Emergency Medicine Toxicology -...
Transcript of Emergency Medicine Toxicology -...
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Emergency Medicine
Toxicology
Dr. Szabó Zoltán University of Debrecen Clinical Center
Institute of Internal Medicine
Division of Emergency Medicine
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Poisoning
• Acute or chronic damage caused by endogenous or
exogenous substances
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Causes
• Accidental
• Overdose
• Suicidal
• Violent
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Statistical data
• Call for the ambulance15-20 %
• Female:male= 2:1
• Age 20- 40 years
• Toxins
– 80-90 % drug
• 85 % sedative (1/3), anxiolytic (2/3)
• Alcohol+drug
• Reason
– Suicidal 80-90%
– 10-15% accidental
– 5% industrial
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Contamination
• Gastrointestinal (oral)
• Inhalation
• Dermal
• Parenteral (iv narcotics, dope!)
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Therapy I.
• Prehospital • General practicioner
• Ambulance
– Task:
» Stabilizing of the vital parameters
» Start the decontamination
» Diagnosis
» Decision about hospitalization
• LIMITATION: within the bounds of possibility
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Therapy II.
• Hospital: EMERGENCY UNIT • Task:
– Stabilizing of the vital functions
– Reaching the diagnosis
» toxicology tests: gastric lavage, vomitus, serum, urine
» Laboratory tests: electrolyte, renal function, liver function, haemostasis, urine
– Detoxication
– Decision making
» Transmit the patient (ICU, Psychiatry)
» Home
• Limitation: TIME
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Intensive Care Unit
• Altered mental status • Intubation needed
• Cerebral hypoperfusion, hypoxia (hypotension, arrhythmias)
• Trauma (subdural haemorrhage)
• Cardio-respiratory system: unstable • Monitoring, DC, pacemaker, respiratory therapy
• Cardiopulmonary depressive substances
• Lethal dose • extracorporeal detoxication
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Possibilities for detoxication
• Decontamination
– Washing the surface with water
– Gastric lavage
– Activated charcoal
– Forced diuresis
• Antidote
• Extracorporeal
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Gastric lavage
•AMS_intubation
•200 mls fluid
•Active charcoal (perforation, ileus, AMS!!!).
Contraindications!!!
•Acids or alkaline
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Poisons and antidotes
Benzodiazepine Flumazenile
Beta blocker Glucagone
Digitalis Digibind
CCB Calcium-chlorid
Ethylenglycol Ethanol
Methanol Ethanol
Opiates Naloxone
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Extracorporeal detoxication
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Hemodialysis
(diffusion, osmosis)
Patient
Dialysate
fluid
ultrafiltrate
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Hemodialysis
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Hemodialysis
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Hemodiafiltration
Convective transport
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Hemodialysis
osmosis, diffusion
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HEMOPERFUSION
• Active charcoal capsule - absorption
Patient Carcoal
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Plasmapheresis
• Protein binding substances
Patient
Plasma filter
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Plasmapheresis
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Examples for the management of a patient
with acute intoxication in the Emergency
Department
1. The patient with antihypertensive (ACEI)
intoxication
2. Digitalis intoxication
3. Altered mental status-antidepressants
4. Intoxication with benzodiazepines
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VASOCONSTRICTION VASODILATATION
Kininogen
Kallikrein
Inactive Fragments
Angiotensinogen
Angiotensin I
RENIN
Kininase II Inhibitor
ALDOSTERONE
SYMPATH. tone
VASOPRESSIN
PROSTAGLANDIN
tPA
ANGIOTENSIN II
BRADYKININ
ACEI- mechanism
A.C.E.
