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

Sponsor

University of Parma (Other)

Overall Status

Completed

CT.gov ID

NCT00921102

Collaborator

(none)

216

Enrollment

Locations

Arms

Duration (Months)

108

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

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

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

216 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, 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

Study Start Date :

May 1, 2007

Actual Primary Completion Date :

Feb 1, 2008

Actual Study Completion Date :

May 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
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 Names: 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 Names: 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 Names: Sodium chloride Drug: Atropine 100 µg of a 1 mg/ml preservative-free solution intrathecally in group Intrathecal Atropine intravenously in group IV Atropine

Arm

Intervention/Treatment

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 Names:

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 Names:

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 Names:

Sodium chloride

Drug: Atropine

100 µg of a 1 mg/ml preservative-free solution intrathecally in group Intrathecal Atropine intravenously in group IV Atropine

Outcome Measures

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). [12 hours post-operatively]

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. [Up to 24 h postoperatively]
Incidence of atropine-related side effects such as xerostomia, anxiety, tachycardia. [Up to 24 h postoperatively]
Postoperative pain expressed as time to first request for supplemental analgesia and as rating on a numerical rating scale. [Up to 24 h postoperatively]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	University of Messina	Messina	ME	Italy	98122
2	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
Principal Investigator: Andrea Cornini, MD, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy