Opioid-related Side Effects Research Articles

FLT3 signaling inhibition abrogates opioid tolerance and hyperalgesia while preserving analgesia

Navigating the duality of opioids’ potent analgesia and side effects, including tolerance and hyperalgesia, is a significant challenge in chronic pain management, often prompting hazardous dose escalation to maintain analgesic effects. The peripheral mu-opioid receptor (MOR) is known to mediate these contradictory effects. Here, we show that the fms-like tyrosine kinase receptor 3 (FLT3) in peripheral somatosensory neurons drives morphine tolerance and hyperalgesia in a male rodent model. We found that chronic morphine treatment increases FLT3 and MOR co-expression, and that inhibiting FLT3 represses MOR-induced hyperactivation of the cyclic adenosine monophosphate (cAMP) signaling pathway, mitigating maladaptive excitatory processes engaged after chronic morphine treatment. Furthermore, in postsurgical or inflammatory models of chronic pain, co-administering morphine with a FLT3-specific inhibitor not only prevents or suppresses tolerance and hyperalgesia but also potentiates the analgesic efficacy of morphine, without aggravating other morphine-induced adverse effects. Our findings suggest that pairing morphine with FLT3 inhibitors could become a promising avenue for chronic pain management to safely harness the power of opioids, without the risk of dose escalation. By enhancing morphine analgesic potency through FLT3 inhibition, this approach could minimize opioid dosage, thereby curtailing the risk of addiction and other opioid-related side effects.

Dermatomal spread in lateral quadratus lumborum blocks versus transversus abdominus plane blocks after laparoscopic colorectal surgery: a randomized clinical trial

IntroductionPostoperative pain after laparoscopic abdominal surgery remains complex. While lateral quadratus lumborum (QL) block and transversus abdominus plane (TAP) block are similar techniques, no studies have examined if one technique...

Nonopioid Drugs for Postoperative Pain: A Selection Governed by Choices of the Authors of Academic Articles

The opioid crisis has profoundly changed the interest in using nonopioid analgesics. This review identified nonopioid drugs receiving the most interest in the treatment of postoperative pain. Publication-based interest, which reflects the authors’ choices of subjects for academic articles, was used to show the shifts in their interest. The authors’ choices of a particular drug for an article’s subject were regarded as reflective of the collective opinion of experts most knowledgeable on the subject. The frequency with which a drug was the topic of an article was measured with the use of specific bibliometric indices. They were employed to select nonopioid drugs for this review. These included acetaminophen, dexmedetomidine, dexamethasone, ketamine, gabapentin, ibuprofen, ketorolac, diclofenac, magnesium sulfate, clonidine, intravenous lidocaine, and meloxicam (in order of most to least bibliometric interest). Individual reviews on these agents described how the bibliometric indices characterized a drug. They also addressed the question of whether a nonopioid analgesic produced a marked opioid-sparing effect. Information relative to this question was presented via the results of meta-analyses with emphasis on the possible reduction of opioid-related side effects. Overall, nonopioid drugs demonstrating the largest popularity among authors and continuous interest growth in 2018-2022 include acetaminophen, dexmedetomidine, dexamethasone, and ibuprofen. The relevant meta-analyses show that nonopioids, administered as components of multimodal analgesia, provided the opioid-sparing effect; they also show that the most common change in the opioid-related side effects was a lower incidence of postoperative nausea and vomiting.

Pronociceptive role of spinal Cav2.3 (R-type) calcium channels in a mouse model of postoperative pain.

