Learning Station 4 Toxicologic Emergencies

1999 American Heart Association

Acknowledgment
Thomas G. Martin, MD, MPH, designed and developed the instructional materials for toxicology in ACLS-EP. He has generously donated this work to the AHA, and we gratefully acknowledge his contribution.

Learning Objectives 1
After completing this learning station you should be able to Recognize Specific drugs and toxins that are major causes of cardiopulmonary emergencies The major signs and symptoms (toxidromes) of each overdose (OD) Toxicology emergencies for which standard ACLS guidelines should be modified Describe Best treatments for these serious ODs Prearrest treatments that prevent arrest
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Learning Objectives 2
After completing this learning station you should be able to describe

Use of the Primary and Secondary ABCD Surveys to assess and manage patients with a drug or toxin overdose Specific modifications to ACLS guidelines, when appropriate

Toxicologic Emergencies

Case 1

Case 1

You are at work in the ED; the EMS unit arrives with 48-year-old man suicidal OD looks bad Friend: overdosed on 2 kinds of pills, got weak and drowsy, called 911 Happened: 2 hours ago VS on ED arrival: HR=30 bpm, BP=50 mm Hg/palp, RR=10/min (shallow) Mental status: obtunded, minimal response to stimuli
Describe your approach to this patient. What are your first steps?
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Case 1
Primary ABCD Survey Airway: no gurgling, seems open Breathing: shallow, slow (10/min) Circulation: slow pulse, low pressure; CPR not needed now Defibrillation: not in VF now

Case 1
Secondary ABCD Survey Airway: intubate If airway cannot be protected If respirations slow more and remain shallow If oxygen saturation continues to decline If unresponsive to coma cocktail as described below Breathing: provide oxygen, ventilate using positive pressure
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Case 1
Secondary ABCD Survey (contd) Circulation: ECG: profound bradycardia, idioventricular rhythm Start 2 large-bore IVs, begin fluid challenge (10 to 20 mL/kg) Give Coma Cocktail as part of C: D50W, IV Narcan 2 mg IV (less if IV drug user: 0.2 to 0.4 mg IV) Thiamine 100 mg IV
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Case 1
Secondary ABCD Survey (contd) Differential Diagnosis DONT regimen: Dextrose, Oxygen, Narcan, Thiamine Friend presents 2 empty bottles:
Verapamil (calcium channel blocker) Propranolol (-blocker)

Correct diagnosis?
What else can cause profound bradycardia, low BP? Are you certain that this patient has been poisoned?

Can you identify a toxidrome?

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D = Differential Diagnosis
What else could this be? Did the patient respond to the coma cocktail? Acute poisoning? Drug withdrawal? Central nervous system pathology? Meningitis, abscess, encephalitis Seizure (ie, generalized tonic) CVA, hematoma, contusion Sepsis?
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++ Ca

Channel Blockers and -Blockers

Define the toxidrome (signs and symptoms) Does it fit with the clinical picture? Bradycardia ( AV block) Hypotension Altered level of consciousness Hyperglycemia/hypoglycemia

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++ Ca

Channel Blockers and -Blockers

Treatment

Critical Actions Ventilate with bag-valve mask Coma cocktail check response intubate if needed Apply transcutaneous pacemaker Fluid challenge: Start 2 large-bore IVs Start wide open; check BP and HR q 5 to 10 min Monitor volume; do not overload!
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++ Ca

Channel Blockers and -Blockers

Treatment Critical Actions (contd)

Start pressors if needed. Which one? How much? Consult a medical toxicologist If at high risk for death: consider heroic therapies

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Channel Blockers and -Blockers: Specific Therapy

Standard ACLS Atropine often not effective Isoproterenol alone may drop pressure more Pacemaker (external or internal) Dopamine Epinephrine Toxicologic Approach High-dose pressors Glucagon: 5 to 10 mg IV bolus:
3 to 5 mg/h drip

++ Ca

Calcium: 1 to 3 g, slow IV bolus Insulin pump: 20 U reg bolus,

0.5 to 1.0 U/kg per hour drip; glucose 25 g bolus, 20 g/h

Amrinone: 0.75 mg/kg 2 to 3 min;

