Effect of Liposomal Bupivacaine for Intercostal Nerve Block on Chronic Postoperative Pain Following Video-Assisted Thoracoscopic Lung Resection: A Retrospective Cohort Study

The analgesic efficacy of liposomal bupivacaine (LB) for ultrasound-guided erector spinae plane block (ESPB) and thoracoscopic intercostal nerve block (ICNB) in thoracic surgery remains uncertain. This study aims to evaluate the analgesic efficacy of anesthesiologist-performed ESPB using LB versus surgeon-administrated ICNB with LB in patients undergoing video-assisted thoracoscopic surgery (VATS) lung resection. This single-center, prospective, randomized, double-blinded trial will include 120 adult patients scheduled for VATS lung resection. Patients will be randomly assigned 1:1 to the ESPB group or ICNB group. Each patient will receive either an ESPB or ICNB at the end of the surgery, along with patients-controlled intravenous analgesia (PCIA) as part of a postoperative multimodal analgesia. The primary outcome is the average numeric rating scale (NRS) pain scores at rest over 72 h postoperatively (average of three 24-h time points: 24, 48, and 72 h). Secondary outcomes include NRS pain scores at rest and during activity at 24, 48, and 72 h postoperatively, Quality of Recovery 15 scores at 24, 48, and 72 h postoperatively, time to first press on the PCIA device, total opioid consumption within 72 h postoperatively, time to initiate independent bedside mobilization, length of postoperative hospital stay, and the incidence of chronic pain (defined as an NRS score ≥ 1) at 3 months post-surgery. Analyses will be performed in the modified intention-to-treat population. We hypothesize that anesthesiologist-performed ultrasound-guided ESPB with liposomal bupivacaine will result in lower average numeric rating scale pain scores over 72 h compared to surgeon-administrated thoracoscopic ICNB in patients undergoing VATS lung resection. The findings of this study aim to provide evidence to optimize postoperative analgesic regimens for patients undergoing VATS lung resection. http://www.chictr.org.cn, identifier ChiCTR2400092927.

Background: Liposomal bupivacaine (LipoB), delivered via intercostal nerve blocks (ICNBs), is increasingly being used for postoperative pain control in thoracic surgery patients, but there is limited data on its effectiveness when compared to standard bupivacaine. Objective: We sought to compare postoperative opioid use, pain control, and length of stay (LOS) in patients undergoing thoracic surgery with LipoB ICNBs vs patients undergoing thoracic surgery with ICNBs using standard bupivacaine. Study Design: A retrospective analysis. Setting: Research took place in a tertiary academic medical center. Methods: A transition in the standard of care from standard bupivacaine to LipoB for ICNBs in March of 2014 allowed us to compare 2 cohorts: patients who received bupivacaine ICNBs from January 2013 through February of 2014 and patients who received LipoB ICNBs from March 2015 through November 2017. We included patients who underwent thoracic surgery for lung cancer using robotic-assisted thoracic surgery (RATS), video-assisted thoracic surgery (VATS), or traditional open thoracotomy, and documentation of ICNB in the operative note. We collected data on pain scores (Visual Analog Scale [VAS]) and opioid consumption (converted to oral morphine equivalents [OMEs]) intraoperatively, on postoperative day (POD) 0, POD 1, POD 2, and POD 3. We also analyzed data on length of stay [LOS]. A primary analysis was performed on the effects of LipoB vs bupivacaine across all surgery types on opioid consumption, pain scores, and LOS with a secondary analysis on the same endpoints per individual surgery type. Results: A total of 129 patients were included from the predefined study periods (n = 62 LipoB and n = 67 standard bupivacaine). Across all surgery types, LipoB decreased opioid utilization vs standard bupivacaine (P < .01). Post-hoc testing revealed that this difference existed intraoperatively (55 ± 5 vs 69 ± 4 mg OME, P = .03) and on POD 0 (44 ± 6 vs 68 ± 6 mg OME, P < .01). Surgical subtype analysis revealed that this difference was mostly driven by lower opioid consumption in patients undergoing RATS. When compared across all surgery types, LipoB vs bupivacaine did not affect postoperative pain scores. However, subgroup analysis showed that pain scores were lower in the LipoB vs standard bupivacaine group undergoing VATS on POD 0, 1, and 2. The LOS across all thoracic surgery types was lower in the LipoB group when compared to the standard bupivacaine group (median, 4 days [IQR 2.0-6.0] vs median, 5 days [IQR 3.0-8.0], P < .01). Subgroup analysis showed that the LOS in patients undergoing VATS with LipoB ICNBs was shorter compared to patients receiving bupivacaine ICNBs. Limitations: The retrospective nature of this study makes it prone to several types of bias. Conclusion: ICNBs with LipoB for thoracic surgery leads to lower opioid consumption and shorter LOS when compared to ICNBs with standard bupivacaine. The benefit of LipoB over standard bupivacaine for ICNBs appears especially relevant in VATS or RATS procedures. Key words: Intercostal nerve block, liposomal bupivacaine, RATS, regional anesthesia, roboticassisted thoracoscopic surgery, thoracotomy, VATS, video-assisted thoracoscopic surgery

