Prehabilitation in Adults Undergoing Cancer Surgery: A Comprehensive Review on Rationale, Methodology, and Measures of Effectiveness.

Cancer surgery places a significant burden on a patients' functional status and quality of life. In addition, cancer surgery is fraught with postoperative complications, themselves influenced by a patient's functional status. Prehabilitation is a unimodal or multimodal strategy that aims to increase a patient's functional capacity to reduce postoperative complications and improve postoperative recovery and quality of life. In most cases, it involves exercise, nutrition, and anxiety-reducing interventions. The impact of prehabilitation has been explored in several types of cancer surgery, most commonly colorectal and thoracic. Overall, the existing evidence suggests prehabilitation improves physiological outcomes (e.g., lean body mass, maximal oxygen consumption) as well as clinical outcomes (e.g., postoperative complications, quality of life). Notably, the benefit of prehabilitation is additional to that of enhanced recovery after surgery (ERAS) programs. While safe, prehabilitation programs require multidisciplinary coordination preoperatively. Despite the existence of numerous systematic reviews and meta-analyses, the certainty of evidence demonstrating the efficacy and safety of prehabilitation is low to moderate, principally due to significant methodological heterogeneity and small sample sizes. There is a need for more large-scale multicenter randomized controlled trials to draw strong clinical recommendations.

Use of a Combination Lavender/Peppermint Aromatherapy Patch During Port Catheter Placement Under Monitored Anesthesia Care Does Not Reduce Time to Discharge Readiness: A Randomized Controlled Trial.

Background: Intraoperative anxiety is a common problem when Monitored Anesthesia Care (MAC) is used instead of general anesthesia during minor surgical procedures such as port catheter placement. Nonpharmacological anxiolytics such as aromatherapy have been studied for their effects on preoperative anxiety, but no placebo-controlled study of aromatherapy during surgeries under MAC has yet been performed. Methods: After IRB approval, 70 patients were randomized 1:1 to receive either a lavender/peppermint aromatherapy patch (Elequil Aromatabs®; Beekley Corporation) or a matching placebo patch. The primary outcome, time to readiness for discharge from postoperative acute care units (PACU; min), was assessed every 15 min until a modified postanesthesia recovery score for ambulatory patients (PARSAP) score of 18 or higher was reached. In the preoperative holding area, the assigned patch/placebo was activated and affixed to a folded towel placed aside the subject's head, contralateral to the side of the planned surgery. The towel and patch/placebo were discarded when the subject left the operating room (OR). Results: No difference was found between the treatment and placebo groups on the primary outcome of time to discharge readiness (mean [standard deviation, SD]: 82 [15] vs. 89 [21] min, respectively, p = 0.131). No difference was found between the treatment and placebo groups on the secondary outcomes of intraoperative midazolam dose, intraoperative opioid dose, intraoperative ondansetron dose, or intraoperative promethazine dose. No difference was found between the treatment and placebo groups in the proportion of subjects requiring rescue postoperative nausea and vomiting (PONV) medication in the PACU or the proportion of subjects requiring opioids in the PACU. No difference was found between the treatment and placebo groups in pain intensity in PACU, average PONV score in PACU, or patient satisfaction in PACU. PACU patient satisfaction was high for both the patch and placebo groups (35/35 [100%] vs. 32/34 [94%] "very satisfied," p = 0.239). Conclusions: Aromatherapy treatment is not indicated intraoperatively to reduce anxiety or the use of antiemetics in patients requiring Port catheter placement. Trial registration: Clinicaltrials.gov, identifier: NCT05328973.

Lost in Translation: Failure of Preclinical Studies to Accurately Predict the Effect of Regional Analgesia on Cancer Recurrence.

The major goal of translational research is to evaluate the efficacy and effectiveness of treatments and interventions that have emerged from exhaustive preclinical evidence. In 2007, a major clinical trial was started to investigate the impact of paravertebral analgesia on breast cancer recurrence. The trial was based on preclinical evidence demonstrating that spinal anesthesia suppressed metastatic dissemination by inhibiting surgical stress, boosting the immunological response, avoiding volatile anesthetics, and reducing opioid use. However, that trial and three more recent randomized trials with a total of 4,770 patients demonstrate that regional analgesia does not improve survival outcomes after breast, lung, and abdominal cancers. An obvious question is why there was an almost complete disconnect between the copious preclinical investigations suggesting benefit and robust clinical trials showing no benefit? The answer is complex but may result from preclinical research being mechanistically driven and based on reductionist models. Both basic scientists and clinical investigators underestimated the limitations of various preclinical models, leading to the apparently incorrect hypothesis that regional anesthesia reduces cancer recurrence. This article reviews factors that contributed to the discordance between the laboratory science, suggesting that regional analgesia might reduce cancer recurrence and clinical trials showing that it does not-and what can be learned from the disconnect.

