OVERDOSE: THE BAND

Mr. RR, 36yo Male Brought in by EMS/CPS Found in appt building foyer asleep with friend who “escaped” Not arousable, no I.D. Smells “fruity” GCS “3” but non-purposefull

movements of all limbs present No signs of trauma, OPA accepted

TOXICOLOGY I

MANAGEMENT OF O.D. AND DECONTAMINATION ISSUES

KEVIN HANRAHAN DR. DAVID JOHNSON

OUTLINE GENERAL CONCEPTS RESUSCITATION HISTORY TOXICOLOGY

PHYSICAL TOXIDROMES INVESTIGATIONS GENERAL

DECONTAMINATION

G.I. DECONTAMINATION -ORAL REMOVAL -BINDING

-MECHANICAL FLUSHING ENHANCED ELIMINATION ANTIDOTES DISPOSITION

Nontoxic Ingestions Only one substance in exposure Substance absolutely defined No hazards on product label Unintentional Route known Approximate amount known Asymptomatic with easy follow-up

Setting Occupational-eg. xylene Recreational Medical environmental

I wonder what this xylene would

taste like

Portals of Entry Ingestion,most common

historically(76%) Inhalation(8%) Cutaneous/mucous membrane(6%) Injection-meds -drugs of abuse Insufflation

PADIS 03/04

Oral74%

Dermal10%

Sting/Bite1% Inhalation

8%

Other, Unknown0%

Parenteral1%

Ocular6%

PREVALENCE 2 Million toxic exposure in U.S.-2000 3rd leading cause of death Mortality from acute poisoning <1% Peds account for 80% 10% admitted, usually accidental Adults-20%,rarely accidental,90%

admitted to hospital Accounts for 1% admission,10% ICU

PADIS APRIL 04/MAR 05 AGE DISTRIBUTION

Unknown11%

<5 year47%

>15 year32%

11-15 year5% 5-10 year

5%

CIRCUMSTANCES- PADIS 03/04

Intentional12%

Other, Unknown3%

Unintentional85%

Major Effect1%

No Effect5%

Minor Effect28%

Non-toxic, Unknown59%

Potentially Toxic, Unknown2%

Death0%

Medical, Unknown5%

PADIS O3/04 OUTCOMES

PADIS 03/04SUBSTANCE %KIDS %ADULTOTC pain & fever meds 15.4 21.3Household cleaning prod 11.4 7.4Cosmetics & personal care 11.1 ----Mental health meds ----- 11.2Alcohols ----- 9.8Anti anx & sedatives ?? ----- 9.1Fumes/gases/vapors ----- 8.3Plants 6.6 ----Foreign bodies 5.1 -----Pesticides 3.6 4.4

RESUSCITATION Occurs simultaneously with Dx Important as support may be only Tx

for most overdoses Vitals, all 6 critical in toxicology T/BP/HR/RR/SAT/BS Airway-patent & protected? -intubate for GCS<9 Breathing-vitals and auscultate Circulation-vitals,establish IV,EKG

RESUSCITATION cont’d Decide:stable/unstable :?heavy hitter eg TCA, Bblocker etc Antidote-rarely takes precedence over

ABC (cyanide toxicity) Coma Cocktail-hypoxia -wernicke’s -opioid intox. -hypoglycemia

“HEAVY HITTERS” Largest number of deaths in 2000 in U.S. -analgesics-antidepressants-sedative/hypnotics/antipsychotics-stimulants-street drugs-CV drugs-alcohols

RESUSCITATION cont’d Seizures-BZD.,phenobarb, not dilantin Hypotension-isotonic fluids,bicarb,hi dose levo/dop Vent. Arhythmia-bicarb bolus,lidocaine,BB in chloral

hydrate-see ACLS for specific toxins

COMA COCKTAIL Cheap Minimal risk Simple Oxygen as per

need D50W,50g,adult 4ml/k D25W or

10ml/k D10W Pediatrics

THIAMINE Not necessary in kids 100mg IV/IM qdaily ?before D50W? Previously thought to prevent

Wernicke’s encephalopathy

WHERE’S THE

EVIDENCE?

