Microglial exosome miR-124-3p in hippocampus alleviates cognitive impairment induced by postoperative pain in elderly mice.

Cognitive impairment induced by postoperative pain severely deteriorates the rehabilitation outcomes in elderly patients. The present study focused on the relationship between microglial exosome miR-124-3p in hippocampus and cognitive impairment induced by postoperative pain. Cognitive impairment model induced by postoperative pain was constructed by intramedullary nail fixation after tibial fracture. Morphine intraperitoneally was carried out for postoperative analgesia. Morris water maze tests were carried out to evaluate the cognitive impairment, while mRNA levels of neurotrophic factors (BDNF, NG) and neurodegenerative biomarker (VILIP-1) in hippocampus were tested by q-PCR. Transmission electron microscope was used to observe the axon degeneration in hippocampus. The levels of pro-inflammatory factors (TNF-α, IL-1ß, IL-6), the levels of anti-inflammatory factors (Ym, Arg-1, IL-10) and microglia proliferation marker cyclin D1 in hippocampus were measured to evaluate microglia polarization. Bioinformatics analysis was conducted to identify key exosomes while BV-2 microglia overexpressing exosome miR-124-3p was constructed to observe microglia polarization in vitro experiments. Exogenous miR-124-3p-loaded exosomes were injected into hippocampus in vivo. Postoperative pain induced by intramedullary fixation after tibial fracture was confirmed by decreased mechanical and thermal pain thresholds. Postoperative pain induced cognitive impairment, promoted axon demyelination, decreased BDNF, NG and increased VILIP-1 expressions in hippocampus. Postoperative pain also increased pro-inflammatory factors, cyclin D1 and decreased anti-inflammatory factors in hippocampus. However, these changes were all reversed by morphine analgesia. Bioinformatics analysis identified the critical role of exosome miR-124-3p in cognitive impairment, which was confirmed to be down-regulated in hippocampus of postoperative pain mice. BV-2 microglia overexpressing exosome miR-124-3p showed decreased pro-inflammatory factors, cyclin D1 and increased anti-inflammatory factors. In vivo, stereotactic injection of exogenous miR-124-3p into hippocampus decreased pro-inflammatory factors, cyclin D1 and increased anti-inflammatory factors. The cognitive impairment, axon demyelination, decreased BDNF, NG and increased VILIP-1 expressions in hippocampus were all alleviated by exogenous exosome miR-124-3p. Microglial exosome miR-124-3p in hippocampus alleviates cognitive impairment induced by postoperative pain through microglia polarization in elderly mice.

Improved Postoperative Pain Management Outcomes After Implementation of Enhanced Recovery After Surgery (ERAS) Protocol for Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC).

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for patients with peritoneal carcinomatosis is promising but has potential for significant morbidity and prolonged hospitalization. Enhanced Recovery After Surgery (ERAS) is a standardized protocol designed to optimize perioperative care. This study describes trends in epidural and opioid use after implementing ERAS for CRS-HIPEC at a tertiary academic center. METHODS: A retrospective analysis of patients undergoing CRS-HIPEC from January 2020 to September 2023 was conducted. ERAS was implemented in February 2022. Medication and outcomes data were compared before and after ERAS initiation. All opioids were converted to morphine milligram equivalents (MMEs). RESULTS: A total of 136 patients underwent CRS-HIPEC: 73 (54%) pre- and 63 (46%) post-ERAS. Epidural usage increased from 63% pre-ERAS to 87% post-ERAS (p = 0.001). Compared with those without epidurals, patients with epidurals had decreased total 7-day oral and intravenous (IV) opioid requirements (45 MME vs. 316 MME; p < 0.001). There was no difference in 7-day opioid totals between pre- and post-ERAS groups. After ERAS, more patients achieved early ambulation (83% vs. 53%; p < 0.001), early diet initiation (81% vs. 25%; p < 0.001), and early return of bowel function (86% vs. 67%; p = 0.012). CONCLUSIONS: ERAS implementation for CRS-HIPEC was associated with increased epidural use, decreased oral and IV opioid use, and earlier bowel function return. Our study demonstrates that epidural analgesia provides adequate pain control while significantly decreasing oral and IV opioid use, which may promote gastrointestinal recovery postoperatively. These findings support the implementation of an ERAS protocol for effective pain management in patients undergoing CRS-HIPEC.

A bundle of opioid-sparing strategies to eliminate routine opioid prescribing in a urogynecology practice.

