Comparison of Bispectral Index and Entropy values with electroencephalogram during surgical anaesthesia with sevoflurane.

BACKGROUND: Concomitantly recorded Bispectral Index® (BIS) and Entropy™ values sometimes show discordant trends during general anaesthesia. Previously, no attempt had been made to discover which EEG characteristics cause discrepancies between BIS and Entropy. We compared BIS and Entropy values, and analysed the changes in the raw EEG signal during surgical anaesthesia with sevoflurane. METHODS: In this prospective, open-label study, 65 patients receiving general anaesthesia with sevoflurane were enrolled. BIS, Entropy and multichannel digital EEG were recorded. Concurrent BIS and State Entropy (SE) values were selected. Whenever BIS and SE values showed ≥10-unit disagreement for ≥60 s, the raw EEG signal was analysed both in time and frequency domain. RESULTS: A ≥10-unit disagreement ≥60 s was detected 428 times in 51 patients. These 428 episodes accounted for 5158 (11%) out of 45 918 analysed index pairs. During EEG burst suppression, SE was higher than BIS in 35 out of 49 episodes. During delta-theta dominance, BIS was higher than SE in 141 out of 157 episodes. During alpha or beta activity, SE was higher than BIS in all 49 episodes. During electrocautery, both BIS and SE changed, sometimes in the opposite direction, but returned to baseline values after electrocautery. Electromyography caused index disagreement four times (BIS > SE). CONCLUSIONS: Certain specific EEG patterns, and artifacts, are associated with discrepancies between BIS and SE. Time and frequency domain analyses of the original EEG improve the interpretation of studies involving BIS, Entropy and other EEG-based indices. CLINICAL TRIAL REGISTRATIONCLINICALTRIALSGOVIDENTIFIER: NCT01077674.

Changes in the electroencephalogram during anaesthesia and their physiological basis.

The use of EEG monitors to assess the level of hypnosis during anaesthesia has become widespread. Anaesthetists, however, do not usually observe the raw EEG data: they generally pay attention only to the Bispectral Index (BIS™) and other indices calculated by EEG monitors. This abstracted information only partially characterizes EEG features. To properly appreciate the availability and reliability of EEG-derived indices, it is necessary to understand how raw EEG changes during anaesthesia. With hemi-frontal lead EEGs obtained under volatile anaesthesia or propofol anaesthesia, the dominant EEG frequency decreases and the amplitude increases with increasing concentrations of anaesthetic. Looking more closely, the EEG changes are more complicated. At surgical concentrations of anaesthesia, spindle waves (alpha range) become dominant. At deeper levels, this activity decreases, and theta and delta waves predominate. At even deeper levels, EEG waveform changes into a burst and suppression pattern, and finally becomes flat. EEG waveforms vary in the presence of noxious stimuli (surgical skin incision), which is not always reflected in BIS™, or other processed EEG indices. Spindle waves are adequately sensitive, however, to noxious stimuli: under surgical anaesthesia they disappear when noxious stimuli are applied, and reappear when adequate analgesia is obtained. To prevent awareness during anaesthesia, I speculate that the most effective strategy is to administer anaesthetic agents in such a way as to maintain anaesthesia at a level where spindle waves predominate.

Cross-frequency coupling during isoflurane anaesthesia as revealed by electroencephalographic harmonic wavelet bicoherence.

