Toxicology Emergencies CDEM

Toxicologic EmergenciesToxicologic

Emergencies

Emergency Medicine Clerkship Lecture SeriesPrimary Authors:

Michael Levine, MD, Susan E. Farrell, MDReviewer: Michael Beeson, MD

EPIDEMIOLOGYEPIDEMIOLOGY

• In 2004, more than 2.4 million toxic exposures reported to U.S. Poison Control Centers• 1183 deaths

• Over half of poisonings occur in children under 5 years of age

EVALUATION OF THE POISONED PATIENTEVALUATION OF THE POISONED PATIENT

• History• Physical Exam

• Vital signs • Pupil exam• Skin findings• Mental status• Search for a toxidrome

MANAGEMENT OF THEPOISONED PATIENT

MANAGEMENT OF THEPOISONED PATIENT

• A-B-C-D-E’s: ACLS measures as appropriate• IV, O2, cardiac monitoring, ECG• Determine blood glucose in all “intoxicated”

patients. (Empiric dextrose administration is indicated for all patients with altered mental status if bedside glucose determination is not available)

• Thiamine and naloxone empirically as indicated• Decontamination• Enhanced elimination• Antidotal therapy• Supportive care

HISTORYHISTORY• Name and amount of agent(s) • Type of agent (immediate release, sustained

release)• Time of ingestion/exposure• Route of ingestion/exposure• Any co-ingestants (including prescription, OTC’s,

recreational drugs, herbals, chemicals, metals)• Reason for ingestion/exposure (e.g. accident,

suicide attempt, therapeutic misuse, occupational)• Search exposure environment for pill bottles, drug

paraphernalia, suicide note, chemical containers

PHYSICAL EXAM: VITAL SIGNSPHYSICAL EXAM: VITAL SIGNS

• Assess and manage the A-B-Cs:• Blood pressure• Heart rate• Respiratory rate

• Tachypnea: Salicylates• Bradypnea: Opioids

• Respiratory depth• Hyperpnea: Salicylates• Shallow respirations: Opioids

• Temperature • Hyperthermia: Serotonin syndrome, NMS, malignant

hyperthermia, anti-cholinergic toxidromes, salicylates • Hypothermia: Narcotic or sedative-hypnotic agents

PHYSICAL EXAM: PUPILSPHYSICAL EXAM: PUPILS

• Size• Large: Anticholinergic or

sympathomimetic toxidrome• Small: Cholinergic toxidrome• Pinpoint: Opioid toxidrome

• Nystagmus: Check for horizontal, vertical, or rotatory (ethanol, phenytoin, ketamine, PCP)

PHYSICAL EXAM: SKINPHYSICAL EXAM: SKIN

• Temperature:• Hyperpyrexia: Anticholinergic or

sympathomimetic toxidromes, salicylates

• Moisture: • Dry: Anticholinergic toxidrome• Moist: Cholinergic, sympathomimetic

• Color: Cyanosis, pallor, erythema

PHYSICAL EXAM: OVERALL EXAMPHYSICAL EXAM: OVERALL EXAM

• Physiologic stimulation: Everything is “up”:• Elevated temperature, HR, BP, RR, agitated

mental status• Sympathomimetics, anticholinergics, central

hallucinogens, some drug withdrawal states• Physiologic depression: Everything is “down”:

• Depressed temperature, HR, BP, RR, lethargy/coma• Sympatholytics, cholinergics, opioids,

sedative-hypnotics• Mixed effects: Polysubstance overdose,

metabolic poisons (hypoglycemic agents, salicylates, toxic alcohols)

TOXIDROMESTOXIDROMES

• Anticholinergic• Cholinergic• Opioid• Sympathomimetic• Serotonin syndrome• Sympatholytic• Sedative-hypnotic

TOXIDROMES: ANTICHOLINERGIC

TOXIDROMES: ANTICHOLINERGIC

• VS: Hyperthermia, tachycardia, elevated BP• CNS: Agitation, delirium, psychomotor activity,

hallucinations, mumbling speech, unresponsive• Pupils: Mydriasis (minimally reactive to light)• Skin: Dry, warm, and flushed• GI/GU: Diminished BS, ileus, urinary retention• Examples: Atropine, antihistamines, CADs,

cyclobenzaprine, phenothiazines, Datura spp.• Remember: “Dry as a bone, Red as a beet,

Blind as a bat, Mad as a hatter, and hotter than hell”

