A deep dive into neonatal well-being and anesthesia in cesarean sections: From procedure to outcome.

This observational study analyzed data from 502 participants undergoing cesarean section (CS) procedures at an obstetrics and gynecology department, aiming to explore anesthesia practices, neonatal outcomes, and demographic characteristics within the cohort. Participants, aged 17 to 59 years with a mean age of 32.23 years, were enrolled based on the clinical necessity for cesarean delivery during the study period. Informed consent was obtained from each participant or their guardians before data collection, which included detailed demographic information, medical histories, specifics of the cesarean section procedure, and APGAR scores of neonates immediately postbirth (at 0 and 5 minutes). Primary outcomes focused on APGAR scores, critical indicators of neonatal health, while secondary outcomes included the distribution of patient ages, reasons for cesarean sections, and the administration of Bupivacaine during anesthesia. Data were rigorously analyzed using descriptive and inferential statistics to summarize participant demographics, anesthesia practices, and neonatal outcomes. Statistical methods included measures of central tendency and dispersion, correlation analyzes to explore associations between variables, and regression models to identify predictors of neonatal APGAR scores. The study identified a range of indications for cesarean sections, with common reasons including fetal distress and maternal health complications. Findings indicated an average APGAR score of 7.02 at 0 minutes and 7.84 at 5 minutes, reflecting generally favorable immediate neonatal outcomes. Anesthesia protocols predominantly involved Bupivacaine, with doses ranging from 1.8 to 2.2 mL, administered based on clinical requirements. In conclusion, this study underscores the importance of comprehensive data collection and rigorous statistical analysis in evaluating cesarean section procedures. Future research could further explore long-term neonatal outcomes and refine anesthesia protocols to optimize maternal and neonatal health during cesarean deliveries.

Superior trunk versus interscalene brachial plexus block in humerus surgery: a randomised controlled trial.

INTRODUCTION: Ultrasound (US)-guided interscalene (IS) block is a commonly performed block for shoulder and humerus surgery. Though it provides excellent analgesia, it is associated with hemidiaphragmatic paralysis and dyspnoea. Superior trunk (ST) block has been described, wherein the local anaesthetic is deposited around the ST block (formed by fusion of C5 and C6 nerve roots). This study aimed to determine whether ST block provides similar analgesic efficacy with lower incidence of diaphragmatic paresis in patients undergoing proximal humerus surgery. MATERIAL AND METHODS: A total of 62 patients scheduled to undergo unilateral internal fixation (plating) for proximal or mid shaft humerus fracture were randomised to 2 groups. Patients in group I received US-guided ST block while those in group II received US-guided IS block. Both groups received 15 mL of 0.5% bupivacaine. Diaphragmatic excursion was noted at baseline and after 30 minutes after the block. Postoperatively, the numerical rating scale score and requirement of opioids were documented. RESULTS: The incidence of complete/incomplete paresis was statistically significantly lower in the ST group. Thirty eight percent of the patients (11) had complete paresis in the IS group, compared to none in the ST group. Partial paresis was observed in 62% of patients in the IS block group and 19% in the ST block group ( P < 0.001). The percentage reduction of movement was significantly higher in the IS group vs. the ST group ( P < 0.001). There was no difference in pain scores or the amount of opioid consumption between groups. CONCLUSIONS: ST block provides similar analgesia to IS block for proximal/mid humerus surgery with better preservation of diaphragmatic function. This could be a viable alternative in patients with compromised respiratory functions scheduled for such surgery.

Intrathecal pain treatment for severe pain in patients with terminal cancer: A retrospective analysis of treatment-related complications and side effects.