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• Symptomatic heart failure
• Asymptomatic left ventricular dysfunction
- LVEF < 35 - 40 %
• high cardiovascular risk
•Hyprtension
•Cardiomyopathies (HCM, DCM)
ACEI indications
AHA / ACC HF guidelines 2001
ESC HF guidelines 2001
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Decreasing mortality with ACEI
Study ACE-i Disease
CONSENSUS Enalapril CHF
SOLVD treatment Enalapril CHF
AIRE Ramipril CHF
Vheft-II Enalapril CHF
TRACE Trandolapril CHF / LVD
SAVE Captopril LVD
SMILE Zofenopril High risk
HOPE Ramipril High risk
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months
30 24 12 18 0 6
10
30
20
0
Placebo
Ramipril
n = 2006
St p AMI
p = 0.002
Mortality
%
Lancet 1993;342:821
ACE-i
AIRE
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Mortality %
4 N Engl J Med 1992;327:669
years
30
20
10
0 1 2 3
Placebo
Captopril
0
n=1115
n=1116
p=0.019 ² -19%
n = 2231 3 - 16 nap post AMI EF < 40 12.5 --- 150 mg / day
post MI
ACEI
SAVE
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50
40
30
20
10
0
months
0 6 12
p = 0.0036
%
Mortality
24 18 30 36 42 48
Enalapril n=1285
Placebo n=1284
N Engl J M 1991;325:293
n = 2589 CHF - NYHA II-III - EF < 35
ACEI
SOLVD (Treatment)
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Drug Bioavaiability Metabolism Excretion HD
Benazepril 27 % yes urine no
Captopril 70 % yes urine 35 %
Cilazapril 70 % yes urine 15 %
Enalapril 40 % yes Urine/stool 40 %
Fosinopril 35 % yes Urine/stool no
Lisinopril 50 % yes urine <25 %
Perindopril 65 % yes urine no
Quinapril 60 % yes Urine/stool no
Ramipril 60 % yes urine yes
Trandolapril 40 % yes Urine/stool No data available
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ACEI
Toxicology
• rare
• Mostly mild symptoms
• Management – Lavage, charcoal
– In case of hypotension • iv. NaCl
• Chatecholamines
• Colloids
– Forced diuresis
– HD
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Na+
K+
K+
Na+
Na+ Ca++
Ca++
Na-K ATPase Na-Ca exchanger
Myofilaments
digitalis
contractility
-
Digitalis
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50
40
30
20
10
0
Placebo n=3403
Digoxin n=3397
48 0 12 24 36
Mortality %
N Engl J Med 1997;336:525 months
p = 0.8
N=6800
NYHA II-III
DIG study
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Toxicology
• Symptoms – Gastrointestinal
• Nausea, vomitus, diaorrhoea
– Neurological • Vertigo, dizziness, blurred vision
– Heart • Palpitation, arrhythmia (VT, VF, SVT), syncope
– Laboratory findings • Serum digoxin, Potassium, Mg, GFR!
– ECG ST-depression, bradycardy, ventricular arrhythmias: bigeminy AV-block,VT,
– atrial tachycardia + block
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Management
• Hyperkalaemia Resonium
– Glucose-inzulin
– Calcium
– Bicarbonate
• Avoid calcium
• Controlling of Ca, Mg
• AV block: – Atropin, pacemaker
• Arrhythmia (VT) – Phenytoin, lidocain
• Gastrointestinal decontamination
• Forced diuresis
• HD: no
• HP: yes
• Digibind
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Tricyclic antidepressants
• 1959: imipramin (Melipramin)
• 1961: amitriptylin (Teperin)
• Michon et al: first case report in 1959
• 50 % of all suicidal cases
• Main problem: prescription
• Lehal outcome: 15 %
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TCAD
Tricyclic Antidepressants (TCAs) for the Treatment of Neuropathic Pain-Medscape Multispeciality
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Tricyclic antidepressants
• Effect (norepinephrine, serotonine, dopamine reuptake inhibitor)
– Cardiovascular (within 24-48 hours)
• Hypotension (alpha blocade)
• Arrhythmias (cholinergic blockade-reentry, automaticity)
• Myocardial toxicity
• Pulse generation and conduction disorders
– Neurological
• Coma , AMS
• Convulsion-generalized
• Hyperthermia
– Other
• Urine retention
• Ileus
• ARDS
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VT
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DG Benditt, UM Cardiac Arrhythmia Center
16.3
sec
Continuous Tracing 1 sec
Asystole, paroxysmal AV block,
Sinus arrest
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Management • Gastrointestinal decontamination
– Total absorption is more than 8 hours
– Active charcoal (50 g)
• Forced diuresis: no
– HD
• Ineffective, strong plasma protein binding
• High distribution
– HP
• Ineffective: high distribution
• Na-bicarbonate
– tissue acidosis –myocardium
• Antidote: cholinesterase inhibitor-physostigmin
– May increase the onset of arrhythmias
• Monitoring!!!
