Resuscitation 85 (2014) 221–226
Contents lists available at ScienceDirect
Resuscitation journal homepage: www.elsevier.com/locate/resuscitation
Clinical Paper
Bispectral index (BIS) and suppression ratio (SR) as an early predictor of unfavourable neurological outcome after cardiac arrest夽 Christoph Selig a,1 , Christian Riegger a,c,1 , Burkhard Dirks a , Michael Pawlik b , Timo Seyfried b , Werner Klingler a,d,∗ a
Section of Emergency Medicine, Department of Anaesthesiology, Ulm University, Germany Department of Anaesthesiology, University of Regensburg, Germany c Department of Anaesthesia and Intensive Care Medicine, University Hospital Basel, Switzerland d Department of Neuroanaesthesiology, Ulm University, Germany b
a r t i c l e
i n f o
Article history: Received 4 September 2013 Received in revised form 8 November 2013 Accepted 12 November 2013
Keywords: Bispectral index Cardiac arrest Neurological outcome Cardiopulmonary resuscitation Cerebral function
a b s t r a c t Introduction: Predicting the neurological outcome after cardiopulmonary resuscitation (CPR) is extremely difficult. We tested the hypothesis whether monitoring of bispectral index (BIS) and suppression ratio (SR) could serve as an early prognostic indicator of neurological outcomes after CPR. Methods: Cerebral monitoring (BIS, SR) was started as soon as possible after initiation of CPR and was continued for up to 72 h. The functional neurological outcome was measured on day 3, day 7 and again one month after CPR via a clinical examination and assessment according to the cerebral performance category score (CPC). Results: In total 79 patients were included. Of these, 26 patients (32.9%) survived the observation period of one month; 7 of them (8.9%) showed an unfavourable neurological outcome. These 7 patients had significantly lower median BIS values (25 [21;37] vs. 61 [51;70]) and higher SR (56 [44;64] vs. 7 [1;22]) during the first 4 h after the initiation of CPR. Using BIS < 40 as threshold criteria, unfavourable neurological outcome was predicted with a specificity of 89.5% and a sensitivity of 85.7%. The odds ratio for predicting an unfavourable neurological outcome was 0.921 (95% CI 0.853–0.985). The likelihood to remain in a poor neurological condition decreased by 7.9% for each additional point of BIS, on average. Conclusion: Our results suggest that BIS and SR are helpful tools in the evaluation of the neurological outcomes of resuscitated patients. Nevertheless, therapeutic decisions have to be confirmed through further examinations due to the far-ranging consequences of false positive results. © 2013 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Each year about 375,000 people suffer a sudden cardiac arrest (CA) in Europe.1,2 For between 9% and 61%, return of spontaneous circulation (ROSC) is achieved through cardiopulmonary resuscitation (CPR). Between 2% and 23% of the patients who experience CA are discharged alive from the hospital.1,3,4 Secondary resuscitation success, which is defined as a patient being discharged without neurological deficits, is much more rare. Up to 33% of the survivors show severe neurological deficits by the time they are discharged from hospital.5–10 Despite technical advances, a severe neurological
夽 A Spanish translated version of the summary of this article appears as Appendix in the final online version at http://dx.doi.org/10.1016/j.resuscitation.2013.11.008. ∗ Corresponding author at: Department of Neuroanaesthesiology, Neurosurgical University Ulm-Günzburg, Ludwig-Heilmeyer-Str. 2, 89312 Günzburg, Germany. E-mail address: [email protected] (W. Klingler). 1 Contributed equally. 0300-9572/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.resuscitation.2013.11.008
deficiency is predicted correctly with a specificity of only 58% and a sensitivity of 81% within the first 24 h after CA, even by experienced emergency specialists.11 Radiological procedures and the measurement of the intracranial pressure as well as the regulation of the cerebral oxygen consumption are still too unspecific to be used as outcome parameters following CPR.12,13 Biochemical markers such as the neuronal specific enolase or the serum protein S-100 are not reliable markers for an unfavourable outcome soon after CPR because of their high variability and the time delay involved, ranging from 12 to 24 h.8,9,14,15 The rapid recovery of brain stem reflexes after successful CPR correlates with good neurological rehabilitation with a positive predictive value of up to 65%.16 Electrophysiological methods show the most promise in the prediction of neurological outcome. That being said, the measurement of the somatosensory evoked potentials (SSEP) or the electroencephalogram (EEG) is a very time consuming method and specialists are needed for interpretation. In these methods strong indicators for an unfavourable neurological outcome are an isoelectric EEG as well as a burst suppression pattern.13 Because of
