7/27/2019 LS4TOX

1/59

7/27/2019 LS4TOX

2/59

2

Acknowledgment

Thomas G. Martin, MD, MPH, designed

and developed the instructional materials

for toxicology in ACLS-EP. He hasgenerously donated this work to the AHA,

and we gratefully acknowledge his

contribution.

7/27/2019 LS4TOX

3/59

3

Learning Objectives 1

Recognize

Specific drugs and toxins that are major causesof cardiopulmonary emergencies

The major signs and symptoms (toxidromes)of each overdose (OD)

Toxicology emergencies for which standardACLS guidelines should be modified

Describe

Best treatments for these serious ODs

Prearrest treatments that prevent arrest

After completing this learning station you shouldbe able to

7/27/2019 LS4TOX

4/59

4

Learning Objectives 2

Use of the Primary and Secondary ABCD

Surveys to assess and manage patients witha drug or toxin overdose

Specific modifications to ACLS guidelines,

when appropriate

After completing this learning station you shouldbe able to describe

7/27/2019 LS4TOX

5/59

5

Toxicologic Emergencies

Case 1

7/27/2019 LS4TOX

6/59

6

Case 1

You are at work in the ED; the EMS unit arriveswith 48-year-old mansuicidal ODlooks bad

Friend: overdosed on 2 kinds of pills, got weakand 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

Descr ibe your approach to this patient.

What are your first steps?

7/27/2019 LS4TOX

7/59

7/27/2019 LS4TOX

8/59

8

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 asdescribed below

Breathing: provide oxygen, ventilate usingpositive pressure

7/27/2019 LS4TOX

9/59

7/27/2019 LS4TOX

10/59

10

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 identi fy a toxidrome?

7/27/2019 LS4TOX

11/59

11

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?

7/27/2019 LS4TOX

12/59

12

Ca++ Channel Blockersand -Blockers

Define the toxidrome (signs and symptoms)

Does it fit with the clinical picture?

Bradycardia ( AV block)

Hypotension

Altered level of consciousness

Hyperglycemia/hypoglycemia

7/27/2019 LS4TOX

13/59

13

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!

Treatment

Critical Actions

Ca++ Channel Blockersand -Blockers

7/27/2019 LS4TOX

14/59

14

Start pressors if needed. Which one?How much?

Consult a medical toxicologist

If at high risk for death: consider heroic therapies

Ca++ Channel Blockersand -Blockers

Treatment

Critical Actions (contd)

7/27/2019 LS4TOX

15/59

15

Ca++ Channel Blockers and-Blockers: Specific TherapyStandard ACLS

Atropineoften 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

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

7/27/2019 LS4TOX

16/59

16

Ca++ Channel and -Blocker ODACLS 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?

7/27/2019 LS4TOX

17/59

17

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-assistdevices

Ca++ Channel and -Blocker OD

Class III (possibly harmful): hemodialysis/

hemoperfusion

7/27/2019 LS4TOX

18/59

18

Toxicologic Emergencies

Case 2

7/27/2019 LS4TOX

19/59

19

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 f irst actions you would take?

7/27/2019 LS4TOX

20/59

20

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; sinustachycardia 130 bpm

Defibrillation: VF not present

How would you manage her airway

and cardiovascular status?

7/27/2019 LS4TOX

21/59

21

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?

7/27/2019 LS4TOX

22/59

22

Drug-Specific Therapy

DONT: coma cocktail is non-specific:

D50W, Oxygen, Narcan, Thiamine

Benzodiazepine antagonist

Flumazenil blocks BZD binding to GABA

receptor

7/27/2019 LS4TOX

23/59

23

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 fromcoingestants (eg, from TCAs)

Unmasks ventricular arrhythmias

7/27/2019 LS4TOX

24/59

24

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)

B di i OD

7/27/2019 LS4TOX

25/59

25

Benzodiazepine OD:Treatment With Flumazenil

Critical Points Hemodynamic compromise unexpected in BZD

OD; when observed search for another cause

Specific central BZD receptor antagonist isavailable: flumazenil May unmask seizures or arrhythmiasNot recommended if

Any recent or remote seizurelike activity

Short-acting BZDsHistory of heavy BZD abuseCoingestion of epileptogenic drug (TCAs,

cocaine)Not indicated in coma of unknown etiology

7/27/2019 LS4TOX

26/59

26

Toxicologic Emergencies

Case 3

7/27/2019 LS4TOX

27/59

27

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?

7/27/2019 LS4TOX

28/59

28

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?

Cl i T id f T i li

7/27/2019 LS4TOX

29/59

29

Classic Toxidrome for TricyclicAntidepressant OD

Anticholinergic effects

Hyperthermia, blurred vision, flushed skin,

hallucinations, tachycardia, status seizures Quinidine-like effects

Negative inotrope, prolonged QT, ventriculararrhythmias (eg, torsades de pointes)

-Adrenergic blockade effects Hypotension

CNS effects

Seizures, coma

T i li A tid t

7/27/2019 LS4TOX

30/59

30

Tricyclic AntidepressantsClinical Features

Mild-to-moderate toxicity

Drowsiness lethargy Slurred speech

BP,HR Hypoventilation

Rapid progression

of toxic symptoms:

characteristic ofTCAsMild

Severe

Next Action?