More than 80% of patients may experience acute pain after a surgical procedure, and this is often refractory to pharmacological intervention. The identification of new targets to treat postoperative pain is necessary. There is an association of polymorphisms in the Cav2.3 gene with postoperative pain and opioid consumption. Our study aimed to identify Cav2.3 as a potential target to treat postoperative pain and to reduce opioid-related side effects. A plantar incision model was established in adult male and female C57BL/6 mice. Cav2.3 expression was detected by qPCR and suppressed by siRNA treatment. The antinociceptive efficacy and safety of a Cav2.3 blocker-alone or together with morphine-was also assessed after surgery. Paw incision in female and male mice caused acute nociception and increased Cav2.3 mRNA expression in the spinal cord but not in the incised tissue. Intrathecal treatment with siRNA against Cav2.3, but not with a scrambled siRNA, prevented the development of surgery-induced nociception in both male and female mice, with female mice experiencing long-lasting effects. High doses of i.t. SNX-482, a Cav2.3 channel blocker, or morphine injected alone, reversed postoperative nociception but also induced side effects. A combination of lower doses of morphine and SNX-482 mediated a long-lasting reversal of postsurgical pain in female and male mice. Our results demonstrate that Cav2.3 has a pronociceptive role in the induction of postoperative pain, indicating that it is a potential target for the development of therapeutic approaches for the treatment of postoperative pain.

Ultrasound-guided transversalis fascia plane block or transversus abdominis plane block for recovery after caesarean section: A randomised clinical trial.

Caesarean section is a widely performed surgical procedure that often results in moderate-to-severe postoperative pain. If left untreated, this pain can lead to short-term and long-term consequences. Transversalis fascia plane (TFP) block and transversus abdominis plane (TAP) block are among the regional anaesthesia techniques employed for managing pain after a caesarean section. We aimed to compare the impact of these two blocks on the quality of recovery in patients undergoing elective caesarean section under spinal anaesthesia. A single-centre, double-blind, randomised trial. Operating room, postanaesthesia recovery unit, and ward in a tertiary hospital. Ninety-three patients (ASA 2 to 3) were recruited. After exclusion, 79 patients were included in the final analysis: 40 in the TFP block group and 39 in the TAP block group. After surgery, participants received either TFP block (20 ml 0.25% bupivacaine for each side) or TAP block (20 ml 0.25% bupivacaine for each side). The primary outcome was the difference in obstetric quality of recovery 11-Turkish (ObsQoR-11T) scores between groups. Secondary outcomes included pain scores, opioid consumption and incidence of opioid-related complications. The mean ObsQoR-11T score was higher in the TFP block group compared with the TAP block group (97.13 ± 6.67 points vs. 87.10 ± 9.84 points, respectively; P < 0.001). The pain scores in the TFP block group were slightly lower between postoperative 4 and 24 h. The mean total morphine consumption was 15.08 ± 2.21 mg in the TFP block group and 22.21 ± 3.04 mg in the TAP block group ( P < 0.001). More patients required rescue analgesia between 4 and 8 h in the TAP block group [2.00 (5.00%) vs. 9.00 (23.08%), P = 0.02]. No significant differences were observed between groups in terms of opioid-related side effects. TFP block used for analgesic purposes yielded a better quality recovery period than TAP block and also reduced opioid consumption. Clinicaltrials.gov (NCT05999981). http://links.lww.com/EJA/B6 .

Benzylpiperidine derivatives as new dual μ-opioid and σ1 receptor ligands with potent antinociceptive effects

Dual-acting μ-opioid receptor (MOR)/sigma-1 receptor (σ1R) ligands have displayed promise in exerting robust antinociceptive effects while reducing opioid-related side effects. To discover safer and more effective analgesics, we designed, prepared, and evaluated 30 benzylpiperidine derivatives as dual MOR and σ1R ligands. The obtained benzylpiperidine analogs were tested for MOR and σ1R binding affinity in vitro. The best compound 52 showed high affinity for both MOR [Ki (MOR) = 56.4 nM] and σ1R [Ki (σ1R) = 11.0 nM] and produced potent antinociceptive effects in the abdominal contraction test (ED50 = 4.04 mg/kg in mice), carrageenan-induced inflammatory pain model (ED50 = 6.88 mg/kg in mice), formalin test (ED50 = 13.98 mg/kg in rats) and complete Freund’s adjuvant (CFA)-induced chronic pain model (ED50 = 7.62 mg/kg in mice). Moreover, 52 had less MOR-related adverse effects than oxycodone, including constipation, acute hyperlocomotion and physical dependence. The above results suggested that 52 may be a promising candidate for the development of safer analgesics.