OBJECTIVES: Two-thirds of patients with advanced cancer experience pain. Some of these patients have severe pain refractory to oral and parenteral medication, for whom intrathecal pain treatment could be an option. While intrathecal therapy is presently used with good results in clinical practice, the current evidence is limited. Hence, increased knowledge of intrathecal pain treatment is needed. This retrospective study aimed to assess complications and side effects related to intrathecal pain treatment in patients with terminal cancer. METHODS: A retrospective study on all patients who received intrathecal treatment with morphine and bupivacaine through externalized catheters for cancer-related pain at a single university hospital during a 5-year period. RESULTS: Treatment-related complications were reported in 24 out of 53 patients. The most common complications were catheter dislocation (13%), catheter occlusion (9%), falls due to bupivacaine-related numbness or weakness (9%), and reversible respiratory depression (8%). There were five serious complications, i.e., meningitis or neurological impairment, of which four were reversible. Side effects related to intrathecal drugs, or the implantation procedure were observed in 35 patients. The most common were bupivacaine-related numbness or weakness (57%) and reversible post-dural puncture headache (19%). Systemic opioid doses decreased during the first 3 weeks of intrathecal treatment, from a median daily dose of 681 to 319 oral morphine milligram equivalents. The median treatment duration time was 62 days. CONCLUSIONS: Complications related to intrathecal treatment are common, but mostly minor and reversible. Side effects are predominantly related to unwanted pharmacological effects from intrathecal drugs. Intrathecal treatment enables the reduction of systemic opioid doses, which indicates a good treatment effect on pain. Hence, intrathecal therapy can be considered a safe pain-relieving treatment in patients with severe refractory cancer-related pain. Future research is warranted on patient acceptability and satisfaction of intrathecal pain treatment.

To Study the Efficacy of Ultrasound Guided Pecto-Intercostal Fascial Plane Block in Patients Undergoing Midline Sternotomy in Open Cardiac Surgery: A Randomized Prospective Comparative Study.

BACKGROUND: The incidence of acute poststernotomy pain after cardiac surgery is 80%1. Pecto-intercostal fascial plane block (PIFB) adjacent to the sternum anesthetizes the anterior cutaneous branches of the intercostal nerves and may provide effective analgesia after sternotomy. METHODOLOGY: A randomized controlled, double-blinded, prospective comparative trial was conducted at a tertiary care center on patients of midline sternotomy between 18 and 65 years and NYHA Class 2 and 3 for open cardiac surgery with the primary aim to evaluate analgesia on deep breathing after 3 hours of PIFB block bilaterally. A total of 60 patients were enrolled and randomly divided into three groups. PIFB was administered bilaterally before extubation, with 15 ml 0.125% bupivacaine plain (Group B), and bupivacaine+ clonidine 0.25 mcg/kg (Group B+C). Group C did not receive any intervention. All patients received acetaminophen 1 gram three times a day and injectable tramadol 1 mg/kg as a rescue analgesic. RESULTS: Baseline characteristics were similar among all the groups. The Numeric Rating Scale (NRS) for pain was statistically lower (P < 0.05) in Groups B and B+C compared to Group C at rest, deep breathing, and coughing at 3, 6, and 12 hours after extubation. NRS on deep breathing in Groups B, B+C, and C was {(2.3, 1.5, 4.4) at 3 hours, (2.3, 1.6, 4.3) at 6 hours, (2.8, 2.1, 3.9) at 12 hrs, and {(4.3, 3.5, 3.6)} at 24 hours after extubation. The peak expiratory flow rate was the highest in Group B. Rescue analgesia was not required in Group B. CONCLUSION: PIFB reduces sternotomy pain compared to the control group on deep breathing at 3 hours after block, with delayed requirement of rescue analgesia and improved respiratory mechanics in terms of peak expiratory flow rate at all time points. There is no benefit from adding clonidine.

The Effect of Dexmedetomidine and Levobupivacaine in an Experimental Ischemia Reperfusion Model.