Bupivacaine local anesthetic to decrease opioid requirements after radical cystectomy: Does formulation matter?

The effectiveness of liposomal bupivacaine for postoperative analgesia in thoracoscopic surgery remains uncertain. We assessed liposomal bupivacaine for erector spinae plane block (ESPB) on pain control after video-assisted thoracoscopic lung resection. In this multicenter, randomized controlled trial, 272 adults were randomly assigned (1:1) to receive either liposomal bupivacaine or bupivacaine hydrochloride for preoperative ultrasound-guided ESPB. The primary outcome was the cumulative numeric rating scale pain score at rest (area under the curve during 0-72h postoperatively). Secondary outcomes included 72-h cumulative activity pain, time to first patient-controlled analgesia, total opioid consumption within 72h, pain scores at multiple postoperative time points, recovery quality at 72h, and activity pain at 14days and 3months. A total of 267 patients were analyzed (median age, 58years; women, 64.8%). The 72-h cumulative rest pain was significantly lower in the liposomal bupivacaine group (205.0 vs 232.5; difference, -26.5; 95% confidence interval, -35.5 to -17.5; P < 0.001) but did not reach the minimal clinically important difference of 72 (predefined) or 42 (anchor-based). Pain scores at 24 and 32h, both at rest and during activity, achieved the clinically important difference of 1. Liposomal bupivacaine was associated with lower opioid consumption and higher recovery quality. The other outcomes did not differ between groups. Among patients undergoing video-assisted thoracoscopic lung resection, liposomal bupivacaine for ESPB led to a statistically significant reduction in 72-h cumulative rest pain compared with bupivacaine hydrochloride. Pain relief at 24 and 32h met the predefined threshold for clinical significance.

ObjectivesTo evaluate whether liposomal bupivacaine provides superior postoperative analgesia compared with ropivacaine following haemorrhoidectomy, reduces the need for rescue analgesics in patients with mixed haemorrhoids and maintains a comparable safety profile.DesignProspective, randomised controlled multicentre trial.SettingThree grade 3A general hospitals in Guangxi, China, conducted between September 2023 and July 2024.ParticipantsEligible patients were aged 18–75 years undergoing elective external dissection and internal ligation for mixed haemorrhoids (grade III and IV mixed haemorrhoids). Key exclusion criteria were severe systemic diseases, history of substance abuse or known allergies to local anaesthetics. A total of 264 patients (male, n=162; mean age, 43.1±12.2 years) were enrolled and completed the study, with 132 randomised to each group.InterventionsPatients received either ropivacaine (100 mg in 20 mL) or liposomal bupivacaine (226 mg in 20 mL) through local infiltration at the end of surgery.Primary and secondary outcome measuresThe primary outcomes were the resting numerical rating scale (NRS) pain scores (0–10) at postoperative 1, 5, 7, 9, 11, 24, 36, 48 and 72 hours. The secondary outcomes included the following: (1) exercise NRS pain scores at the same time points; (2) time to first ambulation, ambulation NRS pain scores on postoperative days 1, 2 and 3 and the proportion of patients having ambulation NRS pain scores ≥4; (3) defecation NRS pain scores and the proportion of of patients having score ≥4; (4) the time to the first administration of rescue analgesics and proportion of patients requiring rescue analgesics; (5) proportion of pain-free patients (NRS pain scores ≤1) 0–24, 24–72 and 0–72 hour after surgery; (6) incision assessments on postoperative days 1, 3 and 7 and postoperative adverse events (AEs); and (7) patients’ and researchers’ satisfaction with pain management.ResultsResting NRS pain scores were significantly lower in the liposomal bupivacaine group at all time points (median, 0–2.0 vs 2.0–4.0 for ropivacaine, p<0.001). Exercise NRS pain scores were also significantly lower in the liposomal bupivacaine group (median, 0–2.0 vs 2.0–5.0, p<0.001). Additionally, median ambulation NRS pain scores were reduced in the liposomal bupivacaine group on postoperative days 1–3 (median, 1.0–2.0 vs 3.0–5.0, p<0.001). By 72 hours after surgery, 78.8% of the patients in the liposomal bupivacaine group had defecated, reporting lower defecation NRS pain scores (median, 3.0 vs 5.0, p<0.001). Fewer patients in this group required rescue analgesics (43.9% vs 83.3%, p<0.001). Incision assessment scores were comparable between groups, with no significant difference in AE rates (3.8% vs 1.5%, p=0.444).ConclusionsPerianal infiltration of liposomal bupivacaine significantly alleviates postoperative resting and exercise pain in patients undergoing surgery for mixed haemorrhoids, enhances comfort during ambulation and defecation, reduces the need for additional analgesics and demonstrates a safety profile comparable to that of ropivacaine.Trial registrationchictr.org.cn # ChiCTR2300075276.

