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ROC ALPS
Amiodarone, Lidocaine, or Placebo Study
Version 24: Rev. 2012-4-24
RESUSCITATION OUTCOMES CONSORTIUM
Learning Objectives
• Understand the rationale for antiarrhythmic use in
out-of-hospital cardiac arrest
• Understand how to carry out the ROC ALPS study
protocol
NOTE: IN ALPS, unless otherwise noted, the
abbreviation “VF/VT” refers to ventricular
fibrillation or pulseless ventricular tachycardia.
2012-4-24 v24
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
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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
Population
Persistent or
recurrent VF/VT*
after >1 shock
Vascular Access
Intervention
Amiodarone
Outcome
* In
RANDOMIZE
Lidocaine
Neither
(saline placebo)
SURVIVAL TO
HOSPITAL DISCHARGE
ALPS, ‘VF/VT’ refers to ventricular fibrillation or pulseless ventricular tachycardia
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Inclusion Criteria
YES:
• Non-traumatic out-of-hospital cardiac arrest
• Vascular access (IV or IO)
• 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.)
1This
also excludes use of IO lidocaine to minimize pain when inserting/flushing IO line
2Under
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local age of consent
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 and non-ROC agency shock(s)
 Not ICD shock(s)
2012-4-24 v24
Inclusion continued…
It’s
baaack!
• 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
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Drug Kit Design
Three (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.
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Width: 4.5 in.
Height: 1.75 in.
ClearLink Adapter
Kits are packaged with a Baxter
CLEARLINK Adapter
Adapter must be
used to ensure
compatibility with all
IV infusion sets
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ClearLink Adapter
View supplemental ALPS training video,
“Mandatory use of CLEARLINK Adapters
with ALPS Syringes”
dated 2012-4-19
Six minute video reviewing
background for CLEARLINK
requirement, method of use, and
reporting potential adverse events
Posted on ROC-web:
https://roc.uwctc.org/tiki/alps-training-materials
Available for download:
Windows Media or QuickTime formats
2012-4-24 v24
Study Protocol
• 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
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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
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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
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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…
• 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
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B) My EMS agency stops to look (peek) after
giving a shock, or uses "see-thru" technology
• Shock→ immediate CPR
• Brief (5-second max) pause at approximately
1 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
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C) My EMS agency stops to look (peek) when
changing compressors at 2 minutes after a shock
• 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
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D) My EMS agency performs a formal rhythm
analysis before each drug or shock intervention
• 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
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Should I give epinephrine or
vasopressin?
• 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
*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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For any ALPS patient, what potential
adverse events must be reported to ROC?
• 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
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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 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*
*Also excludes use of IO lidocaine to minimize pain
when inserting/flushing IO line.
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Should I start an infusion after
achieving ROSC?
• 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
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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. Drugs can make it worse!
• Transport to hospital for definitive diagnosis/care
• If in doubt, consider synchronized
electrical cardioversion
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What if one or more syringes are
broken or do not function?
• 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
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What must be reported when any ALPS
syringe is broken or does not function?
• 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
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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
 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
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Drug Kit
Peel-off Barcode labels
PCR
Affix to…
Hospital Notification Sheet
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FDA Directive
• 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.
LAR Script
May choose to use ROC or own EMS logo here 
Resuscitation Outcomes Consortium
Amiodarone, Lidocaine or Neither (Placebo) for Out-OfHospital Cardiac Arrest Due to Ventricular Fibrillation or
Tachycardia
Principal Investigator:
Study Coordinator:
2012-4-24 v24
“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.”
Do I carry out ALPS and CCC
at the same time?
Yes, both protocols can be done at the same
time.
CCC
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ALPS
Five Take-to-the-Street
Principles of ALPS
Think 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 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
*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/Notify ROC of ALPS use
2012-4-24 v24
Questions?