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Background: Nalbuphine, a synthetic k-agonist and µ-antagonist, provides efficient pain relief while reducing opioid-related adverse effects. This study aims to compare the efficacy of intrathecal nalbuphine (ITN) with intrathecal morphine (ITM) for post-TKA pain. Methods: A retrospective cohort analysis of 131 patients who underwent TKA with spinal anesthesia (SA), a single shot of adductor canal block, and periarticular injections was conducted. The patients were divided into 2 groups, Group N received 0.8 mg nalbuphine, and Group M received 0.2 mg morphine as an adjuvant to SA. Propensity-score matching was employed to compare the visual analog scales (VAS) of postoperative pain intensity, cumulative morphine use (CMU), maximum knee flexion angle, straight leg raise (SLR) ability, incidence of postoperative nausea and vomiting (PONV), and length of hospital stay (LHS). Results: The mean VAS of group M were significantly lower than group N at 6, 12, 18, and 24 h (P < 0.01). Group M had lower CMU than group N at 24 h (P < 0.01) and 48 h (P < 0.01), while there was no significant difference between groups in terms of knee flexion angle and SLR at any time point. Additionally, 29.3 and 57.9% of patients in group N and M experienced PONV, respectively (p = 0.04), and group N had significantly shorter LHS compared to group M (P < 0.001). Conclusion: Although, intrathecal morphine (ITM) still provides better pain control particularly in the first 24 h, patients who received intrathecal nalbuphine (ITN) had significantly fewer incidence of PONV, and shorter LHS. [ABSTRACT FROM AUTHOR]

Addressing suboptimal weight loss post-bariatric surgery poses a challenge. While glucagon-like peptide 1 receptor agonists (GLP1-RA) show promise in managing obesity, their role as an adjuvant treatment after bariatric surgery remains uncertain. We conducted a systematic literature review focused on the efficacy and safety of GLP1-RA in bariatric surgery patients with insufficient weight loss or distant weight regain. Our literature search identified 1167 articles, with 10 (involving 594 patients) meeting inclusion/exclusion criteria for detailed review. GLP1-RA therapy resulted in 5 to 17% weight loss over 6 to 12 months, with 10–50% experiencing non-severe side effects like nausea. Overall, GLP1-RA emerges as an effective adjuvant therapy for patients experiencing inadequate weight loss or regain after bariatric surgery, offering a viable alternative to revision surgery. [ABSTRACT FROM AUTHOR]

This article compares the effects of adding dexmedetomidine or fentanyl to ropivacaine in intrathecal anesthesia for lower limb surgeries. The study found that adding dexmedetomidine resulted in a faster onset of sensory and motor blockade, as well as a longer duration of motor and sensory block, compared to fentanyl. Dexmedetomidine also provided longer post-operative analgesia and higher sedation levels. The study concludes that dexmedetomidine is a safe and effective adjuvant to ropivacaine for intrathecal anesthesia. [Extracted from the article]

Simple Summary: Local anaesthetic nerve blocks can be used to provide pain relief during and after surgery. While specific local anaesthetic techniques are commonplace in humans and some species, it is a relatively new field of research in rabbits. Rabbits are prey species that hide pain well but may express changes in behaviour, food intake, and production of faeces as a result of pain, making them challenging to study. This study aimed to investigate a specific local anaesthetic technique in rabbits undergoing orthopaedic surgery on a front leg. Its effectiveness was investigated by comparing the requirement for extra pain relief during and after surgery and comparing changes in food intake, faeces production, and behaviour after surgery. Both remote filming and direct observation were used. The rabbits who received the block required no additional pain relief during surgery, whereas every rabbit who received intravenous pain relief did require additional pain relief. However, after surgery, the severity of pain and the requirement for extra pain relief were the same, and there was no difference in behaviour between the groups. In conclusion, this local anaesthetic nerve block was easy to administer and provided effective pain relief during surgery, reducing the need for additional drug therapy. Locoregional anaesthetic techniques are invaluable for providing multimodal analgesia for painful surgical procedures. This prospective, randomised study describes a nerve stimulator-guided brachial plexus blockade (BPB) in rabbits undergoing orthopaedic surgery in comparison to systemic lidocaine. Premedication was provided with intramuscular (IM) medetomidine, fentanyl, and midazolam. Anaesthesia was induced (propofol IV) and maintained with isoflurane. Nine rabbits received a lidocaine BPB (2%; 0.3 mL kg−1), and eight received a lidocaine constant rate infusion (CRI) (2 mg kg−1 IV, followed by 100 µg kg−1 min−1). Rescue analgesia was provided with fentanyl IV. Carprofen was administered at the end of the surgery. Postoperative pain was determined using the Rabbit Grimace Scale (RGS) and a composite pain scale. Buprenorphine was administered according to the pain score for two hours after extubation. Rabbits were filmed during the first two hours to measure distance travelled and behaviours. Food intake and faeces output were compared. Every rabbit in CRI required intraoperative rescue analgesia compared to none in BPB. However, rabbits in both groups had similar pain scores, and there was no difference in the administration of postoperative analgesia. There were no significant differences in food intake or faeces production over 18 h, and no significant differences in distance travelled or behaviours examined during the first two hours. BPB seems superior for intraoperative analgesia. Postoperatively, both groups were comparable. [ABSTRACT FROM AUTHOR]

