Resuscitation 80 (2009) 213–216 Contents lists available at ScienceDirect Resuscitation journal homepage: www.elsevier.com/locate/resuscitation Clinical paper Bispectral index monitoring is useless during cardiac arrest patients’ resuscitation夽,夽夽,♦ Charlotte Chollet-Xémard a,∗ , Xavier Combes a , François Soupizet a , Patricia Jabre a,b , Candice Penet a , Catherine Bertrand a , Alain Margenet a , Jean Marty a a Service d’Anesthésie Réanimation et SAMU 94, CHU H Mondor (AP-HP), 94000 Créteil, France b EA 3409, CHU Avicenne (AP-HP), 93000 Bobigny, France a r t i c l e i n f o Article history: Received 21 May 2008 Received in revised form 12 September 2008 Accepted 17 October 2008 Keywords: Advanced life support Cardiac arrest Resuscitation Monitoring a b s t r a c t Aim: It has been suggested that out-of-hospital bispectral (BIS) index monitoring during advanced cardiac life support (ACLS) might provide an indication of cerebral resuscitation. The aims of our study were to establish whether BIS values during ACLS might predict return to spontaneous circulation, and whether BIS values on hospital admission might predict survival. Materials and methods: This was a prospective observational study in 92 patients with cardiac arrest who received basic life support from a fire-fighter squad and ACLS on arrival of an emergency medical team on the scene. BIS values, electromyographic activity, and signal quality index were recorded throughout resuscitation and out-of-hospital management. Results: Seven patients had recovered spontaneous cardiac activity by the time the medical team arrived on scene. Of the 92 patients, 62 patients died on scene and 30 patients returned to spontaneous cardiac activity and were admitted to hospital. The correlation between BIS values and end-tidal CO2 during the first minutes of ACLS was poor (r2 = 0.02, P = 0.19). Of the 30 admitted patients, 27 died. Three were discharged with no disabilities. There was no significant difference in BIS values on admission between the group of patients who died and the group who survived (P = 0.78). Conclusions: Although BIS monitoring during resuscitation was not difficult, it did not predict return to spontaneous cardiac activity, nor survival after admission to intensive care. Its use to monitor cerebral function during ACLS is therefore pointless. © 2008 Elsevier Ireland Ltd. All rights reserved. Introduction Bispectral (BIS) index measurement is a non-invasive procedure for monitoring cerebral function. It has been used for several years in operating rooms to monitor anaesthesia depth and is especially useful in preventing return to awareness during general anaesthesia.1–4 Although initially designed for operating room use 夽 A Spanish translated version of the summary of this article appears as Appendix in the final online version at doi:10.1016/j.resuscitation.2008.10.011. 夽夽 This work was performed in the Service de Médecine d’Urgence et de Réanimation (SMUR) of Henri-Mondor University Hospital and at Paris XII Val-De-Marne School of Medicine, 94000 Créteil. ♦ This work was presented in part at the annual meeting of the Société Française d’Anesthésie et de Réanimation, Paris, France, September 2007, and at the annual meeting of the Société Française de Médecine d’Urgence, Paris, June 2007. ∗ Corresponding author. E-mail address: charlotte.chollet@hmn.aphp.fr (C. Chollet-Xémard). 0300-9572/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.resuscitation.2008.10.011 only, it has also been used in intensive care units (ICU) to monitor prolonged continuous sedation and detect onset of brain death in severely comatose patients.5 In addition, several case reports have suggested that the BIS index might be an indicator of cerebral perfusion during cardiopulmonary resuscitation (CPR).6–11 There may thus be a relationship between BIS values and arterial pressure. However, The results of two recent small case series studying this relationship have been conflicting.12,13 The more recent case series carried out in an emergency department reported that the BIS index was a poor marker of cerebral perfusion during resuscitation, whereas the earlier series suggested that BIS values after resuscitation in the emergency room do predict post-resuscitation outcomes.12,13 We conducted a prospective observational out-of-hospital study in a large series of cardiac arrest patients receiving advanced cardiac life support (ACLS) from a medical emergency team. The primary objective of the study was to establish whether BIS values during resuscitation might predict return to spontaneous circulation. The 214 C. Chollet-Xémard et al. / Resuscitation 80 (2009) 213–216 secondary objective was to determine whether BIS values on hospital admission of patients with a return to spontaneous circulation might predict survival. given by discharge from hospital with no or moderate neurological impairment, was determined. Statistical analysis Methods This was a prospective observational study conducted by the out-of-hospital emergency medical unit (SMUR) of a French university hospital (Henri Mondor Hospital, Créteil) from March 2006 to June 2007. The study was approved by the local ethical committee which waived the informed consent requirement on the grounds that the monitoring was non-invasive and unrandomized. Our SMUR serves 1,300,000 inhabitants and responds to about 10,000 emergency calls a year. It is equipped with five mobile intensive care units (MICU). The minimum MICU team is an ambulance driver, a nurse anaesthetist, and a senior physician specialized in either emergency medicine (>90% of physicians) or anaesthesiology. France is divided into medical regions, each with a call centre which runs the MICUs based in the region’s hospitals. All calls to the centre concerning cardiac arrest are transferred to a physician who