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     

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     

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.     

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.     

Glycopyrrolate during sevoflurane-remifentanil-based anaesthesia for cardiac catheterization of children with congenital heart disease

Background. Remifentanil is recommended for use in procedureswith painful intraoperative stimuli but minimal postoperativepain. However, bradycardia and hypotension are known side-effects.We evaluated haemodynamic effects of i.v. glycopyrrolate duringremifentanil–sevoflurane anaesthesia for cardiac catheterizationof children with congenital heart disease. Methods. Forty-five children undergoing general anaesthesiawith remifentanil and sevoflurane were randomly allocated toreceive either saline, glycopyrrolate 6 µg kg^–1or glycopyrrolate 12 µg kg^–1. After induction ofanaesthesia with sevoflurane, i.v. placebo or glycopyrrolatewas administered. An infusion of remifentanil at the rate of0.15 µg kg^–1min^–1 was started, sevofluranecontinued at 0.6 MAC and cisatracurium 0.2 mg kg^–1 wasgiven. Heart rate (HR) and non-invasive arterial pressures weremonitored and noted every minute for the first 10 min and thenevery 2.5 min for subsequent maximum of 45 min. Results. Baseline HR [mean (SD)] of 117 (20) beats min^–1decreased significantly from 12.5 min onwards after startingthe remifentanil infusion in the control group [106 (18) at12.5 min and 99 (16) beats min^–1 at 45 min]. In the groupsreceiving glycopyrrolate, no significant decrease in HR wasnoticed. Glycopyrrolate at 12 µg kg^–1 induced tachycardiabetween 5 and 9 min after administration. Systolic and diastolicarterial pressures decreased gradually, but there were no significantdifferences in the pressures between groups. Conclusion. I.V. glycopyrrolate 6 µg kg^–1 preventsbradycardia during general anaesthesia with remifentanil andsevoflurane for cardiac catheterization in children with congenitalheart disease. Administering 12 µg kg^–1 of glycopyrrolatetemporarily induces tachycardia and offers no additional advantage.     

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     

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.     

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     

Dolasetron prophylaxis reduces nausea and postanaesthesia recovery time after remifentanil infusion during monitored anaesthesia care for extracorporeal shock wave lithotripsy

Background. Remifentanil is used as an analgesic for differentprocedures performed during monitored anaesthesia care. Opioid-inducednausea and vomiting can be troublesome. Methods. This prospective, randomized, double-blind study wasperformed to evaluate the efficacy of prophylaxis with dolasetronin reducing the frequency of postoperative nausea and durationof discharge time. Forty urological patients, undergoing electiveambulatory extracorporeal shock wave lithotripsy (ESWL) receivedrandomly either dolasetron 12.5 mg i.v. (Group 1) or placebo(Group 2) 10 min before a patient-adapted continuous infusionof remifentanil 0.15–0.4 µg kg^–1 min^–1was administered. Frequency and intensity (VAS 0–100 mm)of nausea, retching, and vomiting were assessed by patientsand blinded investigators during and after the procedure. Results. Patient characteristics, baseline values, durationof ESWL, and total dose of remifentanil did not differ betweengroups. The frequency (Group 1/Group 2; 20/55%; P<0.05) andmean (SD) maximal intensity [15 (9)/45 (14) mm; P<0.05] ofnausea during 24 h was significantly reduced after dolasetronand discharge times in Group 1 were less than Group 2[22 (14)/45 (28) min; P<0.05]. Br J Anaesth 2003; 90: 194–8     

Haemodynamic effects of remifentanil in children with and without intravenous atropine. An echocardiographic study

Background. Remifentanil is known to cause bradycardia and hypotension.We aimed to characterize the haemodynamic profile of remifentanilduring sevoflurane anaesthesia in children with or without atropine. Methods. Forty children who required elective surgery receivedinhalational induction of anaesthesia using 8% sevoflurane.They were allocated randomly to receive either atropine, 20µg kg^–1 (atropine group) or Ringer's lactate (controlgroup) after 10 min of steady-state 1 MAC sevoflurane anaesthesia(baseline). Three minutes later (T0), all children receivedremifentanil 1 µg kg^–1 injected over a 60 s period,followed by an infusion of 0.25 µg kg^–1 min^–1for 10 min then 0.5 µg kg^–1 min^–1 for 10 min.Haemodynamic variables and echocardiographic data were determinedat baseline, T0, T5, T10, T15 and T20 min. Results. Remifentanil caused a significant decrease in heartrate compared with the T0 value, which was greater at T20 thanT10 in the two groups: however, the values at T10 and T20 werenot significantly different from baseline in the atropine group.In comparison with T0, there was a significant fall in bloodpressure in the two groups. Remifentanil caused a significantdecrease in the cardiac index with or without atropine. Remifentanildid not cause variation in stroke volume (SV). In both groups,a significant increase in systemic vascular resistance occurredafter administration of remifentanil. Contractility decreasedsignificantly in the two groups, but this decrease remainedmoderate (between –2 and +2 SD). Conclusion. Remifentanil produced a fall in blood pressure andcardiac index, mainly as a result of a fall in heart rate. Althoughatropine was able to reduce the fall in heart rate, it did notcompletely prevent the reduction in cardiac index.     