Background/Objectives: Managing postoperative pain in patients with obesity is challenging. Although using a combination of pain relief methods is recommended for these patients, the true effectiveness of various intravenous non-opioid analgesics and adjuvants in multimodal anesthesia needs to be better defined. Methods: A systematic review and network meta-analysis was performed to evaluate the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, ketamine, α-2 agonists, lidocaine, magnesium, and oral gabapentinoids in adult surgical patients with obesity. The analysis aimed to compare these treatments to a placebo/no treatment or alternative analgesics, with a primary focus on postoperative pain and secondary endpoints including rescue analgesia, postoperative nausea and vomiting (PONV), and recovery quality. English-language randomized controlled trials across PubMed, Scopus, Web of Science, CINAHL, and EMBASE were considered. Quality and evidence certainty were assessed with the RoB 2 tool and GRADE, and data was analyzed with R software. Results: NSAIDs, along with acetaminophen, lidocaine, α-2 agonists, ketamine, and oral gabapentinoids, effectively reduce early postoperative pain. NSAIDs, particularly ibuprofen, as well as acetaminophen, ketamine, and lidocaine, also show benefits in later postoperative stages. Intravenous non-opioid analgesics and adjuvants show some degree of benefit in reducing PONV and the need for rescue analgesic therapy when using α-2 agonists alone or combined with oral gabapentinoids, notably decreasing the likelihood of PONV. Ketamine, lidocaine, and α-2 agonists are shown to enhance postoperative recovery and care quality. Conclusions: Intravenous non-opioid analgesics and adjuvants are valuable in multimodal anesthesia for pain management in adult surgical patients suffering from obesity. [ABSTRACT FROM AUTHOR]