5 to 10 mg/kg per minute

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Ca++ Channel and -Blocker OD

ACLS treatment differences: consider heroic measures, which include Hemodialysis/hemoperfusion not useful! Ultra-high-dose pressors and/or calcium Intra-aortic balloon pump Extracorporeal life support bypass Ionic channel facilitators?
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Ca++ Channel and -Blocker OD

Summary

Pacers (transcutaneous): useful in drug-induced symptomatic bradycardia Drug-induced shock may require high-dose pressors Special treatments in refractory cases Class IIb (possibly useful): calcium, glucagon, insulin pump, amrinone, circulatory-assist devices Class III (possibly harmful): hemodialysis/ hemoperfusion

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Toxicologic Emergencies

Case 2

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Case 2
30-year-old woman; brought into ED by EMS Boyfriend reports recent anxiety, stress Empty bottles of Ativan (lorazepam) and bourbon whiskey found

Begin to manage this patient now. What are the first actions you would take?
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Case 2
Primary ABCD Survey Airway: open; saliva accumulating; gurgling; smell of alcoholic beverage on breath Breathing: respiration = 8/min; sonorous; decreased gag reflex Circulation: BP = 80/50 mm Hg; sinus tachycardia 130 bpm Defibrillation: VF not present

How would you manage her airway and cardiovascular status?

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Case 2
Secondary ABCD Survey Airway: clearly needs intubation performed Breathing: ETT placement confirmed 2 ways Circulation: 2 large-bore IVs, begin fluid challenge Develop differential diagnosis; note major findings: LOC, RR, and BP HR Not consistent with benzodiazepine OD!

What action steps are now indicated?

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Drug-Specific Therapy

DONT: coma cocktail is non-specific: D50W, Oxygen, Narcan, Thiamine Benzodiazepine antagonist

Flumazenil blocks BZD binding to GABA receptor

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Flumazenil (Romazicon)

Specific BZD antagonist: flumazenil (Romazicon) Dosing for flumazenil: 0.2, 0.3, 0.5, 1.0 slowly, up to 3 mg Adverse effects BZD withdrawal (mild severe) Removes masking of seizures by BZDs from coingestants (eg, from TCAs) Unmasks ventricular arrhythmias
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Contraindications for Flumazenil

History of seizures Recent myoclonus or seizure episode Known addiction to short-acting BZDs Heavy/long-term BZD abuse Coingestion of epileptogenic drugs (TCAs most common)

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Benzodiazepine OD: Treatment With Flumazenil

Critical Points

Hemodynamic compromise unexpected in BZD OD; when observed search for another cause Specific central BZD receptor antagonist is available: flumazenil May unmask seizures or arrhythmias Not recommended if
Any recent or remote seizurelike activity Short-acting BZDs History of heavy BZD abuse Coingestion of epileptogenic drug (TCAs, cocaine)

Not indicated in coma of unknown etiology

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Toxicologic Emergencies

Case 3

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Case 3
23-year-old zoology graduate student Application rejected by medical school Dumped by girlfriend 2 days later Took bottle of some sort of mood lifter 3 hours ago Friend discovered him somnolent, unarousable, barely breathing 911 called; transported by EMS unit How would you begin to manage this patient?

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Case 3
Primary ABCD Survey Not in full cardiac arrest Multiple episodes of nonsustained VT occur One shock converts episode of sustained VT Secondary ABCD Survey Needs intubation and hyperventilation Oxygen, IV, monitor, fluid challenge Continuous grand mal seizures begin

What is the toxicity in this case?

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Classic Toxidrome for Tricyclic Antidepressant OD

Anticholinergic effects Hyperthermia, blurred vision, flushed skin, hallucinations, tachycardia, status seizures Quinidine-like effects Negative inotrope, prolonged QT, ventricular arrhythmias (eg, torsades de pointes) -Adrenergic blockade effects Hypotension CNS effects Seizures, coma
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Tricyclic Antidepressants
Clinical Features

Mild-to-moderate toxicity Drowsiness lethargy Slurred speech Mild BP, HR Hypoventilation Severe toxicity Coma Seizures Arrhythmias Hypotension Severe

Rapid progression of toxic symptoms: characteristic of TCAs

Next Action?

