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