Electroencephalogram Approximate Entropy Correctly Classifies the Occurrence of Burst Suppression Pattern as Increasing Anesthetic Drug Effect

Background: Approximate entropy, a measure of signal complexity and regularity, quantifies electroencephalogram changes during anesthesia. With increasing doses of anesthetics, burst-suppression patterns occur. Because of the high-frequency bursts, spectrally based parameters such as median electroencephalogram frequency and spectral edge frequency 95 do not decrease, incorrectly suggesting lightening of anesthesia. The authors investigated whether the approximate entropy algorithm correctly classifies the occurrence of burst suppression as deepening of anesthesia.

Methods: Eleven female patients scheduled for elective major surgery were studied. After propofol induction, anesthesia was maintained with isoflurane only. Before surgery, the end-tidal isoflurane concentration was varied between 0.6 and 1.3 minimum alveolar concentration. The raw electroencephalogram was continuously recorded and sampled at 128 Hz. Approximate entropy, electroencephalogram median frequency, spectral edge frequency 95, burst-suppression ratio, and burst-compensated spectral edge frequency 95 were calculated offline from 8-s epochs. The relation between burst-suppression ratio and approximate entropy, electroencephalogram median frequency, spectral edge frequency 95, and burst-compensated spectral edge frequency 95 was analyzed using Pearson correlation coefficient.

Results: Higher isoflurane concentrations were associated with higher burst-suppression ratios. Electroencephalogram median frequency (r = 0.34) and spectral edge frequency 95 (r = 0.29) increased, approximate entropy (r = -0.94) and burst-compensated spectral edge frequency 95 (r = -0.88) decreased with increasing burst-suppression ratio.     

Effect of Altered Arterial Carbon Dioxide Tensions on the Electroencephalogram During Hypothermia

The effect of strictly controlled changes in PaC0₂ on the electro-encephalogram was observed in dogs under stable anaesthesia and moderate systemic hypothermia. Pulmonary ventilation and amounts of carbon dioxide given were regulated to produce: (1) relative hypocapnia, (2) a constant PaCO₂, and (3) relative hypercapnia. Changes in PaCO₂ did not significantly affect coldinduced depression of the electro-encephalogram, thereby negating the prospect that the administration of carbon dioxide may prevent the depression of the electrical activity of the brain which accompanies hypothermia. Inertness of raised PaC0₂ on the electro-encephalogram was demonstrated also in hypothermic patients.

ZUSAMMENFASSUNG

Bei Hunden wurde unter gleichbleibenden Narkosebedingungen und mäßiger allgemeiner Hypothermic die Wirkung genau kontrollierter Veränderungen des arteriellen Kohlensäuredrucks auf das EEG untersucht. Die Lungenventilation und Zugabe von Kohlensäure wurden so reguliert, daß sie 1) eine relative Hypokapnie, 2) ein konstantes PaC0₂ und 3) relative Hyperkapnie erzeugten. Veränderungen des PaC0₂ beeinflußten die k#aUlteinduzierte Dämpfung des Elektroenzephalogramms nicht signifikant. Womit die Vorstellung zu negieren ist, daß die Gabe von Kohlensäure imstande ist, die mit der Hypothermic einhergehende Dämpfung der elektrischen Aktivität des Gehirns zu verhindern. Die Wirkungslosigkeit erhöhter arterieller Kohlensäuredrucke auf das EEG wurde auch bei hypothermen Patienten demonstriert.     

Bispectral Index, Entropy, and Quantitative Electroencephalogram during Single-agent Xenon Anesthesia

Background: The aim was to evaluate the performance of anesthesia depth monitors, Bispectral Index (BIS) and Entropy, during single-agent xenon anesthesia in 17 healthy subjects.

Methods: After mask induction with xenon and intubation, anesthesia was continued with xenon only. BIS, State Entropy and Response Entropy, and electroencephalogram were monitored throughout induction, steady-state anesthesia, and emergence. The performance of BIS, State Entropy, and Response Entropy were evaluated with prediction probability, sensitivity, and specificity analyses. The power spectrum of the raw electroencephalogram signal was calculated.

