objectives slides per page.pdf · -treat with controlled infusion of kcl-2 meqper minute for 10...

10/4/18

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ACLS & Beyond

Christa Creech, Pharm.D.PGY-2 Emergency Medicine Pharmacy Resident

October 7th, 2018

ObjectivesList recent changes to ACLS guidelines applicable to pharmacists

Recognize reversible causes of cardiac arrest and be familiar with their treatments

Recommend adjunctive therapies for refractory cases of cardiac arrest

ACLS = Advanced cardiovascular life support

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Outline – ACLS & Beyond

Summary of recent updates to ACLS

guidelines

ACLS algorithm review• Shockable rhythms• Non-shockable rhythms• Reversible causes of

cardiac arrest

Other drugs you may encounter during

cardiac arrest circumstances

Access & routes of administration Procedural support


Summary of Guideline Updates

2010 à 2015

Next update in 2020

Post-cardiac arrest careComatose patients should be cooled for 12-24

hoursComatose patients should be cooled for > 24

hours

Extracorporeal CPRInsufficient information to recommend routine

use of extracorporeal CPRExtracorporeal CPR may be considered instead

of regular CPR for reversible cardiac arrest

VasopressinVasopressin may replace the first or second

dose of epinephrineVasopressin plus epinephrine provides no advantage as a substitute for epinephrine

Depth & FrequencyAt least 2 inches & at least 100 compressions

per minute2-2.5 inches in adults & no less than 100 but no

more than 120 compressions per minute

Sequence

Airway, breathing, circulation Circulation, airway, breathing

2010 2015

Link. Circulation. 2015;132(18 Suppl 2):S444-64.Morrison. Circulation. 2010;122(18 Suppl 3):S665-75.

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Circulation - Airway - Breathing•2-2.5 inches depth for adults•100 - 120 compressions per minuteCPR• Avoid excessive ventilation• 30:2 compression ventilation ratioO2

• Attach monitor• DefibrillatorMonitoring•Peripheral IV, central IV, IO, ETAccess

Marsch. Swiss Med Wkly. 2013;143:w13856.Link. Circulation. 2015;132(18 Suppl 2):S444-64.

IV = intravenousCPR = Cardiopulmonary resuscitation

IO = intraosseousET = endotracheal

Assess Rhythm for Shockability

VF &

pVT

Asystole&

PEA

Link. Circulation. 2015;132(18 Suppl 2):S444-64.VF = Ventricular fibrillation pVT = Pulseless ventricular fibrillation PEA = Pulseless electrical activity

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Electricity Versus Pharmacotherapy“Some antiarrhythmic drugs have been associated with increased rates of ROSC and hospital admission, but

none have yet been proven to increase long-term survival or survival with good neurological outcome.

Thus, establishing vascular access to enable drug administration should not compromise the quality of

CPR or timely defibrillation, which are known to improve survival.”

Link. Circulation. 2015;132(18 Suppl 2):S444-64.

Shockable Rhythm Algorithm

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Shockable Rhythms

VF/pVT

Shock

CPR x 2 minutes

IV/IO access

Link. Circulation. 2015;132(18 Suppl 2):S444-64.IO = intraosseousVF = Ventricular fibrillation pVT = Pulseless ventricular fibrillation

IV = intravenousCPR = Cardiopulmonary resuscitation

VF/pVT s/p 1 shock & 2 min of CPR

Reassess rhythm

Shock

CPR x 2 minEpinephrine 1mg every 3-

5 minutes

Consider advanced

airway

PEA/Asystole ROSC

Not Shockable Shockable

Link. Circulation. 2015;132(18 Suppl 2):S444-64.PEA = Pulseless electrical activityROSC= Return of spontaneous circulation CPR = Cardiopulmonary resuscitation

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VF/pVT s/p 2 shocks & 4 min of CPR

Reassess rhythm

Shock

CPR x 2 min AmiodaroneTreat

reversible causes

PEA/Asystole ROSC

Not ShockableShockable

Link. Circulation. 2015;132(18 Suppl 2):S444-64.PEA = Pulseless electrical activityROSC= Return of spontaneous circulation CPR = Cardiopulmonary resuscitation

Algorithm DrugsDrug Initial Dose Drip MOA

Epinephrine

1 mg IV/IO pushEvery 3-5 minET: 2-2.5 mg every 3-5 min

1-30 mcg/min

(4 mg/250ml)

Stimulates beta-1, beta-2 and alpha-1 adrenergic receptors to produce an increase in cardiac contractility, heart rate, systemic vascular resistance and blood pressure

Amiodarone300 mg IV/IO x 1, may repeat 10 min 150 mg

1 mg/min for 6 h à0.5 mg/min x 18 h900mg in 500ml of D5W (1.8 mg/ml)

Iinhibits adrenergic stimulation, prolongs the action potential, and prolongs the refractory period in myocardial tissue

Link. Circulation. 2015;132(18 Suppl 2):S444-64.IV = IntravenousIO = intraosseous D5W = 5% dextrose in water

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What’s in your crash cart?

