Somatosensory evoked potential for post-arrest neuroprognostication

The most common cause of death amongst comatose post-cardiac arrest patients remains withdrawal of life-sustaining measures (WLSM) because of a predicted poor neurologic prognosis.1 As such, consistent, objective, and evidence-based neuroprognostication is crucial to avoid inappropriate or premature WLSM. Accurate neuroprognostication can also circumvent prolonged, invasive, potentially harmful, and costly therapies that could perpetuate patient and family suffering when there is no realistic chance of a favourable recovery. Several guidelines outline an approach to neuroprognostication of post-arrest patients2–5 that ensure confounders are excluded and sufficient time has passed, while also emphasizing multimodal assessment that includes neurologic examination, neuroimaging, electrophysiological, and biomarker findings that are used in combination to determine a patients’ neurologic prognosis. Somatosensory evoked potentials (SSEPs) are one electrophysiological test that can be used to aid in the process of post-arrest neuroprognostication. Current literature suggests SSEPs are accurate and precise in predicting a poor neurologic prognosis following cardiac arrest.6 While the grade of evidence and strength of recommendation varies amongst guidelines, all make recommendations for utilizing SSEPs, when available, as part of a multimodal approach to neuroprognostication in patients who remain comatose.2–5 There are several considerations for appropriate SSEP testing that merit consideration. This review explores these considerations, including relevant neuroanatomy and physiology, the logistics of performance and interpretation, current data to support their use, and special considerations for post-arrest patients within the intensive care unit. Somatosensory evoked potentials are a complex series of electrical potentials generated in the dorsal column–lemniscal sensory pathway (Figure 1). Analysis of these potentials aids in evaluating the integrity of this sensory pathway at peripheral, spinal, subcortical, and cortical levels. For the purposes of post-arrest neuroprognostication, median nerve SSEPs are most often evaluated. While clinical SSEPs can be elicited by several stimuli including tactile, mechanical, and thermal, electrical stimulation is the most effective. Electrical stimulation preferentially activates proprioceptors and mechanoreceptors, with signals transmitted via first-order afferent nerve fibres through the corresponding dorsal nerve root to then ascend the ipsilateral dorsal column within the spinal cord. These nerve fibres synapse on second-order neurons within the ipsilateral cuneate nucleus (or gracile nucleus when lower extremity nerves are stimulated), located in the caudal medulla. The subsequent second-order nerve fibres cross over to ascend the contralateral medial lemniscus to the ventroposterior nuclei of the thalamus, where they synapse with third-order neurons. Third-order nerve fibres project to the corresponding portion of contralateral primary somatosensory cortex and other networks located within the secondary sensory cortices, posterior parietal cortex, posterior- and mid-insular cortex, and the mid-cingulate cortex. The first cortical potential is the N20 potential, which is generated in the primary somatosensory cortex and indicates integrity of the thalamocortical neurons synapsing on the cortical neurons. Somatosensory evoked potentials. (A) Neuroanatomy of the dorsal column–lemniscal pathway with relevant anatomical structures and corresponding evoked potentials. (B) Diagram of electrode placement and somatosensory evoked potential recording. REP, right Erb’s point; LEP, left Erb’s point; C5s, fifth cervical spinous process; C3′ and C4′, scalp electrodes placed between 10–20 C3/4 and P3/4 locations; Fz, frontal electrode (for reference if needed); +, anode; −, cathode. Four-channel recording. Montage can vary, but typically consists of channel 1: Cc′ (C′ electrode contralateral to stim)–Ci′ (C′ electrode ipsilateral to stim); channel 2: Ci′ (C′ electrode ipsilateral to stim)–reference electrode (which can be frontal electrode, mastoid electrode, or Erb’s point electrode contralateral to stim); channel 3: C5s (spinal electrode C5 vertebrae)–reference electrode (similar to previous); and channel 4: iEP (Erb’s point electrode ipsilateral to stim)-reference electrode (similar to previous). (C) Methods/requirements for somatosensory evoked potential performance in post-arrest patients. NMBA, neuromuscular blocking agent. Several societies have published guidelines for the performance and reporting of all types of evoked potentials, including somatosensory, auditory, and visual.7–9 For upper extremity SSEPs, recording electrodes are placed over the brachial plexus bilaterally [Erb’s point— left Erb’s point (LEP) and right Erb’s point (REP)] and the spinal cord at the C5 spinous process (C5s) bilaterally on the scalp over the somatosensory cortex (midway between P3/4 and C3/4 electrode positions in accordance with the international 10–20 system; C3′ and C4′ locations), in addition to another reference and ground electrode (Figure 1). Cup or disc electrodes should be used, and inter-electrode impedances should be less than 5000 ohms. Stimulating electrodes are most often placed over the median nerves with the cathode 2 cm proximal to the wrist crease and the anode 2 cm distal from the cathode. The selected nerves are stimulated separately in each arm until the motor threshold (threshold for eliciting a visible motor twitch) is identified. The