Memory priming during light anaesthesia with desflurane and remifentanil anaesthesia

Background: Previous studies of memory priming during anaesthesia with EEGmonitoring have observed implicit memory effects for words presentedduring light and deep anaesthesia with and without surgicalstimulation. We hypothesized that memory priming occurs undereach of five different combinations of anaesthesia and surgery,and no significant differences occur in memory priming amongthe five conditions or between the two test points such as,12 vs 24 h after surgery. Methods: Forty gynaecological patients (aged between 28 and 66 yr, median44.5 yr) were included in the study. They received propofoland remifentanil induction followed by desflurane and remifentanilanaesthesia in conjunction with neuromuscular blocking agents.Each patient was exposed to 60 of 120 nouns in a double-blindrandomized design. These 60 nouns were divided into 5 groupsof 12 words, presented under one of the five different conditions,namely, intubation, skin incision, deep anaesthesia and moderateanaesthesia (both during surgery), and light anaesthesia duringthe emergence phase. The depth of anaesthesia was measured usingthe EEG monitor, Narcotrend^TM. Results: No explicit memories were observed in a free recall or in ayes–no recognition test. A word-stem completion test revealeda significant implicit priming only for light anaesthesia (P< 0.01). No significant differences were detected among thefive conditions. An overall implicit memory effect occurredfor the second test point (P < 0.05). Conclusions: Our hypotheses could not be verified. Implicit memory primingoccurred only under light anaesthesia, when the patients weremost probably conscious. Priming effects may be enhanced afternight's sleep.     

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     

Analgesic and antacid properties of i.m. tramadol given before Caesarean section under general anaesthesia

Background. Intramuscular (i.m.) tramadol increases gastricpH during anaesthesia similar to famotidine. We investigatedthe antacid analgesic value of a single dose of i.m. tramadolgiven 1 h before elective Caesarean section performed undergeneral anaesthesia. Methods. Sixty ASA I parturients undergoing elective Caesareansection were included in a randomized double-blind study. Thepatients were randomly allocated to receive i.m. tramadol 100mg (n=30) or famotidine 20 mg (n=30) 1 h before general anaesthesia. Results. At the beginning and the end of anaesthesia, patientsreceiving tramadol had a median gastric fluid pH of 6.4, whichwas not significantly different from those treated with famotidine(median 6.3). The infant well-being, as judged by Apgar score,cord blood gas analysis, and neurobehavioural assessment showedno significant difference between the two groups. Nalbuphineconsumption in the first 24 h after operation was reduced by35% in the tramadol group. Pain intensity score on sitting andsedation were significantly greater in famotidine group up to24 h after surgery. There was no significant difference in incidenceand severity of nausea and vomiting between the two groups. Conclusion. A single i.m. dose of tramadol is useful pre-treatmentto minimize the risk of acid aspiration during operation, andin improving pain relief during 24 h after surgery.     

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     

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     

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     

Dose of alfentanil needed to obtain optimal intubation conditions during rapid-sequence induction of anaesthesia with thiopentone and rocuronium

Background: The primary aim of the present study was to determine the doseof alfentanil that must be added to a rapid-sequence induction(RSI) regimen using thiopentone and rocuronium to obtain optimalintubation conditions in >95% of the individuals. Methods: A total of 60 ASA I patients were randomly allocated to fivedifferent alfentanil dose groups (0, 15, 30, 45, or 60 µgkg^–1). A blinded dose of alfentanil followed by thiopentone4 mg kg^–1 and rocuronium 1 mg kg ^–1 was administeredin rapid succession, and tracheal intubation was attempted 40s thereafter. The relationship between the alfentanil dose andthe probability of optimal intubation conditions was determinedby non-linear logistic regression analysis. Blood pressure (BP)changes were recorded continuously using an intra-arterial catheter. Results: The success rate of optimal intubation conditions increasedwith increasing doses of alfentanil. The alfentanil dose neededto obtain optimal intubation conditions in >95% of the patientswas 36.4 (CI 33.4–39.4) µg kg^–1. In 12 patients,the systolic BP declined to <90 mm Hg during the 3 min immediatelyafter intubation. Conclusion: Adding 36–40 µg kg^–1 alfentanil to a regimenof thiopentone and rocuronium during RSI of anaesthesia maysignificantly increase the success rate of optimal intubationconditions. Significant hypotension requiring vasopressor treatmentmay occur.     

