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: Claudio Sandroni, Karen Hirsch, Jerry Nolan and Jasmeet Soar were coauthors of the systematic review used for adolopment. They did not participate in assessment of the systematic review for quality for adolopment.
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Methodological Preamble and Link to Published Systematic Review
The continuous evidence evaluation process for the production of Consensus on Science with Treatment Recommendations (CoSTR) started with a systematic review of prognostication after cardiac arrest (PROSPERO: CRD 420 1914 1169). This review was conducted by a systematic review team with the involvement of clinical content experts from the ILCOR ALS Task Force and consisted of two parts. The first part was about prediction of poor neurological outcome and provided evidence for the 2021 ILCOR CoSTR. The second part was about prediction of good neurological outcome and it was completed after the publication of the 2021 ILCOR CoSTR. The two parts of this review have been published separately in 2020 and 2021 respectively (Sandroni C et al, DOIs 10.1007/s00134-020-06198-w and 10.1007/s00134-022-06618-z, respectively). As the systematic review for prognostication of favorable neurologic outcome was recent and met ILCOR criteria for being of sufficient quality, the TF deemed it appropriate to use the adolopment process for systematic reviews. Additionally, an updated search including the dates October 31, 2021- May 20, 2022, to capture any papers published since the search for the original systematic review was conducted. Task force members screened and selected all newly identified papers, extracted data and performed bias assessment using the QUIPS tool, which was also used in the original systematic review. The totality of this identified evidence was considered by the Advanced Life Support task force, and used to determine the certainty of evidence and formulate the Consensus on Science and Treatment Recommendations.
The present chapter of the 2022 CoSTR deals with prediction of good neurological outcome based on electrophysiology and specifically short-latency somatosensory evoked potentials
(Sandroni C, D'Arrigo S, Cacciola S, Hoedemaekers CWE, Westhall E, Kamps MJA, Taccone FS, Poole D, Meijer FJA, Antonelli M, Hirsch KG, Soar J, Nolan JP, Cronberg T. Prediction of good neurological outcome in comatose survivors of cardiac arrest. A systematic review. intensive Care Med. 2022; 48:389-413. DOI: 10.1007/s00134-022-06618-z.)
Population: Adults (≥16 y) who are comatose after resuscitation from cardiac arrest (either in-hospital or out-of-hospital), regardless of target temperature.
Intervention: SSEP N20 wave amplitude assessed within one week from cardiac arrest.
Outcomes: Prediction of good neurological outcome defined as Cerebral Performance Categories (CPC) 1-2 or modified Rankin Score (mRS) 0-3 at hospital discharge/1 month or later. CPC 1-3 or mRS 1-4 was accepted as an indirect outcome.
Study Designs Prognostic accuracy studies where the 2 x 2 contingency table (i.e., the number of true/false negatives and positives for prediction of poor outcome) was reported, or where those variables could be calculated from reported data, are eligible for inclusion. Unpublished studies, reviews, case reports, case series, studies including less than 10 patients, letters, editorials, conference abstracts, and studies published in abstract form were excluded.
Timeframe: In 2015 and 2020, ILCOR evidence reviews identified four categories of predictors of poor neurological outcome after cardiac arrest, namely clinical examination, biomarkers, electrophysiology, and imaging. However, the prediction of good neurological outcome has never been systematically reviewed to date.
In the systematic review DOI: 10.1007/s00134-022-06618-z we searched studies published from January 1, 2001 to October 13, 2021. We updated this review for this CoSTR. Our last search was on May 20, 2022.
Consensus on Science
The original systematic review identified 37 studies on the prediction of good neurological outcome, of which four investigated SSEPs. The updated review identified six studies, of which one investigated SSEPs (total five studies on SSEPs)
The individual studies were all at moderate or serious risk of bias. The overall certainty of the evidence was rated as very low, downgraded due to lack of blinding, serious inconsistency and serious imprecision. Because of the inconsistency in N20 amplitude thresholds and timing of assessment we did not perform meta-analyses. None of the included predictors had the maximum 1% rate of falsely optimistic prediction that most clinicians would consider appropriate based on a survey conducted in 2019 (Steinberg, 2019, 190). However, the panel also considered that achieving a 0% false positive rate with narrow confidence intervals when predicting good outcome is less important than when predicting poor outcome since good outcome predictors are not used to withdrawing life-sustaining treatment.
For the outcome of ICU discharge, we identified one study (Endisch 2015, 1752).
For the outcome of long-term favorable neurological outcome (3 or 6 months), we identified four studies (Benghanem 2022 25; Glimmerveeen 2020, 335; Oh, 2019, 224; Scarpino 2021, 162).
The amplitude was calculated in microvolts (μV) as the difference between the voltage of the N20 negative wave and the voltage of the following positive P25 wave (N20–P25), but in one study [Endisch, 2015, 1752] the baseline-N20 amplitude was occasionally used if it was larger than the N20–P25 difference. One study [Benghanem, 2022, 25] reported both the N20–P25 and the N20–baseline amplitudes. The largest amplitude of the two sides was used, except in one study [Glimmerween, 2020, 335], where the smallest amplitude was used.
