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.     

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     

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     

Effect of remifentanil infusion rate on stress response to the pre-bypass phase of paediatric cardiac surgery

Background. Opioids are used routinely to eliminate the stressresponse in the pre-bypass phase of paediatric cardiac surgery.Remifentanil is a unique opioid allowing a rapidly titratableeffect. No data are available regarding a suitable remifentanildose regimen for obtunding stress and cardiovascular responsesto such surgery. Methods. We recruited 49 infants and children under 5 yr oldwho were randomized to receive one of four remifentanil infusionrates (0.25, 1.0, 2.5, or 5.0 µg kg^–1 min^–1).Blood samples were obtained at induction, pre-surgery, 5 minafter opening the chest, and immediately pre-bypass. Whole bloodglucose was measured at all time points while cortisol and neuropeptideY (NPY) were measured in the first and last samples. Heart rateand arterial pressure were also recorded. Results. There was a significant increase in whole blood glucose5 min after opening the chest and pre-bypass (P=0.009, P=0.002)in patients receiving remifentanil 0.25 µg kg^–1min^–1, but not in those receiving higher doses. Increasedremifentanil dosage was associated with reduced plasma cortisolduring surgery (P<0.001). Baseline NPY showed considerablevariation and there was no association between pre-bypass NPYand remifentanil dose. There was a significantly higher heartrate at the pre-bypass stage of surgery in the remifentanil0.25 µg kg^–1 min^–1 group compared with higherdoses (P=0.0006). Four out of five neonates with complex cardiacconditions showed severe bradycardia associated with remifentanil. Conclusions. In infants and children under 5 yr, remifentanilinfusions of 1.0 µg kg^–1 min^–1 and greatercan suppress the glucose increase and tachycardia associatedwith the pre-bypass phase of cardiac surgery, while 0.25 µgkg^–1 min^–1 does not. Remifentanil should be usedwith caution in neonates with complex congenital heart disease. Br J Anaesth 2004; 92: 187–94     

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.     

Effects of xenon anaesthesia on the circulatory response to hypoventilation

Background. Circulatory response to hypoventilation is aimedat eliminating carbon dioxide and maintaining oxygen delivery(DO₂) by increasing cardiac output (CO). The hypothesis thatthis increase is more pronounced with xenon than with isofluraneanaesthesia was tested in pigs. Methods. Twenty pigs received anaesthesia with xenon 0.55 MAC/remifentanil0.5 µg kg^–1 min^–1 (group X, n=10) or isoflurane0.55 MAC/remifentanil 0.5 µg kg^–1min^–1 (groupI, n=10). CO, heart rate (HR), mean arterial pressure (MAP)and left ventricular fractional area change (FAC) were measuredat baseline, after 5 and 15 min of hypoventilation and after5, 15 and 30 min of restored ventilation. Results. CO increased by 10–20% with both anaesthetics,with an equivalent rise in HR, maintaining DO₂ in spite of a20% reduction in arterial oxygen content. Decreased left ventricular(LV) afterload during hypoventilation increased FAC, and thiswas more marked with xenon (0.60–0.66, P<0.05 comparedwith baseline and isoflurane). This difference is attributedto negative inotropic effects of isoflurane. Increased pulmonaryvascular resistance during hypoventilation was found with bothanaesthetics. Conclusion. The cardiovascular effects observed in this modelof moderate hypoventilation were sufficient to maintain DO₂.Although the haemodynamic response appeared more pronouncedwith xenon, differences were not clinically relevant. An increasein FAC with xenon is attributed to its lack of negative inotropiceffects.     

Pretreatment with remifentanil to prevent withdrawal after rocuronium in children

Background. Pain from rocuronium injection is a common side-effectreported to occur in 50–80% of the patients. This randomized,double-blind, placebo-controlled study was designed to evaluatethe efficacy of pretreatment with i.v. remifentanil on preventionof withdrawal response during rocuronium injection in paediatricpatients. Methods. After obtaining parental consents, 70 paediatric patientswere randomly allocated into two groups to receive either i.v.remifentanil 1 µg kg^–1 (remifentanil group, n=35)or i.v. saline 5 ml (saline group, n=35). Anaesthesia was inducedwith thiopental sodium 2.5% (5 mg kg^–1) and the test drugwas injected over 30 s. One minute after the test drug injection,rocuronium 1% (0.6 mg kg^–1) was injected over 5 s andthe response was recorded. Mean arterial pressure (MAP) andheart rate were recorded on arrival in the operating theatre,before and 1 min after the tracheal intubation. Results. The overall incidence of withdrawal movements was significantlyhigher in the saline group (33 patients; 94%) than that in theremifentanil group (8 patients; 23%) (P<0.001). No patientin the remifentanil group showed generalized movement, whereas51% of patients in the saline group did. Remifentanil preventedsignificant increase in MAP after intubation. Conclusion. This study demonstrated that pretreatment with remifentanil1 µg kg^–1 provided a safe and simple method forreducing the incidence of rocuronium-associated withdrawal movementwith haemodynamic stability in children.     

