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.     

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.     

Effect site concentrations of remifentanil and pupil response to noxious stimulation

Background. Opioid drugs block reflex pupillary dilatation inresponse to noxious stimulation. The relationship between thetarget effect site concentration (Ce_T) of remifentanil and thepupil diameter and reactivity in response to a standard noxiousstimulus were evaluated. Methods. Anaesthesia was induced with propofol TCI to obtainloss of consciousness (LOC) in 12 ASA I/II patients. Thereafter,remifentanil Ce_T was titrated by increments of 1 up to 5 ngml^–1. In the awake state, at LOC and at each plateau levelof remifentanil Ce_T, arterial pressure, heart rate, and BIS(A2000) were recorded. Pupil size and dilatation after a 100Hz tetanic stimulation (T100) were measured at LOC and at eachplateau level of remifentanil Ce_T. Results. LOC was observed at a mean propofol Ce_T of 3.53 (SD0.43) µg ml^–1. Arterial pressure and heart ratedecreased progressively from LOC to 5 ng ml^–1 remifentanilCe_T without any statistical difference between each incrementaldose of remifentanil. Mean BIS values decreased from 96 (2)in the awake state, to 46 (12) at LOC (P<0.05) and then remainedunchanged at all remifentanil Ce_T. Pupil dilatation in responseto 100 Hz tetanic stimulation decreased progressively from 1.55(0.72) to 0.01 (0.03) mm and was more sensitive than pupil diametermeasured before and after 100 Hz tetanus. An inverse correlationbetween pupil dilatation in response to 100 Hz tetanus and anincrease in remifentanil Ce_T from 0 to 5 ng ml^–1 was found(R²=0.68). Conclusions. During propofol TCI in healthy patients, the decreasein pupil response to a painful stimulus is a better measurementof the progressive increase of remifentanil Ce_T up to 5 ng ml^–1than haemodynamic or BIS measurements. Br J Anaesth 2003; 91: 347–52     

Do we need inhaled anaesthetics to blunt arousal, haemodynamic responses to intubation after i.v. induction with propofol, remifentanil, rocuronium?

Background. The aim of this study was to determine whether,after propofol, rocuronium and remifentanil rapid sequence induction,inhaled anaesthetic agents should be started before intubationto minimize autonomic and arousal response during intubation. Methods. One hundred ASA I and II patients were randomized toreceive 1 MAC of desflurane or sevoflurane during manual ventilationor not. Anaesthesia was induced with an effect-site-controlledinfusion of remifentanil at 2 ng ml^–1 for 3 min. Patientsthen received propofol to induce loss of consciousness (LOC).Rocuronium (0.6 mg kg^–1) was given at LOC and the tracheawas intubated after 90 s of manual breathing support (=baseline)with or without inhaled anaesthetics. Vital signs and bispectralindex (BIS) were recorded until 10 min post-intubation to detectautonomic and arousal response. Results. A significant increase in BIS value after intubationwas seen in all groups. The increases were mild, even in thosenot receiving pre-intubation inhaled anaesthetics. However,in contrast to sevoflurane, desflurane appeared to partiallyblunt the arousal response. Heart rate, systolic and diastolicpressure increase similarly in all groups. Conclusions. Desflurane and sevoflurane were unable to bluntthe arousal reflex completely, as measured by BIS, althoughthe reflex was significantly less when desflurane was used.Rapid sequence induction with remifentanil, propofol and rocuroniumand without inhaled anaesthetics before intubation can be donewithout dangerous haemodynamic and arousal responses at intubationafter 90 s.     

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.     

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     

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.     

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     

Influence of peroperative opioid on postoperative pain after major abdominal surgery: sufentanil TCI versus remifentanil TCI. A randomized, controlled study

