Poisoning and Drug Overdoses Current Concepts Timothy Albertson MD, MPH, PhD Chief Division of...
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Transcript of Poisoning and Drug Overdoses Current Concepts Timothy Albertson MD, MPH, PhD Chief Division of...
Poisoning and Drug OverdosesCurrent Concepts
Timothy Albertson MD, MPH, PhD
Chief Division of Pulmonary and Critical Care Medicine and Chief Division Emergency Medicine and Clinical
ToxicologyMedical Director of the Sacramento Division of the
California Poison Control System
Poisoning and Overdoses
Common Problem 4-5 million cases/year estimated2.3 million calls to PCC’s in 2002
Bi-modal age distribution60% < 6 mostly
males(age 1-3 most common)
25% age 10-40 most women(20-30 most common)
Poisoning - Demographics
90% occur in the homeRatio accidental/total exp0.99 for children < 60.50 for teenagers0.30 for adults
92% of all exposures managed with supportive therapy/observation/simple decontamination
Deaths from Exposures
1000 - 2000 deaths a year9.8% under age 57.5% IngestionMost Common: Carbon monoxide, Analgesics, Antidepressants, Stimulants
Poisoning - Fatalities
Depends on the dataset17,692 deaths (CDC – 1997)1153 deaths (AAPCC – 2002)
AAPCC data29 deaths - < 12 years (10%
intentional)76 deaths 13-19 (90% intentional)1048 deaths > 19 (80% intentional)
Fatalities – Drugs involved
Analgesics (57%)Sedatives/hypnotics/psychotics (31%)Stimulants and street drugs (21%)Half of all reported cases !!
Antidepressants (21%)Cardiovascular Drugs (16%)Alcohols (12%)
Clinical Implications of Exposure Data
Most poisonings in children are unintentional.Most fatalities are suicidal or intentional abuse in adultsMost who arrive alive to hospital will survive
Poisoning – Management Principles
Primacy of History and P.E.Tempo of illness in medical toxicologyRate of change
Importance of frequent and repeated observationTime becomes an important test
Lesser emphasis on toxicologic testing.
Find Out What Was Ingested or Used
HistoryOld recordsPoliceEMT’sFriends
Key Points in the History
What?How much?When?Acute, subactue or chronic exposure?Route of exposure?Co-ingestants.Watch for “non-drugs”
Age of patient.
Additional Points in the History
Underlying medical history.Social history.Psychiatric history.Paramedics as history and “evidence” sources.The history can be completely
inaccurate – remain skeptical.Always attempt to correlate the history
with the physical examination
Basic Diagnosis of Poisoning
Physical ExaminationLOCBowel soundsPupilsNailsSmellsIV TracksFasiculations
Toxidromes
Key Points in the Physical Examination
General impression and observations.Use all senses including smell
Six Vital Signs:PulseBlood PressureRespiratory Rate(Rectal) TemperatureMental Status(Room Air) Pulse oximetry
Find Out What Was Ingested or Used
Lab valuesToxicology: screens (urine and blood) and specific drug
levels (e.g. Lithium, theophylline, ASA, digoxin, acetaminophen, etc.)
