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

Cesarean Section Clinical Trial

Official title:

Intrathecal Atropine to Prevent Nausea and Vomiting After Spinal Anesthesia With Morphine for Elective Caesarean Section: a Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00921102
• Other study ID #: ANEST-OST-01
• Status: Completed
• Phase: Phase 4
• First received: June 15, 2009
• Last updated: June 15, 2009
• Start date: May 2007
• Est. completion date: May 2008

Study information

• Verified date: June 2009
• Source: University of Parma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 216
• Est. completion date: May 2008
• Est. primary completion date: February 2008
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anesthesia,Spinal
• Cesarean Section
• Nausea
• Postoperative Nausea and Vomiting
• Vomiting

Intervention

Drug:
• Bupivacaine
12.5 mg of a 5 mg/ml hyperbaric solution, intrathecally
• Morphine
200 µg of a 200 µg/ml solution, intrathecally
• 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
• Atropine
100 µg of a 1 mg/ml preservative-free solution intrathecally in group Intrathecal Atropine intravenously in group IV Atropine

Locations

Country	Name	City	State
Italy	University of Messina	Messina	ME
Italy	University and Hospital of Parma (Azienda Ospedaliero-Universitaria di Parma)	Parma	PR

Sponsors (1)

Lead Sponsor	Collaborator
University of Parma

Country where clinical trial is conducted

Italy, 

References & Publications (4)

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. — View Citation

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. — View Citation

Ramaioli F, De Amici D. Central antiemetic effect of atropine: our personal experience. Can J Anaesth. 1996 Oct;43(10):1079. — View Citation

Salmenperä M, Kuoppamäki R, Salmenperä A. Do anticholinergic agents affect the occurrence of postanaesthetic nausea? Acta Anaesthesiol Scand. 1992 Jul;36(5):445-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of postoperative nausea and vomiting (PONV) as expressed by at least one rating > 3 on a numerical rating scale (0-10).		12 hours post-operatively
Secondary	Incidence and prevalence of PONV up to 24 h postoperatively, expressed as both ratings on a numerical rating scale and as the area under the curve of these ratings over time.		Up to 24 h postoperatively
Secondary	Incidence of atropine-related side effects such as xerostomia, anxiety, tachycardia.		Up to 24 h postoperatively
Secondary	Postoperative pain expressed as time to first request for supplemental analgesia and as rating on a numerical rating scale.		Up to 24 h postoperatively