British Journal of Anaesthesia 1990; 64: 450-^152
EFFECT OF I.V. METOCLOPRAMIDE ON GASTRIC
EMPTYING AFTER OPIOID PREMEDICATION
M. J. McNEILL, E. T. HO AND G. N. C. KENNY
The aim of this study was to investigate the
SUMMARY effects of i.v. metoclopramide on the rate of
Metoclopramide was given i.m. or i.v. to patients gastric emptying in patients who had been given
who had been given an opioid premedication, an opioid premedication.
and the effects on gastric emptying assessed.
Forty patients were a/located randomly to one of
four treatment groups: group 1, oral diazepam
10 mg; group 2, i.m. morphine 10 mg; group 3,
i.m. morphine 10 mg and i.v. metoclopramide
10 mg; group 4, i.m. morphine 10 mg and i.m.
metoclopramide 10 mg. Gastric emptying was
estimated from the absorption of oral para-
cetamol. I.v. metoclopramide antagonized the
reduction in paracetamol absorption caused by
morphine, whereas i.m. metoclopramide did not.
This finding may be of importance in anaesthesia
for emergencies.
KEY WORDS
Gastrointestinal tract: gastric emptying, metoclopramide.
Analgesics: morphine.
The effects of opioids on gastric emptying have
been well documented [1]. Gastric emptying is
reduced in patients who have been given an opioid
premedication [2] and in mothers who have been
given opioids for analgesia during labour [3]. The
result of delayed gastric emptying is an increased
volume of gastric contents at induction of an-
aesthesia and a subsequent increased risk of
regurgitation and aspiration. Metoclopramide is
known to increase the rate of gastric emptying [4].
However, two previous studies have shown that
i.m. metoclopramide did not antagonize the effects
of opioids on gastric emptying [3, 5]. In contrast,
there is evidence that i.v. metoclopramide in-
creases the rate of gastric emptying in labouring
women who have been given pethidine [6]. There
is also evidence that the effectiveness of meto-
clopramide may depend on the route of admin-
istration [7, 8].
PATIENTS AND METHODS
We studied 40 patients, aged 18-65 yr, under-
going elective surgery. Approval of the local
Ethics Committee was obtained, and each patient
gave informed consent.
We excluded from the study: patients with
diabetes or with known gastric outlet obstruction;
those with previous gastric or upper gastroin-
testinal surgery; patients receiving drugs which
affect gastric emptying and those with gastro-
oesophageal reflux; possible pregnancy.
Patients were allocated randomly to receive one
of four premedications, at least 2 h before surgery.
Group I patients were given diazepam 10 mg
orally. Diazepam does not reduce gastric emp-
tying when given orally [9], i.m. [2] or i.v. [10].
This group acted as controls.
Group II patients were given morphine 10 mg
i.m.
Group III patients were given morphine 10 mg
i.m. and were also given metoclopramide 10 mg
i.v., 20 min later.
Group IV patients were given morphine 10 mg
i.m. and at the same time, by a separate injection
into the lateral aspect of the thigh, meto-
clopramide 10 mg i.m.
Gastric emptying was assessed indirectly by
absorption of oral paracetamol 1.5 g given 20 min
after the premedication [11]. As paracetamol is
not absorbed from the stomach but is absorbed
well from the small intestine, the rate of ab-
M. J. MCNEILL, F.F.A.R.C.S.; E. T. Ho, M.R.C.P., F.F.A.R.C.S.I.;
G. N. C. KENNY, B.SC. (HONS), MJ)., F.F.A.R.C.S.; Department
of Anaesthesia, Royal Infirmary, 84 Castle Street, Glasgow
G31 2ER. Accepted for Publication: September 22, 1989.