BACKGROUND/AIM: Although it has been reported that different molecules are effective in preventing ischemia-reperfusion (I/R) injury, the most effective treatment is still unknown. MATERIALS AND METHODS: The rats were divided into four groups of eight rats each. Group C: 1 ml intraperitoneal (IP) isotonic + laparotomy + IP 2 ml isotonic +I/R. Group D: 100 µg kg-1/1 ml IP dexmedetomidine + laparotomy + IP 2 ml isotonic +I/R. Group L: 1 ml IP isotonic + laparotomy + IP levobupivacaine (2.5 mg kg-1/2 ml) +I/R. Group DL: 100 µg kg-1/1 ml IP dexmedetomidine + laparotomy + IP levobupivacaine (2.5 mg kg-1/2 ml) +I/R. Brain, heart, lung, and liver tissue samples were collected for histopathological examination. Biochemically, levels of aspartate amino transaminase, alanine amino transaminase, serum glucose, total antioxidant status (TAS), total oxidant status, ischemia modified albumin, and malondialdehyde were measured in blood samples. RESULTS: Group D mean blood TAS levels were found to be statistically significantly higher than those in Group C and Group L (p=0.037, p=0.048 respectively). Group DL oxidative stress index (OSI) value was found to be statistically significantly lower than that of Group C (p=0.010). CONCLUSION: Both dexmedetomidine and levobupivacaine demonstrated protective effects in I/R injury. When used in combination, the effects of these treatments were further enhanced, reaching statistical significance. As our literature review found no studies on the combined use of dexmedetomidine and levobupivacaine in I/R injury, it is anticipated that supporting these results with clinical studies may significantly contribute to clinical practice.

The preventive efficacy of lipid emulsion on the occurrence of local anesthetic systemic toxicity in patients receiving local infiltration analgesia for total joint arthroplasty.

BACKGROUND: Motor-sparing local infiltration analgesia (LIA) enhances recovery after total hip arthroplasty (THA) and total knee arthroplasty (TKA). However, LIA can induce local anesthetic systemic toxicity (LAST), sometimes necessitating rescue lipid emulsion therapy. Our institute initiated a pilot study to pretreat patients with lipid emulsion (SMOFlipid®) to test its efficacy in mitigating LIA-induced LAST events. METHODS: This retrospective study enrolled 1,621 adult patients who received LIA with bupivacaine (2-3 mg/kg, maximum 300 mg) for unilateral primary THA or TKA under general anesthesia between January 2020 and April 2022. A total of 439 patients received lipid pretreatment, while 1,182 did not. Demographics, surgical and anesthesia profiles, along with LAST events affecting the neurological, cardiovascular, and respiratory systems, were compared after propensity score matching for age, sex, body mass index (BMI), and surgery type. RESULTS: The incidence of severe LAST events requiring rescue lipid emulsion slightly decreased after lipid pretreatment (from 2.54 to 2.28 per 1000). Lipid pretreatment significantly reduced the incidence of bradycardia and new-onset arrhythmia (odds ratio: 0.13, adjusted p-value: 0.024) but increased postoperative opioid requirement (odds ratio: 1.71, adjusted p-value: 0.032) after Benjamini-Hochberg correction for multiplicity. CONCLUSIONS: The efficacy of lipid pretreatment (SMOFlipid® 1.5 ml/kg, maximum 100 ml) in mitigating LIA-induced LAST remains controversial. While lipid pretreatment reduced the incidence of new-onset arrhythmia, it showed no clear benefits for neurologic and respiratory outcomes. Additionally, lipid pretreatment might hinder postoperative recovery by increasing the need for rescue opioid analgesia. Further prospective pharmacokinetic studies are required to assess plasma bupivacaine concentrations following LIA and lipid pretreatment, examine their relationship to LAST events, and establish the efficacy and safety of lipid pretreatment.

Efficacy of Liposomal Bupivacaine Versus a Traditional Local Anesthetic in Periarticular Injections during Total Hip Arthroplasty: A Systematic Review and Meta-analysis.

