Dexamethasone Decreases Vomiting by Children After.4

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Dexamethasone Decreases Vomiting by Children

After Tonsillectomy

William M. Splinter, MD, FRCPC,and David J. Roberts, MD, FRCPC

Department of Anaesthesia, Childrens Hospital of Eastern Ontario and Universi ty of Ottawa, Ottawa, Ontario, Canada

We evaluated the ef fect of dexamethasone on vomiting

after elective tonsil lectomy in 133 healthy children aged

2-12 yr in a randomized, strat ified, blocked, double-

blind, placebo-controlled study. General anesthesia

was induced by inhalation of N,O and halothane or in-

travenously (IV) with propofol. Anesthesia was main-

tained with N,O and halothane. Dexamethasone

150 pg/kg up to a maximum dose of 8 mg, or placebo,

was administered IV before surgery. All patients re-

ceived 1.5 mg/kg codeine intramuscularly (IM) intra-

operat ively. Perioperative IV fluids, management of

emesis, postoperative pain and hospital discharge crite-

ria were all standardized. The groups were similar with

respect to number, age, weight, length of surgery, and

estimated intraoperative blood loss. Dexamethasone

reduced the overall incidence of vomiting from 72%

(placebo) to40% (P < 0.001). Vomiting, both in-hospital

and postdischarge, was decreased by the prophylactic

administration of dexamethasone. Each episode of in-

hospital vomiting prolonged discharge by 13 ? 2 min,

mean ?

SD

(P < 0.001). In conclusion, dexamethasone

markedly decreased vomiting by healthy children after

elective tonsillec tomy in an ambulatory hospital

setting.

(Anesth Analg 1996;83:913-6)

B

cause as many as 73% of children vomit after

,general anesthesia for tonsillectomy (l), anesthe-

siologists and otolaryngologists are seeking

methods that will minimize this problem, especially in

day care surgical programs. Factors that may influ-

ence vomiting include age, surgical procedure, anes-

thetic care, postoperative management, and concur-

rent drugs (2,3). Some of these factors, such as age and

surgical procedure, cannot be altered. Anesthetic care,

especially the administration of prophylactic anti-

emetics, can have a dramatic effect on vomiting after

tonsillectomy in children. For example, Litman et al.

(1) noted a marked decrease in emesis following ton-

sillectomy after the intravenous (IV) administration of

ondansetron 150 pg/kg (23% vs 73%) compared with

placebo. The current study assessed he effect of dexa-

methasone, a potential prophylactic antiemetic, on the

incidence of vomiting by children after tonsillectomy.

Dexamethasone is a corticosteroid that has a pro-

longed antiemetic effect among oncology patients (4).

Its effect on emesis in the perioperative period is

unknown.

Accepte d for publication July 5, 1996.

Address correspondence and reprint requests to William M.

Splinter, MD, FRCPC, Department of Anaes thesia, Childrens Hos-

pital of Eastern Ontario, 401 Smyth Rd., Ottawa, Ontario, Canada

KlH 8Ll.

01996 by the International Anesthesia Research So ciety

0003~2999/96/ 5.00

Methods

With the Hospital Ethics Committees approval, we

enrolled healthy children aged 2-12 yr undergoing

elective tonsillectomy or adenotonsillectomy in

this randomized, stratified, blocked, double-blind,

placebo-controlled study. Within the study design,

blocks of five patients were stratified according to use

of premeditation and induction technique and were

randomly assigned to the placebo or dexamethasone

group, so that a similar number of patients with the

various induction techniques and premeditation were

assigned to each group. Patients were excluded if they

had an allergy to a study drug, had a history of sleep

apnea, or were ASA physical status II or greater.

The children did not ingest solid food on the day of

surgery but were permitted to drink clear fluids for up

to 3 h before anesthesia. In the event that premedica-

tion was required, the child was given midazolam

0.5 mg/kg (maximum dose 15 mg) orally 20-30 min

before induction of anesthesia. To control for any pos-

sible effect of oral midazolam on vomiting, patients

were stratified and blocked (five patients per block)

according to premeditation.

After establishing standard patient monitoring,

induction of general anesthesia was achieved by

inhalation with N,O and halothane or IV with

propofol 2.5-3.5 mg/kg. To control for any effect

of induction technique on vomiting, patients were

Anesth Analg 1996;83:913-6 913


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PEDIATRIC ANESTHESIA SPLINTER AND ROBERTS ANESTH ANALG

DEXAMETHASONE DECREASES EMESIS

1996;83:913-6

Table 1. Demographic and Surgical Data

Age

Group n

(yr)

Placebo

70 6.9 + 2.6

Dexamethasone 63 6.9 -c 2.6

Weight

(kg)

27 5 12

27 5 12

Duration of anesthesia

(min)

34

2 11

34 ? 11

Blood loss

hL)

27 k 27

30 2 31

Data are presented as mean 2 SD; n = number of patients.

stratified and blocked (five patients per block) accord-

ing to induction technique. Mivacurium 0.25 mg/kg

was administered if a muscle relaxant was indicated.