BACKGROUND: Current evidence supports that many patients do not use prescribed opioids following reconstructive pelvic surgery, yet it remains unclear if it is feasible to eliminate routine opioid prescriptions without a negative impact on patients or providers. OBJECTIVE: To determine if there is a difference in the proportion of patients discharged without opioids after implementing a bundle of opioid-sparing strategies and tiered prescribing protocol compared to usual care after minimally invasive pelvic reconstructive surgery (transvaginal, laparoscopic, or robotic). Secondary objectives include measures of patient-perceived pain control and provider workload. STUDY DESIGN: The bundle of opioid-sparing strategies and tiered prescribing protocol intervention was implemented as a division-wide evidence-based practice change on August 1, 2022. This retrospective cohort compares a 6-month postintervention (bundle of opioid-sparing strategies and tiered prescribing protocol) cohort to 6-month preintervention (usual care) of patients undergoing minimally invasive pelvic reconstructive surgery. A 3-month washout period was observed after bundle of opioid-sparing strategies and tiered prescribing protocol initiation. We excluded patients <18 years, failure to consent to research, combined surgery with other specialties, urge urinary incontinence or urinary retention procedures alone, and minor procedures not typically requiring opioids. Primary outcome was measured by proportion discharged without opioids and total oral morphine equivalents prescribed. Pain control was measured by pain scores, postdischarge prescriptions and refills, phone calls and visits related to pain, and satisfaction with pain control. Provider workload was demonstrated by phone calls and postdischarge prescription refills. Data were obtained through chart review on all patients who met inclusion criteria. Primary analysis only included patients prescribed opioids according to the bundle of opioid-sparing strategies and tiered prescribing protocol protocol. Two sample t tests compared continuous variables and chi-square tests compared categorical variables. RESULTS: Four hundred sixteen patients were included in the primary analysis (207 bundle of opioid-sparing strategies and tiered prescribing protocol, 209 usual care). Baseline demographics were similar between groups, except a lower proportion of irritable bowel syndrome (13% vs 23%; P<.01) and pelvic pain (15% vs 24.9%; P=.01), and higher history of prior gynecologic surgery (69.1% vs 58.4%; P=.02) in the bundle of opioid-sparing strategies and tiered prescribing protocol cohort. The bundle of opioid-sparing strategies and tiered prescribing protocol cohort was more likely to be discharged without opioids (68.1% vs 10.0%; P<.01). In those prescribed opioids, total oral morphine equivalents on discharge was significantly lower in the bundle of opioid-sparing strategies and tiered prescribing protocol cohort (48.1 vs 81.8; P<.01). The bundle of opioid-sparing strategies and tiered prescribing protocol cohort had a 20.6 greater odds (confidence interval 11.4, 37.1) of being discharged without opioids after adjusting for surgery type, arthritis/joint pain, IBS, pelvic pain, and contraindication to nonsteroidal anti-inflammatory drugs. The bundle of opioid-sparing strategies and tiered prescribing protocol cohort was also less likely to receive a rescue opioid prescription after discharge (1.4% vs 9.5%; P=.03). There were no differences in opioid prescription refills (19.7% vs 18.1%; P=.77), emergency room visits for pain (3.4% vs 2.9%; P=.76), postoperative pain scores (mean 4.7 vs 4.0; P=.07), or patient satisfaction with pain control (81.5% vs 85.6%; P=.21). After bundle of opioid-sparing strategies and tiered prescribing protocol implementation, the proportion of postoperative phone calls for pain also decreased (12.6% vs 21.5%; P=.02). Similar results were identified when nonadherent prescribing was included in the analysis. CONCLUSION: A bundle of evidence-based opioid sparing strategies and tiered prescribing based on inpatient use increases the proportion of patients discharged without opioids after minimally invasive pelvic reconstructive surgery without evidence of uncontrolled pain or increased provider workload.

Recovery and immune function after low pressure pneumoperitoneum during robot-assisted radical prostatectomy: a randomised controlled trial.

OBJECTIVE: To compare the effectiveness of low intra-abdominal pressure (IAP) facilitated by deep neuromuscular block (NMB) to standard practice in improving the quality of recovery, preserving immune function, and enhancing parietal perfusion during robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS: In this blinded, randomised controlled trial, 96 patients were randomised to the experimental group with low IAP (8 mmHg) facilitated by deep NMB (post-tetanic count 1-2) or the control group with standard IAP (14 mmHg) and moderate NMB (train-of-four 1-2). Recovery was measured using the 40-item Quality of Recovery questionnaire and 36-item Short-Form Health survey. Immune function was evaluated by plasma damage-associated molecular patterns, cytokines, and ex vivo lipopolysaccharide-stimulated cytokine production. Parietal peritoneum perfusion was measured by analysing the recordings of indocyanine-green injection. RESULTS: Quality of recovery was not superior in the experimental group (n = 46) compared to the control group (n = 50). All clinical outcomes, including pain scores, postoperative nausea and vomiting, and hospital stay were similar. There were no significant differences in postoperative plasma concentrations of damage-associated molecular patterns, cytokines, and ex vivo cytokine production capacity. The use of low IAP resulted in better parietal peritoneum perfusion. CONCLUSION: Despite better perfusion of the parietal peritoneum, low IAP facilitated by deep NMB did not improve the quality of recovery or preserve immune function compared to standard practice in patients undergoing RARP.

