Feasibility and optimal choice of stimulation parameters for supramaximal stimulation of motor evoked potentials.

PURPOSE: The aim was to investigate the feasibility and optimal stimulation parameters for supramaximal stimulation of muscle recorded transcranial electrical stimulation motor evoked potentials (mTc-MEP). METHODS: Forty-seven consecutive patients that underwent scoliosis surgery were included. First, the feasibility of supramaximal stimulation was assessed for two settings (setting 1: pulse duration 0.075ms, interstimulus interval (ISI) 1.5ms; setting 2: pulse duration 0.300ms, ISI 3ms). Thereafter, three mTc-MEP parameters were considered for both settings; (1) elicitability, (2) amplitude, and (3) if supramaximal stimulation was achieved with ≥ 20 V below maximum output. Finally, ISIs (1ms-4ms) were optimized for setting 1. RESULTS: Nine patients (19.15%) were excluded. Of the remaining patients, supramaximal stimulation was achieved in all patients for setting 1, and in 26 (68.42%) for setting 2. In one patient, mTc-MEPs were elicitable in more muscles for setting (1) Amplitudes were not significantly different. Stimulation voltage could be increased ≥ 20 V in all 38 patients for setting 1 and in 10 (38.46%) for setting (2) Optimal ISI's differed widely. CONCLUSION: We recommend using setting 1 when monitoring mTc-MEPs with supramaximal stimulation, after which an individualized ISI optimization can be performed. Moreover, when using supramaximal stimulation, short ISI's (i.e. 1ms or 1.5ms) can be the optimal ISI for obtaining the highest mTc-MEP amplitude.

The role of dexmedetomidine in neurosurgery.

Dexmedetomidine can be used for sedation and analgesia and has been approved for this use by the European Medicines Agency since 2017. It causes an arousable state of sedation, which is beneficial during neurosurgical procedures that require the patient to cooperate with neurological tests (i.e. tumor surgery or implantation of deep brain stimulators). During procedures where monitoring of somatosensory evoked potentials and/or motor evoked potentials is required, dexmedetomidine can be used as an adjunct to general anesthesia with GABAergic drugs to decrease the dose of the latter when these drugs impair the monitoring signals. The use of dexmedetomidine has also been associated with neuroprotective effects and a decreased incidence of delirium, but studies confirming these effects in the peri-operative (neuro-)surgical setting are lacking. Although dexmedetomidine does not cause respiratory depression, its hemodynamic effects are complex and careful patient selection, choice of dose, and monitoring must be performed.

The influence of depth of anesthesia and blood pressure on muscle recorded motor evoked potentials in spinal surgery. A prospective observational study protocol.

For high-risk spinal surgeries, intraoperative neurophysiological monitoring (IONM) is used to detect and prevent intraoperative neurological injury. The motor tracts are monitored by recording and analyzing muscle transcranial electrical stimulation motor evoked potentials (mTc-MEPs). A mTc-MEP amplitude decrease of 50-80% is the most common warning criterion for possible neurological injury. However, these warning criteria often result in false positive warnings. False positives may be caused by inadequate depth of anesthesia and blood pressure on mTc-MEP amplitudes. The aim of this paper is to validate the study protocol in which the goal is to investigate the effects of depth of anesthesia (part 1) and blood pressure (part 2) on mTc-MEPs. Per part, 25 patients will be included. In order to investigate the effects of depth of anesthesia, a processed electroencephalogram (pEEG) monitor will be used. At pEEG values of 30, 40 and 50, mTc-MEP measurements will be performed. To examine the effect of blood pressure on mTc-MEPs the mean arterial pressure will be elevated from 60 to 100 mmHg during which mTc-MEP measurements will be performed. We hypothesize that by understanding the effects of depth of anesthesia and blood pressure on mTc-MEPs, the mTc-MEP monitoring can be interpreted more reliably. This may contribute to fewer false positive warnings. By performing this study after induction and prior to incision, this protocol provides a unique opportunity to study the effects of depths of anesthesia and blood pressure on mTc-MEPs alone with as little confounders as possible. Trial registration number NL7772.

Comparison of haemodynamic- and electroencephalographic-monitored effects evoked by four combinations of effect-site concentrations of propofol and remifentanil, yielding a predicted tolerance to laryngoscopy of 90.

