Satoshi Hagihira

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.

The relationship between bispectral index and electroencephalographic parameters during isoflurane anesthesia

Bispectral index (BIS) integrates various electroencephalographic (EEG) parameters into a single variable. However, the exact algorithm used to synthesize the parameters to BIS values is not known. The relationship between BIS and EEG parameters was evaluated during nitrous oxide/isoflurane anesthesia. Twenty patients scheduled for elective ophthalmic surgery were enrolled in the study. After EEG recording with a BIS monitor (A-1050) was begun, general anesthesia was induced and maintained with 0.5%–2% isoflurane and 66% nitrous oxide. Using software we developed, we continuously recorded BIS, spectral edge frequency 95% (SEF95), and EEG parameters such as relative beta ratio (BetaRatio), relative synchrony of fast and slow wave (SynchFastSlow), and burst suppression ratio. BetaRatio was linearly correlated with BIS (r = 0.90; P < 0.01; n = 253) at BIS more than 60. At a BIS range of 30 to 80, SynchFastSlow (r = 0.60; P < 0.01; n = 3314) and SEF95 (r = 0.75; P < 0.01; n = 3339) were linearly correlated with BIS. The correlation between BIS and SEF95 was significantly better than the correlation between BIS and SynchFastSlow (P < 0.01). At BIS less than 30, the burst suppression ratio was inversely linearly correlated with BIS (r = 0.76; P < 0.01; n = 65). At BIS less than 80, burst-compensated SEF95 was linearly correlated with BIS (r = 0.78; P < 0.01; n = 3404). In the range of BIS from 60 to 100, BIS can be calculated from Beta-Ratio. At surgical levels of anesthesia, BIS and Synch-FastSlow (a parameter derived from bispectral analysis) or burst-compensated SEF95 (derived from power spectral analysis) are well correlated. However, our results show that SynchFastSlow has no advantage over SEF95 in calculation of BIS.

Electroencephalographic Bicoherence Is Sensitive to Noxious Stimuli during Isoflurane or Sevoflurane Anesthesia

BackgroundThe authors previously reported changes in electroencephalographic bicoherence during isoflurane anesthesia combined with epidural anesthesia. Here, they examined the influence of noxious stimuli on electroencephalographic bicoherence as well as on the Bispectral Index (BIS) and the 95% spectral edge frequency (SEF95). MethodsThe authors enrolled 48 elective abdominal surgery patients (aged 22–77 years; American Society of Anesthesiologists physical status I or II). Raw electroencephalographic signals as well as BIS and SEF95 were recorded on a computer using a BIS® monitor (A-1050) and Bispectrum Analyzer (BSA) for BIS (the authors’ original software). Using BSA for BIS, the authors evaluated the two peak heights of electroencephalographic bicoherence. Anesthesia was induced with 3 mg/kg thiopental and was maintained with, in air–oxygen, 1.0% isoflurane or 1.5% sevoflurane. After confirming the steady state, the authors recorded baseline values. In experiment 1, they administered 3 &mgr;g/kg fentanyl 5 min after incision and investigated the changes in electroencephalographic derivatives at 5 and 10 min after incision. In experiment 2, they administered a similar dose of fentanyl 5 min before incision and investigated the changes in electroencephalographic derivatives immediately before and 5 min after incision. ResultsIn experiment 1, after incision, both peak heights of electroencephalographic bicoherence significantly decreased but returned to control values after fentanyl administration. By contrast, after incision, BIS and SEF95 showed individual variability. In experiment 2, although fentanyl itself did not affect all electroencephalographic derivatives before incision, the variables remained unchanged after incision. ConclusionNoxious stimuli decreased the peak heights of electroencephalographic bicoherence, an effect that was counteracted by fentanyl analgesia.

The detection of cerebral hypoperfusion with bispectral index monitoring during general anesthesia.

We describe a patient in whom the bispectral index (BIS) decreased to 0 during surgery. A 42-yr-old man with chronic renal failure was scheduled to undergo construction of an arteriovenous shunt. He had a history of acute cerebral hemorrhage. An intracranial hematoma had been removed a month earlier with almost complete neurological recovery. He had uncontrolled hypertension. His systolic blood pressure was 180 mm Hg before anesthesia induction. Anesthesia was induced with 100 mg of propofol and 3% sevoflurane. After laryngeal mask insertion, anesthesia was maintained with nitrous oxide 60% in oxygen and sevoflurane. BIS decreased to near 0 on 2 occasions: after anesthesia induction and shortly after the start of the surgery. His systolic blood pressure decreased to 110 mm Hg and BIS increased when his blood pressure was increased to 130-140 mm Hg. The decrease in BIS was suspected to be the result of decreased cerebral blood flow. The systolic blood pressure of 110 mm Hg (mean blood pressure, 80 mm Hg) was probably less than the lower limit of autoregulation. Although BIS has some limitations as a cerebral monitor, it was useful for detecting possible cerebral hypoperfusion in this case.

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.

