In this study, we assessed the impact of cooling methods at different initial rhythms on the outcome of 1082 OHCA patients, using the database of the JAAM-OHCA registry which included patients from 87 institutions in Japan. The main results of this study are summarised as follows: First, EC was associated with significantly better 30-day neurological outcomes compared with SC in patients with an initial non-shockable rhythm. Second, this difference was no longer apparent in patients with an initial shockable rhythm. Third, this association was constant in terms of patient mortality.
The impact of SC and EC on the neurological outcome of OHCA patients is well-compared in several studies, including three randomised controlled trials showing similar non-significant trends towards the beneficial effect of EC.7–9 Our overall result is consistent with these studies. Furthermore, our study first focused on the heterogeneity of the effectiveness of the cooling method between patients with different initial rhythms and demonstrated that the optimal cooling method for TTM after OHCA may differ depending on the initial rhythm.
Initial non-shockable rhythm is known to be associated with longer no-flow time, which means longer exposure to global ischaemia.12 Patients with an initial non-shockable rhythm are also associated with older age and a higher rate of co-existing chronic conditions that predispose to deterioration in underlying conditions and depletion of physiologic reserves,13 can be more susceptible to ischaemic injury. As ischaemic injury progresses, patients are imminently threatened with reperfusion injury.20, 21 Therefore, the advantages of rapid and tighter temperature control of EC may be more prominent in patients with non-shockable rhythm. Furthermore, our data showed that the initial non-shockable patients treated with PCI benefited more from EC, suggesting that rapid reperfusion with intensive reperfusion injury protection may be more feasible. Consequently, our data might show heterogeneity in the effectiveness of SC and EC in patients with different initial rhythms. Together with recent data that demonstrate the superiority of induced hypothermia to normothermia for the outcome of initial non-shockable patients,22 a certain proportion of initial non-shockable patients may benefit more from intensive treatment strategies.
Our overall cohort showed similar patient demographics with a previous report from a large international registry, while the percentages of patients who presented with shockable rhythm (47% vs. 51%) and those treated with TTM-low (67% vs. 73%) were slightly decreased, possibly because of the secular change in the implementation of TTM.23 However, it is worth mentioning that there was significant heterogeneity in the targeted temperature between the cooling method groups. Clinicians prefer TTM-high when they use SC; this trend was prominent in patients with non-shockable rhythm, whereas there was no significant heterogeneity in patients with shockable rhythm. These results should be interpreted with caution. In our study, as in most observational studies, the decision for the TTM strategy is fully entrusted to the treating clinicians. Aside from various individual indication criteria that affect the decision, it is natural for clinicians to choose a minimally invasive strategy for patients who are or may become critically ill on the presupposition that the target temperature and cooling method do not have a significant impact on the outcome. Our analysis showed that non-shockable patients treated with SC are likely to be targeted at TTM-High; previous trials have shown that patients with several factors known to be associated with poor prognosis, such as absence of bystander CPR, absence of witness, initial non-shockable rhythm, older age, and longer time to return of spontaneous circulation, may tend to be treated with SC at TTM-High.6, 23 However, it can be difficult to retrospectively adjust all of the factors that designate highly vulnerable patients because of the dramatic clinical course of OHCA. From another point of view, clinicians’ decision to treat non-shockable patients with SC at TTM-high itself may occasionally reflect the patients’ desperate status assessed dynamically through primary resuscitation which could not be revealed by retrospective static data. Therefore, clinicians should be aware that a certain proportion of the most severe patients may tend to be included in the group of non-shockable patients treated with SC at TTM-High, the least invasive TTM implementation strategy. Our results imply that there is a need for a randomised clinical trial on the efficacy of cooling methods for TTM among certain groups of patients, given the real-world selection bias observed in those who received this treatment.
At present, guidelines do not recommend a cooling method for the implementation of TTM due to lack of evidence indicating that any specific cooling method improves outcomes after cardiac arrest when compared with any other cooling method.1, 2, 24, 25 Meanwhile, our results suggest that the TTM implementation strategy in accordance with the initial rhythm might be important. Considering the results of recent trials that focused on initial non-shockable patients,24, 26 the optimal TTM strategy may be different in this group of patients. As the mortality of this group of patients is still high,22, 23, 26 they may benefit more from improvement in the TTM strategy. Furthermore, the suggestion to consider TTM for non-shockable patients was reinforced in the latest guideline,1 and the number of patients receiving TTM may increase. Therefore, our results underscore the need for further studies in this patient group.
Our study has several limitations. First, if methods to control the temperature were duplicated, the TTM procedure category was defined as EC in this case. Therefore, several patients treated with both EC and SC were included in the EC group. However, in a real-world setting, SC is often added to the EC to achieve the target temperature more rapidly. Furthermore, since previous studies compared relatively limited cooling methods (e.g. endovascular device vs. conventional cooling method, endovascular device vs. SC device, endovascular device vs. single SC devices) on the outcome of patients showed similar trends without significant difference,5, 6, 9, 10 we believe it is important to focus on the interaction of different mechanisms of heat exchange and initial rhythm on the outcome. Second, we excluded patients requiring ECMO because of completely different invasiveness, effect of cardiac support, and baseline patient severity who needed ECMO. Therefore, our findings cannot be applied to the management and outcomes of OHCA in these patient groups. Third, as mentioned above, patient selection bias may have occurred.