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Coma
• Presentation.
o Defined as a state of unrousable unresponsiveness.
No evidence of arousal:
• No spontaneous eye opening
• No comprehensible speech
• No voluntary limb movements.
Unresponsive to external stimuli, however:
• Abnormal postures may be adopted.
• Eyes may open to pain
• Grunts may be elicited in response to pain.
Involuntary movements.
• Eg. seizure of myoclonic jerks may occur
o GCS is a useful way of assessing and monitoring levels of
consciousness.
• Causes.
o Most usefully categorized as:
Metabolic
Toxic
Infective
Structural lesions.
o In addition, causes can be subdivided into those that cause
Local brainstem signs
Lateralizing cerebral signs
Meningeal irritation
Anoxia/ hypoperfusion
Metabolic causes involve high or low:
• Glucose
• pH
• Sodium
• Hypercalcaemia
• Hepatic failure
• Renal failure
Intoxications.
• Alcohol
• Opiates
• Benzodiazepines
• Tricyclics
• Neuroleptics
• Lithium
• Barbituates
• Carbon monoxide
Hypothyroidism
Hypothermia/ hyperthermia
Epilepsy
Hypertensive encephalopathy.
o Coma with focal/ lateralizing signs.
Due to brainstem or cerebral dysfunction.
Vascular.
• Cerebral haematoma
• Infarction.
Supra – or infratentorialspace – occupying lesion.
• Only cause coma if within brainstem, or
compressing thr brainstem to cause brain shift.
• Tumour
• Haematoma
• Abscess
o Coma with meningism.
Subarachnoid haemorrhage
Meningitis
Encephalitis.
o Examine patient.
• Skin.
o Signs of head trauma
o Basal skull fracture suggested by:
Bruising over scalp and
mastoids
Blood in nostrils
Blood in ears,
o Rash suggests meningococcal
septicaemia
o Look for.
Signs of chronic liver failure.
Sallow discolouration of
uraemia
Needle tracks of IV drug users.
• Heart.
o Occasionally bacterial endocarditis or
vasculitides associated with heart
murmurs can present with coma.
• Abdomen.
o Look for organomegaly.
May suggest causes of coma.
o Important not to miss acute intra –
abdominal event.
Perforation of viscus
Leaking AAA
• Fundi.
o Papilloedema indicates raised ICP
Absence of papilloedema
doesn’t exclude raised ICP.
o Subhyloid bleeds are pathognomonic of
sub – arachnoid haemorrhage.
Rare finding.
o Changes due to diabetes or hypertension
suggest encephalopathy secondary to
these conditions.
• Meningism.
o Neck stiffness assessed on if there has
definitely been no trauma to cervical
spine.
o Increased stiffness suggests meningeal
irritation due to:
Inflammation
Infiltration
Presence of blood.
o Meningism raises possibility of
Meningitis
Encephalitis
Subarachnoid bleeding.
o Start Abx as soon as meningitis is
suspected.
• Assess GCS.
o May reveal brainstem dysfunction or
localizing signs.
o Decorticate or decerebrate posturing
may become clear on assessing motor
function.
o Changing signs may indicated brain
shift.
o Monitoring progress.
Regular observation of vital signs, neurological state and
electrolytes
• Including GCS.
• Deterioration often due to:
o Electrolyte or metabolic changes.
o Hypovolaemia or fluid overload.
Important cause of deterioration in structural lesions is
brain shift and herniation.
• Recognition and treatment of raised ICP to be
discussed later.
o Prognosis.
When coma related to head injury, prognosis closely
related to GCS score.
• Very poor prognosis at GCS < 9.
In non – traumatic coma, GCS alone is not a very good
indocator of prognosis.
• Drug intoxication causes very low scores on
admission, but has generally good outcomes.
Assessment of prognosis in non – traumatic coma is
assisted by simple examination findings.
• For example, a patient at 24 hours who still has
no papillary, corneal or oculovestibular response
has a very poor chance of survival.
Raised ICP.