Remifentanil or propofol for sedation during carotid endarterectomy under cervical plexus block

Background. During carotid endarterectomy under regional anaesthesia,patients often require medication to control haemodynamic instabilityand to provide sedation and analgesia. Propofol and remifentanilare used for this purpose. However, the benefits, side-effects,and optimal dose of these drugs in such patients are unclear. Methods. Sixty patients were included in a prospective, randomized,single blinded study. All patients received a deep cervicalplexus block with 30 ml ropivacaine 0.75% and were randomizedto receive either remifentanil 3 µg kg^–1 h^–1or propofol 1 mg kg^–1 h^–1. The infusions were startedafter performing the regional block and were stopped at theend of surgery. Arterial pressure, ECG, ventilatory rate, andPa_CO2 were measured continuously and recorded at predeterminedtimes. Twenty-four hours after surgery, patient comfort, andsatisfaction were also evaluated. Results. In three patients, the infusion of remifentanil hadto be stopped because of severe respiratory depression or bradycardia.No significant differences were found between the two groupsin haemodynamic variables or sedative effects, but there wasa significantly greater decrease in ventilatory frequency andincrease in Pa_CO2 in the remifentanil group. The patient’ssubjective impressions and pain control were excellent in bothgroups. Conclusion. As a result of the higher incidence of adverse respiratoryeffects with remifentanil and similar sedative effects, propofolis preferable for sedation during cervical plexus block in elderlypatients with comorbid disease at the dosage used. Br J Anaesth 2002; 89: 637–40     

Effect of prophylactic bronchodilator treatment with i.v. carperitide on airway resistance and lung compliance after tracheal intubation

Background. Lung resistance increases after induction of anaesthesia.We hypothesized that prophylactic bronchodilation with i.v.carperitide before tracheal intubation would decrease airwayresistance and increase lung compliance after placement of thetracheal tube in both smokers and nonsmokers. Methods. Ninety-seven adults aged between 24 and 59 yr wererandomized to receive i.v. normal saline (0.9% saline) (control)or carperitide, 0.2 µg kg^–1 min^–1 throughoutthe study. The 97 patients included smokers and nonsmokers.Thus the patients were allocated to one of the four groups:smokers who received normal saline (n=21), nonsmokers who receivednormal saline (n=27), smokers who received carperitide (n=19)or nonsmokers who received carperitide (n=30). Thirty minutesafter starting normal saline or carperitide infusion, we administeredthiamylal 5 mg kg^–1 and fentanyl 5 µg kg^–1to induce general anaesthesia and vecuronium 0.3 mg kg^–1for muscle relaxation. Continuous infusion of thiamylal 15 mgkg^–1 h^–1 followed anaesthetic induction. Mean airwayresistance (R_awm), expiratory airway resistance (R_awe) and dynamiclung compliance (C_dyn) were determined 4, 8, 12 and 16 min aftertracheal intubation and compared between the four groups. Results. At 4 min after intubation, R_awm and R_awe were higherand C_dyn lower in smokers than in nonsmokers in the controlgroup. R_awm and R_awe were lower and C_dyn higher in smokers inthe carperitide group than in smokers in the control group.R_awm and R_awe were lower in nonsmokers in the carperitide groupthan in nonsmokers in the control group. Conclusions. Marked bronchoconstriction occurred in the controlgroups (smokers and nonsmokers) 4 min after tracheal intubation.Prophylactic treatment with carperitide before induction ofanaesthesia and tracheal intubation was advantageous, particularlyin smokers.     

