Regional cerebral oxygen saturation during cardiopulmonary resuscitation as a predictor of return of spontaneous circulation and favourable neurological outcome – A review of the current literature

Resuscitation 125 (2018) 39–47

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Review

Regional cerebral oxygen saturation during cardiopulmonary resuscitation as a predictor of return of spontaneous circulation and favourable neurological outcome – A review of the current literature

T

S. Schnaubelta,c, P. Sulzgruberb, J. Mengera, K. Skhirtladze-Dworschaka, F. Sterzc, ⁎ M. Dworschaka, a

Division of Cardiothoracic and Vascular Anaesthesia and Intensive Care Medicine, Department of Anaesthesia, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, Vienna General Hospital, Austria Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna General Hospital, Austria c Department of Emergency Medicine, Medical University of Vienna, Vienna General Hospital, Austria b

A R T I C L E I N F O

A B S T R A C T

Keywords: Resuscitation Prognostication NIRS CPC Survival ROSC Clinical decision-making Cutoff-values Regional cerebral oxygen saturation

Introduction: Regional cerebral oxygen saturation (rSO2) can be measured non-invasively even at no- or lowflow states. It thus allows assessment of brain oxygenation during CPR. Certain rSO2 values had been associated with return of spontaneous circulation (ROSC) and neurological outcome in the past. Clear-cut thresholds for the prediction of beneficial outcome, however, are still lacking. Methods: We conducted a database search to extract all available investigations on rSO2 measurement during CPR. Mean, median, and ΔrSO2 values were either taken from the studies or calculated. Thresholds for the outcome “ROSC” and “neurological outcome” were sought. Results: We retrieved 26 publications for the final review. The averaged mean rSO2 for patients achieving ROSC was 41 ± 12% vs. 30 ± 12% for non-ROSC (p = .009). ROSC was not observed when mean rSO2 remained < 26%. In ROSC patients, ΔrSO2 was 22 ± 16% vs. 7 ± 10% in non-ROSC patients (p = .009). A rSO2 threshold of 36% predicted ROSC with a sensitivity of 67% and specificity of 69% while ΔrSO2 of 7% showed a sensitivity of 100% and a specificity of 86% (AUC = 0.733 and 0.893, respectively). Mean rSO2 of 47 ± 11% was associated with favourable and 38 ± 12% with poor neurological outcome. There was, however, a great overlap between groups due to scarce data. Conclusion: Higher rSO2 consistently correlated with increased rates of ROSC. The discriminatory power of rSO2 to prognosticate favourable neurological outcome remains unclear. Measuring rSO2 during CPR could potentially facilitate clinical decision-making.

Background Outcome after cardiac arrest (CA) with CPR is a major health issue. It and has seen only minimal change for the better in the last few years. Management of patients suffering from out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA), therefore, leaves room for further enhancement [1–4]. Post-resuscitation ischaemic brain damage and subsequent reperfusion injuries cause further morbidity, depending on the length and the extent of tissue hypoxaemia [5,6]. Accordingly, special techniques and measurement devices to predict neurological outcome after CA have been under investigation in order to be implemented in recommendations and CPR guidelines. One of

those prognosticating tools appears to be cerebral oximetry determined by near-infrared spectroscopy (NIRS). It measures regional brain tissue saturation (rSO2) that seems to be a probate marker for regional cerebral tissue oxygenation [7]. This non-invasive device uses red and infrared light emitted via optodes that are uni- or bilaterally attached to the patient’s forehead, whereby underlying superficial brain areas are interrogated. It provides a continuous, venous weighted signal, which is independent of pulsatile flow and enables estimation of the balance between oxygen delivery and oxygen consumption. It is even applicable in no-flow states such as CA [8,9]. Several different oximeters are on the market for clinical use that employ different algorithms and incorporate their specific technologies [9]. Some researchers claim that

⁎ Corresponding author at: Division of Cardiothoracic and Vascular Anaesthesia and Intensive Care Medicine, Department of Anaesthesia, Intensive Care Medicine and Pain Medicine, Vienna General Hospital, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. E-mail address: [email protected] (M. Dworschak).

https://doi.org/10.1016/j.resuscitation.2018.01.028 Received 18 October 2017; Received in revised form 4 January 2018; Accepted 21 January 2018 0300-9572/ © 2018 Elsevier B.V. All rights reserved.

