Toxicology Emergencies Cdem

Toxicologic Emergencies

Emergency Medicine Clerkship Lecture Series Primary Authors: Michael Levine, MD, Susan E. Farrell, MD Reviewer: Michael Beeson, MD

EPIDEMIOLOGY •

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 PATIENT • •

History Physical Exam • • • • •

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

MANAGEMENT OF THE POISONED 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

HISTORY • •

• • •

•

•

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 SIGNS • • • •

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

•

Respiratory depth • •

•

Tachypnea: Salicylates Bradypnea: Opioids Hyperpnea: Salicylates Shallow respirations: Opioids

Temperature •

•

Hyperthermia: Serotonin syndrome, NMS, malignant hyperthermia, anti-cholinergic toxidromes, salicylates Hypothermia: Narcotic or sedative-hypnotic agents

PHYSICAL 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: SKIN •

Temperature: •

•

Moisture: • •

•

Hyperpyrexia: Anticholinergic or sympathomimetic toxidromes, salicylates Dry: Anticholinergic toxidrome Moist: Cholinergic, sympathomimetic

Color: Cyanosis, pallor, erythema

PHYSICAL 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)

TOXIDROMES • • • • • • •

Anticholinergic Cholinergic Opioid Sympathomimetic Serotonin syndrome Sympatholytic Sedative-hypnotic

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: 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 •

• • •

•

•

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 •

•

• • •

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 •

• • • •

•

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 •

• • •

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 •

•

• • • •

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 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)

DECONTAMINATION •

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 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

ANTIDOTES 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

ANTIDOTES 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 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) •

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 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 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

N-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 •

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 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) •

•

• • • •

•

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 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 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 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 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 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 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 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 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 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) •

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 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 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”

Anion gap

Gap’s Osmolar gap

Time

METHANOL •

•

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 METABOLISM Methanol Alcohol

dehydrogenase*

Formaldehyde Aldehyde

dehydrogenase

Formic acid Folate

CO2 + H2O * Inhibited by 4-methylpyrazole or ethanol

ISOPROPANOL •

Isopropanol (CH3-CHOH-CH3): • • •

The most intoxicating alcohol Osmolar gap, followed by ketosis Metabolized to acetone by alcohol dehydrogenase

ETHYLENE GLYCOL •

Ethylene glycol C(OH2) – C(OH2) sources: •

•

•

If fluorescein has been added to an EGcontaining antifreeze, the patient’s urine may fluoresce under Wood’s lamp Metabolized to: • •

•

Antifreeze, brake fluid, anti-icing solutions, solvents

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 Alcohol

dehydrogenase*

Glycoaldehyde Aldehyde

dehydrogenase

Glycolic acid Lactate

dehydrogenase

Glyoxylic acid Pyridoxine, Mg

Glycine + Benzoic acid

Thiamine

Oxalic acid

α-OH-βketoadipic acid

*Inhibited by 4-methylpyrazole or ethanol Pyridoxine, Mg, and thiamine are co-factors for their respective reactions

TREATMENT •

• •

•

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) •

EG: Other cofactors to enhance nontoxic metabolism: •

•

Methanol: Other cofactors to enhance nontoxic metabolism: •

•

thiamine, pyridoxine, magnesium

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 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) •

•

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) •

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

•

Benzothiazepines: Diltiazem •

•

Benzothiazepines: Effects cardiac myocytes, electrical conduction system, and peripheral vascular smooth muscle cells

Dihydropyridines: Nifedipine, amlodipine, nicardipine •

•

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

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 TOXICITY •

CCBs: • •

•

In overdose: Verapamil or diltiazem: Bradycardia and hypotension • Dihydropyridines: Hypotension and tachycardia Insulin release from pancreatic β-cells depends on Ltype calcium channels; hyperglycemia can occur after CCB overdose The degree of hyperglycemia may correlate with the severity of the overdose •

•

•

Block L-type calcium channels Inhibit intracellular calcium influx

CCBs versus BETA BLOCKERS •

β1 antagonism: • •

•

β2 antagonism: •

•

Increased smooth muscle tone…bronchospasm

Labetolol: •

•

Decreased cardiac contractility Reduced AV nodal conduction

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 • •

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 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) •

•

•

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 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 TOXICITY •

Cardiac glycosides: • •

•

Symptoms of toxicity: • • •

•

Nausea and vomiting Weakness, lethargy, confusion Visual disturbances

Acute toxicity: •

•

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

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 •

• •

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 •

•

• •

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 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) •

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 ingestion

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

TRICYCLIC ANTIDEPRESSANT TOXICITY •

TCA toxicity: • • •

•

•

Treatment: • • •

•

Sodium channel blockade: conduction delay Alpha1 adrenergic blockade: hypotension Cholinergic (muscarinic) blockade: mydriasis, dry mucous membranes, tachycardia, ileus, urinary retention Histamine blockade Sodium bicarbonate Direct alpha1 adrenergic agents as pressors Benzodiazepines as seizure prophylaxis/treatment

NaHCO3 is indicated for any QRS > 100 ms

TRICYCLIC ANTIDEPRESSANT TOXICITY •

•

The risk of ventricular dysrhythmias and seizures correlates with QRS prolongation ECG findings suggestive of TCA toxicity include: Tachycardia Prolonged PR, QRS intervals Tall R wave in aVR Rightward deflection of terminal 40 msec in aVR

•

NaHCO3 is indicated for any QRS > 100 ms

In Summary Approach all patients in a systematic fashion Toxic exposures most often only require supportive care Be aware of toxic exposures that require specific antidotes Most toxic exposures are unintentional Consider contacting a regional poison control center for all but the most straight forward cases