immediately dispatches a MICU as well as a fire department rescue team. Fire-fighter squads are more numerous than MICUs and often closer to the patient. The squad immediately initiates basic life support (BLS) including external cardiac massage with an active compression–decompression device, face mask ventilation, and semi-automatic defibrillator use. On arrival, the MICU provides ACLS according to recent European Resuscitation Council guidelines.14 We defined cardiac arrest as absence of both spontaneous ventilation and carotid palpable pulse. As soon as the first rhythm was recorded, the physician administered an intravenous bolus of 1 mg adrenaline (epinephrine) every 3 min to patients with asystole or pulseless electrical activity, or shock treatment (150J biphasic) to patients with ventricular fibrillation or pulseless ventricular tachycardia. When the procedures for ACLS had been initiated (i.e. tracheal intubation with immediate start of end tidal carbon dioxide (ETCO2 ) monitoring, peripheral venous line placement, administration of the first adrenaline bolus, and cardiac shock when indicated), a member of the MICU applied the BIS monitor sensor electrode (BIS® XP, software version 3.12, four-electrode sensor, Aspect Medical Systems, Newton, MA, US) to the patient’s forehead after cleansing the skin with alcohol. BIS values, electromyographic activity, and signal quality index (SQI) were recorded throughout resuscitation and out-of-hospital management. BIS monitoring did not affect the standard procedures of cardiac arrest management. Outcome measures The following demographic and clinical data were collected from standard forms that had been completed according to Utstein Template Guidelines for data collection15 : sex, age, medical history, temperature, estimated body weight, place where cardiac arrest occurred, first recorded electrical rhythm, presence of person witnessing cardiac arrest, amount of adrenaline administered, principal time intervals and outcomes. ETCO2 values were recorded throughout management. In patients with a return to spontaneous circulation, non-invasive blood pressure was measured every 5 min and pulse oxymetry was recorded continuously. BIS values were taken into account only when the SQI was above 50%. BIS was monitored until the end of ACLS in patients who died on scene and until hospital admission in patients with a return to spontaneous cardiac activity. The survival rate of the patients admitted to the ICU, as Data are reported as means (±1 S.D.) for continuous variables and as percentages for qualitative variables. A Wilcoxon rank-sum test was used to compare initial BIS values between patients who returned to spontaneous cardiac activity and those who died on scene. It was also used to compare the BIS values on hospital admission between patients who died in hospital and patients who survived and were discharged. The Spearman’s rank correlation coefficient has been calculated to test the correlation between the initial BIS and ETCO2 values. All P values were two-sided and the difference was considered significant if P was less than 0.05. Statistical tests were performed using SAS statistical software (version 9.1.3; SAS Institute Inc., Cary, North Carolina). Results Overall, 92 patients were included in this prospective study conducted between March 2006 and March 2007. Their main demographic characteristics are shown in Table 1. Five patients had recovered spontaneous cardiac activity by the time the medical team arrived on scene thanks to early BLS and automatic defibrillation provided by the fire-fighter squad. In most patients (71%), the initial cardiac rhythm recorded by the medical team was asystole. There was no difficulty in monitoring BIS in all of the patients. The mean time to obtain a first BIS value was 120 ± 75 s after application of the sensor. The mean SQI (%) value during monitoring was 90 ± 41. The initial BIS values during ACLS are shown in Figure 1 for the 25 patients who returned to spontaneous cardiac activity and for the 62 patients who did not and who died on scene. There was no significant difference in these values between the two groups of patients (P = 0.78). The correlation between ETCO2 and BIS values during the first minutes of ACLS in all patients was poor (r = 0.21, P = 0.06) (Figure 2). During the pre-hospital time, 1 of the 30 patients who returned to spontaneous cardiac activity was sedated with midazolam and 2 required muscle relaxant. Of the Table 1 Baseline patient characteristics. Gender (male/female) Age (years) (mean ± S.D.a ) Estimated weight (kg) (mean ± S.D.) Place of cardiac arrest, n Home Public place Workplace Temperature ( ◦ C) (mean ± S.D.) Suspected cardiac disease, n (%) First recorded rhythm, n Asystole Ventricular fibrillation Pulseless electrical activity Return to spontaneous cardiac activity Witnessed cardiac arrest, n (%) Bystander CPR, n (%) Automated external defibrillation, n (%) Dead on scene, n (%) Time from collapse (min) (means ± S.D.) To start of BLS To start of ACLS To return of spontaneous circulation (n = 30) To discontinuation of unsuccessful ACLS (n = 62) Total adrenaline dose (mg) (mean ± S.D.) a S.D. = standard deviation. 