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Therapeutic hypothermia does not diminish the vital and necessary role of SSEP in predicting unfavorable outcome in anoxic-ischemic coma
Clinical Neurology and Neurosurgery 126 (2014) 205–209
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Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Therapeutic hypothermia does not diminish the vital and necessary role of SSEP in predicting unfavorable outcome in anoxic-ischemic coma Ted L. Rothstein ∗ Department of Neurology, George Washington University, Washington DC, USA
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Article history: Received 17 January 2014 Received in revised form 20 August 2014 Accepted 26 August 2014 Available online 3 September 2014 Keywords: Anoxic-ischemic coma Cardio-pulmonary arrest Somatosensory evoked potentials Therapeutic hypothermia Outcome prediction
a b s t r a c t Rational medical management of patients who remain comatose following cardio-pulmonary resuscitation (CPR) due to anoxic-ischemic encephalopathy depends upon the early identification of those with a hopeless prognosis – regardless of how aggressively they are managed. Conversely, it is mandatory that we recognize those patients with the potential to recover in order to institute aggressive therapeutic measures. The bilateral absence of the N20 Cortical Somatosensory Evoked Potential has been identified as the most reliable predictor of an unfavorable prognosis in normothermic patients. Two randomized trials have determined that mild therapeutic hypothermia (TH) delivered immediately after CPR improves neurologic outcomes. TH has now become the standard of care in the management of patients with cardio-pulmonary arrest. Eight studies targeting patients who were comatose following CPR, treated with TH, and using SSEP as an outcome predictor are reviewed. There is only one patient treated with TH who appears to have fully recovered following cardiac arrest who was initially found to have bilateral absent cortical potentials. This opinion paper will address whether the criteria that placed reliance upon SSEP to predict unfavorable outcome in post cardio-pulmonary arrest patients after receiving TH, still apply. © 2014 Elsevier B.V. All rights reserved.
1. Introduction
3. Cerebral anoxia
Every year about four hundred fifty thousand Americans suffer from anoxic-ischemic brain injury due to cardio-pulmonary arrest [1]. These patients account for about half the deaths due to cardiovascular disease [2]. Modern resuscitation techniques applied directly to the victims of cardio-pulmonary arrest including bystander cardiac resuscitation, automatic external defibrillators and the use of therapeutic hypothermia (TH) have resulted in increased rates of survival [2–7]. Regrettably, less than 1/3 of the survivors of cardio-pulmonary arrest awaken within the first week [8]. Among those who do awaken, many are left with persistent motor or cognitive deficits [8,9].
When cerebral anoxia occurs after cardio-pulmonary arrest, the duration and severity of the interruption of cerebral blood flow determines the potential for recovery. These factors are usually unknown, or may be difficult to estimate according to the circumstances in any given patient. The extent of brain injury is usually evaluated indirectly by performing a neurological examination and assessing cortical and brainstem function along with recovery over time. The degree of recovery depends upon the localization and extent of permanently damaged brain structures. Cerebral neurons cannot tolerate complete normothermic ischemic anoxia for more than 5 min [10,11]. After this period of time the cerebral cortex and brainstem are destroyed, and brain death ensues. It is more difficult to predict outcome for patients with severe anoxic-ischemic brain damage than to diagnose brain death, which is based on widely accepted criteria [12,13]. Relying on physical examination findings alone, only 1.5% of patients in coma after cardio-pulmonary arrest present with brain death [14]. The adult cerebral cortex is more vulnerable to the effects of anoxia than the more primitive brainstem parenchyma [11,15]. If the brainstem is damaged by an anoxic-ischemic insult, the
2. Methods MEDLINE, EMBASE and Cochrane Library database were searched for outcome studies of post cardiac arrest patients who were treated with TH and in whom SSEP results were available. ∗ Tel.: +1 2027257985; fax: +1 2027412721. E-mail address: [email protected] http://dx.doi.org/10.1016/j.clineuro.2014.08.031 0303-8467/© 2014 Elsevier B.V. All rights reserved.
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Fig. 1. Technique used in recording median nerve somatosensory evoked potential (SSEP), which defines Erb’s point (EP), the N13 and N18 peak, the N13–N20 interpeak latency, and the N20/P23 cortical evoked potential. N13 is the cervical potential recorded referentially from the dorsal neck reflecting post synaptic activity in the cervical cord. N 18 is subcortically generated far field potential reflecting activity from multiple sources in the brainstem [66]. More recent evidence is that the N20/P23 potential recorded from the contralateral parietal cortex originates in the in the sensory cortex or subadjacent thalamocortical projections [67]. Figure adapted with permission from Ref. [17].
cerebral cortex will have sustained an even worse injury and may be completely destroyed [11,14]. It is not unusual for patients to sustain a critical measure of anoxia sufficient to damage or destroy the cerebral cortex while preserving some or all brainstem function. Therefore, those prognostic outcome scales that rely on preserved brainstem function such as the Glasgow Coma Scale and FOUR score scales may be seriously flawed in predicting the extent to which the cerebral cortex has been damaged [16–19]. There remains an urgent need to develop reliable criteria for the early prediction of outcome in comatose patients treated with TH following cardio-pulmonary arrest. An essential early step is to identify those patients whose prognosis is hopeless regardless of how aggressively they are managed. Conversely, it is critical for physicians to recognize those patients with the potential to recover in order to institute aggressive therapeutic measures. Accurate early prognostication allows physicians to direct resources to those who have the potential to benefit, counsel family members with realistic expectations, and allow for the early identification of potential organ donors. 4. Therapeutic hypothermia TH has been used as a means of protecting the brain from anoxicischemic injury as in cardiac surgery with cardiopulmonary bypass. In 2002, two randomized trials utilizing TH were performed on post cardiac arrest patients, lowering their body temperature to 32–34 ◦ C. TH resulted in significant improvement in survival [5,6]. To prevent a single unfavorable neurologic outcome, the need to treat with TH was only 6 patients [7]. Moreover, many of those randomized to the TH group made significant neurologic recovery. The mechanism whereby TH produces benefit is not established, but may reduce cerebral oxygen requirements, prevent free-radical injury and cell membrane damage, or inhibit the release of damaging neurotransmitters. TH is now recommended as the standard of care in the management of all patients with out of hospital cardiac arrest [20]. Practice parameters for predicting outcome after cardiac arrest were developed by the Quality Standards Subcommittee of the American Academy of Neurology and were based on evidence-based reviews of studies between 1966 and 2006 [21].