METOCLOPRAMIDE AND GASTRIC EMPTYING 451
sorption of paracetamol may be used as an indirect premedication in any of the groups. No patient
measurement of gastric emptying. Venous blood vomited before operation.
samples were taken at 15-min intervals for 90 min, Patients in group I, who received oral diazepam,
starting immediately before the paracetamol was had significantly greater plasma concentrations of
given. Plasma concentrations of paracetamol were paracetamol than those who received i.m. mor-
measured using high pressure liquid chromato- phine alone (group II) or those who received both
graphy [12]. i.m. morphine and i.m. metoclopramide (group
The rate of paracetamol absorption was esti- IV). The paracetamol concentrations in group
mated by: the area under the paracetamol III, who received both i.m. morphine and i.v.
concentration-time curve (AUC) at 45 and metoclopramide, were also significantly greater
90 min; mean plasma concentration of paracetamol than those in groups II and IV (table II). There
at each time interval; peak paracetamol concen- were no significant differences in paracetamol
tration; time taken to achieve that peak. concentrations between groups I and III.
Statistical analyses of these data were per- The AUC in group I at 90 min was significantly
formed using MANOVA (paracetamol concen- greater than the corresponding AUC in groups II
trations). Differences between groups were then and IV (table III). The AUC at 90 min in group
analysed by Student's t test with Bonferroni III was also significantly greater than the values in
correction; Student's t test (peak concentrations, groups II and IV. There were no significant
log AUC); chi-square (patient characteristics differences between the AUC at 45 min.
data); Kruskall-Wallis test (time to peak). The greatest peak concentrations of para-
P less than 5 % was taken as significant. cetamol were found in group I (table IV). These
did not differ significantly from the peak values in
group III, but were significantly greater than the
RESULTS
peak values in either group II or group IV. The
There were no statistical differences between peak concentrations of paracetamol in group III
groups in terms of age, sex or body weight (table were significantly greater than those in groups II
I). There were no side effects related to the and IV.
There was a tendency for the time to peak
TABLE I. Demographic data (mean (SD)) concentration of paracetamol to be shorter in
Sex (M/F) Age (yr) Weight (kg)
groups I and III; these differences were not
statistically significant.
Group I 6/4 35 (7.9) 63(10.1)
(n = 10)
Group II 5/5 36(16.1) 68(11.2) TABLE III. Area under the plasma paracetamol concentration-
(n = 10) lime curve (SEM) at 45 and 90 min. * P < 0.05 compared with
Group III 6/4 39(12.7) 68 (9.4) group I; f P < 0.05 compared with group III
(n = 10) AUC 45 AUC 90
Group IV 8/2 36 (10.9) 73(11.9) (ug ml"' min) (ug ml"1 min)
(n = 10)
Group I 471.9(110.6) 1184.9(140.5)
Group II 252.7 (90.6) 573.1 (159.6)*t
TABLE II. Mean (SEM) plasma concentrations of paracetamol Group III 639.2(110.1) 1302.7(180.4)
(jigml~l). *P<0.05 compared with group I; +P<0.05 Group IV 279.4(116.4) 630.2 (185.45)*f
compared with group III
Time (min)
TABLE IV. Peak (SD) plasma concentration of paracetamol and
0 15 30 45 60 75 90 time to peak (median and range). * P < 0.05 compared with
group /; t P < 0.05 compared with group III
Group I 0 11.7 12.6 14.4 15.5 16.4 16.7
(0) (4.1) (3.0) (3.1) (2.2) (1.8) (2.4) Peak concn Time of peak
Group II*t 0 4.4 8.9 7.1 7.7 6.8 6.7 (ug ml"1) (min)
(0) (1.9) (0.8) (2.4) (1.9) (1.6) (1.3)
Group III 0 17.8 16.6 16.5 15.0 14.0 14.0 Group I 26.09 (8.2) 37.5 (15-90)
(0) (4.9) (2.4) (2.4) (2.2) (1.6) (1.7) Group II 12.23 (11.6)*f 45(15-90)
Group IV*f 0 6.7 7.5 8.9 7.7 7.6 7.2 Group III 23.89 (12.2) 30(15-75)
(0) (4.1) (3.1) (2.7) (2.1) (1.6) (1.5) Group IV 13.22 (12.1)*t 45(15-90)
452
DISCUSSION
This study has confirmed that premedication with
i.m. morphine causes a significant decrease in
the absorption of paracetamol compared with
premedication with oral diazepam. We have
confirmed also Nimmo's original conclusion that
i.m. metoclopramide did not prevent a delay
in absorption of paracetamol [3]. We have
demonstrated, however, that i.v. metoclopramide
prevented the delay in paracetamol absorption
after opioid premedication. The route of
administration of metoclopramide may determine
its effectiveness, and Bateman has suggested that
the initial peak concentration achieved by an
i.v. injection may be necessary to achieve a
satisfactory clinical effect [7, 8].