Introduction: Infant spinal anesthesia is an important technique in premature and ex‐premature infants undergoing lower abdominal surgery. Previous studies of infant spinal anesthesia report high failure rates, but fail to adequately identify contributing factors. The aim of this study is to retrospectively review spinal anesthetics from a quaternary anesthetic centre to determine overall spinal failure rate, incidence of second spinal attempts and adverse events associated with a second spinal anesthetic. Methods: A retrospective review of infant spinal anesthetics performed between May 2016 and June 2023. Results: Five hundred and fifty‐one infants (mean postmenstrual age 42.9 weeks and weight 3873 g) were included. The overall success rate on first attempt was 86.5% with a further 5.1% requiring a successful second spinal anesthetic after initial failure. Spinal anesthetic failure requiring conversion to general anesthesia occurred in 9.4% of cases The causes of failed spinal anesthetic were inability to access the subdural space (dry tap 4.2%), inadequate motor blockade (2.9%), and repeated bloody taps (2.2%). Spinal anesthetic failure was significantly increased in cases where the anesthetist was routinely performing less than 5 spinal anesthetics per year [OR 2.21 (95% CI 1.28, 3.83, p =.004)] but only weakly associated with years of pediatric anesthetic experience. Failure rates were 21.4% with styletted spinal needles and 9.2% for non styletted [OR 2.68 (95% CI 1.23–5.86, p =.012)]. The incidence of perioperative apnoea was 6.7% with the highest rate in infants in which failed spinal anesthesia required conversion to general anesthesia (25%). There were 28 cases where initial spinal anesthetic failed to produce adequate anesthesia and a repeat spinal anesthetic was performed. Repeat spinal anesthesia was successful in 92.8% of cases with awake caudal anesthesia successful in 7.2% of cases. In three cases high spinal blockade occurred, one after a single spinal and two after a repeat spinal. Both repeat spinal high block cases required intubation and brief resuscitation. Conclusion: Infant spinal anesthesia is associated with high success rates if experienced anesthetists are present or performing the block. Repeat spinal anesthesia may be associated with an increased incidence of high spinal block. Greater awareness of the slow onset of high block should promote techniques aimed at minimizing cephalad spread of local anesthetic including slight head up positioning during surgery. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Perioperative pain management is very important to achieve patient satisfaction. The ultrasound-guided brachial plexus blocks like inter scalene block, supra and infra clavicular blocks have evolved as safe alternative techniques to general anaesthesia in upper limb surgeries. Long acting local anaesthetic agents like ropivacaine along with adjuvants such as dexmedetomdine have been routinely used in supraclavicular brachial plexus block. MATERIAL & METHODS: Sixty adult patients scheduled for upper limb surgeries were randomised into group A and Group B of 30 patients each. Patients in group A received 0.5% Ropivacaine 20ml + 5 ml normal saline and group B received 0.5% ropivacaine 20ml + 0.5ml (50µg) dexmedetomidine + 4.5ml normal saline. Primary objective of our study was to compare the groups in terms of quality of block, onset and duration of sensory and motor block and post-operative pain management. Secondary objective was to compare the intraoperative hemodynamic changes and post operative adverse effects. RESULTS: Time taken in the onset of the sensory as well as motor block in both the groups was statistically significantly more in the group A compared to the group B. The duration of the sensory as well as the motor block was much higher in group B compared to group A with a statistically significant difference. Total duration of analgesia was slightly higher in group A compared to group B. The mean NRS was significantly lower in group B compared to group A at all time intervals till 24 hrs. No major side effects were observed with study drugs. CONCLUSION: The study confirmed that dexmedetomidine as an adjuvant to ropivacaine in supraclavicular brachial plexus block hastens the onset of the sensory as well as motor block and prolongs the duration of the sensory as well as the motor block in the upper limb surgeries. [ABSTRACT FROM AUTHOR]

Background: When an alpha 2 adrenergic agonist and a local anesthetic are coupled, the analgesic effect's quality and endurance are enhanced. While clonidine's effects on local anesthetics have been thoroughly investigated, there aren't many studies that show how epidural dexmedetomidine affects the same. Materials and Methods: The patients were randomly assigned to two groups, one receiving ropivacaine with clonidine (RC) and the other receiving ropivacaine with dexmedetomidine (RD), Group RC was administered 15 ml of 0.75% ropivacaine with 1 microgram per kilogram of clonidine, while group RD was given 15 ml of 0.75% ropivacaine with 1 microgram per kilogram of dexmedetomidine epidurally. Results: The dexmedetomidine group showed significantly improved start (RD-7.53 ± 1.81, RC-10.93 ± 1.96) and duration (RD-317 ± 29.5, RC-285 ± 37) of sensory blockade sedation. Hemodynamic alterations and the start of motor blockage did not differ significantly. Conclusion: Similar to clonidine, dexmedetomidine works as an efficient adjuvant to ropivacaine for epidural anesthesia at doses of 1 ⃬g/kg. [ABSTRACT FROM AUTHOR]

