General Tox Approach

7/29/2019 General Tox Approach

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GENERAL APPROACH TO THE POISONED

PATIENTPRIMARY SURVEYAIRWAY: LOOK LISTEN FEEL MANAGEBREATHING: LOOK LISTEN FEEL MANAGECIRCULATION: LOOK LISTEN FEEL MANAGEDISABILITY: PUPILS GCS MANAGEEXPOSURE:FULL VITALS:Check chemstrip and temperature

ADJUNCTS TO PRIMARY SURVEY

Universal antidotes (if indicated)

Dextrose: 1g/Kg (D50W in adults, D25W in peds) Oxygen Narcan: 2mg bolus IV/IM/SL/SC/ETT then 10mg repeat if no effect (peds:

0.01mg/kg bolus then 0.1mg/Kg repeat) Thiamine: 100mg IV/IM (before glucose)

Toxicologic Investigations Tox labs: CBC, urea, Cr, lytes, osmolarity, EtOH, glucose, ASA, APAP ECG Liver enzymes/function for hepatotoxins ABG if sick Serum Drug Levels prn Urine tox screen if indicated

SECONDARY SURVEY

Full head - to - toe examination Look for toxidromes Look for trauma Look for signs of medical illness

ADJUNCTS TO SECONDARY SURVEY

Decontamination Gastric Lavage Epicac Shower Irrigation Activated charcoal Multi-dose activated charcoal Whole Bowel Irrigation

Elimination Alkalinization Forced Saline diuresis Dialysis

Specific antidoses or adjuncts
http://www.bcltechnologies.com/easypdf/


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CLINICAL FEATURES OF TOXICOLOGY

TOXICOLOGICAL HISTORY

Overdose details: What, when, route, dose, co-ingestants, why

EMS should bring all prescription bottles

Get pharmacy printout

Identify pills and make sure pills equal label

Look through medications on old chart

Ask family/friend about possible ingestants

Ask what else is available in the house (INH example)

Bring in containers

Search the patient

Have family or police search the patients house

Consider body packing/stuffing if ingestant unknown

Specifically ask about SLOW - RELEASE preparations

TOXICOLOGICAL EXAMINATION

Accurate vital signs essential

Look for signs of trauma: head trauma important

Look for signs of medical illness

Look for body packing/stuffing

Look for toxidromes = constellations of signs and symptoms associated with a class ofdrug or toxin

Level of consciousness

HR, BP, temp Pupils Skin Bowel sounds Reflexes, rigidity

Odors in OverdosesAlmonds CyanideCarrots Water hemlockFishy Zinc or aluminumFruity EtOH, acetone, isopropanol, hydrocarbonsGarlic Arsenic, etcGlue Toluene, solventsPears Chloral hydrate, paraldehydeRotten eggs H2S, NACShoe polish Nitro benzeneWintergreen Methyl salicylate


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TOXINS CAUSING SEIZURES

C Cyclic antidepressantsCholinergics:organophosphatesCaffeineCamphor

A AmphetaminesAntihistaminesAmoxapine

P PhenothiazinesPropranololPhenylpropanolaminePiroxicam

I Isoniazid (think inaboriginals, refractoryseizures, or anyone onTB Rx)

T Theophylline

TOXINS CAUSING TEMP CHANGES

Hyperthermia

Anitcholinergics Sympathomimetics Seritonin syndrome Salicylates Methylxanthines Thyroxoine NMS

Hypothermia CO Opiates Oral hypoglycemics Insulin Alcohol Sedatives Hypnotics Phenothiazines

TOXINS AND CV CHANGES

TACHYCARDIA TCAPhenothiazineTheophyllineChloral HydrateAny stimulantSSRIsSNRIs

BRADYCARDIA CholinergicsBeta BlockersCCBs

DigoxinNa channelblockersOpiatesSedative/hypnoticsAlpha agonistsGHBTrazadone

WCT TCAsAntihistaminesCocaines

Other stimulantsBBCCBDigoxinCarbemazepineQuinineChloroquinePhenothiazines

TOXINS CAUSING PINPOINTPUPILS (MIOSIS)

