Recent advances in intravenous anaesthesia

Efforts to develop new hypnotic compounds continue, althoughseveral have recently failed in development. Propofol has beenreformulated in various presentations with and without preservatives.Pharmacokinetic and pharmacodynamic differences exist betweensome of these preparations, and it is currently unclear whetherany have substantial advantages over the original presentation.The use of target-controlled infusion (TCI) has been extendedto include paediatric anaesthesia and sedation. Applicationof TCI to remifentanil is now licensed. Linking of electroencephalogram(EEG) monitoring to TCI for closed-loop anaesthesia remainsa research tool, although commercial development may follow.The availability of stereoisomer ketamine and improved understandingof its pharmacology have increased non-anaesthetic use of ketamineas an adjunct analgesic. It may be useful in subhypnotic dosesfor postsurgical patients with pain refractory to morphine administration.      

Cerebrospinal fluid and blood propofol concentration during total intravenous anaesthesia for neurosurgery

Background. The aim of this paper is to compare the propofolconcentration in blood and cerebrospinal fluid (CSF) in patientsscheduled for different neurosurgical procedures and anaesthetizedusing propofol as part of a total intravenous anaesthesia technique. Methods. Thirty-nine patients (ASA I–III) scheduled forelective intracranial procedures, were studied. Propofol wasinfused initially at 12 mg kg^–1 h^–1 and thenreduced in steps to 9 and 6 mg kg^–1 h^–1. Duringanaesthesia, bolus doses of fentanyl and cis-atracurium wereadministered as necessary. After tracheal intubation the lungswere ventilated to achieve normocapnia with an oxygen-air mixture(FI_O2=0.33). Arterial blood and CSF samples for propofol examinationwere obtained simultaneously directly after intracranial drainageinsertion and measured using high-performance liquid chromatography.The patients were divided into two groups depending on the typeof neurosurgery. The Aneurysm group consisted of 13 patientswho were surgically treated for ruptured intracranial aneurysm.The Tumour group was composed of 26 patients who were undergoingelective posterior fossa extra-axial tumour removal. Results. Blood propofol concentrations in both groups did notdiffer significantly (P>0.05). The propofol concentrationin CSF was 86.62 (SD 37.99) ng ml^–1 in the Aneurysm groupand 50.81 (26.10) ng ml^–1 in the Tumour group (P<0.005). Conclusions. Intracranial pathology may influence CSF propofolconcentration. However, the observed discrepancies may alsoresult from quantitative differences in CSF composition andfrom restricted diffusion of the drug in the CSF. Br J Anaesth 2003; 90: 84–6     

Remifentanil target-controlled infusion vs propofol target-controlled infusion for conscious sedation for awake fibreoptic intubation: a double-blinded randomized controlled trial

BACKGROUND: Awake fibreoptic intubation (AFOI) is a technique used in patients with difficult airways. This study compares the suitability of remifentanil target-controlled infusion (TCI) to propofol TCI for conscious sedation during AFOI in patients with bona fide difficult airways. METHODS: We recruited 24, ASA I-III patients, who were undergoing sedation for elective AFOI. Patients were randomized to one of the two groups, Group P (n=10) received propofol TCI and Group R (n=14) received remifentanil TCI. Primary outcome measures were conditions achieved at endoscopy, intubation, and post-intubation, which were graded using scoring systems. Other parameters measured were the endoscopy time, intubation time, and number of attempts at intubation. A postoperative interview was conducted to determine recall of events and level of patient satisfaction. RESULTS: Endoscopy scores (0-5) and intubation scores (0-5) were significantly different [Group P 3 (1-4) vs Group R 1 (0-3) P<0.0001, Group P 3 (2-4) vs Group R 1 (0-3) P<0.0001, respectively]; with much better conditions in Group R, endoscopy times and intubation times were also significantly different, being shorter in Group R (P<0.007 and P<0.023, respectively). Patient tolerance of the procedure, judged by the discomfort scores (P<0.004) and the post-intubation scores (P<0.08), was significantly better in Group R. The level of recall for events was higher in Group R. However, there were no significant differences in the patient satisfaction scores. CONCLUSIONS: Remifentanil TCI appears to provide better conditions for AFOI when compared with propofol TCI. The disadvantage of remifentanil in this setting may be a higher incidence of recall.     