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arithmetic algorithms, the bispectral index (BIS) allows for the rapid and standardised assessment of the cerebral function and the cerebral metabolism without specific EEG knowledge. The suppression ratio (SR) is a second parameter measured by the majority of commercially available BIS monitors; it describes the ratio of isoelectric EEG. A number of case reports point out that the BIS could be a useful method for monitoring the cerebral function as well as being a prognostic indicator concerning survival and neurological outcome after CA.21–26 Our study examines the clinical and preclinical application of BIS monitoring during CPR, both in intensive care units and in the field by emergency personnel. 2. Methods The study was carried out at German university hospitals in Ulm and Regensburg between August 2005 and April 2008. Both centres provide an ambulance service with experienced emergency doctors. The study was approved by the ethics commissions of the University of Ulm and the University of Regensburg. Because of the study content, it was not possible to obtain patient consent to participate before starting BIS monitoring. As soon as the patients recovered to an adequate cerebral state, informed consent was obtained. If the patient remained in an unfavourable neurological state, the approval for study participation was obtained from the patient’s legal representative. Exclusion criteria were patients younger than 18 years of age, extreme structural brain damage, hypothermia ( 45 during the first 24 h after ROSC as a good predictor of a favourable neurological outcome.30 Shibata et al. performed BIS monitoring in 10 patients with ROSC after admission to the ICU. The average BIS values of the four patients with favourable neurological outcome achieved values >80 during the first 30 min after admission. The patients who died after
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hours after initiation of CPR Fig. 2. Time course of BIS and SR monitoring. For each hour (after the initiation of CPR), the average BIS and SR values ± standard error of the mean from initiation of CPR, divided into patients with favourable (CPC 1 or 2) and with unfavourable neurological outcome (CPC 3–5) are shown. Regarding BIS, one can see the greatest difference (of 25) between the patients with a CPC 1 or 2 and the patients with CPC 3–5 four hours after initiation of CPR. The SR shows a difference of 37 between the patients with CPC 1 or 2 and the patients with CPC 3–5 four hours after the initiation of CPR.
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Fig. 3. Boxplot of BIS and SR. Boxplot with median, 25th quartile, 75th quartile, range and mean () of the BIS (on the left side) and the SR (on the right side) during the first 4 h after the initiation of CPR. 16 patients were classified as CPC 1, three patients as CPC 2, four patients as CPC 3, three patients as CPC 4 and no patient as CPC 5.
ROSC achieved only an average BIS of 9.7 ± 16 (mean ± standard deviation).25 Seder et al. started BIS monitoring with a median time delay of 280 min after ROSC.32 Furthermore a number of case reports point out the fact that BIS monitoring could be used as a means to monitor cerebral function and cerebral perfusion during CPR.21–24,26 In all of these studies, a BIS > 35–50 was described as a marker for adequate cerebral perfusion during CPR efforts and as a marker for a favourable neurological outcome.29,30 This study
confirms these findings with a comparably high number of cases. Chollet-Xémard et al. were able to show that BIS monitoring is not useful for the prediction of loss of life during or after CPR; neurological recovery in survivors was not investigated in this study.34 BIS is a computed EEG derived parameter and was developed to estimate depth of general anaesthesia. BIS levels below 40 are mainly determined by the ratio of isoelectric EEG, i.e. by the SR.35 Indeed, in the current study there is only a small difference in the
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Fig. 4. Receiver operating characteristic (ROC). ROC analysis of all 26 patients who survived 1 month for the average BIS (on the left side) and the average SR (on the right side) during the first 4 h after initiation of CPR to predict an unfavourable neurological outcome.