This prospective study evaluates haemodynamic and electroencephalographic effects observed when administering four combinations of effect-site concentrations of propofol (CePROP) and remifentanil (CeREMI), all yielding a single predicted probability of tolerance of laryngoscopy of 90% (PTOL = 90%) according to the Bouillon interaction model. We aimed to identify combinations of CePROP and CeREMI along a single isobole of PTOL that result in favourable hypnotic and haemodynamic conditions. This knowledge could be of advantage in the development of drug advisory monitoring technology. 80 patients (18-90 years of age, ASA I-III) were randomized into four groups and titrated towards CePROP (Schnider model, ug⋅ml-1) and CeREMI (Minto model, ng⋅ml-1) of respectively 8.6 and 1, 5.9 and 2, 3.6 and 4 and 2.0 and 8. After eleven minutes of equilibration, baseline measurements of haemodynamic endpoints and bispectral index were compared with three minutes of responsiveness measurements after laryngoscopy. Before laryngoscopy, bispectral index differed significantly (p < 0.0001) between groups in concordance with CePROP. Heart rate decreased with increasing CeREMI (p = 0.001). The haemodynamic and arousal responses evoked by laryngoscopy were not significantly different between groups, but CePROP = 3.6 µg⋅ml-1 and CeREMI = 4 ng⋅ml-1 evoked the lowest median value for ∆HR and ∆SAP after laryngoscopy. This study provides clinical insight on the haemodynamic and hypnotic consequences, when a model based predicted PTOL is used as a target for combined effect-site controlled target- controlled infusion of propofol and remifentanil. Heart rate and bispectral index were significantly different between groups despite a theoretical equipotency for PTOL, suggesting that each component of the anaesthetic state (immobility, analgesia, and hypnotic drug effect) should be considered as independent neurophysiological and pharmacological phenomena. However, claims of (in)accuracy of the predicted PTOL must be considered preliminary because larger numbers of observations are required for that goal.

Intraoperative neurophysiological monitoring during scoliosis surgery in patients with Duchenne muscular dystrophy.

PURPOSE: Little is known about the reliability and value of intraoperative neurophysiological monitoring (IONM) in patients with Duchenne muscular dystrophy (DMD) undergoing scoliosis correction surgery. The aim of this study was to investigate the feasibility of IONM and the cortical excitability in these patients. METHODS: Fifteen patients with DMD and scoliosis and 15 patients with adolescent idiopathic scoliosis (AIS) underwent scoliosis correction surgery with the use of IONM. IONM consisted of transcranial electrical stimulation motor evoked potential (Tc-MEP) and somatosensory evoked potential (SSEP) monitoring. The highest Tc-MEP amplitudes were collected to test the feasibility. Preoperative compound muscle action potentials (CMAPs) and transcranial magnetic stimulation (TMS)-MEPs were recorded to test the cortical excitability. SSEPs were scored as elicitable or not elicitable. RESULTS: Tc-MEP amplitudes were significantly lower in the DMD group for both the gastrocnemius and tibialis anterior muscles. However, the abductor hallucis muscle had similar amplitudes in both the DMD as the AIS group. TMS/CMAP and Tc-MEP/CMAP ratios were similar in the DMD and AIS group (P = 0.126 and P = 0.792 respectively). CONCLUSIONS: Tc-MEP and SSEP monitoring is feasible, particularly when Tc-MEPs are recorded from the abductor hallucis muscle in patients with DMD. Similar TMS/CMAP and Tc-MEP/CMAP ratios show that there were no differences observed in cortical excitability between the groups. IONM seems a feasible and valuable neurophysiological tool to signal possible surgically induced damage to the spinal cord during scoliosis correction surgery in patients with DMD.

Accidental awareness during general anaesthesia - a narrative review.