Early Phase Pharmacokinetics but Not Pharmacodynamics Are Influenced by Propofol Infusion Rate

Background:Conventional compartmental pharmacokinetic models wrongly assume instantaneous drug mixing in the central compartment, resulting in a flawed prediction of drug disposition for the first minutes, and the flaw affects pharmacodynamic modeling. This study examined the influence of the administration rate and other covariates on early phase kinetics and dynamics of propofol by using the enlarged structural pharmacokinetic model. Methods:Fifty patients were randomly assigned to one of five groups to receive 1.2 mg/kg propofol given with the rate of 10 to 160 mg · kg−1 · h−1. Arterial blood samples were taken frequently, especially during the first minute. The authors compared four basic pharmacokinetic models by using presystemic compartments and the time shift of dosing, LAG time. They also examined a sigmoidal maximum possible drug effect pharmacodynamic model. Patient characteristics and dose rate were obtained to test the model structure. Results:Our final pharmacokinetic model includes two conventional compartments enlarged with a LAG time and six presystemic compartments and includes following covariates: dose rate for transit rate constant, age for LAG time, and weight for central distribution volume. However, the equilibration rate constant between central and effect compartments was not influenced by infusion rate. Conclusions:This study found that a combined pharmacokinetic-dynamic model consisting of a two-compartmental model with a LAG time and presystemic compartments and a sigmoidal maximum possible drug effect model accurately described the early phase pharmacology of propofol during infusion rate between 10 and 160 mg · kg−1 · h−1. The infusion rate has an influence on kinetics, but not dynamics. Age was a covariate for LAG time.

Calcium-binding proteins calbindin and parvalbumin in the superficial dorsal horn of the rat spinal cord

Neurons containing the calcium-binding proteins, calbindin or parvalbumin, were studied by immunohistochemistry in the superficial dorsal horn of the rat spinal cord. Calbindin-containing cells were found in laminae I, II and III, being more abundant in laminae I and II. Some of the neurons in lamina I containing calbindin projected to the supraspinal area. Parvalbumin-containing neurons were mainly distributed in laminae IIi and III. Calbindin and parvalbumin were not detected in the same cells. Some 75% of the neurotensin-like immunoreactive neurons contained calbindin, which corresponded to 13% of the calbindin-containing neurons. Calbindin was sometimes found in the same cells with substance P, enkephalin or somatostatin but less frequently (44-46% of the peptide-containing neurons). Parvalbumin was not found together with these peptides. Electron microscopy showed that the immunoreactive products of calbindin or parvalbumin were mostly in the dendrites or cell bodies. Immunoreactive axon terminals were relatively few. In rhizotomized animals, neurons containing one of these proteins in laminae II and III were found to receive direct inputs of primary afferent fibers. These findings indicate that neurons containing these two proteins belong to different subpopulations of dorsal horn neurons. They may be important in primary afferent processing.

Changes in the bispectral index during intraabdominal irrigation in patients anesthetized with nitrous oxide and sevoflurane

Surgical stimulation typically results in an activation of electroencephalographic activity. In some instances, painful stimulation in the presence of inadequate anesthesia results in a suppression of the electroencephalogram. This phenomenon has been referred to as a “paradoxical arousal.” In our daily practice, we have noted a marked decrease in the bispectral index (BIS) with large &dgr; waves during abdominal surgery when the abdominal cavity was irrigated with normal saline. In the present study, we sought to evaluate changes in BIS during intraabdominal irrigation. Eighteen ASA physical status I–II patients scheduled for elective abdominal surgery were enrolled in the study and allocated randomly to the control group (group C) or the fentanyl group (group F). Anesthesia was induced with 3 mg/kg of thiopental and was maintained with sevoflurane and 50% nitrous oxide. BIS, 95% spectral edge frequency (SEF95), and burst-suppression ratio were recorded using a BIS monitor. Near the end of the procedure, but before irrigation of the abdominal cavity, 1.5 &mgr;g/kg fentanyl was given IV to group F. There was no significant change in BIS or SEF95 in group F patients during subsequent irrigation of the abdominal cavity. In contrast, BIS and SEF95 decreased significantly after start of irrigation in group C patients. These data show that the stimulation occurring during intraabdominal irrigation might cause a paradoxical arousal response, as evidenced by a decrease in processed electroencephalographic parameters. Pretreatment with fentanyl suppressed these changes. Anesthesiologists should be aware of this paradoxical arousal response to avoid an inappropriate decrease in the anesthetic concentration in such situations.

Changes of Electroencephalographic Bicoherence during Isoflurane Anesthesia Combined with Epidural Anesthesia

Background The authors previously reported that, during isoflurane anesthesia, electroencephalographic bicoherence values changed in a fairly restricted region of frequency versus frequency space. The aim of the current study was to clarify the relation between electroencephalographic bicoherence and the isoflurane concentration. Methods Thirty elective abdominal surgery patients (male and female, aged 34–77 yr, American Society of Anesthesiologists physical status I–II) were enrolled. After electroencephalogram recording with patients in an awake state, anesthesia was induced with 3 mg/kg thiopental and maintained with oxygen and isoflurane. Continuous epidural anesthesia with 80–100 mg/kg 1% lidocaine was also administered. Using software they developed, the authors continuously recorded the FP1–A1 lead of the electroencephalographic signal and expired isoflurane concentration to an IBM-PC compatible computer. After confirming the steady state of each isoflurane (end-tidal concentration at 0.3, 0.5, 0.7, 0.9, 1.1, 1.3, and 1.5%), electroencephalographic bicoherence values were calculated. Results In a light anesthetic state, electroencephalographic bicoherence values were low (generally ≤ 15.0%). At increased concentrations of isoflurane, two peaks of electroencephalographic bicoherence emerged along the diagonal line (f1 = f2). The peak emerged at around 4.0 Hz and grew higher as isoflurane concentration increased until it reached a plateau (43.8 ± 3.5%, mean ± SD) at isoflurane 0.9%. The other peak, at about 10.0 Hz, also became significantly higher and reached a plateau (32.6 ± 9.2%) at isoflurane 0.9%; at isoflurane 1.3%, however, this peak slightly decreased. Conclusion Changes in the height of two electroencephalographic bicoherence peaks correlated well with isoflurane concentration.

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.