Recovery from propofol anaesthesia supplemented with remifentanil

We have examined the effects on recovery end-points of supplementationof a propofol-based anaesthetic with remifentanil. After inductionof anaesthesia with propofol and remifentanil 1.0 µg kg^–1,15 patients each were randomly allocated to target plasma propofolconcentrations of 2, 3, 4 or 5 µg ml^–1for maintenance of anaesthesia. Remifentanil was administeredby infusion for supplementation in doses required for maintenanceof adequate anaesthesia. All patients received 50% nitrous oxidein oxygen and ventilation was controlled. The total amount ofdrugs used and times to different recovery end-points were recorded.Cognitive function was also assessed using a Mini-Mental Statequestionnaire. The median dose of remifentanil for maintenanceof adequate anaesthesia (excluding the initial bolus dose) inthe four groups was 0.21, 0.15, 0.11 and 0.13 µg kg^–1 min^–1respectively (P=0.0026). The median times to eye opening andorientation were shortest in the 2 µg ml^–1group [6.0 and 6.5 min, 8.5 and 10.8 min, 13.4 and15.8 min, and 14.2 and 19.5 min respectively in thepropofol 2, 3, 4, and 5 µg ml^–1 groups respectively(P<0.001)]. The times to discharge from the recovery wardand the Mini-Mental State scores were not significantly different. Br J Anaesth 2001; 86: 361–5     

Loss of volition and pain response during induction of anaesthesia with propofol or sevoflurane

We compared the time to reach two anaesthetic end-points duringinduction of anaesthesia with a potent inhalation agent (sevoflurane)and an i.v. agent (propofol). We used a method to ensure steadybreathing during inhalation induction, and measured loss oftone in the outstretched arm and loss of response to a painfulstimulus. Thirty-eight female patients (age 39 (9) yr, weight65 (11) kg, and height 165 (8) cm) (mean (SD)) were randomlyallocated to receive either propofol or sevoflurane. The predictedinduction dose of propofol, estimated from age and weight foreach patient, was given at a rate of 1% of the induction doseper second, to a possible maximum of 2.5 times the predictedinduction dose. Sevoflurane was given with an inhaled concentrationof 8%, which was anticipated to cause loss of arm tone within90–120 s. After loss of consciousness, we applied a painfulelectrical stimulus to a finger at 15-s intervals and measuredthe time to loss of motor response. The median times and interquartilevalues for loss of arm tone were 105 (88–121) s for sevofluraneand 65 (58–80) s for propofol. This was equivalent to0.65 of the ED₅₀ of propofol. The time to loss of response topain was 226 (169–300) s for sevoflurane. The variancesof these three measurements were not significantly different,indicating that these dose–response relationships weresimilar. In contrast, only 11 of the patients given propofollost the response to pain after 2.5xED₅₀ had been given. Theseresults support previous evidence of substantial differencesbetween anaesthetic end-points, and show that this evidencecan be obtained using a simple and rapid method. Br J Anaesth 2001; 87: 283–6     

Comparison of isoflurane and propofol-fentanyl anaesthesia in a swine model of asphyxia

Background. There have been few studies comparing the responseto asphyxia and the effectiveness of typical cardiopulmonaryresuscitation (CPR) using exogenous epinephrine administrationand manual closed-chest compression between total intravenousanaesthesia (TIVA) and inhalational anaesthesia. Methods. Twenty pigs were randomly assigned to two study groupsanaesthetized using either 2% end-tidal isoflurane (n=10) orpropofol (12 mg kg^–1 h^–1)–fentanyl (50 µgkg^–1) (n=10). Asphyxia was induced by clamping the trachealtube until the mean arterial pressure (MAP) decreased to 40%of the baseline value (40% MAP time). The tracheal tube wasdeclamped at that point, and CPR was performed. Haemodynamicparameters and blood samples were obtained before the inductionof asphyxia, at 1-min intervals during asphyxia, and 1, 2, 3,5, 10, 30 and 60 min after asphyxia. Results. TIVA maintained the MAP against hypoxia–hypercapniastress significantly longer than isoflurane anaesthesia (mean(SD) 40% MAP time 498 (95) and 378 (104) s respectively). Inall animals in the isoflurane group, spontaneous circulationreturned within 1 min of the start of CPR. In six of the TIVAanimals, spontaneous circulation returned for 220 (121) s; spontaneouscirculation did not return within 5 min in the remaining fouranimals. Conclusions. Although TIVA is less prone than isoflurane anaesthesiato primary cardiovascular depression leading to asphyxia, TIVAis associated with reduced effectiveness of CPR in which resuscitationbecause of asphyxic haemodynamic depression occurs. Br J Anaesth 2003; 91: 871–7     

