Anaesthesia for carotid endarterectomy: comparison of hypnotic- and opioid-based techniques

Background. Although the synergistic interaction between hypnoticsand opioids for total i.v. anaesthesia has been repeatedly demonstrated,questions about different dose combinations of hypnotics andopioids remain. The optimal combination would be based on maximalsynergy, using the lowest dose of both drugs and having thelowest incidence of side-effects. Methods. The major goal of this prospective randomized studywas to compare two different dose combinations of propofol andremifentanil (both administered by target controlled infusion(TCI)) in respect of haemodynamics during surgery and recovery,and the need for cardiovascular treatment in the recovery room.A secondary goal was to compare pain scores (VAS) and morphineconsumption in the recovery room. Anaesthesia was induced inboth groups using TCI propofol, adjusted to obtain a bispectralindex score (BIS) value between 40 and 60. TCI for remifentanilcommenced at an initial effect-site concentration of 0.5 ng ml^–1,and was adjusted according to haemodynamics. Patients were dividedinto one of two groups during anaesthesia: (i) Group H, hypnoticanaesthesia (n=23), propofol effect-site concentration maintainedat 2.4 µg ml^–1; and (ii) Group O, opioidanaesthesia (n=23), propofol effect-site concentration maintainedat 1.2 µg ml^–1. In both groups, remifentanileffect-site concentration was adjusted according to haemodynamicsand changes in BIS value. Results. In Group O, more episodes of intraoperative hypotension(P<0.02) and hypertension (P<0.01), and fewer episodesof tachycardia were observed. More patients in Group O requirednicardipine administration for postoperative hypertension (8patients in Group H vs 15 patients in Group O, P<0.04). Duringrecovery, morphine titration was necessary in     

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     

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     

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 the cough reflex after propofol anaesthesia for colonoscopy

Background. Dysfunction of the cough reflex as a result of thelingering effects of anaesthetics may lead to aspiration pneumoniaor retained secretions after general anaesthesia. It is unknownwhether low concentrations of propofol alter the cough reflexin the early period after anaesthesia. The objective of thisstudy was to investigate the effect of low concentrations ofpropofol on the cough reflex sensitivity as assessed by thecough reflex threshold to an inhaled irritant. Methods. Fifteen, ASA I–II, non-smoking patients undergoingelective colonoscopy were studied. Anaesthesia was induced andmaintained with a blood target-controlled propofol infusion.Cough reflex threshold was measured with citric acid. Increasingconcentrations of nebulized citric acid (2.5, 5, 10, 20, 40,80, 160, 320, and 640 mg ml^–1) were delivered during inspirationuntil a cough was evoked. The citric acid concentration elicitingone cough (C1) was defined as the cough reflex threshold. C1was log transformed for statistical analysis (Log C1). Log C1was measured before anaesthesia and during the recovery periodwith estimated decreasing propofol concentrations of 1.2, 0.9,0.6, and 0.3 µg ml^–1. Results. Log C1 (median; interquartile range) measured withpropofol concentrations of 1.2, 0.9, 0.6, 0.3, and 0 µgml^–1 were 1.9 (0.6), 1.9 (1.0), 1.9 (1.1), 1.9 (0.6),and 1.9 (0.7) mg ml^–1 (NS), respectively. However, lightsedation was observed with propofol concentrations of 1.2 and0.9 µg ml^–1. Conclusion. This study indicates that residual sedation afterpropofol anaesthesia for colonoscopy does not adversely affectthe cough reflex.     

Sevoflurane and propofol decrease intraocular pressure equally during non-ophthalmic surgery and recovery

Background. To provide good control of intraocular pressure(IOP) during anaesthesia and surgery, we conducted a study comparingthe effects on IOP during maintenance and recovery of sevofluranevs propofol anaesthesia in 33 patients (ASA I–II) undergoingelective non- ophthalmic surgery. Methods. Anaesthesia was induced with propofol 2 mg kg^–1,fentanyl 2 µg kg^–1 and vecuronium 0.1 mg kg^–1.Patients were allocated randomly to receive either propofol4–8 mg kg^–1 h^–1 (group P; n=16)or 1.5–2.5 vol% sevoflurane (group S; n=17) for maintenanceof anaesthesia. Fentanyl 2–4 µg kg^–1was added if necessary. The lungs were ventilated with 50% airin oxygen. Blood pressure, heart rate, oxygen saturation andend-tidal carbon dioxide were measured before and throughoutanaesthesia and in the recovery room. IOP was determined withapplanation tonometry (Perkins) by one ophthalmologist blindedto the anaesthetic technique. Results. There was a significant decrease in IOP after inductionand during maintenance of anaesthesia in both groups. No significantdifferences in IOP between the two groups was found. Conclusion. Sevoflurane maintains the IOP at an equally reducedlevel compared with propofol. Br J Anaesth 2002; 89: 764–6     

