SEROTONIN SYNDROME - Nurse CEUs Online - … nursece4less.com nursece4less.com nursece4less.com nursece4less.com 5 Introduction Serotonin syndrome is a group of signs and symptoms

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SEROTONIN SYNDROME

ELIZABETH BOLDON, BSN, MSN

Elizabeth Boldon is a Nursing Education

Supervisor at Mayo Clinic in Rochester,

Minnesota. She oversees the Nurse Educators

in the Intensive and Progressive care units

and the Simulation Center. She has a passion

for nursing education and continues to teach

in areas such as recognition of the deteriorating patient, communication, and the

transition of new staff into practice. She received a BSN from Allen College in

Waterloo, Iowa in 2002 and an MSN with a focus in education from the University of

Phoenix in 2008. She has bedside nursing experience in medical neurology and the

neuroscience ICU.

ABSTRACT

Drugs can react to cause the body to have too much serotonin and

lead to serotonin syndrome, which is a potentially life threatening

condition. Serotonin syndrome is caused by therapeutic doses, drug

interactions, or overdoses of medications that directly or indirectly

affect the serotonergic system. An excess stimulation of the

serotonergic receptors is what causes serotonin syndrome. The

stimulation is excitatory and causes symptoms, such as tachycardia,

hypertension, agitation, excessive muscular activity. There is no

proven antidote for serotonin syndrome that is effective and safe. The

best treatment is supportive care. Health clinicians must consider the

possibility of serotonin syndrome in the setting of serotonergic

medications where mental status changes and neurological

hyperexcitability occur.


Policy Statement

This activity has been planned and implemented in accordance with

the policies of NurseCe4Less.com and the continuing nursing education

requirements of the American Nurses Credentialing Center's

Commission on Accreditation for registered nurses. It is the policy of

NurseCe4Less.com to ensure objectivity, transparency, and best

practice in clinical education for all continuing nursing education (CNE)

activities.

Continuing Education Credit Designation

This educational activity is credited for 2.5 hours. Nurses may only

claim credit commensurate with the credit awarded for completion of

this course activity. Pharmacology content is 30 minutes.

Statement of Learning Need

Health clinician knowledge to identify serotonin syndrome and to help

patients avoid it is imperative to prevent an adverse clinical outcome.

Patients that are prescribed serotonergic medications need to be

educated and warned about the possibility of serotonin syndrome and

subtle changes that could lead to severe physical symptoms.

Course Purpose

To help clinicians identify signs and symptoms of serotonin syndrome

and to follow recommended treatment.


Target Audience

Advanced Practice Registered Nurses and Registered Nurses

(Interdisciplinary Health Team Members, including Vocational Nurses

and Medical Assistants may obtain a Certificate of Completion)

Course Author & Planning Team Conflict of Interest Disclosures

Elizabeth Boldon, BSN, MSN, William S. Cook, PhD,

Douglas Lawrence, MA, Susan DePasquale, MSN, FPMHNP-BC –

All have no disclosures

Acknowledgement of Commercial Support

There is no commercial support for this course.

Please take time to complete a self-assessment of knowledge, on page 4, sample questions before reading the article.

Opportunity to complete a self-assessment of knowledge learned will be provided at the end of the course.


1. Which of the following is the correct definition of serotonin

syndrome?

a. Signs and symptoms caused by excessive stimulation of the serotonergic system.

b. Signs/symptoms caused by serotonergic drug overdose. c. A clinical condition that closely resembles neuroleptic

malignant syndrome. d. A clinical condition characterized hyperthermia, clonus, and

agitation.

2. Which of these classes of drugs inhibits the reuptake of serotonin?

a. Common analgesics

b. Illicit drugs

c. Sympathomimetics d. SSRIs

3. Three illicit drugs that may cause serotonin syndrome are:

a. Methamphetamine, heroin, marijuana

b. Cocaine, LSD, ecstasy c. Marijuana, ecstasy, cocaine

d. Dextromethorphan, LSD, methamphetamine

4. The criteria used to diagnose serotonin syndrome is/are

a. Sternbach’s criteria b. the Hunter criteria

c. Modified Glasgow scale

d. Romberg criteria

5. True or False: Neuroleptic malignant syndrome may be mistaken for serotonin syndrome.

a. True

b. False


Introduction

Serotonin syndrome is a group of signs and symptoms caused by

excessive stimulation of the serotonin receptors. Serotonin syndrome

is caused by therapeutic drug doses, drug interactions, or overdoses of

drugs that directly or indirectly affect the serotonergic system. The

clinical presentation of serotonin syndrome can be intense and

dramatic, but it can also be mild and subtle. Serotonin syndrome can

be mistaken for an infectious or metabolic disorder or for the clinical

syndromes caused by anticholinergic or sympathomimetic poisoning,

and for the neuroleptic malignant syndrome or malignant

hyperthermia. Although it is unusual for serotonin syndrome to cause

a fatality, a severe case is a medical emergency that can rapidly cause

multisystem organ failure. Medical and nursing clinicians must be

aware of serotonin syndrome because drugs that can cause it are in

common use, and intentional overdoses with drugs that can cause

serotonin syndrome are being seen with increasing frequency. This

makes it difficult to detect and clinicians can easily mistake serotonin

syndrome for other pathologies.

Serotonergic System

Serotonin (also called 5-hydroxytryptamine) is a monoamine

neurotransmitter that acts centrally and peripherally. It is synthesized

in the central nervous system and in enterochromaffin cells in the

gastrointestinal (GI) tract. Serotonin has many complex functions, and

the full range and activity of these is not known.1

In the brain, serotonin is involved in mood, personality, appetite,

motor function, temperature regulation, sexual activity, pain


perception, and sleep induction. Serotonin also inhibits gastric

secretion, acts as a smooth muscle stimulant, promotes platelet

aggregation, affects vascular tone, and is a central and peripheral

neurotransmitter.1

Serotonin is stored in vesicles in

presynaptic neurons. It is

released into the synaptic cleft

and binds to a serotonin receptor

on the postsynaptic neuron.

There are seven families of

serotonin receptors (5-HT1 to

5HT7) and several of these have

different subtypes, for example,

5-HT1A. Serotonin binding to a 5-

HT receptor initiates a wide

variety of effects on the post-

synaptic neuron (decreasing or

increasing intracellular cAMP

levels, causing Na+ and Ca2+ influx and depolarization action), however

the basic effect of serotonin is excitatory. After binding to the receptor,

serotonin is transported back to the presynaptic neuron where it

reenters the vesicles or is broken down by monoamine oxidase.1

Neurotransmitters such as serotonin, dopamine, and glycine, function

by binding to receptors on the membranes of post-synaptic neurons.