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TCA Poisoning

Systemic alkalinization (achieve and sustain) Target pH: 7.45 to 7.55 Bicarbonate: superior to hyperventilation Complications: indicative of severe toxicity
Marked conduction disorders (QRS >120 ms) Marked tachycardia/bradycardia Ventricular arrhythmias Significant hypotension Seizures or coma
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Nurse hands you 12-lead ECG (next slide)

Case 3: TCA Overdose

Interpretation?

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Classic Torsades de Pointes

aka Polymorphic VT

Spindle-node pattern

Spindle

Node (point)

Twisting (spindle) about the Points (node)

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Drug-Induced Torsades

Drugs that induce torsades YES: terfenadine (Seldane), astemizole (Hismanal) NO: loratadine (Claritin), cetirizine (Zyrtec), or fexofenadine (Allegra) Erythromycin, Class IA and III antiarrhythmics, TCA, phenothiazines, pentamidine, cisapride Symptoms of torsades Dizziness, syncope, palpitations, sudden death
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Torsades de Pointes
aka Polymorphic VT

Risk factors High levels of torsades-inducing drugs are caused by

Excessive exposure (iatrogenic or intentional) Drug-induced impaired elimination CYP3A4 inhibition (imidazoles, macrolides, SSRIs, protease inhibitors, cimetidine, grapefruit, quinine, zafirlukast, zileuton), hepatic failure

K, Mg, heart disease, congenital long-QT syndrome

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Treatment of Toxin- or Drug-Induced Torsades

Correct K, Mg Overdrive pacing Pacemaker (external or internal) Isoproterenol best avoided Antiarrhythmics Magnesium or lidocaine?

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TCA OD: Effects on the ECG

Typical ECG changes Prolonged QRS and QT intervals Rightward terminal QRS-axis deviation Bundle branch block AV blocks Ventricular arrhythmias Pulseless electrical activity
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TCA Poisoning
Summary

Alkalinize severe cases bicarbonate is best antidote! Use high-dose pressors when necessary Avoid procainamide and physostigmine Stop TCA seizures with bicarbonate, BZDs, phenytoin Use circulatory-assist devices in cases refractory to maximal medical therapy If cardiac arrest occurs, perform prolonged CPR: Buys time for drug to dissipate Good neurologic outcome possible Good heart; good conduction system
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Toxicologic Emergencies

Case 4

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Case 4
30-year-old man; police say he swallowed a handful of rocks Complains of crushing chest pain; shortness of breath for 1 hour Pale, diaphoretic, clutching chest, agitated, delirious HR = 140 bpm, BP = 160/120 mm Hg, RR = 30/min, T = 39C You may begin to manage this patient now. What are your first steps?

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Case 4

Primary ABCD Survey ABCD: clear Secondary ABCD Survey A: No intubation required B: Oxygen given C: IV fluids, monitor, cool him down D: Develop a differential diagnosis; decontaminate, define toxidrome, drugspecific therapy Tanktankpumprate
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Hyperdynamic/ Hyperadrenergic Agents

Cocaine (crack) Ketamine/phencyclidine (PCP) Amphetamine/methamphetamine (ice, crystal meth) Ephedrine and derivatives, 2-agonists Caffeine, nicotine, theophylline Dextromethorphan

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Adrenergic Agent Overdose

Toxidrome Tachycardia Hypertension Hyperthermia Agitation Diaphoresis Complications Angina/infarction Dissecting aorta Seizures Intracranial bleed Rhabdomyolysis

What are critical acute problems?

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Major Problems to Consider

Monitor shows ventricular tachycardia: symptomatic? High blood pressure: urgency vs emergency? Chest pain: r/o angina; cocaine-induced AMI? vs dissection Agitation and delirium Hyperthermia: increases delirium Cocaine: associated with lowered seizure threshold

What critical actions are now indicated?

