Quality of perioperative AEP--variability of expert ratings.

BACKGROUND: Previous studies suggest that auditory evoked potentials (AEP) may be used to monitor anaesthetic depth. However, during surgery and anaesthesia, the quality of AEP recordings may be reduced by artefacts. This can affect the interpretation of the data and complicate the use of the method. We assessed differences in expert ratings of the signal quality of perioperatively recorded AEPs. METHODS: Signal quality of 180 randomly selected AEP, recorded perioperatively during a European multicentre study, was rated independently by five experts as 'invalid' (0), 'poor' (1), or 'good' (2). Average (n=5) quality rating was calculated for each signal. Differences between quality ratings of the five experts were calculated for each AEP: inter-rater variability (IRV) was calculated as the difference between the worst and best classification of a signal. RESULTS: Average signal quality of 57% of the AEPs was rated as 'invalid', 39% as 'poor', and only 4% as 'good'. IRV was 0 in only 6%, 1 in 62%, and 2 in 32% of the AEP, that is in 32% one expert said signal quality was good, whereas a different expert thought the identical signal was invalid. CONCLUSIONS: There is poor agreement between experts regarding the signal quality of perioperatively recorded AEPs and, as a consequence, results obtained by one expert may not easily be reproduced by a different expert. This limits the use of visual AEP analysis to indicate anaesthetic depth and may affect the comparability of AEP studies, where waveforms were analysed by different experts. An objective automated method for AEP analysis could solve this problem.

Systemic 5-fluorouracil producing an inflammatory response in porokeratosis.

Topical 5-fluorouracil has been used as an effective treatment for porokeratosis. Upon its treatment, an inflammatory effect occurs with the topical 5-fluorouracil. We report a case of a patient with disseminated superficial actinic porokeratosis displaying a comparable inflammatory process following therapy with systemic 5-fluorouracil used to manage a metastatic breast cancer.

Slow release iodine preparation and wound healing: in vitro effects consistent with lack of in vivo toxicity in human chronic wounds.

BACKGROUND: Antiseptic agents, particularly slow-release preparations, are increasingly being used in the management of chronic wounds. One such agent, cadexomer iodine, carries iodine (0.9% weight/weight) immobilized in beads of dextrin and epichlorhydrin and has been demonstrated to be highly effective in promoting healing of exudative wounds. However, there have been no studies directly assessing the potential lack of toxicity of cadexomer iodine on human cutaneous tissues. OBJECTIVES: To determine if, within a certain concentration range, cadexomer iodine is non-toxic to human cells and cutaneous tissue and to assess histologically human chronic exudative wounds that are being treated with cadexomer iodine. METHODS: We examined the effects of varying concentrations of cadexomer iodine on the viability of human fibroblasts in culture (by trypan blue exclusion). The morphology, cellular proliferation capacity (measured by [3H]thymidine uptake), ability to produce alpha 1(I) procollagen chain mRNA, and cell outgrowth from neonatal foreskin explants were also evaluated in human fibroblasts after incubation with various concentrations of cadexomer iodine. Moreover, biopsies of chronic exudative wounds concurrently treated with cadexomer iodine were stained with haematoxylin and eosin or a Gram stain and evaluated microscopically. RESULTS: At concentrations of up to 0.45%, cadexomer iodine was found to be non-toxic to fibroblasts in vitro; there were no changes in viability, morphology, cellular proliferation, ability to produce collagen, and cell outgrowth from explants. In vivo, skin biopsies of chronic exudative wounds being treated with cadexomer iodine demonstrated no evidence of cell necrosis, displayed re-epithelialization, and revealed bacteria within the cadexomer beads. CONCLUSIONS: These studies demonstrate that cadexomer iodine has definite non-toxic concentration ranges for fibroblasts in vitro, which are consistent with a lack of cellular toxicity in human chronic exudative wounds treated with cadexomer iodine. Cadexomer iodine may also have the additional property of trapping microorganisms.

Wavelet analysis of middle latency auditory evoked responses: calculation of an index for detection of awareness during propofol administration.

