Cerebral haemodynamic changes during propofol-remifentanil or sevoflurane anaesthesia: transcranial Doppler study under bispectral index monitoring

Background. Sevoflurane or propofol–remifentanil-basedanaesthetic regimens represent modern techniques for neurosurgicalanaesthesia. Nevertheless, there are potential differences relatedto their activity on the cerebrovascular system. The magnitudeof such difference is not completely known. Methods. In total 40 patients, treated for spinal or maxillo-facialdisorders, were randomly allocated to either i.v. propofol–remifentanilor inhalational sevoflurane anaesthesia. Transcranial Dopplerwas used to assess changes in cerebral blood flow velocity,carbon dioxide reactivity, cerebral autoregulation and the bispectralindex to assess the depth of anaesthesia. Results. Time-averaged mean flow velocity (MFV) was significantlyreduced after induction of anaesthesia in both sevoflurane andpropofol–remifentanil groups (P<0.001). At deeper levelsof anaesthesia, MFV increased in the sevoflurane group, suggestingan uncoupling flow/metabolism, whereas it was further reducedin the propofol–remifentanil group (P<0.001). Indicesof cerebral autoregulation were reduced in patients with high-dosesevoflurane whereas autoregulation was preserved in patientsanaesthetized with propofol–remifentanil (P<0.001).Higher CO₂ concentrations impaired cerebral autoregulation inthe sevoflurane group but not in patients anaesthetized withpropofol–remifentanil. Conclusions. Propofol–remifentanil anaesthesia induceda dose-dependent low-flow state with preserved cerebral autoregulation,whereas sevoflurane at high doses provided a certain degreeof luxury perfusion.     

A comparison of bispectral index and entropy monitoring, in patients undergoing embolization of cerebral artery aneurysms after subarachnoid haemorrhage

Background. Processed EEG monitoring of anaesthetic depth couldbe useful in patients receiving general anaesthesia followingsubarachnoid haemorrhage. We conducted an observational studycomparing performance characteristics of bispectral index (BIS)and entropy monitoring systems in these patients. Methods. Thirty-one patients of the World Federation of Neurosurgeonsgrades 1 and 2, undergoing embolization of cerebral artery aneurysmsfollowing acute subarachnoid haemorrhage, were recruited tohave both BIS and entropy monitoring during general anaesthesia.BIS and entropy indices were matched to clinical indicatorsof anaesthetic depth. Anaesthetists were blinded to the anaestheticdepth monitoring indices. Analysis of data from monitoring devicesallowed calculation of prediction probability (P_K) constants,and receiver operating characteristic (ROC) analysis to be performed. Results. BIS and entropy [response entropy (RE), state entropy(SE)] performed well in their ability to show concordance withclinically observed anaesthetic depth. P_K values were generallyhigh (BIS 0.966–0.784, RE 0.934–0.663, SE 0.857–0.701)for both forms of monitoring. ROC curve analysis shows a highsensitivity and specificity for all monitoring indices whenused to detect the presence or absence of eyelash reflex. Areaunder curve for BIS, RE and SE to detect the absence or presenceof eyelash reflex was 0.932, 0.888 and 0.887, respectively.RE provides earlier warning of return of eyelash reflex thanBIS. Conclusion. BIS and entropy monitoring perform well in patientswho receive general anaesthesia after good grade subarachnoidhaemorrhage.     

Clonidine decreases propofol requirements during anaesthesia: effect on bispectral index

Assessment of the effect of clonidine on depth of anaesthesiais difficult because clonidine combines analgesic, sedativeand direct haemodynamic effects. We thus evaluated the influenceof clonidine on the bispectral index (BIS) and its potentialdose-sparing effect on propofol. After induction of anaesthesiawith target-controlled infusion of propofol and obtaining anunchanged bispectral index (pre-BIS), clonidine 4 µg kg^–1or placebo was administered randomly to 50 patients in a double-blindmanner. Subsequently, if there was a decrease in BIS we reducedthe target concentration of propofol until pre-BIS was reached.The pre-BIS was maintained and a remifentanil infusion was addedduring surgery. The courses of the BIS, heart rate and bloodpressure were recorded and the total amounts of intra-operativepropofol and remifentanil were determined. Assessment of implicitmemory during anaesthesia was performed with an auditory implicitmemory test consisting of item sequences. Administration ofclonidine resulted in a decrease in the BIS from 45 (SD 4) to40 (6) (P<0.001), which allowed a reduction of propofol targetconcentration from 3.3 (0.6) to 2.7 (0.7) µg ml^–1(P<0.001) and measured propofol concentration from 2.9 (0.6)to 2.5 (0.7) µg ml^–1 (P=0.009) in order tomaintain the pre-BIS value. During subsequent surgery, propofolrequirements were reduced by 20% (P=0.002) in the clonidinegroup and a similar amount of remifentanil was used in eachgroup. The increase in anaesthetic depth given by clonidinecan therefore be measured with bispectral EEG analysis and allowsreduction of the propofol dose to achieve a specific depth ofanaesthesia. Br J Anaesth 2001; 86: 627–32     