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concerning previous duration of CA and CPR. The highest value that could be obtained during the entire data acquisition period was defined as the maximum rSO2 value achieved during CPR. Mean or median values were taken directly from the publication itself using the data available that were provided in the respective tables and figures. In some cases calculated data was taken from previous reviews. This data was marked accordingly. For the calculation of delta rSO2, only values that differed from the initial measurement until detection of ROSC or termination of CPR because of futility were taken into account, excluding all values aquired after ROSC. Averaged values (averaged means and averaged medians) were calculated from repetitive data collected in the corresponding trials. As mean and median values are not directly comparable, they were treated separately. When papers did not give mean or median values, the initial or the highest measurement was taken for the calculation of the averaged mean rSO2 value determined from all available studies. This review is reported consistent with the PRISMA-guidelines for publishing reviews [41].

measuring rSO2 in the course of CPR facilitated prognostication of return of spontaneous circulation (ROSC) as well as neurological outcome [10,11]. They suggested that rSO2 might be suitable for guidance and for quality improvement during CPR. However, sensitive cut-off levels that correctly predict outcome have not yet been determined [12]. It is also unclear which rSO2 value (initial, mean, highest or the change in rSO2 over the course of CPR) is most informative [13]. Several studies conducted in the field of OHCA and IHCA report rather variable results [6,10–12,14–38]. Although a recent review provided an overview of the topic [13], sensitive thresholds required for prognostication have not been assessed. With this review we tried to overcome these shortcomings. We further included additional data from more recent studies. Methods & statistics Objectives By collecting and analysing published rSO2 data measured during CPR we aimed to determine critical rSO2 thresholds that could be used to predict ROSC and neurological outcome after CPR. We further tried to evaluate the clinical benefit of the use of NIRS during CPR and point towards areas of future research on this topic.

Statistical analysis Receiver Operating Characteristic (ROC) – analysis was utilized to show the discriminatory power of specific cut-off levels and thresholds as potential indicators for clinical decision-making. Data was assessed for normal distribution using a Kolmogorov-Smirnov-Test. Normally distributed data was compared with the Student’s t-test, non-normally distributed data was compared using the Mann-Whitney-U-test. In order to visually compare the weighted results of those trials that provided mean rSO2 values or from which they could be calculated, a forest plot was composed. A two-tailed p-value of < 0.05 was considered to be statistically significant.

Search conduct Following a predefined search protocol (search keys were the following expressions “cardiac arrest AND cerebral oximetry”, “cardiac arrest AND cerebral saturation”, “cardiac arrest AND near infrared spectroscopy”, “cardiac arrest AND NIRS”, “resuscitation AND cerebral oximetry”, “resuscitation AND near infrared spectroscopy”, “resuscitation AND NIRS”). The databases Pubmed/Medline, Embase and CENTRAL were searched for eligible articles. The search was conducted in February 2017. In addition, articles from the reference list of retrieved articles or reviews were also screened in order to detect further sources. Duplicates and papers whose title revealed that they are non-eligible were removed.