• Presentation.
o Normal ICP in adults is 0 – 10 mmHg at rest.
o Treatment is required when ICP > 15 – 20 mmHg for > 5 minutes.
o Signs and symptoms suggestive of raised ICP include.
Headache & vomiting.
• Worse in morning.
o Morning occipital headache could be
raised ICP, or cervical spondylosis
• Exacerbated by bending over.
Focal neurological signs.
• Normally occur in presence of a space occupying
lesion
• May occur with medical conditions, eg. liver
failure.
• Causes.
o Head injury.
Leads to subdural haematoma/ brain swelling/ contusion.
o Stroke.
o Metabolic.
Liver failure
Renal failure
DKA
Hyponatraemia
Etc.
o CNS infection.
Abscess
Encephalitis
Meningitis
Malaria.
o CNS tumour
o Status epilepticus
o Hydrocephalus
o “Benign “ intercranial hyp[ertension.
• Assessment of severity.
o GCS
o Signs of brain shift
o Signs of brainstem compromise.;
• Management.
o Stabalise the patient.
o Consider active measures to reduce ICP
o Attempt to make a diagnosis
o Treat factors which may exacerbate raised ICP
o Observe for signs of deterioration, and try to treat them.
o Consider specific therapies.
o Fluid restrict.
1.5 – 2.0 L/day
Check U&E regularly.
o Cool to 35 oC
Reduces cerebral ischemia.
o Avoid/ treat hypoglycaemia.
Exacerbates ischemia
Presentation.
• Constant, but variable, headache.
• Visual disturbances.
o Diplopia
o Visual obscurations
o Scotoma
• Nausea
• Problems with balance
• Problems with memory
• Tinnitus
• Neck and back pain
• Papilloedema.
o May be unilateral
• BIH can be distinguished from other cause of
raised ICP as there are:
o No focal signs
o No Epilepsy
o No loss of cerebral function.
Compare with bacterial
meningitis
Compare with viral
encephalitis.
• Associations.
o Obesity is present in 90%
o Menstrual problems
o Drugs.
Tetracycline
Isoretinoin
Etretinate
Malidixic acid
Nitrofruantoin
Lithium
o Oral contraceptive pills
o Steroid withdrawl
o Recurrent miscarriage
• Investigations
o CT head and MRI generally normal.
o Lumbar puncture reveals CSF pressure
increased by > 20 cm.
May increase in obesity
anyway.
• Management.
o Seek expert advice.
o Lose weight
o Therapeutic lumbar puncture every 2 –
5 days.
o Prednisolone.
40 – 60 mg/day.
Effective in relieving headache
and visual obscuration
papilloedema.
Steroids shouldn’t be used long
– term.
o Acetazolamide ± Frusemide.
o Surgical shunting.
Eg. lumboperitoneal shunt.
o Hyponatraemia.
Usually result of fluid overload
May be caused by a SIADH secretion.
Treat with DDAVP 1 – 4 μg IV daily
Epidemiology poisoning.
• Immediate management:
o Airway:
Ensure adequate airway and gag reflex.
? Intubate.
Coma position.
o Breathing:
Respiratory rate.
Oxygen Sats.
Blood Gases.
o Circulation.
Assess pulse, BP, perfusion.
Obtain IV access.
Consider IV fluids for hypotension.
• Immediate history.
o Likely to be collateral.
o When did the overdose take place?
o What poisons were involved?
Bottles?
Tablets?
Prescription drugs?
Alcohol?
o Mode and duration of exposure?
Eg. smoke inhalation.
o Symptoms?
Especially vomiting.
• Good sign: Evacuates tablets.
• Bad sign: Shows that the patient is toxic.
Convulsions:
• Tricyclics.
• Theophylline
• Opiods
• Mefenamic acid
• Isoniazid
• Amphetamines
Delerium and hallucinations.
• Anticholinergics.
• Amphetamines
• Cannabis (allegedly)
• Recovery from tricyclic overdose
Blindness:
• Methanol.
• Quinine
Tinnitus and deafness.
