Effect of an intubation dose of rocuronium on Spectral Entropy and Bispectral Index responses to laryngoscopy during propofol anaesthesia

Background. The spectral entropy of the electroencephalogramhas been proposed to monitor the depth of anaesthesia. StateEntropy (SE) reflects the level of hypnosis. Response Entropy(RE), computed from electroencephalogram and facial muscle activity,reflects the response to nociceptive stimulation. We evaluatedthe effect of rocuronium on Bispectral Index^TM (BIS) and entropyresponses to laryngoscopy. Methods. A total of 25 patients were anaesthetized with propofolusing a target-controlled infusion. At steady state, they randomlyreceived 0.6 mg kg^–1 rocuronium (R) or saline (S). After3 min, a 20 s laryngoscopy was applied. BIS, RE and SE wererecorded continuously and averaged over 1 min during baseline,at steady state, 2 min after R or S administration (R/S+2) and0, 1, 2 and 3 min after laryngoscopy (L0, L1, L2, L3). Results. At R/S+2, the RE–SE gradient was higher in GroupS than in Group R. Laryngoscopy provoked an increase in BIS,RE and SE. Comparing R/S+2 and L0 values in Groups R and S,BIS increased from 43 (6) to 49 (8) and 42 (9) to 51 (15), SEincreased from 43 (7) to 50 (8) and 41 (10) to 55 (12), andRE increased from 46 (8) to 54 (9) and 47 (12) to 66 (15), respectively.BIS and SE did not differ between groups. At L0, RE and RE–SEwere higher in Group S [66 (15) and 11 (4), respectively] thanin Group R [54 (9) and 4 (2), respectively]. Conclusions. Rocuronium alters the RE–SE gradient andthe RE and RE–SE responses to laryngoscopy. Muscle relaxationmay confound interpretation of entropy monitoring.     

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.     

Spectral entropy measurement of patient responsiveness during propofol and remifentanil. A comparison with the bispectral index

Background. We compared two spectral entropies, state entropy(SE) and response entropy (RE), based on the irregularity ofthe EEG, to measure loss of response to verbal command (LOR_verbal)and noxious stimulus (LOR_noxious) with the bispectral index(BIS) during propofol infusion with and without remifentanil. Methods. Three groups of 20 patients received an effect-sitecontrolled propofol infusion (Ce_PROP) starting at 1 µgml^–1 and increased in steps of 0.5 µg ml^–1at 4 min intervals. In addition, a remifentanil infusion wasmaintained at a group-dependent, fixed effect-site target concentration(Ce_REMI) (0, 2 or 4 ng ml^–1). The ability of BIS, SE orRE to predict LOR_verbal and LOR_noxious were compared with thechanges in BIS, SE and RE using logistic regression, predictionprobability (P_K), and sensitivity/specificity. Results. In all groups, BIS, SE and RE decreased with increasingCe_PROP. However, BIS decreased more smoothly than SE and REat deeper levels of sedation. At LOR_verbal, BIS₅₀, SE₅₀ andRE₅₀ increased with increasing Ce_REMI. BIS, SE and RE all detectedLOR_verbal accurately but BIS performed better at 100% sensitivity.Sensitivity/specificity for detection of LOR_verbal decreasedfor all methods with increasing Ce_REMI. LOR_noxious was poorlydescribed by all measures. Conclusion. LOR_verbal was detected accurately by BIS, SE andRE except for 100% sensitivity, where BIS performed better.Though BIS, SE and RE were influenced by remifentanil duringpropofol administration, their ability to detect LOR_verbal remainedaccurate. None of the measures predicted LOR_noxious.      

Relationship between bispectral index, electroencephalographic state entropy and effect-site EC50 for propofol at different clinical endpoints

