topical vs n2o for iv access

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P EDIATRIC A NESTHESIA S OCIETY FOR P EDIATRIC A NESTHESIAS ECTION E DITOR

W ILLIAM J. G REELEY

EMLA Versus Nitrous Oxide for Venous Cannulation

in Children

Olivier Paut, MD*, Claire Calmejane, MD*, Jean Delorme, PhD† , Frederic Lacroix, MD*, and Jean Camboulives, MD*

*Departments of Pediatric Anesthesia and Intensive Care and †Pharmacy, La Timone University Hospital,Marseilles, France

We compared EMLA cream with nitrous oxide (N 2 O) forproviding pain relief during venous cannulation in chil-dren. In a prospective, double-blinded, randomizedstudy, 40children, 6–11yr, ASA statusI or II, undergoingscheduled surgery received either EMLA cream and in-haled air and oxygen (Group EMLA) or a placebo creamand inhaled 70% N 2 O in oxygen (Group N 2 O) before ve-nous cannulation. Pain was evaluated with a visual ana-log scale and the Objective Pain Scale. The ease of venouscannulation and the observer’s assessment of its efficacyforpreventing pain were assessed.Heart rate, bloodpres-sure, respiratory rate, and oxygen saturation were com-paredbeforeandaftervenouscannulation.Visualanalog

scale scores (4.4 7.5vs3.9 9.3mm, P 0.85),ObjectivePain Scale scores (median 0 [0–6] vs 0 [0–1], P 0.61),efficacy (median 0 [0–1] vs 0 [0–1], P 0.59), and ease of venous cannulation (0[0–2] vs 0 [0–1], P 0.84) were notdifferent between EMLA and N 2 O groups, respectively.There was no statisticaldifference between thegroups forthe physiologic variables. Minor side effects were signifi-cantly more common in the N 2 O group (11 of 20) than inthe EMLA group (7 of 20) ( P 0.0248). We conclude that both techniques provided adequate painrelief during ve-nous cannulation, as demonstrated by the low painscores.

(Anesth Analg 2001;93:590–3)

V enous cannulation can be a painful and stressfulexperience for children and a difficult challengefor anesthesiologists. Although venous cannula-

tion is most often performed on anesthetized childrenafter an inhaled induction by mask, some childrensometimes prefer an IV induction, often because theyhave some fear of the mask. Furthermore, interest intotal venous anesthesia or computer-assisted continu-ous infusion anesthesia has grown considerably dur-ing the past decade, and both techniques require afirst-class IV access before the induction of IV anes-thesia (1). Currently, for those children sustaining anIV induction, several means for reducing the pain of venous cannulation are available. Local anesthesia ad-

ministered intradermally (2), nitrous oxide (N 2 O) (3),and EMLA cream (AstraZeneca Pharma, Westbor-ough, MA) (4) are effective. Few studies have dealtwith the direct comparison of EMLA and N 2 O inchildren. The results of these studies were conflicting,and they had methodologic bias (5–7).

This study was conducted to compare the efficacy of EMLA cream and inhaled N 2 O for pain relief duringvenous cannulation in pediatric anesthesia, and westarted with the hypothesis that N 2 O would be moreeffective than EMLA for that purpose.

Methods

This study was a prospective, double-blinded, ran-domized trial and was approved by our ethics com-mittee. After obtaining written, informed consentfrom the parents, we studied 40 unpremedicated chil-dren aged between 6 and 11 yr, ASA I or II, undergo-

ing elective surgery. Exclusion criteria were a historyof allergy to any amide local anesthetic, a congenitalmethemoglobinemia, recent use of sulfonamide, andany dermatologic disorder. All children who partici-pated in the study were trained in the use of the visualanalogic scale (VAS) at the time of enrollment.

The children were randomly allocated to one of twogroups: in the EMLA group, children received 2.5 g of EMLA cream at least 1 h before IV catheter insertion inthe operating room (OR), and in the N 2 O group, chil-dren received a placebo cream under the same condi-tions. The cream was applied by a pain nurse in aselected area, preferably on the dorsum of the hands,

Supported, in part, by a grant from Assistance Publique—Hopi-taux de Marseille (AP-HM promoteur, 1997).

Accepted for publication April 10, 2001.Address correspondence and reprint requests to Olivier Paut,

MD, Department of Pediatric Anesthesia and Intensive Care, LaTimone University Hospital, Bd Jean Moulin, 13385 Marseilles Ce-dex 5, France. Address e-mail to [email protected].