These receptors are ligand-gated ion channels or G protein receptors.

When a neurotransmitter binds to a ligand-gated ion channel, the

channel opens and ions enter or leave the cell: depending on which


ions enter or leave, the effect of the neurotransmitter can be

excitatory (causing cell depolarization) or inhibitory (preventing cell

depolarization). When a neurotransmitter binds to a G protein, the

same effects occur.

When serotonin binds to G proteins of the 5-HT1 receptors, potassium

ions channels open, potassium leaves the cell – increasing membrane

potential and inhibiting depolarization – and cAMP concentrations are

decreased, and the effect is inhibitory. It is important to remember

that the terms inhibition and excitation refer to how the

neurotransmitter affects the cell. The physiological action produced by

excitation may be a decrease in a particular function (i.e., decreased

peristalsis) and the physiological action produced by inhibition may be

an increase in a particular function (i.e., muscle tremor or

hyperreflexia).

Serotonin Syndrome: Epidemiology

Serotonin syndrome is not a recent phenomenon. It was first

recognized in animals, and the first case described in a human was

reported in 1959; however, case reports of unrecognized serotonin

syndrome predate that by at least 20 years.2 The term serotonin

syndrome was first used by Insel, et al. in 1982 to describe a patient

who developed serotonin syndrome from a combination of a

monoamine oxidase (MAO) inhibitor and a tricyclic antidepressant.2,3

The exact incidence of serotonin syndrome is not known. Prior

research investigating the use of selective serotonin reuptake

inhibitors (SSRIs) compared to other antidepressant medication report

that SSRIs rarely result in serious outcomes and death. Tricyclic


antidepressants and monoamine oxidase inhibitors (MAOIs) have been

found to be more toxic than SSRIs. It has been found that 31 to 32

percent of TCA ingestions required intubation as compared to 4% to

6% of SSRI ingestions. Similarly, 31% to 35% of TCA ingestions

required intensive care unit admission as compared with 0% to 6% of

SSRI ingestions. Death rates were reported as 1.6 per million for SSRI

prescriptions as compared with 34.8 for TCAs and 20 for MAOIs.4

Serotonin syndrome has been described in all ages groups, including

neonates, children, and the elderly.

Clinical Presentation of Serotonin Syndrome

The essential cause of serotonin syndrome is an excess stimulation of

the serotonergic receptors. The stimulation is excitatory and causes

tachycardia, hypertension, agitation, and excessive muscular activity

and other signs and symptoms of the syndrome. The excess

stimulation occurs by one of the following six mechanisms.4-6

Direct Stimulation of the Serotonergic Receptors

Direct stimulation of the serotonergic receptors occurs with the

medications of buspirone, carbamazapine, lithium, as well as with the

psychedelic drug LSD.

Excessive Release of Serotonin

Excessive release of serotonin occurs with amphetamines, cocaine,

dextromethorphan, levodopa, monoamine oxidase inhibitors,

reserpine, as well as with ecstasy/MDMA.


Decreased Breakdown of Serotonin

Decreased breakdown of serotonin occurs with monoamine oxidase

inhibitors and St. John’s wort.

Enzyme Inhibition

Cytochrome P450 enzymes that metabolize certain serotonergic drugs

can be inhibited by these drugs, i.e., dextromethorphan, methadone,

oxycodone, tramadol, venlafaxine.

Increase in Serotonin Precursors

Increase in serotonin precursors occurs with the essential amino acid,

Tryptophan.

Decreased Serotonin Reuptake

Decreased serotonin reuptake occurs with selective serotonin-reuptake

inhibitors (SSRIs), such as citalopram, escitalopram, fluoxetine,

fluvoxamine, paroxetine, and sertraline, as well as, with

dextromethorphan, monoamine oxidase inhibitors, methadone, and

trazodone. It is not known exactly what families and subtype of

serotonin receptors are involved in serotonin syndrome, which could

be one of the factors accounting for the variability of the clinical

presentation of this pathology. Some authors, however, have identified

the 5-HT1C and the 5-HT2 receptors as the ones affected in cases of

serotonin syndrome.

Although there is a wide range of signs and symptoms that are

possible, serotonin syndrome is definitely characterized and diagnosed


by abnormal autonomic, cognitive, and neuromuscular changes.5,6

These are further outlined below:

• Autonomic:

Autonomic changes include hyperthermia, hypertension,

tachycardia, diaphoresis, flushing, increased bowel sounds,

diarrhea, and mydriasis. The hyperthermia can be very severe

with a body temperature ≥ 38.5° C and higher.

• Cognitive:

There are many cognitive changes associated with serotonin

syndrome such as agitation, drowsiness, coma, hypomania,

anxiety, confusion, hallucinations, and delirium.

• Neuromuscular:

Symptoms may include akathisia, clonus, hyperreflexia,

myoclonus, rigidity, shivering, and tremor.

Clonus (inducible, ocular, or spontaneous) is the most reliable finding

when diagnosing serotonin syndrome. Clonus is defined as alternate

muscular contraction and relaxation in rapid succession. The signs and

symptoms reviewed above have been observed in patients who have

serotonin syndrome. The clinical presentation and the severity of signs

and symptoms are quite variable; serotonin syndrome can be mild and

quite subtle in presentation or severe and life threatening.

Patients with a mild case of serotonin syndrome may feel restless and

anxious, they may have a low-grade fever, and mild, intermittent


tremors, and it is easy to overlook or misdiagnose these types of

cases. A severe case of serotonin syndrome is a medical emergency.

These patients may have a body temperature >41° C. Coma,

metabolic acidosis, renal failure, rhabdomyolysis, and disseminated

intravascular coagulation (DIC) may occur and all of this can develop

very rapidly.7

Serotonin syndrome typically begins very quickly. Onset can be within

minutes after exposure. In most cases the patient will develop signs

and symptoms within six hours after exposure to a drug or drugs, but

a delay of up to 24 hours is possible. Most cases resolve within 24

hours, but there have been reports of serotonin syndrome cases

lasting for several days.7-9

Drugs That Cause Serotonin Syndrome

Certain classes of medications have been definitively identified as

drugs that can cause serotonin syndrome, and this makes sense

because their therapeutic effect is based on their action on the

serotonergic system. The SSRIs such as fluoxetine and sertraline, and

monoamine oxidase inhibitors (MAOIs), such as phenelzine and

moclobemide, are common examples of these drugs.