Background. Sufentanil and remifentanil are characterized bytwo different pharmacokinetic profiles. The aim of this studywas to compare the effects of sufentanil and remifentanil administeredusing target-controlled infusion (TCI) on recovery and postoperativeanalgesia after major abdominal surgery. Methods. Thirty adult patients scheduled for open colorectalsurgery were included in a prospective, randomized study. SufentanilTCI (sufentanil group) or remifentanil TCI (remifentanil group)was administered during surgery. In the remifentanil group,30 min before the anticipated end of surgery, morphine 0.15mg kg^–1 was administered i.v. In the sufentanil group,an effect-site concentration of 0.25 ng ml^–1 wastargeted at extubation. In both groups, postoperative pain wascontrolled by titration of i.v. morphine and then patient-controlledanalgesia with morphine. Results. The extubation time was similar in the two groups (mean(SD) 13 (6) and 14 (6) min in the sufentanil and remifentanilgroups respectively). Visual analogue scale scores were significantlygreater during the first 2 h after tracheal extubation in theremifentanil group than in the sufentanil group. The time tofirst analgesic request in the postanaesthesia care unit wassignificantly longer in the sufentanil group than in the remifentanilgroup (55 (64) (range 2–240) vs 11 (7) (1–29) min;P<0.001). The cumulative morphine dose for titration wassignificantly greater in the remifentanil group (P<0.01).The cumulative morphine dose used during titration and patient-controlledanalgesia was significantly greater in the remifentanil group4, 12 and 24 h after extubation (P<0.05). Conclusion. TCI sufentanil (0.25 ng ml^–1 effect-siteconcentration at extubation) is more effective than the intraoperativecombination of remifentanil TCI infusion with morphine bolus(0.15 mg kg^–1) for postoperative pain relief aftermajor abdominal surgery and does not compromise extubation andrecovery. Br J Anaesth 2003; 91: 842–9     

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     

Pharmacodynamic modelling of the bispectral index response to propofol-based anaesthesia during general surgery in children

Background: This study describes a pharmacodynamic model during generalanaesthesia in children relating the bispectral index (BIS)response to the anaesthetic dosing of propofol, fentanyl, andremifentanil. Methods: BIS, heart rate, mean arterial pressure, sedation scores, andanaesthetic protocols from 59 children aged 1–16 yr undergoinggeneral surgery were considered for the study. Anaesthesia wasperformed with propofol, fentanyl, and remifentanil. A sigmoidmodel assuming additive interaction of propofol, fentanyl, andremifentanil was fitted to individual BIS as effect variable.The pharmacodynamic parameters were estimated by non-linearregression analysis. The ability of BIS to predict anaestheticdrug effect was quantified by the prediction probability Pk. Results: BIS started at a baseline of 90 (9), decreased during inductionto 30 (14) and remained at 57 (10) during anaesthesia. BIS predictedthe anaesthetic drug effect with a Pk of 0.79 (0.08). The EC_50Propofol and the k_{e0 Propofol} were 5.2 (2.7) µg ml^–1and 0.60 (0.45) min^–1, respectively. The k_{e0 Propofol}decreased from approximately 0.91 min^–1 at 1 yr to 0.15min^–1 at 16 yr. The EC_{50 Remifentanil}, k_{e0 Remifentanil},EC_{50 Fentanyl}, and the k_{e0 Fentanyl} were 24.1 (13.0) ng ml^–1,0.71 (0.32) min^–1, 8.6 (7.4) ng ml^–1, and 0.28 (0.46)min^–1, respectively. Conclusions: The effect equilibration half-time of propofol in children wasage dependent. The pharmacodynamics of fentanyl and remifentanilin children were similar to those reported in adults. The BISshowed a close relationship to the modelled effect-site concentration,and therefore, it may serve as a measure of anaesthetic drugeffect in children older than 1 yr.     

Spectral entropy measurement of patient responsiveness during propofol and remifentanil. A comparison with the bispectral index

Background. We compared two spectral entropies, state entropy(SE) and response entropy (RE), based on the irregularity ofthe EEG, to measure loss of response to verbal command (LOR_verbal)and noxious stimulus (LOR_noxious) with the bispectral index(BIS) during propofol infusion with and without remifentanil. Methods. Three groups of 20 patients received an effect-sitecontrolled propofol infusion (Ce_PROP) starting at 1 µgml^–1 and increased in steps of 0.5 µg ml^–1at 4 min intervals. In addition, a remifentanil infusion wasmaintained at a group-dependent, fixed effect-site target concentration(Ce_REMI) (0, 2 or 4 ng ml^–1). The ability of BIS, SE orRE to predict LOR_verbal and LOR_noxious were compared with thechanges in BIS, SE and RE using logistic regression, predictionprobability (P_K), and sensitivity/specificity. Results. In all groups, BIS, SE and RE decreased with increasingCe_PROP. However, BIS decreased more smoothly than SE and REat deeper levels of sedation. At LOR_verbal, BIS₅₀, SE₅₀ andRE₅₀ increased with increasing Ce_REMI. BIS, SE and RE all detectedLOR_verbal accurately but BIS performed better at 100% sensitivity.Sensitivity/specificity for detection of LOR_verbal decreasedfor all methods with increasing Ce_REMI. LOR_noxious was poorlydescribed by all measures. Conclusion. LOR_verbal was detected accurately by BIS, SE andRE except for 100% sensitivity, where BIS performed better.Though BIS, SE and RE were influenced by remifentanil duringpropofol administration, their ability to detect LOR_verbal remainedaccurate. None of the measures predicted LOR_noxious.      