ClonidineOpiates (except demerol)OrganophosphatesPCPPhenothiazinesPilocarpine


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TOXICOLOGY AND THE LAB

DRUG SCREENS NOT ROUTINELY INDICATED

Lab doesnt screen for most drugs Initial screen may be negative if done soon after the ingestion Positive findings may not be the cause of the presentation (cocaine +ve in

urine for days after use) Expensive Rarely change clinical managment

ANION GAP

The difference between measured cations and anions

There truly is no difference b/c electrical neutrality is maintained but we dont measure all cations

and anions thus a measured gap is evident Cations: Na+ is vast majority (Ca, Mg, K are minority)

Anions: Cl-, HC03-

Anion Gap made up mostly of albumin: thus hypoalbuminemic patients have a lower anion gap

and increased AGMA may not be picked up (AG may go from 5 to 10 but is still within the

normal range)

Low anion gap ( +6: simultaneous metabolic alkalosis or respiratory acidosis

low delta G < -6: simultaneous respiratory alkalosis or low AG state

Other

CO/CN: oxidative phosphorylation inhibition

EtOH: ethyl alcohol donates an H+ thus mild direct acidosis; also respiratory

depression and dehydration thus mild indirect acidosis

Paraldehyde: acetic and chloracetic acid

Methanol: formic acid

Ethylene glycol: oxalic acid

Isoniazid: > 30 mg/kg causes lifethreatening acidosis, acidosis is secondary to

lactate production during seizure; pyridoxine and dialysis as treatment

Iron: inhibits oxidative phosphrylation, negative ionotrope, dehydrated, GI

bleeding/hypovolemia, and Fe2+ > F3 + + H+ all contribute to acidosis

ASA: acetylsalicylic acid, salicylic acid, also inhibits oxidative phosphorylation

thus lactic acidosis (major mechanism), ketoacidosis, aminoacids (catabolic state

due to inhibition of oxidative phosphyrlation); note combined A/B disorder b/c of

stimulation of respiratory centers and respiratory alkalosis

Toluene

-inhaled hydrocarbon; often abused


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-acrylic paints, glues, adhesives, paint, varnish, laquers

-sniffing (breath over a container), huffing (sniff from a rag) or bagging

(sniff from a bag)

-rapid absorption to lungs, CNS intoxication for hours-CNS: stupor, intoxication, sz, ataxia, headache, hallucination

-CVS: arrythmias and sudden death (SENSITIZED MYOCARDIUM to

catecholamines); inhaled hydrocarbon then exertion > sudden death

Toxins that increase AGMA independent of lactate

ASA

Methanol

Ethylene glycol

DIFFERENTIAL DIAGNOSIS OF INCREASED AGMA

A AKA, ASA, alcohol intoxication

M Methanol

U Uremia

D DKA

P Paradehyde, Phenformin (Metformin)

I Iron, Isoniazid, Ibuprofen (rare)L Lactic acidosis (any cause)

E Ethylene glycol

C CO, CN

A ASA

T Toluene, Theophylline

O Other

H2S

MetforminOSMOLAR GAP

Osmolality = measured osmolality Lab measurement of moles of solute/kg of solvent Measured by freezing point depression Can also be measured by vapor pressure but this is less reliable b/c

erroneously low results will occur with volatile substances (alcohols)

Osmolarity = osmolarity calculated Calculated moles of solute/L of solution Different formulas exist Calgary lab uses: 1.86Na + BUN + glucose + 9 + EtOH (this assumes

Na+ Cl- ionized forms which is more accurate)


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Edmonton lab uses: 2Na + BUN + glucose + EtOH (this assumes NaClform which is less accurate)

Osmolar Gap

Osmolar Gap = Measure osmolality - Calculated osmolarity Normal osmolar gap = -15 up to + 10 (mean -2) Normal gap due to calcium, lipids, proteins Differential diagnosis of osmolar gap: see table Note that a wide range of osmolar gaps are possible with toxic alcohols;

there may be no osmolar gap if converted to metabolites Indications for measuring toxic alcohols: (note: you can and should still

measure toxic alcohol levels if indicated but you will have to specificallyask for them)

