If a little bit of cooling – or at least Targeted Temperature Management – can preserve brain function, why not start it when the brain is most susceptible to injury? Why not start it when CPR is in progress, and the initial injury from poor perfusion begins?
That was, essentially, the question asked by the RINSE Trial, which randomized out-of-hospital cardiac arrest patients to either rapid infusion of cold saline or standard “ambient” fluid administration. Eligible patients received an initial round of CPR, defibrillation if indicated, and epinephrine if indicated, and were then randomized to one of the two arms.
Unfortunately, there’s not much in this trial favoring the intervention. RINSE was stopped early after receiving hospitals changed their temperature management protocols following the publication of TTM, but still managed to randomize 1,198 patients with similar baseline characteristics between cohorts. About half of patients had non-shockable rhythms, and pre-hospital results were similar. The other half, however, had shockable rhythms, and an excess of 10.2% of these patients died at the scene after cold saline infusion was initiated. Thus, the only trend observed here is one favoring standard care.
There are a few quirks to consider. Only a little more than 10% of all potentially eligible OHCA were enrolled, with no information regarding the unenrolled cohort or reasons for exclusion. The temperature difference between the two groups, based on pre-hospital tympanic membrane measurements, was only 0.7°C. Lastly, the primary outcome measure used was survival to hospital discharge, and not one of neurologic function – which may have been better aligned with the underlying neuropreservation hypothesis.
Regardless, there certainly isn’t anything here to trump up enthusiasm for further exploration, even if the magnitude of harm observed probably exceeds the expected effect of their intervention.
“Induction of Therapeutic Hypothermia During Out-of-Hospital Cardiac Arrest Using a Rapid Infusion of Cold Saline (The RINSE Trial)”