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     

Patient-controlled analgesia for labour using remifentanil: a feasibility study

We have investigated the efficacy and safety of remifentanilin a patient-controlled analgesia device for labour in 21 women.Remifentanil was available in increasing doses (bolus doses0.25–1.0 µg kg^–1) with and without a backgroundinfusion (0.025–0.05 µg kg^–1 min^–1).A lockout time of 2 min was used. Thirteen out of 21 (62%) womenchose to continue using remifentanil up to and during delivery.Nineteen out of 21 (90%) achieved a reduction in pain scorefrom baseline. Using a VAS of 0–10 cm the median maximumreduction in pain score was 3 cm (range 0–8 cm). Therewas a significant reduction (P<0.05) from baseline pain scores(median= 8 cm) to scores at bolus doses in the range 0.25–0.5µg kg^–1 (median=5 cm). There were no significantreductions in the fetal heart rate. Apgar scores and cord bloodgas analyses remained within normal limits. We conclude thata remifentanil patient-controlled analgesia system (bolus doses0.25–0.5 µg kg^–1, without a background infusion)may safely provide worthwhile, although incomplete, analgesiafor labour. Br J Anaesth 2001; 87: 415–20     

Influence of acute normovolaemic haemodilution on the dose-response relationship, time-course of action and pharmacokinetics of rocuronium bromide

Background. Acute normovolaemic haemodilution (ANH) is an effectivestrategy for avoiding or reducing allogeneic blood transfusion.We aimed to study its effect on the pharmacological profileof rocuronium. Methods. In two study centres, 28 patients undergoing majorsurgery with ANH were matched with 28 control patients. In thedose–response groups, using the mechanomyograph, neuromuscularblock of six consecutive incremental doses of rocuronium 50µg kg^–1, followed by 300 µg kg^–1, wasevaluated. In the pharmacokinetics groups, serial arterial bloodsamples were withdrawn for rocuronium assay after a single doseof rocuronium 600 µg kg^–1. Results. ANH resulted in a shift to the left of rocuronium dose–responsecurve. Rocuronium effective dose₉₅ (ED₉₅) was 26% lower (P<0.05)in the ANH group [283.4 (92.0) µg kg^–1] comparedwith the control group [383.5 (127.3) µg kg^–1].Times from administration of last incremental dose until 25%of first response of train-of-four (TOF) recovery (Dur₂₅) and0.8 TOF ratio recovery (Dur_0.8) were 28% longer in the ANH group[39.9 (8.4), 66.7 (14.2) min] compared with the control group[31.1 (6.6), 52.1 (15.8) min] (P<0.01, P<0.05), respectively.Volume of distribution was higher (P<0.01), central clearancewas lower (P<0.05) and terminal elimination half-life waslonger (P<0.0001) in the ANH group [234.97 (47.11) ml kg^–1,4.70 (0.94) ml kg^–1 min^–1, 77.29 (12.25) min] comparedwith the control group [181.22 (35.73) ml kg^–1, 5.71 (1.29)ml kg^–1 min^–1, 56.86 (10.05) min, respectively]. Conclusion. ANH resulted in prolongation of rocuronium time-courseof action, thus careful monitoring of neuromuscular block isrecommended in patients who undergo ANH.     

Comparison of intubating conditions following propofol and succinylcholine with propofol and remifentanil 2 micrograms kg-1 or 4 micrograms kg-1

We evaluated the intubating conditions, haemodynamic responsesand duration of apnoea in 60 healthy adult patients after propofol2 mg kg^–1 combined with either a bolus of remifentanil2 µg kg^–1 or 4 µg kg^–1,or succinylcholine 1 mg kg^–1. Patients intubatedfollowing remifentanil showed dose-dependent intubating conditions,similar at 4 µg kg^–1 to the conditionsproduced with succinylcholine. Post-induction mean arterialpressure decreased from baseline values by 21% (P<0.0001),28% (P<0.0001) and 8% (P>0.05) in the remifentanil 2 µg kg^–1,remifentanil 4 µg kg^–1 and succinylcholine1 mg kg^–1 groups, respectively. The mean (SD)duration of apnoea following induction was 9.3 (2.6) minand 12.8 (2.9) min in the remifentanil 2 µg kg^–1and 4 µg kg^–1 groups, and 6.0 (0.9) minin the succinylcholine group (P<0.001 between groups). Br J Anaesth 2000; 85: 623--5     

Differential effects of thiopental on methacholine- and serotonin-induced bronchoconstriction in dogs