5. Conclusion
Fig. 5. Odds ratio. Odds ratio (95% confidence interval) for the prediction of an unfavourable neurological outcome for the average BIS and SR during the first four hours after the initiation of CPR. The OR for BIS is 0.921 (95% CI 0.87–0.99) and for the SR 1.081 (95% CI 1.02–1.26).
statistical parameters of BIS and SR using a threshold criteria of BIS < 40. A prognostic parameter to predict an unfavourable neurological outcome should achieve a very high specificity. This is necessary to avoid patients with a favourable prognosis being falsely assigned to the patient group with an unfavourable prognosis as this could mean a de-escalation in their medical treatment strategy.14 In our study we measured the average BIS and SR during the first 4 h after the initiation of CPR. We were able to predict an unfavourable neurological outcome with a specificity of 89.5% and a sensitivity of 85.7%. Because of comorbidity, e.g. recurrence of myocardial infarction, it is difficult to predict a favourable outcome. To compare our results, the specificity and sensitivity of the SSEP N20 response after stimulation of the median nerve, which is one of the most established electrophysiological investigation methods for the prediction of an unfavourable neurological outcome, is given below.13,36 The absence of the SSEP N20 response after stimulation of the median nerve within the first 8–24 h after ROSC predicts an unfavourable neurological outcome with a specificity of 72% and a sensitivity of 87%.11 Absence of the SSEP N20 response within the first 7 days after CPR predicts an unfavourable neurological outcome with a specificity of 100%, however the sensitivity is only 28–73%.12 Recently Stammet et al. were able to show that the combination of serum level of S100B and BIS monitoring even more accurately predicts outcome in patients treated using therapeutic hypothermia after successful CPR. The serum level of S100B was measured 48 h after ROSC. The lowest BIS values in patients with unfavourable neurological outcome were measured medially 5 [4.0;14.5] h after ROSC. We were able to predict an unfavourable neurological outcome in a similar timeframe within 4 h after ROSC.37
Predicting the neurological recovery after CPR is difficult despite several established investigations, such as cerebral imaging, determination of intracranial pressure, clinical and biochemical parameters. The results of this study show, that BIS respectively SR monitoring may be a promising electrophysiological tool due to comparably high specificity and other advantages: it is easy to perform, it is low in weight, it is transportable and it delivers data almost in real time. In contrast to SSEP and conventional EEG, interpretation of BIS and SR does not require expert knowledge.17–23,25,30–33 Careful interpretation of BIS and SR early after CPR can help to generate a conclusion about the neurological prognosis. Nevertheless, therapeutic decisions have to be confirmed by further examinations due to the far-ranging consequences of false positive results.
Conflict of interest statement Departmental funding only. None of the author has received any kind of compensation or research support from the manufacturers of BIS equipment.
Acknowledgements We would like to thank the staff of the emergency services, the emergency departments and the intensive care units of the university hospitals in Ulm and Regensburg for their help and support in the carrying out of this work. Special thanks go to Dr. J. Dreyhaupt of the Department of Biometrics of the University of Ulm and to Nathan Ingvalson B.Sc. for linguistic support.
References 1. Handley AJ, Koster R, Monsieurs K, Perkins GD, Davies S, Bossaert L. European Resuscitation Council: European resuscitation council guidelines for resuscitation 2005. Section 2. Adult basic life support and use of automated external defibrillators. Resuscitation 2005;67:7–23. 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. Horsted TI, Rasmussen LS, Meyhoff CS, Nielsen SL. Long-term prognosis after out-of-hospital cardiac arrest. Resuscitation 2007;72:214–8. 4. Nichol G, Steen P, Herlitz J, et al. International Resuscitation Network Registry: design, rationale and preliminary results. Resuscitation 2005;65:265–77. 5. Cohn AC, Wilson WM, Yan B, et al. Analysis of clinical outcome following inhospital adult cardiac arrest. Intern Med J 2004;34:398–402. 6. Herlitz J, Bahr J, Fischer M, Kuisma M, Lexow K, Thorgeirsson G. Resuscitation in Europe: a tale of five European regions. Resuscitation 1999;41:121–31.