Target-controlled infusion of propofol and remifentanil in cardiac anaesthesia: influence of age on predicted effect-site concentrations

Background. Propofol-anaesthesia administrated via target-controlledinfusion (TCI) has been proposed for cardiac surgery. Age-relatedchanges in pharmacology explain why propofol dose requirementis reduced in elderly patients. However, the Marsh pharmacokineticmodel incorporated in the Diprifusor propofol device does nottake age into account as a covariable. In the absence of depthof anaesthesia monitoring, this limitation could cause adversecardiovascular effects resulting from propofol overdose in olderpatients. We assessed the influence of age on effect-site propofolconcentrations predicted by the Diprifusor and titrated to thebispectral index score (BIS) during cardiac anaesthesia. Methods. Forty-five patients received propofol by Diprifusorand remifentanil by software including Minto model. Propofoland remifentanil effect-site concentrations were adapted toBIS (40–60) and haemodynamic profile, respectively. Theinfluence of age on effect-site concentrations was assessedby dividing patients into two groups: young (<65 yr) andelderly (     

Propofol-alfentanil vs propofol-remifentanil for posterior spinal fusion including wake-up test

Background. Wake-up test can be used during posterior spinalfusion (PSF) to ensure that spinal function remains intact.This study aims at assessing the characteristics of the wake-uptest during propofol–alfentanil (PA) vs propofol–remifentanil(PR) infusions for PSF surgery. Methods. Sixty patients with scoliosis and candidates for PSFsurgery were randomly allocated in either alfentanil (PA) orremifentanil (PR) group. After an i.v. bolus of alfentanil 30µg kg^–1 in the PA group or remifentanil 1 µgkg^–1 in the PR group, anaesthesia was induced with thiopentaland atracurium. During maintenance, opioid infusion consistedof alfentanil 1 µg kg^–1 min^–1 or remifentanil0.2 µg kg^–1 min^–1, in the PA group and thePR group, respectively. All patients received propofol 50 µgkg^–1 min^–1. Atracurium was given to maintain therequired surgical relaxation. At the surgeon's request, allinfusions were discontinued. Patients were asked to move theirhands and feet. Time from anaesthetic discontinuation to spontaneousventilation (T₁), and from then until movement of the handsand feet (T₂), and its quality were recorded. Results. The average T₁ and T₂ were significantly shorter inthe PR group [3.6 (2.5) and 4.1 (2) min] than the PA group [6.1(4) and 7.5 (4.5) min]. Quality of wake-up test, however, didnot show significant difference between the two groups studied. Conclusion. Wake-up test can be conducted faster with remifentanilcompared with alfentanil infusion during PSF surgery.     

Tetanic stimulus of ulnar nerve as a predictor of heart rate response to skin incision in propofol remifentanil anaesthesia

Background: To study adequate antinociception during general anaesthesia,tetanic stimulus of 5–10 s duration has been used previouslyas a standardized nociceptive stimulus. However, such stimulihave been found to correlate poorly with intraoperative nociception.We hypothesized that an electrical tetanic stimulus of the ulnarnerve, lasting 30 s, would provide a reliable experimental painmodel. Methods: Thirty-three patients, undergoing open abdominal surgery, werestudied. Propofol and remifentanil were used for anaesthesia.Patients were randomized to receive remifentanil at three target-controlledinfusion levels (1, 3, or 5 ng ml^–1) during short (5 s,Tet5) and a long-lasting (30 s, Tet30) tetanic (50 mA, 50 Hz)stimulus and skin incision. RR intervals (RRI) were obtainedfrom the ECG and the mean RRI before each stimulus (Tet5, Tet30,incision) was compared with that after the stimulus. Results: At remifentanil level 1 ng ml^–1, the RRI responses totetanic stimuli and skin incision were prominent but with higherconcentrations (3 and 5 mg ml^–1), responses were verysmall. Tet30 (r²=0.780) was the best predictor of the RRI responseto skin incision when compared with Tet5 (r²=0.611), remifentanillevel (r²=0.340), or propofol level (r²=0.036). Conclusions: Long-lasting tetanic stimulus of ulnar nerve may provide a betterexperimental pain model for surgical pain during general anaesthesiathan shorter stimuli, which have been applied in earlier studies.     