One of the missions of the Food and Drug Administration (Silver Spring, Maryland) is to protect the public health by assuring the safety, efficacy, and security of human drugs.1 According to Food and Drug Administration guidance, new drugs can be approved as long as they show efficacy compared to placebo, even if there are already drugs approved and available that have been deemed effective.2 Exparel (Pacira Biosciences, Inc., USA), an extended release liposomal formulation of bupivacaine, first approved by the Food and Drug Administration in 2011 for surgical site infiltration, was approved under these circumstances. In this issue, two articles review 10 yr of research on the clinical effectiveness of liposomal bupivacaine. Ilfeld et al.3 provide an extensive narrative review of published randomized controlled trials, and Hussain et al.4 conducted a systemic review and meta-analysis of the clinical effectiveness of liposomal versus nonliposomal bupivacaine for peripheral nerve blocks.The narrative review by Ilfeld et al. included 76 randomized controlled trials. Importantly, they were evaluated using the Cochrane Risk of Bias Version 2 tool. This tool consists of five domains: bias from the randomizing process, bias due to deviations from intended intervention, bias due to missing outcome data, bias in measurement of outcome, and bias in selection of reported results. It does not measure the conduct of a trial. A summary bias judgment can be either “low” or “high” risk of bias, or can express “some concerns,” and a high risk summary judgment generally indicates a finding of high risk in at least one of the domains.5 The authors found that 35 to 40% of randomized controlled trials reviewed had evidence of high risk or some concerns for bias. The chief sources of bias included lack of trial registration, registration after enrollment, failure to define the primary outcome measure, and problems with definition (e.g., discrepancy between registry and published article). Minimization of bias in randomized controlled trials is important to prevent data distortion and erroneous conclusions. The Cochrane Risk of Bias tool does not measure conflicts of interest by industry funding. Almost half of the studies in this review reported either direct funding or financial support for the authors by the manufacturer of liposomal bupivacaine. Not surprisingly, liposomal bupivacaine was found to be superior to comparators in 46% of these conflicted trials but was found to be superior in only 11% of the nonconflicted trials.The primary outcome in these 76 trials varied and was not always designated. There were two types of primary outcome measures used: postoperative pain scales such as the visual analogue scale scores and numeric rating scales scores, or the mean morphine equivalents administered postoperatively to “rescue” the patient from pain. Some studies reported mean values, and others reported area under the curve values.The first 12 studies reviewed compared liposomal bupivacaine surgical site infiltration to placebo. Seven found no statistical difference between liposomal bupivacaine and placebo, and of these, 88% were deemed at low risk for bias. The five that did show statistical differences were all rated with high risk for bias. Thirty-six of the randomized controlled trials compared surgical site infiltration of liposomal bupivacaine to surgical site infiltration of bupivacaine, ropivacaine, or lidocaine. Twenty-seven of these comparisons used a maximum dose of liposomal bupivacaine of 266 mg but used a smaller dose of regular bupivacaine or ropivacaine, possibly biasing the studies toward results favoring liposomal bupivacaine. Only six of the 36 studies of comparing surgical site infiltration with liposomal bupivacaine with nonliposomal local anesthetic infiltration found the liposomal preparation to be superior. Five of these six studies were judged to have high or concerning risk for bias. In five of the six studies, the active comparator dose of bupivacaine was much lower than the liposomal bupivacaine dose, demonstrating that more bupivacaine works better than less bupivacaine. Twelve studies compared liposomal bupivacaine for surgical infiltration with a peripheral nerve block administered with either nonliposomal bupivacaine or ropivacaine. The final group of 16 studies evaluated liposomal bupivacaine for a nerve block or epidural injection compared to placebo or active comparators, nonliposomal bupivacaine, or intrathecal hydromorphone, using the similar outcome measures to all the previous trials. Of these last 28 trials reviewed, 43% showed superiority of liposomal bupivacaine; 82% showed high risk or some concerns for bias. The authors concluded, “Whether introduced by surgical infiltration or as part of a peripheral nerve block, the preponderance of current evidence fails to support the routine use of liposomal bupivacaine over standard local anesthetics when treating postoperative pain.”The systematic review and meta-analysis by Hussain et al. of the clinical effectiveness of liposomal versus nonliposomal bupivacaine for peripheral nerve blocks evaluated the primary outcome of the 24- to 72-h difference in the weighted mean area under the curve rest pain scores between patients receiving perineural analgesia inclusive of liposomal bupivacaine versus nonliposomal local anesthetics. The authors chose this time frame for the primary outcome measure because liposomal bupivacaine is promoted to improve the duration and quality of analgesia beyond the first 24 h.4 A variety of secondary outcomes relating to postoperative pain rating scores and opioid rescues were also evaluated during the postoperative period of 0 to 72 h. Nine trials were included in this meta-analysis. The authors found that the mean difference (95% CI) in area under the curve of rest pain was found to be 1.0 cm/h (0.5 to 1.6; P = 0.003) in favor of liposomal bupivacaine, but this difference failed to meet the predefined threshold for clinical significance (i.e., 2.0 cm/h; P &lt; 0.001). Liposomal bupivacaine was similar to nonliposomal bupivacaine for all other analgesic and functional outcomes. The authors concluded that liposomal bupivacaine used perineurally in peripheral nerve blocks provides a clinically unimportant improvement in the area under the curve of postoperative pain scores compared to nonliposomal bupivacaine.The results of these two articles should not come as a surprise in light of the early studies performed for the regulatory approval of liposomal bupivacaine. In 2006, SkyePharma, later known as Pacira Pharmaceuticals and then Pacira Biosciences, collectively referred to here as Pacira Biosciences, submitted an New Drug Application application to the Food and Drug Administration for Exparel brand liposomal bupivacaine for an indication of relief of postoperative surgical pain, administered as wound infiltration.6 For this indication, Pacira submitted five phase 2 active comparator-controlled studies and three phase 3 active comparator-controlled studies using nonliposomal bupivacaine as the comparator.6 None of these eight studies showed clinical or statistical difference between the two formulations.Unable to demonstrate a benefit over nonliposomal bupivacaine, in 2009, the sponsor submitted two phase 3 placebo-controlled clinical trials showing efficacy of liposomal bupivacaine against placebo.6 As allowed by regulation, despite no greater efficacy of liposomal bupivacaine than nonliposomal bupivacaine, the Food and Drug Administration in 2011 approved liposomal bupivacaine for surgical site infiltration to relieve postoperative pain for hemorrhoidectomy and bunionectomy. For this initial approval, the Food and Drug Administration deemed it not necessary for an advisory committee to meet.7In 2014, Pacira submitted a supplemental New Drug Application application for approval of liposomal bupivacaine for an additional indication of postsurgical analgesia via nerve block, for which they submitted data from two new studies. The first investigated intercostal nerve blocks and found that liposomal bupivacaine was not superior to placebo, based on no differences in area under the curve analysis for pain intensity at rest using a numerical rating scale-R over 72 h. The second investigated femoral nerve blocks and found that liposomal bupivacaine at a dose of 266 mg was superior to placebo for pain relief, based on a primary outcome measure of area under the curve analysis of Numeric Rating Scale-Rest through 72 h but not superior on its secondary outcome measure of time to first opioid rescue. This supplemental New Drug Application was not approved in the first review cycle. In 2017, Pacira submitted two new multicenter, randomized, double-blind, and placebo-controlled nerve block studies.8,9 The first evaluated the efficacy of liposomal bupivacaine for postsurgical analgesia via femoral nerve block in patients undergoing total knee arthroplasty. The second evaluated liposomal bupivacaine for postsurgical analgesia via ultrasound-guided brachial plexus nerve blocks by either supraclavicular or interscalene approach in patients undergoing shoulder surgery. Out of these four studies, both the two in 2014 and the two in 2017, the brachial plexus nerve block study was the only one that met both the primary efficacy endpoint of improved area under the curve estimates of pain relief for the first 48 to 72 h after surgery and decreased opioid rescues.The Food and Drug Administration Anesthetic and Drug Products Advisory Committee met in 2018 to review the supplemental New Drug Application request to approve liposomal bupivacaine for the new indication of regional nerve blocks.10,11 This advisory committee consisted of 10 members with expertise in anesthesiology, pain medicine, pharmacology, or biostatistics, as well as a consumer and industry representative. Concerns raised by this committee included the lack of active comparator groups in the submitted studies, a lack of safety studies, and the lack of evidence for opioid sparing. Most of the voting advisory committee members voted six to four against expanding the indication for liposomal bupivacaine. In 2018, the Food and Drug Administration approved Exparel for “…use as an interscalene brachial plexus nerve block to produce post-surgical regional analgesia following shoulder surgery in adults.”12To summarize, both the review by Ilfeld et al. and the meta-analysis by Hussain et al. concluded that liposomal bupivacaine did not show clinical superiority over existing, active comparators, nonliposomal bupivacaine or ropivacaine. For the indication for infiltration, the studies submitted by Pacira Biosciences did not demonstrate superiority of liposomal bupivacaine compared to these same active comparators. For the indication of peripheral nerve block, they submitted only placebo studies. Although demonstrating efficacy of a new agent is simplest using a randomized placebo-controlled trial design, this design gives no information about the efficacy of a new agent compared to existing agents. Trials that have an active comparator arm as well as a placebo arm can determine efficacy as well as give information about efficacy vis-à-vis existing, effective drugs.Why is all of this important? New drugs can be very financially rewarding for pharmaceutical companies.13 Once Exparel was approved, Pacira Biosciences began an aggressive and powerful marketing strategy. Between 2013 and 2019, they paid $25.8 million to more than 27,000 physicians for a variety of services including compensation for being a speaker or faculty at nonaccredited educational events.14 Sales of liposomal bupivacaine increased during this time with the company reporting a 25% growth in 2019 over 2018 with full-year revenues of $421 million in 2019.15 The cost of a single dose of 266 mg of Exparel brand liposomal bupivacaine is about $334.16 Nonliposomal bupivacaine costs about $3 per dose. In this era of medical austerity, when the benefits and costs of expensive drugs are being considered, one would hope that newly approved expensive drugs would at least be an improvement over existing, inexpensive drugs.The author declares no competing interests. The author was the acting Chair for the Food and Drug Administration Anesthetic and Analgesic Drug Products Advisory Committee February 14 and 15, 2018, which advised on Pacira’s (Pacira Biosciences, Parsippany, New Jersey) sNDA application for expanded indication for Exparel for nerve blocks.