BACKGROUND: Fourier bicoherence has previously been applied to investigate phase coupling in the EEG in anaesthesia. However, there are significant theoretical limitations regarding its sensitivity in detecting transient episodes of inter-frequency coupling. Therefore, we used a recently developed wavelet bicoherence method to investigate the cross-frequency coupling in the EEG of patients under isoflurane anaesthesia; examining the relationship between the patterns of wavelet bicoherence and the isoflurane concentrations. METHODS: We analysed a set of previously published EEG data, obtained from 29 patients who underwent elective abdominal surgery under isoflurane anaesthesia. Artifact-free, 1 min EEG segments at different isoflurane concentrations were extracted from each subject and the wavelet bicoherence calculated for all pairs of frequencies from 0.5 to 20 Hz. RESULTS: Isoflurane caused two peaks in the α (6-13 Hz) and slow δ (<1 Hz) regions of the bicoherence matrix diagonal. Higher concentrations of isoflurane shifted the α peak to lower frequencies [11.3 (0.9) Hz at 0.3% to 7.1 (1.2) Hz at 1.5%], as has been previously observed in the power spectra. Outside the diagonal, we also found a significant α peak that was phase-coupled to the slow δ waves; higher concentrations of isoflurane shifted this peak to lower frequencies [10.8 (1.2) to 7.7 (0.7) Hz]. CONCLUSIONS: Isoflurane caused cross-frequency coupling between α and slow δ waves. Increasing isoflurane concentration slowed the α frequencies where the coupling had occurred. This phenomenon of α-δ coupling suggests that slow cortical oscillations organize the higher α band activity, which is consistent with other studies in natural sleep.

Arytenoid dislocation after cardiac surgery.

Occurring most usually as complications of upper aerodigestive tract instrumentation during endotracheal intubation or extubation, arytenoid cartilage dislocation and arytenoid subluxation are uncommon laryngeal injuries. Their precise cause, however, is usually difficult to determine. We encountered arytenoid dislocation following cardiac surgery requiring the use of transesophageal echocardiography (TEE). This case prompted us to review some of the mechanisms of injury to the cricoarytenoid joint. We conclude that even very subtle force may dislocate the arytenoid cartilage. We speculate that careless insertion of a TEE probe is mechanically capable of causing arytenoid dislocation and arytenoid subluxation. As ideal tools for intra-operative cardiovascular monitoring, TEE probes are increasingly being used routinely during cardiovascular surgery. So far, arytenoid cartilage dislocation and subluxation following TEE probe insertion have been reported rarely, but complications caused by TEE may increase in the near future. We wish to emphasize the pathophysiological risks of TEE monitoring and other procedures associated with anesthesia, and the need for a proper explanation to achieve informed consent before carrying out TEE monitoring during cardiac surgeries.

Ketamine increases the frequency of electroencephalographic bicoherence peak on the alpha spindle area induced with propofol.

BACKGROUND: The reticular and thalamocortical system is known to play a prominent role in spindle wave activity, and the spindle wave is related to the sedative effects of anaesthetics. Recently, bispectral analysis of the EEG has been developed as a better method to indicate nonlinear regulation including the thalamocortical system linking to the cortical area. In the present study, in order to explore the interference of ketamine with the nonlinear regulation of the sub-cortical system, we examined the effect of ketamine on spindle alpha waves through the bispectral analysis. METHODS: The study included 21 patients. Anaesthesia was induced and maintained using a propofol-TCI system (target-controlled infusion, with target concentration 3.5 microg ml(-1)). An A-2000 BIS monitor was used and the raw EEG signals were collected via an RS232 interface on a personal computer. Bicoherence, the normalized bispectrum, and power spectrum were analysed before and after i.v. administration of 1 mg kg(-1) racemic ketamine. RESULTS: Propofol caused alpha peaks in both power and bicoherence spectra, with average frequencies of 10.6 (SD 0.9) Hz and 10.7 (1.0) Hz, respectively. The addition of ketamine significantly shifted each peak to frequencies of 14.4 (1.4) Hz and 13.6 (1.5) Hz, respectively [P < 0.05, mean (SD)]. CONCLUSIONS: Ketamine shifted the alpha peaks of bicoherence induced by propofol to higher frequencies. This suggests that ketamine changes the alpha spindle rhythms through the modulation of the nonlinear sub-cortical reverberating network.

Ketamine, an NMDA-antagonist, increases the oscillatory frequencies of alpha-peaks on the electroencephalographic power spectrum.