BACKGROUND: Middle latency auditory evoked responses (MLAER) as a measure of depth of sedation are critically dependent on data quality and the analysis technique used. Manual peak labeling is subject to observer bias. This study investigated whether a user-independent index based on wavelet transform can be derived to discriminate between awake and unresponsive states during propofol sedation. METHODS: After obtaining ethics committee approval and written informed consent, 13 volunteers and 40 patients were studied. In all subjects, propofol was titrated to loss of response to verbal command. The volunteers were allowed to recover, then propofol was titrated again to the same end point, and subjects were finally allowed to recover. From three MLAER waveforms at each stage, latencies and amplitudes of peaks Pa and Nb were measured manually. In addition, wavelet transform for analysis of MLAER was applied. Wavelet transform gives both frequency and time information by calculation of coefficients related to different frequency contents of the signal. Three coefficients of the so-called wavelet detail level 4 were transformed into a single index (Db3d4) using logistic regression analysis, which was also used for calculation of indices for Pa, Nb, and Pa/Nb latencies. Prediction probabilities for discrimination between awake and unresponsive states were calculated for all MLAER indices. RESULTS: During propofol infusion, subjects were unresponsive, and MLAER components were significantly depressed when compared with the awake states (P < 0.001). The wavelet index Db3d4 was positive for awake and negative for unresponsive subjects with a prediction probability of 0.92. CONCLUSION: These data show that automated wavelet analysis may be used to differentiate between awake and unresponsive states. The threshold value for the wavelet index allows easy recognition of awake versus unresponsive subjects. In addition, it is independent of subjective peak identification and offers the advantage of easy implementation into monitoring devices.

A prototype device for standardized calibration of pulse oximeters.

OBJECTIVE: To develop and test a method for standardized calibration of pulse oximeters. METHODS: A novel pulse oximeter calibration technique capable of simulating the behavior of real patients is discussed. It is based on an artificial finger with a variable spectral-resolved light attenuator in conjunction with an extensive clinical database of time-resolved optical transmission spectra of patients fingers in the wavelength range 600-1000 nm. The arterial oxygen saturation of the patients at the time of recording was derived by analyzing a corresponding blood sample with a CO-oximeter. These spectra are used to compute the modulation of the light attenuator which is attached to the artificial finger. This calibration method was tested by arbitrarily playing back recorded spectra to pulse oximeters and comparing their display to the value they displayed when the spectra were recorded. RESULTS: We were able to demonstrate that the calibrator could generate physiological signals which are accepted by a pulse oximeter. We also present some experience of playing back recorded patient spectra. The mean difference between the original reading of the pulse oximeters and the display when attached to the calibrator is 1.2 saturation points (displayed oxygen saturation SpO2) with a standard deviation of 1.9 saturation points. CONCLUSIONS: The tests have shown the capabilities of a spectral light modulator for use as a possible calibration standard for pulse oximeters. If some improvements of the current prototype can be achieved we conclude from the experience with the device that this novel concept for the calibration of pulse oximeters is feasible and that it could become an important tool for assessing the performance of pulse oximeters.

The antifungal agent butenafine manifests anti-inflammatory activity in vivo.

BACKGROUND: Dermatophyte infections are often accompanied by a striking inflammatory reaction, alleviation of which has often been achieved by the concomitant but controversial use of topical steroidal agents. Recent investigations have suggested the presence of inherent anti-inflammatory properties associated with certain antifungal agents, particularly those within the allylamine class. Butenafine, the first and only approved representative of the benzylamine antifungals, possesses a chemical structure and antifungal activity similar to the allylamines. Although several studies have demonstrated excellent antimycotic efficacy, none has addressed anti-inflammatory properties associated with butenafine. OBJECTIVE: This study was designed to determine whether butenafine, a benzylamine antifungal, expresses anti-inflammatory activity in vivo. METHODS: A randomized single-blinded control investigation comparing the attenuation of UVB irradiation-induced erythema by butenafine, its proprietary base cream, and no application (negative control) was performed in humans. RESULTS: Butenafine demonstrated a significant and marked decrease in UVB-induced erythema as compared with both the base cream and the unaltered control. CONCLUSION: The benzylamine antifungal agent butenafine demonstrates inherent anti-inflammatory properties, in vivo, as demonstrated by reduced cutaneous erythema response after UVB irradiation.

