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     

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.     

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     

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     

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     

Nomogram to estimate age-related MAC

Background. In clinical practice it is difficult to estimaterapidly two important values: (i) the total age-corrected MACmultiple from measured end-expired concentrations of volatileagent and nitrous oxide; (ii) the end-expired concentrationof volatile agent needed to obtain a given total MAC multiple.We have developed a nomogram to do this. Methods. We used standard nomogram methods to construct onesingle nomogram covering wide ranges of age (1–100 yr)and MAC (0.1–1.8 MAC) for halothane, enflurane, isoflurane,sevoflurane, and desflurane, alone or in combination with variousconcentrations of nitrous oxide. The user only has to draw twostraight lines to obtain the desired result. Results. The nomogram is simple to use. End-expired concentrationsof halothane 0.48%, enflurane 1.05%, isoflurane 0.75%, sevoflurane1.18%, or desflurane 4.3% in the presence of nitrous oxide 50%will give 1.4 MAC in a patient of 75 yr vs 0.9 MAC in a 1-yr-old.A reverse example is: a total MAC of 1.3 when using sevofluraneand nitrous oxide 67% in oxygen, requires an end-expired sevofluraneconcentration of 1.8% in a 3-yr-old whereas 0.55% is neededin a patient of 90 yr. Conclusions. The nomogram gives accurate results if it coversa whole A4 sheet in landscape format and could be extended toapply to other agents, for example xenon.     

The effects of i.v. fentanyl administration on the minimum alveolar concentration of isoflurane in horses

Background. Fentanyl decreases the minimum alveolar concentration(MAC) of inhaled anaesthetics and has been used clinically toreduce the requirements of other anaesthetic drugs in humansand small animals. We hypothesized that i.v. fentanyl woulddecrease the MAC of isoflurane in horses in a dose-dependentmanner. Methods. Following determination of baseline MAC of isoflurane,fentanyl was administered i.v. to target plasma concentrationsof 1, 8 and 16 ng ml^–1. Each horse was randomly assignedtwo of three target concentrations administered in ascendingorder. Loading and infusion doses for each horse were determinedfrom previously derived individual pharmacokinetic values. IsofluraneMAC determination began 45 min after fentanyl administrationat each target fentanyl concentration. Venous blood was collectedat fixed intervals during the infusion for measurement of plasmafentanyl concentrations. Results. Mean actual fentanyl plasma concentrations were 0 (baseline),and 0.72 (SD 0.26), 8.43 (3.22), and 13.31 (6.66) ng ml^–1for the target concentrations of 1, 8 and 16 ng ml^–1,respectively. The corresponding isoflurane MAC values were abaseline of 1.57 (0.23), and 1.51 (0.24), 1.41 (0.23) and 1.37(0.09)%, respectively. The fentanyl concentrations of 0.72 and8.43 ng ml^–1 did not significantly alter the MAC of isoflurane,but an 18 (7)% ISO-MAC reduction was observed at the 13.31 ngml^–1 concentration. Conclusions. These results cautiously encourage further studyof fentanyl as an opioid anaesthetic adjunct to inhalant anaesthesiain horses.     

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     

The impact of age on bispectral index values and EEG bispectrum during anaesthesia with desflurane and halothane in children

Background. The relationship between end-tidal sevoflurane concentration,bispectral index (BIS) and the EEG bispectrum in children appearsto be age dependent. The aim of this study was to quantify theBIS values at 1 MAC (minimum alveolar concentration) for desfluraneand halothane, and explore the relationship with age for theseanaesthetic agents in children. Methods. ECG, EEG and BIS were recorded continuously in 90 childrenaged 6–170 months requiring anaesthesia for elective surgery.Fifty children were anaesthetized with desflurane, and 40 childrenwith halothane. Recordings were performed through to a steadystate of 2 MAC, and thereafter at 1 and 0.5 MAC, respectively.The bispectrum of the EEG was estimated using MATLAB© software.A multiple correspondence analysis (MCA) was used. Results. At a steady state of 1 MAC, BIS values were significantlyhigher with halothane 62 (43–80) than desflurane 34 (18–64).BIS values were significantly correlated with age in both groups:DES (r²=0.57; P<0.01) and HALO (r²=0.48; P<0.01). Changesin position in the structured model of the MCA (dependent onthe pattern of the EEG bispectrum) were different for the twovolatile anaesthetic agents. Conclusions. In children, BIS values are linked to age irrespectiveof the volatile anaesthetic agent used. The difference in BISvalues for different agents at the same MAC can be explainedby the specific effect on the EEG bispectrum induced by eachanaesthetic agent, bringing into question the ability of theEEG bispectrum to accurately determine the depth of anaesthesia.     

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.     

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.      

