Effects of Nitrous Oxide on Diazepam Sedation of Young Children

Effects of nitrous oxide on diazepam sedation of youngchildren

Milton I. Houpt, DDS, PhD Ari Kupietzky, DMD,MSc Nanci S. Tofsky, DDS, MS Samuel R. Koenigsberg, DMD,MS

Abstract this technique, there has been relatively little clinical This study was performed to test the hypothesis that study of the influence of nitrous oxide on sedation. This study was performedto test the hypothesis that nitrous nitrous oxide augmentsthe effects of diazepamsedation of oxide would augmentthe effects of oral diazepamused young children by reducing crying and movement and improving the overall quality of sedation. Twenty-four to sedate young children for dental treatment. children (meanage of 32 months) were sedated on two oc- Method casions with two different treatmentregimens. All subjects Subjects received a standardoral dose of O.5 mg/kgof diazepamwith and without nitrous oxide during each of two treatment Twenty-four children (19 male and five female), visits. Duringone visit, the subjects received 50%nitrous ranging in age from 25 to 44 months with a mean age oxide and 50%oxygen for the first 20 min followed by of 31.8 months and a meanweight of 31 lbs (range 24- 100%oxygen for the balance of the procedure and, dur- 36 lbs), participated in the study. These children were ing the secondvisit, the reverse regimenwas used. All sub- selected consecutively as they presented for treatment. jects were restrained in a Papoose BoardTM (Olympic Requirements for participation were: 1) the child was Medical, Seattle, WA)with an auxiliary head restraint. in good health; 2) two separate restorative dentistry Successful sedation, as evidencedby lack of crying or move- appointments were required; and 3) sedation was nec- ment that interrupted treatment, occurred in 83%of ad- essary to manage uncooperative behavior as deter- ministrations. Vital signs remainedessentially unchanged mined during the detailed oral examination, which in- throughoutall treatment with the exception of transitory cluded necessary radiographs. elevation of the pulse and respiratory rates, whichusually Medications occurred whenthe mouth prop was inserted, local anes- All subjects received an oral dose of 0.5 mg/kg of thesia was administered, and the rubber damwas placed. diazepamfor both treatment visits. At the first appoint- Whenthe evaluation of the overall sedation was compared ment, subjects were randomly assigned to receive ei- with and without nitrous oxide, it was better with nitrous ther regimen A or B for the first appointment, with the oxide 56%of the time, worse 13%of the time, and the same alternate regimen administered during the second ap- in the remaining31% of the comparisons.It is concluded pointment. Consequently, a crossover design was used that nitrous oxide mayslightly augmentthe effect of di- with each subject serving as his own control and the azepamsedation of youngchildren, but it does not do so 24 subjects participated in 48 treatment sessions. Treat- uniformlyfor all children receiving sedation. (Pediatr Dent ment regimen A consisted of 50%nitrous oxide and 18:236-41, 1996) 50%oxygen for the first 20 min of treatment, or 65 min after drug administration, followed by 100%oxygen for the remainder of the appointment, which was usually variety of drug regimens are used when young 40-60 min. Treatment regimen B consisted of 100% A children are sedated for dental treatment.1 Ben- oxygen for the first 20 min followed by 50%nitrous zodiazepine drugs have been advocated be- oxide and 50% oxygen. The 20-min time period was cause they produce less sleep, have a wide margin of selected for the time of gas change (nitrous oxide safety with few side effects, and mayhave anterograde turned on or off) as it followed the morestressful pro- amnesic effects. 2-~ These agents frequently are supple- cedures -- mouth prop insertion, injection, and rubber mented with 30-50% nitrous oxide and oxygen to in- damapplication -- thus providing the opportunity to crease the sedative effect. Despite widespread use of examine the effect of nitrous oxide in more and less

