Relationship between clinical endpoints for induction of anesthesia and bispectral index and effect-site concentration values

doi:10.1016/S0952-8180(02)00348-3

Journal of Clinical Anesthesia

Volume 14, Issue 4, June 2002, Pages 241-245

https://doi.org/10.1016/S0952-8180(02)00348-3 Get rights and content

Abstract

Study Objective: To assess the relationship between clinical endpoints for induction of anesthesia and the electroencephalographic (EEG) bispectral index (BIS) and effect-site concentration (C_E) values when using a target-controlled infusion (TCI) of either thiopental sodium or propofol, by hypothesizing that yawning may be a useful alternative to other commonly used clinical signs for determining loss of consciousness.

Design: Randomized observational clinical study.

Setting: Operating room of a university-based hospital.

Patients: 60 healthy adult patients (aged 20–50 yrs) scheduled for elective surgery with general anesthesia.

Interventions: During a TCI of propofol (n = 30) or thiopental (n = 30), clinical endpoints for loss of verbal responsiveness (LOV), loss-of-eyelash reflex (LOE), occurrence of yawning, and apnea were assessed at 15-second intervals. In addition, BIS and C_E values were recorded at each of the endpoints.

Measurements and Main Results: In both anesthetic groups, the sequence of occurrence of the clinical endpoints was similar, namely LOV, LOE, yawning, and, lastly, apnea. Compared with LOV and LOE, yawning was associated with lower BIS and higher C_E values with both anesthetics. The frequency of yawning was higher with thiopental than propofol (83% vs. 63%, respectively). However, the frequency of apnea was higher with propofol than thiopental (77% vs. 53%, respectively).

Conclusion: The correlation of the clinical endpoints with BIS and C_E values was highest for LOV. Yawning was as unreliable as LOE for determining the onset of unconsciousness during induction of anesthesia. This clinical sign failed to be observed in 17% and 37% of patients induced with thiopental and propofol, respectively.

Introduction

Clinical endpoints are commonly used to assess the adequacy of induction of anesthesia with thiopental sodium and propofol. The failure to respond to verbal commands, loss of muscular tone, and/or loss-of-eyelash or corneal reflex are frequently assumed to indicate that a patient is “asleep”.1 It has also been suggested that the electroencephalographic (EEG) bispectral index (BIS) monitor could improve the ability of clinicians to assess the hypnotic state.2, 3

Yawning (i.e., an involuntary reaction involving opening of the mouth and taking a breath) is a common behavioral act which is frequently observed during induction of anesthesia. In normal, unstressed humans, yawning is most often associated with the transition from sleeping to waking and from waking to sleeping.4, 5 Therefore, yawning may be a useful clinical sign that a change has occurred in the patient’s arousal level. However, this clinical sign has not been previously studied as an endpoint for determining unconsciousness after intravenous (IV) induction of anesthesia.

The objective of this study then was to assess the relationship between the common clinical endpoints for induction of anesthesia and the BIS value and effect-site concentration (C_E) following a target-controlled infusion (TCI) of either thiopental or propofol. We hypothesized that yawning might be a useful endpoint for assessing induction of anesthesia with IV drugs.

Section snippets

Materials and methods

Sixty healthy adult patients (aged 20–50 yrs) scheduled for elective surgery with general anesthesia participated in this institutional review board-approved study at St. Vincent Hospital in Seoul, Korea, after giving their written, informed consent. Exclusion criteria included any evidence of hepatic, renal, or neurologic dysfunction; morbid obesity; and chronic use of benzodiazepines, anticonvulsants, alcohol, opioids, or other psychotropic drugs.

All patients were unpremedicated when they

Results

The demographic characteristics and baseline vital signs were similar in both IV anesthetic groups (Table 1). After failing to respond to verbal commends, LOE was observed in 83% and 90% of the patients in the propofol and thiopental sodium groups, respectively. Yawning was more common with thiopental (83% vs. 63%), whereas apnea was more frequent with propofol (77% vs. 53%) (p < 0.05).