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     

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.     

Recovery after remifentanil and sufentanil for analgesia and sedation of mechanically ventilated patients after trauma or major surgery

We investigated the analgesic effect and the neurological recoverytime after administration of remifentanil in mechanically ventilatedpatients in an intensive care unit. Twenty patients, after traumaor major surgery with no intracranial pathology, were randomizedto receive either remifentanil/propofol (n=10) or sufentanil/propofol(n=10). A sedation score and a simplified pain score were usedto assess adequate sedation and analgesia. Medication was temporarilystopped after 24 h. Immediately before and 10 and 30 min after,the degree of sedation and pain score were evaluated. Adequateanalgesia and sedation was achieved with remifentanil 10.6 µgkg^–1 h^–1 and propofol 2.1 mg kg^–1 h^–1,or sufentanil 0.5 µg kg^–1 h^–1 and propofol1.3 mg kg^–1 h^–1. The difference in propofol dosebetween groups was significant. Ten minutes after terminatingthe medication, the degree of sedation decreased significantlyafter remifentanil and all patients could follow simple commands.During the following 20 min, all patients with remifentanilemerged from sedation and complained of considerable pain. Bycontrast, in the sufentanil group, only six (7) responded tocommands after 10 (30) min and their pain score remained essentiallyunchanged during the 30-min observation period. We concludethat, in contrast to sufentanil, remifentanil facilitates rapidemergence from analgesia and sedation, allowing a clinical neurologicalexamination within 10–30 min in mechanically ventilatedpatients with no intracranial pathology. Br J Anaesth 2001; 86: 763–8     

Comparison of alfentanil, fentanyl and sufentanil for total intravenous anaesthesia with propofol in patients undergoing coronary artery bypass surgery

We have studied the pharmacokinetics and pharmacodynamics ofalfentanil, fentanyl and sufentanil together with propofol inpatients undergoing coronary artery bypass graft surgery (CABG).Sixty patients (age 40–73 yr, 56 male) were assignedrandomly to receive alfentanil, fentanyl or sufentanil and propofol.Plasma concentrations of these drugs and times for the plasmaconcentration to decrease by 50% (t₅₀) and 80% (t₈₀) after cessationof the infusion were determined. Times were recorded to awakeningand tracheal extubation. Total dose and plasma concentrationsof propofol were similar in all groups. Mean total doses ofalfentanil, fentanyl and sufentanil were 443, 45 and 4.4 µg kg^–1,respectively. Time to awakening did not differ significantly.In patients receiving fentanyl, the trachea was extubated onaverage 2 h later than in those receiving sufentanil and3 h later than in those receiving alfentanil (P<0.05).The t₈₀ of fentanyl was longer (P<0.05) than that of alfentanilor sufentanil, and there was a linear correlation between thet₈₀ of the opioid and the time to tracheal extubation (r=0.51;P<0.01). However, the t₅₀ values for these opioids were similarand did not correlate with recovery time. In conclusion, patientsundergoing CABG and who were anaesthetized with fentanyl andpropofol needed mechanical ventilatory support for a significantlylonger time than those receiving alfentanil or sufentanil andpropofol. On the basis of the interindividual variation observed,the time to tracheal extubation was most predictable in patientsreceiving alfentanil and most variable in patients receivingfentanyl, a finding which may be important if the patients aretransferred to a step-down unit on the evening of the operation. Br J Anaesth 2000; 85: 533–40. ^* Corresponding author: Department of Anaesthesia, Helsinki UniversityHospital, PO Box 340, FIN-00029 Hus, Finland     

Comparison of remifentanil and alfentanil during anaesthesia for patients undergoing direct laryngoscopy without intubation

