Modelling and multivariable control in anaesthesia using neural-fuzzy paradigms Part II. Closed-loop control of simultaneous administration of propofol and remifentanil

OBJECTIVE: Part II of this research study is concerned with the development of a closed-loop simulation linking the patient model as well as the fuzzy relational classifier already introduced in Part I with a control algorithm. The overall architecture is in fact a system advisor, which provides information to the anaesthetist about the adequate infusion-rates of propofol and remifentanil simultaneously. METHODS AND MATERIAL: The developed fuzzy multivariable controller includes three rule-bases and takes into account the synergetic interactions between the above drugs and uses such knowledge to achieve rapidly the desired depth of anaesthesia (DOA) level. RESULTS: The result of the study is a closed-loop control scheme, which adjusts efficiently the infusion-rates of two drugs in response to DOA changes. This controller can either be used in an advisory mode or closed-loop feedback mode in the operating theatre during surgery. CONCLUSION: It is hoped that this control scheme coupled with the patient model presented in Part I of this study will be used routinely in the operating theatre in the very near future.     

Neuro-fuzzy closed-loop control of depth of anaesthesia

The utility of the auditory evoked potential (AEP) is under investigation as a feedback signal for the automatic closed-loop control of general anaesthesia using neural networks and fuzzy logic. The AEP is a signal derived from the electroencephalogram (EEG) in response to auditory stimulation, which may be useful as an index of the 'depth' of anaesthesia. A simple back-propagation neural network can learn the AEP and provides a satisfactory input to a fuzzy logic infusion controller for the administration of anaesthetic drugs, but the problem remains that of reliable signal acquisition.     

Modelling and multi-parametric control for delivery of anaesthetic agents

This article presents model predictive controllers (MPCs) and multi-parametric model-based controllers for delivery of anaesthetic agents. The MPC can take into account constraints on drug delivery rates and state of the patient but requires solving an optimization problem at regular time intervals. The multi-parametric controller has all the advantages of the MPC and does not require repetitive solution of optimization problem for its implementation. This is achieved by obtaining the optimal drug delivery rates as a set of explicit functions of the state of the patient. The derivation of the controllers relies on using detailed models of the system. A compartmental model for the delivery of three drugs for anaesthesia is developed. The key feature of this model is that mean arterial pressure, cardiac output and unconsciousness of the patient can be simultaneously regulated. This is achieved by using three drugs: dopamine (DP), sodium nitroprusside (SNP) and isoflurane. A number of dynamic simulation experiments are carried out for the validation of the model. The model is then used for the design of model predictive and multi-parametric controllers, and the performance of the controllers is analyzed.     

On-line analysis of middle latency auditory evoked potentials (MLAEP) for monitoring depth of anaesthesia in laboratory rats

In laboratory animals as well as in human beings a depth of anaesthesia, where the subject has no pain or recall of events from the surgery, should be provided. Haemodynamic parameters such as heart rate and blood pressure are not a guarantee for an optimal depth of anaesthesia, especially when using neuromuscular blocking agents (NMBA). A number of studies suggest that the Middle Latency Auditory Evoked Potentials (MLAEP) contain information about the state of consciousness in humans. The purpose of this study was to examine whether the AEP could serve as an indicator of depth of anaesthesia in rats. The AEP was elicited with a click stimulus and monitored in an 80 ms window synchronised to the stimulus. The AEP was extracted applying an Auto Regressive Model with Exogenous Input (ARX-model) from which a Depth of Anaesthesia Index (DAI) was calculated. DAI was normalised to 100 while awake and decreasing gradually to a level between 50 and 20 as the rat was anaesthetised. Nine rats were anaesthetised and included in the study. Four doses of Hypnorm vet. and Dormicum were given as a total, each with 5 minutes interval. Clinical signs of the level of anaesthesia were observed simultaneously with the AEP. The results showed that in four rats DAI decreased to a level below 30 while anaesthetised. In the remaining five rats the AEP was only decreased to a level below 45. The results indicated that a simple dosing regimen based on weight was unable to give the same depth of anaesthesia in individual rats. The decrease in the DAI correlated well with the loss of stimulus response. In conclusion, MLAEP could be used as an indicator of depth of anaesthesia in rats during Hypnorm vet. and Dormicum administration. However studies applying other anaesthetic drugs should be carried out, before a conclusion of the general utility of the method can be made.     