TOXIDROMES: CHOLINERGICTOXIDROMES: CHOLINERGIC

• VS: Bradycardia, high or low BP, tachypnea or bradypnea

• CNS: Agitation, confusion, seizures, coma• Pupils: Miosis, eye pain, lacrimation• Skin: Diaphoresis• GI/GU: Salivation, vomiting, diarrhea, incontinence• Musculoskeletal: muscle fasciculations, weakness,

paralysis• Examples: Organophosphate and carbamate

insecticides, nerve agents, cholinesterase inhibitors (physostigmine, edrophonium), nicotine

• Remember: “SLUDGE” Salivation, Lacrimation, Urinary incontinence, diarrhea, Gastrointestinal emesis

TOXIDROMES:OPIOID

TOXIDROMES:OPIOID

• VS: Hypothermia, bradycardia, normal or low BP, bradypnea

• CNS: Lethargy, coma• Pupils: Miosis (exceptions: meperidine, DXM)• Skin: Cool, pale or moist, evidence of recent or

remote needle injection possible• Misc: Hyporeflexia, pulmonary edema, seizures

(meperidine and propoxyphene), ventricular dysrhythmias (propoxyphene)

• Examples: Morphine and the synthetic opioids; (Note: clonidine can look like an opioid)

TOXIDROMES:SEDATIVE-HYPNOTIC

TOXIDROMES:SEDATIVE-HYPNOTIC

• VS: Hypothermia, normal or bradycardic HR, hypotension, bradypnea

• CNS: Drowsiness, dysarthria, ataxia, lethargy, coma

• Pupils: Midsize or miosis, nystagmus• Misc: Hyporeflexia; (possible breath odors)• Examples: Alcohols, benzodiazepines,

barbiturates, zolpidem, chloral hydrate, ethchlorvynol

TOXIDROMES:SEROTONIN SYNDROME

TOXIDROMES:SEROTONIN SYNDROME

• VS: Hyperthermia, tachycardia, hypertension, tachypnea

• CNS: Confusion, agitation, lethargy, coma• Pupils: Mydriasis• Skin: Diaphoretic, flushed• Neuromuscular: Hyperreflexia, tremor, clonus,

rigidity• Examples: Combinations that increase 5-HT

stimulation (MAOIs, SSRIs, NSRIs, meperidine, L-tryptophan, dextromethorphan, trazadone, linezolid)

TOXIDROMES: SYMPATHOLYTICS

TOXIDROMES: SYMPATHOLYTICS

• VS: Bradycardia, hypotension, bradypnea, hypopnea

• CNS: Normal, lethargy, coma, seizures• Pupils: Mid size to miotic• Examples: Alpha1-adrenergic antagonists,

beta-adrenergic antagonists, alpha2-adrenergic agonists, calcium channel blockers

TOXIDROMES: SYMPATHOMIMETICS

TOXIDROMES: SYMPATHOMIMETICS

• VS: Hyperthermia, tachycardia, hypertension, tachypnea, hyperpnea

• CNS: Enhanced alertness, agitation, delirium, seizures, coma

• Pupils: Mydriasis• Skin: Diaphoretic, hot• Neuromuscular: Hyperreflexia• Examples: Cocaine, phencyclidine,

phenylethylamines (amphetamines)

SEIZURE-INDUCING DRUGSSEIZURE-INDUCING DRUGS

OTIS CAMPBELL• O – Organophosphates• T – TCAs• I – Insulin, Isoniazid (INH)• S – Sympathomimetics, salicylates, sulfonylureas• C – Cocaine, camphor, carbamazepine, carbamates, CO• A – Amphetamines, amantadine• M – Methylxanthines, meperidine, mushrooms (Gyromitra

species)• P – Phenothiazines, propoxyphene, phencyclidine• B – Benzodiazepine/sedative-hypnotic withdrawal• E – Ethanol withdrawal• L – Lidocaine, lead• L – Lithium, Lindane® (hexachlorocyclohexane)

DECONTAMINATIONDECONTAMINATION• Activated charcoal: 1g/kg• The primary means of GI decontamination, IF it is warranted.

