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Toxicity, Selective Serotonin Reuptake Inhibitor: Treatment & Medication
Updated: Oct 22, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Prehospital Care
Prehospital care includes airway management and arrhythmia treatment per ACLS protocols; consider naloxone 2 mg IV, 50 mL of D50W, and thiamine 100 mg IV as well as a fingerstick glucose level for altered mental status. Of prime importance is getting history from any bystanders or family members and collecting ancillary materials, such as pills, empty pill bottles or medication packets, and suicide notes. If given, naloxone should be gradually titrated starting with 0.05 or 0.1 mg, and repeated if needed, to avoid rapid precipitation of opioid withdrawal.
Out-of-hospital management guidelines are available from the American Association of Poison Control Centers.17
Emergency Department Care
As for all care in the emergency department, the patient needs immediate evaluation and stabilization of the airway, breathing, and circulation, even without knowledge of the ultimate diagnosis. Treatment of serotonin syndrome is primarily supportive. The severity of presentation helps to guide appropriate emergency department care.
- Mild cases: Check laboratory results as indicated, intravenous fluids, benzodiazepines for agitation/restlessness, avoidance of all serotonergic medications.
- Moderate cases: Treat hyperthermia with cooling blankets, fans, ice packs, and intravenous fluids. The role for antipyretics is limited, as the mechanism of temperature alteration is centrally mediated. Administer activated charcoal if a potentially lethal amount has been ingested and if presentation is within 1-2 hours. Treat neuromuscular abnormalities with benzodiazepines.
- Severe cases: Patients with hyperthermia, depressed mental status, and vital sign abnormalities should be treated aggressively. All patients should be treated as above, with the addition of airway protection and ventilation if needed. Paralysis and mechanical ventilation are necessary to avoid worsening muscle rigidity and increasing hyperthermia in any patient with a temperature higher than 41ºC. Patients with severe hyperthermia that is unresponsive to aforementioned measures should be immersed into an ice bath to achieve rapid cooling and to prevent development of DIC and multiorgan failure (MOF). Avoid succinylcholine as a paralytic in any patient with possible rhabdomyolysis to prevent development of hyperkalemia.
- Severely ill patients could be treated pharmacologically with 5HT antagonists, such as cyproheptadine18 (see dosing information below). Efficacy has not been established in randomized clinical trials; however, it has shown benefit in animal models and case reports. It is available only in oral form, which can be crushed and infused via nasogastric tube. Caution should be exercised in hyperthermic patients, because cyproheptadine has anticholinergic properties and theoretically can worsen hyperthermia.
- Autonomic instability requires treatment with short-acting agents that are amenable to titration, such as nitroprusside and esmolol.
- Treat rhabdomyolysis with aggressive hydration, and alkalinize urine with sodium bicarbonate for renal protection.19
Consultations
- Medical toxicologist
- Poison Control Center at (800) 222-1222 (US and territories only)
- Psychiatrist
Medication
Pharmacologic treatment of the serotonin syndrome is largely based on anecdotal case reports and on animal models. Supportive care remains the basis of treatment; however, severe cases may benefit from the following interventions.
Adsorbent antidotes
These agents inhibit GI absorption of certain toxic agents or irritants.
Activated charcoal (Liqui-Char)
Emergency treatment used in poisoning caused by drugs and chemicals. Network of pores present in activated charcoal absorbs 100-1000 mg of drug per gram of charcoal. Prevents absorption by adsorbing drug in the intestine. Multidose charcoal may interrupt enterohepatic recirculation and enhance elimination by enterocapillary exsorption. Theoretically, by constantly bathing the GI tract with charcoal, the intestinal lumen serves as a dialysis membrane for reverse absorption of drug from intestinal villous capillary blood into intestine. Does not dissolve in water.
For maximum effect, administer within 30-60 min after ingesting poison. Addition of sorbitol results in hyperosmotic laxative action causing catharsis, further inhibiting intestinal absorption of toxic substances.