Results Twenty-six studies all published in English language were included in the final review [6,10,12,14–20,22–27,29–38]. Twenty-three were reviewed in full length and three through their abstracts. The specific characteristics of each included trial are presented in Table 1. Fig. 1 gives an overview of the search process. Most publications reported mean rSO2 values. The 26 studies represent data from seven Asian and European countries as well as from USA. They therefore encompass different ethnicities. Overall, data from a total of 2620 patients were included, of whom 708 (27%) had ROSC and 51 (2%) a CPC of 1 or 2. Neurologic outcomes were less frequently reported as ROSC. Merely 14 studies (54%) gave detailed results [6,12,14,15,17–19,24,31,32,34–36,38]. Nineteen studies (73%) [10,12,14–16,22–27,29,31,33–38] focused on OHCA, nine (35%) [6,17–20,22,25,30,32] on IHCA, whereas 2 (8%) [22,25] investigated both OHCA and IHCA patients. Fourteen (56%) [12,15,17–19,24–27,33,35–38] stated having used bilateral-, and 10 (40%) [6,10,20,22,23,25,30–32,34] merely unilateral optodes. Two trials [16,29] did not comment. Seven papers (27%) [12,14,18,27,35,36,38] reported only initial rSO2-values, six (23%) [6,10,16,20,30,31] gave only means or medians, and two (8%) [15,26] provided just the highest values that had been determined. Four (15%) [19,22,24,32] reported initial as well as mean/median values, three (12%) [23,25,29] initial and highest values, one (4%) [33] mean/ median and highest values, and 2 (8%) [17,34] provided data on all three measurements (see Table 1).

Selection criteria All selected publications were either read as a whole or as abstract. All trials reporting on IHCA as well as OHCA cases who were monitored by NIRS were included. Data describing cerebral oxymetry after ROSC was excluded. All measurements such as initial, mean and highest rSO2values were eliglible for inclusion. Moreover, we included all types of devices used irrespective of the site of measurement (right or left, unior bilateral). The average of the right and the left rSO2 value was calculated if both had been given. Only cerebral rSO2 measures were accepted. All publications were screened for outcome data, i.e. ROSC, survival to discharge, favourable neurological outcome described as a cerebral perfomance catergory (CPC) index of 1 or 2. Furthermore, dynamics in cerebral oxygen saturation depicted as delta rSO2-values where either taken from the corresponding trials or calculated. All studies independent of sample size were included. Data collection and definitions After assessing every paper’s methodological quality (plausibility of calculations, analysis of methods together with statistics) data was extracted in order to aquire a cumulative pool of rSO2 values. Terms as “cardiac arrest” or “return of spontaneous circulation” were defined according to the updated Utstein Guidelines on uniform reporting upon CA, i.e. as the cessation of cardiac mechanical activity confirmed by the absence of signs of circulation [39]. Only CPC-scores of 1 or 2 qualified as favourable neurological outcome [40]. Initial measurement values were considered to be the first figure obtained after the NIRS-optodes had been placed on the patient’s forehead without further discimination

RSO2-values in patients achieving ROSC vs. those not achieving ROSC In 23 studies (89%) [6,10,15–20,22–27,29–36,38] either the mean or the median rSO2 value of patients achieving ROSC was reported. From this data, the averaged mean rSO2 could be calculated as 41% ( ± 12) and the averaged median as 42% ( ± 11). In contrast, in the 21 studies (81%) [6,10,15,16,19,20,22–27,29–36,38] giving information 40

41

Full-text Full-text Full-text Full-text Full-text Full-text Full-text Full-text Full-text Full-text Full-text (Conference Paper)

Full-text Full-text Abstract Full-text

Full-text (Short Communication) Full-text Full text Abstract Full-text Full-text

Full-text (Case Report)

Full-text Full-text Abstract Full-text (Case Report)

Article type

a

10 27 34 1773 59 49 34 23 7 183 19

23 69 95 34

14 50 31 15 14

9

1

6 16 24 1

No of patients

mean initial, median highest, mean, lowest initial mean initial, mean, highest initial initial initial mean, median n.a.

highest, lowest initial initial, highest mean

mean initial, mean initial, highest initial, mean initial, highest

initial highest mean initial, mean, highest (continuous values) initial (continuous values) initial, median, highest

Reported rSO2 values

3100 3000 96 5100

INVOS Equanox 7600 TOS-OR NIRO Fore-Sight/ Equanox Advanced INVOS 5100 INVOS 5100 NIRO 200 NX Equanox 7600/ INVOS Equanox 7600 INVOS 5100 INVOS 5100 INVOS 5100 Equanox 7600 Equanox 7600 TOS-OR INVOS 5100 HAND ai TOS Equanox 7600 NIRO

