54

Antiemetic prophylaxis with or in paediatric outpatient strabismus Victor Faria Blanc MD FaC~'C, Pierre Ruest MO FRCt'C~, Jean Milot MO Frcsc~, surgery Jean-Louis Jacob MD FRCSC, Alexander Tang MD FRCPC

This randomized, double-blind stu~, evaluated the promethazine (36 per cent) ( P < 0.00 I). Promethazine pretreat- efficacy and the side.effects of promethazine pretreatment (0.5 ment demands the use of an like acetaminophen in rag. kg -I IV + 0.5 rag. kg -I IM) versus droperidol + placebo order to reduce the incidence of postoperative pain and restless- pretreatment (droperidol, 0.075 mg. kg -I IV + physiological ness. With the exception of restlessness, the overall incMence of saline, 0.02 ml. kg -I IM). One hundred unpremedicated ASA side-effects was not statistically different between the two physical status I children ranging from two to ten years, and groups. undergoing outpatient strabismus surgeD' were studied. All children received inhalational anaesthesia with , and oxygen. Neither nor muscle relctrants Cette Etude randomisEe et d double insu a EtE rEalisEe dans le but were used. The incidence of and~or retching and the d' ~valuer et l'efficacitE anti~mdtique et les effets indEsirables du incidence of side-effects were determined in the post- prdtraitement gl la promdthazine (0,5 mg. kg -I IV + 0,5 anaesthesia recover" room (PARR), in the short-stay surgical mg. kg -t IM) versus le prdtraitement au droperidol + placebo unit (SSSU), and after discharge from the hospital (inc&ding the (droperidol, 0,075 rag. kg -I IV + sgrum physiologique, 0.02 journey and the stay at home during the first postoperative day). ml. kg- I IM ). Cent enfants non prdmEdiquEs, d I'dtat physique I Promethazine and droperidol were equally effective in reducing de la classification ASA, dont I'dge variait entre dettr et dix the incidence of vomiting before discharge to nvo and eight per ans et devant subir une correction de so'abisme en court-s~/our cent respectively. On the contrao,, the incidences of vomiting ont did (tudi(s. Tous ces enJ~mts ont dtc; attesth(sic;s c'~ /'aide after discharge and overall were significantly less with prometh- d'halothane, de proto.x3"de d'azote et d'oxygdne. Aucun opiacd azine (ten and ten per cent) than with droperidol pretreatment et aucun curarisant n'a Et~ empl~,(. L incidence de vomisse- (54 and 56 per cent) (P < 0.000 I). Promethazine permitted the ments et l'incidence d'effets indEsirables ftirent d~termin~es d time to discharge from the hospital to be reduced to an average la salle de rdveil, d I'unitE de court-sEjour postopEratoire, et of three hours, without increasing the incidence of vomiting aprds le cotzgc;diement de I'h6pital (transport vers la maison et postdischarge. Promethazine pretreatment is much less expen- sdjour {1 domicile pendant la premiere journde postopc;ratoire). sive than droperidol pretreatment. The incidence of restlessness Le pr(traitement d la promdthazine a rc;duit I'incidence de was significantly less with droperidol (eight per cent) than with vomissements prd-cong(diement de l'h6pital (deu.r pour cent) autant que le prdtraitement au droperidol (huit pour cent). Par contre, l'incidence de vomissements post-congddiement de Key words l' h6pital et I' incidence globale de vomissements postopdratoires ANAESTHESIA: outpatient, paediatric; f~rent significativement plus faibles chez le groupe d'enfants SUrGErY: ophthalmic; prEtraitds avec de la promEthazine (dLr; dix pour cent) que chez VOMITING: , droperidol, promethazine, le groupe prdtraitd avec du droperidol (54:56 pour cent) (P < incidence. 0,0001). Le pr(traitement 6 & promr a permis & raccourcir la moyenne du temps de congEdiement de I'h6pital From the Departments of Anaesthesia and Ophthalmology, aux alentours de trois heures sans augmenter l'incidence de H6pital Sainte-Justine and Universit6 de Montr6al vomissements post-congEdiement. Le prEtraitement a la pro. Montr6al, Qu6bec, Canada. mEthazine cot~te beaucoup moins cher que le prEtraitement au Address correspondence to: Dr. V.F. Blanc, Department droperidol. L' incidence d' agitation postopgratoire ft~t significa- of Anaesthesia, H6pital Sainte-Justine, 3175 C6te tivement plus (levr avec la prom~;thazine (36 pour cent qu'avec Ste-Catherine, Montr6al, Qu6bec, Canada, H3T 1C5 le droperidol (huit pour cent) (P < 0,001). Les etaants pr~;trait~;s Accepted for publication 14th September, 1990. gz la promEthazine doivent recevoir un analgEsique du O'pe acEta-

