Noninvasive Neuromonitoring of Hypothermic Circulatory Arrest in Aortic Surgery.

BACKGROUND AND AIMS: Circulatory arrest carries a high risk of neurological damage, but modern monitoring methods lack reliability, and is susceptible to the generalized effects of both anesthesia and hypothermia. The objective of this prospective, explorative study was to research promising, reliable, and noninvasive methods of neuromonitoring, capable of predicting neurological outcome after hypothermic circulatory arrest. MATERIALS AND METHODS: Thirty patients undergoing hypothermic circulatory arrest during surgery of the thoracic aorta were recruited in a single center and over the course of 4 years. Neuromonitoring was performed with a four-channel electroencephalogram montage and a near-infrared spectroscopy monitor. All data were tested off-line against primary neurological outcome, which was poor if the patient suffered a significant neurological complication (stroke, operative death). RESULTS: A poor primary neurological outcome seen in 10 (33%) patients. A majority (63%) of the cases were emergency surgery, and thus, no neurological baseline evaluation was possible. The frontal hemispheric asymmetry of electroencephalogram, as measured by the brain symmetry index, predicted primary neurological outcome with a sensitivity of 79 (interquartile range; 62%-88%) and specificity of 71 (interquartile range; 61%-84%) during the first 6 h after end of circulatory arrest. CONCLUSION: The hemispheric asymmetry of frontal electroencephalogram is inherently resistant to generalized dampening effects and is predictive of primary neurological outcome. The brain symmetry index provides an easy-to-use, noninvasive neuromonitoring method for surgery of the thoracic aorta and postoperative intensive care.

Responsiveness of the frontal EMG for monitoring the sedation state of critically ill patients.

BACKGROUND: Excessive sedation is associated with adverse patient outcomes during critical illness, and a validated monitoring technology could improve care. We developed a novel method, the responsiveness index (RI) of the frontal EMG. We compared RI data with Ramsay clinical sedation assessments in general and cardiac intensive care unit (ICU) patients. METHODS: We developed the algorithm by iterative analysis of detailed observational data in 30 medical-surgical ICU patients and described its performance in this cohort and 15 patients recovering from scheduled cardiac surgery. Continuous EMG data were collected via frontal electrodes and RI data compared with modified Ramsay sedation state assessments recorded regularly by a blinded trained observer. RI performance was compared with Entropy™ across Ramsay categories to assess validity. RESULTS: RI correlated well with the Ramsay category, especially for the cardiac surgery cohort (general ICU patients ρ=0.55; cardiac surgery patients ρ=0.85, both P<0.0001). Discrimination across all Ramsay categories was reasonable in the general ICU patient cohort [P(K)=0.74 (sem 0.02)] and excellent in the cardiac surgery cohort [P(K)=0.92 (0.02)]. Discrimination between 'lighter' vs 'deeper' (Ramsay 1-3 vs 4-6) was good for general ICU patients [P(K)=0.80 (0.02)] and excellent for cardiac surgery patients [P(K)=0.96 (0.02)]. Performance was significantly better than Entropy™. Examination of individual cases suggested good face validity. CONCLUSIONS: RI of the frontal EMG has promise as a continuous sedation state monitor in critically ill patients. Further investigation to determine its utility in ICU decision-making is warranted.

Wide inter-individual variability of bispectral index and spectral entropy at loss of consciousness during increasing concentrations of dexmedetomidine, propofol, and sevoflurane.