©2001 by the International Anesthesia Research Society590 Anesth Analg 2001;93:590–3 0003-2999/01



at two sites. The tube was coated with an opaqueadhesive so that the child was blinded to the nature of the cream applied. The cutaneous area with the creamwas covered with an occlusive dressing (Tegaderm ® ,3M, St. Paul, MN) that was removed while the cream

was wiped off, at least 15 min before venous puncture.Before entering the OR, the child ’s anxiety was as-sessed with the Yale Preoperative Anxiety Scale (YalePAS) (8). In the OR, standard monitoring was placed.Before venous cannulation, all children breathed a gasmixture administered by the anesthesia machine via aface mask for 3 min before and during venous cannu-lation. EMLA patients breathed air in oxygen (30%),whereas N 2 O patients breathed N 2 O in oxygen (70%/30%). The skin was then cleansed with an isopropylalcohol wipe, and a 22-gauge catheter was placed byone investigator in the selected area. The sole investi-gator who was aware of the nature of the gas mixtureinhaled by the child was the anesthesiologist or nurseanesthetist responsible for maintaining the face maskand administering gas. The anesthesia machine screenand rotameters were hidden from the child and theinvestigators. The following variables were recorded by two blinded investigators: ease of venous cannula-tion was assessed by the anesthetist nurse or the anes-thetist who inserted the venous catheter with a four-point scale (very easy, easy, intermediate, or difficult);the observer ’s assessment of the efficacy of the tech-nique for preventing pain during venous access wasassessed with a four-point scale (very good, good,intermediate, and poor efficacy); and the patient ’spain was assessed with the Objective Pain Scale (OPS)of Hannallah et al. (9) and recorded by another blinded observer. After 2 min of breathing 100% oxy-gen, the patient was asked to rate his or her painexperienced during venous cannulation by using a0–100-mm VAS. Every side effect was noted in theprotocol chart. Physiologic variables —heart rate, re-spiratory rate, mean blood pressure, and Sp o 2 —wererecorded twice: before mask application and 1 minafter catheter insertion. The duration of cream appli-cation and the time from cream removal to venouscannulation were recorded.

Sample size was determined before commencingthe study. In a former group of 10 patients havingvenous cannulation with either EMLA or N 2 O, wefound that the sd for the VAS score was at 9.75 mm.Power analysis indicated that 20 subjects in eachgroup would allow us to detect a 10-mm difference inVAS score, a difference we considered clinically sig-nificant (1- 90%, ␣ risk at 5%). Patient demograph-ics were compared with analysis of variance(ANOVA) (age, weight) or the Mann-Whitney U -test(Yale PAS score). Physiologic variables before andafter puncture were compared by using ANOVA. VASscores from the EMLA and N 2 O groups were com-

pared with ANOVA, whereas OPS scores, efficacy

assessment, and ease of venous puncture were com-pared between groups by the Mann-Whitney U -test.The incidence of side effects was compared with Fish-er’s exact test. P 0.05 was considered statisticallysignificant.

Results

Twenty children were included in each group. Therewas no difference between the two groups in weight,age, Yale PAS, duration of cream application, or timefrom cream removal to venous cannulation (Table 1).Venous cannulation was successful on the first at-tempt for 38 children and on the second attempt for 2children, both from the EMLA group. One of thesetwo children was considered to have a difficult venousaccess. The results of pain assessments with VAS andOPS, overall efficacy, and ease of venous cannulationare reported in Table 2. There was no statistical dif-ference between the EMLA and N 2 O groups for theseprincipal assessment criteria. The two techniques pro-vided very good pain relief as assessed by the zeromedian VAS and OPS scores in each group (Table 2).The distribution of the various pain scores amongchildren is shown in Table 2. Thirty-seven childrenhad an OPS score of 0 or 1. Three children (two in theN 2 O group and one in the EMLA group) rated theirpain during venous cannulation at 30 mm with VAS,the highest value in this series of patients. The con-comitant OPS scores in these children were low, 0 forone child and 1 for two children. One child (groupEMLA) had an OPS score of 6, although he rated hispain with VAS at 0 mm. In fact, this child said that hewas afraid of the venipuncture, and his behavior in-fluenced the OPS score, but he did not sustain pain.The two groups did not differ in physiologic variables before or after venous catheterization. Furthermore, ineach group, heart rate, respiratory rate, mean bloodpressure, and Sp o 2 values were not different before orafter venous access. There was no episode of cough-ing, laryngospasm, bronchospasm, hypotension, bra-dycardia, allergy, or nightmare. Only minor side ef-fects were encountered. There were 22 side effects in

18 children (Table 3). The overall number of childrensustaining at least one side effect was significantlymore in the N 2 O group (11 of 20) than in the EMLAgroup (7 of 20) ( P 0.0248). The most frequent sideeffects were movements and restlessness.

