Efficacy of Intrathecal Clonidine Versus Neostigmine as Adjuvants to Bupivacaine on Postoperative Maternal and Fetal Outcomes After Elective Cesarean Section

July 5, 2023 updated by: Yasser Mamdouh Hassan Badawy, Assiut University

Efficacy of Intrathecal Clonidine Versus Neostigmine as Adjuvants to Bupivacaine on Postoperative Maternal and Fetal Outcomes After Elective Cesarean Section: A Randomized Double Blind Controlled Trial

The delivery of the infant into the arms of a conscious and pain free mother is one of the most exciting and rewarding moments in medicine. Neuraxial anesthesia is now the preferred technique for lower segment cesarean sections (LSCS). Although epidural, spinal, continuous spinal, and combined spinal-epidural techniques have all been advocated, most cesarean sections are performed under single-shot spinal anesthesia.

Even when a long acting local anesthetic like bupivacaine is used, the duration of spinal anesthesia (SA) is short and higher doses of analgesics are required in the postoperative period. Therefore, achieving a subarachnoid block that provides high quality postoperative analgesia of consistently prolonged duration is an attractive goal.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Opioids such as morphine, fentanyl, and sufentanil have been administered intrathecally as adjuvants to increase the duration of postoperative analgesia. Although they ensure superior quality of analgesia, they are associated with many side effects such as pruritus, nausea, vomiting, urinary retention, and especially late and unpredictable respiratory depression.

This has directed the research toward the use of newer and better local anesthetic additives for SA such as neostigmine, ketamine, midazolam, and clonidine.

Neostigmine is an anticholinesterase agent which increases the acetylcholine (Ach) concentration at the cholinergic synapse by blocking the activity of true and pseudocholinesterase enzymes. In postoperative period descending noradrenergic or cholinergic antinociceptive spinal system is activated by ongoing pain causing an increase in the release of Ach, which in the presence of neostigmine results in augmented analgesia. It has no untoward side effects such as respiratory depression, pruritus, and drowsiness as experienced with intrathecal narcotics.Clonidine is an α2-receptor agonist which has gained popularity in recent times as an adjuvant in spinal anesthesia. Analgesic effect of clonidine mediated by α2-adrenoceptors situated in the dorsal horn of spinal cord. The antinociceptive properties of clonidine indicate that it might be useful as an alternative to intrathecal opioids for postoperative analgesia, thus also avoiding the adverse effect of opioids.

Neostigmine was used in different dose ranges from 5 µg to 750 µg intrathecally but a low dose of 5 µg is sufficient to cause early onset of sensory and motor block.

On the other hand, clonidine was used in different doses from 15 µg to 450 µg, and many previous studies concluded that minimum 30 µg dose of clonidine provide a significant increase in the duration of sensory block, motor block, and spinal analgesia without increasing the incidence of side effects.

Dextrose 5% is used to make the adjuvant solutions more hyperbaric because in some studies, when hyperbaric solution of neostigmine was used, the incidence of nausea and vomiting was reduced by preventing cephalic spread of the drug to the brain stem.

Stress responses to surgical trauma and postoperative pain elicit diffuse changes in hormonal secretion such as adrenocorticotropic hormone (ACTH), cortisol and prolactin, with several deleterious metabolic and cardiovascular effects that can be prevented by effective postoperative analgesia.

Cortisol is a key player in the stress response and its secretion is facilitated by the ACTH which interacts with the sympathetic nervous system and the inhibitory control of endogenous opioid peptides, influencing pain processing.(12) Negative associations between cortisol levels and subsequent pain perception suggest the possibility that the hypothalamic-pituitary- adrenal (HPA) axis contributes to attenuating pain perception during acute stressful events, possibly mediated by increased cortisol.

Study Type

Interventional

Enrollment (Estimated)

111

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. Age: ranges from 20 - 35 years old.
  2. ASA physical status II.
  3. Singleton fetus at term.
  4. Parturient scheduled for elective lower segment cesarian section under spinal anethesia

Exclusion Criteria:

  1. Patient refusal.
  2. Contraindications to spinal blockade, such cardiorespiratory problems, coagulopathy, neurological disease, psychological troubles, and allergy to the used drugs.
  3. Morbid obesity.
  4. Failure of spinal blockade.
  5. Emergency CS.
  6. Complicated pregnancy.
  7. Intrauterine fetal compromise.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Group B
control group : will receive 2 ml (10 mg) of intrathecal hyperbaric Bupivacaine (0.5%) and another syringe containing 1 ml of Dextrose 5%.
Drug: Clonidine
compare the effect of intrathecal Clonidine and Neostigmine as adjuvants to Bupivacaine in elective cesarean section
Active Comparator: Group BC
will receive 2 ml (10 mg) of intrathecal hyperbaric Bupivacaine (0.5%) and another syringe containing Clonidine (30 µg) diluted in Dextrose 5% to a total volume of 1 ml.
Drug: Clonidine
compare the effect of intrathecal Clonidine and Neostigmine as adjuvants to Bupivacaine in elective cesarean section
Active Comparator: Group BN
will receive 2 ml (10 mg) of intrathecal hyperbaric Bupivacaine (0.5%) and another syringe containing Neostigmine (10 µg) diluted in Dextrose 5% to a total volume of 1 ml.
Drug: Clonidine
compare the effect of intrathecal Clonidine and Neostigmine as adjuvants to Bupivacaine in elective cesarean section

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
postoperative analgesic efficacy of intrathecal clonidine and neostigmine by use of numerical rating scale (NRS) pain score.
Time Frame: 2 hours after time of sensory block
using numerical rating scale (NRS) pain score that ranges from 0 indicating no pain up to 10 indicating the worst pain
2 hours after time of sensory block

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assiut University

Publications and helpful links

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Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

December 1, 2023

Primary Completion (Estimated)

September 30, 2025

Study Completion (Estimated)

November 30, 2025

Study Registration Dates

First Submitted

June 7, 2023

First Submitted That Met QC Criteria

July 5, 2023

First Posted (Actual)

July 13, 2023

Study Record Updates

Last Update Posted (Actual)

July 13, 2023

Last Update Submitted That Met QC Criteria

July 5, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Clonidine versus Neostigmine

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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