Effects of intraoperative low-dose esketamine on postoperative pain after vestibular schwannoma resection: A prospective randomized, double-blind, placebo-controlled study.

AIMS: Esketamine may reduce acute postoperative pain in several settings. However, the effects of low-dose esketamine on postoperative pain after vestibular schwannoma (VS) resection with propofol/remifentanil total intravenous anaesthesia (TIVA) are unclear. The aim of this study is to observe the effects of intraoperative low-dose esketamine on postoperative pain after vestibular schwannoma resection. METHODS: This single-centre, randomized, placebo-controlled, double-blind trial included 90 adults undergoing VS resection via the retrosigmoid approach with TIVA. The patients were randomly allocated to two groups: esketamine or control (n = 45 in each group). Patients received low-dose esketamine (0.2 mg/kg) or a similar volume of normal saline after dural closure. The primary outcome was the pain score during movement (gentle head movement) at 24 h postoperatively. Secondary outcomes included recovery time, bispectral index (BIS) values and haemodynamic profiles during the first 30 min after esketamine administration, and adverse effects. RESULTS: Low-dose esketamine did not reduce pain scores at rest (P > .05) or with movement (P > .05) within the first 24 h after surgery. Esketamine moderately increased BIS values for at least 30 min after administration (P < .0001) but did not affect heart rate (P = .992) or mean arterial blood pressure (P = .994). Esketamine prolonged extubation time (P = .042, 95% confidence interval: 0.08 to 4.42) and decreased the effect-site concentration of remifentanil at extubation (P = .001, 95% confidence interval: -0.53 to -0.15) but did not affect the time to resumption of spatial orientation. Postoperative nausea and vomiting rates did not differ between groups, and no hallucinations or excessive sedation was observed. CONCLUSION: Intraoperative low-dose esketamine did not significantly reduce acute pain after VS resection with propofol/remifentanil TIVA. However, BIS values increased for at least 30 min after esketamine administration.

A randomized, double-blind study to compare the efficacy and safety of nalbuphine nasal spray and injectable solution in patients after orthopaedic interventions and traumatological procedures.

AIMS: Our previous 3-period crossover study in healthy volunteers comparing the pharmacokinetics of nalbuphine nasal spray Apain with parenteral nalbuphine solution demonstrated high bioavailability of the nasal spray and close similarity of pharmacokinetic profiles after intranasal and intramuscular administration, especially within 30 min postdose. The aim of the present study was a noninferiority assessment of nalbuphine nasal spray vs. intramuscular injection for pain relief in postoperative patients. METHODS: Ninety orthopaedic and traumatology patients were enrolled in this double-blind, randomized study of the effectiveness and tolerance of a single 10.5 mg dose of nalbuphine nasal spray vs. 10 mg intramuscular injection. The summed pain intensity difference (SPID0-6) calculated using visual analogue scale scores was the primary study endpoint. RESULTS: Of 90 subjects enrolled, the per-protocol efficacy population comprised 79 patients; 6 patients in the reference group and 5 patients in the test group were excluded due to remedication. The mean values of study endpoints with 95% confidence interval were as follows in reference and test groups, respectively: SPID0-6 = 228.08 (205.73-250.43) vs. 248.73 9 (225.83-271.63), time to pain relief onset = 0.28 h (0.25-0.31) vs. 0.27 h (0.25-0.29), duration of analgesia = 5.55 h (5.17-5.93) vs. 5.51 h (5.10-5.92), area under the curve = 119.30 (91.17-147.43) vs. 99.81 (74.52-107.10). No statistically significant differences were revealed. CONCLUSION: Nalbuphine nasal spray Apain has been proven to be a safe, noninvasive alternative to intramuscular nalbuphine to relieve severe postoperative pain. Designed for self-administration and dose-adjusting, the noncontrolled opioid analgesic nalbuphine spray can be used for patient-controlled analgesia in out-of-hospital, field and home settings.

Association of Race and Ethnicity With Postoperative Gabapentinoid and Opioid Prescribing Trends for Older Adults.

BACKGROUND: Disparities in opioid prescribing by race/ethnicity have been described in many healthcare settings, with White patients being more likely to receive an opioid prescription than other races studied. As surgeons increase prescribing of nonopioid medications in response to the opioid epidemic, it is unknown whether postoperative prescribing disparities also exist for these medications, specifically gabapentinoids. METHODS: We conducted a retrospective cohort study using a 20% Medicare sample for 2013-2018. We included patients ≥66 years without prior gabapentinoid use who underwent one of 14 common surgical procedures. The primary outcome was the proportion of patients prescribed gabapentinoids at discharge among racial and ethnic groups. Secondary outcomes were days' supply of gabapentinoids, opioid prescribing at discharge, and oral morphine equivalent (OME) of opioid prescriptions. Trends over time were constructed by analyzing proportion of postoperative prescribing of gabapentinoids and opioids for each year. For trends by year by racial/ethnic groups, we ran a multivariable logistic regression with an interaction term of procedure year and racial/ethnic group. RESULTS: Of the 494,922 patients in the cohort (54% female, 86% White, 5% Black, 5% Hispanic, mean age 73.7 years), 3.7% received a new gabapentinoid prescription. Gabapentinoid prescribing increased over time for all groups and did not differ significantly among groups (P = 0.13). Opioid prescribing also increased, with higher proportion of prescribing to White patients than to Black and Hispanic patients in every year except 2014. CONCLUSIONS: We found no significant prescribing variation of gabapentinoids in the postoperative period between racial/ethnic groups. Importantly, we found that despite national attention to disparities in opioid prescribing, variation continues to persist in postoperative opioid prescribing, with a higher proportion of White patients being prescribed opioids, a difference that persisted over time.

