Intravenous Dexmedetomidine as a Perioperative Autonomic-Immune Neuromodulator

Total hip arthroplasty is associated with substantial surgical stress resulting in activation of the sympathetic nervous system, neuroendocrine stress pathways, and systemic inflammation. Excessive perioperative autonomic activation contributes to inflammatory dysregulation, postoperative pain, opioid requirements, delayed functional recovery, and postoperative complications. Strategies capable of attenuating this autonomic stress response may therefore improve postoperative outcomes beyond conventional analgesia.

Dexmedetomidine is a highly selective α2-adrenoceptor agonist with sedative, analgesic, sympatholytic, and anti-inflammatory properties. Experimental and clinical evidence suggests that intravenous dexmedetomidine may reduce sympathetic outflow, attenuate neuroendocrine stress responses, modulate cytokine release, and preserve autonomic homeostasis during the perioperative period. Nevertheless, prospective randomized studies evaluating its effects on both autonomic regulation and systemic inflammatory response in patients receiving contemporary regional anesthesia remain limited.

This prospective, randomized, double-blind, placebo-controlled trial will compare three perioperative strategies in patients undergoing elective primary total hip arthroplasty under spinal anesthesia combined with ultrasound-guided PENG block:

placebo, low-dose intravenous dexmedetomidine, high-dose intravenous dexmedetomidine. All patients will receive identical surgical, anesthetic, and multimodal analgesic management. Intravenous dexmedetomidine administration will constitute the only study intervention.

The primary objective is to determine whether intravenous dexmedetomidine attenuates the perioperative systemic inflammatory response as assessed by changes in the Systemic Immune-Inflammation Index (SII). Secondary objectives include evaluation of additional inflammatory biomarkers including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), monocyte-to-lymphocyte ratio (MLR), Systemic Inflammation Response Index (SIRI), and Aggregate Index of Systemic Inflammation (AISI), together with perioperative hemodynamic stability, vasopressor requirements, postoperative pain intensity, opioid consumption, time to first rescue analgesia, quality of recovery assessed using the Quality of Recovery-15 (QoR-15) questionnaire, postoperative nausea and vomiting, time to first ambulation, length of hospital stay, patient satisfaction, and postoperative complications.

The study is designed to investigate intravenous dexmedetomidine as a perioperative pharmacological autonomic-immune neuromodulatory strategy rather than solely an analgesic adjuvant. The findings may improve understanding of the relationship between autonomic regulation, systemic inflammation, and postoperative recovery, and contribute to optimization of perioperative multimodal anesthesia for patients undergoing total hip arthroplasty.

Inclusion criteria

• Adults aged 50-90 years.
• Scheduled for elective primary total hip arthroplasty due to primary hip osteoarthritis.
• American Society of Anesthesiologists (ASA) physical status I-III.
• Planned spinal anesthesia combined with ultrasound-guided Pericapsular Nerve Group (PENG) block.
• Ability to understand the study procedures and provide written informed consent.

Exclusion criteria

• Refusal to participate or inability to provide written informed consent.
• Contraindications to spinal anesthesia.
• Contraindications to PENG block.
• Allergy or hypersensitivity to dexmedetomidine, ropivacaine, bupivacaine, or study medications.
• Second- or third-degree atrioventricular block without a permanent pacemaker.
• Resting heart rate <50 beats/min.
• Severe hepatic impairment (Child-Pugh class C).
• Severe renal failure requiring dialysis.
• Chronic opioid therapy (>3 months before surgery).
• Chronic treatment with α2-adrenergic agonists.
• Cognitive impairment or inability to complete postoperative questionnaires.
• Infection at the injection site.
• Coagulopathy or ongoing anticoagulation precluding neuraxial anesthesia according to current guidelines.
• Revision total hip arthroplasty.
• Simultaneous bilateral total hip arthroplasty.
• Participation in another interventional clinical trial within the previous 30 days.