CAN J ANAESTH 1991 / 38: I /pp54-60 Blanc etal.: PROMETHAZINE OR DROPERIDOL 55 minoph~ne, dana le but de r~duire l'incidence de douleurs et Children were fasting and unpremedicated. The fol- d'agitation postop~ratoires. Mise ~ part I'agitation, r incidence lowing monitors were used in all children: precordial globale d'effets inddsirables n'a pas ~td statistiquement diffd- stethoscope, continuous ECG (CM-5), pressure rente entre les deux O,pes de pr~traitement. Les auteurs discutent measurements with an automatic cuff (Dinamap| pulse l'dtiopathog~nie des vomissements et la pharmacologie des oxymeter (Ohmeda| and rectal thermometer. anti~mdtiques chez les enfants exposds attr corrections de Induction of anaesthesia was achieved with halothane, strabisme. nitrous oxide and oxygen (40 per cent) by mask. An IV cannula was then inserted and connected to an infusion of Children undergoing for strabismus five per cent dextrose and lactated Ringer's solution (8 surgery have a higher incidence of postoperative vomiting ml. kg- 1. hour- ~). After intravenous , 0.01 mg. than those receiving the same anaesthesia for other types kg -I, children were randomly assigned to one of two of ambulatory surgical procedures.l-4 The incidence of treatment groups: intravenous droperidol, 0.075 mg .kg- i, vomiting following strabismus correction in children not plus intramuscular placebo (physiological saline, 0.02 receiving any antiemetic has been reported to range from ml.kg -~, to a maximum of 0.5 ml), (n = 50); or 60 to 85 per cent. 2"5'6 Droperidol, 0.05 mg'kg -I IV, intravenous promethazine, 0.5 mg. kg -I, plus intramus- given at induction of anaesthesia, does not reduce the cular promethazine, 0.5 mg" kg-', to a total maximum of incidence of emetic symptoms (, retching and 25 mg (n = 50). Both treatments were administered in a vomiting) in preschool children undergoing outpatient double-blind fashion. Tracheal intubation was performed, strabismus surgery. 5 The incidence of retching and/or without the use of muscle relaxants, under halothane vomiting predischarge in children who received droperi- (3.0-3.5 per cent inspired) in oxygen. Anaesthesia was dol, 0.075 mg" kg -~ IV, before manipulation of the eye is maintained with halothane (1.25-1.5 per cent inspired) in less than that observed in children who received the same a mixture of nitrous oxide and oxygen (FIO2 = 0.33) dose of droperidol IV after manipulation of the eye (10 using mechanical ventilation. The tracheal tube was and 43 per cent, respectively). 2'6 The incidence of removed in the operating room, before the cough reflex vomiting predischarge (retching not included) in children returned. who received , 0.15 mg. kg -j IV in the In the post-anaesthesia recovery room (PARR), two post-anaesthesia recovery room, is 35 per cent. 7 Studies trained nurses not aware of the treatment administered to regarding the antiemetic efficacy of intravenous lidocaine each child recorded the recovery scores, 13 the incidence (1.5-2 mg. kg -I) show both benefit and lack of benefit, of vomiting, the incidence of side effects, and the duration the incidence of postoperative vomiting varying from 168 of stay in the PARR. Once the Steward recovery score to 50 per cent. 9 Promethazine has a long history of reached the maximum of six, each child was transferred to usefulness in paediatric anaesthesia. In addition to its the short-stay surgical unit (SSSU) where two trained properties, it has , antihistaminic, nurses not aware of the treatment received by each child antiemetic, and anti- effects. The recom- recorded the incidence of vomiting, the incidence of mended dose for children is 0.5-1.0 mg-kg -I of body side-effects, and the duration of stay in the SSSU. weight, t0-iz We speculated that if intravenous prometh- Children were discharged from the hospital and carried azine were administered before manipulation of the eye home when they met three discharge criteria: (1) stable and combined with intramuscular promethazine, the vital signs; (2) clear sensorium; and (3) absence of incidence of vomiting following strabismus surgery might retching or vomiting during the last hour. Oral fluids were be reduced even more than with intravenous droperidol not offered if the child did not ask for them. Retching was pretreatment. Therefore, the incidence of vomiting after included in the incidence of vomiting. Nausea was not strabismus correction was determined in children who evaluated. Side-effects investigated and recorded includ- received intravenous droperidol pretreatment associated ed the presence or absence of dry mouth, restlessness, with an intramuscular placebo, or intravenous prometha- disorientation, somnolence and miscellaneous (rash, uri- zine pretreatment associated with intramuscular pro- nary retention, cycloplegia, extrapiramidal symptoms, or methazine. others). Restlessness was defined as any state of agitation requiring loving care and/or acetaminophen. Methods Acetaminophen, 10 mg.kg -I , per rectum, was admin- With approval of the hospital Committee on Medical istered to any child who seemed to experience pain after Ethics, informed consent was obtained from the parents of surgery. Narcotics were not administered at any time. 100 children (47 boys and 53 girls), ASA physical status Intramuscular , 1 mg'kg -~, was pre- I, between two to ten years of age, and requiring out- scribed to any child with two or more episodes of patient strabismus surgery. vomiting (and/or retching) per hour. 56 CANADIAN JOURNAL OF ANAESTHESIA