INVOS 5100

Fore-Sight

INVOS INVOS TOS INVOS

Type of oxymeter

OHCA IHCA OHCA OHCA OHCA OHCA OHCA OHCA OHCA IHCA OHCA

OHCA OHCA OHCA IHCA

IHCA OHCA, IHCA OHCA OHCA OHCA, IHCA

IHCA

IHCA

OHCA OHCA OHCA IHCA

Location of CA

yes yes no yes no yes yes yes yes yes no

no no no no

no no no yes no

yes

yes

yes yes no yes

Neurological Outcome reported

unilateral unilateral bilateral bilateral unilateral unilateral bilateral bilateral bilateral unilateral bilateral

bilateral bilateral n.a. unilateral

unilateral unilateral unilateral bilateral uni- (Equanox) and bilateral (Fore-Sight)

bilateral

bilateral

bilateral bilateral n.a. bilateral

Bilat./unilat.

3 (30) 19 (70) 13 (38) 413 (23) 24 (41) 19 (39) 13 (38) 5 (22) 4 (57) 62 (34) 2 (11)

7 (30) 16 (23) 21 (22) 15 (44)

5 (33) 26 (52) 14 (45) 5 (33) 6 (43)

7 (78)

1 (10) 2 (7) – 23 (1) – 3 (6) 1 (3) 2 (9) 1 (14) 13 (7) –

– – – –

– – – 0 (0) –

1 (11)

1 (100)

1 (17) 1 (6) – 1 (100)

– 4 (25) 3 (13) 1 (100) 1 (100)

No. (%) of total patients with CPC 1 or 2

No. (%) of total patients with ROSC

CA = cardiac arrest, OHCA = out-of-hospital cardiac arrest, IHCA = in-hospital cardiac arrest, bilat./unilat. = bilateral/unilateral rSO2 measurement, ROSC = return of spontaneous circulation, CPC = cerebral performance category, n.a. = not available. a 19 Patients, 5 excluded because of no or poor signal.

2014 2015 2015 2015 2015 2015 2015 2016 2016 2016 2016

2012 2013 2013 2013 2013

Parnia [20] Ahn [22] Ehara [23] Koyama [24] Meex [25]

Schewe [31] Ibrahim [32] Kalkan [33] Nishiyama [12] Singer [10] Genbrugge [34] Ogawa [35] Storm [38] Hirose [36] Parnia [6] Yagi [37]

2012

Kämäräinen [19]

2014 2014 2014 2014

2010

Martens [18]

Asim [26] Fukuda [27] Kano [29] Parnia [30]

1995 2004 2008 2010

Publicaion year

Müllner [14] Newman [15] Nakahori [16] Paarmann [17]

Trial

Table 1 Characteristics of all the included studies and frequency of reported outcome.

S. Schnaubelt et al.

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Fig. 1. Flow chart of the systematic search.

Twelve studies (46%) [12,14,15,17,19,20,26,27,30,32,33,38] used an INVOS device, seven (27%) [6,10,22,25,30,31,34] an Equanox device, two (8%) [18,25] a Fore-Sight device, and the remaining used either devices that have no FDA-approval or did not state which one was employed. Thirteen papers (50%) [18–20,23–26,29,31–35] reported temporal changes in rSO2 values that occurred before ROSC or before termination of futile CPR. Thereby, the values referred as ΔrSO2 could either be calculated from the given data or were extracted from the studies. The averaged ΔrSO2 value before ROSC calculated from mean values was 22% ( ± 16) and that calculated from median values was 18% ( ± 19). In patients who were declared dead after attempted CPR, averaged ΔrSO2 values calculated from mean values were 7% ( ± 10; p = .009 compared to initial rSO2 value) and that calculated from medians 3% ( ± 5; p = .149; Fig. 5). Two studies (8%) [25,37] stated that there was a significant correlation between higher rSO2 values and better CPR quality, but did not go into more detail. A forest plot displaying the study results graphically underlines the overall trend towards higher mean sSO2 values in patients chieving ROSC (Fig. 6).