Epinephrine

PARAMEDIC2 Trial• RCT, 8014 patients, out-of-hospital arrest• Epinephrine à increased 30-day survival• No difference in rate of favorable

neurologic outcomes

Perkins. N Engl J Med. 2018;RCT = Randomized controlled trial

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Epinephrine

• Prospective, non-randomized observational propensity analysis

• Included data from 417188 out-of-hospital cardiac arrests

• Epinephrine associated with increased chance of ROSC before hospital arrival

• Reduced chance of survival and good functional outcomes 1 month after event

• Double-blind RCT • 534 out-of-hospital cardiac arrests• Epinephrine vs. placebo

• Epinephrine associated with increased chance of ROSC before hospital arrival

• No significant improvement in survival to hospital discharge

Hagihara. JAMA. 2012;307(11):1161-8. Jacobs. Resuscitation. 2011;82(9):1138-43.RCT = Randomized controlled trial

ROSC= Return of spontaneous circulation

Cumulative Dose of EpinephrineDoes the cumulative

epinephrine dose impact neurologic outcome after

cardiac arrest?

3 retrospective studies show association of

higher cumulative doses and worse neurologic

outcome

Lack of consistency regarding how much

epinephrine is too muchMultiple existing

confounders

Difficult to draw conclusions from the

existing data

Rivers. Chest. 1994;106(5):1499-507.Behringer. Ann Intern Med. 1998;129(6):450-6.

Arrich. Resuscitation. 2012;83(3):333-7.Laureys. Nat Rev Neurosci. 2005;6(11):899-909.

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Cumulative Dose of Epinephrine

Are we giving too much epinephrine?

Evidence is not currently strong enough to support implementation of a dose threshold

Rivers. Chest. 1994;106(5):1499-507.Behringer. Ann Intern Med. 1998;129(6):450-6.Arrich. Resuscitation. 2012;83(3):333-7.

Dose

Cumulative Dose of Epinephrine

Consider giving guideline recommended dose every 5 minutes

Rivers. Chest. 1994;106(5):1499-507.Behringer. Ann Intern Med. 1998;129(6):450-6.Arrich. Resuscitation. 2012;83(3):333-7.

Dose

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Non-ShockableRhythm Algorithm

Non-Shockable Rhythms

Asystole/PEA

CPR x 2 min IV/IO accessConsider advanced

airway

Link. Circulation. 2015;132(18 Suppl 2):S444-64.PEA = Pulseless electrical activityCPR = Cardiopulmonary resuscitation

IV = intravenousIO = intraosseous

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Non-Shockable Rhythms

Reassess rhythm

Asystole/PEA

CPR x 2 minTreat

Reversible causes

VF/pVT ROSC

Link. Circulation. 2015;132(18 Suppl 2):S444-64.CPR = Cardiopulmonary resuscitationROSC= Return of spontaneous circulation

VF = Ventricular fibrillation pVT = Pulseless ventricular fibrillation PEA = Pulseless electrical activity

Reversible Causes

H’s • Hypoxia, hypovolemia, hydrogen ion,

hypo-/hyperkalemia, and hypothermia

T’s • Tension pneumothorax, tamponade, toxins,

thrombosis (pulmonary), and thrombosis (coronary)


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H’s

Hypovolemia Hypoxia Hydrogen ion (acidosis)

Hypo-/hyperkalemia Hypothermia Hypoglycemia


Hypoxia

O2 Albuterol RSI

RSI = Rapid sequence intubation

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H’s




Hypovolemia

Look for obvious fluid loss

• Blood• Dehydration• Severe burns• N/V/D

Obtain IV access

• Most important intervention

• Can also obtain IO if equipmentavailable

Fluidchallenge

• At least 2L of isotonic crystalloid

• +/- pressure bag

N/V/D = Nausea/vomiting/diarrheaIV = intravenousIO = intraosseous

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H’s




Hydrogen Ion (Acidosis)

Respiratoryacidosis

10 breaths per minute

Metabolic acidosis

Sodium bicarbonate 50

mEq/50 mL

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Sodium Bicarbonate • Prolonged CPR can result in profound acidosis• Sodium bicarbonate thought to increase pH to

allow better activity of catecholamines in alkaline environment

Why is it given?

