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     

Testing of a new pneumatic device to cause pain in humans

Background. Surgical pain typically combines superficial anddeep pain. We wished to generate pain that resembled surgicalpain, reliably and reproducibly, in volunteers. Methods. We constructed a computer-controlled pneumatic deviceto apply pressure to the anterior tibia. The reproducibilityof the pain was tested by rating the pressure that caused painrated 4–5 on a visual analogue scale (VAS) on days 0,7, and 24 in 10 volunteers. The effect of remifentanil (0.025,0.05, 0.075, and 0.1 µg kg^–1 min^–1) on paintolerance in another set of volunteers (n=11) was used as anindirect measure of the reliability of pain production. Results. The pressure needed (0.7 (0.3) to 0.9 (0.4) atm (mean(SD)) to induce pain rated 4–5 (VAS) did not vary, showinglong-term reproducibility of the method. When pressure was appliedto cause increasing pain in volunteers (n=11) 0.05 µgkg^–1 min^–1 remifentanil increased pain toleranceby 50%. An approximate doubling of the dose (0.1 µg kg^–1min^–1) increased pain tolerance significantly more. Thelinear logarithmic dose-effect relationship shows that the devicecauses pain reliably, and this can be reduced with opioid treatment. Conclusion. This pneumatic device can apply pain reliably andreproducibly. Br J Anaesth 2004; 92: 532–5     

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     

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     

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     

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     

Pharmacokinetics of remifentanil and its major metabolite, remifentanil acid, in ICU patients with renal impairment

Background. The pharmacokinetics of remifentanil, an opioidanalgesic metabolized by non-specific esterases, and its principalmetabolite, remifentanil acid (RA), which is excreted via thekidneys, were assessed as part of an open-label safety studyin intensive care unit (ICU) patients with varying degrees ofrenal impairment. Methods. Forty adult ICU patients with normal/mildly impairedrenal function (creatinine clearance [CL_cr] 62.9 (SD) 14.5 mlmin^–1; n=10) or moderate/severe renal impairment (CL_cr14.7 (15.7) ml min^–1; n=30) were included. Remifentanilwas infused for up to 72 h, at a starting rate of 6–9µg kg^–1 h^–1 titrated to achieve a target sedationlevel, with additional propofol (0.5 mg kg^–1 h^–1)if required. Intensive arterial sampling was performed for upto 72 h after infusion. Pharmacokinetic parameters obtainedby simultaneous modelling of remifentanil and RA data were statisticallycompared between the two groups. Results. Remifentanil pharmacokinetics were not significantlyaffected by renal status. RA clearance in the moderate/severegroup was reduced to about 25% that of the normal/mild group(41 (29) vs 176 (49) ml kg^–1 h^–1, P<0.0001).Metabolic ratio, a predictor of the ratio of RA to remifentanilconcentrations at steady state, was approximately eight-foldhigher in the moderate/severe group relative to the normal/mildgroup (116 (110) vs 15 (4), P<0.0001). Maximum RA levelsapproached 700 ng ml^–1 in the moderate/severe group. Conclusions. Although RA accumulates in patients with moderate/severerenal impairment, pharmacokinetic modelling predicts that RAconcentrations during a 9 µg kg^–1 h^–1 remifentanilinfusion for up to 15 days would not exceed those reported inthe present study, for which no associated prolongation of µ-opioideffects was observed. Br J Anaesth 2004; 92: 493–503     

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     

No clinical evidence of acute opioid tolerance after remifentanil-based anaesthesia

We have prospectively assessed whether remifentanil-based anaesthesiais associated with clinically relevant acute opioid tolerance,expressed as greater postoperative pain scores or morphine consumption.Sixty patients undergoing elective gynaecological, non-laparoscopic,surgery were randomly assigned to receive remifentanil (groupR, n=30) or sevoflurane (group S, n=30) based anaesthesia. Postoperativeanalgesia was provided with morphine through a patient-controlledinfusion device. Mean (SD) remifentanil infusion rate in groupR was 0.23 (0.10) µg kg^–1 min^–1 and mean inspiredfraction of sevoflurane in group S was 1.75 (0.70)%. Mean (SD)cumulative morphine consumption during the first 24 postoperativehours was similar between groups: 28.0 (14.2) mg (group R) vs28.6 (12.4) mg (group S). Pain scores, were also similar betweengroups during this period. These data do not support the developmentof acute opioid tolerance after remifentanil-based anaesthesiain this type of surgery. Br J Anaesth 2001; 87: 866–9     