Background The bispectral index (BIS) may be unreliable to gauge anesthetic depth when dexmedetomidine is administered. By comparison, the electroencephalogram (EEG) spectrogram enables the visualization of the brain response during anesthesia and may prevent unnecessary anesthetic consumption. Methods This retrospective study included 140 adult patients undergoing elective craniotomy who received total intravenous anesthesia using a combination of propofol and dexmedetomidine infusions. Patients were equally matched to the spectrogram group (maintaining the robust EEG alpha power during surgery) or the index group (maintaining the BIS score between 40 and 60 during surgery) based on the propensity score of age and surgical type. The primary outcome was the propofol dose. Secondary outcome was the postoperative neurological profile. Results Patients in the spectrogram group received significantly less propofol (1585 ± 581 vs. 2314 ± 810 mg, P < 0.001). Fewer patients in the spectrogram group exhibited delayed emergence (1.4% vs. 11.4%, P = 0.033). The postoperative delirium profile was similar between the groups (profile P = 0.227). Patients in the spectrogram group exhibited better in-hospital Barthel’s index scores changes (admission state: 83.6 ± 27.6 vs. 91.6 ± 17.1; discharge state: 86.4 ± 24.3 vs. 85.1 ± 21.5; group–time interaction P = 0.008). However, the incidence of postoperative neurological complications was similar between the groups. Conclusions EEG spectrogram–guided anesthesia prevents unnecessary anesthetic consumption during elective craniotomy. This may also prevent delayed emergence and improve postoperative Barthel index scores.

Background: Fluoropyrimidine-based postoperative adjuvant chemotherapy is globally recommended for high-risk stage II and stage III colon cancer. However, adjuvant chemotherapy is often associated with severe adverse events and is not highly effective in preventing recurrence. Therefore, discovery of novel molecular biomarkers of postoperative adjuvant chemotherapy to identify patients at increased risk of recurrent colorectal cancer is warranted. Autophagy (including mitophagy) is activated under chemotherapy-induced stress and contributes to chemotherapy resistance. Expression of autophagy-related genes and their single-nucleotide polymorphisms are reported to be effective predictors of chemotherapy response in some cancers. Our goal was to evaluate the relationship between single-nucleotide variants of autophagy-related genes and recurrence rates in order to identify novel biomarkers that predict the effect of adjuvant chemotherapy in colorectal cancer. Methods: We analyzed surgical or biopsy specimens from 84 patients who underwent radical surgery followed by fluoropyrimidine-based adjuvant chemotherapy at Saitama Medical University International Medical Center between January and December 2016. Using targeted enrichment sequencing, we identified single-nucleotide variants and insertions/deletions in 50 genes, including autophagy-related genes, and examined their association with colorectal cancer recurrence rates. Results: We detected 560 single-nucleotide variants and insertions/deletions in the target region. The results of Fisher's exact test indicated that the recurrence rate of colorectal cancer after adjuvant chemotherapy was significantly lower in patients with the single-nucleotide variants (c.1018G > A [p < 0.005] or c.1562A > C [p < 0.01]) of the mitophagy-related gene PTEN-induced kinase 1. Conclusions: The two single-nucleotide variants of PINK1 gene may be biomarkers of non-recurrence in colorectal cancer patients who received postoperative adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

In this study, we examined the impact of dexmedetomidine (DEX) on the effectiveness of epidural analgesia and labor outcomes. We administered different doses of DEX combined with 0.1% ropivacaine for epidural analgesia to evaluate the clinical effects and safety. To assess the effects of different concentrations of DEX in parturient women receiving epidural analgesia, we conducted a randomized double‐blind trial. We selected 400 parturient women and randomly assigned them to 4 groups, with 100 parturient women in each group: S0.1 (0.1 µg/mL DEX), S0.2 (0.2 µg/mL DEX), S0.3 (0.3 µg/mL DEX), and a control group (0.3 µg/mL sufentanil). Post‐analgesia, we recorded the Bromage score, duration of labor, method of delivery, bleeding, neonatal Apgar score, adverse reactions, and maternal satisfaction. The number of patients with a Bromage score of ≥2 and the incidence of bradycardia were higher in the S0.3 group compared with the other 3 groups (P <.05), whereas the high satisfaction rate was lower in the S0.3 group (P <.05). Moreover, we found that the number of times that additional patient‐controlled analgesia was administered was higher in the S0.1 group compared with the remaining 3 groups (P <.05). The control group exhibited a higher incidence of pruritus than the other 3 groups (P <.05). In conclusion, when administering spinal anesthesia for the relief of labor pain, epidural analgesia with 0.1% ropivacaine combined with 0.2 µg/mL DEX provides relatively ideal analgesic effects, higher maternal satisfaction, and reduces the incidence of pruritus, compared with the combination of 0.1% ropivacaine and 0.3 µg/mL sufentanil. [ABSTRACT FROM AUTHOR]

