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     

Relationship between bispectral index, electroencephalographic state entropy and effect-site EC50 for propofol at different clinical endpoints

Background. State entropy (SE) is a newly available monitorfor depth of anaesthesia. We investigated whether the relationshipbetween predicted effect-site propofol concentration and bothbispectral index (BIS) and SE values is useful for predictingloss of verbal contact and loss of consciousness during steady-stateconditions. Methods. Twenty unpremedicated patients undergoing electivemajor abdominal surgery were recruited. A target-controlledinfusion of propofol was administered using Schneider's pharmacokineticmodel. The propofol infusion was set at an initial site-effectconcentration of 1.0 µg ml^–1, and increased by 1.0µg ml^–1 steps every 4 min, up to 6.0 µg ml^–1.A 4-min interval was chosen to ensure that steady-state site-effectconcentrations were obtained. Propofol site-effect concentrationsand BIS and SE values were recorded at loss of verbal contact(LVC) and loss of consciousness (LOC). Population values forpredicted effect-site concentrations at the clinical endpointswere estimated and correlated with BIS and SE values. Results. For LVC, the effect-site concentration for 90% of patientswas 1.1 (1.1–3.2) µg ml^–1 and for LOC 2.8(2.8–5.65) µg ml^–1. LVC occurred in 90% ofpatients at a BIS value of 70.2 (70.2–90.2) and an SEvalue of 60.3 (60.3–75.5) and LOC occurred at a BIS valueof 38.2 (38.2–70.4) and an SE value of 42.2 (42.2–60.4). Conclusions. LVC and LOC occurred within a defined range ofpredicted effect-site concentrations. SE had a smaller rangethan BIS and higher correlation with effect-site concentrationand may be more useful than BIS in predicting both LVC and LOC.     

New parameters of skin conductance compared with Bispectral Index monitoring to assess emergence from total intravenous anaesthesia

Background: Arousal after total i.v. anaesthesia (TIVA) has been reportedto be detectable by monitoring the number of fluctuations persecond (NFSC), a parameter of skin conductance (SC). However,compared with monitoring of the bispectral index (BIS^®),the predictive probability of NFSC was significantly lower.The aim of this study was to determine the value of the twonew, not yet published parameters of SC, area under the curve(AUC) methods A and B, for monitoring emergence from TIVA comparedwith monitoring of NFSC and BIS^®. Methods: Twenty-five patients undergoing surgery were investigated. NFSC,AUC A, AUC B, BIS^®, and haemodynamic parameters (mean arterialpressure and heart rate) were recorded simultaneously. The performanceof the monitoring devices in distinguishing between the clinicalstates ‘steady-state anaesthesia’, ‘firstclinical reaction’, and ‘extubation’ werecompared using the method of prediction probability (Pk) calculation. Results: BIS^® showed the best performance in distinguishing between‘steady-state anaesthesia’ vs ‘first reaction’(Pk BIS^® 0.95; NFSC 0.73; AUC A 0.54; AUC B 0.62) and ‘steady-stateanaesthesia’ vs ‘extubation’ (Pk BIS^®0.99; NFSC 0.73; AUC A 0.71; AUC B 0.67). However, the timefrom first BIS^®>60/SC>0 to a first clinical reactionwas significantly shorter for BIS^® (median BIS^® 180s; NFSC 780 s; AUC A 750 s; AUC B 690 s; P < 0.001). Conclusions: AUC A and AUC B did not improve accuracy of SC monitoring inpatients waking after TIVA.     

Performance of entropy and Bispectral Index as measures of anaesthesia effect in children of different ages