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)^TM for automatic control of propofol anaesthesia, usinga proportional-integral-differential control algorithm. As controlwas less than optimal in some patients, we revised the constantsof the control algorithm. The aim of the current study was tomeasure the performance of the revised system in patients undergoingminor surgery under propofol and remifentanil anaesthesia. Methods. Twenty adult patients scheduled for body surface surgerywere enrolled. Anaesthesia was manually induced with target-controlledinfusions (TCI) of propofol and remifentanil. After the startof surgery, when anaesthesia was clinically adequate, automaticcontrol of the propofol TCI was commenced using the revisedclosed-loop system. For patients 11–20, effect-site steeringwas also incorporated into the closed-loop control algorithm.Adequacy of anaesthesia during closed-loop control was assessedclinically, and by calculating the median performance error(MDPE), the median absolute performance error (MDAPE) and themean offset of the control variable. Results. The system provided adequate operating conditions andstable cardiovascular values in all patients during closed-loopcontrol. The mean MDPE and MDAPE were –0.42% and 5.63%,respectively. Mean offset of the BIS^TM from setpoint was –0.2.No patients reported awareness or recall of intraoperative events. Conclusions. The system was able to provide clinically adequateanaesthesia in all patients, with better accuracy of controlthan in the previous study. There was a tendency for more accuratecontrol in those patients in whom the control algorithm incorporatedeffect-site steering. Br J Anaesth 2003; 90: 737–41     

Comparative evaluation of the cerebral state index and the bispectral index during target-controlled infusion of propofol

Background. Cerebral state index (CSI) has recently been introducedas an intra-operative monitor of anaesthetic depth. We comparedthe performance of the CSI to the bispectral index (BIS) inmeasuring depth of anaesthesia during target-controlled infusion(TCI) of propofol. Methods. Twenty Chinese patients undergoing general anaesthesiawere recruited. CSI and BIS, and predicted effect-site concentrationof propofol were recorded. The level of sedation was testedby Modified Observer's Assessment of Alertness/Sedation Scale(MOAAS) every 20 s during stepwise increase (TCI, 0.5 µgml^–1) of propofol. The loss of verbal contact (LVC) andloss of response (LOR) were defined by MOAAS values of 2–3and less than 2, respectively. Baseline variability and theprediction probability (P_K) were calculated for the BIS andCSI. The values of BIS₀₅ and CSI₀₅, BIS₅₀ and CSI₅₀, BIS₉₅ andCSI₉₅ were calculated at each end-point (LVC and LOR). Results. Baseline variability of CSI was more than that of BIS.Both CSI and BIS showed a high prediction probability for thesteps awake vs LVC, awake vs LOR, and LVC vs LOR, and good correlationswith MOAAS values. Conclusion. Despite larger baseline variation, CSI performedas well as BIS in terms of P_K values and correlations with stepchanges in sedation.     

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.     

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.      

Heart rate variability does not discriminate between different levels of haemodynamic responsiveness during surgical anaesthesia

