TOXICOLOGY TEASERS
| EFFICIENT APPROACH TO THE POISONED PATIENT —Carson R. Harris, MD, Associate Professor of Emergency
Medicine and Director of Clinical Toxicology, University of Minnesota Medical School, Minneapolis
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| Initial management: “history MATTERS”—medication or material ingested; amount; time taken; emesis; reason;
signs and symptoms; examination—vital signs; mental status; pupillary response; skin changes; odors
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| Antidotes: O2 ; naloxone (Narcan); N-acetylcysteine (NAC; antidote to acetaminophen); atropine and pralidoxime; calcium;
2,3-dimercaptosuccinic acid (DMSA; antidote to lead, arsenic, and mercury); sodium bicarbonate (antidote to tricyclic
antidepressants [TCAs]); ethanol (usually 10% solution); digoxin-specific Fab; glucose; hydroxocobalamin used
in Europe as antidote to cyanide (cyanide kit available in United States); physostigmine; pyridoxine; glucagon
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| Basics: ABCs, ie, airway/antidote; breathing; circulation; SNOT cocktail (sugar, naloxone, O2 , thiamine) for patients
with altered mental status
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| Indications for dialysis: STUMBLED—salicylates; theophylline; uremia; methanol; barbiturates or bromides; lithium;
ethylene glycol; Depakote (valproic acid; high levels)
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 | Bradycardia: PACED—propofol, other β-blockers, or opiates; anticholinesterase drugs; clonidine or ciguatera; ethanol;
digoxin
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| Tachycardia: FAST—free base or other forms of cocaine; anticholinergics or antihistamines; sympathomimetics; theophylline
or thyroid hormone
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| Agents that affect temperature
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| Hypothermia: COOLS—carbon monoxide (CO) and clonidine; opiates; oral hypoglycemics; liquor; sedative-hypnotics
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| Hyperthermia: NASA—nicotine or neuroleptics (neuroleptic malignant syndrome); antihistamines; salicylates or sympathomimetics;
anticholinergics or antidepressants
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| Agents that affect blood pressure
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| Hypotension: CRASH—clonidine, calcium channel blockers, or β-blockers; reserpine or other antihypertensives; antidepressants,
aminophylline, or theophylline; sedative-hypnotics; heroin or other opiates
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| Hypertension: CT SCAN—cocaine; thyroid supplements; sympathomimetics; caffeine; anticholinergics; nicotine
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| Agents that affect respiration
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| Rapid respiration: PANT—phencyclidine (PCP) or paraquat; aspirin; noncardiogenic pulmonary edema; toxin-induced
metabolic acidosis
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| Slow respiration: SLOW—sedative-hypnotics; liquor; opiates; weed (marijuana)
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| Agents that cause seizures: WITH LA COPS—withdrawal; isoniazid (INH) or insulin; TCAs or theophylline; hypoglycemic
agents, hemlock, or haloperidol (Haldol); lithium; anticholinergics; cocaine; organophosphates; PCP, phenylpropanolamine
(PPA), or propoxyphene; sympathomimetics or strychnine
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| Agents that cause skin changes: SOAP—sympathomimetics; organophosphates; aspirin or salicylates; PCP;
flushed skin—most commonly anticholinergics; cyanide; CO; boric acid; cyanosis—agents that cause methemoglobinemia,
causing bluish-gray discoloration of skin
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| Diagnostic odors: bitter almond—cyanide; carrots—cicutoxin (hemlock); fruity—diabetic ketoacidosis (DKA);
garlic—thallium; organophosphates; arsenic; dimethyl sulfoxide (DMSO); selenium; phosphorus; rotten eggs—sulfur
compounds; wintergreen oil—methyl salicylate
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| Laboratory evaluation: includes toxicology screens (urine and serum) and acetaminophen level; timing of tests primarily
dependent on symptoms; determine whether acidosis present (look at bicarbonate; calculate anion gap)
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| TOXICOLOGY CONCEPTS —Kent R. Olson, MD, Clinical Professor of Medicine and Pharmacy, University of California,
San Francisco, School of Medicine; Medical Director, San Francisco Division, California Poison Control System
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Acetaminophen Ingestion
| Case: 16-yr-old boy presents with nausea and vomiting; may have taken aspirin (patient not giving clear history); vital
signs normal; physical examination unremarkable; laboratory tests normal; salicylate not detectable; urine toxicology
screen negative; diagnosis—likely due to acetaminophen (Tylenol) ingestion (patients often describe any over-the-
counter [OTC] analgesic as aspirin)
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| Presentation of acetaminophen overdose: often no clear history; may be hidden ingredient in other drugs, eg, 1 bottle
of NyQuil contains enough acetaminophen to cause hepatotoxicity; symptoms (usually nausea and vomiting) nonspecific;
initial laboratory tests usually normal; prudent to check acetaminophen level in all patients presenting with drug
overdose