• Some agents for which AC has reduced adsorptive capacity: metals (lead, iron), lithium, pesticides, hydrocarbons, alcohols, caustics, solvents

• Contraindications: bowel obstruction/perforation, unprotected airway, caustics and most hydrocarbons

• Whole bowel irrigation: PEG sol 1 – 2 l/h (adults); 500ml/h (ped) • Indications: toxic foreign bodies (e.g. body packers), sustained

release products, lithium and metals • Contraindications: as for charcoal

• Gastric lavage: • Indications: patients with life threatening ingestions (especially if

no adequate antidote available) presenting within 1 hour of ingestion

• Contraindications: corrosive ingestions, hydrocarbons• Syrup of ipecac: not recommended

ENHANCED ELIMINATIONENHANCED ELIMINATION• Methods to increase the clearance of a substance from

the body:• Multiple dose activated charcoal: phenobarbital,

theophylline, carbamazepine, dapsone, quinine• Urinary alkalinization: salicylates• Hemodialysis:

• Substance characteristics: water-soluble, low molecular weight (<500 D), low protein binding, small volume of distribution (< 1L/kg), low endogenous clearance

• Charcoal hemoperfusion: similar to HD; in addition, substance adsorbed to AC

ANTIDOTESANTIDOTES

TOXIN ANTIDOTE

Acetaminophen N-Acetylcysteine

Anticholinergic agents Physostigmine

Benzodiazepines Flumazenil

Beta blockers or calcium channel blockers

IV fluids, calcium, glucagon, insulin (HIE)

Carbon monoxide O2

Cardiac glycosides Digoxin-specific Fab fragments

Cocaine (or other sympathomimetics)

Benzodiazepines

Cyanide Amyl nitrate, sodium nitrate, sodium thiosulfate, hydroxycobalamin

Ethylene glycol 4-Methylpyrazole, ethanol

ANTIDOTESANTIDOTES

TOXIN ANTIDOTE

Heparin Protamine sulfate

Hydrofluoric acid Calcium gluconate

Iron Desferoxamine

Isoniazid Pyridoxine

Lead DMSA or BAL/CaNa2-EDTA

Mercury BAL

Methanol 4-Methylpyrazole, ethanol

Opioids Naloxone

Organophosphates/

carbamates

Atropine + pralidoxime

Sulfonylureas

(or meglitinides)

Glucose + octreotide

Tricyclic antidepressants Sodium bicarbonate, benzodiazepines

TOXICOLOGY CASE 1TOXICOLOGY CASE 1

• A 23 year old female presents via EMS after ingesting 100 tablets of acetaminophen (APAP) immediate release preparation, 500mg tablets

• The ingestion occurred 24 hours ago • She has had several episodes of non-bloody,

non-biliary emesis • Serum acetaminophen level drawn on arrival:

40mg/dL

TOXICOLOGY CASE 1(cont’d)TOXICOLOGY CASE 1(cont’d)

• Vital signs: T 98.5˚F, HR: 110 bpm, RR 20,

BP 110/68, SaO2: 97% on RA• Labs include:

• PT/INR/PTT: 14.2s/1.4; PTT: 80s• BUN/Creat: 47mg/dL/1.8mg/dL• Serum glucose: 80mg/dL• AST: 5,423 IU/L ALT: 6,087 IU/L

APAP TOXICITYAPAP TOXICITY• Four stages to toxicity:

• I: 0-24 hours: Asymptomatic, or mild anorexia, nausea, vomiting, malaise

• II: 24-48 hours: Transaminase levels start to rise at 12 hours; Abdominal pain, RUQ tenderness, vomiting, oliguria

• III: 72-96 hours: Transaminases peak at 72 hours; PT rises, multi-system organ failure or recovery

• IV: 4d-2 weeks: Resolution of hepatotoxicity• Toxicity results from accumulation of a toxic metabolite:

N-acetyl-para-benzoquinoneimine (NAPQI) relative to endogenous glutathione

• Toxic single ingestion is 150 mg/kg

APAP TOXICITYAPAP TOXICITY

• At therapeutic doses: • 90% of APAP is conjugated and renally

excreted • 2-4% is metabolized via P450 enzymes to

NAPQI• NAPQI is quickly conjugated to glutathione to

a non-toxic metabolite• In an overdose, glutathione stores are depleted,

NAPQI accumulates leading to hepatotoxicity

RUMACK-MATTHEW NOMOGRAM

RUMACK-MATTHEW NOMOGRAM

N-AcetylcysteineN-Acetylcysteine

• PO dosing: 140 mg/kg load, followed by 70mg/kg q4h x17 doses

• IV dosing: 150 mg/kg load over 15 min, followed by 50mg/kg over 4 hours, followed by 100 mg/kg over 16 hours