Unintended accidental awareness during general anaesthesia represents failure of successful anaesthesia, and so has been the subject of numerous studies during the past decades. As return to consciousness is both difficult to describe and identify, the reported incidence rates vary widely. Similarly, a wide range of techniques have been employed to identify cases of accidental awareness. Studies which have used the isolated forearm technique to identify responsiveness to command during intended anaesthesia have shown remarkably high incidences of awareness. For example, the ConsCIOUS-1 study showed an incidence of responsiveness around the time of laryngoscopy of 1:25. On the other hand, the 5th Royal College of Anaesthetists National Audit Project, which reported the largest ever cohort of patients who had experienced accidental awareness, used a system to identify patients who spontaneously self-reported accidental awareness. In this latter study, the incidence of accidental awareness was 1:19,600. In the recently published SNAP-1 observational study, in which structured postoperative interviews were performed, the incidence was 1:800. In almost all reported cases of intra-operative responsiveness, there was no subsequent explicit recall of intra-operative events. To date, there is no evidence that this occurrence has any psychological consequences. Among patients who experience accidental awareness and can later remember details of their experience, the consequences are better known. In particular, when awareness occurs in a patient who has been given neuromuscular blocking agents, it may result in serious sequelae such as symptoms of post-traumatic stress disorder and a permanent aversion to surgery and anaesthesia, and is feared by patients and anaesthetists. In this article, the published literature on the incidence, consequences and management of accidental awareness under general anaesthesia with subsequent recall will be reviewed.

Cognitive decline after major oncological surgery in the elderly.

BACKGROUND: Elderly patients undergoing oncological surgery experience postoperative cognitive decline. The aims of this study were to examine the incidence of cognitive decline 3 months after surgery and identify potential patient-, disease- and surgery-related risk factors for postoperative cognitive decline in onco-geriatric patients. METHODS: A consecutive series of elderly patients (≥65 years) undergoing surgery for the removal of a solid tumour were included (n = 307). Cognitive performance was assessed pre-operatively and 3 months postoperatively. Postoperative decline was defined as a decline in scores of cognitive tests of ≥25% on ≥2 of 5 tests. RESULTS: Of the patients who had completed the assessments, 117 (53%, 95% confidence interval [CI]: 47-60) had improved cognitive test scores, whereas 26 (12%, 95% CI: 7.6-16) showed cognitive decline at 3 months postoperatively. In patients aged >75 years, the incidence of overall cognitive decline 3 months postoperatively was 18% (95% CI: 9.3-27). In patients with lower pre-operative Mini-Mental State Examination (MMSE) score (≤26) the incidence was 37% (95% CI: 18-57), and in patients undergoing major surgery it was 18% (95% CI: 10.6-26). Of the cognitive domains, executive function was the most vulnerable to decline. CONCLUSION: About half of the elderly patients show improvement in postoperative cognitive performance after oncological surgery, whereas 12% show cognitive decline. Advanced age, lower pre-operative MMSE score and major surgery are risk factors for cognitive decline at 3 months postoperatively and should be taken into account in the clinical decision-making progress. Research to develop interventions to preserve quality of life should focus on this high-risk subpopulation.

Influence of Bayesian optimization on the performance of propofol target-controlled infusion.

BACKGROUND: Target controlled infusion (TCI) systems use population-based pharmacokinetic (PK) models that do not take into account inter-individual residual variation. This study compares the bias and inaccuracy of a population-based vs a personalized TCI propofol titration using Bayesian adaptation. Haemodynamic and hypnotic stability, and the prediction probability of alternative PK models, was studied. METHODS: A double-blinded, prospective randomized controlled trial of 120 subjects undergoing cardiac surgery was conducted. Blood samples were obtained at 10, 35, 50, 65, 75 and 120 min and analysed using a point-of-care propofol blood analyser. Bayesian adaptation of the PK model was applied at 60 min in the intervention group. Median (Absolute) Performance Error (Md(A)PE) was used to evaluate the difference between bias and inaccuracy of the models. Haemodynamic (mean arterial pressure [MAP], heart rate) and hypnotic (bispectral index [BIS]) stability was studied. The predictive performance of four alternative propofol PK models was studied. RESULTS: MdPE and MdAPE did not differ between groups during the pre-adjustment period (control group: 6.3% and 16%; intervention group: 5.4% and 18%). MdPE differed in the post-adjustment period (12% vs. -0.3%), but MdAPE did not (18% vs. 15%). No difference in heart rate, MAP or BIS was found. Compared with the other models, the Eleveld propofol PK model (patients) showed the best prediction performance. CONCLUSIONS: When an accurate population-based PK model was used for propofol TCI, Bayesian adaption of the model improved bias but not precision. CLINICAL TRIAL REGISTRATION: Dutch Trial Registry NTR4518.

Pharmacokinetics and pharmacodynamics of propofol: changes in patients with frontal brain tumours.