BackgroundAdequate pain control after video-assisted thoracoscopic surgery (VATS) for lung resection is important to improve postoperative mobilisation, recovery, and to prevent pulmonary complications. So far, no consensus exists on optimal postoperative pain management after VATS anatomic lung resection. Thoracic epidural analgesia (TEA) is the reference standard for postoperative pain management following VATS. Although the analgesic effect of TEA is clear, it is associated with patient immobilisation, bladder dysfunction and hypotension which may result in delayed recovery and longer hospitalisation. These disadvantages of TEA initiated the development of unilateral regional techniques for pain management. The most frequently used techniques are continuous paravertebral block (PVB) and single-shot intercostal nerve block (ICNB). We hypothesize that using either PVB or ICNB is non-inferior to TEA regarding postoperative pain and superior regarding quality of recovery (QoR). Signifying faster postoperative mobilisation, reduced morbidity and shorter hospitalisation, these techniques may therefore reduce health care costs and improve patient satisfaction.MethodsThis multi-centre randomised study is a three-arm clinical trial comparing PVB, ICNB and TEA in a 1:1:1 ratio for pain (non-inferiority) and QoR (superiority) in 450 adult patients undergoing VATS anatomic lung resection. Patients will not be eligible for inclusion in case of contraindications for TEA, PVB or ICNB, chronic opioid use or if the lung surgeon estimates a high probability that the operation will be performed by thoracotomy. Primary outcomes: (1) the proportion of pain scores ≥ 4 as assessed by the numerical rating scale (NRS) measured during postoperative days (POD) 0–2; and (2) the QoR measured with the QoR-15 questionnaire on POD 1 and 2. Secondary outcome measures are cumulative use of opioids and analgesics, postoperative complications, hospitalisation, patient satisfaction and degree of mobility.DiscussionThe results of this trial will impact international guidelines with respect to perioperative care optimization after anatomic lung resection performed through VATS, and will determine the most cost-effective pain strategy and may reduce variability in postoperative pain management.Trial registration The trial is registered at the Netherlands Trial Register (NTR) on February 1st, 2021 (NL9243). The NTR is no longer available since June 24th, 2022 and therefore a revised protocol has been registered at ClinicalTrials.gov on August 5th, 2022 (NCT05491239). Protocol version: version 3 (date 06-05-2022), ethical approval through an amendment (see ethical proof in the Study protocol proof).