Other drugs may cause serotonin syndrome. However, the connection

between the syndrome and the drug is not as obvious because many

drugs affect uptake or metabolism of multiple neurotransmitters that

does not always translate to a measurable or observable clinical effect.

Two such examples are bromocriptine and tramadol. Both drugs do

have an in vivo effect on the serotenergic system, but the therapeutic


effect of bromocriptine is caused by dopamine receptor agonist

activity, and the therapeutic effect of tramadol is caused by agonism

of the mu opioid receptors. Yet, both bromocriptine and tramodol can

cause serotonin syndrome.

A recent study looked at delirium occurring in the ICU where an excess

of serotonin was found, which is associated with altered mental status.

Because drugs with serotonergic properties are frequently, for

extended times, administered to patients in ICUs it was theorized that

central serotonergic toxicity may constitute a predisposing,

contributing or precipitating factor in the emergence of delirium in the

ICU setting. Study findings suggested a significant number of patients

diagnosed with delirium had, in fact, drugs prescribed that potentially

contributed to serotonergic toxicity; 16% of patients showed physical

signs of serotonin toxicity and met the Hunter serotonin toxicity

criteria.

The potential for serotonin toxicity in patients, including in the ICU

setting, needs to be understood by clinicians, including the drugs and

supplements that cause it. Drugs associated with, or suspected of

causing serotonin syndrome include those outlined here.4,9-12

Sympathomimetics:

Fenfluramine, phentermine, phenylpropanolamine

5-HT1 Agonists:

Almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan,

sumatriptan, zolmitriptan


Monoamine Oxidase Inhibitors (MAOIs):

Isocarboxazid, moclobemide, phenelzine, selegiline, and

tranylcypromine

Selective serotonin reuptake inhibitors (SSRIs):

Citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine,

sertraline

Tricyclic Antidepressants:

Amitriptyline, amoxapine, clomipramine, desipramine, doxepin,

imipramine, maprotiline, nortriptyline, protriptyline, trimipramine

Opiates/Analgesics:

Buprenorphine, codeine, levomethorphan, levorphanol, meperidine,

methadone, oxycodone, pentazocine, pethidine, tapentadol, tramadol,

fentanyl, hydrocodone, and meperidine

Antimigraine Medications:

Triptans, carbamazepine and valproic acid

Illicit Drugs:

Amphetamine, bath salts, cocaine, ecstasy/MDMA, LSD (unconfirmed)

Antidepressants and Anxiolytics:

Bupropion, buspirone, duloxetine, mirtazapine, nefazodone, trazodone,

venlafaxine.


Antiemetics:

Droperidol, granisetron, metoclopramide, ondansetron

Dietary Supplements/Herbal Product:

Ginseng, St. John’s wort, tryptophan, yohimbe

Other Drugs:

Amantadine, bromocriptine, carbamazapine, carisoprodol,

chlorpheniramine, dextromethorphan, dihydroergotamine, fluconazole,

levodopa, linezolid, lithium, methylene blue, olanzapine, reserpine,

ritonavir, and 5-methoxydiisopropyltryptamine (a.k.a. foxy methoxy)

An increased dose of a serotonergic drug, or the addition of a

serotonergic drug to the medication regimen of a patient already

taking a SSRI, MAO, or others (discussed further below) usually

causes serotonin syndrome. It can also be a consequence of overdose.

Serotonin syndrome after a single dose of a serotonergic drug is

unusual, but this has been reported. It is far more common for

serotonin syndrome to be caused by a combination of drugs that act at

different 5-HT receptor sites.4-6

Drug interactions can also be a cause of serotonin syndrome, even if

one of the drugs does not affect the serotonergic system. If a patient

who is taking an SSRI is prescribed a medication that inhibits the

cytochrome P450 enzyme that metabolizes the SSRI, serotonin

syndrome is possible.


Furthermore, discontinued serotonergic medications can cause

serotonin syndrome if there is an insufficient period of time between

the discontinuation of one medication and beginning therapy with

another. An example is Norfluoxetine, which is a metabolite of

fluoxetine that has a half-life of approximately 2.5 weeks. Because of

the long half-life of this drug and its metabolite, fluoxetine may cause

serotonin syndrome if a patient is given another serotonergic drug

within several weeks of the discontinuation of fluoxetine.

It’s important for health clinicians to continuously review an approved

drug database for current information when prescribing or

administering any form of mono- or combination drug therapy. Drug-

drug interactions are one possible cause of serotonin syndrome.

Underlying medical conditions must also be considered. The list below

includes known drug combinations that can cause serotonin syndrome,

and the FDA continuously provides updates on drug combinations and

case reports alerting clinicians to the potential for serotonin toxicity.

• MAOIs and amphetamines, dextromethorphan, meperidine,

SSRIs, TCAs, and serotonin-norepinephrine re-uptake inhibitors

(SNRIs).

• SSRIs and amphetamines, buspirone, carbamazapine,

dextromethorphan, fluconazole, MAOIs, opiates, L-tryptophan,

phentermine, SNRIs, other SSRIs, TCAs, or St John’s wort.

• Opiates and ciprofloxacin, MAOIs, SSRIs, SNRIs, or tramadol.

• Tramadol and mirtazapine, olanzapine, opiates, SSRIS, or

sertraline.

• Other antidepressants, such as buspirone and SSRIs;

mirtazapine and SSRIs; trazodone and amitriptyline, buspirone, or

lithium; venlafaxine and amitriptyline, ciprofloxacin, fluoxetine or


other SSRIs, linezolid, lithium, meperidine, methadone,

moclobemide, quietiapine, or trazodone.

• Atypical antipsychotics and mood stabilizers, such as Olanzapine

and citalopram or lithium, risperidone and dextromethorphan,

fluoxetine, or paroxetine.

• Linezolid and amitriptyline, citalopram, duloxetine escitalopram,

fentanyl, fluoxetine, meperidine, paroxetine, sertraline, and

venlafaxine.

Severe cases of serotonin syndrome appear to be more common if

multiple drugs are taken than when a single serotonergic drug is taken

in overdose or therapeutically. Monoamine oxidase inhibitors are

particularly dangerous when combined with selective serotonin-

reuptake inhibitors, ecstasy, dextromethorphan, or meperidine.

Diagnosing Serotonin Syndrome

Serotonin syndrome is a clinical diagnosis. There is no way to confirm

the diagnosis by using laboratory tests. The clinician must make the

diagnosis of serotonin syndrome by: 1) a physical exam, 2) taking a

health and medication history, and 3) ruling out other clinical

syndromes that can resemble serotonin syndrome.