stimulus intensity should then be increased by 10–20%. To optimize the signal-to-noise ratio, it is recommended that a neuromuscular blocking agent (NMBA) be administered. Each nerve should undergo at least two to three trials, consisting of 500–2000 stimulations with 100–300 μs duration and rate between 4 and 7/s. The SSEPs are recorded using a filter bandpass between 10 Hz (or as high as 30 Hz) and 3000 Hz. The sensitivity should be optimized for each recording channel. The sweep is usually set at 10 ms/division, with a duration of at least 40–50 ms to ensure all early potentials are captured. Differential amplifiers are used to amplify signals of interest, with common mode rejection of artefacts. The recorded tracings comprise an average of responses produced by each stimulation within a trial and ideally reveal consistent potentials between trials. The tracings are displayed in at least four channels to ensure peripheral, spinal, subcortical, and cortical activities are recorded. Two electrodes are compared to each other within a channel (Figure 1). Different montages (combinations of specific channels) may be utilized to ensure all potentials are captured. A typical montage is displayed in Figure 1 comprised of: Channel 4: Erb’s point ipsilateral to the stimulated nerve compared to a reference electrode (iEP–Ref) that captures peripheral potentials. Channel 3: C5 spinal electrode compared to a reference electrode (C5s–Ref) that records spinal potentials. Channel 2: cortical electrode ipsilateral to the nerve stimulated (C3′ or C4′) compared to a reference electrode (Ci′–Ref) that is important for capturing far field subcortical potentials. Channel 1: cortical electrode contralateral to the nerve stimulated (C3′ or C4′) compared to the cortical electrode ipsilateral to the nerve stimulated (Cc′–Ci′) that records cortical potentials. Different electrodes can be utilized as reference electrodes within each montage including a frontal electrode (Fz), mastoid electrode, or the contralateral Erb’s point electrode. Each reference has unique advantages and disadvantages. Since the interpreting physician is usually not present at the bedside, the role of the technologist is crucial in obtaining accurate and reliable SSEP results. Training and accreditation by an examining board, in addition to clinical experience, are very important.9,10 Somatosensory evoked potential waveforms are defined by a N or a P indicating the polarity of the response (negative or positive) followed by a numerical post-stimulus latency in milliseconds (Figure 1). Standard responses are based on waveforms recorded in healthy subjects. It is essential that laboratories run a group of at least 10 healthy subjects under the usual recording conditions for the evoked potentials being evaluated. The data obtained should be compared to normative data available in the literature, and if no significant difference exists in mean values or standard deviations, the laboratory can use the published literature to provide age- and gender-specific normative data.9 If children are being tested, the laboratory must ensure sufficient data are available to provide age- and gender-matched normative values, as during infancy and childhood, evoked potentials change rapidly.9 In healthy subjects, the first potential recorded in channel 4 (iEP-Ref) is N9 (Erb’s potential) from the brachial plexus, followed thereafter by N13 that is recorded in channel 3 (C5s-Ref) from the spinal cord (Figure 1). Channel 2 (Ci′-Ref) is important for simultaneous recording of far-field potentials including P14 and N18 from subcortical structures including the lemniscal pathways that can be misinterpreted as N20 potentials (Figure 1). Channel 1 (Cc′-Ci′) records N20 potentials that are thought to be generated by thalamocortical radiations or the cerebral cortex (Figure 1). Later peaks that occur in the range of 40–70 ms, known as middle latency potentials, are generated by cortical relays. While training, certification, and licensing may vary between countries, interpreting physicians should have appropriate training and knowledge pertaining to the performance, limitations, and interpretation of evoked potentials. It is also imperative that interpreting physicians appreciate the impact that test results may have on patients and their families. Great caution and attention to report wording is advised when interpreting post-arrest SSEPs. Minimum requirements for interpreting physicians have been previously published.9,10 When utilized for post-arrest neuroprognostication, SSEP findings that are suggestive of a poor prognosis, are defined as bilaterally absent cortical N20 potentials despite normal peripheral and spinal conduction (Figure 2). Absent N20 potentials should always be confirmed in two separate channels that record cortical potentials (Figure 2). Occasionally, with severe hypoxic ischaemic brain injury, subcortical P14 and N18 responses may also be absent, in addition to absent N20 potentials. Somatosensory evoked potentials with (A) and without (B) cortical N20 potentials. (A) Left median nerve somatosensory evoked potential showing consistent peripheral (N9/Erb), spinal (N13), subcortical (P14/N18), and cortical (N20) potentials between the two trials. (B) Right median nerve somatosensory evoked potential from a different patient showing consistent peripheral (N9/Erb), spinal (N13), and subcortical (P14/N18) potentials, but absence of the cortical N20 potentials in both trials. Absent N20 potentials should always be confirmed in two separate channels that record cortical potentials (e.g. C3′–C4′ and C3′–Fz both confirm absent left N20 cortical potentials from right median nerve stimulation). A review of the literature was completed including all studies with adult (≥18 years of age) patients that had been resuscitated from a cardiac arrest but remained comatose (defined as a Glasgow Coma Scale of ≤8 and inability to follow commands), with or without targeted temperature management (TTM—defined as cooling to 33–36°C). Properly completed and interpreted upper extremity SSEPs showing bilateral absence of N20 potentials were compared to those showing bilaterally present N20 potentials. The outcome of interest was an unfavourable neurologic recovery at a minimum of 30 days following return of spontaneous circulation (ROSC) or hospital discharge. For studies reporting multiple outcome assessment dates, the latest assessment up to 12 months was used. Poor prognosis has been defined a variety of ways in the literature, most often as a Cerebral Performance Category (CPC) of 3–5 (severe disability, coma/vegetative, and brain death), but also CPC 4–5 in earlier literature, and Glasgow Outcome Scores of 1–3 (death, neurovegetative state, and severe disability). Additionally, one study reported poor prognosis as modified Rankin score (mRS) 4–6 (moderate disability, severe disability, and death) and, in another study, just mortality was reported. The accuracy of SSEPs in predicting a poor prognosis based on bilaterally absent N20 potentials is shown in Table 1. Bilaterally absent N20 potentials suggesting dysfunction of the thalamocortical connections predicts a poor neurologic prognosis (defined as a CPC 3–5) at hospital discharge up to 12 months with specificity of 97.6% [95% confidence interval (CI) 95.7, 98.6] and false positive rate of 2.4% (95% CI 1.4, 4.3) in patients treated with TTM. In patients managed without TTM, the specificity and false positive rate are 96.3% (95% CI 88.9, 98.8) and 3.7% (95% CI 1.2, 11.1) respectively (Table 1). When patients treated with or without TTM are combined, bilateral absence of N20 potentials predicts a poor neurologic outcome at hospital discharge up to 12 months with specificity of 95.1% (95% CI 87.7, 98.2) and false positive rate of 2.7% (95% CI 1.6, 4.4). The preservation of bilateral N20 potentials does not imply a favourable outcome after cardiac arrest as sensitivities for the prediction of poor outcome varied between 46.1% (95% CI 40.7, 51.7) and 47.7% (95% CI 37.5, 58.1) for patients treated with and without TTM, respectively (Table 1). The sensitivity of bilateral N20 potentials is 46.5% (95% CI 41.7, 51.3), regardless of the provision of TTM. Studies categorizing good vs. poor prognosis differently either with the CPC (4–5, poor prognosis, vs. 1–3, good prognosis) or other scores are also presented in Table 1 (see Supplementary material online, Appendix for reference list of all included studies). Summary of literature for post-arrest somatosensory evoked potentials GCS, Glasgow Coma Scale; OHCA, out-of-hospital cardiac arrest; IHCA, in-hospital cardiac arrest; TTM, target temperature management; CI, confidence interval; FPR, false positive rate; CPC, Cerebral Performance Category; mRS, modified Rankin score; SSEPs, somatosensory evoked potentials. TTM refers to any targeted temperature between 33 and 36°C. Given similarities between score categories, studies reporting outcomes via the Glasgow Outcome Score were combined with those reporting outcomes via the Cerebral Performance Category. Other components of the SSEPs can potentially be utilized to prognosticate post-arrest patients as discussed in a recent review.11 Components such as middle latency (40–70 ms) potentials,12–14 N20 amplitudes,15–17 and N20–P25 absence18 and amplitude15 demonstrate promising results but remain under investigation and are not reliably obtainable at all institutions. Recent studies have demonstrated that when unilaterally absent N20 potentials are considered a positive test (suggestive of a poor prognosis), they remain equally specific as bilaterally absent N20 potentials.19,20 One major limitation of the literature is that of positive verification bias, as many studies utilize SSEP for decisions regarding WLSM. However, in a select number of studies where WLSM was either not performed or decisions were not made based on SSEP results, SSEPs maintained their high accuracy and precision for predicting a poor neurologic outcome.20–22 Many false positives in the prediction of poor outcome (where patients reportedly had favourable outcomes despite bilaterally absent N20 responses) within the literature have been subsequently disputed.23 A recent review outlines several important considerations pertaining to SSEPs including: Patients must be selected carefully considering the potential for false positives. For example, patients with ischaemic stroke or intracerebral haemorrhage, in addition to their cardiac arrest, may have false positive results, which was the case in the manuscript from Young et al.24 Patients with traumatic brain injury may lack N20 responses, but have been shown in the literature to have a relatively more favourable prognosis than those with the same pattern post-arrest as 10% may regain awareness when cerebral swelling and haemorrhage resolve.25 Extra-axial haematomas, including both epidural and subdural haematomas, may produce false positives by impairing signal conduction and detection of N20 potentials. Patients who suffer cardiac arrest secondary to hypoxemia in the setting of hanging may have associated spinal cord injury.26 If SSEPs are to be performed in these patients, one must