Predictive performance of computer-controlled infusion of remifentanil during propofol/remifentanil anaesthesia

Background. The predictive performance of the available pharmacokineticparameter sets for remifentanil, when used for target-controlledinfusion (TCI) during total i.v. anaesthesia, has not been determinedin a clinical setting. We studied the predictive performanceof five parameter sets of remifentanil when used for TCI ofremifentanil during propofol anaesthesia in surgical patients. Methods. Remifentanil concentration–time data that hadbeen collected during a previous pharmacodynamic interactionstudy in 30 female patients (ASA physical status I, aged 20–65 yr)who received a TCI of remifentanil and propofol during lowerabdominal surgery were used in this evaluation. The remifentanilconcentrations predicted by the five parameter sets were calculatedon the basis of the TCI device record of the infusion rate–timeprofile that had actually been administered to each individual.The individual and pooled bias [median performance error (MDPE)],inaccuracy [median absolute performance error (MDAPE)], divergenceand wobble of the remifentanil TCI device were determined fromthe pooled and intrasubject performance errors. Results. A total of 444 remifentanil blood samples were analysed.Blood propofol and remifentanil concentrations ranged from 0.5to 11 µg ml^–1 and 0.1 to 19.6 ng ml^–1respectively. Pooled MDPE and MDAPE of the remifentanil TCIdevice were –15 and 20% for the parameter set of Mintoand colleagues (Anesthesiology 1997; 86: 10–23), 1 and21%, –6 and 21%, and –6 and 19% for the three parametersets described by Egan and colleagues (Anesthesiology 1996;84: 821–33, Anesthesiology 1993; 79: 881–92, Anesthesiology1998; 89: 562–73), and –24 and 30% for the parameterset described by Drover and Lemmens (Anesthesiology 1998; 89:869–77). Conclusions. Remifentanil can be administered by TCI with acceptablebias and inaccuracy. The three pharmacokinetic parameter setsdescribed by Egan and colleagues resulted in the least biasand best accuracy. Br J Anaesth 2003; 90: 132–41     

Absence of memory for intra-operative information during surgery with total intravenous anaesthesia

While using the isolated forearm technique, we wished to determinewhether patients who did not respond to commands during generalanaesthesia with a total intravenous technique (propofol andalfentanil with atracurium) had any evidence of post-operativeexplicit or implicit memory. Forty women undergoing major gynaecologicalsurgery were randomized, in a double-blind design, to hear twodifferent tapes during surgery. Psychological tests of explicitand implicit memory were conducted within 2 h of surgery. Therewas no evidence of implicit or explicit memory, nor any recall,in the seven women who responded to commands during surgery.We conclude that during total intravenous anaesthesia with propofoland alfentanil, there is no evidence that learning takes placewhen anaesthesia is adequate. Furthermore, with this anaesthetictechnique, it would seem that—provided any period of patientresponsiveness is short and that unconsciousness is inducedrapidly again—there is no evidence of implicit or explicitmemory. Br J Anaesth 2001; 86: 196–202     

EEG-controlled closed-loop dosing of propofol in rats

Background. Based on previous pharmacokinetic and pharmacodynamicstudies, we have developed an EEG-controlled closed-loop systemfor the i.v. hypnotic agent propofol in rats. Methods. Seven adult male Sprague–Dawley rats (weight423–584 g) were included in the study. EEG was recordedwith occipito–occipital needle electrodes and the EEGpower spectrum was estimated. The median frequency (MEF) wasextracted from the power spectrum and was modified MEF (mMEF)to account for the occurrence of spikes and burst suppressionpatterns in the EEG. Propofol infusion was controlled by a model-basedadaptive control algorithm to maintain a set point of mMEF=3.0(SD 0.5) Hz. The performance of the feedback system was characterizedby the median performance error MDPE=median{(mMEF–setpoint)/set point} and the median absolute performance error(MDAPE). The effective therapeutic infusion (ETI) to maintainthe set point was determined from the resulting infusion rates. Results. In all rats a feedback period of 90 min could be performed.Mean MDPE was 1.2 (SE 0.4)% and MDAPE was 13.9 (0.3)%. The ETIwas 0.73 (SD 0.20) mg kg^–1 min^–1. Mean arterialpressure before propofol infusion was 148 (14) mm Hg, with thelowest value during closed-loop infusion being 110 (20) mm Hg. Conclusions. The feedback system presented here may be a usefultool not only for automatic drug control to maintain a definedhypnotic effect but may also be a powerful device in pharmacologicalstudies such as the determination of dose requirements or theassessment of drug–drug interactions. Br J Anaesth 2004; 92: 564–9     