Consideration was given to a number of clinical and electrophysiologic variables. SSEP was obtained by repetitively stimulating median nerves at both wrists and recording the initial cortical response at about 20 ms (see Fig. 1). The bilateral absence of the N20 cortical response was used to reliably predict unfavorable outcome in normothermic patients. The procedure has not been revised to consider the effect that TH might have modified outcome prediction. At issue, then, is whether the rules for relying upon SSEP to predict unfavorable outcome in post cardio-pulmonary arrest patients who have received TH still apply. 5. Electrophysiologic studies The EEG has been the key test for evaluating coma over the past 30 years [19]. However, SSEP has proved to be more reliable than EEG in predicting outcome [16,17,22–24]. Zandbergen et al. reviewed the relevant literature to assess the prognostic value of early neurologic and electrophysiologic studies in anoxic coma [25]. They compared the results of clinical findings, EEG, and SSEP in 563 patients, and concluded that absent cortical evoked potentials (CEP) were the most discriminating predictor of unfavorable outcome. Combined Meta-analysis of 801 patients with bilateral absence of the N20 produced no false positives [25–27]. It has been established that the EEG becomes isoelectric during circulatory arrest which can persist for several hours after restoration of the cerebral circulation [28]. Further, the author reported upon a post arrest patient with an isoelectric EEG but normal SSEP, both obtained 5 h after arrest and resuscitation, who achieved full neurologic recovery after 4 days [23]. Another study described two patients with burst suppression patterns on EEG who recovered with minimal or no neurologic sequelae [27]. Two additional survivors with burst suppression pattern on EEG occurred in cardiac arrest patients treated with TH [29,30]. SSEP is a relatively simple, convenient, non-invasive, and inexpensive bedside technique for assessing the integrity of transmission within the central nervous system, and is commonly used to assess both brainstem and cortical function (Fig. 1). SSEP, and the N20 response that is evoked 20 ms after stimulation of the median nerve at the wrist has been established as the most reliable
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Fig. 2. Somatosensory evoked potentials recorded from the scalp and neck of a normal subject after median nerve stimulation at the wrist (A), and from a 78-year-old male with absent cortical responses after cardiac arrest who died without awakening (B). In B there is a preservation of the brachial plexus (EP) and cervical medullary activity (N13) but N20/P23 is absent (B) in the Fz referenced contralateral cortex (Fz-Cc) as recorded in channel 2. In addition to pseudolaminar necrosis of the cortex, there was severe neuronal loss in the thalamus at necropsy in patient B. Figure adapted with permission from Ref. [68].
predictor of poor outcome in normothermic patients with anoxicischemic encephalopathy [21] (Fig. 2). SSEP provide information limited to the somatosensory pathways and primary sensory cortex, and must be interpreted with caution. Patients with focal brain disease involving the sensory pathways may have SSEP results that are misleading. For example, the author has found bilateral absence of N20 in patients with multiple sclerosis, brainstem hemorrhage and basilar artery occlusion causing bilateral thalamic infarcts. Metabolic factors can also distort the interpretation of SSEP. Kaplan described a patient found pulseless as a result of a heroin overdose, with bilateral absence of N20, who eventually regained cortical potentials and recovered [31]. Numerous studies confirm that the absence of short-latency N20 cortical potentials in normothermic patients are associated with a uniformly unfavorable prognosis [16,17,32–46]. Robinson et al. performed a meta-analysis of 336 normothermic patients with absent cortical SSEP after day 1 and all died or became vegetative [44]. However, Young et al. identified a single patient with bilateral absence of N20 who recovered [47]. Young attributed this unique case to watershed ischemia with selective damage (Young GB, personal communication, 2010). However, in a subsequent paper, Young [48] makes no mention of this case, and identifies the lack of a N20 response as “the most accurate predictor of poor outcome in patients with anoxic-ischemic encephalopathy”. There is second case reported in which a 16-year-old student had a cardiac arrest while playing soccer and received CPR within 3 min. Hypothermia was not used. The N20 response was absent bilaterally at 72 h and on day 9. He experienced constant improvement in neurologic function and eventually recovered with residual dysarthria and impaired fine motor control [49]. The N20 peak represents the earliest cortical response, and its delay or loss signifies an interruption of the connecting pathway between the cervicomedullary junction and the sensory cortex [50]. A neuropathologic study of 7 comatose patients with
bilateral absent N20 revealed diffuse cortical necrosis in each instance, suggesting there were no functioning neurons left to respond to an afferent stimulus [16,17]. Zanderbergen et al. determined that outcome cannot be reliably predicted with long latency potentials which had a false positive rate of 4–15% [51]. Does the bilateral absence of the N20 peak in TH patients have the same significance as in almost all normothermic patients, i.e. does it reliably predict an unfavorable outcome leading to death or persistent vegetative state? A question has been raised about the uncertain effect that TH has on the predictive value of the usual assessments including SSEP [52]. 6. Results SSEP in post cardio-pulmonary arrest patients treated with TH have now been reported in 8 recent studies (Table 1) [53–60]. Bisschops et al. found no survivors among 18 post anoxic patients with absent SSEP treated with TH [53]. Bowes reported 10 patients with no cortical potentials who did not survive [54]. Cronberg studied 14 patients with similar outcome when the N20 was bilaterally absent [55]. Fugate had 2 patients with absent cortical potentials who did not survive [56]. Rossetti et al. studied 3 clinical variables, EEG Table 1 Patients treated with hypothermia after cardiac arrest. References
N
# SEP
Bilateral absent SEP
Survivor
Bisschops [53] Bouwes [54] Cronberg [55] Fugate [56] Leithner [60] Rossetti [57] Samaniego [58] Tiainen [59] Total
46 77 111 103 112 111 53 60 673
38 75 30 14 36 44 44 30 311
18 10 14 2 36 33 24 3 140
0 0 0 0 1 0 0 0 1
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T.L. Rothstein / Clinical Neurology and Neurosurgery 126 (2014) 205–209
and SSEP in 111 post arrest patients, and found that the bilateral absence of N20 on SSEP in 33 patients was significantly associated with death at hospital discharge [57]. Samaniego reported upon 24 additional patients with no cortical potentials and no survivors [58]. Tiernan et al. described 3 patients following cardiac arrest treated with TH with absent N20 responses, and 8 normothermic controls with absent N20 all of whom died without awakening [59]. Leithner et al. assessed retrospectively SSEP in 112 patients treated with hypothermia and identified 36 with bilateral absent N20, 35 of whom died without awakening or entered a persistent vegetative state [60]. However, a single patient with bilateral absence of N20 at day 3 eventually regained consciousness and recovered normal cognitive function. The authors drew the conclusion that bilateral absence of N20 as an outcome predictor in hypothermic patients needs to be re-evaluated and not used as a decision to stop therapy. There is sparse data on their sole survivor. The patient is a 43-year-old man with alcoholism who developed sepsis and had asystole for 10 min. SSEP was not repeated until 18 months later, when the N20 responses were intact. Neuroimaging studies were not done [60–62]. 7. Discussion Can Leithner and colleagues be justified in refuting the role of SSEP as a negative outcome predictor on the basis of a single outlier patient? Could there have been technical factors which might have contributed to this case? Could the patient have had metabolic confounders or “watershed ischemia” which resulted in the elimination of N20? Other factors such as brain trauma with hemorrhage could abolish evoked responses which have been reported to eventually result in clinical and electrical recovery in 10.2% of patients with severe head injury [17]. Neuroimaging, which could have brought clarity to the diagnosis, is not described and presumably not done in Leithner’s report, nor in their subsequent correspondence under “Reply from the Authors” [60,61]. Leithner’s article has been cited as a source for concern over the reliability of SSEP as an outcome predictor [24,30,52]. Blondin and Greer went on to assert that in the setting of TH, “owing to this isolated case of recovery, a bilateral absent N20 at 72 h may not predict poor prognosis with absolute certainty” [52]. 8. Conclusion Clinical and neurologic evaluation alone of patients who remain comatose after cardio-pulmonary arrest does not reliably establish neurologic outcome. Accurate prognostication has been supplemented and enhanced by the use of SSEP. The bilateral absence of N20 cortical potentials in normothermic patients has been used to identify those who will not survive anoxic-ischemic coma no matter how aggressively they are managed. One of 8 recent studies in which therapeutic hypothermia has been used to improve outcome raises concern that SSEP may no longer be unfailingly predictive of an unfavorable outcome. There are now 3 case reports of recovery following cardiopulmonary arrest when SSEP has documented the bilateral absence of N20. These reports by Young et al. provide the basis for the false positive rate of 0.7% (CI 95%) for poor outcome using the absence of N20 as a predictor [47,49,60,61]. However, Young makes no reference to his unique case in subsequent reports in which he identifies the loss of N20 as the most useful predictor of outcome [48,64]. Leithner’s case has not been studied in sufficient detail to be credible. In conclusion, the reliability of SSEP in patients treated with therapeutic hypothermia (TH) has been shown to be comparable to those in patients who have not received treatment with TH [63,65].