On-line analysis of middle latency auditory evoked potentials (MLAEP) for monitoring depth of anaesthesia in laboratory rats

In laboratory animals as well as in human beings a depth of anaesthesia, where the subject has no pain or recall of events from the surgery, should be provided. Haemodynamic parameters such as heart rate and blood pressure are not a guarantee for an optimal depth of anaesthesia, especially when using neuromuscular blocking agents (NMBA). A number of studies suggest that the Middle Latency Auditory Evoked Potentials (MLAEP) contain information about the state of consciousness in humans. The purpose of this study was to examine whether the AEP could serve as an indicator of depth of anaesthesia in rats. The AEP was elicited with a click stimulus and monitored in an 80 ms window synchronised to the stimulus. The AEP was extracted applying an Auto Regressive Model with Exogenous Input (ARX-model) from which a Depth of Anaesthesia Index (DAI) was calculated. DAI was normalised to 100 while awake and decreasing gradually to a level between 50 and 20 as the rat was anaesthetised. Nine rats were anaesthetised and included in the study. Four doses of Hypnorm vet.® and Dormicum® were given as a total, each with 5 minutes interval. Clinical signs of the level of anaesthesia were observed simultaneously with the AEP. The results showed that in four rats DAI decreased to a level below 30 while anaesthetised. In the remaining five rats the AEP was only decreased to a level below 45. The results indicated that a simple dosing regimen based on weight was unable to give the same depth of anaesthesia in individual rats. The decrease in the DAI correlated well with the loss of stimulus response. In conclusion, MLAEP could be used as an indicator of depth of anaesthesia in rats during Hypnorm vet.® and Dormicum® administration. However studies applying other anaesthetic drugs should be carried out, before a conclusion of the general utility of the method can be made.     

Data quality of a wearable vital signs monitor in the pre-hospital and emergency departments for enhancing prediction of needs for life-saving interventions in trauma patients

Abstract

This study was designed to investigate the quality of data in the pre-hospital and emergency departments when using a wearable vital signs monitor and examine the efficacy of a combined model of standard vital signs and respective data quality indices (DQIs) for predicting the need for life-saving interventions (LSIs) in trauma patients. It was hypothesised that prediction of needs for LSIs in trauma patients is associated with data quality. Also, a model utilizing vital signs and DQIs to predict the needs for LSIs would be able to outperform models using vital signs alone. Data from 104 pre-hospital trauma patients transported by helicopter were analysed, including means and standard deviations of continuous vital signs, related DQIs and Glasgow coma scale (GCS) scores for LSI and non-LSI patient groups. DQIs involved percentages of valid measurements and mean deviation ratios. Various multivariate logistic regression models for predicting LSI needs were also obtained and compared through receiver-operating characteristic (ROC) curves. Demographics of patients were not statistically different between LSI and non-LSI patient groups. In addition, ROC curves demonstrated better prediction of LSI needs in patients using heart rate and DQIs (area under the curve [AUC] of 0.86) than using heart rate alone (AUC of 0.73). Likewise, ROC curves demonstrated better prediction using heart rate, total GCS score and DQIs (AUC of 0.99) than using heart rate and total GCS score (AUC of 0.92). AUCs were statistically different (p?<?0.05). This study showed that data quality could be used in addition to continuous vital signs for predicting the need for LSIs in trauma patients. Importantly, trauma systems should incorporate processes to regulate data quality of physiologic data in the pre-hospital and emergency departments. By doing so, data quality could be improved and lead to better prediction of needs for LSIs in trauma patients.     

A New Inhalation Technique for Improved Effect of Aerosolized Drugs in Asthma "The Shrug of the Shoulder Method"

A new, simple technique for inhalation of aerosolized drugs is described: During the breathholding period after inhalation from a pressurized aerosol the patient lifts his right and lowers his left shoulder and vice versa to "disperse" the drug as well as possible in the lungs. Twenty outpatients suffering from reversible bronchial obstruction inhaled two puffs from a pressurized terbutaline aerosol in the morning on two consecutive days using the new inhalation technique on one day and their ordinary technique on the other in this randomised, cross-over trial. Compared with the conventional method the new inhalation technique significantly improved bronchodilation as measured by forced expiratory volume in 1st s and forced vital capacity during a period of 6 h. The new method of inhalation may improve treatment with aerosolized drugs.     

