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Nitrous Oxide Does Not Increase Vomiting After DentalRestorations in ChildrenWilliam M. Splinter, MD, FRCPC, and Lydia Komocar, RNDepartment of Anaesthesia, Childrens Hospital of Eastern Ontario and Universi ty of Ottawa, Ottawa, Ontario, Canada

The ef fect of nitrous oxide on postoperative vomitingwas evaluated in 330 children who underwent outpa-tient dental restorations. There were two groups in thissingle-blind, randomized, controlled study. One groupreceived nitrous oxide during their anesthetic, whilethe non-nitrous oxide group did not receive nitrous ox-ide at any time. Anesthesia was induced by inhalationwith halothane or with propofol intravenously. The in-cidence of vomiting for 24 h after surgery was recorded.

Overall, the incidence of vomiting was similar, with30% of the control patients and 35% of the nitrous-treated patients vomiting after their anesthetic. How-ever, in-hospital vomiting was less in the control group:15% vs 24%, control versus nitrous oxide, P = 0.03. Inconclusion, nitrous oxide does not alter postoperativevomiting after halothane anaesthesia for dental restora-tions in children. (Anesth Analg 1997;84:506-8)

V miting after general anesthesia is very commonamong children. Persistent vomiting may resultin dehydration, metabolic derangements, sei-zures, expensive delays in discharge from the day caresurgical unit (DCSU), and costly, unscheduled hospi-tal admissions. The etiology of postoperative vomitingis multifactorial. Nitrous oxide (N,O) may contributeto this emesis. The possible emetic effect of N,O maybe explained by its ability to increase middle ear pres-sure, by causing bowel distension, by decreasingbowel motility, and through central nervous systemeffects on dopaminergic receptors and opioid peptides(l-3).Several investigators have studied the effect of N,Oon nausea and vomiting (4-7). Most of these investi-gations have significant limitations in their design,and they are often conflicting, controversial, or onlyrelevant to very specific operative procedures. Forexample, in a study involving women undergoinggynecologic procedures, N,O appeared to increasevomiting (4), but exposure to N,O did not increasechildrens vomiting after tonsillectomy (7). The twostudies involving children after a brief exposure toN,O during bilateral myringotomies and tube inser-tion are contradictory. In one study of 104 children,N,O increased vomiting after myringotomy from 4%to 21%, P < 0.05 (8), while in another study of 320

Accepted fo r publication November 12, 1996.Address correspondence and reprint requests to William Splinter,MD, FRCPC, Department of Anaesthesia, Childrens Hospital ofEastern Ontario, 401 Smyth Rd., Ottawa, Ontario, Canada KlH 8Ll.

506 Anesth Analg 1997;84:5~6-8

children, N,O had no effect vomiting after myringot-omy (9).This investigation tested the hypothesis that thepresence of N,O during a halothane anesthetic wouldincrease the incidence of postoperative vomiting inchildren after restorative dental surgery. The effect ofpotential cofactors, such as surgical procedure, sex,and opioid administration on vomiting after exposureto N,O was minimized.

MethodsWith the approval of the hospital ethics committee,healthy children aged 2-12 yr undergoing electivedental restorations with or without extractions wereenrolled in this randomized, stratified, blocked,single-blind study. Parental consent was obtained,and when appropriate, assent of the child was pro-cured. Children were excluded if they had gastroin-testinal disease, if they had an allergy to one of thestudy drugs, or if they were taking medication knownto affect gastric emptying. Within the study design,blocks of five patients were stratified by use of pre-medication and induction technique and randomlyassigned to the two study groups so that similar num-bers of patients with the various induction techniquesand premeditation were assigned to each group.The children did not ingest solids on the day ofsurgery but were permitted to drink clear fluids up to3 h before anesthesia. When a child required premed-ication, he or she was given midazolam 0.5 mg/kg

01997 by the International Anesthesia Research S ociety0003~2993/97/$5.00

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ANESTH ANALG PEDIATRIC ANESTHESIA SPLINTER AND KOMOCAR 5071997;84:506-8 VOMIT ING, NITROUS OXIDE, AND CHILDREN