Race, Ethnicity, and Sustained Opioid Use After Major Abdominal Surgery for Cancer.

Purpose: Sustained opioid use is a well-known complication after surgery. Our objective was to determine whether there is any association between a patient's race or ethnicity and the sustained use of opioids in the year following surgery. Opioid use over the initial 3, 6, and 12 postoperative months was categorized as "sustained early", persistent, and chronic, respectively. Patients and Methods: Single-institution retrospective study of adults (≥18 years) who had undergone open abdominal surgery for cancer. Multivariable logistic regression was used to evaluate the association between race/ethnicity and opioid use. Results: Of the 3523 patients included in the study, 2543 (72.2%) were non-Hispanic (NH) White, 476 (13.5%) were Hispanic or Latino, 262 (7.4%) were NH-Black, 186 (5.3%) were Asian, and 56 (1.6%) belonged to other racial or ethnic groups. The overall rates of sustained early, persistent, and chronic opioid use were 15.9%, 7.1%, and 2.6%, respectively. In the multivariable analysis, patient race/ethnicity was associated with sustained early postoperative opioid use (p-value=0.037), with Hispanics/Latinos having significantly higher odds than NH-Whites (OR = 1.382 [95% CI: 1.057-1.808]; p = 0.018). However, neither persistent nor chronic opioid use was associated with race/ethnicity (p = 0.697 and p = 0.443, respectively). Conclusion: In this retrospective study of adults who had undergone open abdominal surgery, patient race/ethnicity was not consistently associated with the development of sustained opioid use over the first 12 postoperative months.

Enhanced recovery protocols for ambulatory surgery.

INTRODUCTION: In the United States, ambulatory surgeries account for up to 87% of all surgical procedures. (1) It was estimated that 19.2 million ambulatory surgeries were performed in 2018 (https://www.hcup-us.ahrq.gov/reports/statbriefs/sb287-Ambulatory-Surgery-Overview-2019.pdf). Cataract procedures and musculoskeletal surgeries are the most common surgical interventions performed in ambulatory centers. However, more complex surgical interventions, such as sleeve gastrectomies, oncological, and spine surgeries, and even arthroplasties are routinely performed as day cases or in a model of an ambulatory extended recovery. (2-5) The ambulatory surgery centers industry has grown since 2017 by 1.1% per year and reached a market size of $31.2 billion. According to the Ambulatory Surgery Center Association, there is a potential to save $57.6 billion in Medicare costs over the next decade (https://www.ibisworld.com/industry-statistics/market-size/ambulatory-surgery-centers-united-states/). These data suggest an expected rise in the volume of ambulatory (same day) or extended ambulatory (23 h) surgeries in coming years. Similar increases are also observed in other countries. For example, 75% of elective surgeries are performed as same-day surgery in the United Kingdom. (6) To reduce costs and improve the quality of care after those more complex procedures, ambulatory surgery centers have started implementing patient-centered, high-quality, value-based practices. To achieve those goals, Enhanced Recovery After Surgery (ERAS) protocols have been implemented to reduce the length of stay, decrease costs, increase patients' satisfaction, and transform clinical practices. The ERAS fundamentals for ambulatory surgery are based on five pillars, including (1) preoperative patient counseling, education, and optimization; (2) multimodal and opioid-sparing analgesia; (3) nausea and vomiting, wound infection, and venous thromboembolism prophylaxis; (4) maintenance of euvolemia; and (5) encouragement of early mobility. Those pillars rely on interdisciplinary teamwork led by anesthesiologists, surgery-specific workgroups, and safety culture. (2) Research shows that a team of ambulatory anesthesiologists is crucial in improving postoperative nausea and vomiting (PONV) and pain control. (7) This review will summarize the current evidence on the elements and clinical importance of implementing ERAS protocol for ambulatory surgery.

