RESUSCITATION OUTCOMES CONSORTIUM

ROC ALPSAmiodarone, Lidocaine, or Placebo Study

Version 24: Rev. 2012-4-24

• Understand the rationale for antiarrhythmic use in out-of-hospital cardiac arrest

• Understand how to carry out the ROC ALPS study protocol

Learning Objectives

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NOTE: IN ALPS, unless otherwise noted, the abbreviation “VF/VT” refers to ventricular fibrillation or pulseless ventricular tachycardia.

• 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

Reason for the Study

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• 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

Prior Amiodarone Studies

*No significant difference2012-4-24 v24

• 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

New Formulation of Amiodarone

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• 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)

Benefit of Antiarrhythmics Unclear

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Trial Design

* In ALPS, ‘VF/VT’ refers to ventricular fibrillation or pulseless ventricular tachycardia

Vascular Access

SURVIVAL TO HOSPITAL DISCHARGE

Persistent or recurrent VF/VT*

after >1 shock

RANDOMIZE

Neither(saline placebo)

Amiodarone Lidocaine

Population

Intervention

Outcome

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• Non-traumatic out-of-hospital cardiac arrest• Vascular access (IV or IO)• Persistent/recurrent VF/VT after 1 (or more) shocks…

(“it’s baaack!”)

Inclusion CriteriaYES:

• Open label IV amiodarone or lidocaine use in-field1

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

NO:

1This also excludes use of IO lidocaine to minimize pain when inserting/flushing IO line 2Under local age of consent

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• What counts as a “shock”?

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

» ALS delivered a shock

PAD and non-ROC agency shock(s)

Not ICD shock(s)

Inclusion continued…

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• What is persistent/recurrent VF/VT? Confirmed VF/pulseless VT (operationally, pulseless means needing

CPR) seen anytime after first shock» VF/VT seen (see-through CPR in systems that “look” at the

rhythm after a shock before drug treatment ) after ≥1 shock

» VF/VT seen on second or later rhythm analysis (in systems that perform a formal rhythm analysis before each shock or drug intervention, or those who give drugs “blindly” (during CPR) following a shock) after ≥1 shock

If thinking antiarrhythmic drug for VF/pulseless VT… give ALPS drug

Inclusion continued…

It’s baaack!

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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.2012-4-24 v24

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

ClearLink AdapterKits are packaged with a Baxter CLEARLINK Adapter

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Six minute video reviewing background for CLEARLINK requirement, method of use, and reporting potential adverse events

ClearLink AdapterView supplemental ALPS training video, “Mandatory use of CLEARLINK Adapters

with ALPS Syringes” dated 2012-4-19

Posted on ROC-web: https://roc.uwctc.org/tiki/alps-training-materialsAvailable for download:Windows Media or QuickTime formats

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• Cardiac Arrest—VF/pulseless VT

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

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

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

Still in VF/ VT?→ Give Syringe #2

• Move on

Study Protocol

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• “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

What if VF/VT Returns?

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• 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

What about late-occurring VF/VT?

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• Shock→ immediate CPR (without look)

• Give study drug during 2-minute period of CPR after shock, in the belief that VF/ VT is still present The rationale for this approach is that re-fibrillation during

this 2-minute period is likely, even if the shock was initially successful.

• Shock at next scheduled pause

A) My EMS agency does not “stop to look” after giving a shock

VF/pulseless VT seen on second or later rhythm analysis after ≥1 shock…

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• Shock→ immediate CPR

• Brief (5-second max) pause at approximately1 minute into CPR for rhythm check/confirmation

• 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

B) My EMS agency stops to look (peek) after giving a shock, or uses "see-thru" technology

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• After 2 minutes of CPR, as compressors are switched, quickly look at the rhythm

• If VF/VT seen, resume CPR and charge monitor Give ALPS drug while charging→ then shock

If not possible to give drug before shock, give it immediately afterward, as CPR is resumed

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

C) My EMS agency stops to look (peek) when changing compressors at 2 minutes after a shock

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• Analyze rhythm at customary end of 2-minute CPR period (maximum 5 seconds)

• If VF/ VT → start next 2-minute CPR period, give ALPS drug and charge defibrillator

• Shock at next scheduled pause

• If no VF/VT → resume CPR (or check pulse if organized rhythm seen) and treat per local protocol

• If unable to determine rhythm, resume CPR and await next scheduled rhythm analysis

D) My EMS agency performs a formal rhythm analysis before each drug or shock intervention

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• Yes

• Give epinephrine or vasopressin ASAP per local protocol If participating in CCC study, give within 5 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/vasopressin and first dose of ALPS drug back-to-back,* in order to expedite getting ALPS drug on board sooner

Should I give epinephrine or vasopressin?

