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 propofol/remifentanil and sevoflurane/remifentanil for maintenance of anaesthesia for elective intracranial surgery

Background. Propofol and sevoflurane are suitable agents formaintenance of anaesthesia during neurosurgical procedures.We have prospectively compared these agents in combination withthe short-acting opioid, remifentanil. Methods. Fifty unpremedicated patients undergoing elective craniotomyreceived remifentanil 1 µg kg^–1 followed by an infusioncommencing at 0.5 µg kg^–1 min^–1 reducing to0.25 µg kg^–1 min^–1 after craniotomy. Anaesthesiawas induced with propofol, and maintained with either a target-controlledinfusion of propofol, minimum target 2 µg ml^–1 orsevoflurane, initial concentration 2%_ET. Episodes of mean arterialpressure (MAP) more than 100 mm Hg or less than 60 mm Hg formore than 1 min were defined as hypertensive or hypotensiveevents, respectively. A surgical assessment of operating conditionsand times to spontaneous respiration, extubation, obey commandsand eye opening were recorded. Drug acquisition costs were calculated. Results. Twenty-four and twenty-six patients were assigned topropofol (Group P) and sevoflurane anaesthesia (Group S), respectively.The number of hypertensive events was comparable, whilst morehypotensive events were observed in Group S than in Group P(P=0.053, chi-squared test). As rescue therapy, more labetolol[45 (33) vs 76 (58) mg, P=0.073] and ephedrine [4.80 (2.21)vs 9.78 (5.59) mg, P=0.020] were used in Group S. Between groupdifferences in recovery times were small and clinically unimportant.The combined hourly acquisition costs of hypnotic, analgesic,and vasoactive drugs appeared to be lower in patients maintainedwith sevoflurane than with propofol. Conclusion. Propofol/remifentanil and sevoflurane/remifentanilboth provided satisfactory anaesthesia for intracranial surgery.     

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     

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.     

Effect of sevoflurane on the vascular reactivity of rabbit mesenteric artery

Sevoflurane is well known to cause depression of cardiovascularfunction, but detailed information on its actions on the contractilityand reactivity of blood vessels is lacking. We have assessedtherefore the direct effect of this anaesthetic on the functionalreactivity of isolated rabbit mesenteric artery ring preparations.We found that contractions of endothelium intact rings inducedby noradrenaline and phenylephrine were significantly attenuatedby 4% sevoflurane; the observation that the maximal tensiongeneration decreased without a significant reduction in pD₂is consistent with the view that receptor dysfunction was notinvolved. The effect of sevoflurane was not affected by N^G-monomethyl-L-arginine.Sevoflurane 4% also produced attenuation of noradrenaline-inducedcontractions of endothelium denuded ring preparations. The contractionsof endothelium denuded ring preparations produced by noradrenalinein Ca²⁺-free media in the presence of K⁺ were not affected by4% sevoflurane, but sevoflurane depressed external Ca²⁺-dependentcontractions. When vasodilators (acetylcholine and nitroglycerin)were added to the bathing media in the presence of 2% sevoflurane,the endothelium dependent relaxation produced by acetylcholine,but not the endothelium-independent relaxation produced by nitroglycerin,was attenuated; superoxide dismutase inhibited the effect ofsevoflurane on endothelium-dependent relaxation. These resultsare consistent with the view that sevoflurane inhibits     

Analgesia with sevoflurane during labour: ii. Sevoflurane compared with Entonox for labour analgesia

