Introduction

Providing adequate level of unconsciousness (hypnosis) in a surgical patient can be challenging as the clinical methods for evaluating depth of anesthesia do not guarantee that the patient will remain unconscious throughout the anesthetic procedure. The most distressing features of patient awareness during anesthesia are movement, pain perception, and recall.¹

Monitoring Hypnosis with Electroencephalography (EEG)

Analysis of brain electrical activity (EEG) can be used to assess the level of hypnosis produced by general anesthetics. In conscious individuals the EEG is characterized by high frequency/low amplitude waves. During anesthesia qualitative changes are evident in the EEG tracing: at moderate levels of hypnosis the EEG is characterized by low frequency/high amplitude waves while in individuals with profound hypnosis the EEG tracing presents periods of isoelectricity intercalated by bursts of high amplitude waves (EEG burst suppression).² One of the limitations of EEG monitoring during clinical anesthesia is the fact that it involves complex and time consuming interpretation of the EEG unprocessed signal. The development computerized algorithms for interpreting the EEG raw data have allowed human anesthetists to more objectively assess the level of hypnosis in anesthetized patients. The bispectral index (BIS®) is a proprietary algorithm derived from complex analysis of the EEG waveform that was originally developed for monitoring the level of hypnosis in humans.^3,4

BIS Monitoring in Human Anesthesia

The BIS is a numeric variable that ranges from 0 to 100, where 0 reflects cortical silence in the brain and 100 indicates a conscious and fully alert individual.^3,4 In humans, BIS values ranging from 40 to 60 are consistent with surgical depth of anesthesia, in which the level of hypnosis may be enough to inhibit cardiovascular and motor responses to noxious stimuli.^3,4 In human patients, BIS monitoring is a useful ancillary tool for preventing intra-operative awareness, guiding the titration of intravenous (propofol) and inhalational anesthetics.^5-7 The use of BIS monitoring can reduce consumption of volatile anesthetic agent by up to 25% and allows faster recoveries from anesthesia.^5-7

BIS Monitoring in Dogs and Cats: Does it Have the Same Value as in Humans?

Qualitative changes in the EEG signal in anesthetized mammals appear similar to those changes observed in anesthetized human individuals. In cats and dogs, BIS values are decreased with progressing levels of hypnosis induced via increases in the dose of inhalant anesthetics^8-11 (Table 1).

BIS values recorded in anesthetized cats are substantially lower than BIS values recorded in humans under similar conditions. In cats anesthetized with isoflurane or sevoflurane administered at concentrations that produce light depth of anesthesia [0.8 to 1.0 minimum alveolar concentration (MAC)] BIS values are already less than 40, ^10,11 a value that would otherwise indicate profound hypnosis in anesthetized human patients. The range of BIS values indicative of moderate level of hypnosis in humans is 40 to 60, but in cats this range of values is probably less.^10,11 Detection of EEG burst suppression (intermittent spiking on an isoelectric background) should be carefully interpreted as this EEG feature is often recorded during deep levels of inhalational anesthesia. Paradoxically, EEG burst suppression was reported to cause increases in BIS values.^8-12 These inconsistencies were caused by the incapacity of the earlier versions of the BIS algorithm to handle EEG burst suppression. Paradoxical increases in BIS values during deep anesthesia have been reported in dogs^8,9, cats^10,11, and in human patients¹². Newer versions of the BIS software (Version 4.1) have attempted to properly handle the problem of EEG burst suppression causing paradoxical increases in BIS values.¹³

In cats, increasing the dose of inhalant anesthetics decreases BIS values up to a certain point.^10,11,14 In one study, as the end-tidal isoflurane concentration was increased from 1.3 to 1.9%, BIS was negatively correlated with the dose of inhalational agent.¹⁴ At end-tidal isoflurane concentrations ranging from 2.0 to 2.4%, BIS remained constant, while at higher concentrations (2.5 to 3.2%) BIS started to increase gradually.¹⁴

Dogs have substantially higher BIS values than cats anesthetized under similar conditions (Table 1). Also, increasing the dose of inhalational anesthetic appears to have less influence on BIS values in dogs than in cats: as the dose of sevoflurane was increased from 0.8 to 1.5 MAC, mean BIS values were decreased by only 26% (from 77 to 57) in dogs⁹, contrasting with the 83% decrease in BIS (from 30 to 5) recorded in cats¹⁰ (Table 1). In another study comparing 3 different positions of the BIS sensor in the dog's skull, increasing end-tidal isoflurane concentrations from 1.5% to 2.3% did not result in significant changes in mean BIS values; further increases in end-tidal isoflurane to 3.0% caused BIS values to markedly decrease in some animals (minimal BIS values: 7 to 14), while in other animals BIS values were paradoxically high (BIS = 70 to 81).¹³

Propofol was also reported decrease BIS values in dogs, but these decreases were of small magnitude.¹⁵ Increasing the constant rate infusion (CRI) of propofol from 0.2 to 0.8 mg/kg/min lowered mean BIS values from 84 to 69 after 50 minutes of commencing the intravenous infusion.¹⁵

Table 1. BIS values (mean ± SD) recorded in dogs and in cats anesthetized with isoflurane and sevoflurane administered at several minimum alveolar concentration (MAC) multiples.