on either the mean or median values of rSO2 of patients not achieving ROSC, the averaged mean rSO2 was 30% ( ± 12) and the averaged median 25% ( ± 13). Regarding mean rSO2 values in patients achieving ROSC, no association between rSO2 levels and the location of CA (OHCA, IHCA), the time point of measurement, or the type of measurement (initial, mean, highest) could be determined. The same applied to median rSO2-values. There was, however, a significant difference in the mean and the median rSO2 values between patients achieving ROSC and those not achieving ROSC whereby patients with ROSC consistently displayed higher rSO2 values (p = .009). Thresholds for rSO2 below which ROSC- or above which non-ROSC was not probable with a high significance level were given by nine (35%) studies. Originally, seven studies (27%) [20,22,26,29,30,32,34] provided a rSO2 threshold that when exceeded, was associated with a greater likelihood of ROSC (i.e. mean rSO2 of 26% ( ± 12) or a median rSO2 of 30% (15–31)). Mean rSO2 values of patients with ROSC were lying significantly over this given threshold of 26% (p < .001). The averaged lowest level at which ROSC was achieved could be calculated from 12 studies (46%) [6,19,24–27,31–35,38]. The threshold determined for mean rSO2 below which achievement of ROSC became highly unlikely was 23% ( ± 10). The same applied for a median of 23% (16–30). Mean rSO2 values for patients achieving ROSC were lying significantly above this threshold of 23% (p < .001), the same could be shown for median rSO2 values (p = .017; Fig. 4).

RSO2 values in patients achieving CPC 1 or 2 versus rSO2 in patients achieving CPC 3–5 Eleven papers (42%) [6,12,14,17–19,31,32,34,36,38] related mean 42

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Fig. 2. Comparison of mean rSO2-values (%) of patients with CPC 1 or 2 vs. those with CPC 3–5. The 30% line depicts the lowest averaged threshold level for the outcome CPC 1 or 2.

Fig. 3. ROC-analysis for mean rSO2-values to predict ROSC. The cut-off level with the highest sensitivity and specificity (67 and 69%, respectively) was a rSO2 value of 36%.

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Fig. 4. Comparison of mean rSO2-values (%) between patients with and without ROSC. The dashed lines depict thresholds above which ROSC became probable (26%) and below which ROSC became unlikely (23%). The line at 36% shows the cut-off for prediction of ROSC with the greatest sensitivity and specificity.

were significantly above 30% (p = .001; Fig. 2).

or median rSO2 values to CPC-scores after CPR. The averaged mean for CPC 1 or 2 was 47% ( ± 11) and the averaged median 44% ( ± 0). Regarding unfavourable neurological outcome (CPC 3–5), the corresponding data taken from the included studies were close to those reported for favourable outcome, namely 38% ( ± 12) and 42% ( ± 0), respectively. The difference in mean rSO2 values between patients with CPC 1 or 2 and those with CPC 3–5 was significant (p = .018). No significant association could be found between rSO2 values associated with a particular neurological outcome and the location of CA or the start of measurement (pre-clinical vs. after hospital admission). Two studies (8%) [32,34] provided thresholds concerning neurological outcome. CPC 1 or 2 was not observed in patients whose mean rSO2 was ≤30% ( ± 17). Mean rSO2 values in patients with CPC 1 or 2

ROC-analysis ROC-analysis was conducted to determine critical thresholds for mean, median, and calculated ΔrSO2 to predict ROSC and CPC 1 or 2. ROC-analysis showed that mean rSO2 had a significant discriminatory power to predict ROSC (AUC = 0.733, p = .021; Fig. 3). A cut-off of 36% predicted ROSC with a sensitivity of 67% and a specificity of 69%. In addition, averaged ΔrSO2 before ROSC showed significant discriminatory power for the prediction of ROSC (AUC = 0.893, p = .011), with an optimal cut-off of 7% showing a sensitivity of 100% and a specificity of 86%. The predictive value of

Fig. 5. Comparison of mean ΔrSO2-values (%) for the outcomes non-ROSC and ROSC. The dashed line at 7% depicts the cut-off value for prediction of ROSC with the highest sensitivity and specificity.