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.     

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     

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.     

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     

Effects of remifentanil and alfentanil on the cardiovascular responses to induction of anaesthesia and tracheal intubation in the elderly

Background. We compared the effects of remifentanil and alfentanilon arterial pressure and heart rate at induction of anaesthesiaand tracheal intubation in 40 ASA I–III patients agedgreater than 65 yr, in a randomized double-blind study. Methods. Patients received either remifentanil 0.5 µgkg^–1 over 30 s, followed by an infusion of 0.1 µgkg min^–1 (group R) or alfentanil 10 µg kg^–1over 30 s, followed by an infusion of saline (group A). Anaesthesiawas then induced with propofol, rocuronium, and 1% isofluranewith 66% nitrous oxide in oxygen. Results. Systolic arterial pressure (SAP) and mean arterialpressure (MAP) decreased after the induction of anaesthesia(P<0.05) and increased for 3 min after intubation in bothgroups (P<0.05), but remained below baseline values throughout.Heart rate remained stable after induction of anaesthesia butincreased significantly from baseline after intubation for 1and 4 min in groups R and A, respectively (P<0.05). Therewere no significant between-group differences in SAP, MAP, andheart rate. Diastolic pressure was significantly higher in groupA than group R at 4 and 5 min after intubation (P<0.05).Hypotension (SAP <100 mm Hg) occurred in four patients ingroup R and three patients in group A. Conclusions. Remifentanil and alfentanil similarly attenuatethe pressor response to laryngoscopy and intubation, but theincidence of hypotension confirms that both drugs should beused with caution in elderly patients. Br J Anaesth 2002; 88: 430–3     

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     

Reducing stress responses in the pre-bypass phase of open heart surgery in infants and young children: a comparison of different fentanyl doses

High-dose opioids are advocated for paediatric cardiac surgeryto suppress stress responses but they can produce unwanted sideeffects. There are no data on the dose-dependent effects ofopioids on the stress response on which to base rational opioidadministration. We conducted a dose ranging study on 40 childrenless than 4 yr undergoing elective open heart surgery usingone of five fentanyl doses: 2, 25, 50, 100 or 150 µg kg^–1before surgery. The standardized anaesthetic also included pancuroniumand isoflurane. Blood samples were taken at induction, beforeincision, after sternotomy, immediately before, and at the endof cardiopulmonary bypass. Patients in the 2 µg kg^–1group had significant rises in pre-bypass glucose (P<0.01),pre- and post-bypass cortisol (P<0.01), and pre- and post-bypassnorepinephrine (P<0.01). No significant rise occurred inglucose, cortisol and catecholamines in any of the higher dosagegroups. Patients in the 2 µg kg^–1 group had significantlyhigher mean systolic blood pressure (P<0.02) and heart rate(P<0.04). A balanced anaesthetic containing fentanyl 25–50µg kg^–1 is sufficient to obtund haemodynamic andstress responses to the pre-bypass phase of surgery. Higherdoses of fentanyl (100 and 150 µg kg^–1) offer littleadvantage over 50 µg kg^–1, and can necessitate interventionto prevent hypotension.     

Prevention of postoperative nausea and vomiting by continuous infusion of subhypnotic propofol in female patients receiving intravenous patient-controlled analgesia

In this prospective, randomized, double-blind, placebo-controlledstudy, the use of continuous subhypnotic propofol infusion asan antiemetic in fentanyl intravenous patient-controlled analgesia(i.v. PCA) was investigated during the first 24 h after surgery.One hundred female patients, ASA I–II, aged 20–71yr, undergoing major gynaecological or orthopaedic surgery,were included. Either propofol 10 mg or placebo (1 ml of Intralipid)was given and one of the following five regimens was maintainedfor 24 h: propofol 5, 10, 15 or 20 µg kg^–1 min^–1or Intralipid 1 ml h^–1 as a placebo. Fentanyl i.v. PCAwas started in the postanaesthesia care unit for postoperativeanalgesia. Significantly more of the patients given propofol15 and 20 µg kg^–1 min^–1 experienced no nauseaor vomiting compared with those given placebo (65% and 70% versus25%; P<0.05). Patients given propofol 20 µg kg^–1min^–1 reported more sedation than those in the other groups4 h after surgery (P<0.05). Br J Anaesth 2000; 85: 898–900     

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