Original Paper
Accepted: July 2, 2001
Kidney Blood Press Res 2002;25:61–64
Comparison of Ondansetron with
Metoclopramide in the Symptomatic Relief of
Uremia-Induced Nausea and Vomiting
Dragan Ljutić Dijana Perković Zvonko Rumboldt Jugoslav Bagatin
Izet Hozo Nediljko Pivac
Department of Internal Medicine, Clinical Hospital, Split, Croatia
Key Words
Uremia W Nausea W Vomiting W Metoclopramide W
Ondansetron
Abstract
Background: Nausea and vomiting are well-known gas-
trointestinal complications in chronic renal failure and
are frequent indications for the commencement of dialy-
sis. Although the administration of antiemetic drugs
(metoclopramide and, recently, ondansetron) is usually
mentioned, there are scanty data on their effects. Meth-
ods: A double-blind crossover study was done in 10 ure-
mic patients. All the patients were uremic and suffered
from nausea and vomiting. The drugs were randomly
administered intravenously (either metoclopramide
10 mg or ondansetron 8 mg) 2 h after blood drawing for
laboratory tests either on the 1st or on the 3rd study day
at the same time. The outcomes were scored after 24 h of
follow-up by (1) one of us (D.P.; 1–3 points: 1 = no effect;
2 = moderate effect – decreased frequency of vomiting,
and 3 = good effect – no vomiting), and (2) by the patients
(1–5 points). Results: The results obtained showed that
ondansetron was more effective in controlling nausea
and vomiting than metoclopramide, either objectively
(2.80 B 0.422 vs. 1.40 B 0.699, p ! 0.005) or subjectively
© 2002 S. Karger AG, Basel
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(4.10 B 0.738 vs. 2.10 B 0.994, p ! 0.005). Conclusions:
We conclude that at the dosage level studied ondanse-
tron is about twice as effective as metoclopramide in the
symptomatic relief of uremia-induced nausea and vomit-
ing.
Copyright © 2002 S. Karger AG, Basel
Introduction
Nausea and vomiting are well-known gastrointestinal
complications in chronic renal failure; these symptoms
result from direct effects of uremia [1–3]. Although the
pathogenetic mechanism underlying uremic nausea and
vomiting is not completely explained and understood, it is
suggested that uremic toxins induce these effects by stim-
ulating the chemoreceptor trigger zone in the area postre-
ma of the medulla oblongata, in the floor of the fourth
ventricle, which itself activates the vomiting center (lo-
cated in the dorsal portion of the medulla oblongata [4].
The exact neurotransmitter that is released in these cen-
ters is not known, but numerous receptors for various
neurotransmitters and neuropeptides have been identi-
fied, such as muscarinic, dopamine, serotonin, norepi-
nephrine, glutamine, and histamine receptors [4, 5]. The
usual therapy, regardless of the cause of nausea and vom-
Dragan Ljutić, MD, PhD
Division of Nephrology, Department of Internal Medicine
Clinical Hospital, Spinčićeva 1
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Table 1. Baseline clinical characteristics 1st day, 2 h after blood drawing for laboratory tests, the drug under
study (either metoclopramide 10 mg or ondansetron 8 mg) was
Patient Renal disease Concomitant disease Hyper- administered intravenously. The alternative drug was given 2 days
No. volemia after. The patients were followed up and the drugs’ effects were
assessed objectively (by one of us, D.P., who was unaware of the
1 MGN – no patient’s identity and drug used) and subjectively (by the patients).
2 MAPGN – no The effect of the drug was assessed according to the number of
3 FSGS arterial hypertension no vomiting episodes and feeling of nausea. Any vomitus productive of
4 LN hypothyreosis yes liquid or a series of one to five retches (dry heaves) within a 5-min
5 RPGN – yes period was considered to represent a single episode.
6 RPGN – no The objective score ranged from 1 to 3 points (1 = no effect: the
7 CPN cholelithiasis no number of vomiting episodes as it was at the beginning of the study
8 CPN arterial hypertension yes or 5 and more; 2 = moderate effect: decreasing the frequency of vom-
