British Journal of Anaesthesia 1992; 69 (Suppl. 1): 46S-59S



(Br. J. Anaesth. 1992; 69 (Suppl. 1): 46S-59S)

butyrophenones (e.g. droperiodol) have antiemetic properties resulting also from antidopaminergic actions. Central anticholinergic action is associated with antiemetic activity and this is seen not only in classical anticholinergic drugs such as hyoscine and atropine, but also in some antihistamine receptortype 1 antagonists (e.g. cyclizine). It may be that the anticholinergic effects of these drugs are responsible for their antiemetic activity [56]. The pharmacokinetics, efficacy compared with placebo, and side effects, with an emphasis on the postoperative period are reviewed for each antiemetic. Comparative studies are then considered. The effects of5-HT 3 antagonists such as ondansetron [70] on PONY are not considered as this subject is reviewed in detail elsewhere [114]. GASTROINTESTINAL PROKINETIC DRUGS

Gastrointestinal prokinetic drugs enhance gastric and upper intestinal motility. Metoclopramide and domperidone act primarily as antidopaminergics [22,62] and therefore have antiemetic activity, particularly at the chemoreceptor trigger zone. Direct action on the gastrointestinal tract is likely to have some antiemetic effect but the relative importance of this is not clear. Metoclopramide has some antagonistic effect at the 5-HT 3 receptor which may account for some of its antiemetic activity, particularly at high doses [53]. Cisapride is another effective gastrointestinal prokinetic drug but has no antidopaminergic effect and therefore little antiemetic activity [85]. Metoclopramide Metoclopramide was developed in France in the early 1960s and is related structurally to procainamide (2-methoxy-5-chloroprocainamide). It has been used extensively in the treatment and prevention of PONY in the last 30 years and there is an extensive literature on its efficacy. Pharmacokinetics. Metoclopramide was absorbed rapidly after oral administration to volunteers. The mean (range) time to peak concentration (tCmax) was 0.9 (0.5-l.25) h [112]. However, there was substantial variation between individuals in first-


Gastrointestinal tract. Pharmacology: phenothiazines, anticholinergics, butyrophenones, antihistamines. Vomiting: nausea.

D. J. ROWBOTHAM, M.D., M.R.C.P., F.R.C.ANAES., F.F.A.R.C.S.r., University Department of Anaesthesia, Leicester Royal Infirmary, Leicester LEI 5WW.

Downloaded from at University of Bath Library & Learning Centre on July 11, 2015

Before specific antiemetic agents became available, various techniques, including olive oil [51] and insulin-glucose infusions [122], were reported to be effective in reducing the incidence of postoperative nausea and vomiting (PONV). Robert Ferguson [51] described the use of olive oil in 1912. The oil was administered "by mouth immediately after partial restoration of consciousness" and he postulated that oil in the stomach" absorbed any ether that might be there". However, the effect of atropine was appreciated by Brown-Sequard as early as 1883 when he wrote " in the very great majority of cases, the addition of a certain amount of atropine to the morphine prevents the vomiting and also the nausea occasioned by morphine alone" [48]. Antiemetic drugs are now the mainstay of therapy for PONY and this article reviews those in common use. Clearly, many factors affect the incidence of PONY and it is difficult to compare data from different studies. In this review, placebo-controlled studies of satisfactory design only are described. However, some important investigations into the efficacy of older antiemetics were not, by modern standards, well controlled. These studies are included in this review but any shortcomings in design are identified. To aid comparison, many studies are summarized in tables. For clarity, the nature of the anaesthetic agents used in each study is not listed in the tables. However, studies are arranged in chronological order which gives some indication of the type of anaesthetic technique used. In most tables, efficacy is presented as a comparison with placebo. This has been calculated as the percentage difference in the incidence of PONY between placebo and treatment or, if not available, the incidence of vomiting only. The majority of studies have been concerned with the prevention of PONV; only a few have investigated treatment. There are several types of antiemetics used in the management of PONY. Gastrointestinal prokinetic drugs with antidopaminergic actions (e.g. metoclopramide, domperidone) are antiemetics. Phenothiazines (e.g. prochlorperazine, perphenazine) and


CURRENT MANAGEMENT OF PONY TABLE I. Studies demonstrating efficacy of me to clop ramide in the prevention of PONV (° 0 reduction in incidence of PONV compared with placebo). Paed./eyes = Paediatric ophthalmic; Elect. CS = elective Caesarean section; Maj. gynae. = major gynaecological; Min. gynae. = minor gynaecological; Orthop. = orthopaedic; Upper abdo. +NGT = upper abdominal with postoperative nasogastric tube. Before = Given as premedication or at induction of anaesthesia; End = given at the end of anaesthesia. * At 1-3 h after anaesthesia only Year

[59] [41] [128] [29] [3] [33] [39] [69] [27] [92] [21] [17]

1967 1968 1969 1969 1974 1979 1980 1986 1987 1988 1990 1990

Surgery Min. gynae. Upper abdo. +NGT "High risk" Min. gynae. Min. gynae. Elect. CS Orthop. Orthop. /female Elect. CS Min. gynae. Paed./eyes Maj. gynae.

Dose Cmg)


10 20

Lm. Lv. Lv. Lm. Lm. Lv. Oral Lv. Lv. Oral Lv. Lv.


20 10-20 10 20 20 0.15 kg-I 10 0.15 kg-I 10

pass metabolism resulting in a wide range of peak plasma concentrations and oral bioavailability (3297 (Yo) [62]. In a study comparing oral and i.m. absorption in volunteers, tCmax values were similar (oral 97.5 min; i.m. 91.9 min) [28]. Elimination halflife is approximately 4 h and plasma clearance is similar to hepatic plasma flow [62]. Rapid redistribution of metoclopramide after i. v. administration has been reported (T = 4.9 min) [8].


Clinical use. Many workers have investigated the efficacy of metoclopramide in the prevention of PONY and it is surprising that approximately 50 % of studies have shown it to be no more effective than placebo. Table I summarizes those studies in which metoclopramide was effective and table II those in which it was not effective. Although it is difficult to compare studies directly, it may be possible to draw some conclusions from these data. 1. v. administration at induction of anaesthesia appears to be associated with failure (two successes, five failures). Perhaps this is not surprising in view of the rapid redistribution of metoclopramide after Lv. administration [8] resulting in low plasma concentrations in the postoperative period. The recommended dose for metoclopramide in PONY is 10 mg [4] but these data show that 20 mg may be more effective. Oral administration has been shown to be effective [39, 92] but metoclopramide 5 and 10 mg orally was ineffective in patients after outpatient laparoscopy [101]. However, seven treatment groups were included in this study (including various doses of droperidol), and there was a trend for metoclopramide to be effective (65 % nausea or vomiting with placebo; 45 % with metoclopramide 10 mg). Only 20 patients were included in each group and it is likely that the power of this study was insufficient to be certain of these negative findings. Side effects. The most important side effects associated with the use of metoclopramide are extrapyramidal reactions. The incidence of extrapyramidal reactions with metoclopramide reported to the Committee on Safety of Medicines (CSM) has been reviewed by Bateman, Rawlins and Simpson [9]. The reported rate for dystonia was 28.6 per million prescriptions; 94 % of these occurred within

Time End End End End Before Before Before End Post-clamp Before End Before

Reduction ('10)

80 40 50 75 37-60 43 77* 30 67 58 37 41

the first 72 h and were more frequent in females and young patients. For example, the incidence in females aged 12-19 yr was 1 in 5000. The authors stress that this incidence is likely to be a gross underestimation as under-reporting of adverse drug reactions is known to be 90-99 %. Dystonia has been reported [116] after anaesthesia but the incidence is not known. Parkinsonian reactions occur usually in the elderly and are associated with a more prolonged exposure to metoclopramide. The neuroleptic malignant syndrome, usually associated with drugs such as phenothiazines and butyrophenones, can develop in patients receiving metoclopramide [54]. Sedation occurs in approximately 10% of patients receiving long-term therapy [62] and delayed recovery from anaesthesia has been reported [82], but rarely occurs at normal doses when used for PONY. Dundee and Clarke [44] reported a significant incidence of restlessness after metoclopramide 10 and 20 mg i.m. administered as premedication. Extreme agitation in this context is rare but Caldwell, Rains and McKiterick [24] reported severe dysphoria, agitation and akathisia in a 21-yr-old female who

TABLE II. Studies failing to demonstrate significant efficacy of metoclopramide compared with placebo in the prevention of PONV. OP laps. = Outpatient laparoscopy; Maj. gynae. = major gynaecological; Min. gynae. = Minor gynaecological; Orthop. = Orthopaedic; Upper abdo. = upper abdominal; Orthop,; spinal = orthopaedic under spinal anaesthesia; NGT = nasogastric tube. Before = Given as premedication or at induction of anaesthesia; End = given at the end of anaesthesia Reference




[50] [119] [44] [73]

1970 1972 1973 1979

[33] [124]

1979 1984

[32] [133] [89] [131] [101]

1984 1985 1986 1987 1989


Dose Cmg)

Upper abdo., 20 noNGT Min. gynae. 10-20 Min. gynae. 10 Min. gynae. 10-20 Orthop'; 10 female Min. gynae. 10 10 Orthop./ spinal Min. gynae. 10 Min. gynae. 10 Maj. gynae. 10 0.15 kg- 1 Ophthalmic OP laps. 5-10

Route Time Lv.


Lv. Lm. Lm. Lv.

Before End Before End

Lv. Lv.