Outlined in that manner, making the diagnosis of serotonin syndrome

might appear to be relatively simple, but it can be difficult to do. Mild

or even moderately symptomatic cases can easily be overlooked or

misdiagnosed. For example, serotonin syndrome has been frequently

misdiagnosed as neuroleptic malignant syndrome (NMS), which can be

differentiated through careful history taking and physical evaluation,


and by bearing in mind that serotonin syndrome develops over 24

hours as compared to symptom development over days to weeks.

Diagnostic Criteria

Although making the diagnosis of serotonin syndrome can be

challenging, there are different diagnostic criteria available that can

help.

Sternbach’s Criteria

Sternbach’s criteria were the first developed for diagnosing serotonin

syndrome. Sternbach’s criteria involves a list of 10 clinical findings and

three clinical situations.4,5,16 The clinical findings of Sternbach’s criteria

are: 1) ataxia, 2) changes in mental status (agitation, confusion,

hypomania), 3) diaphoresis, 4) diarrhea, 5) fever, 6) hyperreflexia,

7) myoclonus, 8) restlessness, 9) shivering, and 10) tremor.

The clinical situations are: 1) a recent addition, or increase in dose of a

known serotonergic drug, 2) confirmed absence of other etiologies that

could explain the patient’s clinical condition such as an infectious

disease, metabolic abnormality, or substance intoxication or

withdrawal, and 3) no recent addition or increase in dose of a

neuroleptic drug.

According to Sternbach’s criteria, a patient has serotonin syndrome if

the patient has three or more of the clinical findings and the patient

has been exposed to a serotonergic drug, has not been exposed to a

neuroleptic, and other likely causes of the signs and symptoms have

been ruled out.


Hunter Criteria

The Hunter criteria were developed in 2003. The authors were

dissatisfied with Sternbach’s criteria, and they reviewed 2,222 cases of

serotonergic drug overdose. The physical findings in these patients

were noted, and then the ones that were seen most often in patients

who been diagnosed by a clinical toxicologist as having serotonin

syndrome were considered to be the criteria for diagnosing serotonin

syndrome.4,5,16

The Hunter criteria state that a patient has serotonin syndrome if they

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

Radomski Criteria

The Radomski criteria were developed in 2000 and use many of the

same clinical findings as Sternbach’s criteria and the Hunter criteria.

However, the Radomski criteria are intended to provide diagnostic

criteria for establishing the severity of the serotonin syndrome.4,5,16

The Hunter criteria (or those criteria slightly adapted) is the system

that is used most often and is recommended. The Sternbach criteria

appear to be biased towards mental status changes, and the Hunter


criteria are felt to be more sensitive and specific and less likely than

the Sternbach criteria to miss incipient or mild cases of serotonin

syndrome. The Radomski criteria do not appear to be popular and

although other diagnostic criteria have been developed (i.e., the

serotonin syndrome scale) these do not appear to be in common use.

It has been suggested by some researchers that the term serotonin

syndrome may contribute to the confusion surrounding this condition

and the under-diagnosis of serotonin syndrome.5 The work of Dunkley,

et al. has been referenced in ongoing reviews on serotonin syndrome,

which suggested that the diagnostic criteria - or perhaps the

physicians using these criteria - overemphasized the more dramatic

signs of serotonin syndrome. This may result in milder forms of the

THE HUNTER CRITERIA

Ingestion of a serotonergic drug within 5 weeks

or overdose of a serotonergic drug ↓

Spontaneous clonus → Yes → Serotonin syndrome ↓

No ↓

Inducible clonus, ocular clonus → Yes → Agitation,

↓ diaphoresis,

No fever > 38° ↓

Tremor → Yes → Hyperreflexia →

Serotonin Syndrome ↓

No ↓

Not Serotonin Syndrome


syndrome being missed; hence the suggestion that serotonin toxicity

might be a better term than serotonin syndrome as a syndrome is

typically thought of as a defined clinical entity.

The key point clinicians must realize is that serotonin syndrome is a

spectrum of toxicity that is caused by an excess of serotonin.

Serotonin syndrome along the spectrum can be diagnosed by using the

Hunter criteria to look for the characteristic autonomic, cognitive, and

neuromuscular changes.

Health and Medication History

Taking an accurate health and medication history is very important. It

is fundamental to determine what medications the patient is taking

and has been taking. The clinician must be cognizant of the fact that

some drugs can cause serotonin syndrome even when the patient has

not been taking them for many weeks.

It is good practice for clinicians to ask patients whether medication

doses have recently been changed. Additionally, clinicians should ask if

the patient has been taking any dietary or herbal supplements, and

determine if the medication regimen has been changed in the past five

to six weeks. The clinician will also need to determine the recent state

of the patient’s health; for example, whether there was any evidence

of an ongoing infectious process and other medical conditions the

patient may report. Each time clinicians review patient medication

regimes it’s necessary to include both the existing treatment plan (i.e.,

new medications, and how they have been taking their prescriptions)

and any new organic issues in the patient’s health state.


Serotonin Toxicity In The Newborn

Although outside the scope of this study, clinicians should be aware of

current considerations given to serotonin toxicity in newborns. The

literature on SSRI effects on newborns is generally obtained from

health databases and case reports. Investigators note that the

predominant data pertains to paroxetine, fluoxetine and sertraline,

which are the most prescribed SSRIs for pregnant women, correlating

with 10% to 30% of newborn babies showing symptoms of respiratory,

motor, central nervous system and gastrointestinal symptoms,

including tachypnea, cyanosis, jitteriness/tremors, increased muscle

tone, and feeding disturbance. Newborn babies exposed in utero will

manifest mild signs and symptoms of serotonin toxicity usually within

hours that resolve within two weeks. Rarely have seizures been

reported.15

Once the baby is born the exposure to SSRI medication stops. The

signs and symptoms observed in newborns exposed in utero to SSRI

may be due to neonatal withdrawal, neonatal toxicity following in utero

exposure or a combination of both withdrawal and serotoninergic

toxicity. Since symptoms resolve after birth, these signs and

symptoms have been termed neonatal abstinence syndrome. Canadian

researchers also coined the phrase SSRI neonatal behavioural

syndrome (SNBS) to describe these signs and symptoms.15 The most

serious potential outcome related to SSRI in utero exposure noted by

some researchers is persistent pulmonary hypertension of the newborn

(PPHN), which is associated with significant infant morbidity and

mortality.15 However, the association of PPHN to maternal use of SSRI

during pregnancy has not been confirmed by subsequent studies.


