Download treatment of serotonin toxicity

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history of sympathomimetic poisoning is that
the onset of symptoms usually occurs within 2
hours post exposure
Life-threatening complications typically occur
within 2-6 hours postexposure.
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duration of action of illegal sympathomimetic
agents differ based on their chemical structure.
Methamphetamine has the chemical structure
of amphetamine with an additional methyl
group. The half-life of methamphetamine,
however, is much longer (2-24 h) than that of
amphetamine
The route of abuse also contributes to the
duration of action of some of these illegal
sympathomimetic agents.
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the half-life of methamphetamine ranges from
10-20 hours, depending on the urine pH,
history of recent use, and dosage.[11]
Metabolism occurs faster in acidic urine
The majority of methamphetamine is
metabolized to amphetamine, which provides
further CNS stimulation.
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adverse effects of MDMA are not clearly dose
related
some individuals developing life-threatening
toxic syndromes after single doses of drug
MDMA-Induced Serotonin Neurotoxicity
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Acute methamphetamine overdose may result
in sympathetic overdrive, cardiovascular
collapse, rhabdomyolysis, ventricular
tachyarrhythmia, and death.
Injuries from blunt and penetrating trauma are
common
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Cardiovascular
Chest pain, aortic dissection, myocardial
ischemia/infarction
Palpitations, tachyarrhythmia
Dyspnea and edema
Hypertension
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Agitation, violent behavior, self-harm
Coma
New-onset seizure, movement disorders
Emotional lability, confusion, psychosis, paranoia,
hypersexuality, and hallucinations
Headache
Headache and cerebrovascular accidents with focal
neurologic deficits may be caused by hemorrhage
or vasospasm, cerebral edema, and cerebral
vasculitis
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Coma may result from depletion of
catecholamine stores
or concomitant ingestion of sedatives such as
ethanol or narcotics
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Abdominal pain
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Obstruction
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Dyspnea
Wheezing
Pneumothorax
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Hypoxemia
Rhabdomyolysis
Necrotizing angiitis
Acute interstitial nephritis
Cardiovascular shock with subsequent acute
tubular necrosis
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Mydriasis
Tachycardia
Diaphoresis
Acute psychosis
Paranoia
Delirium
Bruxism (amphetamines and bath salts)
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Acute Coronary Syndrome
Acute Respiratory Distress Syndrome
Cardiomyopathy, Dilated
Hypertensive Emergencies
Hyperthyroidism, Thyroid Storm
Seizures
Subarachnoid Hemorrhage
Toxicity, Anticholinergic
Toxicity, Antihistamine
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CBC and chemistry test
To assess renal and electrolyte function
Creatine kinase and/or myoglobin levels
To exclude rhabdomyolysis
Serial troponin levels - If there is concern for
myocardial ischemia
Pregnancy test - In women of childbearing age
Toxicology screens - Useful for patients who
cannot or will not disclose drug use history and for
pediatric patients with new-onset seizure
ECG for patients with chest pain, altered mental
status, and tachycardia.
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Lumbar puncture may be indicated in patients
with altered mental status
to rule out meningitis or subarachnoid
hemorrhage.
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chest radiograph for patients with pulmonary
symptoms or chest trauma.
In patients with altered mental status, perform
a head CT scan to exclude intracranial
bleeding. Such bleeding may be the result of
either methamphetamine-induced
hypertension or associated head trauma.
Patients who are suspected body-packers,
body-stuffers, should undergo abdominal
imaging.
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because no antidote exists.
Assessment of the airway, breathing, and
circulation immediately is recommended.
close monitoring of the vital signs is
recommended.
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Aim :control dangerous behaviour sufficiently
to facilitate accurate assessment and appropriate
management
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benzodiazepines are first line treatment
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agitated patients
induced seizures
cardiac toxicity
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primary aim of management is to reduce the
risk of harm to the patient, staff and other people
physical restraint alone is often not adequate
may actually cause harm if agitation increases.
Stimulant use risk factor for sudden death of
individuals being physically restrained
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Oral diazepam
10-20mgs orally. If no clinical response at 30
MIN
, an additional 10 mgs
this regime until the patient is in a state of
drowsiness or a total dose of 60mgs
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Intravenous diazepam
2.5-5mg to assess patients Sensitivity to BZ
Some patients will respond to this low dose.