SSEP remains the most valuable, and reliable non-invasive bedside test for determining unfavorable neurologic prognosis in patients who are comatose following cardio-pulmonary arrest. SSEP should continue to be the cornerstone of an algorithm, which should also include cEEG findings such as burst suppression or isoelectricity, and physical findings at defined points of time after resuscitation, to identify those patients with a hopeless prognosis who will not respond to aggressive therapy no matter how skillfully applied. Disclosure The author reports no conflicts of interest. References [1] Callans DJ. Out-of-hospital cardiac arrest – the solution is shocking. N Engl J Med 2004;351:632–4. [2] Hicks SD, DeFranco DB, Calloway CW. Hypothermia during reperfusion after asphyxial cardiac arrest improves functional recovery and selectively alters stress-induced protein expression. J Cereb Blood Flow Metab 2000;20:520–30. [3] Thompson RG, Hallstrom AP, Cobb LA. Bystander-initiated cardiopulmonary resuscitation in the management of ventricular fibrillation. Ann Intern Med 1979;90:737–40. [4] Safar P, Kochanek P. Therapeutic hypothermia after cardiac arrest. N Engl J Med 2002;346:612–3. [5] Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, et al. Treatment of comatose survivors of out of hospital cardiac arrest with induced hypothermia. N Engl J Med 2002;346:557–63. [6] The Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002;346:549–56. [7] Sterz F, Holzer M, Roine R. Hypothermia after cardiac arrest: a treatment that works. Curr Opin Crit Care 2003;9(3):205–10. [8] Longstreth Jr WT, Diehr P, Inui TS. Prediction of awakening after out-of-hospital cardiac arrest. N Engl J Med 1983;308:1378–82. [9] Curfman GD. Hypothermia to protect the brain. N Engl J Med 2002;346:546. [10] Heymans C. Survival and revival of nervous tissue after prolonged cerebral ischemia. Physiol Rev 1950;30:375–92. [11] Mullie A, van Hoeyweghen R, Quets A. Influence of time intervals on outcome of CPR. The Cerebral Resuscitation Study Group. Resuscitation 1989;17(Suppl.):S23–33. [12] Plum F, Posner JB. Prognosis in coma. In: Plum F, Posner JB, editors. The diagnosis of stupor and coma. Contemporary neurology series. Philadelphia: FA Davis; 1982. p. 846–69. [13] Bernat JL. A defense of the whole-brain concept of death. Hastings Cent Rep 1998;28:14–23. [14] Longstreth Jr WT. Neurological complications of cardiac arrest. In: Aminoff MJ, editor. Neurology and general medicine. New York: Churchill Livingstone; 1994. p. 166–82. [15] Brierly JB. Cerebral hypoxia. In: Blackwood W, Corsellis JAN, editors. Greenfield’s neuropathology. Edward Arnold: Edinburgh; 1976. p. 43–85. [16] Rothstein TL, Thomas EM, Sumi SM. Predicting outcome in hypoxic-ischemic coma. A prospective clinical and electrophysiologic study. Electroencephalogr Clin Neurophysiol 1991;79:101–7. [17] Rothstein TL. The role of evoked potentials in anoxic-ischemic coma and severe brain trauma. J Clin Neurophysiol 2000;17:486–97. [18] Wijdicks EF, Bamlet WR, Maramatton BV, Manno EM, McClelland RL. Validation of a new coma scale: the FOUR score. Ann Neurol 2005;58:585–93. [19] Murthy TVSP. A new score to valicate coma in emergency department-FOUR score. Indian J Neurotrauma 2009;6:59–61. [20] American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 2005;112(IV):1–203. [21] Wijdicks EFM, Hijdra A, Young GB, Bassetti CL, Wiebe S. Practice parameter: prediction of outcome in comatose survivors after cardiopulmonary resuscitation (an evidence-based review). Neurology 2006;67:203–10. [22] Kaplan PW. Electrophysiological prognostication and brain injury from cardiac arrest. Sem Neurol 2006;26:403–12. [23] Rothstein TL. Recovery from near death following cerebral anoxia: a case report demonstrating superiority of median somatosensory evoked potentials over EEG in predicting a favorable outcome after cardiopulmonary resuscitation. Resuscitation 2004;60:335–41. [24] van Putten MJAM. The N20 in post-anoxic coma: are you listening? Clin Neurophysiol 2012;123:1460–4. [25] Zandbergen EGJ, deHaan RJ, Stoutenbeek CP, Koelman CP, Johannes HTM, Hijdra A. Systematic review of early prediction of poor outcome in anoxic-ischemic coma. Lancet 1998;352:1808–12. [26] Gendo A, Kramer L, Hafner M, Funk G-C, Zauner C, Sterz F, et al. Timedependency of sensory evoked potentials in comatose cardiac arrest survivors. Intensive Care Med 2001;27:1305–11. [27] Chen R, Bolton CF, Young GB. Prediction of outcome in patients with anoxic coma: a clinical and electrophysiologic study. Crit Care Med 1996;24:672–5.