Minimum alveolar concentration (MAC) of xenon in intubated swine

Background. The minimum alveolar concentration (MAC) is a traditionalindex of the hypnotic potency of an inhalational anaesthetic.To investigate the anaesthetic as well as the unwanted effectsof xenon (Xe) in a swine model, it is useful to know MAC_Xe. Methods. The study was performed using ten swine (weight 27.8–35.4kg) anaesthetized with halothane and Xe 0, 15, 30, 40, 50 and65% in oxygen. With each Xe concentration, various concentrationsof halothane were administered in a step-by-step design. Foreach combination, a supramaximal pain stimulus (claw clamp)was applied and the appearance of a withdrawal reaction wasrecorded. The MAC_Xe with halothane was calculated using a logisticregression model. Results. During stable ventilation, haemodynamics and temperature,MAC_Xe value was determined as 119 vol. % (95% confidence limits103–135). Conclusion. MAC_Xe in swine was calculated by extrapolation ofa logistic regression model. Its theoretical value is 119 vol.%. Br J Anaesth 2004; 92: 421–4     

Age-related iso-MAC charts for isoflurane,sevoflurane and desflurane in man

Background. The motivation for this study was the current difficultyin estimating the total age-related MAC for a patient in a clinicalsetting. Methods. Age-related iso-MAC charts for isoflurane, sevofluraneand desflurane were developed for the clinically useful MACrange (0.6–1.6), age range 5–95 yr, and put in aconvenient form for use by practising anaesthetists. The chartsare based on Mapleson’s meta-analysis (1996) of the availableMAC data and can be used to allow for the contribution of nitrousoxide to the total MAC. Results. The charts indicate the influence of age on anaestheticrequirements, showing, for example, that a total MAC of 1.2using isoflurane and nitrous oxide 67% in oxygen requires anend-expired isoflurane concentration of only 0.25% in a patientof 95 yr vs 1% in a 5-yr-old patient. Colleagues found the chartsto be helpful and simple to use clinically. Conclusions. The iso-MAC charts show clearly how patient agecan be used to guide the choice of end-expired agent concentration.They also allow a consistent total MAC to be maintained whenchanging the inspired nitrous oxide concentration, thereby reducingthe chance of inadvertent awareness, particularly at the extremesof age. Br J Anaesth 2003; 91: 170–4     

Effects of halothane and isoflurane on the contraction,relaxation and energetics of rat diaphragmatic muscle

Background. The inotropic effects of halogenated anaestheticson diaphragmatic muscle remain a matter of debate. Their effectson its relaxation are poorly understood, although diaphragmaticrelaxation is recognized as an important physiological processthat may interfere with diaphragmatic performance, fatigue andarterial blood flow. Methods. The effects of halothane and isoflurane (1 or 2x minimumalveolar concentration [1 or 2 MAC]) on contraction and relaxationof rat diaphragm muscle strips (n=40) were studied in vitrofrom force–velocity curves obtained at various loads fromisotonic to isometric conditions. From these curves we determinedthe peak power output and the curvature. Data are mean (SD)percentage of baseline values. Results. At 1 MAC, isoflurane and halothane induced no significantinotropic and lusitropic effects. At 2 MAC, isoflurane induceda negative inotropic effect (active force, 93(5)% of baseline).Halothane and isoflurane induced a significant decrease in thepeak power output at 2 MAC (88(8) and 86(9)% of baseline; P<0.05),without significant changes in the curvature of the force–velocitycurve. At 2 MAC isoflurane under high loads and halothane underlow loads induced moderate negative lusitropic effects. Conclusion. Halothane and isoflurane induced very moderate inotropicand lusitropic effects, suggesting that the decrease in diaphragmfunction observed in vivo is not related to a direct effecton diaphragmatic contractility. Br J Anaesth 2002; 89: 479–85     

DEPRESSION OF HYPOXIC VENTILATORY RESPONSE BY HALOTHANE, ENFLURANE AND ISOFLURANE IN DOGS

The ventilatory responses to isocapnic hypoxia and hypercapniawere studied in six dogs each with a tracheostomy, awake andduring anaesthesia with halothane, enflurane and isoflurane(1–2.5 MAC). Isocapnic hypoxic ventilatory response (HVR)was expressed as the parameter A, such that the greater thevalue of A, the greater the hypoxic response. In the anaesthetizeddogs HVR (A) was reduced significantly from the awake valueof 2010±172 (mean+SEM) to 630±173 by 1 MAC halothane,495± 105 by 1 MAC enflurane and 952±157 by 1 MACisoflurane (P<0.05). All three anaesthetic agents producedsignificant depression of HVR at 1 MAC, but enflurane was moredepressant than isoflurane. At 1.5 MAC all three anaestheticsproduced equal and significant depression of HVR at equianalgesicconcentrations. Further increases in anaesthetic concentrationcaused no increase in depression. Hypercapnic drive, as measuredby the slope of the VE/PA_co2 response curve, was reduced significantlyfrom 9.75 litre min^–1 kPa^–1 ± 2.4 in awakedogs to 0.83 ± 0.56 after 1 MAC halothane, 0.68 ±0.53after 1 MAC enflurane and 1.58 ±0.75 after 1 MAC isoflurane.In addition, hypercapnia-induced augmentation of the hypoxicdrive was abolished by 1 MAC halothane or enflurane and diminishedmarkedly by 1 MAC isoflurane. It may be clinically significantthat hypoxia and hypercapnia during anaesthesia with these agentsdid not produce optimal stimulation of ventilation.     