Anesthesia was maintained with 70% N,O, 0.75%-

2.0% halothane, and midazolam 50 p&kg (maximum

dose 3 mg). Intraoperative midazolam was not given if

the child had received premeditation. Dexamethasone

150 pg/kg (maximum dose 8 mg) or placebo was

administered IV in a double-blind fashion before sur-

gery. Randomization was guided by a computer-

generated random number table. All patients received

codeine 1.5 mg/kg intramuscularly after induction of

anesthesia.

After surgery the airway was examined and any

residual secretions and blood were removed with gen-

tle suction. The endotracheal tube was removed after

spontaneous ventilation returned and before the re-

turn of upper airway reflexes. One patient had resid-

ual neuromuscular block, which was reversed before

extubation.

Perioperative fluid management, control of emesis,

and postoperative pain were all standardized. Intra-

operative IV fluids (lactated Ringers solution) were

administered at maintenance rates, blood loss was

replaced by crystalloids at a 3:l ratio, and half of the

patients fluid deficit was replaced during the first

hour of surgery. Postoperatively, IV fluid (lactated

Ringers solution) was administered at twice the main-

tenance rate in the postanesthesia recovery room and

in the day care surgical unit (DCSU) until discharge.

Patients were encouraged, but not coerced, to drink

clear fluids in the DCSU before discharge. Patients

who vomited twice in the hospital received dimenhy-

drinate 1 mg/kg IV, while those who vomited on four

occasions in the hospital received ondansetron

0.1 mg/kg IV. Pain in the recovery room was treated

with morphine 50 pg/kg IV, while subsequent pain

was treated with acetaminophen and/or codeine in

the DCSU and at home.

Patients were discharged according to standardized

criteria which included a minimum 4-h stay in the

DCSU and tolerance of clear, oral fluids. Patients were

observed for 24 h after their surgery.

Vomiting was defined as the forceful expulsion of

liquid gastric contents. Retching and nausea were not

considered vomiting for the purpose of this investiga-

tion. The nursing staff and parents were aware of this

definition of vomiting. The nursing staff recorded in-

cidents of vomiting in the charts, which is mandatory

Table 2. Confounding Variable Distribution

Induction of

anesthesia

Premedication Propofol Inhaled

Group 62) 62)

(n)

Placebo 10 29 41

Dexamethasone 6

29 34

n = number of patients.

at our institution, and parents used a diary to record

vomiting. The parents were contacted 24 h after sur-

gery by the research assistant who asked the parents

whether the child had problems with vomiting, and, if

so, how many times the child vomited. The parents

were then reminded to return the diary.

Sample size was predetermined. We expected a 22%

difference in vomiting. The (Y error was set at 0.05

(one-sided) and the p error at 0.20. The projected

sample size was 140 patients. Data were compared

with one-way analysis of variance, 2 analysis, Fish-

ers exact tests, and logistic regression analysis,

whichever was appropriate. Data are presented as

mean * so.

Results

We enrolled 140 patients in the study. Seven patients

were subsequently excluded because the parents

opted out of the study (n = 3), because they were ASA

physical status II (n = 3), or because they received

neostigmine (n = 1). The groups were similar with

respect to age, weight, length of surgery, and esti-

mated intraoperative blood loss (Table 1). Most pa-

tients underwent adenotonsillectomy, as only 15 pa-

tients in the placebo group and 20 in the

dexamethasone group underwent tonsillectomy. The

distribution of patients after stratification is shown in

Table 2.

Dexamethasone reduced the overall incidence of

vomiting (P < 0.001) (Table 3) and, in a more detailed

analysis, dexamethasone decreased vomiting in the

hospital and after discharge from the hospital (Table

3). Each episode of in-hospital vomiting prolonged

discharge by 13 t 2 min (P < 0.001). (Patients admit-

ted to the hospital were not included in the analysis of

the effect of vomiting on hospital discharge.) The in-

cidence of vomiting after premeditation was 62%,


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1996;83:913-6

PEDIATRIC ANESTHESIA SPLINTER AND ROBERTS 915


Table 3. Incidence of Postoperative Vomiting

Postdischarge Induction of anesthesia

Group

In-hospital Same day

Day 1

Overall

Propofol Inhaled

Placebo 46% 36% 26% 71% 62% 78%

Dexamethasone 25%* 17%* lo%* 40%t 28%*

50%*

*I i 0.02, placebo versus dexamethasone; t P < 0.001, placebo versus dexamethasone; P i 0.05, propofol versus inhaled induction.

which was similar to the 56% incidence of vomiting

among the children who received intraoperative IV

midazolam. After due consideration of the effect of

study intervention (placebo versus dexamethasone),

induction with propofol was noted to have a lower

incidence of postoperative vomiting compared with

induction with halothane (P = 0.04, by logistic regres-

sion analysis) (Table 3).