Background: Hypnotic depth but not haemodynamic responsiveness is measuredwith EEG-based monitors. In this study we compared heart ratevariability (HRV) in unstimulated patients and stimulation-inducedHRV at different levels of anaesthesia. Methods: A total of 95 ASA I or II patients were randomly assigned tofive groups (Group 1: BIS 45(5), remifentanil 1 ng ml^–1;Group 2: BIS 45(5), remifentanil 2 ng ml^–1; Group 3: BIS45(5), remifentanil 4 ng ml^–1; Group 4: BIS 30(5), remifentanil2 ng ml^–1; Group 5: BIS 60(5), remifentanil 2 ng ml^–1).A time- and frequency-domain analysis of the RR interval (RRI)from the electrocardiogram was performed. HRV before induction,before and after a 5 s tetanic stimulus of the ulnar nerve,and before and after tracheal intubation was compared betweengroups, between stimuli, and between responders to intubation[systolic arterial pressure (SAP) increase >20 mm Hg, a maximalheart rate (HR) after intubation >90 min^–1 or both]and non-responders (ANOVA). Results: Induction of anaesthesia significantly lowered HR and HRV. MeanRRI before stimulation was higher in G3 than in G1, G2, andG4 (P < 0.001), whereas the other HRV parameters were similar.Intubation induced a greater HRV response than tetanic stimulation.The mean RRI after intubation was lower in G3 compared withthe other groups and the SD of the RRI after tetanic stimulationwas lower in G3 compared with G5. Otherwise, unstimulated HRVand stimulation-induced HRV were similar in responders and non-responders. Conclusion: HRV parameters discriminate between awake and general anaesthesia,are different after tracheal intubation and a 5 s ulnar nervestimulation, but do not discriminate between different levelsof haemodynamic responsiveness during surgical anaesthesia.     

Bispectral index is a topographically dependent variable in patients receiving propofol anaesthesia

Background. As very strong agreement has been reported betweenbispectral index (BIS) values measured from the occipital andfrontal skull areas, we compared BIS values measured from centraland parietal areas with those from frontal area to investigatewhether BIS is really a topographically dependent or topographicallyindependent variable. Methods. Twenty patients, ASA I–II, non-obese, aged 18–62yr and with no neurological disorders were enrolled. Based onthe 10–20 international landmarks, five silver dome electrodeswere positioned: F7, C3, P7, Cz (common reference) and Fp1 (ground).Using frontal (F7–Cz), central (C3–Cz) and parietal(P7–Cz) electrode montages, the corresponding BIS valueswere simultaneously recorded with an Aspect A-1000 monitor (softwarev3.12). The BIS values were recorded at the propofol concentrationallowing laryngeal mask insertion, which was maintained duringthe 10 min data collection period in absence of additional externalstimuli. Data were analysed using the Kruskall–Wallis,Wilcoxon paired sign with Bonferroni correction, Bland–Altmanand linear correlation tests. Results. At the predicted effect target propofol concentration4–8 µg ml^–1, the 10 min mean BIS (median [min–max])were 32 [20–44], 46 [28–68] and 58 [41–72]for the frontal, central and parietal leads, respectively. Differencesbetween these BIS recordings were statistically significant(P<0.0001, Kruskall–Wallis; P<0.005, Wilcoxon pairedsign test). Conclusions. The present results provide evidence that BIS indexis a topographically dependent variable in patients receivingpropofol anaesthesia.     

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.     

Variation of bispectral index under TIVA with propofol in a paediatric population

BACKGROUND: In this prospective observational study, we aim to explore the relationship between age and bispectral index (BIS) values at different plasma concentrations of propofol. METHODS: Fifty children aged from 3 to 15 yr were included. Anaesthesia was induced using a target-controlled infusion of propofol with the Kataria pharmacokinetic model together with a bolus of remifentanil followed by a continuous infusion rate at 0.2 microg kg(-1) min(-1). Target plasma propofol concentration was initially stabilized to 6 microg ml(-1) and continued for 6 min. The target was then decreased and stabilized to 4 microg ml(-1) and then to 2 microg ml(-1). BIS values, plasma propofol concentration, and EEG were continuously recorded. In order to explore the relationship between variations in propofol concentration and the EEG bispectrum, we used a multiple correspondence analysis (MCA). Results are shown in median (range). RESULTS: We found no statistical difference between BIS values with propofol 6 microg ml(-1) [23 (12-40)] and 4 microg ml(-1) [28 (9-67)]. At 2 microg ml(-1), BIS was significantly different [52 (24-71)], but a significant correlation between the age of children and BIS values was found (r2=0.66; P<0.01). There was little change in children's position between 6 and 4 microg ml(-1) in the structure model of the MCA. From 4 to 2 microg ml(-1), the position of children moved only on axis 2. CONCLUSIONS: These results showed the difficulty to interpret BIS values because of the absence of significant change for higher plasma propofol concentration variation or because of the link with age for the lower plasma concentration.     

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 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     

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.     