BACKGROUND: The bispectral index (BIS) and the spectral entropy (state entropy, SE, and response entropy, RE) are depth-of-anaesthesia monitors derived from EEG and have been developed to measure the effects of anaesthetics on the cerebral cortex. We studied whether they can differentiate consciousness from unconsciousness during increasing doses of three different anaesthetic agents. METHODS: Thirty healthy male volunteers aged 19-30 yr were recruited and divided into three 10-volunteer groups to receive either dexmedetomidine, propofol, or sevoflurane in escalating concentrations at 10 min intervals until loss of consciousness (LOC) was reached. Consciousness was tested at 5 min intervals and after drug discontinuation at 1 min intervals by requesting the subjects to open their eyes. LOC was defined as unresponsiveness to the request and pre-LOC as the last meaningful response. The first meaningful response to the request after drug discontinuation was defined as regaining of consciousness (ROC). For the statistical analysis, pre-LOC and ROC values were pooled to represent the responsive state while LOC values represented the unresponsive state. Prediction probability (P(K)) was estimated with the jack-knife method. RESULTS: The lowest mean values for BIS, SE, and RE were recorded at LOC with all three drugs. The P(K) values were low for dexmedetomidine (BIS 0.62, SE 0.58, RE 0.59), propofol (BIS 0.73, SE 0.72, RE 0.72), and sevoflurane (BIS 0.70, SE 0.52, RE 0.62). CONCLUSIONS: Because of wide inter-individual variability, BIS and entropy were not able to reliably differentiate consciousness from unconsciousness during and after stepwise increasing concentrations of dexmedetomidine, propofol, and sevoflurane.

Electroencephalogram spindle activity during dexmedetomidine sedation and physiological sleep.

BACKGROUND: Dexmedetomidine, a selective alpha(2)-adrenoceptor agonist, induces a unique, sleep-like state of sedation. The objective of the present work was to study human electroencephalogram (EEG) sleep spindles during dexmedetomidine sedation and compare them with spindles during normal physiological sleep, to test the hypothesis that dexmedetomidine exerts its effects via normal sleep-promoting pathways. METHODS: EEG was continuously recorded from a bipolar frontopolar-laterofrontal derivation with Entropy Module (GE Healthcare) during light and deep dexmedetomidine sedation (target-controlled infusions set at 0.5 and 3.2 ng/ml) in 11 healthy subjects, and during physiological sleep in 10 healthy control subjects. Sleep spindles were visually scored and quantitatively analyzed for density, duration, amplitude (band-pass filtering) and frequency content (matching pursuit approach), and compared between the two groups. RESULTS: In visual analysis, EEG activity during dexmedetomidine sedation was similar to physiological stage 2 (S2) sleep with slight to moderate amount of slow-wave activity and abundant sleep spindle activity. In quantitative EEG analyses, sleep spindles were similar during dexmedetomidine sedation and normal sleep. No statistically significant differences were found in spindle density, amplitude or frequency content, but the spindles during dexmedetomidine sedation had longer duration (mean 1.11 s, SD 0.14 s) than spindles in normal sleep (mean 0.88 s, SD 0.14 s; P=0.0014). CONCLUSIONS: Analysis of sleep spindles shows that dexmedetomidine produces a state closely resembling physiological S2 sleep in humans, which gives further support to earlier experimental evidence for activation of normal non-rapid eye movement sleep-promoting pathways by this sedative agent.

Assessing the depth of dexmedetomidine-induced sedation with electroencephalogram (EEG)-based spectral entropy.

BACKGROUND: Adequate sedation of critically ill patients improves the outcome of intensive care. Maintaining an optimal level of sedation in the intensive care unit (ICU) is difficult because of a lack of appropriate monitoring methods to guide drug dosing. Dexmedetomidine, a selective alpha(2)-adrenoceptor agonist, has recently been introduced for the sedation of ICU patients. This study investigated the utility of electroencephalogram (EEG)-based spectral entropy monitoring (with M-ENTROPY, GE Healthcare, Helsinki, Finland) for the assessment of dexmedetomidine-induced sedation. METHODS: Eleven healthy, non-smoking men, aged 23.9 +/- 2.5 years (mean +/- standard deviation), were recruited. Spectral entropy was recorded before and during low (0.5 ng/ml) and high (5 ng/ml) plasma concentrations of dexmedetomidine. At the end of the infusion, subjects were awakened by verbal command and light shaking. RESULTS: Spectral entropy decreased from 84 +/- 5 to 66 +/- 16 (P= 0.029) during low dexmedetomidine levels and from 84 +/- 5 to 20 +/- 12 (P < 0.001) during high dexmedetomidine levels. Transitions during loss and regaining of consciousness were analysed separately. Entropy decreased from 76 +/- 8 before to 43 +/- 10 (P < 0.001) after loss of consciousness, and increased from 14 +/- 4 to 63 +/- 13 (P < 0.001) on regaining of consciousness. These changes were consistent across all subjects. Prediction probability and sensitivity values indicated a high predictive performance of the method. CONCLUSION: The depth of dexmedetomidine-induced sedation can be monitored with EEG-based spectral entropy. These results should be confirmed in a clinical setting.

