Respiratory Mechanics During Sevoflurane Anesthesia in Children With and Without Asthma

Respiratory Mechanics During Sevoflurane Anesthesia in Children With and Without AsthmaWalid Habre,MD*,Pietro Scalfaro,MD†,Craig Sims,FANZCA‡,Katrina Tiller,BMath†,and Peter D.Sly,MD,FRACP†*Division of Anaesthesia,Geneva Children’s Hospital,Geneva,Switzerland;†Division of Clinical Sciences,Institute for Child Health Research,Perth,Australia;and‡Department of Anaesthesia,Princess Margaret Hospital for Children, Perth,Western AustraliaWe studied lung function in children with and without asthma receiving anesthesia with sevoflurane.Fifty-two children had anesthesia induced with sevoflurane (up to8%)in a mixture of50%nitrous oxide in oxygen and then maintained at3%with children breathing spontaneously via face mask and Jackson-Rees modifi-cation of the T-piece.Airway opening pressure and flow were then measured.After insertion of an oral en-dotracheal tube under5%sevoflurane,measurements were repeated at3%,as well as after increasing to4.2%. Respiratory system resistance(Rrs)and compliance during expiration were calculated using multilinear re-gression analysis of airway opening pressure and flow, assuming a single-compartment model.Data from44 children were analyzed(22asthmatics and22normal children).The two groups were comparable with re-spect to age,weight,ventilation variables,and baseline respiratory mechanics.Intubation was associated with a significant increase in Rrs in asthmatics(17%Ϯ49%), whereas in normal children,Rrs slightly decreased (Ϫ4%Ϯ39%).At4.2%,Rrs decreased slightly in both groups with almost no change in compliance system resistance.We concluded that in children with mild to moderate asthma,endotracheal intubation during sevoflurane anesthesia was associated with increase in Rrs that was not seen in nonasthmatic children.Impli-cations:Tracheal intubation using sevoflurane as sole anesthetic is possible and its frequency is increasing. When comparing children with and without asthma, tracheal intubation under sevoflurane was associated with an increase in respiratory system resistance in asthmatic children.However,no apparent clinical ad-verse event was observed.(Anesth Analg1999;89:1177–81)S evoflurane is a volatile anesthetic often used for anesthesia in children(1–3).It provides rapidand smooth inhaled induction(4,5)because of a low blood:gas solubility coefficient,and maintains blood pressure and heart rate during induction and maintenance of anesthesia(6).With the world-wide increase in asthma prevalence (7,8),more asthmatic children are likely to require anesthesia for surgical procedures.Asthmatics are prone to bronchospasm induced by different irritant stimuli.Tracheal intubation can induce an increased release of acetylcholine from postganglionic cholin-ergic nerves and produce bronchospasm via vagal reflex pathways(9).Clinically,halothane has been the volatile anesthetic of choice in asthmatics because of its bronchodilator actions.Recently,we demonstrated that sevoflurane was as effective as halothane in pre-venting methacholine-induced increase in lung resis-tance in an animal model(10).The safety of the use of sevoflurane in asthmatic children has not yet been reported.This study was designed to measure lung function in asthmatic and nonasthmatic children receiving sevoflurane for induction of anesthesia and endotra-cheal intubation.Measurements were performed be-fore and after intubation to determine if sevoflurane would limit the increase in airway resistance that may occur under these circumstances.MethodsPatientsAfter institutional ethics committee approval and pa-rental written consent,we studied52children aged2 to12yr.All children were ASA physical status I or IIThis work was achieved in the Department of Anaesthesia,Prin-cess Margaret Hospital for Children,Perth,Western Australia.Presented in part at the annual meeting of the American Societyof Anesthesiology Orlando,FL,October17,1998.Accepted for publication July1,1999.Address correspondence and reprint requests to Walid Habre,MD,Division of Paediatric Anaesthesia,Geneva Children’s Hospi-tal,6,rue Willy Donze,1205Geneva,Switzerland.Address e-mail toWalid.Habre@hcuge.ch.