Influence of volatile anaesthetics on hypercapnoeic ventilatory responses in mice with blunted respiratory drive

Background. Subanaesthetic concentrations of volatile anaestheticssignificantly affect the respiratory response to hypoxia andhypercapnoeia. Individuals with an inherited blunted respiratorydrive are more affected than normal individuals. To test thehypothesis that subjects with blunted hypercapnoeic respiratorydrive are diversely affected by different anaesthetics, we studiedthe effects of three volatile anaesthetics on the control ofbreathing in C3H/HeJ (C3) mice, characterized by a blunted hypercapnoeicrespiratory response. Methods. Using whole body plethysmography, we assessed respiratoryrate (RR) and pressure amplitude in 11 male C3 mice at rest,during anaesthesia with isoflurane, sevoflurane or desflurane,and during recovery. To test respiratory drive, mice were exposedto 8% carbon dioxide. Data were analysed by two-way-analysisof variance with post hoc tests and Bonferroni correction. Results. RR was unaffected during sevoflurane anaesthesia upto 1.0 MAC. Likewise, sevoflurane at 1.5 MAC affected RR lessthan either isoflurane (P=0.0014) or desflurane (P=0.0048).The increased RR to a carbon dioxide challenge was blocked byall three anaesthetics even at the lowest concentration, andremained depressed during recovery (P<0.0001). Tidal volumewas unaffected by all three anaesthetics. Conclusions. In C3 mice, spontaneous ventilation was less affectedduring sevoflurane compared with either isoflurane or desfluraneanaesthesia. However, the RR response to hypercapnoeia was abolishedat 0.5 MAC for all the anaesthetic agents and remained depressedeven at the end of recovery. Our data suggest that differentvolatile anaesthetics have varying effects on the control ofbreathing frequency but all block the respiratory response tocarbon dioxide. Therefore, a genetic predisposition to a bluntedcarbon dioxide response represents a susceptibility factor thatinteracts with hypercapnoeic hypoventilation during maintenanceof anaesthesia and in the emergence from anaesthesia, regardlessof the agent used. Br J Anaesth 2004; 92: 697–703     

Animal dependence of inhaled anaesthetic requirements in cats

Background. The minimum alveolar concentration (MAC) of an inhaledanaesthetic describes its potency as a general anaesthetic.Individuals vary in their sensitivity to anaesthetics and wesought to determine whether an individual animal’s sensitivityto inhaled anaesthetics would be maintained across differentagents. Methods. Six female mongrel cats, age 2 yr (range 1.8–2.3)and mean weight 3.5 (SD 0.3) kg, were studied on three separateoccasions over a 12-month period to determine the MAC of isoflurane,sevoflurane and desflurane. Induction of anaesthesia in a chamberwas followed by orotracheal intubation and maintenance of anaesthesiawith the inhaled agent in oxygen delivered via a non-rebreathingcircuit. MAC was determined in triplicate using standard tail-clamptechnique. Results. Mean MAC values for isoflurane, sevoflurane and desfluranewere 1.90 (SD 0.18), 3.41 (0.65) and 10.27 (1.06)%, respectively.Body temperature, systolic pressure and Sp_O2 recorded at thetime of MAC determinations for isoflurane, sevoflurane and desfluranewere 38.3 (0.3), 38.6 (0.1) and 38.3 (0.3)°C; 71.2 (8.3),74.6 (15.9) and 88.0 (12.0) mmHg; 99.2 (1.1), 99.1 (1.3) and99.4 (0.8)%, respectively. Both the anaesthetic agent and theindividual cat had significant effects on MAC. Correlation coefficientsfor comparisons between desflurane and isoflurane, desfluraneand sevoflurane, and sevoflurane and isoflurane were 0.90, 0.89and 0.97, respectively. Conclusions. These findings show that an individual has a consistentdegree of sensitivity to a variety of inhaled anaesthetics,suggesting a genetic basis for sensitivity to inhaled anaestheticeffects. Br J Anaesth 2004; 92: 275–7     

