Effect of intravenous alizapride on spinal morphine-induced pruritus

M. L. Horta1,2 and P. T. G. Vianna3

1 Department of Anesthesiology, Santa Casa de Misericórdia de Pelotas, Brazil. 2 Department of Anesthesiology, Hospital Universitário São Francisco de Paula da UCPEL, Pelotas, RS, Brazil. 3 Department of Anesthesiology of the School of Medicine of Botucatu, UNESP, Botucatu, SP, Brazil

Corresponding author: Rua Anchieta 4043, 96015.420, Pelotas, RS, Brazil. E-mail: marciolhorta@uol.com.br

Accepted for publication: April 7, 2003


    Abstract
 Top
 Abstract
 Introduction
 Methods and results
 Comment
 References
 
Background. This double-blind study was undertaken to determine whether alizapride inhibits spinal morphine-induced pruritus.

Methods. Eighty-four patients undergoing Caesarean section under spinal anaesthesia (100 mg of hyperbaric lidocaine 5% plus morphine 0.2 mg) were randomly allocated to one of two groups. Just after birth, alizapride—50 mg (alizapride group) or metoclopramide—10 mg (metoclopramide group) were injected i.v. Patients were assessed after surgery for pruritus (absent, mild, moderate or severe) or other untoward symptoms.

Results. In the metoclopramide group, pruritus was absent in 5 (12%) patients, mild in 23 (55%), moderate in 11 (26%), and severe in 3 (7%), while in the alizapride group, these incidences were, respectively, 5 (12%), 33 (79%), 4 (10%), and 0 (P=0.045, {chi}2-test). There was no difference in the incidence of side-effects, which were all minor.

Conclusions. Alizapride reduced the severity of morphine-induced pruritus.

Br J Anaesth 2003; 91: 287–9

Keywords: anaesthesia, obstetric; analgesics opioid, morphine; complications, pruritus; pharmacology, alizapride


    Introduction
 Top
 Abstract
 Introduction
 Methods and results
 Comment
 References
 
Pruritus is an important side-effect of the epidural or spinal use of opioids.1 There is interest in drugs that can counteract pruritus without interacting with µ-opioid receptors, such as droperidol, a dopamine D2 receptor antagonist.2

Metoxibenzamides inhibit dopaminergic D2 receptors. The first drug in this group to be used in clinical practice was metoclopramide. Others include bromopride, cisapride, domperidone, sulpiride and alizapride. Though they all inhibit D2 receptors, small pharmacodynamic differences lead to different uses and characteristics. Alizapride is about three times more potent against emesis induced by ergot alkaloids or apomorphine and about four times less effective in inducing central effects such as catalepsy3 than metoclopramide. As both these effects depend on dopaminergic D2 receptors, the reason for this difference is not yet clear. Although, in another study, we found no effect of metoclopramide,4 we thought it was important to investigate whether, in patients undergoing Caesarean section, alizapride had any effect on morphine-induced pruritus compared with metoclopramide.


    Methods and results
 Top
 Abstract
 Introduction
 Methods and results
 Comment
 References
 
This study was approved by the local ethics committees and all patients gave written informed consent.

Using a double-blind design, 84 ASA I or II patients undergoing Caesarean section were studied. When the patients arrived in the operating room, an i.v. infusion of lactated Ringer’s solution was established and fentanyl 50 µg was administered i.v. Patients received spinal anaesthesia with hyperbaric lidocaine 2 ml (100 mg, 5%), to which morphine sulphate 0.2 mg (1 ml of a preservative-free solution) was added. Left uterine displacement was established until birth. If hypotension (systolic arterial pressure <70% of control values or <90 mm Hg) persisted in spite of trying to improve left uterine displacement or occurred after birth, bolus doses of metaraminol 1 mg were given. Just after delivery, synthetic oxytocin (15 IU) was administered.

From a random number table, an allocation table was made distributing the 84 patients into two groups of 42. Just after delivery, patients received either alizapride 50 mg i.v. or metoclopramide 10 mg i.v. The patients were not aware of which drug was injected. Metoclopramide was used as a control group because, as it was shown to be ineffective against morphine-induced pruritus,4 it would be able to afford protection against nausea and vomiting without interfering with our primary outcome measure.

Patients were assessed after surgery by one or more of a group of six blinded medical students specially trained for this task. Patients were assessed at least twice in the first 24 h (preferably 3 and 6 h after anesthesia) and at least once a day until discharge from hospital.