Background. Entropy and Bispectral Index^TM (BIS^TM) have beenpromoted as EEG-based anaesthesia depth monitors. The EEG changeswith brain maturation, but there are limited published datadescribing the characteristics of entropy in children, and somedata suggest that BIS is less reliable in young children. Theaim of this study was to compare the performance of entropyas a measure of anaesthetic effect in different age groups.The performance of entropy was compared with BIS. Methods. Fifty-four children receiving a standard sevofluraneanaesthetic for cardiac catheter studies were enrolled. Theentropy and BIS were recorded pre-awakening and at 1.5%, 2%and 2.5% steady-state end-tidal sevoflurane concentrations.For analysis children were divided into four age groups: 0–1yr, 1–2 yr, 2–4 yr and 4–12 yr. Results. The pre-awakening values were obtained in 46 children.The median pre-awakening values for entropy and BIS varied significantlyacross ages with the values being lowest in the 0–1 yrage group (response entropy: 45 vs 84, 87 and 89, P=0.003; stateentropy: 36 vs 78, 74 and 77, P=0.009; BIS: 56 vs 78, 76.5 and72, P=0.02). Values were recorded at all three sevoflurane concentrationsin 48 children. Compared with older groups, the 0–1 yrage group had the least significant difference in BIS and entropywhen compared among different sevoflurane concentrations. Thecalculated sevoflurane concentrations to achieve mid-scale valuesof entropy and BIS were highest in the 1–2 yr age group,lower in the 0–1 yr age group and progressively lowerin the 2–4 and 4–12 yr age groups. Conclusions. For both entropy and BIS the measure of anaestheticeffect was significantly different for children aged <1 yrcompared with older children. There was no difference in performanceof entropy and BIS. Both should be used cautiously in smallchildren.      

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.     

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.     

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     

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.     

Correlation and agreement between bispectral index and state entropy of the electroencephalogram during propofol anaesthesia

Background. Bispectral index (BIS) and state entropy (SE) monitorhypnosis. We evaluated the correlation and the agreement betweenthose parameters during propofol anaesthesia and laryngoscopywith and without muscle relaxation. Methods. A total of 25 patients were anaesthetized with propofol.At steady state (SS: BIS 40–50), they randomly receivedrocuronium (R) or saline (S); 3 min thereafter, a 20 s laryngoscopywas performed. Correlation (regression analysis) and agreement(Bland–Altman analysis) were evaluated before induction(baseline), at loss of eyelash reflex (LER), at SS and duringthe first 3 min after laryngoscopy (L). Results. The correlation coefficient r (95% CI), the mean difference(MD) (95% CI), and the limits of agreement [lower-upper limitsof 95% CI of MD (SD 1.96)] between BIS and SE were as follows.Overall recordings: 0.87 (0.83 to 0.90), 2.5 (1.2 to 3.0), and[–19.5 to 24.6]; Baseline: 0.45 (0.06 to 0.72), 7.6 (6.0to 9.2), and [–2.7 to 17.9]; LER: 0.74 (0.47 to 0.88),8.3 (3.5 to 13.2), and [–22.6 to 39.3]; SS, all patients:0.41 (0.14 to 0.63), 2.0 (–0.5 to 4.6), and [–19.0to 23.3]; SS, Group S: 0.36 (–0.07 to 0.68), 1.9 (–2.5to 6.3), and [–25.0 to 28.8]; SS, Group R: 0.63 (0.32to 0.82), 0.2 (–2.0 to 2.3), and [–14.0 to 14.4];L, all patients: 0.49 (0.32 to 0.63), 0.7 (–1.6 to 3.0),and [–25.6 to 27.1]; L, Group S: 0.41 (0.13 to 0.63),2.3 (–2.4 to 7.1), and [–36.7 to 41.3]; L, GroupR: 0.72 (0.56 to 0.83), –0.6 (–2.2 to 1.0), and[–14.3 to 13.1]. The correlation was good except for SSin Group S. The MD was significantly different from 0 for overallrecordings, during baseline and LER, but not for the other conditions.The agreement was poor except for baseline, and SS and L inGroup R. Conclusions. BIS and SE are globally well correlated. In contrast,agreement is poor as differences of more than 20 units are frequentlyobserved, except for awake and paralysed patients.     

Bispectral index, serum drug concentrations and emergence associated with individually adjusted target-controlled infusions of remifentanil and propofol for laparoscopic surgery

