Intraoperative Lidocaine or Dexmedetomidine for Postoperative Pain Modulation After Urethral Reconstruction.

Lidocaine and dexmedetomidine are drugs with a long history of clinical use in anesthesiology and intensive care medicine, and their safety has been extensively documented. Intravenous lidocaine infusion at therapeutic doses constitutes an established component of multimodal perioperative analgesia. Its efficacy in reducing postoperative pain intensity, decreasing opioid requirements, and attenuating the inflammatory response to surgical injury has been demonstrated in numerous prospective randomized trials and meta-analyses. Dexmedetomidine, a selective α₂-adrenergic receptor agonist, is routinely used both for sedation and analgesia in intensive care units and as a component of balanced anesthesia in a wide range of surgical procedures. Its analgesic, sympatholytic, and opioid-sparing properties, together with its favorable effects on hemodynamic stability, have been supported by a substantial body of clinical evidence. The dose ranges employed in the present protocol fall within the limits recommended by current guidelines and are consistent with established clinical practice.

The objective of this study is to determine whether the pharmacological properties of these two agents may be beneficial in preventing chronic postsurgical pain in patients undergoing urethral reconstructive surgery, an area in which high-quality methodological evidence remains scarce.

b) Detailed Methodology Study population The study will enroll patients aged 18-75 years with physical status classification of American Society of Anesthesiology status (ASA) I-III who are scheduled to undergo urethral surgery (e.g., urethral reconstruction, urethroplasty, or treatment of urethral strictures).

Study Design

1. Recruitment

Participants will be recruited from among patients of the Department of Urology, Centre of Postgraduate Medical Education, Orlowski Hospital, Warsaw, who are scheduled for urethral reconstructive surgery. During the pre-anesthetic clinic visit or following hospital admission on the day preceding surgery, patients will receive detailed information about the study and an informed consent form for participation in the clinical trial. They will have the opportunity to ask questions and receive comprehensive answers. Signed consent forms will be collected on the morning of surgery. 2. Randomization and Blinding

Patients will be randomly assigned to one of three groups:

Dexmedetomidine group: intravenous dexmedetomidine bolus of 0.6 μg/kg administered over 10 minutes before induction of anesthesia, followed by continuous infusion at 0.6 μg/kg/h until the end of surgery; Lidocaine group: intravenous lidocaine bolus of 1.5 mg/kg administered over 10 minutes before induction of anesthesia, followed by continuous infusion at 1.5 mg/kg/h until the end of surgery; Control group: placebo consisting of 0.9% sodium chloride administered according to an identical volume-based regimen.

Randomization will be performed using the website www.randomizer.org with equal allocation among the three study groups.

Blinding will be ensured using opaque, sealed envelopes containing the randomization number. The envelope will be opened immediately before preparation of the study infusion on the day of surgery, following acquisition of informed consent, by a physician who is a member of the research team but will not be involved in the patient's subsequent intraoperative or postoperative care. This physician will prepare the study medication in a 50-mL syringe according to the coded allocation:

1. \- dexmedetomidine 4 μg/mL 2. \- lidocaine 10 mg/mL 3. \- 0.9% sodium chloride (NaCl)

Neither the patient nor the clinical staff involved in perioperative care will be aware of treatment allocation (double-blind design).

Patient data will be collected in a secure database inaccessible to unauthorized individuals and will include demographic data (age, height, body weight, ASA status, comorbidities, substance use, location of urethral stricture), surgical data (fluid administration, duration of surgery, blood loss), and intervention-related data (total amount of study drug administered and anesthesia-related complications such as hypotension or bradycardia requiring vasoactive treatment).

3\. Perioperative Management

Upon arrival in the operating room, standard monitoring of vital signs will be initiated and prophylactic antibiotics administered according to institutional protocols.

The study drug infusion will then be started at a rate of 0.9 mL/kg/h and continued for 10 minutes, corresponding to a dose of 0.6 μg/kg dexmedetomidine or 1.5 mg/kg lidocaine.

Subsequently, the infusion will be continued until placement of the final skin suture at a rate of 0.15 mL/kg/h, corresponding to 0.6 μg/kg/h dexmedetomidine or 1.5 mg/kg/h lidocaine.

General anesthesia will be induced and maintained using standard doses of opioids and anesthetic agents, with maintenance by inhalational anesthesia using sevoflurane.

Postoperatively, all patients will receive standardized multimodal analgesia consisting of paracetamol 1 g every 6 hours, metamizole 1 g every 6 hours, and intravenous dexketoprofen 50 mg three times daily. In cases of insufficient analgesia (pain intensity \>3 on the Numeric Rating Scale \[NRS\]), buprenorphine 0.3 mg intravenously or intramuscularly will be administered at intervals no shorter than 2 hours, with an additional intravenous bolus of 0.3 mg permitted for breakthrough pain if required.

4\. Assessment of Acute Pain and Quality of Recovery

During the first 48 postoperative hours, pain intensity will be assessed using the Numeric Rating Scale (NRS 0-10) both at rest and during coughing at predefined time points: 2, 4, 8, 24, and 48 hours after surgery.

Total opioid consumption (buprenorphine) during the first 24 hours and time to first opioid administration will be recorded.

Before discharge, patients will complete the Polish version of the Quality of Recovery questionnaire (QoR-15).

• Number of patients with at least one episode of bradycardia [Time frame: 24 hours]
• Number of patients with at least one episode of hypotension [Time frame: 24 hours]
• Intensity of postoperative pain assesses by Numeric Rating Scale (NRS, 0-10; 0 = no pain, 10 = worst pain imaginable) [Time frame: 48 hours]
• Time to first opioid request [Time frame: 24 hours]
• Number of patients with at least one reported episode of nausea [Time frame: 24 hours]
• Number of patients with at least one episode of vomiting [Time frame: 24 hours]
• Quality of Recovery - 15 score (QoR-15, 0-150, 0 = very poor recovery, 150 = excellent recovery) [Time frame: 48 hours]