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     

Respiratory response to skin incision during anaesthesia with infusions of propofol and alfentanil

Background. The ventilatory response to skin incision duringanaesthesia with enflurane is an increase in tidal volume withouta change in frequency. As opioids affect respiratory frequencyand also affect the processing of pain, we investigated if thebreathing response to a painful stimulus could be differentduring anaesthesia using opioids. Methods. We studied 12 patients during anaesthesia with target-controlledinfusions of propofol (plasma target concentration 4–6 µg ml^–1)and alfentanil (plasma target concentration 40–60 ng ml^–1),having varicose vein surgery. Results. After the initial skin incision, tidal volume increasedpromptly by 17 (4, 81)% (median, quartile values) (P<0.01).Respiratory frequency changed variably with no significant changeoverall [median change 2 (–8, +50)%]. The duration ofinspiration was virtually unaltered, and the duration of expirationdecreased gradually by 5 (–7, 32)%. Patients who showedmore response also showed more change in tidal volume, so thatthere was a significant relationship between increased inspiratoryflow rate and reduced expiratory time (P<0.05). Conclusions. During opioid anaesthesia, the mechanism of ventilatoryincrease after stimulation involves changes in both drive andtiming of breathing. This pattern of response does not resemblethe changes seen during anaesthesia with potent volatile agents. Br J Anaesth 2002; 88: 649–52     

Effect of clonidine pre-medication on propofol requirements during lower extremity vascular surgery: a randomized controlled trial

Background. Pre-medication with clonidine reduces the requirementfor volatile agents during general anaesthesia. This may alsobe true for anaesthesia with propofol, but the amount of dosereduction has not been measured. Because clonidine also affectscardiac output and thus regional blood flow it could alter thepharmacokinetics of propofol. This randomized, double-blindplacebo-controlled trial aimed to study the effect of clonidinepre-medication on dose requirement for propofol during lowerextremity vascular surgery using the bispectral index (BIS)as a measure of anaesthetic depth. Methods. After oral pre-medication with either clonidine 3 µgkg^–1 or placebo, 39 subjects had lower limb vascular surgeryusing propofol infusion for anaesthesia. Anaesthetic depth wasadjusted to a BIS of 45. Predicted plasma propofol concentrationswere noted every 30 min from a target-controlled propofol infusionpump and arterial samples were taken at the same time for propofolmeasurements. Results. Patients in both groups were anaesthetized to similardepths of anaesthesia as indicated by BIS readings (P=0.44).The groups had comparable mean (95% CI) arterial concentrationsof propofol, 4.8 (3.5–6.1) µg ml^–1 in thepatients given clonidine, and 4.6 (3.4–5.7) µg ml^–1in the patients given placebo (P=0.81). However, the averageplasma concentration predicted by the target-controlled infusionwas less in the clonidine group [3.2 (2.9–3.5)] than inthe group given placebo [3.6 (3.3–3.9)] µg ml^–1(P<0.05). Conclusions. Pre-medication with clonidine reduces the requirementfor propofol, which is a pharmacokinetic effect and not a pharmacodynamiccentral sedative effect.     

Evaluation of effects of magnesium sulphate in reducing intraoperative anaesthetic requirements

Background. The present randomized, placebo-controlled, double-blindstudy was designed to assess the effect of peroperatively administeredi.v. magnesium sulphate on anaesthetic and analgesic requirementsduring total i.v. anaesthesia. Methods. Eighty-one patients (36 women, 45 men) undergoing electivespinal surgery were included in one of two parallel groups.The magnesium group received magnesium sulphate 30 mg kg^–1as a bolus before induction of anaesthesia and 10 mg kg^–1h^–1 by continuous i.v. infusion during the operation period.The same volume of isotonic solution was administered to thecontrol group. Anaesthesia was maintained with propofol (administeredaccording to the bispectral index) and remifentanil (adjustedaccording to heart rate and arterial blood pressure) infusions. Results. A significant reduction in hourly propofol consumptionwas observed with magnesium administration. For example, themean infusion rate of propofol in the second hour of the operationwas 7.09 mg kg^–1 h^–1 in the controlgroup vs 4.35 mg kg^–1 h^–1 in themagnesium group (P<0.001). The magnesium group required significantlyless remifentanil (P<0.001) and vecuronium (P<0.001).No side-effects were observed with magnesium administration. Conclusion. The administration of magnesium led to a significantreduction in the requirements for anaesthetic drugs during totali.v. anaesthesia with propofol, remifentanil and vecuronium. Br J Anaesth 2002; 89: 594–8     