Thiamine/Glucose Originally came from 5 case reports of

Wernicke’s precipitated or made worse by glucose before thiamine

All 5 had severe nutritional deficiencies, several comorbid illnesses and received glucose for several days before thiamine was administered

Therefore don’t delay glucose in ED for thiamine

Hack,JB,JAMA 1988

NALOXONE (NARCAN) 0.1-2.0MG IV/IM, +/- restraints 20-60 min. response time 2nd dose 2/3 of first Observe 2-3h Triad of dec. LOC,miosis,resp dep. Resp status only reliable way to

determine effect of narcan. Other drugs affect LOC and some opioids

can cause mydriasis

NALOXONE 730 pts prehospital tapes/sheets reviewed in

AMS pts. for response to Narcan and clinical presentation.

RR<12,pinpoint pupils,circumstantial evidence of opiate abuse all predictive of response

Use of these criteria would decrease Narcan use by75-90% without missing any responders

Hoffman,JR,Annals of Emergency Med., 1991

FLUMAZENIL AS PART OF THE COMA COCKTAIL? Retrospective analysis of 35 consecutive

comatose pts Divided into low and non-low risk for sz. based

on clinical and ECG(proconvulsive OD’s) Only 4 were assessed as low risk High risk of sz. In non-low risk group Low risk might benefit but very small minority

of pts.Gueye,PN,Annals of Emergency Medicine, 1996 Flum. May also precip. Arrythmia in TCA

TOXICOLOGICAL HISTORY MOST IMPORTANT DIAGNOSTIC TEST # of pts/type of exp/

amounts,dose/route/intent “all OD’s are liars” Corroborate with

MD/pharmacist/EMS/witnesses Info on environment:empty bottles, odours,material,hobbies,notes AMPLE

Toxic Features History-suicide, prev. O.D. or abuse-psychiatric or polypharmacy Physical-arrest,bronchospasm,dysrythm nyd- thermia/tension-AMS,sz.,rigidity,dsytonia,rotary nystagmus Investigation-anion/osmolar gap, K-Na-gluc-renal/hepatic failure,rhabdo,aspiration

TOXICOLOGICAL PHYSICAL Expose, look for hidden substances Waist bands,skin folds,groin Watch for sharps

NEEDLE COLLECTION

Bright yellow disposal boxes in easily accessible locations encourage IV drug users to safely discard used syringes. The project collected 22,245 needles in 2001.

GENERAL APPEARANCE LOC;agitation,obtundation,confus. Skin;cyanosis,flushing,diaphoresis dryness, Injuries,injections,bullae,bruising (may be from trauma,dec LOC

longterm or coagulopathy)

ODOURS Almonds Eggs Fish Garlic Fresh hay Geraniums Swimming pool Mothball Violets Wintergreeen peanuts

Cyanide Hydrogen sulf Sinc sulfide Org phosporous Phosgene Lewisite Chlorine gas Camphor,naptha Turpentine Methyl salicylate vacor

SKIN FINDINGSCyanosis Deoxyhemoglobin or

methemoglobinYellowing Carotene veg.,cigs,picric acid,

Dinitrophenolflushing Antichol,scombroid,rectal F.B,

Disulfiram,niacin,nitratresGray Metallic silver or goldEschar Anthrax,radioactive,brown

recluse spider,Bullae Barbs,chemotherapiesRed skin Cholinerg,vanco,CO,boric acidNail lines Arsenic,chemotherapy

CNS LOC/cognition Tone Reflexes Coordination Ambulation

Toxins Causing Seizures Amphetamines

Antihistamines/ anticholinergics Caffeine/theoph Antipsychotics Carbamates CO

Cocaine Hypoglycemics Chlorambucil Propranolol salicylates

Cyclic antidepress Ethylene glycol Isoniazid Lead

Lidocaine Lithium Methanol Organophosphates Phencyclidine

Withdrawal from ETOH/sedatives

Toxins Affecting Tone

Dystonic reactions

Dsykinesias Rigidity

Haldol Anticholinergic Black widowMetoclopramide

Cocaine Malign hyperth

Olanzapine Phencyclidine Neur malig synPhenothiazines Risperidone StrychnineRisperidone Fentanyl

phencyclidine

Toxins Causing AMSDEPRESSED AGITATED DELIRIUMSympatholytics Sympathomim

eticsETOH/drug withdrawal

Adrenergics bl Adrenergic ag AnticholinergicsAntiarrhythmic Amphet AntihistAntihypertens Caffeine COAntipsychotics Cocaine Cimetidine