Middle latency auditory evoked responses and electroencephalographic derived variables do not predict movement to noxious stimulation during 1 minimum alveolar anesthetic concentration isoflurane/nitrous oxide anesthesia.

UNLABELLED: The electroencephalogram (EEG) and middle latency auditory evoked responses (MLAER) have been proposed for assessment of the depth of anesthesia. However, a reliable monitor of the adequacy of anesthesia has not yet been defined. In a multicenter study, we tested whether changes in the EEG and MLAER after a tetanic stimulus applied to the wrist could be used to predict subsequent movement in response to skin incision in patients anesthetized with 1 minimum alveolar anesthetic concentration (MAC) isoflurane in N2O. We also investigated whether the absolute values of any of these variables before skin incision was able to predict subsequent movement. After the induction of anesthesia with propofol and facilitation of tracheal intubation with succinylcholine, 82 patients received 1 MAC isoflurane (0.6%) in N2O 50% without an opioid or muscle relaxant. Spontaneous EEG and MLAER to auditory click-stimulation were recorded from a single frontoparietal electrode pair. MLAER were severely depressed at 1 MAC isoflurane. At least 20 min before skin incision, a 5-s tetanic stimulus was applied at the wrist, and the changes in EEG and MLAER were recorded. EEG and MLAER values were evaluated before and after skin incision for patients who did not move in response to tetanic stimulation. Twenty patients (24%) moved after tetanic stimulation. The changes in the EEG or MLAER variables were unable to predict which patients would move in response to skin incision. Preincision values were not different between patients who did and did not move in response to skin incision for any of the variables. MLAER amplitude increased after skin incision. We conclude that it is unlikely that linear EEG measures or MLAER variables can be of practical use in titrating isoflurane anesthesia to prevent movement in response to noxious stimulation. IMPLICATIONS: Reliable estimation of anesthetic adequacy remains a challenge. Changes in spontaneous or auditory evoked brain activity after a brief electrical stimulus at the wrist could not be used to predict whether anesthetized patients would subsequently move at the time of surgical incision.

Concept for an intelligent anaesthesia EEG monitor.

Considering the fundamental difficulties to define the term 'depth of anaesthesia', a more feasible concept for assessment of 'adequacy of anaesthesia' will be explained. The basic requirements for a monitoring index are definite response, gradual scaling and independence from the anaesthetic technique used. Additionally the index should be predictive for appearance of clinical signs of an inadequate anaesthesia. Different signal-processing methods will be discussed to extract the relevant information from both the spontaneous and the evoked brain electrical activity. In this context well established methods like spectral analysis are investigated in combination with new and more sophisticated methods like bispectral analysis or wavelet decomposition. Since no single-parameter index has been defined for monitoring depth of anaesthesia, a set of EEG parameters may be more useful to take into account intra- and interindividual variability. In parallel to the description of the monitor concept, the investigation of neural nets and fuzzy techniques, in addition to or in substitution of conventional statistical methods, will be introduced. Examples are given for data quality assessment, parameter extraction and re-classification.

Irrigation fluid absorption during transurethral resection of the prostate: spinal vs. general anaesthesia.

