Nerve Block and Perioperative Myocardial Injury in Elderly Hip Fracture

Study Rationale and Background Hip fracture represents a major public health burden among aging populations worldwide, with rapidly rising incidence driven by global demographic shifts. In older adults, hip fracture is associated with substantially elevated morbidity and mortality, with 1-year mortality rates reaching 20-30% even after surgical treatment. Current clinical guidelines uniformly recommend surgery within 48 hours of injury as the standard of care to improve outcomes. However, delayed surgery - defined as surgery performed more than 48 hours after injury - remains highly prevalent globally, particularly in resource-limited settings, affecting up to 60-80% of patients in some regions.

Accumulating evidence demonstrates that delayed surgery is associated with a dose-dependent increase in postoperative complications and mortality, with each 24-hour delay linked to a 12% higher risk of major adverse cardiovascular events (MACE) and a 5% relative increase in 30-day mortality. A key mediator of this elevated risk is perioperative myocardial injury, also termed myocardial injury after noncardiac surgery (MINS). MINS is defined as troponin elevation above the 99th percentile upper reference limit attributable to ischemic mechanisms, and it is one of the most common serious perioperative complications in older surgical patients. In hip fracture populations, the incidence of myocardial injury is particularly high, and it is strongly associated with short- and long-term mortality. The elevated cardiac risk in delayed surgery is driven primarily by sustained severe pain leading to sympathetic overactivation, heightened systemic inflammation, hypercoagulability, and physiological stress from prolonged preoperative immobilization.

Peripheral nerve block (PNB) is the gold standard for perioperative pain management in hip fracture, strongly recommended by international anesthesiology and orthopedic guidelines. Ultrasound-guided PNB techniques, including pericapsular nerve group (PENG) block, fascia iliaca compartment block, and femoral nerve block, provide effective analgesia and reduce opioid consumption. A recent landmark two-center cohort study published in Anesthesiology in 2026 found that preoperative single-injection PNB reduced the risk of postoperative myocardial injury by 40% in high-risk older adults undergoing hip fracture surgery.

Nevertheless, critical evidence gaps remain. The prior study included a mixed population of both early and delayed surgery patients, and did not specifically evaluate the cardiac protective effect of PNB in the delayed surgery subgroup - a population at markedly higher baseline cardiac risk. It also did not distinguish preoperatively existing myocardial injury from new-onset postoperative injury, nor did it examine the potential impact of block timing or different block techniques on cardiac outcomes. It remains unknown whether PNB still confers cardiac benefit in patients who have already sustained prolonged pain and stress from delayed surgery, and whether it can attenuate progression of myocardial injury in patients with preoperatively elevated troponin.

Study Objectives This single-center retrospective cohort study aims to investigate the effect of preoperative single-injection peripheral nerve block on perioperative myocardial injury in older patients undergoing delayed hip fracture surgery (time from injury to surgery \> 48 hours).

The primary objective is to compare the incidence of in-hospital postoperative myocardial injury between patients who receive preoperative single-injection PNB and those who do not.

Secondary objectives include:

Comparing the incidence of new-onset myocardial injury within 72 hours postoperatively among patients with normal preoperative troponin Evaluating the effect of PNB on troponin trajectory in patients with preoperatively elevated troponin Comparing peak troponin levels and the area under the troponin time-concentration curve between groups Comparing 30-day MACE and all-cause mortality Comparing other postoperative complications, intensive care unit admission rates, and length of hospital stay Exploring the time-window effect of PNB (block performed within 24 hours of injury vs. 24-48 hours after injury) Comparing the efficacy of different PNB techniques Assessing the interaction between preoperative troponin status and the therapeutic effect of PNB Study Design and Population This is a single-center retrospective cohort study conducted at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China. The study will include patients aged 65 years or older who underwent surgery for non-pathological hip fracture (femoral neck, intertrochanteric, or subtrochanteric fracture) between January 1, 2019 and December 31, 2025, with a time from injury to surgery exceeding 48 hours. Patients must have at least one troponin measurement during the preoperative or postoperative hospital stay. Patients will be excluded if they have preoperative acute myocardial infarction, acute heart failure, or sepsis; multiple fractures or concurrent surgery at other sites; nerve block used as the sole anesthetic technique; continuous nerve block or epidural analgesia; or missing critical data.

Eligible patients will be divided into two groups based on whether they received a single-injection preoperative peripheral nerve block:

PNB group: Patients who received single-shot peripheral nerve block as an adjunct to anesthesia and analgesia, including but not limited to PENG block, fascia iliaca compartment block, femoral nerve block, and lumbar plexus block.

Non-PNB group: Patients who did not receive any peripheral nerve block. Prespecified subgroup analyses will be performed according to preoperative troponin status (normal vs. elevated), timing of block administration, type of block technique, duration of surgical delay, and Revised Cardiac Risk Index (RCRI) score.

Outcome Measures The primary outcome is the incidence of in-hospital postoperative myocardial injury, defined as any troponin value above the 99th percentile upper reference limit during postoperative hospitalization, consistent with the definition used in the prior landmark study to ensure comparability.

