TOXIC EMERGENCIES
| COMMON TOXIDROMES —Frank LoVecchio, DO, MPH, Associate Professor, Arizona College of Osteopathic
Medicine, Medical Director, Banner Good Samaritan Regional Poison Center, Director of Research, Department
of Emergency Medicine, Maricopa Medical Center, Phoenix, AZ
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| The poisoned patient: initial evaluation—check airway, breathing, and circulation (ABCs); if patient stable, perform
rapid physical examination; look for pattern consistent with toxidrome; obtain complete history, physical examination,
and laboratory tests as indicated; consider creatine kinase (CK) test if drug-induced rhabdomyolysis
suspected; specific treatment and/or antidote rarely required (<1% of patients who overdose get antidote); if patient
unstable, test blood glucose level; consider supplemental O2 ; consider naloxone (Narcan); assess patient for odor
characteristic of specific toxidrome (eg, acetone, garlic, or bitter almonds); evaluate skin color (cherry pink in carbon
monoxide poisoning; blue in methemoglobinemia; cetacaine can induce methemoglobinemia in some patients)
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| Anticholinergic syndrome: suspect if armpits dry, patient agitated, and hyperthermia present; treat with ABCs,
supportive care, and rapid cooling (water and large fan); consider benzodiazepines to treat agitation; paralytic
agents—aid cooling by stopping muscle fasciculations; include vercuronium or rocuronium (succinylcholine
can trigger malignant hyperthermia); physostigmine—onset in 1 min; temporarily (lasts ≈90 min) reverses anticholinergic
poisoning; may mask another conditon; may cause cholinergic syndrome, ie, salivation, lacrimation,
urination, defecation, gastrointestinal (GI) distress, and emesis (SLUDGE), as well as conduction delay or
bradycardia; anticholinergic agents—include plants (eg, Jimson weed), antihistamines, antidepressants, and
scopolamine; tricyclic antidepressants (TCAs) and some antipsychotics do not cause dilated pupils
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 | Clinical presentation: peripheral signs include dry skin, dry mucous membranes, and hyperpyrexia; central signs
include confusion and psychomotor agitation; peripheral and central signs do not always present simultaneously
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| Treatment: includes ABCs, supportive care, GI decontamination, benzodiazepines, and cooling measures; rule out rhabdomyolysis;
use physostigmine with caution; “antimuscarinic syndrome”—better name; physostigmine reverses
muscarinic stimulation, resulting in unopposed nicotinic agonism that can result in SLUDGE and arrhythmia
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| Causative agents: include diphenhydramine (Benadryl), cyclobenzaprine (Flexeril), TCAs, and carbamazepine (associated
with less widening of QRS complex, compared to TCA toxicity); effects include á-blockade, anticholinergic,
antihistamine, and sodium channel blockade in varying degrees; pearl—consider giving intravenous (IV)
sodium bicarbonate to comatose patient, patient with decreased level of consciousness, or if source of toxicity
unknown and patient has widened QRS complex
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| Sympathomimetic toxidrome: causes include amphetamines, cocaine, ephedra, ma huang, and pseudoephedrine
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| Differential diagnosis: malignant hyperthermia—not usually seen in emergency department (ED); can occur after
administration of inhalational anesthetic agent or succinylcholine; history best way to diagnose; associated with
genetic defect involving sarcoplasmic reticulum in skeletal muscle cells that regulate calcium (Ca2+) release;
can treat with dantrolene (nonspecific muscle relaxant); neuroleptic malignant syndrome (NMS)—usually seen
in patient taking dopamine blocker; if unsure whether patient has NMS, treat with benzodiazepine; serotonin
syndrome (SS)—usually occurs in patients taking 2 proserotonergic drugs, eg, selective serotonin reuptake inhibitors
(SSRIs); can result from combining meperidine (Demerol) with serotonin-enhancing agent; also can occur
with lithium or monoamine oxidase inhibitor (MAOI); usually resolves on its own, but can give
cyproheptadine 4 mg by mouth q6h; acute anticholinergic syndrome (ACS)—look for dry skin and axilla; sympathomimetic
toxidrome—associated with altered mental status, hyperthermia, moist skin, and usually dilated
pupils