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7. Peberdy MA, Kaye W, Ornato JP, et al. Cardiopulmonary resuscitation of adults in the hospital: a report of 14720 cardiac arrests from the national registry of cardiopulmonary resuscitation. Resuscitation 2003;58:297–308. 8. Pfeifer R, Borner A, Krack A, Sigusch HH, Surber R, Figulla HR. Outcome after cardiac arrest: predictive values and limitations of the neuroproteins neuronspecific enolase and protein S-100 and the Glasgow Coma Scale. Resuscitation 2005;65:49–55. 9. Reisinger J, Hollinger K, Lang W, et al. Prediction of neurological outcome after cardiopulmonary resuscitation by serial determination of serum neuronspecific enolase. Eur Heart J 2007;28:52–8. 10. Van Alem AP, de Vos R, Schmand B, Koster RW. Cognitive impairment in survivors of out-of-hospital cardiac arrest. Am Heart J 2004;148:416–21. 11. Madl C, Kramer L, Domanovits H, et al. Improved outcome prediction in unconscious cardiac arrest survivors with sensory evoked potentials compared with clinical assessment. Crit Care Med 2000;28:721–6. 12. Kaye P. Early prediction of individual outcome following cardiopulmonary resuscitation: systematic review. Emerg Med J 2005;22:700–5. 13. Wijdicks EF, Hijdra A, Young GB, Bassetti CL, Wiebe S, Quality Standards Subcommittee of the American Academy of Neurology. 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. 14. Schoerkhuber W, Kittler H, Sterz F, et al. Time course of serum neuron-specific enolase. A predictor of neurological outcome in patients resuscitated from cardiac arrest. Stroke 1999;30:1598–603. 15. Zingler VC, Krumm B, Bertsch T, Fassbender K, Pohlmann-Eden B. Early prediction of neurological outcome after cardiopulmonary resuscitation: a multimodal approach combining neurobiochemical and electrophysiological investigations may provide high prognostic certainty in patients after cardiac arrest. Eur Neurol 2003;49:79–84. 16. Jorgensen EO. Course of neurological recovery and cerebral prognostic signs during cardio-pulmonary resuscitation. Resuscitation 1997;35:9–16. 17. Misis M, Raxach JG, Molto HP, Vega SM, Rico PS:. Bispectral index monitoring for early detection of brain death. Transplant Proc 2008;40:1279–81. 18. Vivien B, Paqueron X, Le Cosquer P, Langeron O, Coriat P, Riou B. Detection of brain death onset using the bispectral index in severely comatose patients. Intensive Care Med 2002;28:419–25. 19. Fabregas N, Gambus PL, Valero R, et al. Can bispectral index monitoring predict recovery of consciousness in patients with severe brain injury? Anesthesiology 2004;101:43–51. 20. Gilbert TT, Wagner MR, Halukurike V, Paz HL, Garland A. Use of bispectral electroencephalogram monitoring to assess neurological status in unsedated, critically ill patients. Crit Care Med 2001;29:1996–2000. 21. Azim N, Wang CY. The use of bispectral index during a cardiopulmonary arrest: a potential predictor of cerebral perfusion. Anaesthesia 2004;59:610–2. 22. Chakravarthy M, Patil T, Jayaprakash K, Shivananda N, Jawali V. Bispectral index is an indicator of adequate cerebral perfusion during cardiopulmonary resuscitation. J Cardiothorac Vasc Anesth 2003;17:506–8. 23. Kluger MT. The bispectral index during an anaphylactic circulatory arrest. Anaesth Intensive Care 2001;29:544–7.
24. Merat S, Levecque JP, Le Gulluche Y, Diraison Y, Brinquin L, Hoffmann JJ. BIS monitoring may allow the detection of severe cerebral ischemia. Can J Anaesth 2001;48:1066–9. 25. Shibata S, Imota T, Shigeomi S, Sato W, Enzan K:. Use of the bispectral index during the early postresuscitative phase after out-of-hospital cardiac arrest. J Anesth 2005;19:243–6. 26. Szekely B, Saint-Marc T, Degremont AC, Castelain MH, Fischler M. Value of bispectral index monitoring during cardiopulmonary resuscitation. Br J Anaesth 2002;88:443–4. 27. Cummins RO, Chamberlain DA, Abramson NS, et al. Recommended guidelines for uniform reporting of data from out-of-hospital cardiac arrest: the Utstein style. A statement for health professionals from a task force of the American heart association, the European resuscitation council, the heart and stroke foundation of Canada, and the Australian resuscitation council. Circulation 1991;84: 960–75. 28. Jacobs I, Nadkarni V, Bahr J, et al. Cardiac arrest and cardiopulmonary resuscitation outcome reports: update and simplification of the Utstein templates for resuscitation registries. A statement for healthcare professionals from a task force of the International Liaison Committee on Resuscitation (American Heart Association, European Resuscitation Council, Australian Resuscitation Council, New Zealand Resuscitation Council, Heart and Stroke Foundation of Canada, Inter. American Heart Foundation, Resuscitation Council of Southern Africa). Resuscitation 2004;63:233–49. 