TABLE I Demographic Data

Droperidol Promethazine Statistical significance n 50 50 NS't Sex (females/males) (27/23) (30/20) NS- Age (yr) 4.6 ~ 2.3 4.7 - 2.3 NS~ Weight (kg) 18.6 -'- 5.8 19.6 - 7.7 NS:I: Duration of anaesthesia (min) 55.6 -+ 14.8 56.2.4- 12.9 NS:I: Muscles repaired* 2 (I-4) 2 (I-4) NSw

Mean "- SD; *median (range); NS = no significant difference; +chi-squarc analysis; ~:unpaircd t test; w rank sum test (two-tailed).

TABLE II Post-anaesthesia times

Droperidol Promethazine P value

Time in PARR (min) 50.2 • 9.6 (35-75) 64.2 '- 18.7 (40-120) P < 0.01" Time in SSSU (min) 149.6 --- 59.4 (70-375) 139. I - 45.9 (65-310) NS* Time to discharge (min) 199.8 --- 60.2 (I 10-420) 203.3 - 48.9 (140-355) NS*

PARR = post-anaesthesia recoveryroom; SSSU = short-staysurgical unit. Mean --- SD; numbers in parentheses indicate minimum-maximumvalues; *Mann-Whitneyrank sum test (two- tailed).

The parents of each child were contacted 24 hr after than with promethazine (ten per cent). The overall discharge from the hospital by a research assistant (RN) to incidence of vomiting was also higher with droperidol (56 determine the incidence of vomiting or retching and the per cent) than with promethazine (ten per cent) (Figure 1). incidence of side-effects after discharge. Both the parents One child in the promethazine group (two per cent) and and the research assistant were unaware of the treatment three children in the droperidol group (six per cent) had administered to each child. one episode of vomiting in the SSSU followed by one to Statistical significance (P < 0.05) was determined three episodes of vomiting during the postdischarge using Chi-square analysis, unpaired t test, Mann-Whitney period (NS). rank sum test (two-tailed), and Wilcoxon signed-rank test The incidence of vomiting after discharge, in children (two-tailed) with the Bonferroni correction to make treated with droperidol (54 per cent), was significantly pairwise comparisons, where appropriate. Because the higher than the incidence of vomiting predischarge in this data were not normally distributed, the Mann-Whitney same treatment group (eight per cent) (Figure 2). In the rank sum test (two-tailed) was used to determine differ- group of children treated with promethazine, the inci- ences between post-anaesthesia times. dence of vomiting postdischarge (ten per cent) was not different from the incidence of vomiting before discharge Results (two per cent) (NS). The number of children (n), sex (females/males), the Children treated with promethazine presented a higher mean age and weight, duration of anaesthesia, and the incidence of restlessness (36 per cent) than children number of extraocular muscles operated upon did not treated with droperidol (eight per cent) (Table III). This differ between the two treatment groups (Table I). higher incidence of restlessness occurred principally in Children treated with promethazine stayed longer in the the PARR and was prevented or relieved by using rectal PARR than children treated with droperidol, while time in acetaminophen (10 mg-kg-t): each child who presented the SSSU and time to discharge from the hospital (time in restlessness was calmed with acetaminophen; none of the the PARR + time in the SSSU) did not differ significantly children who received acetaminophen on the arrival at the among the two treatment groups (Table lI). PARR presented restlessness (n = 25). With the excep- There was no vomiting or retching in the PARR. The tion of restlessness, the overall incidence of side-effects incidence of vomiting predischarge (in the PARR + in the was not statistically different between the two treatment SSSU) was eight per cent with droperidol and two per cent groups (Table III). with promethazine (NS). The incidence of vomiting None of the children included in this study required postdischarge was higher with droperidol (54 per cent) intramuscular dimenhydrinate. None of the children who Blanc etal.: PROMETHAZINE OR DROPERIDOL 5"7

