Intravenous lidocaine has spurred an increased interest in the use of alternative perioperative nonopioid analgesia after major surgery [
1]. Morphine has long been considered the gold standard to relieve pain after most surgical procedures. However, opioid-related adverse events, such as postoperative nausea and vomiting (PONV), constipation, itching, sedation, drowsiness, dizziness, and respiratory depression, may disturb postoperative recovery and extend the length of hospital stay. Furthermore, neuronal activation and central neuroplasticity generated by intense nociceptive stimulation and high-dose opioid administration can result in hyperalgesia and chronic postsurgical pain (CPSP) [
2]. Thus, opioid sparing by an antihyperalgesic compound such as lidocaine could prevent CPSP [
3‐
5]. Systemic lidocaine, used initially as an antiarrhythmic drug, has a very short half-life and a favorable safety profile for systemic administration [
6]. Through its analgesic and anti-inflammatory activities, systemic lidocaine enhances postoperative recovery by opioid sparing and by reducing immune alterations [
7]. A recent meta-analysis found that the efficacy of perioperative intravenous lidocaine for postoperative pain varies between surgical procedures [
8]. Indeed, opioid sparing was observed after lidocaine infusion in open abdominal [
9,
10] and laparoscopic [
11,
12] procedures, thyroid surgery [
13], and cardiac [
14], thoracic [
15], and major spine [
16] procedures. Moreover, data suggest a reduction of CPSP development in breast surgery [
4,
17]. The published data being inconsistent, the efficacy of lidocaine infusion has to be assessed for each surgical procedure. There is no published study that has evaluated intravenous lidocaine in major head and neck cancer surgery. In these procedures, acute and CPSP are major and underestimated issues [
18‐
20]. Patients are not eligible for a full multimodal pain management with locoregional anesthesia. The head and neck region is widely innervated. Erosive tumor, inflammation, and extended surgical resections can lead to acute postoperative pain that has various characteristics (nociceptive, neuropathic, and psychological). Insufficient pain relief, nerve lesions, and high opioid consumption can result in hyperalgesia and chronicization of the pain. We hypothesized that perioperative intravenous lidocaine would lead to opioid sparing and CPSP reduction, and therefore designed a study to investigate this, the protocol of which is reported herein.