Cholinergics Ergots Heavy metals

Bethanechol MAOI’s LithiumCarbamates Theophylline SalicylatesNicotine Anticholiner

DEPRESSED AGITATED DELIRIUMOrganophos antihistaminePhysostigmine AntiparkinsonPilocarpine AntipsychoticSedat/hypnot AntispasmodicAlchohols Cyclic antideprBarbs CyclobezaprineBZD Drug withdrawGamma Hydrox B-blockersEthchlorvynol ClonidineNarcotics EthanolAnalgesics OpioidsAntidiarheal Sed/hypnotic

DEPRESSED AGITATED DELIRIUM

Cyanide Marijuana

Hydrogen sulfide

Mescaline

Hypoglycemic

LSD

lithium

EYES Pupils: size, reactivity,equality Dysconjugate gaze lacrimation

Toxins Affecting Pupil SizeMiosis MydriasisBarbiturates AmphetaminesCarbamates AnticholinergicsClonidine Antihistamines

Ethanol CocaineIsopropyl alcohol Cyclic antidepressantOrganophosphates Dopamine

Opioids Glutethimide

Phencyclidine LSDPhenothiazines MAOI’sPhysostigmine PhencyclidinePilocarpine demerol

MOUTH (with suction) Retained contents or pills Gag Dryness/salivation

Lungs Air entry oxygenation wheezing bronchorhea

TOXINS CAUSING HYPOVENTILLATION Alcohols Barbs Botulinum Cyclic

antidepress Neuromuscular blockade

Opioids Sedative/hypnot Snake bite Strychnine tetanus

HEART/PULSES Rate Rhythm Regularity Peripheral pulses/perfusion

TOXINS AFFECTING PULSE TachycardiaCommon -

TCA -CO -anticholinerg eg. Gravol -adrenergic eg. cocaine

BradycardiaCommon -opioids -cholinergics -BBlockers

ABDOMEN Bowel sounds Rigidity Urinary retention tenderness

TOXIDROMES Physiological groups Based on VS,general appearance, skin,eyes,mm,etc. Also basic labs

DO THE BASIC FINDINGS MATCH WITH A POISON ? Basis for toxidrome Eg. Autonomic syndromes

sympatheticparasympathetic

Adrenergic symptoms,eg. cocaine

Cholinergic,eg organophospates

Anticholinergic,eg. gravolNo bowel sounds,dry skin,blurry vis,fever etc

S.L.U.D.G.ETahycardia,htn, diaphoresis, mydriasis,etc

Autonomic Nervous System

NIC

NES

NICMUSC

PS

NIC

NMJ

Toxidrome Agent Findings

Opioids Heroine Dec. loc,miosis,dec.RRSympatho Cocaine Agitation,mydriasis,diap

horesis,tachy,etcCholinergic Organoph S.L.U.D.G.E.Antichol Atropine Dry,red,AMS,hyper-t etcSalicylates ASA AMS,resp alk,met acid et

Hypoglyc Insulin AMS,diaph,tachy,etcSerotonin SSRI AMS,inc tone,hyper-t

Toxins Affecting Temperature Hypothermia-TCA,Li,Phenothiazin-alcohol,barbs,opium-hypoglycemics colchicine,akee fruit-AMS in winter

Hyperthermia-LSD,cocaine,PCP, amphetamines-antichol,antihist-TCA,MAOI,SSRI phenothiazines-ASA-malign hyper/NMS

TOXINS AFFECTING BREATHING Hypoventilation-eg alcohols,BZD., opioids Bronchospasm- eg cocaine, BB, aspiration from AMS