Intercostal nerve cryoablation reduces opioid utilization after thoracotomy in children with cancer.

BACKGROUND: Intercostal nerve cryoablation (INC) has shown promise as an adjunct method for analgesia in adults undergoing thoracotomy, but has yet to be widely used in children for this indication. We hypothesize that INC decreases opioid utilization in children undergoing thoracotomy for cancer operations. METHODS: A retrospective review was performed of children who underwent thoracotomy for cancer diagnosis at a freestanding children's hospital from 2018 to 2023. Patient characteristics, intraoperative data, and data on clinical course were collected. Patients were divided into those who underwent INC and those who underwent routine care for comparison. RESULTS: Twenty-six patients underwent 38 procedures at a median age of 16 years (range 5-21 years). INC was performed in 23 cases over a median of five intercostal levels (range 2-7). Total oral morphine equivalents during inpatient admission were significantly lower in INC patients (137.6 vs. 514.5 mg, p = .002). Routine care patients were more likely to be discharged with an opioid prescription (30.4% vs. 80.0%, p = .008). Length of stay was similar between patients with INC and routine care (4 vs. 5 days, p = .15). There were no differences in rates of reoperation or 30-day re-admission (emergency department or inpatient). CONCLUSTIONS: INC is a feasible and safe adjunct for children undergoing thoracotomy for cancer. INC is associated with reduced postoperative opioid utilization with respect to both inpatient use and outpatient prescriptions.

Intravenous versus perineural dexamethasone to prolong analgesia after interscalene brachial plexus block: a systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: The efficacy of perineural vs intravenous dexamethasone as a local anaesthetic adjunct to increase duration of analgesia could be particular to specific peripheral nerve blocks because of differences in systemic absorption depending on the injection site. Given this uncertainty, we performed a systematic review with meta-analysis and trial sequential analysis comparing dexamethasone administered perineurally or intravenously combined with local anaesthetic for interscalene brachial plexus block. METHODS: Following a search of various electronic databases, we included 11 trials (1145 patients). The primary outcome was the duration of analgesia defined as the time between peripheral nerve block or onset of sensory blockade and the time to first analgesic request or initial report of pain. RESULTS: The primary outcome, duration of analgesia, was greater in the perineural dexamethasone group, with a mean difference (95% confidence interval) of 122 (62-183) min, I2=73%, P<0.0001. Trial sequential analysis indicated that firm evidence had been reached. The quality of evidence was downgraded to low, mainly because of moderate inconsistency and serious publication bias. No significant differences were present for any of the secondary outcomes, except for onset time of sensory and motor blockade and resting pain score at 12 h, but the magnitude of differences was not clinically relevant. CONCLUSIONS: There is low-quality evidence that perineural administration of dexamethasone as a local anaesthetic adjunct increases duration of analgesia by an average of 2 h compared with intravenous injection for interscalene brachial plexus block. Given the limited clinical relevance of this difference, the off-label use of perineural administration, and the risk of drug crystallisation, we recommend intravenous dexamethasone administration. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42023466147).

Comparison of postoperative pain in children after maintenance anaesthesia with propofol or sevoflurane: a systematic review and meta-analysis.

BACKGROUND: Propofol and sevoflurane are two of the most commonly used anaesthetics for paediatric surgery. Data from some clinical trials suggest that postoperative pain incidence is lower when propofol is used for maintenance of anaesthesia compared with sevoflurane, although this is not clear. METHODS: This meta-analysis compared postoperative pain following maintenance of anaesthesia with propofol or sevoflurane in paediatric surgeries. PubMed Medline, Embase, Scopus, Web of Science and Cochrane Library were searched for randomised controlled trials (RCTs) that compared postoperative pain between sevoflurane and propofol anaesthesia in children. After quality assessment, a meta-analysis was carried out using bias-adjusted inverse heterogeneity methods, heterogeneity using I2 and publication bias using Doi plots. RESULTS: In total, 13 RCTs with 1174 children were included. The overall synthesis suggested nearly two-fold higher odds of overall postoperative pain in the sevoflurane group compared with the propofol group (odds ratio [OR] 1.88, 95% confidence interval [CI] 1.12-3.15, I2=58.2%). Further, children in the sevoflurane group had higher odds of having higher pain scores (OR 3.18, 95% CI 1.83-5.53, I2=20.9%), and a 60% increase in the odds of requiring postoperative rescue analgesia compared with propofol (OR 1.60, 95% CI 0.89-2.88, I2=58.2%). CONCLUSIONS: Children maintained on inhalational sevoflurane had higher odds of postoperative pain compared with those maintained on propofol. The results also suggest that sevoflurane is associated with higher odds of needing postoperative rescue analgesia compared with propofol. REGISTRATION: The protocol for this systematic review and meta-analysis was registered on the International Prospective Register of Systematic Reviews (PROSPERO) with registration ID CRD42023445913.