69/23 60 ± 17 80 ± 19 74 16 2 35 ± 2 52 (56) 73 1 13 5 62 (67) 26 (28) 23 (25) 62 (67) 9±7 23 ± 12 30 ± 19 50 ± 20 9±6 C. Chollet-Xémard et al. / Resuscitation 80 (2009) 213–216 215 Discussion Figure 1. Initial BIS values during ACLS. Figure 2. Correlation between initial BIS and ETCO2 values during ACLS. 30 patients who returned to spontaneous cardiac activity and were admitted to intensive care, 27 died. Three were discharged with no disabilities. There was no significant difference in BIS values on admission between the group of patients who died and the group who survived (P = 0.78) (Figure 3). Figure 3. BIS values on hospital admission in survivors who were later discharged from hospital and in patients who returned to spontaneous cardiac activity but who died in hospital. Our results show, first, that BIS values during out-of-hospital CPR do not predict return to spontaneous cardiac activity and are not correlated with end-tidal CO2 during resuscitation, and second that early BIS values in the patients who returned to spontaneous cardiac activity after initial resuscitation do not predict survival. These results confirm the conclusions of Fatovitch et al. on 21 patients who underwent out-of-hospital resuscitation after cardiac arrest. The BIS values they recorded on arrival in the emergency department were a poor indicator of cerebral perfusion.13 Although the main explanation given by the authors for this negative result was the role of mechanical artefacts induced by head movement during resuscitation, another possible explanation could have been the delay between the onset of cardiac arrest and the start of BIS monitoring which only began once the patient had received initial resuscitation and been transported to hospital. This alternative explanation, however, is not borne out by our study. We did not observe a relationship between BIS values and ETCO2 , a highly reliable haemodynamic parameter during resuscitation, even though we initiated BIS monitoring much earlier and on scene. Moreover, our BIS values were not predictive of return to spontaneous cardiac activity at any time during the resuscitation process. A few reported cases have suggested that BIS values might reflect cerebral oxygenation. Rapid decreases in BIS values have been described in anaesthetized patients during severe hypoxia, severe hypotension or cardiac arrest.8–10 These cases differ from ours as cardiac arrest occurred during BIS monitoring in the operating room and was treated immediately. In our 30 patients who survived on scene, we did not observe any increase in BIS values in the minutes before or after return to spontaneous cardiac activity. We thus confirm that BIS monitoring during resuscitation seems pointless. BIS monitoring was originally validated in patients sedated with drugs such as propofol, midazolam, isoflurane and alfentanil. Further validation was obtained in larger trials in patients under general anaesthesia and paralysed with muscle relaxants.16,17 We do not think that our results might have been distorted by different drugs used in the resuscitated patients. Only one patient required administration of midazolam after return of spontaneous circulation and epinephrine which was administrated in several patients is not supposed to influence BIS level. Muscle electromyographic activity is known to lead to overestimation of BIS values. A sharp decrease in BIS values has been reported just after muscle relaxant administration in deeply sedated patients in intensive care.18 Most of our patients who recovered on scene and were admitted to hospital were not sedated and only two required a muscle relaxant. BIS may have been overestimated in these two patients because of electromyographic activity although other factors may also have been involved. For instance, the use of electric devices such as forced airwarming blankets or cardiac pacers before hospital admission can increase BIS values.19,20 Movement in patients with spontaneous cardiac activity can cause artefacts whether it is due to external chest compression or to shivering, stretcher transportation or vehicle vibration. On several occasions we observed a sharp increase in BIS values when we started the ambulance engine. Our study has several limitations. First, our series of cardiac arrest patients may not have been statistically large enough. We were unable to formulate a strict hypothesis to calculate the number of patients to be included as published data on BIS are limited. Despite this, our results were significantly negative. No trend was observed between BIS values and probability of return to spontaneous cardiac activity. Second, we discontinued BIS monitoring on admission of the patient to hospital, i.e. monitoring lasted for about 1 h after resuscitation. Extending monitoring for several 216 C. Chollet-Xémard et al. / Resuscitation 80 (2009) 213–216 hours after admission might predict outcomes better. Third, most of our patients were already in asystole, thus reflecting the delay in initiating ACLS. It is well established that initial rhythm is a key prognostic factor in cardiac arrest patients and that the prognosis is better for ventricular fibrillation. BIS values might be a good indicator of cerebral perfusion only in patients who are resuscitated immediately, as happens in an operating room. Their value may be lost after several minutes without BLS, i.e. with minimal cerebral perfusion and oxygenation. In conclusion, our results indicate that BIS use in indications other than the validated indication of monitoring the depth of anaesthesia should be the subject of great caution in the absence of further clinical investigations. In our hands, BIS values in patients who recovered from cardiac arrest did not predict survival. Because of this, cerebral monitoring with BIS should not be used during out-of-hospital resuscitation. Conflict of interest statement None to declare. References 1. Kearse Jr LA, Manberg P, Chamoun N, deBros F, Zaslavsky A. Bispectral analysis of the electroencephalogram correlates with patient movement to skin incision during propofol/nitrous oxide anesthesia. Anesthesiology 1994;81: 1365–70. 2. Gan TJ, Glass PS, Windsor A, et al. Bispectral index monitoring allows faster emergence and improved recovery from propofol, alfentanil, and nitrous oxide anesthesia. BIS Utility Study Group. Anesthesiology 1997;87:808–15. 3. Liu J, Singh H, White PF. 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