Results: The mean (SD) xenon concentration during anesthesia was 66.4% (2.4%). BIS, State Entropy, and Response Entropy demonstrated low prediction probability values at loss of response (0.455, 0.656, and 0.619) but 1 min after that the values were high (0.804, 0.941, and 0.929). Thereafter, equally good performance was demonstrated for all indices. At emergence, the prediction probability values to distinguish between steady-state anesthesia and return of response for BIS, State Entropy, and Response Entropy were 0.988, 0.892, and 0.992. No statistical differences between the performances of the monitors were observed. Quantitative electroencephalogram analyses showed generalized increase in total power (P < 0.001), delta (P < 0.001) and theta activity (P < 0.001), and increased alpha activity (P = 0.003) in the frontal brain regions.     

Cholinergic Reversal of Isoflurane Anesthesia in Rats as Measured by Cross-approximate Entropy of the Electroencephalogram

Background: Pharmacologic modulation of the state of consciousness is of interest for clinical practice and for a better understanding of anesthetic mechanisms. The cholinergic activating system is an important regulator of the state of consciousness during general anesthesia. Entropy of the electroencephalogram has been proposed as a promising measure of anesthetic depth. The authors have shown that volatile anesthetics decrease cross-approximate entropy (C-ApEn) of the bihemispheric frontal electroencephalogram in rats. The effect of cholinergic agents on C-ApEn has not been examined. Here, the authors test the hypothesis that cholinergic activation reverses the effect of isoflurane anesthesia on C-ApEn.

Methods: An electroencephalogram in the 1- to 100-Hz range was recorded bipolarly, with epidural leads from the frontal cortex of both hemispheres, and used to calculate C-ApEn, which reflects statistical independence of bihemispheric electroencephalographic activity. Cholinesterase inhibitor, neostigmine (25 [mu]g), or the muscarinic agonist oxotremorine (25 [mu]g) were infused intracerebroventricularly while the rats were inhaling 1.0% (0.7 minimum alveolar concentration) isoflurane. In other animals, isoflurane was lowered to 0.4% (0.3 minimum alveolar concentration) to assess the electroencephalogram in a sedated, waking state.

Results: At 1.0% isoflurane, C-ApEn decreased by 54% compared with that at 0.4%, but the motor reflex response to tail pinch was still present. Cholinergic agents reversed the electroencephalogram-depressant effect of isoflurane, i.e., C-ApEn rose to the level measured at 0.4% isoflurane. The rise in C-ApEn was paralleled by the appearance of spontaneous limb and orofacial explorative movements, suggesting a return of consciousness. In contrast, cholinergic agents fully blocked the motor reflex to tail pinch.     

Behavior of Entropy/Complexity Measures of the Electroencephalogram during Propofol-induced Sedation: Dose-dependent Effects of Remifentanil

Background: Several new measures based on the regularity of the electroencephalogram signal for the assessment of depth of anesthesia/sedation have been proposed recently. In this study we analyze the influence of remifentanil and electroencephalogram frequency content of the performance of a set of such measures.

Methods: Forty-five patients with American Society of Anesthesiologists physical status I were randomly allocated to one of three groups according to the received dose of predicted effect compartment-controlled remifentanil (0, 2, and 4 ng/ml). All 45 patients received stepwise increased effect site concentration-controlled dose of propofol. At every step of propofol increase, the Observer's Assessment of Alertness/Sedation score was assessed. The following measures were calulated from the electroencephalographic signal: spectral entropy, approximate entropy, Higuchi fractal dimension, Lempel-Ziv complexity, relative [beta] ratio, and SyncFastSlow measure.

Results: The behavior of the electroencephalogram-based measures is highly sensitive to the frequency content of the signal and the dose of remifentanil. The prediction probability with respect to the Observer's Assessment of Alertness/Sedation score of the most discriminative measure, the Higuchi fractal dimension, dropped from 0.90 (electroencephalographic frequency band 6-47 Hz, no remifentanil) to 0.55 when the frequency band was changed to 0.5-19 Hz and to 0.83 when remifentanil concentration was increased to 4 ng/ml. The coeffect of remifentanil on electroencephalographic regularity is bimodal depending on the frequency band of the signal.     

Electroencephalographic Approximate Entropy Changes in Healthy Volunteers during Remifentanil Infusion

Background: The aim of this study was to investigate the independent effect of remifentanil on the approximate entropy (ApEn) in frontoparietal montages. The authors investigated which montages were relevant to assess the remifentanil effect on the electroencephalogram. Spectral edge frequency and the canonical univariate parameter were used as comparators.