The impact of timing, type, and method of instillation of intraperitoneal local anaesthetic in laparoscopic abdominal surgery: a systematic review and network meta-analysis.

BACKGROUND: Pain is common after laparoscopic abdominal surgery. Intraperitoneal local anaesthetic (IPLA) is effective in reducing pain and opioid use after laparoscopic surgery, although the optimum type, timing, and method of administration remains uncertain. We aimed to determine the optimal approach for delivering IPLA which minimises opioid consumption and pain after laparoscopic abdominal surgery. METHODS: MEDLINE, Embase, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were systematically searched for randomised controlled trials comparing different combinations of the type (bupivacaine vs lidocaine vs levobupivacaine vs ropivacaine), timing (pre-vs post-pneumoperitoneum at the beginning or end of surgery), and method (aerosol vs liquid) of IPLA instillation in patients undergoing any laparoscopic abdominal surgery. A network meta-analysis was conducted to ascertain the optimum approach for delivering IPLA resulting in the least cumulative opioid consumption and pain (overall and localising to the shoulder) 24 h after surgery. Certainty of evidence was evaluated using Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) assessments (PROSPERO ID: CRD42022307595). RESULTS: Twenty-five RCTs were included, among which 15 different combinations of delivering IPLA were analysed across 2401 participants. Aerosolised bupivacaine instilled at the end of surgery, before deflation of the pneumoperitoneum, was associated with significantly less postoperative opioid consumption compared with all other approaches for delivering IPLA (98.7% of comparisons; moderate certainty), aside from liquid levobupivacaine instilled before surgery and during or after creation of the pneumoperitoneum (mean difference -11.6, 95% credible interval: -26.1 to 2.5 i.v. morphine equivalent doses). There were no significant differences between different IPLA approaches regarding overall pain scores and incidence of shoulder pain up to 24 h after surgery. CONCLUSIONS: There are limited studies and low-quality evidence to conclude on the optimum method of delivering IPLA in laparoscopic abdominal surgery. While aerosolised bupivacaine instilled at the end of surgery but before deflation of the pneumoperitoneum minimises postoperative opioid consumption, pain scores up to 24 h did not differ between the different modalities of delivering IPLA. The generalisability of these results is limited by the lack of utilisation of non-opioid analgesics in most trials. SYSTEMATIC REVIEW PROTOCOL REGISTRATION: PROSPERO CRD42022307595.

Long term opioid use after burn injury: a retrospective cohort study.

BACKGROUND: Patients who have survive a burn injury might be at risk of opioid dependence after discharge. This study examined the use of opioids in patients who suffer burn injury and explored factors associated with persistent opioid use after hospital discharge. METHODS: This retrospective cohort study compared adults admitted with a burn injury from 2009 to 2019 with two matched comparison cohorts from the general population and adults with a diagnosis of acute pancreatitis. Pre-admission prescription opioid use was determined, and a multivariable negative binomial regression analysis used to explore post-discharge opioid use. RESULTS: A total of 7147 burn patients were matched with 6810 pancreatitis patients and with 28 184 individuals from the general population. Pre-admission opioid use was higher in the burn and pancreatitis cohorts (29% and 40%, respectively) compared with the general population (17%). Opioid use increased in both burn and pancreatitis cohorts after discharge (41% and 53%, respectively), although patients with pancreatitis were at even higher risk of increased opioid use in an adjusted analysis (incidence rate ratio 1.43). Female sex, lower socioeconomic status, ICU admission, pre-injury opioid use, and a history of excess alcohol use were all associated with an increase in opioid prescriptions after discharge. CONCLUSIONS: Opioid use is high in those admitted with a burn injury or acute pancreatitis when compared with the general population, increasing further after hospital discharge. Female sex and socioeconomic deprivation are among factors that make increased opioid use more likely, although this phenomenon seems even more pronounced in those with acute pancreatitis compared with burn injuries.

Preoperative psychological symptoms and chronic postsurgical pain: analysis of the prospective China Surgery and Anaesthesia Cohort study.