ensure Erb’s and cervical potentials are confirmed prior to concluding that N20 potentials are absent. When performing SSEPs, rigorous technique is as many false positives can from electrode sweep and stimulation intensity or nerve or a combination of positive results in two studies have been of When interpreting SSEPs, should be including of peripheral and spinal potentials prior to concluding N20 potentials are absent. The absence of cortical N20 potentials should always be confirmed in at least two channels using different montages (Figure 2). As with other caution should be maintained during If any one should on reporting an study, the potential of a positive test absent in neuroimaging, the use of all evoked potentials auditory, and has over SSEPs have a role within the intensive care for the of comatose post-arrest patients. are and can be performed at the However, physicians must be of special considerations that may the performance and interpretation of SSEPs in post-arrest patients. to SSEP compared to other neuroprognostication may be an for A of of the of of use SSEPs for post-arrest This was by both and of the as of SSEPs were one of the three to prognosis after cardiac international consisting of from the that of had to SSEPs, compared to and were the test less available to A recent by et suggests that compared to other SSEPs are less available In this study, of SSEPs were both available and at their One of SSEPs were not available and over SSEPs were available, but that there were in obtaining when This was different from such as and which were reported as available and to and of Patients in SSEPs are most to be are those that remain comatose post-arrest with no to stimulation motor score If a patient were to or to one could that they are the and N20 responses should be It is those patients who not or that may have absent N20 responses and in SSEP testing may be Several studies have also that in patients with of or N20 potentials are present and SSEPs may be to Patients with and with or without or or absent may from SSEP testing in the of multimodal Given the and of until more and are available, this is not recommended as a for when SSEPs should or should not be patients often have and associated the median nerve which may electrode If the can be and electrodes placed to the the ipsilateral median nerve can be stimulated the ipsilateral nerve can be In the experience, both are should the be it is that the performing has normative values for evoked potentials. Several may the and of N20 potentials. One limitation of SSEP interpretation is as in several In one study, the of was to emphasizing the of One that the signal-to-noise can be is by the number of stimuli during each To that may potentials, electrical should be when In it is recommended that a be for the test as another of from or by nerve In patients by a significant of the motor threshold may be than and must be prior to of a should also be made of to ensure are to a may potential The temperature a must be recorded during the performance of the This may be relevant in patients TTM, if to While it is that SSEPs are less by and compared to or the neurologic examination, these can cortical potential and This is a of of and also a in the between and is that cortical potentials are far more than peripheral, spinal, or subcortical and all have on the and of cortical potentials. can cortical potential up to 10% and the may have an more cortical potential and by as as has also been reported to and of cortical potentials. of absent cortical responses in patients with traumatic brain injury while on but with favourable neurologic have been such as and have a on cortical responses when at but at (e.g. up to an in cortical potential has been Several studies have the of performing SSEPs within post-arrest and during TTM as in Table 1. on review of the literature presented SSEPs are specific at predicting a poor prognosis of they were performed within or post-arrest regardless of TTM (Table 2). However, to the potential of TTM, in addition to and that are often used in during the first combined with other such as as a of patient the potential for a false positive during this a significant guidelines SSEPs be performed from and of evoked potentials based on of CI, confidence interval; FPR, false positive of predicting Cerebral Performance Category 3–5 vs. regardless of with TTM. Somatosensory evoked potentials, when available, are an accurate and precise test for predicting a poor neurologic prognosis following cardiac Bilaterally absent cortical N20 potentials are specific for a poor prognosis, while the of N20 potentials does not imply a favourable outcome to poor sensitivity of the other components of SSEPs that can be utilized to prognosticate post-arrest patients is and interpreting these must their considerations, limitations, and the impact the results may have on post-arrest patients and their families. Supplementary material is available at to the and of the review and interpretation of and the manuscript for and the of the to the of the review and the manuscript for and the of the to the and interpretation of and the manuscript for and the of the to the and interpretation of and the manuscript for and the of the to the and interpretation of and the manuscript for and the of the to the and interpretation of and the manuscript for and the of the to the and of the review and interpretation of and the manuscript for and the of the This was not The data that the findings of this review are available from the corresponding

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.