The Bispectral Index in children: comparing isoflurane and halothane

Background. The Bispectral Index (BIS) has been calibrated forseveral general anaesthetic agents including isoflurane. Halothaneis still used in paediatric anaesthesia. Compared with othervolatile anaesthetics, halothane has a different receptor affinityand differing effects on the EEG. There are limited data evaluatingthe BIS with halothane. We set out to compare the BIS usinghalothane and isoflurane at a clinically relevant equipotentconcentration (1 MAC) and at a reproducible measure of anaestheticeffect (awakening). Methods. Forty children aged between 2 and 15 yr were enrolledin a masked randomized trial—20 in each group. Anaesthesiawas induced with sevoflurane or propofol. Either halothane orisoflurane were given to obtain an end-tidal concentration of1 MAC for 15 min. The BIS was then recorded. The BIS was alsorecorded at awakening. Values (mean (SD)) were compared witha t test. Results. At 1 MAC the BIS for halothane was significantly greaterthan isoflurane (56.5 (8.1) vs 35.9 (8.5), P<0.0001). Atawakening there was no significant difference (BIS halothane;81.1 (11.9), BIS isoflurane; 82.5 (16.4)). The difference inmeans at awakening was 1.4 (95% CI –8.2 to 11.1). Conclusions. At equipotent concentrations of halothane and isofluraneBIS valves were significantly greater with halothane. At awakeningthe BIS values were equivalent for each agent. This findingis consistent with the BIS being more affected by the agentused at higher concentrations of anaesthetic. The BIS must beinterpreted with caution when using halothane. Br J Anaesth 2004; 92: 14–17     

Nitrous oxide decreases shivering threshold in rabbits less than isoflurane

Background. Comparable minimum alveolar concentration (MAC)fractions of volatile anaesthetics produce similar thermoregulatoryimpairment. Nitrous oxide, however, decreases the vasoconstrictionthreshold less than sevoflurane or isoflurane. We tested thehypothesis that nitrous oxide also decreases shivering thresholdless than isoflurane alone or in combination. Methods. Twenty-four rabbits were assigned randomly to one ofthree 0.3 MAC anaesthetic regimens: (i) nitrous oxide 69%; (ii)nitrous oxide 35% and isoflurane 0.3%; or (iii) isoflurane 0.6%.Body temperature was lowered by perfusing 10°C water througha U-shaped thermode positioned in the colon. Shivering was evaluatedby inspection. Results. The rabbits anaesthetized with nitrous oxide aloneshivered at 37.0 (0.5)°C (P<0.01 vs other groups). Inthose given the nitrous oxide and isoflurane combination, theshivering threshold was 36.4 (0.5)°C and that in the isofluranegroup was 35.9 (0.4)°C. Conclusion. This study indicates that nitrous oxide reducesthe shivering threshold less than isoflurane. Br J Anaesth 2003; 90: 88–90     

Effects of propofol and sevoflurane on the excitability of rat spinal motoneurones and nociceptive reflexes in vitro

Background. Spinal actions of halogenated ethers are widelyrecognized, whereas spinal actions of intravenous anaestheticslike propofol are less clear. The aim of this study was to comparethe spinal effects of propofol and sevoflurane. Methods. We used an isolated spinal cord in vitro preparationfrom rat pups and superfused the anaesthetics at known concentrations.Responses of motoneurones to single and repetitive C-fibre intensitystimulation (trains of 20 stimuli at 1 Hz) of a lumbar dorsalroot were recorded from the corresponding ventral root via asuction electrode. Results. Stimulation trains produced a wind-up of action potentialsin motoneurones. Both propofol and sevoflurane produced a significantconcentration-dependent depression of the evoked wind-up, althoughat clinically relevant concentrations sevoflurane exhibiteda larger intrinsic efficacy. Applied at anaesthetic concentrations,sevoflurane 250 µM abolished action potentials whereaspropofol 1 µM only produced a reduction close to 50%.At these concentrations, sevoflurane produced a large depressanteffect on the monosynaptic reflex whereas propofol was ineffective. Conclusions. Sevoflurane produces large inhibitory effects onnociceptive and non-nociceptive reflexes which are likely tocontribute to immobility during surgery. Compared with sevoflurane,propofol appears to have much weaker effects on spinal reflexessuch as those recorded in an isolated preparation.     

