serotoninsyndrome
Table of Contents
serotonin syndrome
Introduction
- Serotonin syndrome is due to excess activation of post-synaptic 5HT1A in lower brain stem & spinal cord, perhaps with some dopaminergic involvement.
- 5HT is derived from L-tryptophan via tryptophan hydroxylase which converts it to 5-OH tryptophan which is then decarboxylated to form 5HT (5-OH tryptamine or serotonin).
- 5HT is degraded by monoamine oxidase A & is actively absorbed by circulating platelets.
- see also Serotonin physiology physiology.
Aetiology
- may be caused by one or more of the following:
- increased substrate supply:
- high doses of L-tryptophan or 5-OH tryptophan
- inhibition of serotonin metabolism:
- MAOI & a serotonin precursor combination (eg. tryptophan)
- MAOI & either SSRI or tricyclic
- NB. even if SSRI/TCA stopped < 2wks ago or fluoxetine in past 5wks!
- inhibition of serotonin reuptake
- SSRI/SNRI antidepressants, TCA's
- potentiation of serotonin activity
- activation of serotonin receptors by agents other than serotonin
- full 5HT1A agonist (8-OH DPAT, 5 Me ODMT) but not partial agonist (buspirone)
- 5HT agonists:
- clomipramine
- dextromethorphan (Actifed)
- fenfluramine (Ponderax) (no longer sold in Australia as of Sept 1997 as assoc. with valvulopathies)
- pentazocine (Fortral)
- pethidine
- Risk increased in pts with:
- ? disease states with decreased serotonin metabolism
- genetically slow metabolisers of serotonin (7% pop.)
Diagnostic criteria for the serotonin syndrome:
- recent addition or increase in dosage of an agent that enhances serotonin activity or availability
- absence of abused substances or other causes of hyperthermia
- no recent addition or increase in the dose of a neuroleptic (otherwise consider neuroleptic malignant syndrome (NMS))
- presence of at least 3 of:
- altered mental state
- agitation
- tremor
- shivering
- diarrhoea
- hyperreflexia (legs > UL)
- myoclonus - esp. ocular
- ataxia
- fever
Differential diagnosis of the serotonin syndrome:
- sepsis / septicaemia (esp. meningitis)
- drug abuse/withdrawal (esp. delirium tremens)
- malignant hyperthermia due to general anaesthesia
-
- NMS presents in a more toxic state, with more severely impaired consciousness, more likely to be febrile and at higher temperature than serotonin syndrome, with lead-pipe rigidity rather than myoclonus with raised WCC, LFT's & CK more likely, but nystagmus and diarrhoea is rare.
- hyper-reflexia tends to be UL > LL in contrast to serotonin syndrome
- sympathomimetic or anticholinergic overdose
- heat illness and heat stroke - exposure to heat, dehydration
- baseline psychiatric symptoms
- lethal catatonia
- akinetic, frequently exhibit rigidity and even fever +/- bizarre choreoform movements & torsion spasms.
- usually preceded by 2-3wks increasing depression & withdrawal
Mx of the serotonin syndrome:
- stop all serotoninergic drugs
- do not give antiemetics which will exacerbate the serotonin syndrome such as ondansetron, granisetron, and metoclopramide (Maxolon) (which is a 5-HT3 antagonist + 5-HT4 agonist + CNS dopamine antagonist)
- oxygen to maintain SaO2 > 93%
- IV fluids to treat volume depletion and hyperthermia
- sedate with benzodiazepines such as diazepam
- patients whose temperature is above 41.1ºC require immediate sedation, paralysis, and endotracheal intubation
- patients with severe hypertension and tachycardia should be treated with short-acting agents, such as esmolol or sodium nitroprusside - avoid long acting beta adrenergic blockers
- hypotension from MAOIs should be treated with low doses of direct-acting sympathomimetic amines such as phenylephrine, epinephrine, or norepinephrine
- Indirect agents (eg, dopamine) should be avoided because they are metabolized to epinephrine and norepinephrine; when monoamine oxidase is inhibited, epinephrine and norepinephrine production at the cellular level is not controlled, possibly leading to an exaggerated hemodynamic response
- limit muscle contractions (else risk of fever, rhabdomyolysis & resp. compromise):
- if mild: consider benzodiazepines, home & r/v 1 day
- if mod/severe: benzodiazepine ( consider lorazepam o/IV, or clonazepam as useful in myoclonus)
- if very severe: consider muscle paralysis & sedation with intubation
- other options:
- cyproheptadine orally
- cyproheptadine is a histamine-1 receptor antagonist with nonspecific 5-HT1A and 5-HT2A antagonistic properties. It also has weak anticholinergic activity.
- when administered as an antidote for serotonin syndrome, an initial dose of 12 mg is recommended, followed by 2 mg every two hours until clinical response is seen1).
- cyproheptadine is only available in an oral form, but it may be crushed and given through a nasogastric tube.
- chlorpromazine (Largactil) , although having 5-HT2A antagonist activity, is currently NOT recommended as risk of hyperthermia3).
- there is NO role for antipyretic agents, such as paracetamol (acetaminophen) - the increase in body temperature is not due to an alteration in the hypothalamic temperature set point, but rather an increase in muscular activity
- 40% require ICU
- 70% resolve within 24hrs
serotoninsyndrome.txt · Last modified: 2019/06/27 07:44 by 127.0.0.1