236 AmericanAcademy of PediatricDentistry PediatricDentistry - 18.3, 1996 stressful situations. A BrownTM scavenging hood (Por- TABLE1. RATING SCALES FOR SLEEPp MOVEMENTp ter Instrument Company,Hatfield, PA) was used dur- CRYING AND OVERALL BEHAVIOR ing all procedures and all children were restrained in a Papoose BoardTM (Olympic Medical, Seattle, WA) RatingScale for Sleep Score with auxiliary head restraint. Subjects were without food or fluids for at least 4 hr prior to treatment. After Fully awake,alert 1 Drowsy,disoriented 2 each subject arrived, vital signs and behavior were Asleep 3 evaluated then oral diazepam was administered. On 15 occasions, the child was coaxed into drinking the di- Rating Scale for Movement azepamsolution, and for the remaining 33, the solution Violent movementthat interrupts treatment was administered orally with a syringe. The dosages Continuous movementthat makes of diazepam ranged from 6 to 8 mg with a mean of 7.3 treatment difficult mg. The child then remainedwith the parent for 45 min, Controllable movementthat does not interfere during which the vital signs were monitored at 15-min with treatment intervals. After 45 min, the child was transferred to the No movement 4 operatory for the start of treatment. RatingScale for Crying Evaluation The degree of sleep, body movement,crying, pulse, Hysterical crying that interrupts treatment Continuous, persistent crying that makes respiration rate, and color were evaluated before, dur- treatment difficult ing, and after operative procedures. In the operatory Intermittent, mild crying that does not these variables, together with the blood oxygen satu- interfere with treatment ration level, were rated by an independent observer No crying and recorded during mouth prop insertion, administration of local anesthesia, placement of rubber dam, RatingScale for OverallBehavior and every 15 min thereafter using separate rating scales Aborted No treatment 1 (Table 1). Each behavioral rating represented a sum- Poor Treatmentinterrupted, only partial 2 mary of behavior exhibited since the previous rating. treatment completed An overall rating was madeusing a separate scale for Fair Treatmentinterrupted but eventually 3 each of the two segments of treatment, that is, before all completed and after the gas change (Table 1). Both the operator Good Difficult, but all treatment performed 4 and the independent observer were kept blind as to Very Good Somelimited crying or movement, 5 whether the patient was receiving nitrous oxide or e.g. during anesthesia or mouth 100%oxygen by having a third person responsible for prop insertion all settings to the nitrous oxide machine. Further, the Excellent No crying or movement 6 flow meters were kept covered at all times. An average of 6 months later, a consensus rating was madeby surement with related samples, the nonparametric sign two investigators (MHand SK) from videotapes of the test was used to comparethe groups for statistically procedures to verify the reliability of the rating scales, significant differences at the 0.05 level of significance. which had been established previously?, 10 In the operatory, pulse and blood oxygen saturation Results TM level were continuously monitored with the Nelcor The results of this study are presented in Figs 1, 2, pulse oximeter; respiration was monitored with the and 3 and in Tables 2 and 3. Since each of the 24 sub- TrimedTM apnea monitor (Trimed Inc, Bellevue, WA)connected to the nitrous oxide nasal hood. A precordial stethoscope also was used to moni- Asleep 3 - tor respiration. Data analysis Drowsy, 2 - This experiment was designed so that each Disoriented subject served as his owncontrol with the same time of day, the same operator, and similar Fully 1 - types of procedures performed during both AwaRe treatment sessions. The independent variable ~ Regimen B was the administration of nitrous oxide and the dependent variable was the effectiveness of se- o 45 Inj. 60 75 90 105 Min. Min. Min. Min. Min. Min. dation as measuredby the degree of crying and Drug Mouth movementthat interfered with treatment. Since Admin. Prop the rating scales used the ordinal scale of mea- Fig 1. Evaluationof sleep.