BACKGROUND: The absorption of irrigation fluid during transurethral resection of the prostate (TURP) is determined primarily by hydrostatic pressure in the bladder and prostatic venous pressure. In comparison to spontaneously breathing patients, patients undergoing mechanical ventilation with positive pressure have a raised central venous pressure and a reduced venous return, both of which can influence intravascular absorption. The purpose of the prospective study was to compare the effects of general (GA) and spinal anaesthetic (SA) techniques on the perioperative absorption of irrigating fluid in patients undergoing TURP. METHODS: Forty patients undergoing TURP were randomised and assigned either to group GA or SA. Irrigating fluid absorption was traced by adding 1.5% (w/v) ethanol to the irrigating fluid. Perioperative blood ethanol concentration (BEC), haemoglobin concentration, haematocrit, serum sodium concentration and central venous pressure (CVP) were measured at 10-min intervals during TURP and at 30-min intervals while patients were recovering. Absorption routes were indexed by the BEC and changes in serum sodium concentrations. Where the BEC was greater than 0.05 mg.mL-1, absorption of irrigating fluid was assumed. For assessing the volume of irrigating fluid absorbed, the maximum BEC, the absorption rate, the area under the BEC curve (AUC), and the volumes calculated according to the Hahn nomogram (Volin) for each patient were taken into consideration. RESULTS: There were 15 cases of irrigating fluid absorption in patients receiving GA (75%), and 11 in those receiving SA (55%). CVP was significantly lower in spontaneously breathing patients with SA as compared to those with GA (P < 0.05). In patients with irrigating fluid absorption the maximum BEC (P < 0.02), as well as the rate of irrigant fluid absorption (P < 0.01), were significantly higher amongst patients receiving SA. In this group, the calculated area under the curve and the absorbed fluid volumes determined with the nomogram were significantly increased (P < 0.05). CONCLUSION: The absorption of irrigation fluid during the TURP is significantly more marked amongst spontaneously breathing patients with regional anaesthesia in comparison to patients undergoing general anaesthesia with positive pressure ventilation. The markedly lower central venous pressure before the start of irrigation should be considered as a possible cause of this effect.

Irrigating fluid absorption during percutaneous nephrolithotripsy.

BACKGROUND: The most common complication during percutaneous nephrolithotripsy (PNL) is the destruction of organ structures with extravasation of the irrigation fluid into the retroperitoneal space. Consequently, there is an increased risk of a urosepsis and a complicated therapeutic course. In this study we aimed to show that extravascular absorption could be differentiated from intravascular absorption due to their unique absorption characteristics, and that these characteristics enable a prediction of possible post-operative complications. METHODS: In a prospective study of 31 patients with PNL, ethanol was added to the irrigating fluid and blood ethanol concentration (BEC) was measured by gas chromatography during the endoscopic procedure and in the recovery room. Following the guidelines of Hahn, patients were divided into two groups: group EVA, in whom extravasation had occurred with subsequent absorption; group IVA, those with intravascular absorption. Patients' post-operative progress along with diagnoses of renal perforations or bleeding, or signs of infection or sepsis, were comprehensively listed. RESULTS: EVA was diagnosed in 19 cases, and IVA in 12 cases. Maximum BEC levels were achieved after 20 min (median) in the IVA group, and 75 min in the EVA group (P < 0.05). Apart from their significantly higher demand for opioids (P < 0.05), EVA patients had been hospitalised for a substantially and significantly longer period of time (P < 0.01). Although without statistical significance, there was a higher rate of peri-operatively confirmed complications and prolonged intensive therapeutic treatment in the extravasation group. CONCLUSION: Retroperitoneal extravasation can be identified by using ethanol monitoring during and after PNL. Afflicted patients require considerably longer hospitalisation, probably because of the additional injury to surrounding organ structures.

Nonobligate role of early or sustained expression of immediate-early gene proteins c-fos, c-jun, and Zif/268 in hippocampal mossy fiber sprouting.

Axon sprouting in dentate granule cells is an important model of structural plasticity in the hippocampus. Although the process can be triggered by deafferentation, intense activation of glutamate receptors, and other convulsant stimuli, the specific molecular steps required to initiate and sustain mossy fiber (MF) reorganization are unknown. The cellular immediate early genes (IEGs) c-fos, c-jun, and zif/268 are major candidates for the initial steps of this plasticity, because they encode transcription factors that may trigger cascades of activity-dependent neuronal gene expression and are strongly induced in all experimental models of MF sprouting. The mutant mouse stargazer offers an important opportunity to test the specific role of IEGs, because it displays generalized nonconvulsive epilepsy and intense MF sprouting in the absence of regional cell injury. Here we report that stargazer mice show no detectable elevations in c-Fos, c-Jun, or Zif/268 immediate early gene proteins (IEGPs) before or during MF growth. Experimental results in stargazer, including (1) a strong IEGP response to kainate-induced convulsive seizures, (2) no IEGP response after prolongation of spike-wave synchronization, (3) no IEGP increase at the developmental onset of seizures or after prolonged seizure suppression, and (4) unaltered levels of the intracellular Ca2+-buffering proteins calbindin-D28k or parvalbumin, exclude the possibility that absence of an IEGP response in stargazer is either gene-linked or suppressed by known refractory mechanisms. These data demonstrate that increased levels of these IEGPs are not an obligatory step in MF-reactive sprouting and differentiate the early downstream molecular cascades of two major seizure types.

