The Role of Timing of Dexamethasone Administration on Pain Scores and Quality of Recovery in Cesarean Section.
Condition: Pregnancy
Study type: Interventional

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.
    

Detailed 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.
    

Intervention name(s): Control; Intervention
Intervention type(s): Drug; Drug
Intervention description(s): The control group will receive 0.15 mg/kg of intravenous dexamethasone (maximum dose 20mg) in 100ml normal saline immediately prior to skin incision.; 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.
Other intervention name(s): 0.15 mg/kg dexamethasone IV prior to skin incision.; 0.15 mg/kg of dexamethasone IV 60 minutes prior to the OR.
Intervention MeSH terms: Dexamethasone; Dexamethasone acetate; BB 1101
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Parturients