PediatricDentistry - 18:3,1996 AmericanAcademy of PediatricDentistry 237 No which received regimen B. Consequently, in Movement Figs 1, 2, and 3, the data for the first segment of the appointment (mouthprop, injection and Slight 60 min) represent average values for regimen 3 A (nitrous oxide) compared with regimen (100% oxygen); and the data for the second segment of the appointment (75, 90 and 105 Continuous 2-- minutes) represent average values for regi- Gas men B (nitrous oxide) compared with regi- lChange~ ¯ ¯ ¯ WithoutNitrous Oxide men A (100% oxygen). Violent 1 -- Table 2 summarizesthe data for all visits, m Regimen B regardless of which regimen was used; whereas, Table 3 reports findings when both 1 I I I 45 Inj. 60 75 90 105 within-appointment comparisons (nitrous Min. Min. Min. Min. Min. Min. Drug Mouth oxide versus 100%oxygen) and between-ap- Admin. Prop pointment comparisons (by appointment or Fig 2. Evaluationof movement. by regimen) were used. Raterreliability

TABLE 2. DISTRIBUTION OF RATINGS (PERCENT- Whenthe ratings made in the operatory were com- AGE) FOR THE VARIOUS VARIABLES MEASURED pared with the ratings made from videotapes, 647 ratings were identical, 155 differed by one scale point, and Nitrous Oxide 38 differed by two scale points, producing 77%agree- Administration ment between the two sets of ratings. Evaluation Score With Without Evaluationof sleep Sleep Of the 48 treatment sessions, on eight occasions pa- Asleep 3 37 22 tients fell asleep in the waiting area after an averageof Drowsy 2 17 19 29 min; in the remaining 40 treatment sessions, patients Awake 1 46 59 were awake when brought into the operatory. In 29% of the 288 occasions that sleep was evaluated during Movelnent treatment, subjects were asleep. However,in 18%of the No Movement 4 63 45 ratings, subjects were drowsy and disoriented, and in Slight 3 25 38 52%of the ratings, subjects were fully awake. The Continuous 2 12 11 means for ratings of sleep at various times of evalua- Violent 1 0 6 tion appear in Fig 1. For subjects receiving nitrous ox- Crying ide, the meanratings at the six periods of observation No crying 4 42 25 were1.3, 1.2, 2.2, 2.3, 2.3, and 2.2, whereas,for subjects Intermittent 3 24 22 receiving only oxygen, the meanratings were 1.3, 1.1, Continuous 2 23 38 1.4, 2.3, 2.0, and 1.9. Theseratings indicate that subjects Hysterical 1 11 16 were more fully awake during the early than during Overall Evaluation Excellent 6 19 4 TABLE3. EFFECTSOF 50% N~TrOus OxiDE/ Very good 5 52 27 50%OXYGEN vErsUs 100%OXYGEN Good 4 19 46 Fair 3 8 15 Nitrous Oxide~OxygenIs: Poor 2 2 8 Aborted 1 0 0 Better SameWorse Total jects was treated twice, data were obtained from 48 By Appointment sedations. In addition, each visit was divided into two 1st Appt. 11 8 5 2nd Appt. 16 7 1 segments representing procedures before and procedure after the gas change. By Regimen The data were analyzed by within-visit comparisons Regimen A 9 10 5 and between-visit comparisons. Figs 1, 2, and 3 illus- Regimen B 18 5 1 trate between-visit comparisons of procedures with Combined 27 15 6 48 and without nitrous oxide regardless of which visit (56%)(31%)(13%) received regimen A (first or second appointment) and