Antiemetic prophylaxis with droperidol in morphine-based intravenous patient-controlled analgesia: a propensity score matched cohort study.

BACKGROUND: There are limited real-world data regarding the use of droperidol for antiemetic prophylaxis in intravenous patient-controlled analgesia (IV-PCA). This study aimed to evaluate the antiemetic benefits and sedation effects of droperidol in morphine-based IV-PCA. METHODS: Patients who underwent major surgery and used morphine-based IV-PCA at a medical center from January 2020 to November 2022 were retrospectively analyzed. The primary outcome was the rate of any postoperative nausea and/or vomiting (PONV) within 72 h after surgery. Propensity score matching was used to match patients with and without the addition of droperidol to IV-PCA infusate in a 1:1 ratio. Multivariable conditional logistic regression models were used to calculate adjusted odds ratios (aORs) with 95% confidence intervals (CIs). RESULTS: After matching, 1,104 subjects were included for analysis. The addition of droperidol to IV-PCA reduced the risk of PONV (aOR: 0.49, 95% CI: 0.35-0.67, p < 0.0001). The antiemetic effect of droperidol was significant within 36 h after surgery and attenuated thereafter. Droperidol was significantly associated with a lower risk of antiemetic uses (aOR: 0.58, 95% CI: 0.41-0.80, p = 0.0011). The rate of unintentional sedation was comparable between the patients with (9.1%) and without (7.8%; p = 0.4481) the addition of droperidol. Postoperative opioid consumption and numeric rating scale acute pain scores were similar between groups. CONCLUSIONS: The addition of droperidol to IV-PCA reduced the risk of PONV without increasing opiate consumption or influencing the level of sedation. However, additional prophylactic therapies are needed to prevent late-onset PONV.

METTL3-mediated N6-methyladenosine exacerbates ferroptosis via m6A-IGF2BP2-dependent mitochondrial metabolic reprogramming in sepsis-induced acute lung injury.

Neutrophil extracellular traps (NETs), released by polymorphonuclear neutrophils (PMNs), exert a robust antimicrobial function in infectious diseases such as sepsis. NETs also contribute to the pathogenesis and exacerbation of sepsis. Although the lung is highly vulnerable to infections, few studies have explored the role of NETs in sepsis-induced acute lung injury (SI-ALI). We demonstrate that NETs induce SI-ALI via enhanced ferroptosis in alveolar epithelial cells. Our findings reveal that the excessive release of NETs in patients and mice with SI-ALI is accompanied by upregulation of ferroptosis depending on METTL3-induced m6A modification of hypoxia-inducible factor-1α (HIF-1α) and subsequent mitochondrial metabolic reprogramming. In addition to conducting METTL3 overexpression and knockdown experiments in vitro, we also investigated the impact of ferroptosis on SI-ALI caused by NETs in a caecum ligation and puncture (CLP)-induced SI-ALI model using METTL3 condition knockout (CKO) mice and wild-type mice. Our results indicate the crucial role of NETs in the progression of SI-ALI via NET-activated METTL3 m6A-IGF2BP2-dependent m6A modification of HIF-1α, which further contributes to metabolic reprogramming and ferroptosis in alveolar epithelial cells.

Effect of neoadjuvant chemotherapy on intraoperative core temperature in patients with breast cancer: a retrospective cohort study.

Background: Clinical evidence suggests that chemotherapeutic agents are associated with neuropathy and peripheral autonomic dysfunction. However, the possible effects of neoadjuvant chemotherapy on intraoperative temperature remain poorly characterised. Methods: We evaluated patients who underwent a mastectomy for breast cancer between April 2016 and July 2020. Propensity scores were used to match patients who received neoadjuvant chemotherapy with those who did not, and intraoperative core temperature patterns were analysed in the matched cohort. The independent associations between vasopressor use and heart rate during general anaesthesia in the matched cohort were also analysed. Results: Data from 1764 patients were analysed (882 patients in each group). Both groups presented a similar pattern of heat redistribution and subsequent rewarming; however, the neoadjuvant chemotherapy group did not reach the same intraoperative plateau temperature as the group that did not receive prior chemotherapy, with differences of up to 0.4°C (95% confidence interval: 0.11-0.63°C; P=0.005). In a subgroup analysis, neuropathy in patients who received neoadjuvant chemotherapy was associated with increased use of vasopressors and higher heart rate. Conclusions: In patients with breast cancer, neoadjuvant chemotherapy is associated with lower plateau core temperatures, increased vasopressor use, and higher heart rates during general anaesthesia, which is more severe in the presence of neuropathy.

