

hallmarks of serotonin syndrome. So we're using short-acting ones so that we don't get into a situation where we then have hypotension. So some short-acting antihypertensives commonly used are esmalol and nicardipine. In cases of hypotension related to MAOIs, which can occur, vasopressors such as norepinephrine are used. And then what are we doing about that temperature? Well, we're going to use cooling measures. And this would be things like cooling blankets.

ice packs at the groin and the axila, and cool IV fluids. Notice I did not say acetamenophen or any antipyratic That's because these antipyretics are ineffective in serotonin syndrome because the main causes of hyperthermia is because of that increased muscle activity and central deregulation.

So an antipyretic isn't going to work on those things. What we need to do in a lot of cases is get that muscle activity to decrease. And some patients will need to be sedated to prevent that excess muscle activity and rigidity. So speaking of sedation, benzodiazepines are generally what is considered the best sedative to use, and they again decrease muscle contractions. They also do have a little added benefit of reducing heart rate and blood pressure as well.

And then in really severe cases, this patient may need to be intubated, heavily sedated, maybe even given a neuromuscular blockade or a paralytic to decrease muscular activity. That would be an incredibly severe case. And in cases where supportive measures are not treating the patient effectively, they could get a serotonin antagonist. And let's see if I can pronounce it.

Cyproheptidine. We're going to call that one good. That's the name of the medication that is utilized. It is a serotonin antagonist. So also just as important as what you do for the patient is what you are going to not do for the patient. So some key things to avoid include physical restraint.

And then we're also avoiding succinylcholine. This is a medication that is given for rapid sequence intubation in order to briefly paralyze the muscles. And the problem with succinylcholine is that there is a risk of hyperkalemia if the patient already has kind of a high ish potassium level, and they definitely would have a high ish potassium level if they were having rhabdomyolysis. So you're going to avoid those things. Physical restraints, haloperidol, and succinyl choline.

So the next letter in the latte method is an E, and this is for patient education. The most important thing to teach your patient who is prescribed a serotonergic agent is to avoid other substances that increase serotonin levels. This includes that cough syrup containing dextromethorphan.

herbal supplements such as St. John's Ward, that's a big one, and of course illicit and recreational So in addition to that, it's really important to remind the patient that they communicate all their medications, all their supplements to each physician that they see to avoid over-prescribing of serotoninergic medications or

prescribing something that could have a potential reaction. And along with that, it's really important that patients use one single pharmacy. And the reason for this is if the patient gets all their meds through one pharmacy, that pharmacist can see all the meds they're taking and what potential interactions could occur. So it's another safety mechanism.

Now, I mentioned earlier that it's also really important that patients know the signs of serotonin syndrome so they can seek medical care quickly. So again, some things to teach them to watch for would be. Suddenly getting restless, agitated, or confused, their heart rate increasing if they develop a high temperature, if they have that muscle twitching. Stiffness in the muscles or any lack of coordination, if they're sweating, have diarrhea, nauseous, or vomiting, and dilated pupils.

So now that you have a great overview of serotonin syndrome, let's go through a quick little case study scenario. So you have your patient Margaret. She's a 58-year-old woman admitted to the medical floor for a methicillin-resistant staphylococcus aureus or MRSA wound infection. Her past medical history includes a major depressive disorder, fibromyalgia, and type two diabetes.

Her home medications include Certrale one hundred milligrams daily, Tremadol fifty milligrams every six hours, PRN for pain, and metformin daily. The hospitalist orders Lenezolid 600 milligrams IV every 12 hours for the MRSA cover. Three hours after the first dose of the antibiotic, the nurse notes that the patient is increasingly restless, sweating through her gown, and complaining of jumping legs and nausea.

So I'm going to tell you some vital signs and I want you to mentally think of which ones would be cause for concern. So her temperature is 38.9 degrees Celsius or 102 degrees Fahrenheit. Her heart rate went from 84 baseline to 118. Her blood pressure went from 128. over 78 at baseline to 158 over 94, and her SPO2 is 96% on room air and has been steady. So which of these vital signs are cause for concern?

So that's going to be the temperature, the tachycardia, and the hypertension. All of these things can occur in serotonin syndrome. So we do a little bit of an assessment on this patient and we find that she's alert but agitated, repeatedly pulling at her IV tubing, picking at her gown. Pupils are equal and reactive. She has inducible ankle clonus bilaterally.

She is diaphoretic, her skin is flushed and warm, and she reports, I can't stop my legs from twitching, and I feel like I'm going to throw. So, if we look at the Hunter criteria for serotonin syndrome, do any of these assessment findings align with that? And the answer is yes. She's agitated. She has inducible clonus and diaphoresis. Those are all things that tell me that she's looking like she's got serotonin syndrome. On top of that, she's also nauseous, which can come with it as well.

So which drug combination is responsible for triggering this reaction? Do you remember the drugs that she was taking? So that would be the serotonergic medications, Certraline and Tramadol. And then adding in that antibiotic, the lanezolid. is going to cause a drug interaction that increases serotonin levels. And now we're in serotonin syndrome. So what is your priority nursing action right now? What are you gonna do about this?

So what I'm gonna do, and hopefully you too, is I'm gonna let the MD know right away and anticipate that we're gonna be holding some or all of the serotonergic medications. We may be switching over to a different antibiotic. I may anticipate some IV fluids for this patient and potential benzodiazepine to reduce the muscle twitching and also getting her on a cardiac monitor.

So there you have it, your quick overview of serotonin syndrome. I hope that helped you understand this complex but interesting complication of very, very common medications. I will see you again very soon. Bye for now.