238American Academy of PediatricDentistry PediatricDentistry- 18:3, 1996 times. For subjects receiving nitrous oxide, No the meanratings at the six periods of obser- Crying vation were2.6, 2.0, 3.0, 3.4, 3.4, and3.3 (range I to 4). For subjects receiving only oxygen,the Intermittent meanratings were2.4,1.9, 2.5, 3.3, 2.7, and 2.7 (range 1 to 4). Whennitrous oxide was administered, subjects exhibited no crying 42%of Continuous the time or occasional mild crying 24%of the Change .... " time, comparedwith 25 and 22%respectively ~ ¯ = = WithoutNih’ous Oxide when subjects did not receive nitrous oxide Hysterical ===|l= RegimenA (Table 2). Continuous persistent crying was exhibited 23%of the time with nitrous oxide and 38%without, and hysterical crying oc- I curred 11%of the time with nitrous oxide and 45 Inj. 60 75 90 10s 16%of the time with only oxygen. Crying was Min. Min. Min. Min. Min. Min. Drug Mouth more evident during the early part of the Admin. Prop treatment when the more stressful proce- Fig3. Evaluationof crying. dures of mouthprop insertion, injection, and rubber dam application were performed. the later part of each appointment, regardless of which However, differences in crying between regimen was being used. Overall subjects were awake groups were not statistically significant. 46%of the time, drowsy 17%of the time, and asleep Overall evaluations 37%of the time that they received nitrous oxide, com- Overall evaluations were madeof the periods before pared with 59, 19, and 22%respectively whenthey received pure oxygen(Table 2). Differences in the scores and after change of the gas from 100%oxygen to nitrous oxide or the reverse. A separate rating scale for betweenthe two groups were slight and not statistically significant accordingto the sign test. overall behavior, which combinedthe scales for crying and movement, was used. In addition, the overall Evaluation of movement evaluations combined three individual assessments Whensubjects received nitrous oxide, they exhib- before the gas change (mouth prop, injection and 60 ited no movement63% of the time or slight movement rain) and three assessments after gas change (75, 90 and 25% of the time, compared with 45 and 38% respec- 105 min). The results are illustrated in Fig 4. Mostsub- tively when only oxygen was administered (Table 2). jects demonstratedgood, very good, or excellent effects Continuous movement was evident 12% of the time of the sedation; however, in 17%of the patients the with nitrous oxide compared with 11%continuous and overall evaluation was less than good and treatment 6% violent movementwhen nitrous oxide was not ad- had to be interrupted. With nitrous oxide, 71%of the ministered. Such violent movementoccurred when the overall ratings were very good or excellent, whereas child struggled and, by squirming, was able to free a hand or leg. The means of ratings of movementfor all subjects at the various 0.5 mg/kg Diazepam times of evaluation are illustrated in Fig 2. 25 i.,,~ 50%Nitrous Oxide/50% Oxygen For subjects receiving nitrous oxide, the [] 100%Oxyoen meanratings at the six periods of observation were3.5, 3.2, 3.3, 3.6, 3.8, and 3.6, and the range of ratings at all periods was 1 to 4. For subjects receiving only oxygen, the meanratings were 3.1, 2.9, 3.0, 3.5, 3.2 and 3.5, and the range similarly was I to 4. These ratings indicated that subjects moved ~ 10 slightly more during the early than during - the later part of each appointment. Differ- ences in ratings between the two groups were slight and not statistically significant 0 according to the sign test. 1 2 3 4 5 6 Evaluationof crying Aborted Poor Fair Good Very Excellent Fig 3 shows the meansof ratings of crying for all subjects at the various evaluation Fig 4. Overallevaluation of sedation.

