A Novel and Effective Balanced Intravenous-Inhalant Anaesthetic Protocol in Swine by Using Unrestricted Drugs

Nowadays, because of increasing employment of swine for experimental studies and medical training, it is hopeful to investigate novel and effective anaesthetic protocols for preserving the animal welfare in medical investigation and concurrently improving the quality of research. Therefore, the aim of this study was to investigate a novel and effective anaesthetic protocol in swine undergoing major surgery, by translating know-how of combined anaesthesia from human protocols. Seven landrace swine were anaesthetized for three hours by a combined trial anaesthetic protocol (sedation: medetomidine, acepromazine, atropine and tramadol; induction: propofol, medetomidine and acepromazine; anaesthesia: isofluorane, propofol, medetomidine and acepromazine) and both clinical and haemodynamic parameters were compared with those of five swine anaesthetized with a control protocol (sedation: diazepam, ketamine and atropina; induction: diazepam and ketamine; anaesthesia: isofluorane). Both cardiac frequency (CF) and mean blood pressure (MBP) were significantly (P<0.05) more stable in trial protocol (CF: 78.3 ± 4.6-81.1 ± 5, MBP: 63.9 ± 10.7-96.4 ± 13.0) compared to control protocol (CF: 93.7 ± 5.5-102.5 ± 8.5, MBP: 71.0 ± 6.6-108.7 ± 7.2). The body temperature remained stable in trial protocol (°C: 36.9 ± 0.7-37.2 ± 0.3) compared to control anaesthesia (°C: 36.4 ± 0.3-37.3 ± 0.2, P<0.05). Haematosis improved undergoing combined anaesthesia (+2%, P<0.05) whereas did not change in control animals. There were no differences in respiratory rate between trial and control protocols. This study demonstrates that the proposed balanced intravenous-inhalant protocol permits to carry out a very effective, stable and safe anaesthesia in swine undergoing deep anaesthesia.     

Validation of a system for monitoring individual feeding and drinking behaviour and intake in young cattle

The objective of this study was to validate an electronic system for monitoring individual feeding and drinking behaviour and intake developed for young cattle housed in group. A total of 35 Holstein–Gyr crossbred heifers (BW: 180±52 kg; age: 121.5±32.5 days), fitted with an ear tag containing a unique passive transponder, were distributed in three groups of 12, 12 and 11 animals per period and had free access to 12 electronic feed bins and two electronic water bins (Intergado® Ltd). The dimensions of feed and water bins, as well as the sensors position were appropriate for young cattle. The system documented the visit frequency and duration, as well as the feed and water intakes, by recording the animal’s identification tag, bin number, initial and final times of visits and the difference of feed/water weight at the start and end of each bin visit. Feed bins were monitored using time-lapse video recording over 4 days and the water bins were monitored over 6 days. For each feed bin, two feeding events were monitored using manual weighings with an external scale immediately before and after the animal’s visit and the difference between them was assumed as feed intake (n=24 observations). For the water bins, 60 manual weighings were made. Video and manual weighing data were regressed on the electronic feeding and drinking behaviour and intake data to evaluate the system’s precision and accuracy. The system showed high specificity (98.98% and 98.56% for the feed and water bins, respectively) and sensitivity (99.25% and 98.74%, respectively) for identifying an animal’s presence or absence. Duration of feed and water bin visits as well as feed and water consumption per visit estimated by the system were highly correlated and precise compared with the observed video and manual weighing data (r²=0.917, 0.963, 0.973 and 0.986, respectively). It was concluded that Intergado® system is a useful tool for monitoring feeding and drinking behaviour as well as water and feed intakes in young cattle housed in groups.     