Periarticular injections (PAI) are a common component to multimodal regimens in total hip arthroplasty (THA), although the efficacy of adding liposomal bupivacaine (LB) remains unclear. A meta-analysis of total knee arthroplasty did not find LB superior, but a similar study has not been performed in THA. The purpose of this study was to compare opioid consumption, pain scores, and length of stay between PAIs with LB and traditional PAIs in THA. Eleven included studies showed LB to have minor decreases in opioid consumption and length of stay. No clinically significant benefits were achieved in pain control based on minimal clinically important difference thresholds. There is not adequate evidence to suggest that the increased cost of LB merits its utilization over traditional PAI in THA. The variability in the study designs, as well as results, calls for more consistent randomized clinical trials to ascertain the true efficacy of LB. (Journal of Surgical Orthopaedic Advances 33(3):143-153, 2024).

The impact of epidural ropivacaine versus levobupivacaine for labor analgesia on maternal and fetal outcomes: a meta-analysis.

INTRODUCTION: Newer neuraxial local anesthetic agents which have been used as epidural analgesia have shown to provide reliable pain relief during labor. Ropivacaine and levobupivacaine are newer agents now used for labor analgesia. However, even though few studies have made their comparison with bupivacaine, ropivacaine and levobupivacaine have seldom systematically been compared. Therefore, in this analysis, we aimed to systematically show the impact of epidural ropivacaine versus levobupivacaine for labor analgesia on maternal and fetal outcomes. METHODS: http://www. CLINICALTRIALS: gov , Web of Science, MEDLINE, EMBASE, Cochrane database and Google Scholar were searched for studies comparing ropivacaine versus levobupivacaine for labor analgesia. Maternal and fetal outcomes were considered as the endpoints in this analysis. The RevMan software 5.4 was used to analyze data in this study. Risk ratio (RR) with 95% confidence intervals (CI) were used to represent the data post analysis. RESULTS: A total number of 2062 participants were included in this analysis whereby 1054 participants were assigned to ropivacaine and 1008 participants were assigned to levobupivacaine. The main results of this analysis showed that epidural ropivacaine was not associated with significantly higher risk of hypotension (RR: 0.71, 95% CI: 0.43 - 1.17; P = 0.18) and pruritus (RR: 1.12, 95% CI: 0.89 - 1.42; P = 0.34) when compared to levobupivacaine for labor analgesia. However, the risk of nausea and vomiting was significantly higher with ropivacaine (RR: 1.60, 95% CI: 1.05 - 2.44; P = 0.03). Spontaneous vaginal delivery (RR: 0.99, 95% CI: 0.89 - 1.42; P = 0.83), instrumental vaginal delivery (RR: 1.13, 95% CI: 0.89 - 1.45; P = 0.32) and the risk for cesarean section (RR: 0.76, 95% CI: 0.42 - 1.37; P = 0.35) were not significantly different. When fetal outcomes were assessed, Apgar score < 7 at 1 min (RR: 1.01: 95% CI: 0.57 - 1.80; P = 0.97), abnormality of fetal heart rate (RR: 1.45, 95% CI: 0.55 - 3.79; P = 0.45) and neonatal asphyxia (RR: 0.35, 95% CI: 0.10 - 1.18; P = 0.09) were also similarly manifested. CONCLUSIONS: To conclude, our analysis showed both epidural ropivacaine and levobupivacaine to be equally effective for labor analgesia in terms of maternal and fetal outcomes. No major adverse maternal and fetal outcome was observed in this analysis. However, considering the several limitations of this analysis, further larger studies should be able to solve and clarify this issue.

Real-Time Ultrasonography for the Placement of Caudal Epidurals for Thoracic Surgery in Infants: A Description of the Technique and Case Series.

