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

This study has been completed.
Sponsor:
Information provided by:
University of Parma
ClinicalTrials.gov Identifier:
NCT00921102
First received: June 15, 2009
Last updated: NA
Last verified: June 2009
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Cesarean Section
Anesthesia,Spinal
Postoperative Nausea and Vomiting
Drug: Bupivacaine
Drug: Morphine
Drug: Isotonic saline solution
Drug: Atropine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Intrathecal Atropine to Prevent Nausea and Vomiting After Spinal Anesthesia With Morphine for Elective Caesarean Section: a Randomized Controlled Trial

Resource links provided by NLM:


Further study details as provided by University of Parma:

Primary Outcome Measures:
  • Incidence of postoperative nausea and vomiting (PONV) as expressed by at least one rating > 3 on a numerical rating scale (0-10). [ Time Frame: 12 hours post-operatively ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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. [ Time Frame: Up to 24 h postoperatively ] [ Designated as safety issue: No ]
  • Incidence of atropine-related side effects such as xerostomia, anxiety, tachycardia. [ Time Frame: Up to 24 h postoperatively ] [ Designated as safety issue: Yes ]
  • Postoperative pain expressed as time to first request for supplemental analgesia and as rating on a numerical rating scale. [ Time Frame: Up to 24 h postoperatively ] [ Designated as safety issue: Yes ]

Enrollment: 216
Study Start Date: May 2007
Study Completion Date: May 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Control
Patients in this group will receive both an intrathecal and intravenous injection of saline solution, as a placebo comparator.
Drug: Bupivacaine
12.5 mg of a 5 mg/ml hyperbaric solution, intrathecally
Other Names:
  • Local Anesthetic
  • Hyperbaric Bupivacaine
  • Marcain Heavy Injection
Drug: Morphine
200 µg of a 200 µg/ml solution, intrathecally
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

Other Name: Sodium chloride
Experimental: 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.
Drug: Bupivacaine
12.5 mg of a 5 mg/ml hyperbaric solution, intrathecally
Other Names:
  • Local Anesthetic
  • Hyperbaric Bupivacaine
  • Marcain Heavy Injection
Drug: Morphine
200 µg of a 200 µg/ml solution, intrathecally
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

Other Name: Sodium chloride
Drug: Atropine

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

  • intrathecally in group Intrathecal Atropine
  • intravenously in group IV Atropine
Active Comparator: 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.
Drug: Bupivacaine
12.5 mg of a 5 mg/ml hyperbaric solution, intrathecally
Other Names:
  • Local Anesthetic
  • Hyperbaric Bupivacaine
  • Marcain Heavy Injection
Drug: Morphine
200 µg of a 200 µg/ml solution, intrathecally
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

Other Name: Sodium chloride
Drug: Atropine

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

  • intrathecally in group Intrathecal Atropine
  • intravenously in group IV Atropine

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00921102

Locations
Italy
University of Messina
Messina, ME, Italy, 98122
University and Hospital of Parma (Azienda Ospedaliero-Universitaria di Parma)
Parma, PR, Italy, 43126
Sponsors and Collaborators
University of Parma
Investigators
Study Chair: Guido Fanelli, MD University of Parma, Italy
Principal Investigator: Andrea Cornini, MD Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
  More Information

Publications:
Responsible Party: Guido Fanelli, MD, University of Parma
ClinicalTrials.gov Identifier: NCT00921102     History of Changes
Other Study ID Numbers: ANEST-OST-01
Study First Received: June 15, 2009
Last Updated: June 15, 2009
Health Authority: Italy: Ethics Committee

Keywords provided by University of Parma:
Atropine
Morphine
Analgesics, Opioid
Antiemetics

Additional relevant MeSH terms:
Nausea
Vomiting
Postoperative Nausea and Vomiting
Signs and Symptoms, Digestive
Signs and Symptoms
Postoperative Complications
Pathologic Processes
Anesthetics
Bupivacaine
Anesthetics, Local
Antiemetics
Atropine
Morphine
Pharmaceutical Solutions
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Sensory System Agents
Peripheral Nervous System Agents
Autonomic Agents
Gastrointestinal Agents
Adjuvants, Anesthesia
Anti-Arrhythmia Agents
Cardiovascular Agents
Bronchodilator Agents
Anti-Asthmatic Agents
Respiratory System Agents
Mydriatics

ClinicalTrials.gov processed this record on August 28, 2014