While the research is ongoing on the effects of in utero exposure to

SSRI, to date, studies have shown that paroxetine and fluoxetine have

been found to cause neonatal abstinence syndrome more than any of

the other serotonergic drugs. PPHN may be a rare occurrence related

to fetal exposure to SSRIs, although this remains under investigation.

Also, other potential health outcomes to newborns exposed to SSRIs in

utero include low birth weight and gestational age, respiratory distress

and possible admission to the neonatal intensive care unit (NICU).

There is no evidence of adverse effects on the infant exposed to SSRIs

during the course of breastfeeding. All of the current research and

hypotheses related to infant exposure to SSRIs require ongoing review

involving population-based studies and case outcomes.

Clinical Conditions Resembling Serotonin Syndrome

This section covers some clinical conditions that can resemble

serotonin syndrome.2,10,16

Neuroleptic Malignant Syndrome

Neuroleptic malignant syndrome (NMS) is an idiosyncratic drug

reaction to treatment with, or withdrawal from drugs such as levodopa

and antipsychotics that act as dopamine antagonists. Important

differences between serotonin syndrome and NMS are:

• The causative agents act on a different neurotransmitter

• NMS develops slowly over several days

• The clinical findings are different than those of serotonin

syndrome, i.e., the pupils are not mydriatic, the patient will have

normal bowel sounds, and bradyreflexia and a rigid “lead-pipe

like” muscle tone will be noted

• NMS is not caused by an overdose


Anticholinergic Syndrome

The anticholinergic toxidrome (or syndrome caused by a dangerous

drug level) is caused by overdose of drugs that act as antagonists of

acetylcholine at peripheral and central muscarinic receptors; examples

are antihistamines, benztropine, and phenothiazines. Important

differences between serotonin syndrome and anticholinergic syndrome

are highlighted below.

• The causative agents act on a different neurotransmitter

receptor site

• The temperature is usually 38.8°C or less

• The patient will have dry mucous membranes, hot, dry, and

flushed skin, decreased or absent bowel sounds, normal

muscular tone and reflexes, and urinary retention

Malignant Hyperthermia

Malignant hyperthermia is an idiosyncratic response to inhalational

anesthesia. Important differences between serotonin syndrome and

malignant hyperthermia are:

• The causative agent

• Malignant hyperthermia is an idiosyncratic response, but

serotonin syndrome is a normal physiological response to an

excess of a neurotransmitter

• The patient will have hyporeflexia and the temperature is

extremely high, as high as 46°C

Other clinical conditions that could be mistaken for serotonin syndrome

include acute baclofen overdose, cocaine or ecstasy intoxication, drug

withdrawal, dystonic reactions, encephalitis, meningitis, non-


convulsive seizures, sympathomimetic syndrome caused by a large

dose (or an overdose of sympathomimetic drugs), sepsis, serotonin

discontinuation syndrome, thyroid storm, and tetanus.

There are many clinical conditions that can be mistaken for serotonin

syndrome, and trying to remember them all and their distinguishing

features can be difficult for clinicians. However, by far the most

commonly occurring are NMS and anticholinergic syndrome. To

distinguish between NMS, anticholinergic syndrome and serotonin

syndrome, the clinician needs to pay special attention to: 1) The drug

ingested, 2) Body temperature, 3) Onset and development of the signs

and symptoms, 4) Bowel sounds, 5) Presence or absence of

hyperreflexia, and 5) Presence or absence of clonus.

Serotonin Discontinuation Syndrome

When checking for the presence of serotonin syndrome, it is important

to know what medications the patient has been taking, as was

previously raised. However, if a symptomatic patient had been taking

an SSRI or another drug that affects the serotonergic system, this can

confuse the issue of assessment because if these drugs are not

tapered correctly the patient may develop serotonin discontinuation

syndrome. The syndrome occurs in approximately 20% to 33% of all

patients who stop taking a serotonergic drug.18

The signs and symptoms of serotonin discontinuation syndrome

usually start within one to seven days of decreasing the dose or

discontinuing the drug and they last approximately two weeks.

Somatic signs and symptoms of serotonin discontinuation syndrome

include chills, diarrhea, dizziness, fatigue, fever, nausea, paresthesias,


unsteady gait, and vomiting. Mood disturbances such as agitation,

anxiety, insomnia, irritation, and lethargy are common, as well.18 Most

cases are mild, but severe effects have been reported.

Treatment Of Serotonin Syndrome

Most cases of serotonin syndrome will improve dramatically or resolve

within 24 hours but if the patient has taken a drug with a long half-life,

a drug with pharmacologically active metabolites, or an extended

release form of a drug, the signs and symptoms can last for weeks.

Mild cases can be observed for six hours and if the patient responds

well to treatment or improves spontaneously, he/she can be

discharged. Those with moderate and severe cases should be

admitted, and patients who have ingested an extended release

preparation should be admitted or observed for longer than six

hours.2,4-6,20

Serotonin syndrome can be caused by an overdose of serotonergic

medications, but what is considered to be an overdose? The amount of

medication that could cause serotonin syndrome cannot be precisely

quantified, but evidence-based clinical guidelines for the SSRIs are

available to help guide clinical decision-making. The U.S. Food and

Drug Administration (FDA) publishes updated safety alerts relative to

drugs that can cause serotonin toxicity, and list serotonergic drugs to

avoid or monitor, if prescribed. For example, in March 2016 a FDA

Safety Alert announced that “Opioids can interact with antidepressants

and migraine medicines to cause a serious central nervous system

reaction called serotonin syndrome, in which high levels of the

chemical serotonin build up in the brain and cause toxicity.”19


The majority of serotonin syndrome cases occur because of the

ingestion of synergistic medication either unintentionally or

intentionally. Drugs known to inhibit the cytochrome P450 2D6 and/or

3A4 (CYP3A4) isoenzymes are often implicated as causing serotonin

syndrome when added to therapeutic regimens of selective serotonin

reuptake inhibitors (SSRIs). In one case report, serotonin syndrome

was precipitated in a 12-year-old patient taking a stable dosage of

sertraline when erythromycin, a CYP3A4 inhibitor, was also prescribed.

A remarkable number of drugs from different classes have been

implicated as causing serotonin syndrome.21 Most reported cases are

in patients taking multiple serotonergic agents or who have had

considerable exposure to a single serotonin-augmenting drug.