Secondary outcomes include new-onset myocardial injury within 72 hours postoperatively, change in peak troponin from baseline in patients with preoperative elevation, peak troponin level and area under the troponin curve, 30-day MACE (composite of nonfatal myocardial infarction, heart failure, cardiac death, and ischemic stroke), 30-day all-cause mortality, other postoperative complications (pneumonia, delirium, venous thromboembolism, urinary tract infection, etc.), intensive care unit admission rate, and length of hospital stay.

Data Collection and Statistical Analysis All study data will be retrospectively extracted from the hospital electronic medical record system, including demographic characteristics, comorbidities, preoperative laboratory results, fracture and surgical details, nerve block characteristics (type, timing, local anesthetic dose), serial troponin measurements, and postoperative clinical outcomes. No additional testing or intervention beyond standard clinical care will be performed.

Descriptive statistics will be used to present baseline characteristics. Absolute standardized difference (ASD) will be applied to assess baseline balance between groups, with ASD \> 0.1 indicating meaningful imbalance. Inverse probability of treatment weighting (IPTW) will be used to adjust for confounding variables. Propensity scores will be estimated using a multivariable logistic regression model incorporating demographic, comorbidity, preoperative, and intraoperative variables.

For the primary outcome, IPTW-adjusted multivariable logistic regression will be performed to calculate the adjusted odds ratio and 95% confidence interval. Appropriate adjusted regression models will be used for binary, continuous, and time-to-event secondary outcomes. Stratified analyses and interaction tests will be conducted to explore effect heterogeneity across subgroups. Multiple sensitivity analyses, including complete-case analysis, propensity score matching, alternative troponin thresholds, and E-value analysis, will be performed to test the robustness of the findings.

Sample size calculation is based on previously published effect estimates and baseline event rates in delayed surgery populations. A total of 500 patients will be enrolled, accounting for an expected 15% data missing rate and 20% sample reserve for subgroup analyses. This sample size provides at least 80% statistical power to detect the hypothesized difference in the primary outcome at a two-sided significance level of 0.05.

Ethical Considerations This is a retrospective observational study that does not alter routine clinical practice or impose any additional risk on patients. The study protocol has been submitted to the Institutional Review Board of Tongji Hospital for ethical approval, and a waiver of written informed consent will be requested due to the retrospective design. All patient data will be de-identified prior to analysis to protect patient privacy and confidentiality, in accordance with the Declaration of Helsinki. Study results will be disseminated through peer-reviewed publications and academic presentations, without disclosure of identifiable patient information.

Expected Significance This study will provide targeted evidence on the cardiac protective effect of preoperative single-injection PNB specifically in older hip fracture patients with delayed surgery - a high-risk population that has been understudied. The findings will clarify whether PNB reduces myocardial injury in this vulnerable group, identify optimal timing and technique for maximum benefit, and determine whether benefit extends to patients with preexisting myocardial injury. These results will help clinicians refine perioperative management strategies, allocate analgesic resources to highest-risk patients, and improve cardiovascular outcomes in older adults with hip fracture who cannot receive timely surgery. The study will also inform future guideline updates and support the design of prospective interventional trials.

• The incidence of new myocardial injury within 72 hours after the operation [Time frame: Before the operation, 24 hours after the operation, 48 hours after the operation, 72 hours after the operation; at discharge (up to 2 weeks); 30 days after the operation]
• The magnitude of the increase in postoperative troponin levels compared to the baseline in patients with elevated troponin levels before the operation [Time frame: The amplitude of the increase in postoperative troponin levels compared to the baseline in patients with elevated troponin levels before the operation at 24 hours, 48 hours, 72 hours, at discharge (up to 2 weeks) and 30 days after the operation.]
• The area under the curve of the peak value and dynamic changes of troponin [Time frame: The area under the curve of peak troponin levels and their dynamic changes before surgery, 24 hours after surgery, 48 hours after surgery, 72 hours after surgery; at discharge (up to 2 weeks); and 30 days after surgery]
• 30 days after the surgery, the incidence of major adverse cardiovascular events (MACE) and all-cause mortality [Time frame: 30 days after the operation]
• ICU admission [Time frame: 24 hours after the operation, 48 hours after the operation, 72 hours after the operation; at discharge (up to 2 weeks); 30 days after the operation]
• The type of blocking techniques [Time frame: During the operation]
• The interaction between preoperative troponin status and the efficacy of nerve block [Time frame: Before the operation, 24 hours after the operation, 48 hours after the operation, 72 hours after the operation; at discharge (up to 2 weeks); 30 days after the operation]
• Hospital stay [Time frame: 24 hours after the operation, 48 hours after the operation, 72 hours after the operation; at discharge (up to 2 weeks); 30 days after the operation]
• Other adverse effects [Time frame: 24 hours after the operation, 48 hours after the operation, 72 hours after the operation; at discharge (up to 2 weeks); 30 days after the operation]