Thoracic paravertebral block (TPVB) can provide effective analgesia for patients undergoing video-assisted thoracoscopic surgery (VATS). However, the duration of analgesia achieved with conventional local anesthetics combined with dexamethasone remains limited. This study aimed to determine if liposomal bupivacaine (LB) is superior to bupivacaine combined with dexamethasone (BD) with respect to duration of postoperative analgesia in VATS patients. Adults scheduled for VATS were randomized to treatment with LB or BD. The primary outcome was duration of analgesia. Secondary outcomes involved Numeric Rating Scale (NRS) pain scores, cumulative oxycodone consumption, total intraoperative sufentanil consumption, first times to ambulation and flatus, length of hospital stay, patient satisfaction level, and incidence of adverse reactions. Of 93 total subjects, 78 were randomized into two groups (n=39 each). The LB group demonstrated a significantly prolonged duration of analgesia compared with the BD group (1160.4±403.8 min vs 743.1±216.8 min, p<0.001), with a mean increase of 417 min (a 56% extension). LB was associated with lower resting and cough NRS pain scores on the first postoperative day. The 72-hour area under the curve values for scores for resting pain (67.5 vs 87.9) and pain during cough (213.9 vs 244.0) were lower for the LB group versus the BD group. In exploratory analyses, cumulative oxycodone consumption on the first postoperative day was numerically lower in the LB group. Subjects receiving treatment LB had lower cumulative oxycodone consumption on the first postoperative day, earlier times to first ambulation and first flatus, and higher satisfaction scores as compared with subjects receiving BD. There was no significant difference between the two groups in terms of total intraoperative sufentanil consumption, duration of hospital stay, or incidence of adverse events. In VATS patients receiving TPVB, LB significantly prolonged the duration of postoperative analgesia compared with BD. Exploratory secondary outcomes suggested modest improvements in early pain profiles and potential opioid-sparing and early recovery benefits. ChiCTR2500095090.