Death from serotonin syndrome is unusual, but severe cases do occur

and the condition of patients who have severe serotonin syndrome

deteriorates very quickly. Patients who have severe serotonin

syndrome should be admitted to intensive care. The use of the drugs

suspected of causing the serotonin syndrome must be immediately

stopped; in mild cases this may be enough to allow the patient to

recover.4,5

In order to avoid serious harm and to successfully treat serotonin

syndrome, it is critical to quickly identify serotonin syndrome and

aggressively provide supportive care. Antidotal therapies have been

tried, but supportive care is the keystone of caring for a patient who

has serotonin syndrome.


Supportive Care

The mainstay of treatment for serotonin syndrome is supportive care.

It includes the following diagnostic tests and therapy.4-6

Laboratory Tests

If the diagnosis of serotonin syndrome is thought to be likely or the

diagnosis seems certain, BUN and creatinine, coagulation studies,

complete blood count (CBC), creatine phosphokinase, and serum

transaminases should be obtained.

Other tests that may be needed for making the diagnosis of serotonin

syndrome would be blood cultures, urinalysis and urine culture,

cerebrospinal fluid analysis and culture, chest X-ray, and CT scan of

the head.

Aggressive Cooling

Aggressive cooling should be used for patients who are hyperthermic.

Acetaminophen will not help because hyperthermia in serotonin

syndrome is caused by excessive muscular activity, not by a change in

central thermoregulation.

Intubation and Neuromuscular Paralysis

Intubation and neuromuscular paralysis will treat the hyperthermia as

well as the basic cause of hyperthermia. The neuromuscular blocker

succinylcholine should not be used during the intubation process. A

nondepolarzing drug such as vercuronium should be used.


Patients who are hyperthermic often have rhabdomyolysis.

Rhabdomyolysis increases serum potassium and increases the risk of

arrhythmias, and succinylcholine can cause hyperkalemia.

Benzodiazepines

Benzodiazpines are one of the mainstays of treatment for serotonin

syndrome, and in animal models they have been shown to increase

survival rates. They decrease muscular rigidity, provide sedation and

their use alone may be all that is needed for a mild to moderate case

of serotonin syndrome.

Direct-acting Sympathomimetic

If the patient is hypotensive a direct-acting sympathomimetic should

be used; i.e., epinephrine, norepinephrine, or phenylephrine.

Dopamine acts indirectly. It must be metabolized to epinephrine and

norepinephrine before it can work and in cases of serotonin syndrome

the metabolizing enzyme (monoamine oxidase) may be inhibited.

Nitroprusside

Nitroprusside is a good drug to use for treating hypertension caused

by serotonin syndrome because its effects are very short-acting; the

half-life of nitroprusside is two to three minutes. The autonomic

instability in severe cases of serotonin syndrome means that blood

pressure can be very unstable and unpredictable so using a drug that

can be tightly controlled is a big advantage.


Hydration Status

Hydration is a very important treatment for serotonin syndrome.

Intravenous infusion for severe volume depletion is recommended.

Complications of Serotonin Syndrome

There should be monitoring of the complications of serotonin

syndrome, which are coma, disseminated intravascular coagulation

(DIC), metabolic acidosis, renal failure, and rhabdomyolysis.

Special Therapies

There is no antidote for serotonin syndrome that has been proven to

be effective and safe or for which there is extensive clinical evidence.

Bromocriptine, chlorpromazine, cyproheptadine, dantrolene,

intravenous lipid, olanzapine, propranolol, and other drugs/therapies

have been used. However, the evidence that supports or does not

support the use of these drugs can be categorized as Level II, and

there are no controlled studies that compare these drugs or truly

determine their efficacy. For example, there are case reports that

suggest use of chlorpromazine, cyproheptadine, and olanzapine helped

control and shorten the duration of the signs and symptoms of

serotonin syndrome, but it may simply be that these cases

represented a natural process of recovery and the drugs had no effect.

The drugs associated with the treatment of serotonin syndrome are

reviewed below.

Chlorpromazine

Chlorpromazine (commonly known as Thorazine®) is an antipsychotic.

The therapeutic effect of chlorpromazine is due to its action as a


centrally acting dopamine antagonist. But chlorpromazine also blocks

serotonin binding to 5-HT2A receptors and there are several case

reports of chlorpromazine being an effective drug for treating

serotonin syndrome. However, chlorpromazine can cause hypotension,

it can cause dystonias, and it may aggravate hyperthermia, so it

should be used cautiously when treating serotonin syndrome.

Chlorpomazine is contraindicated for treating NMS because it is a

dopamine antagonist.

Cyproheptadine

Cyproheptadine (Periactin®) is an antihistamine that acts as a 5-HT2A

antagonist, and it has been successfully used to treat cases of

serotonin syndrome, and, in some of these case reports, the resolution

of the signs and symptoms was rapid and considerable. However,

treatment failures have been noted, and several authors point out that

although cyproheptadine may be helpful it does not shorten the time

course of serotonin syndrome. Cooper, B.E. (2013) noted there are no

controlled studies that have evaluated the use of cyproheptadine for

the treatment of serotonin syndrome, the evidence for its efficacy is all

from case reports, and these case reports described mild to moderate

cases of serotonin syndrome.20 Despite these uncertainties,

cyproheptadine is still recommended as an adjunct, as it is a serotonin

receptor antagonist and has sedative properties.

Cyproheptadine is given orally, and if the patient cannot tolerate oral

intake it can be crushed and given via a nasogastric tube. The dose is

12 mg followed by 2 mg doses every two hours if the symptoms

persist. The maintenance dose is 8 mg every six hours. The pediatric


dosing is 0.25 mg/kg/day, every two hours until improvement of

symptoms.

Olanzapine

Olanzapine (Zyprexa®) is an atypical antipsychotic. One of its actions

is 5-HT2 receptor antagonism, and sublingual olanzapine has been

used successfully to treat cases of serotonin syndrome. Although most

of the patients studied had a very quick and complete resolution of

their signs and symptoms, the clinical experience with using

olanzapine to treat these cases consists of small case trials.

Bromocriptine

Bromocriptine has been used to treat serotonin syndrome. However, it

has serotonergic effects and its use has caused one fatality. The drug

should not be used to treat serotonin syndrome.

Dantrolene

Dantrolene is a skeletal muscle relaxant that is used to treat malignant

hyperthermia. It should not be used to treat serotonin syndrome.

There is no clinical evidence that it is effective, and, animal studies

showed that it is not effective. Dantrolene may actually cause

serotonin syndrome, and its use in a suspected case of serotonin

syndrome was associated with a fatality.

Propranolol

Propranolol acts as a 5-HT1A antagonist but it can cause hypotension.

