ROC ALPSAmiodarone, Lidocaine, or Placebo Study

ROC - ALPS

Learning Objectives• Understand the rationale for antiarrhythmic use in

out-of-hospital cardiac arrest

• Understand how to carry out the ROC ALPS study protocol

ROC - ALPS

Reason for the Study• About 24% of cardiac arrests are due to VF/VT*

• 70% will re-fibrillate after the first shock

• Antiarrhythmic drugs (good or bad?):

– Unlikely to chemically convert patients out of VF/VT– May increase probability of shock success– May prevent VT/VF recurrence after defibrillation– May result in higher incidence of bradycardia/asystole– May improve, not change, or worsen patient outcome

• Current options:– Lidocaine– Amiodarone

* In ALPS, the abbreviation “VF/VT” is defined to mean VF or pulseless VT

ROC - ALPS

Prior Amiodarone Studies• Seattle/King County medics (ARREST)

– Amiodarone vs. placebo– Amiodarone improved admission alive to hospital→ NSD* in survival to

discharge

• Toronto medics (ALIVE)– Amiodarone vs. lidocaine– Amiodarone improved admission alive to hospital→ NSD* in survival to

discharge

• Oslo medics – IV/drugs vs. no IV– IV/drugs improved admission alive to hospital → NSD* in survival to discharge

• All trials underpowered to address survival

*No significant difference

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New Formulation of Amiodarone• Amiodarone previously diluted in Polysorbate 80

(“Tween”) as Cordarone® & now generic formulations– Caused hypotension– Foaming issues– Adherent to plastic—requires all-glass packaging

• New formulation: Nexterone® (PM101)– Amiodarone diluted in Captisol – Does not cause hypotension – Safe for bolus administration– Plastic-friendly—allows for prefilled non-glass syringes in future– Currently FDA-approved only in glass syringe

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Benefit of Antiarrhythmics Unclear• American Heart Association 2010 ACLS Guidelines

– Amiodarone or lidocaine (each is a class IIb weak “may be considered” recommendation for shock-refractory VF/VT)

• Amiodarone and lidocaine may have other adverse effects

• Neither drug ever proven to improve survival

• Unproven therapies may be . . .– Beneficial– Inconsequential (make no difference)– Harmful

• The only way to know if lidocaine or amiodarone “work” is to compare either against neither (placebo)

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Trial Design

Vascular Access

SURVIVAL TO HOSPITAL DISCHARGE

Persistent or recurrent VF/VT*

after >1 shock

RANDOMIZE

Neither(saline placebo)

Amiodarone Lidocaine

Population

Intervention

Outcome

* In ALPS, the abbreviation “VF/VT” refers to ventricular fibrillation or pulseless v-tach.

ROC - ALPS

Inclusion Criteria

YES:• ≥ 18 years• Non-traumatic out-of-hospital cardiac arrest ( hanging and

electrocutions can be included unless severe trauma is involved)• Vascular access • Persistent/recurrent VF/VT after 1 (or more) shocks…

(“it’s baaack!”)NO:• Open label IV amiodarone or lidocaine use in-field1

• Known hypersensitivity or allergy to amiodarone or lidocaine• Protected population (prisoners, children2 pregnancy, etc.)

ROC - ALPS

Inclusion continued…

• What counts as a “shock”?

– ROC-EMS agency administered shock(s)• First responder or BLS-AED delivered a shock

• ALS delivered a shock

– PAD/non-ROC agency shock(s)

– Not ICD shock(s)

ROC - ALPS

Inclusion continued…

• What is persistent/recurrent VF/VT?– Confirmed VF/pulseless VT seen anytime after first shock

• VF/VT seen via see-through CPR and “VF, VT detected prompt” after ≥ 1 shock. MUST STOP CPR to confirm VF or VT (5 seconds max)

It’s baaack!

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Inclusion continued…

• Note!• If patient was shocked ≥ 1 times prior to your arrival by any person

and you can establish an IV during the 2 minutes immediately following the last shock, you can administer Epinephrine and ALPS drugs if the patient is in VF/VT as noted in the see thru tracing (stop for 5 seconds to confirm)

• If the patient was shocked ≥ 1 times prior to your arrival and upon your arrival is in a non-shockable rhythm, you cannot give ALPS until you see recurrence of VF or VT during the arrest.

ROC - ALPS

Drug Kit DesignThree (3) identical (blinded) syringes

SYRINGE # AMIODARONE KIT LIDOCAINE KIT PLACEBO KIT

1A Amiodarone 150 mg (3 cc) Lidocaine 60 mg (3 cc) Placebo (3 cc)

1B Amiodarone 150 mg (3 cc) Lidocaine 60 mg (3 cc) Placebo (3 cc)

2 Amiodarone 150 mg (3 cc) Lidocaine 60 mg (3 cc) Placebo (3 cc)

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Drug Kit Design continued…

Length: 7.75 in. Width: 4.5 in. Height: 1.75 in.

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ClearLink Adapter

• Kits will be packaged with a Baxter ClearLink Adapter

• Adapter must be used to ensure compatibility with all IV infusion sets

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Tracking of Kit• Paramedic Daily Responsibility

– Document on the Narcotic tracking sheet daily stock– Document usage on the Narcotic tracking sheet

• Count• Breakage• Run#

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Restocking of ALPS Kit

• Contact Supervisor post call and request replacement kit– Record usage on Narcotic tracking sheet (run #) and new

tracking number for the new kit (similar to the restocking of controlled drugs).