• Salicylates.
• Quinine.
• Later history.
o Not collateral.
o Why was the overdose taken?
o Past history of self harm?
o Attempt at concealment?
Timing.
Precautions against discovery.
Medical help sort?
• Did patient seek help, or were they found and brought in?
Final acts performed?
• Will
• Life insurance.
Suicide note?
Overdose expected to be fatal?
Wanted to die?
Premeditation?
Symptoms of psychiatric illness?
Isolation?
o Perform quantative Bede’s suicide risk test.
• Methods available.
o Activated charcoal.
o Gastric aspiration/ lavage.
o Induced emesis with Ipecacuanha.
• Theory.
o Aim to reduce absorption of oral poisons.
o Only required when ingested poison carries significant risk.
o Little evidence for benefit unless used within 1 hour (depends on poison).
o Cannot be used in patient with reduced LOC unless airway is protected.
Induced emesis.
• Uses syrup of ipecacuanha.
• Two doses produced vomiting in > 90% of people.
• However.
o Probably least effective way of removing poisons.
o Induced vomiting may mask the fact that patient is still vomiting due to being toxic.
• Complications
o Persistent vomiting.
o Diarrhoea.
o Lethargy.
o Aspiration.
o Mallory – Weiss tear of stomach/ oesophageal mucosa.
o Gastric herniation
o Foetal abortion.
• Contraindications.
o Adults.
o Patients with reduced LOC and poor gag reflex.
• Rarely, if ever, appropriate.
Activated charcoal.
• Charcoal activated by heating in steam/ air/ carbon dioxide at 600 – 900 oC.
• Adsorbs poison onto surface from GI tracts by direct contact.
• Required charcoal:drug ratio is variable:
o In rats, an 8:1 ratio needed for>80% reduction in concentration.
o Normally use a 10:1 ratio in humans, up to 50g in one dose.
• Good for:
o Phenobarbitone.
o Chloroquine.
o Isoniazid.
• Preferred method of evacuation due to simplicity.
• Unpalatable, so often suspended in flat cola.
• Can be delivered by NG tube in unconscious patients.
o Airway should be protected by cuffed endotracheal tube if gag reflex poor.absent.
• Should be given as early as possible to increase efficacy:
o 56% concentration reduction from control if given at 1 hour.
o 22% concentration reduction from control if given at 2 hours.
o 8% concentration reduction from control if given at 4 hours.
• Complications:
o Aspiration pneumonitis.
o Reduced absorption of therapeutic agents (eg. methionine in paracetamol poisoning).
o Briquette formation, causing bowel obstruction.
• Contraindications.
o Poor bowel motility (particularly if bowel sounds absent).
o Impaired gag reflex.
o Inability to swallow.
• Ineffective in:
o Elemental metals/salts.
Lithium.
Iron
Boron
o Insecticides:
Malathion
DDT
N – methyl carbamate
o Cyanide
o Strog acids/ alkalis.
o Alcohols
o Hydrocarbons.
Methods for increasing drug elimination
• Methods used:
o Multiple dose activated charcoal (MDAC).
o Haemodialysis.
o Haemoperfusion.
o Haemofiltration
o Combined methods.
Haemodiafiltration.
MARS
MDAC
• 50g activated charcoal, followed by 25 g every two hours.
o Give laculose or magnesium sulphate to prevent constipation.
• Reduced elimination half life by:
o ‘Gastrointestinal dialysis’.
o Interfering with enterohepatic circulation.
Bile salts (containing poison) circulate from gut to liver.
Having a gut full of charcoal will mean that poison will be adsorbed by the
charcoal every time it passes through the gut.
• Good evidence of efficacy in:
o Carbemazipine.
o Dapsone.
o Phenobarbitone.
o Quinine.
o Theophylline.
• Sometimes used for:
o Alicylates.
o Phenytoin.
• Can lead to intestinal obstruction.
Haemodialysis/ Haemoperfusion.