(maximum dose 15 mg) orally 20-30 min before induc-tion of anesthesia. After standard patient monitoringwas established, induction of general anesthesia wasprimarily achieved by inhalation. In the treatmentgroup, induction was with N,O/O, and halothane,while the control group received 0, and halothane. Inthe event that the child refused an inhalation induc-tion, the patient received propofol 2.5-3.5 mg/kg in-travenously (IV). Mivacurium, 0.25 m&kg, was ad-ministered if a muscle relaxant was indicated.Anesthesia was maintained with 70% N,O in oxygenplus 0.75%-2.0% halothane in the treatment group,while the control group had the N,O replaced withN,. Randomization was guided by a computer-generated random number table.

Table 1. Demographic Data and Incidence ofPostoperative VomitingNitrousoxide Control

ige (yr)Weight (kg)Premeditation (midazolam)Propofol inductionInhalation inductionLength of anesthesia min)SpontaneousventilationOral fluid ingested n DCSUIn-hospital vomitingAllPropofol inductionInhalation inductionVomiting out of hospital(sameday)Vomiting out of hospital(Day 1)Overall vomiting

165 1654.7 2 1.9 4.6 t 2.018 t 5 19 t 684 8230 30135 13582 k 28 70 t 24

123 130130 119

Ventilation was either spontaneous or supportedwhen indicated. The surgical technique was unalteredby this study. In the event that the children had dentalextractions, local anesthetics (lidocaine with adrena-line) were utilized before extraction of the decayedteeth. No patient received opioids. At the end of thesurgery, any residual muscle relaxation was reversedwith ah-opine 20 pg/kg plus neostigmine 50 pg/kgwhen indicated, and the endotracheal tube was re-moved before the return of airway reflexes and afterthe airway was examined and any residual secretionsand blood were removed with gentle suction.

24% 15%*24% 13%24% 15%23% 20%4% 3%

35% 30%Values are listed as mean + SD or n.DCSU = day care surgical unit. * P = 0.03, nitrous oxide versus control

gr0Lp.

Perioperative fluid management, control of emesis,and postoperative pain were all standardized. Intra-operative IV lactated Ringers solution was adminis-tered at maintenance rates, and half of the patientsfluid deficit was replaced during the first hour ofsurgery. Postoperatively, IV lactated Ringers solutionwas administered at maintenance rates in the postan-esthesia recovery room (PARR) and in the DCSU untildischarge. Patients were permitted but not encour-aged to drink clear fluids in the DCSU before dis-charge. Patients who vomited twice in hospital re-ceived dimenhydrinate 1 mg/kg IV, while patientswho vomited on four occasions in hospital receivedondansetron 0.1 m&kg IV. Postoperative pain wastreated with acetaminophen, lo-15 mg/kg PO or PR.Patients were followed for 24 h after their surgery.

and of 20% in the non-N,0 group. The a error was setat 0.05 (one-sided), and /3 error was set at 0.20. Theprojected sample size was 145 patients. To allow formissing data and noncompliance, the sample size wasset at 165 patients per group. Data were comparedwith one-way analysis of variance, 2 analysis, Fish-ers exact test, and linear regression analysis, which-ever was appropriate. Data are presented as mean +SD.

Results

Vomiting was defined as the forceful expulsion ofliquid gastric contents. Retching and nausea were notconsidered vomiting for the purpose of this investiga-tion. In the hospital charts, nursing staff recorded eachepisode of vomiting, and after discharge from thehospital, parents noted in a diary each episode ofvomiting by their child. The parents were contacted24 h after surgery by the research assistant, who askedthe parents whether the child had problems with vom-iting, and if so, how many times the child hadvomited.

We enrolled 330 patients into the study. The distribu-tion of patients after stratification is shown in Table 1.The groups were similar with respect to demographicdata (Table I), including a similar preoperative fast.Eight patients in the N,O group and five patients inthe control group were administered atropine andneostigmine. The groups were observed for almost theidentical period of time in the PARR and DCSLJ,which was 110 + 28 min. All patients were dischargedhome on the day of surgery.

