Atropine to Prevent Nausea and Vomiting After Spinal Anesthesia for Caesarean Section

NCT ID: NCT00921102

Last Updated: 2009-06-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

216 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-05-31

Study Completion Date

2008-05-31

Brief Summary

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The aim of this study is to assess the efficacy of atropine in preventing nausea and vomiting after spinal anesthesia with local anesthetic and morphine for elective Caesarean section.

Patients enrolling in the study will be assigned to one of three groups. One will receive a small dose of intrathecal atropine; another will receive small-dose intravenous atropine; the third group will receive placebo.

Detailed Description

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Intrathecal (IT) morphine grants effective, durable and safe analgesia after Caesarean section. The most common adverse effects after IT morphine are widespread pruritus and postoperative nausea and vomiting (PONV).

Postoperative nausea and vomiting is multifactorial in origin; in addition to general and pre-existing risk factors, such as elevated gonadotropin and progesterone serum levels, parturients undergoing Caesarean section are exposed to drug-induced, hemodynamic and surgical (manipulation of the uterus) stimuli.

Anticholinergic agents, and particularly scopolamine, have long been known to decrease opioid-related nausea and vomiting, although their narrow therapeutic range and inconvenient route of administration (typically transdermal) has limited their application. Anticholinergic agents are thought to act via inhibition of muscarinic receptors in several regions of the medulla oblongata, which are implicated with nausea and vomiting generation; in addition to the chemoceptor trigger zone, these receptors are particularly concentrated in, but not limited to the nucleus tractus solitarius. Cholinergic receptors have been typically associated with motion sickness, but cholinergic agonists such as neostigmine have been shown to increase the incidence of PONV, especially when injected intrathecally.

Anticholinergic agents with muscarinic selectivity may be effective in preventing and treating PONV. Intravenous (IV) administration of scopolamine or atropine, but not glycopyrrolate, reduces the incidence of PONV. Intuitively, as glycopyrrolate does not cross the blood-brain barrier, most postoperative anti-emetic effects of anticholinergic drugs should be mediated by central receptors.

Few studies have specifically evaluated the antiemetic effect of IV atropine after balanced general or opioid-based regional anesthesia, with conflicting results. Atropine may represent a valid alternative to scopolamine and its adverse effects; however, its apparent duration of action is "brief" (minutes to 1 hour) when administered IV.

After we became aware of several observations by Ramaioli and De Amici on the efficacy of small-dose intrathecal (IT) atropine for the treatment of PONV after IT morphine administration, we set out to investigate the use of this agent for prophylaxis of PONV in a high-risk population, such as patients receiving IT morphine for postoperative analgesia after elective Caesarean section.

Conditions

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Cesarean Section Anesthesia,Spinal Postoperative Nausea and Vomiting

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Control

Patients in this group will receive both an intrathecal and intravenous injection of saline solution, as a placebo comparator.

Group Type PLACEBO_COMPARATOR

Bupivacaine

Intervention Type DRUG

12.5 mg of a 5 mg/ml hyperbaric solution, intrathecally

Morphine

Intervention Type DRUG

200 µg of a 200 µg/ml solution, intrathecally

Isotonic saline solution

Intervention Type DRUG

0.9% NaCl solution

0.1 ml, intrathecally in group Control and IV Atropine

0.1 ml, intravenously in group Control and Intrathecal Atropine

Intrathecal Atropine

Patients in this group will receive intrathecal atropine as a prophylactic antiemetic agent. They will also receive intravenous saline solution to maintain blinding.

Group Type EXPERIMENTAL

Bupivacaine

Intervention Type DRUG

12.5 mg of a 5 mg/ml hyperbaric solution, intrathecally

Morphine

Intervention Type DRUG

200 µg of a 200 µg/ml solution, intrathecally

Isotonic saline solution

Intervention Type DRUG

0.9% NaCl solution

0.1 ml, intrathecally in group Control and IV Atropine

0.1 ml, intravenously in group Control and Intrathecal Atropine

Atropine

Intervention Type DRUG

100 µg of a 1 mg/ml preservative-free solution

* intrathecally in group Intrathecal Atropine
* intravenously in group IV Atropine

IV Atropine

Patients in this group will receive a small dose of atropine via the intravenous route to examine its possible antiemetic activity. They will also receive intravenous saline solution to maintain blinding.