Intrathecal administration of MCRT produced potent antinociception in chronic inflammatory pain models via μ-δ heterodimer with limited side effects

An important goal in the opioid field is to discover effective analgesic drugs with minimal side effects. MCRT demonstrated potent antinociceptive effects with limited side effects, making it a promising candidate. However, its pharmacological properties and how it minimizes side effects remain unknown. Various mouse pain and opioid side effect models were used to evaluate the antinociceptive properties and safety at the spinal level. The targets of MCRT were identified through cAMP measurement, isolated tissue assays, and pharmacological experiments. Immunofluorescence was employed to visualize protein expression. MCRT displayed distinct antinociceptive effects between acute and chronic inflammatory pain models due to its multifunctional properties at the μ opioid receptor (MOR), µ-δ heterodimer (MDOR), and neuropeptide FF receptor 2 (NPFFR2). Activation of NPFFR2 reduced MOR-mediated antinociception, leading to bell-shaped response curves in acute pain models. However, activation of MDOR produced more effective antinociception in chronic inflammatory pain models. MCRT showed limited tolerance and opioid-induced hyperalgesia in both acute and chronic pain models and did not develop cross-tolerance to morphine. Additionally, MCRT did not exhibit addictive properties, gastrointestinal inhibition, and effects on motor coordination. Mechanistically, peripheral chronic inflammation or repeated administration of morphine and MCRT induced an increase in MDOR in the spinal cord. Chronic administration of MCRT had no apparent effect on microglial activation in the spinal cord. These findings suggest that MCRT is a versatile compound that provides potent antinociception with minimal opioid-related side effects. MDOR could be a promising target for managing chronic inflammatory pain and addressing the opioid crisis.

Buprenorphine: The Opioid that Cried 'Partial Agonist'.

Although buprenorphine use has increased dramatically over the past decade, its unique pharmacologic and pharmacokinetic profile often leads to misconceptions about its overall utility and has created a drastic underrepresentation in patients with chronic non-can- cer pain. A common misnomer associated with buprenorphine is because of 'partial agonist' activity, it exhibits a plateauing of typical opioid-related side effects (including respiratory depression, constipation, euphoria, and hypogonadal axis suppression), but additionally it must exhibit a plateauing effect of overall analgesic potential. However, novel downstream molecular and cellular mechanisms offer new insights that help support the clinical potential that buprenorphine's analgesic actions may not have a ceiling, like its side effect profile. This interactive symposium will provide an enhanced review of the evolving research that helps unravel the complexity around buprenorphine's varying pharmacologic effects including actions on various opioid receptors, promiscuity to elicit varying actions on mu-opioid receptors coupled with different isoforms of G~ subunits, role in the intracellular recruitment of beta-arrestin, binding to different splice variants of mu-opioid receptors, and greater spinal versus supraspinal activity. The final half of this symposium will be designed to substantiate evidence with various human clinical trial data to further support buprenorphine's place on the analgesic ladder.

Comparison Of Ketorolac Versus Ibuprofen For Postoperative Pain Management In Total Abdominal Hystrectomy Surgeries