30 30 "k 25 25

Z 20 0 h- z 20 i t- o 15 Z uJ o 15 a 10 z m.J m -t- r 10 O 5 .J

0 ~ 5 PARR SSSU POSTDISCHARGE OVERALL

Prom01hozino IV + IM [~ Droperidol IV + Placobo IM PARR SSSU POSTDISCHARGE

FIGURE I Incidences of postoperative vomiting in children under- going outpatient strabismus surgery with promethazinc IV + IM versus FIGURE 2 Postoperative incidences of vomiting in children dropcridol IV + placebo IM. PARR = in the post-anaesthesia recovery pretreated with droperidol IV + placebo IM. PARR = in the post- room; SSSU = in the short-stay surgical unit; * = P < 0.0001. anaesthesia recovery room; SSSU = in the short-stay surgical unit; * = P < 0.01 when compared with the incidences of vomiting in the PARR and in the SSSU (Wilcoxon signed-rank test - two-tailed - with vomited after discharge from the hospital required re- the Bonferroni correction for three comparisons). admission for vomiting. charge and overall which was not higher than the Discussion incidence of vomiting in the PARR and/or in the SSSU. Postoperative emesis is a complex problem. Several Thus, movement from the PARR to the SSSU, and from factors, related or not to anaesthesia, may influence the the SSSU to home, tends to increase the incidence of incidence of postoperative nausea, retching and vomiting more easily after droperidol than after prometh- vomiting.t i,t4 azine. In a previous study by Hardy et al. ,5 the incidence In the present study, the incidence of vomiting predis- of postoperative emetic symptoms in patients given charge (vomiting and/or retching in the PARR + SSSU) droperidol, was only six per cent in the PARR, but 42 per was only eight per cent with droperidoi and two per cent cent in the SSSU, and 56 per cent in the postdischarge with promethazine. The incidence of vomiting postdis- period of Day 1. charge was less with promethazine (ten per cent) than with The incidences of vomiting predischarge observed in droperidol (54 per cent) (Figure I). In the group of this study were similar to that of the group pretreated with children pretreated with droperidol IV + placebo IM, intravenous droperidol in the study by Lerman et al. 6 there was a sudden increase in the incidence of postopera- (Table IV). But the incidence of vomiting postdischarge, tive vomiting when children were discharged from the in our group of children pretreated with droperidol IV + SSSU and taken home (postdischarge period) (Figure 2). placebo IM (54 per cent) was higher. Two obvious In contrast to droperidol IV + placebo IM, promethazine differences existed between our protocol and that reported IV + IM maintained an incidence of vomiting postdis- by Lerman et al. Firstly, in their study anaesthesia was induced with intravenous thiopentone, atropine (0.02 TABLE Ill The overall incidence of side effects (%) mg. kg-t) and succinylcholine, while in the present study anaesthesia was induced with halothane, nitrous oxide and Statistical oxygen by mask, followed by intravenous atropine (0.01 Droperidol Promethazine significance mg-kg-i), and tracheal intubation was performed, with- Dry mouth 22 16 NS* out the use of succinylcholine, under deep halothane- Restlessness 8 36 P < 0.001" oxygen anaesthesia. Secondly, in the study by Lerrnan et Disorientation 6 6 NS* al., discharge criteria were more strict than in the present Somnolence 68 62 NS* study and, consequently, time for discharge from the Miscellaneous (rash) 4 2 NS* hospital (6.4 - !.6 hr) was almost twice as long as that Values in percentage (absolute value = value % x 50/100); *Mann- observed in the present study (3.3 +- 1 hr). Whether or not Whitney rank sum test (two-tailed). the type of anaesthesia influences the incidence of 58 CANADIAN JOURNAL OF ANAESTHESIA