T.L. Rothstein / Clinical Neurology and Neurosurgery 126 (2014) 205–209 ´ ´ [28] Jørgenson EO, Malchow-Møller A. Natural history of global and critical brain ischemia. Resuscitation 1981;9:133–8. [29] Crepeau AZ, Rabinstein AA, Fugate JE, Mandrekar J, Wijdicks EF, White R, et al. Continuous EEG in therapeutic hypothermia after cardiac arrest: prognostic and clinical value. Neurology 2013;80(4):339–44. [30] Lucas JM, Cocchi MN, Salciccioli J, Stanbridge JA, Geocardin R, Romergryko GH, et al. Neurologic recovery after therapeutic hypothermia in patients with postcardiac arrest. Resuscitation 2012;83:265–9. [31] Kaplan PW. Stupor and coma: metabolic encephalopathies. Suppl Clin Neurophysiol 2004;57:667–80. [32] Ahmed I. Use of somatosensory evoked responses in the prediction of outcome from coma. Clin Electroencephalogr 1988;19:78–86. [33] Bassetti C, Bomio F, Mathis J, Hess CW. Early prognosis in coma after cardiac arrest: a prospective clinical, electrophysiological, and biochemical study of 60 patients. J Neurol Neurosurg Psychiatry 1996;61:610–5. [34] Berek K, Jeschow M, Aichner F. The prognostication of cerebral hypoxia after out-of hospital cardiac arrest in adults. Eur Neurol 1997;37:135–45. [35] Brierly JB, Graham DI, Adams JH, Simpson JA. Neocortical death after cardiac arrest: a clinical, neurophysiological and neuropathological report of two cases. Lancet 1971;2:560–5. [36] Brunko E, Zegers de Beyl D. Prognostic value of early cortical somatosensory evoked potentials after resuscitation from cardiac arrest. Electroencephalogr Clin Neurophysiol 1987;66:15–24. [37] Cheliout–Héraut F, Durand MC, Clair B, Gajdos P, Raphaël JC. Intérêt des potentiels évoqués dans le pronostic évolutif des comas par anoxie cérébrale chez l’adulte. Neurophysiol Clin 1992;22:269–80. [38] Fischer C, Luaute J, Nemoz C. Improved prediction of awakening or nonawakening from severe anoxic coma using tree-based classification analysis. Crit Care Med 2006;34:1520–4. [39] Ganji S, Peters G, Frazier E. Somatosensory and brainstem auditory evoked potential studies in non-traumatic coma. Clin Electroencephalogr 1988;19:55–66. [40] Kano T, Shimoda O, Morioka T, Yagashita Y, Hashiguchi A. Evaluation of the central nervous function in resuscitated comatose patients by multilevel evoked potentials. Resuscitation 1992;23:235–48. [41] Madl C, Grimm G, Kramer al. Early prediction of individual outcome after cardiopulmonary resuscitation. Lancet 1993;341:855–8. [42] Marcus EM, Stone B. Short-latency median nerve somatosensory evoked potentials in coma: relationship to BAEP, etiology, age, and outcome. In: Nodar RH, Barber C, editors. Evoked potentials Vol. II. The Second International Evoked Potentials Symposium. Stoneham: Butterworth; 1984. p. 609–23. [43] Ragazzoni A, Cincotta M, Chiaramonti R. Electrophysiological early predictors of outcome in patients with anoxic coma: EEG and SEPs. Clin Neurophysiol 1999;110:S245–6. [44] Robinson LR, Micklesen PJ, Tirschwell DL, Lew HL. Predictive value of somatosensory evoked potentials for awakening from coma. Crit Care Med 2003;31:960–7. [45] Walser H, Mattle H, Keller HM, Janzer R. Early cortical median nerve somatosensory evoked potentials. Prognostic value in anoxic coma. Arch Neurol 1986;42:32–8. [46] Ying Z, Schmid UD, Schmid J, Hess CW. Motor and somatosensory evoked potentials in coma: analysis and relation to clinical status and outcome. J Neurol Neurosurg Psychiatry 1992;55:470–4. [47] Young GB, Doig G, Ragazzoni A. Anoxic-ischemic encephalopathy and electrophysiological associations with outcome. Neurocrit Care 2002;2:5–10. [48] Young GB. Neurologic prognosis after cardiac arrest. N Engl J Med 2009;361(6):605–11. [49] Bender A, Howell K, Frey M, Berlis A, Naumann M, Buheitel G. Bilateral loss of cortical SSEP responses is compatible with good outcome after cardiac arrest. J Neurol 2012;259:2481–3.
209
[50] Nuwer MR, Aminoff M, Desmedt J. IFCN recommended standards for short latency somatosensory evoked potentials. Report of an IFCN committee. International federation of clinical neurophysiology. Electroencephalogr Clin Neurophysiol 1994;9:6–11. [51] Zanderbergen EG, Koelman JH, de Haan RJ, Hijdra A. SSEPs and prognosis in post anoxic coma: only short or also long latency responses. Neurology 2006;67:583–6. [52] Blondin NA, Greer DM. Neurologic prognosis in cardiac arrest patients treated with hypothermia. Neurologist 2011;17:241–8. [53] Bisschops LLA, van Alfen N, Bons S, van der Hoeven JG, Hoedemakers CWE. Predictors of poor neurologic outcome in patients after cardiac arrest treated with hypothermia: a retrospective study. Resuscitation 2011;82: 696–701. [54] Bouwes A, Binnekade JM, Zandstra DF, Koelman JHTM, van Schaik IN, Hijdra A, et al. Somatosensory evoked potentials during mild hypothermia after cardiopulmonary resuscitation. Neurology 2009;73:1457–61. [55] Cronberg T, Lilja G, Rundgren M, Friberg H, Widdner H. Long-term neurological outcome after cardiac arrest and therapeutic hypothermia. Resuscitation 2009;80:1119–23. [56] Fugate JE, Wijdicks EF, Mandrekar J, Claassen DO, Manno EM, White RD, et al. Predictors of neurologic outcome in hypothermia after cardiac arrest. Ann Neurol 2010;68:907–14. [57] Rossetti AO, Oddo M, Logroscino F, Kaplan PW. Prognostication after cardiac arrest and hypothermia. A prospective study. Ann Neurol 2010;67: 301–7. [58] Samaniego EA, Mlynash M, Caulfield AF, Eyngorn I, Wijman CA. Sedation confounds outcome prediction in cardiac arrest survivors treated with hypothermia. Neurocrit Care 2011;15:113–9. [59] Tiainen M, Kovala TT, Takkunen OS, Roine RO. Somatosensory and brainstem auditory evoked potentials in cardiac arrest patients treated with hypothermia. Crit Care Med 2005;33:1736–40. [60] Leithner C, Ploner CJ, Hasper D, Storm C. Does hypothermia influence the predictive value of bilateral absent N20 after cardiac arrest? Neurology 2010;74:965–9. [61] Leithner C, Ploner CJ, Hasper D, Storm C. Does hypothermia influence the predictive value of bilateral absent N20 after cardiac arrest. Neurology 2010;75:575–6. [62] Rothstein TL. Does hypothermia influence the predictive value of bilateral absent N20 after cardiac arrest? Neurology 2010;75:575. [63] Wijdicks EFM, Young GB, Wang JT, Connolly J. Prognostic determination in anoxic-ischemic and traumatic encephalopathies. J Clin Neurophysiol 2004;21:379–90. [64] Young GB, Doig G, Ragazzoni A. Anoxic-ischemic encephalopathy: clinical and electrophysiological associations with outcome. Neurocrit Care 2005;2:159–64. [65] Kamps MJA, Horn J, Oddo M, Fugate JE, Storm C, Cronberg G, et al. Prognostication of neurologic outcome in cardiac arrest patients after mild therapeutic hypothermia: a meta-analysis of the current literature. Intensive Care Med 2013;39:1671–82. [66] Desmedt JE, Cheron G. Noncephalic reference recording of early SSEP to finger stimulation in adult or aging normal man: differentiation of widespread N18 and contralateral N20 from pre rolandic P22 and N30 components. Electroencephalogr Clin Neurophysiol 1981;52:533–70. [67] Vanderzant CW, Beydoun AA, Domer PA, Hood TW, Abou-Khalil BW. Polarity reversal of N20 and P23 somatosensory evoked potentials between scalp and depth recordings. Electroencephalogr Clin Neurophysiol 1991;78: 234–9. [68] Rothstein TL, Thomas EM, Sumi SM. Predicting outcome in hypxic-ischemic coma. A prospective clinical and electrophysiologic study. Electroencephalogr Clin Neurophysiol 1991;79:101–7.