INVESTIGATIONSPROGRESSIVE TESTING CBC&D,CHEM 7,ABG,LFT osmolality EKG CXR FLAT PLATE XR SPECIFIC DRUG LEVELS Tox. Screens

Anion Gap Acidosis Toxins

Acetominophen Amiloride Ascorbic acid CO Colchicine Nipride Dapsone Epi

Ethanol Ethylene glycol Formaldehyde Hydrogen sulfide Iron isoniazid

Ketamine Metformin

Methanol Niacin NSAIDS Papaverine Paraldehyde Phenformin Propofol

Salicylates Terbutaline Tetracycline Toluene verapamil

OSMOLAR GAP VARIABILITY “NORMAL” OSMOLAR GAP 8-10 Distribution curve puts real normal

between -?1 and +10-11 Therefore gap of 10 in someone

who’s “resting” gap is 2 may contain error of 8

Methanol toxic >6.2mmol/l

Toxins with Inc. Osmolal gap Ethanol Ethylene glycol

glycoaldehyde Glycine IV immunoglobulin

Isopropanol

2(NA)+Gluc+bun+/-1.25(etoh)

Mannitol

Methanol/fromaldehyde

Propylene glycol Radiocontrast Hypermagnesemia sorbitol

EKG EKG findings in TCA:sinus tach,inc.

QRS/QTc intervals, inc PR interval RAD in the T40ms frontal QRS plane I neg/AVR pos, in T40ms Due to quinidine like effect on RBBB in TCA 8.6 times more likely in TCA OD 83%sens, 63% spec

Wolfe, TR, Ann of Emerg Med, 1989

EKG

Scan0002.jpgScan0002.jpg

EKG IN TCA

ACLS Rx of Toxic Dysrythmias

Stimulant/Sympathomimetics-consider BZD,Ablockers,Lidocaine NaHCo3, not Bblockers CCB’s-consider mixed A/B agonists, pacer, Ca++,insulin euglycemia Bblockers-consider pacer,mixed A/B agonists, glucagon/insulin euglycemia

ACLS Handbook of Emerg Card Care 2000

RADIOLOGY CXR if prompted by Hx, Px or

specific other findings like hypoxia Flat plat may be considerred for FB

or ingestions of radiopaque toxins eg iron CT scan for AMS r/o HI and ICP if indicated

TOX SCREENS Marijuana/opioids/cocaine/amphetamine/

TCA/barbs/BZD/phencyclidine Usually does not affect assessment or

outcome acutely False +:amphet-propranolol,cpz etc TCA-flexeril,mellaril,etc False -:opioid-demerol,heroin amphet-MDMA, benzo-rohypnol

TOX SCREENS cont’d Slow to return Most OD’s treated with support alone Chronic ingestion eg. Marijuana may confuse

issue Less frequent intoxicants not quickly

available May be helpful in persistant sick without

obvious etiology In kids may be helpful for neglect/abuse

situations

APAP/ASA/ETOH Frequent co-ingestants Relatively quick May help sort out multiple ingestion

scenario May help psych. with ongoing

assessment

GENERAL DECONTAMINATION

It’s great the fire department

provides us with these sprinklers

on hot days

GROSS DECONTAMINATION Remove patient from substance Remove substance from patient Undress(including jewelry,watches –

biohazard) Wash, head to toe In mass casualty done in field or in

isolation area outside ambulance bays in most hospitals

Staff need full PPE

GROSS DECONTAMINATION

Colonoscopy booth

EYES Copious (usually 2L) irrigation Normal saline best but tap will do 0.5% tetracaine, lid retractors

helpful 1ml tetracaine in 100ml saline

EYE IRRIGATION

EYES cont’d Alkali exposure may require 1-2h of

irrigation given deep penetration NS ph 5.6 After equilibration (10min) Tear film ph<8

GI DECONTAMINATION Oral removal-emesis -lavage Binding Mechanical flushing

EMESIS Derived from

emetine and cephaline (plants)