TABLE IV The incidence of vomiting predischarge according to the antiemetic used in children undergoing outpatient strabismus correction

Antiemetic used (dose; time) Incidence of vomiting References

Droperidol (0.075 mg. kg -~ IV; 30 min before end of surgery) 43% Abramowitz et al. 2 Metoclopramide (0.15 mg kg- ~IV; in PARR) 35% Broadman et al. 7 Droperidol (0.075 mg. kg -~ IV; 10 min before surgery) 10% Lerman et al. 6 Droperidol (0.075 mg. kg -~ IV; 10 min before surgery) 8% Present study Promethazine (0.5 mg. kg-i + 0.5 mg- kg- IM; 10 min before surgery) 2% Present study

vomiting, in children pretreated with intravenous droper- Hi-receptors and, practically, no antimuscarinic ac- idol (0.075 mg.kg -I) and undergoing strabismus sur- tivity, io-i 1.21-23 Consequently, the higher incidence of gery, remains to be investigated. But it seems unlikely vomiting postdischarge, in the group of children treated that the type of anaesthesia influences the incidence of with droperidol IV + placebo IM, may be attributed, in vomiting postdischarge without influencing the incidence part, to the low antimuscarinic and antihistaminic effects of vomiting predischarge. As far as time for discharge is of droperidol. As motion sickness seems to involve concerned, it must be admitted that children pretreated muscarinic cholinergic and H t-receptors, ~o we with intravenous droperidol require a longer period of rest suggest that the aetiology of vomiting following strabis- in the SSSU, if one wants to reach the low incidence of mus surgery comprises two different mechanisms. Vom- vomiting postdischarge reported by Lerman et al. (six per iting in the PARR, during and following awakening, cent). 6 However, the present study shows that children when the patient is undisturbed by motion, may be pretreated with promethazine IV + IM can be discharged attributed to the surgical stimulation of the sensory from hospital after an average of three postoperative hours receptors of the eye and, through them, to the stimulation with a very low incidence of vomiting postdischarge and of the D2-receptors of the area prostrema. overall (ten per cent). If we wish to obtain an acceptable Vomiting after discharge is better explained as a form of incidence of vomiting postdischarge (< ten per cent) there motion sickness resulting from acute eye imbalance and are two choices: pretreatment with droperidol IV, and diplopia (optokinetically induced motion sickness), s rath- prolonged stay in the hospital or a brief stay with anti- er than from direct labyrinthine stimulation, leading to emetic protection by promethazine IV + IM. stimulation of histamine HI and muscarinic cholinergic Why is promethazine IV + IM more effective than receptors which activate the vestibular nuclei and the droperidol IV + placebo IM against vomiting postdis- emetic centre. Indeed, it is known that there is a powerful charge in children staying no more than 3.3 --- ! hr in the convergence of information from the eye to the vestibular hospital and why is promethazine more prone to induce nuclei and, through the brainstem reticular formation, to postoperative restlessness than droperidol? It is tempting the vomiting centre. ~4-~5 to admit that promethazine IV + IM acts for longer than As far as restlessness is concerned, it has been droperidol IV + placebo IM. Promethazine has been demonstrated that central muscarinic cholinergic recep- reported to have a much longer elimination half-life (9.73 tors comprise two different populations: Mrreceptors are -+ 3.4 hr) 15 than droperidol (2.2 hr), t6 and promethazine, more concentrated in the cortex and M2-receptors are due to a pKa of 9.1, is very slowly absorbed from the IM more abundant in the ports. Hyoscine and promethazine injection site. ~7-~8 However, several clinical reports are effective anti-motion sickness agents producing a high claim that the antiemetic effect of intravenous droperidol, incidence of restlessness because they are equipotent in 0.005-0.07 mg-kg -l, is as long as 24 hr, tl whereas the both the cortex and ports. Thus, they probably cause duration of the antiemetic action of promethazine is restlessness because they are not highly selective Ms- considered to last from 6 to 12 hr. 19-2o Promethazine has antagonists. 26 On the other hand, droperidol has no high affinity for histamine H~ and muscarinic cholinergic antimuscarinic activity and has been shown to enhance receptors and has some affinity for dopamine D2-re- analgesia. 27 This last action seems to be due to ceptors, lo-t~ On the contrary, droperidol has dopamine- its alpha2- and dopamine-antagonist properties. antagonist, 5-hydroxytryptamine-antagonist, and alpha2- Alpha2- are effective and potentiate agonist properties, with a very weak affinity for histamine opioid-induced analgesia. 2s-3t Central and spinal de- Blanc etal.: PROMETHAZINE OR DROPERIDOL 59