Group Type ACTIVE_COMPARATOR

Bupivacaine

Intervention Type DRUG

12.5 mg of a 5 mg/ml hyperbaric solution, intrathecally

Morphine

Intervention Type DRUG

200 µg of a 200 µg/ml solution, intrathecally

Isotonic saline solution

Intervention Type DRUG

0.9% NaCl solution

0.1 ml, intrathecally in group Control and IV Atropine

0.1 ml, intravenously in group Control and Intrathecal Atropine

Atropine

Intervention Type DRUG

100 µg of a 1 mg/ml preservative-free solution

* intrathecally in group Intrathecal Atropine
* intravenously in group IV Atropine

Interventions

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Bupivacaine

12.5 mg of a 5 mg/ml hyperbaric solution, intrathecally

Intervention Type DRUG

Morphine

200 µg of a 200 µg/ml solution, intrathecally

Intervention Type DRUG

Isotonic saline solution

0.9% NaCl solution

0.1 ml, intrathecally in group Control and IV Atropine

0.1 ml, intravenously in group Control and Intrathecal Atropine

Intervention Type DRUG

Atropine

100 µg of a 1 mg/ml preservative-free solution

* intrathecally in group Intrathecal Atropine
* intravenously in group IV Atropine

Intervention Type DRUG

Other Intervention Names

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Local Anesthetic Hyperbaric Bupivacaine Marcain Heavy Injection Sodium chloride

Eligibility Criteria

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Inclusion Criteria

* Patients scheduled for elective Cesarean section at up to 42 weeks and 2 days
* Patients in ASA Physical Status Class I or II
* Informed written consent to participation
* No known gestosis

Exclusion Criteria

* Any known fetal pathology
* Indication to general anesthesia
* Known allergy to any of the study drugs
* Baseline bradycardia or any cardiovascular disease
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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University of Parma

OTHER

Sponsor Role lead

Responsible Party

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University of Parma

Principal Investigators

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Guido Fanelli, MD

Role: STUDY_CHAIR

University of Parma

Andrea Cornini, MD

Role: PRINCIPAL_INVESTIGATOR

Azienda Ospedaliero-Universitaria di Parma, Parma, Italy

Locations

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University of Messina

Messina, ME, Italy

Site Status

University and Hospital of Parma (Azienda Ospedaliero-Universitaria di Parma)

Parma, PR, Italy

Site Status

Countries

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Italy

References

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Ramaioli F, De Amici D. Central antiemetic effect of atropine: our personal experience. Can J Anaesth. 1996 Oct;43(10):1079. doi: 10.1007/BF03011915. No abstract available.

Reference Type BACKGROUND
PMID: 8896865 (View on PubMed)

Salmenpera M, Kuoppamaki R, Salmenpera A. Do anticholinergic agents affect the occurrence of postanaesthetic nausea? Acta Anaesthesiol Scand. 1992 Jul;36(5):445-8. doi: 10.1111/j.1399-6576.1992.tb03494.x.

Reference Type BACKGROUND
PMID: 1632167 (View on PubMed)

Moscovici R, Prego G, Schwartz M, Steinfeld O. Epidural scopolamine administration in preventing nausea after epidural morphine. J Clin Anesth. 1995 Sep;7(6):474-6. doi: 10.1016/0952-8180(95)00056-n.

Reference Type BACKGROUND
PMID: 8534463 (View on PubMed)

Kotelko DM, Rottman RL, Wright WC, Stone JJ, Yamashiro AY, Rosenblatt RM. Transdermal scopolamine decreases nausea and vomiting following cesarean section in patients receiving epidural morphine. Anesthesiology. 1989 Nov;71(5):675-8. doi: 10.1097/00000542-198911000-00009.

Reference Type BACKGROUND
PMID: 2817461 (View on PubMed)

Griffiths JD, Gyte GM, Popham PA, Williams K, Paranjothy S, Broughton HK, Brown HC, Thomas J. Interventions for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section. Cochrane Database Syst Rev. 2021 May 18;5(5):CD007579. doi: 10.1002/14651858.CD007579.pub3.

Reference Type DERIVED
PMID: 34002866 (View on PubMed)

Other Identifiers

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ANEST-OST-01

Identifier Type: -

Identifier Source: org_study_id

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