Works centrally on chemotactic trigger zone and stomach

Dose 30ml (15ml in 1-12) with sips

IPECAC cont’d Can repeat once 90% vomit in 20m 97% 2nd dose Ave. 3-5 vomits Done in 2h If 30m 18-52% If 60m 31-36%

IPECAC CONTRAINDICATIONS AMS or drugs that can cause

rapid(<60mins) AMS (TCA,eucalyptus,strychnine)

Active or prior vomiting Caustic/corrosive ingestion >pulmonary than GI toxicity (hydrocarbons) Ingestion which can cause sz. Debilitated/elderly or medical made worse

by vomiting

IPECAC COMPLICATIONS Boerhaves’

syndrome Malory-Weiss

tears Intractable

vomitting Inability to give

oral treatments

IPECAC INDICATIONS Very limited in hospital setting Rare-larger pills than orogastric tube

in recent ingestion(<60min) that can’t be absorbed by charcoal on a Tuesday when the moon is full!

At home if remote, recent and no contraindications

IPECAC INDICATIONS cont’“syrup of Ipecac should not be administered

routinely in the management of poisoned patients…There is no evidence from clinical studies that ipecac improves the outcome of poisoned patients and its routine administration in the ED should be abandonned”

AACT Position paper, Journal of Toxicology, 2004AMERICAN ACADEMY OF CLINICAL TOXICOLOGY (AACT)

OROGASTRIC LAVAGE LL decubitus position 36-40F(adult),22-24F(kids) Chin to xyphoid measurement Room temp tap water untill clear Instillation of charcoal before

removing if indicated

OG LAVAGE CONTRAINDICATIONS Pills too big Non-toxic ingestion Non-life threatening ingestion GI hem, perf or recent Sx Airway not assured Material lung danger>GI tract

(hydrocarbon,corrosive)

OG LAVAGE COMPLICATIONS Tracheal lavage Aspiration, tension pneumo, charcoal

empyema Atrial/ventricular ectopy Esoph, trach or gastric trauma or

perforation Desaturation, laryngospasm Tube knot formation fluid/lyte imbalance

OG LAVAGE EVIDENCE

Prospective study of 808 pts with presumed OD

Odd/even day gastric emptying(GE) with either ipecac or lavage based on LOC. Others got charcoal

GE did not alter LOS,length of intubation,ICU LOS,

GE increased ICU admits for asp. Pneum

Merigian, KS, Amer. J. of Emerg. Med. 1990

GE EVIDENCE cont’d PRCT of 876 pts with OD Odd/even day randomization for

GE/AC or just AC GE was lavage or ipecac No difference in outcome regardless

of time to presentation

Pond,SM,Medical J. of Australia,1995

AACT INDICATIONS Not routinely recommended Not if greater than 60mins Not if not life threatenning Must have assured airway No definite evidence that it improves

outcome and may cause morbidity

CHARCOAL (GUT TOXIN ADSORPTION)(GI DIALYSIS)

ACTIVATED CHARCOAL(AC) Pyrolysis of carbanaceous material Steam cleaned to increase the surface

area (activated) Adsorbs (holds to surface) toxins in the

gut lumen Improves gut/blood gradient (GI dialysis)

for previously absorbed Binds substances excreted in bile

interrupting enterohepatic circ.

Toxins Not Adsorbed by AC Alcohols Hydrocarbons Organophosphates Carbamates acids

Potassium DDT Alkali Iron lithium

AC cont’d Decreased benefit with time as toxin

travels beyond pylorus At 30 min mean bioavailability

decreased by 70% At 60 min by 37% No good studies that show clinical

benefit of single dose AC (AACT)

AC BENEFITS Decontaminating gut non-invasively Rapid administration Safe in adults and kids Can be administered with juice,

water or by OG 1g/kg or 50g in most adults +/- cathartic with first dose

AC EVIDENCE RCT with 1479 pts. randomized to AC +

supportive measures or support alone Measured clinical deterioration, LOS in ED

or hospital, complications and length of intubation

Trial done over 24 mos., lge urban center

Merigian,KS, Amer. J. of Therapeutics, 2002

AC EVIDENCE cont’d No sig. difference in length of

intubation,LOS for hospital and complication rate

Longer ED stay (6.2vs5.3h) and more vomiting (23vs13%)in AC group

No benefit of AC over support alone

Merigian, KS, Am.J.Therepeutics, 2002

AC CONTRAINDICATIONS Perforation or abnormal GI tract If emergency endoscopy planned

e.g. caustics Unprotected airway Increased risk from aspiration (eg

Hydrocarbons)