Is prolongation of the QTc interval during isoflurane anaesthesia more prominent in women pretreated with anthracyclines for breast cancer?

Background. Inhalation anaesthetics and anthracycline chemotherapeuticdrugs may both prolong the QT interval of the electrocardiogram.We investigated whether isoflurane may induce or augment QTcprolongation in patients who had previously received cancerchemotherapy including anthracycline drugs. Methods. Forty women undergoing surgery for breast cancer wereincluded in the study. They were divided into two groups: (A)women previously treated with anthracyclines (n=20); and (B)women not treated with antineoplastic drugs (n=20). All patientsreceived a standardized balanced anaesthetic in which isoflurane0.5 vol% was used. The QT and corrected QT intervals were measuredbefore anaesthesia, after induction and tracheal intubation,after 1, 5, 15, 30, 60 and 90 min of anaesthesia, and duringrecovery. Results. In both groups we observed a tendency to QTc prolongation,but statistically significant differences among baseline valuesand values observed during isoflurane-containing anaesthesiawere seen only in group A. During anaesthesia, significant differencesin QTc values between the two groups were observed. Conclusion. In female patients pretreated with anthracyclinesfor breast cancer, the tendency to QTc prolongation during isoflurane-containinggeneral anaesthesia was more strongly expressed than in patientswithout previous chemotherapy. Br J Anaesth 2004; 92: 658–61     

Blood/gas partition coefficients of halothane,isoflurane and sevoflurane in horse blood

Background. Blood/gas partition coefficients (_b/g) for volatileagents in horse blood are reported for halothane but not forisoflurane and sevoflurane. We measured the _b/g of halothane,isoflurane and sevoflurane in the blood of fasted horses. Thecorrelation with age, weight and some haematological and biochemicalvariables was studied. The temperature correction factor forisoflurane solubility was calculated. Methods. Twenty-four horses were randomly allocated to halothane(n=8), isoflurane (n=8) or sevoflurane (n=8). Blood sampleswere taken after 10 h’ fasting. Calculation of _b/g wasbased on the measurement of anaesthetic partial pressures inblood at 37 °C, which was achieved with tonometer equilibrationand headspace gas chromatography. Results. Mean _b/g was 1.66 (SD 0.06) for halothane, 0.92 (0.04)for isoflurane, and 0.47 (0.03) for sevoflurane. The _b/g valueswere all significantly lower than in humans (P<0.001). Nocorrelation was found between _b/g and weight, age, haematocrit,plasma triglycerides, cholesterol or total bilirubin. The changein isoflurane solubility per 1 °C temperature increase was–2.63 (0.13)%. Conclusion. The _b/g values of halothane, isoflurane and sevofluranein fasted horses are significantly lower than those reportedin humans. The _b/g for halothane in this study agrees with valuesreported in the literature but a positive correlation with plasmatriglycerides could not be confirmed. Knowledge of _b/g can refinemodels of anaesthetic uptake. Br J Anaesth 2003; 91: 276–8     

Propofol and halothane versus sevoflurane in paediatric day-case surgery: induction and recovery characteristics