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| Case: 60-year-old executive brought to ED complaining of generalized weakness; he appears ill; diaphoretic with
wheezing; pulse 45 bpm, blood pressure 160/100 mm Hg, and O2 saturation 89% on room air; physical examination
revealed rales and rhonchi and fasciculations; carbamate or organophosphate poisoning suspected
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| Organophosphate/carbamate poisoning: carbamates—eg, roach insecticide; patients usually recover within 6
to 8 hr; organophosphates (nerve agents)—inhibit acetylcholineesterase, leading to excess acetylcholine, and
resulting in overstimulation of organs (eg, skeletal muscles, smooth and cardiac muscles, and exocrine glands);
treat patients suspected of carbamate or organophosphate poisoning with supportive care and atropine until bronchorrhea
resolves
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| Cholinergic toxidrome: includes bronchorrhea, confusion, diarrhea, muscle fasciculations, and seizure; causal substances
include carbamates ) and organophosphates
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| Hallucinogenic toxidrome: symptoms include hallucinations and sensory disorientation; causative substances include
cannabinoids, psilocybin mushrooms, cocaine, and amphetamines
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| Opiate toxidrome: patients have pinpoint pupils and apnea; treatment—naloxone, 0.4 to 0.8 mg, for naturally occuring
opiates, 2 to 10 mg for synthetic opiates, eg, fentanyl, codeine; opiate drug screen—does not test for presence
of meperidine (Demerol), hydrocodone (Vicodin), oxycodone (OxyContin, Percocet), methadone, Lomotil,
and tramadol (Ultran); propoxyphene—causes pinpoint pupils, decreased respiration, decreased consciousness,
wide QRS complex; only opiate that can cause seizures
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| Elimination of toxin: after assessment and management of ABCs, prevent toxic or further toxic effects of poison
by preventing absorption, eg, gastric emptying, use of charcoal, enhancing elimination; avoid using syrup of ipecac
or gastric lavage; subset of patients receive activated charcoal to prevent toxin absorption (effective only if given
<1 hr after ingestion)
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| Antidotes: used in <1% of patients; N-acetylcysteine (Mucomyst) and naloxone most commonly used antidotes;
Acetadote—intravenous (IV) N-acetylcysteine; new agent approved for use in acetaminophen overdose; package insert
recommends initial bolus of 150 mg/kg over 15 min; recommended dose given too fast and has led to anaphylactoid
reactions; speaker recommends giving 150 mg/kg over 1 hr; administer within 8 hr of overdose to avoid liver
failure
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| Summation: cathartic agents not useful; drug levels only helpful if overdose involves acetaminophen, acetylsalicylic
acid (ASA), lithium, and ethanol; benzodiazepines best treatment for seizures (give barbiturates and vitamin B6 if
benzodiazepines ineffective); manage overdose-induced hypotension with IV fluids, epinephrine, and norepinephrine;
avoid dopamine in patients with disulfiram and MAOI overdoses; nondepolarizing agents best paralytics; serum
alkalinization enhances elimination in ASA, chlorpropamide, and phenobarbital overdoses; β blockers harmful
to patients with ischemic chest pain after cocaine overdose; no indications for whole bowel irrigation; consider multidose
activated charcoal in theophylline, phenobarbital, ASA, or dapsone overdose to decrease levels (not proven to
improve outcome); do not use Dome nomogram for salicylate poisoning (aggressive therapy indicated); consider
ethanol drip or fomepizole (18 mg/kg) as antidote for methanol and ethylene glycol poisoning; thiamine and vitamin
B6 indicated for ethyline glycol poisoning, folinic acid for methanol
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| CHALLENGING TOXICOLOGY CASES —Jeffrey R. Suchard, MD, Associate Professor of Clinical Emergency
Medicine, Director of Medical Toxicology, Department of Emergency Medicine, University of California,
Irvine, School of Medicine
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| Acetaminophen overdose: most common cause of fulminant hepatic failure, excluding viral hepatitides; case—
15-yr-old girl with acetaminophen ingestion and delayed presentation to ED; serum acetaminophen level 140 mg/
mL 12 hr after ingestion of overdose; Rumack-Matthew nomogram indicates patient at increased risk for hepatotoxicity;