Background. Target-controlled infusions (TCI) are used to simplifyadministration and increase precision of i.v. drugs during generalanaesthesia. However, there is a limited relationship betweenpreset targets and measured concentrations of drugs and betweenmeasured concentrations and measures of brain function, suchas the bispectral index (BIS). Methods. We set out to evaluate the performance of TCI devicesfor propofol (Diprifusor^®) and remifentanil (Remifusor,prototype), during laparoscopic cholecystectomy in 21 patients.We also checked if there was any correlation between serum concentrationsof propofol and BIS during individually adjusted anaesthesia. Results. The Diprifusor and Remifusor had a median absoluteperformance error of 60% and 25% respectively. Propofol concentrationswere underpredicted by a median of 60%, and remifentanil concentrationswere slightly overpredicted by a median of 7%. When anaesthesiawas adjusted to keep BIS values between 45 and 60, no correlationexisted between measured concentrations of propofol and thecorresponding BIS values, although both BIS and serum propofolconcentration discriminated well between the awake and asleepstates. Emergence was rapid and uneventful in all patients.Female patients had a more rapid emergence than male patients(6.6 and 11.6 min respectively). Conclusions. TCI devices for remifentanil and propofol resultin large variation in measured serum concentrations. The lackof correlation between BIS and serum concentrations of propofoladds to the debate about whether BIS measures hypnosis as agraded state during surgery. This study confirms that womenwake up faster than men, but provides no explanation for thisrepeatedly shown difference. Br J Anaesth 2003; 91: 773–80     

Skin conductance monitoring compared with Bispectral Index to assess emergence from total i.v. anaesthesia using propofol and remifentanil

Background. Arousal after sevoflurane anaesthesia has been detectableby monitoring changes in skin conductance (SC) with similaraccuracy as monitoring Bispectral Index (BIS^®). As SC monitoringdetects changes in sympathetic tone, the measurements mightbe confounded by the sympatholytic properties of propofol, acomponent of total i.v. anaesthesia (TIVA). Therefore in thisstudy, monitoring of SC during emergence from TIVA was comparedwith the monitoring of BIS^®. Methods. Twenty-five patients undergoing plastic surgery wereinvestigated. The number of fluctuations of SC per second (NFSC),BIS^® and haemodynamic variables [systolic blood pressure(SBP) and heart rate (HR)] were recorded simultaneously. Theperformance of the monitoring devices in distinguishing betweenthe clinical states ‘steady-state anaesthesia’,‘first clinical reaction’ and ‘extubation’were compared using the method of prediction probability (Pk)calculation. Results. BIS^® showed the best performance in distinguishingbetween ‘steady-state anaesthesia’ and ‘firstreaction’ (Pk BIS^® 0.99 vs NFSC 0.80; P<0.01),and ‘steady-state anaesthesia’ and ‘extubation’(Pk BIS^® 1.00 vs NFSC 0.91; P<0.05); the time from firstchange of BIS^® or NFSC to a first clinical reaction wassignificantly longer for NFSC (median BIS^® 135 s vs NFSC191 s; P<0.05). BIS^® and NFSC performed better in distinguishingbetween the investigated clinical states than SBP and HR. Conclusions. In this study, BIS^® was found to predict arousalwith a higher probability but slower response times than NFSCin patients waking after TIVA.     

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 (     

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     

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.     

Effect of an intubation dose of rocuronium on Spectral Entropy and Bispectral Index responses to laryngoscopy during propofol anaesthesia

Background. The spectral entropy of the electroencephalogramhas been proposed to monitor the depth of anaesthesia. StateEntropy (SE) reflects the level of hypnosis. Response Entropy(RE), computed from electroencephalogram and facial muscle activity,reflects the response to nociceptive stimulation. We evaluatedthe effect of rocuronium on Bispectral Index^TM (BIS) and entropyresponses to laryngoscopy. Methods. A total of 25 patients were anaesthetized with propofolusing a target-controlled infusion. At steady state, they randomlyreceived 0.6 mg kg^–1 rocuronium (R) or saline (S). After3 min, a 20 s laryngoscopy was applied. BIS, RE and SE wererecorded continuously and averaged over 1 min during baseline,at steady state, 2 min after R or S administration (R/S+2) and0, 1, 2 and 3 min after laryngoscopy (L0, L1, L2, L3). Results. At R/S+2, the RE–SE gradient was higher in GroupS than in Group R. Laryngoscopy provoked an increase in BIS,RE and SE. Comparing R/S+2 and L0 values in Groups R and S,BIS increased from 43 (6) to 49 (8) and 42 (9) to 51 (15), SEincreased from 43 (7) to 50 (8) and 41 (10) to 55 (12), andRE increased from 46 (8) to 54 (9) and 47 (12) to 66 (15), respectively.BIS and SE did not differ between groups. At L0, RE and RE–SEwere higher in Group S [66 (15) and 11 (4), respectively] thanin Group R [54 (9) and 4 (2), respectively]. Conclusions. Rocuronium alters the RE–SE gradient andthe RE and RE–SE responses to laryngoscopy. Muscle relaxationmay confound interpretation of entropy monitoring.     

