Efficacy and safety of intravenous administration of dexamethasone on post-cesarean delivery pain: a systematic review and meta-analysis of current literature

The Takeaway

Evidence suggests that intravenous dexamethasone not only decreases nausea and vomiting, but delays first request for analgesia after cesarean section. It also reduces total analgesic demand and pain scores up to 24 hours post delivery.

Study Design

• PRISMA statement and adhering to the Cochrane Collaboration methodology
• 17 RCTs in the qualitative analysis
• 15 RCTs in the quantitative analysis.
• Primary outcome: the effect of the IV dexamethasone on:
  • the time interval to the first analgesic request
  • the total opioid consumption up to 24 hours after cesarean delivery.
• Secondary end-points:
  • pain severity at rest at pre-defined time intervals
  • occurrence of postoperative nausea and vomiting (PONV), pruritus, shivering, or wound infections/healing

Abstract

Background: Surgical tissue trauma induced by cesarean delivery serves as a pivotal stimulus for initiating the activation of nociceptors, leading to severe postoperative pain. Dexamethasone seems to mitigate pain-elicited inflammatory response and potentially serve as an analgesic adjunct in the post-cesarean period. This systematic review and meta-analysis aimed to assess the administration of intravenous dexamethasone for post-cesarean pain management.

Methods: An electronic database search involving PubMed, Scopus, CENTRAL, and the Public Library of Science was conducted to identify all randomized controlled trials (RCTs) pertinent to the analgesic efficacy of intravenous dexamethasone compared with placebo for cesarean delivery. The risk of bias and certainty of evidence in eligible trials were assessed using the ROB2 tool and the GRADE approach, respectively.

Results: Seventeen RCTs were included in the qualitative analysis, and 15 in the quantitative analysis. Intravenous dexamethasone was associated with prolonged time to first request for rescue analgesia (mean difference [MD] 3.33 hours, 95% CI 1.67 to 4.99; I² = 92.7%), lower opioid analgesic consumption (MD, -3.23 mg; 95% CI, -4.04 to -2.41; I² = 67.5%) within 24 hours and improved pain scores up to 24 hours postoperatively compared with placebo, however prediction intervals failed to confirm these favorable effects. The risk of postoperative nausea and vomiting was reduced with intravenous dexamethasone, but not that of pruritus.

Conclusions: Intravenous perioperative dexamethasone seems to be a promising adjunct to established analgesic modalities in cesarean delivery, with prolonged time to first request for rescue analgesia, reduced analgesic consumption, and reduced pain scores at rest up to 24 hours postoperatively. However, the substantial heterogeneity and low certainty of available evidence preclude any definite conclusions from being drawn.

Physiology Refresh

Intravenous dexamethasone reduces postoperative pain through several mechanisms—primarily its anti-inflammatory effects, but also through actions that modulate pain perception.

First, dexamethasone is a potent glucocorticoid. It works by binding to intracellular glucocorticoid receptors, leading to suppression of pro-inflammatory gene transcription. This downregulates cytokines like IL-1, IL-6, and TNF-α, which are typically elevated after surgical trauma and contribute to local inflammation, edema, and sensitization of peripheral nociceptors. By reducing these inflammatory mediators, dexamethasone lowers peripheral sensitization and decreases the input of nociceptive signals from the surgical site.

Second, it inhibits the enzyme phospholipase A2. This blocks the conversion of membrane phospholipids into arachidonic acid, which is the precursor to prostaglandins and leukotrienes. Inhibiting this pathway reduces prostaglandin synthesis, especially PGE2, which normally sensitizes nociceptors. So, this effect directly dampens pain transmission.

There’s also evidence for central effects. Dexamethasone may cross the blood-brain barrier and act at the spinal level to reduce neuroinflammation and central sensitization. This can help prevent the “wind-up” phenomenon where repeated peripheral stimuli cause amplified responses in the dorsal horn of the spinal cord.

In short: dexamethasone helps by reducing both inflammation and pain pathway sensitization, while also improving tolerance of the postoperative period. This is why it's often included in multimodal analgesic strategies.

Excerpts

Patients undergoing cesarean delivery are at risk of acute severe postoperative pain compared with patients with vaginal delivery, with a reported incidence of approximately 85% and 57%, respectively

The transition from acute to chronic pain following cesarean delivery constitutes a major concern, as the reported incidence within the first postoperative year affects 11.2% of the cases

adequate pain management is essential for maternal-infant bonding and breastfeeding initiation, as acute pain could elicit postpartum depression and/or chronic pain.

Intravenous dexamethasone was associated with prolonged time to first request for rescue analgesia (mean difference [MD] 3.33 hours, 95% CI 1.67 to 4.99; I2 = 92.7%), lower opioid analgesic consumption (MD, −3.23 mg; 95% CI, −4.04 to −2.41; I2 = 67.5%) within 24 hours and improved pain scores up to 24 hours postoperatively compared with placebo, however prediction intervals failed to confirm these favorable effects. The risk of postoperative nausea and vomiting was reduced with intravenous dexamethasone, but not that of pruritus.

Article Link

Citation

Ioannopoulos D, Tsani Z, Chatsiou E, Arnaoutoglou E, Tsaousi G. Efficacy and safety of intravenous administration of dexamethasone on post-cesarean delivery pain: a systematic review and meta-analysis of current literature. Int J Obstet Anesth. 2025 May 12;63:104682. doi: 10.1016/j.ijoa.2025.104682. Epub ahead of print. PMID: 40398157.