Orcadian Changes in Stimulus Threshold and in the Effect of a Local Anaesthetic Drug in Human Teeth: Studies with an Electronic Pulptester

An electronic puiptester with constant testing current was used to study the stimulus threshold in human teeth of 28 healthy volunteers and the duration of local anaesthesia by articaine plus epinephrine in 55 patients with caries who underwent a filling therapy. In 21 out of the 28 volunteers, significant daily variations in stimulus threshold were detected by cosinor analysis. Acrophases, however, were scattered over the 24-hr scale. In patients, the local anaesthetic effect was studied at four different times of day (0800,1100,1400 and 1700 hr). The electronic device allowed one to accurately determine the time to peak effect (T_max), duration of effect (E_max, time to return to baseline threshold (T_ret) and the area under the time-effect curve (AUC) as a measure of the total local anaesthetic effect. Significant diurnal variations in AUC and E_max were found in 36 patients with the 0.8 ml dose, with peak and trough values at 1400 and 1700 hr, respectively. No differences in effect were found with the low dose of 0.4 ml applied to 19 patients either at 1400 or 1700 hr giving evidence for a circadian phase-dependency in the dose-response relationship of a local anaesthetic drug. The results clearly demonstrate that this electronic device is suitable for exact evaluation of circadian changes in local anaesthetic effects. Under drug-free control conditions, however, the low stimulus frequence of 5 Hz of this device obviously does not allow to discriminate between stimuli modified by pain perception and/or alertness.     

Liquid chromatography-electrospray mass spectrometry determination of free and total concentrations of ropivacaine in human plasma

A specific and sensitive liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) method was developed for the determination of free and total ropivacaine in human plasma. The work-up procedure involved a simple precipitation of plasma proteins with methanol. Etidocaine served as the internal standard. After microscale equilibrium-dialysis, measurement of free ropivacaine levels was performed after direct injection of the dialysate into the chromatograph. The system used a Zorbax eclipse XD8 C8 analytical column packed with 5 microm diameter particles as the stationary phase. The mobile phase consisted of a 15-min gradient (mobile phase A: 0.05% (v/v) trimethylamine in acetonitrile, mobile phase B: 2mM ammonium formate buffer (pH 3)). Mass spectrometric data were acquired in single ion monitoring mode at m/z 275 for ropivacaine and m/z 277 for etidocaine. The drug/internal standard peak area ratios (plasma) or peak areas (dialysate) were linked via a quadratic relationship to concentrations. Precision ranged from 1 to 7.6% accuracy was between 92.6 and 109%. The lower limits of quantitation were 1 microg/l in plasma and 2 microg/l in the dialysate. This method was found suitable for the analysis of plasma samples collected during a clinical trial performed in 30 infants undergoing epidural anaesthesia or continuous psoas compartment block.     

Four methods for general anaesthesia in the rabbit: a comparative study

The efficacy and safety of pentobarbitone, ketamine/xylazine, fentanyl/fluanisone/diazepam, and halothane/nitrous oxide anaesthesia were compared in 4 groups of six New Zealand White rabbits. Heart and respiratory rates, body temperature, reflexes, blood pressure and blood gases were measured. Pentobarbitone appeared to be unsuitable for anaesthesia in rabbits, as 5 of the 6 rabbits to whom it was administered, required artificial respiration or died. The combinations of ketamine/xylazine and fentanyl-fluanisone/diazepam both produced unpredictable levels of anaesthesia together with a substantial decline in arterial blood pressure and PO2. Despite a severe drop in blood pressure (up to 37.5%), anaesthesia with halothane and nitrous oxide was found to be superior to the other anaesthetic agents.     

Bispectral analysis does not differentiate between anaesthesia EEG and a linear random process]

Bispectral analysis of the electroencephalogram (EEG) has been used to monitor depth of anaesthesia. In the majority of publications this has involved the use of the so called BIS-Index TM (Aspect Medical Systems, Inc.). The exact relationship of this index to such bispectral parameters as the bispectrum and bicoherence has not yet been reported. If the EEG is considered as a linear random process, bicoherence is trivial, i.e. it is independent of the EEG frequency. The aim of this study was to determine the proportion of EEG epochs with non-trivial bicoherence during isoflurane/N20 anaesthesia. We reanalyzed 25.5 hours of digitalised EEG signal from 9 patients undergoing gynaecological surgery. The test developed by Hinich for Gaussian distribution and linearity was then applied. The test was validated using various synthetic surrogate data: Gaussian random data, the z-component of the Lorenz attractor, the phase randomized EEG and the phase randomized z-component of the Lorenz attractor. The percentage of epochs (8.192 s, 1024 data points) with non-trivial bicoherence was: Lorenz data 95.4%, phase randomized Lorenz data 9.4%, synthetic Gaussian data 14.8%, original EEG 9.1%, phase randomized EEG 5.1%. The original EEG data were not found to contain a higher percentage of epochs with non-trivial bicoherence than the phase randomized data and the synthetic Gaussian data. We conclude that bispectral analysis does not substantially add to the information obtained with other methods of quantitative EEG analysis.     