Rectal acetaminophen does not reduce morphine consumption after major surgery in young infants

BACKGROUND: The safety and value of acetaminophen (paracetamol) in additionto continuous morphine infusion has never been studied in newbornsand young infants. We investigated the addition of acetaminophento evaluate whether it decreased morphine consumption in thisage group after major thoracic (non-cardiac) or abdominal surgery. METHODS: A randomized controlled trial was performed in 71 patients giveneither acetaminophen 90–100 mg kg^–1 day^–1orplacebo rectally, in addition to a morphine loading dose of100 µg kg^–1 and 5–10 µg kg^–1h^–1 continuous infusion. Analgesic efficacy was assessedusing Visual Analogue Scale (VAS) and COMFORT scores. Extramorphine was administered if VAS was 4. RESULTS: We analysed data of 54 patients, of whom 29 received acetaminophenand 25 received placebo. Median (25–75th percentile) agewas 0 (0–2) months. Additional morphine bolus requirementsand increases in continuous morphine infusion were similar inboth groups (P = 0.366 and P = 0.06, respectively). There wasno significant difference in total morphine consumption, respectively,7.91 (6.59–14.02) and 7.19 (5.45–12.06) µg kg^–1 h^–1for the acetaminophen and placebo group (P = 0.60). COMFORT[median (25–75th percentile) acetaminophen 10 (9–12)and placebo 11 (9–13)] and VAS [median (25–75thpercentile) acetaminophen 0.0 (0.0–0.2) and placebo 0.0(0.0–0.3)] scores did not differ between acetaminophenand placebo group (P = 0.06 and P = 0.73, respectively). CONCLUSIONS: Acetaminophen, as an adjuvant to continuous morphine infusion,does not have an additional analgesic effect and should notbe considered as standard of care in young infants, 0–2months of age, after major thoracic (non-cardiac) or abdominalsurgery.     

Predictive performance of computer-controlled infusion of remifentanil during propofol/remifentanil anaesthesia

Background. The predictive performance of the available pharmacokineticparameter sets for remifentanil, when used for target-controlledinfusion (TCI) during total i.v. anaesthesia, has not been determinedin a clinical setting. We studied the predictive performanceof five parameter sets of remifentanil when used for TCI ofremifentanil during propofol anaesthesia in surgical patients. Methods. Remifentanil concentration–time data that hadbeen collected during a previous pharmacodynamic interactionstudy in 30 female patients (ASA physical status I, aged 20–65 yr)who received a TCI of remifentanil and propofol during lowerabdominal surgery were used in this evaluation. The remifentanilconcentrations predicted by the five parameter sets were calculatedon the basis of the TCI device record of the infusion rate–timeprofile that had actually been administered to each individual.The individual and pooled bias [median performance error (MDPE)],inaccuracy [median absolute performance error (MDAPE)], divergenceand wobble of the remifentanil TCI device were determined fromthe pooled and intrasubject performance errors. Results. A total of 444 remifentanil blood samples were analysed.Blood propofol and remifentanil concentrations ranged from 0.5to 11 µg ml^–1 and 0.1 to 19.6 ng ml^–1respectively. Pooled MDPE and MDAPE of the remifentanil TCIdevice were –15 and 20% for the parameter set of Mintoand colleagues (Anesthesiology 1997; 86: 10–23), 1 and21%, –6 and 21%, and –6 and 19% for the three parametersets described by Egan and colleagues (Anesthesiology 1996;84: 821–33, Anesthesiology 1993; 79: 881–92, Anesthesiology1998; 89: 562–73), and –24 and 30% for the parameterset described by Drover and Lemmens (Anesthesiology 1998; 89:869–77). Conclusions. Remifentanil can be administered by TCI with acceptablebias and inaccuracy. The three pharmacokinetic parameter setsdescribed by Egan and colleagues resulted in the least biasand best accuracy. Br J Anaesth 2003; 90: 132–41     