Background. State entropy (SE) is a newly available monitorfor depth of anaesthesia. We investigated whether the relationshipbetween predicted effect-site propofol concentration and bothbispectral index (BIS) and SE values is useful for predictingloss of verbal contact and loss of consciousness during steady-stateconditions. Methods. Twenty unpremedicated patients undergoing electivemajor abdominal surgery were recruited. A target-controlledinfusion of propofol was administered using Schneider's pharmacokineticmodel. The propofol infusion was set at an initial site-effectconcentration of 1.0 µg ml^–1, and increased by 1.0µg ml^–1 steps every 4 min, up to 6.0 µg ml^–1.A 4-min interval was chosen to ensure that steady-state site-effectconcentrations were obtained. Propofol site-effect concentrationsand BIS and SE values were recorded at loss of verbal contact(LVC) and loss of consciousness (LOC). Population values forpredicted effect-site concentrations at the clinical endpointswere estimated and correlated with BIS and SE values. Results. For LVC, the effect-site concentration for 90% of patientswas 1.1 (1.1–3.2) µg ml^–1 and for LOC 2.8(2.8–5.65) µg ml^–1. LVC occurred in 90% ofpatients at a BIS value of 70.2 (70.2–90.2) and an SEvalue of 60.3 (60.3–75.5) and LOC occurred at a BIS valueof 38.2 (38.2–70.4) and an SE value of 42.2 (42.2–60.4). Conclusions. LVC and LOC occurred within a defined range ofpredicted effect-site concentrations. SE had a smaller rangethan BIS and higher correlation with effect-site concentrationand may be more useful than BIS in predicting both LVC and LOC.     

Pharmacokinetics and haemodynamics of ketamine in intensive care patients with brain or spinal cord injury

Background. Ketamine is used as an anaesthetic agent for shortsurgical procedures, and as a sedative and analgesic in intensivecare patients. Intensive care patients with brain or spinalcord injury may have physiological changes that could alterthe pharmacokinetics of ketamine. The pharmacokinetics of ketaminehave been studied in healthy volunteers and in patients undergoingdifferent types of surgery, but no data are available in intensivecare patients. Methods. We determined the pharmacokinetics of ketamine andits active metabolites, norketamine and dehydronorketamine,in 12 intensive care patients with brain or spinal cord injury.The effect of ketamine on haemodynamic variables was also investigated. Results. The total clearance of ketamine, mean (SD), was 36.0(13.3) ml min^–1 kg^–1, the volume of distribution(Vß) was 16.0 (8.6) litre kg^–1, and the eliminationhalf-life was 4.9 (1.6) h. Ketamine did not alter any haemodynamicvariables in the patients studied. Conclusions. Pharmacokinetic variables of ketamine in intensivecare patients are greater than in healthy volunteers and insurgical patients. The increase in the volume of distributionis greater than the increase in clearance, resulting in a longerestimated half-life of ketamine in this patient group. Br J Anaesth 2003; 90: 155–60     

Relationship between Bispectral Index, electroencephalographic state entropy and effect-site EC50 for propofol at different clinical endpoints

Background. State entropy (SE) is a newly available monitorfor depth of anaesthesia. We investigated whether the relationshipbetween predicted effect-site propofol concentration and BispectralIndex (BIS) and SE values is useful for predicting loss of verbalcontact and loss of consciousness during steady-state conditions. Methods. Twenty unpremedicated patients undergoing electivemajor abdominal surgery were recruited. A target-controlledinfusion of propofol was administered using Schneider's pharmacokineticmodel. The propofol infusion was set at an initial site effectconcentration of 1.0 µg ml^–1 and increased by 1.0µg ml^–1 steps every 4 min up to 6.0 µg ml^–1.A 4-min interval was chosen to ensure that steady-state effect-siteconcentrations were obtained. Propofol site effect concentrationsand BIS and SE values were recorded at loss of verbal contact(LVC) and loss of consciousness (LOC). Population values forpredicted effect-site concentrations at the clinical endpointswere estimated and correlated with BIS and SE values. Results. For LVC, the effect-site concentration for 90% of patientswas 1.1 (1.1–3.2) µg ml^–1 and for LOC it was2.8 (2.8–5.65) µg ml^–1. LVC occurred in 90%of patients at a BIS value of 70.2 (70.2–90.2) and anSE value of 60.3 (60.3–75.5), and LOC occurred at a BISvalue of 38.2 (38.2–70.4) and an SE value of 42.2 (42.2–60.4). Conclusions. LVC and LOC occurred within a defined range ofpredicted effect-site concentrations. SE had a smaller rangethan BIS and greater correlation with effect-site concentrationand may be more useful than BIS in predicting both LVC and LOC.     

Do we need inhaled anaesthetics to blunt arousal, haemodynamic responses to intubation after i.v. induction with propofol, remifentanil, rocuronium?

