Resuscitation 85 (2014) 716–717
Contents lists available at ScienceDirect
Resuscitation journal homepage: www.elsevier.com/locate/resuscitation
Editorial
Is continuous EEG-monitoring value for money for cardiac arrest patients in the intensive care unit?
More than a decade ago, two pivotal trials convinced clinicians that cardiac arrest induced brain injury was amenable to treatment which set off the era of hypothermia treatment.1,2 In parallel to improvements in care and the introduction of new treatment options, the general interest for cardiac arrest patients in the intensive care unit (ICU) has increased and survival for outof-hospital cardiac arrest has doubled.3 Improvements in all parts of the chain of survival are likely to be accountable for this success story, although lowering the temperature as far down as 33 ◦ C recently was challenged in a randomised trial.4 More than half of all patients who are admitted to an ICU after out-of-hospital cardiac arrest eventually die and hypoxicischaemic brain injury is the predominant cause of death. Most patients die after a decision to withdraw life supportive treatment based on a presumed poor neurological prognosis.5 The American Academy of Neurology issued guidelines for prognostication after cardiac arrest in 2006 and included a much-cited algorithm with several predictors for a poor prognosis with false positive ratio 0.6 Subsequently, this algorithm has been outdated since predictors such as a poor motor score (GCS-M 1-2), myoclonus status and serum levels of neuron specific enolase >33 g/l were found compatible with good recovery in some patients treated with hypothermia.7,8 It is still quite unclear whether the lost reliability of these predictors is related to lowering of the body temperature or if it is merely an effect of sedation.9 Most standard treatment protocols for induced hypothermia include sedation during the first two days and in addition neuromuscular blocking agents on demand.10 During the intervention period the patient is therefore inaccessible for neurological testing and clinical seizures may be masked. Thus, the ICU-physician caring for comatose cardiac arrest patients is in a challenging situation. On the one hand, a developing brain injury is the foremost threat to the patient but on the other hand the means to measure and monitor the extent of brain injury are restricted by the treatment itself. Continuous EEG (cEEG)-monitoring has been advocated as a method to monitor post-hypoxic brain injury and the development of different patterns was found to correlate with good as well as poor outcome.11,12 In addition, cEEG allows for detection of epileptic activity but whether treatment of detected activity by sedative or antiepileptic drugs has any effect on outcome is yet not known. A large fraction of all cardiac arrest patients are reported to have electrographic epileptic activity, seizure-activity or even status epilepticus.12–14 The reported numbers vary widely http://dx.doi.org/10.1016/j.resuscitation.2014.03.301 0300-9572/© 2014 Elsevier Ireland Ltd. All rights reserved.
between studies and this discrepancy is probably best explained by a lack of consensus regarding definition of patterns. The majority of all posthypoxic epileptic activity is encephalopathic and adheres poorly to standard definitions of seizures or status. A classification for critical care EEG has recently been developed by the American Clinical Neurophysiology Society and may enhance comparisons between studies in the future.15 cEEG implicates extensive amounts of accumulated data and variations in which EEG-fractions are selected for evaluation by an EEG-expert might affect the amount of detected epileptic activity. In the present edition of Resuscitation, Crepeau and colleagues report that the systematic implementation of cEEG for all cardiac arrest patients in an academic US-centre increased the total cost of EEG threefold with a very low yield of detected seizures and with no apparent effect on overall survival.10 The authors used 21-channel recordings with concomitant video-recordings that were continuously monitored by an EEG-technologist and an epileptologist read the EEGs and reported results at least daily. From a cost-benefit standpoint the results are discouraging and the authors rightly question the routine use