EKGX-Ray’sElectrolytesAnion gapOsmalar gapArterial blood gas
Always consider trauma or medical dx’s
Toxicology Screens
Specific drug levels are often valuableCost and usefulness of routine Tox screens is case specificKnow your lab’s capabilities
Toxicology Screening
Usually done by some form of spectrophotometryUrine – widest number of drugs/metabolitesCannot “back calculate” to a blood level
Blood – Few screens alter therapySpecific levels important – single assaysTheophyline, methanol, EG, ASA,
acetaminophen, Iron
The Laboratory in Toxicology
Over reliance on “Tox Screens”A negative tox screen ≠ no ingestionMost screens do not alter
managementExpensive and labor intense
Key Tests/Calculations required:Anion GapOsmolar GapSelected levels e.g. Acetaminophen, Li,
digoxin, theophylline, ASA
Anion Gap
Anion Gap = [Na] –([Cl ]+ [HCO3])Normal 5-12 meq/L
Elucidates the “unmeasured anions” - albumin contributes up to 11 at 4 gm/dlUsually organic acids – lactate, ketones
Overdoses with AG critical to identifyHigh lethality – ASA, MethOH, EG, Theophyline,
CN, Iron, Several have specific antidotes
Osmolar Gap
Osm Gap = 2x[Na] + [BUN]/2.8 + [Glucose]/18 + EtOH/4.6Normal Gap 0-10 mosm/LElevated Gap = Volatile drug screenMUST measure using freezing point depressionFor other osmotically active substances = MW/10Conversion factors for alcohol substitutes: methanol 3.2, ethylene glycol 6.2, isopropyl alcohol 6.0
X-Rays in Toxicology
AspirationsIron or metals in GI tractEnteric coated medicinesChloral hydrateBody packers
Adult Drug Poisonings
EthanolBenzodiazepinesAnalgesicsOpiatesAntidepressants and antipsychoticsAnticonvulsantsStimulantsCombinations of drugs
Toxidromes(Toxic Syndromes)
Definition: A pattern of signs and symptoms which tend to consistently result from a particular toxic exposure.Allows the clinician to work from physical findings to a toxicologic diagnosis.
Key Toxidromes
CNS DepressionCNS StimulationAltered CNS - confusionDisassociation from the EnvironmentSpecial ToxidromesSalicylatesAcetaminophenIron
CNS Depression
“Brain Death”Barbiturates, Glutethimide, Ethchlorvinyl
OpioidPinpoint pupils
With Anticholinergic findingsTCA’s and related Drugs
With relatively normal VSBZP’s, EtOH, combinations
Basic Diagnosis of Poisoning
Pinpoint pupils ToxidromeRespirations vs no respirationsComa vs awakeMuscle fasiculations and wheezingIV Tracks presentDifferential Diagnosis:
opioids pontine hemmorhageorganophosphate pesticides
Basic Diagnosis of Poisoning
Toxic causes of seizuresLSDLithiumAmphetamine and cocaineTCA’sTheophyllineBupropionCarbon MonoxideOral hypoglycemicsAnticholinergics
Basic Diagnosis of Poisoning
Smells in ToxicologyETOH and bloodBitter almonds - cyanideWintergreen - methyl salicylateRotten eggs - hydrogen sulfide
Specific Toxicological Treatments
Benzodiazepine overdose - flumazenil agonist and antagonist at BZP receptorOpioid overdose - naloxone agonist and antagonist at opioid receptorsacetaminophen overdose - n-acytelcysteine replaces glutithione in liverdigoxin overdose - digoxin Fab fragments from sheep that bind the digoxin
Specific Toxicological Treatments
Methanol and ethylene glycol - ethanol or 4-MP (fomepizole) and hemodialysis, ethanol or 4-MP inhibits ADHArsenic - dimercaprol (BAL) im and/or dimercaptosuccinic (DMSA or succimer) po, chelates arsenic
Specific Toxicological Problems
Methamphetamine - “Ice” a CNS stimulant of abuseOverdose: CNS stimulation, seizures, abnormal behavior, cardiac arrhythmias, tachycardia, hypertension, hyperthermia, myocardial ischemia and infarctionChronic use: increased tolerance, tachyphylaxis, paranoid, weight loss, psychiatric disorders, pulmonary HTN, cardiomyopathy
Basic Principles of Poisoning Treatment
Airway, Breathing, Circulation DecontaminationTreat symptomsProtect from further harm including self-inflicted.Use Common Sense
… Don’t lose sight of the patient trying to treat the toxin…….
Decontamination (Don’t just do something… just stand there !!)