Background. The aim of this study was to determine whether,after propofol, rocuronium and remifentanil rapid sequence induction,inhaled anaesthetic agents should be started before intubationto minimize autonomic and arousal response during intubation. Methods. One hundred ASA I and II patients were randomized toreceive 1 MAC of desflurane or sevoflurane during manual ventilationor not. Anaesthesia was induced with an effect-site-controlledinfusion of remifentanil at 2 ng ml^–1 for 3 min. Patientsthen received propofol to induce loss of consciousness (LOC).Rocuronium (0.6 mg kg^–1) was given at LOC and the tracheawas intubated after 90 s of manual breathing support (=baseline)with or without inhaled anaesthetics. Vital signs and bispectralindex (BIS) were recorded until 10 min post-intubation to detectautonomic and arousal response. Results. A significant increase in BIS value after intubationwas seen in all groups. The increases were mild, even in thosenot receiving pre-intubation inhaled anaesthetics. However,in contrast to sevoflurane, desflurane appeared to partiallyblunt the arousal response. Heart rate, systolic and diastolicpressure increase similarly in all groups. Conclusions. Desflurane and sevoflurane were unable to bluntthe arousal reflex completely, as measured by BIS, althoughthe reflex was significantly less when desflurane was used.Rapid sequence induction with remifentanil, propofol and rocuroniumand without inhaled anaesthetics before intubation can be donewithout dangerous haemodynamic and arousal responses at intubationafter 90 s.     

Combined use of Bispectral Index and A-Line Autoregressive Index to assess anti-nociceptive component of balanced anaesthesia during lumbar arthrodesis

Background. This study evaluated the A-Line Autoregressive Index(AAI) response to surgical stimulation during lumbar arthrodesis,as an estimate of the anti-nociceptive component of a BispectralIndex (BIS) guided anaesthesia combined with epidural analgesia. Methods. An epidural catheter was inserted in 23 patients allocatedrandomly to receive ropivacaine plus clonidine (Group R) ornormal saline (Group S) epidurally. General anaesthesia wasinduced with propofol, cis-atracurium and a remifentanil infusionthat was stopped 3 min after tracheal intubation, and maintainedusing sevoflurane to keep BIS at 50 (range 40–60). Meanarterial pressure, heart rate, end-tidal sevoflurane, BIS andAAI were analysed from 2 min before to 17 min after surgicalincision. Results: While BIS was maintained at 50, AAI significantly increasedfrom a 2 min averaged value of 12 (4) to 21 (7) in Group S withinthe first 5 min after surgical incision, but did not changein Group R. Maximum AAI values reached during the study periodwere significantly higher in Group S than in Group R [38 (12)and 27 (10), respectively]. Binary logistic regression analysisallowed the calculation of AAI threshold values above whichthe probability of predominant nociception over anti-nociceptionwas higher than 95%. At 1 MAC sevoflurane concentration, a 2min averaged AAI of 35 or an AAI peak value of 62 were associatedwith such a probability. Conclusions. During a BIS-guided constant level of hypnosis,AAI response to the onset of surgical stimulation significantlydiffers according to the analgesic regimen. Further studiesare needed to refine the estimation of sensitivity and specificityof this variable in assessing the balance between nociceptionand anti-nociception during general anaesthesia.     

Efficacy of prophylactic ketamine in preventing postoperative shivering

Background. Treatment with ketamine and pethidine is effectivein postoperative shivering. The aim of this study was to comparethe efficacy of low-dose prophylactic ketamine with that ofpethidine or placebo in preventing postoperative shivering. Methods. A prospective randomized double-blind study involved90 ASA I and II patients undergoing general anaesthesia. Patientswere randomly allocated to receive normal saline (Group S, n=30),pethidine 20 mg (Group P, n=30) or ketamine 0.5 mg kg^–1(Group K, n=30) intravenously 20 min before completion of surgery.The anaesthesia was induced with propofol 2 mg kg^–1, fentanyl1 µg kg^–1 and vecuronium 0.1 mg kg^–1. It wasmaintained with sevoflurane 2–4% and nitrous oxide 60%in oxygen. Tympanic temperature was measured immediately afterinduction of anaesthesia, 30 min after induction and beforeadministration of the study drug. An investigator, blinded tothe treatment group, graded postoperative shivering using afour-point scale and postoperative pain using a visual analoguescale (VAS) ranging between 0 and 10. Results. The three groups did not differ significantly regardingpatient characteristics. The number of patients shivering onarrival in the recovery room, and at 10 and 20 min after operationwere significantly less in Groups P and K than in Group S. Thetime to first analgesic requirement in Group S was shorter thanin either Group K or Group P (P<0.005). There was no differencebetween the three groups regarding VAS pain scores. Conclusion. Prophylactic low-dose ketamine was found to be effectivein preventing postoperative shivering.     