Feasibility study for the administration of remifentanil based on the difference between response entropy and state entropy

Background: Facial electromyography (FEMG) may have utility in the assessmentof nociception during surgery. The difference between stateentropy (SE) and response entropy (RE) is an indirect measureof FEMG. This study assesses an automated algorithm for remifentaniladministration that is based on maintaining an entropy difference(ED) that is less than an upper boundary condition and greaterthan a lower boundary condition. Methods: The algorithm was constructed with a development set (n = 40),and then automated and studied with a validation set (n = 20)of patients undergoing anterior cruciate ligament repair. Thepercentage of time that the ED was maintained between the twoboundary conditions was determined. Remifentanil and propofolpredicted effect-site concentrations (Ce) were determined atsurgical milestones and, after drug discontinuation, the timeto response to verbal stimulation and orientation was measured. Results: The median (25th–75th percentile) per cent of time thatthe ED was recorded between the boundary conditions was 99.3%(98.1–99.8%). Predicted propofol (µg ml^–1)and remifentanil (ng ml^–1) Ce (SD), respectively, were3.5 and 4.0 at induction, 1.9 (0.8) and 7.2 (3.7) at the endof surgery, and 1.1 (0.5) and 3.2 (2.2) at eye opening. Themedian time to eye opening and orientation was 3.8 and 6.8 min,respectively. Conclusion: This feasibility study supports the concept that remifentanilmay be delivered using an algorithm that maintains the differencebetween SE and RE between the upper and lower boundary condition.     

Remifentanil or propofol for sedation during carotid endarterectomy under cervical plexus block

Background. During carotid endarterectomy under regional anaesthesia,patients often require medication to control haemodynamic instabilityand to provide sedation and analgesia. Propofol and remifentanilare used for this purpose. However, the benefits, side-effects,and optimal dose of these drugs in such patients are unclear. Methods. Sixty patients were included in a prospective, randomized,single blinded study. All patients received a deep cervicalplexus block with 30 ml ropivacaine 0.75% and were randomizedto receive either remifentanil 3 µg kg^–1 h^–1or propofol 1 mg kg^–1 h^–1. The infusions were startedafter performing the regional block and were stopped at theend of surgery. Arterial pressure, ECG, ventilatory rate, andPa_CO2 were measured continuously and recorded at predeterminedtimes. Twenty-four hours after surgery, patient comfort, andsatisfaction were also evaluated. Results. In three patients, the infusion of remifentanil hadto be stopped because of severe respiratory depression or bradycardia.No significant differences were found between the two groupsin haemodynamic variables or sedative effects, but there wasa significantly greater decrease in ventilatory frequency andincrease in Pa_CO2 in the remifentanil group. The patient’ssubjective impressions and pain control were excellent in bothgroups. Conclusion. As a result of the higher incidence of adverse respiratoryeffects with remifentanil and similar sedative effects, propofolis preferable for sedation during cervical plexus block in elderlypatients with comorbid disease at the dosage used. Br J Anaesth 2002; 89: 637–40     

Influence of the baricity of a local anaesthetic agent on sedation with propofol during spinal anaesthesia

Background: This study examined the effect of different levels of spinalanaesthesia, induced by solutions of different baricity butcontaining the same amount of local anaesthetic agent, on therequirement for sedation with propofol. Methods: Thirty-six patients undergoing varicose vein surgery under spinalanaesthesia were randomly allocated to receive tetracaine 15mg in 3 ml of either glucose 5% (hyperbaric) or CSF (isobaric).I.V. propofol was started 5 min after the intrathecal injectionand was titrated to maintain a bispectral index (BIS) scoreof 65–75. The propofol requirements to maintain this rangein the two groups were compared every 5 min. Results: The propofol requirement was always lower in the hyperbaricgroup, with the differences becoming statistically significant20 min after the intrathecal injection. Total consumption ofpropofol over the 55 min of the study was also less in the hyperbaricgroup. Conclusion: The known difference in level of spinal anaesthetic block inducedby solutions of different baricity, but the same dose of localanaesthetic, was associated with different requirements forpropofol sedation as determined by BIS assessment.     