BACKGROUND: Both preoperative psychological symptoms and chronic postsurgical pain (CPSP) are prevalent conditions and major concerns among surgery patients, with inconclusive associations. METHODS: Based on the China Surgery and Anaesthesia Cohort (CSAC), we recruited 8350 surgery patients (40-65 yr old) from two medical centres between July 2020 and March 2023. Patients with preoperative psychological symptoms (i.e. anxiety, depression, stress reaction, and poor sleep quality) were identified using corresponding well-established scales. We then examined the associations of individual preoperative psychological symptoms and major patterns of preoperative psychological symptoms (identified by k-means clustering analysis) with CPSP, and different pain trajectories within 3 months. Lastly, mediation analyses were conducted to elucidate the mediating role of surgery/anaesthesia-related factors and the presence of 1-month postoperative psychological symptoms on the studied associations. RESULTS: We included 1302 (1302/8350, 15.6%) CPSP patients. When analysed separately, all studied preoperative psychological symptoms were associated with increased CPSP risk, with the most pronounced odds ratio noted for anxiety (1.52, 95% confidence interval [CI] 1.23-1.86). Compared with patients clustered in the minor symptom group, excess risk of CPSP and experiencing an increasing pain trajectory was increased among patients with preoperative psychological symptoms featured by sleep disturbances (odds ratio=1.46, 95% CI 1.25-1.70 for CPSP and 1.58, 95% CI 1.20-2.08 for increasing pain trajectory) and multiple psychological symptoms (1.84 [95% CI 1.48-2.28] and 4.34 [95% CI 3.20-5.88]). Mediation analyses revealed acute/subacute postsurgical pain and psychological symptoms existing 1 month after surgery as notable mediators of the observed associations. CONCLUSIONS: The presence of preoperative psychological symptoms might individually or jointly increase the risk of chronic postsurgical pain or experiencing deterioration in pain trajectory. Interventions for managing acute/subacute postsurgical pain and psychological symptoms at 1 month after surgery might help reduce such risk. CLINICAL TRIAL REGISTRATION: ChiCTR2000034039.

Preoperative pain sensitivity and its correlation with postoperative acute and chronic pain: a systematic review and meta-analysis.

BACKGROUND: Preoperative pain sensitivity (PPS) can be associated with postsurgical pain. However, estimates of this association are scarce. Confirming this correlation is essential to identifying patients at high risk for severe postoperative pain and for developing analgesic strategy. This systematic review and meta-analysis summarises PPS and assessed its correlation with postoperative pain. METHODS: PubMed, Scopus, Cochrane Library, and PsycINFO were searched up to October 1, 2023, for studies reporting the association between PPS and postsurgical pain. Two authors abstracted estimates of the effect of each method independently. A random-effects model was used to combine data. Subgroup analyses were performed to investigate the effect of pain types and surgical procedures on outcomes. RESULTS: A total of 70 prospective observational studies were included. A meta-analysis of 50 studies was performed. Postoperative pain was negatively associated with pressure pain threshold (PPT; r=-0.15, 95% confidence interval [CI] -0.23 to -0.07]) and electrical pain threshold (EPT; r=-0.28, 95% CI -0.42 to -0.14), but positively correlated with temporal summation of pain (TSP; r=0.21, 95% CI 0.12-0.30) and Pain Sensitivity Questionnaire (PSQ; r=0.25, 95% CI 0.13-0.37). Subgroup analysis showed that only TSP was associated with acute and chronic postoperative pain, whereas PPT, EPT, and PSQ were only associated with acute pain. A multilevel (three-level) meta-analysis showed that PSQ was not associated with postoperative pain. CONCLUSIONS: Lower PPT and EPT, and higher TSP are associated with acute postoperative pain while only TSP is associated with chronic postoperative pain. Patients with abnormal preoperative pain sensitivity should be identified by clinicians to adopt early interventions for effective analgesia. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42023465727).

Regional anaesthesia truncal blocks for acute postoperative pain and recovery: a narrative review.

Significant acute postoperative pain remains prevalent among patients who undergo truncal surgery and is associated with increased morbidity, prolonged patient recovery, and increased healthcare costs. The provision of high-quality postoperative analgesia is an important component of postoperative care, particularly within enhanced recovery programmes. Regional anaesthetic techniques have become increasingly prevalent within multimodal analgesic regimens and the widespread adoption of ultrasonography has facilitated the development of novel fascial plane blocks. The number of described fascial plane blocks has increased significantly over the past decade, leading to a burgeoning area of clinical investigation. Their applications are increasing, and truncal fascial plane blocks are increasingly recommended as part of procedure-specific guidelines. Some fascial plane blocks have been shown to be more efficacious than others, with favourable side-effect profiles compared with neuraxial analgesia, and are increasingly utilised in breast, thoracic, and other truncal surgery. However, use of these blocks is debated in regional anaesthesia circles because of limitations in our understanding of their mechanisms of action. This narrative review evaluates available evidence for the analgesic efficacy of the most commonly practised fascial plane blocks in breast, thoracic, and abdominal truncal surgery, in particular their efficacy compared with systemic analgesia, alternative blocks, and neuraxial techniques. We also highlight areas where investigations are ongoing and suggest priorities for original investigations.