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Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Therapeutic hypothermia does not diminish the vital and necessary role of SSEP in predicting unfavorable outcome in anoxic-ischemic coma Ted L. Rothstein ∗ Department of Neurology, George Washington University, Washington DC, USA
a r t i c l e
i n f o
Article history: Received 17 January 2014 Received in revised form 20 August 2014 Accepted 26 August 2014 Available online 3 September 2014 Keywords: Anoxic-ischemic coma Cardio-pulmonary arrest Somatosensory evoked potentials Therapeutic hypothermia Outcome prediction
a b s t r a c t Rational medical management of patients who remain comatose following cardio-pulmonary resuscitation (CPR) due to anoxic-ischemic encephalopathy depends upon the early identification of those with a hopeless prognosis – regardless of how aggressively they are managed. Conversely, it is mandatory that we recognize those patients with the potential to recover in order to institute aggressive therapeutic measures. The bilateral absence of the N20 Cortical Somatosensory Evoked Potential has been identified as the most reliable predictor of an unfavorable prognosis in normothermic patients. Two randomized trials have determined that mild therapeutic hypothermia (TH) delivered immediately after CPR improves neurologic outcomes. TH has now become the standard of care in the management of patients with cardio-pulmonary arrest. Eight studies targeting patients who were comatose following CPR, treated with TH, and using SSEP as an outcome predictor are reviewed. There is only one patient treated with TH who appears to have fully recovered following cardiac arrest who was initially found to have bilateral absent cortical potentials. This opinion paper will address whether the criteria that placed reliance upon SSEP to predict unfavorable outcome in post cardio-pulmonary arrest patients after receiving TH, still apply. © 2014 Elsevier B.V. All rights reserved.
1. Introduction
3. Cerebral anoxia
Every year about four hundred fifty thousand Americans suffer from anoxic-ischemic brain injury due to cardio-pulmonary arrest [1]. These patients account for about half the deaths due to cardiovascular disease [2]. Modern resuscitation techniques applied directly to the victims of cardio-pulmonary arrest including bystander cardiac resuscitation, automatic external defibrillators and the use of therapeutic hypothermia (TH) have resulted in increased rates of survival [2–7]. Regrettably, less than 1/3 of the survivors of cardio-pulmonary arrest awaken within the first week [8]. Among those who do awaken, many are left with persistent motor or cognitive deficits [8,9].
When cerebral anoxia occurs after cardio-pulmonary arrest, the duration and severity of the interruption of cerebral blood flow determines the potential for recovery. These factors are usually unknown, or may be difficult to estimate according to the circumstances in any given patient. The extent of brain injury is usually evaluated indirectly by performing a neurological examination and assessing cortical and brainstem function along with recovery over time. The degree of recovery depends upon the localization and extent of permanently damaged brain structures. Cerebral neurons cannot tolerate complete normothermic ischemic anoxia for more than 5 min [10,11]. After this period of time the cerebral cortex and brainstem are destroyed, and brain death ensues. It is more difficult to predict outcome for patients with severe anoxic-ischemic brain damage than to diagnose brain death, which is based on widely accepted criteria [12,13]. Relying on physical examination findings alone, only 1.5% of patients in coma after cardio-pulmonary arrest present with brain death [14]. The adult cerebral cortex is more vulnerable to the effects of anoxia than the more primitive brainstem parenchyma [11,15]. If the brainstem is damaged by an anoxic-ischemic insult, the
2. Methods MEDLINE, EMBASE and Cochrane Library database were searched for outcome studies of post cardiac arrest patients who were treated with TH and in whom SSEP results were available. ∗ Tel.: +1 2027257985; fax: +1 2027412721. E-mail address: [email protected] http://dx.doi.org/10.1016/j.clineuro.2014.08.031 0303-8467/© 2014 Elsevier B.V. All rights reserved.
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Fig. 1. Technique used in recording median nerve somatosensory evoked potential (SSEP), which defines Erb’s point (EP), the N13 and N18 peak, the N13–N20 interpeak latency, and the N20/P23 cortical evoked potential. N13 is the cervical potential recorded referentially from the dorsal neck reflecting post synaptic activity in the cervical cord. N 18 is subcortically generated far field potential reflecting activity from multiple sources in the brainstem [66]. More recent evidence is that the N20/P23 potential recorded from the contralateral parietal cortex originates in the in the sensory cortex or subadjacent thalamocortical projections [67]. Figure adapted with permission from Ref. [17].
cerebral cortex will have sustained an even worse injury and may be completely destroyed [11,14]. It is not unusual for patients to sustain a critical measure of anoxia sufficient to damage or destroy the cerebral cortex while preserving some or all brainstem function. Therefore, those prognostic outcome scales that rely on preserved brainstem function such as the Glasgow Coma Scale and FOUR score scales may be seriously flawed in predicting the extent to which the cerebral cortex has been damaged [16–19]. There remains an urgent need to develop reliable criteria for the early prediction of outcome in comatose patients treated with TH following cardio-pulmonary arrest. An essential early step is to identify those patients whose prognosis is hopeless regardless of how aggressively they are managed. Conversely, it is critical for physicians to recognize those patients with the potential to recover in order to institute aggressive therapeutic measures. Accurate early prognostication allows physicians to direct resources to those who have the potential to benefit, counsel family members with realistic expectations, and allow for the early identification of potential organ donors. 4. Therapeutic hypothermia TH has been used as a means of protecting the brain from anoxicischemic injury as in cardiac surgery with cardiopulmonary bypass. In 2002, two randomized trials utilizing TH were performed on post cardiac arrest patients, lowering their body temperature to 32–34 ◦ C. TH resulted in significant improvement in survival [5,6]. To prevent a single unfavorable neurologic outcome, the need to treat with TH was only 6 patients [7]. Moreover, many of those randomized to the TH group made significant neurologic recovery. The mechanism whereby TH produces benefit is not established, but may reduce cerebral oxygen requirements, prevent free-radical injury and cell membrane damage, or inhibit the release of damaging neurotransmitters. TH is now recommended as the standard of care in the management of all patients with out of hospital cardiac arrest [20]. Practice parameters for predicting outcome after cardiac arrest were developed by the Quality Standards Subcommittee of the American Academy of Neurology and were based on evidence-based reviews of studies between 1966 and 2006 [21].
