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