Changes in cortical electrical activity during induction of anaesthesia with thiopental/fentanyl and tracheal intubation: a quantitative electroencephalographic analysis

Background. There are regional differences in the effects ofanaesthetics agents and perioperative stimuli on the EEG. Westudied the topography of the EEG during induction of anaesthesiaand intubation in patients receiving thiopental and fentanylto document regional electrical brain activity. Methods. EEG was recorded in 25 patients in the awake state,after pre-medication, during induction, at loss of consciousnessand after intubation. Eight bipolar recordings were made andthe relative power of the frequency bands delta, theta, alpha,and beta were used (after z-score transformation for age) tomeasure changes in regional EEG activity. Results. Noxious stimulation during tracheal intubation partiallyreversed the slowing of the EEG caused by anaesthesia. Duringinduction of anaesthesia alpha activity was most reduced intemporal and occipital regions. The most prominent EEG changesafter intubation were an increase in alpha and a decrease indelta power (P<0.001). The largest changes were in the frontaland temporal leads for alpha and in the frontal and centralleads for delta. Heart rate and arterial pressure remained constantduring intubation. Conclusions. Changes in alpha and delta power were identifiedas the most sensitive EEG measures of regional changes in electricalbrain activity during anaesthesia and noxious stimulation. Br J Anaesth 2004; 92: 33–8     

Comparison of ocular microtremor and bispectral index during sevoflurane anaesthesia

Background. A practical and reliable monitor of depth of anaesthesiawould be a major advance on current clinical practice. Noneof the present monitors is both simple to use and accurate.Ocular microtremor (OMT) is a physiological tremor that is suppressedby propofol in a dose-dependent manner. We studied OMT duringpropofol induction and nitrous oxide– oxygen–sevofluranemaintenance of anaesthesia in 30 patients, and compared OMTwith the bispectral index (BIS) as a predictor of response toverbal command. Methods. OMT was measured using the closed-eye piezoelectricstrain-gauge technique. OMT and BIS were measured at specifictimes during the anaesthetic, including at loss of consciousness,at end-tidal sevoflurane 1 and 2%, and at emergence. Results. OMT decreased significantly after induction, did notdecrease as end-tidal sevoflurane was increased from 1 to 2%,and increased at emergence in all patients. By logistic regression,OMT was more sensitive and specific than BIS in distinguishingthe awake from the anaesthetized state (OMT, 84.9 and 93.1%respectively; BIS, 75.7 and 69.0%). Conclusions. OMT is suppressed by sevoflurane and accuratelypredicts response to verbal command. OMT may be a useful monitorof depth of hypnosis. Br J Anaesth 2002; 89; 551–5     

Tramadol disposition in the very young: an attempt to assess in vivo cytochrome P-450 2D6 activity