Adult
1 g/kg PO or per nasogastric tube mixed with sorbitol or in aqueous solution
Pediatric
1 g/kg PO; 15-30 g/dose maximum
May inactivate syrup of ipecac if used concomitantly; effectiveness of other medications decrease with coadministration; do not mix charcoal with sherbet, milk, or ice cream (decreases absorptive properties of activated charcoal)
Documented hypersensitivity; aspiration risk/unprotected airway; acid or alkali ingestions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Check for bowel sounds prior to administering activated charcoal; aspiration of charcoal is highly irritable to lungs; not for administration to anyone without a secured airway; not very effective in poisonings of ethanol, methanol, and iron salts; induce emesis before giving activated charcoal; after emesis with ipecac, patient may not tolerate activated charcoal for 1-2 h; can administer in early stages of gastric lavage; without sorbitol, gastric lavage returns will be black
Serotonin antagonists
Cyproheptadine, chlorpromazine, and methylsergide have all been reported to be useful in SS to block postsynaptic serotonin receptors. No formalized dosing regimens have been established; the following recommendations are based on case reports and reviews of serotonin toxicity treatment.
Cyproheptadine (Periactin)
A 5HT (2a) antagonist. Has been shown in animal studies and case reports to reduce symptoms of SS. May be helpful in mild-to-moderate cases of serotonin syndrome.
Adult
8-12 mg PO initially, followed by 2-4 mg q2h until symptoms resolve; not to exceed 0.5 mg/kg/d
Pediatric
<2 years: Not recommended
2-6 years: 2 mg PO bid/tid; not to exceed 12 mg/d
7-14 years: 4 mg PO bid/tid; not to exceed 16 mg/d
>14 years: Administer as in adults
Potentiates effects of CNS depressants; MAO inhibitors may prolong and intensify anticholinergic and sedative effects of antihistamines
Documented hypersensitivity; narrow-angle glaucoma; stenosing peptic ulcer; symptomatic prostatic hypertrophy; symptomatic BPH; bladder neck obstruction; pyloroduodenal obstruction; lower respiratory tract symptoms
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in patients with a predisposition to urinary retention, history of bronchial asthma, increased intraocular pressure, hyperthyroidism, cardiovascular disease, or hypertension; may thicken bronchial secretions caused by anticholinergic properties and may inhibit expectoration and sinus drainage; antihistamines may cause hallucinations and CNS depression in children, and less often may produce paradoxical excitation
Sedatives and anticonvulsants
Benzodiazepines are considered mainstay treatment in treating SS, particularly neuromuscular symptoms and seizures. They are also excellent for controlling agitated behavior.
Lorazepam (Ativan)
Sedative with rapid onset and relatively long half-life. By increasing the action of gamma-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter in the brain, may depress all levels of CNS, including limbic and reticular formation.
Anticonvulsant effects last longer than diazepam or midazolam (4-6h).
Adult
0.5-2 mg IV over 2-5 min; repeat q10-15min prn
Pediatric
0.05-0.1 mg/kg/dose IV over 2-5 min; not to exceed 4 mg/dose; repeat dose of 0.05 mg/kg q10-15 min prn
Toxicity of benzodiazepines in CNS increases when used concurrently with alcohol, phenothiazines, barbiturates, and MAO inhibitors
Documented hypersensitivity; CNS depression; hypotension; acute narrow-angle glaucoma
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in patients with hepatic or renal dysfunction, myasthenia gravis, Parkinson disease, or organic brain syndrome; may cause respiratory depression, especially in combination with other sedatives; patients with significant respiratory/mental status depression may require endotracheal intubation for airway protection
Diazepam (Valium)
Modulates postsynaptic effects of GABA-A transmission, resulting in an increase in presynaptic inhibition. Appears to act on part of the limbic system, thalamus, and hypothalamus to induce a calming effect. Also has been found to be an effective adjunct for the relief of skeletal muscle spasm caused by upper motor neuron disorders.
Rapidly distributes to other body fat stores. Twenty minutes after initial IV infusion, serum concentration drops to 20% of Cmax.
Individualize dosage and increase cautiously to avoid adverse effects.
Adult
0.02-0.05 mg/kg IV q10-15min until symptoms resolve; not to exceed 30 mg in 8-h period; some clinicians are comfortable even with the larger cumulative doses; however, risk of respiratory depression increases with doses larger than 30 mg over 8 h
Pediatric
30 days to 5 years: 0.05-0.3 mg/kg/dose IV over 2-3 min q10-15min; not to exceed total dose of 5 mg
>5 years: 1 mg/dose IV over 2-3min q10-15min; not to exceed total dose of 10 mg
Phenothiazines, barbiturates, alcohols, and MAO inhibitors increase CNS toxicity when administered concurrently
Documented hypersensitivity; CNS depression; hypotension; acute narrow-angle glaucoma
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution with other CNS depressants, low albumin levels, or hepatic or renal dysfunction (may increase toxicity)
Antihypertensives
Used for the treatment of autonomic instability and malignant hypertension as evidenced by end-organ damage of the brain, heart, and/or kidneys.