The pain experience for total shoulder arthroplasty (TSA) patients in the first 2 weeks after surgery has not been well described. Many approaches to pain management have been used, with none emerging as clearly superior; it is important that any approach minimizes postoperative opioid use. (1) With a long-acting nerve block and comprehensive multimodal analgesia, what are the pain levels after TSA from day of surgery until postoperative day (POD) 14? (2) How many opioids do TSA patients take from the day of surgery until POD 14? (3) What are the PainOUT responses at POD 1 and POD 14, focusing on side effects from opioids usage? From January 27, 2017 to December 6, 2017, 154 TSA patients were identified as potentially eligible for this prospective, institutional review board-approved observational study. Of those, 46 patients (30%) were excluded (either because they were deemed not appropriate for the study, research staff were not available, patients were not eligible, or they declined to participate), and another six (4%) had incomplete followup data and could not be studied, leaving 102 patients (66%) for analysis here. Median preoperative pain with movement was 7 (interquartile range [IQR], 5-9) and 13 of 102 patients used preoperative opioids. All patients received a single-injection bupivacaine interscalene block with adjuvant clonidine, dexamethasone, and buprenorphine. Multimodal analgesia included acetaminophen, NSAIDs, and opioids. The primary outcome was the Numerical Rating Scale (NRS) pain score with movement on POD 14. The NRS pain score ranges from 0 (no pain) to 10 (worst pain possible). Secondary outcomes included NRS pain scores at rest and with movement (day of surgery, and PODs 1, 3, 7 and 14), daily analgesic use from day of surgery to POD 14 (both oral and intravenous), Opioid-Related Symptom Distress Scale (which assesses 12 symptoms ranging from 0 to 4, with 4 being the most distressing; the composite score is the mean of the 12 symptom-specific scores) on POD 1, and the PainOut questionnaire on POD 1 and POD 14. The PainOut questionnaire includes questions rating nausea, drowsiness, itching from 0 (none) to 10 (severe), as well as rating difficulty staying asleep from 0 (does not interfere) to 10 (completely interferes). The median NRS pain scores with movement were 2 (IQR, 0-5) on POD 1, 5 (IQR, 3-6) on POD 3, and the pain score was 3 (IQR, 1-5) on POD 14. Median total opioid use (converted to oral morphine equivalents) was 16 mg (4-50 mg) for the first 24 hours, 30 mg (8-63 mg) for the third, and 0 mg (0-20 mg) by the eighth 24-hour period, while the most frequent number of activations of the intravenous patient-controlled analgesia device was 0. Median PainOut scores on POD 1 and POD 14 for sleep interference, nausea, drowsiness and itching were 0, and the median composite Opioid-Related Symptom Distress Scale score on day 1 was 0.3 (IQR, 0.1-0.5). Clinicians using this protocol, which combines a long-acting, single-injection nerve block with multimodal analgesia, can inform TSA patients that their postoperative pain will likely be less than their preoperative pain, and that on average they will stop using opioids after 7 days. Future research could investigate what the individual components of this protocol contribute. Larger cohort studies or registries would document the incidence of rare complications. Randomized controlled trials could directly compare analgesic effectiveness and cost-benefits for this protocol versus alternative strategies, such as perineural catheters or liposomal bupivacaine. Perhaps most importantly, future studies could seek ways to further reduce peak pain and opioid usage on POD 2 and POD 3. Level IV, therapeutic study.

