Our prospective study reports a 21.2% incidence of NDEs in out-of-hospital cardiac arrest survivors. It also suggests that the occurrence of NDEs is connected to higher initial petCO 2 , higher arterial blood pCO 2 , and previous NDEs. Higher serum levels of potassium might also play a role.

To our knowledge, this is the first prospective study to report a possible correlation between NDEs and CO 2 . It is still not clear whether NDEs occur before, during, or after the period of cardiac arrest [3]. During cardiac arrest, the petCO 2 falls to very low levels, reflecting the very low cardiac output achieved with cardiopulmonary resuscitation [31]. Higher levels of petCO 2 therefore indicate better cardiac output and higher coronary perfusion pressure [32]. Our findings concerning the association between initial petCO 2 and the occurrence of NDEs therefore support the hypothesis that NDEs occur during the cardiac arrest.

On the other hand, the association between higher pCO 2 upon admission and the occurrence of NDEs might suggest that NDEs occurs after the cardiac arrest. But higher pCO 2 upon admission might simply reflect higher initial petCO 2 . Nevertheless, it is known that CO 2 changes the acid-base equilibrium in the brain, which can provoke unusual experiences in the form of bright light, visions, and out-of-body or even mystical experiences [3, 5]. Some earlier studies have shown that inhaled CO 2 , used as a psychotherapeutic agent, could cause NDE-like experiences [33, 34]. Therefore, we can conclude that CO 2 might be one of the major factors for provoking NDEs, regardless of when NDEs occur. As far as we know, serum levels of potassium were assessed only in one study [3]. The mean level of potassium in the NDE group was slightly lower in comparison to the control group, but no significant differences were found. As our study managed to associate serum levels of potassium only with the higher NDE score, and not also with the higher incidence of NDEs, no firm conclusions can be drawn at this point. Also, the possible mechanism of the effect of potassium in the NDEs has not yet been established. Alternative theories found the explanation for NDEs in quantum theory, which suggests that consciousness may arise from quantum processes within neuronal microtubules [35]. The recent work of Bernroider and Roy suggests that quantum entanglement in the ion channels (especially in the potassium channel) of brain cells underlies information processing in the brain and, ultimately, also consciousness [36]. Although untenable and purely theoretic, this possible connection between potassium channels in the brain and the mechanism of consciousness (and therefore the possible mechanism of NDEs) deserves further investigation.

Available data on the role of oxygen in provoking NDEs is ambiguous. Although one physiological theory [5] suggests that anoxia (or hypoxia) might be the cause for NDEs, Parnia and colleagues [3] found a higher mean pO 2 in peripheral blood; however, due to an insufficient sample quantity, a univariate analysis was not performed. In our study, the NDE group had a lower mean pO 2 than the non-NDE group, but this difference was not statistically significant (Table 2). Nevertheless, this finding is in favour of the theory of anoxia [5] and supported by several studies that reported NDE-like experiences in decreased cerebral perfusion (resulting in local cerebral hypoxia) in rapid acceleration during training of fighter pilots [37], in hyperventilation followed by the valsalva maneuver [38], and in people exposed to high altitudes [6]. The proposed mechanism is the induction of hyperactivity of N-methyl D-aspartate (NMDA) receptors by hypoxia, which induces hallucination and might induce NDEs [10].

Previous prospective studies on NDEs reported an 11 to 23% incidence between cardiac arrest survivors [3, 25–27], which is consistent with the incidence found in our study. We have not demonstrated the connection between younger age and a higher incidence of NDEs. In fact, the mean age of the NDE group was lower than the non-NDE group, but this difference was not statistically significant. Previous studies have shown that NDEs more often occur in patients younger than 60 years of age [3, 27, 28]. The age difference in our study might be overlooked due to an insufficient number of subjects. It is also true that almost 70% of patients in our sample were younger than 60 years. The mean age of patients in our sample was lower (for almost 10 years) than in the two largest prospective studies of NDEs in cardiac arrest survivors [25, 27]. This difference might also be the reason why we were not able to demonstrate any age differences in the occurrence of NDEs.

Our study confirmed the findings of other studies on NDEs that sex [25, 27], level of education [25, 28], fear of death [25], time until ROSC [25, 28], medication during resuscitation [25, 28], serum level of sodium [3], and religious belief [25] are not associated with NDE occurance. It also confirmed previously reported findings [25] that patients with previous NDEs are more likely to have repeated NDEs in case of a new cardiac arrest episode.

The questionnaire proved to be a reliable instrument for assessing NDEs also in Slovenian. The Cronbach's α of the questionnaire in the original study was 0.88 [20] and our result (0.875) was almost the same.

Our study suggests that some physiological factors or processes might be important in provoking NDEs. On the other hand, the experiences induced by neurophysiological processes mostly consist of fragmented and random memories and confused experiences unlike the real NDEs that are clear, highly structured and easily recalled [3, 25]. It is not thought possible to explain NDEs only in terms of physiological processes. Most likely multiple physiological factors are involved [5]. Clearly, the presence of NDEs pushes the current knowledge of human consciousness and mind-brain relation to the edge of our understanding.

The main strength of our study is its prospective design. With a consecutive recruitment of the patients and the inclusion of three of the largest Slovenian hospitals, the selection bias was reduced as much as possible. The use of a standardised scale for NDEs ensured the consistency of NDEs reports. The number of patients in the sample is the main weakness of our study. Therefore, some important differences might have been overlooked and the results should be interpreted with care. Also, receiver-operator characteristic curves for defining a threshold CO 2 were not produced due to too small a number of patients. The weakness is also the fact that almost 70% of the patients in a sample were younger than 60 years old, which could affect the incidence and the demonstration of age differences in NDEs.