of multi-channel cEEG for cardiac arrest patients. Are we now to abandon this novel and promising technique? This important study by Crepeau et al. should alert us to how costly the introduction of a new technique may become. National charge data for the respective procedures were used for the calculations and we are not given details on the underlying calculations. Our assumption is that hardware and software costs account for only a small fraction of the total cost in this labour intensive setup. In the present study, the authors used their own conservative definition of seizures, excluding several types of encephalopathic epileptiform discharges commonly seen after cardiac arrest which may explain the low yield of seizures. They did not show an effect on outcome but the study was not powered to do that and whether the quality of prognostication and decisions regarding withdrawal of life supportive treatment were improved by the collected information from cEEG was not addressed. At our institution we introduced cEEG to monitor all hypothermia treated CA-patients in 2004 and have reported a high frequency (27%) of electrographic status epilepticus with occasional survivors. In our model, the involvement of the ICU staff is instrumental and a key to success. Our ICU has its own cEEG monitor and consults the EEG-specialists for aid in interpretation of registrations when necessary. We use a simplified electrode montage (2 channels)
Editorial / Resuscitation 85 (2014) 716–717
which is hooked up by the ICU-nurse when the patient arrives in the ICU as part of his/her routine duties. An amplitude integrated (aEEG) curve facilitates the rapid surveillance of extended time-periods but interpretation of patterns is done on the original EEG-tracings, one from each hemisphere. Pattern recognition is facilitated by categorization into four simplified patterns; flat, continuous, burst-suppression and electrographic status epilepticus.12 The monitor is available bedside for the ICU-physician as part of the routine ICU-monitoring and the ICU-physician orders interpretations by EEG-specialists daytime and on demand.16 For a patient without clinical or suspected electrographic seizures who wakes up after weaning of sedation, we would typically not involve an external EEG-specialist and thus limit costs since no additional labour would be necessary. For complicated patients who develop electrographic seizures and/or status epilepticus and who remain in coma after weaning of sedation, we find cEEG a useful tool to guide and monitor treatment effects. A daily review of the cEEG-recording has become a central part of our multimodal prognostication17 and governs decisions on what other prognostic investigations to perform and when to consider withdrawal of life supportive care. Given the common occurrence and irrevocable nature of the latter we find the cost of these interpretations in our setting (130 euro/24 h) well motivated. In conclusion we find that the study by Crepeau et al. shows that introducing cEEG may become a very costly affair with limited gains and the authors should be credited for their study approach, yet uncommon in the medical field. The results emphasise the need to develop a common and user-friendly standard classification of EEG-patterns for cardiac arrest patients in order for cEEG to become the routine bedside brain monitor that it has the potential to be. Conflict of interest statement Tobias Cronberg and Erik Westhall declare no conflicts of interest. Hans Friberg received lecture fees from Natus Inc. References 1. Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002;346:557–63. 2. 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. 3. Adielsson A, Hollenberg J, Karlsson T, et al. Increase in survival and bystander CPR in out-of-hospital shockable arrhythmia: bystander CPR and female gender are predictors of improved outcome. Experiences from Sweden in an 18-year perspective. Heart 2011;97:1391–6. 4. Nielsen N, Wetterslev J, Cronberg T, et al. Targeted temperature management at 33 degrees C versus 36 degrees C after cardiac arrest. N Engl J Med 2013;369:2197–206. 5. Dragancea I, Rundgren M, Englund E, Friberg H, Cronberg T. The influence of induced hypothermia and delayed prognostication on the mode of death after cardiac arrest. Resuscitation 2013;84:337–42.