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Study Protocol• Cardiac Arrest—VF/pulseless VT

• After Shock #1 (or more)– NSR/ROSC/Asystole/PEA?→ Move on

– Still in VF/pulseless VT?→ Give Syringes #1A and #1B

• After Subsequent shock(s)– NSR/ROSC/Asystole/PEA?→ Move on

– Still in VF/pulseless VT?→ Give Syringe #2

• Move on

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What if VF/VT Returns?• “It’s baaaack…”

– Carry out the full ALPS Protocol

• What if I gave Syringes #1A and #1B, got pulses (ROSC) back, but VF/pulseless VT later returns?– Shock again– If this shock fails to stop VF/VT, give Syringe #2

ROC - ALPS

What about late-occurring VF/VT?• VF/pulseless VT is treated the same way anytime it

recurs after 1 or more prior shocks. This applies to:– VF/VT on EMS arrival

– VF/VT arrest after EMS arrival

– Late-occurring VF/VT

• Anytime VF/pulseless VT returns after 1 or more prior shocks (“it’s baaack”)→ give ALPS drug ASAP

ROC - ALPS

"see-thru" technology• Shock→ immediate CPR

• Brief (5-second max) pause in CPR to check rhythm if prompted by “VF/VT detected” and an IV is in place and it is an appropriate time for ALPS.

• If VF/VT, resume CPR and give ALPS drug

• Shock at next scheduled pause

• If no VF/VT or unable to determine, resume CPR and await next scheduled rhythm analysis

ROC - ALPS

Should I give epinephrine?• Yes.

• Give epinephrine or vasopressin ASAP per local protocol – If participating in CCC study, give within 10 minutes of arrival of ALS-

capable EMS provider

• ALPS drug does not cause hypotension; does not require concurrent vasopressor

• If vasopressor not already just given, may administer epinephrine and first dose of ALPS drug back-to-back,* in order to expedite getting ALPS drug on board sooner

*After flushing between drugs.

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Is the first dose of the study drug two syringes or one?

• Two syringes

• First Dose = Syringe #1A and Syringe #1B

• Second Dose = Syringe #2

• Exception = Small persons

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What if the patient is small? (<100 lbs/45 kg)

• Change from standard protocol

• First Dose = Syringe #1A only

• Second Dose = Syringe #1B only

• Do not use Syringe #2

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What if VF/VT persists (or recurs) after I give all the study drug?Further management at discretion of providers…• May use other antiarrhythmics if you receive an

order from the BHP

• NO open label amiodarone or lidocaine in field permitted before or after ALPS drug (no ALPS if antiarrhythmic was given prior to the arrest – follow standard treatment of cardiac arrest)

ROC - ALPS

What to do about wide complex tachycardia with pulse/BP?• ALPS is strictly for shock-resistant VF/pulseless VT needing

CPR. This applies to all doses of ALPS drug.

• If the rhythm doesn’t need CPR it shouldn’t get ALPS

• A perfusing wide complex tachycardia can be a supraventricular rhythm with BBB and not need further treatment. (patch for orders/consult if rhythm is suggestive of VT)

• Transport to hospital for definitive diagnosis/care

• If in doubt, consider electrical cardioversion (patch required)

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What if one or more syringes is broken, or gets broken before/while being given?• If any syringe in the kit is broken upon opening…

Patient excluded from study (DC ALPS)

Open label lidocaine or amiodarone, if needed

Usual drug doses

• If at least 1 ALPS syringe has already been given… Patient excluded from study (DC ALPS)

Open label lidocaine or amiodarone, if needed

Limit lidocaine to ≤ 200 mg (total dose)

May use amiodarone at usual doses

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What should the Emergency Department do?

• Notify ED that the patient may have received amiodarone or lidocaine or neither in the field

• Written script left with ED

• The script will indicate the drugs/doses the patient may have received in the field– Limit lidocaine to an additional 100–120 mg over the next 2

hours in ED

– No restriction on additional amiodarone in ED

– All other ED treatments may be given as required

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The Emergency Department really wants to know what drug we gave?

• The ED script will include a ROC physician name and phone number for the ED physician to contact for more information or questions

• Defer such questions to local ROC staff

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Study Kit LabelsDrug Kit

Hospital Notification Sheet

• Peel-off Barcode labels

Affix to…

Document the randomization # on

EPCR

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Do I carry out ALPS and CCCat the same time?

• Yes, both protocols can be done at the same time.

CCC ALPS

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Five Take-to-the-Street Principles of ALPSThink of the ALPS drug as you would about any antiarrhythmic for VF/pulseless VT and use it accordingly…• Prioritize vascular access

• Expedite ALPS drug for shock-resistant VF/VT rhythms requiring CPR– VF/pulseless VT that persists/recurs after ≥1 shocks (“It’s baaack!”)– OK to give Epinephrine plus ALPS back-to-back to speed treatment*– Give ALPS drug ASAP from when recurrent VF/VT last seen (≤2 minutes)

• Judge patient’s size– Normal: 2 syringes→ 1 syringe rescue– Small (<100 lbs/45 kg): 1 syringe→ 1 syringe rescue

*After flushing between drugs

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Five Take-to-the-Street Principles of ALPS continued…

• Document when ALPS drug given– Time-stamp each dose of ALPS drug– Document shock number that follows each dose of ALPS

drug

• Inform ED that ALPS drugs were given and provide them with the hospital notification sheet.

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REMEMBER!You must stop CPR to perform a rhythm

analysis (5 seconds max)

See-thru-CPR cannot be used to analyze a rhythm while CPR is ongoing

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Questions?