Before Before

Lv. Lv. Lv. Lv. Oral

Before Before End End Before

Downloaded from at University of Bath Library & Learning Centre on July 11, 2015



48S had received metoclopramide 10 mg and glycopyrronium 0.2 mg as premedication. Her symptoms were reversed by benztropine. Similar symptoms were reported in three patients who had received both metoclopramide and droperidol as preoperative medication for eye surgery [7]. I.v. administration of metoclopramide may be associated with significant cardiovascular side effects. Four patients suffered significant episodes of hypotension when metoclopramide 10 mg was given i. v. during dural closure after the use of hypotensive agents had ceased [102]. This was confirmed in 16 patients undergoing similar surgery when metoclopramide 10 mg, given 20 min before the end of surgery, resulted in a mean decrease of 20 % in both systolic and diastolic pressures [104]. Mean time of maximal decrease was 44 s after administration. Ellis and Spence reported a significant increase in heart rate in patients given metoclopramide i.v. before induction of anaesthesia [50]. Supraventricular tachycardia after i.v. administration occurred also in a patient scheduled for laparoscopic tubal ligation [15]. Paradoxically, severe bradycardia has occurred also after i.v. metoclopramide [137]. It is therefore recommended that i.v. administration of metoclopramide should be over 1-2 min [4]. In view of the efficacy data presented in tables I and II, and these potential side effects, perhaps the indications for i.v. administration of metoclopramide are few, particularly at induction of anaesthesia. However, significant supraventricular ectopics have been reported after i.m. administration also [120].

usually for chemotherapy-induced emesis [25, 58, 67, 100, 113]. Domperidone in now available only as an oral and rectal preparation and interest in its use for PONY has waned. PHENOTHIAZINES

Prochlorperazine Pharmacokinetics. The pharmacokinetics of prochlorperazine were first described in detail in 1987, over 30 years after its introduction into anaesthetic practice. After i.v. administration to volunteers of prochlorperazine 12.5 mg, mean (SEM) elimination half-life was 6.8 (0.7) h, volume of distribution 1548 (155) litre and plasma clearance 2.7 (0.3) litre min- I [125]. Surprisingly, oral bioavailabilty was poor; after 25 mg orally, plasma prochlorperazine was detectable in only 50 % of subjects (lower limit of detection of assay 1 ng ml- I ) and tCmax was 1.5-5 h.

Domperidone Domperidone is less likely to cross the blood-brain barrier than metoclopramide and therefore extrapyramidal reactions should not occur [22]. This was the logic responsible for the development and introduction into clinical practice of this drug. Unfortunately, extrapyramidal reactions with domperidone have been reported [88] although less frequently than with metoclopramide. Only a few studies have compared domperidone with placebo in the prevention of PONY and most of these showed no significant effect [73,89, 124, 133]. However, efficacy was demonstrated in patients undergoing Caesarean section [33]. Further work on domperidone was prevented by the withdrawal of the parenteral preparation. This was the result of several reports of serious cardiac arrhythmias after i.v. administration of large doses,

Clinical use. Prochlorperazine was introduced for the prevention of PONY in the 1950s [23], but there are only limited data on its efficacy. Studies comparing prochlorperazine with placebo are summarized in table III. In 1959, Robbie was able to demonstrate only a trend towards efficacy [111]. However, vomiting, and not nausea, was investigated and the incidence of vomiting was surprisingly low for such an early study (control 19 %, prochlorperazine 11 %). Other investigations, some more recent, have shown prochlorperazine to be effective in the prevention of PONY [64,65, 128]. However,

III. Studies investigating the effect of prochlorperazine on PONV (% reduction in incidence of PONV compared with placebo). Gen. surg. = General surgery; Gynae. lap. = gynaecologicallaparoscopies. Before = Given as premedication or at induction of anaesthesia; End = given at the end of anaesthesia. *No statistics available; ns = no significant effect





Dose (mg)



Reduction ('Yo)

[111] [65]

1959 1960

Various Gen. surg.

12.5 12.5

Lm. Lv.

[128] [34] [64]

1969 1989 1989

Various Gen. surg. Gynae. lap.


Lm. Lv. Lv.

End Before, end End Before End

Trend only 43* 41* 50 ns 73



Downloaded from at University of Bath Library & Learning Centre on July 11, 2015

Phenothiazines were synthesized originally in the late 19th century by chemists working in the dye industry [6]. In the late 1930s promethazine, a phenothiazine derivative, was found to have profound hypnotic properties and was introduced into anaesthetic practice. Promethazine is still administered as premedication and significant effects on PONY have been demonstrated [16,23,65]. However, its sedative action limits its use considerably. Charpentier synthesized chlorpromazine in 1949 [6] and it was introduced into clinical practice shortly afterwards. Its many side effects, particularly sedation and hypotension, limit its use as an antiemetic also, but efficacy in the prevention of PONY has been demonstrated [2, 19, 26, 42, 65, 72, 77]. Prochlorperazine and perphenazine are phenothiazine derivatives which have been used extensively in the management of PONY.



TABLE IV. Studies investigating the effect of perphenazine on PONV (~o reduction in incidence of PONV compared with placebo). Min. gynae. = Minor gynaecological. Before = Given as premedication or at induction of anaesthesia; End = given at the end of anaesthesia. *No statistics available




[95) [117) [lll) [109) [59)

1958 1958 1959 1960 1967

Various Various Various Min. gynae. Min. gynae.


Dose (mg)


5 5 5 5 5

Lm. Lm. Lm. Lm. Lm.

Side effects. Side effects of any phenothiazine include, cholestatic jaundice, haematological abnormalities, skin sensitization, hyperprolactinaemia and neuroleptic malignant syndrome. However, these are rare, but sedation, extrapyramidal reactions and cardiovascular effects are important side effects in anaesthesia. Acute dystonias have been reported after prochlorperazine; children, young adults and females are most frequently affected [10,14,106]. During the period 1967-1982, 104 extrapyramidal reactions were reported to the CSM, during which time there were an estimated 37 million prescriptions (2.8 per million) [10]. Most of these were acute dystoniadyskinesia reactions and developed within 3 days of treatment. Approximately 25 % of reactions occurred after a single parenteral dose. Porter and Jick investigated adverse drug reactions in 32812 patients admitted consecutively to hospitals in Boston, U. S .A. [106]. The incidence of extrapyramidal side effects associated with prochlorperazine was 0.3 %. The relative proportions of patients receiving prochlorperazine in large (psychiatric indications) or smaller doses (PONV) are not clear, but no reactions were reported in patients receiving less than 10 mg. Akathisia was reported by five of eight volunteers who were given prochlorperazine 12.5 mg i.v. during a pharmacokinetic study [125]. The effect of prochlorperazine on recovery from anaesthesia has not been investigated extensively but early reports give some indication of its effects. Recovery was" prolonged" in two of 56 patients [65] receiving prochlorperazine compared with none of 53 receiving saline, and excess postoperative sedation in a small number of patients was reported by Tornetta [128]. However, Robbie reported a mean

Before and 6-hourly End End Before End

eX,) 65 67 63 73* 90

recovery time of 17.1 min in patients receiving prochlorperazine compared with a control value of 18.5 min [111].

Perphenazine Pharmacokinetics. The pharmacokinetics of perphenazine have been investigated in 18 patients and five volunteers [60]. After i.v. administration of 5 or 6 mg, mean (range) elimination half-life was 9.4 (8.4--12.3) h, plasma clearance 107 (49-183) litre h- 1 and volume of distribution 20.2 (9.8-34.6) litre kg-I. Oral bioavailability was poor. After a single oral dose of 6 mg, no perphenazine was detectable in plasma (lower limit of assay detection 0.2 J.!g ml-I). However, perphenazine was absorbed well after i.m. administration. Clinical use. Only a small number of studies investigating the efficacy of perphenazine in PONY is available in the literature [20, 40, 59, 95, 109, Ill, 117]. Those which were placebo-controlled are summarized in table IV. Most of these studies were performed 30 years ago but the results are impressive. Perphenazine was effective in all these studies and the percentage change in the incidence of PONY compared with placebo was large. The design of some of these studies would be considered poor by modern standards but large numbers of patients were investigated. Side effects. There can be no doubt that perphenazine is an effective antiemetic but there is a general impression that it is more likely to cause extrapyramidal side effects than other antiemetics [66]. Is there any evidence for this? Braly and Moore [20] gave perphenazine to 2794 patients undergoing general and local anaesthesia for a wide variety of surgical procedures. Four cases (0.14%) of acute dystonia were reported. Robbie [Ill] gave perphenazine to 166 patients and prochlorperazine to 105 patients. Acute dystonias did not occur after prochlorperazine but two cases were described after perphenazine (l.2 %). No cases of dystonias were reported in the studies summarized in table III describing the effects of prochlorperazine. Furthermore, many cases of extrapyramidal reactions, especially in young patients, were reported in the literature when perphenazine was first used extensively as an antiemetic for PONY [37,71,93, 108, 123]. It is likely therefore that the incidence of extrapyramidal reactions is relatively greater with

Downloaded from at University of Bath Library & Learning Centre on July 11, 2015

Cramb, Fargas-Babjak and Hirano [34], showed no significant effect when prochlorperazine 10 mg i.v. was given 10 min after induction of anaesthesia in patients undergoing major general surgery. The duration of anaesthesia was not reported in this study but it is likely that patients were emerging from anaesthesia some time after prochlorperazine administration. Prochlorperazine 10 mg has been shown to be effective in the treatment of established vomiting after anaesthesia [83]. The incidence of continued vomiting 0.5-1 h after prochlorperazine was only 7 % compared with 70 % after saline. Antiemetic effects continued for at least 4 h (13 % vomiting compared with 50 %).



BRITISH JOURNAL OF ANAESTHESIA TABLE V. Studies demonstrating efficacy of droperidol in the prevention of PONV (':Co reduction in incidence of PONV coillpared with placebo). Paed./ eyes = Paediatric ophthalmic; Paed./ ortho. = paediatric orthopaedic; Elect. CS = elective Caesarean section; Maj. gynae. = major gynaecological; Min. gynae. = minor gynaecological; Orthop. = orthopaedic. Before = Given as premedication or at induction of anaesthesia; End = given at the end of anaesthesia. * Dose (mg) per 70 kg



[103] [136] [73] [110] [97]

1973 1977 1979 1981 1982

Maj. gynae. Min. gynae./urological Female orthop. Paed./orthop. (11-15 yr) Min. gynae.

