Value of near-infrared spectroscopy during pediatric in- and out-of-hospital cardiac arrest (PLS): Scoping Review

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This Review is a draft version prepared by ILCOR, with the purpose to allow the public to comment and is labeled “Draft for Public Comment". The comments will be considered by ILCOR. The next version will be labelled “draft" to comply with copyright rules of journals. The final Review will be published on this website once a summary article has been published in a scientific Journal and labeled as “final”.

Conflict of Interest Declaration

The ILCOR Continuous Evidence Evaluation process is guided by a rigorous ILCOR Conflict of Interest policy. The following Task Force members and other authors were recused from the discussion as they declared a conflict of interest: none applicable

The following Task Force members and other authors declared an intellectual conflict of interest and this was acknowledged and managed by the Task Force Chairs and Conflict of Interest committees: none applicable

Task Force Scoping Review Citation

Kool M, Atkins DL, Van de Voorde P, Maconochie I, Aicken R, Bingham R, Couto TB, de Caen A, Guerguerian AM, Nadkarni V, Ng KC, Nuthall G, Ong G, Reis A ,Schexynader S, Tijssen J , Scholefield B on behalf of the International Liaison Committee on Resuscitation Paediatric Life Support Task Force.

Scoping review: value of near-infrared spectroscopy during pediatric in- and out-of-hospital cardiac arrest. Brussels, Belgium: International Liaison Committee on Resuscitation (ILCOR) Pediatric Life Support Task Force, 2020 January 09. Available from: http://ilcor.org

Methodological Preamble and Link to Published Scoping Review

The continuous evidence evaluation process started with a scoping review of near-infrared spectroscopy (NIRS) and NIRS directed resuscitation in paediatric cardiac arrest, conducted by the ILCOR PLS Task Force Scoping Review team. Evidence from adult and paediatric literature was sought and considered by the PLS Task Force.

Scoping Review

Pending

PICOST

The PICOST (Population, Intervention, Comparator, Outcome, Study Designs and Timeframe)

Population: Infants & Children in any setting (in-hospital or out-of-hospital) with cardiac arrest

Intervention: the presence of variables -images, cut-off values or trends- during CPR (intra-arrest) that can provide physiologic feedback to guide resuscitation efforts, namely:

1/ Near-infrared spectroscopy / cerebral oxygen saturation monitoring

Comparators: the absence of such factors -images, cut-off values or trends.

Outcomes: Any clinical outcome.

Study Designs: STEP 1: Randomized controlled trials (RCTs) and non-randomized studies (non-randomized controlled trials, interrupted time series, controlled before-and-after studies, cohort studies) that concern directly the population and intervention described above were eligible for inclusion. As we anticipated that there would be insufficient studies from which to draw a conclusion, case series with greater than 5 cases were included in the initial search. Unpublished studies (e.g., conference abstracts, trial protocols) were excluded.

STEP 2: the same study designs and/or existing systematic or scoping reviews not directly concerning the population or intervention defined above but considered informative as additional evidence – taking into account severe indirectness- for the development of the final taskforce insights.

Timeframe: For STEP 1, all years and all languages were included, as long as there was an English abstract. For STEP 2, as a systematic review of high quality (as per AMSTAR 2 tool) was identified, searches were limited to beyond data and/or scope of that review. Literature search was updated until October 14, 2019.

Previous Treatment Recommendation

NIRS/Cerebral oxygen saturation monitoring is not included in the 2010 or 2015 paediatric or adult COSTR or AHA/ERC resuscitation guideline.

Adult 2015 COSTR (appendix A) mentions cerebral oxygen saturation monitoring within the ‘Physiological monitoring during cardiac arrest’. However no treatment recommendations are made due to limited studies of very low quality evidence (Callaway et al., 2015, s84).

Search Strategies

We searched PUBMED, Embase, CINAHL and Medline with consideration of the predefined inclusion criteria (14/10/2019). We combined the following terms using Bolean operators: life support care, cardiopulmonary resuscitation, ROSC, heart arrest, cardiac arrest using both individual (ti,ab,kw) and related MESH terms, as well as exploded terms within Embase and CINAHL. We combined these with the terms: near-infrared spectroscopy, cerebral oximetry, regional cerebral oxygenation, regional cerebral oxygen saturation (again both individual and MESH terms, and Embase and CINAHL exploded terms). The full search strategies are included in Appendix B1.

We identified 132 articles after duplicates were removed. The titles and abstracts were independently screened by two reviewers for inclusion (Rayyan.qrci.org). Disagreements were resolved by consensus and 8 studies were selected. After full text review, six further studies were eliminated. A PRISMA flow diagram of the systematic search and selection is provided in separate document.