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Fig. 6. Forest plot depicting differences in mean rSO2-values between patients with ROSC and non-ROSC.

addition, a low threshold of 23% ( ± 10) was calculated below which ROSC became highly unlikely. The corresponding threshold for CPC 1 or 2 was 30% ( ± 17). In a recent review Cournoyer et al. gave an overview of NIRS measurement in CA victims. However, some studies using the same patient groups and studies reporting on rSO2 well after ROSC may have been included [13]. Nevertheless, data of over 2600 patients was summarized. It confirms other findings that higher rSO2 is associated with better outcomes [10,30,32,44]. Furthermore, it has been suggested that dynamic changes in rSO2 in the course of CPR may also prove to be a valid prognosticator for ROSC, which has been observed by other researchers [6,29,30,34]. Asim et al. even state that there can be no survival from CA without a rise of cerebral oxygenation during CPR [26]. On the opposite, a drop of rSO2 might depict recurrent cessation of global oxygen delivery after ROSC [9]. However, it is unclear how big the difference in rSO2 must be to impact outcome. In our review, we could calculate an average mean rSO2 value for ROSC patients of 41% and 30% for non-ROSC. Mean ΔrSO2 in ROSC patients was 22% vs. 7% for non-ROSC. It is unclear whether the greater increase in rSO2 during CPR in ROSC patients was due to imminent or already existing but clinically undetected ROSC. Even though the CPC index has been criticized lately [45] it is widely used to characterize neurologic function. Higher rSO2 values might be predictive for favourable neurological outcome defined as CPC 1 or 2 [11,12]. From all the included studies, the calculated averaged mean rSO2 for patients with CPC 1 or 2 was 47% and showed a significant difference (p = .018) in relation to rSO2 for CPC 3–5 patients (38%). ROC analysis for neurological outcome, however, could not confirm a significant discriminatory power for mean rSO2 values, which may be due to the limited number of trials providing information on such a relation. It remains unclear whether rSO2 during CPR determined by NIRS is also affected by the quality of CPR. According to Kämäräinen et al. no association exists [19] while Parnia et al. accounted improving rSO2 values to better CPR quality [20]. Ehara et al. showed that there was no increase in rSO2 when they applied chest-compression only CPR instead of a standard 30:2 protocol [23]. On the other hand, Meex et al. found that rSO2 varied with the quality of chest compressions [25]. Yagi et al even observed synchronous waveforms in rSO2 during chest compressions [37]. Although Genbrugge et al. stressed the potential of NIRS to measure CPR quality, improvements in rSO2 may just reflect the better physical conditions of an individual before CA [44]. In summary, none