Background. Thiopental sometimes causes bronchospasm duringinduction of anaesthesia. In addition, we have reported previouslythat thiopental produced transient bronchospasm, which was blockedby atropine pretreatment, and worsened histamine-induced bronchoconstrictionin dogs. Previous in vitro reports suggest that synthesis ofcontractile cyclooxygenase products, such as thromboxane A₂,may be involved in the mechanism of bronchospasm. However, thein vivo spastic effects have not been defined comprehensively. Methods. Twenty-seven mongrel dogs were anaesthetized with pentobarbital.Bronchoconstriction was elicited with methacholine (0.5 µg kg^–1+5.0µg kg^–1 min^–1; Mch group, n=7) orserotonin (10 µg kg^–1+1 mg kg^–1 h^–1;5HT group, n=20), and assessed as percentage changes in bronchialcross-sectional area (BCA, basal=100%) using a bronchoscope.In the 5HT group, dogs were subdivided into four groups of fiveeach: S-5HT, I-5HT, 5HT-S and 5HT-A. In the S-5HT and I-5HTgroups, 30 min before serotonin infusion dogs were given salineand indomethacin respectively at 5 mg kg^–1 i.v. Inall groups, 30 min after bronchoconstrictor infusion started,dogs were given thiopental at doses between 0 (saline) and 20mg kg^–1. In the 5HT-S and 5HT-A groups, dogs weregiven saline or atropine 0.2 mg kg^–1 i.v. 5 min afterthiopental 20 mg kg^–1. Results. Methacholine and serotonin reduced BCA by about 50and 40% respectively. Thiopental 20 mg kg^–1 increasedand decreased BCA by about 20 and 10% in the Mch and 5HT groupsrespectively. Indomethacin and atropine did not attenuate thepotentiation of serotonin bronchoconstriction produced by thiopental. Conclusion. The present study indicates that thiopental mayattenuate or worsen bronchoconstriction induced by muscarinicor serotonin receptor stimulation, respectively. The synthesisof contractile cyclooxygenase products and cholinergic stimulationmay not be involved in the contractile effect of thiopentalon serotonin bronchoconstriction. Br J Anaesth 2003; 91: 379–84     

Pharmacokinetics of levobupivacaine 0.25% following caudal administration in children under 2 years of age

Background. Levobupivacaine, the S(–)enantiomer of racemicbupivacaine is less cardiotoxic than racemic bupivacaine andthe R(+)enantiomer dexbupivacaine, while retaining similar localanaesthetic properties and potency to racemic bupivacaine. Thepharmacokinetic profiles of the two bupivacaine enantiomersdiffers and that of racemic bupivacaine may be age dependent.We examined the pharmacokinetics of levobupivacaine after itssingle shot caudal epidural administration in children. Methods. An open-label phase 2 study was undertaken to examinethe pharmacokinetics of levobupivacaine 0.25% 2 mg kg^–1in 49 children aged less than 2 yr, after single shot caudalepidural administration. Plasma concentrations were determinedat intervals up to 60 min after caudal injection. Results. Time to peak plasma concentration (T_max) ranged between5 and 60 min (median 30 min) and was reached later in childrenaged less than 3 months (P<0.005). Peak plasma concentration(C_max) ranged between 0.41 and 2.12 µg ml^–1 (median0.80, mean (SD) 0.91 (0.40) µg ml^–1). Conclusion. After the caudal epidural administration of levobupivacaine2 mg kg^–1 in children less than 2 yr of age, C_max waswithin the accepted safe range for racemic bupivacaine. T_maxvaried and occurred later in some children, particularly thoseaged less than 3 months. Sampling in future pharmacokineticstudies in this age group should extend beyond 60 min. Br J Anaesth 2004; 92: 218–22     

Activation of electrocorticographic activity with remifentanil and alfentanil during neurosurgical excision of epileptogenic focus