BACKGROUND: Ketamine, an N-methyl-D-aspartate (NMDA) antagonist, is known to activate the electroencephalogram (EEG), despite its sedative effects. Spindle oscillations are known to be related to the sedative actions of the reticular thalamic nucleus with links to thalamocortical neurons. This study was designed to examine the effect of ketamine on the spindle oscillations to understand the simultaneous sedative effect and EEG activation that occurs with ketamine, by comparing the EEG in emergence. METHODS: Anesthesia was induced with propofol using a target-controlled infusion (TCI) system (3.5 microg/ml). Seventeen patients, scheduled for non-cranial surgery under general anesthesia combined with epidural anesthesia, were randomly divided into two groups: (i) anesthesia was maintained with TCI-propofol alone (n= 8) and (ii) anesthesia was maintained with TCI-propofol and intravenously administered ketamine (n= 9). The EEG was continuously monitored and EEG indices and power spectra were determined. RESULTS: Propofol alone caused the alpha-peaks of the power spectra to occur at an average frequency of 10.4 +/- 0.9 Hz; the addition of ketamine shifted the peaks to higher frequencies of 15.1 +/- 1.4 Hz (P < 0.05). On the other hand, when the EEG was activated by discontinuation of propofol, the corresponding alpha-peaks disappeared. CONCLUSIONS: Ketamine increased the frequencies of alpha-spindle waves induced by propofol, but did not block their formations. The phenomena have the possibility to underlie the cooperative effect between propofol and ketamine concerning sedation and anesthesia.

Practical issues in bispectral analysis of electroencephalographic signals.

IMPLICATIONS: The aim of this report was to confirm the methodology of bispectral analysis of electroencephalogram. In developing a software for real-time bispectral analysis, we encountered several practical problems in bispectrum calculation. We settled those and concluded that 3 min of monitoring are required to obtain reliable and reproducible bicoherence values.

Infrared transmission of electronic information via LAN in the operating room.

Recent advances in technology have brought many kinds of monitoring devices into the operating room (OR). The information gathered by monitors can be channeled to the operating ward information system via a local area network (LAN). Connecting patients to monitors and monitors to the LAN, however, requires a large number of cables. This wiring is generally inconvenient and particularly troublesome if the layout of the OR is rearranged. From this point of view, wireless transmission seems ideally suited to clinical settings. Currently, two modes of wireless connectivity are available: radio-frequency (RF) waves or infrared (IR) waves. Some reports suggest that RF transmission is likely to cause electromagnetic interference (EMI) in medical devices such as cardiac pacemakers or infusion pumps. The risk of malfunctioning life-sustaining devices and the catastrophic consequences this would have on seriously ill patients rules out the use of RF. Here, we report an IR system using IR modems for LAN connectivity in the OR. In this study, we focused on the possible detrimental effects of EMI during wireless connectivity. In our trial, we found no evidence of EMI of IR modems with any of the medical devices we tested. Furthermore, IR modems showed similar performance to a wired system even in an electrically noisy environment. We conclude that IR wireless connectivity can be safely and effectively used in ORs.

Circadian secretion patterns of melatonin after major surgery.

Biorhythms, such as regular variation in core body temperature and the pattern of the secretion of melatonin, are thought to be mediated by the same biological clock. Core body temperature is affected by the inflammatory response to major surgery. Apart from the well-known inhibitory effect of bright light on its secretion, melatonin is an exceedingly good marker of one of the central generating systems of circadian rhythms. We sequentially measured the plasma melatonin concentration pattern in patients who had undergone esophagectomy with thoracotomy to elucidate the circadian rhythm after major surgery. From seven patients who had received esophagectomy with thoracotomy for esophageal cancer, plasma concentrations of melatonin were measured using an RIA method. Blood samples were collected via each patient's arterial line at 00.00, 02.00, 04.00, 06.00, 08.00, 12.00, 16.00, 20.00, and 24.00 hr on the first postoperative day for six of the patients, and, for one patient, every 2 hr until the third postoperative day and every 4 hr thereafter until the sixth postoperative day. Four patients out of seven had melatonin concentrations of over 30 pg/ml (mean 34 pg/ml) at 24.00 hr on the first postoperative day. Five patients showed circadian secretion patterns of melatonin during the first postoperative day. One patient whose melatonin concentrations were measured consecutively for 6 days showed a regular circadian secretion pattern through the 6 days of the study. Even the stress caused by extremely invasive surgery did not significantly disturb the melatonin secretion pattern.