If no clinical response at 10 min an
Additional higher dose of 5-10 mg
Repeat this higher dose of 5-10mg every 10 min
to a maximum dose of 60mg
if the patient is not sedated adequately.
 Consider alternate agent
 Midazolam 5 -10mg IM at 10 min or
2/5-5 IV (to a maximum dose of 25mg)
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droperidol 2.5mg intravenously or olanzapine
10mg intramuscular (IM) if no response
ORAL DIAZEPAM
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10-20mgs orally. If no
clinical response at 30 min
, an additional 10 mgs
should be administered.
this regime until the patient
is in a state of
drowsiness or a total dose
of 60mgs
INTRAVENOUS DIAZEPAM
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2.5-5mg to assess patients Sensitivity to BZ
Some patients will respond to this low dose.
If no clinical response at 10 min an
Additional higher dose of 5-10 mg
Repeat this higher dose of 5-10mg every 10
min to a maximum dose of 60mg
if the patient is not sedated adequately.
Consider alternate agent
droperidol 2.5mg intravenously or
olanzapine
10mg intramuscular (IM) if no response
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Patients should then be monitored for four hours,
Observations should be
every 10 minutes for 30 minutes
then every 15 minutes for 30 minutes
, then every 30 minutes for 60 minutes
then hourly for four hours or until awake.
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airway
patient colour
continuous oxygen saturation
respiration rate
blood pressure
pulse
temperature
Glasgow Coma Scale score
bedside BSL.
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uncontrolled hypertension might be at risk for
subarachnoid and intracerebral haemorrhage
chest pain
benzodiazepines
Sublingual nitroglycerine
Beta-blockers, should be avoided
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Serotonin involved in a range of functions
including:
mood, appetite and sleep regulation
cognition; perception; motor activity;
temperature regulation; pain control
sexual behaviour and hormone secretion
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early recognition
prompt supportive care
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hyperthermia above 39.5OC
intubation with deep intravenous sedation
IV fluids/volume resuscitation for dehydration,
hypotension or
rhabdomyolysis (ensure adequate urine output in
1.5-2mls/kg/hr)
mechanical ventilation for respiratory compromise
and sedation with IV
benzodiazepines might be indicated
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5-HT2 antagonists such as olanzapine (24),
chlorpromazine or
cyproheptadine (3) may be indicated (these
specific antagonists should
only be used if the diagnosis of serotonin toxicity
has been established
and anticholinergic agents have not been coingested)
paralysis and intubation may have a role in cases
of severe intractable
rigidity
management of secondary cardiac arrhythmias or
seizures involves
standard measures
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measure the core temperature of
sympathomimetic poisoned patients.
If hyperthermia is present, standard cooling
measures should be initiated.
Controlling agitation significantly helps in
cooling a hyperthermic patient.
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Hypertension unresponsive to sedation
should be treated with a rapidly acting and
easily titrated agent (eg, sodium nitroprusside).
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Seizures should be rapidly controlled with
benzodiazepines and/or barbiturates.
Obtaining a CT scan of the brain for all
sympathomimetic toxic patients who seize,
develop a focal neurologic deficit, or
experience a severe headache with or without
accompanying hypertension is recommended
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Prolonged critical care management often is
required for the numerous complications that
may occur with the severe overdose (eg,
hyperthermia, seizures, advanced respiratory
distress syndrome [ARDS], renal failure,
rhabdomyolysis, CNS dysfunction).
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A 19-year-old man was arrested after a traffic
violation
and taken to the local jail.
he had ingested 8 "balls" (8 g) of
methamphetamine
Personnel at the scene said that the man had
had no seizures
but they did witness severe rigors with
diaphoresis for approximately 30 minutes
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Initially the patient was able to communicate
with difficulty.
his last use was at least 10 hours earlier
patient as red, cool, and diaphoretic,
with severe shakes and incontinent of urine
His lungs were clear, and RR 60/min
EKG revealed a sinus tachycardia of 200/min.
Pulse oximetry 2.5 Llmin of oxygen was 91 %.
blood glucose was 81 mg/dL
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On arrival at the emergency department
patient's rectal temperature was greater than
108°F,respirations were 45/min,
pulse was 180/min
, blood pressure was 186/96 mm Hg.