©1999by the International Anesthesia Research Society0003-2999/99Anesth Analg1999;89:1177–811177and were scheduled for elective surgery under general anesthesia requiring tracheal intubation.Children were classified during the preoperative anesthetic as-sessment into two groups:1)children with a history of physician-diagnosed asthma,and2)children with normal lungs and no history of asthma or atopy(hay fever,allergy,eczema).All asthmatic children had a history of multiple asthma episodes in the last12mo diagnosed clinically and treated by their physician, but none was symptomatic at the time of enrollment into the study.Children with recent upper respiratory infection in the previous2weeks were excluded,as well as children scheduled for adenotonsillectomies or having obstructive apnea disorders.Anesthetic ManagementNo premedication or␤2-agonist or other asthma med-ication was given as per our routine.All children had anesthesia induced with sevoflurane(up to8%)in a mixture of50%nitrous oxide in oxygen then main-tained at3%sevoflurane(1.2minimum alveolar anes-thetic concentration[MAC])with children breathing spontaneously via face mask and Jackson-Rees modi-fication of the T-piece.Airway opening pressure(Pao) and flow(VЈ)were then measured.Sevoflurane was delivered at a concentration of5%to obtain the95% effective dose for tracheal intubation(4.68%with95% confidence interval[CI]of3.91%–12.74%)(11).After insertion of an oral endotracheal tube(ETT),regular spontaneous respiration was reestablished under3% (1.2MAC)sevoflurane in a mixture of50%nitrous oxide in oxygen,and measurements of respiratory mechanics were repeated.Sevoflurane was then in-creased to4.2%(1.7MAC)and a final set of mea-surements was collected after allowing the patient to reach a new steady state.All measurements were achieved under the same concentration of carrier gas, 50%nitrous oxide in oxygen.During preliminary studies,sevoflurane concentration was measured us-ing an AS3Datex monitor.In the setup,a steady state, as judged from end-tidal gas concentration,was achieved after3min of initiating sevoflurane or changing the concentration.EquipmentA pressure port and transducer were used to measure Pao and a heated screen pneumotachograph(Hans Rudolph,Inc.,Kansas City,MO)to measure VЈ.This equipment was placed between the patient’s facial mask or tracheal tube and the Jackson-Rees modifica-tion of the T-piece.The Pao and VЈsignals were sam-pled at100Hz and low-pass filtered using scientific respiratory equipment(amplifier and signal condi-tioner SC-14C,pressure transducers TG-40and TD-05; SCIREQ,Inc.,Montreal,Quebec,Canada)and stored through a12-bit AD converter on a PC computer(Data Translation,DT2801-A).All data were collected and analyzed using a data acquisition software package (Anadat&Labdat,RHT Infodat,Montreal,Quebec, Canada).Measurement of Respiratory Mechanics Respiratory mechanics were calculated by apply-ing a single-compartment model using multilinear re-gression analysis to calculate dynamic compliance (Crs,dyn)and respiratory system resistance(Rrs)dur-ing the expiration phase only,based on:PaoϭV/Crs,dynϩVЈRrsϩP A,EE.V is the volume and P A,EE reflects the end-expiratory alveolar pressure(12).The Crs,dyn is the reciprocal of respiratory system elastance(Ers).To allow for venti-lation up to the nonlinear portion of the volume-pressure curve,elastance was allowed to vary by the inclusion of a volume-dependent term(E2⅐V).Thus, 1/CrsϭErsϭE1ϩE2⅐V.The multilinear regression(MLR)analysis calcu-lates the coefficients Crs,dyn,Rrs,and P A,EE by fitting the equation of motion of the model to Pao,V,and VЈmeasured at the airway opening.The quality of fit of the model to the data is judged by the coefficient of determination r2(Fig.1).We only included data ep-ochs in which r2Ն0.96.The MLR produces a weighted average for Crs and Rrs throughout the respiratory cycle.We used data collected in expiration only to avoid influence of leak around the tracheal tube and as subjects were spontaneously breathing. During spontaneous breathing,the pressure during inspiration is the transpulmonary pressure,requiring measurement of the esophageal pressure.However, during expiration,the Pao is the pressure applied to the respiratory system and can be used to calcu-late respiratory mechanics using the MLR without measuring esophageal pressure when expiration is passive.StatisticsA difference of25%in Rrs between asthmatic and nonasthmatic children would be considered clinically significant.Based on our previous study in normal children under muscle relaxation(13),a group size of 20–23subjects would have85%–90%power to detect such a difference.Unpaired two-tailed t-tests were used to compare demographic data and respiratory variables between asthmatic and nonasthmatic chil-dren,and paired two-tailed t-tests were used to compare respiratory mechanical outcomes between children at different times.A multilevel modeling ap-proach was then used to analyze differences in respi-ratory mechanics between asthmatics and nonasth-matics,and before and after oral tracheal intubation.1178PEDIATRIC ANESTHESIA HABRE ET AL.ANESTH ANALG SEVOFLURANE AND RESPIRATORY MECHANICS1999;89:1177–81The two outcomes analyzed were Rrs and Crs.The models were fitted using Mln v1.0(14).Separate and combined effects for group (asthmatic/control)and time were considered for