Tension pneumopericardium following tracheoplasty for congenital tracheal stenosis.

Tension pneumopericardium is a rare complication of mechanical ventilation following tracheoplasty for congenital tracheal stenosis. This case report describes fatal tension pneumopericardium in a three-month-old male infant some 24 hours following tracheoplasty for this condition. Because of persisting stenosis of the left main bronchus, ventilation pressures of PIP 23 cm H2O and PEEP 5 cm, progressing to PIP 28 cm and PEEP 7 cm were needed to maintain adequate respiratory exchange. Partial relief of the pneumopericardium was achieved by vigorous cardiac massage, but three days later the infant died of massive airway haemorrhage.

Inhalation anesthetics suppress the expression of c-Fos protein evoked by noxious somatic stimulation in the deeper layer of the spinal cord in the rat.

The effects of inhalation anesthetics, nitrous oxide (N2O) and halothane, on the expression of c-Fos protein evoked by formalin injection were studied in the spinal cord in the rat. The expression of c-Fos protein was detected by immunocytochemistry following the injection of formalin (5%, 100 microliters) into the plantar surface of the left hindpaw. After 15 min of halothane (F) anesthesia, the anesthetics was switched to 40% or 70% of N2O, 0.5% or 1.5% of F or room air (for control) immediately following the formalin injection. Two hours later the rats were sacrificed and perfused. Sections of the L4 level of spinal cord were immunostained with anti c-Fos antibody. We counted the number of Fos-like immunoreactive (FLI) cells in every specific lamina as follows: superficial layer (laminae I and II), nucleus proprius (laminae III and IV), neck of the dorsal horn (laminae V and VI) and ventral gray (laminae VII-X). Then we compared the results of each category of sample. Both N2O and halothane suppressed the expression of c-Fos in the neck of the dorsal horn and ventral gray in a dose-dependent manner, but no effects were seen at the superficial layer or nucleus proprius. Suppression of c-Fos expression was greater under N2O than halothane anesthesia. This finding suggests that N2O had a stronger analgesic effect than halothane. The current study indicates that inhalation anesthetics do not act equally on every kind of spinal neurons. Both N2O and halothane have effects on spinal neurons in the deeper layers but not on the neurons existed in laminae I-II, some of which directly receive noxious inputs. Pretreatment with 2 mg/kg of naloxone, which completely reversed the effects of morphine, did not alter the effect of 70%N2O, suggesting that the analgesic effect of N2O is not mediated by an intrinsic opioid mechanism at the spinal cord level.

[Hemodynamic effects of amrinone combined with dopamine in patients undergoing living renal transplantation].

Systemic hypertension is a constant feature of chronic renal failure, mediated by renin and exacerbated by salt and fluid loading. Vascular atherosclerosis appears to accelerate in patients on long-term dialysis. Therefore, it is important to control hypertension and keep appropriate renal blood flow during living renal transplantation surgery. Amrinone, a phosphodiesterase inhibitor, produces vasodilation in arterial smooth muscle as well as venodilation in the capacitance bed. By increasing myocardial contractility it increases inotropic effect. Amrinone has potent inodilator effects because of its dual mechanism of action. The current study is aimed to compare hemodynamic effects between amrinone (3-5 mg.kg-1.min-1) (AMR group, n = 4) and nitroglycerin (0.3-1.0 mg.kg-1.min-1) (NTG group, n = 5), combined with dopamine (3-5 mg.kg-1.min-1) in nine patients undergoing living renal transplantation. Increase in cardiac index in AMR group was significantly larger than that in NTG group. Values of systemic and pulmonary vascular resistance in AMR group were significantly smaller than those in NTG group. No significant difference was found in renal function in the post-operative period.

[Anesthetic management of a patient complicated with restrictive cardiomyopathy for gastrectomy].

