Perioperative Dexmedetomidine or Lidocaine Infusion for the Prevention of Chronic Postoperative and Neuropathic Pain After Gynecological Surgery: A Randomized, Placebo-Controlled, Double-Blind Study

Abstract

Introduction: The transition of acute to chronic postoperative pain (CPP) remains a significant burden to the rehabilitation of patients. The research for adjuvants to prevent CPP continues; among others, dexmedetomidine and lidocaine seem promising agents.

Methods: This is a long-term follow-up of a randomized, placebo-controlled, double-blind study on women who underwent open abdominal gynecological surgery and received dexmedetomidine or lidocaine or placebo infusion perioperatively (n = 81). The effect of these adjuvants on the development of CPP and neuropathic pain was assessed during a 12-month follow-up. Eighty-one (81) women ASA I-II, aged between 30 and 70 years, were randomly assigned to receive either dexmedetomidine (DEX group) or lidocaine (LIDO group) or placebo (CONTROL group) perioperatively. Before anesthesia induction, all patients received a loading intravenous dose of either 0.6 μg/kg dexmedetomidine or 1.5 mg/kg lidocaine or placebo, followed by 0.6 μg/kg/h dexmedetomidine or 1.5 mg/kg/h lidocaine or placebo until last suture. Patients were followed up to obtain the long-term outcomes at 3, 6, and 12 months. At these time-points, pain intensity was assessed with the Numerical Rating Scale, (NRS: 0-10) and the development of neuropathic elements with the Douleur Neuropathique 4 (DN4) score. Prognostic parameters that could affect chronic pain and its components were also identified.

Results: Data from 74 women were analyzed. Dexmedetomidine significantly reduced NRS scores comparing to placebo at 3 months (p = 0.018), while at 6 months, lidocaine was found superior to placebo (p = 0.02), but not to dexmedetomidine, in preventing neuropathic pain (DN4 < 4). Regarding secondary endpoints, higher NRS cough scores at 48 h were associated with statistically significant NRS and DN4 scores at 3, 6, and 12 months (p < 0.02). At 6 months, a statistically significant correlation was also found between higher NRS values and older age (p = 0.020).

Conclusions: Dexmedetomidine was superior to placebo regarding the duration and severity of CPP, while lidocaine exhibited a protective effect against neuropathic elements of CPP.

Trial registration: ClinicalTrials.gov identifier, NCT03363425.

Keywords: Chronic postoperative pain; Dexmedetomidine; Lidocaine; Long-term follow-up; Neuropathic pain.