Nitroprusside (Nitropress)
Produces arterial and venous vasodilation. Decreases afterload and preload and may produce a reflex tachycardia.
Adult
0.1-8 mcg/kg/min IV, titrate to effect; not to exceed 10 mcg/kg/min
Pediatric
Administer as in adults
Effects are additive when administered with other hypotensive agents
Documented hypersensitivity; subaortic stenosis; decreased cerebral perfusion; arteriovenous shunt or coarctation of aorta (eg, compensatory hypertension); atrial fibrillation or flutter
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in increased intracranial pressure, hepatic failure, severe renal impairment, and hypothyroidism; in renal or hepatic insufficiency, nitroprusside levels may increase and can cause cyanide toxicity; sodium nitroprusside has the ability to lower blood pressure and thus should be used only in patients with mean arterial pressures >70 mm Hg
Neuromuscular Blockade, Paralytic
To control hyperreflexia, clonus, and hyperthermia, total neuromuscular paralysis may be required. Succinylcholine should be avoided in SS given the risk of hyperkalemia secondary to rhabdomyolysis.
Rocuronium (Zemuron)
Nondepolarizing neuromuscular blocking agent with rapid to intermediate onset (depending on dose) and intermediate duration. Competes for cholinergic receptors at motor end-plate to antagonize action of acetylcholine, which in turn blocks neuromuscular transmission. Acetylcholinesterase inhibitors such as neostigmine and edrophonium antagonize action.
Adult
0.6 mg/kg IV
Pediatric
Administer as in adults
Coadministration with antibiotics (eg, aminoglycosides, vancomycin, tetracyclines, bacitracin, polymyxin, colistin, sodium colistimethate), verapamil, succinylcholine, magnesium sulfate, quinidine, and ketamine, may enhance neuromuscular blocking action of rocuronium; coadministration with azathioprine, carbamazepine, phenytoin, and theophyllines may decrease neuromuscular blocking action
Documented Hypersensitivity; inability to ventilate
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Administer carefully adjusted dosages by or under supervision of experienced clinicians familiar with drug's actions and possible complications of use; drug should not be administered unless facilities for intubation, artificial respiration, oxygen therapy, and an antagonist are immediately available; recommended that clinicians administering neuromuscular blocking agents such as rocuronium use peripheral nerve stimulator to monitor drug response, need for additional relaxant, and adequacy of spontaneous recovery or antagonism; use caution in patients with pulmonary hypertension or valvular heart disease (may be associated with increased pulmonary vascular resistance)
Vecuronium (Norcuron)
Prototypic, non-depolarizing neuromuscular blocking agent that reliably results in muscular paralysis. For intubation and maintenance of paralysis a continuous infusion may be used.
Infants are more sensitive to neuromuscular blockade activity and although the same dose is used, recovery is prolonged by 50%. Drug is not recommended for use in neonates.
Adult
0.08-0.1 mg/kg IV; may reduce to 0.05 mg/kg if patient has been treated with succinylcholine
Maintenance for paralysis: 0.025-0.1 mg/kg/h IV, and can be titrated to desired train-of-four response (commonly 2 of 4 twitches)
Pediatric
<7 weeks: Not established
7 weeks to 1 year: 0.08-0.1 mg/kg/dose IV followed by maintenance dose of 0.05-0.1 mg/kg q1h prn
1-10 years: May require higher initial dose and more frequent supplementation
>10 years: Administer as in adults
When vecuronium is used concurrently with inhalational anesthetics, neuromuscular blockade is enhanced; renal or hepatic failure, as well as, concomitant administration of steroids, may result in prolonged blockade despite withdrawal of the agent
Documented hypersensitivity; myasthenia gravis or related syndromes
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
In myasthenia gravis or myasthenic syndrome, small doses of vecuronium may have profound effects
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| Differential Diagnoses & Workup: Toxicity, Selective Serotonin Reuptake Inhibitor |
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Further Reading
Keywords
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