Severe toxicity

Coma Seizures

Arrhythmias

Hypotension

7/27/2019 LS4TOX

31/59

31

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

Nurse hands you 12-lead ECG (next sl ide)

C 3 TCA O d

7/27/2019 LS4TOX

32/59

32

Case 3: TCA OverdoseInterpretation?

Cl i T d d P i t

7/27/2019 LS4TOX

33/59

33

Classic Torsades de Pointesaka Polymorphic VT

Twisting (spindle) about the Points (node)

Spindle-node pattern Spindle

Node (point)

7/27/2019 LS4TOX

34/59

34

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

Torsades de Pointes

7/27/2019 LS4TOX

35/59

35

Torsades de Pointesaka Polymorphic VT

Risk factors

High levels of torsades-inducing drugs are

caused byExcessive 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-QTsyndrome

Treatment of Toxin or

7/27/2019 LS4TOX

36/59

36

Treatment of Toxin- orDrug-Induced Torsades

CorrectK,Mg

Overdrive pacing

Pacemaker (external or internal)

Isoproterenolbest avoided

Antiarrhythmics

Magnesium or lidocaine?

7/27/2019 LS4TOX

37/59

37

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

TCA Poisoning

7/27/2019 LS4TOX

38/59

38

TCA PoisoningSummary

Alkalinize severe casesbicarbonate is bestantidote!

Use high-dose pressors when necessary

Avoid procainamide and physostigmine

Stop TCA seizures with bicarbonate, BZDs,phenytoin

Use circulatory-assist devices in cases refractory tomaximal medical therapy

If cardiac arrest occurs, perform prolonged CPR:

Buys time for drug to dissipate

Good neurologic outcome possible

Good heart; good conduction system

7/27/2019 LS4TOX

39/59

39

Toxicologic Emergencies

Case 4

7/27/2019 LS4TOX

40/59

40

Case 4

30-year-old man; police say he swalloweda 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 f irst steps?

7/27/2019 LS4TOX

41/59

Hyperdynamic/

7/27/2019 LS4TOX

42/59

42

Hyperdynamic/Hyperadrenergic Agents

Cocaine (crack)

Ketamine/phencyclidine (PCP)

Amphetamine/methamphetamine

(ice, crystal meth)

Ephedrine and derivatives, 2-agonists

Caffeine, nicotine, theophylline

Dextromethorphan

7/27/2019 LS4TOX

43/59

43

Adrenergic Agent Overdose

Toxidrome

Tachycardia

Hypertension Hyperthermia

Agitation

Diaphoresis

Complications

Angina/infarction

Dissecting aorta Seizures

Intracranial bleed

Rhabdomyolysis

What are critical acute problems?

7/27/2019 LS4TOX

44/59

44

Major Problems to Consider

Monitor shows ventricular tachycardia:symptomatic?

High blood pressure: urgency vs emergency?

Chest pain: r/o angina; cocaine-induced AMI? vsdissection

Agitation and delirium

Hyperthermia: increases delirium Cocaine: associated with lowered seizure threshold

What cr itical actions are now indicated?

7/27/2019 LS4TOX

45/59

45

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 physicalrestraints

Agents: BZDs, haloperidol, or droperidol

Drug-Induced Acute

7/27/2019 LS4TOX

46/59

46

Drug-Induced AcuteCoronary Syndromes

Treatment Benzodiazepines: first-line agents

Nitrates (NTG) Phentolamine (Regitine): -blocker

Avoid propranolol: leaves unopposed-adrenergic stimulation; mayBP

IV thrombolytics: Caution!

PTCA:preferable to systemic thrombolytics

Case 4 Assessment

7/27/2019 LS4TOX

47/59

47

Case 4 AssessmentRuns of Ventr icular Premature Contractions

Overdose With Adrenergic Agents

7/27/2019 LS4TOX

48/59

48

Overdose With Adrenergic AgentsSummary

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

7/27/2019 LS4TOX

49/59

49

Toxicologic Emergencies

Case 5

7/27/2019 LS4TOX

50/59

50

Case 5

Prehospital

O2, IV, naloxone, D50W, shock trousers

What is your management approach?

Scene

40-year-old woman drank eucalyptus tea2 hours ago

ED 300 mL saline, atropine 0.5 4 no response

Isoproterenol 2 g/min VT (140/min) VF

Confused, pale, HR 30 bpm, BP nonpalp,

RR 36/min

7/27/2019 LS4TOX

51/59

51

Case 5

Primary ABCD Survey

Vital signs

Secondary ABCD Survey

OxygenIVmonitorfluid challenge

Tank (content)tank (size)ratepump

Causes of drug-induced bradycardia?

Differential Diagnosis

7/27/2019 LS4TOX

52/59

52

Differential DiagnosisDrugs 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

7/27/2019 LS4TOX

53/59

53

Cardiac Glycoside Plants

Foxglove (Digitalis purpurea)

Lily of the valley (Convallaria majalis)

Oleander(Nerium oleander)

Red squill (Urginea maritima)

Yellow oleander(Thevetia peruviana)

7/27/2019 LS4TOX

54/59

7/27/2019 LS4TOX

55/59

Digoxin Toxicity

7/27/2019 LS4TOX

56/59

56

Digoxin ToxicityI ndications 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.

Digoxin Toxicity

7/27/2019 LS4TOX

57/59

57

Digoxin ToxicityEssentials

CorrectK,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)

7/27/2019 LS4TOX

58/59

T i l i E i

7/27/2019 LS4TOX

59/59

Toxicologic Emergencies

Questions?