IpecacActivated CharcoalSingle dose vs. multidose
CatharticsGastric LavageWhole Bowel Lavage
IpecacDerived from the rhizome of Cephaelia ipecacuanhaContains cephaeline and emetineCardiotoxins & abuse potential
Little use in either home or EDProlonged vomitingDelay other therapy and disposition
No longer recommended for routine use by either the AAP or ACMT
Gastric Lavage (aka the “stomach pump”)
Uses Large Bore tube (ewald tube and others) with tap water to remove ingested toxinsMay require intubation for airway protectionUse in high lethality ingestions presenting promptly after exposureRelegated to the domain of “punitive toxicology?”
Activated Charcoal
Carbonaceous material activated by steam to increase surface area.Surface area 950-2000 m2/gm.
Thought to work by multiple mechanisms.Direct binding, GI hemoperfusion,
others?
Minimal risk – mostly via additives
Activated Charcoal - Dosing
50 – 100 gm in water slurry (1 gm/kg in children)Multiple Dose Activated Charcoal (MDAT)Dosed q 1 – 3 hours until charcoal stoolTheophylines, barbiturates, dapsone, and
sustained release pharmaceuticals
Cathartics
No data to support use.Osmotic cathartics (sorbitol) vs. Saline catharsis (Mg salts usually)Does not reduce “charcoal briquettes”Has potential toxicitySingle dose in premixed charcoal probably ok.
Whole Gut or Bowel Lavage
Uses large (4-8 Liters) of polyethylene glycol solution at 500 ml/hrSame protocol as GI prep.May require gastric tube
May be useful in sustained release pharmaceuticals, body packers, toxic heavy metal ingestionLittle data to support wide use.
Antidotal Therapy
Infrequently neededEasily misusedSome are high cost/high riskToxicologic consultation should be sought in ALL cases of antidotal use
N-Acetyl Cysteine (NAC)
Specific antidote for acetaminophenSupplies sulfur for glucuronationDosage based on Rumack nomogramUseful for ACUTE ingestions only
Dosed at 140 mg/kg load and 70 mg/kg for 17 doses (classically)Oral vs. IV therapy
Digibind
Fab to digoxinIndicated mostly for acute intoxicationsRemember the reason for digoxin useComplex dosing calculation based on steady state digoxin level.Whole digoxin levels subsequent for
administration will be erroneous.
4- MethylPyrazole (Fomepizole)
Inhibitor of Alcohol DehdrogenaseIndicated for methanol and EG
intoxication
Easier to dose than ethyl alcohol – especially in pediatrics15 mg/kg load, 10 mg/kg q 12 x 4 dosesExpensive ($4000.00/vial)
Pesticide Intoxications
Organophosphates inactivate acetocholinestrerase at the synaptic junctions.Produce muscarinic and nicotinic
symptoms
Nerve agents also inhibit enzymeAtropine blocks muscarinic effectsPralidoxime (2-PAM) regenerates enzyme.
Organophosphate Antidotes
Administered via autoinjectors in the field.IV infusion (intermittent vs. continuous) in the hospital.Hypertension, tachycardia, muscle rigidity
Envenomations
Need to know toxic critters in the area.Not all envenomations need to be treated.Little objective data to guide therapy.