Measuring depth of anaesthesia using changes in directional connectivity: a comparison with auditory middle latency response and estimated bispectral index during propofol anaesthesia

General anaesthesia is associated with changes in connectivity between different regions of the brain, the assessment of which has the potential to provide a novel marker of anaesthetic effect. We propose an index that quantifies the strength and direction of information flow in electroencephalographic signals collected across the scalp, assess its performance in discriminating ‘wakefulness’ from ‘anaesthesia’, and compare it with estimated bispectral index and the auditory middle latency response. We used a step-wise slow induction of anaesthesia in 10 patients to assess graded changes in electroencephalographic directional connectivity at propofol effect-site concentrations of 2 μg.ml⁻¹, 3 μg.ml⁻¹ and 4 μg.ml⁻¹. For each stable effect-site concentration, connectivity was estimated from multichannel electroencephalograms using directed coherence, together with middle latency response and estimated bispectral index. We used a linear support vector machine classifier to compare the performance of the different electroencephalographic features in discriminating wakefulness from anaesthesia. We found a significant reduction in the strength of long-range connectivity (interelectrode distance > 10 cm) (p < 0.008), and a reversal of information flow from markedly postero-frontal to fronto-posterior (p < 0.006) between wakefulness and a propofol effect-site concentration of 2 μg.ml⁻¹. This then remained relatively constant as effect-site concentration increased, consistent with a step change in directed coherence with anaesthesia. This contrasted with the gradual change with increasing anaesthetic dose observed for estimated bispectral index and middle latency response. Directed coherence performed best in discriminating wakefulness from anaesthesia with an accuracy of 95%, indicating the potential of this new method (on its own or combined with others) for monitoring adequacy of anaesthesia.     

Reduction of pain during induction with target-controlled propofol and remifentanil

BACKGROUND: Pain on injection of propofol is unpleasant. We hypothesized that propofol infusion pain might be prevented by infusing remifentanil before starting the propofol infusion in a clinical setting where target-controlled infusions (TCI) of both drugs were used. A prospective, randomized, double-blind, placebo-controlled trial was performed to determine the effect-site concentration (Ce) of remifentanil to prevent the pain without producing complications. METHODS: A total of 128 patients undergoing general surgery were randomly allocated to receive normal saline (control) or remifentanil to a target Ce of 2 ng ml(-1) (R2), 4 ng ml(-1) (R4), or 6 ng ml(-1) (R6) administered via TCI. After the target Ce was achieved, the infusion of propofol was started. Remifentanil-related complications were assessed during the remifentanil infusion, and pain caused by propofol was evaluated using a four-point scale during the propofol infusion. RESULTS: The incidence of pain was significantly lower in Groups R4 and R6 than in the control and R2 groups (12/32 and 6/31 vs 26/31 and 25/32, respectively, P<0.001). Pain was less severe in Groups R4 and R6 than in the control and R2 groups (P<0.001). However, both incidence and severity of pain were not different between Groups R4 and R6. No significant complications were observed during the study. CONCLUSIONS: During induction of anaesthesia with TCI of propofol and remifentanil, a significant reduction in propofol infusion pain was achieved without significant complications by prior administration of remifentanil at a target Ce of 4 ng ml(-1).     

Propofol sparing effect of remifentanil using closed-loop anaesthesia

Background. General anaesthesia is a balance between hypnosisand analgesia. We investigated whether an increase in remifentanilblood concentration would reduce the amount of propofol requiredto maintain a comparable level of anaesthesia in 60 patientsundergoing ambulatory surgery. Methods. Patients were allocated randomly to receive remifentanilto a target blood concentration of 2 ng ml^–1 (low), 4ng ml^–1 (medium), or 8 ng ml^–1 (high), administeredby target-controlled infusion (TCI). After equilibration, propofolTCI was commenced in closed-loop control, with auditory evokedpotentials (AEPex) as the input signal, aiming for an AEPexof 35. This was to ensure a comparable and unbiased level ofanaesthesia in all patients. Results. We found a dose-dependent decrease in propofol requirementswith increasing remifentanil concentrations. The mean (95% CI)propofol target blood concentration during adequate anaesthesiawas 4.96 (3.85–6.01) µg ml^–1 in the low, 3.46(2.96–3.96) µg ml^–1 in the medium, and 3.01(2.20–3.38) µg ml^–1 in the high group. Therewas no significant difference when recovery end points wereachieved between the groups. Cardiovascular changes were moderate,but most pronounced in the high concentration group, with adecrease in heart rate of 21% compared with baseline. The meancalculated effect site propofol concentration at loss of consciousnesswas 2.08 (1.85–2.32) µg ml^–1, and at recoveryof consciousness was 1.85 (1.68–2.00) µg ml^–1. Conclusions. This study confirms a synergistic interaction betweenremifentanil and propofol during surgery, whereas the contributionof remifentanil in the absence of stimulation seems limited.In addition, our results suggest that the propofol effect siteconcentration provides a guide to the value at which the patientrecovers consciousness. Br J Anaesth 2003; 90: 623–9     

