some children need sedation because of fear or anxiety in pediatric dentistry.13 in pediatric dental practice , for which analgesia is accomplished by local or regional anesthesia , sedation application is considerably different from medical practice.15 to assess the depth of the sedation , physiological signs such as heart rate , blood pressure , and respiratory rate are important . but physiological signs exhibit large inter - patient variability and are quite dependent on the medications used . also , they are only indirect expressions of the drugs effects on the brain and other major systems . the use of sedation scales is the most frequent method of quantifying the sedative effect . most commonly , subjective clinical scoring methods are used.57 the most popular is the observer s assessment of alertness and sedation ( oaa / s ) scale ( table 1).810 it measures the level of alertness in sedated subjects based on the assessment of 4 categories : responsiveness , speech , facial expression and ocular appearance . also , the ramsay sedation scale ( rss)11 ( table 2 ) is well established for the evaluation of sedation . the bispectral index ( bis ) offers a potential alternative to subjective scales when they do not work well or may not be sufficiently sensitive to evaluate sedation level . bispectral index is a processed electroencephalographic ( eeg ) parameter , expressed as a numeric value ranging from 0 ( isoelectric ) to 100 ( awake with eyes open ) that is used clinically as a measure of hypnosis . it is currently used most commonly intraoperatively to monitor the effects of anesthetic and sedative agents as a means of judging the depth of sedation or anesthesia.12,13 bispectral index monitoring is suggested to non anesthesiologist in order to avoid too deep sedation.14 some studies have shown a significant correlation between bis and oaa / s scores by using different sedative drugs with n2o / o2 , but others have shown that n2o has no effect on bis in human volunteers when used solely.10,13,15,16 the other researchers showed that paradoxical changes might occur at bis values during induction of anesthesia.13,1719 although n2o has been widely used as an anesthetic adjuvant , its effect on eeg activity is poorly understood because it is usually studied in the presence of additional anesthetics , including inhaled anesthetics . leduc et al20 showed that n2o / o2 at peri - mac partial pressures prevents eeg activation resulting from noxious electrical stimulation in rats . however , hall et al21 found correlation with increasing doses of n2o from approximately 35 to 70% . the aim of the current study was to assess any bis changes during n2o / o2 sedation in pediatric dentistry . this prospective research was performed in gazi university faculty of dentistry . after obtaining gazi university faculty of dentistry ethic committee approval and informed parental consent , 45 children having asa physical status i , aged 7 to 12 years , weighing 21 to 33 kg ( table 1 ) , and scheduled for primary teeth extraction were enrolled into the study . the participant were seen for their initial exam and it was determined that they definitely exhibited  definitely negative  behavior according to the frankl scale23 ( table 3 ) . exclusion criteria were refusal to have application of nasal hood or insufficient sedation ( body movements , complaints , moaning , and crying ) . sedation levels were evaluated and graded according to the oaa / s4 ( table 1 ) and rss7 ( table 2 ) scales . no other premedication was given . before sedation procedure , patients were assessed with rss and then monitored with pulse oximetry ( datex - ohmeda tuffsat ) and bis ( aspect medical systems , a 2000 bis ) . a disposable bis sensor was applied to the patient s forehead . sedation was induced in standardized manner for all patients by nasal hood inhalation of 40% n2o in o2 , and continued with 4060% n2o in o2 ( inspired n2o fraction ) with high fresh flow of 5 l min . the patient s heart rate ( hr ) , peripheral oxygen saturation ( spo2 ) , and bis measurements were recorded before ( t0=initial base values ) and during the sedation ( t1=third minute after initiation of n2o inhalation through a nasal hood and , respectively , t2=4 min , t3=5 min , t4=6 min ) , and recovery period ( t5=7 min , t6=8 min ) at one minute intervals . paired measurements of bis , rss and oaa / s scores were obtained during the sedation period and recorded at one minute intervals . the investigator who performed the rss and oaa / s assessments was blinded to the bis values and n2o / o2 concentration . at the end of the extraction , n2o inhalation was discontinued and 100% o2 inhalation was performed for two minutes . nasal hood and monitors were removed when the patient was alert and hr and spo2 values were within the normal range . if any complication was observed , it was noted down . topical anesthesia in the form of benzocaine gel 20% was applied to the dried mucosa adjacent to the tooth . lidocaine 2% with 1:80000 adrenaline was then given in a standardized manner to each quadrant just before acquiring the bis values ( t2=4 min after initiation