Multi-level approach to anaesthetic effects produced by sevoflurane or propofol in humans: 2. BIS and tetanic stimulus-induced withdrawal reflex

Background: General anaesthesia could be assessed at two sites: corticalstructures and the spinal cord. However, the practicalitiesof measurement at these two sites differ substantially. Methods: We simultaneously analysed effects of sevoflurane (Group S;n = 16) or propofol (Group P; n = 17) on bispectral index (BIS)and the tetanic stimulus-induced withdrawal reflex (TIWR). TIWRwas quantified by the area under the curve of the electromyogramof the biceps femoris muscle after electrical stimulation ofthe sural nerve. After loss of consciousness, TIWR was evokedonce per minute. The anaesthetic was increased until TIWR disappeared.After discontinuation of the anaesthetic and reappearance ofTIWR, the amount of anaesthetic was increased again. Using asigmoid E_max model and a first-order rate constant k_e0, we characterizedthe dose–response relationships for BIS and TIWR. Results: Concentration-dependent depression of TIWR was reasonably wellmodelled for sevoflurane, but poorly for propofol. TIWR wascompletely suppressed by sevoflurane, but not propofol. Sevofluranereduced TIWR to 5 mV ms (very weak movement) at 1.68 vol% end-expiredconcentration [ minimum alveolar concentration (MAC value)].The k_e0s for TIWR were smaller than those for BIS: 0.25 (0.16–0.39)vs 0.41 (0.33–0.51) min^–1 for Group S; 0.25 (0.22–0.30)vs 0.34 (0.29–0.40) min^–1 for Group P [geometricmean (95% CI)]. Conclusions: High concentrations of sevoflurane depress TIWR more than propofol.With propofol, we frequently observed a paradoxical behaviourof muscles of the lower leg. TIWR lags behind BIS, indicatingdifferent effect sites for two intended anaesthetic effects:unresponsiveness to noxious stimulation and unconsciousness.     

Measuring the costs of inhaled anaesthetics

The cost of inhalation anaesthesia has received considerablestudy and is undoubtedly reduced by the use of low fresh gasflows. However, comparison between anaesthetics of the economiesachievable has only been made by computer modelling. We havecomputed anaesthetic usage for MAC-equivalent anaesthesia withisoflurane, desflurane, and sevoflurane in closed and open breathingsystems. We have compared these data with those derived duringclinical anaesthesia administered using a computer-controlledclosed system that measures anaesthetic usage and inspired concentrations.The inspired concentrations allow the usage that would haveoccurred in an open system to be calculated. Our computed predictionslie within the 95% confidence intervals of the measured data.Using prices current in our institution, sevoflurane and desfluranewould cost approximately twice as much as isoflurane in opensystems but only about 50% more than isoflurane in closed systems.Thus computer predictions have been validated by patient measurementsand the cost saving achieved by reducing the fresh gas flowis greater with less soluble anaesthetics. Br J Anaesth 2001; 87: 559–63     

Desflurane affords greater protection than halothane against focal cerebral ischaemia in the rat

Background. We studied the potential neuroprotective effectsof halothane and desflurane, compared with the awake state,on infarct size following 2 h of intraluminal middle cerebralartery occlusion (MCAo) and 22 h of reperfusion. Methods. Male Sprague–Dawley rats were anaesthetized withdesflurane or halothane, intubated, and mechanically ventilated.Mean arterial pressure (MAP), blood gases, and pH were controlled.Body temperature was maintained at 37.5–38°C. Animalswere assigned to one of four groups according to the anaesthetictype (halothane or desflurane) and the duration of anaesthesia:‘short-duration’, during the preparation only; ‘long-duration’,during both preparation and ischaemia. Twenty-four hours afterMCAo, infarcts were visualized by staining with 2,3,5-triphenyltetrazoliumchloride. Two additional groups of rats were subjected to thesame protocol as that of long-duration halothane and long-durationdesflurane with additional pericranial temperature measurementsmade. Results. Physiological parameters were comparable between thegroups but MAP was higher (P<0.0001) in the short-durationgroups. In the short-duration groups, cerebral infarct volumeswere not significantly different between anaesthetics (short-durationhalothane: 288 (61) mm³, mean (SD); short-duration desflurane:269 (71) mm³, P>0.56). Compared with the awake state (short-durationgroups), halothane and desflurane significantly reduced infarctvolumes (long-duration halothane: 199 (54) mm³, P<0.0047vs short-duration halothane; long-duration desflurane: 121 (55)mm³, P<0.0001 vs short-duration desflurane). The mean infarctvolume in the long-duration desflurane group was significantlylower than that in the long-duration halothane group (P<0.0053).Pericranial temperatures were similar in the desflurane andhalothane long-duration groups (P>0.17). Conclusions. In rats, desflurane-induced neuroprotection againstfocal cerebral ischaemia was greater than that conferred byhalothane. Br J Anaesth 2003; 91: 390–6     

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.     

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