Background and Aims: Many strategies are available to prevent spinal-induced hypotension in cesarean section, especially the use of a low dose of spinal anesthesia combined with adjuvants. This study investigated the effect of adding either dexmedetomidine or dexamethasone to the intrathecal bupivacaine-fentanyl mixture on the postoperative analgesia duration, after elective cesarean section. Material and Methods: This prospective, randomized, double-blind study was conducted on 90 full-term parturients undergoing elective cesarean section, who were randomly distributed into three groups. They all received spinal anesthesia with the bupivacaine-fentanyl mixture (2.5 ml), in addition to 0.5 ml normal saline (control group), 5 µg dexmedetomidine dissolved in 0.5 ml normal saline (dexmedetomidine group), or 2 mg dexamethasone (dexamethasone group). The time to the first request of morphine rescue analgesia was recorded, in addition to the total dose of morphine consumed in the first 24 h after surgery, the postoperative numerical rating score (NRS), and maternal and fetal outcomes. Results: As compared to the control group and the dexamethasone group, the use of dexmedetomidine as an additive to the bupivacaine-fentanyl mixture significantly prolonged the time to the first request of rescue analgesia, decreased postoperative morphine consumption, and decreased the pain score 4 and 6 h after surgery. There was an insignificant difference between the control and dexamethasone groups. Conclusion: The use of dexmedetomidine as an additive to bupivacaine-fentanyl mixture in spinal anesthesia for cesarean section prolonged the postoperative analgesia and decreased the postoperative opioid consumption in comparison to the addition of dexamethasone or normal saline. [ABSTRACT FROM AUTHOR]

[Display omitted] • Short- (SAI) and long-latency (LAI) afferent inhibition result from cortical integration of sensory inputs and motor output. • This work shows that SAI and LAI depend on type of sensory receptors, muscle function and cortical motor area. • This finding has pathophysiological implications in motor disorders involving specific muscular districts, such as focal dystonia. To compressively investigate sensorimotor integration in the cranial-cervical muscles in healthy adults. Short- (SAI) and long-latency afferent (LAI) inhibition were probed in the anterior digastric (AD), the depressor anguli oris (DAO) and upper trapezius (UT) muscles. A transcranial magnetic stimulation pulse over primary motor cortex was preceded by peripheral stimulation delivered to the trigeminal, facial and accessory nerves using interstimulus intervals of 15–25 ms and 100–200 ms for SAI and LAI respectively. In the AD, both SAI and LAI were detected following trigeminal nerve stimulation , but not following facial nerve stimulation. In the DAO, SAI was observed only following trigeminal nerve stimulation, while LAI depended only on facial nerve stimulation, only at an intensity suprathreshold for the compound motor action potential (cMAP). In the UT we could only detect LAI following accessory nerve stimulation at an intensity suprathreshold for a cMAP. The results suggest that integration of sensory inputs with motor output is profoundly influenced by the type of sensory afferent involved and by the functional role played by the target muscle. Data indicate the importance of taking into account the sensory receptors involved as well as the function of the target muscle when studying sensorimotor integration, both in physiological and neurological conditions. [ABSTRACT FROM AUTHOR]

Pediatric regional anesthesia has become an integral part of perioperative pain management strategies in children. Adjuvants play a pivotal role in augmenting the efficacy and prolonging the duration of regional anesthesia techniques, thereby improving postoperative pain control, and reducing opioid consumption. This review provides a comprehensive overview of the various adjuvants utilized in pediatric regional anesthesia, highlighting their mechanisms of action, clinical applications, efficacy, and safety profiles. [ABSTRACT FROM AUTHOR]

