Hip Osteoarthritis
Conditions
Brief summary
Surgical trauma induces activation of the sympathetic nervous system and triggers a systemic inflammatory response that may adversely affect postoperative recovery. Dexmedetomidine, a highly selective α2-adrenoceptor agonist, has been proposed as a pharmacological neuromodulatory strategy capable of attenuating sympathetic activation and modulating neuroimmune interactions during the perioperative period. However, the extent to which intravenous dexmedetomidine influences perioperative inflammatory biomarkers and clinical recovery in patients undergoing total hip arthroplasty under regional anesthesia remains unclear. This prospective, randomized, double-blind, placebo-controlled trial aims to evaluate the effects of two doses of intravenous dexmedetomidine administered during spinal anesthesia combined with ultrasound-guided pericapsular nerve group (PENG) block on autonomic regulation, systemic inflammatory response, postoperative pain, opioid consumption, and quality of recovery following elective primary total hip arthroplasty.
Detailed description
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.
Interventions
DRUGPlacebo
Intravenous administration of 0.9% saline according to the study protocol during elective primary total hip arthroplasty performed under spinal anesthesia combined with ultrasound-guided Pericapsular Nerve Group (PENG) block. The placebo solution will be identical in appearance and volume to dexmedetomidine to maintain blinding.
DRUGDexmedetomidine
Intravenous dexmedetomidine administered according to the randomized study protocol during elective primary total hip arthroplasty performed under spinal anesthesia combined with ultrasound-guided Pericapsular Nerve Group (PENG) block. Participants will receive low-dose dexmedetomidine according to group allocation.
Sponsors
Poznan University of Medical Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 90 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Systemic Immune-Inflammation Index (SII) | 24 24 hours after surgery | Comparison of the change in the Systemic Immune-Inflammation Index (SII) from baseline to 24 hours after surgery among the three study groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Systemic Immune-Inflammation Index (SII) | 12 hours after surgery | Comparison of the change in the Systemic Immune-Inflammation Index (SII) from baseline to 12 hours after surgery |
| Neutrophil-to-Lymphocyte Ratio (NLR) | 12 hours after surgery | Neutrophil-to-lymphocyte ratio (NLR), calculated from routine peripheral blood counts |
| Platelet-to-Lymphocyte Ratio (PLR) | 12 hours after surgery | Platelet-to-lymphocyte ratio (NLR), calculated from routine peripheral blood counts |
| C-reactive protein (CRP) | 24 hours after surgery | postoperative C-reactive protein (CRP) concentrations |
| Postoperative opioid consumption | 48 hours after surgery | Cumulative postoperative opioid consumption expressed as intravenous morphine milligram equivalents (MME). |
| Time to first rescue opioid analgesia | 48 hours after surgery | Comparison of the time from the end of surgery to the first administration of rescue opioid analgesia among the three study groups. |
| QoR-15 | 24 hours after surgery | Comparison of postoperative quality of recovery assessed using the Quality of Recovery-15 (QoR-15) questionnaire among the three study groups. |
| Postoperative pain intensity at rest | 2 hours after surgery | Comparison of postoperative pain intensity at rest assessed using the 11-point Numeric Rating Scale (NRS), where 0 indicates no pain and 10 indicates the worst pain imaginable, among the three study groups. |
| Postoperative pain intensity at movement | 2 hours after surgery | Comparison of postoperative pain intensity at rest assessed using the 11-point Numeric Rating Scale (NRS), where 0 indicates no pain and 10 indicates the worst pain imaginable, among the three study groups. |
| Incidence of postoperative nausea and vomiting | 48 haours after surgery | Comparison of the incidence of postoperative nausea and vomiting (PONV) within the first 48 hours after surgery among the three study groups. |
| Intraoperative vasopressor requirement | durring surgery | Comparison of cumulative vasopressor requirements administered to maintain adequate arterial blood pressure during surgery. |
| Incidence of intraoperative hypotension | durring surgery | Comparison of the incidence of intraoperative hypotension defined as a mean arterial pressure below 65 mmHg requiring therapeutic intervention. |
| Systemic Inflammation Response Index (SIRI) | 24 hours after surgery | Comparison of the Systemic Inflammation Response Index (SIRI), calculated from routine peripheral blood counts, among the three study groups as a marker of the perioperative systemic inflammatory response. |
| Aggregate Index of Systemic Inflammation (AISI) | 24 hours after surgery | Comparison of the Aggregate Index of Systemic Inflammation (AISI), calculated from routine peripheral blood counts, among the three study groups as a marker of the perioperative systemic inflammatory response. |
Countries
Poland
Contacts
CONTACTMAlgorzata Reysner, MD PhD
CONTACTMalgorzata Reysner, MD PhD
STUDY_CHAIRMalgorzata Reysner, MD PhD
Poznan University of Medical Sciences
Outcome results
None listed