• Useful when:
o Poison has a small volume of distribution.
o Has low clearance rate.
o Is sufficiently toxic.
o Is either:
Small enough to cross dialysis membrane (HD).
Bound to activated charcoal (HP).
• Haemodyalisis.
o Consider in life – threatening overdoses of:
Methanol
Ethylene glycol.
Isopropanol.
Salicylate
Sodium valproate.
Lithium
• Charcoal haemoperfusion.
o Consider in life – threatening overdoses of:
Theophylline.
Aminophylline.
Phenytoin.
Carbemazepine.
Phenobarbitone.
Amylobarbitone.
Antidotes.
Paracetamol.
• Most popular analgesic in Britain.
• Accounts for half of all overdoses presenting to hospital.
• One of the leading causes of mortality from poisoning.
o 100 – 200 deaths per year.
o However, mortality from paracetamol OD < 1%.
Mechanism of toxicity.
• Most paracetamol conjugated with glucuronide or sulphate.
• Small amount metabolised to reactive species N – acetyl – para – benzo – quinoneimine (NAPQI).
• NAPQI then detoxified by conjugation with glutathione to form mercapturic acid.
• In overdose, the major pathway is saturated; so lots of paracetamol goes down the minor pathway
producing large amounts of NAPQI.
• The liver’s stores of glutathione become exhausted, meaning that much of the NAPQI produced
does not become detoxified, and so causes heapatocyte cell death by oxidation damage.
• Induction of hepatic enzymes increases toxicity by pushing more paracetamol down the minor
pathway.
o Alcohol.
o Phenytoin.
o Rifampicin
o Short term under – nutrition, due to decreased glutathione stores.
Clinical Features.
• Early:
o Non – specific.
o Nausea/ vomiting/ Abdo pain.
o NO IMPAIRMENT OF CONCIOUSNESS
• Delayed:
o Hepatic necrosis after 2 – 3 days.
Jaundice.
Liver pain.
Encephalopathy.
Fulminant hepatic failure.
Death (3 – 6 days after overdose).
o Renal failure.
Less common.
Presents 2 – 7 days after OD.
Oliguria
Loin pain.
o Hypoglycaemia
o Metabolic acidosis.
Investigations.
• Paracetamol levels.
o Best early predictor of prognosis.
o Determines need for antidotes.
In normal patients, treat if blood paracetamol > 200 at 4 hours.
In high risk patients treat if blood paracetamol > 125 at 4 hours.
Always be aware of the staggered dose overdose.
• Will cause blood paracetamol to continue increasing over a longer
period so, for example, blood levels could be 150 at 4 hours, but 250 at
6 hours.
• Clotting studies.
o Especially INR or PT.
Increased due to reduced production of clotting factors II, V and VII.
• U&E and Creatinine.
o Creatinine elevated in renal failure.
o Urea may be artificially low in severe hepatic failure as the liver will stop producing it.
• Blood gases.
o Metabolic acidosis in severe poisoning.
• LFTs.
o Elevated transaminases are common.
Poor prognostic indicator.
o Raised bilirubin indicates significant hepatic necrosis.
Not as sensitive or specific as clotting studies.
Treatment
• Prevention of absorption.
o Activated charcoal is dose was large.
o Gastric lavage ± activated charcoal if dose was very large (>50g)
o Only indicated if less than 1 hour post OD.
• Antidotes.
o Provide glutathione for detoxification of NAPQI.
o Value of antidotes decreases with time.
• N – Acetylecysteine.
o Given IV over 20 hours in the UK.
o Given orally over 72 hours in the US.
o Very effective up to 8 hours post OD.
o Some effect up to 24 hours post OD, but value decreases with time.
o Current thinking is to treat at any point in severe poisoning.
o Beneficial in patients with fulminant hepatic failure.
o Complications.
Anaphylactoid reaction.
• Urticaria.
• Wheezing.
• Hypotensions.
Not true allergy, but dose – related histamine release.
Reduce infusion rate and give antihistamines.
• Methionine.
o Given orally in 4 doses.
o Probably less effective than NAC.
o Much less effective after 10 hours.
o Rarely used in the UK.