PediatricDentistry - 18:3,1996 AmericanAcademy of PediatricDentistry 239 without nitrous oxide only 31%of ratings were very Diazepamis an anxiolytic type drug rather than a good or excellent. Using the overall evaluations, the hypnotic. Consequently, it was not unexpected, al- effect of the nitrous oxide was comparedwith the ef- though it maybe undesirable, to find that subjects were fect of 100%oxygen in Table 2. Overall, nitrous oxide awake most of the time. Being awake could have pro- augmented the sedation in 27 (56%) of 48 treatment duced more crying, however, this disadvantage might sessions, it had no effect in 15 (31%) sessions, and be ameliorated if amnesia is produced as has been sug- produced worse behavior in six (13%) sessions. Of the gested for diazepam. Future research should investi- 27 sessions in which the nitrous oxide increased the gate the amnesic properties of the drug whenit is used effect of the diazepam, 11 (41%) occurred during first to sedate young children. appointments, with the remainder during the second During this study, the Papoose BoardTM with auxil- appointments. Eighteen (67%) occurred with regimen iary head restraint was used, and this device, in addi- B when nitrous oxide was administered during the sec- tion to an auxiliary VelcroTM strap placed across the ond part of the procedure compared with nine with knees, tremendously restricted movement. Insofar as regimen A. Although the nitrous oxide was beneficial one of the measures of sedation success was lack of for somepatients someof the time, it was not uniformly movement,the use of this device could explain the rela- beneficial for all patients all of the time. tively good results of sedation on movement.It appears All of these findings maybe summarizedas follows: that there is a distinct advantage to using the special 1. Behavior was better during the second segments supplemental head holder attached to the Papoose of appointments. BoardTM in that not only does the head restraint pre- 2. With this combination of sedative agents, chil- vent someundesirable movement,but it also facilitates dren were generally fully awake or drowsy and the delivery of nitrous oxide by keeping the nasal hood disoriented. directly over the nose. The auxiliary Velcro strap placed 3. Subjects movedlittle during treatment, but cried on the knees restricted squirming and usually pre- continuously one-third of the time. vented the legs from slipping out of the restraint. 4. Few differences in sleep, crying and movement In this study behavior was assessed in two differ- were statistically significant at specific points in ent ways, sleep, crying, and movementwere measured time, however, half of the overall evaluations at six different points in time, and overall behavior was demonstrateda beneficial effect of nitrous oxide. evaluated at the end of each of two segments of the Vital signs sedation. It was surprising that these different methods did not produce similar findings, and this opens There were few changes in the vital signs through- to question the validity of each method. The overall out the procedures. Blood oxygen saturation level re- assessment might allow the forest to be seen in spite of mained essentially unchangedand pulse rate exhibited the manytrees and, consequently, it might be a more transitory, although dramatic increases, for example valid measure. Whereas there was generally no statis- spiking from 100 to 195, which were linked to specific tically significant effect of nitrous oxide as measured occurrences when the child was stimulated. at distinct points in time, there was a measurable ef- The increase in pulse rate was transitory and quickly fect when the overall assessment was used. Using both returned to normal whenthe stimulus ended. In regard methods demonstrates that nitrous oxide can have an to respiratory rate, similar transitory changes (for ex- effect on diazepamsedation, but whenit does, the ef- ample, from 24 to 40) occurred at a time of particular fect is small. stimulus. Howsuccess is defined will determine whether or Adverseeffects not to include diazepamwith nitrous oxide as success- Two subjects coughed up small amounts of fluid ful agents to sedate children for dental treatment. Some during treatment and one spit up slightly at the end of practitioners reject the use of a restraint such as the treatment; otherwise vomiting or respiratory depres- Papoose Board suggesting that if external restraint was sion was not evident during this study. One child de- necessary, the sedation was a failure. Others suggest veloped a hiccup that lasted through the procedure. that, crying is an indication of failure of the sedation, and they are concerned about causing possible psycho- Discussion logical trauma. However, there are those who expect This study produced expected and unexpected find- some crying and/or movementand consider it a suc- ings. It was expected that behavior during the first seg- cess if they are able to complete necessary treatment. ment would not be as good as behavior during the sec- In this study, whensuccess of sedation was defined as lack of crying or movementthat interrupted treatment, ond segment, since the first part of the appointment had the more noxious stimuli of mouth prop insertion, success occurred in 83%of administrations. These in- injection, and rubber damapplication. In addition, by cluded sedations that received an overall rating of good the time of the second segment, children whohad cried (difficult, but all treatment performed). However,if the from the beginning often became tired and, conse- good group of sedations was considered to be unsuc- quently, cried less. cessful -- that is, although treatment was not inter-