Postsurgical pain control can have a significant impact on patient outcomes and hospital-associated costs. We sought to evaluate the effect of intercostal nerve blocks using liposomal bupivacaine on length of stay (LOS) in patients undergoing video-assisted thoracoscopic surgery (VATS). We retrospectively reviewed outcomes in 80 patients undergoing VATS wedge resection, VATS lobectomy, or minimally-invasive esophagectomy (MIE). Patients received either liposomal bupivacaine (n=40) or standard-release bupivacaine with epinephrine (n=40) via intercostal nerve block. The LOS, 24-hour postoperative pain scores, overall opioid usage, and patient ambulation rates at 24 hours were compared for the two groups. The median LOS was significantly shorter in patients receiving liposomal bupivacaine, at 1.35 days (IQR, 1.28 to 1.53 days) compared to 2.45 days (IQR, 2.08 to 3.51 days) in patients receiving standard-release bupivacaine (P<0.0001). Average post-operative pain score during the first 24 hours was 3.4±1.8 for the liposomal bupivacaine group and 2.3±1.2 for the control group (P=0.002). This difference, though statistically significant, is likely not clinically significant, as there was no difference in 24-hour postoperative intravenous morphine equivalent usage between the liposomal bupivacaine and control groups (29.8±21.0 vs. 31.9±20.9 mg, respectively, P=0.664). Interestingly, however, 93% (37/40) of patients receiving liposomal bupivacaine were able to ambulate within 24-hours after surgery, compared to 65% (26/40) of patients in the control group (P=0.003). The use of liposomal bupivacaine is associated with decreased LOS in postoperative thoracic surgery patients and earlier return to ambulation. It does not, however, decrease 24-hour postoperative pain scores or opioid usage.

BackgroundThere is still a controversy about the superiority of liposomal bupivacaine (LB) over traditional local anesthetics in postoperative analgesia after thoracic surgery. This study aims to determine the effect of LB versus bupivacaine hydrochloride (HCl) for preoperative ultrasound-guided erector spinae plane block (ESPB) on postoperative acute and chronic pain in patients undergoing video-assisted thoracoscopic lung surgery.MethodsThis multicenter, randomized, double-blind, controlled trial will include 272 adult patients scheduled for elective video-assisted thoracoscopic lung surgery. Patients will be randomly assigned, 1:1 and stratified by site, to the liposomal bupivacaine (LB) group or the bupivacaine (BUPI) HCl group. All patients will receive ultrasound-guided ESPB with either LB or bupivacaine HCl before surgery and patient-controlled intravenous analgesia (PCIA) as rescue analgesia after surgery. The numeric rating scale (NRS) score will be assessed after surgery. The primary outcome is the area under the curve of pain scores at rest for 0–72 h postoperatively. The secondary outcomes include the total amount of opioid rescue analgesics through 0–72 h postoperatively, time to the first press on the PCIA device as rescue analgesia, the area under the curve of pain scores on activity for 0–72 h postoperatively, NRS scores at rest and on activity at different time points during the 0–72 h postoperative period, Quality of Recovery 15 scores at 72 h after surgery, and NRS scores on activity on postsurgical day 14 and postsurgical 3 months. Adverse events after the surgery are followed up to the postsurgical day 7, including postoperative nausea and vomiting, fever, constipation, dizziness, headache, insomnia, itching, prolonged chest tube leakage, new-onset atrial fibrillation, severe ventricular arrhythmia, deep venous thrombosis, pulmonary embolism, pulmonary atelectasis, cardiac arrest, ileus, urinary retention, chylothorax, pneumothorax, and organ failure. Analyzes will be performed first according to the intention to treat principle and second with the per-protocol analysis.DiscussionWe hypothesize that LB for preoperative ultrasound-guided ESPB would be more effective than bupivacaine HCl in reducing postoperative pain in video-assisted thoracoscopic lung surgery. Our results will contribute to the optimization of postoperative analgesia regimens for patients undergoing video-assisted thoracoscopic lung surgery.Clinical trial registration:http://www.chictr.org.cn, identifier ChiCTR2300074852.