*After flushing between drugs. 2012-4-24 v24

• Two syringes

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

• Second Dose = Syringe #2

• Exception = Small persons

Is the first dose of the study drugtwo syringes or one?

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• Change from standard protocol

• First Dose = Syringe #1A only

• Second Dose = Syringe #1B only

• Do not use Syringe #2

What if the patient is small? (<100

lbs/45 kg)

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• Non-function of ALPS syringe

• Anaphylaxis (severe allergic reaction)

• Pacing started in field

• Seizures, shivering, myoclonus

• Complications of IV or IO administration after ALPS given

For any ALPS patient, what potential adverse events must be reported to ROC?

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• May use other antiarrhythmics available to the agency (e.g., magnesium, beta blockers and/or procainamide)

• Additional shock(s)

• NO open label amiodarone or lidocaine in field permitted before or after ALPS drug*

What if VF/VT persists (or recurs) after I give all the study drug?

Further management at discretion of providers…

*Also excludes use of IO lidocaine to minimize pain when inserting/flushing IO line.

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• No known value of prophylactic antiarrhythmic drug infusions after cardiac arrest

• Since no open label amiodarone or lidocaine can be given in the field, no infusions of these drugs should be given by EMS providers (includes no IO administration of lidocaine given to minimize pain when inserting or flushing IO line)

• Duration of drug effect (“half-life”) should last until ED arrival

• Use of open label lidocaine or amiodarone is permitted in hospital

Should I start an infusion after achieving ROSC?

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• 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. Drugs can make it worse!

• Transport to hospital for definitive diagnosis/care

• If in doubt, consider synchronized electrical cardioversion

What to do about wide complex tachycardia with pulse/BP?

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• If any syringe in the kit is broken upon opening, or does not function prior to giving… Stop ALPS, shut the box, and move on

Use open label lidocaine or amiodarone, if needed

Usual drug doses

• If any portion of any ALPS syringe has already been given and syringe breaks or does not function… Stop ALPS, shut the box, and move on

Use open label lidocaine or amiodarone, if needed

Limit lidocaine to ≤ 200 mg total dose

May use amiodarone at usual doses

What if one or more syringes are broken or do not function?

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• Quarantine ALPS kit with the damaged syringe • Document circumstances

On patient record

ROC-report form

• Promptly notify ROC coordinator• Return ALPS kit with syringes to ROC coordinator

What must be reported when any ALPS syringe is broken or does not function?

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• 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

What should the Emergency Department do?

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• The ED script will include

ROC physician name and phone number for the ED physician to contact for more information or questions

Contact information for rare request to un-blind study drug

• Defer questions to local ROC staff

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

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Drug Kit

Peel-off Barcode labelsPCR

Affix to…

Hospital Notification Sheet

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• When feasible, this written script will be presented to the LAR by the prehospital provider.

• The acute circumstances of cardiac arrest may rarely, if ever, afford such opportunity on-scene without compromising patient care.

• Accordingly, determining if or when presenting this script on-scene is feasible …will be left to clinical discretion of the provider.

FDA Directive

LAR Script

May choose to use ROC or own EMS logo here

Resuscitation Outcomes Consortium

Amiodarone, Lidocaine or Neither (Placebo) for Out-Of-

Hospital Cardiac Arrest Due to Ventricular Fibrillation or Tachycardia

Principal Investigator: Study Coordinator: “Your family member is having a cardiac arrest due to a very dangerous heart rhythm. We will do everything possible to save his/her life. [Local EMS Agency] are also performing an important study to find the best heart rhythm medication to use for this condition, in hope of saving more lives. Unless you say no, we will give this treatment, in addition to all other standard treatments for your family member. You will receive more information about this later, and a chance to ask questions.”

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

Do I carry out ALPS and CCCat the same time?

CCC ALPS

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• 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 vasopressor 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

Five Take-to-the-StreetPrinciples of ALPSThink of the ALPS drug as you would about any antiarrhythmic for VF/pulseless VT and use it accordingly…

*After flushing between drugs2012-4-24 v24

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

ALPS drug

• Inform ED/Notify ROC of ALPS use

Five Take-to-the-StreetPrinciples of ALPS continued…

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Questions?