Richard K. Ellerkmann

Spectral entropy and bispectral index as measures of the electroencephalographic effects of sevoflurane.

Background:Recently, entropy algorithms have been proposed as electroencephalographic measures of anesthetic drug effects. Datex-Ohmeda (Helsinki, Finland) introduced the Entropy Module, a new electroencephalographic monitor designed for measuring depth of anesthesia. The monitor calculates a state entropy (SE) computed over the frequency range of 0.8–32 Hz and a response entropy (RE) computed over the frequency range of 0.8–47 Hz. The authors investigated the dose–response relation of SE and RE during sevoflurane anesthesia in comparison with the Bispectral Index (BIS). Methods:Sixteen patients were studied without surgical stimulus. Anesthesia was induced by sevoflurane inhalation with a tight-fitting facemask. Sevoflurane concentrations were increased and subsequently decreased and increased two to four times until the measurement was stopped and patients were intubated for surgery. The performances of SE, RE, and BIS to predict the estimated sevoflurane effect site concentration, obtained by simultaneous pharmacokinetic and pharmacodynamic modeling, were compared by calculating the correlation coefficients and the prediction probability. Results:State entropy, RE, and BIS values decreased continuously over the observed concentration range of sevoflurane. Correlation coefficients were slightly but not significantly better for entropy parameters (0.87 ± 0.09 and 0.86 ± 0.10 for SE and RE, respectively) than for BIS (0.85 ± 0.12). Calculating the prediction probability confirmed these results with a prediction probability of 0.84 ± 0.05 and 0.82 ± 0.06 for SE and RE, respectively, and 0.80 ± 0.06 for BIS. Conclusion:State entropy and RE seem to be useful electroencephalographic measures of sevoflurane drug effect.

Slow recovery from inactivation regulates the availability of voltage-dependent Na+ channels in hippocampal granule cells, hilar neurons and basket cells

1 Fundamental to the understanding of CNS function is the question of how individual neurons integrate multiple synaptic inputs into an output consisting of a sequence of action potentials carrying information coded as spike frequency. The availability for activation of neuronal Na+ channels is critical for this process and is regulated both by fast and slow inactivation processes. Here, we have investigated slow inactivation processes in detail in hippocampal neurons. 2 Slow inactivation was induced by prolonged (10‐300 s) step depolarisations to ‐10 mV at room temperature. In isolated hippocampal dentate granule cells (DGCs), recovery from this inactivation was biexponential, with time constants for the two phases of slow inactivation τslow,1 and τslow,2 ranging from 1 to 10 s and 20 to 50 s, respectively. Both τslow,1 and τslow,2 were related to the duration of prior depolarisation by a power law function of the form τ(t) =a (t/a)b, where t is the duration of the depolarisation, a is a constant kinetic setpoint and b is a scaling power. This analysis yielded values of a= 0.034 s and b= 0.62 for τslow,1 and a= 24 s and b= 0.30 for τslow,2 in the rat. 3 When a train of action potential‐like depolarisations of different frequencies (50, 100, 200 Hz) was used to induce inactivation, a similar relationship was found between the frequency of depolarisation and both τslow,1 and τslow,2 (a= 0.58 s, b= 0.39 for τslow,1 and a= 3.77 s and b= 0.42 for τslow,2). 4 Using nucleated patches from rat hippocampal slices, we have addressed possible cell specific differences in slow inactivation. In fast‐spiking basket cells a similar scaling relationship can be found (a= 3.54 s and b= 0.39) as in nucleated patches from DGCs (a= 2.3 s and b= 0.48) and non‐fast‐spiking hilar neurons (a= 2.57 s and b= 0.49). 5 Likewise, comparison of human and rat granule cells showed that properties of ultra‐slow recovery from inactivation are conserved across species. In both species ultra‐slow recovery was biexponential with both τslow,1 and τslow,2 being related to the duration of depolarisation t, with a= 0.63 s and b= 0.44 for τslow,1 and a= 25 s and b= 0.37 for τslow,2 for the human subject. 6 In summary, we describe in detail how the biophysical properties of Na+ channels result in a complex interrelationship between availability of sodium channels and membrane potential or action potential frequency that may contribute to temporal integration on a time scale of seconds to minutes in different types of hippocampal neurons.