Caudal epidural catheters threaded to the thoracic levels are increasingly utilized in infants undergoing thoracic and abdominal surgery, compared to lumbar or thoracic epidural techniques. Estimating catheter length traditionally relies on anatomical landmarks, but the lack of spine ossification in infants makes ultrasonography a valuable and noninvasive tool. We present 3 cases where real-time ultrasonography facilitated caudal to thoracic epidural catheter placement in infants undergoing thoraco-abdominal surgeries. Incision-congruent placement of the catheter tip ensured effective perioperative analgesia with low doses of bupivacaine administered as intermittent boluses resulting in potent and prolonged analgesia with reduced opioid requirements.

Pharmacologic or genetic targeting of peripheral nerves prevents peri-articular traumatic heterotopic ossification.

Heterotopic ossification (HO) is a pathological process that commonly arises following severe polytrauma, characterized by the anomalous differentiation of mesenchymal progenitor cells and resulting in the formation of ectopic bone in non-skeletal tissues. This abnormal bone growth contributes to pain and reduced mobility, especially when adjacent to a joint. Our prior observations suggested an essential role of NGF (Nerve Growth Factor)-responsive TrkA (Tropomyosin Receptor Kinase A)-expressing peripheral nerves in regulating abnormal osteochondral differentiation following tendon injury. Here, we utilized a recently developed mouse model of hip arthroplasty-induced HO to further validate the role of peripheral nerve regulation of traumatic HO. Nerve ingrowth was either modulated using a knockin transgenic animals with point mutation in TrkA, or local treatment with an FDA-approved formulation of long acting Bupivacaine which prevents peripheral nerve growth. Results demonstrate exuberant sensory and sympathetic nerve growth within the peri-articular HO site, and that both methods to reduce local innervation significantly reduced heterotopic bone formation. TrkA inhibition led to a 34% reduction in bone volume, while bupivacaine treatment resulted in a 50% decrease. Mechanistically, alterations in TGFß and FGF signaling activation accompanied both methods of local denervation, and a shift in macrophages from M1 to M2 phenotypes was observed. In sum, these studies reinforce the observations that peripheral nerves play a role in the etiopathogenesis of HO, and that targeting local nerves represents a potential therapeutic approach for disease prevention.

Intrathecal Dexmedetomidine as an Adjuvant to Low Dose Hyperbaric 0.5% Bupivacaine on Haemodynamic Parameters in Patients Undergoing Transurethral Resection of Prostate.

OBJECTIVE: To determine the role of dexmedetomidine in potentiating the local anaesthetic efficacy of a low dose of bupivacaine when used as an adjuvant. STUDY DESIGN: A prospective, double-blind, randomised study. Place and Duration of the Study: Department of Anaesthesia, Sindh Institute of Urology and Transplantation, Karachi, Pakistan, from July 2021 to February 2022. METHODOLOGY: One hundred and eight patients of ASA physical class I-III undergoing transurethral resection of the prostate (TURP) under sub-arachnoid block (SAB) were enroled and distributed into two equal groups. Group BUPIPURE (BP) was given 7.5 mg of pure 0.5% hyperbaric bupivacain whereas group BUPIDEX (BD) was given 6 mg of 0.5% hyperbaric bupivacain with 3 µg dexmedetomidine intrathecally. The effects in Both groups were compared using chi-square and unpaired t-tests. A significance level of p <0.05 was used to evaluate the statistical significance. RESULTS: Both groups demonstrated a steady decrease in mean heart rate (mean HR 98.9-62.7 per minute as compared to 79.1-59.4 per minute in groups BP and BD, respectively), however, no patient reached to HR <50/min. Group BP had a higher HR variability than group BD. The two groups' median peak sensory levels were similar. However, a statistically significant difference was revealed in the time taken for 2-segment regression (87.5 ± 11.3 min vs. 115.5 ± 6.2 min p <0.001 in BP and BD), as well as the time to reach T10 sensory level (13.56 ± 2.5 min vs. 10.9 ± 3.0 min p <0.001). CONCLUSION: In patients having TURP, intrathecal dexmedetomidine combined with low-dose bupivacaine results in a quicker start, extended sensory and motor block, and a decreased need for rescue analgesics. KEY WORDS: Adjuvants, Dexmedetomidine, Spinal anaesthesia, Transurethral Resection of Prostate.