29. Fatovich DM, Jacobs IG, Celenza A, Paech MJ. An observational study of bispectral index monitoring for out of hospital cardiac arrest. Resuscitation 2006;69:207–12. 30. Leary M, Fried D, Gaieski D, et al. Neurologic prognostication and bispectral index monitoring after resuscitation from cardiac arrest. Resuscitation 2010;81:1133–7. 31. Pawlik M, Seyfried T, Riegger C, Klingler W, Selig C. Bispectral index monitoring during cardiopulmonary resuscitation repeated twice within 8 days in the same patient: a case report. Int J Emerg Med 2008;1:209–12. 32. Seder D, Fraser G, Robbins T, Libby L, Riker R. The bispectral index and suppression ratio are very early predictors of neurological outcome during therapeutic hypothermia after cardiac arrest. Intensive Care Med 2010;36:281–8. 33. Stammet P, Werer C, Mertens L, Lorang C, Hemmer M. Bispectral index (BIS) helps predicting bad neurological outcome in comatose survivors after cardiac arrest and induced therapeutic hypothermia. Resuscitation 2009;80:437–42. 34. Chollet-Xémard C, Combes X, Soupizet F, et al. Bispectral index monitoring is useless during cardiac arrest patients’ resuscitation. Resuscitation 2009;80:213–6. 35. Bruhn J, Bouillon TW, Shafer SL. Bispectral index (BIS) and burst suppression: revealing a part of the BIS algorithm. J Clin Monit Comput 2000;16:593–6. 36. Zandbergen EG, Hijdra A, Koelman JH, et al. Prediction of poor outcome within the first 3 days of postanoxic coma. Neurology 2006;66:62–8. 37. Stammet P, Wagner DR, Gilson G, Devaux Y. Modeling serum level of S100B and bispectral index to predict outcome after cardiac arrest. J Am Coll Cardiol 2013;62:851–8.
Contents lists available at ScienceDirect
Resuscitation journal homepage: www.elsevier.com/locate/resuscitation
Clinical Paper
Bispectral index (BIS) and suppression ratio (SR) as an early predictor of unfavourable neurological outcome after cardiac arrest夽 Christoph Selig a,1 , Christian Riegger a,c,1 , Burkhard Dirks a , Michael Pawlik b , Timo Seyfried b , Werner Klingler a,d,∗ a
Section of Emergency Medicine, Department of Anaesthesiology, Ulm University, Germany Department of Anaesthesiology, University of Regensburg, Germany c Department of Anaesthesia and Intensive Care Medicine, University Hospital Basel, Switzerland d Department of Neuroanaesthesiology, Ulm University, Germany b
a r t i c l e
i n f o
Article history: Received 4 September 2013 Received in revised form 8 November 2013 Accepted 12 November 2013
Keywords: Bispectral index Cardiac arrest Neurological outcome Cardiopulmonary resuscitation Cerebral function
a b s t r a c t Introduction: Predicting the neurological outcome after cardiopulmonary resuscitation (CPR) is extremely difficult. We tested the hypothesis whether monitoring of bispectral index (BIS) and suppression ratio (SR) could serve as an early prognostic indicator of neurological outcomes after CPR. Methods: Cerebral monitoring (BIS, SR) was started as soon as possible after initiation of CPR and was continued for up to 72 h. The functional neurological outcome was measured on day 3, day 7 and again one month after CPR via a clinical examination and assessment according to the cerebral performance category score (CPC). Results: In total 79 patients were included. Of these, 26 patients (32.9%) survived the observation period of one month; 7 of them (8.9%) showed an unfavourable neurological outcome. These 7 patients had significantly lower median BIS values (25 [21;37] vs. 61 [51;70]) and higher SR (56 [44;64] vs. 7 [1;22]) during the first 4 h after the initiation of CPR. Using BIS < 40 as threshold criteria, unfavourable neurological outcome was predicted with a specificity of 89.5% and a sensitivity of 85.7%. The odds ratio for predicting an unfavourable neurological outcome was 0.921 (95% CI 0.853–0.985). The likelihood to remain in a poor neurological condition decreased by 7.9% for each additional point of BIS, on average. Conclusion: Our results suggest that BIS and SR are helpful tools in the evaluation of the neurological outcomes of resuscitated patients. Nevertheless, therapeutic decisions have to be confirmed through further examinations due to the far-ranging consequences of false positive results. © 2013 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Each year about 375,000 people suffer a sudden cardiac arrest (CA) in Europe.1,2 For between 9% and 61%, return of spontaneous circulation (ROSC) is achieved through cardiopulmonary resuscitation (CPR). Between 2% and 23% of the patients who experience CA are discharged alive from the hospital.1,3,4 Secondary resuscitation success, which is defined as a patient being discharged without neurological deficits, is much more rare. Up to 33% of the survivors show severe neurological deficits by the time they are discharged from hospital.5–10 Despite technical advances, a severe neurological