• Can result in paradoxical acidosis• Will not resolve underlying cause of acidosis

Rapid Push

• Tricyclic antidepressant overdose• Aspirin overdose• Wide QRS

Best used for

H’s




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Hypokalemia

- Excessive N/V/D & excessive use of diuretics

- Blunted T waves, prominent U waves, and possible wide QRS on EKG

- Treat with controlled infusion of KCl

- 2 mEq per minute for 10 minutes

- Followed by 10 mEq over 5-10 minutes

K+

EKG = ElectrocardiographyKCl = Potassium chlorideN/V/D = Nausea/vomiting/diarrhea Truhlář . Resuscitation. 2015;95:148-201.

Hyperkalemia

Calcium chloride or gluconate-Stabilizes

cardiac membranes

Beta 2 agonists &

Bicarbonate-Shift K+ into

cells

Insulin & Glucose

-Shifts K+ into cells

-Prevent hypoglycemia

Kayexalate-Binds K in

gut, excretion through feces

Dialysis or diuretics

-If refractory to all other

options

C IG K DIB

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T’s

Tension Pneumothorax

Tamponade (cardiac) Toxins

Thrombosis (pulmonary)

Thrombosis (coronary) Trauma



Tracheal deviation, unequal breath sounds, pulseless, narrow QRS, bradycardia, JVD

Needle decompression

Chest tube

JVD = Jugular vein distention

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T’s






Tamponade (Cardiac)

Signs

EKG

Treatment

• JVD• Muffled heart

sounds

• Tachycardia• Narrow QRS

• Ultrasound• Pericardiocentesis

JVD = Jugular vein distentionEKG = electrocardiography

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T’s






Toxins

Opioids

Pinpoint pupils, respiratory depression

Naloxone IN/IV

QT prolonging drugs

QTC >500 ms

Magnesium Sulfate 2g IV

bolus

Benzodiazepines

CNS depression

Flumazenil 0.2 mg IV over 30s

CNS = Central nervous systemIN/IV = Intranasal / intravenous

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Additional Toxins

Beta Blockers

Bradycardia, hypotension, hypoglycemia

Glucagon, insulin, atropine,

catecholamines, calcium, pacing

Calcium Channel BlockersHypotension,

bradycardia, acidosis, hypoglycemia

Calcium chloride, insulin, glucagon, catecholamines, methylene blue

Serotonergic Drugs

Tremor, hyperreflexia, muscle rigidity,

hyperthermia, AMS

Supportive care, benzodiazepines cyproheptadine

AMS = Altered mental status

T’s






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Thrombosis (Pulmonary)

Thrombolytic TherapyHypotensionTachycardia

Narrow QRS

Shortness of breath

Respiratory Support O2 >90%

IV Fluids 500mL-1L

NS

Wells score & risk of bleeding

IV = intravenousNS = normal saline

Thrombolytic Therapy for Pulmonary EmboliCitation Study Design Drug Dose

Kurkciyanet al.

Retrospective cohort Alteplase 100 mg (either two 50 mg boluses OR 15 mg

bolus followed by 85 mg over 90 min)

Ruiz-Bailenet al.

Case series (6 pts) Alteplase 50 mg bolus, repeat 50 mg in 30 min

Janata et al.

Retrospective cohort

Alteplase 0.6-1.0 mg/kg bolus (up to 100 mg)

Sharifi et al. Case series (23 pts)

Alteplase 50 mg bolus

Sharifi . Am J Emerg Med. 2016;34(10):1963-1967.Kürkciyan. Arch Intern Med. 2000;160(10):1529-1535.

Janata. Resuscitation. 2003;57(1):49-55.Ruiz-Bailén. Resuscitation. 2001;51(1):97-101.

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Thrombolytic Therapy for Pulmonary Emboli

• Retrospective cohort study (n = 3768)• Adult critically ill patients with acute PE treated with

systemic alteplase therapy• 50 mg (n = 699) vs. 100 mg (n = 3069)

• Patients that received 50 mg (half-dose) alteplase• Similar mortality rates • Similar rates of major bleeding

• Half-dose may provide similar efficacy & improved safety

PE = pulmonary embolism Kiser. Crit Care Med. 2018;46(10):1617-1625.