Background. Tramadol is potentially a very useful pain reliefmedication in neonates and infants. It is primarily metabolizedinto O-demethyl tramadol (M1) by CYP2D6. Data concerning tramadoldisposition and CYP2D6 activity in young infants are not available. Methods. A population pharmacokinetic analysis of tramadol andM1 time–concentration profiles was undertaken using non-linearmixed-effects models (NONMEM), based on newly collected dataon tramadol and M1 time–concentration profiles in neonatesand young infants (n=20) and published studies on intravenoustramadol in children and adults. M1 formation served as a surrogatefor CYP2D6 activity. Results. Tramadol clearance was described using a two-compartmentlinear model with zero-order input and first-order elimination.Clearance increased from 25 weeks post-conception age (PCA)(5.52 litre h^–1 [70 kg]^–1) to reach 84% of the maturevalue by 44 weeks PCA (standardized to a 70 kg adult using allometric‘1/4 power’ models). The central volume of distributiondecreased from 25 weeks PCA (256 litre [70 kg]^–1) to reach120% of its mature value by 87 weeks PCA. Formation clearanceto M1 contributed 43% of tramadol clearance, but had no relationshipwith PCA. There was a weak non-linear relationship between PCAand M1 metabolite clearance. Conclusions. Maturational clearance of tramadol is almost completeby 44 weeks PCA. A target concentration of 300 µg litre^–1is achieved after a bolus of tramadol hydrochloride 1 mg kg^–1and can be maintained by infusion of tramadol hydrochloride0.09 mg kg^–1 h^–1 at 25 weeks PCA, 0.14 mg kg^–1h^–1 at 30 weeks PCA, 0.17 mg kg^–1 h^–1 at 35weeks PCA, 0.18 mg kg^–1 h^–1 at 40 weeks, 0.19 mgkg^–1 h^–1 at 50 weeks PCA to 1 yr, 0.18 mg kg^–1h^–1 at 3 yr and 0.12 mg kg^–1 h^–1 in adulthood.CYP2D6 activity was observed as early as 25 weeks PCA, but theimpact of CYP2D6 polymorphism on the variability in pharmacokinetics,metabolism and pharmacodynamics of tramadol remains to be established.     

Adjunctive analgesia with intravenous propacetamol does not reduce morphine-related adverse effects

Background. Propacetamol is widely used in the management ofpostoperative pain. It decreases morphine requirements but itseffect on the incidence of morphine-related adverse effectsremains unknown. Methods. Patients (550) were randomly assigned to receive propacetamolor a placebo over the first 24 h after operation in a blindedstudy. Intravenous morphine titration was performed, after whichmorphine was administered s.c. every 4 h according to theirpain score. Pain was assessed using a visual analogue scale(VAS). The primary end-point was the incidence of morphine-relatedadverse effects. The main secondary end-points were morphinerequirements and VAS score. Results. After morphine titration, the VAS score and the numberof patients with pain relief did not differ between groups.Morphine requirements were decreased in the propacetamol group(21 vs 14.5 mg, P<0.001) but the incidence of morphine-relatedadverse effects did not differ between groups (42 vs 46%, notsignificant). In patients with moderate pain (n=395), morphinerequirements decreased by 37% (P<0.001) and the percentageof patients requiring no morphine was greater (21 vs 8%, P=0.002)in the propacetamol group. In patients with severe pain (n=155),morphine requirements decreased by 18% (P=0.04) in the propacetamolgroup and the number of patients who did not require morphine(3 vs 8%) did not differ significantly. Conclusions. Although propacetamol induced a small morphine-sparingeffect, it did not change the incidence of morphine-relatedadverse effects in the postoperative period. Moreover, no benefitcould be demonstrated in patients with severe postoperativepain. Br J Anaesth 2003; 90: 314–19     

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     

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     

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.     

Saliva cyclic GMP increases during anaesthesia

Background. Cyclic GMP (cGMP) has been implicated in modulatingthe effects of general anaesthesia. Changes in cGMP in humansundergoing anaesthesia have not been reported previously. Methods. In this pilot study we measured cGMP in the salivaof six healthy volunteers and eight patients undergoing generalanaesthesia for minor gynaecological procedures. Samples wereobtained using a commercially available sampling device andcGMP was determined with an enzyme immunoassay and results expressedas a cGMP per mg protein. Results. There was no statistically significant variation insalivary cGMP either day-to-day or between time points in healthyvolunteers. Analysis of variance of salivary cGMP of patientsundergoing general anaesthesia showed that cGMP increased significantlyintraoperatively and returned to preoperative levels after surgery(P=0.03). Conclusions. This is the first time that real time in vivo changesin salivary cGMP levels during general anaesthesia in humanshave been demonstrated and may allow an alternative techniquefor measuring depth of anaesthesia in the future. Br J Anaesth 2002; 89: 635–7     

