BJA Advance Access originally published online on September 21, 2006
British Journal of Anaesthesia 2006 97(6):842-847; doi:10.1093/bja/ael253
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Effect of an intubation dose of rocuronium on Spectral Entropy and Bispectral IndexTM responses to laryngoscopy during propofol anaesthesia
University Department of Anaesthesia and Intensive Care Medicine, CHR de la Citadelle Liege, Belgium
*Corresponding author: Boulevard du 12eme de Ligne, 1, 4000 Liege, Belgium. E-mail: pol.hans{at}chu.ulg.ac.be
Accepted for publication July 13, 2006.
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Background. The spectral entropy of the electroencephalogram has been proposed to monitor the depth of anaesthesia. State Entropy (SE) reflects the level of hypnosis. Response Entropy (RE), computed from electroencephalogram and facial muscle activity, reflects the response to nociceptive stimulation. We evaluated the effect of rocuronium on Bispectral IndexTM (BIS) and entropy responses to laryngoscopy.
Methods. A total of 25 patients were anaesthetized with propofol using a target-controlled infusion. At steady state, they randomly received 0.6 mg kg–1 rocuronium (R) or saline (S). After 3 min, a 20 s laryngoscopy was applied. BIS, RE and SE were recorded continuously and averaged over 1 min during baseline, at steady state, 2 min after R or S administration (R/S+2) and 0, 1, 2 and 3 min after laryngoscopy (L0, L1, L2, L3).
Results. At R/S+2, the RE–SE gradient was higher in Group S than in Group R. Laryngoscopy provoked an increase in BIS, RE and SE. Comparing R/S+2 and L0 values in Groups R and S, BIS increased from 43 (6) to 49 (8) and 42 (9) to 51 (15), SE increased from 43 (7) to 50 (8) and 41 (10) to 55 (12), and RE increased from 46 (8) to 54 (9) and 47 (12) to 66 (15), respectively. BIS and SE did not differ between groups. At L0, RE and RE–SE were higher in Group S [66 (15) and 11 (4), respectively] than in Group R [54 (9) and 4 (2), respectively].
Conclusions. Rocuronium alters the RE–SE gradient and the RE and RE–SE responses to laryngoscopy. Muscle relaxation may confound interpretation of entropy monitoring.
Keywords: anaesthetic techniques, laryngoscopy; anaesthetics i.v., propofol; monitoring, bispectral index; neuromuscular block, rocuronium; pain, acute; spectral entropy
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The Bispectral IndexTM (BIS) is a processed EEG variable commonly used to monitor the hypnotic component of anaesthesia and guide the administration of volatile and i.v. anaesthetics.1–3 Spectral entropy is another processed EEG variable that has been introduced recently in clinical practice for monitoring depth of anaesthesia. The Entropy module (M-EntropyTM; Datex-Ohmeda, Helsinki, Finland) provides two different Entropy values: the State Entropy (SE) and the Response Entropy (RE). SE is computed over the EEG dominant frequency band of the EEG (0.8–32 Hz) and ranges between 0 and 91. It is thought to reflect the hypnotic component of anaesthesia. RE is computed over a larger frequency domain (0.8–47 Hz) including both the EEG activity and the EMG activity of facial muscles, and ranges between 0 and 100. RE and the RE–SE gradient increase in response to nociceptive stimulations and are thought to reflect the nociceptive–anti-nociceptive balance during general anaesthesia.
