University Department of Anaesthesia, Glasgow Royal Infirmary, Glasgow, UK
LMA® is the property of Intavent Limited.
Accepted for publication: February 19, 2003
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Abstract |
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Methods. Twenty adult patients scheduled for body surface surgery were enrolled. Anaesthesia was manually induced with target-controlled infusions (TCI) of propofol and remifentanil. After the start of surgery, when anaesthesia was clinically adequate, automatic control of the propofol TCI was commenced using the revised closed-loop system. For patients 1120, effect-site steering was also incorporated into the closed-loop control algorithm. Adequacy of anaesthesia during closed-loop control was assessed clinically, and by calculating the median performance error (MDPE), the median absolute performance error (MDAPE) and the mean offset of the control variable.
Results. The system provided adequate operating conditions and stable cardiovascular values in all patients during closed-loop control. The mean MDPE and MDAPE were 0.42% and 5.63%, respectively. Mean offset of the BISTM from setpoint was 0.2. No patients reported awareness or recall of intraoperative events.
Conclusions. The system was able to provide clinically adequate anaesthesia in all patients, with better accuracy of control than in the previous study. There was a tendency for more accurate control in those patients in whom the control algorithm incorporated effect-site steering.
Br J Anaesth 2003; 90: 73741
Keywords: anaesthesia, general; anaesthetics i.v., propofol; monitoring, bispectral index
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Introduction |
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Materials and methods |
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For the second group of 10 patients, the control algorithm was altered to enable effect-site steering in an attempt to reduce the problems of oscillation seen in the previous study. With effect-site steering, the system adjusts the target blood concentration taking into account the estimated effect-site concentration. With the original version of the algorithm used in the first 10 patients, if anaesthesia was inadequate (BISTM>setpoint), the system increased the target concentration above the previous target blood concentration, regardless of the estimated effect-site concentration. If the effect-site concentration was above the blood concentration, then until the blood concentration had surpassed it, the effect-site concentration would decrease, causing even more inadequate levels of anaesthesia. Under the same conditions in the second group of 10 patients, the system immediately increased the target blood concentration to the effect-site concentration, with further increases after that as necessary. This avoids the inappropriate reduction in effect-site concentration mentioned above, and results in a faster rise in this concentration when anaesthesia is inadequate. The opposite applies if the BISTM is below the setpoint, and the blood propofol concentration above that at the effect site. Under these circumstances in the second group of 10 patients, the target blood concentration would immediately be set to below that at the effect-site, in order to reduce the effect-site concentration as quickly as possible.
Clinical protocol
After obtaining local research ethics committee approval and written informed consent, 20 adults presenting for body surface surgery were enrolled. To be included, patients had to be of ASA status I or II, and aged between 18 and 80 yr. Exclusion criteria included BMI greater than 30 kg m2, a history of neurological disease and use of psychoactive medication. No sedative premedication was used. Two anaesthetists were involved with each case one was in charge of the clinical management of the patient, while the other took care of the research equipment and manually recorded the BISTM, physiological data and the blood and effect-site propofol concentrations every 5 min.
Anaesthesia was induced in the operating theatre. A 20-gauge cannula was inserted into a vein on the dorsum of the hand, and the patient was connected to the BISTM monitor using four Zipprep electrodes (Aspect MS, Newton, USA) in the standard montage. While other monitors were being connected, the closed-loop anaesthesia system was started in manual mode, with the target propofol concentration set at 12 µg ml1 to provide a degree of anxiolysis. Routine physiological monitoring (pulse oximetry, ECG, non-invasive arterial pressure) was started and baseline values recorded while the patient breathed 100% oxygen. The target remifentanil concentration was then set at 2 ng ml1 and the target propofol concentration at 4 µg ml1 in younger patients and at 2.5 µg ml1 in the elderly. The target propofol concentration was increased by 0.5 µg ml1 every 30 s until the patient had lost consciousness and was able to tolerate insertion of the laryngeal mask airway (LMA). Once the LMA had been inserted, the target remifentanil concentration was increased to 4 ng ml1 and the lungs were mechanically ventilated with oxygen 40% in air via a circle breathing system. The target propofol concentration was reduced to approximately 0.5 µg ml1 above the estimated effect-site concentration during LMA insertion.
Once surgery had started, a note was made of the BISTM value at which the level of anaesthesia was clinically adequate (no patient movement, haemodynamic stability, absence of signs of autonomic activation). Automatic control of the propofol TCI was initiated using this BISTM value as the setpoint. The target remifentanil concentration was left unchanged at 4 ng ml1. When the surgeon began the final skin sutures, the closed-loop system was switched to manual mode and the target propofol and remifentanil concentrations were set to zero. Patients remained in the operating room until they had regained consciousness, the LMA had been removed and they had correctly stated their date of birth.
The time, BISTM and estimated blood and effect-site propofol concentrations during the following events were recorded manually: loss of consciousness (eyelash reflex), just before intubation, just before skin incision, start of closed-loop control, end of surgery, eye opening, response to command and patient able to state date of birth.