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Background: The supraclavicular nerve block is a useful alternative to general anesthesia for upper limb surgery. Previous research investigated the effect of adjuvant, but its role in the context of a reduced volume of a local anaesthetic drug under ultrasound-guided blocks remains unknown.Aim of the Study: To determine the enhancing effect of dexmedetomidine or midazolam as a local anaesthetic adjuvant to bupivacaine.Patients and Methods: A prospective double-blind randomized clinical trial, included 90 patients arranged for upper limb vascular surgery. Two groups are comprised; BD group [45 patients]: patients who received ultrasound-guided supraclavicular regional block with injection of 20 ml Bupivacaine 0.25% + 10 ml Lidocaine Hydrochloride 2% + 1µ/kg Dexmedetomidine, and BM group [45 patients]: Patients received ultrasound-guided supraclavicular regional block with an injection of 20 ml Bupivacaine 0.25% + 10 ml Lidocaine Hydrochloride 2% + 50µ/kg Midazolam. The primary outcome was duration of post-operative analgesia.Results: The BD group had a statistically significant longer duration of analgesia compared to the BM group. Patients in the BD group had significantly higher scores on the Ramsay Sedation Scale and VAS starting from 30 and 45 minutes intraoperatively, respectively, and these scores continued to be higher until 6 hours postoperatively. However, there were no significant differences between the two groups regarding blood pressure measurement along the follow-up period.Conclusion: Adding dexmedetomidine to bupivacaine for supraclavicular brachial plexus block was found to be more effective than adding midazolam in extending the duration of both sensory and motor block.

Aim: This study of our study was to evaluate the onset and duration of sensory and motor block and side effects of clonidine or dexmedetomidine when used as an adjuvant in epidural anaesthesia in total knee replacement. Materials and methods: 60 patients of ASA status I and II, posted for total knee replacement were randomly allocated into two groups of 30 each. Group BC group patients received 18 ml of 0.5% bupivacaine and clonidine 2mcg/kg. Group BD group patients received 18 ml of 0.5% bupivacaine and dexmedetomidine 1.5mcg/kg. Preoperative and postoperative block characteristics as well as hemodynamic parameters were observed and recorded. Results: Dexmedetomidine resulted earlier onset and longer duration of sensory and motor block on comparison to clonidine as adjuvant in epidural anesthesia. Sedation scores were statistically significant with dexmedetomidine group in comparison to clonidine group. Conclusion: Dexmedetomidine was a better than clonidine as an adjuvant to bupivacaine in epidural anaesthesia in total knee replacement. [ABSTRACT FROM AUTHOR]

Purpose: To assess the antitumor activity of neoadjuvant chemotherapy in conjunction with PD-1 inhibitors (neoadjuvant chemoimmunotherapy) among patients with oropharyngeal and hypopharyngeal squamous cell carcinoma (OPHSCC) and compare its efficacy with neoadjuvant chemotherapy alone. Methods: We conducted a retrospective analysis using data from patients diagnosed with OPHSCC and treated at the Sun Yat-sen University Cancer Center between September 2012 and August 2022. We included patients who received neoadjuvant chemotherapy alone or combined with PD-1 inhibitors. We assessed the clinical response using the Response Evaluation Criteria in Solid Tumors and evaluated progression-free survival (PFS) and overall survival (OS). Results: Preliminary results demonstrate that neoadjuvant chemoimmunotherapy exhibited robust antitumor activity in OPHSCC, with an impressive overall response rate (ORR) of 81.0%. Complete response and partial response rates were 14.9% and 65.9%, respectively. Notably, neoadjuvant chemoimmunotherapy demonstrated superior PFS and OS to neoadjuvant chemotherapy alone. The 1-year PFS rate was 80.7%, and the 2-year rate was 61.1%. Additionally, the 1-year OS rate reached 92.3%. Finally, a multivariate analysis identified the American Joint Committee on Cancer stage reduction post-treatment as a favorable predictor of PFS. Conclusion: Our results underscore the promising potential of neoadjuvant chemoimmunotherapy in enhancing antitumor activity in patients with OPHSCC. The robust ORR, along with improved PFS and OS, supports the utility of this combined approach. These results pave the way for further investigations to validate and refine the application of neoadjuvant chemoimmunotherapy in this challenging clinical context. [ABSTRACT FROM AUTHOR]