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     

Assessment of surgical stress during general anaesthesia

Background: Inadequate analgesia during general anaesthesia may presentas undesirable haemodynamic responses. No objective measuresof the adequacy of analgesia exist. We aimed at developing asimple numerical measure of the level of surgical stress inan anaesthetized patient. Methods: Sixty and 12 female patients were included in the developmentand validation data sets, respectively. All patients had electivesurgery with propofol–remifentanil target controlled anaesthesia.Finger photoplethysmography and electrocardiography waveformswere recorded throughout anaesthesia and various waveform parameterswere extracted off-line. Total surgical stress (TSS) for a patientwas estimated based on stimulus intensity and remifentanil concentration.The surgical stress index (SSI) was developed to correlate withthe TSS estimate in the development data set. The performanceof SSI was validated within the validation data set during andbefore surgery, especially at skin incision and during changesof the predicted remifentanil effect-site concentration. Results: SSI was computed as a combination of normalized heart beat interval(HBI_norm) and plethysmographic pulse wave amplitude (PPGA_norm):SSI = 100–(0.7*PPGA_norm+0.3*HBI_norm). SSI increased atskin incision and stayed higher during surgery than before surgery;SSI responded to remifentanil concentration changes and washigher at the lower concentrations of remifentanil. Conclusions: SSI reacts to surgical nociceptive stimuli and analgesic drugconcentration changes during propofol–remifentanil anaesthesia.Further validation studies of SSI are needed to elucidate itsusefulness during other anaesthetic and surgical conditions.     

Early recovery after remifentanil-pronounced compared with propofol-pronounced total intravenous anaesthesia for short painful procedures

Background. We compared recovery from high-dose propofol/low-doseremifentanil (‘propofol-pronounced’) compared withhigh-dose remifentanil/low-dose propofol (‘remifentanil-pronounced’)anaesthesia. Methods. Adult patients having panendoscopy, microlaryngoscopy,or tonsillectomy were randomly assigned to receive either propofol-pronounced(propofol 100 µg kg^–1 min^–1; remifentanil0.15 µg kg^–1 min^–1) or remifentanil-pronounced(propofol 50 µg kg^–1 min^–1; remifentanil 0.45µg kg^–1 min^–1) anaesthesia. In both groups,the procedure was started with remifentanil 0.4 µg kg^–1,propofol 2 mg kg^–1, and mivacurium 0.2 mg kg^–1.Cardiovascular measurements and EEG bispectral index (BIS) wererecorded. To maintain comparable anaesthetic depth, additionalpropofol (0.5 mg kg^–1) was given if BIS values were greaterthan 55 and remifentanil (0.4 µg kg^–1) if heartrate or arterial pressure was greater than 110% of pre-anaestheticvalues. Results. Patient and surgical characteristics, cardiovascularmeasurements, and BIS values were similar in both groups. Therewere no differences in recovery times between the groups (timeto extubation: 12.7 (4.5) vs 12.0 (3.6) min, readiness for transferto the recovery ward: 14.4 (4.4) vs. 13.7 (3.6) min, mean (SD)). Conclusions. In patients having short painful surgery, lesspropofol does not give faster recovery as long as the same anaestheticlevel (as indicated by BIS and clinical signs) is maintainedby more remifentanil. However, recovery times were less variablefollowing remifentanil-pronounced anaesthesia suggesting a morepredictable recovery. Br J Anaesth 2003; 91: 580–2     

Relationship between bispectral index,auditory evoked potential index and effect-site EC50 for propofol at two clinical end-points

Background. Many anaesthetists are deterred from using totali.v. anaesthesia because of uncertainty over the concentrationof propofol required to prevent awareness. We predicted bloodand effect-site concentrations of propofol at two clinical end-points:loss of consciousness and no response to a painful stimulus. Methods. Forty unpremedicated Caucasian patients were anaesthetizedwith i.v. propofol delivered by a Diprifusor target-controlledinfusion (TCI). Bispectral index (BIS) and auditory evoked potentialindex (AEPex) were measured and blood and effect-site propofolconcentrations were predicted. Logistic regression was usedto estimate population values for predicted blood and effect-sitepropofol concentrations at the clinical end-points and to correlatethese with BIS and AEPex. Results. The effect-site EC₅₀ at loss of consciousness was 2.8 µm ml^–1with an EC₀₅ and an EC₉₅ of 1.5 and 4.1 µm ml^–1,respectively. The predicted EC₅₀ when there was no responseto a tetanic stimulus was 5.2 µm ml^–1 withan EC₀₅ and an EC₉₅ of 3.1 and 7.2 µm ml^–1,respectively. Conclusions. Unconsciousness and lack of response to a painfulstimulus occur within a defined range of effect-site concentrations,predicted by Diprifusor TCI software. Br J Anaesth 2003; 90: 127–31     

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     

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).