scending pathways probably involved in for strabismus in children. Trans Ophthalmol Soc UK pain modulation have been demonstrated. 32-33 1977; 97: 23-5. All these physiological and pharmacological data 5 Hard), JF, Charest J, Girouard G, Lepage Y. Nausea and explain why promethazine may be more effective than vomiting after strabismus surgery in preschool children. droperidol in reducing the incidence of vomiting after Can Anaesth Soc J 1986; 33: 57-62. discharge following strabismus surgery, and why droper- 6 Lerman J, Eustis S, Smith DR. Effect of droperidol idol pretreatment may enhance postoperative analgesia pretreatment on postanesthetic vomiting in children and contribute to a lower incidence of postoperative undergoing strabismus surgery. Anesthesiology 1986; 65: restlessness (eight per cent) than promethazine (36 per 322-5. cent). Also, it seems easier to understand why the 7 Broadman LM, Ceruzzi W, Patane PS, Hannallah RS, incidence of restlessness with promethazine pretreatment Ruttimann U, Friendly D. Metoclopramide reduces the may be greatly reduced or prevented by reducing the incidence of vomiting following stracismus surgery in incidence of postoperative pain with an analgesic-like children. Anesthesiology 1990; 72: 245-8. rectal acetaminophen ( I 0 mg. kg-t ). 8 Warner LO, Rogers GL, Martino JD, Bremer DL, Beach The cost of treatment is also important. One phial of TB. Intravenous lidocaine reduces the incidence of droperidol (2 ml = 5 rag) costs 4.24 SCan. One phial of vomiting in children after surgery to correct strabismus. promethazine (I ml = 25 mg) costs 0.17 SCan. Anesthesiology 1988; 68: 618-21. In conclusion, we have shown that promethazine 9 Christensen S, Farrow-Gillespie A, Lerman J. Incidence pretreatment (0.5 mg'kg -t IV + 0.5 mg.kg -~ IM) of emesis and postanesthetic recovery after strabismus reduces the incidence of postoperative vomiting in unpre- surgery in children: a comparison of droperidol and medicated children undergoing outpatient strabismus lidocaine. Anesthesiology 1989; 70:25 I-4. correction. Promethazine pretreatment permits reduction 10 Peroutka SJ, Snyder SH. Antiemetics: neurotransmitter of the time for discharge from the hospital to three hours receptor binding predicts therapeutic actions. Lancet while keeping a low incidence of vomiting. In addition, 1982; !: 658-9. pretreatment with promethazine is less expensive than I I Palazzo MGA, Strunin L. Anaesthesia and emcsis I1: with droperidol. Finally, promethazine pretreatment re- prevention and management. Can Anaesth Soc J 1984; quires the use of an analgesic such as acetominophen to 31: 407-15. reduce the incidence of postoperative pain and restless- 12 Ryan JF, Todres ID, CoM C J, Goudsouzian NG. A ness. An ideal antiemetic and anti-motion sickness , Practice of Anaesthesia for Infants and Children. without the untoward effects of droperidol and prometh- Orlando; Grune & Stratton, 1986. azine, would be welcome. 13 Steward DJ. A simplified scoring system for the post- operative recovery room. Can Anaseth Soc J 1975; 22: 111-3. Acknowledgements 14 Palazzo MGA, Suunin L. Anaesthesia and emesis l: We thank Mrs. Louise Lortie, RenEe Deboer, Diane Roy, etiology. Can Anaesth Soc J 1984; 31: 178-87. and the nurses of the operating room, post-anaesthesia 15 Scwinghammer TL, Juhl R, Dittert LW, Melethil SK, recovery room and short-stay surgical unit, who devoted- Kroboth FJ, Chung VS. Comparison of the bioavaila- ly assisted us. Also, we extend a note of appreciation to bility of oral, rectal and intramuscular promethazinc. the anaesthesia and inhalotherapy staff for their coopera- Biopharm Drug Dispos 1984; 5: 185-94. tion. 16 JOrgensen A. and of anti- psychotic . In: Bridges JW, Chasseaud LF (Eds.). Progress in . London and Philadelphia: References Taylor & Francis, 1986; 9,4: I I 1-74. I Powley MP, Brown TCK. Postoperative vomiting in 17 Katzung BG. Basic and Clinical . 2nd ed, children. Anaesth Intensive Care 1982; 22: I 1I-3. Los Altos, California: Lange Medical Publications, 2 Abramowitz MD, Oh TH, Epstein BS, Ruttimann UE, 1984. Friendly DS. The antiemetic effect of droperidol 18 Speight TM. Avery's Drug Treatment; Principles and following outpatient strabismus surgery in children. Anes- Practice of Clinical Pharmacology and Therapeutics. thesiology 1983; 59: 579-83. 3rd ed, Baltimore: Williams and Wilkins; 1987. 3 lwamoto K, Schwartz H. Antiemetic effect of droperidol 19 Wood CD. Antimotion sickness and antiemetic drugs. after ophthalmic surgery. Arch Ophthalmol 1978; 96: Drugs 1979; 17: 471-9. 1378-9. 20 Barnhart LR. Physicians' Desk Reference. 44th ed, Ora- 4 Hadaway EG, lngram RM, Traynar MJ. Day case surgery dell, NJ: Medical Economics Company Inc, 1990. 60 CANADIAN JOURNAl. OF ANAESTHESIA