Effects of anaesthetic MS 222 on the orientation of juvenile salmon, Oncorhynchus tschawytscha Walbaum

Juvenile salmon, Oncorhynchus tschawytscha Walbaum, were trained to orientate in a direction (270°) and then anaesthetized with ethyl m–aminobenzoate methane sulphonate (MS 222) in a test to determine whether anaesthesia affected the learnt orientation.
Before anaesthesia the control group of twelve fish showed a mean unimodal orientation of 264° and a bimodal axis of orientation of 258°/78° with a confidence limit (second order analysis) of 218°←→285°. After administration of MS 222 nine out of ten fish showed marked changes in orientation and random behaviour, persisting in two fish for more than 14 days. The mean of means unimodal orientation, after anaesthesia, was 337° (random) and the bimodal axis of orientation was 337°/157° (random).
Eight weeks after completion of the anaesthesia trial the fish were retested. Each fish, except one, showed a mean bimodal axis of orientation that fell within the confidence limit of the control. The mean axis of orientation for ten fish over a 3–day period was 270°/90°, (r) = 0.28.
The results support the view that the reference orientation in this study (270°) was a learnt, not an innate directional preference. The effects anaesthesia may have on salmon behaviour during migration are discussed.     

Setting up a pragmatic clinical trial in a low-resource setting: A qualitative assessment of GoLBeT,a trial of podoconiosis management in Northern Ethiopia

BackgroundClinical trials are often perceived as being expensive, difficult and beyond the capacity of healthcare workers in low-resource settings. However, in order to improve healthcare coverage, the World Health Organization (WHO) World Health Report 2013 stated that all countries need to become generators as well as recipients of data. This study is a methodological examination of the steps and processes involved in setting up the Gojjam Lymphoedema Best Practice Trial (GoLBeT; ISRCTN67805210), a highly pragmatic clinical trial conducted in northern Ethiopia. Challenges to the trial and strategies used to deal with them were explored, together with the reasons for delays.Methodology and principal findingsQualitative research methods were used to analyse emails and reports from the period between trial inception and recruitment. This analysis was complemented by interviews with key informants from the trial operational team. The Global Health Research Process Map was used as a framework against which to compare the steps involved in setting up the trial. A mini-group discussion was conducted with the trial operational team after study completion for reflection and further recommendations.This study showed that the key areas of difficulty in setting up and planning this trial were: the study design, that is, deciding on the study endpoint, where and how best to measure it, and assuring statistical power; recruitment and appropriate training of staff; planning for data quality; and gaining regulatory approvals. Collaboration, for example with statisticians, the trial steering committee, the study monitors, and members of the local community was essential to successfully setting up the trial.Conclusions and significanceLessons learnt from this trial might guide others planning pragmatic trials in settings where research is not common, allowing them to anticipate possible challenges and address them through trial design, planning and operational delivery. We also hope that this example might encourage similar pragmatic studies to be undertaken. Such studies are rarely undertaken or locally led, but are an accessible and efficient way to drive improved outcomes in public health.     

Electronic communication between providers of primary and secondary care.