• Supportative therapies.
o Vitamin K.
Discussion as to appropriateness, as will artificially lower PT/INR, and so these
will not be able to be used as markers of hepatic damage.
o Fresh frozen plasma.
Only in active bleeding.
o Hepatic intensive care.
Fluid balance.
Inotropic support.
Intercranial pressure monitoring.
o Dyalysis for renal failure.
o Orthotopic liver transplantation.
Aspirin.
Investigations.
• Plasma salicylate concentration.
• U&E
• Bicarbonate.
• BM
• ABG.
Treatment.
• Gastric decontamination.
o 50g activated charcoal.
o ? gastric lavage + activated charcoal if very large OD (rarely used)
o Within 1 hour of OD.
• Enhanced elimination.
o Repeated doses of activated charcoal.
• No longer use forced alkaline diuresis as is dangerous and ineffective.
• Haemodyalisis.
o Highly effective at removing salicylate.
o Also corrects metabolic abnormalities.
o Consider when:
pH < 7.3
Salicylate > 750 mg/l
• Salicylate > 600 mg/l in children.
Presence of renal failure.
• Supportative treatment.
o Airway.
o IV fluids.
o Ventilation.
o Glucose for hypoglycaemia.
o KCl for hypokalaemia.
o IV bicarbonate for less aggressive alkaline diuresis.
Opiates.
• The common opiates used in overdose are:
o Heroin.
o Morphine.
o Methadone.
o Dihydrocodiene.
o Codiene.
o Pathidine.
o Dipipanone
o Dextropropoxyphene
• They are normally taken:
o Orally.
o Smoked.
o IV.
• Effects:
o CNS and respiratory depression.
o Pin point pupils.
o Hypotension with tachycardia.
o Hallucinations.
o Rhabdomyolysis.
o Non – cardiac pulmonary oedema.
• Management:
o Naloxone.
o Supportative care.
o IPPV + PEEP
o Blood bourn virus precautions in IV drug users.
• Naloxone:
o Use in suspected opiate intoxication.
Diagnosis.
Treatment.
o Aim is to rouse the patient enough to maintain their own airway and breathing.
o Use adequate doses.
Adults: 2.4 mg or more.
Children: Titrate up from 0.01 mg/kg.
o Repeat as necessary or use infusion.
IV infusion dose per hour is 2/3 of bolus dose required for rousing.
o Dangers:
Pain due to antagonism of analgesics.
Acute withdrawl symptoms.
• Muscle aches.
• Diarrhoea
• Palpatations.
• Rhinorrhoea.
• Yawning
• Irritability
• Nausea
• Fever
• Tremor
• Cramps.
Self discharge due to waking from coma.
• Leads to coma and death outside hospital when naloxone wears off.
Hypertension.
Behavioural disturbances.
• At high doses.
Rarely:
• Fits.
• Arrythmias.
• Pulmonary oedema.
Tricylcic Antidepressants.
Clinical features.
• Hot, dry skin.
• Dilated pupils.
• Tachycardia
• Urinary retention.
• Cardiac arrythmias.
o VT
o VF
o Wide QRS complexes on ECG due to delaying of Na channels, due to acidosis.
• Agitation.
• Delerium.
• Fits.
• Coma.
• Hypertonia
• Hypereflexia.
Investigations.
• U&E.
• BM
• ABG
• ECG
o QRS duration < 160 ms (4 squares) suggests a high risk of arrythmias.
o ECG should be regularly monitored in CCU or ITU if overdose large, or initial ECG
abnormal.
o Initial ECG is often normal, so repeat regularly whatever the initial result.
Ttreatment.
• General
o Activated charcoal, if within 1 hour of overdose.
o Further doses of activated charcoal every two hours may enhance elimination of some
drugs.
Amitryptiline.
Nortryptiline.
• Arrythmias.
o Arrythmias more likely if pH < 7.4
o Give sodium bicarbonate in presence of:
Acidosis.
