1. ROC ALPS Amiodarone, Lidocaine, or Placebo Study
Version 24: Rev

2. 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.
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3. 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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4. 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
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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5. 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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6. 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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7. Trial Design
* In ALPS, ‘VF/VT’ refers to ventricular fibrillation or pulseless ventricular tachycardia
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8. Inclusion Criteria YES: NO:
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 local age of consent
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9. 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)
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10. Inclusion continued… What is persistent/recurrent VF/VT? It’s baaack!
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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11. Three (3) identical (blinded) syringes
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 2
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12. Length: 7.75 in. Width: 4.5 in. Height: 1.75 in.
Drug Kit Design continued…
Length: 7.75 in. Width: 4.5 in. Height: 1.75 in.
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13. 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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14. ClearLink Adapter View supplemental ALPS training video,
“Mandatory use of CLEARLINK Adapters with ALPS Syringes”
dated
Six minute video reviewing background for CLEARLINK requirement, method of use, and reporting potential adverse events
Posted on ROC-web:
Available for download:
Windows Media or QuickTime formats
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15. 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)
Still in VF/ VT?→ Give Syringe #2
Move on
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16. 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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17. 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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18. 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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19. 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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20. 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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21. 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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22. 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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23. Is the first dose of the study drug two syringes or one?
First Dose = Syringe #1A and Syringe #1B
Second Dose = Syringe #2
Exception = Small persons
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24. 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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25. 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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26. 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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27. 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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28. 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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29. 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…
Limit lidocaine to ≤ 200 mg total dose
May use amiodarone at usual doses
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30. 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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31. 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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32. 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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33. Peel-off Barcode labels
Drug Kit
Peel-off Barcode labels
PCR
Affix to…
Hospital Notification Sheet
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34. 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.
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35. Do I carry out ALPS and CCC at the same time?
Yes, both protocols can be done at the same time.
CCC
ALPS
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36. 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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37. 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
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38. Questions?