Effects of intramuscular administration of lidocaine or bupivacaine on induction and maintenance doses of propofol evaluated by bispectral index

Background. Interest in combining local and general anaesthesiahas lead to studies investigating possible interactions. Ina prospective, randomized, double-blind study, we tested whetherlocal anaesthetics administered i.m. potentiate the hypnoticeffect of propofol. Methods. Sixty patients (three groups, n=20) undergoing lowerabdominal surgery with total i.v. propofol anaesthesia wereinvestigated. Patients in Group B received i.m. bupivacaine(5 mg ml^–1) 1 mg kg^–1, patients in Group Lreceived i.m. lidocaine (100 mg ml^–1) 2 mg kg^–1and patients in Group C received i.m. saline 5 ml beforeoperation. Hypnosis was measured with bispectral index (BIS). Results. The induction (BIS <45), and the maintenance dosesof propofol (BIS between 40 and 50) were significantly lessin Group B and Group L compared with the control group. Inductiondoses were 1.58 (SD 0.39), 1.56 (0.24) and 2.03 (0.33) mg kg^–1respectively; P<0.0001. Maintenance doses were 6.33 (2.06),7.08 (1.23) and 9.95 (2.02) mg kg^–1 respectively in thefirst hour; P<0.0001. Groups B and L were associated withan attenuated haemodynamic response to both induction and intubation. Conclusion. I.M. administered local anaesthetics are associatedwith a decrease in both the induction and maintenance dosesof propofol during total i.v. anaesthesia and a reduction inhaemodynamic responses. Br J Anaesth 2002; 89: 849–52     

Multi-level approach to anaesthetic effects produced by sevoflurane or propofol in humans: 1. BIS and blink reflex

Background: The relative roles of forebrain and brainstem in producing adequateanaesthesia are unclear. Methods: We simultaneously analysed the effects of sevoflurane (GroupS; n = 18) or propofol (Group P; n = 29) on the bispectral index(BIS) and the first component of the blink reflex (R1). Thedose of anaesthetic agent was increased until loss of blinkreflex. After discontinuation and reappearance of blink reflexactivity, the amount was increased again. The area under curveR1 (area-R1) of the electromyogram of the orbicularis oculimuscle after electrical stimulation of the supraorbital nervewas measured. Using a sigmoid E_max model and a first-order rateconstant k_e0, we characterized the dose–response relationshipsfor BIS and area-R1. Results: Concentration-dependent depression of BIS and area-R1 was adequatelymodelled. The concentration that causes an effect midway betweenminimum and maximum (EC₅₀) for area-R1 was smaller than EC₅₀for BIS in both groups [0.34 (0.19) vs 1.29 (0.19) vol% and1.78 (0.65) vs 2.69 (0.67) µg ml^–1; mean (SD)].At doses of sevoflurane and propofol with equivalent depressionof BIS, sevoflurane depressed area-R1 more than propofol. Thek_e0 for area-R1 was about half that for BIS in both groups:0.24 (0.19–0.29) vs 0.48 (0.38–0.60) min^–1for Group S; 0.28 (0.23–0.34) vs 0.46 (0.40–0.54)min^–1 for Group P, geometric mean (95% CI). Conclusions: The blink reflex (brainstem function) is more sensitive to sevofluraneor propofol than BIS (forebrain function). Sevoflurane suppressesthe blink reflex more than propofol. Different k_e0s for blinkreflex vs BIS indicate different effect sites.     

Multi-level approach to anaesthetic effects produced by sevoflurane or propofol in humans: 2. BIS and tetanic stimulus-induced withdrawal reflex