Background. Remifentanil and alfentanil are opioids often usedduring direct laryngoscopy (DL). This prospective, randomizedstudy compared these agents with respect to haemodynamic andBispectral Index (BIS) responses, glottic visualization, andrapidity of recovery (spontaneous ventilation, eye opening)in DL without intubation. Methods. A total of 60 patients undergoing DL were randomizedinto two groups: remifentanil (R) and alfentanil (A). Anaesthesiawas induced with propofol 2.5 mg kg^–1 and the opioid wasadministered 1 min later (R=2 µg kg^–1 or A=30 µgkg^–1 over 30 s). DL was commenced 1 min after (correspondingto 3 min after the beginning of induction). Glottic visualization,opioid and/or propofol re-injection, spontaneous ventilationrecovery, and eye opening were recorded. Results. During DL, mean arterial pressure (MAP) increased by6% in the R group vs 20% in the A group (P<0.05) when comparedwith post-induction values without affecting heart rate or BIS.No significant difference was observed between groups with respectto glottic exposure, opioid and/or propofol re-injection, andspontaneous ventilation recovery (mean (SEM) 3.8 (0.6) min,R group vs 3.2 (0.7) min, A group, NS) or eye opening (7.1 (1.1)min, R group vs 7.4 (0.9) min, A group, NS). Thirty minutesafter postanaesthesia care unit (PACU) admission, MAP returnedto its pre-induction value in the R group (104 (3) vs 109 (3)at baseline, NS), whereas in the A group MAP remained significantlylower at this time point (96 (4) vs 106 (3) at baseline, P<0.05). Conclusion. This study showed that only remifentanil preventedMAP increase without adverse effects such as bradycardia duringDL, and prevented MAP decrease 30 min after PACU admission. Br J Anaesth 2003; 91: 421–3     

Predictive performance of 'Servin's formula' during BIS-guided propofol-remifentanil target-controlled infusion in morbidly obese patients

Background. The aim of this study was to assess the predictiveperformance of ‘Servin's formula’ for bispectralindex (BIS)-guided propofol-remifentanil target-controlled infusion(TCI) in morbidly obese patients. Methods. Twenty patients (ASA physical status II–III,age 32–64 yr) undergoing bilio-intestinal bypass surgery,were recruited. Anaesthesia was induced by using a TCI of propofolwith an initial target plasma concentration of 6 µg ml^–1,then adapted to maintain stable BIS values ranging between 40and 50. A TCI of remifentanil was added to achieve pain controland haemodynamic stability. For propofol, weight was correctedas suggested by Servin and colleagues. With ideal body weight(IBW) corrected according to formula suggested by Lemmens andcolleagues. For remifentanil, weight was corrected accordingto IBW. Arterial blood samples for the determination of bloodpropofol concentrations were collected at different surgicaltimes. The predictive performance of propofol TCI was evaluatedby examining performance accuracy. Results. Median prediction error and median absolute predictionerror were –32.6% (range –53.4%; –2.5%) and33.1% (10.8%; 53.4%), respectively. Wobble median value was5.9% (2.5%; 25.2%) while divergence median value was –1.5%h^–1 (–7.7; 33.8% h^–1). Conclusion. Significant bias between predicted and measuredplasma propofol concentrations was found while the low wobblevalues suggest that propofol TCI system is able to maintainstable drug concentrations over time. As already suggested before,a computer simulation confirmed that the TCI system performancecould be significantly improved when total body weight is used.     

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     

Relation between fentanyl dose and predicted EC50 of propofol for laryngeal mask insertion

Background. This study sought to determine the effective concentrationfor 50% of the attempts to secure laryngeal mask insertion (predictedEC_50LMA) of propofol using a target-controlled infusion (Diprifusor^TM)and investigated whether fentanyl influenced these requiredconcentrations, respiratory rate (RR) and bispectral index (BIS). Methods. Sixty-four elective unpremedicated patients were randomlyassigned to four groups (n = 16 for each group) and given saline(control) or fentanyl 0.5, 1 or 2 µg kg^–1.Propofol target concentration was determined by a modificationof Dixon’s up-and-down method. Laryngeal mask airway insertionwas attempted without neuromuscular blocking drugs after equilibrationhad been established for >10 min. Movement was defined aspresence of bucking or gross purposeful muscular movement within1 min after insertion. EC_50LMA values were obtained by calculatingthe mean of 16 patients in each group. Results. Predicted EC_50LMA of the control, fentanyl 0.5, 1 and2 µg kg^–1 groups were 3.25 (0.20), 2.06 (0.55),1.69 (0.38) and 1.50 (0.54) µg ml^–1 respectively;those of all fentanyl groups were significantly lower than thatof control. RR was decreased in relation to the fentanyl doseup to 1 µg kg^–1. BIS values after fentanyl1 and 2 µg kg^–1 were significantly greaterthan in the control and 0.5 µg kg^–1 groups. Conclusions. A fentanyl dose of 0.5 µg kg^–1is sufficient to decrease predicted EC_50LMA with minimum respiratorydepression and without a high BIS value. Br J Anaesth 2004; 92: 238–41