AUTOPILOT-BT: a system for knowledge and model based mechanical ventilation.

A closed-loop system (AUTOPILOT-BT) for the control of mechanical ventilation was designed to: 1) autonomously achieve goals specified by the clinician, 2) optimize the ventilator settings with respect to the underlying disease and 3) automatically adapt to the individual properties and specific disease status of the patient. The current realization focuses on arterial oxygen saturation (SpO(2)), end-tidal CO(2) pressure (P(et)CO(2)), and positive end-expiratory pressure (PEEP) maximizing respiratory system compliance (C(rs)). The "AUTOPILOT-BT" incorporates two different knowledge sources: a fuzzy logic control reflecting expert knowledge and a mathematical model based system that provides individualized patient specific information. A first evaluation test with respect to desired end-tidal-CO(2)-level was accomplished using an experimental setup to simulate three different metabolic CO(2) production rates by means of a physical lung simulator. The outcome of ventilator settings made by the "AUTOPILOT-BT" system was compared to those produced by clinicians. The model based control system proved to be superior to the clinicians as well as to a pure fuzzy logic based control with respect to precision and required settling time into the optimal ventilation state.     

Genetic fuzzy modelling and control of bispectral index (BIS) for general intravenous anaesthesia

Based on an adaptive genetic fuzzy clustering algorithm, a derived fuzzy knowledge model is proposed for quantitatively estimating the systolic arterial pressure (SAP), heart rate (HR), and bispectral index (BIS) using 12 patients and it validates them according to pharmacological reasoning. Also, a genetic proportional integral derivative controller (GPIDC) to adaptive three controller parameters and a genetic fuzzy logic controller (GFLC) to adaptive controller rules using genetic algorithms (GAs) were simulated and compared each other in a patient model using the BIS value as a controlled variable. Each controller was tested using a set of 12 virtual patients undergoing a Gaussian random surgical disturbance repeated with BIS targets set at 40, 50, and 60. Controller performance was assessed using mean absolute error (MAE) of the BIS target, the percentage of time with acceptable BIS control (PTABC), and drug consumption (DC). It was found that the MAE value of the BIS target was significantly lower (P < 0.05) and the values of PTABC and DC of BIS target were significantly higher (P < 0.05) in BIS targets set at 40 than at 50 or 60 in both GPIDC and GFLC. However, when compared with two controllers in terms of the values of MAE, PTABC, and DC each other in BIS targets set at 40, 50, and 60, there were no significant differences (P > 0.05). Furthermore, when the simulation results in these two controllers were compared with routine standard practice of 12 clinical trials (i.e., manual control) in BIS target set at 50, the values of PTABC in both GPIDC and GFLC groups were significantly higher (P < 0.05) than in the manual control group. In contrast, there were no significant differences (P > 0.05) for these three groups in terms of drug consumption. This indicates that either GPIDC or GFLC can control the BIS target set at 50 better than manual control, although the similar drug consumption is used.     

经皮椎体成形手术体位对患者生命体征和血氧饱和度的影响

背景：尽管有学者肯定了侧卧位行经皮椎体成形的效果及安全性,但对于手术体位在术中对生命体征影响变化尚未见报道。 目的：观察经皮椎体成形手术中不同体位对患者生命体征和血氧饱和度的影响。 方法：将30例胸腰椎骨质疏松性压缩骨折患者随机分组为2组,分别以俯卧位和侧卧位行经皮椎体成形手术。观察并记录患者在术前仰卧位(T1)、转变手术体位后5 min(T2)、穿刺进针过程(T3)、注射骨水泥过程(T4)、骨水泥注射结束(T5)和术后仰卧5 min(T6)生命体征和血氧饱和度的变化。 结果与结论：俯卧位组T1、T2、T3、T4、T5时间点心率、呼吸频率均高于侧卧位组(P < 0.05)。俯卧位组T2、T3时间点收缩压高于侧卧位组(P < 0.05)。俯卧位组T5时间点血氧饱和度低于侧卧组(P < 0.05)。说明行经皮穿刺椎体成形手术时采用侧卧位较俯卧位对患者生命体征和血氧饱和度的影响小,且侧卧位有利于提高患者手术耐受性。     