Sample size was predetermined. The predicted dif-ference in vomiting was 13%, i.e., a projected inci-dence of vomiting of 33% in the N,O-treated group

Exposure to N,O increased the in-hospital incidenceof vomiting (P = 0.03), but the overall incidence ofvomiting was similar for the control and study groups(Table 1). The 95% confidence intervals for the overallincidences of vomiting were 23%-37% and 27%-43%for the control and study groups, respectively. Induc-tion technique did not alter in-hospital vomiting (Ta-ble 1). The subgroup of patients present in bothgroups that vomited while in hospital had their dis-charge prolonged by 5 _t 2 min, P = 0.01 (linear

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508 PEDIATRIC ANESTHESIA SPLINTER AND KOMOCARVOM ITING, NITROUS OXIDE, AND CHILDREN ANESTH ANALG1997;&1:506-8

regression analysis). The incidence of vomit ing afterpremeditation was 28%, which was similar to the 37%incidence of vomiting among the children who d id notreceive oral midazolam. Only 1 of the 13 patients thatreceived neostigmine vomited.In-hospital vomit ing required treatment with di-menhydrinate in 13 patients in the N,O group and 6patients in the control group. Two patients in the N20group continued to vomit and received ondansetron0.1 mg/kg IV.

DiscussionOverall, prolonged exposure to N20 did not increasepostoperative vomiting among children undergoingdental restorations under inhaled anesthesia, but N,Oexposure was associated with increased vomit ing dur-ing the initial, in-hospital postoperative course. Theseresults concur with those of Tram&r et al. (lo), whoconcluded that N,O increased vomiting only if theinitial risk of vomit ing is high. Also, these resultsagree with those of Pandit et al. (7), who noted thatprolonged exposure to N,O did not increase vomitingin children.

The children studied underwent dental restorationsand extractions. This type of operation was chosen forseveral reasons. It is a common operat ion. The proce-dure usually requires 45-120 minutes of general anes-thesia, which allows for adequate time for the diffu-sion of N,O into areas of the body such as the boweland middle ear, where it is thought to have an emeticeffect. The dental procedure alone does not causevomit ing, so vomit ing after dental surgery is pre-sumed to be directly attributed to general anesthesia.Also, the analgesic requirement is usually minima l,with only acetaminophen required in a few patients.Postoperative opioids, which are known emetics, areonly rarely required.

As stated earlier , many factors lead to vomit ingafter general anesthesia and surgery. The study designattempted to control for all the important factors.Other potential confounders were premeditation andthe mode of induction of anesthesia. To control forthese variables, subjects were stratified according tothe use of premeditation and mode of induction tocreate a balanced design.This investigation has potentia l flaws in design. Theanesthesiologists could not be blinded because theyhad to monitor the patients inspired and expiredgases. The nurses in the PARR and DCSU could dis-cover the patients group by reviewing the chart; how-ever, they are obligated to accurately record all epi-sodes of vomit ing, and thus their charting of data hadto be precise. Although the study was balanced withrespect to premeditation and mode of induction, thestudy could be criticized for permitting premeditation

in some of the patients and allowing two modes ofinduction. These variations in premeditation and in-duction were allowed to enable optimal clinical carewithin the study design. It probably would have cre-ated greater bias and markedly reduced the power ofthe study if the patients who had an IV induction orwere given premeditation were eliminated from thestudy after their enrollment. Finally, this study hadadequate power to detect a 13% or greater differencein the incidence of vomit ing, which is what was con-sidered to be a clinical ly significant difference. It wasnot designed to detect a lesser difference. Thus, i t canonly be concluded that exposure to N,O does notincrease the incidence of vomiting by 13% or more.This concurs with observations in clin ical practice,where it is rare for children to vomit after the admin-istration of N,O analgesia.In conclusion, N,O had no overall influence onvomiting by children having dental restorations underhalothane anesthesia, except for a brief, early emeticeffect. Based on the current studys results, N,O useshould continue for general anesthesia for childrenhaving surgery associated with a low risk of vomiting,unless N,O is otherwise contraindicated.The authors gratefully acknowledge the marked cooperation andcollaboration of their colleagu es in the Department of Anaes thesiaand Dentistry, without which this project c ould not have beencompleted. Also, a spe cial thanks to research assista nts MarilynParkin, BA, and Laura Wha len, BA.

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