Discussion
The most common limitation in CA studies is the lack of either pre-hospital or in-hospital standardised protocols to manage these patients. This also applies to TH. Most studies on cooling after CA were limited to the in-hospital setting, where patients were treated after admission to the Emergency Department or ICU and evaluation of outcome is restricted to hospital discharge and corrected for several in-hospital factors.[27,28] This approach may of course create different confounders; indeed, pre-hospital factors have a significant impact on survival of resuscitated patients and the presence of different types of EMS may provide unbalanced quality of CPR and pre-hospital care that could later affect the measured outcomes.[29,30] On the other hand, pre-hospital studies generally lacked a standardised in-hospital management of these patients while post-resuscitation care can also substantially alter neurological recovery after anoxic injury.[19,31] Moreover, in some studies, cooling was also interrupted after hospital arrival, thus limiting its potential benefits.[19] These are all important issues to consider when discussing the optimal time to start TH after CA.
The importance of this trial is the comprehensive approach where the whole chain of factors and management of the patient is investigated. This is indeed the largest trial investigating a brain selective cooling approach, initiated in the pre-hospital setting, and involving numerous people in the treatment of such patients from the field until ICU admission. The rationale behind the PRINCESS study is to confirm the promising results observed in the PRINCE trial, although with the ambition to improve the management of the patients in terms of earlier initiation of cooling, limited cooling interruptions from the pre-hospital to the in-hospital setting, a standardised in-hospital management and a longer follow-up period for improved neurological evaluation. Importantly, we aimed to limit the number of centres to ensure that the use of TNEC and patients management should be as standardised as possible. The risk of having many centres with low inclusion rate and poor skills with Rhinochill use may influence the final results.
Few data are available on the optimal timing to initiate TH after CA. The PRINCESS study will test the effect of TNEC during CPR on patient neurologically intact survival when compared to standard in-hospital cooling. If brain selective cooling will improve brain recovery after anoxic injury, an important improvement in the pre-hospital management of such patients will be obtained.
Trial registration
NCT01400373.
Abbreviations
ALS: Advanced life support; CA: Cardiac arrest; CPC: Cerebral performance category; CRF: Clinical report form; CPR: Cardiopulmonary resuscitation; DNAR: Do not attempt to resuscitate; EMS: Emergency medical service; etCO2: end-tidal carbon dioxide; IATH: Intra-arrest therapeutic hypothermia; ICU: Intensive care unit; OHCA: Out-of-hospital cardiac arrest; PEA: Pulseless activity; PEEP: Positive end-expiratory pressure; PI: Principal investigator; PFC: Perfluorocarbon; ROSC: Return of spontaneous circulation; SAE: Serious adverse event; SSEP: Somato-sensory evoked potential; TH: Therapeutic hypothermia; TNEC: Trans-nasal evaporative cooling; VF: Ventricular fibrillation; VT: Ventricular tachycardia.
Authors' contributions
PN, FST, MC and LS prepared this paper; PN, FST, SF, JH, MC and LS collaborated in the design of the trial and organized the initial ethics applications; MC and LS were responsible for funding and paramedic education. PN and LS are responsible for study governance and roll out of the trial. PN is responsible for logistical support of the study. AT, DD, JLV and PN are Site Investigators for Hradec Kralove, Leuven, Brussels and Stockholm, respectively. All authors contributed substantially to the design and methodology of this study and to the writing of this manuscript. All authors have read and approved the final manuscript.
BMC Emerg Med. 2013;13(21) © 2013 BioMed Central, Ltd.