Integration of a handheld based anaesthesia rounding system into an anaesthesia information management system

BACKGROUND: At the University Hospital Giessen, an anesthesia information management system (AIMS) is used for online record keeping of perioperative patient care, but preoperative anaesthesia assessments were still being recorded on paper and subsequently entered into the AIMS. Personal digital assistants (PDAs) seem to be useful instruments to establish a seamless digital anesthesiological documentation. OBJECTIVES: We decided to implement a solution for direct integration of data gathered during the preoperative assessment into the existing data management infrastructure. Parallel to the development of the system, we surveyed the future users to match their wishes and needs as far as possible. SYSTEM DESCRIPTION: A C program embedding the preoperative AIMS' data fields was developed. Data alignment with the Hospital information system (HIS) is controlled by a Java desktop software. The anaesthesiologist completes the available fields at the patient's bedside following the same algorithm and integrity check as the PC version. STATUS REPORT: Overall, 68% of the surveyed physicians supported the implementation of the system. The PDA solution has been available since May 2002. Data replication into the handheld and integration of mobile collected data into the AIMS generally work without problems. The HIS interconnection software converts the PDA file into the AIMS format for further processing. DISCUSSION: The preoperative anaesthetic assessment is a standardised task well suitable for conversion to an electronic data storage medium. Changing from redundant data entry in the OR to direct electronic recording at the patient's bedside seems simply logical. Handheld computers are inexpensive, flexible gadgets to realize this.     

Telespirometry: novel system for home monitoring of asthmatic patients.

OBJECTIVES: To describe a newly developed telespirometry system consisting of a portable spirometer that transmits the lung ventilatory values by telephone from the patient's home to a remote monitoring center and to assess the ability of the telespirometry system to detect early signs of asthmatic deterioration. METHODS: Thirty-nine patients with moderate to severe asthma were monitored with the telespirometry system. The lung function testing and transmission of the spirometric data by telephone from the patient's home to a remote monitoring center were performed according to the patient's judgment. All previous transmissions of the spirometric data were analyzed retrospectively to detect early signs of asthmatic deterioration, which resulted in dispatch of the mobile intensive care unit (MICU) to the patient's home. RESULTS: In 19 patients (49%), analysis of the spirometric data detected early signs of asthmatic deterioration. Analysis of the spirometric data correlated with decisions to dispatch the MICU in 22 of 39 (56%) patients. In patients with severe asthma, the decision was made during oral communication between the patient and the operator and was based on clinical impression rather than functional results. CONCLUSION: Home monitoring of asthmatic patients with the telespirometry system may improve the management of the disease and the quality of life and reduce costly hospitalizations.     

Apparent anaphylactoid reaction after treatment with a single dose of telithromycin.

BACKGROUND: Telithromycin, the first ketolide antimicrobial agent available in the United States, is related to the macrolide class of antibiotics. Reports of immediate-type hypersensitivity reactions with macrolides or ketolides are rare overall. OBJECTIVE: To describe a patient with a severe, apparent mast cell-mediated reaction to telithromycin. METHODS: A 54-year-old woman with a history of hypertension was prescribed telithromycin by her primary care physician for presumed bacterial sinusitis. Shortly after ingesting the first dose of telithromycin she developed severe shortness of breath, wheezing, and angioedema. Her allergic history was significant for the development of a maculopapular rash after taking sulfonamide antibiotics, but she had received erythromycin and azithromycin in the past with no adverse effects. She was intubated with difficulty and was treated with epinephrine, diphenhydramine, and corticosteroids. The patient made a full recovery. RESULTS: Although not confirmed, the patient's severe symptoms were anaphylactoid and were ascribed to an immediate-type hypersensitivity reaction to telithromycin. No other causative agents, including other drugs, foods, and environmental exposures, were implicated in this case. Her history of tolerability to macrolide antibiotics is of interest considering the chemical similarities between these drugs and telithromycin. CONCLUSION: To our knowledge, this is the first reported case of a severe, immediate-type hypersensitivity reaction to telithromycin. Physicians prescribing this drug should be aware of this rare but serious effect.     