This effect may be important in the patient with
a full stomach, treated with opioids before
emergency surgery. It should be considered also
in the obstetric patient who has received opioids
during labour and then requires emergency
Caesarean section under general anaesthesia [13].
The effect of metoclopramide on the lower
oesophageal sphincter is an additional indication
for its use before emergency surgery, when there
is a risk of regurgitation and aspiration.
The potential side effects of metoclopramide
have been well documented [4]. The incidence of
extrapyramidal side effects is approximately 1 %
when used in low dose [4]. The safety of
metoclopramide is confirmed by its use in doses of
up to 30 mg kg"1 for patients receiving cytotoxic
chemotherapy.
The role of cisapride in anaesthetic practice has
recently been reviewed [14]. I.m. cisapride may
antagonize the effects of opioids on gastric
emptying. However, a parenteral preparation of
this drug is not available at present.
In conclusion, we have shown that the effects of
opioid premedication on gastric emptying may be
antagonized by i.v. metoclopramide. The use of
i.v. metoclopramide should be considered in
BRITISH JOURNAL OF ANAESTHESIA
patients undergoing emergency surgery, even if
they have already received an opioid.
REFERENCES
1. Ninuno WS. Effect of anaesthesia on gastric raotility and
emptying. British Journal of Anaesthesia 1984; 56: 29-36.
2. Todd JG, Nimmo WS. Effect of premedication on drug
absorption and gastric emptying. British Journal of
Anaesthesia 1983; 55: 1189-1193.
3. Nimmo WS, Wilson J, Prescott LF. Narcotic analgesics
and delayed gastric emptying during labour. Lancet 1975;
1: 890-893.
4. Harrington RA, Hamilton CW, Brogde RN, Luchewick
JA, Romankiewicz JA, Heel RC. Metoclopramide. Drugs
1983; 25: 451-194.
5. Rowbotham DJ, Bamber PA, Nimmo WS. Comparison of
the effect of cisapride and metoclopramide on morphine-
induced delay in gastric emptying. British Journal of
Clinical Pharmacology 1988; 26: 741-746.
6. Murphy DF, Nally B, Gardiner J, Unwin A. Effect of
metoclopramide on gastric emptying before elective
and emergency Caesarean section. British Journal of
Anaesthesia 1985; 56: 1113-1116.
7. Bateman D N , Kahn C, Davies DS. Concentration-effect
studies with oral metoclopramide. British Journal of
Clinical Pharmacology 1979; 8: 179-182.
8. Bateman D N , Kahn C, Mashiter K, Davies DS. Pharma-
cokinetics and concentration-effect studies of intravenous
metoclopramide. British Journal of Clinical Pharmacology
1978; 6: 401-W7.
9. Schurizek BA, Kraglund K, Andreasen F, Jensen LV,
Juhl B. Gastrointestinal motility and gastric pH and
emptying following ingestion of diazepam. British Journal
of Anaesthesia 1988; 61: 712-719.
10. Adelhoj B, Pctring OU, Brynnum J, Jensen BN, Ibsen M,
Poulson HE. Effect of diazepam on gastric emptying and
drug absorption in man. British Journal of Anaesthesia
1985; 57: 1107-1109.
11. Heading RC, Nimmo J, Prescott LF, Tothill P.
Dependence of paracetamol absorption on the rate of
gastric emptying. British Journal of Pharmacology 1973;
47: 415-421.
12. Howie D, Adrianssens PI, Prescott LF. Paracetamol
absorption following overdosage: application of high
performance liquid chromatography. Journal of Pharma-
ceutical Pharmacology 1977; 29: 235-237.
13. Scottish Home and Health Department. Report on
Maternal and Perinatal Deaths in Scotland 1981-
1985. London: HMSO, 1988.
14. Rowbotham DJ. Cisapride and anaesthesia. British
Journal of Anaesthesia 1989; 62: 121-123.