Pruritus was classified as absent, mild (restricted to one area, such as face or arms, and not troubling the patient; often reported only after prompting), moderate (affecting a larger area, such as face and arms or face and anterior surface of thorax, but not disturbing the patient, and therefore not requiring treatment) or severe (extensive or generalized, often disturbing the patient to the point that treatment was indicated). All other postoperative events were also recorded. Adverse events were recorded when they were directly observed or reported by the patient.

Means were compared using analysis of variance. Proportions were compared using the {chi}2-test, with Yates correction for 2x2 tables. Differences were considered as statistically significant when P<0.05.

There was no difference between the metoclopramide and alizapride groups with respect to patient characteristics (age, height, weight, BMI, and the proportion of ASA I and II patients) and volumes of lactated Ringer’s solution infused. For the metoclopramide and alizapride groups, respectively, the mean (SD) volumes infused were 256 (128) ml vs. 276 (140) ml until lumbar puncture, 461 (151) ml vs. 506 (156) ml until birth, and 985 (231) ml vs. 1085 (234) ml by end of surgery. The incidence of hypotension was similar in the two groups (21 vs. 19%), and when metaraminol was needed, there was no difference between the mean doses (metoclopramide group 1.3 mg, alizapride group 1.7 mg).

In the metoclopramide group, pruritus was absent in five (12%) patients, mild in 23 (55%) patients, moderate in 11 (26%) patients and severe in three (7%) patients. In the alizapride group, the incidences were five (12%); 33 (79%); four (10%); and none, respectively (Fig. 1; P=0.045).



View larger version (11K):
[in this window]
[in a new window]
 
Fig 1 Incidence of pruritus (P<0.05, {chi}2-test).

 
As for complications during surgery (19% metoclopramide group and 26% alizapride group) and in the postoperative period (31% metoclopramide group and 33% alizapride group) there was no difference between the two groups. No adverse events were considered serious.


    Comment
 Top
 Abstract
 Introduction
 Methods and results
 Comment
 References
 
Alizapride did not alter the incidence of pruritus, but there was a significant reduction in the severity of this symptom. As mild pruritus is sometimes denied by patients,5 we believe this is a significant improvement.

We were unable to detect any side-effect attributable to alizapride with the dose used (50 mg i.v.). Other authors6 used much larger doses in adults (200–300 mg) and reported no side-effects also, which suggests that the doses used in this study may be safely increased to improve efficacy.


    Acknowledgement
 
The authors thank doctors Alexandro Irala Nunes, Camile Amaral Camargo, Cheila Mayorca de Faria, Giovani Roman, Renata Machado Volpato and Tatiane Kauffmann Papaleo, who, as medical students, were in charge of the postoperative assessment of the patients. Their dedication was essential for the development of this research. We also thank Dr Bernardo Lessa Horta for assistance in the statistical analysis of this paper.


    References
 Top
 Abstract
 Introduction
 Methods and results
 Comment
 References
 
1 Lema MJ. Opioid effects and adverse effects. Reg Anesth 1996; 21 (6S): 38–42[ISI][Medline]

2 Horta ML, Horta BL. Inhibition of epidural morphine-induced pruritus by intravenous droperidol. Reg Anesth 1993; 18: 118–20[ISI][Medline]

3 Laville Cl, Margarit J. Étude pharmacodynamique de l’alizapride. Sem Hôp Paris 1982; 58: 323–31

4 Horta ML, Faria CM, Nunes AI, Papaleo TK. Influência da metoclopramida sobre o prurido provocado pela morfina subaracnóidea. Rev Bras Anestesiol 2000; 50 [Suppl. 25]: CBA 034A

5 Ballantyne JC, Loach AB, Carr DB. Itching after epidural and spinal opiates. Pain 1988; 33: 149–60[CrossRef][ISI][Medline]

6 Casanova P. Étude de l’activité d’um nouvel antiémétique, l’alizapride. Ann Gastroentérol Hépatol 1980; 16: 381–6





This Article
Abstract
Full Text (PDF)
E-Letters: Submit a response to the article
Alert me when this article is cited
Alert me when E-letters are posted
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in ISI Web of Science
Similar articles in PubMed
Alert me to new issues of the journal
Add to My Personal Archive
Download to citation manager
Search for citing articles in:
ISI Web of Science (2)
Disclaimer
Request Permissions
Google Scholar
Articles by Horta, M. L.
Articles by Vianna, P. T. G.
PubMed
PubMed Citation
Articles by Horta, M. L.
Articles by Vianna, P. T. G.