Neuromuscular blocking drugs may influence depth of anaesthesia monitoring through two main mechanisms: the direct effect of neuromuscular block on the depth of anaesthesia itself and the effect of EMG activity on the depth of anaesthesia indices such as BIS. The first mechanism is probably related to a decrease in muscle-generated sensory inputs to the brain. It could explain why pancuronium has been demonstrated to decrease halothane requirement and to deepen the level of anaesthesia.4 Second, EMG activity has been shown to falsely elevate BIS values both in anaesthetized and sedated patients5 6 and overestimation of BIS in sedated intensive care unit patients has been revealed by the administration of neuromuscular blocking agent.7 These effects of neuromuscular blocking agents on depth of anaesthesia monitoring probably depend on the background anaesthetic level, and may be less marked at deep levels of anaesthesia. At deep levels of anaesthesia, central afferentation and EMG activity are suppressed by anaesthetic agents. This would explain why it has been reported that antagonism of neuromuscular block but not muscle relaxation affects the depth of anaesthesia.8
In so far as RE is influenced by the degree of facial muscles activity, one may question whether RE and its response to nociceptive stimulation is affected by muscle paralysis.
The present study was designed to assess the effect of an intubation dose of rocuronium on EEG spectral entropy and BIS responses to laryngoscopy in patients undergoing surgery under general anaesthesia.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
After approval by the Regional Hospital Ethics Committee and informed consent, 25 adult (ASA status I or II) patients undergoing routine surgery under general anaesthesia were enrolled in this double-blind randomized study.
Premedication consisted in alprazolam 0.5 mg and atropine 0.5 mg given orally 1 h before surgery. Upon arrival in the operating room, non-invasive arterial pressure monitoring, ECG and pulse oximetry were instituted in all patients (Datex-OhmedaTM S/5TM, Helsinki, Finland). BIS was monitored using the XP device (version 4.0) and a specific quatro sensor (Aspect Medical Systems, Newton, MA, USA and Leiden, The Netherlands). RE and SE were monitored with the Datex-Ohmeda S/5 Entropy Module (M-EntropyTM), using a specific entropy sensor (Datex-Ohmeda Division, Instrumentarium Corporation, Helsinki, Finland). Both sensors were applied appropriately to the patient's forehead, the BIS sensor on the left side and the Entropy sensor on the right side.
In all patients, general anaesthesia was induced using a propofol target-controlled infusion (PPF TCI, model of Marsh,9 DiprifusorTM; Alaris Medical Systems, Hants, UK). The initial target was set at 2.5 µg ml–1. After loss of the eyelash reflex, patients' lungs were ventilated with a face mask. The target concentration was increased by steps of 0.5 µg ml–1 every 4 min until obtaining a stable BIS value between 40 and 50. The steady state was considered as achieved once stable BIS values were observed during at least 4 min and once DiprifusorTM-estimated plasma and effect-site concentrations were equal. The propofol target concentration was not changed further. One minute after having achieving steady state, patients randomly received either rocuronium 0.6 mg kg–1 (Group R; n=13) or the same volume of saline (Group S; n=12). Three minutes later, laryngoscopy was applied for 20 s by the same anaesthetist, blinded to the anaesthesia protocol, without attempting to intubate the trachea. BIS, RE and SE, mean arterial pressure (MAP) and heart rate (HR) were recorded continuously using the Rugloop II© monitor software (Demed, Temse, Belgium) at a sampling rate of 1 s–1 for BIS and 1 per 5 s for the other variables. Each variable was averaged over the minute after pre-defined time points: before induction (Baseline), at steady state before rocuronium or saline administration (SS), 2 min after rocuronium or saline administration (R/S+2) and 0, 1, 2 and 3 min after laryngoscopy (L0, L1, L2 and L3). Propofol effect-site concentrations at steady state were noted. Neuromuscular transmission was monitored by accelerography and assessed using the train of four (TOF) stimulation mode. Data expressed as mean (SD) were analysed using two-tailed unpaired t-tests or two-way mixed design ANOVA and Tuckey's HSD tests, as appropriate. P<0.05 was considered statistically significant.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
One patient from Group S was excluded from the study because of unreliable entropy recording. Mean age, weight and height were 43 (18) and 46 (12) yr [t(22)=0.62, NS], 68 (17) and 74 (17) kg [t(22)=0.37, NS], and 169 (9) and 171 (11) cm [t(22)=0.56, NS] in Groups R and S, respectively. Gender distribution was also similar in the two Groups [6/7 and 6/5 male/female in Groups R and S,
]. There was no significant difference in propofol effect-site concentrations in Groups R and S at steady state [2.7 (0.4) and 2.6 (0.4) µg ml–1, t(22)=0.61, NS]. When laryngoscopy was performed, the TOF count was 0 in all but two patients in Group R (in whom it was 3), and 4 in all patients in Group S. A substantial number of patients moved in response to laryngoscopy in both groups [5/13 in Group R and 6/11 in Group S, 
, NS]. Movements ranged between slight movements of extremities to larger purposeful movements and coughing. Weak movements were even observed in four patients with a TOF count of 0. The patients of Group R who moved in response to laryngoscopy and those who had not a TOF count of 0 were not excluded from the analysis. BIS significantly decreased from Baseline to SS in Groups R and S (Table 1 and Fig. 1). Two minutes after rocuronium or normal saline administration (R/S+2), BIS was unchanged in both groups. Laryngoscopy induced an immediate and significant increase in BIS that rapidly faded, returning to R/S+2 value at L3, but there was no significant difference between groups.