Background. The aim of this study was to compare the inductionand recovery characteristics associated with propofol inductionand halothane maintenance with sevoflurane anaesthesia in paediatricday surgery. Methods. In total, 322 children were assigned randomly to i.v.propofol induction and halothane/nitrous oxide maintenance orsevoflurane/nitrous oxide alone. The patients’ age, sex,and type of surgery were recorded, as were the times requiredfor anaesthetic induction, maintenance, recovery and time todischarge home. Postoperative nausea and vomiting, and the incidenceof adverse events during induction and recovery were also noted. Results. No significant differences were detected in age, sex,type of surgery performed or intraoperative opioid administration.Excitatory movement was more common during induction with sevoflurane.The mean time required for induction with propofol was 3.1 mincompared with 5 min in the sevoflurane group (P<0.001). Therecovery time was shorter in the sevoflurane group comparedwith propofol/halothane (23.2 vs 26.4 min, P<0.002). Theincidence of delirium in recovery was greater in the sevofluranegroup (P<0.001). There was no difference between groups inthe time spent on the postoperative ward before discharge home.On the postoperative ward the incidence of both nausea and vomitingwas significantly higher in the sevoflurane group (P=0.034).Five children were admitted to hospital overnight, none foranaesthetic reasons. Conclusions. The increased incidence of adverse events duringinduction, postoperative nausea and vomiting and postoperativedelirium in the sevoflurane group suggests that sevofluraneis not ideal as a sole agent for paediatric day case anaesthesia. Br J Anaesth 2003; 90: 461–6     

Differential effects of halothane and isoflurane on lumbar dorsal horn neuronal windup and excitability

Background. Windup of spinal nociceptive neurones may underlietemporal summation of pain, influencing the minimum alveolarconcentration (MAC) of anaesthetics required to prevent movementto supramaximal stimuli. We hypothesized that halothane andisoflurane would differentially affect windup of dorsal hornneurones. Methods. We recorded 18 nociceptive dorsal horn neurones exhibitingwindup to 1 Hz electrical hindpaw stimuli in rats. Effects of0.8 and 1.2 MAC isoflurane and halothane were recorded in thesame neurones (counterbalanced, crossover design). Windup wascalculated as the total number of C-fibre (100–400 mslatency) plus afterdischarge (400–1000 ms latency) spikes/20stimuli (area under curve, AUC) or absolute windup (C-fibreplus afterdischarge–20xinitial response). Results. Increasing isoflurane from 0.8 to1.2 MAC did not affectAUC, but increased absolute windup from 429 (62) to 618 (84)impulses/20 stimuli (P<0.05) and depressed the initial C-fibreresponse from 14 (3) to 8 (2) impulses (P<0.05). Increasinghalothane from 0.8 to1.2 MAC depressed AUC from 690 (79) to537 (65) impulses/20 stimuli (P<0.05) and the initial responsefrom 18 (2) to 13 (2) impulses (P<0.05), but absolute windupwas not affected. Absolute windup was 117% greater during 1.2MAC isoflurane compared with 1.2 MAC halothane. Conclusions. Windup was significantly greater under isofluranethan halothane anaesthesia at 1.2 MAC, whereas the initial C-fibreresponse was suppressed more by isoflurane. These findings suggestthat these two anaesthetics have mechanistically distinct effectson neuronal windup and excitability.     

Effects of halogenated anaesthetics on diaphragmatic actin-myosin cross-bridge kinetics

Background. The effects of halogenated anaesthetics on cross-bridge(CB) kinetics are unclear. As halogenated anaesthetics do notmarkedly modify the intracellular calcium transient in the diaphragm,we used an isolated rat diaphragm preparation to assess theeffects of halothane and isoflurane on CB kinetics. Methods. The effects of halothane and isoflurane (1 and 2 minimumalveolar concentration (MAC)) on rat diaphragm muscle stripswere studied in vitro (Krebs–Henseleit solution, 29°C,oxygen 95%/carbon dioxide 5%) in tetanus mode (50 Hz). Fromthe force–velocity curve and using A. F. Huxley’sequations, we determined the main mechanical and energetic variablesand calculated CB kinetics. Results. At 1 and 2 MAC, isoflurane and halothane induced nosignificant inotropic effects. Whatever the concentrations tested,halothane and isoflurane did not significantly modify the CBnumber, the elementary force per CB, the attachment and detachmentconstants, the duration of the CB cycle and mean CB velocity. Conclusion. In the rat diaphragm at therapeutic concentrations,halogenated anaesthetics do not significantly modify CB mechanicaland kinetic properties. Br J Anaesth 2003; 90: 759–65     