Methods: Twenty-eight healthy volunteers were enrolled. With recording of the electroencephalogram at the F3, F4, Cz, P3, and P4 montages, remifentanil was infused at the rate of 1-8 [mu]g [middle dot] kg-1 [middle dot] min-1 for 15-20 min. The relation between remifentanil concentration and the electroencephalographic parameters were tested by Spearman correlation. Signal-to-noise ratio, artifact robustness, coefficient of variation of the median baseline and maximal electroencephalographic effects, and ratio of average maximal electroencephalographic effect to interindividual baseline variability were measured. The performance of ApEn as an index of remifentanil effect site concentrations was tested by prediction probability.

Results: Approximate entropy showed significant correlation (R = -0.6465, P < 0.0001) with remifentanil concentration. It provided comparable signal-to-noise ratio, artifact robustness, and ratio of average maximal electroencephalographic effect to interindividual baseline variability to 95% spectral edge frequency. The coefficients of variation of the median baseline and maximal electroencephalo graphic effects were smallest in ApEn. Parietal montages showed higher ratios of average maximal electroencephalographic effect to interindividual baseline variability for all electroencephalographic parameters and lower coefficients of variation of the baseline values for ApEn and 95% spectral edge frequency than frontal montages. The prediction probability of ApEn was 0.7730.     

Approximate Entropy as an Electroencephalographic Measure of Anesthetic Drug Effect during Desflurane Anesthesia

Background: The authors hypothesized that the electroencephalogram (EEG) during higher anesthetic concentrations would show more "order" and less "randomness" than at lower anesthetic concentrations. "Approximate entropy" is a new statistical parameter derived from the Kolmogorov-Sinai entropy formula which quantifies the amount of regularity in data. The approximate entropy quantifies the predictability of subsequent amplitude values of the EEG based on the knowledge of the previous amplitude values. The authors investigated the dose-response relation of the EEG approximate entropy during desflurane anesthesia in comparison with spectral edge frequency 95, median frequency, and bispectral index.

Methods: Twelve female patients were studied during gynecologic laparotomies. Between opening and closure of the peritoneum, end-tidal desflurane concentrations were varied between 0.5 and 1.6 minimum alveolar concentration (MAC). The EEG approximate entropy, median EEG frequency, spectral edge frequency 95, and bispectral index were determined and the performance of each to predict the desflurane effect compartment concentration, obtained by simultaneous pharmacokinetic-pharmacodynamic modeling, was compared.

Results: Electroencephalogram approximate entropy decreased continuously over the observed concentration range of desflurane. The performance of the approximate entropy (prediction probability PK = 0.86 +/- 0.06) as an indicator for desflurane concentrations is similar to spectral edge frequency 95 (PK = 0.86 +/- 0.06) and bispectral index (PK = 0.82 +/- 0.06) and is statistically significantly better than median frequency (PK = 0.78 +/- 0.06).     

心率变异性近似熵分析法与脑电双频谱指数间的相关性

目的:观察全身麻醉时心率变异性分析中近似熵分析法与脑电双频谱指数(BIS)在监测麻醉深度时的相关性。方法:对40例全身麻醉病人测定麻醉前(T1)、诱导插管(T2)、术中(T3)、苏醒(T4)4个时间点各5min的心率(HR)、平均动脉压(MAP)、脑电双频谱指数(BIS)和近似熵(ApEn)变化。结果:HR在T2、T3和T4均较T1值升高(P0.01～0.05)。MAP在T2时较T1值降低(P0.05),T3、T4较T1值升高(P0.05),而T4比T3明显升高(P0.01)。BIS值在麻醉后各时点均较T1值下降明显(P0.01),其中T4也较T1下降(P0.05),T3与T2时相比明显降低(P0.01),而T4较T3明显升高(P0.01)。近似熵值的T1值均大于其他各时点(P0.01～0.05),其T4较T3时点升高(P0.01),T3较T2时点降低(P0.05)。结论:作为心率变异性的非线性分析方法指标的近似熵分析法,能描述围术期心脏自主神经功能状态的变化,但其与BIS并无相关性。     