[1] [99] [115] [74]

1983 1984 1984 1985

Paed.jeyes Min. dental Elect. CS/spinal Female orthop.

[130] [69] [89] [101]

1985 1986 1986 1989

Dental Female orthop. Maj. gynae. Min. gynae.




perphenazine, particularly compared with prochlorperazine. Whether or not this effect is more frequent when compared with metoclopramide is open to question. Metoclopramide or perphenazine was given to approximately 200 patients undergoing gynaecological laparotomies [82] and to 584 women in labour [87], and no extrapyramidal side effects were reported with either agent. Perphenazine has been shown to delay recovery from anaesthesia. Mean recovery time after various surgical procedures was 17 min in a placebo group compared with 27 min in the group receiving perphenazine [117]. In a comparative study by Robbie [111], mean recovery times were 18.5 min (control group), 22.3 min (perphenazine) and 17.1 min (prochlorperazine). Unfortunately, no statistical analysis is available for these data but it would tend to support the view that more sedation occurs with perphenazine compared with prochlorperazine when used in doses appropriate for PONY. BUTYROPHENONES

Many butyrophenones are potent neuroleptics but droperidol is the only drug of this class used extensively in anaesthesia.

TABLE VI. Studies demonstrating no effect of droperidol compared with placebo in the prevention of PONV. Paed.jeyes = Paediatric ophthalmic; Min. gynae. = minor gynaecological. Before = Given as premedication or at induction of anaesthesia. * Dose (mg) per 70 kg Reference


[96] [99] [32] [61] [131] [101] [90]

1970 1984 1984 1986 1987 1989 1989

Surgery Min. gynae. Min. dental Min. gynae. Paed./eyes Adult eyes Min. gynae. Min. gynae.

Dose (mg) 5,10 1.25 1.25 3.5* 2.45 0.35* 1.25



Lm. Lv. Lv. l.v. Lv. Lv. Lv.

Before Before Before Before Before Before Before

Dose (mg)


5.0 5.0 1.25 0.35* 2.5 5.0 5.25* 0.25 2.5 2.5 1.25 1.0* 1.25 2.5 0.7* 1.4* 5.25*

Lv./i.m. Lm. Lv. Lv. Lv. Lv. Lv. Lv. Lv. Lm. Lv. Lv. Lv. Lv. Lv. Lv. Lv.

Time Before Before End End Before Before End Before After delivery Before End Before End End Before Before End

Reduction ('Yo) 46 55 55 51 56 60 50 72 70 41 37 33 58 35 66 75 27

Droperidol Pharmacokinetics. After i.v. administration of droperidol, the redistribution half-life is approximately 10 min [35], elimination half-life approximately 2 h and plasma clearance approximately 15 ml min- 1 kg- 1 [35,52]. A study investigating the pharmacokinetics of droperidol 10 mg in patients undergoing anaesthesia suggested that elimination half-life, plasma clearance and volume of distribution were not influenced significantly by volatile anaesthetic agents (halothane, enflurane), body weight (48-90 kg) or age (14-65 yr) [80]. Droperidol is well absorbed after oral administration [Janssen Pharmaceuticals, personal communication] and Lm. absorption is rapid (tCmax approximately 30 min [35]). Droperidol is metabolized extensively (1 % unchanged in urine) and significant biliary excretion has been described (approximately 10 % appearing in faeces) [35]. Clinical use. The majority of studies have found that droperidol is more effective than placebo in the prevention of PONY (table V). Efficacy has been demonstrated after administration of droperidol both before and at the end of surgery. I.m. administration has been shown to be effective [74, 136], and also combined i. v. and Lm. administration at induction of anaesthesia [103]. Studies failing to show efficacy of droperidol are summarized in table VI. Droperidol was administered at induction of anaesthesia in every study suggesting that, despite the evidence in table V, efficacy will be improved if droperidol is administered towards the end of surgery. Van den Berg and colleagues [131] failed to show an effect not only of droperidol but also of metoclopramide and prochlorperazine after ophthalmic surgery. The study design was complicated by the inclusion of groups who were denied fluids after operation. Data reported by Hardy and coworkers [61] indicated a trend towards reduction of vomiting in the recovery room

Downloaded from at University of Bath Library & Learning Centre on July 11, 2015




VII. Comparison of recovery times (min) after i.v. droperidol and placebo. *Dose (mg) per 70 kg Mean recovery time



Dose (mg)

[32] [99] [61]

1984 1984 1986

1.25 1.25 3.5*

Placebo Droperidol 3 8 27

6 10 34


< 0.01 < 0.05 0.036

Side effects. The side effects ofbutyrophenones are very similar to those associated with phenothiazines. Several workers have reported a statistically significant delay in recovery from anaesthesia after droperidol [32,61,97,99]. Time to recovery was not defined in precisely the same manner in these studies but it is informative to compare these data (table VII). In addition, Mortensen [97] found that, after minor gynaecological surgery and droperidol 2.5 or 5.0 mg i.v., significantly more patients were rated as excessively drowsy in recovery but there was no difference between placebo and droperidol in duration of stay in the recovery ward. It may be argued, therefore, that although recovery may be significantly delayed, the differences may not be important clinically. However, the effect of droperidol has been demonstrated later in the postoperative period. In the same study, Mortensen found an increase in excessive drowsiness reported by patients after discharge to the ward of approximately 50 % (P < 0.00l). Valanne and Korttila [130] investigated recovery of young healthy patients after anaesthesia for minor dental surgery who were given droperidol 0.014 mg kg- 1 (1 mg/70 kg) i.v. or placebo. Although recovery times were similar (approximately 14 min), ability to perform psychomotor speed tests was impaired significantly in patients who received droperidol. The addition of droperidol 0.2 mg kg- 1 to trimeprazine given as oral premedication to children was associated with a significant increase in preoperative sedation [71] and recovery time after anaesthesia [132]. Extrapyramidal reactions are recognized side effects of droperidol. The true incidence when used to prevent PONY is not known, but it is relatively rare. For example, none of the studies discussed above reported such effects. Dupre and Stieglitz [49] described extrapyramidal reactions in four children after relatively large doses (0.1-0.17 mg kg- 1 (711.9 mg/70 kg) as premedication). However, extrapyramidal effects have been reported also after small doses (e.g. 0.65 mg) [91]. It is important to realize that these reactions can occur some time after the administration of droperidol. For example, a 10yr-old boy, premedicated with droperidol 0.16 mg kg- 1 before halothane anaesthesia for removal of dental cyst, developed opisthotonos and oculogyric spasms 14 h after anaesthesia [49]. Melnick [91] described a 24-yr-old lady who underwent outpatient laparoscopy and was given droperidol 0.65 mg i.v. for prevention of PONY. She was

Downloaded from at University of Bath Library & Learning Centre on July 11, 2015

(placebo 23 % (n = 7), droperidol 6 % (n = 2)) but statistical significance was not achieved. A similar trend was reported by Melnick and colleagues [90] (placebo, seven patients nauseated; droperidol 1.25 mg, four patients). It is likely that insufficient patients were investigated in these studies to be confident of a negative result. Therefore, many of the studies which failed to show efficacy of droperidol can be criticized. However, the failure of droperidol in preventing nausea after minor gynaecological surgery was shown convincingly by Cohen, Woods and Wyner [32] (placebo 70 %; droperidol 1.25 mg 72%). Because of the side effects of droperidol, there has been some interest in discovering the most effective dose. The summaries of both successful and unsuccessful studies shown in table V and VI show that both relatively large doses have been associated with failure and relatively small doses with success. Many factors affect PONY including age, sex, procedure and anaesthetic technique and clearly it is difficult to draw conclusions based on comparisons between these studies. However, comparisons have been made within single studies [97, 99, 101]. Two groups have investigated patients undergoing minor gynaecological surgery. Mortensen [97] gave droperidol 2.5 and 5 mg i.v. at induction of anaesthesia and reduced the incidence of nausea by 56 and 60 %, respectively. After outpatient laparoscopies, Pandit and colleagues [101] gave 5, 10 and 20 ~g kg- 1 (0.35, 0.7 and 1.4 per 70 kg). The 10- and 20-~g kg- 1 doses were very effective (66 and 75 % reduction in nausea, respectively). In this study ofrelatively few patients, droperidol 5 ~g kg- 1 reduced nausea by 33 %, but this was not statistically significant. O'Donovan and Shaw [99] reported curious data after day-case dental surgery. Patients were given droperidol 1.25 mg, droperidol 0.25 mg or placebo, at induction of anaesthesia in a double-blind, placebo-controlled study. Surprisingly, it was concluded that droperidol 0.25 mg reduced nausea whilst droperidol 1.25 mg had no significant effect. The incidence of PONY was measured by staff observations and a patient questionnaire. There was a low incidence of vomiting (five patients (11 %) after placebo) but the incidence of nausea reported by patients was greater (16 patients (35 %) after placebo). Both doses of droperidol tended to reduce the incidence of both nausea and vomiting but the only significant difference found by the authors was the effect of droperidol 0.25 mg on the incidence of nausea reported by the patients during their hospital stay. It cannot be concluded reliably from this study of relatively low power that droperidol 1.25 mg was less effective than droperidol 0.25 mg.

The literature does not enable us to make firm conclusions as to the most appropriate dose of droperidol for prevention of PONY but it is likely that droperidol is an effective antiemetic, even at relatively small doses. Loeser and colleagues [83] investigated the efficacy of droperidol 5 mg i.m. in the treatment of vomiting in the recovery room after standardized anaesthesia. Compared with placebo, emesis scores were significantly improved after 0.5-1 h. Peak effectiveness was at 4 h and a significant difference from placebo could be demonstrated even after 24 h.