[Measuring lateral skin temperature profile of premature infants in incubators with thermography]. / Messung seitlicher Hauttemperaturprofile von Frühgeborenen in Inkubatoren mittels Thermographie.

Thermography enables the measurement of patients skin temperature profiles without stress caused by direct contact of probes to the skin. In previous incubator studies, frontal recordings were made through a hole in the top wall of the incubator hood. Using this method it is not possible to record the lateral temperature gradient from the back to the abdomen of the infant (in supine position), which is due to very limited heat loss near the incubator mattress. In this study temperature recordings were made from a lateral position. For this purpose a new front door of the incubator (Draeger 8000) was designed, which replaced the standard front door during measurements. In a clinical study thermography was compared to temperature measurements by standard thermistors. The mean difference between thermography and thermistors was 0.16 degree C. These results verify the use of thermography for measuring skin temperature of preterm infants in incubators.

[Model for simulation of heat loss by premature infants]. / Modell zur Simulation der Wärmeabgabe von Frühgeborenen.

A prerequisite for the further improvement in the quality of warming therapy is an accurate knowledge of the interactions between the microclimate in warming therapy devices and the thermal balance of the infant. For generating this knowledge, thermal manikins can be helpful. Suitable models capable of also simulating evaporative heat loss in preterm infants have, however, not been available to date. A thermal manikin representing an infant weighing 530 g and capable of simulating convective, radiative and also evaporative heat loss has now been developed. It comprises an outer shell made of porous, anatomically shaped clay, and is divided into six compartments each of which can be heated individually. Water-filled Gore-Tex bags located immediately beneath the shell are provided to simulate evaporation. In a clinical study, temperature profiles of 8 very small preterm infants were measured thermographically. Measurements in the manikin showed that highly comparable temperature profiles with only minor differences could be obtained. Total heat and water losses by the manikin were in good agreement with clinical values. Using the model described here it is possible to simulate the heat exchange of premature infants under extreme and accurately reproducible environmental conditions. This manikin may thus serve as a tool for comparative studies, for the development of warming therapy equipment, or for training purposes.

[The effect of temperature and humidity on breath samples. Measurement of breath ethanol concentration in artificially respirated patients]. / Einfluss von Temperatur und Luftfeuchtigkeit auf die Probenentnahme. Messung der Atem-Alkoholkonzentration bei beatmeten Patienten.

UNLABELLED: When looking for the possible cause of distortions in values measured for the determination of breath ethanol concentration (BEC) in artificially respirated patients, consideration must be given to the humidity and temperature of the gas examined. In the present study, the effects of humidified and warmed and of dry and cold air on the accuracy of a newly developed BEC measuring device, as compared to a reference model and to a conventional system, were examined in a lung model. METHODS: A temperature-regulated pediatric incubator was used containing a 10 I gas reservoir and a breath humidifier with temperature regulated water bath. This setup provided constant temperature and humidity in the gas examined during measurement period. In the 'expiration' the air was directed from the breath humidifier through a measuring unit via a 'mouthpiece' into the reference system (Alcotest 7110, Dräger Inc., Lübeck) and then out. The measuring unit consisted of sensors for the temperature and relative humidity, and of a connector for the three sample extraction systems (PES). PES I was the conventional system with a 100-cm gas-sample pipe (Alcomed 3010), PES II the newly developed system (AlcoMed 3011, both from Envitec, Wismar) with a 10-cm gas-sample pipe, and PES III with a 20-cm heated gas-sample pipe. During 'inspiration' 2 l of air was fed into the system to rinse the measuring unit and to fill the reservoir. 61 measurements were performed with dry and cold air, and 71 with humidified and warmed air, in the course of which the ethanol concentration was increased from 0 to 1.5/1000. Data were evaluated using regression analysis and the Bland & Altman method. RESULTS AND CONCLUSIONS: The constancy of the values set for temperature, relative humidity and absolute humidity in the lung model was given for all measurements. In the dry and cold air, the results from all three test systems coincided almost perfectly with the reference values. The measured BEC in the humidified and warmed air using sample-extraction systems II and III corresponded to a high degree with the reference, while in the case of PES I, only a moderate linear correlation was achieved. The temperature and humidity of the expired gas during artificial respiration influence the gas samples extracted for the purposes of BEC measurement. Newly developed sample-extraction systems II and III coincide with the reference system, even under respiration-simulated gas conditions.