Inclusion and Exclusion criteria

This scoping review focusses on those cerebral parameters that are measured or monitored during the provision of ALS and before return of spontaneous circulation (ROSC). These variables might provide aetiologic, physiologic and/or hemodynamic feedback to the resuscitating team, potentially guiding their actions to improve outcome, and might predict outcome. Inclusion criteria are as per PICOST.

Outcomes considered included: Feasibility of obtaining measurements, ROSC, survival to discharge, (changes in) functional outcome at discharge or other time points.

Exclusions include studies which addressed:

1/ Newborn at Delivery

2/ Pre-arrest ‘case’ features, not influenced by ALS: time of day, location, bystander CPR, gasping, age, aetiology, initial rhythm, unwitnessed…

3/ The ALS interventions themselves, performed to influence the parameters mentioned e.g. ventilation strategies, fluids, firm surface, medications given, eCPR, length and Quality of CPR….

4/ Post-ROSC parameters such as lactate clearance, post-arrest rhythm, hypotension nor any actions to provide neuroprotective care post-ROSC.

Adult data was reviewed through a separate search strategy, with the same inclusion and exclusion criteria except for age. This was only considered in step 2 as both the aetiology and pathophysiology of paediatric arrest differs substantially (serious indirectness).

Data tables

Relevant Guidelines or Systematic Reviews: None available

RCT: None available

Table 1: NIRS observations during CPR in children with CA

Non-randomized controlled trials, Observational Studies;

Author; Year

Design, country

Population

Intervention/Comparator

Main findings

1. Abramo 2014 1439.e1

Case series

United States of America

CSF shunt patients in cardiac arrest or with severe bradycardia who had rcSO2 with BVI monitoring, admitted to ED (n=14)

Compared NIRS monitoring with ETCO2 and cerebral BVI

Cerebral physiology changes can be detected using rcSO2 with BVI during cardiac arrest, ICP reduction, arrest resolution, and post arrest.

2. Çağlar 2017 642

Prospective cohort study

Turkey

Inclusion Criteria:

All patients younger than 18 years of age with OHCA, admitted to ED between March 2014 to March 2016

Exclusion Criteria:

Patients with chronic cyanotic cardiac disease, pulmonary disease, frontal head trauma or intracranial injury.

(n=10)

NIRS monitoring was compared with pulse oximetry and ECG in all patients, ETCO2 in three out of ten patients

Minimum rcSO2 values during CPR were significantly higher in ROSC patient group (median (IQR) 30±1in ROSC vs. 20.7±5.7 in non-ROSC population, p=0.02).

Only 3 out of 10 patients achieved sustained ROSC, only 1 survived to hospital discharge. rcSO2 increased with ROSC and following blood transfusion.

OHCA=Out-of-Hospital Cardiac Arrest, CA=Cardiac Arrest, ED=emergency department, BVI= blood volume index, EtCO2=end-tidal CO2, rcSO2 = regional cerebral tissue oxygen saturation, NIRS=Near-infrared spectroscopy, CPR= cardiopulmonary resuscitation, CSF= cerebrospinal fluid, ROSC = return of spontaneous circulation, ICP = Intracranial pressure, ECG=electrocardiogram

Task Force Insights

1. Why this topic was reviewed.

Ideally, physiologic monitoring of cerebral parameters and feedback to the clinician during cardiac arrest resuscitation would allow rescuers to monitor (and adjust) quality of cardiopulmonary resuscitation (CPR), and to predict (and influence) the likelihood of return of spontaneous circulation and subsequent neurologic recovery. As such, this physiologic monitoring could lead to a form of ‘individualised’ CPR, where actions are altered to match with individual needs and responses of the victim in cardiac arrest.

2. Narrative summary of evidence identified

Near-infrared spectroscopy is a non-invasive way of estimating regional cerebral oxygen saturations (rcSO2) and can be detected in cardiac arrest state when flow is absent. There are several different non-invasive devices on the market that report either the cerebral tissue oxygenation index (TOI), or rcSO2. Both are expressed as ratio of oxygenated haemoglobin (Hb) to total Hb using a modification of the Beer-Lambert law {Green 2017 48; Nagdyman 2008 160}. Nagdyman et al. published a comparison between two NIRS devices, NIRO 200 (measuring TOI) and INVOS 5100 (measuring rcSO2), and two invasive measurements of venous oxygen saturation: jugular venous bulb saturation and central venous oxygen saturation in 31 children undergoing cardiac catheterisation. Although a significant correlation was shown between non-invasive and invasive venous oxygen measurements, a considerable bias was also found in both NIRS devices. Furthermore, the study demonstrated a significant difference between the two NIRS devices, with lower mean percentages in TOI as compared to rcSO2 {Nagdyman 2008 160}.