A comparison of the SNAP II and BIS XP indices during sevoflurane and nitrous oxide anaesthesia at 1 and 1.5 MAC and at awakening

Background. Monitoring level of consciousness during anaesthesia,with the ability to predict the intentional or unintentionalreturn to consciousness, is desirable. The purpose of this studywas to compare two processed electroencephalographic depth ofanaesthesia monitors (SNAP II^TM and BIS XP^TM) during sevofluraneand sevoflurane/nitrous oxide anaesthesia. Methods. In total, 42 subjects received an interscalene block,followed by general anaesthesia with sevoflurane or sevoflurane/nitrousoxide. The indices were recorded at baseline, at 1.5 and 1.0minimum alveolar concentration (MAC) equivalents, and duringemergence. Results. The SNAP and BIS indices decreased from baseline at1.5 and 1.0 MAC equivalents, but there was no difference withingroups between subjects who received nitrous oxide and thosewho did not. The SNAP index returned to baseline by 1 min beforeawakening and was higher than baseline at eye opening, but theBIS index remained below baseline at awakening. There was abias of –1 (95% CI: –3 to 1) between the SNAP andBIS at baseline; this increased to 21 (95% CI: 19–23)during maintenance of anaesthesia and was 6 (95% CI: 4–8)at awakening. Conclusions. The SNAP index tracks loss of consciousness andemergence from sevoflurane and sevoflurane/nitrous oxide anaesthesia.There is significant bias between the SNAP and BIS indices andtherefore, the indices are not interchangeable. The SNAP indexreturns to baseline before awakening, whereas the BIS indexremains below baseline at awakening, suggesting that the SNAPindex may be more sensitive to unintentional awareness.      

Novel multiparameter approach for measurement of nociception at skin incision during general anaesthesia

Background. Direct indicators for the evaluation of the nociceptive–anti-nociceptivebalance during general anaesthesia do not exist. The aim ofthis study was to combine physiological parameters to obtainsuch an indicator. Methods. Fifty-five females scheduled for surgery under generalanaesthesia combining target-controlled infusions of propofoland remifentanil were studied. Propofol was given to maintainstate entropy (SE) at 50 and remifentanil was targeted at 1,3 or 5 ng ml^–1. The patients' reactions and clinical signsof nociception, remifentanil levels and estimation of noxiousintensity of incision were combined into a clinical score [ClinicalSigns–Stimulus–Antinociception (CSSA)] to evaluatethe nociceptive–anti-nociceptive balance. ECG, photoplethysmography(PPG), response entropy (RE) and SE were recorded from 60 sbefore to 120 s after skin incision. Differences between post-and pre-incision values of heart rate variability (HRV), PPGand pulse transition time related parameters were analysed off-lineto evidence the best predictors of CSSA. Those best predictorsof CSSA served to develop a response index of nociception (RN),scaled from 0 to 100. This index was further tested in 10 additionalpatients. Results. HRV, RE, RE–SE and PPG variability were the bestpredictors of CSSA. The prediction probability of RN at predictingCSSA was 0.78. RN response was higher after larger incision,in movers and with lower remifentanil concentrations. Conclusions. The empirically developed algorithm of RN leadsto an index that seems to adequately estimate the nociceptive–anti-nociceptivebalance at skin incision during general anaesthesia. In thefuture, CSSA may serve as a reference for studies investigatingmethods aimed at evaluating this pharmacodynamic component ofanaesthesia.      