Background. We determined the optimal inspired sevoflurane concentrationfor use during labour as 0.8% in our previous study. This studycompared sevoflurane at a concentration of 0.8% and Entonox^®(nitrous oxide 50%: oxygen 50%) for analgesia during labourin 32 healthy parturients. Methods. Each mother underwent two open-label, three-part sequencesin random order, Entonox-sevoflurane-Entonox or sevoflurane-Entonox-sevoflurane.In each part the agent was self-administered during 10 contractions.A 100 mm visual analogue scores for pain relief and sedationwas completed immediately after each contraction. Results. Two patients withdrew during administration of sevoflurane(because of its odour) and five during Entonox (requesting epiduralanalgesia). Of the remaining women, data were available foranalysis from 29 participants: median (IQR [range]) pain reliefscores were significantly higher for sevoflurane 67 (55–74[33–100]) mm than for Entonox 51 (40–69.5 [13–100])mm (P<0.037). Nausea and vomiting were more common in theEntonox group [relative risk 2.7 (95% CI 1.3–5.7); P=0.004].No other adverse effects were observed in the mothers or babies.There was significantly more sedation with sevoflurane thanwith Entonox {74 (66.5–81 [32.5–100]) and 51 (41–69.5[13–100]) mm, respectively; P<0.001}. Twenty-nine patientspreferred sevoflurane to Entonox and found its sedative effectshelpful. Conclusions. We conclude that self-administered sevofluraneat subanaesthetic concentration (0.8%) can provide useful painrelief during the first stage of labour, and to a greater extentthan Entonox. Although greater sedative effects were experiencedwith sevoflurane, it was preferred to Entonox.      

Differential vascular reactivity of canine mesenteric arteries and veins to sevoflurane

Purpose The aim of this study was to compare the vascular reactivities of canine mesenteric arteries and veins to sevoflurane and to elucidate the underlying mechanism that is responsible for sevoflurane-induced hypotension. Methods Vascular rings of canine mesenteric arteries and veins were suspended in organ baths, and the effect of 2.3% and 4.6% sevoflurane on the contractile responses to transmural electrical stimulation (ES) and to norepinephrine (NE) were determined by recording isometric tension changes. The rings were contracted to a stable tension by the addition of NE and then exposed to increasing concentrations of sevoflurane (0%–5.1%). Results Sevoflurane attenuated the contractile responses to transmural ES in veins but not in arteries. The concentration responses to NE were not affected by sevoflurane in arteries or in veins. At stable precontraction induced by NE, when sevoflurane was placed in the bathing medium, arteries with intact endothelium had significant contraction at 1.7% and 3.4% sevoflurane, followed by relaxation at 5.1%. On the contrary, sevoflurane produced dose-dependent relaxation in endothelium-denuded arteries and endothelium-intact veins Conclusion It is suggested that the relaxation of the veins by sevoflurane may be due to the inhibition of NE release from sympathetic nerve endings and to the direct inhibition of the contractile mechanisms of vascular smooth muscle. In arteries, sevoflurane causes endothelium-dependent vasocontraction, probably by inhibiting the release of basal endothelium-derived relaxing factor (EDRF).     

Influence of sepsis on sevoflurane minimum alveolar concentration in a porcine model

Sevoflurane is widely used in anaesthetic protocols for patientsundergoing surgical procedures. However, there are no reportson the influence of sepsis on minimum alveolar concentrationof sevoflurane (MAC_SEV) in animals or in humans. The aim ofthis study was to test the hypothesis that sepsis could alterthe MAC_SEV in a normotensive septic pig model. Twenty young,healthy pigs were used. After they had received 10 mg kg^–1of ketamine i.m. for premedication, anaesthesia was establishedwith propofol 3 mg kg^–1 and the trachea wasintubated. Sevoflurane was used as the sole anaesthetic agent.Baseline haemodynamic recording included electrocardiography,carotid artery blood pressure and a pulmonary thermodilutioncatheter. Baseline MAC_SEV in each pig was evaluated by pinchingwith a haemostat applied for 1 min to a rear dewclaw. MAC_SEVwas determined using incremental changes in sevoflurane concentrationuntil purposeful movement appeared. Pigs were assigned randomlyto two groups: the saline group (n=10) received a 1-h i.v. infusionof sterile saline solution while the sepsis group (n=10) receiveda 1-h i.v. infusion of live Pseudomonas aeruginosa. Epinephrineand hydroxyethylstarch were used to maintain normotensive andnormovolemic haemodynamic status. In both groups, MAC_SEV wasevaluated 5 h after infusion. Significant increases inmean artery pulmonary pressure, filling, epinephrine and vascularpulmonary resistances occurred in the sepsis group. MAC_SEV forthe saline group was 2.4% [95% confidence interval (CI) 2.1–2.55%]and the MAC_SEV for the sepsis group was 1.35% (95% CI 1.2–1.45%,P<0.05). These data indicate that MAC_SEV is significantlydecreased in this normotensive septic pig model. Br J Anaesth 2001; 86: 832–6     