In one study (Oh, 2019, 224) an N20-P25 amplitude threshold >2.31 µV at 48-72h after ROSC predicted good outcome at six months with 96.5% [91.9–98.8] specificity and 52.9% [38.5–67.1] sensitivity.
In one study [Benghanem, 2022, 25], an amplitude threshold >3.2 μV measured at 72h after ROSC predicted good outcome at six months with 93% [90–96] specificity and 29% [23–34] sensitivity.
In one study [Glimmerveen 2020; 335] an amplitude threshold >3.6 μV (smallest of the two sides) at 48-72h after ROSC predicted a good outcome at six months with 95.9% [89.9–98.9] specificity 32.3% [16.7–51.4] sensitivity.
In one study [Scarpino, 2021, 162], an amplitude threshold >4 μV at 12 h, 24 h, and 72 h after ROSC predicted good outcome at six months with specificities between 86 and 91%, with 48–51% sensitivity.
In one study [Endisch, 2015, 1752] an N20 amplitude threshold >4.2 μV at 24–96h predicted good outcome at ICU discharge with 92.1% [86.5–95.8] specificity and 27.5% [20.3–35.6] sensitivity.
In three studies [Endisch, 2015, 1752; Scarpino, 2021, 162; Oh, 2019, 224] higher amplitude thresholds above 5 μV and up to 10 μV were investigated. Specificities ranged from 93% [88.1–96.3] and 100% [97.8-100], while sensitivities ranged from 5.9% [1.9–13.2] to 37.1% [27.1–48].
In one study [Benghanem, 2022, 25], an N20-baseline amplitude >2 μV at 72h after ROSC predicted good outcome at six months with 73% [68–78] specificity and 39% [33–44] sensitivity while an N20 baseline amplitude >2.7 μV predicted good outcome at six months with 87% [83–91] specificity and 28% [23–33] sensitivity.
In all but one study, an N20 Amplitude >4.0 µV threshold yielded a specificity >90% for prediction of good neurological outcome.
• We suggest against using the amplitude of the N20 SSEP wave to predict good neurological outcome of adults who are comatose after cardiac arrest (weak recommendation, very-low-certainty evidence).
Justification and Evidence to Decision Framework Highlights
Although very-low-certainty evidence suggests that a high N20 amplitude predicts good neurological outcome after cardiac arrest with high specificity, the amplitude threshold for this prediction varied widely across studies. The methods to calculate the N20 amplitude were inconsistent. Observational evidence shows that sedative agents, especially Midazolam, decrease the N20 amplitude. Finally, the optimal timing for predicting good outcome using SSEP amplitude has yet to be established.
- ● The methods to calculate the N20 SSEP amplitude need to be standardized.
- ● The optimal N20 SSEP amplitude for predicting good outcome needs to be established
- ● The interrater variability in the assessment of the N20 SSEP amplitude must be investigated
- ● The effects of sedation on the N20 SSEP amplitude must be investigated.
- ● There is still limited evidence on the correlation between time after ROSC and the N20 SSEP amplitude.
Benghanem, S., L. S. Nguyen, M. Gavaret, J. P. Mira, F. Pène, J. Charpentier, A. Marchi and A. Cariou (2022). "SSEP N20 and P25 amplitudes predict poor and good neurologic outcomes after cardiac arrest." Ann Intensive Care 12: 25
Endisch, C., C. Stor.m, C. J. Ploner and C. Leithner (2015). "Amplitudes of SSEP and outcome in cardiac arrest survivors: A prospective cohort study." Neurology 85(20): 1752-1760.
Glimmerveen, A. B., H. M. Keijzer, B. J. Ruijter, M. C. Tjepkema-Cloostermans, M. van Putten and J. Hofmeijer (2020). "Relevance of Somatosensory Evoked Potential Amplitude After Cardiac Arrest." Front Neurol 11: 335.
Oh, S. H., K. N. Park, S. P. Choi, J. S. Oh, H. J. Kim, C. S. Youn, S. H. Kim, K. Chang and S. H. Kim (2019). "Beyond dichotomy: patterns and amplitudes of SSEPs and neurological outcomes after cardiac arrest." Crit Care 23: 224.
Scarpino, M., F. Lolli, G. Lanzo, R. Carrai, M. Spalletti, F. Valzania, M. Lombardi, D. Audenino, S. Contardi, M. G. Celani, A. Marrelli, O. Mecarelli, C. Minardi, F. Minicucci, L. Politini, E. Vitelli, A. Peris, A. Amantini, A. Grippo, C. Sandroni and the ProNeCA study group (2021). "SSEP amplitude accurately predicts both good and poor neurological outcome early after cardiac arrest; a post-hoc analysis of the ProNeCA multicentre study." Resuscitation 163: 162-171.