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

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

Recovery from propofol anaesthesia supplemented with remifentanil

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

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

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

Influence of propofol concentrations on multipulse transcranial motor evoked potentials

Background. Motor evoked potentials can be affected by propofolanaesthesia. We studied how increasing target concentrationsof propofol altered transcranial motor evoked potentials (tcMEP)during scoliosis surgery. Methods. Fifteen patients undergoing surgery for scoliosis wereanaesthetized with remifentanil and propofol without nitrousoxide or neuromuscular blocking agents (BIS<60). tcMEP wereelicited by transcranial electric multipulse stimulation ofthe motor cortex and recording of compound action potentialsfrom the anterior tibialis muscle. tcMEP were obtained beforesurgery with propofol target values set from 4 to 8 mg litre^–1,and then during surgery. Arterial propofol concentrations weremeasured for each tcMEP recording. Results. Before surgery, increasing propofol reduced tcMEP amplitudein a dose-dependent manner, with no effect on latency. Duringsurgery, at equivalent propofol concentrations, tcMEP were notstatistically different from those obtained before surgery.In all except one patient, tcMEP signals were present duringthe entire procedure. In this patient the loss of tcMEP wasunfortunately related to an anterior spinal cord lesion, whichwas confirmed by a wake-up test. Conclusion. We found that, although propofol had a dose-dependenteffect on tcMEP amplitude, anaesthesia could be maintained withremifentanil and propofol to allow recording and interpretationof tcMEP signals. Br J Anaesth 2003; 91: 493–7     

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

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

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.     

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     

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     

Recent advances in intravenous anaesthesia

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

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

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

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

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

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     

Comparative efficacy and safety of remifentanil and fentanyl in 'fast track' coronary artery bypass graft surgery: a randomized, double-blind study

This multi-centre, parallel group, randomized, double-blindstudy compared the efficacy and safety of high-dose remifentaniladministered by continuous infusion with an intermittent bolusfentanyl regimen, when given in combination with propofol forgeneral anaesthesia in 321 patients undergoing elective coronaryartery bypass graft surgery. A significantly lower proportionof the patients who received remifentanil had responses to maximalsternal spread (the primary efficacy endpoint) compared withthose who received fentanyl (11% vs 52%; P<0.001). More patientswho received remifentanil responded to tracheal intubation comparedwith those who received fentanyl (24% vs 9%; P<0.001). However,fewer patients who received remifentanil responded to sternalskin incision (11% vs 36%; P<0.001) and sternotomy (14% vs60%; P <0.001). Median time to extubation was longer in thesubjects who received remifentanil than for those who receivedfentanyl (5.1 vs 4.2 h; P=0.006). There were no statisticallysignificant differences between the two groups in the timesfor transfer from intensive care unit or hospital dischargebut time to extubation was significantly longer in the remifentanilgroup. Overall, the incidence of adverse events was similarbut greater in the remifentanil group with respect to shivering(P<0.049) and hypertension (P<0.001). Significantly moredrug-related adverse events were reported in the remifentanilgroup (P=0.016) There were no drug-related adverse cardiac outcomesand no deaths from cardiac causes before hospital dischargein either treatment group. Br J Anaesth 2001; 87: 718–26     

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     

Assessment of tracheal intubating conditions in children using remifentanil and propofol without muscle relaxant

BACKGROUND: Tracheal intubation in children can be achieved by deep inhalational anaesthesia or an intravenous anaesthetic and a muscle relaxant, suxamethonium being widely used despite several side-effects. Studies have shown that oral intubation can be facilitated safely and effectively in children after induction of anaesthesia with propofol and alfentanil without a muscle relaxant. Remifentanil is a new, ultra-short acting, selective mu-receptor agonist that is 20-30 times more potent than alfentanil. This clinical study was designed to assess whether combination of propofol and remifentanil could be used without a muscle relaxant to facilitate tracheal intubation in children. METHODS: Forty children (5-10 years) admitted for adenotonsillectomy were randomly allocated to one of two groups to receive remifentanil 2 microg.kg(-1) (Gp I) or remifentanil 3 microg.kg(-1) (Gp II) before the induction of anaesthesia with i.v. propofol 3 mg.kg(-1). No neuromuscular blocking agent was administered. Intubating conditions were assessed using a four-point scoring system based on ease of laryngoscopy, jaw relaxation, position of vocal cords, degree of coughing and limb movement. Mean arterial pressure (MAP) and heart rate (HR) measured noninvasively before induction of anaesthesia to 5 min after intubation (seven time points). RESULTS: Tracheal intubation was successful in all patients without requiring neuromuscular blocking agent. Intubating conditions were clinically acceptable in 10 of 20 patients (50%) in Gp I compared with 18 of 20 patients (90%) in Gp II (P < 0.05). MAP and HR decreased in both groups after induction of anaesthesia (P < 0.01). Both HR and MAP were significantly lower in Gp II compared with Gp I after tracheal intubation (P < 0.01). No patient in the present study developed bradycardia or hypotension. CONCLUSIONS: We conclude that remifentanil (3 microg.kg(-1)), administered before propofol (3 mg.kg(-1)) provides acceptable tracheal intubating conditions in children, and completely inhibited the increase in HR and MAP associated with intubation.     