Data compiled from references 8-11.
*BIS value reported at 2.0 MAC did not include animals that presented paradoxical increases in BIS associated with EEG burst suppression.
NR: not reported because of paradoxical increases in BIS

Are BIS Values Reliable Indicators of the Hypnotic State in Animals Not Undergoing Noxious Stimulation?

In spite of the low BIS values observed in anesthetized cats not undergoing noxious stimulation, these values may be misleading. In cats anesthetized with isoflurane, although BIS values were less than 20, these values were markedly increased when supramaximal noxious stimulation was applied; suggesting that low BIS values recorded before surgery have little predictive value for patient awareness in response to surgical incision.^4,14 On the other hand, the fact that the increase in BIS caused by noxious stimulation can be obtunded by increasing end-tidal isoflurane concentrations, shows that post stimulation BIS values are more important than pre-stimulation BIS values for accessing the level of unconsciousness in this species.^4,14 On the basis of the current state o knowledge, BIS values that do not increase to values above 60 after in cats undergoing noxious stimulation (e.g., surgery) appear compatible with an adequate level of hypnosis.

The average of the end-tidal anesthetic concentrations that prevents and that allows increases in BIS after a supramaximal noxious stimulus (MAC_BIS) is significantly higher than the average of the end-tidal anesthetic concentrations that prevents and that allows gross purposeful movement (MAC).^16-17 These results suggest that, during progressive lightning of anesthesia in animals undergoing noxious stimulation, increases in BIS above a certain threshold [> 60 in cats (16) or > 70 in dogs¹⁶] will occur before movement is observed.

What Are the Potential Applications of BIS Monitoring in Veterinary Patients?

In veterinary patients, BIS monitoring has the potential for guiding titration of general anesthetics in order to ensure an adequate level of unconsciousness. One must understand that, depending on the anesthetic technique and of other factors (health status, species) the requirement of general anesthetics to produce unconsciousness can vary substantially.

Analysis of dynamic BIS changes caused by noxious stimuli in dogs and cats appears more important to evaluate the level o hypnosis than absolute BIS values recorded in individuals not subjected to painful stimulation. Further research is necessary to establish the range of BIS values that are associated with adequate hypnosis in dogs and cats.

How to Prevent Patient Awareness?

For animals under inhalational anesthesia, signs of adequate level of unconsciousness include the absence of protective reflexes (palpebral reflex, swallowing reflex), absence of spontaneous movement and decreased responsiveness of the CNS respiratory center to increased CO₂ levels. Anesthetized animals can be aroused from an apparent "unconscious state" by supramaximal noxious stimulation (e.g., surgery). Indeed, signs of arousal from anesthesia (tachypnea, active palpebral reflexes, swallowing, movements), that were not present after induction of anesthesia, may unexpectedly become evident once surgery starts.

Because noxious stimulation can cause patient awareness, indirect signs of pain perception must be closely monitored before and during surgery. Excessive increases heart rate and in arterial blood pressure that are coincident with surgical stimulation are suggestive of poor analgesia and/or of inadequate depth of anesthesia. In animals undergoing noxious stimulation, increases in sympathetic drive occur at inhalational anesthetic concentrations that are higher than those anesthetic concentrations that allow movement. Increasing the dose of general anesthetic or administering an opioid analgesic to inhibit the cardiovascular stimulation caused by surgery should be considered to prevent patient awareness/movement.

The use of regional anesthesia techniques (e.g., epidural and brachial plexus blocks) causes reversible inhibition of nociception, blocking conscious perception of painful stimulation. When regional blocks are combined with inhalational anesthesia, the dose of inhalational anesthetic necessary to produce signs of unconsciousness is greatly reduced.

References

1.  Ghoneim MM. Anesthesiology 2000;92:597-602

2.  Rampil IJ. Anesthesiology 1998;89:980-1002

3.  Johansen JW, Sebel PS. Anesthesiology 2000;93:1336-1344

4.  March PA, Muir WW. Vet Anaesth Analg 2005;32:241-255.

5.  Song D, Joshi GP, White PF. Anesthesiology 1997;87:842-848.

6.  Yli-Hankala A, Vakkuri A, Annila P, et al. Acta Anaesthesiol Scand 1999;43:545-549.

7.  Guignard B, Coste C, Menigaux C, et al. Acta Anaesthesiol Scand 2001;45:308-314.

8.  Greene SA, Benson GJ, Tranquilli WJ, et al. Vet Anaesth Analg 2002a;29:100-101.

9.  Greene SA, Benson GJ, Tranquilli WJ, et al. Comp Med 2002b;52:424-428.

10. Lamont LA, Greene SA, Grimm KA, et al. Am J Vet Res 2004;65:93-98.

11. Lamont LA, Greene SA, Grimm KA, et al. Comp Med 2005;55:269-274.

12. Detsch O, Schneider G, Kochs E, et al. Br J Anaesth 2000;84:33-37.

13. Campagnol D, Teixeira Neto FJ, Monteiro ER, et al. Am J Vet Res 2007;68:1300-1307.

14. March PA, Muir WW 3rd. Am J Vet Res 2003;64:1534-1541.

15. Lopes PCF, Nunes N, Paula DP. Vet Anaesth Analg 2008;35:288-231.

16. March PA, Muir WW 3rd. Am J Vet Res 2003;64:1528-1533.

17. Campagnol D, Teixeira Neto FJ, Giordano T, et al. Proceedings of the 9th World Congress of Veterinary Anesthesiology, Santos, Brazil, p. 138.