mean rSO2-values for the outcome CPC 1 or 2 could not be determined as there was too few data available for an adequately powered analysis (AUC = 0.770, p = .098). Discussion The rate of ROSC in the studies we included was 27% with 2% of survivors having favourable neurological outcome, which compares well with current data in the western world [2,3,42,43]. Over 20 years of research on the use of NIRS during CA [9] has brought about a bulk of very heterogenic data and hard evidence for clinically meaningful conclusions regarding patient management is scarce. As early as 1995, Müllner et al. reported that higher median rSO2 values measured in the emergency department during continuous CPR after OHCA were associated with better one-week survival [14]. Since then, studies accumulated that fostered the idea of a significant relation between increased rates of ROSC and survival after CA and higher rSO2 values during CPR [13,20,30]. Kalkan et al. even used abdominal measurements in order to successfully predict ROSC and ischaemic injury in the splanchnic region [33]. Fewer trials also reported an association between higher rSO2 during CPR and favourable neurological outcome, the eventual goal of CPR. Still, the following questions remain: How high is high enough for a good outcome and how precise is the predictive power of rSO2 value during CPR? Some researchers have already calculated thresholds for specific outcomes from a small sample size. Ito et al. for example stated, that for prediction of favourable neurological outcome 90 days after OHCA, patients should have reached rSO2 ≥ 42% at hospital arrival [11]. Moreover, a study by Parnia et al. from 2016 on IHCA reported a > 50–65% cut-off level predicting ROSC with high certainty. The authors further mentioned that survival was poor in patients with persisting rSO2 < 25% despite all interventions [6]. Parnia et al. also stressed that levels should be stable for at least five minutes in order to be eligible for decision-making, thereby underscoring the dynamic character of rSO2-values in the course of CPR [20]. Others like Koyama et al. mention cut-offs of 40–50% to attain ROSC [24]. Recently, Storm et al. underlined that even very low rSO2 levels during CPR were compatible with ROSC and even favourable neurological outcome, albeit in a small group of patients [38]. This may indicate that cerebral blood flow begins to normalize only after institution of ROSC. From all the included trials that reported thresholds, we calculated a threshold of 26% ( ± 12) which, when exceeded made ROSC very likely. In 45

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References

of these studies could give a significant and valid recommendation about rSO2 values that reflect improved CPR quality. Nevertheless, greater increases of rSO2 during CPR apparently make ROSC more likely. It remains unclear, however, if greater ΔrSO2 is due to improved CPR quality, a faster recovery from cerebral ischaemia or simply reflects clinically unapparent ROSC [46,47]. ROC-analysis classifies the accuracy of predicting ROSC by the measured mean rSO2-values. We found that mean rSO2 have good and ΔrSO2 values have excellent predictive value for the occurrence of ROSC yet not for CPC 1 and 2 [48].

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Limitations Merely 24% of the included studies mentioned initial rSO2 values, which might have influenced our calculations. Selection bias, unclear reporting of therapeutic interventions and post-ROSC management, as well as underpowered studies occasionally make interpretation of original data difficult [49]. Furthermore, comparing results from different devices – each employing its own technology – could produce results that might be misleading. In addition, inclusion of different countries (with their specific emergency systems) and ethnicities increases heterogeneity and may therefore be a further risk for bias. As we were interested to assess the predictive power of rSO2 during CPR some Japanese studies [11,12,50] could only partially be included in this review due to overlapping patient data sets and the fact that in some cases rSO2 assessment was still performed after ROSC. A potential future indication for NIRS monitoring in the field of CPR might be early detection of ROSC and re-arrest [31,37]. It is frequently mentioned that rSO2 rose just immediately before ROSC [9]. If, however, the reported rSO2 increase was actually due to clinically undetected ROSC, rSO2 would be a less reliable predictor for ROSC. Other confounders like therapeutic hypothermia, certain medication, endotracheal intubation, altered microcirculation, patient ventilation and oxygenation, etc. still require further investigation [13,20]. Conclusion and recommendations Measuring rSO2- and ΔrSO2 during on-going CPR may be helpful to terminate presumably futile CPR. Cournoyer et al. extending a previous review by Sanfilippo et al. [51] gave NIRS monitoring during CPR a class IIb, C recommendation when used in a multimodal approach to terminate CPR [13]. However, prediction of poor outcome may be easier than prognostication of desirable outcome, e.g. survival of a neurologically intact patient. Furthermore, in order to obtain useful data it is essential that NIRS optodes be applied carefully. In combination with other predictors of outcome, e.g. etCO2-levels, current CPR methods and new strategies can be evaluated [21,27,30]. Nevertheless, further research preferentially with studies having a more uniform design extending into the post-ROSC period are still needed to clarify the usefulness of NIRS for the purpose of CPR management and prognostication of favourable outcome [44,52]. Conflict of interest None of the mentioned authors have any conflict of interest regarding the manuscript content. Funding information None provided. Acknowledgements None. 46

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