It’s about - Semmelweis...
Transcript of It’s about - Semmelweis...
It’s about
• Epidemiology, ways of poisoning• Aspecific symptoms, aspecific therapy• Toxidromes• Specific therapy• Some more frequent poisonings:
– alcohol– street drugs, opiates– paracetamol– tricyclic antidepressants– benzodiazepins– ethylen-glycol and methanol– carbon monoxide
Poisons, decoctions and brews
Paracelsus: „Alle Ding' sind Gift, und nichts ohn' Gift; allein die Dosis macht, daß ein Ding kein
Gift ist.”
in other words:
Size do matter!
Epidemiology: “the numbers” Nearly 90% of medicinal exposures occur at home
During pre-adolescence: slight male predominance
This reverses in ages 13-19 with females accounting for 55 %
Children, especially under age 6, are more likely to have unintentional poisonings
About half of all poisonings among teens are classified as suicide
Approximately 1/3 of ingestions of toxic medications occur with meds intended for someone else
Contamination and poisoning
acute
chronic
unintentional intentional
LD50, LD95
Volume of distribution (Vd)
The nominal volume where the agent can be distributed
If Vd>5 L/kg low plasma cc. tissue binding ↑
Protein binding
If >90% low free fraction
Clearance (Cl)
The amount of plasma that can get rid of the agent during a given periodof time
e.g. renal clearance =
Half life
T(½) = 0.693 x Vd / Cl
urine conc. x urine volume.serum conc.
Some necessary basic pharmacology
Dose-response curve
NOAEL
LOAEL
NOAEL: No Observed Adverse Effect Level - safeLOAEL:Lowest Observed Adverse Effect Level – notrecommended
cum
ula
tive
resp
on
se(%
)
Dose (mg/kg)
Examples (LD50)
*
What happens inreality?
Primaryinsult
• recognition, unknown circumstances, associated injuries, mass intoxication
Secondarydamage
• circulatoiry, respiratory arrest, organdamage (direct and indirect), trauma during transport
Definitivecare
• aspecific therapy
• specific therapy
Scheme of care
SYMPTOMATIC, ASPECIFIC TREATMENT
DECONTAMINATION
ELIMINATION
ANTIDOTE
Aspecific symptoms
• (D)ABCDE
• Applies to ANY episode of poisoning
• WHAT
• HOW MUCH (Ideally mg/kg)
• WHEN
• WHAT ELSE (Including alcohol)
• WHY
• Use paramedics, friends, relatives, anyone!!
General Management -1
• A (Airway)
• B (Breathing)
• C (Circulation)
• D (Disability-AVPU/ Glasgow Coma Scale)
• DEFG ( Don’t Ever Forget the Glucose)
• G (Get a set of basic observations)
General Management -2
• Use all your senses, search for the clues• LOOK
– Track Marks– Pupil Size
• Hear– Type Breathing (Kussmaul, Hyperventilation)
• FEEL– Temperature, Sweating
• SMELL– Alcohol– Fruity– I would NOT taste
Airways in danger!
Aspecific therapy
• Ventilation
– As long as it’s required
– special cases:
• CO poisoning
• aspiration
• inhalation of direct irritants
Aspecific therapy
• Maintain circulation
– Ensure DO2, increase CaO2
– EGDT
– CPR
Toxidromes
ToxidromesSigns and symptoms
HR BP RR pupil size GIT sweating temp
ANTICHOLINERGIC ↑ ↑ ↓ ↓
CHOLINERGICSLUDGE (Salivation, Lacrimation, Urinary incontinence, Diarrhea/Diaphoresis, GI upset/hyperactive bowel, Emesis)
↓ ↑ ↑
OPIOID ↓ ↓ ↓ ↓ ↓ ↓ ↓
SYMPAThO-MIMETIC
↑ ↑ ↑ ↑ ↑ ↑ ↑
SEDATO-HIPNOTIC
↓ ↓ ↓ ↓ ↓ ↓
Toxidromes, cont’dToxidrome Most frequent poison
ANTICHOLINERGIC atropin, scopolamin
CHOLINERGIC carbamates, mushrooms, organophosphates
OPIOID opiates
Toxidrome Most frequent poison
SYMPATHOMIMETIC salbutamol, amphetamins, cocain, ephedrine (Ma Huang), metamphetamine, phenylpropanolamin(PPA), pseudoephedrin.