Calgary lab: osmolar gap > 10 Edmonton lab: osmolar gap > 2; ethylene glycol level done

osmoar gap > 5; methanol level done

Ethanol and the Osmolar Gap Osmolarity formulas account for EtOH level New evidence that EtOH actually increases the osmolar gap more than

expected from the EtOH level alone Purssell Ann Emerg Med 2001

Correlated osmolality with rising levels of EtOH Determined that EtOH X 1.25 should be used when

calculating osmolarity EtOH results in higher osmolality than expected from

simple EtOH level: why? Ethanol in solution has a nonidealosmotic behaviour (ie; they form bonds with each otherwhen put in solution thus changing the osmotic effect). In

other words, 1 mmol/L (osmolarity) leads to 1.25 mOsm/kg(osmolality)


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P Proteins

A Alcohols- Ethanol- Methanol- Isopropanol- Propylene glycol (plumming antifreeze, diluant for many drugs)- Diethylene glycol- Triethylene glycol

S Surgars- Mannitol- Glycerol- Sorbitol

C Contrast dye

A Acidosis- Lacticacidosis- Ketoacidosis (DKA, AKA)

L Lipids

A Acetone


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TOXICOLOGICAL TESTS

Immunoassays Uses antibodies to detect drugs or metabolites

Chromatography Analyte specificity is achieved by physical separation Major advantage: multiple substances can be detected in a single

procedure Can look for many different compounds thus more useful for general

screening Thin Layer Chromatography: substance put on thin layer plate, solvent is

drawn up the plate by capillary action; compared to controls; slow andlabor intensive

High Performance Liquid Chromatography: similar idea but the mobilephase is pumped through under high pressure; peaks are detecteddepending on how far the substance moved down the plate and are

compared to controls Gas Chromatography: similar idea but the moving phase is a gas Mass spectrometer: a highly sensitive detector to detect very small

quantities; mas spec uses electromagnetic filtering to determine the massof the ions; ultimately produces peaks on graph that are characteristic ofcertain drugs

Urine Tox screens Vary with each lab Most urine screens use immunoassays Confirmatory Gas chromatography and mass spec is done if

immunoassay is +ve


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DECONTAMINATION

GENERAL

Definition Decontamination is the prevention of absorption into the bloodstream

Factors to consider Is this a dangerous toxin? Is there likely to be further absorption? How long from the time of ingestion? Is there an effective antidote? Has the clinical course excluded the posibility of toxicity?

Gastric Emptying

Most studies show that minimal drug is in stomach after 2-4 hours Time in stomach varies with drug Drugs that SLOW gastric emptying and increase the possible time for

gastric empyting to be effective Anticholinergics Opiates Sedative/hypnotics Gastric concretions: ASA, iron, phenobarbital

Vomiting Self induced vomiting and ipecac are never indicated Unlikely to removed significant amount of toxin Risk of aspiration

Ipecac hinds administration of charcoal Risk of MWTs, esophageal rupture

GASTRIC LAVAGE

Technique of Gastric Lavage Large gastric tube (36 french) Left lateral position Tap water or saline 300 cc in, clamp, drain by gravity Continue until clear; follow lavage with activated charcoal

Potential Complications Injury to pharynx

Esophageal tears Gastric perforation Aspiration

Evidence Behind and Controversies Shown to decrease drug absorption in volunteers Only (limited) clinical benefit has been shown if done LESS than one hour Has been trends toward clinical improvements in serious overdoses Some people advocate never using gastric lavage, BUT!! ACEP policy statement: little to indicate value; selective use only Study limitations

Small sample sizes thus not powered to exclude clinicallyimportant differences


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Include multiple different overdoses Exclude critically ill patients (where it is really needed!!) Poor controls, poor randomization

Hasnt been specifically studied where it makes moresense (enteric coated, pylorospasms, gastric concretions,etc)

Indications for gastric lavage No universal indications can be given Case-by-case consideration is appropriate Considerations FOR gastric lavage