• Prolonging the initial loading period for IV NAC may reduce the incidence of anaphylactoid reactions

APAP TRANSPLANT GUIDELINES

APAP TRANSPLANT GUIDELINES

• King’s College guidelines• pH < 7.3 after fluid resuscitation

or• PT > 100• Creatinine > 3.4• Grade III or IV encephalopathy• Lactate > 3.5mmol/L

TOXICOLOGY CASE 2TOXICOLOGY CASE 2

• A 20 year old male presents via EMS after his neighbor found him unresponsive. The patient is comatose

• The neighbor developed a headache and nausea after spending 10 minutes in the patient’s house

• It is winter, and the patient had been using a camp stove for heat

TOXICOLOGY CASE 2 (cont’d)TOXICOLOGY CASE 2 (cont’d)• VS: T: 98.9˚F, HR: 110 bpm, RR: 6,

BP: 150/100 mmHg, SaO2: 99%. • Moans to painful stimuli with no focal neurologic

deficits• Pupils 4mm, sluggishly reactive• Skin notable for central cyanosis• Blood glucose: 90mg/dL• ECG: Sinus tachycardia, normal intervals,no

evidence of acute ischemia• Labs include: COHb: 60%

CO TOXICITYCO TOXICITY

• 17,115 cases of CO exposure reported to US Poison Control Centers in 2004

• CO is a colorless, odorless, non-irritating gas• Sources of CO exposure include:

• Smoke• Car exhaust• Propane powered vehicles or engines• Hibachi grills and kerosene heaters• Methylene chloride

CO TOXICITYCO TOXICITY• CO combines with Hgb to form

carboxyhemoglobin (COHb)• COHb has 240 X the affinity for O2• CO + Hgb shifts the O2 dissociation curve to

the left: oxygen delivery to tissues is reduced• CO can cause hypotension via CO-induced

cGMP production and increased NO production• CO can inhibit electron transport which limits

ATP production• CO is associated with microvascular damage

and inflammation in the CNS

CLINICAL EFFECTS OF COCLINICAL EFFECTS OF CO

COHb% Signs/Symptoms

<5% None or mild HA

10% Slight HA, dyspnea on vigorous exertion

20% Throbbing headache, dyspnea with moderate exertion

30% Severe HA, irritability, fatigue, dim vision

40-50% Tachycardia, confusion, lethargy, syncope

50-70% Coma, seizures, death

> 70% Rapidly fatal

CO TOXICITYCO TOXICITY• CO poisoning is frequently misdiagnosed: symptoms are

nonspecific• Need a high index of suspicion• Consider CO poisoning:

• Multiple patients with similar complaints, especially from the same household

• Vague, flu like symptoms without fever or lymphadenopathy

• Winter, environmental history and exposures• Uncommon presentation of syncope

• Normal COHb levels• 0-5% in non-smokers• up to 10% in smokers > 1ppd

PULSE OXIMETRYPULSE OXIMETRY

• Noninvasive measure of functional hemoglobin oxygen saturation

• Does not measure hemoglobin species that cannot carry oxygen • MetHb • COHb

• Co-oximeter measures fractional hemoglobin oxygen saturation

PULSE OXIMETRY GAPPULSE OXIMETRY GAP

Severe CO poisoning• Significant dyshemoglobinemia results in a

divergence between functional and fractional hemoglobin oxygen saturation

• In patients with markedly elevated COHb levels, pulse oximetry can overestimate O2Hb%

• In severe CO poisoning, the pulse oximetry gap approaches the COHb level

CO TREATMENTCO TREATMENT

• Oxygen!!• The half life of COHb decreases with

inspired O2 concentration:• t1/2 at room air: 4-6 hours

• t1/2 at “100%” O2 via NRB at 1 ATM: 90 min

• t1/2 at 100% O2 via ETT at 1 ATM: 60 min

• t1/2 at 100% O2 at 3 ATM (HBO): 23 minutes

HYPERBARIC OXYGENHYPERBARIC OXYGEN

• The rationale behind HBO therapy for CO:• Decrease the incidence of delayed neurologic

sequelae• Should be started within 6 hours

• HBO indications are controversial, but generally include:• COHgb > 25-40%• Altered Mental Status or history of same (syncope)• Arrhythmias• Symptoms of cardiac ischemia• COHgb > 15% if pregnant