Esmolol prevents movement and attenuates the BIS response to orotracheal intubation

Background. Beta-adrenergic agonists enhance behavioural andelectroencephalographic arousal reactions. We explored whetheradding esmolol, a short-acting ß₁-adrenoceptor antagonist,to propofol anaesthesia modified the bispectral index (BIS)during induction of anaesthesia and orotracheal intubation. Methods. Fifty patients were randomly allocated, in a double-blindfashion, to receive esmolol 1 mg kg^–1 followed by 250µg kg^–1 min^–1 or saline (control). Esmololor saline was started 6 min after a target-controlled infusion(TCI) of propofol (effect-site concentration 4 µg ml^–1).After loss of consciousness, and before administration of vecuronium0.1 mg kg^–1, a tourniquet was applied to one arm and inflatedto 150 mm Hg greater than systolic pressure. Eleven minutesafter the TCI began, the trachea was intubated; gross movementwithin the first min after orotracheal intubation was recorded.BIS was recorded at 10-s intervals. Mean arterial pressure (MAP)and heart rate were measured non-invasively every min. Results. There were no intergroup differences in BIS, heartrate or MAP before laryngoscopy. BIS increased significantlyafter orotracheal intubation (compared with the pre-laryngoscopyvalues) in the control group only, with a maximum increase of40 (SD 18)% vs 8 (11)% in the esmolol group (P<0.01). Maximumchanges in heart rate [45 (19)% vs 23 (14)%] and MAP [62 (24)%vs 45 (23)%] with orotracheal intubation were also significantlygreater in the control group than in the esmolol group. Morepatients in the control than in the esmolol group moved afterorotracheal intubation (23 vs 12, P<0.01). Conclusion. Esmolol not only attenuated haemodynamic and somaticresponses to laryngoscopy and orotracheal intubation, but alsoprevented BIS arousal reactions in patients anaesthetized withpropofol. Br J Anaesth 2002; 89: 857–62     

Performance of entropy and Bispectral Index as measures of anaesthesia effect in children of different ages

Background. Entropy and Bispectral Index^TM (BIS^TM) have beenpromoted as EEG-based anaesthesia depth monitors. The EEG changeswith brain maturation, but there are limited published datadescribing the characteristics of entropy in children, and somedata suggest that BIS is less reliable in young children. Theaim of this study was to compare the performance of entropyas a measure of anaesthetic effect in different age groups.The performance of entropy was compared with BIS. Methods. Fifty-four children receiving a standard sevofluraneanaesthetic for cardiac catheter studies were enrolled. Theentropy and BIS were recorded pre-awakening and at 1.5%, 2%and 2.5% steady-state end-tidal sevoflurane concentrations.For analysis children were divided into four age groups: 0–1yr, 1–2 yr, 2–4 yr and 4–12 yr. Results. The pre-awakening values were obtained in 46 children.The median pre-awakening values for entropy and BIS varied significantlyacross ages with the values being lowest in the 0–1 yrage group (response entropy: 45 vs 84, 87 and 89, P=0.003; stateentropy: 36 vs 78, 74 and 77, P=0.009; BIS: 56 vs 78, 76.5 and72, P=0.02). Values were recorded at all three sevoflurane concentrationsin 48 children. Compared with older groups, the 0–1 yrage group had the least significant difference in BIS and entropywhen compared among different sevoflurane concentrations. Thecalculated sevoflurane concentrations to achieve mid-scale valuesof entropy and BIS were highest in the 1–2 yr age group,lower in the 0–1 yr age group and progressively lowerin the 2–4 and 4–12 yr age groups. Conclusions. For both entropy and BIS the measure of anaestheticeffect was significantly different for children aged <1 yrcompared with older children. There was no difference in performanceof entropy and BIS. Both should be used cautiously in smallchildren.      

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     

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.     

Reflex pupillary dilatation in response to skin incision and alfentanil in children anaesthetized with sevoflurane: a more sensitive measure of noxious stimulation than the commonly used variables