inclusion in the models.Time was treated as a categorical variable with three levels:baseline (3%before ETT),3%after ETT,and 4.2%after ETT.The significance level was taken as 5%.Data are presented as means Ϯsd .ResultsBaselineData from eight patients could not be used (five asth-matics and three children with normal lungs)because they failed to satisfy the inclusion criteria or the fitting in the multilinear regression analysis model.Four of the eight patients had a coefficient of correlation less than 95%,the other four had either clinical evidence of active expiration or technical problems.Thus,the analysis was performed using data from 44children (22in each group).The two groups of patients were comparable with respect to age,weight,gender,and size of ETT (Ta-ble 1).Among the 22asthmatics,8had salbutamol on demand,1had beclomethasone,and 7had both.In addition,cromoglycate was prescribed to 1patient,combined with beclomethasone to 2patients and with salbutamol to 3other patients.Ventilation variables and respiratory mechanics were comparable between asthmatics and children with normal lungs when breathing spontaneously via face mask at 3%sevoflurane in a mixture of 50%nitrous oxide in oxygen (Table 2).Changes with IntubationVentilation Variables.After intubation,there was a significant decrease in Vt in both children with and without asthma (respectively,Ϫ10.8%[95%CI:Ϫ23.1%,ϩ1.4%,P ϭ0.019]and Ϫ14.7%[95%CI:Ϫ23.9%,Ϫ5.4%,P ϭ0.001]).There was no differencein the mean tidal volume between groups (respec-tively 4.2Ϯ1.2mL ⅐kg Ϫ1vs.4.7Ϯ1.2mL ⅐kg Ϫ1,P ϭ0.85).There was a change in breathing pattern (ex-pressed by an increase in Ti/Te,with Ti and Te being,respectively,inspiratory and expiratory times)with no changes in frequency.At 4.2%,we observed further decreases in tidal volume values in both groups,with a significant increase in respiration rate in both groups (Table 2).Respiratory Mechanics.After intubation under 3%sevoflurane,there was a statistically significant in-crease in Rrs in children with asthma,whereas in normal children,Rrs decreased slightly (but did not reach statistical significance).The percentage change in Rrs was ϩ17%Ϯ49%(95%CI for mean:Ϫ4.4%,ϩ39.1%)in asthmatics and Ϫ4%Ϯ39%in children with normal lungs (95%CI for mean:Ϫ21.2%,ϩ13.5%)(Fig.2).After intubation,the mean value in Rrs was signif-icantly higher in the asthmatics compared with nor-mal children (0.49Ϯ0.2Pa ⅐mL Ϫ1⅐s Ϫ1vs 0.40Ϯ0.15,P ϭ0.042).There were no systematic changes in Crs in either group.The changes in individual children in both groups varied widely after intubation.Ninety-five percent CI for means were (Ϫ19.7%,ϩ265%)for normal children and (ϩ14%,ϩ219%)for asthmatic children.The increase in sevoflurane concentration to 1.7MAC resulted in a small decrease in Rrs in both groups (Ϫ4.1%Ϯ0.18%in children with asthma vs Ϫ5%Ϯ0.15in children without asthma,P ϭ0.865),and no systematic changes in the Crs.DiscussionIn our study,before intubation,respiratory mechanics were comparable after inhaled induction of anesthesia with sevoflurane in normal children and children with asymptomatic asthma.Endotracheal intubation under sevoflurane was followed by a small but significant increase in Rrs in children with asthma that was not seen in the nonasthmatic group,suggesting that sevoflurane did not prevent this increase in resistance after intubation.This increase in Rrs was reversed once anesthesia wasdeepened.Figure 1.Example of a model fit:airway opening pressure during expiration.Table 1.Anthropometric DataControl (n ϭ22)Asthma (n ϭ22)P value Age (mo)57.9Ϯ2571.9Ϯ310.1(24–118)(32–132)Weight (kg)18.6Ϯ4.622Ϯ7.60.08(12.4–30.5)(13.1–45)Gender (male/female)9/1311/110.54ETT size (median ϮIQR)5.5Ϯ0.55.5Ϯ10.2Data are expressed as means Ϯsd (range).ETT ϭendotracheal tube,IQR ϭinterquartile range.ANESTH ANALG PEDIATRIC ANESTHESIA HABRE ET AL.11791999;89:1177–81SEVOFLURANE AND RESPIRATORY MECHANICSOur anesthetic management was that which would be used clinically in children with asthma (15).The major departure from normal practice was that neu-romuscular blocking drugs were not administered prior to intubation.This was done to avoid the con-founding effect of comparing respiratory mechanics during spontaneous breathing prior to intubation,with measurements taken during positive pressure ventilation postintubation.We would not expect our results to have been different if muscle relaxants had been used (16).The increase in Rrs after intubation seen in asth-matic children in the present study is at odds with the findings of Rooke et al.