AC COMPLICATIONS Aspiration Impaction with abnormal motility Vomiting Corneal abrasions

AC INDICATIONS Ingestion of any drug known to be

adsorbed by charcoal with toxic ingestion Does not work for lithium, iron, lead Unknown ingestion with protected airway Lack of good clinical data for or againstTherefore Not routine (AACT) Best within 1 hour (AACT) No evidence it improves outcome (AACT)

MULTIPLE DOSE CHARCOAL .25-.5G/kg on subsequent doses Q1-4h Only first dose has cathartic Indications-large ingestions -substances that form bezoars or are injurious -slow release toxins -enterohepatic/enteric circul. substances

Multi-dosable AC Amytrityline Amoxapine Baclofen? BZD’s? Buproprion?

Carbamazepine Chlordecone Dapsone Dig Disopyramide Glutethimide Maprotiline

Theophylline sotalol

Meprobamate Methyprylon Nadolol Nortriptyline Phencyclidine

Phenobarb Phenylbutazone

Phenytoin Pyroxicam Propoxyphene Quinine Salicylates?

MULTI-DOSE AC cont’d Contraindicated in non-life-

threatening ingestions and toxins which slow GI motility as these increase risk of aspiration from gastric distention and impaction of charcoal

No specific AACT position statement

CATHARTICS

CATHARTICS Sorbitol 70% (1g/kg) or 250ml of 10% mag

citrate (4ml/kg in kids) Studies consistently show decreased transit

time for charcoalKrenzolok,EP,Ann Em Med, 1985Harchelroad,F,J.Clin. Tox., 1989 Cathartic alone not effectiveMinton,NA, J Clin Tox.,1995Al-Shareef,AH,Hum Exp Tox.,1990 Peak plasma concentrations decrease with catharticsPicchioni, AL, J Toxicol Clin Toxicol, 1982Goldberg, MJ, Clin Pharmacol Ther, 1987

Cathartics Indications Same as single dose charcoal Ingestions unknown or known to be

adsorbed by charcoal with protected airway

AACT-not alone, not endorsed routinely with or w/o charcoal, single dose if used

Cathartics complications Nausea, vomitting, abdo cramps Volume depletion, electrolyte disturb Hypermagnesemia in renal impaired

if magnesium product Hypernatremia if Na product

Cathartics Contraindications Ingestions that cause diarhea Kids <1 or very old Mag citrate in renal failure Obstruction, no BS, abdo

trauma,recent abdo Sx,perf. corrosive ingestion Heart block Hypotense,vol. deplete, lyte imbal.

WHOLE BOWEL IRRIGATION (WBI)

Electrolyte/osmotic balanced polyethylene glycol (Golytely)

Mechanically forces ingested toxins through the bowel

2L/h (adult), 50-250ml/h(peds) Until clear rectal fluid

WBI Indications-AACT 1997 No controlled clinical studies showing

improved outcomes but some volunteer studies

Not routine Consider in slow release or enteric coated

toxic ingestions Theoretic potential in iron and other non-

adsorbables(Li,lead,zinc) Theoretic in delayed presentation, large

amounts, drug packers(Farmer, JW, J Clin Gastro, 2003)

WBI complications Nausea, vomiting, cramps,bloating Pulmonary aspiration Rectal irritation Increased nursing care !!