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     

Effects of magnesium sulphate and clonidine on propofol consumption, haemodynamics and postoperative recovery

Background. This placebo-controlled, double-blind study wasdesigned to assess the effects of magnesium sulphate and clonidineon peroperative haemodynamics, propofol consumption and postoperativerecovery. Methods. Sixty ASA I–II patients undergoing spinal surgerywere randomized into three groups. Group M received magnesiumsulphate 30 mg kg^–1 as a bolus before induction and 10mg kg^–1 h^–1 by infusion. Group CL received clonidine3 µg kg^–1 as a bolus before induction and 2 µgkg^–1 h^–1 by infusion during the operation period.The same volume of isotonic solution was administered to thecontrol group (group CT). Anaesthesia was induced with propofoland was maintained with propofol infusion [dose according tothe bispectral index (BIS)], fentanyl and cisatracurium. Analysisof variance and the Bonferroni test were used for statisticalanalysis. Results. Induction of anaesthesia with propofol was rapid inthe presence of magnesium sulphate and clonidine. The time forBIS to reach 60 was significantly shorter in group M and groupCL (P<0.0001) but postoperative recovery was slower withmagnesium sulphate compared with the clonidine and control groups(P<0.0001). There was no statistical difference in heartrate and arterial blood pressure between the groups. Propofolrequirements for induction and maintenance of anaesthesia weresignificantly lower with magnesium and clonidine (P<0.0001). Conclusion. Clonidine caused bradycardia and hypotension andmagnesium sulphate caused delayed recovery, but can be usedas adjuvant agents with careful management.     

Safety of patient-maintained propofol sedation using a target-controlled system in healthy volunteers{dagger}

We investigated the safety of a patient-maintained system thatallows individuals to operate a target-controlled infusion ofpropofol to achieve sedation. Ten healthy volunteers were recruitedand instructed to try to anaesthetize themselves with the system.A target-controlled infusion of propofol was set to delivera target propofol concentration of 1 µg ml^–1,and the subjects allowed to increase the target in incrementsof 0.2 µg ml^–1 by pressing a control button twicein 1 s. There was a lockout time of 2 min and a maximum permittedtarget concentration of 3 µg ml^–1. Heartrate and pulse oximetry oxygen saturation (Sp_O2) were monitored continuously,and non-invasive arterial pressure, ventilatory frequenciesand sedation scores were measured every 5 min. Sedation wascontinued until the subject stopped pressing the button. A keywordwas then read for the individual to remember and sedation discontinued.There were no instances of significant decrease of Sp_O2 or lossof airway control. Maximum target blood concentration of propofolrecorded ranged from 1.4 to 3 µg ml^–1.Two subjects became oversedated, one of whom was unrousablewith loss of eyelash reflex. No subject could recall the keyword,although one recognized it from a list of 10 words. We concludethat the patient-maintained sedation system described couldnot be guaranteed to produce only conscious sedation in all patients,and that close clinical supervision by an anaesthetist would stillbe required for safe operation. Br J Anaesth 2000; 85: 299–301 Footnotes ^* Corresponding author: Department of Anesthesiology, Duke UniversityMedical Center, Box 3094, Durham, North Carolina 27710, USA     

Stimulation induced variability of pulse plethysmography does not discriminate responsiveness to intubation

Background. Hypnotic depth but not haemodynamic response topainful stimulation can be measured with various EEG-based anaesthesiamonitors. We evaluated the variation of pulse plethysmographyamplitude induced by an electrical tetanic stimulus (PPG variation)as a potential measure for analgesia and predictor of haemodynamicresponsiveness during general anaesthesia. Methods. Ninety-five patients, ASA I or II, were randomly assignedto five groups [Group 1: bispectral index (BIS) (range) 40–50,effect site remifentanil concentration 1 ng ml^–1;Group2: BIS 40–50, remifentanil 2 ng ml^–1; Group 3: BIS40–50, remifentanil 4 ng ml^–1; Group 4: BIS 25–35,remifentanil 2 ng ml^–1; Group 5: BIS 55–65, remifentanil2 ng ml^–1]. A 60 mA tetanic stimulus was applied for 5s on the ulnar nerve. From the digitized pulse oximeter waverecorded on a laptop computer, linear and non-linear parametersof PPG variation during the 60 s period after stimulation werecomputed. The haemodynamic response to subsequent orotrachealintubation was recorded. The PPG variation was compared betweengroups and between responders and non-responders to intubation(ANOVA). Variables independently predicting the response weredetermined by logistic regression. Results. The probability of a response to tracheal intubationwas 0.77, 0.47, 0.05, 0.18 and 0.52 in Groups 1–5, respectively(P<0.03). The PPG variability was significantly higher inresponders than in non-responders but it did not improve theprediction of the response to tracheal intubation based on BISlevel and effect site remifentanil concentration. Conclusion. Tetanic stimulation induced PPG variation does notreflect the analgesic state in a wide clinical range of surgicalanaesthesia.     