Effect of three anaesthetic techniques on isometric skeletal muscle strength

Background. Our aim was to quantify human involuntary isometricskeletal muscle strength during anaesthesia with propofol, sevoflurane,or spinal anaesthesia using bupivacaine. Methods. Thirty-three healthy patients undergoing anaesthesiafor elective lower limb surgery were investigated. Twenty-twopatients received a general anaesthetic with either propofol(n=12) or sevoflurane (n=10); for the remaining 11 patientsspinal anaesthesia with bupivacaine was used. We used a non-invasivemuscle force assessment system before and during anaesthesiato determine the contractile properties of the ankle dorsiflexormuscles after peroneal nerve stimulation (single, double, triple,and quadruple stimulation). We measured peak torques; contractiontimes; peak rates of torque development and decay; times topeak torque development and decay; half-relaxation times; torquelatencies. Results. Males elicited greater peak torques than females, medians6.3 vs 4.4 Nm, respectively (P=0.0002, Mann-Whitney rank-sumtest). During sevoflurane and propofol anaesthesia, muscle strengthdid not differ from pre-anaesthetic values. During spinal anaesthesia,torques were diminished for single-pulse stimulation from 3.5to 2.0 Nm (P=0.002, Wilcoxon signed rank test), and for double-pulsefrom 7.6 to 5.6 Nm (P=0.02). Peak rates of torque developmentdecreased for single-pulse stimulation from 113 to 53 Nm s^–1and for double pulse from 195 to 105 Nm s^–1. Torque latencieswere increased during spinal anaesthesia. Conclusions. At clinically relevant concentrations, propofoland sevoflurane did not influence involuntary isometric skeletalmuscle strength in adults, whereas spinal anaesthesia reducedstrength by about 20%. Muscle strength assessment using a devicesuch as described here provided reliable results and shouldbe considered for use in other scientific investigations toidentify potential effects of anaesthetic agents. Br J Anaesth 2004; 92: 367–72     

Comparison of the effects of sevoflurane and propofol on cooling and rewarming during deliberate mild hypothermia for neurosurgery

Background. Because the time available for cooling and rewarmingduring deliberate mild hypothermia is limited, studies of therate of the cooling and rewarming are useful. The decrease incore hypothermia caused by heat redistribution depends on theanaesthetic agent used. We therefore investigated possible differencesbetween sevoflurane and propofol on the decrease and recoveryof core temperature during deliberate mild hypothermia for neurosurgery. Methods. After institutional approval and informed consent,26 patients were assigned randomly to maintenance of anaesthesiawith propofol or sevoflurane. Patients in the propofol group(n=13) received propofol induction followed by a continuousinfusion of propofol 3–5 mg kg^–1 h^–1.Patients in the sevoflurane group (n=13) received propofol inductionfollowed by sevoflurane 1–2%. Nitrous oxide and fentanylwere also used for anaesthetic maintenance. After inductionof anaesthesia, patients were cooled and tympanic membrane temperaturewas maintained at 34.5°C. After surgery, patients were activelyrewarmed. Results. There was no difference in the rate of decrease andrecovery of core temperature between the groups. There was alsono difference in skin surface temperature gradient (forearmto fingertip), heart rate and mean arterial blood pressure betweenthe groups. Conclusions. Sevoflurane-based anaesthesia did not affect coolingand rewarming for deliberate mild hypothermia compared withpropofol-based anaesthesia. Br J Anaesth 2003; 90: 32–8     