patient started on N-acetylcysteine with good tolerance; patient discharged with instructions to take N-acetylcysteine
q4h; after 4 doses, patient returned to ED with nausea and vomiting; patient admitted to hospital and started
on IV metoclopramide (Reglan) 1 mg/kg 30 min before each dose of N-acetylcysteine; patient developed cyanosis
and fasciculations of neck and leg muscles after 12 doses; high-dose metoclopramide increases risk for dystonic reaction
(due to dopamine receptor antagonism); akathisia another possible side effect; cyanosis without respiratory
distress usually result of toxin-induced methemoglobinemia; methemoglobinemia—caused by metoclopramide,
phenazopyridine (Pyridium), and benzocaine; environmental causes include well water containing nitrates or nitrites;
treat with IV methylene blue 1 mg/kg initial dose; cyanosis persists after patient given IV methylene blue; laboratory
tests showed methemoglobin level before IV methylene blue administration <1%, total hemoglobin 12.5 g/
dL, aterial blood gas (ABG) normal, PCO 2 33 mm Hg, and pulse oximetry ≈90%; sulfhemoglobinemia—also produces
cyanosis without respiratory distress; amount of sulfhemoglobin required to produce cyanosis one third
amount of methemoglobin required for cyanosis; requires presence of exogenous sulfur compound (eg, N-acetylcysteine);
irreversible condition; transfusion required in some patients if hemolysis also present; more difficult to detect
than methemoglobinemia; patient transferred to tertiary medical center; laboratory test showed sulfhemoglobin level
16%; observed patient for 48 hr; patient still looked cyanotic at discharge, but vital signs stable
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| Ethylene glycol (EG) ingestion: case—25-yr-old man presented to ED after ingestion of EG; patient describes
taking 2 small sips of antifreeze; basic metabolic panel, ethanol level, and EG level ordered; basic metabolic panel
and ethanol level normal; patient medically cleared and test for EG level cancelled; patient discharged after psychiatric
consultation; calculating amount of EG ingested—25 mg/dL serum level of EG considered “action level”
(level at which treatment necessary); literature shows average volume per swallow in adult ≈25 mL; specific gravity
of EG 1.125; assume instantaneous absorption and distribution; estimated serum EG level ≈50 mg/dL; EG level
high enough to warrant admission to hospital and administration of antidote; what went wrong—ED physician ordered
tests looking for anion gap and osmolal gap; tests normal, so patient discharged from ED; EG-poisoned patients
develop metabolic acidosis; however, this happens over time, and patient presented to ED immediately after
ingestion of EG; serum ethanol level useful only in combination with serum osmolality in determining osmolal
gap; toxic alcohols can create anion gap and osmolal gap; both gaps not always present at same time; osmolal gap
decreases as acidic metabolites accumulate and anion gap increases; patient arrived at ED before anion gap developed;
EG metabolism—EG metabolized by alcohol dehydrogenase and aldehyde dehydrogenase; EG metabolism
produces acidic metabolites that chelate calcium, resulting in hypocalcemia and deposition of calcium oxalate crystals;
case continued—patient returned to work, but began to feel sick; patient experienced abdominal pain, vomiting,
and headache; patient returned to same ED almost exactly 24 hr later; patient evaluated by another physician;
tests show anion gap 24, pH 7.25, creatinine 1.2 mg/dL, and urine contains crystals; treatment with ethanol—
prevents reaction of toxic alcohols with alcohol dehyrogenase; goal serum ethanol level 100 to 150 mg/dL; loading
dose of ethanol 0.8 g/kg; IV ethanol in 70-kg patient given in 10% solution with D-5-W; patient given 560 mL over
1 hr; 140 mL 80 proof ethanol diluted in water if given by mouth; treatment with fomepizole—has fewer side effects
than ethanol (no hypoglycemia, no central nervous system [CNS] intoxication, and does not induce acute hepatitis);
easier to maintain safe levels, compared to IV ethanol; much more expensive than ethanol; loading dose 15
mg/kg in 100 mL saline given over 30 min; increase dosing frequency in dialyzed patient; hemodialysis—no validated
indications in patients with toxic alcohol poisoning; consider in patients getting worse despite supportive
care, who persistently have metabolic acidosis, in presence of renal failure, or electrolyte disturbances unresponsive