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| Metabolism: acetaminophen normally metabolized to nontoxic metabolites; however, small proportion metabolized to
toxic intermediate N-acetylbenzoquinoneimine (NAPQI), which can cause liver cell damage if not bound to glutathione
and made into nontoxic product; NAC treatment—binds NAPQI and promotes glutathione formation; best started <8 hr
after ingestion; reduction in effectiveness seen at 12 to 16 hr, but evidence that late treatment (24 hr after ingestion) beneficial
in restoring liver to normal function; vomiting often complicates dosing (antiemetics, nasogastric administration,
or intravenous [IV] administration may be useful)
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| Intravenous NAC: conventional product, Mucomyst, not approved by Food and Drug Administration (FDA) for IV use;
new product, Acetadote, approved for IV use; similar efficacy and safety profiles; administer IV Mucomyst through micropore
filter; side effects—Mucomyst and Acetadote associated with anaphylactoid-type reactions, eg, redness around site of administration
and generalized redness on chest and face, wheezing, and generalized hypotension; likely infusion-rate related
(speaker recommends giving initial loading dose over 45-60 min)
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| Oral vs IV NAC: <7 hr after overdose—if patient not vomiting, oral regimen indicated; switch to IV only if patient
begins vomiting; >7 hr after overdose—speaker believes immediate IV dosing indicated with either product
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| Treatment duration: traditional protocol oral NAC every 4 hr for 17 doses, ie, 3 days; in Canada and Europe, 20-hr
treatments used; speaker has used 24- to 36-hr treatments for many years; Acetadote package insert states 20-hr infusion;
speaker recommends 20-hr IV or oral treatment for patients who present early and have uncomplicated course and no evidence
of liver toxicity; longer treatment indicated for patients presenting late with complications
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| Other issues: early presentations not associated with liver failure—acetaminophen level >500 mg/L associated with
metabolic acidosis early after ingestion; levels of 1500 mg/L associated with coma and hypotension; transient rise in international
normalized ratio (INR) or prothrombin time (PT) that often returns to normal after 24 hr likely due to acute effects
of acetaminophen on production of factor VII)
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Carbon Monoxide
| Case: 55-yr-old man found unresponsive in bedroom; wife experiencing headache, dizziness, and nausea; charcoal stove
used to heat room; diagnosis—likely CO poisoning
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| Presentation of CO poisoning: cherry-red skin not reliable; PaO 2 and pulse oximetry readings usually normal; symptoms
often nonspecific, eg, gastrointestinal (GI) upset, flu-like symptoms; look for clues, eg, >1 person affected in room,
type of heating system
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| Treatment of CO poisoning: standard treatment—highest flow O2 available, eg, 15-L nonrebreather mask or endotracheal
intubation and 100% O2 ; hyperbaric O2 (HBO)—potentially removes CO more rapidly and prevents delayed
neurologic sequelae
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| HBO vs normobaric O2 : Scheinkestel study—found no difference between HBO and normobaric O2 ; Weaver study—
HBO associated with statistically significant improvement in symptoms (albeit soft findings, eg, irritability, headaches,
memory difficulties), compared to normobaric O2 ; clinical effect small, ie, after 6 wk, patients treated with HBO had improved
score on only 1 of 5 neuropsychiatric subtests; when to consider HBO—history of loss of consciousness; older
age (>55 yr); pregnancy; presence of metabolic acidosis; carboxyhemoglobin level >25%; possibly, cerebellar findings;
for patients with 1 of these factors, discuss course of treatment with poison control center and with patient’s family, and
consider whole patient and severity of symptoms
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Methemoglobinemia
| Case: 65-yr-old woman undergoing transesophageal echocardiography; complicated history; taking many medications;
during procedure, O2 saturation fell to 90%, then declined further, and patient appeared cyanotic despite receiving 100%
O2 ; arterial blood gas (ABG) analysis revealed PaO 2 of 293 mm Hg; diagnosis—methemoglobinemia
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| Classic presentation: oxidized hemoglobin (Hb); blood appears chocolate brown; hypoxemia; acidosis; symptoms include
anxiety, dyspnea, dizziness, syncope, coma, and seizures; normal PaO 2 ; even if methemoglobin (MetHb) level
40%, pulse oximetry reading 89%
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| Treatment: methylene blue
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| Causes: oxidizing agents—poisons; chemicals, eg, aniline dyes, nitrites (part of cyanide antidote kit because they create
MetHb, which binds to cyanide in blood); drugs—dapsone; sulfonamides; phenazopyridine (Pyridium); some local anesthetics,
eg, in this case, patient received topical anesthetic spray containing benzocaine
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Opioid Intoxication
| Case: 34-yr-old man found unconscious with respiratory depression and pinpoint pupils; patient awakens rapidly after administration