Effects of different concentrations of sevoflurane and desflurane on subcortical somatosensory evoked responses in anaesthetized, non-stimulated patients

Twenty-four patients were recruited and given either sevofluraneor desflurane as their sole anaesthetic. Each patient was givensequentially increasing or decreasing doses at 0.5 MAC intervals,and the median nerve somatosensory evoked response recordedafter an equilibration at each concentration. The N₂₀-P₂₅ andP₂₅-N₃₅ amplitudes decreased with increasing agent concentration.However, for both agents the P₁₅-N₂₀ amplitude response wasquadratic in shape. The peak inflection points were at 3.2%for sevoflurane and 4.9% for desflurane. There were no differencesbetween the ascending and descending groups. This increase inactivity in the midbrain at ‘surgical’ end-tidalanaesthetic concentrations suggests more complex neuroelectricalresponses to anaesthesia than simple global suppression. Br J Anaesth 2001; 86: 59–62     

Effects of sevoflurane and propofol on left ventricular diastolic function in patients with pre-existing diastolic dysfunction

Background. The effects of anaesthetics on left ventricular(LV) diastolic function in patients with pre-existing diastolicdysfunction are not well known. We hypothesized that propofolbut not sevoflurane will worsen the pre-existing LV diastolicdysfunction. Methods. Of 24 randomized patients, 23 fulfilled the predefinedechocardiographic criterion for diastolic dysfunction. Theyreceived general anaesthesia with sevoflurane 1 MAC (n=12) orpropofol 4 µg ml^–1 (n=11). Echocardiographic examinationswere performed at baseline and in anaesthetized patients underspontaneous breathing and under positive pressure ventilation.Analysis focused on peak early diastolic velocity of the mitralannulus (E_a). Results. During spontaneous breathing, E_a was higher in thesevoflurane than in the propofol group [mean (95% CI) 7.0 (5.9–8.1)vs 5.5 (4.7–6.3) cm s^–1; P<0.05], reflectingan increase of E_a from baseline only in the sevoflurane group(P<0.01). Haemodynamic findings were similar in both groups,but the end-tidal carbon dioxide content was more elevated inthe propofol group (P<0.01). During positive pressure ventilation,E_a was similarly low in the sevoflurane and propofol groups[5.3 (4.2–6.3) and 4.4 (3.6–5.2) cm s^–1, respectively]. Conclusions. During spontaneous breathing, early diastolic functionimproved in the sevoflurane but not in the propofol group. However,during positive pressure ventilation and balanced anaesthesia,there was no evidence of different effects caused by the twoanaesthetics.     

Sevoflurane anaesthesia does not induce the formation of sister chromatid exchanges in peripheral blood lymphocytes of children

Background. Compound A, a degradation product of sevoflurane,has been demonstrated to induce sister chromatid exchanges (SCE)in Chinese hamster ovary cells in vitro as a marker for possiblegenotoxicity. We investigated the formation of SCE in mitogen-stimulatedT-lymphocytes of 40 children undergoing sevoflurane anaesthesiafor minor surgical procedures. Methods. Anaesthesia was induced by inhalation of up to 8% sevofluraneand maintained at 2.5–3% in oxygen/nitrous oxide (65/35%)at a fresh gas flow of 3 litre min^–1. Soda lime (humidity12–15%) was used as a carbon dioxide absorbent. Bloodwas drawn directly before induction and after termination ofanaesthesia. Twenty-five second division metaphases of mitogen-stimulatedT-lymphocytes per blood sample were screened for SCE rates usingstandard techniques. Results. Average duration of anaesthesia was 49.6 (SD 24.0)min. Before anaesthesia induction, 7.93 (1.23) SCE per metaphasewere determined. After sevoflurane anaesthesia [1.40 (0.77)MAC h] 7.92 (1.19) SCE per metaphase were observed. Additionally,no differences were evident between male or female children. Conclusion. Short-term administration of sevoflurane anaesthesiadid not induce SCE in T-lymphocytes of children. No indicationfor a possible genotoxic effect has been observed. Br J Anaesth 2003; 90: 233–5     