Mg2+ dependence of Ca2+ release from the sarcoplasmic reticulum induced by sevoflurane or halothane in skeletal muscle from humans susceptible to malignant hyperthermia

Background. In normal resting muscle, cytosolic Mg²⁺ exertsa potent inhibitory influence on the sarcoplasmic reticulum(SR) Ca²⁺ release channel (ryanodine receptor, RyR1). ImpairedMg²⁺-regulation of RyR1 has been proposed as a causal factorin malignant hyperthermia (MH). The aim of this study was tocompare the effects of cytosolic Mg²⁺ on SR Ca²⁺ release inducedby halothane or sevoflurane in normal (MHN) and MH susceptible(MHS) human skeletal muscle fibres. Methods. Samples of vastus medialis muscle were obtained frompatients under investigation for MH susceptibility. Single fibreswere mechanically skinned and perfused with solutions mimickingthe intracellular milieu. Changes in [Ca²⁺]_i were detected usingfura-2 fluorescence after application of equimolar halothaneor sevoflurane. Results. In MHN fibres, concentrations of sevoflurane or halothaneas high as 10 mM typically failed to induce SR Ca²⁺ releaseat physiological free [Mg²⁺] (1 mM). However, when [Mg²⁺] wasdecreased to 0.4 mM, SR Ca²⁺ release occurred in 51% (16/33)and 6% (2/33) of MHN fibres after the addition of 1 mM halothaneor 1 mM sevoflurane, respectively. Further decreases in [Mg²⁺]increased the proportion of responsive fibres. In the presenceof 0.1 mM [Mg²⁺], Ca²⁺ release occurred in all fibres (33/33)after the introduction of 1 mM halothane or 1 mM sevoflurane.In MHS fibres, 1 mM halothane or 1 mM sevoflurane-induced Ca²⁺release in 54% (7/13) or 15% (2/13) of fibres, respectively,at 1 mM Mg²⁺. A decrease in [Mg²⁺] to 0.2 mM Mg²⁺ was sufficientto render 100% of MHS fibres (13/13) responsive to 1 mM halothaneor 1 mM sevoflurane. Conclusions. In both MHS and MHN fibres (i) halothane is a morepotent activator of SR Ca²⁺ release than sevoflurane and (ii)as with halothane, the efficacy of sevoflurane-induced SR Ca²⁺release exhibits a marked dependence on cytosolic [Mg²⁺]. Themarked potentiation of SR Ca²⁺ release after a moderate reductionin cytosolic [Mg²⁺] suggests that conditions which cause hypomagnesaemiawill increase the probability and possibly severity of an MHevent. Conversely, maintenance of a normal or slightly increasedcytosolic [Mg²⁺] may reduce the probability of MH.     

Sevoflurane preconditions stunned myocardium in septic but not healthy isolated rat hearts

Background. Recent evidence indicates that sevoflurane treatmentbefore prolonged ischaemia reduces infarct size in normal hearts,mimicking ischaemic preconditioning. We examined whether exposureto sevoflurane before brief ischaemia, inducing a ‘stunnedmyocardium’, provided such protective effects in an isolatedworking heart from normal or septic rats. Methods. With institutional approval, 91 rats were randomlyallocated into one of either caecal-ligation and perforation(CLP: n=50) or sham (Sham: n=41) procedure groups 24 h beforethe study. After determination of baseline measurements, includingcardiac output (CO), myocardial oxygen consumption (mV^·O₂)and cardiac efficiency (CE; COxpeak systolic pressure/mV^·O₂),each isolated heart was perfused with or without 2% sevofluranefor 15 min before global ischaemia (pre-ischaemia). After 15min ischaemia and 30 min reperfusion, all hearts were assessedfor functional recovery of myocardium (post-reperfusion). Results. During the pre-ischaemia period, 2% sevoflurane causeda significant reduction of CO in the CLP group compared withthe Sham group. During the post-reperfusion period, both CO(16.9 vs 11.0 ml min^–1) and CE (11.2 vs 7.7 mm Hg ml^–1(µl O₂)^–1) was higher in the sevoflurane-treatedvs -untreated hearts from CLP rats, and was accompanied by lowerincidence of reperfusion arrhythmia compared with control hearts(8 vs 32%). In contrast, 2% sevoflurane did not provide cardioprotectiveeffects in normal rats. Conclusions. The current study demonstrates that pre-treatmentwith sevoflurane minimizes myocardial dysfunction and the incidenceof reperfusion arrhythmia after brief ischaemic insults in septichearts. Br J Anaesth 2002; 89: 896–903     