The effect of heparin on lysosomes of the dog pancreas during acute experimental pancreatitis.

In 12 dogs with acute experimental pancreatitis (AEP) and 6 control animals the "free", "latent" and "total" activity of acid phosphatase, beta-glucuronidase and cathepsins in whole homogenates of the pancreas, in a lysosomal-enriched subfraction and the supernatant of pancreatic tissue was estimated. AEP was induced by injection of bile salts and thrombin solution into the pancreatic duct. In 6 dogs the protection with heparin (1.5 mg/kg/body weight) immediately after producing AEP was applied. In AEP without any protection the free activity of hydrolases in the whole homogenate (80--90%) and in the lysosomal enriched subfraction (75--90%) was higher than in the controls (60--70% and 55--75% respectively), suggesting an augmented lysosomal fragility during the course of AEP. Heparin depressed the free activity of hydrolases to 60--80% in whole homogenates, and 64--75% in the lysosomal enriched subfraction. The release of cathepsins during incubation of the lysosomal-enriched subfraction in acidic medium was lower in the group with heparin treatment. The data obtained suggest the stabilising effect of heparin on the lysosomes of the pancreas during acute experimental pancreatitis in dogs.     

Comparison of E-selectin expression at mRNA and protein levels in murine models of inflammation

Background:Drug targeting to activated endothelial cells via E-selectin is currently being explored as a new approach to treat chronic inflammatory disorders. This approach uses E-selectin directed antibodies as carrier molecules to selectively deliver anti-inflammatory drugs into activated endothelial cells, thereby theoretically decreasing drug-associated side-effects. Therapeutic effects of developed drug targeting constructs will have to be tested in animal models of inflammation, in which E-selectin is expressed during the course of the disease. In this study several murine models of inflammation were investigated regarding expression of E-selectin.Methods:E-selectin expression was determined both at the mRNA level using RT-PCR and at the protein level by immunohistochemistry using two monoclonal antibodies (10E9.6 and MES-1). The models studied included delayed type hypersensitivity induced skin inflammation, dextran sodium sulphate induced colitis, kidney ischemia/reperfusion injury, atherosclerosis in ApoE knockout mice, and collagen induced arthritis.Results:In all animal models E-selectin mRNA expression was detected, although to a different extent. In contrast, only the delayed type hypersensitivity model and, to a minor extent, the collagen induced arthritis model showed E-selectin protein expression.Conclusion:These results stress the need to determine E-selectin protein expression and not only mRNA expression, when choosing an animal model for testing E-selectin directed drug targeting preparations. In addition, in the arthritis model, E-selectin protein detection was dependent on the particular anti-E-selectin antibody used. This finding may not only have implications for the development and/or choice of homing devices to be used in E-selectin directed drug targeting preparations, but also for inflammation research in general.     

On the non-specific antiinflammatory effects of other-than-antirheumatic drugs. Psychotropic drugs, inflammation and antiinflammatory drugs

The interference of non-antiinflammatory drugs with inflammation and with the effects of antiinflammatory/antirheumatic drugs (AIDs) is exemplified by various psychotropic drugs (PTDs). The antiinflammatory action was evaluated in 3 ways: (i) drug effects on bentonite raw-paw oedema after a prophylactic and a therapeutic dose in the same rat, (ii) effect on bentonite oedema of single and repeated administrations (oedema induction in the contralateral paw 7 days later, drug administration continued in the interim), and (iii) effects on traumatic rat-ear oedema of single and repeated pretreatment. Most of the PTDs tested (neuroleptics, anxiolytics, psychostimulants, etc.) suppressed significantly the acute oedema, and some of them (caffeine, nomifensine, lisuride, etc.) also suppressed the fully developed oedema. Many PTDs, when given repeatedly, lost their effects or even aggravated the later phase of inflammation. PTDs can interfere also with the antiinflammatory effects of AIDs, since caffeine and guaifenesin, but not nomifensine, increased the antiinflammatory effects of aspirin and paracetamol, although neither caffeine nor nomifensine interfered with the effect of Auranofin. Therefore in clinical practice the interference of PTDs must be taken account: a PTD taken by the patient can mask signs of acute inflammation (including posttraumatic and postsurgical states). Moreover, the antiinflammatory potential of various analgesic/antipyretic combinations containing a PTD should be considered in view of this interference, since this can sometimes be exploited therapeutically.     