717
6. Wijdicks EF, Hijdra A, Young GB, Bassetti CL, Wiebe S. Practice parameter: prediction of outcome in comatose survivors after cardiopulmonary resuscitation (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2006;67:203–10. 7. Kamps MJ, Horn J, Oddo M, 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. 8. Sandroni C, Cavallaro F, Callaway CW, et al. Predictors of poor neurological outcome in adult comatose survivors of cardiac arrest: a systematic review and meta-analysis. Part 2: Patients treated with therapeutic hypothermia. Resuscitation 2013;84:1324–38. 9. 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. 10. Crepeau AZ, Fugate JE, Mandrekar J, White RD, Wijdicks EF, Rabinstein AA, et al. Value analysis of continuous EEG in patients during therapeutic hypothermia after cardiac arrest. Resuscitation 2014. 11. Cloostermans MC, van Meulen FB, Eertman CJ, Hom HW, van Putten MJ. Continuous electroencephalography monitoring for early prediction of neurological outcome in postanoxic patients after cardiac arrest: a prospective cohort study. Crit Care Med 2012;40:2867–75. 12. Rundgren M, Westhall E, Cronberg T, Rosen I, Friberg H. Continuous amplitudeintegrated electroencephalogram predicts outcome in hypothermia-treated cardiac arrest patients. Crit Care Med 2010;38:1838–44. 13. Rittenberger JC, Popescu A, Brenner RP, Guyette FX, Callaway CW. Frequency and timing of nonconvulsive status epilepticus in comatose post-cardiac arrest subjects treated with hypothermia. Neurocrit Care 2012;16:114–22. 14. Mani R, Schmitt SE, Mazer M, Putt ME, Gaieski DF. The frequency and timing of epileptiform activity on continuous electroencephalogram in comatose post-cardiac arrest syndrome patients treated with therapeutic hypothermia. Resuscitation 2012;83:840–7. 15. Hirsch LJ, LaRoche SM, Gaspard N, Gerard E, Svoronos A, Herman ST, et al. American Clinical Neurophysiology Society’s Standardized Critical Care EEG Terminology: 2012 version. J Clin Neurophysiol 2013;30:1–27. 16. Friberg H, Westhall E, Rosen I, Rundgren M, Nielsen N, Cronberg T. Clinical review: continuous and simplified electroencephalography to monitor brain recovery after cardiac arrest. Crit Care 2013;17:233. 17. Friberg H, Rundgren M, Westhall E, Nielsen N, Cronberg T. Continuous evaluation of neurological prognosis after cardiac arrest. Acta Anaesthesiol Scand 2013;57:6–15.
Tobias Cronberg ∗ Department of Clinical Sciences, Division of Neurology, Lund University, Lund, Sweden Erik Westhall Department of Clinical Sciences, Division of Clinical Neurophysiology, Lund University, Lund, Sweden Hans Friberg Department of Clinical Sciences, Division of Intensive- and Perioperative Care, Lund University, Lund, Sweden ∗ Corresponding author. E-mail addresses: [email protected] (T. Cronberg), [email protected] (E. Westhall), [email protected] (H. Friberg).
25 March 2014
Contents lists available at ScienceDirect
Resuscitation journal homepage: www.elsevier.com/locate/resuscitation
Editorial
Is continuous EEG-monitoring value for money for cardiac arrest patients in the intensive care unit?
More than a decade ago, two pivotal trials convinced clinicians that cardiac arrest induced brain injury was amenable to treatment which set off the era of hypothermia treatment.1,2 In parallel to improvements in care and the introduction of new treatment options, the general interest for cardiac arrest patients in the intensive care unit (ICU) has increased and survival for outof-hospital cardiac arrest has doubled.3 Improvements in all parts of the chain of survival are likely to be accountable for this success story, although lowering the temperature as far down as 33 ◦ C recently was challenged in a randomised trial.4 More than half of all patients who are admitted to an ICU after out-of-hospital cardiac arrest eventually die and hypoxicischaemic brain injury is the predominant cause of death. Most patients die after a decision to withdraw life supportive treatment based on a presumed poor neurological prognosis.5 The American Academy of Neurology issued guidelines for prognostication after cardiac arrest in 2006 and included a much-cited algorithm with several predictors for a poor prognosis with false positive ratio 0.6 Subsequently, this algorithm has been outdated since predictors such as a poor motor score (GCS-M 1-2), myoclonus status and serum levels of neuron specific enolase >33 g/l were found compatible with good recovery in some patients treated with hypothermia.7,8 It is still quite unclear whether the lost reliability of these predictors is related to lowering of the body temperature or if it is merely an effect of sedation.9 Most standard treatment protocols for induced hypothermia include sedation during the first two days and in addition neuromuscular blocking agents on demand.10 During the intervention period the patient is therefore inaccessible for neurological testing and clinical seizures may be masked. Thus, the ICU-physician caring for comatose cardiac arrest patients is in a challenging situation. On the one hand, a developing brain injury is the foremost threat to the patient but on the other hand the means to measure and monitor the extent of brain injury are restricted by the treatment itself. Continuous EEG (cEEG)-monitoring has been advocated as a method to monitor post-hypoxic brain injury and the development of different patterns was found to correlate with good as well as poor outcome.11,12 In addition, cEEG allows for detection of epileptic activity but whether treatment of detected activity by sedative or antiepileptic drugs has any effect on outcome is yet not known. A large fraction of all cardiac arrest patients are reported to have electrographic epileptic activity, seizure-activity or even status epilepticus.12–14 The reported numbers vary widely http://dx.doi.org/10.1016/j.resuscitation.2014.03.301 0300-9572/© 2014 Elsevier Ireland Ltd. All rights reserved.