(17),who reported that sevoflurane (1.1MAC)decreased Rrs after intubationin a group of normal adults.The nonasthmatic chil-dren in our study also showed a small decrease (ap-proximately 4%)in Rrs after intubation,which,al-though it approached statistical significance,was clinically insignificant.In contrast,the increase in Rrs after intubation in the asthmatic group was larger (approximately 18%)and was statistically significant.This difference also approached our a priori definition of clinical significance (25%).These children had sta-ble mild to moderate asthma.One might expect the increase in Rrs after intubation to be greater in chil-dren with less stable asthma.No systematic changes were seen in Crs after endo-tracheal intubation in either group.The lack of effect of sevoflurane in both groups on the compliance may be explained by the fact that changes in functional residual capacity occur immediately after induction of anesthesia (before our first set of measurements),with no further effect of the depth of anesthesia (18,19).The second part of our study was designed to es-tablish whether an increase in sevoflurane concentra-tion to 1.7MAC induced further changes in res-piratory mechanics.Increasing the concentration of sevoflurane was followed by a similar decrease in Rrs in both groups.There was also a reduction in tidal volume with increased sevoflurane,which may be related to a great depression of intercostal muscle function with increasing depth of anesthesia (20).There was a significant tachypnea in both groups,which has recently been reported after induction of sevoflurane in adults (21).Whether the tachypneic properties of sevoflurane result,like halothane,from the effect of the anesthetic on the suprapontine struc-tures is unknown (22).Table 2.Changes in Ventilation Variables and Respiratory Mechanics After Endotracheal Intubation with Sevoflurane at 3%and 4.2%3%on mask3%on ETT 4.2%on ETT Tidal volume (mL/kg)Control 5.8Ϯ1.8 4.7Ϯ1.2* 3.2Ϯ0.7†Asthma5.0Ϯ1.8 4.2Ϯ1.2* 2.9Ϯ0.7†Respiration rate (breaths/min)Control 35Ϯ636Ϯ641Ϯ7†Asthma 33Ϯ532Ϯ635Ϯ7†Ti/TeControl 0.48Ϯ0.090.51Ϯ0.08*0.52Ϯ0.08Asthma0.46Ϯ0.090.49Ϯ0.110.49Ϯ0.11Compliance (mL/Pa)Control 1.86Ϯ1.66 1.82Ϯ0.92 1.79Ϯ1.23Asthma2.00Ϯ2.39 1.90Ϯ1.80 1.91Ϯ2.30Resistance (Pa ⅐mL Ϫ1⅐s Ϫ1)Control 0.44Ϯ0.120.40Ϯ0.150.38Ϯ0.15Asthma0.42Ϯ0.090.49Ϯ0.20*‡0.45Ϯ0.15Data are expressed as means Ϯsd .ETT ϭendotracheal tube.*Significance at 3%before and after ETT.†Significance between 3%and 4.2%with ETT.‡Significance between bothgroups.Figure 2.Point estimates and standard errors for Rrs in children with and without asthma.(*Significance between value before and after intubation in asthmatics;‡significance at 1.2minimal alveolar anesthetic concentration after intubation between both groups.)1180PEDIATRIC ANESTHESIA HABRE ET AL.ANESTH ANALG SEVOFLURANE AND RESPIRATORY MECHANICS 1999;89:1177–81Among the different techniques used to measuredynamic respiratory mechanics that have been vali-dated for use in children under anesthesia,MLR tech-niques are the most easily implemented(13,23,24).Because the children in our study were spontaneouslybreathing,we limited our analysis to the expiratoryphase only.This does not imply that respiratory me-chanics are the same during inspiration and expira-tion;however,measurements made during expirationcan be used to follow changes in lung function(25).We did not correct Rrs for the resistance of the ETT,because this required exact knowledge of the tuberesistance.As demonstrated by Chang and Mortola(26),the tube resistance measured in vitro often over-estimates its resistance in vivo.This is particularly truefor small tubes.Because the ages of the children andthe size of the tubes used were the same in bothgroups,we felt it was preferable not to attempt tocorrect Rrs for the tube resistance.We considered only children with a definite historyof physician-diagnosed asthma with at least one epi-sode of wheezing requiring the use of␤-adrenergic agonist in the last12mo.This pattern is generallyassociated with bronchial hyperresponsiveness whenassessed by a physiological test such as exercise(27).Because none of the children received a␤-adrenergic agonist on the day of surgery,we can conclude that changes in respiratory patterns and mechanics are only related to the effect of sevoflurane.In conclusion,in asymptomatic children with mildto moderate asthma,endotracheal intubation undersevoflurane followed by maintenance at1.2MAC,wasassociated with an increase in Rrs(18%)during spon-taneous breathing.Although this increase was notassociated with any clinically apparent adverse event,one should be cautious when using sevoflurane forendotracheal intubation in asthmatic children,espe-cially those with more severe or unstable asthma.Further investigation is being performed to evaluatethe ability of pretreatment with a␤-adrenergic agonist to prevent the increase in Rrs seen after tracheal intu-bation under sevoflurane in asthmatic 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