Trial of isolation of sick house syndrome and unclassified multiple chemical sensitivities--Definition of sick house syndrome, and symptoms]

PURPOSE: This study was designed to clarify the definition of sick house syndrome (SHS). METHODS: SHS was defined based on the disease related to habitation as follows. 1. The cause of the onset of a disease relates to house. 2. Symptoms appear within house. 3. Symptoms will be less serious or disappear if patient away from house. 4. If patient goes into house, symptoms will appear repeatedly. When it corresponded to all above, it was defined to SHS, and it classified as MCS (multiple chemical sensitivities) without above conditions. Even if SHS is isolated from similar disease completely, characteristic symptoms of MCS are hard to be detected because MCS are combination of two or more diseases. Based on this working hypothesis, the logistic regression by setting MCS as reference was performed so that characteristic symptoms of SHS show odds ratios with exceeding one. RESULTS: The odds ratios with more than two of characteristic symptoms in SHS were "nausea or vomiting" "Troublesome in everything" and the causative substances to which symptoms get worse was "The smell of a perfume and cosmetics". Characteristic symptoms of an allergy disease were detected by comparison with the allergic conjunctivitis, allergic rhinitis, and bronchial asthma, respectively. CONCLUSION: These results showed that the classification method was appropriate. This definition is not fundamentally differed from the definition of the sick-building syndrome of WHO.     

Serologic investigation of fatal hemolytic anemia associated with a multiple drug history and Rh-like autoantibody

A patient who expired during an episode of gross intravascular hemolysis had a complex medical history, including renal disease, Coombs positive anemia of unclear etiology, recent transfusion, and cholecystectomy. Drug history included 21 different medications, including penicillin, acetaminophen, procainamide, furosemide, sulindac, and tolmetin, all of which have been associated with a positive direct antiglobulin test or drug-induced hemolytic anemia. The patient had a history of recent use of three chemically similar nonsteroidal anti-inflammatory drugs: tolmetin (Tolectin), sulindac (Clinoril), and ketorolac (Toradol). Only tolmetin and furosemide (Lasix) antibodies were demonstrable in the patient's serum at the time of her final admission. The patient's serum at final admission contained panagglutinating IgG and IgM antibody with a titer of 1:80 using a pool of R1R1 and R2R2 screening cells. When tolmetin was added to the test system, the titer increased to 1:2,560. The direct antiglobulin test was 3+ (IgG and C3d,b). Eluates contained an Rh-like antibody compatible only with Rh deletion cells, and anti-tolmetin antibodies detected when the drug was added to the eluate in the presence of Rh deletion cells. Allogeneic adsorbed sera contained anti-tolmetin antibodies with a titer of 1:10 and a weakly reactive IgM antibody to furosemide. Antibodies to tolmetin and furosemide were apparent only when the drugs were added to sera or eluates, not with drug-coated cells. Because of the patient's complex medical history, it was not possible to attribute the fatal autoimmune hemolytic anemia solely to drug antibody.     

Scalp recordings of mid-latency AEP and auditory gating in the G?ttingen minipig: a new animal model in information processing research.

Early central information processing, measured in humans by the gating of the middle latency auditory evoked potential (AEP) P50 and the effect of attention on AEP N100, is affected in schizophrenia. Exploring the possibility of using miniature pigs in longitudinal studies of chronic neuropsychiatric disorders, we present a method for recording seven channel surface middle latency AEP in the awake animal. The AEP and the AEP gating measured in a paired stimulus paradigm similar to the P50 gating paradigm used in humans, were recorded in six adult male minipigs in two sessions. The AEP had a stable N40/P60/N120/P200 configuration and in the gating paradigm the difference between stimulus one (S1) and two (S2) P60 and N120 amplitudes were significant. Mean AEP P60 gating ratio (S2/S1) at the posterior central electrode was 0.66 (std 0.29) range 0.21-1.08 and corresponding N120 was 0.60 (std 0.19) range 0.28-0.76. The method presented is feasible for scalp recordings of middle latency evoked potentials in the awake animal, but further studies of interval sensitivity and the effect of arousal manipulation are needed to assess the equivalence of the pig components to those of the human at similar latencies.