BACKGROUND: Models of propofol pharmacokinetics and pharmacodynamics developed in patients without brain pathology are widely used for target-controlled infusion (TCI) during brain tumour excision operations. The goal of this study was to determine if the presence of a frontal brain tumour influences propofol pharmacokinetics and pharmacodynamics and existing PK-PD model performance. METHODS: Twenty patients with a frontal brain tumour and 20 control patients received a propofol infusion to achieve an induction-emergence-induction anaesthetic sequence. Propofol plasma concentration was measured every 4 min and at each transition of the conscious state. Bispectral index (BIS) values were continuously recorded. We used non-linear mixed-effects modelling to analyse the effects of the presence of a brain tumour on the pharmacokinetics and pharmacodynamics of propofol. Subsequently we calculated the predictive performance of Marsh, Schnider, and Eleveld models in terms of median prediction error (MdPE) and median absolute prediction error (MdAPE). RESULTS: Patients with brain tumours showed 40% higher propofol clearance than control patients. Performance of the Schnider model (MdPEpk -20.0%, MdAPEpk 23.4%) and Eleveld volunteer model (MdPEpk -8.58%, MdAPEpk 21.6%) were good. The Marsh model performed less well (MdPEpk -14.3%, MdAPEpk 41.4%), as did the Eleveld patient model (MdPEpk -30.8%, MdAPEpk 32.1%). CONCLUSIONS: Brain tumours might alter the pharmacokinetics of propofol. Caution should be exerted when using propofol TCI in patients with frontal brain tumours due to higher clearance. TRIAL REGISTRY NUMBER: NCT01060631.

Differences in Blood Pressure in Infants After General Anesthesia Compared to Awake Regional Anesthesia (GAS Study-A Prospective Randomized Trial).

BACKGROUND: The General Anesthesia compared to Spinal anesthesia (GAS) study is a prospective randomized, controlled, multisite, trial designed to assess the influence of general anesthesia (GA) on neurodevelopment at 5 years of age. A secondary aim obtained from the blood pressure data of the GAS trial is to compare rates of intraoperative hypotension after anesthesia and to identify risk factors for intraoperative hypotension. METHODS: A total of 722 infants ≤60 weeks postmenstrual age undergoing inguinal herniorrhaphy were randomized to either bupivacaine regional anesthesia (RA) or sevoflurane GA. Exclusion criteria included risk factors for adverse neurodevelopmental outcome and infants born at <26 weeks of gestation. Moderate hypotension was defined as mean arterial pressure measurement of <35 mm Hg. Any hypotension was defined as mean arterial pressure of <45 mm Hg. Epochs were defined as 5-minute measurement periods. The primary outcome was any measured hypotension <35 mm Hg from start of anesthesia to leaving the operating room. This analysis is reported primarily as intention to treat (ITT) and secondarily as per protocol. RESULTS: The relative risk of GA compared with RA predicting any measured hypotension of <35 mm Hg from the start of anesthesia to leaving the operating room was 2.8 (confidence interval [CI], 2.0-4.1; P < .001) by ITT analysis and 4.5 (CI, 2.7-7.4, P < .001) as per protocol analysis. In the GA group, 87% and 49%, and in the RA group, 41% and 16%, exhibited any or moderate hypotension by ITT, respectively. In multivariable modeling, group assignment (GA versus RA), weight at the time of surgery, and minimal intraoperative temperature were risk factors for hypotension. Interventions for hypotension occurred more commonly in the GA group compared with the RA group (relative risk, 2.8, 95% CI, 1.7-4.4 by ITT). CONCLUSIONS: RA reduces the incidence of hypotension and the chance of intervention to treat it compared with sevoflurane anesthesia in young infants undergoing inguinal hernia repair.

Neuronal damage biomarkers in the identification of patients at risk of long-term postoperative cognitive dysfunction after cardiac surgery.

