Although there is no definite explanation for the lack of association of our intervention with better performance, several explanations may be considered. First, this may be due to the relatively small sample size and lack of power. Although the intervention demonstrated a 10% relative increase in performance, this difference did not reach statistical significance; this was true overall and in different subgroups (Figure 3). Second, the intervention was very short, including only two questions the

participants were expected to ask themselves. It is possible that the intensity of this intervention was not high enough to affect performance. This explanation Inhibitors,research,lifescience,medical is supported by the IDO inhibitor finding that stress levels, although decreasing overall during the resuscitation,

did not significantly decrease during the most vulnerable and most stressful period, that is, when CPR was started; this was true in the intention-to-treat and the per protocol analysis. Thus, the intervention may not have been intense enough to influence Inhibitors,research,lifescience,medical stress levels to such a degree that stress-induced impairments of performance were successfully countered. Inhibitors,research,lifescience,medical Still, it has to be noted that the effect of the intervention on hands-on time was close to statistical significance (P = .059) in quartile of students that was most highly stressed. Furthermore, if the difference of 5.5 seconds in hands-on time between experimental and control group (and of Inhibitors,research,lifescience,medical 13.1 seconds in the most highly stressed quartile) can be confirmed in future

studies, this would indicate a notable improvement in performance considering the low intensity of the intervention. Interestingly, within this study we found that more leadership statements (such as commands, decisions what and how to do, task distribution among others) were associated with earlier start and longer duration of uninterrupted CPR performance. This validates previous observational research [8] and a randomized controlled trial that demonstrated a benefit from a brief leadership debriefing in terms of CPR performance Inhibitors,research,lifescience,medical PAK6 [5,35]. Within the present trial, the task-focusing strategy did not increase the number of leadership statements, which may partly explain the lack of improvement in CPR performance. Perhaps a combination of stress-related and leadership-related instructions would yield stronger results. This study has a number of limitations. The small number of participants included in this study limited the power of our analyses and increased the risk for type II errors. Although previous studies showed that participants rated the simulated resuscitation in a high fidelity simulator as highly realistic [36,37] and also perceived substantial stress [39], participants might still have perceived the simulated resuscitation as less stressful than a real life resuscitation.