The analgesic effectiveness of perioperative lidocaine infusions for acute and chronic persistent postsurgical pain in patients undergoing breast cancer surgery: a systematic review and meta-analysis.

BACKGROUND: Breast cancer is the most common cancer among women and tumour resection carries a high prevalence of chronic persistent postsurgical pain (CPSP). Perioperative i.v. lidocaine infusion has been proposed as protective against CPSP; however, evidence of its benefits is conflicting. This review evaluates the effectiveness of perioperative lidocaine infusions for breast cancer surgery. METHODS: Randomised trials comparing perioperative lidocaine infusions with parenteral analgesia in breast cancer surgery patients were sought. The two co-primary outcomes were the odds of CPSP at 3 and 6 months after operation. Secondary outcomes included rest pain at 1, 6, 12, and 24 h; analgesic consumption at 0-24 and 25-48 h; quality of recovery; opioid-related side-effects; and lidocaine infusion side-effects. Hartung-Knapp-Sidik-Jonkman (HKSJ) random effects modelling was used. RESULTS: Thirteen trials (1039 patients; lidocaine: 518, control: 521) were included. Compared with control, perioperative lidocaine infusion did not decrease the odds of developing CPSP at 3 and 6 months. Lidocaine infusion improved postoperative pain at 1 h by a mean difference (95% confidence interval) of -0.65 cm (-0.73 to -0.57 cm) (P<0.0001); however, this difference was not clinically important (1.1 cm threshold). Similarly, lidocaine infusion reduced oral morphine consumption by 7.06 mg (-13.19 to -0.93) (P=0.029) over the first 24 h only; however, this difference was not clinically important (30 mg threshold). The groups were not different for any of the remaining outcomes. CONCLUSIONS: Our results provide moderate-quality evidence that perioperative lidocaine infusion does not reduce CPSP in patients undergoing breast cancer surgery. Routine use of lidocaine infusions for perioperative analgesia and CPSP prevention is not supported in this population. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42023420888.

Prophylactic dexamethasone for rebound pain after peripheral nerve block in adult surgical patients: systematic review, meta-analysis, and trial sequential analysis of randomised controlled trials.

BACKGROUND: Rebound pain occurs after the resolution of peripheral nerve block and hampers patient recovery in the postoperative period. We sought to synthesise available data from randomised controlled trials (RCTs) evaluating the efficacy of prophylactic dexamethasone for rebound pain in adult patients undergoing surgery with a peripheral nerve block. METHODS: In this systematic review and meta-analysis, RCTs reporting rebound pain and use of dexamethasone in the context of a peripheral nerve block were searched in various databases and updated in May 2023. The primary outcome was the incidence of rebound pain; secondary outcomes included the severity and time to onset of rebound pain, patient satisfaction with pain control, sleep disturbance because of pain, and adverse effects of dexamethasone. Subgroup analysis was conducted based on the effect of route of administration (intravenous or perineural) on the incidence of rebound pain. Trial sequential analysis was performed to rule out the possibility of a false positive result. RESULTS: Seven RCTs comprising 574 patients were included in this review. The dexamethasone group was associated with a reduction in the incidence of rebound pain with an odds ratio of 0.16 (95% confidence interval 0.10-0.27, P=0.00, I2=0%) compared with the control group. Trial sequential analysis confirmed the adequate information size for the beneficial effect of dexamethasone. Subgroup analysis showed that both intravenous and perineural administration were associated with a significant reduction in the incidence of rebound pain. CONCLUSIONS: Current evidence suggests that both intravenous and perineural dexamethasone reduce the incidence of rebound pain after a peripheral nerve block provided for postoperative analgesia. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42023424031.

Dose-response relationships of intravenous and perineural dexamethasone as adjuvants to peripheral nerve blocks: a systematic review and model-based network meta-analysis.

BACKGROUND: Superiority of perineural over intravenous dexamethasone at extending nerve block analgesia has been suggested but without considering the dose-response relationships for each route of administration. METHODS: Randomised control studies that evaluated intravenous or perineural dexamethasone as an adjuvant to unilateral peripheral nerve blocks in adults were searched up to October 2023 in MEDLINE, Central, Google Scholar, and reference lists of previous systematic reviews. The Cochrane Risk-of-Bias tool was used. A maximum effect (Emax) model-based network meta-analysis was undertaken to evaluate the dose-response relationships of dexamethasone. RESULTS: A total of 118 studies were selected (9284 patients; 35 with intravenous dexamethasone; 106 with perineural dexamethasone; dose range 1-16 mg). Studies with unclear or high risk of bias overestimated the effect of dexamethasone. Bias-corrected estimates indicated a maximum fold increase in analgesia duration of 1.7 (95% credible interval (CrI) 1.4-1.9) with dexamethasone, with no difference between perineural and intravenous routes. Trial simulations indicated that 4 mg of perineural dexamethasone increased the mean duration of analgesia for long-acting local anaesthetics from 11.1 h (95% CrI 9.4-13.1) to 16.5 h (95% CrI 14.0-19.3) and halved the rate of postoperative nausea and vomiting. A similar magnitude of effect was observed with 8 mg of intravenous dexamethasone. CONCLUSIONS: Used as an adjuvant for peripheral nerve block, intravenous dexamethasone can be as effective as perineural dexamethasone in prolonging analgesic duration, but is less potent, hence requiring higher doses. The evidence is limited because of the observational nature of the dose-response relationships and the quality of the included studies. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42020141689.