Consideration was given to a number of clinical and electrophysiologic variables. SSEP was obtained by repetitively stimulating median nerves at both wrists and recording the initial cortical response at about 20 ms (see Fig. 1). The bilateral absence of the N20 cortical response was used to reliably predict unfavorable outcome in normothermic patients. The procedure has not been revised to consider the effect that TH might have modified outcome prediction. At issue, then, is whether the rules for relying upon SSEP to predict unfavorable outcome in post cardio-pulmonary arrest patients who have received TH still apply. 5. Electrophysiologic studies The EEG has been the key test for evaluating coma over the past 30 years [19]. However, SSEP has proved to be more reliable than EEG in predicting outcome [16,17,22–24]. Zandbergen et al. reviewed the relevant literature to assess the prognostic value of early neurologic and electrophysiologic studies in anoxic coma [25]. They compared the results of clinical findings, EEG, and SSEP in 563 patients, and concluded that absent cortical evoked potentials (CEP) were the most discriminating predictor of unfavorable outcome. Combined Meta-analysis of 801 patients with bilateral absence of the N20 produced no false positives [25–27]. It has been established that the EEG becomes isoelectric during circulatory arrest which can persist for several hours after restoration of the cerebral circulation [28]. Further, the author reported upon a post arrest patient with an isoelectric EEG but normal SSEP, both obtained 5 h after arrest and resuscitation, who achieved full neurologic recovery after 4 days [23]. Another study described two patients with burst suppression patterns on EEG who recovered with minimal or no neurologic sequelae [27]. Two additional survivors with burst suppression pattern on EEG occurred in cardiac arrest patients treated with TH [29,30]. SSEP is a relatively simple, convenient, non-invasive, and inexpensive bedside technique for assessing the integrity of transmission within the central nervous system, and is commonly used to assess both brainstem and cortical function (Fig. 1). SSEP, and the N20 response that is evoked 20 ms after stimulation of the median nerve at the wrist has been established as the most reliable
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Fig. 2. Somatosensory evoked potentials recorded from the scalp and neck of a normal subject after median nerve stimulation at the wrist (A), and from a 78-year-old male with absent cortical responses after cardiac arrest who died without awakening (B). In B there is a preservation of the brachial plexus (EP) and cervical medullary activity (N13) but N20/P23 is absent (B) in the Fz referenced contralateral cortex (Fz-Cc) as recorded in channel 2. In addition to pseudolaminar necrosis of the cortex, there was severe neuronal loss in the thalamus at necropsy in patient B. Figure adapted with permission from Ref. [68].
predictor of poor outcome in normothermic patients with anoxicischemic encephalopathy [21] (Fig. 2). SSEP provide information limited to the somatosensory pathways and primary sensory cortex, and must be interpreted with caution. Patients with focal brain disease involving the sensory pathways may have SSEP results that are misleading. For example, the author has found bilateral absence of N20 in patients with multiple sclerosis, brainstem hemorrhage and basilar artery occlusion causing bilateral thalamic infarcts. Metabolic factors can also distort the interpretation of SSEP. Kaplan described a patient found pulseless as a result of a heroin overdose, with bilateral absence of N20, who eventually regained cortical potentials and recovered [31]. Numerous studies confirm that the absence of short-latency N20 cortical potentials in normothermic patients are associated with a uniformly unfavorable prognosis [16,17,32–46]. Robinson et al. performed a meta-analysis of 336 normothermic patients with absent cortical SSEP after day 1 and all died or became vegetative [44]. However, Young et al. identified a single patient with bilateral absence of N20 who recovered [47]. Young attributed this unique case to watershed ischemia with selective damage (Young GB, personal communication, 2010). However, in a subsequent paper, Young [48] makes no mention of this case, and identifies the lack of a N20 response as “the most accurate predictor of poor outcome in patients with anoxic-ischemic encephalopathy”. There is second case reported in which a 16-year-old student had a cardiac arrest while playing soccer and received CPR within 3 min. Hypothermia was not used. The N20 response was absent bilaterally at 72 h and on day 9. He experienced constant improvement in neurologic function and eventually recovered with residual dysarthria and impaired fine motor control [49]. The N20 peak represents the earliest cortical response, and its delay or loss signifies an interruption of the connecting pathway between the cervicomedullary junction and the sensory cortex [50]. A neuropathologic study of 7 comatose patients with
bilateral absent N20 revealed diffuse cortical necrosis in each instance, suggesting there were no functioning neurons left to respond to an afferent stimulus [16,17]. Zanderbergen et al. determined that outcome cannot be reliably predicted with long latency potentials which had a false positive rate of 4–15% [51]. Does the bilateral absence of the N20 peak in TH patients have the same significance as in almost all normothermic patients, i.e. does it reliably predict an unfavorable outcome leading to death or persistent vegetative state? A question has been raised about the uncertain effect that TH has on the predictive value of the usual assessments including SSEP [52]. 6. Results SSEP in post cardio-pulmonary arrest patients treated with TH have now been reported in 8 recent studies (Table 1) [53–60]. Bisschops et al. found no survivors among 18 post anoxic patients with absent SSEP treated with TH [53]. Bowes reported 10 patients with no cortical potentials who did not survive [54]. Cronberg studied 14 patients with similar outcome when the N20 was bilaterally absent [55]. Fugate had 2 patients with absent cortical potentials who did not survive [56]. Rossetti et al. studied 3 clinical variables, EEG Table 1 Patients treated with hypothermia after cardiac arrest. References
N
# SEP
Bilateral absent SEP
Survivor
Bisschops [53] Bouwes [54] Cronberg [55] Fugate [56] Leithner [60] Rossetti [57] Samaniego [58] Tiainen [59] Total
46 77 111 103 112 111 53 60 673
38 75 30 14 36 44 44 30 311
18 10 14 2 36 33 24 3 140
0 0 0 0 1 0 0 0 1
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and SSEP in 111 post arrest patients, and found that the bilateral absence of N20 on SSEP in 33 patients was significantly associated with death at hospital discharge [57]. Samaniego reported upon 24 additional patients with no cortical potentials and no survivors [58]. Tiernan et al. described 3 patients following cardiac arrest treated with TH with absent N20 responses, and 8 normothermic controls with absent N20 all of whom died without awakening [59]. Leithner et al. assessed retrospectively SSEP in 112 patients treated with hypothermia and identified 36 with bilateral absent N20, 35 of whom died without awakening or entered a persistent vegetative state [60]. However, a single patient with bilateral absence of N20 at day 3 eventually regained consciousness and recovered normal cognitive function. The authors drew the conclusion that bilateral absence of N20 as an outcome predictor in hypothermic patients needs to be re-evaluated and not used as a decision to stop therapy. There is sparse data on their sole survivor. The patient is a 43-year-old man with alcoholism who developed sepsis and had asystole for 10 min. SSEP was not repeated until 18 months later, when the N20 responses were intact. Neuroimaging studies were not done [60–62]. 7. Discussion Can Leithner and colleagues be justified in refuting the role of SSEP as a negative outcome predictor on the basis of a single outlier patient? Could there have been technical factors which might have contributed to this case? Could the patient have had metabolic confounders or “watershed ischemia” which resulted in the elimination of N20? Other factors such as brain trauma with hemorrhage could abolish evoked responses which have been reported to eventually result in clinical and electrical recovery in 10.2% of patients with severe head injury [17]. Neuroimaging, which could have brought clarity to the diagnosis, is not described and presumably not done in Leithner’s report, nor in their subsequent correspondence under “Reply from the Authors” [60,61]. Leithner’s article has been cited as a source for concern over the reliability of SSEP as an outcome predictor [24,30,52]. Blondin and Greer went on to assert that in the setting of TH, “owing to this isolated case of recovery, a bilateral absent N20 at 72 h may not predict poor prognosis with absolute certainty” [52]. 8. Conclusion Clinical and neurologic evaluation alone of patients who remain comatose after cardio-pulmonary arrest does not reliably establish neurologic outcome. Accurate prognostication has been supplemented and enhanced by the use of SSEP. The bilateral absence of N20 cortical potentials in normothermic patients has been used to identify those who will not survive anoxic-ischemic coma no matter how aggressively they are managed. One of 8 recent studies in which therapeutic hypothermia has been used to improve outcome raises concern that SSEP may no longer be unfailingly predictive of an unfavorable outcome. There are now 3 case reports of recovery following cardiopulmonary arrest when SSEP has documented the bilateral absence of N20. These reports by Young et al. provide the basis for the false positive rate of 0.7% (CI 95%) for poor outcome using the absence of N20 as a predictor [47,49,60,61]. However, Young makes no reference to his unique case in subsequent reports in which he identifies the loss of N20 as the most useful predictor of outcome [48,64]. Leithner’s case has not been studied in sufficient detail to be credible. In conclusion, the reliability of SSEP in patients treated with therapeutic hypothermia (TH) has been shown to be comparable to those in patients who have not received treatment with TH [63,65].
