Since the Hagihara study was published, there is a lot more support for a study of epinephrine. One of the problems with studying epinephrine is the religious devotion that some have to maintaining the status quo.
How do we prevent paramedics from violating the study protocol?
I have been told of paramedics testing the study drug to see if it produces the cocaine-type of numbness to the tongue, since epinephrine produces effects similar to cocaine without the euphoria. If the study drug is not epinephrine, the syringe is broken, or replaced, or . . . .
How much epinephrine is needed on an ALS (Advanced Life Support) ambulance?
We generally carry a bunch of 1:10,000 epinephrine (1 mg in 10 ml) for cardiac arrest. Maybe 5 – 10 with a multi-dose 30 ml vial of 1:1,000 (1 mg in 1 ml) epinephrine for those prolonged arrests, so that 1 mg at a time can be drawn up and given to the patient.
We also carry some ampules of 1:1,000 epinephrine for IM (IntraMuscular), SC (SubCutaneous), or IV (IntraVenous) administration for anaphylaxis or asthma.
We can easily replace the 1:10,000 epinephrine and the multi-dose vial with just one study drug packet. After each code, a new packet would be placed in the ambulance’s drug bag/box. This would discourage the tendency to switch kits if the study drug is not epinephrine – not that there is any good reason for the medic to know what is being given.
For anaphylaxis/asthma, participating ambulances would be assigned only autoinjectors. This would decrease the availability of epinephrine available to violate protocol.
Supervisors would only carry study kits and autoinjectors.
Is it still possible to intentionally violate protocol? Yes, but anyone thinking that far ahead should be smart enough to realize that they are only harming patients by possibly requiring that the study be repeated. The maturity of the medics should be the best protection against protocol violation, but true believers can be immune to maturity.
What would the study kits include?
Patients are not entered into the study unless they have reached the point in the algorithm where epinephrine would be given. When the kit is opened, the recording beginsand the first syringe of the study drug is given.
Monitors capable of recording the quality of CPR would also be used. The ROC (Resuscitation Outcomes Consortium) should already be using these, so it would not be an added expense.
What about patients who remain in a shockable rhythm after the syringes of study drug are all used? Transport them to the hospital. Let the hospital do whatever they want with these rare patients.
What if there is a problem with the study kit? Then the patient should not be receiving any medication and should be unblinded participants in the group not receiving epinephrine.
What about amiodarone/lidocaine? There is no good reason to give these derivative magic treatments until there is evidence that they work. This is to try to find out if the
primary magic treatment epinephrine works, not to support the whole Chain of Magic.
Maybe the last part of that chain should not be there.
See also –
 Prehospital epinephrine use and survival among patients with out-of-hospital cardiac arrest.
Hagihara A, Hasegawa M, Abe T, Nagata T, Wakata Y, Miyazaki S.
JAMA. 2012 Mar 21;307(11):1161-8. doi: 10.1001/jama.2012.294.
PMID: 22436956 [PubMed - indexed for MEDLINE]
 Intramuscular versus intravenous therapy for prehospital status epilepticus.
Silbergleit R, Durkalski V, Lowenstein D, Conwit R, Pancioli A, Palesch Y, Barsan W; NETT Investigators.
N Engl J Med. 2012 Feb 16;366(7):591-600.
PMID: 22335736 [PubMed - in process]