Clinical Toxicology

Presentation overview

Epidemiology of poisoning General approach to the poisoned patient Update on poison treatment methods Most common errors in Medical Toxicology Specific Poisoning

Medical Toxicology

Predominately comprised of physicians from the specialties of: Emergency Medicine Internal Medicine Pediatrics Occupational Medicine Critical care

Clinical Toxicology

Significant role for scientists, analytical chemists, industrial hygienists, nurses and pharmacists Poison center management and specialists Poison prevention (industrial and home directed education) Industrial/ occupational toxicology

Epidemiology of Poisoning

Approximately 1,500 cases of fatal poisoning are reported to the American Association of Poison Control Centers each year Settings include workplace, home and recreational 2 to 3 million people poisoned annually, most ingestions managed by poison centers Accidental poisoning occurs mainly in children Half of poisoning fatalities are intentional

Most common substances ingested

Analgesic agents Cosmetics/ personal care products Household cleaning products Sedative hypnotics/ antipsychotics Foreign bodies/ toys Cough/ cold OTC preparations Topical preparations Pesticides
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Most common substances ingested Fatal Cases 2005

Analgesic agents Sedative hypnotics/ antipsychotics Antidepressant agents Stimulant and street drugs Cardiovascular drugs Alcohols Anticonvulsants Antihistamines Fumes/ vapors/ gases
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General Approach to the Poisoned Patient

Systematic Treatment and Diagnostic Actions in Parallel Goal is rapid stabilization, categorization of poison class, initiation of general treatment then specific treatment when available

General Approach to the Poisoned Patient

1. Stabilization 2. Rapid Patient Evaluation (Physical, Lab) 3. Prevention of further toxin absorption 4. Enhancement of toxin elimination 5. Specific antidote 6. Supportive therapy

2. Rapid Patient Evaluation

History is often absent or unreliable Information from any source usually helpful Physical exam is very important

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Physical Examination in Clinical Toxicology

General appearance Vital Signs Skin HEENT (head, ears, eyes, nose, throat) Pulmonary Cardiovascular Abdomen Neurologic
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Characteristic odors in poisoning

Odor
Bitter almonds Eggs Mothballs Wintergreen Garlic

Poison
cyanide hydrogen sulfide, mercaptans naphthalene, camphor methylsalicylate As, org- phosphates, DMSO, Thallium

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Toxic Syndromes

Sympathomimetic Anticholinergic Cholinergic (muscarinic) Narcotic

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Sympathomimetic Toxic Syndrome

Vital signs: Tachycardia, hypertension, hyperpyrexia.

Clinical appearance: diaphoresis (sweating), piloerection, mydriasis and hyperreflexia. In severe cases, seizures, hypotension (later effect) and dysrhythmias may occur.
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Anticholinergic Toxic Syndrome

Vital signs: Tachycardia, hypertension, hyperpyrexia

Clinical appearance: Hot, dry skin, mydriasis, diminished or absent bowel sounds, urinary retention, confusion and delirium. Sinus tachycardia is most common but other cardiac conduction abnormalities may occur. Seizures may occur with agents that enter the CNS.

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Cholinergic Toxic Syndrome

Vital signs: Bradycardia, increased respiratory rate (initially) Clinical appearance:

SLUDGE

Salivation Lacrimation Urination Defecation Diaphoresis Gastrointestinal distress Edema (Pulmonary)

Also see: miosis (pinpoint pupils), muscle fasciculations, CNS depression
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Narcotic Toxic Syndrome

Vital signs: Bradycardia, hypotension, hypothermia and hypoventilation.

Clinical appearance: altered mental status coma, miosis, diminished bowel sounds, needle tracks, pulmonary edema, hyporeflexia.

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Case Example

A 29-year-old male is brought to the emergency department by friends who report he has had several generalized seizures in the last 30 minutes. The patient is awake, hyper-alert and unwilling to provide a history. BP= 200/110. P=140/ min, RR = 22min, T=38.1C Skin is cool. Pupils are dilated and reactive. CV reveals tachycardia only. Abdomen reveals present bowel sounds, nontender. Neurologic exam reveals a resting tremor, brisk (3/4) reflexes and nonfocal exam.

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Toxic Syndrome

Anticholinergic Sympathomimetic Cholinergic (muscarinic) Narcotic

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Laboratory Evaluation in Clinical Toxicology

Very few diagnostic lab tests are available STAT Salicylate Acetaminophen Digoxin Iron Ethanol Theophylline Lithium

Important clues are usually found in routine labs NEVER DELAY THERAPY WHILE WAITING FOR LAB DATA

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Anion Gap

Valuable information from a routine lab test Calculated from serum electrolytes Anion Gap = [Na] ([HCO3 ] + [CI]) Normal anion gap = 12 2mEq/L

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Differential Diagnosis of Elevated Anion Gap with Metabolic Acidosis