21 Hyttel J, Arht J. Characterisation of binding of 3H-SCH 23390 to dopamine D~-receptors. J Neural Transm 1987; 68: 171-89. 22 Leysen JE, Gommeren W. Drug-receptor dissociation time, a new tool for drug research. Drug Dev Res 1986; 8:119-31. 23 lson PJ, Preoutka SJ. Neurotransmitter receptor binding studies predict antimetic efficacy and side effects. Treat Rep 1986; 70: 637-41. 24 Brandt T, Dichgans J, Wagner W. Drug effectiveness on experimental optokinetic and vestibular motion sick- ness. Aerospace Med 1974; 45: 1291-7. 25 Barnes JH. The physiology and pharmacology of emesis. Mol Aspect Med 1984; 7: 397-508. 26 McCarthy B, Peroutka SJ. Differentiation of muscarinic cholinergic receptor subtypes in human cortex and pons: implications for anti-motion sickness therapy. Aviat Space Environ Med 1988; 59: 63-6. 27 Bach V, Carl P, Ravlo O, Crawford M, Kruse L. Extra- dural droperidol potentiates extradural opioids. Br J Anacsth 1985; 57: 238. 28 Yash TL. Pharmacology of spinal adrenergic systems which modulate spinal nociceptivc processing. Phar- macol Biochem Behav 1985; 22: 845-58. 29 Glynn CJ, Jamous MA, Teddy PJ, Moore RA, Lloyd JW. Role of spinal noradrenergic system in transmis- sion of pain in patients with spinal cord injury. Lancet 1986; 1: 1249-50. 30 Tamsen A, Gordh T. Epidural clonidine produces analge- sia. Lancet 1984; 2: 231-2. 31 Eisenach JC, Lysak SZ, Viscomi CM. Epidural clonidine analgesia following surgery: phase 1. Anesthesiology 1989; 71: 640-6. 32 H6kfelt T, Phillipson O, Goldstein M. Evidence for a dopaminergic pathway descending from All cell group to the spinal cord. Acta Physiol Scand 1979; 107: 393. 33 Tulunay FC, ischiro Y, Takemori EE. The effect of biogenic amine modifiers on morphine analgesia. Eur J Pharmacol 1976; 35: 285-7.