Increase in high frequency EEG activity explains the poor performance of EEG spectral entropy monitor during S-ketamine anesthesia.

OBJECTIVE: To study the effects of S-ketamine on the EEG and to investigate whether spectral entropy of the EEG can be used to assess the depth of hypnosis during S-ketamine anesthesia. METHODS: The effects of sub-anesthetic (159 (21); mean (SD) ng/ml) and anesthetic (1,959 (442) ng/ml) serum concentrations of S-ketamine on state entropy (SE), response entropy (RE) and classical EEG spectral power variables (recorded using the Entropy Module, GE Healthcare, Helsinki, Finland) were studied in 8 healthy males. These EEG data were compared with EEG recordings from 6 matching subjects anesthetized with propofol. RESULTS: The entropy values decreased from the baseline SE 85 (3) and RE 96 (3) to SE 55 (18) and RE 72 (17) during S-ketamine anesthesia but both inter- and intra-individual variation of entropy indices was wide and their specificity to indicate unconsciousness was poor. Propofol induced more pronounced increase in delta power (P<0.02) than S-ketamine, whereas anesthetic S-ketamine induced more high frequency EEG activity in the gamma band (P<0.001). Relative power of 20-70 Hz EEG activity was associated with high SE (P=0.02) and RE (P=0.03) values during S-ketamine anesthesia. CONCLUSIONS: These differences in low and high frequency EEG power bands probably explain why entropy monitor, while adequate for propofol, is not suitable for assessing the depth of S-ketamine anesthesia. SIGNIFICANCE: The entropy monitor is not adequate for monitoring S-ketamine-induced hypnosis.

Correlation of EEG spectral entropy with regional cerebral blood flow during sevoflurane and propofol anaesthesia.

ENTROPY index monitoring, based on spectral entropy of the electroencephalogram, is a promising new method to measure the depth of anaesthesia. We examined the association between spectral entropy and regional cerebral blood flow in healthy subjects anaesthetised with 2%, 3% and 4% end-expiratory concentrations of sevoflurane and 7.6, 12.5 and 19.0 microg.ml(-1) plasma drug concentrations of propofol. Spectral entropy from the frequency band 0.8-32 Hz was calculated and cerebral blood flow assessed using positron emission tomography and [(15)O]-labelled water at baseline and at each anaesthesia level. Both drugs induced significant reductions in spectral entropy and cortical and global cerebral blood flow. Midfrontal-central spectral entropy was associated with individual frontal and whole brain blood flow values across all conditions, suggesting that this novel measure of anaesthetic depth can depict global changes in neuronal activity induced by the drugs. The cortical areas of the most significant associations were remarkably similar for both drugs.

Application of spectral entropy to EEG and facial EMG frequency bands for the assessment of level of sedation in ICU.

The applicability and performance of spectral entropy as a measure of the depth of sedation was studied by comparison to the Richmond sedation and agitation scale (RASS). A biopotential signal was measured from the forehead of eight ICU patients. From this biopotential four different frequency bands were defined using trend fitting to the low and high frequency limits of the pooled power spectra, two frequency bands representing EEG and the other two representing fEMG. The spectral entropy from the EEG bands correlated very well with the sedation levels of RASS. From levels 0 to -5 the decrease was almost linear (r=0.51 and r=0.53). A similar comparison for the spectral entropy of the fEMG bands did not produce any clear correlation (r=0.07 for both fEMG bands), however there was still some clear interaction at some levels. It seems that the RASS is dependent upon both EEG and fEMG effects. That is; RASS is related to both cortical and sub-cortical components of sedation.

Sevoflurane mask induction of anaesthesia is associated with epileptiform EEG in children.

