Prehospital initiation of mild therapeutic hypothermia for out-of-hospital cardiac arrest (OHCA): where are we now?

Abstract

Over the past decade, much research has been devoted to the field of mild therapeutic hypothermia (MTH) and targeted temperature management (TTM) for patients resuscitated from out-of-hospital cardiac arrest (OHCA). Two studies indicating benefit for MTH were simultaneously published in 2002, sparking a wave of global excitement and research in this field and subsequent widespread clinical implementation of this therapy. Despite questions of the true effect of subnormal temperatures on outcomes and whether the available evidence justified the endorsement by international resuscitation organizations, 1 the advent of MTH undoubtedly impacted survival and neurological outcomes, even if indirectly. Many observational studies, most often using historical controls, demonstrated benefits in mortality and neurological outcomes after incorporating MTH for OHCA management. Based on the success of animal models, 23,24 the two landmark prospective controlled clinical studies were based on the theory that post-arrest hypothermia mitigated the effects of cerebral reperfusion injury. 25,26 These trials enrolled unresponsive adult patients resuscitated from OHCA of presumed cardiac etiology with initial shockable rhythms, and compared the use of MTH at goal temperatures of 32°C − 34°C (89.6°F − 93.2°F) to usual care (unregulated temperature). 25,26 Bernard et al. included 77 patients, with MTH initiated by emergency medical services in the intervention group and continued for 12 hours. 25 At 2 hours, the group mean temperature was at 33.5°C (92.3°F). The hypothermia-after-cardiac-arrest group randomized 275 patients after witnessed OHCA. 26 MTH was commenced in the hospital, had a median time to target temperature of 8 hours, and continued for 24 hours. Benefits in neurological outcomes were seen in both studies.With evidence supporting the use of MTH, it is not surprising that the assumption was made that earlier MTH initiation and faster induction could provide even greater benefit, as was demonstrated in controlled animal studies. [27][28][29][30] Several observational studies were performed to investigate this hypothesis; however, results ranged from demonstrating benefit, 31-34 no benefit, 35,36 or even worse outcomes. [37][38][39][40] Observational studies have significant biases, however, because 1) patients with lower initial temperatures prior to MTH initiation appear to have worse outcomes than their comparators 39,41,42 ; and 2) those with worse anoxic brain injuries may be "easier to cool" 43 ; both of which may be due to impaired thermoregulation, a possible marker of more profound brain injury and therefore a reduced likelihood of survival.Several randomized controlled trials (RCTs) were performed, enrolling consecutive patients in the prehospital setting to examine the effects of earlier MTH initiation. [44][45][46][47][48][49] While these studies demonstrated that modestly lower temperatures at hospital arrival can be achieved, there were no differences in patient outcomes. In the largest of these studies,...

New Developments in the Treatment of Acute Myocardial Infarction Associated with Out-of-Hospital Cardiac Arrest. A Review

“…As yet no clinical benefit has been proven for this approach, which was also associated with longer times from therapy initiation to hospital arrival. [57][58][59]…”