Spectral entropy and bispectral index as measures of the electroencephalographic effects of propofol

Recently, Datex-Ohmeda introduced the Entropy Module™ for measuring depth of anesthesia. Based on the Shannon entropy of the electroencephalogram, state entropy (SE) and response entropy (RE) are computed. We investigated the dose-response relationship of SE and RE during propofol anesthesia in comparison with the Bispectral Index™ (BIS). Twenty patients were studied without surgical stimulus. Anesthesia was induced by a constant propofol infusion of 2000 mg/h (451 ± 77 &mgr;g·min−1·kg−1) via a large forearm vein. Propofol was infused until substantial burst suppression occurred (more than 50%) or mean arterial blood pressure decreased to <60 mm Hg. Hereafter, infusions were stopped until recovery of BIS values up to 60 was reached. Subsequently, the constant propofol infusion of 2000 mg/h was restarted to increase depth of anesthesia and again decreased (infusion was stopped) within the BIS value range of 40–60. The coefficient of determination (R2) and the prediction probability (PK) were calculated to evaluate the performance of SE, RE, and BIS to predict changing propofol effect-site concentrations. R2 values for SE, RE, and BIS of 0.88 ± 0.08, 0.89 ± 0.07, and 0.92 ± 0.06, respectively, were similar. The calculated PK values, however, revealed a significant difference between SE and RE compared with BIS, with PK = 0.77 ± 0.09, 0.76 ± 0.10, and 0.84 ± 0.06, respectively. BIS seems to show slight advantages in predicting propofol effect-site concentrations compared with SE and RE, as measured by PK but not as measured by R2.

Comparison between Bispectral Index and Patient State Index as Measures of the Electroencephalographic Effects of Sevoflurane

Background: The Bispectral Index (BIS) and the Patient State Index (PSI) quantify depth of anesthesia by analyzing the electroencephalogram. The authors examined the response of BIS and PSI to sevoflurane anesthesia. Methods: In 22 patients, sevoflurane anesthesia was induced by inhalation with a tight-fitting facemask and was maintained via a laryngeal mask. Sevoflurane concentrations were increased until burst suppression occurred and subsequently decreased until BIS recovered to values above 60. This procedure was repeated twice until patients underwent intubation for subsequent surgery. End-tidal sevoflurane concentrations, BIS, and PSI were recorded simultaneously. The performance of PSI and BIS to predict the estimated sevoflurane effect site concentration, as derived from simultaneous pharmacokinetic and pharmacodynamic modeling, was compared by determination coefficients (&rgr;2) and prediction probabilities (PK). Results: A significant (P < 0.001) correlation between BIS and PSI was found (r2 = 0.75), and a close sigmoid relation between sevoflurane effect site concentration and both BIS (&rgr;2 = 0.84 ± 0.09) and PSI (&rgr;2 = 0.85 ± 0.15) was observed. The maximum sevoflurane electroencephalographic effect resulted in PSI values (1.3 ± 4.3) that were significantly (P = 0.019) lower than BIS values (7.9 ± 12.1), and the effect site efflux constant ke0 was significantly smaller (P = 0.001) for PSI (0.13 ± 0.08 min−1) than for BIS (0.24 ± 0.15 min−1). The probability of BIS (PK = 0.80 ± 0.11) to predict sevoflurane effect site concentration did not differ (P = 0.76) from that of PSI (PK = 0.79 ± 0.09). Conclusions: The BIS reacted faster to changes in sevoflurane concentrations, whereas the PSI made better use of the predefined index range. However, despite major differences in their algorithms and minor differences in their dose–response relations, both PSI and BIS predicted depth of sevoflurane anesthesia equally well.

The response of the composite variability index to a standardized noxious stimulus during propofol-remifentanil anesthesia.

BACKGROUND:Recently the Composite Variability Index (CVI) was developed to quantify nociception. This index is derived from the standard deviations (s) of the Bispectral Index (sBIS) and the electromyogram (sEMG). The primary aim of our study was to compare CVI before and after a noxious stimulus. As secondary end points, we investigated the influence of remifentanil on the CVI and tested the ability of the CVI to indicate patient movement after a noxious stimulus under changing remifentanil concentrations. Furthermore, we measured the increase in CVI after a noxious stimulus in comparison to other clinical variables (BIS, sBIS, sEMG, heart rate [HR], and systolic blood pressure [BPsys]). METHODS:Twenty-four patients without a history of cardiac disease were investigated. Anesthesia was induced with propofol administered by target-controlled infusion. A standardized noxious electrical stimulus was applied (50 Hz, 70 mA, 30 seconds) to the ulnar nerve at increasing or decreasing remifentanil effect-compartment concentrations (Ceremi). Changes in baseline and poststimulus CVI, BIS, sBIS, sEMG, HR, and BPsys were investigated. Parameters’ ability to indicate movement after a noxious stimulus was evaluated with the prediction probability (PK). RESULTS:All investigated parameters (except BPsys) increased significantly after a noxious stimulus at 0, 1, 2, or 3 ng·mL−1 Ceremi. The association between poststimulus maximal parameters and movement were PK = 0.81 for HR, PK = 0.78 for sEMG, and PK = 0.72 for CVI (pairwise difference to CVI statistically nonsignificant). The association between &Dgr;sEMG or &Dgr;CVI (poststimulus value minus baseline value) and movement was significantly higher (PK = 0.76 and 0.75, respectively) compared with &Dgr;HR (PK = 0.53) (P = 0.008 and P = 0.01, respectively). Receiver operating characteristic analysis revealed a threshold value for movement for &Dgr;CVI of >0.39 (sensitivity of 0.71, specificity of 0.74) and for &Dgr;sEMG of >0.31 (sensitivity of 0.68, specificity of 0.78). CONCLUSION:In paralyzed patients, &Dgr;sEMG and &Dgr;CVI might help identify inadequately low levels of analgesia with an acceptable sensitivity and specificity. The impact of profound neuromuscular block on the CVI should be investigated in further studies.