OBJECTIVE--To study the effects of the introduction of electronic data interchange between primary and secondary care providers on speed of communication, efficiency of data handling, and satisfaction of general practitioners with communication. DESIGN--Comparison of traditional paper based communication for laboratory reports and admission-discharge reports between hospital and general practitioners and electronic data interchange. SETTING--Twenty-seven general practitioners whose offices were equipped with a practice information system and two general hospitals. OUTCOME MEASURES--Paper based communication was evaluated by questionnaire responses from and interviews with care providers; electronic communication was evaluated by measuring time intervals between generation and delivery of messages and by assessing doctors'' satisfaction with electronic data interchange by questionnaire. RESULTS--Via paper mail admission-discharge reports took a median of 2-4 days, and laboratory reports 2 days, to reach general practitioners. With electronic data interchange almost all admission-discharge reports were available to general practitioners within one hour of generation. When samples were analysed on the day of collection (as was the case for 174/542 samples in one hospital and 443/854 in the other) the laboratory reports were also available to the general practitioner the same day via electronic data interchange. Fifteen general practitioners (of the 24 who returned the questionnaire) reported that the use of electronic admission-discharge reports provided more accurate and complete information about the care delivered to their patients. Ten general practitioners reported that electronic laboratory reports lessened the work of processing the data. CONCLUSION--Electronic communication between primary and secondary care providers is a feasible option for improving communication.     

Research on a cluster system for binary data frames of wireless sensor network

As the development of network became more complex, protocol reverse engineering has attracted increasing attention and widely applied in intrusion detection, vulnerability discovery, and electronic countermeasures. To separate the obtained binary data frames under complex wireless network environment so as to provide prerequisite for the following reverse protocol analysis, cluster system of complex protocol suites was implemented. First, AC algorithm was utilized to mine the frequent sequence characteristics in binary data frames. Then Apriori algorithm was employed innovatively to analyze the association relationships between these characteristics. In addition, combining with the features of binary frames, the results were conducted by four-step pruning. Finally, the selected characteristics were applied for cluster by the improved K-means algorithm. Results indicated that: the clustering effect of the system for binary protocol data frames is favorable. Meanwhile, as for the multilayer protocol suites with TYPE fields, the system is able to further distinguish the hierarchical relations between multiple protocols.     

Comparative efficacy of clove oil and other chemicals in anaesthetization of Pomacentrus amboinensis, a coral reef fish

The efficacy of quinaldine, benzocaine, MS-222, 2-phenoxyethanol and clove oil was compared for anaesthetizing settlement stage Pomacentrus amboinensis , a frequently studied coral reef fish. Induction to anaesthesia, behaviour during anaesthesia, recovery times and survival rates of fish treated with the different chemicals were compared. Clove oil was only marginally less effective than quinaldine and was more effective than other chemicals tested, except at high concentrations. In addition, fish exposed to clove oil exhibited a much calmer induction to anaesthesia than fish exposed to quinaldine. Therefore, clove oil may be an effective alternative to quinaldine as a fish anaesthetic. Recovery time after anaesthesia with clove oil was two to three times longer than recovery from other chemicals, a desirable charcteristic for use in field studies. Survival rates were excellent for all chemicals.     

Rapid, easy, and cheap randomization: prospective evaluation in a study cohort

Background

Incisional hernia is a frequent complication in abdominal surgery. This article describes the development of a prospective randomized clinical trial designed to determine whether watchful waiting is an acceptable alternative to surgical repair for patients with oligosymptomatic incisional hernia.

Methods/Design

This clinical multicenter trial has been designed to compare watchful waiting and surgical repair for patients with oligosymptomatic incisional hernia. Participants are randomized to watchful waiting or surgery and followed up for two years. The primary efficacy endpoint is pain/discomfort during normal activities as a result of the hernia or hernia repair two years after enrolment, as measured by the hernia-specific Surgical Pain Scales (SPS). The target sample size of six hundred thirty-six patients was calculated to detect non-inferiority of the experimental intervention (watchful waiting) in the primary endpoint. Sixteen surgical centers will take part in the study and have submitted their declaration of commitment giving the estimated number of participating patients per year. A three-person data safety monitoring board will meet annually to monitor and supervise the trial.

Discussion

To date, we could find no published data on the natural course of incisional hernias. To our knowledge, watchful waiting has never been compared to standard surgical repair as a treatment option for incisional hernias. A trial to compare the outcome of the two approaches in patients with oligosymptomatic incisional hernias is urgently needed to provide data that can facilitate the choice between treatment options. If watchful waiting was equal to surgical repair, the high costs of surgical repair could be saved. The design for such a trial is described here. This multicenter trial will be funded by the German Research Foundation (DFG). The ethics committee of the Charité has approved the study protocol. Approval has been obtained from ten study sites at time of this submission. The electronic Case Report Forms have been created. The first patient was to be randomized November 14^th, 2011. An initiation meeting took place in Berlin January 9^th, 2012.

