Outcome after cardiac arrest, time will matter

Successful resuscitation from a cardiac arrest (CA) is generally associated with a good or at least an acceptable quality of life (QoL), but a large fraction of survivors nevertheless suffers from complications such as cognitive impairment [[1], [2]] and psychological distress [[3], [4]].Today most researchers in this field agree that it is important to describe the life situation of those that survives [[5], [6]].

This task is however complicated by several factors. For an observer to be able to describe the life situation of a given person in great detail would necessitate observation of that person for 24?h, over several weeks, or maybe for months and years. Such an exhausting experiment would still leave the observer with little information on several important aspects such as; How satisfied is this person? How is the observed level of function compared to the pre-arrest function? And; How would this person function in novel situations other than those observed? In reality, we are restricted by ethical and practical limitations and able to obtain very limited information on the survivor’s life. To provide valid estimates of outcome based on such fragments of information several important factors need to be considered. We must ask the right questions, at the right time-point/s and without unnecessarily burdening the patients and their families.

Cognitive function is suggested to be one of the most important factors for a successful recovery after cardiac arrest [5].Presently, the optimal time-point for evaluation of cognitive function after cardiac arrest is not clear [7], but it is well-known that the time for assessment matters. In this issue of Resuscitation Steinbusch et al. [8]presents the results from a study were they performed cognitive assessments at several time-points during the first year after CA. Their results confirms previously published data that many cardiac arrest survivors will eventually make a full recovery of their cognitive function [[1], [2]], and that most of this recovery occurs during the first 3 months following the arrest [[9], [10], [11]]. This information is useful in the design of clinical trials, suggesting that an assessment of cognitive function at 3 months is relevant also for more long-term cognitive outcome. Could we then conclude that 3 months post-arrest should be regarded as the optimal time-point to assess cognitive outcome after cardiac arrest? Maybe. But there are some more aspects to consider before a final verdict.

In the clinical practice, patients and their family members will ask us questions about prognosis, as how much better they will become or at what time-point most of the expected recovery have occurred. Although most cognitive recovery on a group level takes place within the first 3 months post-arrest, this result is difficult to transfer to the individual CA survivor, since important individual patterns of later recovery may be masked behind the non-significant results. In one of the landmark studies on neuropsychological sequels after CA, Roine et al. [9] performed cognitive assessments at 3 and 12 months post-arrest. Although they, similar to Steinbusch et al., [8] found no difference in the level of cognitive performance between the two time-points, further descriptive information revealed that 1/5 of the patients (21%) actually improved. Conversely, 7% performed worse at 12 months, and in addition, many of those initially included died before the last assesment [9]. In 2016 Ørbo and colleagues presented a small, but well-designed, study with cognitive assessments again at 3 and 12 months post-arrest. They concluded overall stability of cognitive performance between the two measurement time-points, but also presented that 1/3 of the cardiac arrest survivors had a reliable improvement in at least one cognitive domain.

These seemingly contradictory data indicate a need to better understand individual differences in recovery and decline, and the contributing factors. Recovery from hypoxic-ischemic brain injury is likely to occur in parallel with a progressing cognitive decline due to cardiovascular burden in a substantial number of patients [12]. In support of this assumption, a follow-up study at 17 years after CA [13] reported that most patients had died due to cardiovascular disease, and that 7 out of 8 survivors had scores below-normal on a cognitive screening test.

Missing data is another important factor to consider when evaluating results on outcome after CA. In the current study [8] the levels of missing data were high, in particular when comparing the original sample [14] with the patients included in this analysis. Loss of patients is a very common problem in studies collecting outcome beyond the discharge from hospital and may lead to bias [15].It is therefore necessary to provide as much information as possible about patients who are not included or lost. Patients may be lost for a systematic reason, and for example Steinbusch et al. [8] presents that those dropping-out from their study had initially lower score on all cognitive tests compared to those completing the whole follow-up. This is important, and may at least partly explain some of the reported improvement.

To understand outcome after cardiac arrest is with no doubt difficult, and all studies in this area have limitations. Some may argue that this research assignment is actually too difficult to perform, others may choose to stay on the safe side and rely on methods that are easy to use such as crude outcome scales performed at “comfortable” time-points such as the hospital discharge. Crude outcome scales are however known to mask important effects [[1], [7]] and, as illustrated by e.g. Steinbusch et al., [8] initial levels of cognitive impairment (<1 month after the cardiac arrest) are unlikely to be representative for the patients long-term outcome [16]. Instead it is essential that we continue to explore this exciting and challenging field, so that we better can serve patients and their families in our clinical work. In addition we need to refine our methodology and instruments so that clinically important effects are not missed in clinical trials.

In all, cognitive function seems to recover mostly within the first three months from the CA, but individual differences are important. Measuring cognitive function is however not sufficient to describe the life-situation of those that survives. In addition, we need to explore relevant effects on the patients and their families’ daily life. For example it seems reasonable to assume that when the patients’ returns to more demanding activities in daily life, consequences by an eventual cognitive impairment may become more apparent. A such effect was suggested by Steinbusch et al. [8] to explain why subjective cognitive complains increased, although the measured cognitive impairment decreased during the first year after cardiac arrest. Similarly, Ørbo et al. [11]found worse mental quality of life and increased rates of depression with time after cardiac arrest. These results suggests that a single time-point assessment of cognitive function after cardiac arrest may be inaccurate or at least insufficient. Preferably, outcome after cardiac arrest should include the recovery process over longer periods of time and include also other important factors for the patients’ outcome, as emotional status, participation in the society and quality of life. Presently, the optimal time-points to evaluate these other outcomes is even less known. This argues for well-designed, large studies investigating outcome after cardiac arrest from many perspectives and over prolonged periods to give us more information on how to choose wisely.