November 29, 2025
Background: Rebound pain following peripheral nerve block resolution is a distressing phenomenon that impairs recovery and
commonly arises at night when treatment options are limited.
Objective: To evaluate whether intravenous esketamine and/or dexamethasone, as adjuvants to interscalene ropivacaine block, reduce rebound pain after arthroscopic shoulder surgery.
Design: A patient- and outcome assessor–blinded, randomized, controlled, 2×2 factorial clinical trial.
Setting: A single tertiary-care academic hospital.
Patients: A total of 160 adult patients undergoing arthroscopic shoulder surgery under general anaesthesia with single-shot interscalene brachial plexus block.
Interventions: Patients were randomized to receive intravenous combinations of esketamine–placebo, placebo–dexamethasone,
esketamine–dexamethasone, or placebo–placebo, in addition to ropivacaine block after induction of general anaesthesia and before
surgical incision.
Main Outcome Measures: Co-primary outcomes were: (1) the increase in pain score from before to after the ISB resolved; and (2)
the incidence of severe rebound pain, defined as numerical rating scale (NRS) pain score ≥7.
Results: All 160 patients completed the trial. Rebound pain occurred in 32% of patients, with no interaction between esketamine and
dexamethasone. The pain score increased by 6.2 ± 2.5 in the placebo–placebo group versus 4.4 ± 2.5 in the esketamine dexamethasone group (difference –1.8; 95% CI –2.9 to –0.7; P = 0.002). Dexamethasone significantly reduced the pain score increase compared to placebo (–1.7; 95% CI –2.8 to –0.6; P = 0.003), while esketamine alone did not. Severe rebound pain occurred in 22/80 (27%) of patients receiving esketamine versus 26/80 (32%) without (RR 0.84; 95% CI 0.50 to 1.41; P = 0.459), and in 18/80 (22%) of patients receiving dexamethasone versus 29/80 (36%) without (RR 0.62; 95% CI 0.38 to 0.89; P = 0.016).
Conclusion: Intravenous dexamethasone, but not esketamine (low dose), significantly reduced the incidence and severity of rebound pain following interscalene nerve block.
Trial Registration: Chinese Clinical Trial Registry (ChiCTR2300072416).
Keywords: esketamine, dexamethasone, peripheral nerve block, rebound pain, central sensitization, factorial trial
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