to therapy, in patients where alcohol dehydrogenase inhibition not available or not possible or patient cannot
tolerate it, or in patient with extremely high toxic alcohol levels; case continued—patient given IV ethanol loading
dose in ED; transferred to intensive care unit (ICU) without further incident; discovered from laboratory that EG
level 101 mg/dL upon arrival at ED 24 hr ago; current EG level 0 mg/dL; IV ethanol drip discontinued because no
more EG in patient’s system (already metabolized); hemodialysis considered, but not done because patient stable;
patient’s peak serum creatinine level 2.2 mg/dL (indicates significant renal impairment); patient discharged, appeared
to do well, and lost to follow-up; pearl—if patient presents late and/or EG level shows parent compound no
longer present, ethanol or fomepizole not helpful; however, methanol and ethylene glycol have long half-lives (18-
20 hr for methanol, 8-12 hr for EG); so best to assume toxic alcohol still present, especially if patient showing signs
of renal impairment (EG) or retinal toxicity (methanol), arrange for dialysis (if parent compound gone, toxic metabolites
will be cleared)
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| Questions: how long after ingestion do calcium oxalate crystals appear in urine? in ≈2 hr; look for abundance of
crystals in urine of patient with toxic alcohol poisoning; to which organs do oxalate crystals bind? crystals believed
to deposit throughout body; some patients develop cranial neuropathies from crystals in brain
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Suggested Reading
Betten DP et al: Antidote use in the critically ill poisoned patient. J Intensive Care Med 21:255, 2006; Daly FF et
al: A risk assessment based approach to the management of acute poisoning. Emerg Med J 23:396, 2006; Duncan R
et al: New recommendation for N-acetylcystiene dosing may reduce incidence of adverse effects. Emerg Med J
23:584, 2006; Eldridge DL et al: Utilizing the laboratory in the poisoned patient. Clin Lab Med 26:13, 2006;
Heard K: The changing indications of gastrointestinal decontamination in poisonings. Clin Lab Med 26:1-12, 2006;
LoVecchio F: Onset of symptoms after methadone overdose. Am J Emerg Med 25:57, 2007; Pizon AF et al: Adverse
reaction from use of intravenous N-acetylcysteine. J Emerg Med 31:434, 2006; Sivilotti ML et al: Toxicokinetics
of ethylene glycol during fomepizole therapy: implications for management. For the Methylpyrazole for Toxic
Alcohols Study Group. Ann Emerg Med 36:114, 2000; Suchard JR: Assessing physostigmine's contraindication in
cyclic antidepressant ingestions. J Emerg Med 25:185, 2003; Tanen DA et al: Failure of intravenous N-acetylcysteine
to reduce methemoglobin produced by sodium nitrite in human volunteers: A randomized controlled trial. Ann
Emerg Med 35:369, 2000; Worthley LI: Clinical toxicology: part I. Diagnosis and management of common drug
overdosage. Crit Care Resusc 4:192-215, 2002.
Educational Objectives
| The goal of this program is to improve the emergency care of common toxidromes, including sympathomimetic toxidrome,
anticholinergic syndrome, organophosphate poisoning, and acetaminophen and ethylene glycol poisoning.
After hearing and assimilating this program, the clinician will be better able to:
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| 1. Evaluate the poisoned patient.
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| 2. Describe the clinical features of the anticholinergic syndrome.
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| 3. Perfom differential diagnosis of the patient with the sympathomimetic toxidrome.
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| 4. Discuss the challenges of managing a patient who took an overdose of acetaminophen.
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| 5. Provide appropriate management of the patient who ingested a toxic alcohol.
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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.
Acknowledgements
Dr. LoVecchio was recorded at Emergency Medicine 2006-Moving Forward, held March 30-April 1, 2006, in Scottsdale,
AZ, and sponsored by the Mayo Clinic College of Medicine and the Mayo School of Continuing Medical Education.
Dr. Suchard was recorded at CAL/ACEP’s 35th Annual Scientific Assembly, held June 1-3, 2006, in San
Diego, CA, sponsored by the American College of Emergency Physicians, State Chapter of California, Incorporated.
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