BACKGROUND: Sevoflurane inhalation induction of anaesthesia is widely used in paediatric anaesthesia. We have found that this method is frequently associated with epileptiform electroencephalogram (EEG) in adults, especially if controlled hyperventilation is used. METHODS: We assessed EEG during sevoflurane inhalation induction in 31 children, aged 2-12 yr. Anaesthesia was induced with 8% sevoflurane in O2 in N2O 1:2. The patients were randomized to undergo controlled ventilation (CV group), or to breathe spontaneously (SB group) for 5 min. EEG was recorded as were noninvasive blood pressure and heart rate (HR). EEG recordings were classified by a clinical neurophysiologist. RESULTS: Three different types of interictal epileptiform discharge were detected. Suppression with spikes (SSP) was found in 25% and 0% in the CV and SB groups, rhythmic polyspikes (PSR) in 44% and 20%, and periodic epileptiform discharges (PED) in 44% and 0% (P<0.01), respectively. The incidence of all different types of interictal epileptiform discharge (SSP+PSR+PED) was 88% and 20% (P<0.001), respectively. Epileptiform EEG was associated with increased heart rate and blood pressure during anaesthetic induction. CONCLUSION: Both ventilation modes produced epileptiform EEG. With controlled ventilation, epileptiform discharges were seen in 88% of children. This warrants further studies of the suitability of this induction type in general, and especially in children with epilepsy.

Epileptiform EEG during sevoflurane mask induction: effect of delaying the onset of hyperventilation.

BACKGROUND: Hyperventilation during sevoflurane-N2O-O2 mask induction in adults is associated with a hyperdynamic circulatory response and epileptiform electroencephalogram (EEG). We tested the hypothesis that delaying onset of hyperventilation will prevent severe (periodic) epileptiform EEG and hyperdynamic response. METHODS: Thirty patients were randomized to receive either delayed (group D, n=15) or immediate (group I, n=15) onset of hyperventilation during sevoflurane (8% in N2O 50%) mask inhalation induction with single-breath method for unconsciousness. Fifteen patients were allowed to breathe spontaneously for 2 min after loss of consciousness and controlled hyperventilation (ETCO2 <4%) was started thereafter. In 15 patients controlled hyperventilation was started immediately after loss of consciousness. EEG was recorded, and mean arterial pressure (MAP) and heart rate (HR) registered. RESULTS: Epileptiform EEG patterns were seen in 13 patients in group I and in 9 patients in group D (n.s.). Periodic epileptiform discharges (PED) tended to occur more often in group I (P=0.07). Heart rate and MAP were higher in group I than in group D from 2 min to 3 min (P < 0.05), and both HR and MAP rose significantly from the baseline in group I. In group D, HR but not MAP rose significantly from baseline. CONCLUSION: Regardless of its timing, hyperventilation at a high sevoflurane concentration produced severe epileptiform EEG with a hyperdynamic response. PED tended to occur more often with immediate onset of hyperventilation.

Epileptiform electroencephalogram during mask induction of anesthesia with sevoflurane.

BACKGROUND: Sevoflurane is suggested as a suitable anesthetic agent for mask induction in adults. The authors recently found that hyperventilation during sevoflurane-nitrous oxide-oxygen mask induction is associated with cardiovascular hyperdynamic response. We tested the hypothesis that the hyperdynamic response can be explained by electroencephalography (EEG) findings. METHODS: Thirty women were randomly allocated to receive sevoflurane-nitrous oxygen-oxygen mask induction using a single-breath method, followed by either spontaneous breathing (n = 15) or controlled hyperventilation (n = 15) for 6 min. EEG was recorded. Blood pressure and heart rate were recorded at 1-min intervals. RESULTS: Epileptiform EEG activity (spikes or polyspikes) was seen in all patients with controlled hyperventilation, and in seven patients with spontaneous breathing (P < 0.01). Jerking movements were seen in three patients with controlled hyperventilation. In the controlled hyperventilation group, heart rate increased 54% from baseline at 4 min after induction (P < 0.001). Mean arterial pressure increased 17% (P < 0.05), peaking at 3 min. In the spontaneous breathing group, heart rate showed no change, and mean arterial pressure decreased by 14% (P < 0.01) at 6 min. Heart rate and mean arterial pressure differed significantly between the groups from 2 min after beginning of the induction to the end of the trial. An increase in heart rate of more than 30% from baseline always was associated with epileptiform EEG activity. CONCLUSIONS: Sevoflurane mask induction elicits epileptiform EEG patterns. These are associated with an increase in heart rate in patients with controlled hyperventilation and also during spontaneous breathing of sevoflurane.