Sevoflurane promotes endothelium-dependent smooth muscle relaxation in isolated human omental arteries and veins

Anesthesia with sevoflurane is accompanied by vasodilatation. This could be due to the effects of sevoflurane on endothelium-dependent relaxation. We measured muscle tension of isolated human omental arteries and veins in response to substance P or glyceryl trinitrate in the presence of sevoflurane (0%, 1%, 2%, or 4%). Vascular levels of guanosine 3', 5'-cyclic monophosphate were measured with enzyme-linked immunosorbent assay. Substance P induced an endothelium- and concentration-dependent relaxation in omental vessels that was not affected by sevoflurane. In the presence of L-N(G)-nitroarginine methyl ester (nitric oxide synthase inhibitor), KCl (prevention of hyperpolarization), or both, sevoflurane at 4% enhanced the relaxation in the arteries (P < 0.05). In the vein segments, the relaxation was enhanced by sevoflurane at 4% in the presence of KCl and 2% and 4% in the presence of both L-N(G)-nitroarginine methyl ester and KCl (P < 0.05). The glyceryl trinitrate-induced endothelium-independent relaxation was enhanced by sevoflurane at 4% in both artery and vein segments (P < 0.05). Substance P increased the levels of guanosine 3', 5'-cyclic monophosphate similarly in the presence and absence of sevoflurane. These results show that sevoflurane, in contrast to its effect in animal models, promotes endothelium-dependent relaxation in human omental arteries and veins via an enhancement of the smooth muscle response to relaxing second messengers.     

Analgesia with sevoflurane during labour: i. Determination of the optimum concentration

Background. Sevoflurane has favourable physical qualities forinhaled analgesia during labour pain. The aim of this preliminarystudy was to identify its optimum concentration. Methods. In this open-labelled escalating-dose study, 22 parturientsin labour self-administered sevoflurane at 10 contractions usingan Oxford Miniature Vaporiser. The inspired concentration wasincreased by 0.2% after each contraction from 0% to 1.4% ordecreased if sedation occurred. Visual analogue scores (0–100mm) for pain intensity, pain relief, sedation, mood and copingwere measured after each contraction. Results. The median (IQR [range]) pain relief and sedation scoresincreased from 44 (43–56 [4–93]) mm and 55 (43–56[0–98]) mm at 0.2% sevoflurane, to 74 (72–78 [50–80])mm and 71 (71–73 [33–97]) mm at 1.2% sevoflurane,respectively. Pain relief scores did not show any significantincrease above 0.8% whilst sedation continued to increase, withexcessive sedation occurring at 1.2% sevoflurane. No significantchanges in other scores were measured. Conclusions. We concluded that the optimal sevoflurane concentrationin labour was 0.8%. This concentration allows a safety marginand balances the risk of sedation with the benefit of pain reliefin labour.      

Effects of halothane, sevoflurane and propofol on left ventricular diastolic function in humans during spontaneous and mechanical ventilation