TOXICOLOGY CASE 3TOXICOLOGY CASE 3

• A 22 year old male brought via EMS after being found “drunk.” He was found near an empty bottle of window-washer fluid

• The patient had threatened suicide earlier in the day

TOXICOLOGY CASE 3 (cont’d)TOXICOLOGY CASE 3 (cont’d)

• Labs include:• Serum glucose: 124 mg/dL• Sodium: 130 mEq/L; K: 3.7 mEq/L; Cl: 88

mEq/L; Bicarbonate: 12 mEq/L; BUN: 22 mg/dL; Creatinine 1.5 mg/dL

• Anion gap of 30• Serum ethanol: non-detectable• Serum APAP/ASA: non-detectable• Serum osmolality: 324 mOsm/kg

TOXIC ALCOHOLSTOXIC ALCOHOLS

• Most commonly: methanol, isopropanol, and ethylene glycol (EG)

• Should be suspected based on:• history, physical exam, lab abnormalities

• The degree of intoxication correlates with the number of carbons in the alcohol:• Methanol < ethanol or ethylene glycol

< isopropanol

TOXIC ALCOHOL LABSTOXIC ALCOHOL LABS

• All toxic alcohols cause an osmolar gap• Methanol and EG cause an increased anion gap

acidosis• Isopropanol causes ketosis without acidosis• Osmolar gaps can be present early after

ingestion, but will be absent after the alcohol is metabolized

• Anion gap acidosis can be absent early after ingestion, but will develops after methanol or EG metabolism

“GAPS”“GAPS”

Anion gap

Gap’s

Osmolar gap

Time

METHANOLMETHANOL

• Methanol (CH3OH): • window-washer fluid, anti-icing agents,

solvents, varnish/paint removers, some anti-freezes

• Methanol intoxication:• “Snow storm” blindness (edema of the

optic disk/nerve)• Abdominal pain, nausea, vomiting• Lethargy, coma

METHANOL METABOLISMMETHANOL METABOLISM

Methanol Alcohol dehydrogenase*

Formaldehyde Aldehyde dehydrogenase

Formic acid Folate

CO2 + H2O* Inhibited by 4-methylpyrazole or ethanol

ISOPROPANOLISOPROPANOL

• Isopropanol (CH3-CHOH-CH3):• The most intoxicating alcohol• Osmolar gap, followed by ketosis• Metabolized to acetone by alcohol

dehydrogenase

ETHYLENE GLYCOLETHYLENE GLYCOL• Ethylene glycol C(OH2) – C(OH2) sources:

• Antifreeze, brake fluid, anti-icing solutions, solvents• If fluorescein has been added to an EG-

containing antifreeze, the patient’s urine may fluoresce under Wood’s lamp

• Metabolized to:• Glycolic acid: anion gap acidosis• Oxalic acid, combines with calcium, causing calcium

oxylate crystal deposition and hypocalcemia• Calcium oxylate deposition in the renal tubules

causes acute renal failure

ETHYLENE GLYCOL METABOLISM

ETHYLENE GLYCOL METABOLISM

Ethylene glycolAlcohol dehydrogenase*

GlycoaldehydeAldehyde dehydrogenase

Glycolic acidLactate dehydrogenase

Glyoxylic acid Pyridoxine, Mg Thiamine

Glycine + α-OH-β- Benzoic acid Oxalic acid ketoadipic acid

*Inhibited by 4-methylpyrazole or ethanol

Pyridoxine, Mg, and thiamine are co-factors for their respective reactions

TREATMENTTREATMENT• Methanol or EG: 4-methyl-pyrazole (4-MP,

fomepizole)• 4-MP inhibits alcohol dehydrogenase activity• Ethanol also competes for active sites on alcohol

dehydrogenase and inhibits methanol and EG metabolism

• Potential adverse effects of ethanol infusion:• Intoxication, hypotension, pancreatitis, gastritis,

hypoglycemia, or phlebitis• Hemodialysis clears the toxic alcohol and

corrects acid/base abnormalities

TREATMENT (cont’d)TREATMENT (cont’d)

• EG: Other cofactors to enhance nontoxic metabolism:• thiamine, pyridoxine, magnesium

• Methanol: Other cofactors to enhance nontoxic metabolism: • folic acid (or folinic acid)