|
|
SE followed a trend similar to that of BIS (Table 1 and Fig. 2). In contrast, RE had an initial trend comparable with BIS and SE, but increased more markedly in Group S than in Group R after laryngoscopy (Table 1 and Fig. 3). Similarly, the RE–SE gradient (Table 1 and Fig. 4) was initially comparable between groups but a significant difference appeared between Groups R and S at R/S+2. Laryngoscopy did not increase the RE–SE gradient in Group R compared with Group S, where this gradient increased and remained significantly higher than in Group R from L0 to L2. The maximum value of the RE–SE gradient observed between L0 and L3 was significantly higher in Group S than in Group R [12 (5) and 4 (2), respectively]. This value was higher than 10 in 6/11 and 0/13 patients in Groups S and R, respectively.
|
|
|
Rocuronium administration produced an increase in HR that remained significantly higher in Group R than in Group S from R/S+2 to L3 (Table 1). After an initial decrease from Baseline to SS and R/S+2, laryngoscopy was associated with a moderate significant increase in MAP at L1 and L2, but there was no difference between groups.
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The main findings of the present study are that, although BIS and SE were not affected, rocuronium administration affects RE and the RE–SE gradient during a steady-state anaesthesia achieved with a propofol TCI and the response of those indices to a nociceptive stimulation. An intubating dose of rocuronium reduces the magnitude of the RE–SE gradient in the absence of nociceptive stimulation. The increase in RE and in the RE–SE gradient induced by a nociceptive stimulation was significantly lower in patients who received rocuronium than in patients who did not.
One could argue that rocuronium administration may deepen the anaesthetic level and, therefore, blunt the response of EEG-derived indices to nociceptive stimulation, independent of the depth of the neuromuscular block. BIS and SE are primarily considered as indicators of electrocortical activity. The BIS device used in the present study was the BIS XP, software version 4.0, which should eliminate artifacts generated by the EMG activity. It is worth noting that overestimation of BIS has been suggested by the administration of neuromuscular blocking agents in intensive care patients.7 Those patients were sedated with midazolam and sufentanil to achieve a Sedation-Agitation Scale value equal to 1 and the decrease in BIS value after neuromuscular block was significantly correlated with BIS and EMG values before administration of the neuromuscular blocking agent. In that study, BIS overestimation related to high EMG activity was still present with the new BIS XP monitor. In another study performed in intensive care patients receiving light sedation (BIS 65–80), it has also been shown that muscle relaxation deepens the level of anaesthesia as assessed by BIS monitoring.10 In contrast, it has been reported that antagonism of neuromuscular block but not muscle relaxation affects the depth of anaesthesia monitored by BIS and middle-latency auditory evoked potentials.8 In that study, patients scheduled for routine surgery were anaesthetized with propofol and remifentanil TCI to reach a BIS value around 55. These may explain why we did not observe any significant change in BIS or in SE value after rocuronium administration. The conflicting results regarding BIS and EMG activity are likely explained by a lower degree of sedation in intensive care than in surgical patients. According to the afferentation theory, neuromuscular blocking agents may affect electrocortical activity by decreasing proprioceptive afferent activity from muscles,11 and afferentation probably has a weak central effect.8 Therefore, the effect of neuromuscular blocking agents on BIS and SE can be seen in lightly sedated patients but is undetectable during anaesthesia. However, the power of our study might not have been high enough to detect an effect of muscle relaxation on BIS and SE values during steady-state propofol anaesthesia in the absence of nociceptive stimulation. The modest response of BIS and SE to nociceptive stimulation was present in both. However, these differences were not significant. Again, the power of our study may not have been enough to detect an effect on the response of those variables to laryngoscopy and no conclusion can be drawn.