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Overdose With Adrenergic Agents

Critical Actions

Reduce the hyperdynamic state Monitor/reduce temperature Physical cooling: spray and fan Dantrolene 1 to 10 mg/kg Prevent or treat seizures Restrain to prevent harm Chemical restraints preferred over physical restraints Agents: BZDs, haloperidol, or droperidol
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Drug-Induced Acute Coronary Syndromes

Treatment

Benzodiazepines: first-line agents Nitrates (NTG) Phentolamine (Regitine): -blocker Avoid propranolol: leaves unopposed -adrenergic stimulation; may BP IV thrombolytics: Caution! PTCA: preferable to systemic thrombolytics
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Case 4 Assessment
Runs of Ventricular Premature Contractions

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Overdose With Adrenergic Agents

Summary

Hyperthermia: cooling and dantrolene Seizures: BZDs, phenobarbital Delirium: BZDs, droperidol Drug-induced acute coronary syndrome: BZDs, nitrates, phentolamine ST elevation with enzyme release: PTCA preferred over IV thrombolytics BP: BZD, nipride, phentolomine, labetalol Avoid propranolol
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Toxicologic Emergencies

Case 5

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Case 5
Scene 40-year-old woman drank eucalyptus tea 2 hours ago Confused, pale, HR 30 bpm, BP nonpalp, RR 36/min Prehospital O2, IV, naloxone, D50W, shock trousers ED 300 mL saline, atropine 0.5 4 no response Isoproterenol 2 g/min VT (140/min) VF

What is your management approach?

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Case 5
Primary ABCD Survey Vital signs Secondary ABCD Survey OxygenIVmonitorfluid challenge Tank (content)tank (size)ratepump

Causes of drug-induced bradycardia?

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Differential Diagnosis
Drugs That Can Cause Bradycardias

-Adrenergic blockers Calcium channel blockers Digoxin or other cardiac glycosides Quinidine and other antiarrhythmics Opiates Gamma-hydroxybutyrate (GHB) Organophosphates, carbamates Clonidine
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Cardiac Glycoside Plants

Foxglove (Digitalis purpurea) Lily of the valley (Convallaria majalis) Oleander (Nerium oleander) Red squill (Urginea maritima) Yellow oleander (Thevetia peruviana)

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Digoxin Toxicity
Define the Toxidrome
CV: Bradycardia, heart block, junctional tachycardia, PVCs, VF, VT, BP, asystole GI: Anorexia, nausea/vomiting, cramps CNS: Lethargy, delirium, weakness, hallucinations, paranoia, agitation Ocular: Yellow halos (chronic cases)

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Digoxin Toxicity
Management

Give activated charcoal GI absorption Enterohepatic recirculation Correct K, Mg, ischemia Treat ventricular arrhythmias Lidocaine, Mg+, phenytoin Bradycardia: atropine, pacemaker Digoxin-specific antibody
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Digoxin Toxicity
Indications for Dig Fab Fragments

Life-threatening CV toxicity K+ >5.5 mEq/L (except CRF) Steady-state level >10 ng/mL? Ingested dose >10 mg (adult)? A caution: If digoxin toxicity is questionable, confirm diagnosis, especially if calcium channel blocker overdose is possible.
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Digoxin Toxicity
Essentials

Correct K, Mg, ischemia Ventricular arrhythmias: Lidocaine, Mg+, phenytoin Bradycardia Atropine, pacemaker Digoxin-specific antibody Use for life-threatening CV toxicity Use for K+ >5.5 mEq/L (except CRF)
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Cardiac Arrest Due to Drug ODs

Codes Due to Poisoning

Consider medical toxicology consultation early Consider prolonged CPR Sodium bicarbonate Use for any wide-complex rhythms High-dose pressors may be required Inotropes if refractory to high-dose pressors Insulin pump, glucagon, amrinone Circulatory-assist devices: last resort
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Toxicologic Emergencies

Questions?

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