T’s






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Acute MI à Arrest Citation Study Design Drug Dose

Ledereret al.

Retrospective cohort Alteplase 100 mg (15 mg followed by 85 mg over 90 min)

Ruiz-Bailenet al.

Retrospective cohort Alteplase 100 mg (either two 50 mg boluses OR

15 mg bolus followed by 85 mg over 90 min)

Schreiber et al.


Alteplase 100 mg (15 mg followed by 85 mg over 90 min)

Kurkciyanet al.


Alteplase 100 mg (15 mg followed by 85 mg over 90 min)

MI = Myocardial infarctionLederer . Resuscitation. 2001;50(1):71-76.

Ruiz-Bailén. Intensive Care Med. 2001;27(6):1050-1057.Schreiber. Resuscitation. 2002;52(1):63-69.Kurkciyan. J Intern Med. 2003;253(2):128-135.

Thrombosis (Coronary)

Morphine• 2-4 mg IV every 5-

15 minutes• Reserve use for

patients with an unacceptable level of pain

• CRUSADE - higher adjusted risk of death

Oxygen• If <90%• No difference in

mortality• AVOID – no reduction

in size of infarction• Shown to cause

direct vasoconstriction ofcoronaries

Nitroglycerin• Up to 3 sublingual

NTG tablets (1 every 5 minutes)

• Avoid if hypotensive, or if taken a PDEiwithin past 24 hours

Aspirin•324 mg chewed• Significant reduction in 5 week vascular mortality• Reduction in non-fatal re-infarction•No increase in risk of major bleeding

Meine . Am Heart J. 2005;149(6):1043-9.Stub. Circulation. 2015;131(24):2143-50.

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Thrombolysis Takeaways (PE & MI)

The dose of alteplase for cardiac arrest is between 50

and 100 mg given as a bolus +/-an infusion

Continued CPR is not an absolute contraindication for

fibrinolysis

Some studies suggest allowing 15 minutes of

CPR for the drug to work

Anticoagulants (primarily heparin) were used in most studies with the

fibrinolytic

PE = pulmonary embolismMI = myocardial infarction CPR = cardiopulmonary resuscitation

T’s






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Trauma

Advanced Trauma Life Support

Target audience: surgeons in hospitals & trauma centers

Removed from H’s & T’s but still important be aware of

Traumatic arrests typically due to hypovolemia

Copyright © 1996-2018 by the American College of Surgeons, Chicago, IL 60611-3295

Other DrugsFOR OTHER CIRCUMSTANCES OUTSIDE OF THE H’S & T’S

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Other DrugsMagnesium sulfate

Recommended for torsades de pointes associated with a long QT interval

Magnesium sulfate 1-2 g diluted in 10 mL D5W IV/IO

Vasopressin

Previously recommended as a substitute for the first or second dose of epinephrineThought to sensitize to catecholamines and work at a lower pH than other pressors

Recently removed recommendation from new guidelines

IV = intravenousIO = intraosseous D5W =5% dextrose in water

Vasopressin No Longer Recommended

• Small RCT (n = 44)

• Epinephrine & vasopressin vs. epinephrine + vasopressin + nitroglycerin vs. epinephrine alone

• The combination(s) did not achieve a higher diastolic blood pressure than epinephrine alone

• Larger RCT (n = 727)

• Vasopressin vs. epinephrine

• No difference in rate of survival at discharge

• Vasopressin not worse than epinephrine

Ducros. J Emerg Med. 2011;41(5):453-9.Ong. Resuscitation. 2012;83(8):953-60.RCT = Randomized controlled trial

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Esmolol

For “refractory” ventricular fibrillation

Excessive catecholamines thought to have harmful effects on myocardium via β-1 receptor agonism• Increased myocardial oxygen requirements, worsening ischemic injury,

lowering of VF threshold, and worse post-resuscitation myocardial function

Antagonism of β-1 receptors theoretically mitigate the above potentially harmful effects of epinephrine while preserving beneficial alpha-receptor actions

VF = Ventricular fibrillation Evans. Emerg Med J. 2016;33(5):367-8.