SSEP remains the most valuable, and reliable non-invasive bedside test for determining unfavorable neurologic prognosis in patients who are comatose following cardio-pulmonary arrest. SSEP should continue to be the cornerstone of an algorithm, which should also include cEEG findings such as burst suppression or isoelectricity, and physical findings at defined points of time after resuscitation, to identify those patients with a hopeless prognosis who will not respond to aggressive therapy no matter how skillfully applied. Disclosure The author reports no conflicts of interest. References [1] Callans DJ. Out-of-hospital cardiac arrest – the solution is shocking. N Engl J Med 2004;351:632–4. [2] Hicks SD, DeFranco DB, Calloway CW. Hypothermia during reperfusion after asphyxial cardiac arrest improves functional recovery and selectively alters stress-induced protein expression. J Cereb Blood Flow Metab 2000;20:520–30. [3] Thompson RG, Hallstrom AP, Cobb LA. Bystander-initiated cardiopulmonary resuscitation in the management of ventricular fibrillation. Ann Intern Med 1979;90:737–40. [4] Safar P, Kochanek P. Therapeutic hypothermia after cardiac arrest. N Engl J Med 2002;346:612–3. [5] Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, et al. Treatment of comatose survivors of out of hospital cardiac arrest with induced hypothermia. N Engl J Med 2002;346:557–63. [6] The Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002;346:549–56. [7] Sterz F, Holzer M, Roine R. Hypothermia after cardiac arrest: a treatment that works. Curr Opin Crit Care 2003;9(3):205–10. [8] Longstreth Jr WT, Diehr P, Inui TS. Prediction of awakening after out-of-hospital cardiac arrest. N Engl J Med 1983;308:1378–82. [9] Curfman GD. Hypothermia to protect the brain. N Engl J Med 2002;346:546. [10] Heymans C. Survival and revival of nervous tissue after prolonged cerebral ischemia. Physiol Rev 1950;30:375–92. [11] Mullie A, van Hoeyweghen R, Quets A. Influence of time intervals on outcome of CPR. The Cerebral Resuscitation Study Group. Resuscitation 1989;17(Suppl.):S23–33. [12] Plum F, Posner JB. Prognosis in coma. In: Plum F, Posner JB, editors. The diagnosis of stupor and coma. Contemporary neurology series. Philadelphia: FA Davis; 1982. p. 846–69. [13] Bernat JL. A defense of the whole-brain concept of death. Hastings Cent Rep 1998;28:14–23. [14] Longstreth Jr WT. Neurological complications of cardiac arrest. In: Aminoff MJ, editor. Neurology and general medicine. New York: Churchill Livingstone; 1994. p. 166–82. [15] Brierly JB. Cerebral hypoxia. In: Blackwood W, Corsellis JAN, editors. Greenfield’s neuropathology. Edward Arnold: Edinburgh; 1976. p. 43–85. [16] Rothstein TL, Thomas EM, Sumi SM. Predicting outcome in hypoxic-ischemic coma. A prospective clinical and electrophysiologic study. Electroencephalogr Clin Neurophysiol 1991;79:101–7. [17] Rothstein TL. The role of evoked potentials in anoxic-ischemic coma and severe brain trauma. J Clin Neurophysiol 2000;17:486–97. [18] Wijdicks EF, Bamlet WR, Maramatton BV, Manno EM, McClelland RL. Validation of a new coma scale: the FOUR score. Ann Neurol 2005;58:585–93. [19] Murthy TVSP. A new score to valicate coma in emergency department-FOUR score. Indian J Neurotrauma 2009;6:59–61. [20] American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 2005;112(IV):1–203. [21] Wijdicks EFM, Hijdra A, Young GB, Bassetti CL, Wiebe S. Practice parameter: prediction of outcome in comatose survivors after cardiopulmonary resuscitation (an evidence-based review). Neurology 2006;67:203–10. [22] Kaplan PW. Electrophysiological prognostication and brain injury from cardiac arrest. Sem Neurol 2006;26:403–12. [23] Rothstein TL. Recovery from near death following cerebral anoxia: a case report demonstrating superiority of median somatosensory evoked potentials over EEG in predicting a favorable outcome after cardiopulmonary resuscitation. Resuscitation 2004;60:335–41. [24] van Putten MJAM. The N20 in post-anoxic coma: are you listening? Clin Neurophysiol 2012;123:1460–4. [25] Zandbergen EGJ, deHaan RJ, Stoutenbeek CP, Koelman CP, Johannes HTM, Hijdra A. Systematic review of early prediction of poor outcome in anoxic-ischemic coma. Lancet 1998;352:1808–12. [26] Gendo A, Kramer L, Hafner M, Funk G-C, Zauner C, Sterz F, et al. Timedependency of sensory evoked potentials in comatose cardiac arrest survivors. Intensive Care Med 2001;27:1305–11. [27] Chen R, Bolton CF, Young GB. Prediction of outcome in patients with anoxic coma: a clinical and electrophysiologic study. Crit Care Med 1996;24:672–5.