Regional anaesthesia for postoperative pain management following laparoscopic, visceral, non-oncological surgery a systematic review and meta-analysis.

BACKGROUND: Postoperative pain management following laparoscopic, non-oncological visceral surgery in adults is challenging. Regional anaesthesia could be a promising component in multimodal pain management. METHODS: We performed a systematic review and meta-analysis with GRADE assessment. Primary outcomes were postoperative acute pain intensity at rest/during movement after 24 h, the number of patients with block-related adverse events and the number of patients with postoperative paralytic ileus. RESULTS: 82 trials were included. Peripheral regional anaesthesia combined with general anaesthesia versus general anaesthesia may result in a slight reduction of pain intensity at rest at 24 h (mean difference (MD) - 0.72 points; 95% confidence interval (CI) - 0.91 to - 0.54; I2 = 97%; low-certainty evidence), which was not clinically relevant. The evidence is very uncertain regarding the effect on pain intensity during activity at 24 h (MD -0.8 points; 95%CI - 1.17 to - 0.42; I2 = 99%; very low-certainty evidence) and on the incidence of block-related adverse events. In contrast, neuraxial regional analgesia combined with general anaesthesia (versus general anaesthesia) may reduce postoperative pain intensity at rest in a clinical relevant matter (MD - 1.19 points; 95%CI - 1.99 to - 0.39; I2 = 97%; low-certainty evidence), but the effect is uncertain during activity (MD - 1.13 points; 95%CI - 2.31 to 0.06; I2 = 95%; very low-certainty evidence). There is uncertain evidence, that neuraxial regional analgesia combined with general anaesthesia (versus general anaesthesia) increases the risk for block-related adverse events (relative risk (RR) 5.11; 95%CI 1.13 to 23.03; I2 = 0%; very low-certainty evidence). CONCLUSION: This meta-analysis confirms that regional anaesthesia might be an important part of multimodal postoperative analgesia in laparoscopic visceral surgery, e.g. in patients at risk for severe postoperative pain, and with large differences between surgical procedures and settings. Further research is required to evaluate the use of adjuvants and the additional benefit of regional anaesthesia in ERAS programmes. PROTOCOL REGISTRATION: PROSPERO CRD42021258281.

Effect of an intravenous acetaminophen/ibuprofen fixed-dose combination on postoperative opioid consumption and pain after video-assisted thoracic surgery: a double-blind randomized controlled trial.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) often induces significant postoperative pain, potentially leading to chronic pain and decreased quality of life. This study aimed to evaluate the acetaminophen/ibuprofen combination effectiveness in reducing analgesic requirements and pain intensity in patients undergoing VATS. STUDY DESIGN: This is a double-blinded randomized controlled trial. METHODS: Adult patients scheduled for elective VATS for lung resection were randomized to receive either intravenous acetaminophen and ibuprofen (intervention group) or 100 mL normal saline (control group). Treatments were administered post-anesthesia induction and every 6 h for three cycles. The primary outcome was total analgesic consumption at 24 h postoperatively. Secondary outcomes were cumulative analgesic consumption at 2 and 48 h; analgesic-related side effects at 2, 24, and 48 h; quality of recovery at 24 h and 48 h postoperatively; pain intensity at rest and during coughing; and rescue analgesics use. Chronic postsurgical pain (CPSP) was assessed through telephone interviews 3 months postoperatively. RESULTS: The study included 96 participants. The intervention group showed significantly lower analgesic consumption at 24 h and 48 h postoperatively (24 h: median difference: - 100 µg equivalent intravenous fentanyl [95% confidence interval (CI) - 200 to - 5 µg], P = 0.037; 48 h: median difference: - 140 µg [95% CI - 320 to - 20 µg], P = 0.035). Compared to the controls, the intervention group exhibited a significantly lower quality of recovery 24 h post-surgery, with no significant difference at 48 h. All pain scores except for coughing at 48 h post-surgery were significantly lower in the intervention group compared to the controls. No significant differences were observed between the groups in postoperative nausea and vomiting occurrence, hospital stay length, and CPSP. CONCLUSION: Perioperative administration of acetaminophen/ibuprofen significantly decreased analgesic needs in patients undergoing VATS, providing an effective postoperative pain management strategy, and potentially minimizing the need for stronger analgesics.