Wide QRS complex.
Arrythmias.
Works by reducing acidosis and providing sodium load.
o Correct disorders of potassium concentration.
o If bicarbonate fails to correct acidosis and arrythmias, consider:
DC cardioversion.
Overdrive pacing
o DO NOT give antiarrythmics, as they will actually make the arrythmias worse.
• Fits.
o Diazepam.
o Lorazepam
o If drugs fail, consider paralysis and artificial ventilation.
Benzodiazepines..
• Deliberate overdose is very common.
• Effects are generally mild.
o Unless combined with other sedatives, eg.
Alcohol
Tricyclics
• Presentation
o Drowsiness
o Slurred speech
o Nystagmus
o Mild hypotension
o Ataxia
o Coma
o Respiratory depression
o Cardiopulmonary arrest.
If administered intravenously.
Elderly are most at risk of developing this sypmotom.
• Management.
o If patients present within an hour of ingestion.
50 g activated charcoal
Ensure patient can protect airway
o Flumazenil.
Benzodiazepine antagonist.
May be used to revers significant cardiorespiratory depression
in severe overdose.
Given as IV bolus of 0.2 mg.
• If no response, give 0.3 mg IV.
• If still no response, give 0.5 mg IV every 30 seconds.
• Maximum 3 mg.
Most benzodiazepines have a longed half life than flumezanil.
• To maintain effects of antagonist, start IV infusion at
0.1 – 0.4 mg/h
Should not be used as diagnostic test in comatose patients
where benzodiazepine overdose is not very likely.
• Can cause fits or death.
Avoid excessive doses to completely antagonise
benzodiazepines.
• Can cause.
o Marked agitation in chronic benzodiazepine
use.
o Convulsions in patients who have also taken
pro – convulsant drugs.
Dextropropoxyphene
Theophyilline
Tricyclics.
• Serotonin syndrome.
o Potentially life – threatening ADR due to.
Therapeutic drug use.
Drug interactions
Drug overdose
Recreational drug use.
o More accurate term is serotonin toxicity of hyperserotonaemia.
o Consequence of excessive serotonin activity at CNS and peripheral
serotonin receptors.
Produces spectrum of specific symptoms, ranging from mild
to near fatal, including.
• Cognitive effects
o Confusion
o Hypomania
o Hallucinations
o Agitation
o Headache
o Coma
• Autonomic effects
o Shivering
o Sweating
o Pyrexia
o Hypertension
o Tachycardia
o Nausea
o Diarrhoea
• Somatic effects.
o Myoclonus
o Hyperreflexia
o Tremor
• Epidemiology
o Unclear, as syndrome is often not recognised
o Incidence may be increasing due to larger numbers of serotonergic
drugs available
o Thought that 14 – 16% of SSRI overdoses lead to serotonin syndrome.
• Presentation
o Characteristic picture, but may be mistaken for other problems.
Eg. neuroleptic malignant syndrome.
o Often rapid onset within minutes.
o Mild symptoms may include.
Tachycardia
Shivering
Sweating
Dilated pupils
Myoclonus.
• Intermittent tremor or twitching.
Brisk reflexes.
o Moderate symptoms.
All the mild symptoms.
Hyperactive bowel
Hypertension
Pyrexia.
• Temperature > 40 oC is common.
Reflexes and clonus may be more severe in lower than upper
limbs.
Mental state changes.
• Hypervigilance
• Agitation
o Severe symptoms.
Severe hypertension
Severe tachycardia.
Shock
Delerium
Muscular rigidity
Very tense muscles.
Pyrexia > 41 oC.
• Metabolic acidosis
• Rhabdomyolysis
• Seizures
• Renal failure
• DIC
• Pathophysiology.
o Serotonin is a neurotransmittter involved in many states, including:
Aggression
Pain
Sleep
Appetite
Anxiety
Depression
Migraine
Vomiting
o Serotonin excess was first noticed in humans in 1960, due to increased
levels in the CNS.