Effectiveness of intra-articular analgesia in reducing postoperative pain after minimally invasive sacroiliac joint fusion: a double-blind randomized controlled trial.

During the first postoperative days following minimally invasive sacroiliac joint fusion (MISJF), patients often report serious pain, which contributes to high utilization of painkillers and prevention of early mobilization. This prospective, double-blind randomized controlled trial investigates the effectiveness of intraoperative SIJ infiltration with bupivacaine 0.50% versus placebo (NaCl 0.9%) in 42 patients in reducing postoperative pain after MISJF. The primary outcome was difference in pain between bupivacaine and placebo groups, assessed as fixed factor in a linear mixed model. Secondary outcomes were opioid consumption, patient satisfaction, adverse events, and length of hospital stay. We found that SIJ infiltration with bupivacaine did not affect postoperative pain scores in comparison with placebo, neither as group-effect (p = 0.68), nor dependent on time (group*time: p = 0.87). None of the secondary outcome parameters were affected in the postoperative period in comparison with placebo, including opioid consumption (p = 0.81). To conclude, intra-articular infiltration of the SIJ with bupivacaine at the end of MISJF surgery is not effective in reducing postoperative pain. Hence, we do not recommend routine use of intraoperative SIJ infiltration with analgesia in MISJF.

Pocket warming of bupivacaine with fentanyl to shorten onset of labor epidural analgesia: A double-blind randomized controlled clinical trial.

Shortening analgesic onset has been researched and it has been documented that prewarming epidural medications to body temperature (37°C) prior to administration increases medication efficacy. Our double-blind randomized controlled trial was designed to investigate if a lower degree of prewarming in providers' pockets could achieve similar results without the need of a bedside incubator. A total of 136 parturients were randomized into either the pocket-warmed group or the room temperature group to receive 10 mL of 0.125% bupivacaine with 2 µg/mL fentanyl epidural bolus at either the 27.8 ±1.7°C or 22.1 ±1.0°C temperatures, respectively. Primary outcome, time to analgesic onset (verbal rating scale pain score ≤ 3) was recorded in 0-, 5-, 10-, 15-, 20-, 30-, and 60-minutes intervals. It was observed that the pocket-warming group (n = 64) and room temperature group (n = 72) had no significant difference of analgesic onset time (median 8 vs. 6.2 minutes; p = 0.322). The incidence of adverse events such as hypotension, fever (≥ 38°C), nausea, vomiting, and number of top-off epidural boluses, as well as patient satisfaction rates and mode of delivery, were not significantly different between the groups as well. Further research is warranted to confirm these findings and explore the impact of different temperatures on analgesic onset time as well as the logistical issues associated with their clinical implementations.

Liposomal Bupivacaine Does Not Decrease Postoperative Pain in Patients with Intracapsular Femoral Neck Fracture Treated with Hemiarthroplasty: HEAT-A Randomized, Controlled Trial.