between studies and this discrepancy is probably best explained by a lack of consensus regarding definition of patterns. The majority of all posthypoxic epileptic activity is encephalopathic and adheres poorly to standard definitions of seizures or status. A classification for critical care EEG has recently been developed by the American Clinical Neurophysiology Society and may enhance comparisons between studies in the future.15 cEEG implicates extensive amounts of accumulated data and variations in which EEG-fractions are selected for evaluation by an EEG-expert might affect the amount of detected epileptic activity. In the present edition of Resuscitation, Crepeau and colleagues report that the systematic implementation of cEEG for all cardiac arrest patients in an academic US-centre increased the total cost of EEG threefold with a very low yield of detected seizures and with no apparent effect on overall survival.10 The authors used 21-channel recordings with concomitant video-recordings that were continuously monitored by an EEG-technologist and an epileptologist read the EEGs and reported results at least daily. From a cost-benefit standpoint the results are discouraging and the authors rightly question the routine use of multi-channel cEEG for cardiac arrest patients. Are we now to abandon this novel and promising technique? This important study by Crepeau et al. should alert us to how costly the introduction of a new technique may become. National charge data for the respective procedures were used for the calculations and we are not given details on the underlying calculations. Our assumption is that hardware and software costs account for only a small fraction of the total cost in this labour intensive setup. In the present study, the authors used their own conservative definition of seizures, excluding several types of encephalopathic epileptiform discharges commonly seen after cardiac arrest which may explain the low yield of seizures. They did not show an effect on outcome but the study was not powered to do that and whether the quality of prognostication and decisions regarding withdrawal of life supportive treatment were improved by the collected information from cEEG was not addressed. At our institution we introduced cEEG to monitor all hypothermia treated CA-patients in 2004 and have reported a high frequency (27%) of electrographic status epilepticus with occasional survivors. In our model, the involvement of the ICU staff is instrumental and a key to success. Our ICU has its own cEEG monitor and consults the EEG-specialists for aid in interpretation of registrations when necessary. We use a simplified electrode montage (2 channels)
Editorial / Resuscitation 85 (2014) 716–717
which is hooked up by the ICU-nurse when the patient arrives in the ICU as part of his/her routine duties. An amplitude integrated (aEEG) curve facilitates the rapid surveillance of extended time-periods but interpretation of patterns is done on the original EEG-tracings, one from each hemisphere. Pattern recognition is facilitated by categorization into four simplified patterns; flat, continuous, burst-suppression and electrographic status epilepticus.12 The monitor is available bedside for the ICU-physician as part of the routine ICU-monitoring and the ICU-physician orders interpretations by EEG-specialists daytime and on demand.16 For a patient without clinical or suspected electrographic seizures who wakes up after weaning of sedation, we would typically not involve an external EEG-specialist and thus limit costs since no additional labour would be necessary. For complicated patients who develop electrographic seizures and/or status epilepticus and who remain in coma after weaning of sedation, we find cEEG a useful tool to guide and monitor treatment effects. A daily review of the cEEG-recording has become a central part of our multimodal prognostication17 and governs decisions on what other prognostic investigations to perform and when to consider withdrawal of life supportive care. Given the common occurrence and irrevocable nature of the latter we find the cost of these interpretations in our setting (130 euro/24 h) well motivated. In conclusion we find that the study by Crepeau et al. shows that introducing cEEG may become a very costly affair with limited gains and the authors should be credited for their study approach, yet uncommon in the medical field. The results emphasise the need to develop a common and user-friendly standard classification of EEG-patterns for cardiac arrest patients in order for cEEG to become the routine bedside brain monitor that it has the potential to be. Conflict of interest statement Tobias Cronberg and Erik Westhall declare no conflicts of interest. Hans Friberg received lecture fees from Natus Inc. References 1. Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002;346:557–63. 2. 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. 3. Adielsson A, Hollenberg J, Karlsson T, et al. Increase in survival and bystander CPR in out-of-hospital shockable arrhythmia: bystander CPR and female gender are predictors of improved outcome. Experiences from Sweden in an 18-year perspective. Heart 2011;97:1391–6. 4. Nielsen N, Wetterslev J, Cronberg T, et al. Targeted temperature management at 33 degrees C versus 36 degrees C after cardiac arrest. N Engl J Med 2013;369:2197–206. 5. Dragancea I, Rundgren M, Englund E, Friberg H, Cronberg T. The influence of induced hypothermia and delayed prognostication on the mode of death after cardiac arrest. Resuscitation 2013;84:337–42.