Background - Postoperative pain management is crucial for ensuring patient comfort and promoting faster recovery. Pharmacological interventions, such as NSAIDs, play an essential role in reducing pain intensity while minimizing opioid-related side effects. Ketorolac, a potent NSAID, and ibuprofen are both commonly used for pain relief. This study focuses on comparing the efficacy of these two drugs for pain management in total abdominal hysterectomy surgeries. Aim -To assess and compare the effects of intravenous ketorolac and intravenous ibuprofen on postoperative pain management in total abdominal hysterectomy patients. Materials and Methods: A randomized single-blind study was conducted on 30 patients, divided into two groups (Group K: ketorolac, Group I: ibuprofen). Various parameters, including VAS pain scores, sedation, time for rescue analgesia, and the number of rescue analgesics, were compared. Participants: 30 patients undergoing total abdominal hysterectomy, randomized into two groups (Group K: ketorolac, Group I: ibuprofen). Inclusion Criteria: Patients between 18 and 65 years of age undergoing elective surgery, ASA grade I or II. Exclusion Criteria: Patients with NSAID hypersensitivity, coagulation disorders, bronchial asthma, hepatic or renal failure, and peptic ulcers. Methodology: Patients received lumbar subarachnoid block, followed by either 30 mg of ketorolac or 800 mg of ibuprofen postoperatively. Rescue analgesics were provided if needed. Results: The postoperative pain scores were significantly lower in the ibuprofen group. Time for first rescue analgesia and the total number of rescue analgesics required were also lower in the ibuprofen group

Optimizing Regional Anesthesia for Cancer Patients: A Comprehensive Review of Current Practices and Future Directions.

Regional anesthesia has emerged as a pivotal component in the perioperative management of cancer patients, offering several advantages over traditional general anesthesia. By providing targeted pain relief and minimizing systemic exposure to opioids, regional anesthesia reduces the risk of opioid-related side effects and enhances postoperative recovery. Regional anesthesia may positively influence oncological outcomes by attenuating the surgical stress response and preserving immune function, potentially reducing cancer recurrence and metastasis. This review comprehensively explores the current practices and benefits of regional anesthesia in the oncology setting, including various techniques such as nerve blocks, epidural anesthesia, and spinal anesthesia. It examines the challenges associated with its application in cancer patients, including technical difficulties and patient-related factors. It evaluates the existing evidence regarding its impact on cancer progression and patient survival. Additionally, the review discusses future directions in the field, emphasizing the need for personalized anesthesia strategies, further research into the long-term effects of regional anesthesia on cancer outcomes, and the development of innovative approaches to enhance its efficacy and safety. By addressing these areas, this review aims to provide a thorough understanding of how to optimize regional anesthesia for cancer patients, ultimately contributing to improved perioperative care and better long-term outcomes.

Comparison of erector spinae plane and transversus abdominis plane block for postoperative analgesia after caesarean delivery under spinal anaesthesia: A randomised controlled trial

BackgroundTruncal blocks contribute to multimodal analgesia that enhances early recovery after caesarean delivery. The transversus abdominis plane (TAP) block is an established technique that offers somatic abdominal wall analgesia. The erector spinae plane (ESP) block is a fascial plane technique that may offer additional visceral analgesic effects. This study hypothesized that ESP block would offer superior analgesic efficacy to TAP block in women undergoing caesarean delivery under spinal anaesthesia. MethodsSixty-six ASA physical status grade 1–3 (≥18 years) patients undergoing elective caesarean delivery under spinal anaesthesia were randomly allocated to receive either bilateral ultrasound-guided TAP (N = 33) or ESP blocks at the T9 vertebral level (N = 35). The primary outcome measure was 24-hour cumulative morphine consumption. The secondary outcomes included time to first analgesic request, duration of block placement, numeric rating scale (NRS) pain scores at rest and movement, effect of pain on activities of daily living (ADLs) and care for the infant, patient analgesic satisfaction, frequency and severity of opioid-related side effects. ResultsThere was no statistically significant difference in mean (95% CI) 24-hour cumulative morphine consumption between groups: 32.0 (27.0 to 37.0) mg with TAP versus 27.0 (19.9 to 34.0) mg with ESP (p = 0.16). The mean (SD) duration of block placement was longer for ESP than for TAP blocks (10.7 (2.2) minutes versus 9.0 (2.5) minutes; p = 0.004). There were no significant differences in the other secondary outcomes. ConclusionThis study found similar postoperative opioid use and analgesic efficacy between ESP and TAP block after caesarean delivery performed under spinal anaesthesia.Trial Registration: South African National Clinical Trial Registry (DOH-27-102022-5278): https://sanctr.samrc.ac.za/TrialDisplay.aspx?TrialID=8100, Pan African Clinical Trials Registry (PACTR202301645957324): https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=24267.