Discussion

This study shows that the use of EMLA cream or 70%N 2 O in oxygen are two effective means of providingpain relief during venous cannulation in children.There was no difference between the two methods asdetermined by VAS or OPS. Median pain assessment

ratings were as low as 0 in both groups. Side effects

ANESTH ANALG PEDIATRIC ANESTHESIA PAUT ET AL. 5912001;93:590–3 EMLA VS NITROUS OXIDE FOR VENOUS CANNULATION



were minor in each group, and their incidence wassignificantly increased in the N 2 O group comparedwith the EMLA group.

EMLA is effective for providing pain relief duringvenepuncture at the IV induction of anesthesia withsmall needles (10,11). EMLA cream is also effective forreducing the pain associated with insertion of a ve-nous cannula in children: in two randomized, con-trolled studies, EMLA provided significantly morepain-free cannula insertions than placebo cream(12,13). The main disadvantage of EMLA cream is thelong application time —at least 1 h — before venouspuncture, which means that application of the creamshould be anticipated and included in the premedica-tion protocol of a given institution (12). EMLA use islogistically feasible in clinical practice in most institu-

tions (11).

N 2 O is still widely used in pediatric anesthesia. Hen-derson et al. (3) evaluated the effects of N 2 O in oxygenfor providing analgesia for venous cannulation in chil-dren in a prospective, randomized study. They showedthat N 2 O, 50% or 70% in oxygen, was effective in de-creasing the pain associated with venous cannulationwhen compared with control groups of patients breath-ing oxygen or room air. The Children ’s Hospital of East-ern Ontario Pain Scale (CHEOPS) score (14) was 7 in15% of children breathing room air, in 16% of children breathing oxygen, in 56% of children breathing 50%N 2 O, and in 77% of children breathing 70% N 2 O (3). Theincidence of side effects wassignificantly more with 70%N 2 O than in all other groups (3). These side effects wereminor —mainly restlessness and movements (3), as wehave seen in this study. From our point of view, thisincrease in the incidence of minor side effects associatedwith the use of 70% N 2 O does not represent a major

argument for selecting one technique over the other.Although both EMLA cream and N 2 O are effective atdecreasing the pain associated with venous cannulation,few studies have directly compared these two tech-niques. In a prospective randomized trial, N 2 O (70% inoxygen) was compared with EMLA cream in 50 childrenaged 6 to 12 years (5). The pain scores generated by boththe investigator and the children (by using VAS) weresignificantly lower in the N 2 O group than in the EMLAgroup. The authors concluded that N 2 O provided supe-rior analgesia for pediatric venous cannulation com-pared with EMLA (5). However, there are some meth-odologic concerns with that study. First, neither the child

nor the investigators were blinded, which could have

Table 1. Demographic Data

VariableEMLA group

(n 20)N 2 O group

(n 20) P value

Age (yr) 8.45 1.5 8.8 1.5 0.46Weight (kg) 32.3 7.3 31.9 9.1 0.88Patch application duration (min) 87.2 24 82.4 20 0.5Time from patch removal to venous cannulation (min) 46.9 36 29.8 19 0.07Anxiety (Yale Pediatric Anxiety Scale) 6 (5 –18) 5 (5–12) 0.32

Age, weight, and duration are expressed as mean sd . Anxiety is expressed as median (range).N 2 O nitrous oxide.

Table 2. Pain Scores and Ease of VenousCannulation Assessment

VariableEMLAgroup

N 2 Ogroup

P

value

VAS score (mm) 4.4 7.5 3.9 9.3 0.85OPS score

0 13 141 4 62 0 03 0 04 0 05 0 06 1 0

6 0 0Median (range) 0 (0 –6) 0 (0–1) 0.61

Observor ’s assessment0 14 161 6 42 0 03 0 0Median (range) 0 (0 –1) 0 (0–1) 0.84

Ease of venous cannulation0 15 171 4 32 1 03 0 0Median (range) 0 (0 –2) 0 (0–1) 0.59

Visual analog scale (VAS) is expressed as mean sd . Objective Pain Scale(OPS), observor ’s assessment of efficacy of the technique to provide painrelief, and ease of venous cannulation are expressed as median (range).

N 2 O nitrous oxide.

Table 3. Description of Side Effects During the WholeProcedure (3 min Gas Inhalation and Venous Cannulation)

VariableGroupEMLA

GroupN 2 O

Restlessness, movements 3 8Nausea, vomiting 0 1Dysphoria 0 3Scared by the face mask or refused

it temporarily3 1

Miscellaneous 1 2Total 7 15*

N 2 O nitrous oxide.* P 0.0248.