of IV naloxone 0.2 mg, and signs out of hospital against medical advice (AMA) 15 min after arrival;
diagnosis—opioid intoxication
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| Presentation: characteristic signs include small pupils, respiratory depression, coma, and response to naloxone; toxicology
screen not required for diagnosis
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| Signing out AMA: patient awake, alert, and coherent after administration of naloxone; however, important to inform patient
that drug ingested may have longer duration of effect than naloxone (especially true for long-acting opioids, eg, methadone)
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| Treatment: start with small doses of naloxone and awaken patient gradually; patient less likely to sign out AMA if lethargic
and drowsy; try to convince patient to remain in emergency department (ED) for 3 hr after last dose of naloxone
(naloxone likely to wear off within 3 hr)
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| Methadone: long half-life; not included in all opiate tests and urine toxicology screens (check with hospital laboratory to
confirm whether methadone included in toxicology screen)
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| New opioids: buprenorphine (Subutex)—buprenorphine plus naloxone called Suboxone; used for treatment of opioid
dependence (similar to methadone; substitute opioid); licensed for physicians in private practice; longer duration of action;
considered safer than methadone due to partial agonist and antagonist effects, which create lower maximum effect
and reduce potential for abuse; however, can cause acute withdrawal in patients on heroin, morphine, or methadone who
do not go through washout period before starting buprenorphine; likely scenario involves patients taking buprenorphine
presenting to ED with sudden pain and withdrawal symptoms (switch patients to methadone or other opioid for hospitalization
and restart buprenorphine at later date)
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Metabolic Acidosis
| Case: 23-yr-old woman with confusion, agitation, and tachycardia; temperature 100°F; bicarbonate level 16 mmol/L, anion
gap 18; diagnosis—metabolic acidosis
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| Causes: MUDPILES—methanol or metformin; uremia; DKA; phenformin (no longer used), paraldehyde, or paracetamol
(acetaminophen); isoniazid (INH) or iron; lactic acidosis; ethylene glycol; salicylate
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| Salicylate poisoning: can result from acute overdose or long-term accidental overmedication; signs and symptoms—
anion gap acidosis; hyperventilation; typically, ABG shows primary respiratory alkalosis, ie, pH >7.4
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| Case continued: patient’s roommate brings in empty bottle of aspirin (bottle originally contained 300 tablets)
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| Treatment: activated charcoal to drug ratio of 10:1 optimal for achieving thorough binding; in example patient, 300 x
325 mg tablets = 97.5 g, so dose of activated charcoal = 975 g (too much to give at one time)
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| Gut decontamination: gastric lavage—de-emphasized in current practice (ipecac also no longer used in hospital) but
indicated for example patient to debulk some aspirin from gut; generally, indicated for recent or large ingestion (other
variables to consider include opioids and anticholinergic drugs, which slow stomach emptying); activated
charcoal—recommended in most circumstances if it can be administered early and airway protected; unlikely to
benefit mildly symptomatic patients in whom drug likely already absorbed; whole bowel irrigation—potentially
useful procedure for administering large volumes of charcoal over short time; utilizes nonabsorbable electrolyte solution
containing polyethylene glycol to maintain iso-osmolality (no net gain or loss of fluids and electrolytes); usually
given at 2 L/hr for several hours; important to initiate as early as possible; indicated for large ingestions, sustained-release
preparations, and drugs not well adsorbed by charcoal (eg, iron or lithium tablets)
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Poison Control Center
| Nationwide access number: 1-800 222 1222 to reach regional poison control center
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| Center services: free service providing 24-hr access to advice on diagnosis and treatment, eg, when to use antidote and
what dose to administer; physician-toxicologist back-up available
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Educational Objectives
| The goal of this activity is to educate the listener about approaches to the poisoned patient and concepts in toxicology. After
hearing and assimilating this program, the clinician will be better able to:
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| 1. Evaluate patients presenting to the emergency department with suspected poisoning.
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| 2. List known antidotes to a number of poisonous agents.
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| 3. Diagnose and treat patients with acetaminophen poisoning.
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| 4. Describe the diagnosis and treatment of patients with opioid or carbon monoxide poisoning.
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| 5. Discuss the diagnosis and treatment of patients with methemoglobinemia or metabolic acidosis.