Target concentrations of remifentanil with propofol to blunt coughing during intubation, cuff inflation, and tracheal suctioning

Background. The target blood concentrations of propofol andremifentanil, when used in combination, required to blunt thecough response to tracheal intubation, cuff inflation, and trachealsuctioning without neuromuscular blocking agents are not known. Methods. In a randomized prospective study, 81 patients wereenrolled to determine which of three target remifentanil bloodconcentrations was required to blunt coughing during intubation,cuff inflation, and tracheal suctioning. Anaesthesia was achievedwith propofol at a steady effect-site concentration of 3.5 µgml^–1. The target blood remifentanil concentrations were5, 10, or 15 ng ml^–1. These concentrations were maintainedfor 12 min before intubation. Results. There was no cough response to intubation in more than74% of patients and no significant difference in the incidenceof coughing with intubation between the three groups. Significantdifference in coughing, diminishing with increasing remifentaniltarget concentration, was observed with cuff inflation (P=0.04)and tracheal suctioning (P=0.007). Bradycardia and hypotensionwas more frequent with the remifentanil target concentrationof 15 ng ml^–1. Tracheal suctioning resulted in more coughingthan intubation (P=0.01) or cuff inflation (P=0.004). Conclusion. Target remifentanil blood concentrations of 5, 10,and 15 ng ml^–1 associated with a 3.5 µg ml^–1propofol target blood concentration provided good intubatingconditions and absence of cough about 75% of the time. Highertarget remifentanil concentrations were associated with lesscoughing during tracheal tube cuff inflation and tracheal suctioning.     

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.     

Esmolol prevents movement and attenuates the BIS response to orotracheal intubation

Background. Beta-adrenergic agonists enhance behavioural andelectroencephalographic arousal reactions. We explored whetheradding esmolol, a short-acting ß₁-adrenoceptor antagonist,to propofol anaesthesia modified the bispectral index (BIS)during induction of anaesthesia and orotracheal intubation. Methods. Fifty patients were randomly allocated, in a double-blindfashion, to receive esmolol 1 mg kg^–1 followed by 250µg kg^–1 min^–1 or saline (control). Esmololor saline was started 6 min after a target-controlled infusion(TCI) of propofol (effect-site concentration 4 µg ml^–1).After loss of consciousness, and before administration of vecuronium0.1 mg kg^–1, a tourniquet was applied to one arm and inflatedto 150 mm Hg greater than systolic pressure. Eleven minutesafter the TCI began, the trachea was intubated; gross movementwithin the first min after orotracheal intubation was recorded.BIS was recorded at 10-s intervals. Mean arterial pressure (MAP)and heart rate were measured non-invasively every min. Results. There were no intergroup differences in BIS, heartrate or MAP before laryngoscopy. BIS increased significantlyafter orotracheal intubation (compared with the pre-laryngoscopyvalues) in the control group only, with a maximum increase of40 (SD 18)% vs 8 (11)% in the esmolol group (P<0.01). Maximumchanges in heart rate [45 (19)% vs 23 (14)%] and MAP [62 (24)%vs 45 (23)%] with orotracheal intubation were also significantlygreater in the control group than in the esmolol group. Morepatients in the control than in the esmolol group moved afterorotracheal intubation (23 vs 12, P<0.01). Conclusion. Esmolol not only attenuated haemodynamic and somaticresponses to laryngoscopy and orotracheal intubation, but alsoprevented BIS arousal reactions in patients anaesthetized withpropofol. Br J Anaesth 2002; 89: 857–62     

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 BispectralIndex (BIS) and SE values is useful for predicting loss of verbalcontact and loss of consciousness during steady-state conditions. 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 effect-siteconcentrations 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 it was2.8 (2.8–5.65) µg ml^–1. LVC occurred in 90%of patients at a BIS value of 70.2 (70.2–90.2) and anSE value of 60.3 (60.3–75.5), and LOC occurred at a BISvalue of 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 greater correlation with effect-site concentrationand may be more useful than BIS in predicting both LVC and LOC.     

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