SEDATO-HYPNOTIC anticonvulsants, barbiturates (?), BDs, GHB, metaqualon, ethanol
Symptomorientated
differentiation
Main groups of symptoms
• Mental state
• CNS symptomes
• Muscles
• Circulation
• Respiration
• Kidney
• Liver
• Heat balance
• Carbohydratemetabolism
• Ion balance
MENTAL STATE
CONFUSION PREDOMINANT CONFUSIONDELIRIUM
PREDOMINANT AGITATIONPSYCHOSIS
AMANTADINANTICHOLINERG/HYCIMETIDINCOLITHIUM
AMPHETAMINCOCAINCOFFEINPCPMARIJUANATHEOPHYLLIN
MENTAL STATE
COMA CNS DEPRESSION
CELLULAR HYPOXIA
SYMPATHOLYTICS
OTHERS
BARBITURATEALCOHOLTCADSEDATO-HYPNOTICS
COCIANIDE
OPIATEMETHYLDOPA
BROMINEDIQUATLITHIUMSALICYLATE
CNS
SEIZURESADRENERGIC
ANTIDEPRESSANT
OTHER
AMPHETAMINCOFFEINTHEOPHYLLIN
TCADHALOPERIDOLPHENOTHIAZIN
ANTIHYSTAMINCARBAMAZEPINCHOLINERGICSORGANIC SOLVENTS
CNS
MUSCLE TONEDYSTONIA
RIGIDITY
DYSKYNESIS
HALOPERIDOLMETOCLOPRAMIDPHENOTHIAZIN
LITHIUMMAO-INHIBITORPCPNMS / MHSPIDER – TOXIN (BLACK W.)
AMPHETAMINCOCAINTCADPCP
CIRCULATION
ARRHYTHMIACONDUCTION DISTURBANCES
LONG QT
TORSADE DE POINTES
VT/VF
BETA-BLOCKERTCADDIGITALISQUINIDINE
ARSENICCITRATETCADORGANOPHOSPHAT
AMPHETAMINCOCAINDIGITALISFLUORIDETHEOPHYLLIN
RESPIRATION
ACUTE RESP. FAILURE
MUSCULAR
CENTRAL
PULMONARY
HYPOXIAINHALATIONCARDIOGENICCELLULARPULMONARY
BOTULINUMORGANOPHOSPHATCARBAMAT
BARBITURATOPIATEALCOHOL
ORGANOPHOSPHATEBETA-BLOCKERCHLORINE
METHANETCADCYANIDEOPIATE
LIVER
ACUTEHEPATICFAILURE
ACETAMINOPHENAMATOXINAROMATIC COMPOUNDSHALOGENIZED CARBOHYDRONSCOPPERETHANOLHALOTHANEIRONPHOSPHORUSVALPROATE
MUSCLE
RHABDOMYO-LYSIS
CELLULAR
MUSCULAR
OTHER
AMATOXINCOCOLCHICINGLYCOL
AMPHETAMINECOCAINTCADLITHIUMMAO-INHIBITORPCPSTRYCHNINETETANUS
BARBITURATEETHANOLSEDATO-HYPNOTICS
HEAT BALANCE
HYPERTHERMIA
MUSCULAR
METABOLIC
REGULATION
OTHER
AMPHETAMINECOCAINTCADLITHIUM LSDPCP
DINITROPHENOLSALICYLATE
ANTICHOLINERGICSANTIHYSTAMINTCADPHENOTHIAZIN
METALLIC VAPOURMNS / SS / MH
CARBOHYDRATE BALANCE
BLLOD SUGARHYPO
HYPER
BETA-BLOCKERSETHANOLINSULINOADSALICYL
BETA-ADRENERGICSCOFFEINCORTICOSTEROIDSDIAZOXIDEEPINEPHRINEGLUCAGONTHEOPHYLLINTHIAZIDE
ION BALANCE
POTASSIUM
HYPER
HYPO
ADRENERGIC AGENTSACEIDIGITALISFLUORIDELITHIUM
BARIUMCOFFEINDIURETICUSTHEOPHYLLINEPINEPHRINE
Specifictherapy
Specific care
• Starts with the aspecific therapy
• Sometimes they run parallel with frequentchecks
• „Semi-specific” therapy along with the toxi ABC– Oxygen!