AT MUD PILES
A ALCOHOL (ETHANOL KETOACIDOSIS) T TOLUENE M METHANOL U UREMIA D DIABETIC KETOACIDOSIS P I L E S PARALDEHYDE IRON, ISONIAZID LACTIC ACID ETHYLENE GLYCOL SALICYLATE
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Arterial Blood Gases

pH pCO2 pO2

identify acidemia, alkalemia identify hypo-or hypercapnia - identify hypoxia

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Osmolar Gap

Difference between measured and calculated serum osmolality Seen in the presence of low molecular weight toxins

Osmolar gap Osm

where:

= Measured Ser Osm Calc Ser

normal = 0-10 mOsm Calc Ser Osm = 2 [Na] + [ Glucose/ 18] + [BUN]/ 2.8

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Osmolar Gap Example

Na = 140 mEq/L Glucose = 100 mg/ dl Blood urea nitrogen (BUN) = 12mg / dl Serum Osmolarity (measured) = 330 mOsm OSM GAP = 330 mOSM [[2x140] + [100/18] + [12/2.8]] OSM GAP = 330 - [280 + 5.6 + 4.3] =330-290 OSM GAP = 40 mOsm (elevated)

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Differential Diagnosis of Elevated Osmolar Gap

Methanol Ethanol Ethylene Glycol Isopropanol

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Radiology Evaluation

Overall limited diagnostic role:

ingested lead paint chips ingested radiodense oral meds ingested foreign bodies ingested chloroform or CCI4

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Radiology Evaluation

CHIPES
C chloral hydrate, chloroform, CCI4 H heavy metals I iron P phenothiazines E enteric coated S sustained release

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Illegal Drug / Substance Abuse Terminology

Body packer: Smuggle large quantities of illicit drugs in uniform tightly sealed containers Body stuffers: When faced with imminent arrest, hurriedly ingests illicit drugs in insecure packages

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3. Prevention of Further Absorption

Emesis with syrup of ipecac Gastric lavage Activated charcoal Whole bowel irrigation

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Induction of Emesis

Syrup of Ipecac Former standard of home use, now use is rare and considered controversial in 2006 Largely replaced by activated charcoal or no treatment Contraindications: Children less than 6 months old Seizures or absent gag reflex Ingestion of corrosives, hydrocarbons or sedating drugs if past 30 minutes post ingestion

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Induction of Emesis

Bottom line:

Not perfomed in ED or inpatient setting

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Case Example

The parents of a 3-year-old male weighing 13 kg call the Arizona poison control center to report that their child just ingested several prescription of iron tablets. The poison control specialist determines the prescription was filled 3 days ago, the bottle contained 100 ferrous sulfate tablets, each containing 65 mg of elemental iron. The mother (patient) used 4 tablets, 62 tablets remain in the bottle. The ingestion occurred approximately 10 minutes ago. The child is assymptomatic. The family lives in a remote area, the closest health care facility is 3 to 4 hours away.

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Case Example

Dose estimation: 100 4 = 96 -62 = 32 Fe tablets missing 34 Fe tablets x 65 mg Fe/tablets = 2,210 mg elemental Fe 2,210 mg Fe/13 kg = 170 mg Fe/ kg

Refer to hospital if > 20-30 mg Fe/ kg High likelihood of severe toxicity if > 50 mg/ kg ingested

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Gastric Lavage

Former ER standard, now very limited role Accomplished with an orogastric tube Airway protection important Contraindications:
Ingestion of corrosives Possibly ingestion of hydrocarbons

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Activated Charcoal

Recommended for almost all ingestion Inadequate dosage is the most common error Initial dose with cathartic

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Activated Charcoal

Not effective for: Li, Fe and other metals K+ , I and other halides Corrosives

Minimally effective for EtOH, ethylene glycol, MeOH

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Whole Bowel Irrigation

Procedure:
use PEG ELS solution 1.5 2 L/ hr in adults (0.5 L/hr children) oral administration or via NG tube 6 hrs or clear effluent

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Whole Bowel Irrigation

Uses: Body packers (best evidence) Oral OD with sustained release compounds Oral OD with agents not absorbed by activated charcoal

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Whole Bowel Irrigation

Contraindications: Hemodynamic instability Diarrhea or anticipated diarrhea GI obstruction, perforation or hemorrhage Unprotected or comprised airway

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4. Enhancement of Poison Elimination

Alteration of urine pH Hemodialysis Hemoperfusion Serial oral activated charcoal

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Alteration of Urine pH

ONLY ALKALINIZATION

Ion trapping 2 amps NaHCO3 in D5W at 70 to 150 cc/hr Target: urine pH 7.5 to 8.5 Uses: salicylate OD (best evidence)

American Association of Poison Control Centers and the European Association of Poisons Centers and Clinical Toxicologists 2004 Position Paper on Urinary Alkalinization recommends this procedure for moderately severe salicylate poisoning for patient not meeting criteria for hemodialysis

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Characteristics of Toxins Favoring Removal by Hemodialysis

High water solubility Low volume of distribution Low molecular weight Low protein binding