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Benzodiazepines
• Sedato-hypnotic effects, myorelaxant, anxiolytic, anticonvulsive
• 1955: chlordiazepoxide (Elenium, Librium)
• 1963: diazepam (Seduxen)
• 3000 types of benzodiazepines, 30 used as medicine
• 500 million tablets/year
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Benzodiazepines
• Pharmacocinetics – Rapid absorption
– Bioavaiability: 70-100 %
– >90% plasmaproteine binding, only the free is active
– Renal excretion under 1%
– postsynaptic neuron: increased GABA-erg activity
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BZD-Toxicity
• Symptoms
– Sedation, lethargy, headache, fatigue, sleepiness, sopor, coma
• Therapy
– Gastrointestinal decontamination
– Active charcoal
– Forced diuresis no
– Extracorporeal: no
– Antidote: flumazenil (Anexate)
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Altered mental status
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GLASGOW COMA SCALE
Eye opening
4. Spontaneous
3. To speech
2. To pain
1. None
Verbal response
5. Oriented convesation
4. Confused speech
3. Inappropriate words
2. Incomrehensive
sounds
1. none
Motor response
6. Obeys simple
commands
5. Localized pain
4. Withdraws (normal
flexion)
3. Stereotyped flexion
2. Stereotyped extension
1. None
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Organic brain syndrome
Delirium Dementia
Onset Rapid Slow
Pattern Fluctuating Fluctuating or stable
Oriented No Yes
Attention Disordered Normal
Cognition Disordered impairedImpaired
Speech Incoherent Perseveration
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OBS – Common causes of dementia
• ALZHEIMER’s DISEASE
• PICK’s DISEASE
• EXTRAMYRAMIDAL SYNDROMES WITH SUBCORTICAL DEMENTIA (M. Parkinson)
• MULTIPLE-INFACT DEMENTIA
• VIRUSES AND OTHER INFECTIOUS AGENTS (Creutzfeld, Syphilitic, HIV, TBC etc.)
• TOXIC AGENTS (heavy metal, dug abuse)
• METABOLIC DISORDERS (dialysis, hypothyreoidism, porphyria, uraemia, hepatic encephalopathia)
• VITAMIN DEFICIENCY (Vit. B12, Folate)
• CNS STRUCTURAL CHANGES (hydrocephalus)
• PSYCHIATRIC DISORDERS (SCH, MDS)
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OBS – Common causes of delirium
• DRUG INDUCED: anticholinergics, narcotic analgesics, sedatives, hypnotics, corticosteroids, histamin blockers, antibiotics, etc.
• INFECTION: pneumonia, sepsis, meningitis
• FLUID AND ELECTROLYTE IMBALANCE: dehydratation, hypoglycaemia/hyperglycaemia, hyponatraemia
• DRUG WITHDRAWAL: alcohol, narcotics
• CNS DISTURBANCES: seizures, CVA,
• PYCHIATRIC DISEASE: sensory deprivation, depression, mania
• OTHER CAUSES: vasculitis, collagen vascular disease
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OBS – ID management
1. Search and correct life - threatening causes
2. Discover and treat the underlying cause of delirium
3. Protect patient while diagnostic evaluation and therapy
proceed
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Thank you for your attention!