Level of consciousness and the use of Entropy monitoring

Welcome back to the third installment in the podcast series on perioperative safety. My name is Dr. Robert Bilkovski and in this episode, we will review the topic of intraoperative depth of anesthesia monitoring and the use of Entropy^TM monitoring. Specifically, we will get a better understanding of this technology that is one of several solutions available to the anesthesiologist and how it can support improved patient outcomes. 

In an attempt to minimize patient risk and to standardize practice, anesthesiology associations have issued guidelines for monitoring during sedation.^[1] These associations include the American Society of Anesthesiologists (ASA), the Association of Anesthetists of Great Britain and Ireland (AAGBI), the European Society of Anesthesiologists (ESA), the Australian and New Zealand College of Anesthetists (ANZCA), and the Anesthesia Patient Safety Foundation (APSF). The guidelines universally require assessment of the depth of sedation and the use of pulse oximetry and non-invasive arterial pressure monitoring. 

Taking aim at the depth of sedation monitoring, there are several means by which this can be accomplished which includes:

1. Clinical scales such as the Modified Observer's Assessment of Alertness/Sedation Scale (MOASS), and the Ramsay Sedation Scale (RSS), and
2. Processed EEG, which is based on the understanding that the EEG waveform changes in accordance to varying depths of sedation.

There are several EEG-based sedation monitoring technologies and one such technique is Entropy monitoring, where Entropy collects both the EEG and frontal EMG signals to provide two readings: State Entropy and Response Entropy. Simply stated, Entropy monitoring measures the amount of irregularity in the EEG and frontal EMG waveforms. Entropy values have been shown to correlate to the patient’s anesthetic state. High values of Entropy indicate high irregularity of the signal, signifying that the patient is awake. A more regular signal produces low Entropy values which can be associated with low probability of consciousness.^[2][3]

Response Entropy is sensitive to the activation of facial muscles, namely the frontal EMG and its response time is very fast at less than 2 seconds. Frontal EMG is especially active during the awake state but may also activate during surgery. Facial muscles may also give an early indication of emergence, and this can be seen as a quick rise in RE. The display range is from 0-100.

In comparison, the State Entropy value is always less than or equal to Response Entropy. During general anesthesia the hypnotic effect of certain anesthetic drugs on the brain may be estimated by the State Entropy value. Of note, State Entropy is less affected by sudden reactions to the facial muscles because it is mostly based on the EEG signal. The display range is from 0-91. In addition, neuromuscular blocking agents (NMBA), administered in surgically appropriate doses are not known to affect the EEG, but are known to affect the EMG signal.

The clinically relevant target range during general anesthesia for Entropy monitoring values is 40-60. RE and SE values near 40 indicate a low probability of consciousness.^[4] In addition, both Entropy measures and other EEG-based sedation monitoring technologies have shown a strong ability to discriminate between consciousness and unconsciousness states during propofol, sevoflurane and thiopental anesthesia.⁴ Lastly, Vakkuri et al concluded that Response Entropy informed emergence from anesthesia faster than State Entropy or other EEG-based sedation monitoring signals.

The use of Entropy monitoring has been shown in a variety of studies to inform clinical benefits and some of these benefits include:

1. Improved hemodynamic stability. Where a 2008 study found that Entropy monitoring provides more reliable hemodynamic control, specifically need for antihypertensive medications and fewer occurrences of hemodynamic fluctuations during total knee replacement surgery.^[5]
2. Reduction in the use of anesthetics. Studies have shown that Entropy monitoring is associated with a 30% reduction in Sevoflurane/Isoflurane and a 15% reduction in Propofol.^[6]
3. A lower risk of postoperative delirium. The use of Entropy monitoring may help avoid reaching unnecessarily deep states of hypnosis, including burst suppression that has been associated with increased risk of delirium.^[7]