Background. There is limited knowledge of the effects of anaestheticson left ventricular (LV) diastolic function in humans. Our aimwas to evaluate these effects in humans free from cardiovasculardisease. Methods. Sixty patients (aged 18–47 yr) who had no historyor signs of cardiovascular disease were randomized to receivegeneral anaesthesia with halothane, sevoflurane or propofol.Echocardiography was performed at baseline and during spontaneousrespiration at 1 minimum alveolar concentration (MAC) of theinhalational agents or propofol 4 µg ml^–1 (step1), and repeated during positive-pressure ventilation with 1and 1.5 MAC of the inhalational agents or with propofol 4 and6 µg ml^–1 (steps 2A and 2B). Analysis of echocardiographicmeasurements focused on heart rate corrected isovolumic relaxationtime (IVRT_c) and early diastolic peak velocity of the lateralmitral annulus (E_a). Results. IVRT_c decreased from baseline to step 1 in the halothanegroup (82 [95% CI, 76–88] ms and 74 [95% CI, 68–80]ms respectively; P=0.02), remained stable in the sevofluranegroup (78 [95% CI, 72–83] ms and 73 [95% CI, 67–81]ms; n.s.) and increased in the propofol group (80 [95% CI, 74–86]ms and 92 [95% CI, 84–102] ms; P=0.02). E_a decreased inthe propofol group only (18.8 [95% CI, 16.5–19.9] cm s^–1and 16.0 [95% CI, 14.9–17.9] cm s^–1; P=0.003). Fromstep 2A to step 2B, IVRT_c increased further in the propofolgroup (109 [95% CI, 99–121] ms and 119 [95% CI, 99–135]ms; P=0.04) but remained stable in the other two groups. E_adid not change from step 2A to step 2B. Conclusions. Halothane and sevoflurane did not impair LV relaxation,whereas propofol caused a mild impairment. However, the impairmentby propofol was of a magnitude that is unlikely to cause clinicaldiastolic dysfunction.      

Sevoflurane and propofol decrease intraocular pressure equally during non-ophthalmic surgery and recovery

Background. To provide good control of intraocular pressure(IOP) during anaesthesia and surgery, we conducted a study comparingthe effects on IOP during maintenance and recovery of sevofluranevs propofol anaesthesia in 33 patients (ASA I–II) undergoingelective non- ophthalmic surgery. Methods. Anaesthesia was induced with propofol 2 mg kg^–1,fentanyl 2 µg kg^–1 and vecuronium 0.1 mg kg^–1.Patients were allocated randomly to receive either propofol4–8 mg kg^–1 h^–1 (group P; n=16)or 1.5–2.5 vol% sevoflurane (group S; n=17) for maintenanceof anaesthesia. Fentanyl 2–4 µg kg^–1was added if necessary. The lungs were ventilated with 50% airin oxygen. Blood pressure, heart rate, oxygen saturation andend-tidal carbon dioxide were measured before and throughoutanaesthesia and in the recovery room. IOP was determined withapplanation tonometry (Perkins) by one ophthalmologist blindedto the anaesthetic technique. Results. There was a significant decrease in IOP after inductionand during maintenance of anaesthesia in both groups. No significantdifferences in IOP between the two groups was found. Conclusion. Sevoflurane maintains the IOP at an equally reducedlevel compared with propofol. Br J Anaesth 2002; 89: 764–6     

Agitation and changes of Bispectral Index and electroencephalographic-derived variables during sevoflurane induction in children: clonidine premedication reduces agitation compared with midazolam

Background. This double-blind randomized study was undertakento assess agitation, Bispectral Index^TM (BIS^TM) and EEG changesduring induction of anaesthesia with sevoflurane in childrenpremedicated with midazolam or clonidine. Methods. Children were allocated randomly to receive rectalmidazolam 0.4 mg kg^–1 (n=20) or oral clonidine 4µg kg^–1 (n=20) as premedication. Rapid inductionof anaesthesia was achieved with inhalation of sevoflurane 8%in nitrous oxide 50%–oxygen 50%. After tracheal intubation,the children’s lungs were mechanically ventilated andthe inspired sevoflurane concentration was adjusted to achievean end-tidal fraction of 2.5%. The EEG and BIS^TM were recordedduring induction until 10 min after tracheal intubation. TheEEG was analysed using spectral analysis at five points: baseline,loss of eyelash reflex, 15 s before the nadir of the BIS^TM (BIS_nadir),when both pupils returned to the central position (immediatelybefore intubation), and 10 min after intubation. Results. Agitation was observed in 12 midazolam-treated andfive clonidine-treated patients (P=0.05). At baseline, EEG rhythmswere slower in the clonidine group. Induction of anaesthesiawas associated with similar EEG changes in the two groups, withan increase in total spectral power and a shift towards lowfrequencies; these changes were maximal around the end of thesecond minute of induction (BIS_nadir). When the pupils had returnedto the central position, fast EEG rhythms increased and BIS^TMwas higher than BIS_nadir (P<0.05). In both groups, agitationwas associated with an increase in slow EEG rhythms at BIS_nadir. Conclusions. Compared with midazolam, clonidine premedicationreduced agitation during sevoflurane induction. During inductionwith sevoflurane 8% (oxygen 50%–nitrous oxide 50%), thenadir of the BIS^TM occurred at the end of the second minuteof inhalation. Agitation was associated with a more pronouncedslowing of the EEG rhythms at BIS_nadir compared with inductionsin which no agitation was observed. The BIS^TM may not followthe depth of anaesthesia during sevoflurane induction in children. Br J Anaesth 2004; 92: 504–11     