592 PEDIATRIC ANESTHESIA PAUT ET AL. ANESTH ANALGEMLA VS NITROUS OXIDE FOR VENOUS CANNULATION 2001;93:590 –3



introduced bias. Second, although the mean VAS scoresintheN 2 O group were very low (mean 3.2 mm, maximalvalue 25 mm), in agreement with the VAS scores wefound in this study, those in the EMLA group weremuch higher (mean 23 mm, maximal value 100 mm).

These latter values are very different from those weobserved in the EMLA group (mean 4.4 mm, maximalvalue 30 mm), suggesting that a technical problem dur-ing EMLA application could have occurred (5). In an-other prospective, randomized, double-blinded study,three groups of young children aged three months tofive years received either EMLA cream, N 2 O (50% inoxygen), or both EMLA and N 2 O (6). Although EMLAand N 2 O provided better CHEOPS scoresduring venouscannulation than with the two other techniques, no dif-ference in pain scoreswas found between the EMLA andthe N 2 O groups. Behavioral issues (e.g., anxiety) couldhave interacted with pain assessment and could explainthe high median CHEOPS scores seen in both groups (6).

Pain is difficult to assess in this young age group. Inthe past decade, several methods for measuring painhave been developed for the youngest children, but un-fortunately, none is completely accepted as an objectivemeasure (15). Furthermore, the youngest children showsome anxiety with needles, leading to difficulties forpain assessment. This is why, in our study, we focusedon those older children who are able to rate their painwith a VAS. Recently, EMLA has been compared withN 2 O (50% in oxygen) for routine preoperative laboratorytesting. Both EMLA and N 2 O were found to be effectivein reducing CHEOPS scale rates during venipuncturewhen compared with a parallel control group, but nodifference was shown between these two analgesia tech-niques except in children one to four years old, forwhom EMLA cream was more effective than 50% N 2 O(7). However, the experimental design of this latterstudy —unblinded and without randomization —limitedconsiderably the extent of the conclusions (7).

Although both techniques are equally efficient for re-ducing pain at venous cannulation, which technique tochoose will depend on several other variables: the child ’schoice, the anesthesiologist ’s preference, the existence of a contraindication for one medication, the concern for

room pollution, an unanticipated time for surgery thatmakes it impossible to wait one hour for cream applica-tion, and the cost. Although EMLA cream is not by itself expensive, its cost is considerably more than that of N 2 O.

In summary, we conclude that the administration of EMLA cream or of N 2 O (70% in oxygen) are two effec-tive tools for providing pain relief for venous cannula-tion in pediatric anesthesia. Although there is no signif-icant difference between the two analgesia techniques

(except an increased incidence of minor side effects as-sociated with N 2 O, but these are considered clinicallynegligible), other variables, such the child or anesthetist ’spreference, should dictate the choice between EMLAand N 2 O.

The authors thank Wanda Paredero, pain service nurse, and SydneyMelka, nurse anesthetist, for their contribution to this study. Specialthanks to Bernard Giusiano, MD, for his help in statistical analysis.

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5. Vetter TR. A comparison of EMLA cream versus nitrous oxidefor pediatric venous cannulation. J Clin Anesth 1995;7:486 –90.

6. Mjahed K, Sadraoui A, Benslama A, et al. Association cremeEMLA et protoxyde d ’azote pour l ’abord veineux chez l ’enfant.Ann Fr Anesth Re´anim 1997;16:488–91.

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1999;9:305–10.8. Kain Z, Mayes L, Cicchetti D, et al. The Yale PreoperativeAnxiety Scale: how does it compare with a “gold standard ”?Anesth Analg 1997;85:783 –8.

9. Hannallah RS, Broadman LM, Belman AB, et al. Comparison of caudal and ilioinguinal/iliohypogastric nerve blocks for controlof post-orchiopexy pain in pediatric ambulatory surgery. Anes-thesiology 1987;66:832–4.

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11. Cooper C, Gerrish S, Hardwick M, Kay R. EMLA cream reducesthe pain of venepuncture in children. Eur J Anaesthesiol 1987;4:441–8.

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painfree insertion of IV catheters in children? Anesthesiology1982;57:340–2.13. Manner T, Kanto J, Lisalo E, et al. Reduction of pain at venous

cannulation in children with a eutectic mixture of lidocaine andprilocaine (EMLA cream): comparison with placebo cream andno local premedication. Acta Anaesthesiol Scand 1987;31:735 –9.

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topical vs n2o for iv access

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