The Role of Timing of Dexamethasone Administration on Pain Scores and Quality of Recovery in Cesarean Section.

Pregnancy Clinical Trial

Official title:

The Role of Timing of Dexamethasone Administration on Pain Scores and Quality of Recovery in Cesarean Section.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02112422
• Other study ID #: B2013:159
• Status: Completed
• Phase: N/A
• First received: April 8, 2014
• Last updated: April 29, 2015
• Start date: April 2014
• Est. completion date: November 2014

Study information

• Verified date: April 2015
• Source: University of Manitoba
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Ethics Review Committee
• Study type: Interventional

Clinical Trial Summary

The purpose of our study was to evaluate the hypothesis that single dose dexamethasone given sixty minutes preoperatively reduces visual analog scale (VAS) pain scores and improves quality of recovery in patients undergoing elective cesarean section as compared to the same dose given immediately prior to skin incision.

Description:

Dexamethasone, a potent synthetic glucocorticoid with minimal mineralocorticoid effects, is commonly administered as an anesthesia adjunct for the prevention of postoperative nausea and vomiting (PONV). Over the last two decades the analgesic effects of dexamethasone have also been demonstrated in the treatment of acute and chronic pain. Two recent meta-analyses of over thirty randomized clinical trials (close to 5,000 subjects) concluded that dexamethasone at doses more than 0.1 mg/kg is an effective adjunct in multimodal strategies to reduce postoperative pain and opioid consumption after a variety of surgeries.

Cesarean section is a common surgical procedure and associated with a moderate amount of postoperative pain (Visual analogue score (VAS) of 3-5, on a 10 point scale). Patients' postoperative experience closely correlates with their perception of pain management. Controlling postoperative pain after cesarean section remains an important clinical challenge. A multimodal approach to reduce pain has become a standard of care and includes varying doses of intrathecal local anesthetic, intrathecal morphine, co-administration of opioids or other adjuncts such as non-steroidal anti-inflammatory drugs and acetaminophen. Dexamethasone is typically administered in the elective cesarean section population for the prevention of intrathecal opioid induced PONV. Recently however, the potential benefit of single dose dexamethasone has been demonstrated in improving postoperative analgesia in this patient population.

The analgesic effect of dexamethasone in post-cesarean section parturients is likely to be mediated via its anti-inflammatory actions. This does not come as a surprise given the profound inflammatory changes associated with the peripartum period and cesarean sections. Until the late third trimester. pregnancy is thought to be associated with suppression of a variety of humoral and cell-mediated immunological functions to accommodate the "foreign" semi-allogeneic fetal graft. The proinflammatory milleu becomes up regulated in late pregnancy and around the time of delivery. Specifically, during the third trimester, the percentage of granulocytes and cluster of differentiation 8 (CD8+) T lymphocytes are significantly increased, along with a concomitant reduction in the percentages of cluster of differentiation 4 (CD4+) T lymphocytes and monocytes. During the peripartum and delivery period, leukocyte count may become markedly elevated, attaining levels of 25,000/μL or greater. Moreover, circulating leukocytes undergo significant phenotypic changes including the upregulation of adhesion molecules. Other markers of inflammation including C-reactive protein, erythrocyte sedimentation rate (ESR) and complement factors C3 and C4 are all increased in normal pregnancy and significantly so during labour.

Cesarean section itself causes significant surgical stress and results in a profound inflammatory response. Inflammation is triggered not only by direct tissue injury from surgical incision and deeper tissue trauma but also by "spillage" of highly pro-inflammatory mediators from amniotic fluid and placental tissue into the pelvic cavity as well as systemic circulation.

As a result of the inflammatory insults of pregnancy and cesarean section, dexamethasone has emerged as an important adjunct in postoperative pain control in this patient population. Unanswered, however, is the role that the timing of dexamethasone administration may play in its analgesic action. Dexamethasone peak effect is delayed by 60-90 minutes reflecting its unique pharmacodynamics. Unbound dexamethasone crosses cell membranes and binds with high affinity to specific cytoplasmic glucocorticoid receptors. This complex binds to DNA elements (glucocorticoid response elements) which results in a modification of transcription and protein synthesis. This leads to inhibition of leukocyte infiltration at the site of inflammation, interference in the function of mediators of inflammatory response, suppression of humoral immune responses, and reduction in edema or scar tissue. Direct anti-inflammatory actions of dexamethasone are thought to involve phospholipase A2 inhibitory proteins and lipocortins (which control the biosynthesis prostaglandins and leukotrienes). This multistep mechanism of action may explain why administration of dexamethasone prior to the stress of surgery may optimize its therapeutic effects including analgesia and anti-emesis. However, the vast majority of studies on dexamethasone administer the drug immediately prior to or during surgery.

The purpose of this randomized, double-blinded trial is to determine if single dose dexamethasone given 45-60 minutes preoperatively reduces VAS pain scores and improves quality of recovery in patients undergoing elective cesarean section as compared to the same dose given immediately after surgical incision.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• •Over 18 years of age

• American Society of Anesthesiologists class I-III

• Presenting for elective cesarean section.

Exclusion Criteria:

• •Contraindication to regional anesthesia

• Allergy to study drug

• Uncontrolled diabetes

• Active infection

• Adrenal axis pathology

• Active treatment with steroids

• Treatment with oral or parenteral steroids within the previous 6 months

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pregnancy

Intervention

Drug:
• Control
The control group will receive 0.15 mg/kg of intravenous dexamethasone (maximum dose 20mg) in 100ml normal saline immediately prior to skin incision.
• Intervention
Patients in the intervention group will receive 0.15 mg/kg of intravenous dexamethasone (maximum dose 20mg) in 100ml normal saline 45-60 minutes prior to the OR.

Locations

Country	Name	City	State
Canada	Health Sciences Center	Winnipeg	Manitoba
Canada	Winnipeg Health Sciences Center	Winnipeg	Manitoba

Sponsors (1)

Lead Sponsor	Collaborator
University of Manitoba

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Postoperative Pain using visual analogue score.		24 hours	No
Secondary	Number of episodes of Nausea and Vomiting		24 hours post-operative	No