Sevoflurane anaesthesia in children after induction of anaesthesia with midazolam and thiopental does not cause epileptiform EEG

Background. Sevoflurane is a methyl ether anaesthetic commonlyused for induction and maintenance of general anaesthesia inchildren. Sevoflurane is a non-irritant and acts quickly soinduction is usually calm. However, inhalation induction withhigh concentrations of sevoflurane can cause convulsion-likemovements and seizure-like changes in the electroencephalogram(EEG). Little is known about the EEG during maintenance of anaesthesiawith sevoflurane, so we planned a prospective trial of sevofluranemaintenance after i.v. induction with benzodiazepine and barbiturate,which is another common induction technique in children. Methods. EEG recordings were made before premedication withmidazolam (0.1 mg kg^–1 i.v.), during induction ofanaesthesia with thiopental (5 mg kg^–1), and duringmaintenance with sevoflurane (2% end-tidal concentration inair/oxygen without nitrous oxide) in 30 generally healthy, 3-to 8-year-old children having adenoids removed. Noise-free EEGdata of good quality were successfully recorded from all 30children. Results. Two independent neurophysiologists did not detect epileptiformdischarges in any of the recordings. Conclusion. Premedication with midazolam, i.v. induction withthiopental and maintenance of anaesthesia with 2% sevofluranein air does not cause epileptiform EEG patterns in children. Br J Anaesth 2002; 89: 853–6     

Comparison of 1% and 2% lidocaine epidural anaesthesia combined with sevoflurane general anaesthesia utilizing a constant bispectral index

Background. The authors compared the effects of epidural anaesthesiawith lidocaine 1% and lidocaine 2% on haemodynamic variables,sevoflurane requirements, and stress hormone responses duringsurgery under combined epidural/general anaesthesia with bispectralindex score (BIS) kept within the range 40–50. Methods. Thirty-three patients undergoing lower abdominal surgerywere randomly divided into two groups to receive lidocaine 1%or 2% by epidural with sevoflurane general anaesthesia. Sevofluranewas adjusted to achieve a target BIS of 40–50 during maintenanceof anaesthesia with nitrous oxide 60% in oxygen. Measurementsincluded the inspired (FI_SEVO) and the end-tidal sevofluraneconcentrations (E'_SEVO), blood pressure (BP), and heart rate(HR) before surgery and every 5 min during surgery for2 h. Plasma samples were taken immediately before and duringsurgery for measurements of catecholamines, cortisol, and lidocaine. Results. During surgery, both groups were similar for HR, BPand BIS, but FI_SEVO and E'_SEVO were significantly higher andmore variable with lidocaine 1% than with 2%. Intraoperativeplasma concentrations of epinephrine and cortisol were foundto be higher with lidocaine 1% as compared with 2%. Conclusions. To maintain BIS of 40–50 during combinedepidural/general anaesthesia for lower abdominal surgery, sevofluraneconcentrations were lower and less variable with lidocaine 2%than with 1%. In addition, the larger concentration of lidocainesuppressed the stress hormone responses better. Br J Anaesth 2003; 91: 825–9     

Inhibition of glutamate transporters increases the minimum alveolar concentration for isoflurane in rats