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.     

Comparison of the role of endothelin, vasopressin and angiotensin in arterial pressure regulation during sevoflurane anaesthesia in dogs

Background. In this study we aimed to clarify the role of endothelinin arterial pressure regulation during anaesthesia with increasingconcentrations of sevoflurane (1–3 MAC) and compare itwith those of vasopressin and angiotensin. Methods. After an awake control period, on different days, sixdogs underwent each of the following four interventions: sevofluraneanaesthesia alone (1–3 MAC), sevoflurane after block ofeither endothelin receptors using tezosentan (3 mg kg^–1followed by 3 mg kg^–1 h^–1), vasopressinV_1a receptors using [d(CH₂)₅Tyr(Me²)]AVP (40 µg kg^--1)or angiotensin receptors using losartan (6 mg kg^–1 h^–1).Plasma concentrations of endothelin, big endothelin, vasopressinand renin were measured. Effects of sevoflurane in the presenceand absence of the respective receptor block were analysed andcompared using analysis of variance for repeated measures (ANOVAfollowed by Fisher’s PLSD (protected least significantdifference) (P<0.05)). Results. Mean arterial pressure decreased in a dose-dependentmanner with sevoflurane during all interventions. At 1 MAC,this decrease was greatest during angiotensin receptor block(mean (SEM), –41 (3) mm Hg), intermediate duringvasopressin and endothelin receptor block (–31 (4) and–30 (2) mm Hg respectively), and least during sevofluranealone (–24 (3) mm Hg). The course of systemic vascularresistance mirrored the course of arterial pressure, while cardiacoutput did not differ between groups. Plasma concentrationsof endothelin, big endothelin and renin did not change duringany intervention, whereas vasopressin concentration increasedfrom     

Inhalation anaesthetics increase heart rate by decreasing cardiac vagal activity in dogs

Inhalation anaesthetics decrease heart rate in isolated heartsbut mostly increase heart rate in the intact organism, althoughmost inhibit sympathetic drive. Differences in the degree ofincrease in heart rate between agents may be related to differencesin their vagolytic action. To test this hypothesis, we studied theeffects of halothane (H), isoflurane (I), enflurane (E), sevoflurane (S)and desflurane (D) [1–3 MAC (minimum alveolar concentration)]on heart rate and heart rate variability (HRV) as a measureof cardiac vagal activity in seven dogs. HRV was analysed inthe time domain as the standard deviation of the RR interval(SDNN) and in the frequency domain as power in the high-frequency(HF, 0.15–0.5 Hz) and low-frequency (LF, 0.04–0.15 Hz)ranges. Heart rate increased with anaesthetic concentrationand there were corresponding decreases in SDNN, HF power and LFpower. Heart rate increased most with D (+40 beats min^–1),least with H (+8 beats min^–1) and to an intermediate extentwith S, I and E. SDNN and HF power, as measures of vagal activity, changedin the opposite direction and decreased in the same order asheart rate increased. However, SDNN and HF power correlatedsignificantly with heart rate [r=–0.81 (0.04) and –0.81 (0.03)respectively] and were independent of the anaesthetic and its concentration(P<0.05). Consistent with our hypothesis, these results suggestthat differences between agents in the degree of increase inheart rate are explained by differences in their vagolytic action. Br J Anaesth 2001; 87: 748–54     

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.