Hyoscine or scopolamine (tropic acid ester of scopine) and hyoscyamine or atropine (tropic acid ester of tropine) are centrally and peripherally acting anticholinergics used extensively in anaesthetic practice. They are derived from solanaceous plants and have antiemetic activity. Hyoscine Racemic mixtures of hyoscine occur naturally but only the laevoisomer is active pharmacologically. Pharmacokinetics. Pharmacokinetic data on hyoscine are limited, despite its widespread use in medicine. Plasma hyoscine concentrations are difficult to measure but using an enzyme immunoassay technique, pharmacokinetic values after i.v. administration (5 J.lg kg-I) in patients undergoing Caesarean section have been reported [105]. Mean (SD) distribution and elimination half-life were 5.0 (3.2) min and l.9 (2.2) h, respectively, plasma clearance 14.4 (17.4) ml kg I min- J and volume of distribution l.1 (0.6) litre kg-I. Mean (SEM) elimination half-life, plasma clearance and volume of distribution in six male volunteers were 4.5 (l.7) h, 65.3 (5.2) litre h- l and l.4 (0.3) litre kg-1, respectively [107]. After i.m administration in four of these volunteers, absorption was rapid and reliable (tCmax 10 min in each

volunteer). Oral bioavailability of hyoscine 0.4 mg in six volunteers was 10.7-48.2 % and mean (range) tCmax was 0.78 (0.33-2.0) h [108]. A similar range of tCmax values was reported by Muir and Metcalfe [98]. 1.m. administration. Hyoscine has been used for many years as premedication, often administered with morphine or pethidine. The efficacy of hyoscine in this situation as an antiemetic has not been investigated extensively under controlled conditions, but two studies from Belfast demonstrated clear efficacy [30,47]. When administered with pethidine 100 mg, hyoscine 0.4 mg reduced the incidence of vomiting and retching in the 6 h after anaesthesia from 34 % to 20 %. It was even more effective in the first hour after anaesthesia (23 % vs 5 %). Similar data were obtained when hyoscine was given with morphine 10 mg. Hyoscine was more effective than atropine but there was a tendency for patients to be more drowsy on induction of anaesthesia and for delay in recovery from anaesthesia. Tachycardia was not reported. Transdermal administration. The development of a trans dermal preparation of hyoscine is an attempt to alleviate the problems of short plasma half-life and dose-dependent side effects. Plasma concentrations of hyoscine during transdermal administration are small. Using a radio receptor assay, plasma hyoscine was detected in only four of 12 subjects (mean concentration 0.42 nmollitre- l after 8 h) [98]. These data reflect not only the small plasma concentrations of hyoscine achieved during transdermal administration, but also the need for a more sensitive assay. However, only relatively small concentrations are required as it has been shown that the antiemetic effect occurs at a urinary excretion rate of hyoscine < 1 J.lg h- l compared with dry mouth (> 1 J.lg h- l ), drowsiness (3 J.lg h- 1 ) and tachycardia (> 5 J.lg h- 1 ) [121]. Transdermal hyoscine has been used effectively in the prevention of motion sickness but dry mouth (about 67 %) and drowsiness (16 %) have been reported [31, 36]. Its use in the prevention ofPONV has been reported by several authors. Most doubleblind, placebo-controlled studies have found transdermal hyoscine to be more effective than placebo after surgery. An impressive reduction in the incidence of severe nausea and vomiting was reported after day-case laparoscopy [5]; the incidence of PONV in the placebo group was high (62 %, placebo; 37 %, trans dermal hyoscine). Efficacy after major gynaecological surgery and papaveretum analgesia was demonstrated also; the incidence of vomiting and severe nausea in the placebo group was 100 % (trans dermal hyoscine 68 %) [129]. After Caesarean section under extradural analgesia followed by morphine 4 mg extradurally, transdermal hyoscine reduced the incidence of nausea and vomiting by approximately 50 %, 2-10 h after surgery [76]. No effect was demonstrable at 10-24 h. However, trans dermal hyoscine was very effective for 24 h in patients receiving morphine extradurally after major gynaecological surgery [84]. Efficacy has

Downloaded from at University of Bath Library & Learning Centre on July 11, 2015

discharged home only to be readmitted later that day with acute dystonia (spasm of neck and tongue muscles) which responded to diphenhydramine. Acute akathisia occurring with droperidol taken with metoclopramide has been described also [7]. Morrison, Clarke and Dundee assessed apprehension, excitement and restlessness immediately before induction of anaesthesia in patients undergoing minor gynaecological surgery after droperidol premedication [96]. After droperido15 mg i.m., 19 % complained of marked apprehension (placebo 8 %) and 30 'Yo of excitement or restlessness (placebo 2 (Yo). The incidence of the latter was increased with droperidol 10 mg (45 %). Melnick and colleagues [90] followed-up their case report with a fascinating study. Patients received either droperidol 1.25 mg or saline at induction of standardized anaesthesia for minor gynaecological surgery. No extrapyramidal side effects occurred on recovery and all were discharged home. A nurse, blinded to the treatment groups, telephoned the patients at home 24-36 h after surgery. Twentythree percent of patients complained of unpleasant sensations of anxiety during the day and night after discharge. All these patients had received droperidol; no patient who received placebo experienced such symptoms. These data, particularly if confirmed by others, must raise doubts as to the suitability of droperidol as an antiemetic in day-case surgery. Droperidol has alpha-adrenergic blocking properties and may cause hypotension when administered during anaesthesia. Surprisingly, little attention has ,'been paid to this and its incidence and severity is not known. It is not likely to be a significant problem when given in relatively low doses to fit patients.


53S mean elimination half-life of 2.2-4.3 h, volume of distribution of 1.0-1.6 litre kg-I and plasma clearance of 5.9-6.4 ml min- 1 kg- 1 have been reported. Distribution half-life after i.v. administration is small (mean 1.0-1.7 min) and Berghem and colleagues [13] calculated that only 5 % of the administrated i.v. dose remains in the circulation. There is considerable variability in absorption after i.m. administration in both Cmax and tCmax. Mean tCmax values of 0.33-1.59 h have been reported [68]. Atropine is well absorbed after oral administration. Only a small number of studies have compared the effectiveness of atropine with placebo in the prevention of PONY and in most of these atropine was administered as a premedication. Riding [109] investigated the effect of atropine 0.3-1.2 mg given in combination with morphine 5-10 mg in patients undergoing minor gynaecological surgery. Compared with placebo, atropine had a significant effect on the incidence of nausea and retching when given alone in all doses (0.3, 0.6 and 1.2 mg). However, atropine 1.2 mg only reduced the incidence significantly when morphine 5 mg was administered. There was no significant effect in patients given morphine 10 mg. Investigators in Belfast compared the effect of atropine given with morphine 10 mg [30] and pethidine 100 mg [47]. After morphine premedication and methohexitone anaesthesia for short procedures, there was a trend, but not a statistically significant decrease, in the incidence of vomiting and retching during the first 6 h after operation in patients receiving atropine 0.6 mg. However, there was a significant decrease in the first hour (morphine only 28 %, morphine with atropine 12 %). After similar anaesthesia and surgery but with premedication with pethidine 100 mg, the incidence of vomiting and retching in the 6 h after surgery was 34 %. Atropine 0.6 mg had no effect on this incidence (30 %). Tachycardia was associated with the use of atropine in these studies but delayed recovery from anaesthesia was not reported. Atropine is not used after anaesthesia in the management of PONY because of its cardiovascular effects. However, many workers investigating the efficacy of anti emetics have used atropine during and before anaesthesia and its likely effect on the incidence of PONY should be considered when assessing their data. However, the effect of atropine may not be great after i.v. administration because of its rapid redistribution half-life.

Atropine The pharmacokinetics of atropine have been investigated extensively and reviewed in great detail by Kanto and Klotz [68]. After i.v. administration,

Cyclizine Cyclizine is a piperazine derivative. It has antimuscarinic actions also, and it is possible that the antiemetic activity of this and other antihistamines


Drugs of several types (e.g. ethanolamines, piperazines, phenothiazines) exhibit histamine type-l receptor antagonist activity and many are antiemetics. The use of promethazine (a phenothiazine) has been described above. Many antihistamines have been used for the prevention of motion sickness but only cyclizine has been used extensively for PONV.

Downloaded from at University of Bath Library & Learning Centre on July 11, 2015

been claimed in patients after major gynaecological surgery receiving morphine by patient-controlled analgesia [63]. Although there was a significant decline in severity of nausea compared with placebo and fewer patients demanded escape antiemetic therapy at 6 and 24 h after surgery, there was no significant difference in the incidence of nausea or vomiting. It may be that the power ofthis study was insufficient to detect a difference reliably. Steadystate concentrations are not achieved for at least 5 h after application of the patch [31] and this may have been an important factor in the equivocal findings, as patches were applied at induction of anaesthesia. Similar results were reported by Semple and colleagues who applied the patch 2 h before anaesthesia [ll8]. Two double-blind, placebo-controlled studies have failed to show any significant effect of transdermal hyoscine compared with placebo. Tigerstedt, Salmela and Aromaa applied the patch only 50 min before anaesthesia in patients undergoing a wide range of surgical procedures [126]. (Patches were applied several hours before anaesthesia in several of the studies demonstrating efficacy [5, 129, 135].) However, Koski and colleagues failed to show efficacy of trans dermal hyoscine applied on the evening before surgery compared with placebo [75]. Unfortunately, premedication (promethazine or flunitrazepam), postoperative analgesia (buprenorphine i.m. or sub lingually, or oxycodone) and type of surgery (gynaecological, upper abdominal, thyroid, breast and others) and dose of intraoperative fentanyl were not controlled. Duration of anaesthesia varied widely also (20-337 min). A significant incidence of dry mouth was reported by some authors [5,63,75,76, 135] but not by others [126, 129]. Visual disturbances were relatively common also [5,75, 126, 129]. Drowsiness was reported only by Bailey and colleagues in patients undergoing day-case laparoscopies [5]. In fact, the incidences of dry mouth, somnolence, amblyopia, mydriasis and dizziness were all increased significantly in this study. However, these effects, although significant statistically, were not significant clinically as the patients receiving transdermal hyoscine were discharged significantly earlier compared with the placebo group (mean (SD) 4.0 (1.3) h vs 4.5 (1.5) h, respectively; P < 0.05). This may have resulted from the significant improvement in the incidence of PONY in the trans dermal hyoscine group. Hyoscine-induced psychosis has been reported during administration of transdermal hyoscine, particularly in elderly patients [86]. However, it has occurred in a lO-yr-old child [31]. These data suggest that trans dermal hyoscine has at least some efficacy in the prevention of PONY, particularly if applied several hours before surgery. Although relatively frequent, side effects are likely to be minimal and insignificant compared with other antiemetics.