Incidence of acute kidney injury after noncardiac surgery in patients receiving intraoperative dexmedetomidine: a retrospective study.

Background: Postoperative acute kidney injury (AKI) is a common complication and is associated with increased hospital length of stay and 30 day all-cause mortality. Unfortunately, we have neither a defined strategy to prevent AKI nor an effective treatment. In vitro, animal, and human studies have suggested that dexmedetomidine may have a renoprotective effect. We conducted a retrospective cohort study to evaluate if intraoperative dexmedetomidine was associated with a reduced incidence of AKI. Methods: We collected data from 6625 patients who underwent major non-cardiothoracic cancer surgery. Before and after propensity score matching, we compared the incidence of postoperative AKI in patients who received intraoperative dexmedetomidine and those who did not. AKI was defined according to the Kidney Disease Improving Global Outcomes (creatinine alone values) criteria and calculated for postoperative Days 1, 2, and 3. Results: Twenty per cent (n=1301) of the patients received dexmedetomidine. The mean [standard deviation] administered dose was 78 [49.4] mcg. Patients treated with dexmedetomidine were matched to those who did not receive the drug. Patients receiving dexmedetomidine had a longer anaesthesia duration than the non-dexmedetomidine group. The incidence of AKI was not significantly different between the groups (dexmedetomidine 8% vs no dexmedetomidine 7%; P=0.333). The 30 day rates of infection, cardiovascular complications, or reoperation attributable to bleeding were higher in patients treated with dexmedetomidine. The 30 day mortality rate was not statistically different between the groups. Conclusions: The administration of dexmedetomidine during major non-cardiothoracic cancer surgery is not associated with a reduction in AKI within 72 h after surgery.

Effect of colchicine on perioperative atrial fibrillation and myocardial injury after non-cardiac surgery in patients undergoing major thoracic surgery (COP-AF): an international randomised trial.

BACKGROUND: Higher levels of inflammatory biomarkers are associated with an increased risk of perioperative atrial fibrillation and myocardial injury after non-cardiac surgery (MINS). Colchicine is an anti-inflammatory drug that might reduce the incidence of these complications. METHODS: COP-AF was a randomised trial conducted at 45 sites in 11 countries. Patients aged 55 years or older and undergoing major non-cardiac thoracic surgery were randomly assigned (1:1) to receive oral colchicine 0·5 mg twice daily or matching placebo, starting within 4 h before surgery and continuing for 10 days. Randomisation was done with use of a computerised, web-based system, and was stratified by centre. Health-care providers, patients, data collectors, and adjudicators were masked to treatment assignment. The coprimary outcomes were clinically important perioperative atrial fibrillation and MINS during 14 days of follow-up. The main safety outcomes were a composite of sepsis or infection, and non-infectious diarrhoea. The intention-to-treat principle was used for all analyses. This trial is registered with ClinicalTrials.gov, NCT03310125. FINDINGS: Between Feb 14, 2018, and June 27, 2023, we enrolled 3209 patients (mean age 68 years [SD 7], 1656 [51·6%] male). Clinically important atrial fibrillation occurred in 103 (6·4%) of 1608 patients assigned to colchicine, and 120 (7·5%) of 1601 patients assigned to placebo (hazard ratio [HR] 0·85, 95% CI 0·65 to 1·10; absolute risk reduction [ARR] 1·1%, 95% CI -0·7 to 2·8; p=0·22). MINS occurred in 295 (18·3%) patients assigned to colchicine and 325 (20·3%) patients assigned to placebo (HR 0·89, 0·76 to 1·05; ARR 2·0%, -0·8 to 4·7; p=0·16). The composite outcome of sepsis or infection occurred in 103 (6·4%) patients in the colchicine group and 83 (5·2%) patients in the placebo group (HR 1·24, 0·93-1·66). Non-infectious diarrhoea was more common in the colchicine group (134 [8·3%] events) than the placebo group (38 [2·4%]; HR 3·64, 2·54-5·22). INTERPRETATION: In patients undergoing major non-cardiac thoracic surgery, administration of colchicine did not significantly reduce the incidence of clinically important atrial fibrillation or MINS but increased the risk of mostly benign non-infectious diarrhoea. FUNDING: Canadian Institutes of Health Research, Accelerating Clinical Trials Consortium, Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario, Population Health Research Institute, Hamilton Health Sciences, Division of Cardiology at McMaster University, Canada; Hanela Foundation, Switzerland; and General Research Fund, Research Grants Council, Hong Kong.