Background: General anaesthesia could be assessed at two sites: corticalstructures and the spinal cord. However, the practicalitiesof measurement at these two sites differ substantially. Methods: We simultaneously analysed effects of sevoflurane (Group S;n = 16) or propofol (Group P; n = 17) on bispectral index (BIS)and the tetanic stimulus-induced withdrawal reflex (TIWR). TIWRwas quantified by the area under the curve of the electromyogramof the biceps femoris muscle after electrical stimulation ofthe sural nerve. After loss of consciousness, TIWR was evokedonce per minute. The anaesthetic was increased until TIWR disappeared.After discontinuation of the anaesthetic and reappearance ofTIWR, the amount of anaesthetic was increased again. Using asigmoid E_max model and a first-order rate constant k_e0, we characterizedthe dose–response relationships for BIS and TIWR. Results: Concentration-dependent depression of TIWR was reasonably wellmodelled for sevoflurane, but poorly for propofol. TIWR wascompletely suppressed by sevoflurane, but not propofol. Sevofluranereduced TIWR to 5 mV ms (very weak movement) at 1.68 vol% end-expiredconcentration [ minimum alveolar concentration (MAC value)].The k_e0s for TIWR were smaller than those for BIS: 0.25 (0.16–0.39)vs 0.41 (0.33–0.51) min^–1 for Group S; 0.25 (0.22–0.30)vs 0.34 (0.29–0.40) min^–1 for Group P [geometricmean (95% CI)]. Conclusions: High concentrations of sevoflurane depress TIWR more than propofol.With propofol, we frequently observed a paradoxical behaviourof muscles of the lower leg. TIWR lags behind BIS, indicatingdifferent effect sites for two intended anaesthetic effects:unresponsiveness to noxious stimulation and unconsciousness.     

Ketamine increases the frequency of electroencephalographic bicoherence peak on the alpha spindle area induced with propofol

Background: The reticular and thalamocortical system is known to play aprominent role in spindle wave activity, and the spindle waveis related to the sedative effects of anaesthetics. Recently,bispectral analysis of the EEG has been developed as a bettermethod to indicate nonlinear regulation including the thalamocorticalsystem linking to the cortical area. In the present study, inorder to explore the interference of ketamine with the nonlinearregulation of the sub-cortical system, we examined the effectof ketamine on spindle waves through the bispectral analysis. Methods: The study included 21 patients. Anaesthesia was induced andmaintained using a propofol-TCI system (target-controlled infusion,with target concentration 3.5 µg ml^–1). An A-2000BIS monitor was used and the raw EEG signals were collectedvia an RS232 interface on a personal computer. Bicoherence,the normalized bispectrum, and power spectrum were analysedbefore and after i.v. administration of 1 mg kg^–1 racemicketamine. Results: Propofol caused peaks in both power and bicoherence spectra,with average frequencies of 10.6 (SD 0.9) Hz and 10.7 (1.0)Hz, respectively. The addition of ketamine significantly shiftedeach peak to frequencies of 14.4 (1.4) Hz and 13.6 (1.5) Hz,respectively [P < 0.05, mean (SD)]. Conclusions: Ketamine shifted the peaks of bicoherence induced by propofolto higher frequencies. This suggests that ketamine changes the spindle rhythms through the modulation of the nonlinear sub-corticalreverberating network.     

BIS guided sedation with propofol during spinal anaesthesia: influence of anaesthetic level on sedation requirement

Background. In this prospective, clinical study we tested thehypothesis whether two different doses of spinal administeredbupivacaine and accordingly, two different levels of spinalanaesthesia can affect the dose requirement of propofol duringBIS guided sedation. Methods. Fifty women undergoing vaginal hysterectomy (high spinalgroup, HS) or transvaginal tape (TVT) procedure for urinaryincontinence (low spinal group, LS) under spinal anaesthesiawere enrolled to the study. In group HS, 17.5 mg and in groupLS, 7.5 mg of hyperbaric bupivacaine were given intrathecally.After 15 min to obtain the appropriate level of spinal anaesthesia,propofol infusion was started at a rate of 100 µg kg^–1min^–1 to reach a BIS level of less than 75 (onset time),and titrated to maintain the BIS value between 65 and 75. Propofolinfusion was stopped 45 min after placing the spinal to measurethe time to reach a BIS level of 90 (recovery time). Results. Median anaesthetic level was T3 (T1–4) in theHS group and T10 (T9-11) in the LS group. In both the HS andthe LS groups, onset time was 226 (47) vs 273 (48) s (P=0.001),recovery time was 234 (47) vs 202 (56) s (P=0.03), total doseof propofol was 2.17 (0.43) vs 3.14 (0.56) mg kg^–1 (P<0.001),respectively. Conclusion. A high spinal block obtained with hyperbaric bupivacaine17.5 mg was associated with a faster onset, delayed recoveryand lower doses of propofol sedation compared with a low spinalblock with 7.5 mg of the same drug.