Data analysis
Physiological data are presented as mean (SD) and time intervals as median (range). Performance of the system was assessed using the measures recommended by Varvel and colleagues:3 median prediction error (MDPE), median absolute prediction error (MDAPE), wobble and the mean offset. These variables were calculated for each patient and then summarized as mean (95% confidence interval [CI]). MDPE and MDAPE are measures of bias and precision, respectively; wobble is a measure of the intra-individual variability in performance error; offset is the difference between the measured value and the setpoint of the control variable. The proportion of time (during automatic control) that the BISTM was within 5, 10 and 15% of the setpoint was also calculated.
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Results |
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Discussion |
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This is the second study during general anaesthesia of the performance of this feedback system that automatically delivers propofol by TCI, using the BISTM as control variable. In the first study, the patients (n=10) were older (mean age 67 yr) and were undergoing hip or knee replacements under computer-controlled propofol anaesthesia supplemented by regional blockade.1 Overall control was satisfactory in that study (MDPE, MDAPE and wobble were 2.2%, 8.0% and 7.3%, respectively), but in three cases there was oscillation of the BISTM around the setpoint, with concomitant cycling of the blood and effect-site propofol concentrations. Also, a third patient regained consciousness briefly when the hip was manipulated vigorously, causing the surgical stimulus to increase suddenly. To reduce the likelihood of these problems, we altered the gain constants of the control algorithm and have incorporated effect-site steering; these alterations were associated with an improvement in control performance and a reduced incidence of oscillation. However, it would be unwise to conclude firmly that the revised algorithm is better, as it was tested in a younger and healthier patient group under different surgical and anaesthetic conditions.
As far as we are aware, there are no published, agreed limits for acceptability of the bias and precision of control systems in human studies. However, control performance in this study compares very favourably with that reported by others who used similar methods of assessing performance. Using the BISTM as the control variable, an adaptive control algorithm and a propofol TCI, Struys and colleagues4 reported a MDPE of 6.6%, a MDAPE of 7.7% and median wobble of 5.9%. Morley and colleagues5 used the BISTM (target of 50) and a proportional-integral-differential (PID) control algorithm to control the rate of infusion of a mixture of propofol and alfentanil, and reported a median absolute unweighted residual of 6.8. This equates to a MDAPE of 13.6%. Finally, an adaptive model-based feedback controller has been used to control muscle relaxation using administration of various drugs; MDPE, MDAPE, wobble and offset all varied between 0.3% and 1.9%.6
Kenny and Mantzaridis7 evaluated the performance of an auditory evoked potential (AEP)-based closed-loop anaesthesia system in 100 patients by calculating the proportion of time that the measured AEP was within 5%, 10% and 15% of the target AEP value. They reported figures of 65%, 90% and 99%, respectively somewhat better than the corresponding figures found in the current study (Table 2). The control algorithm used in the AEP system was identical to that used in our first study of BISTM-guided propofol anaesthesia,1 but differs from that used in the current study only in respect of changes to the gain constants and the addition of effect-site steering. The AEP system also used a propofol TCI as the control actuator. Although the figures from the two studies are not directly comparable, they may reflect some of the differences between the two control variables. The AEP, by definition, continuously measures the EEG response to an auditory stimulus, whereas the BISTM measures phase and frequency relationships among component frequencies in the spontaneous surface EEG. This may explain why spontaneous-EEG-based variables are no better than chance alone at predicting a response to noxious stimulus, whereas the AEP index is able to predict a response better than chance.811 It may also explain the greater fluctuation of the control variable, possibly in response to varying levels of stimulus, when the BISTM is the control variable compared with the AEP as control variable.
At the start of automatic control of the propofol infusion, we judged the adequacy of anaesthetic depth according to some of the traditional clinical signs of anaesthetic depth: lack of patient movement, haemodynamic stability and absence of signs of autonomic activation. Although these signs are the main measures by which many anaesthetists judge the adequacy of anaesthesia in their day-to-day anaesthetic practice, they are not particularly sensitive or specific predictors of the presence or lack of awareness. Thus it is hardly surprising that a broad range of BISTM values was associated with these conditions at the time of skin incision (2972) and a broad range of values used as the setpoint for automatic control of anaesthesia (4065). Aspect Medical Systems recommends that the BISTM is maintained between 40 and 60 in order to prevent awareness. Although it can be argued that the setpoint was thus too high in two patients (62 and 65), and that higher setpoints may be associated with less stability of the control variable, the data from our study do not show this.
Effect-site targeting has the potential for making a feedback system respond more quickly and accurately than blood concentration targeting. In the current study the trend was for effect-site targeting to be associated with slightly worse bias but improved precision and reduced wobble but these changes did not reach statistical significance. A study with larger subject groups is required to definitively test with adequate power if effect-site steering is superior.
In conclusion, a closed-loop computer system using the BISTM as the control variable provided satisfactory control of propofol anaesthesia in patients having minor body surface surgery, with analgesia provided by a fixed blood concentration of remifentanil.
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Acknowledgements |
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References |
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