MNK inhibitor eFT508 (Tomivosertib) suppresses ectopic activity in human dorsal root ganglion neurons from dermatomes with radicular neuropathic pain.

Spontaneous activity in dorsal root ganglion (DRG) neurons is a key driver of neuropathic pain in preclinical models and in patients suffering from this largely untreated disease. While many intracellular signaling mechanisms have been examined in preclinical models that drive this spontaneous activity (SA), none of these have been tested directly on spontaneously active human nociceptors. Using cultured DRG neurons recovered during thoracic vertebrectomy surgeries, we show that inhibition of mitogen activated protein kinase interacting kinase (MNK) with eFT508 (25 nM) reverses SA in human sensory neurons associated with painful dermatomes. MNK inhibition in spontaneously active nociceptors decreased action potential amplitude and produced alterations in the magnitude of afterhyperpolarizing currents suggesting modification of Na+ and K+ channel activity downstream of MNK inhibition. The effects of MNK inhibition on SA took minutes to emerge and were reversible over time with eFT508 washout. MNK inhibition with eFT508 led to a profound loss of eIF4E Serine 209 phosphorylation, a specific target of the kinase, within 2 min of drug treatment, consistent with the rapid action of the drug on SA in electrophysiology experiments. Our results create a compelling case for the future testing of MNK inhibitors in clinical trials for neuropathic pain.

Nasal continuous positive pressure versus simple face mask oxygenation for adult obese and obstructive sleep apnea patients undergoing colonoscopy under propofol-based general anesthesia without tracheal intubation: A randomized controlled trial.

STUDY OBJECTIVE: To determine if a nasal positive airway pressure (nasal CPAP) mask would decrease the number of hypoxemic events in obese and obstructive sleep apnea patients undergoing colonoscopy. DESIGN: Single-center prospective randomized controlled trial. SETTING: Tertiary academic center. PATIENTS: We enrolled 109 patients with diagnosis of obesity and/or obstructive sleep apnea scheduled to undergo colonoscopy under propofol general anesthesia without planned tracheal intubation. INTERVENTION: Patients were randomly allocated (1:1 ratio) to receive supplementary oxygen at a flow of 10 L/min, either through a nasal CPAP or a simple facemask. MEASUREMENTS: The primary endpoint was the difference in the mean percentage of time spent with oxygen saturation below 90% between the two groups. Secondary outcomes included the need for airway maneuvers/interventions, average SpO2 during the case, duration and severity of oxygen desaturation, incidence and duration of procedural interruptions, and satisfaction and tolerance scores. MAIN RESULTS: 54 were allocated to the simple face mask and 55 to the nasal CPAP mask arms, respectively. A total of 6 patients experienced a hypoxemic event. Among these patients, the difference in the percentage of time spent with oxygen saturation below 90% was not clinically relevant (p = 1.0). However, patients in the nasal CPAP group required less chin lift (20% vs. 42.6%; p = 0.01) and oral cannula insertion (12.7% vs.29.6%; p = 0.03). The percentage of patients with at least one airway maneuver was higher in the simple face mask arm (68.5% vs. 41.8%; p = 0.005). Patient tolerance to device score was lower in the nasal CPAP group (8.85 vs. 9.56; p = 0.003). CONCLUSIONS: A nasal CPAP did not prevent hypoxemia and should not be used routinely for colonoscopy in obese or OSA patients if a simple face mask is an alternative therapy. However, potential advantages of its use include fewer airway maneuvers or interventions, which may be desirable in certain clinical settings. TRIAL REGISTRATION: Clinicaltrials.gov, identifier: NCT05175573.

The Role of Opioid Receptors in Cancer.