Relative effects of serratus anterior plane block performed with dexmedetomidine combined with ropivacaine or ropivacaine alone on quality of recovery in children undergoing ear reconstruction

BackgroundDexmedetomidine (Dex) as a local anesthesia adjuvant for nerve block procedures can improve the quality of patient recovery. However, the impact of utilizing Dex as a local anesthetic adjuvant for serratus anterior plane block (SAPB) procedures on recovery quality for children undergoing ear reconstruction remains unclear. MethodsEighty-four patients undergoing ear reconstruction with autogenous costal cartilage (ACC) were randomized into two groups (n = 42/group) in which SAPB was performed with ropivacaine alone (R group) and one in which SAPB was performed with Dex and ropivacaine (DR group). Primary outcomes were patient 15-item quality of recovery (QoR-15) scale scores on days 1 and 2 post-surgery. Secondary outcomes included postoperative rest and coughing numerical rating scale (NRS) chest pain scores, duration of analgesia, oral rescue analgesic usage, and opioid-related side effects. ResultsForty patients per group completed the study. QoR-15 scores on days 1 and 2 post-surgery in the DR group were significantly increased relative to the R group (126.35±9.81 vs 115.53±8.58 and 131.78±8.67 vs 122.80±8.59, all P<0.001). Rest and coughing NRS chest pain scores at 2, 4, 8, 12, and 24h postoperatively in the DR group were all significantly lower relative to the R group (all P<0.05). The DR group also exhibited a significantly longer analgesic duration (P<0.001), and significantly reduced oral rescue analgesic usage and opioid-related side effect incidence (all P<0.05). ConclusionCombining Dex and ropivacaine for SAPB in children undergoing ear reconstruction with ACC can significantly improve quality of recovery, quality of analgesia, and analgesic duration.

Assessing the impact of opioid-free anesthesia using the modified Mulimix technique on postoperative pain in bariatric surgery patients: a correlative randomized double-blinded trial

Background &amp; objective: The effective management of postoperative pain in bariatric surgery poses significant challenges to the anesthesiologists and the surgeons. Opioids have been the mainstay of postoperative pain management; but recently, opioid-free anesthesia (OFA) has been a popular option in an effort to prevent the opioid related side-effects. The objective of this study was to assess the effects of OFA utilizing the modified mulimix technique on the levels of plasma interleukin-2 (IL-2) and interleukin-6 (IL-6). In addition, the study aimed to evaluate the duration of analgesia and the analgesic requirements during the first 24 hours postoperatively. Methodology: A total of 60 patients were randomly assigned to the OFA Group, which received opioid-free anesthesia, and the OBA Group, which received Opioid-Based Anesthesia. The modified Mulimix technique was used in both groups. Serum samples were collected from all patients during skin incision and after the surgical procedure. Subsequently, these samples were assessed for IL-2 and IL-6 levels. The postoperative analgesic consumption was compared in both groups. Results: Regarding serum IL-2 and IL-6 levels in the two study groups, there was a statistically significant difference after the conclusion of surgery, and the skin incision was made. Regarding the initial rescue analgesia postoperatively assessment, the OBA group demonstrated a substantially greater overall consumption of analgesics within the first 24 h. The study revealed a significant difference in VAS values between the OBA Group and the OFA Group at 2 h, 4 h, and 6 h postoperatively. Conclusion: The modified mulimix technique effectively reduces postoperative plasma inflammatory mediators, interleukin-2 and interleukin-6, and results in decreased postoperative pain, thus reducing the postoperative analgesia consumption Abbreviations: OBA - Opioid based anesthesia; OFA - opioid-free anesthesia; IL-2 - interleukin-2; IL-6 - interleukin-6; VAS - visual analogue scale Keywords: Bariatric surgery, interleukin, Mulimix, opioid, pain, immunological response. Citation: Seyam SHA, Hassan AE, Elsayed MM. Assessing the impact of opioid-free anesthesia using the modified Mulimix technique on postoperative pain in bariatric surgery patients: a correlative randomized double-blinded trial. Anaesth. pain intensive care 2024;28(4):721−726; DOI: 10.35975/apic.v28i4.2516 Received: March 04, 2024; Reviewed: May 18, 2024; Accepted: May 19, 2024