夽 A Spanish translated version of the summary of this article appears as Appendix in the final online version at http://dx.doi.org/10.1016/j.resuscitation.2013.11.008. ∗ Corresponding author at: Department of Neuroanaesthesiology, Neurosurgical University Ulm-Günzburg, Ludwig-Heilmeyer-Str. 2, 89312 Günzburg, Germany. E-mail address: [email protected] (W. Klingler). 1 Contributed equally. 0300-9572/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.resuscitation.2013.11.008
deficiency is predicted correctly with a specificity of only 58% and a sensitivity of 81% within the first 24 h after CA, even by experienced emergency specialists.11 Radiological procedures and the measurement of the intracranial pressure as well as the regulation of the cerebral oxygen consumption are still too unspecific to be used as outcome parameters following CPR.12,13 Biochemical markers such as the neuronal specific enolase or the serum protein S-100 are not reliable markers for an unfavourable outcome soon after CPR because of their high variability and the time delay involved, ranging from 12 to 24 h.8,9,14,15 The rapid recovery of brain stem reflexes after successful CPR correlates with good neurological rehabilitation with a positive predictive value of up to 65%.16 Electrophysiological methods show the most promise in the prediction of neurological outcome. That being said, the measurement of the somatosensory evoked potentials (SSEP) or the electroencephalogram (EEG) is a very time consuming method and specialists are needed for interpretation. In these methods strong indicators for an unfavourable neurological outcome are an isoelectric EEG as well as a burst suppression pattern.13 Because of
222
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arithmetic algorithms, the bispectral index (BIS) allows for the rapid and standardised assessment of the cerebral function and the cerebral metabolism without specific EEG knowledge. The suppression ratio (SR) is a second parameter measured by the majority of commercially available BIS monitors; it describes the ratio of isoelectric EEG. A number of case reports point out that the BIS could be a useful method for monitoring the cerebral function as well as being a prognostic indicator concerning survival and neurological outcome after CA.21–26 Our study examines the clinical and preclinical application of BIS monitoring during CPR, both in intensive care units and in the field by emergency personnel. 2. Methods The study was carried out at German university hospitals in Ulm and Regensburg between August 2005 and April 2008. Both centres provide an ambulance service with experienced emergency doctors. The study was approved by the ethics commissions of the University of Ulm and the University of Regensburg. Because of the study content, it was not possible to obtain patient consent to participate before starting BIS monitoring. As soon as the patients recovered to an adequate cerebral state, informed consent was obtained. If the patient remained in an unfavourable neurological state, the approval for study participation was obtained from the patient’s legal representative. Exclusion criteria were patients younger than 18 years of age, extreme structural brain damage, hypothermia ( 45 during the first 24 h after ROSC as a good predictor of a favourable neurological outcome.30 Shibata et al. performed BIS monitoring in 10 patients with ROSC after admission to the ICU. The average BIS values of the four patients with favourable neurological outcome achieved values >80 during the first 30 min after admission. The patients who died after
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hours after initiation of CPR Fig. 2. Time course of BIS and SR monitoring. For each hour (after the initiation of CPR), the average BIS and SR values ± standard error of the mean from initiation of CPR, divided into patients with favourable (CPC 1 or 2) and with unfavourable neurological outcome (CPC 3–5) are shown. Regarding BIS, one can see the greatest difference (of 25) between the patients with a CPC 1 or 2 and the patients with CPC 3–5 four hours after initiation of CPR. The SR shows a difference of 37 between the patients with CPC 1 or 2 and the patients with CPC 3–5 four hours after the initiation of CPR.
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Fig. 3. Boxplot of BIS and SR. Boxplot with median, 25th quartile, 75th quartile, range and mean () of the BIS (on the left side) and the SR (on the right side) during the first 4 h after the initiation of CPR. 16 patients were classified as CPC 1, three patients as CPC 2, four patients as CPC 3, three patients as CPC 4 and no patient as CPC 5.
