Serotonin Syndrome


Inhibitors of serotonin reuptake

Selective serotonin reuptake inhibitors (SSRIs): fluoxetine, paroxetine, sertraline, citalopram, fluvoxamine

Serotonin-norepinephrine reuptake inhibitors (SNRIs): venlafaxine, desvenlafaxine, duloxetine, milnacipran

Tricyclic antidepressants (TCAs): amitriptyline, nortriptyline, protriptyline clomipramine, imipramine, desipramine, trimipramine, amoxapine, doxepin, maprotiline

Dopamine-norepinephrine reuptake inhibitors: bupropion

Serotonin modulators: trazodone, nefazodone

Phenylpiperidine opioids: fentanyl, dextromethorphan

5-HT3 receptor antagonists: ondansetron, granisetron

Local anesthetics: cocaine

Herbal supplements: St. John’s wort (Hypericum perforatum)

Tramadol

Meperidine

Methadone

MDMA (ecstasy)

Inhibitors of serotonin metabolism

Monoamine oxidase inhibitors (MAOIs): St. John’s wort, linezolid, methylene blue, tranylcypromine, selegiline, phenelzine, isocarboxazid, furazolidone, Syrian rue

Increase serotonin synthesis

L-tryptophan

Increase serotonin release

Amphetamines and amphetamine derivatives: methamphetamine, fenfluramine, phentermine

Dopamine agonists: L-dopa and bromocriptine

MDMA (ecstasy)

Ethanol

Cocaine

Lithium

Serotonin receptor agonism

Antidepressants: buspirone, trazodone, mirtazapine

Antimigraines: triptans, valproic acid, carbamazepine

Ergot alkaloid derivatives: methylergonovine, ergotamine

Fentanyl

Metoclopramide

Buspirone

Lysergic acid diethylamide (LSD)

Increases sensitivity of postsynaptic receptor

Lithium


Adapted from reference [3]





Clinical Features and Diagnosis


The diagnosis of serotonin syndrome is purely clinical. Therefore, clinical suspicions should rise when a patient displays signs and symptoms of the syndrome following administration or dose increase of drugs known to act on the serotonergic system. Clinical manifestations of serotonin syndrome are described in terms of changes in mental status, autonomic function, and neuromuscular status (Table 49.2). The clinician should have high index of suspicion of this diagnosis should a patient who has been exposed to drugs with serotonergic activity develop a fever and altered mental status, autonomic instability, and increased (lower) limb rigidity [14].


Table 49.2
Clinical manifestations associated with serotonin syndrome























































Changes in mental status b

Agitation a

Delirium

Anxiety

Disorientation

Restlessness

Lethargy

Hallucinations

Autonomic dysfunction b

Hypertension

Tachycardia

Tachypnea

Hyperthermia a (temperature above 38 °C)

Arrhythmias

Flushed skin

Diaphoresis a

Dilated pupils

Vomiting

Shivering

Neuromuscular changes b

Clonus a (spontaneous or inducible, ocular)

Tremor a

Muscle rigidity

Hyperreflexia a

Hypertonia


Adapted from reference [13]

aItalics are signs/symptoms fulfilling Hunter Criteria for serotonin syndrome (see text for details of specific combination of symptoms)

bClinical pearl for remembering signs and symptoms of serotonin syndrome: acronym CAN (Changes in mental status, Autonomic dysfunction, Neuromuscular changes)

Several diagnostic criteria have been proposed for serotonin syndrome. The most recent diagnostic criteria are the Hunter Serotonin Toxicity Criteria (HSTC). When compared to the gold standard of diagnosis by a medical toxicologist, the HSTC are sensitive (84 %) and specific (97 %). The Hunter Criteria include the use of a serotonergic agent plus one out of five of the following: spontaneous clonus, inducible clonus plus agitation or diaphoresis, ocular clonus plus agitation or diaphoresis, tremor and hyperreflexia, hypertonia, and a temperature above 38 °C plus ocular or inducible clonus [3, 10, 11]. The presence of clonus and hyperreflexia is most important for the diagnosis; however, severe muscle rigidity may mask these symptoms. Prominent features of life-threatening cases include hyperthermia (>38.5 °C), peripheral hypertonicity, and truncal rigidity. These symptoms have shown a high risk of progression to respiratory failure [11]. There are some nonspecific laboratory abnormalities that may be seen in serotonin syndrome which include leukocytosis, low bicarbonate, and elevated creatinine and transaminases. Serum serotonin concentrations do not correlate with the severity of this syndrome [3, 15].

The differential diagnoses for serotonin syndrome are extensive. It includes neuroleptic malignant syndrome (NMS), malignant hyperthermia, anticholinergic toxicity, serotonergic discontinuation syndrome, sympathomimetic drug intoxication, meningitis, encephalitis, heat stroke, and central hyperthermia [3]. The main differential diagnosis is NMS which often has a slower onset, is associated with hyperthermia (>38 °C), and has a much higher mortality [16]. Table 49.3 summarizes some of the clinical features and diagnostic aids that differentiate NMS, malignant hyperthermia, and serotonin syndrome.


Table 49.3
Differentiating serotonin syndrome among common presentations




































 
Serotonin syndrome

Neuroleptic malignant syndrome

Malignant hyperthermia

Onset and resolution

Develops within 24 h

Develops over days to weeks

Develops in minutes or within 24 h

Resolves within 24 h of treatment

Resolves within days to weeks with treatment

Causative agents

Serotonin agonists

Dopamine antagonists

Halogenated inhalational anesthetics or depolarizing muscle relaxants

Neuromuscular changes

Hyperreactivity

Muscular rigidity and bradyreflexia

Rigidity and hyporeflexia

Treatment agents

Discontinue serotonergic agents; benzodiazepinesa; cyproheptadineb

Bromocriptine

Dantrolene


Adapted from references [3, 13, 15]

aBenzodiazepines for sedation (i.e., lorazepam 1–2 mg IV per dose in adults)

bCyproheptadine if agitation and abnormal vital signs persist with benzodiazepines and supportive care (initial adult dose 12 mg PO or OGT)

During the preoperative evaluation, emphasis should be placed on the history of ingested substances including prescription drug use, over-the-counter medication and dietary supplement use, illicit substance use, and any recent changes in dosing or addition of new drugs to a drug regimen. The onset and description of symptoms and the presence of any comorbidity are of utmost importance. Certain comorbidities, such as depression and chronic pain, may clue the clinician into the use of drugs that can precipitate serotonin syndrome [3]. Hypertension, atherosclerosis, and hyperlipidemia are all associated with reduced endothelial MAO activity which affects serotonin metabolism [17]. Also, a higher incidence of serotonin syndrome has been reported in patients with end-stage renal disease who are on selective serotonin reuptake inhibitors (SSRIs) and hemodialysis. These patients are prone to developing serotonin toxicity, suggesting that this increased toxicity could be related to a decrease in renal function [3, 4]. Furthermore, predisposing factors such as inherited or acquired deficits in peripheral serotonin metabolism may contribute to the development of serotonin syndrome. The preexisting conditions illustrated above coupled with the use of serotonergic drugs increase the chances of serotonin syndrome [17].

Only gold members can continue reading. Log In or Register to continue

Stay updated, free articles. Join our Telegram channel

Sep 18, 2016 | Posted by in ANESTHESIA | Comments Off on Serotonin Syndrome

Full access? Get Clinical Tree

Get Clinical Tree app for offline access