It also decreases heart rate, making it difficult to assess the patient’s

condition. It should not be used to treat serotonin syndrome.


Intravenous Lipid

There is one case report of intravenous lipid being used for the

treatment of serotonin syndrome. The authors noted that there was a

temporal association between administration of the lipid therapy and a

decrease in hyperreflexia and rigidity.

Summary

Serotonin syndrome is a group of signs and symptoms caused by

excessive stimulation of serotonin receptors. Serotonin syndrome is

caused by therapeutic doses, overdoses, or drug interactions between

medications that directly or indirectly affect the serotonergic system.

Direct stimulation of serotonin receptors, decreased breakdown of

serotonin, increased inhibition of serotonin reuptake, an increase in

serotonin precursors, or an excessive release of serotonin cause

serotonin syndrome.

Medications that can cause serotonin syndrome include SSRIS, MAOIs,

illicit drugs such as cocaine and amphetamines, atypical

antipsychotics, and analgesics such as fentanyl, meperidine, and

tramadol, and dextromethorphan. The incidence and severity of

serotonin syndrome are greatest when multiple drugs have been

ingested. A particularly dangerous drug combination is the MAOIs

combined with SSRIs, dextromethorphan, ecstasy, or meperidine.

Serotonin syndrome is characterized by autonomic, cognitive, and

neuromuscular derangements. Agitation, tachycardia, hypertension,

hyperthermia, muscle rigidity, clonus, hyperreflexia, diaphoresis,

diarrhea are commonly seen. Signs and symptoms usually start within


six hours, and typically last 24 hours. Clonus (inducible, spontaneous

or ocular) is the most reliable clinical finding for diagnosing serotonin

syndrome.

To distinguish serotonin syndrome, determine what drug was ingested,

determine when the signs and symptom started, observe for clonus

and hyperreflexia, and check body temperature and bowel sounds. A

severe case of serotonin syndrome is a medical emergency; patients

who have severe serotonin syndrome should be admitted to the

intensive care unit.

The best treatment for serotonin syndrome is supportive care.

Epinephrine, norepinephrine, or phenylephrine is recommended to

treat hypotension; alternatively, nitroprusside is recommended to

control hypertension. Additionally, aggressive cooling, neuromuscular

paralysis and intubation, benzodiazepines, and IV hydration were

raised as the most important and effective therapies.

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syndrome?


b. Signs/symptoms caused by serotonergic drug overdose. c. A clinical condition that closely resembles neuroleptic

malignant syndrome. d. A clinical condition characterized hyperthermia, clonus, and

agitation.


a. Common analgesics

b. Illicit drugs

c. Sympathomimetics d. SSRIs


a. Methamphetamine, heroin, marijuana

b. Cocaine, LSD, ecstasy c. Marijuana, ecstasy, cocaine

d. Dextromethorphan, LSD, methamphetamine

4. The criteria most often used and recommended to diagnose serotonin syndrome are the

a. Sternbach criteria.

b. Hunter criteria.

c. Radomski criteria. d. Romberg criteria.

5. True or False: Neuroleptic malignant syndrome may be

mistaken for serotonin syndrome.

a. True b. False


6. The diagnostic sign that is most reliably noted in cases of

serotonin syndrome is:

a. Hyperthermia b. Hallucinations

c. Tremor d. Clonus

7. The best therapy for serotonin syndrome and three specific

treatments include:

a. Supportive care: intubation, fluids, dantrolene b. Supportive care: aggressive cooling, benzodiazepines,

cyproheptadine c. Antidotal therapy: cyproheptadine, chlorpromazine

d. Discontinuation of the drug: supportive care

8. Drugs that should not be used to treat serotonin syndrome

are:

a. Cyproheptadine, acetaminophen b. Dopamine, epinephrine, chlorpromazine

c. Olanzapine, tramadol, phenylephrine d. Bromocriptine, dantrolene, propranolol

9. The causes of serotonin syndrome are:

a. Prolonged use of drugs that affect the serotonergic system.

b. Therapeutic use, overdose, or drug interaction c. Improper tapering of medications that affect the serotonergic

system.

d. It is an inevitable consequence for some people who take serotonergic drugs.

10. The three categories of signs/symptoms that are

diagnostic of serotonin syndrome are:

a. Cardiovascular, autonomic, cognitive b. Metabolic, neuromuscular, cognitive

c. Cognitive, neuromuscular, autonomic d. Psychiatric, metabolic, cardiovascular


11. True or False: Serotonin is synthesized in the central

nervous system and in enterochromaffin cells in the gastrointestinal (GI) tract.

a. True

b. False

12. When treating serotonin syndrome hyperthermia, during the intubation process the clinician should use

a. the neuromuscular blocker succinylcholine.

b. chlorpomazine. c. acetaminophen.

d. a nondepolarzing drug such as vercuronium.

13. Patients who are hyperthermic often have rhabdomyolysis,

which

a. leads to decreased or absent bowel sounds. b. causes bradyreflexia and a rigid, lead-pipe like muscle tone.

c. increases serum potassium and the risk of arrhythmias. d. leads to hypokalemia and urinary retention.

14. When a patient, who has the symptoms of serotonin

syndrome, has been taking an SSRI or another drug that affects serotonergic system, the patient may develop

serotonin discontinuation syndrome

a. if these drugs are not stopped immediately. b. if these drugs are not tapered correctly.

c. unless the dosage is increased.

d. if these drugs are combined with succinylcholine.

15. ______________ may actually cause serotonin syndrome, and its use in a suspected case of serotonin syndrome was

associated with a fatality.

a. Dantrolene b. Vercuronium

c. Chlorpromazine d. Cyproheptadine


CORRECT ANSWERS:


syndrome?


“Serotonin syndrome is a group of signs and symptoms

caused by excessive stimulation of the serotonin receptors. The essential cause of serotonin syndrome is an excess

stimulation of the serotonergic receptors. The stimulation is excitatory and causes the tachycardia, hypertension,

agitation, and excessive muscular activity and the other signs and symptoms of the syndrome.”


d. SSRIs

“Decreased serotonin reuptake occurs with selective

serotonin-reuptake inhibitors (SSRIs), such as citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and

sertraline; as well as, dextromethorphan, monoamine oxidase inhibitors, methadone, and trazodone.”


b. Cocaine, LSD, ecstasy

“The essential cause of serotonin syndrome is an excess stimulation of the serotonergic receptors. The stimulation is

excitatory and causes the tachycardia, hypertension, agitation, and excessive muscular activity and the other signs

and symptoms of the syndrome. The excess stimulation occurs by one of the following six mechanisms: ... Direct

stimulation of the serotonergic receptors occurs with the medications of buspirone, carbamazapine, lithium, as well as

with the psychedelic drug LSD.... Excessive release of serotonin occurs with amphetamines, cocaine,

dextromethorphan, levodopa, monoamine oxidase inhibitors, reserpine, as well as with ecstasy/MDMA.”