Patient state index vs bispectral index as measures of the electroencephalographic effects of propofol

BACKGROUND The patient state index (PSI) and the bispectral index (BIS) quantify anaesthetic depth based on the EEG using different algorithms. We compared both indices with regard to the prediction of the depth of propofol anaesthesia. METHODS In 17 patients, propofol was infused until burst suppression occurred and stopped thereafter until BIS recovered to values above 60. This was repeated; afterwards, patients were intubated, for subsequent surgery. Without surgical stimulus, PSI and BIS were measured simultaneously and compared with the estimated effect-site concentrations of propofol. These were derived from simultaneous pharmacokinetic and -dynamic modelling in an individual two-stage and a population-based NONMEM approach. RESULTS A close sigmoid relationship was observed between the propofol effect-site concentration and both PSI [coefficient of determination rho(2)=0.91 (sd 0.05)] and BIS [rho(2)=0.92 (0.03)], which was significantly steeper for PSI [gamma=2.2 (0.6)] than for BIS [gamma=1.8 (0.4)], and reached significantly lower values for PSI [E(max)=0.3 (1.1)] than for BIS [E(max)=5.3 (6.7)] at maximal propofol concentrations. A significantly smaller k(e0) was obtained for PSI [0.09 (0.03) min(-1)] compared with BIS [0.10 (0.02) min(-1)]. PSI and BIS correlated significantly with each other (rho(2)=0.866) and predicted propofol effect-site concentration with a comparable probability [P(K)=0.87 (0.05) and 0.86 (0.05), respectively]. NONMEM revealed E(0)=89.3 and 92.3, E(max)=1.9 and 8.6, C(e50)=1.38 and 1.92 microg ml(-1), gamma=1.6 and 1.48, and k(e0)=0.103 and 0.131 min(-1) as typical values for PSI and BIS, respectively. CONCLUSIONS The PSI and the BIS monitors performed equally well in predicting depth of propofol anaesthesia. However, PSI was lower than BIS by approximately 10-15 points at high propofol concentrations.

Monitoring of cerebral oxygen saturation during resuscitation in out-of-hospital cardiac arrest: a feasibility study in a physician staffed emergency medical system

BackgroundDespite recent advances in resuscitation algorithms, neurological injury after cardiac arrest due to cerebral ischemia and reperfusion is one of the reasons for poor neurological outcome. There is currently no adequate means of measuring cerebral perfusion during cardiac arrest. It was the aim of this study to investigate the feasibility of measuring near infrared spectroscopy (NIRS) as a potential surrogate parameter for cerebral perfusion in patients with out-of-hospital resuscitations in a physician-staffed emergency medical service.MethodsAn emergency physician responding to out-of-hospital emergencies was equipped with a NONIN cerebral oximetry device. Cerebral oximetry values (rSO2) were continuously recorded during resuscitation and transport. Feasibility was defined as >80% of total achieved recording time in relation to intended recording time.Results10 patients were prospectively enrolled. In 89.8% of total recording time, rSO2 values could be recorded (213 minutes and 20 seconds), thus meeting feasibility criteria. 3 patients experienced return of spontaneous circulation (ROSC). rSO2 during manual cardiopulmonary resuscitation (CPR) was lower in patients who did not experience ROSC compared to the 3 patients with ROSC (31.6%, ± 7.4 versus 37.2% ± 17.0). ROSC was associated with an increase in rSO2. Decrease of rSO2 indicated occurrence of re-arrest in 2 patients. In 2 patients a mechanical chest compression device was used. rSO2 values during mechanical compression were increased by 12.7% and 19.1% compared to manual compression.ConclusionsNIRS monitoring is feasible during resuscitation of patients with out-of-hospital cardiac arrest and can be a useful tool during resuscitation, leading to an earlier detection of ROSC and re-arrest. Higher initial rSO2 values during CPR seem to be associated with the occurrence of ROSC. The use of mechanical chest compression devices might result in higher rSO2. These findings need to be confirmed by larger studies.