BACKGROUND: Liposomal bupivacaine (LB) is a long-lasting local anesthetic agent that was developed for use in the surgical setting to help manage postoperative pain. The objective of this study was to evaluate the effect of LB on postoperative pain, function, and overall hospital course in patients with intracapsular hip fractures who were treated with hip hemiarthroplasty. METHODS: This was a single-center, randomized prospective double-blinded study of 50 patients with an isolated intracapsular femoral neck fracture who were treated with hip hemiarthroplasty from 2018 to 2022. The study group consisted of 25 patients who were treated with intraoperative LB and bupivacaine hydrochloride injections, while the control group consisted of 25 patients who were treated with intraoperative bupivacaine hydrochloride injections only. Primary outcomes were a visual analog scale (VAS) score for pain, total morphine milligram equivalents (MME), delirium, and time to ambulation with physical therapy. RESULTS: No significant differences between the study and control groups were found in any of the outcomes measured. Most notably, there were no differences in the average postoperative pain score (VAS, 2.26 versus 2.7; p = 0.34), total MME used postoperatively (11.73 versus 9.98 MME; p = 0.71), and postoperative day of discharge (4.00 versus 3.88 days; p = 0.82). CONCLUSIONS: The results of our study suggest that use of LB is not associated with substantially improved postoperative pain or function or with a shorter hospital course following hip hemiarthroplasty for a femoral neck fracture. Given the higher cost of LB compared with standard postoperative pain modalities, it is worth questioning its use in the setting of geriatric hip fractures. LEVEL OF EVIDENCE: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Efficacy of local pain management strategies for patients undergoing anterior iliac crest bone harvesting: a systematic review.

Anterior Iliac crest bone harvesting (AICBH) is a common surgical procedure with applications in various medical specialties, but it is often accompanied by significant postoperative pain. Effective pain management is therefore essential for optimising patient outcomes. This systematic literature review aimed to evaluate the effectiveness of local donor site pain management interventions in AICBH procedures. It followed the Cochrane Handbook for Systematic Reviews of Interventions version 6.4 guidelines and adhered to the PRISMA 2020 statement for comprehensive and high-quality reporting. A comprehensive search was conducted across PubMed, Cochrane, and Embase to identify relevant studies. Inclusion criteria encompassed randomised controlled trials assessing pain management strategies in AICBH patients. The methodological quality of the included studies was assessed using the Jadad scale. Data extraction focused on medication types, administration modes, pain scores, and use of narcotics. Fourteen eligible studies were included. Methodological quality varied, with most studies demonstrating a low risk of bias. Medication types included amide and opioid groups, administered via single-shot injections or infusion systems. Results indicated that indwelling iliac crest catheters with bupivacaine showed significant postoperative reductions in pain scores and narcotics use compared with other techniques. The findings suggest that use of an indwelling catheter with bupivacaine is an effective pain management strategy for AICBH patients. However, heterogeneity among the studies and a lack of standardised methodologies pose limitations. Further homogeneous and standardised studies are therefore needed to strengthen the evidence base and inform clinical practice.

Fentanyl induces analgesic effect through miR-381-3p/TRPM7 when combined with bupivacaine in subarachnoid injection.

Fentanyl combined with bupivacaine in subarachnoid anesthesia exerts a strong synergistic analgesic effect, extending the duration of analgesia. However, the mechanism of enhanced analgesic effect of fentanyl remains elusive. The present study investigated the potential mechanism of the analgesic effect of fentanyl when combined with bupivacaine. The subarachnoid injection (SI) rat model was employed, and SI of fentanyl or/and bupivacaine was used to investigate their analgesic effect. Dorsal root ganglion (DRG)' RNA sequencing (RNA-Seq) and bioinformatics analysis were performed to evaluate the downstream mechanisms of MicroRNAs (miRNAs). Further validation tests included RT-PCR, Western blot, and immunofluorescence. A single SI of fentanyl or bupivacaine decreased the positive responses to stimulation when used alone or in combination. RNA-seq results revealed that miR-381-3p played a role in the fentanyl-driven promotion of analgesia. Bioinformatics analysis and dual-luciferase reporter identified TRPM7 as a direct downstream target gene of miR-381-3p. In vitro, overexpression of miR-381-3p could further block fentanyl-induced expression of TRPM7, p-ERK1/2, CGRP, and SP. In addition, antagomir-381-3p reversed the inhibitory effect of fentanyl on the expression of TRPM7, p-ERK1/2, CGRP, and SP, in vivo; however, TRPM7 siRNA rescued the effect of antagomir-381-3p. In conclusion, fentanyl inhibits p-ERK by targeting TRPM7 via miR-381-3p, lowering the production of CGRP and SP, and ultimately inducing analgesic effects.