BRITISH JOURNAL OF ANAESTHESIA TABLE VIII. Studies investigating the effect of cyclizine on PONV (% reduction in incidence of PONV compared with placebo). Min. gynae = Minor gynaecological. Before = Given as premedication or at induction of anaesthesia; ? = not stated. *N 0 statistics available; ns = no significant effect




(38) (94)

1955 1956

Various Various

(127) [11)

1956 1959

Various Various

[Ill) [109)

1959 1960

Various Min. gynae.

Dose (mg) 50 50

50 100 50 50


After a visit to mainland China, Dundee observed a woman in an antenatal clinic being treated for morning sickness by acupuncture [45]. This experience inspired several studies investigating its effect on PONY in Belfast, although attention was drawn to the efficacy of acupuncture at the same time by Fry [55]. Acupuncture for nausea is performed on the P6 or Neiguan point. This is situated between the tendons of the flexor carpi radialis and palmaris longus, 2 Chinese inches from the distal wrist skin crease. A Chinese inch is the width of the interphalangeal joint of the thumb [45]. Several studies have demonstrated efficacy of acupuncture in the prevention of PONY [43,45, 57, 64]. After nalbuphine premedication and i.v. methohexitone anaesthesia for minor gynaecological sur-

S.c. I.m. "Parenteral" ? ? I.m. I.m.



End Before and 4-hour1y End ? ? End Before

24 44 ns 39* 39* ns 77*

gery, preoperative acupuncture reduced PONY significantly in the first 6 h after surgery compared with controls (32 % vs 82 %) [45]. The incidence of PONY after acupuncture applied away from the P6 point was 90 %. The extraordinary high incidence of PONY by modern standards can presumably be explained by the use of agents such as nalbuphine and methohexitone, but the effect of acupuncture in these circumstances is clear. These data originate from 317 patients; the result of pooling data from previous studies. Such a study compared the effect of acupuncture with cyclizine 50 mg on PONY in patients undergoing identical anaesthesia and surgery [57]. Both manual and electrical acupuncture at the P6 point reduced the incidence of PONY significantly and had similar efficacy to cyclizine. U sing a more conventional anaesthetic technique, Ho and colleagues [64] demonstrated a beneficial effect of acupuncture in patients undergoing gynaecological laparoscopies. The incidence of PONY during the first 3 h after surgery was 44 % in the control group, 12 % after electroacupuncture and 12 % after prochlorperazine premedication. Stimulation of the P6 point by transcutaneous electrical stimulation was less effective (36 %). However, other workers have failed to demonstrate efficacy [81,134,138]. In a well designed study, Lewis and colleagues [81] showed no effect in children undergoing strabismus surgery. However, acupuncture was administered by elasticated wrist bands (" Sea Bands") and not by conventional acupuncture techniques. Failure was reported also in children after tonsillectomy [138] but in this study acupuncture was administered during anaesthesia. Acupuncture may not be effective under these circumstances. The use of acupuncture in the prevention of PONY has stimulated considerable debate but it seems clear that it is effective in some circumstances and, compared with conventional pharmacological therapies, is free from side effects. Further evaluation is beyond the scope of this article and the reader is referred to the review by Dundee and McMillan [46]. COMPARATIVE STUDIES

An appreciation of the relative efficacies of antiemetic drugs used in the management of PONY is important, particularly when side effects can be significant. The literature is not of great help in this regard but it is possible to draw some conclusions.

Downloaded from at University of Bath Library & Learning Centre on July 11, 2015

are largely the result of this antimuscarinic activity [56]. Surprisingly, little is known of the pharmacokinetics of cyclizine. The efficacy of cyclizine in the prevention of PONY was investigated 30 years ago (table VIII). Most of these studies were poorly controlled, involved a variety of anaesthetic techniques and operations, and statistical analysis was sometimes lacking. However, patient numbers were large and some useful information can be extracted from them. Most workers demonstrated efficacy [11, 38, 94, 109]. Cyclizine has been shown to be effective in the treatment of established PONY. In a placebocontrolled, double-blind study, Bonica and colleagues [18] relieved PONY completely after rectal administration of cyclizine in 50.8 % of patients with severe symptoms (placebo 7.6 %). Efficacy was demonstrated also in patients with moderate or mild symptoms. In fact, cyclizine was associated with complete or partial relief in 93 % of all patients (placebo 60 %). Extrapyramidal side effects are not associated with cyclizine. Sedation and dry mouth are a consequence of its antimuscarinic action but the importance of these side effects in the perioperative period is not know with any certainty. Moore and colleagues [94] described "occasional drowsiness" and Bellville, Bross and Howland [11] showed a slight tendency to delayed recovery from anaesthesia. In light of these early studies and relative lack of side effects, perhaps the place of cyclizine in modern anaesthetic practice should be re-appraised.

Reduction Route


CURRENT MANAGEMENT OF PONY TABLE IX. Comparisons of metoclopramide (M) and droperidol (D). Orthop. = Orthopaedic; Min. gynae. = minor gynaecological; Maj. gynae. = major gynaecological. *Not statistically significant (but see text); ns = no significant difference. NR = Not recorded

Dose (mg) Reference






Recovery from anaesthesia

(73) (32) (69) (89) (101)

1979 1984 1986 1986 1989

Female orthop. Min. gynae. Female orthop. Maj. gynae. Min. gynae.

10 10 20 10 5-10

1.25 1.25 1.25 2.5 Various

D>M D>M* D>M D>M D>M

D>M D>M NR ns ns

Approximate pharmacokinetic values for drugs used in the prevention and treatment of PONV. T ~ = Elimination half-life; Vd = volume of distribution; Clearance (el) = total body clearance. * Variable first-pass metabolIsm. NA = Not available


Drug Metoclopramide Prochlorperazine Perphenazine Droperidol

4 7 9 2

Hyoscine Atropine

2-4 2-4

Vd (litre kg-I)

Cl (ml min-I kg-I)




2.2 21 20 1.6

10 2.7 1.8 10

Good* Poor Poor Good

Good NA Good Good

15 6

Fair Good

Good Variable

[8,28,62, 112) (125) (60) [35,52,80, Janssen Pharmaceuticals) [98, 105, 107) (68)

1.2 1.3

Metoclopramide and droperidol It has been suggested previously in this review that metoclopramide has not shown reliable efficacy; comparisons of metoclopramide and droperidol are consistent with this. Several recent well controlled comparative studies are available [32,69,73,89, 101] and are summarized in table IX. The efficacy of droperidol in four of five or these studies was significantly greater than metoclopramide. Cohen, Woods and Wyner [32] failed to demonstrate statistical significance but there was a definite trend (nausea: placebo 60 %; metoclopramide 64 % ; droperidol41 %) and the power of the study was small (30 patients in each group). However, these data suggest that improved efficacy may be at the expense of prolonged recovery from anaesthesia (table IX). Statistically significant prolongation of recovery was reported in two of the four studies which measured this variable. Other comparisons There are only a few studies which have compared other combinations of antiemetics and these are over 20 years old. Metoclopramide and perphenazine were compared by Handley [59], and Lind and Breivik [82]. Metoclopramide 10 mg or perphenazine 5 mg was given i.m. at the end of surgery in patients undergoing minor gynaecological surgery [59]. Both drugs were far superior to placebo but there was no difference between them in efficacy (perphenazine 96 % no PONV; metoclopramide 92 %; placebo 60 %). However, Lind and Breivik [82] found metoclopramide 10 mg more effective than perphenazine 5 mg in patients undergoing gynaecological laparoscopies. Treatment was given at the end of operation and both mean nausea scores (1.7 vs 3.4) and incidence of retching and vomiting (12.6 % vs 26.9 %) were reduced in the metoclopramide

group. However, recovery time was significantly greater in the metoclopramide group (22 min vs 16 min). No firm conclusions can be based on these two early studies and more work is needed if the relative efficacy of metoclopramide and perphenazine is to be defined. One of the first investigations into the efficacy of metoclopramide in PONY compared metoclopramide 20 mg and prochlorperazine 10 mg given i.m. at the end of surgery [128]. Both treatments were superior to placebo and metoclopramide was significantly better than prochlorperazine (PONV: placebo 38 %; prochlorperazine 19 %; metoclopramide 7 %). Recovery times were not affected and there was no difference in the incidence of side effects. The efficacy ofprochlorperazine 12.5 mg, cyclizine 50 mg and perphenazine 5 mg were compared by Robbie in 1959 [111]. This study was not well controlled but involved over 500 patients. The incidence of PONY in the "control" group was 19 %, and after perphenazine 7 %, prochlorperazine 11 % and cyclizine 13 %. Mean recovery times were increased in the perphenazine and cyclizine groups (22.3 min and 24.5 min, respectively compared with control (18.5 min)). The statistical significance of these data is difficult to assess. The relative efficacies of droperidol 5 mg and prochlorperazine 10 mg in the treatment of established PONY was assessed by Loeser and colleagues in 1979 [83]. Both were more effective than placebo. However, onset of action of droperidol tended to be later than prochlorperazine but duration of action was longer. CONCLUSION