Comparison of propofol/remifentanil and sevoflurane/remifentanil for maintenance of anaesthesia for elective intracranial surgery

Background. Propofol and sevoflurane are suitable agents formaintenance of anaesthesia during neurosurgical procedures.We have prospectively compared these agents in combination withthe short-acting opioid, remifentanil. Methods. Fifty unpremedicated patients undergoing elective craniotomyreceived remifentanil 1 µg kg^–1 followed by an infusioncommencing at 0.5 µg kg^–1 min^–1 reducing to0.25 µg kg^–1 min^–1 after craniotomy. Anaesthesiawas induced with propofol, and maintained with either a target-controlledinfusion of propofol, minimum target 2 µg ml^–1 orsevoflurane, initial concentration 2%_ET. Episodes of mean arterialpressure (MAP) more than 100 mm Hg or less than 60 mm Hg formore than 1 min were defined as hypertensive or hypotensiveevents, respectively. A surgical assessment of operating conditionsand times to spontaneous respiration, extubation, obey commandsand eye opening were recorded. Drug acquisition costs were calculated. Results. Twenty-four and twenty-six patients were assigned topropofol (Group P) and sevoflurane anaesthesia (Group S), respectively.The number of hypertensive events was comparable, whilst morehypotensive events were observed in Group S than in Group P(P=0.053, chi-squared test). As rescue therapy, more labetolol[45 (33) vs 76 (58) mg, P=0.073] and ephedrine [4.80 (2.21)vs 9.78 (5.59) mg, P=0.020] were used in Group S. Between groupdifferences in recovery times were small and clinically unimportant.The combined hourly acquisition costs of hypnotic, analgesic,and vasoactive drugs appeared to be lower in patients maintainedwith sevoflurane than with propofol. Conclusion. Propofol/remifentanil and sevoflurane/remifentanilboth provided satisfactory anaesthesia for intracranial surgery.     

Low-dose remifentanil to suppress haemodynamic responses to noxious stimuli in cardiac surgery: a dose-finding study

Background: High-dose remifentanil (1–5 µg kg^–1 min^–1),commonly used for cardiac surgery, has been associated withmuscle rigidity, hypotension, bradycardia, and reduced cardiacoutput. The aim of this study was to determine an optimal lowerremifentanil dose, which should be accompanied by fewer adverseevents, that still effectively suppresses haemodynamic responsesto typical stressful stimuli (i.e. intubation, skin incision,and sternotomy). Methods: Total i.v. anaesthesia consisted of a target-controlled propofol(2 µg ml^–1) and a remifentanil infusion. Forty patientswere allocated to receive either a constant infusion of remifentanilat 0.1 µg kg^–1 min^–1 or up-titrations to 0.2,0.3, or 0.4 µg kg^–1 min^–1, respectively, 5min before each stimulus. Subsequently, changes in heart rateand mean arterial blood pressure were recorded for 8 min. Increasesexceeding 20% of baseline were considered to be of clinicalrelevance. Patients who exhibited these alterations were termedresponders. Results: The number of responders was less with the two higher remifentanildosages (P < 0.05) while propofol target doses could eitherbe kept at the same level or even be reduced without affectingthe plane of anaesthesia. Although single phenylephrine bolushad to be applied more frequently in these two groups (P <0.05), no severe haemodynamic depression was observed. Conclusions: Remifentanil at 0.3 and 0.4 µg kg^–1 min^–1in combination with a target-controlled propofol infusion inthe pre-bypass period is well tolerated. It appears to mitigatepotentially hazardous haemodynamic responses from stressfulstimuli equally well as higher doses when compared with datafrom the literature.     

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     

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     

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

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