STEP 1

We identified two pediatric studies for final inclusion (Table 1). Abramo et al. published a case series of 14 patients with CSF shunts and raised intracranial pressure presenting in CA and describes NIRS values reflecting changes in observations e.g. end tidal CO2, cerebral blood volume index {T. Abramo 2014 1439.e1}. The cohort study by Çağlar et al. of 10 OHCA patients, suggests minimum rcSO2 were lower in the population who did not achieve ROSC {Çağlar 2017 642}. There were insufficient studies identified to support a more specific systematic review.

STEP 2

Due to the limited evidence available in paediatric studies, we also looked at indirect evidence from adult studies. Data extraction tables are included in appendix C.

RCTs

No RCT’s were identified to evaluate the association between NIRS and quality of CPR or ROSC in adults or children. Nevertheless, an adult RCT is pending which will review if NIRS guided CPR (with the aim to optimize NIRS values) is superior compared to the current standard practice according to published CPR guidelines (NCT03911908), which is due to finish July 2021.

Systematic reviews

Two systematic reviews were identified: the latest was published in 2018 and comprised of studies published before February 2017. The systematic reviews concluded that a higher NIRS is associated with a higher chance of ROSC and survival and a lower NIRS is linked with an increased mortality {Schnaubelt 2018 39; Cournoyer 2016 851}. However, there seems to be no consensus on specific thresholds of rcSO2 at which a prediction can be made regarding different outcomes: ROSC, survival or neurologic outcome {Schnaubelt 2018 39}. Furthermore, there was a wide overlap of mean or median rcSO2 values between patients with ROSC and patients where ROSC was not achieved. This is also reflected in the cohort studies {Prosen 2018 141; Tsukuda 2019 33; Yazar 2019 311; Engel 2019 174}. However, an increasing trend in rcSO2 seems more reliable as a predicting factor for ROSC, with suggested increase of at least 7 – 15% from baseline {Genbrugge 2018 107; Schnaubelt 2018 39; Takegawa 2019 201}.

Observational studies

Only one study compared the rates of ROSC in the use of NIRS versus no NIRS monitoring and found no differences in the occurrence of ROSC {Singer 2018 403}. All the other studies compared NIRS in patients who achieved ROSC versus no ROSC achieved. Many different NIRS devices were used throughout the studies which complicates comparisons as the saturation indices are not interchangeable {Nagdyman 2008 160}. The findings of the observational studies since February 2017 correlate with those published in both systematic reviews.

3. Narrative Reporting of the task force discussions

Cardiac arrest, and especially OHCA, still has a very poor prognosis. High quality CPR improves outcome, but what constitutes the best possible CPR for an individual patient is still based on limited evidence and probably differs between patients and aetiologies. Having better parameters to guide CPR and adjust it to the need of the individual patient is therefore essential.

There is limited pediatric evidence available for the use of NIRS during cardiac arrest. Pathophysiological differences between adults and children are such that extrapolation from this literature should be done with caution (serious indirectness presumed), and even the adult evidence is limited. At present, there is no consensus on a cut off threshold of rcSO2 that can be used as an indicator to terminate CPR, nor is there a single rcSO2 value that can be used as a target during CPR or an argument to continue CPR. The adult literature suggests a trend of rcSO2 to be the most useful prognostic indicator, although this has not yet been validated in adults or pediatrics.

The existing evidence is too limited to advocate for any more thorough evaluation of the pediatric evidence by systematic review, however a systematic review of adult literature may be indicated.

Knowledge Gaps

Large observational studies evaluating rcSO2 directed resuscitation in children are lacking. The value of rcSO2 in evaluating CPR quality and modifications in CPR technique still needs to be clarified in future research. Furthermore studies are needed that measure the effect of rcSO2 monitoring to guide resuscitation on ROSC and survival with good neurological outcome. Importantly its place will also have to be evaluated in relation to other intra-arrest factors and monitoring techniques.