Opioids are one of the most potent drugs for treating moderate to severe pain. Despite irrefutable clinical application in chronic pain management, the long-term use of opioids has been increasingly questioned due to undesired side effects that demand attention. Opioids such as morphine mediate clinically relevant effects primarily through the µ-opioid receptor that go beyond their classical role as analgesics, causing potentially fatal side effects such as tolerance, dependence, and addiction. Furthermore, there is growing evidence that opioids affect immune system function, cancer progression, metastasis, and recurrence. Though a biological plausibility, the clinical evidence for the action of opioids on cancer is mixed, revealing a more complex picture as researchers struggle to establish a vital link between opioid receptor agonists, cancer progression, and suppression, or both. Thus, in light of the uncertainty of opioid effects on cancer, in this review, a focused overview of the role of opioid receptors in modulating cancer progression, their underlying signaling mechanisms, and the biological activity of opioid receptor agonists and antagonists is provided.

Association of regional anesthesia with oncological outcomes in patients receiving surgery for bladder cancer: A meta-analysis of observational studies.

Background: This meta-analysis was conducted to compare cancer recurrence and survival rates in patients with bladder cancer receiving surgery under general anesthesia alone (i.e., GA group) or regional anesthesia (RA) with or without GA (i.e., RA ± GA group). Methods: Literature search on Cochrane library, EMBASE, Google scholar, and Medline databases was performed to identify all relevant studies from inception to April 30, 2022. The primary outcome was cancer recurrence rate, while the secondary outcomes included overall survival rate and cancer-specific survival rate. Subgroup analyses were performed based on study design [(Propensity-score matching (PSM) vs. no-PSM)] and type of surgery [transurethral resection of bladder tumor (TURBT) vs. radical cystectomy]. Results: Ten retrospective studies with a total of 13,218 patients (RA ± GA group n=4,884, GA group n=8,334) were included. There was no difference between RA ± GA group and GA group in age, the proportion of males, severe comorbidities, the proportion of patients receiving chemotherapy, and the pathological findings (all p >0.05). Patients in the RA ± GA group had significantly lower rate of bladder cancer recurrence [odds ratio (OR): 0.74, 95%CI: 0.61 to 0.9, p=0.003, I2 = 24%, six studies] compared to those in the GA group. Subgroup analyses based on study design revealed a consistent finding, while the beneficial effect of RA ± GA on reducing cancer recurrence was only significant in patients receiving TURBT (p=0.02), but not in those undergoing radical cystectomy (p=0.16). There were no significant differences in overall survival rate and cancer-specific survival rate between RA ± GA and GA groups. Conclusions: For patients receiving surgery for bladder cancer, the application of regional anesthesia with or without general anesthesia is associated with significant decrease in cancer recurrence, especially in patients undergoing TURBT for non-muscle invasive bladder cancer. Because of the limited number of studies included and potential confounding factors, our results should be interpreted carefully. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022328134.

The Impact of the Need for Language Assistance Services on the Use of Regional Anesthesia, Postoperative Pain Scores and Opioid Administration in Surgical Oncology Patients.

Language barriers can negatively impact the quality of healthcare. In surgical patients, limited English proficiency (LEP) can lead to disparities in acute postoperative pain management. Interpreters are often used for communication with LEP patients to help alleviate these disparities. We aimed to investigate the impact of the need for language assistance services (LAS) in acute postoperative pain management in patients undergoing oncologic surgery. We retrospectively collected data on adult patients undergoing open abdominal oncologic surgery between March 2016 and August 2021. The need for LAS, patient demographics, treatment and clinical outcomes were obtained from the patient's electronic medical record. The primary endpoint was pain intensity, while secondary endpoints included opioid use in PACU and regional anesthesia. Post-matching analysis (n = 590) demonstrated no significant difference in preoperative variables between patients needing LAS and those not needing LAS. The rate of regional use was slightly lower but not statistically significant in patients needing LAS. Patients needing LAS had significantly lower opioid consumption and reported lower pain intensity in PACU than subjects not requiring translation. In this study, LAS may have aided in the patient decision process regarding the acceptance of regional anesthesia. Although the need for LAS was associated with statistically significant lower pain intensity scores and a corresponding lesser opioid use than no LAS, the margin of differences, especially in pain intensity scores, may not be clinically significant. This may suggest that LAS allowed for better patient-provider communication and appropriate pain management.