A new long-acting analgesic formulation for postoperative pain management.

Local anesthetics (LA), as part of multimodal analgesia, have garnered significant interest for their role in delaying the initiation of opioid therapy, reducing postoperative opioid usage, and mitigating both hospitalization duration and related expenses. Despite numerous endeavors to extend the duration of local anesthetic effects, achieving truly satisfactory long-acting analgesia remains elusive. Drawing upon prior investigations, vesicular phospholipid gels (VPGs) emerge as promising candidates for extended-release modalities in small-molecule drug delivery systems. Therefore, we tried to use the amphiphilicity of phospholipids to co-encapsulate levobupivacaine hydrochloride and meloxicam, two drugs with different hydrophilicity, to obtain a long-term synergistic analgesic effect. Initially, the physicochemical attributes of the formulation were characterized, followed by an examination of its in vitro release kinetics, substantiating the viability of extending the release duration of the dual drugs. Sequentially, in vivo investigations encompassing pharmacokinetic profiling and assessment of analgesic efficacy were undertaken, revealing a prolonged release duration of up to 120 h and attainment of optimal postoperative analgesia. Subsequently, inquiries into the mechanism underlying synergistic analgesic effects and safety evaluations pertinent to the delivery strategy were pursued. In summation, we successfully developed a promising formulation to achieve long-acting analgesia.

Evaluation of preoperative rectus sheath block with bupivacaine for analgesia in cats undergoing ovariohysterectomy: a cadaveric and randomized clinical study.

OBJECTIVE: Phase 1: to determine the feasibility of desensitizing ventral branches of spinal nerves within the rectus sheath using an ultrasound-guided rectus sheath block (USRSB). Phase 2: to determine the effect of preoperative USRSB on intraoperative responses to surgical stimulation and postoperative pain. STUDY DESIGN: Cadaveric study and prospective, randomized, blinded, parallel-arm clinical trial. ANIMALS: A group of five cat cadavers and 37 shelter-owned cats undergoing ovariohysterectomy. METHODS: Phase 1: anatomical dissection was performed on one uninjected cadaver. Abdominal walls were dissected in four cadavers (eight hemiabdomens) following bilateral USRSB using 1:1 new methylene blue and 0.5% bupivacaine (0.8 mL kg-1 total). Phase 2: preoperative bilateral USRSB was performed with 0.8 mL kg-1 of 0.25% bupivacaine (RSB) or equivalent volume of 0.9% saline (CONTROL). Intraoperative systolic arterial blood pressure (SAP), heart rate (HR), respiratory rate (fR) and vaporizer setting (vap%) were recorded before skin incision, during celiotomy and abdominal wall closure. In recovery, cats were administered robenacoxib (2 mg kg-1; CONTROL) or 0.9% saline (0.1 mL kg-1; RSB) subcutaneously. Postoperative pain was evaluated for 6 hours using the Glasgow Composite Measure Pain Scale. RESULTS: Phase 1: spinal nerves T9-L3 were identified within the rectus sheath, and stained in 0%, 40%, 63%, 75%, 100%, 88%, 50% and 13% of hemiabdomens, respectively. Phase 2: 37 cats were included (RSB, n = 17; CONTROL, n = 20). Intraoperatively, SAP, HR and fR were not significantly different between groups. Vap% was significantly lower in RSB during celiotomy (p = 0.036) and closure (p = 0.044). Postoperatively, RSB cats were 5.3 times (95% CI 1.8-8.3) more likely to require rescue analgesia than CONTROL cats. CONCLUSIONS AND CLINICAL RELEVANCE: During surgery, USRSB with bupivacaine offered minor benefits and provided markedly less postoperative analgesia than robenacoxib, indicating that relying on USRSB provides insufficient postoperative analgesia for ovariohysterectomy in cats.