– DEFG ( Don’t Ever Forget the Glucose)
– Thiamine (vitamin B1) 100 mg IV/IM
– Naloxone (Narcan) ADULT 0.2 mg IV/IM/ETT, CHILD: 0.01mg/kg IV/IO/ETT
Further steps
SYMPTOMATIC TREATMENT
DECONTAMINATION
ELIMINATION
ANTIDOTE
PLASMA COMPARTMENT
PROTEIN BOUNDFREE
LIVER
METABOLISM
KIDNEY
EXCRETION(MATERIAL / METABOL)
PHARMAC.ACTIVE
RECEPTOR
BOUNDFREE
TISSUE STOREBIO.INACTIVE
TISSUE
BOUNDFREEFREE FREE
FREE METAB/FREE
FREE
INGESTED AMOUNT
PATIENT COMPLIANCE
ABSORPTION
BIO. AVAILABILITY(NOT ABSORBED; FIRST PASS)
INDIVIDUALFACTORS
PLASMA COMPARTMENT
PROTEIN BOUNDFREE
LIVER
METABOLISM
KIDNEY
EXCRETION(MATERIAL / METABOL)
PHARMAC.ACTIVE
RECEPTOR
BOUNDFREE
TISSUE STOREBIO.INACTIVE
TISSUE
BOUNDFREEFREE FREE
FREE METAB/FREE
FREE
INGESTED AMOUNT
PATIENT COMPLIANCE
ABSORPTION
BIO. AVAILABILITY(NOT ABSORBED; FIRST PASS)
DECONTAMINATION
DecontaminationExternal
– clothes
– skin
– mucousmembranes
– oral cavity
Internal- induced emesis: NO!
- gastric lavage
Within 60 minutes, except drugs delaying gastricemptying: ANTICHOLINERGICS, TCA, BARBITURATES, OPIATES
- gut washoutPOLYETHYLENE GLYCOL 1500-2000 ml/h
- activated charcoal(1g = 1000-2000 m2 surface) 1 g / ttkg
Further steps
SYMPTOMATIC TREATMENT
DECONTAMINATION
ELIMINATION
ANTIDOTE
ELIMINATION – KIDNEYS
FORCED DIURESISNEUTRAL, ALKALINE, ACIDOTIC
Indication:
If the agent is filtrated by the kidneys(target: GFR ↑)
small molecular weight– small volume of distribution– low prot. binding
electrically charged molecules– ION TRAPPING
Method:
Monitor fluid balance, ion- and pH balance
Close observation
In: 300-500 mL/h Target urine output: 300 mL/h
(Furosemid, Etacrinic acid, Mannitol, Theophyllin /GFR↑/)
Alkalinization/acidification PRN
ELIMINATION - GIT
If the poison is excreted by bile:
20 g of activated charcoal/ 4 h
Observation!! (ileus, bleeding, check INR !)
ELIMINATION – EXTRACORPOREAL TECHNIQUES:
PERFUSION (HP),
ACT. CHARCOAL
ACETAMINOPHEN,AMMANITA TOX., AMOBARBITAL, ATENOLOL, CCl4, CHLORAMPHENICOL, CHOLHICIN, COFFEIN, DIGITOXIN, DYSOPYRAMID, DIPHEN.HYDANTOIN, GLUTETHIMID,INH,MEPBROMAT,NADOLOL, ORGANOPHOSPHAT,PARAQUAT, PHENYLBUTHAZON, PHENOBARBITAL, PHENYTOIN, QUININ, SALICYLAT , SOTALOL, THEOPHYLLIN, THYROXIN, CARBAMAZEPIN
If the agent binds to thematerial of the capsule(charcoal, resin)
HEMODIALYSIS
• SMALL MOLECULAR WEIGHT(< 500 D)
» WATER SOLUBLE
» SMALL Vd; LOW PROT. BIND.