717
6. Wijdicks EF, Hijdra A, Young GB, Bassetti CL, Wiebe S. Practice parameter: prediction of outcome in comatose survivors after cardiopulmonary resuscitation (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2006;67:203–10. 7. Kamps MJ, Horn J, Oddo M, 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. 8. Sandroni C, Cavallaro F, Callaway CW, et al. Predictors of poor neurological outcome in adult comatose survivors of cardiac arrest: a systematic review and meta-analysis. Part 2: Patients treated with therapeutic hypothermia. Resuscitation 2013;84:1324–38. 9. 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. 10. Crepeau AZ, Fugate JE, Mandrekar J, White RD, Wijdicks EF, Rabinstein AA, et al. Value analysis of continuous EEG in patients during therapeutic hypothermia after cardiac arrest. Resuscitation 2014. 11. Cloostermans MC, van Meulen FB, Eertman CJ, Hom HW, van Putten MJ. Continuous electroencephalography monitoring for early prediction of neurological outcome in postanoxic patients after cardiac arrest: a prospective cohort study. Crit Care Med 2012;40:2867–75. 12. Rundgren M, Westhall E, Cronberg T, Rosen I, Friberg H. Continuous amplitudeintegrated electroencephalogram predicts outcome in hypothermia-treated cardiac arrest patients. Crit Care Med 2010;38:1838–44. 13. Rittenberger JC, Popescu A, Brenner RP, Guyette FX, Callaway CW. Frequency and timing of nonconvulsive status epilepticus in comatose post-cardiac arrest subjects treated with hypothermia. Neurocrit Care 2012;16:114–22. 14. Mani R, Schmitt SE, Mazer M, Putt ME, Gaieski DF. The frequency and timing of epileptiform activity on continuous electroencephalogram in comatose post-cardiac arrest syndrome patients treated with therapeutic hypothermia. Resuscitation 2012;83:840–7. 15. Hirsch LJ, LaRoche SM, Gaspard N, Gerard E, Svoronos A, Herman ST, et al. American Clinical Neurophysiology Society’s Standardized Critical Care EEG Terminology: 2012 version. J Clin Neurophysiol 2013;30:1–27. 16. Friberg H, Westhall E, Rosen I, Rundgren M, Nielsen N, Cronberg T. Clinical review: continuous and simplified electroencephalography to monitor brain recovery after cardiac arrest. Crit Care 2013;17:233. 17. Friberg H, Rundgren M, Westhall E, Nielsen N, Cronberg T. Continuous evaluation of neurological prognosis after cardiac arrest. Acta Anaesthesiol Scand 2013;57:6–15.
Tobias Cronberg ∗ Department of Clinical Sciences, Division of Neurology, Lund University, Lund, Sweden Erik Westhall Department of Clinical Sciences, Division of Clinical Neurophysiology, Lund University, Lund, Sweden Hans Friberg Department of Clinical Sciences, Division of Intensive- and Perioperative Care, Lund University, Lund, Sweden ∗ Corresponding author. E-mail addresses: [email protected] (T. Cronberg), [email protected] (E. Westhall), [email protected] (H. Friberg).
25 March 2014