Attachments

Peds-814 NIRS PRISMA

References

Abramo, T. J., Meredith, M., Jaeger, M., Schneider, B., Bagwell, H., Ocal, E., & Albert, G. (2014). Cerebral oximetry with blood volume index in asystolic pediatric cerebrospinal fluid malfunctioning shunt patients. American Journal of Emergency Medicine. https://doi.org/10.1016/j.ajem.2014.04.007

Caglar, A., Er, A., Ulusoy, E., Akgul, F., Citlenbik, H., Yilmaz, D., & Duman, M. (2017). Cerebral oxygen saturation monitoring in pediatric cardiopulmonary resuscitation patients in the emergency settings: A small descriptive study. The Turkish Journal of Pediatrics, 59(6), 642–647. https://doi.org/10.24953/turkjped.2017.06.004

Callaway, C. W., Soar, J., Aibiki, M., Böttiger, B. W., Brooks, S. C., Deakin, C. D., … Zimmerman, J. (2015). Part 4: Advanced life support: 2015 International consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations. Circulation. https://doi.org/10.1161/CIR.0000000000000273

Cournoyer, A., Iseppon, M., Chauny, J.-M., Denault, A., Cossette, S., & Notebaert, E. (2016). Near-infrared Spectroscopy Monitoring During Cardiac Arrest: A Systematic Review and Meta-analysis. Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine, 23(8), 851–862. https://doi.org/10.1111/acem.12980

Engel T., Thomas C, Medado P, Bastani A, Reed B, Millis S, O’Neil BJ, Http://orcid.org/0000-0001-637... O. End tidal CO2 and cerebral oximetry for the prediction of return of spontaneous circulation during cardiopulmonary resuscitation. Resuscitation [Internet]. 2019;139:174–181. Available from: http://www.elsevier.com/locate/resuscitation

Genbrugge, C., De Deyne, C., Eertmans, W., Anseeuw, K., Voet, D., Mertens, I., … Dens, J. (2018). Cerebral saturation in cardiac arrest patients measured with near-infrared technology during pre-hospital advanced life support. Results from Copernicus I cohort study. Resuscitation, 129, 107–113. https://doi.org/10.1016/j.resuscitation.2018.03.031

Green, D. W., & Kunst, G. (2017). Cerebral oximetry and its role in adult cardiac, non-cardiac surgery and resuscitation from cardiac arrest. Anaesthesia, 72, 48–57. Retrieved from http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1365-2044

Nagdyman, Nicole, Ewert, P., Peters, B., Miera, O., Fleck, T., & Berger, F. (2008). Comparison of different near-infrared spectroscopic cerebral oxygenation indices with central venous and jugular venous oxygenation saturation in children. Paediatric Anaesthesia. https://doi.org/10.1111/j.1460-9592.2007.02365.x

Nishiyama K, Ito N, Orita T, Hayashida K, Arimoto H, Abe M, Unoki T, Endo T, Murai A, Ishikura K, Yamada N, Mizobuchi M, Anan H, Watanabe T, Yasuda H, Homma Y, Shiga K, Tokura M, Tsujimura Y, Hatanaka T, Nagao K. Characteristics of regional cerebral oxygen saturation levels in patients with out-of-hospital cardiac arrest with or without return of spontaneous circulation: A prospective observational multicentre study. Resuscitation. 2015;

Prosen, G., Strnad, M., Doniger, S. J., Markota, A., Stozer, A., Borovnik-Lesjak, V., & Mekis, D. (2018). Cerebral tissue oximetry levels during prehospital management of cardiac arrest - A prospective observational study. Resuscitation, 129, 141–145. https://doi.org/10.1016/j.resuscitation.2018.05.014

Schnaubelt, S., Sulzgruber, P., Menger, J., Skhirtladze-Dworschak, K., Sterz, F., & Dworschak, M. (2018). 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, 39–47. https://doi.org/10.1016/j.resuscitation.2018.01.028

Singer, A. J., Nguyen, R. T., Ravishankar, S. T., Schoenfeld, E. R., Thode Jr, H. C., Henry, M. C., … Thode, H. C. J. (2018). Cerebral oximetry versus end tidal CO2 in predicting ROSC after cardiac arrest. American Journal of Emergency Medicine, 36(3), 403–407. https://doi.org/10.1016/j.ajem.2017.08.046

Takegawa, R., Shiozaki, T., Ogawa, Y., Hirose, T., Mori, N., Ohnishi, M., … Shimazu, T. (2019). Usefulness of cerebral rSO2 monitoring during CPR to predict the probability of return of spontaneous circulation. Resuscitation, 139, 201–207. https://doi.org/10.1016/j.resuscitation.2019.04.015

Tsukuda, J., Fujitani, S., Morisawa, K., Shimozawa, N., Lohman, B. D., Okamoto, K., … Taira, Y. (2019). Near-infrared spectroscopy monitoring during out-of-hospital cardiac arrest: can the initial cerebral tissue oxygenation index predict ROSC? Emergency Medicine Journal : EMJ, 36(1), 33–38. https://doi.org/10.1136/emermed-2018-207533

Yazar, M. A., Acikgoz, M. B., & Bayram, A. (2019). Does chest compression during cardiopulmonary resuscitation provide sufficient cerebral oxygenation?. Turkish Journal of Medical Sciences, 49(1), 311–317.


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