Trial Registration

ClinicalTrials.gov: NCT01349400     

Endocrine stress response in rats subjected to singular orbital puncture while under diethyl-ether anaesthesia.

In an attempt to assess possible discomfort in rats subjected to orbital puncture while under diethyl-ether anaesthesia, their endocrine stress response was determined. Concentrations of corticosterone, adrenaline and noradrenaline were measured in plasma obtained via a jugular catheter from rats subjected to diethyl-ether anaesthesia with or without orbital puncture. No statistically significant differences were found between the punctured and non-punctured rats as to peak levels of plasma corticosterone and adrenaline as well as for the times required by the increased concentrations to return to baseline values. The rate by which the plasma noradrenaline level returned to baseline values was somewhat decreased by orbital puncture. Diethyl-ether anaesthesia alone produced a marked endocrine response when compared with handling and novelty stress associated with the induction of anaesthesia. It is concluded that diethyl-ether anaesthesia causes pronounced increases in the plasma levels of the selected stress hormones and that orbital puncture does not amplify this response. It is suggested that diethyl-ether anaesthesia masks any effects of orbital puncture.     

Development of a probe for the in vivo measurement of airway humidity during anaesthesia

Airway drying can arise during long-term respiration of anaesthetic dry gases and this may have implications for the function of the airway wall. Monitoring airway humidity can identify drying trends, although previous attempts have been limited for technical reasons. The design and development of a probe to measure mid-tracheal air humidity is described. The device comprises a commercially available capacitive humidity sensor and a thermocouple. The assembled probe is catheter-like with a diameter of 9.5 mm and a length of 312 mm. Water vapour transfer response times of 1.4 s (absorption) and 3.6 s (desorption) were evaluated for the probe. A preliminary trial to record airway humidity in ambient air and involving six patients was performed during anaesthesia.     

NeuMonD: a tool for the development of new indicators of anaesthetic effect.

Electroencephalogram (EEG) signals and auditory evoked potentials (AEPs) have been suggested as a measure of depth of anaesthesia, because they reflect activity of the main target organ of anaesthesia, the brain. The online signal processing module NeuMonD is part of a PC-based development platform for monitoring "depth" of anaesthesia using EEG and AEP data. NeuMonD allows collection of signals from different clinical monitors, and calculation and simultaneous visualisation of several potentially useful parameters indicating "depth" of anaesthesia using different signal processing methods. The main advantage of NeuMonD is the possibility of early evaluation of the performance of parameters or indicators by the anaesthetist in the clinical environment which may accelerate the process of developing new, multiparametric indicators of anaesthetic "depth".     

Prevention of Deep Vein Thrombosis by Intermittent Pneumatic Compression of Calf

A consecutive, randomly allocated, controlled clinical trial of the prophylactic effect of intermittent pneumatic compression of the calf on the incidence of postoperative deep vein thrombosis showed that in patients without malignant disease there was a highly significant reduction in the incidence of thrombosis. In patients with malignant disease the incidence of thrombosis was higher than in those without, and there was no reduction in incidence by the application of intermittent compression. In the absence of malignant disease, severity of operation and the age of the patient were the most significant aetiological factors. We found no relation between the incidence of deep venous thrombosis and obesity, length of preoperative stay, location of hospital, or duration of anaesthesia. We suggest that intermittent pneumatic compression as used in this trial is a safe, effective, and extremely practical method of preventing postoperative deep vein thrombosis in patients not suffering from malignant disease.     