In-hospital vomiting required treatment with di-

menhydrinate among 13 patients in the placebo group

and nine in the dexamethasone group. Two patients in

each group continued to vomit and received ondan-

setron 0.1 mg/kg IV. Two patients in the placebo

group were admitted to the hospital because of vom-

iting. One of these patients was discharged late in the

evening, while the other required a 48-h hospitaliza-

tion. One patient in the dexamethasone group was

admitted briefly because of vomiting and was dis-

charged from the hospital late in the evening of the

day of surgery.

Discussion

Dexamethasone markedly decreasesvomiting by chil-

dren after tonsillectomy. The decreased incidence in

vomiting was observed in the hospital and after

discharge.

The observed incidence of vomiting after tonsillec-

tomy is similar to the wide range of 12%-75% noted in

the literature (1,5). After tonsillectomy in an ambula-

tory surgical setting, the initial in-hospital vomiting

rate has been from 10% to 30%, but 20% to 40% of

patients vomit after discharge from the hospital (6,7).

The opposite trend was observed in the current inves-

tigation, especially in the dexamethasone group,

which had a markedly lower incidence in vomiting

after discharge from the hospital. This prolonged ef-

fect is quite desirable in an ambulatory care setting,

and is consistent with dexamethasones pharmacoki-

netic and pharmacodynamic half-lives of about 3 h

and 48 h, respectively.

There have been many investigations of dexametha-

sanes antiemetic effect outside of the perioperative

setting. The abundant research in the oncology litera-

ture demonstrates its efficacy with minimal adverse

events. For example, the complete antiemetic response

rate was reported to be 73% with ondansetron and

66% with dexamethasone (4). Nevertheless, dexa-

methasone was superior in suppressing delayed nau-

sea (4). Similarly, when compared to another seroto-

nin antagonist, granisetron, dexamethasone had a

similar effect on overall vomiting plus greater protec-

tion from delayed chemotherapy-induced nausea and

vomiting (8).

Investigations of the perioperative use of dexameth-

asone are surprisingly uncommon. McKenzie et al. (9)

observed that the combination of ondansetron plus

dexamethasone was more effective than ondansetron

with placebo in preventing vomiting for women after

major gynecologic surgery. Catlin and Grimes (10)

compared the effect of dexamethasone to placebo in

the recovery from tonsillectomy in 25 children. This

small number of patients was observed for 1 wk and

evaluated for pain, emesis, fever, and appetite. The

two groups were similar, except that the 10 patients in

the dexamethasone-treated group had a more rapid

return to their normal diet. Baxendale et al. (11) ob-

served that dexamethasone decreased pain, swelling,

and vomiting after extraction of third molars in adults.

Rothenburg et al. (12) compared the prophylactic an-

tiemetic effect of droperidol to dexamethasone among

adults undergoing outpatient surgery. The overall an-

tiemetic effects were similar, but there was a trend for

a more prolonged antiemetic effect in the dexametha-

sone group (12).

Adverse effects with a single dose of dexametha-

sone are extremely rare and generally minor. After

reviewing the United States Pharmacopeia Drug In-

formation handout and performing a literature search,

we were unable to find a report of a side effect asso-

ciated with the use of a single dose of dexamethasone.

The dose of dexamethasone used in children is not

well established. Most studies had a dose similar to

that of Catlin and Grimes (lo), which is about 8 mg/

m2, or approximately 0.15 mg/kg up to 8 mg.

Cost is an ever-increasing concern in todays health

care system. Dexamethasone is relatively inexpensive,

costing only 0.20 CDN for 4 mg. This is less expen-

sive than a similar dose per kilogram of an alternate

antiemetic, such as ondansetron, which costs 17.20

CDN for 4 mg. The costs associated with vomiting are

difficult to assess. Treatment with antiemetics has

costs associated with the drug itself, plus adminis-

tration fees. Certainly hospital admission adds to


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PEDIATRIC ANESTHESIA SPLINTER AND ROBERTS


ANESTH ANALG

1996;83:913-6

expenses. The variable costs associated with delayed

discharge of 13 t 2 minutes due to each episode of

vomiting is almost impossible to assess. Finally, there

is the physical and mental costs to the patient and

family connected with vomiting.