Long-term efficacy and reduced side-effects of buprenorphine in patients with moderate and severe chronic pain.

Chronic pain significantly impacts quality of life and poses substantial public health challenges. Buprenorphine, a synthetic analog of thebaine, is recognized for its potential in managing moderate to severe chronic pain with fewer side effects and a lower incidence of tolerance compared to traditional opioids. This retrospective study aimed to assess the long-term efficacy and safety of buprenorphine transdermal patches in patients with moderate and severe chronic pain, with a focus on pain relief sustainability and tolerance development. This retrospective observational study involved 246 patients prescribed buprenorphine transdermal patches. We evaluated changes in pain intensity using the Numeric Rating Scale (NRS), assessed opioid tolerance based on FDA guidelines for morphine-equivalent doses, and measured patient-reported outcomes through the Patients' Global Impression of Change (PGIC). Any adverse events were also recorded. Over the 36-month period, there was a significant reduction in NRS scores for both moderate and severe pain patients, demonstrating buprenorphine's sustained analgesic effect. Tolerance measurement indicated that no patients required increases in morphine-equivalent doses that would meet or exceed the FDA's threshold for opioid tolerance (60mg/day of morphine or equivalent). Additionally, patient satisfaction was high, with the PGIC reflecting significant improvements in pain management and overall wellbeing. The side effects were minimal, with skin reactions and nausea being the most commonly reported but manageable adverse events. The study findings validate the long-term use of buprenorphine transdermal patches as an effective and safe option for chronic pain management, maintaining efficacy without significant tolerance development. These results support the continued and expanded use of buprenorphine in clinical settings, emphasizing its role in reducing the burdens of chronic pain and opioid-related side effects. Further research is encouraged to refine pain management protocols and explore buprenorphine's full potential in diverse patient populations.

Opioid alternatives in spine surgeries.

The escalating opioid crisis has intensified the need to explore alternative pain management strategies for patients undergoing spine surgery. This review is timely and relevant as it synthesizes recent research on opioid alternatives for perioperative management, assessing their efficacy, side effects, and postoperative outcomes. A systematic search was conducted to capture articles from the past 18 months that examined opioid-sparing strategies. Findings indicate that multimodal analgesia, incorporating nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, lidocaine, gabapentinoids, N-methyl-D-aspartate (NMDA) antagonists, dexmedetomidine, and emerging regional block techniques like the erector spinae block and TLIF (thoraco lumbar interfascial block), can significantly reduce opioid consumption without compromising pain relief. Additionally, these approaches reduce opioid-related side effects such as postoperative nausea, vomiting, and prolonged hospital stays. The use of multimodal analgesia aligns with current pain management guidelines and addresses public health concerns related to opioid misuse. While effective, these alternatives are not without side effects, and the ultimate outcome depends on balancing benefits and risks. Future research should focus on the long-term outcomes of opioid alternatives, their effectiveness across diverse populations, and further validation and optimization of these strategies.