Pulse oximetry on 10 Llmin of oxygen was
98% saturated.
The patient displayed diffuse rigidity
and tremulousness, his skin was hot and
diaphoretic,
his pupils were dilated and he did not respond to
verbal or painful stimuli
A Foley catheter returned minimal urine output.
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Ice packs on the patient's groin, axillae, and
neck
lowered his temperature to 105.5°F. During
resuscitation
he received sequential trials of
lorazepam, labetalol, and 50% dextrose in
water.
His blood pressure decreased to 86/44 mm Hg
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After a trial of lidocaine for his tachycardia, the
patient's heart rate decreased to 140 beats per
minute.
Intravenous normal saline was rapidly infused.
His respiratory status worsened, and pulse
oximetry dropped to 63 % saturation on 10 Llmin
of oxygen.
He was intubated orally with difficulty because of
teeth clenching.
Gastric lavage produced a string, but there were
no pill fragments.
Sorbitol and activated charcoal were administered,
and the patient was given intravenous famotidine.
rectal examination showed no pill fragments or
other foreign bodies.
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A chest radiograph CT scan of the head were
negative
An electrocardiogram continued to show sinus
tachycardia..
Initial chemistry and coagulation laboratory
values were all essentially normal
Arterial blood gases indicated metabolic
acidosis.
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The patient was transferred to the critical care
unit 3 hours after his arrest by police,
when it is presumed that he had swallowed
the 8 "balls" to avoid detection
. A drug-screening test of blood drawn 8 hours
after admission was negative for alcohol.
Cannabinoids were present. His blood was
positive for amphetamines, with a serum value
of 3,500 ng/mL (3.5 mglL).
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patient's liver function tests continued to
worsen from day 2, with enzyme levels reaching
their highest on day 4 at an AST level of 4,422 UIL
and alanine aminotransferase (ALT) of2,786 UIL.
The transaminase levels subsequently decreased
rapidly with a delayed increase in total bilirubin.
Serum creatine kinase levels exceeded 20,000 UIL
on day 2
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Dialysis was begun on day 4.
His neurologic status never improved during
hospitalization
Multiple cardiac arrests occurred
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start with the ARCs (airway, breathing, and
circulation)
when apnea, cardiac arrest, dysrhythmias, or
seizures are the initial signs
Although urinary acidification can increase
the elimination of amphetamines,
is no recommended because of the possibility of
worsening renal insult from
rhabdomyolysis.
 better to promote urine output with
rapid, generous intravenous fluid resuscitation
to maintain an alkaline urine to alleviate the
effects of myoglobin on the kidneys
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It is important to recognise that
psychostimulant toxicity can occur among
both experimental and regular users of
psychostimulants
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type of psychostimulant used
amount of psychostimulant used1
time of administration
route of administration (intranasal, intravenous, oral, inhalation)
frequency of use (e.g. regular daily use, binge pattern, recreational,
experimental, etc)
duration of current use and age of first use
obtain a urine sample for a drug screen if possible.
2. Other drug use
concurrent use of other drugs (particularly alcohol, benzodiazepines,
opiates, party drugs), including criteria above
concurrent use of antidepressant medication (e.g. TCAs, MAOIs,
SSRIs, bupropion, venlaxafine) which may increase the serotonergic
or catecholamine mediated effects of psychostimulants
signs might indicate the patient has recently used
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dilated pupils that react sluggishly to light
clenched jaw or muscle rigidity
restlessness, agitation, tremor or repetitive
movements
rapid speech
motor agitation or pacing
hypertension
tachycardia
sweaty palms, flushed diaphoretic facial skin
hypervigilance, paranoia.
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Dantrolene was prescribed for temperatures of
104°F and higher.
Temperature decreased to 103.6°F with cooling
measures and the paralytic.
He remained comatose with a Glasgow score of 3
He began to ooze blood from various orifices
His fibrinogen decreased from 128 mg/dL to 85
during the first 14 hours.
His BUN and CR levels elevated on day 2 of
hospitalization.
His AST level was elevated to 1,927
urine became positive for myoglobin
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Managing the airway and controlling agitation
are the two main prehospital treatment
concerns.
any patients with sympathomimetic poisoning
present in an agitated state.
In these cases, physical and/or chemical
restraint may be required