It was interesting to observe that the children who

received propofol on induction of anesthesia in the

current study had a decreased incidence of vomiting

when compared to those who had inhaled induction.

This was especially true among the patients who re-

ceived dexamethasone. These results may represent

an isolated event, or they may be due to an interaction

between dexamethasone and propofol. Further inves-

tigation appears warranted.

The evaluation of the severity of postoperative vom-

iting can be performed in a variety of ways. Within the

current investigation we evaluated the need for addi-

tional antiemetics, delay in discharge from the hospi-

tal and the need for unscheduled hospital admission.

Alternat ive methods, such as comparing the mean

number of episodes of vomiting per patient, are con-

founded by the administration of antiemetics

postoperatively.

The current study had a rather complex, balanced

design with stratification and blocking to control for

confounding variables. Critically important variables

such as age, anesthetic maintenance, and surgical pro-

cedure were restricted to a narrow range. Variables of

lesser importance, such as induction technique and

premeditation, were regulated by stratification and

blocking to min imize the differences between groups

for these variables, but permitted optimal clinical

management within a study setting. Other variables,

such as perioperative fluid management and analgesic

management, were similar among the study patients

and under strict guidelines. The policy of encouraging

the ingestion of oral fluids postoperatively was ap-

plied to all patients, and probably contributed to the

high incidence of postoperative vomiting (13). Al-

though there is no evidence to support this policy, we

believe it is necessary to establish the abi lity to tolerate

oral fluids before discharge among day care surgical

patients undergoing tonsillectomy.

In summary, dexamethasone decreases vomiting by

children after tonsillectomy in a day care surgical

setting. This effect on vomiting was significant even

after discharge from the hospital. Although dexameth-

asone decreased vomiting, it did not minimize vom-

iting after tonsillectomy.

References

1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

11.

12.

13.

Litman RS, Wu CL, Catanzaro FA. Ondansetron decrease s eme-

sis after tonsillectomy in children. Anesth Analg 1994;78:

478-81.

Baines D. Postoperative nausea and vomiting in children. Pae-

diatr Anaesth 1996;6:7-14.

Cohen MM, Cameron CB, Duncan PG. Pediatric anesthe sia

morbidity and mortality in the perioperative period. Anesth

Analg 1990;70:160-7.

Jone s A, Hill AS , Soukop M, et al. Comparison of dexametha-

sone and ondansetron in the prophylaxis of eme sis induced by

moderately e metogen ic chemotherapy. Lancet 1991;338:483-6.

Grunwald Z, Guarnieri K, Torjman M. Comparison of the anti-

eme tic effect of I.V. droperidol given in the PACU versus a

double dose regimen in children having tonsillectomy and ad-

enoidectomy [abstract]. Anesth Analg 1992;74:S124.

Splinter WM, R hine EJ, Roberts DW, et al. Ondansetron is a

better prophylactic antiemetic than droperidol for tonsillectomy

in children. Can J Anaesth 1995;42:848-51.

Splin ter WM, Ba xter MRN, Gould HM, et al. Oral onda nsetron

decrease s vo miting after tonsillectomy in children. Can J An-

aesth 1995;42:277-80.

The Italian Group for antieme tic research. Dexamethasone,

granisetron, or both of the prevention of nausea and vomiting

during chemotherapy for cancer. N Engl J Med 1995;332:1-5.

McKenzie R, Tantisira B, Karambelkar DJ, et al. Comparison of

ondansetron with ondansetron plus dexamethasone in the pre-

vention of postoperative nausea and vomiting. Anesth Analg

1994;79:961-4.

Catlin FI, Grimes WJ. The effect of steroid therapy on recovery

from tonsillectomy in children. Arch Otolaryngol Head Neck

Surg 1991;117:649-52.

Baxendale BR, Vater M, Lavery KM. Dexamethasone reduces

pain and swelling following extraction of third molar teeth.

Anaesthesia 1993;48:961-4.

Rothenburg DM, Peng CC, Normoyle DA, et al. Dexamethasone

minimizes postoperative nausea and vomiting in outpatients

[abstract]. Anesth Analg 1996;82:5388.

Schreiner MS, Nicholso n SC, Martin T, Whitney L. Should chil-

dren drink before d ischarge from day stay? Anesthes iology

1992;76:528-33.

Dexamethasone Decreases Vomiting by Children After.4

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