Efficacy and Safety of Extended-Release Dinalbuphine Sebacate for Postoperative Analgesia: A Systematic Review and Meta-analysis

Abstract Background Multimodal analgesia, which combines multiple medications with different analgesic mechanisms, is recommended for optimizing postoperative pain control and minimizing opioid-related side effects. Dinalbuphine sebacate (DNS), a prodrug of nalbuphine, has a 7-day long-acting analgesic effect on moderate to severe postoperative pain. We conducted a systematic review and meta-analysis to analyze the efficacy and safety of dinalbuphine sebacate for postoperative pain management. Materials and Methods We systematically searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials (RCTs) of DNS for postoperative analgesia. We assessed the quality of all included studies using the risk-of-bias tool. The primary outcome was postoperative pain score, and the secondary outcomes included analgesic consumption, need for rescue analgesics, adverse events, and length of hospital stay. A meta-analysis was performed for the pooled data, and the level of evidence was rated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Results We included five RCTs with 497 patients who underwent surgery. Compared with the control group, DNS significantly reduced the visual analog scale (VAS) through postoperative 48 hours {mean difference (MD) -37.54 (95% confidence interval [CI]: -70.47, -4.62)} to 7 days [MD -165.99 (95% CI: -231.44)], and decreased the requirement for rescue analgesics [RR 0.89 (95% CI: 0.81, 0.97)]. No significant difference was noted in VAS scores within postoperative 24 hours [MD -10.13 (95% CI: -30.11, 9.85)] or in total analgesic consumption. Patients receiving DNS had a higher risk of dizziness and injection site reactions, without an increased occurrence of other adverse events. Conclusions With a low-to-moderate level of evidence, intramuscular DNS provides long-lasting analgesia from postoperative 48 hours to 7 days and may reduce the requirement for postoperative rescue analgesics. However, DNS does not offer additional pain relief within the first 24 hours postoperatively. Further high-quality studies are warranted. International Prospective Register of Systematic Reviews (PROSPERO) registry: identifier: CRD42023494130

A smart device application for acute pain service in surgical patients at a tertiary hospital in South Korea: a prospective observational feasibility study.

Pain assessment and patient education are essential for successful postoperative pain management. However, the provision of personnel for performing these tasks is often insufficient. Recently, attempts have been made to implement smartphone applications for educating and monitoring surgical patients. We developed a smartphone application (app) for postoperative pain management, and conducted a feasibility study. This single-center prospective observational study included 60 patients aged < 70 years who underwent elective surgery. This study evaluated the SmartAPS application, which offers tools for postoperative pain assessment and educational materials for pain management. The primary outcome was the active usage rate, defined as responding at least twice daily on postoperative days (PODs) 1 and 2. Additionally, we investigated patient satisfaction with the app and educational videos as well as any challenges encountered during use. Sixty patients were enrolled in the study and active app use was achieved in 56.7% of them. Response rates peaked at 85.0% for pain intensity and 83.3% for opioid-related side effects at 14:00 on POD 1 but dropped to 56.7% and 58.3%, respectively, at 18:00 on POD 2. Among the patients who responded to the survey regarding the app usage, 84.0% reported satisfaction with the app and 80% found it beneficial for managing postoperative pain. Furthermore, 92.0% did not encounter difficulties using the app, indicating a generally positive user experience. Our findings support the utility of the SmartAPS application in acute pain services, highlighting its potential for improving postoperative pain management.

Comparison of Pericapsular Nerve Group and Lateral Quadratus Lumborum Blocks for Analgesia after Primary Total Hip Arthroplasty: A Randomized Controlled Trial.