Intercostal Blocks with Liposomal Bupivacaine in Thoracic Surgery: A Retrospective Cohort Study

Ultrasound-guided paravertebral block with liposomal bupivacaine vs. non-liposomal bupivacaine for postoperative pain control after the Nuss procedure in children: A randomized clinical trial.

To determine whether liposomal bupivacaine, a long-acting anesthetic indicated for single-dose wound infiltration to produce postoperative analgesia, has an impact on postoperative pain in patients undergoing total knee arthroplasties (TKAs). Single-center retrospective cohort study. Large tertiary and quaternary care hospital. A total of 120 adults who underwent TKA between March 1, 2013, and October 31, 2013; of those patients, 55 patients received an intraoperative dose of liposomal bupivacaine 266mg (active treatment group), and 65 did not receive the drug (control group). The primary end point was the mean area under the curve (AUC) of numeric rating scale (NRS) pain scores from the end of surgery to 48hours after surgery. Secondary end points included measures of postoperative pain up to 24hours after surgery, opioid consumption within 48hours after surgery, duration of hospitalization, and ambulation distance from the end of surgery to discharge. No significant differences were noted in the primary or secondary end points between patients who received or did not receive an intraoperative dose of liposomal bupivacaine. The mean±SD AUC of NRS pain scores was 199.59±67.11 and 192.94±70.41 for the liposomal bupivacaine and control groups, respectively (p=0.658). Use of adjunctive analgesics was higher among patients in the control group, particularly for those receiving celecoxib, pregabalin, and continuous regional ropivacaine infusions, which may have minimized any differences in pain control between the treatment groups. Liposomal bupivacaine did not improve pain control in patients undergoing TKA when compared with historical management strategies; however, differences may have been obscured by increased utilization of adjunctive analgesics among patients in the control group.

Even minimally invasive thoracic surgeries carry a postoperative cost in pain. While regional anesthesia may alleviate this anticipated pain, especially intercostal nerve blocks (ICNB), the timing of block administration for optimal effect (at the beginning of surgery vs. before wound closure) remains controversial. Here, we plan (1) to test the hypothesis that performing ICNB at the beginning of surgery provides superior postoperative analgesic effects compared to before wound closure and (2) to observe perioperative outcomes to determine whether the timing affects acute and chronic postoperative pain, or intraoperative patient management. This single-blinded, single-center, randomized, controlled trial will be conducted at the Department of Thoracic Surgery, University of Tsukuba Hospital from Sep 29, 2024, to June 30, 2026. Patients 16-79years old within the regular population of patients undergoing lung wedge resection via video-assisted thoracoscopic surgery (VATS) without a utility window approach and who are ASA-PS classes 1-3 will be enrolled to receive ICNB either pre-operatively or before wound closure. Groups will be single-blinded (patient only) at random, and the primary outcome will be assessment by Numerical Rating Scale (NRS) pain scores during movement, measured 4h after returning to the ward. Secondary outcomes will be (1) any additional analgesic use within the 4-h return window, (2) intraoperative measurements (including amounts of remifentanil used, time from surgery completion to extubation, occurrence of shivering or nausea after extubation, use of antiemetics, and maximum blood pressure/heart rate), (3) acute pain during hospitalization (using routinely administered NRS), (4) postoperative analgesic use, and (5) quality of life (QOL) scores on EQ-5D and SF-36 questionnaires at preoperative and 3-month postoperative timepoints. Chronic pain at 3months post-surgery will also be determined by NRS. A complete evaluation of ICNB efficacy as a preemptive analgesic approach will contribute to the development of improved perioperative pain management techniques. A reduction in the duration of surgery-related symptoms and an improvement in postoperative QOL will be the result. Japan Registry of Clinical Trials: identifier jRCT1031240358.Registered on 29 Sep 2024. https://jrct.niph.go.jp/latest-detail/jRCT1031240358 .