Management of Chronic Orofacial Pain: A Survey of General Dentists in German University Hospitals

AIM This survey assessed procedures performed by general dentists in German university hospitals treating patients with chronic orofacial pain (COP). METHODS A standardized questionnaire was sent to dentists at all 42 German universities. Doctors were asked to describe demographics, diagnoses, etiologies, diagnostic, and treatment procedures for their patients seen over a 3-month period. RESULTS A total of 34,242 patients from 19 responding university hospitals were enrolled. COP of greater than 6 months duration was identified in 1,767 patients (5.2%), of whom 64% were female, 76% were between 20 and 59 years old, 66.3% frequently changed doctors, and 29.5% demonstrated psychological comorbidities. The most common causes of COP were temporomandibular disorders, atypical odontalgia, and atypical facial pain accounting for 83.4% of the sample, with purported etiologies of surgery or trauma (52.4%), musculoskeletal disorders (24.2%), prosthetics (11.4%), or psychosomatic causes (11.7%). A secondary pain syndrome was found in 25% of patients. Before admission to the universities, 59.4% of patients reported inadequate pain control. Following admission, the number of patients receiving specialized therapies significantly increased from 40.6% to 88.2% (chi(2) test; P < 0.001), and improved pain was reported in 71.4% of patients. Multimodal therapy included treatment of malocclusion (47.1%), surgery (37.7%), analgesics (27.5%), and physiotherapy (22%). Specialized pain assessment (26.5%) or visual analog scales (16.9%) were applied irregularly and pain therapists were rarely consulted (8.9%). Despite the high psychological comorbidity (29.5%), psychological treatments were obtained for only 11%. CONCLUSIONS The prevalence of COP is 5% in German University dental practices, where current guidelines of COP treatment are followed incompletely, and patients with psychological disorders are usually not treated. Interdisciplinary practice principles should be encouraged.

Reduction in anaesthetic drug consumption is correlated with mean titrated intra-operative Bispectral Index values.

Background:  Several studies have shown a reduction in anaesthetic drug consumption with Bispectral Index (BIS) titration compared with standard clinical practice. However, the amount of reduction varied widely between 1% and 40%. We investigated the correlation between reduction in anaesthetic drug consumption and mean titrated BIS values.

The Correlation of the Bispectral Index with Propofol Effect Site Concentrations is not Altered by Epochs Indicated as Artefact-Loaded by Narcotrend

Objective. Artefact detection is an essential feature of automatic EEG monitoring systems used in anaesthesia. Clinical experience indicates that Narcotrend monitoring (MonitorTechnik, Bad Bramstedt, Germany, version 4.0) excludes more EEG epochs because of artefacts than bispectral index monitoring (BIS, Aspect Medical Systems, Newton, MA, version XP). Whether this increased exclusion of epochs is justified has not been investigated yet. Methods. Eighteen adult patients undergoing radical prostatectomy were investigated. Induction of anaesthesia was performed with a fentanyl bolus and a propofol infusion. Additionally, following intubation patients received 15 ml bupivacaine 0.5% epidurally. After a waiting period of 45 min depth of anaesthesia was varied two times by increasing and decreasing propofol concentrations. Narcotrend index, BIS values and calculated propofol effect site concentrations were automatically recorded at intervals of 5 s. We tested the hypothesis whether exclusion of artefacts detected by the Narcotrend monitor would possibly improve the prediction probability of the BIS monitor, justifying the necessity of artefact suppression. Results. Simulated propofol effect site concentrations ranged from 2 μ g/ml to 6 μ g/ml. The Narcotrend monitor excluded a significantly higher percentage of epochs because of artefact detection (12.6 ± 1.0%) than the BIS monitor (0.4 ± 0.1%). The performance of BIS as an indicator of predicted propofol effect site concentrations did not differ when including (PK = 0.86 ± 0.05) or excluding (PK = 0.85 ± 0.04) the data pairs where Narcotrend monitor but not BIS monitor indicated an artefact. Artefacts were evenly distributed over the investigated range of propofol effect site concentrations. Conclusion. Exclusion of data pairs that were detected as artefacts by Narcotrend but not by BIS did not change the performance of bispectral index as an indicator of propofol effect site concentration.