Was originally thought that agonism of 5 – HT1a receptors in
central grey nuclei and medulla was responsible for
development of the syndrome
Further study suggests that overstimulation of 5 – HT2a
receptors have a significant contribution.
5 – HT1a receptors may contribute through a
pharmacodynamic interaction
• Increased synaptic concentrations or serotonin
agonist saturate all receptor subtypes.
Additionally, noradrenergic CNS hyperactivity may play a
role.
• CNS noradrenaline concentration increased in
serotonin syndrome.
• Levels appear to correlate with the clinical outcome.
Other neurotransmitters may also play a role in development
of the syndrome.
• NMDA
• GABA
Serotonin toxicity is more pronounced in supra – therapeutic
doses and overdose
• Mereg in continuum with toxic effects of overdose.
5 – HT1a receptors may contribute through a
pharmacodynamic interaction
• Causes
o Many drugs and drug combinations have been reported to produce
serotonin syndrome.
Antidepressants
• Monoamine oxidase inhibitors
• Tricyclic antidepressants
• SSRIs
• SNRIs
• Bupropion
Opioids.
• Tramadol
• Pethidine
• Fentanyl
• Pentazocine
• Buprenorphine
CNS stimulants.
• Phentermine
• Diethylpropion
• Amphetamines
• Sibutramine
• Methylphenidate
5 – HT1 agonists.
• Triptans
Psychedelics.
• MDMA
• MDA
• MDEA
• PMA
• Psilocybin
• LSD
Herbs
• St. John’s Wort
• Yohimbe
• Boswellia
• Panax ginseng
• Ginkgo bilba
Others.
• Tryptohan
• Valproate
• Montelukast
• Buspirone
• Kanna
• Lithium
• Linezolid
• Dextomethorphan
• 5 - Hydroxtryptophan
• Chlorpheniramine
• Risperidone
• Olanzapine
• Ondansetron
• Granisetron
• Metoclopramide
o Many cases of serotonin toxicity occur in patients who have taken drug
combinations
Combination of MAOIs with other serotonin agonists or
precursors may be particularly dangerous.
Many MAOI irreversibly inhibit monoamine oxidase, so will
take at least 4 weeks for the enzyme levels to return to normal.
o May also occur in patients who overdose on a single serotonergic
agent.
o Was formerly thought that atypical antipsychotics could cause
serotonin syndrome, but this is not believed any more.
• Spectrum concept.
o Suggested spectrum concept of serotonin toxicity emphasises the fact
that increasing serotonin levels cause a progressively worse clinical
pictures.
o Dose effect relationship between drugs may produce large elevation in
serotonin levels.
• Diagnosis
o No test for serotonin syndrome
o Diagnosis on history and examination.
o Most important symptoms which suggest serotonin syndrome are
Tremor
Akathisia
Clonus
• Spntanous
• Inducible
• Ocular
o Examination should include assessment of
Reflexes
Muscle rigidity
Oral mucosal dryness
Size and reactivity of pupils
Intensity of bowel sounds
Skin colour
Sweating
• Differential diagnosis
o Gives a classical picture, so hard to confuse with anything else.
o Occasionally mistaken for
Neuroleptic malignant syndrome
• Most commonly confused diagnosis due to them both
causing features of
o Altered mental state
o Autonomic dysfunction
• Can be distinguished by:
Serotonin syndrome Neuroleptic malignant syndrome
Onset Rapid onset after ingestion of Onset over several days after
serotonergic drugs ingestion of neuroleptics
Responds to Chlopromazine Bromocriptine
Cyproheptadine
Clinical features Hyperkinesia Bradykinesia
Clonus “Lead pipe” rigidity.
Viral illness
Anxiety
Acute neurological disorder
Anticholinergic poisoning
Worsening psychiatric conditions
• Management.
o No antidote to condition itself.
o Management involves
Removal of precipitating drug
Supportative care
.
o Supportative care.
Control of agitation
Administration of serotonin antagonists.
• Cyproheptadine
• Methysergide
Control of autonomic instability
Control of hyperthermia