of n2o inhalation through a nasal hood ) . once analgesia had been achieved , the primary teeth were extracted ( t4=6 min after initiation of n2o / o2 inhalation through a nasal hood ) . the time course of the parameters during the t1 - 6 periods of the bis , spo2 and hr and control sessions ( t0 ) were evaluated using one - way analysis of variance ( anova ) with repeated measurements and then the post hoc tamhane test was performed if difference was significant . using cross tabulation , a chi - square analysis was done between bis levels and oaa / s scores in all time periods and correlation was calculated with pearson correlation coefficient ( r ) value ( r=00.25 weak correlation , 0.251 < r < 0.500 moderate correlation , 0.501 < r < 0.750 strong correlation , 0.751 < r < 1.00 most strong correlation ) . no other premedication was given . before sedation procedure , patients were assessed with rss and then monitored with pulse oximetry ( datex - ohmeda tuffsat ) and bis ( aspect medical systems , a 2000 bis ) . a disposable bis sensor was applied to the patient s forehead . sedation was induced in standardized manner for all patients by nasal hood inhalation of 40% n2o in o2 , and continued with 4060% n2o in o2 ( inspired n2o fraction ) with high fresh flow of 5 l min . the patient s heart rate ( hr ) , peripheral oxygen saturation ( spo2 ) , and bis measurements were recorded before ( t0=initial base values ) and during the sedation ( t1=third minute after initiation of n2o inhalation through a nasal hood and , respectively , t2=4 min , t3=5 min , t4=6 min ) , and recovery period ( t5=7 min , t6=8 min ) at one minute intervals . paired measurements of bis , rss and oaa / s scores were obtained during the sedation period and recorded at one minute intervals . the investigator who performed the rss and oaa / s assessments was blinded to the bis values and n2o / o2 concentration . at the end of the extraction , n2o inhalation was discontinued and 100% o2 inhalation was performed for two minutes . nasal hood and monitors were removed when the patient was alert and hr and spo2 values were within the normal range . if any complication was observed , it was noted down . topical anesthesia in the form of benzocaine gel 20% was applied to the dried mucosa adjacent to the tooth . lidocaine 2% with 1:80000 adrenaline was then given in a standardized manner to each quadrant just before acquiring the bis values ( t2=4 min after initiation of n2o inhalation through a nasal hood ) . once analgesia had been achieved , the primary teeth were extracted ( t4=6 min after initiation of n2o / o2 inhalation through a nasal hood ) . the time course of the parameters during the t1 - 6 periods of the bis , spo2 and hr and control sessions ( t0 ) were evaluated using one - way analysis of variance ( anova ) with repeated measurements and then the post hoc tamhane test was performed if difference was significant . using cross tabulation , a chi - square analysis was done between bis levels and oaa / s scores in all time periods and correlation was calculated with pearson correlation coefficient ( r ) value ( r=00.25 weak correlation , 0.251 < r < 0.500 moderate correlation , 0.501 < r < 0.750 strong correlation , 0.751 < r < 1.00 most strong correlation ) . five patients who refused to have application of nasal hood were excluded from the study , and finally 40 patients were studied . demographic properties are presented in table 4 . at baseline ( t0 ) and during the sedation procedure ( t1-t6 ) vital signs , including spo2 and hr were recorded . the comparison of time dependent mean values of spo2 and hr ( t1 , t2 , t3 , t4 , t5 and t6 time points between t0 sessions ) were similar ( p > .05 ) and statistically not different in normal clinical range . the comparison of time dependent mean bis values at t1 , t2 , t3 , t4 , t5 and t6 time points between t0 sessions were similar and statistically not different ( p > .05 ) . / o2 sedation , patients rss were determined as 1 but after the administration of n2o / o2 , at the t1 - 6 time points patients rss were 2 and oaa / s scores of patients were 4 or 5 . during t1 - 6 although administration of 4060% n2o concentration is enough to provide sedation according to the oaa / s scores in 40 children during the study period , no changes were obtained in bis values . no correlation was found between bis and the oaa / s scores levels at the t1 - 6 periods ( p = .126 , r = 0.1 ) . ramsay sedation scores and oaa / s correlations can not be computed because at least one of the variables is constant . figure 1 shows all the pearson correlation coefficients between bis levels and oaa / s scores during the study period . pearson coefficient values indicate that weak correlation was obtained between bis levels and oaa / s scores at all time periods ( r < 0.25 ) . there was no complication except nausea and vomiting at two patients during the recovery period . in this research , children were clinically sedated with 4060% n2o / o2 according to the rss and oaa / s , but bis values did not alter or paradoxical changes occur during the sedation procedure . pediatric patients who are referred to the dental clinics are especially anxious with dental extractions . administration of n2o in o2 is widely used to induce both analgesia and sedation and to improve patient cooperation during dental treatments.1,2,24,25 investigations were recognized that bis scores were decreased by different sedation or hypnosis techniques . 