RE measures both EEG and facial EMG activity and an increase in RE and in the RE–SE gradient indicates frontal EMG activation, which may occur during painful stimulation with inadequate anaesthesia.12 Recently, RE increase during painful stimulation has been suggested to be independent of recovery from muscle paralysis and to occur more frequently in patients anaesthetized with isoflurane 0.8% than with 1.4%.13 Those results are not in agreement with our study. An important difference between the two studies relates to the intensity of the nociceptive stimulation, laryngoscopy or a 5 s 50 Hz tetanic stimulation at the wrist. In our study, patients received propofol only and no anti-nociception. Therefore, absence of analgesia combined to an intense nociceptive stimulation should result in a higher frontal EMG activity than a weak painful stimulation in patients anaesthetized with isoflurane. We have demonstrated that this response can be almost abolished by muscle relaxation, as a RE–SE gradient higher than 10 was not seen in any of the patients who received neuromuscular blocking agent. We demonstrated also that muscle relaxation clearly affects the RE–SE gradient in the absence of nociceptive stimulation and during stable steady-state hypnotic conditions.
Despite the analysis of Group R including two patients who were incompletely paralysed and five patients who moved in response to laryngoscopy, we observed significant differences in RE–SE between groups of patients during steady-state propofol anaesthesia, in the presence and in the absence of nociceptive stimulation. Thus, the effect of neuromuscular blocking agent on the RE–SE gradient may be considered as robust. Further studies should establish dose–response curves between the depth of neuromuscular block, the nociceptive–anti-nociceptive balance and the RE–SE gradient. We agree with the conclusion of Wheeler and colleagues13 that RE may be useful in identifying inadequate balance between nociception and anti-nociception but our results strongly suggest that the RE response can be affected by muscle relaxation.
The HR was significantly higher in Group R than in Group S after rocuronium administration but was not clinically relevant and did not change in response to laryngoscopy. Finally, laryngoscopy provoked a significant although not clinically relevant increase in MAP in both groups. The increase peaked 1–2 min later than the increase in BIS and entropy and was similar in both groups.
In conclusion, a 20 s laryngoscopy provokes an increase in MAP, BIS, RE, SE and RE–SE gradient. Low values of BIS and entropy during stable general anaesthesia does not necessarily mean that those indices will not increase in response to nociceptive stimulation. The increase in RE and the RE–SE gradient observed during stable nociceptive–anti-nociceptive balance conditions are affected by rocuronium. We suggest that muscle relaxation may be a confounding factor when using entropy to assess the patient's response to nociceptive stimulations.