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     

Effects of fentanyl, alfentanil, remifentanil and sufentanil on loss of consciousness and bispectral index during propofol induction of anaesthesia

The bispectral index (BIS) and a sedation score were used todetermine and compare the effect of propofol in the presenceof fentanyl, alfentanil, remifentanil and sufentanil. Seventy-fivenon-premedicated patients were assigned randomly into five groups(15 in each) to receive fentanyl, alfentanil, remifentanil,sufentanil or placebo. Opioids were administered using a target-controlledinfusion device, to obtain the following predicted effect-siteconcentrations: fentanyl, 1.5 ng ml^–1; alfentanil, 100ng ml^–1; remifentanil, 6 ng ml^–1; and sufentanil,0.2 ng ml^–1. After this, a target-controlled infusionof propofol (Diprifusor) was started to increase concentrationgradually, to achieve predicted effect-site concentrations of1, 2, and 4 µg ml^–1. At baseline and at each successivetarget effect-site concentration of propofol, the BIS, sedationscore and haemodynamic variables were recorded. At the momentof loss of consciousness (LOC), the BIS and the effect-siteconcentration of propofol were noted. The relationship betweenpropofol effect-site concentration and BIS was preserved withor without opioids. In the presence of an opioid, LOC occurredat a lower effect-site concentration of propofol and at a higherBIS₅₀ (i.e. the BIS value associated with 50% probability ofLOC), compared with placebo. Although clinically the hypnoticeffect of propofol is enhanced by analgesic concentrations ofµ-agonist opioids, the BIS does not show this increasedhypnotic effect. Br J Anaesth 2001; 86: 523–7     

Remifentanil and nitrous oxide reduce changes in cerebral blood flow velocity in the middle cerebral artery caused by pain

Background. Cerebral blood flow is affected by painful stimuli,and analgesic agents may alter the response of cerebral bloodflow to pain. We set out to quantify the effects of remifentaniland nitrous oxide on blood flow changes caused by experimentalpain. Methods. We simulated surgical pain in 10 conscious volunteersusing increasing mechanical pressure to the tibia. We measuredchanges in cerebral blood flow velocity in the middle cerebralartery (CBFV_MCA) caused by the pain, using transcranial Dopplersonography. We gave increasing doses of remifentanil (0.025,0.05 and 0.1 µg kg^–1 min^–1)or nitrous oxide [20%, 35% and 50% end-tidal concentration (FE'_N2O)]and compared these effects on blood flow changes. Results. Nitrous oxide increased CBFV_MCA only when given at50% FE'_N2O. Remifentanil did not affect CBFV_MCA. Pain increasedCBFV_MCA. Both agents attenuated this pain-induced change inCBFV_MCA with the exception of nitrous oxide at 20% FE'_N2O. Conclusions. Inhalation of nitrous oxide or adminstration ofremifentanil attenuated pain-induced changes in CBFV_MCA. Br J Anaesth 2003: 90: 296–9     

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     

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     

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     

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.     

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     

Tramadol does not modify the Bispectral Index during anaesthesia with sevoflurane and remifentanil

Background. The aim of this study was to investigate the effectsof tramadol administered with ketorolac on the Bispectral Index(BIS) during anaesthesia with sevoflurane and remifentanil. Methods. Forty-six adult patients, ASA I–III, scheduledfor elective minor surgical procedures were studied. Patientswere premedicated with remifentanil infusion 0.4 µg kg^–1min^–1 and anaesthesia was induced 4–5 min laterwith propofol 1.5 mg kg^–1 and maintained with air–oxygen( 0.4), remifentanil 0.1–0.15 µg kg^–1 min^–1 and sevoflurane, adjusted to keep theBIS between 40 and 50. After 20 min of stable anaesthesia, thesubjects were allocated randomly to receive i.v. tramadol 1.5mg kg^–1 and i.v. ketorolac 0.3 mg kg^–1 (tramadolgroup) or saline (control group). BIS values, mean arterialpressure, heart rate and end-tidal carbon dioxide were recordedevery 5 min for 20 min. Results. Mean BIS values after tramadol administration werenot significantly different from those recorded in patientsreceiving saline throughout the period of observation. Therewere no patients who presented explicit recall of events underanaesthesia. No significant changes in mean arterial pressure,heart rate and end-tidal carbon dioxide were noted after tramadolinjection. Conclusion. Tramadol, given with ketorolac to prevent postoperativepain, during anaesthesia maintained with sevoflurane and remifentanilat BIS between 40 and 50, does not modify the BIS value.     

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     

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