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Agents for which Hemodialysis is Effective for Poisoning

Alcohols Antibiotics Boric Acid Bromide Calcium Chloral Hydrate Fluorides Iodides Isoniazid Lithium Meprobamate Metformin Paraldehyde Phenobarbital Potassium Salicylates Strychnine Theophylline Thiocynates Valoproic acid
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Characteristics of Toxins Favoring Removal by Hemoperfusion

Low volume of distribution High toxin affinity to absorbent Can be effective with less water soluble poisons Can be effective with high molecular weight toxins

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The Hemoperfusion Circuit

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Hemoperfusion

Cartridge availability limited (medical centers): Uses: Severe theophylline Amanita toxin Paraquat Meprobamate

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Serial Oral Activated Charcoal

0.5 1.0 gm/ kg every 2-4 hours by mouth / NG Interrupts enterohepatic circulation Gut dialysis Enhances the clerance of several drugs including: Carbamazepine Dapsone Digoxin Digitoxin - Nadolol - Phenobarbital - Salicylates - Theophylline

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5. Use of a Specific Antidote

Available for relatively few poisons Includes: Antibody fragments Chelating Agents Pharmacologic Antidotes Biochemical Antidotes

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Antidotes reverse pharmacologic effect

Naxone: reverses narcotic effects Sodium bicarbonate: tricyclic antidepressants Methylene blue: methemoglobin forming toxins Glucagon, atropine, isoproterenol: reverses bradycardia causing toxins Alpha and beta adrenergic blockers (not pure beta only): reverses sympathomimetic agents hypertensive effects

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Antidotes biochemical prevention of organ toxicity

N - acetylcysteine: - prevents acetaminophen liver necrosis Ethanol, 4-methylpyrazole: - prevents methanol and ethylene glycol acidosis and blindness Nitrites, thiosulfate or hydroxycobalamin: - prevents cyanide induced tissue death
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Methanol Metabolism

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Ethylene Glycol Metabolism

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Antidotes antagonism of enzyme inhibition

Vitamin K for warfarin induced bleeding Vitamin B6 for isoniazid induced seizures Atropine and pralidoxime for cholinesterase inhibitors Reduced folates and thymidine for methotrexate induced leukopenia

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Antidotes chelation of toxic metals

Deferoxamine for Fe Dimercaptosuccinic acid, Dimercaprol, CaEDTA, penicillamine for Pb DMSA, DMPS, N- acetylpenicillamine, BAL for Hg

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Some Commercially Available Antidotes

12/8/97 Fomepazole (Antizole) for ethylene glycol poisoning (orphan, 12/22/88), Orphan Medical, Minnetonka, MN 1/30/91 Succimer (Chemet) for leading poisoning in children (orphan, 05/09/84), Bock Pharmacal Company, St Louis, MO 3/21/86 Digoxin Fab fragments (Digibind), digitalis intoxication (orphan, 11/01/84), Glaxo Wellcome Inc. 1/31/85 Acetylcysteine (Mucomyst) for acetaminophen overdose, Apothecon Pharmaceuticals Divison of Bristol Meyers Squibb 2/8/54 Pre 1938 thiosulphate, Antivenin (Crotalidae) Polyvalent antivenin, Wyeth-Ayerst Laboratories Cyanide Antidote Package, Combination pack: sodium nitrite, sodium amyl nitrite, Eli Lilly & Co. 56

New FDA Approved Antidotes - 1

IV N-acetylcysteine (NAC) acetaminophen Fomepizole ethylene glycol and methanol Glucagon or insulin glucose Ca/ beta blockers Octreotide oral hypoglycemic agents
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New FDA Approved Antidotes - 2

L carnitine valproate liver toxicity Physostigmine gammo hydroxybutyric acid and pure anticholinergics Crotalid polyvalent immune Fab crotalid envenomation Hydroxocobalamin cyanide chelator (approved 12/06)
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6. Supportive Care

Close monitoring for late toxic effects Vigilance for hospital acquired disease Nosocomial infections Aspiration pneumonia Latrogenic fluid / electrolyte abnormalities Psychiatric consultation for intentional ODs

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Update highlights

GI decontamination: Ipecac now less commonly used Gastric lavage seldom used Whole bowel irrigation Expanded use of activated charcoal Toxin elimination: Hemodialysis >> Hemoperfusion Expanded use of multiple dose activated charcoal
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Most common errors in medical Toxicology

Minimizing the potential amount of toxin ingested Failure to consider mixed ingestion of toxin Inadequate dosage of activated charcoal Inappropriate use of gastric lavage procedure Failure to protect airway prior to gastric intubation Failure to periodically reassess patient clinically (numbers game)
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SUMMARY

A systematic approach has proven to be the most efficacious way to treat critically ill poisoned patients. Categorization of the poisoned patients clinical appearance into a toxic syndrome allows the clinician to initiate effective treatment without knowing the specific poison involved. More research is needed to develop new and more effective treatments for poisoning.

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