T.L. Rothstein / Clinical Neurology and Neurosurgery 126 (2014) 205–209 ´ ´ [28] Jørgenson EO, Malchow-Møller A. Natural history of global and critical brain ischemia. Resuscitation 1981;9:133–8. [29] Crepeau AZ, Rabinstein AA, Fugate JE, Mandrekar J, Wijdicks EF, White R, et al. Continuous EEG in therapeutic hypothermia after cardiac arrest: prognostic and clinical value. Neurology 2013;80(4):339–44. [30] Lucas JM, Cocchi MN, Salciccioli J, Stanbridge JA, Geocardin R, Romergryko GH, et al. Neurologic recovery after therapeutic hypothermia in patients with postcardiac arrest. Resuscitation 2012;83:265–9. [31] Kaplan PW. Stupor and coma: metabolic encephalopathies. Suppl Clin Neurophysiol 2004;57:667–80. [32] Ahmed I. Use of somatosensory evoked responses in the prediction of outcome from coma. Clin Electroencephalogr 1988;19:78–86. [33] Bassetti C, Bomio F, Mathis J, Hess CW. Early prognosis in coma after cardiac arrest: a prospective clinical, electrophysiological, and biochemical study of 60 patients. J Neurol Neurosurg Psychiatry 1996;61:610–5. [34] Berek K, Jeschow M, Aichner F. The prognostication of cerebral hypoxia after out-of hospital cardiac arrest in adults. Eur Neurol 1997;37:135–45. [35] Brierly JB, Graham DI, Adams JH, Simpson JA. Neocortical death after cardiac arrest: a clinical, neurophysiological and neuropathological report of two cases. Lancet 1971;2:560–5. [36] Brunko E, Zegers de Beyl D. Prognostic value of early cortical somatosensory evoked potentials after resuscitation from cardiac arrest. Electroencephalogr Clin Neurophysiol 1987;66:15–24. [37] Cheliout–Héraut F, Durand MC, Clair B, Gajdos P, Raphaël JC. Intérêt des potentiels évoqués dans le pronostic évolutif des comas par anoxie cérébrale chez l’adulte. Neurophysiol Clin 1992;22:269–80. [38] Fischer C, Luaute J, Nemoz C. Improved prediction of awakening or nonawakening from severe anoxic coma using tree-based classification analysis. Crit Care Med 2006;34:1520–4. [39] Ganji S, Peters G, Frazier E. Somatosensory and brainstem auditory evoked potential studies in non-traumatic coma. Clin Electroencephalogr 1988;19:55–66. [40] Kano T, Shimoda O, Morioka T, Yagashita Y, Hashiguchi A. Evaluation of the central nervous function in resuscitated comatose patients by multilevel evoked potentials. Resuscitation 1992;23:235–48. [41] Madl C, Grimm G, Kramer al. Early prediction of individual outcome after cardiopulmonary resuscitation. Lancet 1993;341:855–8. [42] Marcus EM, Stone B. Short-latency median nerve somatosensory evoked potentials in coma: relationship to BAEP, etiology, age, and outcome. In: Nodar RH, Barber C, editors. Evoked potentials Vol. II. The Second International Evoked Potentials Symposium. Stoneham: Butterworth; 1984. p. 609–23. [43] Ragazzoni A, Cincotta M, Chiaramonti R. Electrophysiological early predictors of outcome in patients with anoxic coma: EEG and SEPs. Clin Neurophysiol 1999;110:S245–6. [44] Robinson LR, Micklesen PJ, Tirschwell DL, Lew HL. Predictive value of somatosensory evoked potentials for awakening from coma. Crit Care Med 2003;31:960–7. [45] Walser H, Mattle H, Keller HM, Janzer R. Early cortical median nerve somatosensory evoked potentials. Prognostic value in anoxic coma. Arch Neurol 1986;42:32–8. [46] Ying Z, Schmid UD, Schmid J, Hess CW. Motor and somatosensory evoked potentials in coma: analysis and relation to clinical status and outcome. J Neurol Neurosurg Psychiatry 1992;55:470–4. [47] Young GB, Doig G, Ragazzoni A. Anoxic-ischemic encephalopathy and electrophysiological associations with outcome. Neurocrit Care 2002;2:5–10. [48] Young GB. Neurologic prognosis after cardiac arrest. N Engl J Med 2009;361(6):605–11. [49] Bender A, Howell K, Frey M, Berlis A, Naumann M, Buheitel G. Bilateral loss of cortical SSEP responses is compatible with good outcome after cardiac arrest. J Neurol 2012;259:2481–3.
209
[50] Nuwer MR, Aminoff M, Desmedt J. IFCN recommended standards for short latency somatosensory evoked potentials. Report of an IFCN committee. International federation of clinical neurophysiology. Electroencephalogr Clin Neurophysiol 1994;9:6–11. [51] Zanderbergen EG, Koelman JH, de Haan RJ, Hijdra A. SSEPs and prognosis in post anoxic coma: only short or also long latency responses. Neurology 2006;67:583–6. [52] Blondin NA, Greer DM. Neurologic prognosis in cardiac arrest patients treated with hypothermia. Neurologist 2011;17:241–8. [53] Bisschops LLA, van Alfen N, Bons S, van der Hoeven JG, Hoedemakers CWE. Predictors of poor neurologic outcome in patients after cardiac arrest treated with hypothermia: a retrospective study. Resuscitation 2011;82: 696–701. [54] Bouwes A, Binnekade JM, Zandstra DF, Koelman JHTM, van Schaik IN, Hijdra A, et al. Somatosensory evoked potentials during mild hypothermia after cardiopulmonary resuscitation. Neurology 2009;73:1457–61. [55] Cronberg T, Lilja G, Rundgren M, Friberg H, Widdner H. Long-term neurological outcome after cardiac arrest and therapeutic hypothermia. Resuscitation 2009;80:1119–23. [56] Fugate JE, Wijdicks EF, Mandrekar J, Claassen DO, Manno EM, White RD, et al. Predictors of neurologic outcome in hypothermia after cardiac arrest. Ann Neurol 2010;68:907–14. [57] Rossetti AO, Oddo M, Logroscino F, Kaplan PW. Prognostication after cardiac arrest and hypothermia. A prospective study. Ann Neurol 2010;67: 301–7. [58] Samaniego EA, Mlynash M, Caulfield AF, Eyngorn I, Wijman CA. Sedation confounds outcome prediction in cardiac arrest survivors treated with hypothermia. Neurocrit Care 2011;15:113–9. [59] Tiainen M, Kovala TT, Takkunen OS, Roine RO. Somatosensory and brainstem auditory evoked potentials in cardiac arrest patients treated with hypothermia. Crit Care Med 2005;33:1736–40. [60] Leithner C, Ploner CJ, Hasper D, Storm C. Does hypothermia influence the predictive value of bilateral absent N20 after cardiac arrest? Neurology 2010;74:965–9. [61] Leithner C, Ploner CJ, Hasper D, Storm C. Does hypothermia influence the predictive value of bilateral absent N20 after cardiac arrest. Neurology 2010;75:575–6. [62] Rothstein TL. Does hypothermia influence the predictive value of bilateral absent N20 after cardiac arrest? Neurology 2010;75:575. [63] Wijdicks EFM, Young GB, Wang JT, Connolly J. Prognostic determination in anoxic-ischemic and traumatic encephalopathies. J Clin Neurophysiol 2004;21:379–90. [64] Young GB, Doig G, Ragazzoni A. Anoxic-ischemic encephalopathy: clinical and electrophysiological associations with outcome. Neurocrit Care 2005;2:159–64. [65] Kamps MJA, Horn J, Oddo M, Fugate JE, Storm C, Cronberg G, et al. Prognostication of neurologic outcome in cardiac arrest patients after mild therapeutic hypothermia: a meta-analysis of the current literature. Intensive Care Med 2013;39:1671–82. [66] Desmedt JE, Cheron G. Noncephalic reference recording of early SSEP to finger stimulation in adult or aging normal man: differentiation of widespread N18 and contralateral N20 from pre rolandic P22 and N30 components. Electroencephalogr Clin Neurophysiol 1981;52:533–70. [67] Vanderzant CW, Beydoun AA, Domer PA, Hood TW, Abou-Khalil BW. Polarity reversal of N20 and P23 somatosensory evoked potentials between scalp and depth recordings. Electroencephalogr Clin Neurophysiol 1991;78: 234–9. [68] Rothstein TL, Thomas EM, Sumi SM. Predicting outcome in hypxic-ischemic coma. A prospective clinical and electrophysiologic study. Electroencephalogr Clin Neurophysiol 1991;79:101–7.
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