Cortical somatosensory evoked potential amplitudes and clinical outcome after cardiac arrest: a retrospective multicenter study

Objective Bilaterally absent cortical somatosensory evoked potentials (SSEPs) reliably predict poor outcome in comatose cardiac arrest (CA) patients. Cortical SSEP amplitudes are a recent prognostic extension; however, amplitude thresholds, inter-recording, and inter-rater agreement remain uncertain. Methods In a retrospective multicenter cohort study, we determined cortical SSEP amplitudes of comatose CA patients using a standardized evaluation pathway. We studied inter-recording agreement in repeated SSEPs and inter-rater agreement by four raters independently determining 100 cortical SSEP amplitudes. Primary outcome was assessed using the cerebral performance category (CPC) upon intensive care unit discharge dichotomized into good (CPC 1–3) and poor outcome (CPC 4–5). Results Of 706 patients with SSEPs with median 3 days after CA, 277 (39.2%) had good and 429 (60.8%) poor outcome. Of patients with bilaterally absent cortical SSEPs, one (0.8%) survived with CPC 3 and 130 (99.2%) had poor outcome. Otherwise, the lowest cortical SSEP amplitude in good outcome patients was 0.5 µV. 184 (42.9%) of 429 poor outcome patients had lower cortical SSEP amplitudes. In 106 repeated SSEPs, there were 6 (5.7%) with prognostication-relevant changes in SSEP categories. Following a standardized evaluation pathway, inter-rater agreement was almost perfect with a Fleiss’ kappa of 0.88. Interpretation Bilaterally absent and cortical SSEP amplitudes below 0.5 µV predicted poor outcome with high specificity. A standardized evaluation pathway provided high inter-rater and inter-recording agreement. Regain of consciousness in patients with bilaterally absent cortical SSEPs rarely occurs. High-amplitude cortical SSEP amplitudes likely indicate the absence of severe brain injury. Supplementary Information The online version contains supplementary material available at 10.1007/s00415-023-11951-4.


Supplementary Figure 1. Pathway 1 for evaluation of SSEPs based on noise level and technical preconditions.
We previously established this pathway and evaluated the SSEPs according to an adapted version.Importantly, the cortical SSEP amplitude threshold of 0.62 µV was chosen as this was the lowest cortical SSEP amplitude in good outcome patients in Endisch et al. 2015Endisch et al. (doi.org/10.1212/wnl.0000000000002123)/wnl.0000000000002123).Our pragmatic pathway hereby follows recent guidelines of the International Federation of Clinical Neurophysiology and American Clinical Neurophysiology Society.SSEP -somatosensory evoked potential.Aarhus University Hospital, Aarhus, Denmark.SSEP -somatosensory evoked potential.
g. rule out cervical lesion) * Determination of noise level in cortical recording: difference of maximum and minimum value 5 -10 ms after stimulus, if representative for entire recording length **Use pathway on determination of cortical determination of cortical SSEP amplitudes.In accordance to our pathway 1, this pathway was established in Endisch et al. 2015 and used in the present study to determine cortical SSEP amplitudes.N1 is the first negative peak of the cortical SSEP and P1 the first positive peak.Nmax is the maximum value and Pmin the minimum value of the cortical SSEP recording 4.5 ms after the cervival N13 potential and within 50 ms.SSEP -somatosensory evoked potential.See doi.org/10.1212/wnl.0000000000002123for the reference of Endisch et al. 2015.max -P min (i.e.global field potential) in case of atypical SSEP morphology at least 4.5 ms after N13 potential Cortical SSEP amplitude = highest cortical SSEP amplitude (1) -(4) of all cortical recordings (C) Center 3: Skåne University Hospital, Lund, Sweden.CPC 5 patients had a median cortical SSEP amplitude of 0.25 µV (0 -1.1), which was lower compared to CPC 2 and CPC 3 patients (median 5.6 µV and 5.4 µV, respectively).(D) Center 4: Aarhus University Hospital, Aarhus, Denmark.CPC 5 patients had a median cortical SSEP amplitude of 0.49 µV (0 -2.5), which was lower compared to all other four CPC groups.SSEP -somatosensory evoked potential, CPC -Cerebral performance category.SSEP amplitudes and recording timing.This figure illustrates the association between cortical SSEP amplitudes and day of recording for different clinical outcomes.We present the data as scatterplots (black dots) and box plots (grey) with interquartile range, median, and whisker bars representing the 5 th and 95 th percentile as appropriated.(A) All included patients.(B) Patients with a CPC outcome of 1 -3.(C) CPC 4 patients.(D) CPC 5 patients.SSEP -somatosensory evoked potential, CPC -Cerebral performance category.This figure shows the 20 exemplary SSEPs of the supervised training for the interrater analysis.Each subfigure shows a cortical (black) and a cervical (grey) recording.For interest of clarity, we show only one cortical and one cervical recording for each patient.(A) Typical middle-amplitude SSEP with N1-P1 configuration.(B) Absent cortical SSEP with tolerable noise.(C) Low-amplitude SSEP with tolerable noise.(D) High-amplitude SSEP.(E -H) Double peaked SSEPs with different peak configurations.(I) SSEP with Baseline-N1 configuration without return to baseline.(J) SSEP with Baseline-N1 configuration with nearly return to baseline.(K) Low-frequency noise with slow trend, but tolerable noise to classify as absent cortical SSEP.(L) Low-frequency noise with

Technical parameter Center 1 Center 2 Center 3 Center 4 Indication of SSEP after cardiac arrest
Supplementary Table 1.Technical details of SSEP recording stratified by the four centers.This table provides the technical SSEP recordings details of each center.Center 1: Charité University Hospital, Berlin, Germany, Campus Virchow-Klinikum; Center 2: Charité University Hospital, Berlin, Germany, Campus Mitte; Center 3: Skåne University Hospital, Lund, Sweden; and Center 4: Aarhus University Hospital, Aarhus, Denmark.SSEP -somatosensory evoked potential.

Table 2 . Patient flow for the first SSEP.
For the first SSEP, this table shows the flow of enrolled patients according to the two pathways on noise level, technical preconditions, and determination of cortical SSEP amplitudes.Results are stratified by the four centers.

Table 3 . Patient flow for the repeated SSEP.
For the repeated SSEP, this table shows the flow of enrolled patients according to the two pathways on noise level, technical preconditions, and determination of cortical SSEP amplitudes.Results are stratified by the four centers.