Background. Estimation of analgesia in anaesthetized childrenis often imprecise, and consequently, anaesthesiologists commonlyevaluate children's response to surgical stimulation by movementor haemodynamic changes. In adults reflex pupillary dilatationhas been demonstrated to be a very sensitive measure of noxiousstimulation, correlated with opioid concentrations. The autonomicnervous control changes with age, raising the hypothesis thatmechanisms involved in pupillary autonomic functions regardingboth sympathetic and parasympathetic components may also differbetween adults and children. In this pilot study, we testedthe hypothesis that the pupillary reflex dilatation might allowassessment of noxious stimulation and analgesic effect of alfentanilin children under sevoflurane anaesthesia, as an alternativeto haemodynamic and bispectral measures. Methods. After sevoflurane induction, 24 children were maintainedin steady-state conditions at 1.5 MAC of sevoflurane in O₂–N₂O(50–50). An intense noxious stimulation was provided bystandardized skin incision on the lower limb. A bolus of alfentanil(10 µg kg^–1) was administered either 1 min (n=16)or 2 min (n=8) after skin incision. Haemodynamic values, bispectralindex (BIS) and pupillary diameter (PD) were recorded just beforestimulation and at 30–60 s intervals during 4 subsequentminutes. Results. In all children PD increased significantly after noxiousstimulation [+200 (40)%, at 60 s]. In contrast, mean heart rateand blood pressure increased only 11 (7)% and 10 (8)% respectively,60 s after stimulation. BIS did not change significantly. Inall children, alfentanil injection induced a rapid decreaseof PD and restored pre-incision values in 2 min. Conclusion. PD is a more sensitive measure of noxious stimulationthan the commonly used variables of heart rate, arterial bloodpressure and BIS in children anaesthetized with sevoflurane.     

A comparison of bispectral index and entropy monitoring, in patients undergoing embolization of cerebral artery aneurysms after subarachnoid haemorrhage

Background. Processed EEG monitoring of anaesthetic depth couldbe useful in patients receiving general anaesthesia followingsubarachnoid haemorrhage. We conducted an observational studycomparing performance characteristics of bispectral index (BIS)and entropy monitoring systems in these patients. Methods. Thirty-one patients of the World Federation of Neurosurgeonsgrades 1 and 2, undergoing embolization of cerebral artery aneurysmsfollowing acute subarachnoid haemorrhage, were recruited tohave both BIS and entropy monitoring during general anaesthesia.BIS and entropy indices were matched to clinical indicatorsof anaesthetic depth. Anaesthetists were blinded to the anaestheticdepth monitoring indices. Analysis of data from monitoring devicesallowed calculation of prediction probability (P_K) constants,and receiver operating characteristic (ROC) analysis to be performed. Results. BIS and entropy [response entropy (RE), state entropy(SE)] performed well in their ability to show concordance withclinically observed anaesthetic depth. P_K values were generallyhigh (BIS 0.966–0.784, RE 0.934–0.663, SE 0.857–0.701)for both forms of monitoring. ROC curve analysis shows a highsensitivity and specificity for all monitoring indices whenused to detect the presence or absence of eyelash reflex. Areaunder curve for BIS, RE and SE to detect the absence or presenceof eyelash reflex was 0.932, 0.888 and 0.887, respectively.RE provides earlier warning of return of eyelash reflex thanBIS. Conclusion. BIS and entropy monitoring perform well in patientswho receive general anaesthesia after good grade subarachnoidhaemorrhage.     

Antagonism of neuromuscular blockade but not muscle relaxation affects depth of anaesthesia

Background. Conflicting effects of neuromuscular blocking drugsand anticholinesterases on depth of anaesthesia have been reported.Therefore we evaluated the effect of atracurium and neostigmineon bispectral index (BIS) and middle-latency auditory evokedpotentials (AAI). Methods. We studied 40 patients (ASA I–II) aged 18–69yr. General anaesthesia consisted of propofol and remifentanilby target-controlled infusion and neuromuscular function wasmonitored by electromyography. When BIS reached stable values,patients were randomly assigned to one of two groups. Group1 received atracurium 0.4 mg kg^–1 and, 5 min later, thesame volume of NaCl 0.9%; group 2 received saline first andthen atracurium. When the first twitch of a train of four reached10% of control intensity, patients were again randomized: onegroup (N) received neostigmine 0.04 mg kg^–1 and glycopyrrolate0.01 mg kg^–1, and the control group (G) received onlyglycopyrrolate. Results. Injection of atracurium or NaCl 0.9% had no effecton BIS or AAI. After neostigmine–glycopyrrolate, BIS andAAI increased significantly (mean maximal change of BIS 7.1[SD 7.5], P<0.001; mean maximal change of AAI 9.7 [10.5],P<0.001). When glycopyrrolate was injected alone BIS andAAI also increased (mean maximal change of BIS 2.2 [3.4], P=0.008;mean maximal change of AAI 3.5 [5.7], P=0.012), but this increasewas significantly less than in group N (P=0.012 for BIS; P=0.027for AAI). Conclusion. These data suggest that neostigmine alters the stateof propofol–remifentanil anaesthesia and may enhance recovery.     