The literature enables some conclusions to be made regarding current treatment of PONY. Metoclopramide is a popular antiemetic but its performance

Downloaded from at University of Bath Library & Learning Centre on July 11, 2015


T! (h)




1. Abramowitz MD, Oh TH, Epstein GS, Turriman UE, Friendly DS. The antiemetic effect of droperidol following outpatient strabismus surgery in children. Anesthesiology 1983; 59: 579-583. 2. Albert SN, Coakley CS. The use of chlorpromazine to control postanaesthetic vomiting. Current Researches in Anesthesia and Analgesia 1954; 33: 285-288. 3. Assaf RAE, Clarke RSI, Dundee JW, Samuel 10. Studies of drugs given before anaesthesia XXIV: Metoclopramide with morphine and pethidine. British Journal of Anaesthesia 1974; 46: 514-519. 4. Association of the British Pharmaceutical Industry. Data Sheet Compendium 1991-92. London: Datapharm Publications Limited, 1991; 148. 5. Bailey PL, Steisand JB, Pace NL, Bubbers SJM, East KA, Mulder S, Stanley TH. Transdermal scopolamine reduces nausea and vomiting after outpatient laparoscopy. Anesthesiology 1990; 72: 977-980.

6. Baldessarini RJ. Drugs and the treatment of psychiatric disorders. In: Gilman AG, Rail TW, Nies AS, Tayler P, eds. Goodman and Gilman's The Pharmacological Basis of Therapeutics. New York: Pergamon Press, 1990; 386. 7. Barnes TRE, Braude WM, Hill DJ. Acute akathisia after oral droperidol and metoclopramide preoperative medication. Lancet 1982; 1: 48-49. 8. Bateman DN, Kahn C, Mashiter K, Davies DS. Pharmacokinetic and concentration-effect studies with intravenous metoclopramide. British Journal of Clinical Pharmacology 1978; 6: 401--407. 9. Bateman DN, Rawlins MD, Simpson JM. Extrapyramidal reactions with metoclopramide. British Medical Journal 1985 ; 291: 930-932. 10. Bateman DN, Rawlins MD, Simpson JM. Extrapyramidal reactions to prochlorperazine and haloperidol in the United Kingdom. Quarterly Journal of Medicine 1986; 230: 549-556. 11. Bellville JW, Bross IDI, Howland WS. The antiemetic efficacy of cyclizine (Marezine) and triflupromazine (Vesprin). Anesthesiology 1959; 20: 761-766. 12. Bellville JW, Bross IDI, Howland WS. Postoperative nausea and vomiting IV: Factors related to postoperative nausea and vomiting. Anesthesiology 1960; 21: 186-193. 13. Berghem L, Bergman U, Schildt B, Sorbo B. Plasma atropine concentrations determined by radioimmunoassay after single dose i. v. and i.m. adminstration. British Journal of Anaesthesia 1980; 52: 597-601. 14. Berk BZ. Reaction to prochlorperazine? Lancet 1969; 1: 776. 15. Bevacqua BK. Supraventricular tachycardia associated with postpartum metoclopramide administration. Anesthesiology 1988; 68: 124-125. 16. Blanc VF, Ruest P, Milot J, Jacob J-L, Tang A. Antiemetic prophylaxis with promethazine or droperidol in paediatric outpatient strabismus surgery. Canadian Journal of Anaesthesia 1991; 38: 53-60. 17. Bone ME, Wilkinson DI, Young JR, Charlton S. Ginger root-a new antiemetic; The effect of ginger root on postoperative nausea and vomiting after major gynaecological surgery. Anaesthesia 1990; 45: 669-671. 18. Bonica n, Crepps W, Monk B, Bennett B. Postanesthetic nausea, retching and vomiting; Evaluation of cyclizine (Marezine) suppositories for treatment. Anesthesiology 1958; 19: 532-540. 19. Boulton TB. Oral chlorpromazine hydrochloride; A clinical trial in thoracic surgery. Anaesthesia 1955; 10: 233-246. 20. Braly BB, Moore DC. The use of intramuscular perphenazine to control postoperative vomiting. American Journal of Surgery 1961; 102: 120--123. 21. Broadman LM, Ceruzzi W, Patane PS, Hannallah RS, Ruttimann U, Friendly D. Metoclopramide reduces the incidence of vomiting following strabismus surgery in children. Anesthesiology 1990; 77: 245-248. 22. Brogden RN, Carmine AA, Heel RC, Speight TM, Avery GS. Domperidone. A review of its pharmacological activity, pharmacokinetics and therapeutic efficacy in the symptomatic treatment of chronic dyspepsia and as an antiemetic. Drugs 1982; 24: 360--400. 23. Burtles R, Peckett BW. Postoperative vomiting; Some factors affecting its incidence. British Journal of Anaesthesia 1957; 29: 114-123. 24. Caldwell C, Rains G, McKiterick K. An unusual reaction to preoperative metoclopramide. Anesthesiology 1987; 67 : 854-855. 25. Cameron HA, Reyntjens AI, Lake-Bakaar G. Cardiac arrest after treatment with intravenous domperidone. British Medical Journal 1985; 290: 160. 26. Caplin D, Smith C. A comparison of the anti-emetic effects of dimenhydrinate, promethazine hydrochloride and chlorpromazine following anaesthesia. Canadian Anaesthetists Society Journal 1955; 2: 193-197. 27. Chestnut DH, Vandewalker GE, Owen CL, Bates IN, Choi WW. Administration of metoclopramide for prevention of nausea and vomiting during epidural anesthesia for elective cesarian section. Anesthesiology 1987; 66: 563-566. 28. Citron ML, Reynolds JR, Kaira I, Kay BG, Nathan KA, Jaffe ND, Miller FR. Pharmacokinetic comparison of intranasal, oral and intramuscular metoclopramide in healthy volunteers. Cancer Treatment Reports 1987; 71: 317-319.

Downloaded from at University of Bath Library & Learning Centre on July 11, 2015

in well controlled clinical trials is disappointing. There seems to be no indication for i.v. administration of metoclopramide at induction of anaesthesia for the prevention ofPONV. The literature indicates that droperidol is more effective than metoclopramide. Chlorpromazine and perphenazine are effective also, but modern well designed studies confirming this would be welcome. The limited data available on cyclizine indicate efficacy and it would be worthwhile investigating this drug further. Transdermal hyoscine has been proven to be of benefit in several studies and perhaps its more widespread use should be encouraged in order to ascertain its true role in the prevention of PONY. Extrapyramidal reactions are uncommon but extremely unpleasant. However, the less spectacular problem of agitation and apprehension noted in some studies is likely to be more frequent and this should be investigated further. Sedation is a frequent finding, but apart from day-case surgery, this is not likely to be a significant problem in most patients. Despite these and other side effects, it should be remembered that many millions of patients have been treated safely with these drugs. However, it is clear that, despite being better than placebo, the efficacy of currently available antiemetics is often poor. Many patients continue to experience severe PONY. Two important factors contribute to this failure. There are many causes of PONY and antagonizing only dopaminergic or cholinergic receptors is not sufficient in many patients. Further research is needed in this area. The development of 5-HT 3 receptor antagonists is likely to be a considerable advance in the treatment of PONY. Antiemetics are often not administered effectively. An appreciation of the enormous variability in the pharmacokinetics of opioids has led to the development of drug delivery systems such as variable rate infusions and PCA. In contrast, there has been little interest in the pharmacokinetics of antiemetics and clearly this is an important consideration in many cases of therapeutic failure. Pharmacokinetics of these drugs are summarized in table X. Perhaps greater emphasis should be placed on the pharmacokinetic variability of these drugs in order to optimize delivery of antiemetic therapy in the postoperative period.