Biomarkers of neurological injury can potentially predict postoperative cognitive dysfunction. We aimed to identify whether classical neuronal damage-specific biomarkers, including brain fatty acid-binding protein, neuron-specific enolase and S100 calcium-binding protein ß, as well as plasma-free haemoglobin concentration as a measure of haemolysis, could be used to predict the risk of long-term cognitive decline after coronary artery bypass grafting with or without cardiopulmonary bypass. We assessed cognitive function using the CogState brief computerised cognitive test battery at 3 months and at 15 months after surgery. Blood samples were obtained pre-operatively, after sternal closure, and at 6 h and 24 h postoperatively. We found signs of cognitive decline at 3 months in 15 of 57 patients (26%), and in 13 of 48 patients (27%) at 15 months. Brain fatty acid-binding protein was already significantly higher before surgery in patients with postoperative cognitive dysfunction at 15 months, with pre-operative plasma levels of 22.8 (8.3-33.0 [0-44.6]) pg.ml-1 compared with 9.7 (3.9-17.3 [0-49.0]) pg.ml-1 in patients without cognitive dysfunction. This biomarker remained significantly higher in patients with cognitive decline throughout the entire postoperative period. At 3 months after surgery, high levels of plasma-free haemoglobin at sternal closure were associated with a negative influence on cognitive performance, as were high baseline scores on neuropsychological tests, whereas a higher level of education proved to beneficially influence cognitive outcome. We found that postoperative cognitive dysfunction at 3 months was associated with cognitive decline at 15 months after surgery, and served as a valuable prognostic factor for declines in individual cognitive performance one year later. Classical neuronal injury-related biomarkers were of no clear prognostic value.

A pilot study of cerebral tissue oxygenation and postoperative cognitive dysfunction among patients undergoing coronary artery bypass grafting randomised to surgery with or without cardiopulmonary bypass*.

Coronary artery bypass surgery, performed with or without cardiopulmonary bypass, is frequently followed by postoperative cognitive decline. Near-infrared spectroscopy is commonly used to assess cerebral tissue oxygenation, especially during cardiac surgery. Recent studies have suggested an association between cerebral desaturation and postoperative cognitive dysfunction. We therefore studied cerebral oxygen desaturation, defined as area under the cerebral oxygenation curve < 40% of > 10 min.%, with respect to cognitive performance at 4 days (early) and 3 months (late) postoperatively, compared with baseline, using a computerised cognitive test battery. We included 60 patients, of mean (SD) age 62.8 (9.4) years, scheduled for elective coronary artery bypass grafting, who were randomly allocated to surgery with or without cardiopulmonary bypass. Cerebral desaturation occurred in only three patients and there was no difference in cerebral oxygenation between the two groups at any time. Among patients who received cardiopulmonary bypass, 18 (62%) had early cognitive decline, compared with 16 (53%) in the group without cardiopulmonary bypass (p = 0.50). Three months after surgery, 11 patients (39%) in the cardiopulmonary bypass group displayed cognitive dysfunction, compared with four (14%) in the non-cardiopulmonary bypass group (p = 0.03). The use of cardiopulmonary bypass was identified as an independent risk factor for the development of late cognitive dysfunction (OR 6.4 (95% CI 1.2-33.0) p = 0.027. In conclusion, although cerebral oxygen desaturation was rare in our population, postoperative cognitive decline was common in both groups, suggesting that factors other than hypoxic neuronal injury are responsible.

Bispectral index values and propofol concentrations at loss and return of consciousness in patients with frontal brain tumours and control patients.

BACKGROUND: The influence of frontal brain tumours on bispectral index (BIS) measurements and propofol requirements is unknown. The primary aim of our study was to determine whether BIS values recorded at loss and return of consciousness (LOC and ROC, respectively) differ between patients with unilateral frontal brain tumours and control patients. Secondary goals were to compare propofol requirements for LOC and to determine whether there were significant inter-hemispheric differences between BIS values in tumour and control patients. METHODS: We enrolled 20 patients with a frontal brain tumour and 20 control patients. Bilateral BIS measurements were done during induction of propofol anaesthesia, during recovery of consciousness, and during a second induction of anaesthesia. The isolated-forearm test was used to determine the moments of LOC1, ROC, and LOC2. Arterial blood samples were obtained every 4 min for determination of measured propofol concentrations. RESULTS: The median BIS values recorded at LOC1, ROC, and LOC2 did not differ between the groups. There were no significant inter-hemispheric differences in BIS in tumour and control patients. The median [inter-quartile range (IQR)] total propofol doses at LOC1 were 82 (75-92) and 78 (68-91) mg in tumour and control patients, respectively. The median (IQR) measured plasma propofol concentrations at LOC1 were 12 (9-14) and 13 (11-15) µg ml(-1) in the tumour and control groups, respectively. CONCLUSIONS: The presence of a frontal brain tumour did not affect ipsilateral BIS values, and so need not influence the placement of unilateral BIS electrodes if BIS monitoring is used to titrate propofol anaesthesia.