The quadratus lumborum block (QLB) and the pericapsular nerve group (PENG) block both provide effective postoperative analgesia after hip surgery while minimizing impact on motor function. This study aimed to compare QLB and PENG in patients undergoing primary total hip arthroplasty. This superiority trial randomized patients scheduled for elective total hip arthroplasty to receive a lateral QLB or PENG with lateral femoral cutaneous nerve blocks for postoperative analgesia. Perioperative analgesic protocols were standardized. The primary outcome was postoperative cumulative opioid consumption at 72 hours. Secondary outcome was postoperative pain scores. Additional outcomes of interest included time to first ambulation, length of stay, patient reported outcome measures, and opioid-related side effects. This trial consented and randomized 106 subjects and 101 were included in analysis: PENG (n=50), QLB (n=51). Mean (95% CI) opioid consumption (IV MME) in the first 72 hours did not differ between PENG [109.6 (93.6, 125.6)] and QL [92.3 (76.6, 107.9)] groups (p=0.129) There were no significant differences between treatment arms in average pain score, time to ambulation, distance ambulated, rate of same day discharge, or hospital length of stay. There were also no differences in patient reported outcomes using HOOS-JR and PROMIS-10 scores. Patients undergoing primary THA receiving preoperative PENG vs QLB had similar opioid consumption, pain scores, time to ambulation, and hospital length of stay. Both QL and PENG blocks are analgesic options in patients undergoing primary THA. NCT05710107; www.ClinicalTrial.gov IRB Protocol ID: Pro00124880. Pericapsular nerve group (PENG) block may provide analgesia after hip arthroplasty and improve early functional recovery. This study evaluated postoperative opioid consumption in patients randomized to PENG or lateral quadratus lumborum block (QLB).Opioid consumption, pain scores, motor recovery, and functional outcome measures did not differ in patients randomized to PENG vs lateral QLB.PENG and lateral QLBs are analgesic options following total hip arthroplasty with similar rates of same day discharge.

Molecular Transformers: Adaptive Multitarget Ligands for Esterase-Induced Transition from Analgesics to Anesthetics.

Multitarget strategies are essential in addressing complex diseases, yet developing multitarget-directed ligands (MTDLs) is particularly challenging when aiming to engage multiple therapeutic targets across different tissues. Here, we present a molecular transformer strategy, enhancing traditional MTDLs. By utilizing esterase-driven hydrolysis, this approach mimics the adaptive nature of transformers for enabling molecules to modify their pharmacological effects in response to the biological milieu. By virtual screening and biological evaluation, we identified KGP-25, a novel compound initially targeting the voltage-gated sodium channel 1.8 (Nav1.8) in the peripheral nervous system (PNS) for analgesia, and later the γ-aminobutyric acid subtype A receptor (GABAA) in the central nervous system (CNS) for general anesthesia. Our findings confirm KGP-25's dual efficacy in cellular and animal models, effectively reducing opioid-related side effects. This study validates the molecular transformer approach in drug design and highlights its potential to overcome the limitations of conventional MTDLs, paving new avenues in innovative therapeutic strategies.

Clinical Analysis of Different Anesthesia and Analgesia Methods for Patients Undergoing Uniportal Video-assisted Lung Surgery

PurposeA comparison of three intra-op modalities to determine a best and convenient pain control for uniportal lung surgery. This study compared general anesthesia with serratus plane block, general anesthesia with epidural and general anesthesia alone to look at post-operative pain scores in patients. Methods80 patients were enrolled and statistically analyzed. There were three interventions studied: Group S: General Anesthesia with Serratus Plane Block, Group E: General Anesthesia with thoracic epidural, Group G: General Anesthesia only. Outcome measures compared among 3 groups included demographic characters; surgical types; anesthesia and operative time; postoperative pain scores; vitals sign; morphine consumption at 0, 2, 6 hours, day1 and day2 postoperative; incidence of opioid-related adverse events and chronic pain; LOS hospital and overall expenses.The numerical rating scale was used to assess the degree of pain on the first and second postoperative days. Postoperative morphine consumption, incidence of opioid-related side effects, LOS(length of stay) hospital and overall hospital expenses were documented, as well as incidence of chronic postoperative pain. FindingsThere was no difference in incidence of opioid-related adverse events and chronic pain, LOS hospital and overall expenses among 3 groups. After investigating factors that may influence LOS hospital and overall expenses, the multivariable analysis indicated only longer operative time was associated with longer hospital stay and more hospital expenses. ImplicationsThis prospective study demonstrates that general anesthesia alone offers an easy and efficient approach resulting in similar postoperative pain scores and morphine consumption compared with nerve block and epidural. Longer operative time was associated with longer hospital stay and more hospital expenses.