54. Friedman LS, Weinrauch LA, D'Elia JA. Metoclopramideinduced neuroleptic malignant syndrome. Archives of Internal Medicine 1987; 147: 1495. 55. Fry ENS. Acupressure and postoperative vomiting. Anaesthesia 1986; 41: 661-662. 56. Garrison Je. Histamine, bradykinin, 5-hydroxytryptamine and their antagonists. In: Gilman AG, Rail TW, Nies AS, Tayler P, eds. Goodman and Gilman's The Pharmacological Basis of Therapeutics. New York: Pergamon Press, 1990; 584. 57. Ghaly RG, Fitzpatrick KTJ, Dundee JW. Antiemetic studies with traditional Chinese acupuncture: A comparison of manual needling with electrical stimulation and commonly used emetics. Anaesthesia 1987; 42: 1108-1110. 58. Giaconne G, Bertetto 0, Calciati A. Two sudden deaths during prophylactic antiemetic treatment with high doses of domperidone and methylprednisolone. Lancet 1984; ii: 1336-1337. 59. Handley AI. Metoclopramide in the prevention of postoperative nausea and vomiting. British Journal of Clinical Practice 1967; 67: 460-462. 60. Hansen CE, Christensen TR, Elley 1, Hansen LB, KraghSorensen, Larsen NE, Naestoft 1, Hvidberg EF. Clinical pharmacokinetic studies of perphenazine. British Journal of Clinical Pharmacology 1976; 3: 915-923. 61. Hardy JF, Charest 1, Girouard G, Lepage Y. Nausea and vomiting after strabismus surgery in preschool children. Canadian Anaesthetists Society Journal 1986; 33: 57-62. 62. Harrington RA, Hamilton CW, Brogden RN, Linkewich JA, Romankiewicz JA, Heel Re. Metoclopramide: An updated review of its pharmacological properties and clinical use. Drugs 1983; 25: 451-494. 63. Harris SN, Sevarino FB, Sinatra RS, Preble L, O'Connor TZ, Silverman D. Nausea prophylaxis using trans dermal scopolamine in the setting of patient-controlled analgesia. Obstetrics and Gynecology 1991; 4: 673-677. 64. Ho RT, Jawan B, Fung ST, Cheung JK, Lee JH. Electroacupuncture and postoperative emesis. Anaesthesia 1989; 45 : 327-329. 65. Howat DDC. Anti-emetic drugs in anaesthesia; a double blind trial of two phenothiazine derivatives. Anaesthesia 1960; 15: 289-297. 66. Hudson SA, Barnett DB. Drugs affecting the autonomic nervous system. In: Aitkenhead AA, Smith G, eds. Textbook of Anaesthesia. Edinburgh: Churchill Livingstone, 1990; 242. 67. Joss RA, Goldhirsch A, Brunner KW, Galeazzi RL. Sudden death in cancer patient on high-dose domperidone. Lancet 1982; i: 1019. 68. Kanto 1, Klotz U. Pharmacokinetic implications for the clinical use of atropine, scopolamine and glycopyrrolate. Acta Anaesthesiologica Scandinavica 1988; 32: 69-78. 69. Kauste A, Tuominen M, Heikkinen H, Gordin A, Korttila K. Droperidol, alizapride and metoclopramide in the prevention and treatment of postoperative emetic sequelae. European Journal of Anaesthesiology 1986; 3: 1-9. 70. Kenny GNC, Oates JDL, Leeser 1, Rowbotham D1, Lip H, Rust M, Saur P, Onsrud M, Haigh CG. Efficacy of orally administered ondansetron in the prevention of postoperative nausea and vomiting: A dose-ranging study. British Journal of Anaesthesia 1992; 68: 464-468. 71. Kimerling II, Patel SR. Oculogyric crisis after phenothiazines. British Medical Journal 1967; 4: 554. 72. Knapp MR, Beecher HK. Postanesthetic nausea, vomiting and retching. Journal of the American Medical Association 1956; 160: 376-385. 73. Korttila K, Kauste A, Auvinen J. Comparison of domperidone, droperidol, and metoclopramide in the prevention and treatment of nausea and vomiting after balanced general anesthesia. Anesthesia and Analgesia 1979; 58: 396-400. 74. Korttila K, Kauste A, Touminen M, Salo H. Droperidol prevents and treats nausea and vomiting after enflurane anaesthesia. European Journal of Anaesthesiology 1985; 2: 379-385. 75. Koski EM1, Mattila MAK, Knapik D, Toivanen T, Ruusukallio H, Andersson P, Freudenthal Y. Double blind comparison of trans dermal hyoscine and placebo for the prevention of postoperative nausea. British Journal of Anaesthesia 1990; 64: 16-20. 76. Kotelko DM, Rottman RL, Wright WC, Stone II, Yamashiro AY, Rosenblatt RM. Transdermal scopolamine decreases

Downloaded from at University of Bath Library & Learning Centre on July 11, 2015

29. Clarke MM, Storrs JA. The prevention of postoperative vomiting after abortion: Metoclopramide. British Journal of Anaesthesia 1969; 41: 890-893. 30. Clarke RS1, Dundee JW, Love WJ. Studies of drugs given before anaesthesia VIII: Morphine 10 mg alone and with atropine or hyoscine. British Journal of Anaesthesia 1965; 37: 772-777. 31. Clissold SP, Heel RC. Transdermal hyoscine (Scopolamine). A preliminary review of its pharmacodynamic properties and therapeutic efficacy. Drugs 1985; 29: 189-207. 32. Cohen SE, Woods WA, Wyner J. Anti-emetic efficacy of droperidol and metoclopramide. Anesthesiology 1984; 60: 67-69. 33. Cooke RD, Comyn D 1, Ball RW. Prevention of postoperative nausea and vomiting by domperidone. A double-blind randomised study using domperidone, metoclopramide and a placebo. South African Medical Journal 1979; 56: 827-829. 34. Cramb R, Fargas-Babjak A, Hirano G. Intraoperative prochlorperazine for prevention of postoperative nausea and vomiting. Canadian Journal of Anaesthesia 1989; 36: 565-567. 35. Cressman WA, Plostnieks 1, Johnson PC. Absorption, metabolism and excretion of droperidol by human subjects following intramuscular and intravenous administration. Anesthesiology 1973; 38: 363-369. 36. Cronin CM, Sallan SE, Wolfe L. Transdermal scopolamine in motion sickness. Pharmacotherapy 1982; 2: 29-31. 37. Davies DM. Treatment of drug-induced dyskinesias. Lancet 1970; 1: 567-568. 38. Dent S1, Ramachandra V, Stephen CR. Postoperative vomiting: Incidence, analysis, and therapeutic measures in 3,000 patients. Anesthesiology 1955; 16: 564-572. 39. Diamond M1, Keeri-Szanto M. Reduction of postoperative vomitmg by preoperative administration of oral metoclopramide. Canadian Anaesthetists Society Journal 1980; 27: 36-39. 40. Dobkin AB. Perphenazine in clinical anaesthesia. Canadian Anaesthetists Society Journal 1959; 6: 341-346. 41. Dobkin AB, Evers W, Israel JS. Double-blind evaluation of metoclopramide (NK 745, Sinemet), trimethobenzamide (Tigan), and a placebo as postanaesthetic anti-emetics following methoxyflurane anaesthesia. Canadian Anaesthetists Society Journal 1968; 15: 80-91. 42. Dryberg V, Johansen SH. Pre-anaesthetic medication with chlorpromazine. Acta Anaesthesiologica Scandinavica 1958; 2: 133-147. 43. Dundee JW, Chestnutt WN, Ghaly RG, Lynas AGA. Traditional Chinese acupuncture: a potentially useful antiemetic. British Medical Journal 1986; 293: 583-584. 44. Dundee JW, Clarke RSJ. The premedicant and anti-emetic action of metoclopramide. Postgraduate Medical Journal 1973; (Supp!.): 34-37. 45. Dundee JW, Ghaly RG, Bill KM, Chestnutt WN, Fitzpatrick KTJ, Lynas AGA. Effect of stimulation of the P6 antiemetic point on postoperative nausea and vomiting. British Journal of Anaesthesia 1989; 63: 612-618. 46. Dundee JW, McMillan CM. Positive evidence for P6 acupuncture anti emesis. Postgraduate Medical Journal 1991; 67: 417-422. 47. Dundee JW, Moore 1, Clarke RSJ. Studies of drugs given before anaesthesia V: Pethidine 100 mg alone and with atropine or hyoscine. British Journal of Anaesthesia 1964: 36: 703-710. 48. Duncum BM. The Development of Inhalational Anaesthesia. London: Oxford University Press, 1947; 391. 49. Dupre L1, Stieglitz P. Extrapyramidal syndromes after premedication with droperidol in children. British Journal of Anaesthesia 1980; 52: 831-833. 50. Ellis FR, Spence AA. Clinical trials of metoclopramide (Maxolon) as an antiemetic in anaesthesia. Anaesthesia 1970; 25: 368-371. 51. Ferguson RH. The use of olive oil to prevent or relieve postanesthetic vomiting. New York Medical Journal 1912; 95: 1395-1361. 52. Fischler M, Bonnet F, Trang H, Jacob L, Levron JC, Flaisler B, Vourc'h G. The pharmacokinetics of droperidol in anesthetized patients. Anesthesiology 1986; 64: 486-489. 53. Fozard JR. Neuronal 5-HT receptors in the periphery. Neuropharmacology 1984: 23; 1473-1486.