Esmolol

• Case series • 6 RVF patients received esmolol• 19 RVF control patients

• Overall 4/6 patients achieved sustained ROSC following a 500 mcg bolus & infusion of esmolol

• The other 2 patients that received esmolol achieved temporary ROSC• Subsequently re-arrested & expired

Driver. Resuscitation. 2014;85(10):1337-41..

RVF = refractory ventricular fibrillationROSC = return of spontaneous circulation

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Esmolol

Conclusions – esmolol vs. standard of care• Esmolol increased temporary ROSC (67% vs. 42%)• Esmolol increased sustained ROSC (67% vs. 32%)• Esmolol increased survival to hospital discharge (50% vs. 16%)• Esmolol increased survival to discharge with a favorable neurological

outcome (50% vs. 11%)

Driver. Resuscitation. 2014;85(10):1337-41..

ROSC = return of spontaneous circulation

Esmolol

• Pre- & Post-cohort study following implementation of esmolol for RVF in out-of-hospital cardiac arrest

• Esmolol bolus of 500 mcg à continuous infusion• Esmolol (n = 16) non-esmolol (n = 25)

• Esmolol group demonstrated a higher rate of temporary ROSC, sustained ROSC, & survival to the intensive care unit

RVF = refractory ventricular fibrillationROSC = return of spontaneous circulation Lee. Resuscitation. 2016;107:150-5.

.

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Access & Routes of Administration

Intraosseous

Proximal humerus

Proximal tibia

Distal tibia

• All medications (including blood products) may be safely administered through the IO line

• Onset & peak drug levels are comparable to IV• Important to be mindful of compatibility

IV = intravenousIO = intraosseous

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MC-002864

IO Infusion Pain Management

LidocaineInitialdose120seconds

Dwell60seconds RapidFlush

Lidocaine½initialdose60seconds

2%lidocaine(preservative-freeandepinephrine-free)

Adult:Typically40mgInfant/Child:Typically0.5mg/kg(NOTtoexceed40mg)

≥4minutestotaltime

Epinephrine• May be asked for during a thoracotomy in traumatic arrest • Dosing is the same as in ACLS

• à 1 mg every 3-5 minutes • Both concentrations acceptable

• 1:10,000 (1 mg/10 mL)• 1:1,000 (1 mg/mL)

• Needle• 18-22 gauge• 1.5 inches

• Injection• Directly into chamber of left ventricle as a rapid push

Intracardiac


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• Stop chest compressions, spray drug down the tube• Immediately give 5 manual ventilations to create

aerosol Drug Delivery

• Can affect the rate of absorption of the drug• Use saline rather than distilled waterDiluents

• The ideal volume for ET drug delivery has not been determined

• ~10 mL to avoid insufficient absorption or hypoxia Volume

• Drugs given the ET route should be about 2-1.5 times the recommended doseDose

• The duration of actions of drugs given ET is prolonged (depot effect) Duration

Endotracheal Tube

idocaine 2-3 mg/kgpinephrine 2-2.5 mgtropine 1-2 mgaloxone 0.8-5 mg

Ward. Am J Emerg Med. 1983;1:71-82.ET = endotracheal tube

Procedural Support

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Pharmacologic Considerations During ECMO

Anticoagulation

Bolus of unfractionated heparin 50-100 units/kg (max ~ 5000 units)

Data does not support the use of anti-thrombin III

May be monitored via anti-Xa, ACT, or PTT

Sedation & Analgesia

Higher doses typically required

Cannulation location can influence goal level of sedation

Always use minimum necessary to avoid delirium if possible

Paralytics

May be needed if patient is centrally cannulated

Long acting paralytic pushes

Paralytic infusion

ACT = Activated clotting timePTT = Partial thromboplastin time

ELSO. Version 1.4 . 2017. Byrnes. ASAIO J. 2014;60(1):57-62.

Summary

• Most pharmacy relevant update is the removal of vasopressin from the algorithm

ACLS guidelines

• H’s: hypovolemia, hypoxia, hydrogen ion (acidosis), hyper-/hypokalemia, hypothermia, & hypoglycemia

• T’s: toxins, tamponade (cardiac), tension pneumothorax, thrombosis (coronary & pulmonary), & trauma

Reversible causes of cardiac arrest

• May be treated with esmolol

Refractory ventricular fibrillation


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ACLS & Beyond

Christa Creech, Pharm.D.PGY-2 Emergency Medicine Pharmacy Resident

October 7th, 2018

objectives slides per page.pdf · -treat with controlled infusion of kcl-2 meqper minute for 10...

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