Spiders
Virtually all species are “toxic”Most cannot deliver venom effectively
Black Widow (Lactrodectus)Antivenin rarely needed
Brown Recluse (Loxoceles)NOT present in Northern California
Snakes
North America home to only 20 speciesCrotulius – rattlesnakesSistrurus – massasauguasAgkistrodon – Copperhead
and cottonmouthMicrurus – coral snakes
Snakebites
Rattlesnake bite is most common in young men purposely handling a venomous snake while intoxicated.25% of all rattlesnake bites will be dry (no venom deposited)Probable basis for
effectiveness of “home remedies”
How nature says ‘Do not Touch”
Crotalid Envemmonation
Complex hematologic effectsInduces a DIC like pictureNormal thrombin, no activated XIIINo decrease in antithrombin III
2 AntiveninsWyeth – equine originCro-Fab – porcine Fab product
Indications
Evidence of envemonationPain, swelling, ecchymosis
Progression of swellingEvidence of systematic effectsLab parameters
LeadLead
Absorption • Oral
• Lungs
• Skin
Lead (Continued)
Distribution - blood, soft tissue and boneDistribution - blood, soft tissue and bone
• Blood - 95% associated with RBC - (t 1/2 = 35 days)Blood - 95% associated with RBC - (t 1/2 = 35 days)
• Bone - at steady 90% of total body load in bone - difficult to mobilize (t1/2 Bone - at steady 90% of total body load in bone - difficult to mobilize (t1/2 = 20 years)= 20 years)
• Tissues - kidney, liver, nervous tissue; 10% body load (t 1/2 = 40 days)Tissues - kidney, liver, nervous tissue; 10% body load (t 1/2 = 40 days)
Lead (Continued)
Toxicity of lead G.I. Mucosa
• CNS
• G.I. Mucosa
• Renal tube degeneration
• Erythrocyte
• Mechanism
1. Reduces conversion d-ALA to porphobilinogen
2. Reduces conversion protoporphyrin IX to heme
3. During lead exposure d-ALA and free protoporphyrin (FEP) accumulate in blood
Effect of Lead on Enzymes in the Heme Synthetic Pathway
Succinyl CoA+ -aminolevulinic porphobilinogen
glycine acid
uroporphyrinogen III
heme protoporphyrin IX coproporphyrinogen III +Fe- -
“EP” +Zn- - Blocked by lead
Partial block by lead
Lead Lead (Continued)(Continued)
Diagnosis
Adult
1. Signs and symptoms - colicky abdominal pain, parasthesias, anemia, metallic taste
2. Severe toxicity - hepatic and cardiac effects plus renal damage to glomeruli and tubules
3. Most striking finding in chronic exposure is peripheral motor neuron disease
Childhood
1. Symptoms - anorexia, lethargy, vomiting, abdominal pain, irritability, ataxia, anemia, learning disabilities and convulsions
2. Severe toxicity - renal disease and encephalopathy
Childhood Populations to Test for Lead Childhood Populations to Test for Lead PoisoningPoisoning
All children with pica
All children with anemia
All children living in houses built before 1940 - test early in the second year of life
All children during the second year of life
All children with hyperkinetic behavior and learning disorders
All children with neurologic disease, including seizures
California - all children before start of school
April 1987 - March 1989April 1987 - March 1989
>6,000 elevated blood lead levels (25 mcg/dl)
95% adults with occupational exposures
“Scores of reports” greater than 80 mcg/dl
Occupations with known lead exposures (lead smelting, gun firing ranges, lead battery manufacturing, etc.)
Elevated lead levels must be reported to the California Department of Health Services (H and S Code, Chapter 481, Section 309.7)
Lead Lead (Continued)(Continued)
Diagnosis
Laboratory
1. Acute hemolysis
2. Chronic - hypochromic anemia, basophilic stippling and eosinophilia
3. Free protoporphyrin (FEP) - > 50 g/100 ml to 750 g/100 ml
4. - ALA ( - aminolevulinic acid)
5. Lead levels -Symptoms > 60 g% children; > 80 g% adults -Renal effects > 100-125 g%
Laboratory - LeadLaboratory - Lead
Acute Exposures
Whole blood lead levelsWhole blood lead levels
Chronic Exposures
FEP - best screening testFEP - best screening test
Delta ALA - most sensitiveDelta ALA - most sensitive
RBC zinc protoporphyrinRBC zinc protoporphyrin
EDTA mobilization testEDTA mobilization test
Timed urine levelsTimed urine levels
Lead TreatmentLead Treatment
Symptomatic
BAL and EDTA
Asymptomatic
EDTA alone
Consider D-penicillamine oral (second line)
Succimer oral for children
History and Development of theCalifornia Poison Control System