The order of occurrence of the clinical endpoints for induction of anesthesia were similar in both anesthetic

Discussion

With the TCI delivery system, the BIS values at LOV (i.e., onset of hypnosis) were higher than the values typically associated with unconsciousness following bolus dosing with thiopental and propofol.2, 3, 8 Although easier to detect clinically than LOE, the yawn response did not occur in 17% and 37% of the patients following the loss of verbal responsiveness with thiopental and propofol, respectively. These data suggest that yawning is even less reliable than the LOE with propofol.9

Based on

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Research has shown that arousal responses in laboratory rats, as measured by electrocorticogram, are accompanied by yawning behavior following electrical, chemical, and light stimulation of the PVN of the hypothalamus (Kita et al., 2008; Sato-Suzuki et al., 1998, 2002; Seki et al., 2003). Furthermore, yawning is a common response among patients undergoing anesthesia (Kim et al., 2002), and actually produces a transient arousal shift as measured by electroencephalographic (EEG) bispectral index (Kasuya et al., 2005). This result has been interpreted as yawning representing a mechanism to enhance arousal during the progressive loss of consciousness caused by induction of anesthesia.
Various studies and researchers have proposed a link between contagious yawning and empathy, yet the conceptual basis for the proposed connection is not clear and deserves critical evaluation. Therefore, we systematically examined the available empirical evidence addressing this association; i.e., a critical review of studies on inter-individual differences in contagion and self-reported values of empathy, differences in contagion based on familiarity or sex, and differences in contagion among individuals with psychological disorders, as well as developmental research, and brain imaging and neurophysiological studies. In doing so, we reveal a pattern of inconsistent and inconclusive evidence regarding the connection between contagious yawning and empathy. Furthermore, we identify study limitations and confounding variables, such as visual attention and social inhibition. Future research examining links between contagious yawning and empathy requires more rigorous investigation involving objective measurements to explicitly test for this connection.
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Although anesthetic-induced yawning is commonly observed during induction of anesthesia, systemic investigation of this universal phenomenon in human beings is still lacking. In a recent study, the proportion of propofol-induced yawning was reported to be 63% (30 patients in each group) [4]. Similarly, our results from 386 patients show that the proportion of propofol-induced yawning was 53.5%.
To investigate the proportion of propofol-induced yawning and sympathovagal balance during propofol-induced yawning.
Prospective, observational, clinical study.
University hospital and 2400-bed tertiary medical center.
546 ASA physical status I and II patients undergoing elective surgery with general anesthesia.
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Pretreatment with fentanyl may inhibit propofol-induced yawning. Fluctuations in autonomic function have been noted during propofol-induced yawning.
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Although yawning occurs frequently during the IV induction of general anesthesia, the significance of this response remains unknown. In this study, we induced 30 surgical patients with 4 mg/kg thiopental IV, and 30 patients with 2 mg/kg propofol IV. Thereafter, the occurrence of yawning was continuously assessed, as the only clinical end-point, for 1 min. The electroencephalographic bispectral index was monitored throughout the observation period. The criterion for an arousal response was a transient increase during a continuing decrease in the bispectral index value. On the basis of this criterion, the sensitivity and specificity of the yawning response as an arousal sign were 77% and 80%, respectively. If a patient exhibited a yawning response, the chance of arousal was 84% (positive predictive value). With no yawning response, the chance of nonarousal was 71% (negative predictive value). According to simple logistic regression, the yawning response was predictive of a transient arousal-shift with an odds ratio of 13.5 (95% confidence interval: 3.8–48; P < 0.001). The occurrence of a yawning response during IV induction may be a clinical indicator of a transient arousal-shift during progressive loss of consciousness.
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^☆: Financial support for this report was provided by The Catholic University of Korea, St. Vincent Hospital, Seoul, Korea and The White Mountain Institute of Los Altos, Los Altos, California (Dr. P.F. White, President).

^∗: Associate Professor, Department of Anesthesiology, St. Vincent Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea

^†: Professor, Department of Anesthesiology, School of Medicine, Hallym University, Seoul, Korea

^‡: Professor and Holder of the Margaret Milam McDermott Distinguished Chair in Anesthesiology, Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center at Dallas

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Original contributionRelationship between clinical endpoints for induction of anesthesia and bispectral index and effect-site concentration values☆

Abstract

Introduction

Section snippets

Materials and methods

Results

Discussion

Physiol Behav

Br J Anaesth

Eur J Pharmacol

Pharmacol Biochem Behav

Monitoring depth of anaesthesia

Bispectral analysis measures sedation and memory effects of propofol, midazolam, isoflurane, and alfentanil in healthy volunteers

Anesthesiology

Bispectral analysis of the electroencephalogram predicts conscious processing of information during propofol sedation and hypnosis

Anesthesiology

On the context of yawningwhen, where and why?

Psych Rec

Original contribution
Relationship between clinical endpoints for induction of anesthesia and bispectral index and effect-site concentration values☆