Intravenous Lidocaine Fails to Reduce Pain Burden After Oral Cancer Free-Flap Surgery
Intraoperative intravenous lidocaine did not lower postoperative opioid use or pain after major oral cancer surgery with free perforator flap reconstruction, despite the drug’s long-standing role in multimodal anesthesia. In this blinded, randomized, placebo-controlled trial, the lidocaine strategy was tested in a setting where postoperative analgesia is often difficult to manage because patients face large surgical wounds, reconstructive donor sites, airway considerations, and a heavy perioperative symptom burden.
The trial enrolled 64 patients from 102 screened between August 2024 and December 2024. Participants were assigned to receive either intravenous lidocaine or normal saline during surgery, and baseline characteristics as well as surgery-related data were similar across groups. The primary endpoint was cumulative opioid consumption during the first 24 hours after surgery, with pain scores, later opioid exposure, chronic pain, neuropathic pain, and safety outcomes tracked as secondary measures.
The primary result moved in the wrong direction for the intervention, not the one anesthesiologists would hope to see.
Median 24-hour morphine equivalent consumption was 43.38 mg in the lidocaine group versus 35.15 mg in the control group. The median difference was 5.31 mg, with a 95% confidence interval from -3.45 to 11.95 mg, and the _P_ value was 0.295. In practical terms, intraoperative lidocaine did not demonstrate a statistically significant opioid-sparing effect in this cohort, and the confidence interval crossed no effect. For a treatment chosen specifically to blunt postoperative nociceptive signaling, that absence of separation matters because the surgical stress response after oral cancer reconstruction is intense and often prolonged.
Pain Scores Stayed Flat Across the First 72 Hours
The pattern persisted when pain intensity was examined directly. NRS pain scores at 24, 48, and 72 hours did not differ significantly between groups. The reported median difference for acute pain was 0.00, with a 95% confidence interval from -1.00 to 0.00 and a _P_ value of 0.762. Those numbers suggest that lidocaine, at least in the regimen used here, did not shift the early postoperative pain experience in a clinically meaningful way.
The biological rationale for using lidocaine in surgery is straightforward. As a sodium channel blocker with systemic anti-inflammatory and antihyperalgesic effects, it has been used to dampen peripheral and central sensitization, reduce ectopic neural firing, and potentially lower opioid requirements after some operations. Oral cancer surgery with free perforator flap reconstruction is an especially demanding test of that theory because tissue injury is extensive, postoperative edema can be substantial, and nociceptive input may arise from multiple operative fields. A drug that succeeds in less complex procedures may still fail when the pain generator is broader, deeper, and more persistent.
No Signal for Chronic or Neuropathic Pain Prevention
The longer follow-up also offered no evidence that intraoperative lidocaine changed the trajectory of persistent pain. At 3 months, there were no significant differences in chronic pain or neuropathic pain incidence between groups. The relative risk for chronic pain was 1.13, with a 95% confidence interval from 0.50 to 2.55 and a _P_ value of 0.777. Neuropathic pain likewise failed to separate meaningfully between treatment arms.
This is clinically important because prolonged pain after head and neck cancer surgery can affect swallowing, speech, rehabilitation, nutrition, and overall recovery. Chronic postsurgical pain often reflects a complex blend of nerve injury, ongoing inflammation, altered tissue mechanics, and central sensitization. If intravenous lidocaine were going to prevent that cascade, one would expect at least some separation in the early postoperative phase or in later pain outcomes. No such pattern emerged here.
Safety and Trial Design in Context
The study did not identify a beneficial analgesic signal, and it also did not report a meaningful safety advantage that would compensate for the lack of efficacy. The trial was conducted as a blinded, randomized, placebo-controlled study, which strengthens the validity of the negative result. Randomization reduces selection bias, blinding limits expectation effects, and placebo control provides a clean comparator when pain outcomes are highly susceptible to subjective and perioperative influences.
Still, the findings should be interpreted within the boundaries of the enrolled population and the treatment approach that was actually tested. Only 64 patients were included, which leaves limited power to detect smaller effects or subgroup responses. Even when a therapy is biologically plausible, a narrow sample can fail to capture heterogeneity in surgical extent, anesthetic technique, perioperative opioid protocols, or individual susceptibility to analgesic benefit. The study was designed around oral cancer surgery with free perforator flap reconstruction, so its result is highly relevant to that operation but not automatically transferable to every head and neck procedure.
The trial was registered in the Chinese Clinical Trial Registry on August 22, 2024 under ChiCTR2400088614. Funding came from the Key Project of the Natural Science Foundation of Hunan Province and the National Natural Science Foundation of China. No competing interests were declared.
What This Means for Perioperative Analgesia
For anesthesiologists and surgical teams, the most useful message is plain: intraoperative intravenous lidocaine did not improve postoperative analgesia in this specific high-burden cancer reconstruction setting. The result argues against assuming that a drug with benefits in other operations will automatically translate to free-flap oral cancer surgery. Analgesic pathways in this population may require different strategies, or a more tailored multimodal plan that better addresses the combined effects of tissue trauma, nerve disruption, and reconstructive surgery.
The lack of effect on opioid consumption, acute pain scores, and 3-month chronic pain leaves an uncomfortable but valuable conclusion in place. In this trial, intravenous lidocaine did not change the postoperative pain course after oral cancer surgery with free perforator flap reconstruction, and the next step is not to generalize the intervention more broadly, but to ask which patients, if any, might still benefit under different dosing, timing, or surgical conditions.