Background: The effectiveness and safety of neoadjuvant PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors is controversial. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors as neoadjuvant therapy for malignant solid tumors. Methods: This study has been registered with the number CRD42023407275 on PROSPERO. Systematic searches were conducted in PubMed, Embase, Web of Science and Cochrane Library databases until March 17, 2023. In addition, manual searches were performed. The inclusion criteria encompassed randomized controlled trials (RCTs) that assessed the utilization of neoadjuvant PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors PD-1/PD-L1 inhibitors for patients with solid malignancies. The Cochrane Collaboration's tool for assessing risk of bias in randomized trials (ROB1) were used. Risk ratios (RRs), hazared ratios (HRs) and their respective 95% confidence intervals were calculated using Stata17.0 MP and Review Manager 5.4 software. Results: A total of 2780 records were identified, and ultimately 10 studies involving 273 patients were included. The meta-analysis showed that the addition of CTLA-4 inhibitors to PD-1/PD-L1 inhibitors did not demonstrate a significant effect on overall response rate, main pathological response, pathological complete response, surgical resection, radical resection, overall survival, progression-free survival, recurrence-free survival, grade 3–4 adverse events, all-cause mortality, and completed treatment (P > 0.05). However, further subgroup analysis indicated that the combination of PD-1 with CTLA-4 inhibitors significantly increased the occurrence of grade 3–4 adverse events in patients (P < 0.05). Conclusions: As neoadjuvant therapy for malignant solid tumors, the addition of CTLA-4 inhibitors to PD-1/PD-L1 inhibitors does not appear to enhance efficacy.Moreover, there is a potential increase in the risk of grade 3–4 adverse events associated with this combination. However, it is important to note that the studies included in this analysis suffer from limitations such as small samples and single-center designs, which are inherent constrains with the available published literature. Further research involving large-sample and multicenter RCTs are warranted to obtain more reliable results. [ABSTRACT FROM AUTHOR]

Introduction: Intrathecal fentanyl and dexmedetomidine are adjuvants that can be used along with bupivacaine in spinal anesthesia to enhance the quality and duration of analgesia. Fentanyl is a potent opioid that acts on the muopioid receptors in the spinal cord, which inhibits the transmission of pain signals. Dexmedetomidine is a selective alpha-2 adrenergic agonist that acts on the spinal cord to reduce sympathetic outflow and modulate pain transmission. Material and Methods: 100 ASA I and II patients scheduled for major surgeries under spinal anaesthesia were chosen for the study. Under strict asepsis, using 25 G Quincke spinal needle, lumbar puncture was performed at L 3 - L 4 space. Group F received 3ml, 0.5 % hyperbaric bupivacaine + 25 μg Fentanyl (vol 0.5ml). Group D received 3ml, 0.5 % hyperbaric bupivacaine + 5 μg Dexmedetomidine (vol 0.5 ml). Intra-operatively pulse rate, non-invasive blood pressure, electrocardiogram, SpO2 was recorded. 50 patients in Group F (Fentanyl) and 50 patients in Group D (Dexmedetomidine) were taken to study the changes in haemodynamics and side effects. Chi-square test, Anova test and student' 't' test was done to analyse the data and p value was determined. Results: Dexmedetomidine performed better than Fentanyl as an adjuvant based on the various parameters. Conclusions: Dexmedetomidine is a safe and effective adjuvant for intrathecal administration in the management of postoperative pain as compared to Fentanyl. [ABSTRACT FROM AUTHOR]

To compare the anesthesia effect of compound ketamine and pentobarbital sodium in orthopedic surgery, 30 specific pathogen free C57BL/6J male mice were included and randomly enrolled into group A (compound ketamine group) and group B (pentobarbital sodium group). The changes of respiratory frequency, heart rate, body temperature, blood oxygen saturation, anesthesia duration, and anesthesia depth among mice in the two groups were compared. It was demonstrated that respiratory frequency declined in the two groups. Heart rate showed no apparent changes as anesthesia was continued. Heart rate was high in group A at 50 min while it was low in group B at 90 min. Body temperature among mice in the two groups generally declined. After 90 min, it dramatically declined in group A. Body temperature was the lowest in group B at 90 min. Blood oxygen saturation generally raised in the two groups. As to anesthesia duration, induction and anesthesia periods were relatively longer in group B. The score for anesthesia depth of group B remained above 3 points 20 min after rectification disappeared and anesthesia duration of group B was notably longer. The research findings revealed that compound ketamine and pentobarbital sodium showed excellent anesthesia effects and physiological indicators. The latter one was characterized by long anesthesia duration, low safety, and high fatality. [ABSTRACT FROM AUTHOR]