• Treatment of Isopropanol ingestion:• Supportive care• H2 blockers or proton-pump inhibitors• Ensure that no other toxic alcohol is present

TOXICOLOGY CASE 4TOXICOLOGY CASE 4

• A 3 year old male is brought by his parents 1 hour after he is found with one of his grandmother’s sustained – release verapamil tablets in his mouth

• A pill count shows 1 additional tablet might be missing

• The child is asymptomatic

TOXICOLOGY CASE 4 (cont’d)TOXICOLOGY CASE 4 (cont’d)• Vital signs: T: 98.6˚F, HR: 80 bpm, RR: 22,

BP:100/60, SaO2: 99% • Initial labs:

• Na: 140 mEq/L; K: 3.7 mEq/L; Cl: 113 mEq/L; Bicarbonate: 22 mEq/L; BUN: 12 mg/dL; Creatinine 0.8 mg/dL. Serum glucose: 120mg/dL

• ECG: normal sinus rhythm, normal intervals.• Two hours later: the patient is less arousable• Vital signs: HR: 50 bpm, RR: 18, BP: 70/40

SaO2: 99% • ECG: junctional bradycardia, normal QRS and QTc

intervals • Serum glucose: 190 mg/dL

CALCIUM CHANNEL BLOCKER (CCB)

CALCIUM CHANNEL BLOCKER (CCB)

• Classes of CCB approved in the US:• Phenylalkylamines: Verapamil

• Verapamil: Effects cardiac myocytes and electrical conduction system ( decreased contractility, AV nodal conduction delay and block)

• Benzothiazepines: Diltiazem• Benzothiazepines: Effects cardiac myocytes, electrical

conduction system, and peripheral vascular smooth muscle cells

• Dihydropyridines: Nifedipine, amlodipine, nicardipine• Dihydropyridines: Effects peripheral vascular smooth muscle

cells ( peripheral vasodilation, decreased peripheral vascular resistance)

• In overdose, the selectivity of the CCB classes may be lost

CCB TOXICITYCCB TOXICITY

• CCBs: • Block L-type calcium channels• Inhibit intracellular calcium influx

• In overdose: • Verapamil or diltiazem: Bradycardia and hypotension• Dihydropyridines: Hypotension and tachycardia

• Insulin release from pancreatic β-cells depends on L-type calcium channels; hyperglycemia can occur after CCB overdose

• The degree of hyperglycemia may correlate with the severity of the overdose

CCBs versus BETA BLOCKERSCCBs versus BETA BLOCKERS

• β1 antagonism: • Decreased cardiac contractility • Reduced AV nodal conduction

• β2 antagonism:• Increased smooth muscle tone…bronchospasm

• Labetolol: • 7:1 β:α antagonist activity

• Βeta adrenergic antagonists: • Inhibit gluconeogenesis and glycogenolysis• Hypoglycemia can occur in overdose• Seizures can occur in overdose (propranolol)

CCB and BETA BLOCKER TREATMENT

CCB and BETA BLOCKER TREATMENT

• Ensure ABCs• Improve heart rate and blood pressure:

• Atropine: Often fails to improve HR• Calcium: Used in both CCB and Beta blocker toxicity;

Improves HR and contractility• Glucagon: Improves myocardial contractility• Direct α agonist agents: Increase peripheral vascular

resistance • (Epinephrine has both β1 and α1 agonist effects)

CCB/BETA BLOCKER TXCCB/BETA BLOCKER TX• Therapies unique to CCB or β blocker involve:

• IV fluids – Offsets hypotension induced by peripheral vasodilation

• Calcium – Calcium competitively overcomes blockade of the voltage-sensitive calcium channels

• Glucagon: Acts on adenylate cyclase independently of the β receptor to convert ATP into cAMP

• Epinephrine: Binds to β receptors to convert adenylate cyclase into cAMP

• Insulin: Promotes increased uptake and utilization of carbohydrates by cardiac myocytes (primarily used only for CCB toxicity

Hyperinsulinemic Euglycemia (HIE)Hyperinsulinemic Euglycemia (HIE)

• Normally: Cardiac myocytes preferentially metabolize glucose; in shock states, metabolism is dependent on free fatty acids

• Hyperinsulinemic euglycemic (HIE) therapy: shifts myocardial metabolism from FFA to carbohydrates

• HIE: • Insulin (0.5-1 unit/kg bolus, followed by 0.5-1 unit/kg/hr)• Dextrose (1 amp D50, or continuous D10 infusion)• Watch for hypokalemia and hypophosphatemia