脑电图双谱分析技术监测异丙酚镇静时大脑皮层电活动变化

目的:探讨EEG双谱分析技术的临床应用价值,提供恰当的异丙酚镇静方法。方法:50例ASA Ⅰ～Ⅱ级下腹部手术患者,随机分5组,硬膜外麻醉效果确切后,首先静注负荷量异丙酚,之后微量泵连续静注维持镇静水平。监测数量化脑电图参数、病人镇静分数、血流动力学参数。结果:随镇静浓度升高,BIS和SEF降低(P<0.01),镇静分数升高,MAP降低,心率无明显变化。病人苏醒后BIS和SEF即刻升高(P<0.01)。异丙酚静注速度为3.6～5.4mg·kg~(-1)·h~(-1)时,BIS和SEF分别为76.3±2.8～67.6±5.8和16.7±6.9～14.5±6.6。镇静分数3～5分。呼吸及血流动力学变化小,镇静效果较理想。结论:数量化脑电图(BIS、SEF)能较准确地监测异丙酚的镇静深度及病人清醒状态。异丙酚静注速度为3.6～5.4mg·kg~(-1)·h~(-1)时,镇静效果理想。     

Hypothermia and the trauma patient.

Hypothermia has profound effects on every system in the body, causing an overall slowing of enzymatic reactions and reduced metabolic requirements. Hypothermic, acutely injured patients with multisystem trauma have adverse outcomes when compared with normothermic control patients. Trauma patients are inherently predisposed to hypothermia from a variety of intrinsic and iatrogenic causes. Coagulation and cardiac sequelae are the most pertinent physiological concerns. Hypothermia and coagulopathy often mandate a simplified approach to complex surgical problems. A modification of traditional classification systems of hypothermia, applicable to trauma patients is suggested. There are few controlled investigations, but clinical opinion strongly supports the active prevention of hypothermia in the acutely traumatized patient. Preventive measures are simple and inexpensive, but the active reversal of hypothermia in much more complicated, often invasive and controversial. The ideal method of rewarming is unclear but must be individualized to the patient and institution specific. An algorithm reflecting newer approaches to traumatic injury and technical advances in equipment and techniques is suggested. Conversely, hypothermia has selected clinical benefits when appropriately used in cases of trauma. Severe hypothermia has allowed remarkable survivals in the course of accidental circulatory arrest. The selective application of mild hypothermia in severe traumatic brain injury is an area with promise. Deliberate circulatory arrest with hypothermic cerebral protection has also been used for seemingly unrepairable injuries and is the focus of ongoing research.     

Hypothermia and the approximate entropy of the electroencephalogram

BACKGROUND: The electroencephalogram is commonly used to monitor the brain during hypothermic cardiopulmonary bypass and circulatory arrest. No quantitative relationship between the electroencephalogram and temperature has been elucidated, even though the qualitative changes are well known. This study was undertaken to define a dose-response relationship for hypothermia and the approximate entropy of the electroencephalogram. METHODS: The electroencephalogram was recorded during cooling and rewarming in 14 patients undergoing hypothermic cardiopulmonary bypass and circulatory arrest. Data were digitized at 128 Hz, and approximate entropy was calculated from 8-s intervals. The dose-response relationship was derived using sigmoidal curve-fitting techniques, and statistical analysis was performed using analysis of variance techniques. RESULTS: The approximate entropy of the electroencephalogram changed in a sigmoidal fashion during cooling and rewarming. The midpoint of the curve averaged 24.7 degrees C during cooling and 28 degrees C (not significant) during rewarming. The temperature corresponding to 5% entropy (T 0.05 ) was 18.7 degrees C. The temperature corresponding to 95% entropy (T 0.95 ) was 31.3 degrees C during cooling and 38.2 degrees C during rewarming ( P < 0.02). CONCLUSIONS: Approximate entropy is a suitable analysis technique to quantify the electroencephalographic changes that occur with cooling and rewarming. It demonstrates a delay in recovery that is of the same magnitude as that seen with conventional interpretation of the analog electroencephalogram and extends these observations over a greater range of temperatures.     

Hypothermia and cerebrovascular reactivity

Editor—Lavinio and colleagues¹ have touched upon an importanttopic by suggesting that temperatures above 37°C may causehyperaemic derangement of cerebrovascular reactivity in severelyhead-injured patients. However, one of the major limitationsof their retrospective analysis lies in the fact that the effectsof temperature could not be separated from any temporal changesthat occurred in the brain after injury. Rewarming took placeat a time when inflammatory responses in the brain presumablyhad evolved significantly compared with when the patients werecooled.² Indeed,