[Measuring breath alcohol concentration during artificial ventilation. Model studies of the effect of temperature and humidity on measurements by various sampling systems]. / Messung der Atem-Alkoholkonzentration während der Beatmung. Modelluntersuchungen zum Einfluss von Temperatur und Luftfeuchtigkeit auf die Messungen verschiedener Probenentnahmesysteme.

The present paper examined the question as to the extent to which the taking of gas samples for the purpose of measuring the breath alcohol concentration (BAC) in the expired air of patients on artificial respiration is influenced by temperature and humidity. For this purpose a lung model standardized at different alcohol concentrations was used, in which the temperature (T: 25, 30 and 35 degrees C) and the relative humidity (RH: 50, 75 and 95%) were varied.

[Electrophysiologic arousal reactions during sufentanil-/isoflurane anesthesia]. / Elektrophysiologische Arousalreaktionen während Sufentanil-/Isofluran-Anästhesien.

PURPOSE: There is controversy about relevant EEG signal changes indicating adequate or inadequate anaesthesia. Differences of drug-induced and nociceptive mediated signal changes have not been studied in detail. The present study investigates whether signal changes during decreases of depth of anaesthesia due to surgical stimulation depend on different isoflurane concentrations during sufentanil anaesthesia. METHODS: Following IRB approval and written informed consent 28 patients (ASA: I; age 43 +/- 11 y) scheduled for elective abdominal surgery were included in the study. Anaesthesia: propofol (2.0 mg/kg) and sufentanil (1.0 micrograms/kg). Following endotracheal intubation (vecuronium 0.1 mg/kg) patients were normoventilated (P(ET)CO2: 36-38 mmHg). Randomly assigned to steady-state anaesthesia (group 1: P(ET)Isoflurane 0.2%, (14n); group 2: P(ET)Isoflurane 0.6%, (14n) during the start of surgery. Monitoring: heart rate (HF), mean arterial blood pressure (MAP), P(ET)CO2, arterial oxygen saturation and rectal temperature. EEG (16 channels referenced to Cz; CATEEM, Medisyst, Linden) recorded 5 min before until 10 min after the start of surgery. EEG-analysis (FFT: 4s, 256/s, 0.45-35.0 Hz): topographical distribution of power spectral densities (delta, theta, alpha 1, and alpha 2). Artifact control: ECG and EOG. RESULTS: Surgical stimulation resulted in increases of MAP in both groups (p < 0.05 vs BL), whereas HR was only slightly affected in group 2 when compared with BL. Other variables except of EEG data did not change over time. In group 1 (0.2% isoflurane) surgical stimulation resulted in decreases of delta over the whole cortex (F2, C3, P3, O1) and in marked increases of alpha predominantly at central leads (C3)(p < 0.05 vs BL). In group 2 (0.6% isoflurane) nociceptive stimulation was associated with decreases of faster waves (alpha: F3)(p < 0.05 vs BL) and increases in delta at fronto-central areas (F3, C3)(p < 0.05 vs BL). CONCLUSIONS: EEG recordings are useful in assessing pharmacodynamic drug effects. In contrast, intraoperative EEG recordings have a low correlation to clinical signs of changes in the anaesthetic state. Previous studies demonstrate paradoxical EEG-arousal reactions during isoflurane anaesthesia. The present data suggest that classical or even paradoxical EEG arousal due to nociceptive stimulation may depend on the isoflurane concentration. It seems reasonable that the ascending reticular formation is functionally blocked by isoflurane in a dose-dependent manner.