4. The criteria most often used and recommended to diagnose

serotonin syndrome are the

b. Hunter criteria.

“... the Radomski criteria are intended to provide diagnostic criteria for establishing the severity of the serotonin

syndrome. The Hunter criteria (or those criteria slightly adapted) is the system that is used most often and is

recommended. The Sternbach criteria appear to be biased towards mental status changes, and the Hunter criteria are

felt to be more sensitive and specific and less likely than the Sternbach criteria to miss incipient or mild cases of serotonin

syndrome. The Radomski criteria do not appear to be popular and although other diagnostic criteria have been developed

(i.e., the serotonin syndrome scale) these do not appear to be

in common use.... Serotonin syndrome along the spectrum can be diagnosed by using the Hunter criteria to look for the

characteristic autonomic, cognitive, and neuromuscular changes.”

5. True or False: Neuroleptic malignant syndrome may be

mistaken for serotonin syndrome.

a. True

“Serotonin syndrome can be mistaken for an infectious or metabolic disorder or for the clinical syndromes caused by

anticholinergic or sympathomimetic poisoning, or for the neuroleptic malignant syndrome or malignant hyperthermia.”

6. The diagnostic sign that is most reliably noted in cases of serotonin syndrome is:

d. Clonus

“Clonus - inducible, spontaneous or ocular- is the most

reliable clinical finding for diagnosing serotonin syndrome.”


7. The best therapy for serotonin syndrome and three specific

treatments include:

b. Supportive care: aggressive cooling, benzodiazepines, cyproheptadine

“The mainstay of treatment for serotonin syndrome is

supportive care. It includes the following diagnostic tests and therapy.... Aggressive cooling should be used for patients who

are hyperthermic.... Benzodiazpines are one of the mainstays of treatment for serotonin syndrome, and in animal models

they have been shown to increase survival rates.... Cyproheptadine (Periactin®) is an antihistamine that acts as

a 5-HT2A antagonist, and it has been successfully used to treat cases of serotonin syndrome, and, in some of these case

reports, the resolution of the signs and symptoms was rapid

and considerable.”

8. Drugs that should not be used to treat serotonin syndrome are:

d. Bromocriptine, dantrolene, propranolol

“Bromocriptine has been used to treat serotonin syndrome.

However, it has serotonergic effects and its use has caused one fatality. The drug should not be used to treat serotonin

syndrome.... Dantrolene is a skeletal muscle relaxant that is used to treat malignant hyperthermia. It should not be used

to treat serotonin syndrome. There is no clinical evidence that it is effective, and, animal studies showed that it is not

effective. Dantrolene may actually cause serotonin syndrome,

and its use in a suspected case of serotonin syndrome was associated with a fatality.... Propranolol acts as a 5-HT1A

antagonist but it can cause hypotension. It also decreases heart rate, making it difficult to assess the patient’s condition.

It should not be used to treat serotonin syndrome.”

9. The causes of serotonin syndrome are:

b. Therapeutic use, overdose, or drug interaction

“Serotonin syndrome is caused by therapeutic doses, drug interactions, or overdoses of medications that directly or

indirectly affect the serotonergic system.”


10. The three categories of signs/symptoms that are

diagnostic of serotonin syndrome are:

c. Cognitive, neuromuscular, autonomic

“Serotonin syndrome is characterized by autonomic, cognitive, and neuromuscular derangements.... Serotonin

syndrome along the spectrum can be diagnosed by using the Hunter criteria to look for the characteristic autonomic,

cognitive, and neuromuscular changes.”

11. True or False: Serotonin is synthesized in the central nervous system and in enterochromaffin cells in the

gastrointestinal (GI) tract.

a. True

“Serotonin (also called 5-hydroxytryptamine) is a monoamine

neurotransmitter that acts centrally and peripherally. It is synthesized in the central nervous system and in

enterochromaffin cells in the gastrointestinal (GI) tract.”

12. When treating serotonin syndrome hyperthermia, during the intubation process the clinician should use

d. a nondepolarzing drug such as vercuronium.

“Aggressive cooling should be used for patients who are

hyperthermic. Acetaminophen will not help because hyperthermia in serotonin syndrome is caused by excessive

muscular activity, not by a change in central

thermoregulation.... Intubation and Neuromuscular Paralysis: This will treat the hyperthermia as well as the basic cause of

hyperthermia. Do not use the neuromuscular blocker succinylcholine during the intubation process. Use a

nondepolarzing drug such as vercuronium.... chlorpromazine can cause hypotension, it can cause dystonias, and it may

aggravate hyperthermia, so it should be used cautiously when treating serotonin syndrome. Chlorpomazine is

contraindicated for treating NMS because it is a dopamine antagonist.”


13. Patients who are hyperthermic often have rhabdomyolysis,

which

c. increases serum potassium and the risk of arrhythmias.

“Patients who are hyperthermic often have rhabdomyolysis. Rhabdomyolysis increases serum potassium and increases the

risk of arrhythmias, and succinylcholine can cause hyperkalemia.”

14. When a patient, who has the symptoms of serotonin

syndrome, has been taking an SSRI or another drug that affects serotonergic system, the patient may develop

serotonin discontinuation syndrome

b. if these drugs are not tapered correctly.

“When checking for the presence of the serotonin syndrome,

it is important to know what medications the patient has been taking; this was previously discussed. However, if a

symptomatic patient had been taking an SSRI or another drug that affects serotonergic system, this can confuse the

issue of assessment because if these drugs are not tapered correctly the patient may develop serotonin discontinuation

syndrome. The syndrome occurs in approximately 20%-25% of all patients who stop taking a serotonergic drug.”

15. ______________ may actually cause serotonin syndrome,

and its use in a suspected case of serotonin syndrome was associated with a fatality.

a. Dantrolene

“Dantrolene may actually cause serotonin syndrome, and its use in a suspected case of serotonin syndrome was

associated with a fatality.”


References Section

The References below include published works and in-text citations of

published works that are intended as helpful material for your further reading.

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SEROTONIN SYNDROME - Nurse CEUs Online - … nursece4less.com nursece4less.com nursece4less.com nursece4less.com 5 Introduction Serotonin syndrome is a group of signs and symptoms