» LOW CLEARANCE
ARSENIC, BORIC ACID, BROMINE, CHLORAT, DISOPYRAMID, ETHYLENGLYCOL, FLECAINID, INH, ISOPROPIL ALKOHOL, MAGNESIUM, OXALATE, SALICYLIC ACID, SOTALOL,
VALPROAT
APHERESIS / PLASMAPHERESIS
If the agent’s protein binding > 90 % AMMANITA TOXIN, SNAKE POISONS, METHAEMOGLOBIN, NEUROLEPTICS, NIFEDIPIN, PARAQUAT, PHENYTOIN, SEDATO-HYPNOTICS, THYROXIN, TCA,VERAPAMIL
Molecular Adsorbents Recirculation System (MARS)
• two separate dialysis circuits– first circuit consists of human serum albumin, is in
contact with the patient's blood through a semipermeable membrane and has two special filters to clean the albumin after it has absorbed toxins from the patient's blood
– second circuit consists of a hemodialysis machine -used to clean the albumin in the first circuit before it is recirculated to the semipermeable membrane in contact with the patient's blood
„ANTI-TOXINS”
SYMPTOMATIC TREATMENT
DECONTAMINATION
ELIMINATION
ANTIDOTE
ANTIDOTES
ACETAMINOPHEN NAC
ACEI ANGITENSINAMID
ANTICHOLINERG PHYSOSTIGMIN
NEOSTIGMIN
ARSEN BAL-MERCAPTOL
BENZODIAZEPIN FLUMANEZIL
ß-BLOCKER GLUCAGON
ISOPROTERENOL
BOTULINUS TOXIN ANTITOXIN
CARBAMATE ATROPIN
CA-CSATORNA BLOCK CALCIUM
ANTIDOTES
COUMARINS VITAMIN K
DIGITALIS Fab
CYANIDE 4-DMA
DICOBALT EDTA
HEPARIN PROTAMINE-SULPHATE
FORMALDEHYDE FOLATE
ETHYLEN GLYCOL ETHYLALCOHOL
FOMEPIZOL
MERCURY BAL-DIMERCAPTOL
HYDROGEN-FLUORIDE CALCIUM
INSULIN GLUCAGON
GLUCOSE
ANTIDOTES
OPIATES NALOXONE
METHGB METHYLENE BLUE
METHYL ALCOHOL ETHANOL
FOLIC ACID
PLUMB BAL-MERCAPTOL
ORGANOPHOSPHATE PAM
PARAQUAT FULLER EARTH
THEOPHYLLIN ADENOSIN
OXALATE CALCIUM
IRON DEFEROXAMIN
…
Special
poisonings
Alcohol
Level of alcohol (g/l) Level of alcohol (‰) Degree of drunkness
0,6-1,8 0,75-2,25 mild
1,8-3,0 2,25-3,75 medium
3,0-4,2 3,75-5,25 severe
>4,2 >5,25 life threatening
Therapy: supportive, frequent BM check, fluid administrationwith mechanical ventilation and circulatory support if requiredDisposition: depends merely on the initial state and theresponse to therapy but mainly home
Ethylene glycol and methanol
Ethylene glycol and methanol
• Treatment:– blocking alcohol dehydrogenase (with ethanol or fomepizol)
– PPI
– Bicarbonate (methanol)
– Hemodialysis, if• arterial pH < 7.10,
• pH decreases despite bicarb.infusion>
• pH < 7.3 despite bicarb.
• increase in serum creatinine
• if the initial plasma ethylenglycol/methanol level≥ 500 mg/l.
• Disposition: ITU
Ethylene glycol and methanol
fomepizol
Mg, B6
folate
thiamine
NaHCO3
Benzodiazepins
• The most frequent drug of choice in suicide• Symptoms: dizziness, confusion, somnolence, blurred
vision, loss of contact, anxiety, agitation• Treatment:
– Decontaminatiom: • gastric lavage within 60 seconds
– Aspec. and spec. therapy• single dose of 1 g/kg activated charcoal (aspiration!)• mechanival ventilation if required• flumazenil (0,3 + 0,1 mg), BUT REMEMBER: pts with BD abuse it might
trigger fits, in TCA overdose it may cause fits and arrhythmias!
– Differential diagnosis: other sedatives, controlled drugs
• Disposition: ED, ITU, psychiatry
Tricyclic antidepressants
Main pharmacodynamic effects:– Alfa1-blockade– Na-channel blockade– Inhibition of reuptake of biogen
amines (NADR, SER)– Muscarinic receptor blockade
(anticholinergic)– Histamin receptor blockade
(antihistamin)– Inhibition of K-efflux– Indirect GABAA -blockade
• Effects on peripheral nervoussystem– Anticholinergic effects
• tachycardia,hyperthermia,midriasis, anhydrosis, skin flush, ileus, urinaryretention
– Alfa1-blockade• reflex tachycardia,myosis
• CNS effects– Excitative
• agitation, delirium, myoclonus, hyperreflexia, generalized fits, hyperthermia
– Inhibitory• sedation, coma
Tricyclic antidepressantsPROBLEM/SYMPTOM TREATMENT
Hypertension Usually transient, no need to treat
Hypotension Crystalloid, NaHCO3, if QRS>100 ms, NADR, DA
Tachycardia Usually no need to treat
Monomorphic VT NaHCO3, syncDCCV, overdive pacing
Polymorphic VT (torsades) MgSO4
Bradydysrhythmia (late, usually notfrequent )
ACLS bradycardia protocol
QRS and QT prolongation If symptomatic: NaHCO3
Coma ETT, ventilatory support
Seizures diazepam, midazolam or propofol inf.
