Disheartening result for cyclosporine A in nonshockable cardiac arrest
medwireNews: Administering cyclosporine A at the time of resuscitation of patients with nonshockable out-of-hospital cardiac arrest does not reduce the likelihood of subsequent multiple organ failure, shows the results of the CYRUS trial.
As reported in JAMA Cardiology, cyclosporine A affected neither Sequential Organ Failure Assessment (SOFA) score nor survival in the 794 patients in the CYRUS (Cyclosporine A in Out-of-Hospital Cardiac Arrest Resuscitation) randomised trial.
The researchers – Laurent Argaud (Hôpital Edouard Herriot, Lyon, France) and co-workers – attribute this mainly to delays in administration. Although the emergency medical team administered the drug a median of just 8 minutes after their arrival, the median time between patient collapse and receipt of cyclosporine A was 27 minutes, which Argaud et al say may be too long a delay to prevent reperfusion injury.
The authors of an accompanying commentary, Lance Becker and Peter Berger (both from Hofstra Northwell School of Medicine in New York, USA) say: “While that may well be true, it is hard to imagine that this can be substantially improved with our current level of emergency medical system capabilities.”
However, they believe that the dose used – 2.5 mg/kg – is just as likely to underlie the negative findings, saying that the collective evidence in human suggests “that the number of cyclosporine A molecules in a dose of 2.5 mg/kg is simply not timely or sufficient to provide the target tissues the dose of cyclosporine A needed for protection.”
Of the patients treated with cyclosporine A or no additional intervention, 129 were alive at 24 hours and assessed for the primary endpoint of SOFA score; this was 10.0, on average, in the cyclosporine A group and 11.0 in the control group, which was not a significant difference. There was also no difference when the analysis was restricted to patients treated according to study protocol and to those treated within 29 minutes after collapse.
There were also no significant differences between the cyclosporine A and control groups in the proportion of patients surviving to 24 hours (16.8 vs 15.7%), 7 days (5.5 vs 5.3%) or 28 days (3.3 vs 2.0%).
Despite contesting the cyclosporine A dose used, Becker and Berger commend the researchers for having successfully completed such a difficult trial. But they also speculate that, to prevent reperfusion injury, “a single agent directed at a single molecular pathway” might be an oversimplified approach, suggesting that a multiple drug approach could yield better results.
They point out that hypothermia, “considered by many to be the most effective therapy for cardiac arrest” has multiple modes of action.
“Overall, we believe that the evidence suggests that reperfusion injury will require multiple agent therapies for effective treatment”, they conclude.
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