WBI Contraindications Diarhea or substances that cause it Absent bowel sounds Intractable vomiting Obstruction, ileus,perforation,hem Hemodynamic instability Compromised airway

ENHANCED ELIMINATION Urinary-diuresis -alkalinization -acidification Dialysis Hemoperfusion hemofiltration

DIURESIS Not been well studied Consists of achieving 3-6ml/k/h u/o Isotonic fluids and diuretics Not recommended Causes electrolyte

imbalance,pulmonary edema,raised ICP

Also doesn’t work

Urinary Alkalinization Helpful in some ingestions Weak acids held within renal tubule and

excreted with bicarb 3 amps (150 ml) of bicarb in 850 D5W at

250/h Goal urine pH 7.5-8.0 Must have normal K+ so add 40 meq kcl

to bag after initially correcting hypokal.

URINARY ALKALINIZATIONTissues Plasma Urine

pH 6.8

HA

H+ + A-

pH 7.4

HA

H+ + A-

pH 8.0 (alkalinized)

HA

H+ + A-

GOAL PH

Alkalinizable ToxinsASA Uranium Quinolones PrimidonePhenobarb methotrexate

2,4 dichorphenoxy-acetic acid

Flouride Isoniazid methobarbitol

Urinary Alk. Complications Dec. K+ Volume overload (CHF) pH shifts

Urinary Alk. Containdication Can’t tolerate fluid or Na+ load Hypokalemia Renal failure Toxin known not to respond

Acidification of Urine Virtually never used Potential for myoglobinuric renal

tubular injury Systemic acidosis additive Arginine/lysine hydrochloride or

ammonium chloride ? Use in amphetamine/phencyclidine

DIALYSIS

I am sure happy to be here today

Dialysis Removes both the toxin and it’s

metabolites Removes toxins that can’t be

adsorbed by charcoal Less effective with lge mol wgt,

protein bound, large vol. dist.

Hemodialysis Indications Dialysable toxin that is life

threatenning Peritoneal dialysis rarely used

Dialysis Contraindications Hemodynamic instability Small children (exchange transfusion

better) Poor vascular access Profound bleeding diathesis

Dialysis Complications Fluid shifts Electrolyte imbalance Bleeding at access site Infection Intracranial hemorhage

Hemoperfusion Charcoal filter in dialysis machine Works better for large molecule size

and protein bound if adsorbable Needs small volume of distribution Must not be highly tissue bound Rarely used

Hemoperfusion Complications Cartridge saturation Thrombocytopenia (plt dec by 30%) Hypoglycemia, hypocalcemia Access complications Hypothermia (pump not heated) Charcoal embolization

Hemoperfusion cont’dWorks Phenobarb,phenytoin,theophylline,

carbamazepine,paraquat, glutethimideDoesn’t Work Heavy metals,ethanol,methanol,CO, cocaine

Hemofiltration Removes toxins by convection

through a highly porous membrane Works well with toxins with large

volume of distribution, extensive tissue binding

Works well for large molecular wgt substances

Not well studied

ANTIDOTES Increases the mean lethal dose of a

toxin or favorably affects the effect of the toxin

Specific indications Beyond the scope of this lecture

ANTIDOTES eg.Drug/Poison AntidoteAcetominophen N-acetylcysteineAntichonergics PhysostigmineAnticholinesterases AtropineBenzodiazepines FlumazenilBlack Widow Bite Equine AntiveninCarbon Monoxide OxygenCoral Snake Bite AntiveninCyanide Amyl Nitrate,etc

Antidotes cont’dDigoxin DigibindEthylene glycol Ethanol/fomepizoleHeavy metals Dimercaprol,EDTAHypoglycemics DextroseIron DeferoxamineIsoniazid PyridoxineMethanol Ethanol,fomepizoleMethemoglobinemia Methylene blueOpioids NaloxoneOrganophospates Atropine,pralodox.Rattlesnake bite antivenin

INDICATIONS FOR THE ICU PaCo2 >45 (Brett, AS, Arch Int Med,1987) Intubation need Seizures Arrhythmias Prolonged QRS >.12s SBP <80 2nd or 3rd degree AV block GCS <12 (unresponsive to verbal) Dialysis Staffing (babysitting suicidal) Hypo/Hyperthermia Naloxone drip

EXCELLENT REVIEW ARTICLE Babak, M, Jerrold, BL, Patrick, M, “Adult Toxicology in Critical Care” Chest, 2003;123:577-592.

??? QUESTIONS ???