99. O'Donovan N, Shaw J. Nausea and vomiting in day-case dental surgery. Anaesthesia 1984; 39: 1172-1176. 100. Osborne RJ, Slemn ML, Hunter RW, Hamer J. Cardiotoxicity of intravenous domperidone. Lancet 1985; ii: 385. 101. Pandit SJ, Kothary SP, Pandit UA, Randel G, Levy L. Dose-response study of droperidol and metoclopramide as antiemetics for outpatient anesthesia. Anesthesia and Analgesia 1989; 68: 798-802. 102. Park GR. Hypotension following metoclopramide administration during hypotensive anaesthesia for intracranial aneurysm. British Journal of Anaesthesia 1978; 50: 12681269. 103. Patton CM, Moon MR, Dannemiller FJ. The prophylactic antiemetic effect of droperidol. Anesthesia and Analgesia 1974; 53: 361-364. 104. Pegg MS. Hypotension following metoclopramide injection. Anaesthesia 1980; 35: 614-616. 105. Pihlajamaki KK, Kanto JH, Oksman-Caldentey K-M. Pharmacokinetics and clinical effects of scopolamine in caesarean section patients. Acta Pharmacology et Toxicology 1991; 59: 259-262. 106. Poner J, Jick H. Drug-induced anaphylaxis, convulsions, deafness, and extrapyramidal symptoms. Lancet 1977; 1: 587-588. 107. Putcha L, Cintron, Tsui J, Vanderploeg JM, Kramer WG. Pharmacokinetics and oral bioavailability of scopolamine in normal subjects. Pharmaceutical Research 1989; 6: 481-485. 108. Ramsden PD, Froggatt DL. Idiosyncratic responses to phenothiazines. British Medical Journal 1972; 1: 246. 109. Riding JE. Postoperative vomiting. Proceedings of the Royal Society of Medicine: Section of Anaesthetics 1960; 53: 671-677. 110. Rita L, Goodarzi M, Seleny F. Effect of low dose droperidol on postoperative vomiting in children. Canadian Journal of Anaesthesia 1981; 28: 259-262. Ill. Robbie DS. Postanaesthetic vomiting and anti-emetic drugs. Anaesthesia 1959; 14: 349-354. 112. Ross-Lee LM, Hooper WD, Bochner F. Single-dose pharmacokinetics of metoclopramide. European Journal of Clinical Pharmacology 1981; 20; 465-471. 113. Roussak JB, Carey P. Cardiac arrest after treatment with intravenous domperidone. British Medical Journal 1984; 289: 1579. 114. Russell D, Kenny GNC. 5HT3 antagonists in postoperative nausea and vomiting. British Journal of Anaesthesia 1992; 69 (Suppl. 1): 63S-68S. 115. Santos A, Datta S. Prophylactic use of droperidol for control of nausea and vomiting during spinal anesthesia for cesarean section. Anesthesia and Analgesia 1984: 63: 85-87. 116. Scheller MS, Sears KL. Postoperative neurologic dysfunction associated with preoperative administration of metoclopramide. Anesthesia and Analgesia 1987; 66: 274-276. 117. Scurr CF, Robbie DS. Trials of perphenazine in the prevention of postoperative vomiting. British Medical Journal 1958; 1: 922-923. 118. Semple P, Madej TH, Wheatley RG, Jackson UB, Stevens J. Transdermal hyoscine with patient-controlled analgesia. Anaesthesia 1992; 47: 399-401. 119. Shah ZP, Wilson J. An evaluation of metoclopramide (Maxolon) as an antiemetic in minor gynaecological surgery. British Journal of Anaesthesia 1972; 44: 865-868. 120. Shaklai M, Pinkhas J, De Vries A. Metoclopramide and cardiac arrhythmia. British Medical Journal 1974; 1: 385. 121. Shaw J, Urquhart J. Programmed, systemic drug delivery by the transdermal route. Pharmacotherapy 1982; 2: 29-31. 122. Smith GFR. Post-operative vomiting. British Journal of Anaesthesia 1934; 11: 132-139. 123. Smith WD, Tobias MA. Tetany, tetanus or drug reaction? British Journal of Anaesthesia 1976; 48: 703-705. 124. Spelina KR, Gerber HR, Pagels IL. Nausea and vomiting during spinal anaesthesia; Effect of metoclopramide and domperidone: a double blind trial. Anaesthesia 1984; 39: 132-137. 125. Taylor WB, Bateman DN. Preliminary studies of the pharmacokinetics and pharmacodynamics of prochlorperazine in healthy volunteers. British Journal of Clinical Pharmacology 1987; 23: 137-142. 126. Tigerstedt I, Salmela L, Aromaa U. Double-blind com-

Downloaded from at University of Bath Library & Learning Centre on July 11, 2015

nausea and vomiting following cesarean section in patients receiving epidural morphine. Anesthesiology 1989; 71: 675-678. 77. Kvisselgaard N. Chlorpromazine and chlorcyclizine in the prevention of postoperative nausea and vomiting. Acta Anaesthesiologica Scandinavica 1958; 2: 153-162. 78. Larsson S, Jonmarker C. Postoperative emesis after pediatric strabismus surgery: the effect of dixyrazine compared to droperidol. Acta Anaesthesiologica Scandinavica 1990; 34: 227-230. 79. Layfield DJ, Walker AKY. Premedication for children with oral trimeprazine and droperidol. Anaesthesia 1984; 39: 32-34. 80. Lehmann K, Van Peer A, Ikonomakis M, Gasparini R, Heykants J. Pharmacokinetics of droperidol in surgical patients under different conditions of anaesthesia. British Journal of Anaesthesia 1988; 61: 297-301. 81. Lewis IH, Pryn SJ, Reynolds PI, Pandit UA, Wilton NCT. Effect ofP6 acupressure on postoperative vomiting in children undergoing outpatient strabismus correction. British Journal of Anaesthesia 1991; 67: 73-78. 82. Lind B, Breivik H. Metoclopramide and perphenazine in the prevention of postoperative nausea and vomiting; A double blind comparison. British Journal of Anaesthesia 1970; 42: 614-617. 83. Loeser EA, Bennett G, Stanley TH, Machin R. Comparison of droperidol, haloperidol and prochlorperazine as postoperative anti-emetics. Canadian Anaesthetists Society Journal 1979; 26: 125-127. 84. Loper KA, Ready BL, Doman BH. Prophylactic trans dermal scopolamine patches reduce nausea in postoperative patients receiving epidural morphine. Anesthesia and Analgesia 1989; 68: 144-146. 85. McCallum RW, Chakrapani P, Campoli-Richards DM, Goa KL. Cisapride. A preliminary review of its pharmacodynamic and pharmacokinetic propenies, and therapeutic use as a prokinetic agent in gastrointestinal motility disorders. Drugs 1988; 36: 652-681. 86. MacEwan GW, Remick RA, Noone JA. Psychosis due to transdermally administered scopolamine. Canadian Medical Association Journal 1985; 133: 431-433. 87. McGarry JM. A double-blind comparison of the anti-emetic effect during labour of metoclopramide and perphenazine. British Journal of Anaesthesia 1971; 43: 613-615. 88. Madej TH. Domperidone--an acute dystonic reaction. Anaesthesia 1985; 40: 202. 89. Madej TH, Simpson KH. Comparison of the use of domperidone, droperidol and metoclopramide in the prevention of nausea and vomiting following major gynaecological surgery. British Journal of Anaesthesia 1986; 58: 884-887. 90. Melnick B, Sawyer R, Karambelkar D, Phitayakorn P, Lim Uy NT, Patel R. Delayed side effects of droperidol after ambulatory general anesthesia. Anesthesia and Analgesia 1989; 69: 748-751. 91. Melnick BM. Extrapyramidal reactions to low-dose droperidol. Anesthesiology 1988; 69: 424-426. 92. Miller CD. Silent regurgitation in day case gynaecological patients. Anaesthesia 1988; 43: 321-323. 93. Montgomery RD, Sutherland VL. Acute dystonic reaction to perphenazine. British Medical Journal 1959; 1: 215. 94. Moore DC, Bridenbaugh LD, Piccioni VF, Adams PA, Lindstrom CA. Control of postoperative vomiting with marezine: A double blind study. Anesthesiology 1956; 17: 690-695. 95. Moore DC, Bridenbaugh LD, Van Ackeren EG, Cole FV. Control of postoperative vomiting with perphenazine (Trilafon): A double blind study. Anesthesiology 1958; 19: 72-74. 96. Morrison JD, Clarke RSJ, Dundee JW. Studies of drugs given before anaesthesia XXI: droperidol. British Journal of Anaesthesia 1970; 42: 730-735. 97. Mortensen PT. Droperidol (Dehydrobenzperidol): Postoperative anti-emetic effect when given intravenously to gynaecological patients. Acta Anaesthesiologica Scandinavica 1982; 26: 48-52. 98. Muir C, Metcalfe R. A comparison of plasma levels of hyoscine after oral and trans dermal administration. Journal of Pharmaceutical and Biomedical Analysis 1983; 1: 363-367.













137. 138.

Oral premedication in children. Anaesthesia and Intensive Care 1987; 15: 151-157. Waldmann CS, Verghese C, Short SM, Goldhill DR, Evans SJW. The evaluation of domperidone and metoclopramide as antiemetics in day care abortion patients. British Journal of Clinical Pharmacology 1985; 19: 307-310. Weightman WM, Zacharias M, Herbison P. Traditional Chinese acupuncture as an antiemetic. British Medical Journal 1987; 295: 1379-1380. Wilkinson AR, Frampton CMA, Glover PW, Davis FM. Preoperative trans dermal hyoscine for the prevention of postoperative nausea and vomiting. Anaesthesia and Intensive Care 1989; 17: 285-289. Winning TJ, Brock-Utne JG, Downing JW. Nausea and vomiting after anesthesia and minor surgery. Anesthesia and Analgesia 1977; 56: 674-677. Withington DE. Dysrhythmias following intravenous metoclopramide. Intensive Care Medicine 1981; 12: 378-379. Yentis SM, Bissonnette B. P6 acupuncture and postoperative vomiting after tonsillectomy in children. British Journal of Anaesthesia 1991; 67: 779-780.

Downloaded from at University of Bath Library & Learning Centre on July 11, 2015


parison of trans dermal scopolamine, droperidol and placebo against postoperative nausea and vomiting. Acta Anaesthesiologica Scandinavica 1988; 32: 454-457. Tillman WW, Wise FG, Crawford OB. Evaluation of Marezine and Bonamine in lowering the incidence of postoperative nausea and vomiting. Anesthesiology 1956; 17: 112-115. Tornetta FJ. Clinical studies with the new anti-emetic, metoclopramide. Anesthesia and Analgesia 1969; 48 : 198-204. Uppington J, Dunnet J, Blogg CEo Transdermal hyoscine and postoperative nausea and vomiting. Anaesthesia 1986; 41: 16-20. Valanne J, Korttila K. Effect ofa small dose of droperidol on nausea, vomiting and recovery after outpatient enflurane anaesthesia. Acta Anaesthesiologica Scandinavica 1985; 29: 359-362. Van Den Berg AA, Lambourne A, Yazji NS, Laghari NA. Vomiting after ophthalmic surgery; effects of intraoperative antiemetics and postoperative oral fluid restriction. Anaesthesia 1987; 42: 270-276. Van Der Walt JH, Nicholls B, Bentley M, Tomkins DP.

Current management of postoperative nausea and vomiting.

British Journal of Anaesthesia 1992; 69 (Suppl. 1): 46S-59S CURRENT MANAGEMENT OF POSTOPERATIVE NAUSEA AND VOMITING D. J. ROWBOTHAM (Br. J. Anaesth...
2MB Sizes 0 Downloads 0 Views