6,9,12,26 sadhasivam et al9 researched the validation of bis for sedation with oral chloral hydrate , in meperidine + promethazine , iv midazolam + fentanyl , and iv pentobarbital + mida zolam + fentanyl , and it demonstrates that the bis scores were significantly correlated with their paired oaa / s scores . religa et al27 conducted a study on pediatric patients , requiring dental restorations , between 3 to 6 years of age who received oral sedation with chloral hydrate or meperidine or hydroxyzine intraoperatively and n2o / o2 was also administrated . a significant association was detected between observed patient behaviors during sedation and levels of sedation as measured by bis . in an earlier study including 2 of 13 volunteers , bis did not change with inspired n2o concentrations up to 50% . the authors emphasized the stimulatory changes at lower and higher frequency ranges of eeg , which decreased at low n2o concentration.15 ramesh at al28 suggested that n2o affects bis values in patients under isoflurane anesthesia . park et al10 reported that n2o when used for sedation during epidural anesthesia does not have the expected effect on bis signals . two research showed that no change in bis or cerebral state index value while the participants breathed 70% n2o in o2 although all of them lost consciousness clinically.29,30 in their research on 22 healthy volunteers who were sedated by low n2o , hall et al21 reported that no correlation was found with oaa / s and bis . but a correlation was found when n2o concentration was increased from 35% up to 70% . however puri has reported paradoxical changes in bis during n2o administration.22 previous data regarding the use of bis during n2o sedation remain insufficient . probably , the conflicting results of various studies may be explained by the differential effects of n2o on eeg when administered at high / low concentrations or alone / in combination with sedative or anesthetics . in this research , the administration of n2o alone was adequate to perform teeth extraction but no alteration or paradoxical changes were observed at bis values . nitrous oxide is effective and the anesthetic effect wears off quickly so there is no extended recovery time.13 in our study none of the patients were observed to exceed the level of 3 with respect to oaa / s which is described as patient who responds only after loud or repeated calling . morse et al31 assessed the use of bis monitoring in 22 patients undergoing conscious sedation with midazolam or midazolam plus ketamine for dental surgery and found that the bis values remained close to baseline . in this research mean bis value was 97.4 and it was similar to results of morse et al . in children , especially at the little age group , it is difficult to perform bis and its devices.27 in our study group , children were aged between 712 years old . although the results of our study showed that n2o / o2 is enough to sedate children according to the rss and oaa / s scores , we did not observe any significant changes bis values . / o2 to sedate children undergoing dental extractions without any sedative agents does not require measuring the depth of sedation with bis monitor . further investigations are needed for the validity and clinical applicability of bis assessment with n2o / o2 sedation at different concentrations or combined with other sedative drugs of in a larger pediatric population under dental treatments .
objectivesto determine whether bispectral analysis ( bis ) changes during nitrous oxide ( n2o ) sedation in anxious children undergoing extraction of primary teeth.methodsin this prospective study 45 , asa physical status i children , aged between 7 to 12 years and scheduled for primary teeth extraction under n2o / o2 sedation are included . at baseline ( t0 ) and 
 during the sedation procedure ( t1 - 6 ) ; bis levels , ramsay sedation scores ( rss ) , oxygen saturation ( sp02 ) , and heart rate ( hr ) were recorded at one - minute intervals . forty percent n2o in o2 was given by a nasal hood , and n2o concentration was enhanced to 60% in a two - minute period . 
 paired measurements of bis levels with observer s assessment of alertness and sedation ( oaa / s ) scores were obtained during sedation procedure.resultssince 5 patients refused application of the nasal hood , a total 40 of the original 45 subjects completed the study . mean age and weight of the children were 9.5  1.4 years and 23.7  9.7 kg , respectively . 
 nitrous oxide inhalation produced no changes in bis levels despite a sedation level in oaa / s scores were observed at 4060% n2o concentrations.conclusionsbis values do not change during n2o / o2 sedation and the bis monitor is not appropriate to evaluate the depth of sedation provided by n2o 
 / o2 during primary teeth extraction in children .