Background. Glutamate transporters [also named excitatory aminoacid transporters (EAATs)] bind and take up extracellular glutamate,a major excitatory neurotransmitter, and can regulate glutamatergicneurotransmission in synapses. As anaesthesia is proposed tobe induced by enhancing inhibitory neurotransmission, inhibitingexcitatory neurotransmission, or both we hypothesize that inhibitionof EAAT activity can increase the anaesthetic requirement. Methods. The minimum alveolar concentration (MAC, the anaestheticconcentration required to suppress movement in response to noxiousstimulation in 50% of subjects) for isoflurane was determinedin adult male Sprague–Dawley rats after intrathecal administrationof EAAT inhibitors. Results. Application of DL-threo-ß-benzyloxyaspartate,a selective EAAT inhibitor, dose- and time-dependently increasedthe MAC for isoflurane. The MAC was 109 (1)% and 116 (4)% ofthe baseline, respectively, for 0.2 and 0.4 µmol of DL-threo-ß-benzyloxyaspartate15 min after the injection of the drug (n=5, P<0.05 comparedwith the baseline MAC). Intrathecal injection of dihydrokainate,a selective inhibitor of EAAT type 2, also increased the MACfor isoflurane. Conclusions. These results suggest that EAAT in the spinal cordcan regulate the requirement of isoflurane to induce immobility.EAAT2 may be involved in this effect.     

Fluoride excretion in children after sevoflurane anaesthesia

Background. Defluorination of sevoflurane is catalysed by thehepatic enzyme cytochrome P450 2E1 (CYP2E1). Data about theontogenesis (developmental variations in activity) of this enzymesuggest a low metabolism of sevoflurane during the first monthsof life. Methods. To test this hypothesis, 45 children less than 48 monthsof age undergoing sevoflurane anaesthesia were enrolled in aprospective open clinical trial. The 24 h urine fluoride excretionwas measured in five groups of children (A, <4 months; B,4 to <8 months; C, 8–12 months; D, >12–24months; and E, >24–48 months old). An index of sevofluranemetabolism (ISM) was calculated as the ratio of fluoride excretion,cumulative expiratory sevoflurane concentrations measured everyminute during anaesthesia, and body surface area. ISM valueswere median (IQ 25–75%). Results. ISM was lower in group A (n=9, 18.9 (11.2–29.5)than group C (n=11, 44.2 (37.5–53.5), P<0.05), groupD (n=7, 52.6 (45.8–68.4), P<0.01) and group E (n=9,53.6 (50.7–85), P<0.001). Median ISM expressed as afunction of median age, exponentially increased with a rapidincrease during the first months of life, followed by a slowerincrease after 10 months of age. Conclusion. These results suggest that, in children less than48 months, sevoflurane metabolism parallels postnatal developmentof CYP2E1. Br J Anaesth 2002; 89: 693–6     

The Patient State Index as an indicator of the level of hypnosis under general anaesthesia

Background. This retrospective study describes the performanceof the Patient State Index (PSI), under standard clinical practiceconditions. The PSI is comprised of quantitative features ofthe EEG (QEEG) that display clear differences between hypnoticstates, but consistency across anaesthetic agents within thestate. Methods. The PSI was constructed from a systematic investigationof a database containing QEEG extracted from the analyses ofcontinuous 19 channel EEG recordings obtained in 176 surgicalpatients. Induction was accomplished with etomidate, propofol,or thiopental. Anaesthesia was maintained by isoflurane, desflurane,or sevoflurane, total i.v. anaesthesia using propofol, or nitrousoxide/narcotics. It was hypothesized that a multivariate algorithmbased on such measures of brain state, would vary significantlywith changes in hypnotic state. Results. Highly significant differences were found between meanPSI values obtained during the different anaesthetic statesselected for study. The relationship between level of awarenessand PSI value at different stages of anaesthetic delivery wasalso evaluated. Regression analysis for prediction of arousallevel using PSI was found to be highly significant for the combinationof all anaesthetics, and for the individual anaesthetics. Conclusions. The PSI, based upon derived features of brain electricalactivity in the anterior/posterior dimension, significantlyco-varies with changes in state under general anaesthesia andcan significantly predict the level of arousal in varying stagesof anaesthetic delivery. Br J Anaesth; 2004 92: 393–9