Comparison of Alaris AEP index and bispectral index during propofol-remifentanil anaesthesia

Background. The Alaris AEP monitor^TM (Alaris, UK, version 1.4)is the first commercially available auditory evoked potential(AEP) monitor designed to estimate the depth of anaesthesia.It generates an ‘Alaris AEP index’ (AAI), whichis a dimensionless number scaled from 100 (awake) to 0. Thisstudy was designed to compare AAI and BIS^TM (Aspect, USA, versionXP) values at different levels of anaesthesia. Methods. Adult female patients were premedicated with diazepam0.15 mg kg^–1 orally on the morning of surgery. Electrodesfor BIS and Alaris AEP monitoring and a headphone to give auditorystimuli were applied as recommended by the manufacturers. Anaesthesiawas induced with remifentanil (0.4 µg kg^–1 min^–1)and a propofol target-controlled infusion (Diprifusor^TM TCI,AstraZeneca, Germany) to obtain a predicted concentration ofinitially 3.5 µg ml^–1. After loss of consciousnessthe patients were given 0.5 mg kg^–1 of atracurium. Aftertracheal intubation, remifentanil was given at 0.2 µgkg^–1 min^–1 and the propofol infusion was adjustedto obtain BIS target values of 30, 40, 50, and 60. AAI and BISvalues were recorded and matched with the predicted propofoleffect-site concentrations. Prediction probability was calculatedfor consciousness vs unconsciousness. Values are mean (SD). Results. Fifty female patients, 53 (15), range 18–78 yr,ASA I or II were studied. Mean values before induction of anaesthesiawere 95 (4), range 99–82 for BIS and 85 (12), range 99–55for AAI. With loss of eyelash reflex both values were significantlyreduced to 64 (13), range 83–39 for BIS (P<0.05) and61 (22), range 99–15 for AAI (P<0.05). The predictionprobability P_K for consciousness vs unconsciousness (i.e. lossof eyelash reflex) was better for BIS (P_K=0.99) than for AAI(P_K=0.79). At a BIS of 30, 40, 50, and 60 the correspondingAAI values were 15 (6), 20 (8), 28 (11), and 40 (16), and thesewere significantly different. Conclusions. During propofol-remifentanil anaesthesia a decreaseof the depth of anaesthesia as indicated by BIS monitoring isaccompanied by corresponding effects shown by the AAI. However,wide variation in the awake values and considerable overlapof AAI values between consciousness and unconsciousness, suggestsfurther improvement of the AAI system is required. Br J Anaesth 2003; 91: 336–40     

Accuracy of the 'Paedfusor' in children undergoing cardiac surgery or catheterization

Background. A prototype paediatric propofol target-controlledinfusion (TCI) system, the ‘Paedfusor’ has beendeveloped. This system incorporates a paediatric pharmacokineticdata set and algorithm specific for children in a Graseby 3500anaesthesia syringe driver. In this study we have evaluatedthe accuracy of the Paedfusor TCI system in children who underwenteither cardiac surgery or cardiac catheterization procedures. Methods. Twenty-nine children aged 1–15 yr were investigated.General anaesthesia was provided using propofol administeredby the Paedfusor system. Accuracy of the system was evaluatedby obtaining up to 9 arterial samples for measurement of propofolconcentration both during anaesthesia and in the recovery period.Measured arterial propofol concentrations were then comparedwith values calculated by the Paedfusor. Results. The predictive indices of median performance error(MDPE), and median absolute performance error (MDAPE) of thePaedfusor system were found to be 4.1% and 9.7%, respectivelyand the median value for wobble was 8.3%. These values are muchbetter than those found with the adult ‘Diprifusor’system. Conclusion. The Paedfusor performance was found to be withinthe accepted limits for use as a TCI system. Br J Anaesth 2003; 91; 507–13