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Discussed on This Program
Acetaminophen (N-acetyl-P-aminophenol; APAP) [several trade names]
Acetylcysteine (N-acetylcysteine) [Acetadote, Mucomyst, Mucosil-10, -20]
Aminophylline (theophylline ethylenediamine) [Phyllocontin, Truphylline]
Aspirin (acetylsalicylic acid; ASA) [several trade names]
Atropine sulfate, scopolamine HBr, hyoscyamine HBr or sulfate [several trade names]
Buprenorphine HCl [Buprenex, Subutex]
Buprenorphine/naloxone [Suboxone]
Charcoal, activated [several trade names]
Clonidine HCl [Catapres, Duraclon]
Digoxin [Digitek, Lanoxicaps, Lanoxin]
Digoxin immune Fab (ovine) [Digibind, DigiFab]
Dimercaptosuccinic acid (DMSA)
Dimethyl sulfoxide (DMSO) [Rimso-50]
Glucagon (rDNA origin) [Glucagon Diagnostic Kit, Glucagon Emergency Kit]
Haloperidol [Haldol, Haldol Decanoate 50, Haldol Decanoate 100]
Hydroxocobalamin, crystalline (vitamin B12) [Hydro Cobex, Hydro-Crysti-12, LA-12]
Isoniazid (isonicotinic acid hydrazide; INH) [Nydrazid]
Lithium [Eskalith, Eskalith CR, Lithobid, Lithonate, Lithotabs]
Metformin HCl [Fortamet, Glucophage, Glucophage XR, Riomet]
Naloxone HCl [Narcan]
Phencyclidine HCl (PCP) [Sernylan] (withdrawn 1978)
Physostigmine salicylate [Antilirium]
Polyethylene glycol solution [MiraLax]
Pralidoxime chloride (2-PAM) [Protopam Chloride]
Propofol [Diprivan]
Pyridoxine HCl (B6) [Aminoxin, Vitelle Nestrex]
Reserpine [Rau-Sed, Sandril, Serpasil, Serpiloid]
Selenium [Sele-Pak, Selepen]
Theophylline [several trade names]
Valproic acid [Depacon, Depakene, Depakote, Depakote ER]
Suggested Reading
Barceloux DG et al; Committee on the Treatment Guidelines for Methanol Poisoning: American Academy
of Clinical Toxicology practice guidelines on the treatment of methanol poisoning. J Toxicol Clin Toxicol 40:415,
2002; Barry JD: Diagnosis and management of the poisoned child. Pediatr Ann 34:937, 2005; Buajordet I et al: Adverse
events after naloxone treatment of episodes of suspected acute opioid overdose. Eur J Emerg Med 11:19, 2004;
Caravati EM et al: Ethylene glycol exposure: an evidence-based consensus guideline for out-of-hospital management.
Clin Toxicol (Phila) 43:327, 2005; Eizadi-Mood N et al: Evaluation of relationship between arterial and venous blood
gas values in the patients with tricyclic antidepressant poisoning. Clin Toxicol (Phila) 43:357, 2005; Eldridge DL,
Holstege CP: Utilizing the laboratory in the poisoned patient. Clin Lab Med 26:13, 2006; Eldridge DL et al: Utilizing
diagnostic investigations in the poisoned patient. Med Clin North Am 89:1079, 2005; Graham CA et al: Paracetamol
and salicylate testing: routinely required for all overdose patients? Eur J Emerg Med 13:26, 2006; Hegedus F,
Herb K: Benzocaine-induced methemoglobinemia. Anesth Prog 52:136, 2005; Kao LW, Nanagas KA: Toxicity associated
with carbon monoxide. Clin Lab Med 26:99, 2006; Kapur N et al: Emergency department management and
outcome for self-poisoning: a cohort study. Gen Hosp Psychiatry 26:36, 2004; Katz KD et al: Aniline and methanol
toxicity after shoe dye ingestion. J Emerg Med 27:367, 2004; Lushine KA et al: Methanol ingestion: prevention of
toxic sequelae after massive ingestion. J Emerg Med 24:433, 2003; Osterhoudt KC et al: Risk factors for emesis after
therapeutic use of activated charcoal in acutely poisoned children. Pediatrics 113:806, 2004; Rowden AK et al: Updates
on acetaminophen toxicity. Med Clin North Am 89:1145, 2005; Smith MY et al: Clinician validation of Poison
Control Center (PCC) intentional exposure cases involving prescription opioids. Am J Drug Alcohol Abuse 32:465, 2006;
Sporer KA: Buprenorphine: a primer for emergency physicians. Ann Emerg Med 43:580, 2004; Stacey R et al: Secondary
contamination in organophosphate poisoning: analysis of an incident. QJM 97:75, 2004.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial relationship
with the manufacturer or provider of any commercial product or service discussed. For this issue, the faculty reported
nothing to disclose.
Dr. Harris spoke at Toxicology Review for Acute Care, presented October 14-15, 2005, in Minneapolis, MN, by the
HealthPartners Institute for Medical Education. Dr. Olson spoke at Topics in Emergency Care, presented October 24-
27, 2005, in San Francisco, CA, by the University of California, San Francisco, School of Medicine. The Audio-Digest
Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.
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