• HIE therapy: Associated with rapid, dramatic improvement in cardiovascular hemodynamics

CARDIAC GLYCOSIDESCARDIAC GLYCOSIDES• Digoxin: A cardiac glycoside used for the

treatment of CHF and atrial fibrillation• Mechanism of action:

• Inhibits Na/K/ATPase, leading to:• Increased intracellular sodium/calcium exchange• Increased intracellular calcium• Increased extracellular potassium

• Digoxin • Increases excitability and automaticity of cardiac

myocytes• Decreases conduction velocity at the AV node

CARDIAC GLYCOSIDE TOXICITYCARDIAC GLYCOSIDE TOXICITY

• Cardiac glycosides: • Foxglove, oleander, lily of the valley, red squill• Secretions of Bufo toads (e.g. Colorado river toad)

• Symptoms of toxicity:• Nausea and vomiting• Weakness, lethargy, confusion • Visual disturbances

• Acute toxicity:• Serum potassium is elevated, predictive of mortality.

• Chronic toxicity: • Precipitated by hypokalemia, hypomagnesemia, renal failure• Digoxin toxicity can occur with therapeutic digoxin levels

CARDIAC GLYCOSIDE TOXICITY: THE ECG

CARDIAC GLYCOSIDE TOXICITY: THE ECG

• Nearly every dysrhythmia has been associated with digoxin toxicity

• PVCs are the most common ECG abnormality• Bidirectional ventricular tachycardia and

accelerated junctional rhythms with nodal block are relatively specific for cardiac glycoside toxicity, but are less common

CARDIAC GLYCOSIDE TOXICITY:TREATMENT

CARDIAC GLYCOSIDE TOXICITY:TREATMENT

• Digoxin-specific Fab fragments indications:• Hyperkalemia (K > 5.0)• Life-threatening arrhythmias

• Phenytoin or lidocaine:• May suppress ventricular dysrhythmias if

digoxin-specific Fab is unavailable• Correct hypokalemia, hypomagnesemia• Calcium therapy for hyperkalemia should be

avoided with concomitant digoxin toxicity

TOXICOLOGY CASE 5TOXICOLOGY CASE 5• A 42 year old woman presents via EMS after

she was found unresponsive at home

• Vital signs: T 99.8˚ F, HR: 121 bpm, RR: 14; BP: 97/52; SaO2: 93% on RA

• PE: Disheveled, minimally responsive female; pupils: 8 mm, minimally reactive; dry lips and mucous membranes; tachycardia, absent bowel sounds; skin warm and flushed

TOXICOLOGY CASE 5 (cont’d)TOXICOLOGY CASE 5 (cont’d)

• The patient is placed on a cardiac monitor and IV access is obtained

• Shortly after an ECG is performed, the patient has a brief, generalized tonic-clonic seizure

TCA ingestionTCA ingestion

Note the tachycardia, QRS prolongation, tall R wave in aVR, and the rightwarddeflection of the terminal 40 msec of aVR.

TRICYCLIC ANTIDEPRESSANT TOXICITY

TRICYCLIC ANTIDEPRESSANT TOXICITY

• TCA toxicity:• Sodium channel blockade: conduction delay• Alpha1 adrenergic blockade: hypotension• Cholinergic (muscarinic) blockade: mydriasis, dry

mucous membranes, tachycardia, ileus, urinary retention

• Histamine blockade• Treatment:

• Sodium bicarbonate• Direct alpha1 adrenergic agents as pressors• Benzodiazepines as seizure prophylaxis/treatment

• NaHCO3 is indicated for any QRS > 100 ms

TRICYCLIC ANTIDEPRESSANT TOXICITY

TRICYCLIC ANTIDEPRESSANT TOXICITY

• The risk of ventricular dysrhythmias and seizures correlates with QRS prolongation

• ECG findings suggestive of TCA toxicity include:

TachycardiaProlonged PR, QRS intervalsTall R wave in aVRRightward deflection of terminal 40 msec in aVR

• NaHCO3 is indicated for any QRS > 100 ms

In SummaryIn Summary

Approach all patients in a systematic fashionToxic exposures most often only require supportive careBe aware of toxic exposures that require specific antidotesMost toxic exposures are unintentionalConsider contacting a regional poison control center for all but the most straight forward cases