Background. Opioids are known to stimulate surface electroencephalographicactivity in patients with temporal lobe epilepsy. The objectiveof the current study was to compare the electrocorticographicactivation effects of the newer short-acting opioid remifentanilwith those of alfentanil during epilepsy surgery under generalanaesthesia. Methods. Thirteen patients undergoing temporal lobe epilepsysurgery under general anaesthesia received alfentanil 30 µg kg^–1and remifentanil 1 µg kg^–1 as i.v. bolusesin sequence. The design was a randomized double-blind cross-overstudy. After opening the dura, electrocorticogram (ECoG) electrodecontact strips were placed over the temporal and supratemporalneocortex and depth electrodes were inserted in the amygdalaand hippocampus. Alfentanil 30 µg kg^–1or remifentanil 1 µg kg^–1 were administeredrandomly in a blinded fashion. The ECoG was recorded continuouslybefore and after the injection of each drug. The interictalepileptiform activity (spikes and sharp waves) above baselinewas analysed. Results. Both drugs increased epileptiform activity especiallythat recorded from depth electrodes in the temporal limbic structures.No epileptiform activity was recorded from the electrodes overlyingthe supratemporal neocortex before or after drug administration.The more potent activator was alfentanil, which caused an increasein activation from baseline of 99.8% compared with 67.4% forremifentanil. In addition, alfentanil activated the epileptiformactivity in 3 patients in which remifentanil had no effect.There were no changes in heart rate after the opioid boluses.Both remifentanil and alfentanil caused significant reductionsin blood pressure at 3 and 5 min after administration. Conclusion. We conclude that at the doses used in this study,alfentanil is the better opioid for intraoperative activationof the ECoG in neurosurgical patients undergoing resection ofa temporal lobe epileptic focus. This pharmacological activationof epileptiform activity assists in localizing and confirmingthe site of surgical excision. Neither alfentanil nor remifentanilactivated epileptiform activity in non-epileptic brain tissue. Br J Anaesth 2003; 91: 651–5     

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     

Comparison of the role of endothelin, vasopressin and angiotensin in arterial pressure regulation during sevoflurane anaesthesia in dogs

Background. In this study we aimed to clarify the role of endothelinin arterial pressure regulation during anaesthesia with increasingconcentrations of sevoflurane (1–3 MAC) and compare itwith those of vasopressin and angiotensin. Methods. After an awake control period, on different days, sixdogs underwent each of the following four interventions: sevofluraneanaesthesia alone (1–3 MAC), sevoflurane after block ofeither endothelin receptors using tezosentan (3 mg kg^–1followed by 3 mg kg^–1 h^–1), vasopressinV_1a receptors using [d(CH₂)₅Tyr(Me²)]AVP (40 µg kg^--1)or angiotensin receptors using losartan (6 mg kg^–1 h^–1).Plasma concentrations of endothelin, big endothelin, vasopressinand renin were measured. Effects of sevoflurane in the presenceand absence of the respective receptor block were analysed andcompared using analysis of variance for repeated measures (ANOVAfollowed by Fisher’s PLSD (protected least significantdifference) (P<0.05)). Results. Mean arterial pressure decreased in a dose-dependentmanner with sevoflurane during all interventions. At 1 MAC,this decrease was greatest during angiotensin receptor block(mean (SEM), –41 (3) mm Hg), intermediate duringvasopressin and endothelin receptor block (–31 (4) and–30 (2) mm Hg respectively), and least during sevofluranealone (–24 (3) mm Hg). The course of systemic vascularresistance mirrored the course of arterial pressure, while cardiacoutput did not differ between groups. Plasma concentrationsof endothelin, big endothelin and renin did not change duringany intervention, whereas vasopressin concentration increasedfrom     

Low-dose remifentanil infusion does not impair natural killer cell function in healthy volunteers

Background. Mu opioid agonists suppress natural killer (NK)cell activity in animal models. Studies in human volunteers,however, have yielded conflicting results, with morphine suppressingand fentanyl increasing NK cell activity. This study evaluatedthe effect of a constant 8-h infusion of remifentanil on NKcell number and function in human volunteers. Methods. After IRB approval and informed consent was obtained,10 healthy volunteers underwent an 11 pm to 7 am infusion ofsaline, and at least 1 week later an infusion of 0.02–0.04µg kg^–1 min^–1 remifentanil. Blood was collectedat 7 am for measurement of NK cell cytotoxicity using a ⁵¹Crrelease assay and measurement of NK cell number using fluorescentflow cytometry. Results. Median and range of the total NK cell cytoxicity (KUml^–1) was 745.0 (498.3–1483.6) on the control morningand 818.6 (238.5–1454.5) on the morning following theremifentanil infusion. Neither the number of NK cells ml^–1(2.5x10⁵ (1.4x10⁵–4.2x10⁵) vs 2.7x10⁵ (1.1x10⁵–4.4x10⁵))nor the cytotoxicity per 1000 NK cells (KU 1000 NK cells^–1)(3.0 (1.8–5.2) vs 2.9 (0.9–6.7)) changed betweenthe control and remifentanil conditions. Conclusions. An 8-h infusion of remifentanil did not affectNK cell activity in normal volunteers. This result differs fromprevious findings of morphine-induced NK cell activity suppressionand fentanyl-induced NK cell activity enhancement in normalvolunteers. Br J Anaesth 2003; 91: 805–9     

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