240 AmericanAcademy of PediatricDentistry PediatricDentistry - 18:3,1996 rupted, there was too much crying or movement to be Dr. Houptis professor, Dr. Tofskyis clinical associate professor, considered a successful sedation -- then only 53% of and Dr. Koenigsbergis professor, departmentof pediatric dentistry, University of Medicine& Dentistry of NewJersey, New- administrations that were "very good" or "excellent" ark, NewJersey. Dr. Kupietzkywas a postdoctoral student and would be successful. If practitioners expected that di- currently is in private practice in Jerusalem,Israel. azepam supplemented with nitrous oxide produced a 1. HouptMI: Project USAP--theuse of sedative agents in pe- sedation with little or no crying, they would be disap- diatric dentistry: 1991 update. Pediatr Dent 15(1):36-40, pointed to find that in almost half the cases, that crite- 1993. rion was not achieved. It is particularly important that 2. Auil B, Cornejo G, Gallardo F: Flunitrazepam and diazepam criteria for success be defined carefully when clinicians compared as sedatives in children. ASDCJ Dent Child 50:442-44,1983. compare the effects of different drug regimens and 3. Gallardo F, Cornejo G, Auil B: Premedication with when researchers compare the results of different clini- flunitrazepam, diazepam and placebo in the apprehensive cal studies. The results of this study indicate that diaz- child. ASDCJ Dent Child 51:208-10, 1984. epam and nitrous oxide sedation is successful at least 4. Flaitz CM,Nowak AJ: Evaluation of the sedative effect of half the time and as much as 83% of the time. The re- rectally administered diazepamfor the young dental patient. Pediatr Dent7:292-96, 1985. sults suggest that practitioners should use nitrous ox- 5. Koenigsberg SR, GuelmannM, Shapira J, Kagan A, Holon ide in an attempt to augment the effect of diazepam G: Assessing diazepam sedation in children. J Dent Res sedation. Although the beneficial effect would be small, 67:128, 1988. [Abst No. 126] there would likely be a positive effect with the addi- 6. Badalaty MM,Houpt MI, Koenigsberg SR, Maxwell KC, tion of nitrous oxide and only a small chance of a nega- Desjardins PJ: A comparisonof chloral hydrate and diazepamsedation in youngchildren. Pediatr Dent 12(1):33-7, tive effect. 1990. 7. Loeffier PM:Oral benzodiazepinesand conscious sedation: Conclusion a review. J Oral MaxillofacSurg 50(9):989-97, 1992. From the results of this study, it may be concluded 8. Krafft TC, Kr~imer N, KunzelmannKH, Hickel R: Experi- ence with midazolamas sedative in the dental treatment of that nitrous oxide may slightly augment the effect of uncooperative children. ASDCJ Dent Child 60(4 &5):295- oral diazepam sedation in young children; however, it 99, 1993. does not do so uniformly for all children receiving se- 9. Houpt MI, Rosivack RG, Rozenfarb N, Koenigsberg S: Ef- dation. fects of nitrous oxide on chloral hydrate sedation of young children. AnesthProg 33:298-302, 1986. This study was approvedby the NewJersey Dental SchoolInsti- 10. Badalaty M, Houpt MI, Koenigsberg SR, Maxwell KC, tutional ReviewBoard. All benefits and risks were fully explained Desjardins PJ: A comparisonof chloral hydrate and diaz- to the parents or guardiansof the patients involved. The study was epamsedation in young children. Pediatr Dent 12:33-37, conducted in accordance with the AmericanAcademy of Pediat- 1990. ric Dentistry Guidelinesfor ConsciousSedation.

EarnCE credits while you read this journal

Earn credits from your home on your The CE logos on the cover of the journal and own time. No need to travel; no long on the title pages indicate which articles will be lectures to attend. Pediatric Dentistry tested. Annual subscription price is $60. now offers up to 18 continuing educa- A related service, the Continuing Education tion credits per year for demonstrating Registry, helps you keeps track of your CE cred- an understanding of topics discussed in its. Subscribers will receive reporting forms on selected journal articles. which to record continuing education credits. For It couldn’t be easier! As a subscriber, you will $30 per year, credit information submitted to receive a multiple-choice test covering seve~’al ar- AAPDwill be entered into a confidential record. ticles around the same time you receive flae journal. Reports will be furnished annually or by request. Simply read the selected articles and ~:eturn your If you subscribe to both services, your journal CE answer sheets to AAPDfor grading. We will notify credits will be entered automatically into the CE you of the number of credits you earned for your Registry. See advertisement on p. 262 to sub- correct answers. scribe to both new member services.

PediatricDentistry - 18:3, 1996 AmericanAcademy of Pediatric Dentistry 241