Neutrophil Chemotaxis in Cord Blood of Term and Preterm Neonates Is Reduced in Preterm Neonates and Influenced by the Mode of Delivery and Anaesthesia

Bacterial infections, even without any perinatal risk factors, are common in newborns, especially in preterm neonates. The aim of this study was to evaluate possible impairment of neutrophil chemotaxis in term and preterm neonates compared with adults as well as neonates with different modes of delivery and anaesthesia. We analysed the expression of the adhesion molecule L-Selectin as well as shape change, spontaneous and N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced transmigration of neutrophils in a flow cytometric assay of chemotaxis after spontaneous delivery with Cesarian Section (CS) under spinal anaesthesia (mepivacaine, sufentanil), epidural anaesthesia (ropivacaine or bupivacaine, sufentanil) or general anaesthesia (ketamine, thiopental, succinylcholine). Chemokinesis was higher (p=0.008) in cord blood neutrophils than in the adult ones, whereas those could be more stimulated by fMLP (p=0.02). After vaginal delivery neutrophils showed a higher spontaneous and fMLP-stimulated chemotactic response compared to neonates after CS without labor. Comparing different types of anaesthesia for CS, spinal anaesthesia resulted in less impairment on chemotaxis than general anaesthesia or epidural anaesthesia. The new flow cytometric assay of neutrophil chemotaxis is an appropriate and objective method to analyse functional differences even in very small volumes of blood, essential in neonatology. Term neonates do not show reduced chemotaxis compared to adults. Preterm neonates present with reduced chemotaxis and chemokinesis, confirming the well known deficits in their neutrophil function. The side effects of maternal drugs on the neonatal immune system have to be considered especially when the immune response is already impaired, as in preterm infants.     

Pinch skin grafting or porcine dermis in venous ulcers: a randomised clinical trial.

Chronic venous ulcers are common, and even with effective compression or elevation large ulcers may take months to heal. Pinch skin grafting may allow healing from epithelial islands throughout the surface area of the ulcer, and a prospective randomised trial was therefore conducted comparing this treatment with porcine dermis dressings. Most patients were treated as outpatients, 25 ulcers being randomised to treatment with pinch skin grafts and 28 to treatment with porcine dermis. Though the groups were well matched, the mean healing rate in the first week was 15 cm2 for pinch skin grafts compared with 3.5 cm2 with porcine dermis (p less than 0.02). By life table analysis 64% of ulcers treated by pinch grafts were healed at six weeks and 74% by 12 weeks compared with 29% and 46% of ulcers, respectively, treated with porcine dermis dressings (chi2 = 4.1; p less than 0.05). All ulcers that failed to heal within 12 weeks included an area posterior to the medial malleolus, where local compression may have been inadequate. Pinch skin grafting improves the rate of healing in large venous ulcers and is a simple technique that may be performed as an outpatient procedure under local anaesthesia.     

Effect of anaesthesia on the pattern of breathing.

The pattern of breathing of male rats was studied after stimulating respiration with carbon dioxide at different levels of general anaesthesia. Anaesthesia was induced by the inhalation of halothane or by the i.p. injection of urethane. Ventilation values were measured in intubated rats in body plethysmograph. It was found that a linear relationship between minute ventilation and tidal volume was maintained during the decrease of minute ventilation due to deepening of anaesthesia. The slope of the relationship after stimulating respiration with carbon dioxide also diminished during deeper anaesthesia. The duration of inspiration did not alter significantly, despite marked changes in tidal volume. Tidal volume correlated with the duration of expiration at different anaesthesia levels. In vagotomized rats, the duration of expiration shortened as ventilation was depressed by deepening anaesthesia.     

Preventing fat embolism syndrome (FES) in implantation of cemented hip endoprosthesis shafts with a trans-prosthetic drainage system (TDS)]

In vitro studies with the transprosthetic drainage system (TDS) have revealed a reduction in intrafemoral pressure in cemented total hip prosthesis. The aim of the present study was to establish whether the incidence of fat embolic syndrome (FES) is also reduced. Ten patients underwent standardized cemented total hip replacement using TDS under standardized general anaesthesia. The usual peri-operative monitoring measures were extended to include cardiopulmonary monitoring (pulmonary artery catheter, intra-arterial blood pressure) and two-dimensional transoesophageal echocardiography. Previous studies had reported an increased risk for fat embolic syndrome with conventional, and even with vacuum cementing techniques. Our recorded cardiopulmonary data and the data provided by two-dimensional transoesophageal echocardiography show a significant reduction in pulmonary embolism with TDS. This technique can be recommended in particular for high-risk patients (osteoporosis, elderly patients) and the implantation of long femoral stems. On the basis of the clinical data, a new femoral stem allowing the use of the TDS technique is being developed.