The use of Entropy monitoring has been shown to benefit the hospital as well, via reductions in drug consumption,reducing perioperative adverse events and improved recovery time and operating room throughput.⁵  In a UK-based Health Technology Assessment amongst the general surgical population undergoing general anesthesia with TIVA (or total intravenous anesthesia). Entropy monitoring was modeled as being associated with 3.8 cases of awareness, compared with 16 cases for patients receiving standard clinical monitoring and the incremental cost-effectiveness ratio ICER for Entropy monitoring compared with standard clinical monitoring was £14,421.^[8]  It is likely that these patient and hospital benefits supported the implementation of entropy monitoring use in guidelines published by the Enhanced Recovery After Surgery Society.^[9] Implementation of the ERAS protocol, notably in head and neck surgery as shown a significant impact in the reduction of hospital lengths of stay.

This ends this podcast on the topic of intraoperative sedation and the use of entropy monitoring. You were able to take away the fact that intraoperative sedation is recommended by many international anesthesia societies globally and that there are several approaches including EEG-based entropy levels of consciousness monitoring. Thank you for listening and be sure to visit again on other topics pertaining perioperative safety in coming podcasts. 

References:

[1]     C. G. Sheahan , D. M. Mathews, Monitoring and delivery of sedation, BJA: British Journal of Anaesthesia, Volume 113, Issue suppl_2, December 2014, Pages ii37–ii47.

[2]     Viertiö-Oja et al. Description of the Entropy algorithm as applied in the Datex-Ohmeda S/5 Entropy Module. Acta Anaesthesiologica Scandinavica, 48 (2): 154-161 (2004).

[3]    Entropy Monitoring: A Valuable Tool for Guiding Delivery of Anesthesia; ClinicalView GE Healthcare, https://clinicalview.gehealthcare.com/quick-guide/entropy-monitoring-valuable-tool-guiding-delivery-anesthesia

[4]     Vakkuri, A., Yli‐Hankala, A., Talja, P., Mustola, S., Tolvanen‐Laakso, H., Sampson, T. and Viertiö‐Oja, H., 2004. Time‐frequency balanced spectral entropy as a measure of anesthetic drug effect in central nervous system during sevoflurane, propofol, and thiopental anesthesia. Acta Anaesthesiologica Scandinavica, 48(2), pp.145-153.

[5]     Wu et al, 2008, Use of Spectral Entropy Monitoring in Reducing the Quantity of Sevoflurane as Sole Inhalational Anesthetic and in Decreasing the Need for Antihypertensive Drugs in Total Knee Replacement Surgery

[6]     Vakkuri A. et al.. Spectral Entropy Monitoring Is Associated with Reduced Propofol Use and Faster Emergence in Propofol–Nitrous Oxide–Alfentanil Anaesthesia. Anesthesiology. 2005;103:274–9. El Hor, Tarek. Impact of Entropy Monitoring on Volatile Anesthetic Uptake. Anesthesiology. 2013;118:868-73 Aiméet al. Does Monitoring BispectralIndex or Spectral Entropy Reduce Sevoflurane Use? AnesthAnalg. 2006;103:1469 –77

[7]     Daiello LA, et al.. Postoperative Delirium and Postoperative Cognitive Dysfunction: Overlap and Divergence. Anesthesiology. 2019 Sep;131(3):477-491.

[8]     Shepherd J, Jones J, Frampton G, Bryant J, Baxter L, Cooper K. Clinical effectiveness and cost-effectiveness of depth of anaesthesia monitoring (E-Entropy, Bispectral Index and Narcotrend): a systematic review and economic evaluation. Health Technol Assess. 2013 Aug;17(34):1-264. 

[9]     Bertazzoni G, Testa G, Tomasoni M, Mattavelli D, Del Bon F, Montalto N, Ferrari M, Andreoli M, Morello R, Sbalzer N, Vecchiati D, Piazza C, Nicolai P, Deganello A. The Enhanced Recovery After Surgery (ERAS) protocol in head and neck cancer: a matched-pair analysis. Acta Otorhinolaryngol Ital. 2022 Aug;42(4):325-333.