Potentially lethal overdose NO effective antidote Patient currently symptomatic Time since ingestions < 1-2 hours Charcoal ineffective (Li, Fe)

Gastric concretions (ASA, Fe, enteric coated, phenobarb) Pylorospasm (ASA) No antecedant vomiting Delayed gastric absorption (anticholinergics, narcotics,

enteric coated preparations)

Contraindications Inability to protect airway (ie; must intubate)

ACTIVATED CHARCOAL Dose

No universal correct dose; no maximum dose known Ideal charcoal:drug ratio is 10:1 Most common initial doses: 0.5 - 1.0 g/kg (Adults = 50 gm) Use larger doses (1.5 - 2.0 g/kg) for dangerous large ingestions of agents

well absorbed by charcoal: ASA, theophylline, verapamil SR

How beneficial is activated charcoal? Lowers absorption, lower peak serum levels, decreased area under the

curve Beneficial only if substance still present in the GI tract and binds to

charcoal

Many animal studies showing benefit Many human studies showing decreased absorption Limited studies to show clinical benefit

Indications Should be administered in virtually all cases ofpotentially toxic overdoses More effective earlier but history is so inaccurate, reasonable to give even

with later presentations Consider using for overdose of toxin that doesnt bind charcoal b/c of

possibility of co-ingestant

Drugs NOT absorbed by charcoal C Caustics H Hydrocarbons


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I Iron L Lithium, Lead

E Ethanol

Multidose Activated Charcoal (MDAC) Doses and frequency varies with indication Can be given by continuous NG infusion Massive ingestion: one dose wont be enough Sustained release: delayed release of drug Gastric concretions Enhanced elimination: prevents enterohepatic reabsorption of active drug

or metabolites?

Contraindications Caustic ingestions: doesnt bind, obscures endoscopy Unprotected airway Hydrocarbons: increased risk of aspiration and ARDS

Complications Very safe GI upset Bowel obstruction: case reports with MDAC Aspiration is biggest risk

Trivial aspiration very common Significant aspiration rare

CATHARTICS

Purpose = increase GI transit speed, decrease transit time

No proven benefit

Effect on activated charcoal: occasionally benefitial, usually no effect, occasionallyharmful

Only three used with any frequency: sorbital, magnesium sulfate, magnesium citrate

Sorbital: 1 gm/kg; repeat dose X 1 only at 0.5 mg/kg with MDAC if no ileus/obstruction

No evidence of harm for single use if no contraindications

Complications: dehydration, electrolyte changes, GI upset, abdominal distension

Children have more problems with fluid and electrolyte shifts

Relative contraindications: Bowel obstruction Ileus (absent bowel sounds) Diarrhea (uneccessary) Infants and young children

WHOLE BOWEL IRRIGATION

General More effective than clearing bowel than cathartic PEG-ELS solution is electrolyte and osmolarity balanced thus no

fluid/electrolyte shifts (isotonic components); huge volumes are notdangerous

Components are not absorbed Mechanical washout of bowel (doesnt draw in fluid or stimulate motility)

Indications for WBI: serious overdoses, poor binding to charcoal, sustained release


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Iron Lithium Body packers

Body stuffers Slow release preparations

ASA CCBs Valproic acid

OTHER GI DECONTAMINATION

Endoscopic removal: difficult to remove concretions and body packs; complications ofprocedure usually outweigh potential benefit; rarely indicated (very durable packs withbody packers)

Surgical removal: rarely body packs causing bowel obstruction or intestinal ischemia

Surgery post GI perforation after caustic ingestions

ELIMINATION

GENERAL

Elimination = removal of toxin after it has been absorbed

Indications Patients who fail supportive care Patients in whom the normal route of elimination is impaired (renal failure) Patients in whom the toxin is expected to be very significant Patients that are not expected to tolerate the physiologic effects

Methods of Elimination MDAC Hemodialysis Urine alkalinization Peritoneal dialysis Charcoal hemoperfusion Hemofiltration Plasmapheresis Exchange transfusion Diuresis Chelation

Ion Trapping = Urine Alkalinization

ASA Barbituates Formic acid (methanol): minor role Methotrexate

Chlorpropamide (Diabenese - oral hypoglycemic)

HEMODIALYSIS

What are features of dialyzable drugs?