Cerebral autoregulation in children during sevoflurane anaesthesia

Introduction. Little is known about cerebral autoregulationin children. The aim of this study was to examine cerebral autoregulationin children. Methods. Cerebral autoregulation testing was performed duringless than 1 MAC sevoflurane anaesthesia in children (from 6months to 14 yr) and in adults (18–41 yr). Mean middlecerebral artery flow velocities (V_MCA) were measured using transcranialDoppler ultrasonography. Mean arterial pressure (MAP) was increasedto whichever was greater: 20% above baseline or (i) 80 mm Hgfor less than 9 yr, (ii) 90 mm Hg for 9–14 yr, and (iii)100 mm Hg for adults. Cerebral autoregulation was consideredintact if the autoregulatory index was     

Mid-latency auditory evoked response during propofol and alfentanil anaesthesia

Background. Propofol has been shown to affect the mid-latencyauditory evoked response (MLAER) in a dose-dependant manner.Few studies have investigated the addition of alfentanil. Myogenicresponses, such as the post-auricular responses (PAR), can confoundthe MLAER but there has been little investigation as to whichelectrode site reduces this interference. Methods. We studied the MLAER in 27 women. They received aninfusion of alfentanil 15 µg kg^–1 h^–1, followedby either a high or low infusion regimen of propofol (finalinfusion rates 6 and 3 mg kg^–1 h^–1). We comparedthe results with those of our study using propofol alone. Wecollected the data from two electrode sites: vertex–inionand vertex–mastoid. We evaluated the occurrence of thePAR and the shape of the MLAER at each electrode site. Results. The infusion rate of propofol associated with lossof the eyelash response in 50% of subjects was 3.3 mg kg^–1h^–1. This was significantly lower than using propofolalone (5.8 mg kg^–1 h^–1). Nb latency was the bestMLAER discriminator of unconsciousness (sensitivity 94%, specificity88%), with a threshold of 46 ms (propofol alone was 53 ms).The addition of alfentanil did not alter the relationship betweenpropofol infusion rate and MLAER. The vertex–inion electrodesite gave the best protection against PAR in awake subjects(P=0.0003), and after 30 min of propofol infusion (P=0.06).The magnitude of the MLAER obtained from the vertex–mastoidelectrodes was larger than from the other site, although theincrease was not consistent throughout the waveform (brain stem100%, Nb 14%). Conclusions. Addition of alfentanil lowers the propofol infusionrate required to produce unconsciousness and the Nb latencythat predicts it. The better of the two sites to reduce theincidence of PAR is the vertex–inion electrode site. Br J Anaesth 2004; 92: 25–32     

Comparison of different quantitative sensory testing methods during remifentanil infusion in volunteers

Background. The aim of this study was to compare thermal andcurrent sensory testing stimuli with respect to opioid responsiveness. Methods. Eighteen healthy volunteers were randomized in a placebo-controlled,double-blind crossover study to receive an infusion of remifentanil0.08 µg kg^–1 min^–1 or saline for 40 min. Testprocedures included determination of pain perception thresholds(PPT) and pain tolerance thresholds (PTT) to heat, cold, andcurrent at 5, 250 and 2000 Hz, at baseline and at the end ofthe infusion. Results. Both current at 5 Hz (PPT 3.69 (SD 2.48) mA vs 2.01(1.52) mA; PTT 6.42 (2.79) mA vs 3.63 (2.31) mA; P<0.001)and 250 Hz (PPT 4.31 (2.42) mA vs 2.89 (1.57) mA; PTT 7.08 (2.68)mA vs 4.81 (2.42) mA; P<0.001) and heat (PPT 47.4 (2.7)°Cvs 45.2 (3)°C; PTT 51.1 (1.8)°C vs 49.7 (1.8)°C;P<0.05) detected a significant analgesic effect of remifentanilcompared with placebo. No analgesic effect was shown on coldor current at 2000 Hz. The magnitude of responsiveness of currentstimuli at 5 Hz and 250 Hz was superior to heat stimuli. Conclusion. Both current (5 and 250 Hz) and heat sensory testingdetected a significant analgesic effect of a remifentanil infusioncompared with saline. There was more response to current testing. Br J Anaesth 2003; 91: 203–8