9 CTIN – no iting episodes from 4 to 1 or decreasing in the number of vomiting
10 HNP ischemic cardiomyopathy yes episodes by 2 from the number at the beginning of the study, and 3 =
good effect: no vomiting) and the subjective score (ranged from 1 to 5
MGN = Membranous glomerulonephritis; MAPGN = membra- points rated by the patients on an analogue scale (1 = very intensive
noproliferative glomerulonephritis; FSGS = focal segmental glomer- nausea: as bad as it could be; 2 = intensive nausea; 3 = moderate
ulosclerosis; LN = lupus nephritis; RPGN = rapidly progressing glo- nausea; 4 = mild nausea, and 5 = no nausea). Vital signs, numbers of
merulonephritis; CPN = chronic pyelonephritis; CTIN = chronic vomiting and nausea episodes, laboratory values, side effects, and
tubulointerstitial nephritis; HNP = hypertensive nephroangiosclero- other drug intakes were followed up for 4 days (96 h). The patients
sis. recorded all the informations in the appropriate diary.
Complete blood cell count, serum urea, creatinine, electrolyte,
and uric acid concentrations, and acid-base status were determined
using standard laboratory techniques and an automatic analyzer.
The results obtained are presented as mean values B SD. The
differences between the drug effects were calculated using a paramet-
iting, consists of restoration of fluid and electrolyte bal- ric paired t test and the nonparametric Wilcoxon test. p ! 0.05 was
ance, treatment of underlying disorders, and prescription considered statistically significant.
of antiemetic agents (e.g., metoclopramide, ondansetron,
etc.) [4]. In uremia, the occurrence of nausea and vomit-
ing signals the need for the commencement of dialysis. Results
There are scanty data on the effects of antiemetic drugs in
the treatment of uremic nausea and vomiting [1, 3, 6] – The main laboratory data before the study are shown
only the letter to the editor by Andrews et al. [7] reported in table 2. As it can be seen, there are no significant differ-
a beneficial effect of ondansetron in the amelioration of ences in the data between the study groups except for the
these symptoms. serum creatinine level. The assessment of efficacy, in
Therefore, this study was designed in order to assess points given by the patients themselves and us, is shown
the effects of two different antiemetics (metoclopramide in table 3. There was no statistically significant difference
and ondansetron) on nausea and vomiting in terminal in the number of vomiting episodes before administration
renal failure. of either drug (4.400 B 1.350 before metoclopramide vs.
4.000 B 1.054 before ondansetron; p = 0.470). The anti-
emetic efficacy of ondansetron was clearly superior to that
Patients and Methods of metoclopramide scored either objectively (2.80 B
0.422 vs. 1.40 B 0.699; p ! 0.005) or subjectively (4.10 B
Ten uremic patients (5 females and 5 males, age range 25–77 0.738 vs. 2.10 B 0.994; p ! 0.005). The full antiemetic
years) after obtaining local ethics committee approval and written
effect, when achieved, lasted from 20 to 29 (23.9 B
informed consent were studied. In 7 of them glomerular and in 3 of
them tubulointerstitial diseases were the cause of their chronic renal 2.923) h.
failure (table 1). Before inclusion in this study, all patients were hos- There were no adverse effects of either drug during the
pitalized and thoroughly clinically evaluated, fulfilling the clinical observation period 1–4 (2.444 B 1.130) days after the
and laboratory characteristics of uremia; all were in metabolic acido- study, all patients but 1 commenced the maintenance
sis and had nausea and vomiting [8].
dialysis program which resulted in immediate resolution
The study was randomized (sealed envelopes with written in-
structions about the drug to be used first, based on random numbers), of nausea and vomiting. This patient (with chronic tubu-
crossover, and double-blind. Just by chance, exactly 5 patients have lointerstitial nephritis as underlying disease) who did not
received metoclopramide and 5 ondansetron as the first drug. On the start the dialysis program actually had acute on chronic

