EMS World

FEB 2017

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34 FEBRUARY 2017 | EMSWORLD.com rologically intact); they found no significant difference between amiodarone and lido- caine: 5% vs. 3%, p=0.34. Again, interpret this cautiously, since this study was not adequately powered to determine a differ- ence this small. There were no differences in adverse events between the agents. This was a well-designed study that showed amiodarone improved survival to hospital admission better than lidocaine. There were some significant limitations to the study, however. Most important, the outcome isn't one we particularly care about. While it is nice to have more patients survive to admission, we want to see improved survival to a meaningful discharge. Unfortunately this study showed no benefit in this more important measure. This study is also now more than 14 years old. Much has changed in how we address cardiac arrest. For example, we no longer recommend three stacked shocks. Currently we instruct medics to pay close attention to providing high-quality CPR, but this was not likely a focus when this study was done. These two studies (ALIVE and ARREST) provided enough evidence of benefit to amiodarone that its use became prevalent in cardiac arrest. What was needed, though, was an RCT comparing both amiodarone and lidocaine to placebo in relation to neu- rologically intact survival. Fortunately that exact study was recently published. PAPER #3 Amiodarone, Lidocaine or Placebo in Out-of-Hospital Cardiac Arrest 9 Authors: Kudenchuk PJ, Daya M, Dorian P. Published in: N Engl J Med, 2016 Aug 25; 375(8): 802–3. Dr. Peter Kudenchuk was the lead author on this large, federally funded study done through the Research Outcomes Con- sortium (ROC). This consortium includes 55 EMS agencies in the U.S. and Canada. The trial was conducted between 2012–2015 simultaneously with another trial that com- pared continuous vs. interrupted-compres- sion CPR (and found no difference between the approaches). 10 It was a randomized, pla- cebo-controlled, double-blind trial compar- ing amiodarone, lidocaine and placebo. Since this trial was done very recently, providers were using current AHA guidelines. This trial also reported on compression metrics, including rate, depth, interruptions and com- pression fractions. They enrolled adult patients with non- traumatic cardiac arrest who had an ini- tial rhythm of VF/VT that was still present after one or more shocks. Their primary outcome was survival to hospital discharge. To achieve a power sufficient to detect a difference in this outcome, they needed to enroll 3,000 patients. The main finding was that there was no overall advantage with either lidocaine or amiodarone compared with placebo or with lidocaine vs. amiodarone in terms of either survival to hospital discharge or neurologi- cally intact survival. There were some differences in second- ary outcomes, though. Neither lidocaine nor amiodarone had higher admission rates than placebo. Lidocaine (but not amioda- rone) had higher return of spontaneous circulation (ROSC) rates than placebo. There was a planned subgroup analysis based on whether the arrest was witnessed, and patients in this witnessed group had better survival to discharge with either amiodarone or lidocaine than placebo, but there was no significant differences between the two agents. Additionally there was more bradycardia that needed pacing in the amiodarone group than in either the lidocaine or placebo group. This trial may, on first glance, appear to have different results than the first two trials, which both showed an advantage to using amiodarone. It turns out, though, that they don't disagree. All three found an advantage to amiodarone in survival to hospital admission. They also agree there was no improvement in survival to hospital discharge. Although the first two trials weren't powered to detect this more meaningful outcome, this larger trial was. Often, early, small trials will find impres- sive results, and subsequent larger trials see these improvements go away. This trial also was conducted in a time when there was a focus on high-quality, minimally inter- rupted compressions. The compression fraction in all arms of this study averaged 83%, which is likely much better than in the early studies, although it wasn't possible to measure this in the earlier trials. Perhaps the higher-quality CPR reduced the poten- tial effects of the drugs and poor-quality CPR might have produced a more noticeable effect with antidysrhythmics. Overall this trial is the best evidence to date on the effectiveness of antidysrhyth- mics in cardiac arrest. We aren't likely to see a better study than this, considering the expense involved. So What Do We Know? So what do we know based on this research? We have seen that amiodarone and lido- caine promote survival to hospital admis- sion but not to discharge or neurologically intact survival. We have some evidence from a small trial that amiodarone does this better than lidocaine, but this was not confirmed in a much larger trial. In a subgroup of patients with witnessed arrest, both amiodarone and lidocaine improved survival to discharge, but neither was better than the other. There was also no differ- ence in effectiveness in unwitnessed arrest. There is also a hint, merely a suggestion, that the longer the code has been going on, the more effective the agents may be. Given what we know, what should we do differently? We know there is not, to say the least, strong evidence that any antidysrhyth- mic agent improves meaningful survival. With that in mind, for an agency that is resource-limited and faced with the choice of buying more amiodarone or lidocaine instead of spending that money on, say, training on high-quality minimally inter- rupted CPR or AEDs, the choice is clear: Stop using these drugs and spend the money on things you know matter more. If, how - ever, your system has the budget to purchase drugs without compromising other needed resources, it probably makes sense to keep one of these agents available. There are several reasons for this. First, the largest prospective trial we have demonstrated an improvement in meaning- O verall this trial is the best evidence to date on the ef fectiveness of antidysrhy thmic s in cardiac arrest.

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