A review of postoperative cognitive dysfunction and neuroinflammation associated with cardiac surgery and anaesthesia.

Postoperative cognitive dysfunction is receiving increasing attention, particularly as it mainly affects the (growing) elderly population. Until recently, cognitive deficits after cardiac surgery were thought to be caused by physiological disturbances associated with the cardiopulmonary bypass technique. Although the technique of 'off-pump' coronary revascularisation may potentially be associated with improved outcome, long-term follow-up studies have failed to demonstrate a significant reduction in the incidence of postoperative cognitive dysfunction. The focus of research is thus shifting from cardiopulmonary bypass to other factors common to both techniques, such as surgery, anaesthesia and patient-related predisposing factors. Priming of the immune system by ageing and atherosclerosis may result in an exaggerated systemic and cerebral inflammatory response to cardiac surgery and anaesthesia, causing neuronal loss or dysfunction resulting in cognitive dysfunction. We briefly discuss the evidence for cardiopulmonary bypass-related neuronal injuries in adult cardiac surgery patients, and review the evidence that immune priming is a key factor in the pathogenesis of cognitive dysfunction after cardiac surgery.

Performance evaluation of paediatric propofol pharmacokinetic models in healthy young children.

BACKGROUND: The performance of eight currently available paediatric propofol pharmacokinetic models in target-controlled infusions (TCIs) was assessed, in healthy children from 3 to 26 months of age. METHODS: Forty-one, ASA I-II children, aged 3-26 months were studied. After the induction of general anaesthesia with sevoflurane and remifentanil, a propofol bolus dose of 2.5 mg kg(-1) followed by an infusion of 8 mg kg(-1) h(-1) was given. Arterial blood samples were collected at 1, 2, 3, 5, 10, 20, 40, and 60 min post-bolus, at the end of surgery, and at 1, 3, 5, 30, 60, and 120 min after stopping the infusion. Model performance was visually inspected with measured/predicted plots. Median performance error (MDPE) and the median absolute performance error (MDAPE) were calculated to measure bias and accuracy of each model. RESULTS: Performance of the eight models tested differed markedly during the different stages of propofol administration. Most models underestimated propofol concentration 1 min after the bolus dose, suggesting an overestimation of the initial volume of distribution. Six of the eight models tested were within the accepted limits of performance (MDPE<20% and MDAPE<30%). The model derived by Short and colleagues performed best. CONCLUSIONS: Our results suggest that six of the eight models tested perform well in young children. Since most models overestimate the initial volume of distribution, the use for TCI might result in the administration of larger bolus doses than necessary.

Effect-site targeted patient-controlled sedation with propofol: comparison with anaesthetist administration for colonoscopy.

Patient-controlled sedation (PCS) allows patients to match their sedation requirement to perceived discomfort. The significant delay in onset of sedation may be overcome with effect-site steered target controlled infusion, but previously only trials in volunteers have been carried out. We therefore conducted a randomised, double-blind controlled trial comparing effect-site steered propofol PCS with anaesthetist-administered propofol sedation in 40 patients presenting for colonoscopy. The initial effect-site target in the PCS group was 0.8 microg.ml(-1), increment was 0.1 microg.ml(-1) and lockout was 3 min. Patient and endoscopist satisfaction and operating conditions were similar between the two groups. PCS patients were sedated more slowly (13 [7.1] vs. 3 [1.1] min; p < 0.0001) and less deeply (minimum BIS value: 71 [16] vs. 58 [15]; p = 0.13) than anaesthetist-administered propofol sedation patients. More of the latter patients were hypotensive, but all patients had similar recollection of events during the procedure and similar quality of recovery.

Closed-loop control of propofol anaesthesia using bispectral index: performance assessment in patients receiving computer-controlled propofol and manually controlled remifentanil infusions for minor surgery.

BACKGROUND: In a previous study we used the bispectral index (BIS) for automatic control of propofol anaesthesia, using a proportional-integral-differential control algorithm. As control was less than optimal in some patients, we revised the constants of the control algorithm. The aim of the current study was to measure the performance of the revised system in patients undergoing minor surgery under propofol and remifentanil anaesthesia. 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 11-20, 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 BIS 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.