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Table 2. Laboratory data on the 1st and
3rd days of the study 1st day 3rd day p

Hematocrit, % 27.3B5.2 27.8B3.3 0.504

Urea, mmol/l 56.590B10.894 57.760B11.255 0.447
Creatinine, Ìmol/l 874.900B178.802 933.700B179.899 0.001
Sodium, mmol/l 136.900B4.067 135.200B3.393 0.324
Potassium, mmol/l 5.080B0.590 5.010B0.603 0.390
Calcium, mmol/l 2.107B0.288 2.107B0.301 1.000
Phosphorus, mmol/l 2.659B0.448 2.659B0.399 1.000
Uric acid, mmol/l 544.800B93 555.000B105.556 0.244

Table 3. The patients’ (1–5 points) and the

examiner’s (1–3 points) ratings of the Pa- Vomiting Metoclopramide Vomiting Ondansetron
efficacy of metoclopramide and ondansetron tient episodes before episodes before
patients examiner patients examiner
as well as the number of vomiting episodes No. metoclopramide ondansetron
before metoclopramide and ondansetron
1 5 1 1 3 4 3
2a 4 3 2 3 4 3
3 5 2 1 4 5 3
4a 3 3 2 4 5 3
5 7 1 1 5 4 3
6a 4 2 1 5 3 2
7a 4 2 1 3 4 3
8a 3 4 3 4 3 2
9 6 1 1 6 5 3
10 3 2 1 3 4 3

a Ondansetron as the first drug.

renal failure – abolishing of nausea and vomiting im-
proved the patient’s well-being (with a subsequent decre-
ment in the serum creatinine level), returning to compen-
sated preterminal renal failure. From time to time she is
still using ondansetron orally for her nausea in order to
prevent vomiting.
Discussion
The results presented here support previous observa-
tions that ondansetron is a powerful antiemetic drug to be
used in uremic patients [7]. It has also been shown that
metoclopramide exerts only mild, if any, effects in relief
of these uremic symptoms – significantly less than ondan-
setron. These two drugs mediate their antiemetic actions
through different receptors: metoclopramide is a dopa-
mine D2 and ondansetron a serotonin S3 receptor antago-
nist [4, 5]. It is well established that metoclopramide has a
good antiemetic effect in treating chemotherapy-associat-
ed emesis and emesis associated with gastroparesis or
pseudoobstruction [5, 9]. On the other hand, ondansetron
is very effective in controlling nausea and vomiting
induced by chemotherapy (even in the case of refractori-
ness to conventional therapy) and radiotherapy or nausea
and vomiting occurring during the postoperative period
[9–13]. There is no clinical study on the antiemetic effects
of either drug in uremia, although metoclopramide is
often mentioned as a possibility in this entity [2, 3]. It is
also known that some of the effects of metoclopramide are
mediated by the serotonin receptors in the vomiting cen-
ter, but only at a higher dosage [5], which was not the case
in this study. Further, the results obtained indirectly show
that serotonin appears to be one of the mediators of ure-
mic nausea and vomiting.
The results of this study also support the predicted
duration of ondansetron’s antiemetic effects: it has a half-
life of 3–6 h, and its antiemetic effect can be lost as early

Ondansetron vs. Metoclopramide in Kidney Blood Press Res 2002;25:61–64 63

Uremia
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as after 9 h [10, 12]. In our patients this effect lasted at
least 24 h. It should be stressed that metoclopramide has a
half-life of about 4–5 h (in uremia up to 14–18 h) and
ondansetron one of about 3–4 h (in uremia 5–9 h), so that
a carryover phenomenon of these two drugs is excluded
beyond any reasonable doubt after 48 h [14].
There were no side effects that could be attributed to
either ondansetron or metoclopramide in our uremic
patients. Metoclopramide causes adverse effects in 10–
30% of the patients, ranging from mild anxiety and ner-
vousness to dystonia or tardive dyskinesia [4, 9]. Adverse
effects of ondansetron are headache, constipation, diar-
rhea, and transient elevation of liver enzyme concentra-
tions.
In conclusion, (1) ondansetron is superior to metoclo-
pramide and possesses a beneficial effect in the ameliora-
tion of uremic nausea and vomiting and can be suggested
as a drug of choice in the relief of such symptoms, and
(2) serotonin seems to be the main neurotransmitter me-
diating uremic nausea and vomiting.

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