Bispectral index changes following etomidate induction of general anaesthesia and orotracheal intubation

Background. Etomidate-associated hypnosis has only been studiedusing standard clinical criteria and raw EEG variables. We conducteda BIS-based investigation of etomidate induction of generalanaesthesia. Methods. Thirty hydroxyzine-premedicated ASA I patients wererandomly allocated to receive etomidate 0.2, 0.3, or 0.4 mgkg^–1 intravenously over 30 s. The BIS was continuouslyrecorded. A tourniquet was placed on a lower limb to recordpurposeful movements and myoclonia. Tracheal intubation wasfacilitated using rocuronium 0.6 mg kg^–1 when the BISvalue was 50. The times to disappearance of the eyelash reflex,to a decrease in the BIS to 50, and to tracheal intubation werecompared. The BIS values 30 s following tracheal intubation,and mean arterial pressure (MAP) and heart rate (HR) at alltime points were also recorded. Results. The BIS value decreased to 50 for tracheal intubationwith no purposeful movement in all but one patient in the 0.2mg kg^–1 group. There was no difference between the etomidategroups (0.2, 0.3, and 0.4 mg kg^–1) in regards to timeto loss of the eyelash reflex (103 (67), 65 (34), 116 (86) s,P=0.2), or to a decrease in BIS to 50 (135 (81), 82 (36), 150(84) s, P=0.1). Also, the BIS value 30 s after intubation (41(10), 37 (4), 37 (4), P=0.4), and plasma etomidate concentrations(161 [29–998], 308 [111–730], 310 [90–869]ng ml^–1, P=0.2) did not differ between groups. The timeto loss of the eyelash reflex was 12–140 s shorter thanthe time to a decrease in BIS to 50 in three patients in eachgroup who received etomidate 0.2 and 0.4 mg kg^–1, andin four patients who received 0.3 mg kg^–1. No awarenesswas recorded. MAP and HR increases following tracheal intubationwere comparable between groups. Conclusions. Etomidate induction doses do not predict the timefor BIS to decrease to 50 as this variable varies markedly followingthree etomidate dose regimen. Br J Anaesth 2003; 91: 341–6     

Propofol metabolism is enhanced after repetitive ketamine administration in rats: the role of cytochrome P-450 2B induction

Background. In a series of ex vivo and in vivo studies we investigatedthe ability of repetitive ketamine administration to alter themetabolism and anaesthetic effect of propofol and the role ofketamine-mediated P-450 2B induction in rats. Methods. Male Wistar rats were pretreated with 80 mg kg^–1ketamine i.p. twice daily for 4 days. Pentoxyresorufin O-dealkylation(PROD), P-450 2B protein and mRNA were determined. Residualpropofol concentration was measured after incubating hepaticmicrosomes with 100 µM propofol. Sleeping times inducedby i.p. 80 mg kg^–1 propofol were determined. Orphenadrine,a P-450 2B inhibitor, was added in both ex vivo and in vivostudies. Finally, serial whole blood propofol concentrationswere determined after i.v. infusion of 15 mg kg^–1 propofol. Results. Ketamine pretreatment produced 5.4-, 3.4- and 1.7-foldincreases in hepatic PROD activity, P-450 2B protein and mRNA,respectively. Residual propofol concentration was 46% lowerafter incubation with microsomes from ketamine-pretreated ratsthan in the control group. The addition of orphenadrine to ketamine-pretreatedmicrosomes produced an increase in residual propofol concentrationin a concentration-dependent manner. Ketamine pretreatment reducedpropofol sleeping time to 12% of the control, which was reversedby orphenadrine. The whole blood propofol concentration in ketamine-pretreatedrats was significantly lower than that of control rats at 1,2, 4 and 8 min after cessation of propofol infusion. Conclusions. Repetitive ketamine administration enhances propofolmetabolism and reduces propofol sleeping time in rats. We suggestthat P-450 2B induction may produce ketamine–propofolinteraction in anaesthetic practice.