Hyperthermia GA, cooling
Disposition: depends on the initial state and the response to treatment
Paracetamol• Abssorption:
– Rapidly from GIT– Peak conc. between
60-120 min. • Half life:
– 0.9 -3.25 hours• Metabolism:
– Indepenedent of age– Not influenced by renal
disease– May be up to 17 hrs in liver
disease!
• Factors influencingtoxicity
– total quantity ingested– time from ingestion to
treatment– age of the patient– alcohol– enzyme inducing
medications
Paracetamol
Potential liver damage
– Adults: > 150 mg/kg in acute dose
– Adults: > 7.5 Grams in 24 hours (chronic)
– Children (<10 yrs): > 200 mg/k
4 Stages of Acetaminophen Poisoning
• Phase I (30 minutes to 4 hours)
– Within a few hours after ingestion, patients experience anorexia, nausea, pallor, vomiting, and diaphoresis. Malaise may be present.
Patient may appear normal
• Phase II (24 to 48 hours)
– Symptoms less severe. May seem like recovery. Right upper quadrant pain may be present due to hepatic damage.
– Liver enzymes become abnormal. Prothrombin time may be prolonged. Renal function may begin to deteriorate.
• Phase III (3 to 5 days)
– Characterized by symptoms of hepatic necrosis. Coagulation defects, jaundice, and renal failure have been noted. Hepatic encephalopathy has been noted. Centrilobular necrosis. Nausea and vomiting . Death due to hepatic failure.
• Phase IV (4 days to 2 weeks)
–Complete resolution or death
Rumack-Matthew nomogram
Based on this:N-acetil-cisztein (NAC)Tretment with NAC should be started ASAP withan initial dose of 150 mg/ttkg, followed by 50 mg/ttkg maintenace dosebased on the nomogramIf levesl can not be measured: 72 hDisposition: ITU
Treatment
– activated charcoal
– cathartics, bowel washout
– Haemodialysis
• Limited results due to rapid progression
– Haemoperfusion
• Ineffective
– Peritoneal dialyisis
• Ineffective
Amphetamin, metamphetamin, mefedron
• Symptoms:– CNS: headache, agitation, anxiety– dsykinesis– stroke-like symptoms– chest pain– palpitation– dry mouth– nausea/vomiting– diarrhoea– urinary retention– sweating– mydriasis
Treatment:• Gastric lavage: general indications• Bowel washout (body packers)• Supportive treatment:
– BZDs, circulatory support– beta-blockers are contrainidcated –
unopposed alpha effects!!– cooling– haloperidol?
Disposition: depends on symptomsand response to treatment
Opiates
• Versatile „usage”
• Quite severe dependency
• Conjugates in the liver–prolonged effects in liverdisease
• Quite often taken withsomething else
• Tipycal signs and symptoms:
– „skin popping, mainlining”
– nasal mucosa damage,
– poor general condition
– myosis (but mydrisasis insymp. tone!)
– RR: 4-6/min
– mild hypotension (if severelook for other causes!)
Opiates
• Treatment:
– supportive
– airway safety! mechanical ventilation if required–respiratory depression is the main cause of death
– naloxone: • 0,1-0,4 mg /1-2 min.
• rapid and specific antagonist
• Disposition: depends on the very complexbackground (dependency, amount, etc)
Carbon monoxide
• Might be a diagnosticchallenge
• Aspecific symptoms
• Quick poison
• Results from incompletecombustion
• Other sources
• Binds 230-270 timesbetter to Hb than oxygen
• 100 ppm causessymptoms
• Direct toxic effect on CIP-C and CIP 450
• Half-lives:– in room air: 3-4 h
– in 100 % oxygen: 30-90’
– in 100 % oxigénben AND at2,5 atm pressure:15-23’
Carbon monoxide• Symptoms
– fatigue– weakness– palpitation– chest pain– nausea– vomiting– visual disturbances– incontinence– tachypnoe
• Diagnosis:– think of the possibility!– co-oxymetry: 5-10 % CoHb
is significant (smokers!)
• Treatment:– immediate rescue– fresh air– O2!!– hiperbaric oxygen
chamber: 100% oxygen at2.4-3 atm pressure for 90-120 minutes
Disposition: ITU/ED
And at last:
Situation.
Background.
Assessment.
Recommendation.
S
B
A
R