ROSC achieved only an average BIS of 9.7 ± 16 (mean ± standard deviation).25 Seder et al. started BIS monitoring with a median time delay of 280 min after ROSC.32 Furthermore a number of case reports point out the fact that BIS monitoring could be used as a means to monitor cerebral function and cerebral perfusion during CPR.21–24,26 In all of these studies, a BIS > 35–50 was described as a marker for adequate cerebral perfusion during CPR efforts and as a marker for a favourable neurological outcome.29,30 This study
confirms these findings with a comparably high number of cases. Chollet-Xémard et al. were able to show that BIS monitoring is not useful for the prediction of loss of life during or after CPR; neurological recovery in survivors was not investigated in this study.34 BIS is a computed EEG derived parameter and was developed to estimate depth of general anaesthesia. BIS levels below 40 are mainly determined by the ratio of isoelectric EEG, i.e. by the SR.35 Indeed, in the current study there is only a small difference in the
C. Selig et al. / Resuscitation 85 (2014) 221–226
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Fig. 4. Receiver operating characteristic (ROC). ROC analysis of all 26 patients who survived 1 month for the average BIS (on the left side) and the average SR (on the right side) during the first 4 h after initiation of CPR to predict an unfavourable neurological outcome.
5. Conclusion
Fig. 5. Odds ratio. Odds ratio (95% confidence interval) for the prediction of an unfavourable neurological outcome for the average BIS and SR during the first four hours after the initiation of CPR. The OR for BIS is 0.921 (95% CI 0.87–0.99) and for the SR 1.081 (95% CI 1.02–1.26).
statistical parameters of BIS and SR using a threshold criteria of BIS < 40. A prognostic parameter to predict an unfavourable neurological outcome should achieve a very high specificity. This is necessary to avoid patients with a favourable prognosis being falsely assigned to the patient group with an unfavourable prognosis as this could mean a de-escalation in their medical treatment strategy.14 In our study we measured the average BIS and SR during the first 4 h after the initiation of CPR. We were able to predict an unfavourable neurological outcome with a specificity of 89.5% and a sensitivity of 85.7%. Because of comorbidity, e.g. recurrence of myocardial infarction, it is difficult to predict a favourable outcome. To compare our results, the specificity and sensitivity of the SSEP N20 response after stimulation of the median nerve, which is one of the most established electrophysiological investigation methods for the prediction of an unfavourable neurological outcome, is given below.13,36 The absence of the SSEP N20 response after stimulation of the median nerve within the first 8–24 h after ROSC predicts an unfavourable neurological outcome with a specificity of 72% and a sensitivity of 87%.11 Absence of the SSEP N20 response within the first 7 days after CPR predicts an unfavourable neurological outcome with a specificity of 100%, however the sensitivity is only 28–73%.12 Recently Stammet et al. were able to show that the combination of serum level of S100B and BIS monitoring even more accurately predicts outcome in patients treated using therapeutic hypothermia after successful CPR. The serum level of S100B was measured 48 h after ROSC. The lowest BIS values in patients with unfavourable neurological outcome were measured medially 5 [4.0;14.5] h after ROSC. We were able to predict an unfavourable neurological outcome in a similar timeframe within 4 h after ROSC.37
Predicting the neurological recovery after CPR is difficult despite several established investigations, such as cerebral imaging, determination of intracranial pressure, clinical and biochemical parameters. The results of this study show, that BIS respectively SR monitoring may be a promising electrophysiological tool due to comparably high specificity and other advantages: it is easy to perform, it is low in weight, it is transportable and it delivers data almost in real time. In contrast to SSEP and conventional EEG, interpretation of BIS and SR does not require expert knowledge.17–23,25,30–33 Careful interpretation of BIS and SR early after CPR can help to generate a conclusion about the neurological prognosis. Nevertheless, therapeutic decisions have to be confirmed by further examinations due to the far-ranging consequences of false positive results.
Conflict of interest statement Departmental funding only. None of the author has received any kind of compensation or research support from the manufacturers of BIS equipment.
Acknowledgements We would like to thank the staff of the emergency services, the emergency departments and the intensive care units of the university hospitals in Ulm and Regensburg for their help and support in the carrying out of this work. Special thanks go to Dr. J. Dreyhaupt of the Department of Biometrics of the University of Ulm and to Nathan Ingvalson B.Sc. for linguistic support.
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