|
Acknowledgments |
|---|
This study was funded by the Department of Anaesthesia and ICM, Liege University Hospital, Liege, Belgium.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1 Glass PS, Bloom M, Kearse L, Rosow C, Sebel P, Manberg P. Bispectral analysis measures sedation and memory effects of propofol, midazolam, isoflurane, and alfentanil in healthy volunteers. Anesthesiology 1997; 86:836–47[CrossRef][Web of Science][Medline]
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[CrossRef][Web of Science][Medline]
3 Song D, Joshi GP, White PF. Titration of volatile anesthetics using bispectral index facilitates recovery after ambulatory anesthesia. Anesthesiology 1997; 87:842–8[CrossRef][Web of Science][Medline]
4 Forbes AR, Cohen NH, Eger EI. Pancuronium reduces halothane requirement in man. Anesth Analg 1979; 58:497–9
5 Bruhn J, Bouillon TW, Shafer SL. Electromyographic activity falsely elevates the bispectral index. Anesthesiology 2000; 92:1485–7[CrossRef][Web of Science][Medline]
6 Riess ML, Graefe UA, Goeters C, van Aken H, Bone HG. Sedation assessment in critically ill patients with bispectral index. Eur J Anaesthesiol 2002; 19:18–22[CrossRef][Web of Science][Medline]
7 Vivien B, Di Maria S, Ouattara A, Langeron O, Coriat P, Riou B. Overestimation of Bispectral Index in sedated intensive care unit patients revealed by administration of muscle relaxant. Anesthesiology 2003; 99:9–17[CrossRef][Web of Science][Medline]
8 Vasella FC, Frascarolo P, Spahn DR, Magnusson L. Antagonism of neuromuscular blockade but not muscle relaxation affects depth of anaesthesia. Br J Anaesth 2005; 94:742–7
9 Marsh B, White M, Morton N, Kenny GN. Pharmacokinetic model driven infusion of propofol in children. Br J Anaesth 1991; 67:41–8
10 Simmons LE, Riker RR, Prato BS, Fraser GL. Assessing sedation during intensive care unit mechanical ventilation with the Bispectral Index and the Sedation-Agitation Scale. Crit Care Med 1999; 27:1499–504[CrossRef][Web of Science][Medline]
11 Lanier WL, Iaizzo PA, Milde JH, Sharbrough FW. The cerebral and systemic effects of movement in response to a noxious stimulus in lightly anesthetized dogs. Possible modulation of cerebral function by muscle afferents. Anesthesiology 1994; 80:392–401[Web of Science][Medline]
12 Viertio-Oja H, Maja V, Sarkela M, et al. Description of the Entropy algorithm as applied in the Datex-Ohmeda S/5 Entropy Module. Acta Anaesthesiol Scand 2004; 48:154–61[CrossRef][Web of Science][Medline]
13 Wheeler P, Hoffman WE, Baughman VL, Koenig H. Response entropy increases during painful stimulation. J Neurosurg Anesthesiol 2005; 17:86–90[CrossRef][Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  D. M. Mathews, A. J. Aho, A. Yli-Hankala, L.-P. Lyytikainen, and V. Jantti Response entropy-state entropy difference and nociception: a matter of context Br. J. Anaesth., July 1, 2009; 103(1): 135 - 137. [Full Text] [PDF]
|
|
|
|
|
|
M. Kawaguchi, I. Takamatsu, and T. Kazama Rocuronium dose-dependently suppresses the spectral entropy response to tracheal intubation during propofol anaesthesia Br. J. Anaesth., May 1, 2009; 102(5): 667 - 672. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kawaguchi, I. Takamatsu, K. Masui, and T. Kazama Effect of landiolol on bispectral index and spectral entropy responses to tracheal intubation during propofol anaesthesia Br. J. Anaesth., August 1, 2008; 101(2): 273 - 278. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Andrzejowski and T. A. Carroll Inappropriate elevation of bispectral index and disruption of neurosurgery after irrigation-induced facial nerve irritation Br. J. Anaesth., November 1, 2007; 99(5): 750 - 751. [Full Text] [PDF]
|
|
|
|
|
|
V. Bonhomme and P. Hans Muscle relaxation and depth of anaesthesia: where is the missing link? Br. J. Anaesth., October 1, 2007; 99(4): 456 - 460. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||