Restrictive cardiomyopathy is a rare condition characterized with endomyocardial fibrosis, which interferes diastolic ventricular filling. A 52-year-old man with a 38 year history of dyspnea on effort presented with advanced gastric cancer. Subtotal gastrectomy under general anesthesia was scheduled. Preoperative examination showed biventricular dysfunction, impaired liver function and chronic renal failure. General anesthesia was induced using fentanyl, pancuronium and isoflurane, and maintained with nitrous oxide/oxygen, isoflurane and fentanyl. Extensive invasive monitoring included arterial blood pressure, central venous pressure, pulmonary artery pressure and oxygen saturation of mixed venous blood as indices of left-sided pump function. Dopamine and nitroglycerin infusion was also started after the tracheal intubation. Although a transient improvement of cardiac function was noted after the removal of ascites 5 liter, restricted fluid administration induced desaturation of mixed venous blood and tachycardia. The start of low dose prostaglandin E1 markedly improved cardiac output without hypotension, while an increase of intravenous nitroglycerin did not prove to be beneficial. PGE1 was more selective in decreasing left ventricular afterload, while nitroglycerin produces greater decrease of preload.

Fine structure of noradrenergic terminals and their synapses in the rat spinal dorsal horn: an immunohistochemical study.

Noradrenergic fibers in the spinal dorsal horn originate from neurons in the A5-7 cell groups, and may participate in the modulation of pain. Here we studied the fine structure of noradrenergic terminals in the rat by immunohistochemistry using antiserum against dopamine-beta-hydroxylase (DBH). We also investigated the relationship between such terminals and primary afferent terminals. DBH-like immunoreactive terminals were found in lamina I and the outer layer of lamina II of the dorsal horn and they contained many clear round vesicles and some large granular vesicles. More than half of these terminals made synaptic contact with other neuronal elements with membrane specialization. Most of the postsynaptic structures of these terminals were small dendrites (69%); 28% were spines, and no synaptic contact was made with primary afferent terminals. These findings suggest that noradrenaline acts on the spinal dorsal horn neurons postsynaptically mainly via a direct synaptic mechanism.

Appearance of substance P-like immunoreactive neurons in the rat superior colliculus after neonatal eye enucleation.

The possibility that eye enucleation within one day after birth has an effect on the postnatal development of substance P (SP)-like-immunoreactive (SP-I) structures in the superior colliculus (SC) was investigated in the rat. Results were compared with those in animals enucleated at postnatal day 15. All the animals were allowed to survive until postnatal day 90, after which changes in SP-I neurons and fibers were identified immunohistochemically. In colchicine-treated rats, the most remarkable changes occurred in SP-I neurons following eye enucleation at birth; large numbers of SP-I neurons appeared in the ventral part of the stratum griseum superficiale (SGS), stratum opticum (SO) and stratum griseum intermediale (SGI) of the deafferentated SC. SP-I neurons did not appear in these layers, when deafferentation of the SC was carried out in rats at postnatal day 15. These findings suggest strongly that eye enucleation at birth affects the production of SP of neurons in the ventral part of the SGS, SO and SGI at the deafferentated SC. The appearance of SP-I neurons in the neonatal eye enucleation may be due, at least partially, to reorganization of another neuronal system in the SC.

Localization of GABAA-receptor alpha 1 subunit mRNA-containing neurons in the lower brainstem of the rat.

The localization of gamma-aminobutyric acid-A (GABAA) receptors (GABAA-R) in the lower brainstem of the rat was examined by means of in situ hybridization histochemistry using an oligonucleotide probe to the sequence of the alpha 1 subunit (GABAA-R alpha 1). Strongly labeled neurons were found in the cranial motor nuclei, the dorsal motor nucleus of the vagus, reticular formation (large neurons), lateral vestibular nucleus, dorsal nucleus of the lateral lemniscus, central nucleus of the inferior colliculus, intermediate and white layers of the superior colliculus, red nucleus and substantia nigra. In addition, moderately labeled cells were abundant in the nucleus of the solitary tract, medial and inferior vestibular nuclei, parabrachial area, dorsal and ventral tegmental nuclei of Gudden, central gray matter, ventral nucleus of the lateral lemniscus, and reticular formation (small neurons). This study has therefore revealed some of the target neurons of GABA-containing fibers in the lower brainstem.