Low Vd

Low protein binding

Small molecular weights

Water soluble


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Single compartment kinetics

Low endogenous clearance

Adv of hemodialysis over other extracorporeal techniques

Corrects acid - base abnormalities Corrects electrolyte abnormalities

Removes MORE drug than CRRT (continous hemofiltration)

Toxins well removed by HEMODIALYSIS

Methanol

Ethylene Glycol

Isopropranol

ASA

Lithium

Valproic acid

Theophyllin

Possibly effective dialysis Amanita mushroom toxin Tegretol BB: atenolol, sotalol Paraquat Phenytoin Phenobarbital Procainamide Methotrexate

DIALYZABLE OVERDOSES

M Methanol

E Ethylene Glycol

T Theophylline

I Isopropranol

V Valproic AcidA ASA

L Lithium


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DIAGNOSTIC IMAGING AND TOXICOLOGYRADIOPAQUE INGESTIONS

C Chloral hydrate, Calcium carbonateH Heavy metals (iron, lead, arsenic, lithium, zinc), barium, bisthmus

I IronP Play-doh

P Phenothiazines, Potassium chloride

E Enteric coated pills

D Dental amalgam

ED MANAGEMENT

Approach: see ToNotes

Decontamination

(1) Ipecac: NO role in ED b/c emesis will only dec absp by 30%. May be

indicated for use at the home

(2) Gastric Lavage

orogastric hose 30 - 40 F

infuse 300ml until fluid is clear

adv: immediate recovery of gastric material, control lavage

duration, direct access for instillation of charcol

disadv: invasive, efficacy is questionable a/f 1-2h post-ingestion, aspiration risk (decreased by trendelenberg)

(3) Shower

Decrease Absorption

(1) Activated Charcol

agent of choice for gastrointestinal decontamination in

acute

may reduce absorption by 50% alone

dose: 1g/Kg

disadv: poor pt acceptance, messy

(5) Cathartics

theory: speed up GI motility :. shortening time forabsorption

but: not shown to improve pt outcome and may increase

absortpion

disadv: frequent liquid stools, dehydration and lyte

imbalances esp in children

(6) Whole Bowel Irrigation

used in body stuffers and sustained-release or enteridc-

coated medication overdoses

NG tube then goGo-Litely @ 1-2 L/hr until objects


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removed or effluent clear

Increased Elimination

(1) Dialysis

(2) Forced Diuresis

(3) Alkalinization of serum

TCA example: changing pH from 7.45 to 7.50 increases

albumin binding from 95 - 96% of drug :. free drug (which

is active) goes from 5% to 4% which is a 20% reduction in

the amount of free drug.

Alkalinization also changes the intracellular pH and allows

the open of H/M ? gates of the Na+ channel and release of

the TCA

(4) Alkalinization of the urine

Ion Trapping of ASA in the urine b/c the alkalinized formis not reabsorbed as well.

Supportive Care

(1) Oxygen, IV, Monitor

(2) Management of Respiratory Complications

Airway protection: intubation if necessary

Ventilation may be necessary

ARDS: high-flow oxygen, +ve pressure ventilation,

consider PEEP

(3) CV Complications

arrythmias as per ACLS

hypotension: fluids only (vassopressors rare) hypertension: nitroprusside, CCBs

(4) Neuro Complications

coma: airway etc

seizures: very dangerours, standard tx w/ benzos and

phenobarb, paralyzing agents may be needed initially to

control prolonged sz (pancuronium)

behavioural abnormailities: chemical sedation is dangerous

b/c of cardioresp compromise :. use physical restraints if

possible: ativan and haloperidol are effective if necessary

Diagnostic Studies

Drug Screens: urine and blood

Routine labs

ABGs important

Definitive Care

Antagonists: see table 129-2, pp740

All poisoned pts should get oxygen, glucose, and naloxozone (narcan)

Elimination: example is alkalinization of urine in ASA od

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General Tox Approach