Background: Fluoropyrimidine-based postoperative adjuvant chemotherapy is globally recommended for high-risk stage II and stage III colon cancer. However, adjuvant chemotherapy is often associated with severe adverse events and is not highly effective in preventing recurrence. Therefore, discovery of novel molecular biomarkers of postoperative adjuvant chemotherapy to identify patients at increased risk of recurrent colorectal cancer is warranted. Autophagy (including mitophagy) is activated under chemotherapy-induced stress and contributes to chemotherapy resistance. Expression of autophagy-related genes and their single-nucleotide polymorphisms are reported to be effective predictors of chemotherapy response in some cancers. Our goal was to evaluate the relationship between single-nucleotide variants of autophagy-related genes and recurrence rates in order to identify novel biomarkers that predict the effect of adjuvant chemotherapy in colorectal cancer. Methods: We analyzed surgical or biopsy specimens from 84 patients who underwent radical surgery followed by fluoropyrimidine-based adjuvant chemotherapy at Saitama Medical University International Medical Center between January and December 2016. Using targeted enrichment sequencing, we identified single-nucleotide variants and insertions/deletions in 50 genes, including autophagy-related genes, and examined their association with colorectal cancer recurrence rates. Results: We detected 560 single-nucleotide variants and insertions/deletions in the target region. The results of Fisher's exact test indicated that the recurrence rate of colorectal cancer after adjuvant chemotherapy was significantly lower in patients with the single-nucleotide variants (c.1018G > A [p < 0.005] or c.1562A > C [p < 0.01]) of the mitophagy-related gene PTEN-induced kinase 1. Conclusions: The two single-nucleotide variants of PINK1 gene may be biomarkers of non-recurrence in colorectal cancer patients who received postoperative adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Background and objects: Patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) are often old and poor in physical fitness. The purpose of this study was to investigate the anesthetic effect of different doses of alfentanil combined with ciprofol in elderly patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). Methods: In this clinical trial, 137 patients, who were candidates for ERCP were randomly divided into three groups. Group A were given 0.15 μg/kg/min of alfentanil in maintenance stage, Group B were given 0.25 μg/kg/min and Group C were given 0.35 μg/kg/min. Mean arterial pressure (MAP), heart rate (HR), oxygen saturation (SpO2) of the patients at each time point including the entry into the operation room (T0), at the beginning of surgery(T1), 10 min after surgery(T2), 20 min after surgery(T3), 30 min after surgery(T4),endoscopy withdrawal (T5) were recorded. Adverse events(including respiratory depression, body movement and hypoxemia),the dosage of ciprofol, the time of operation time and awakening were recorded. Results: Compared with Group A, MAP and HR in Group B and Group C was decreased during T1-T5 (P < 0.05). Compared with group B, MAP and HR in group C was decreased during T1-T5 (P < 0.05). Compared with Group A and Group C,the number of adverse reactions of Group B was decreased(P < 0.05). There was no statistical difference in surgical time among the three groups(P > 0.05),but a statistically significant difference in recovery time (P < 0.05). Conclusion: The adverse events of alfentanil 0.25μg/kg/min combined with ciprofol were low, and the anesthetic effect was the best. [ABSTRACT FROM AUTHOR]

Background: Ropivacaine is a long-acting local anesthetic that is used to treat postoperative pain. Adjuvant use of dexmedetomidine in regional anesthesia may prolong the duration of analgesia. The objective of this systematic review and meta-analysis was to investigate the duration and effect of ropivacaine alone vs. ropivacaine in combination with dexmedetomidine for postoperative analgesia. Methods: The PubMed, EMBASE, Web of Science, and Google Scholar databases were searched for randomized controlled trials (RCTs) of ropivacaine alone or ropivacaine in combination with dexmedetomidine for regional anesthesia. The primary outcome was duration of analgesia, defined as the time from onset of the block to the time of the first analgesic request or initial pain report. Secondary outcomes were duration of sensory block, duration of motor block, consumption of sufentanil for analgesia, length of hospital stay, and incidence of postoperative nausea and vomiting. Results: Eighteen studies with 1148 patients were included. Overall quality of the RCTs, as assessed by the Jadad scale, was high. The meta-analysis demonstrated that ropivacaine combined with dexmedetomidine significantly prolonged the duration of postoperative analgesia from local anesthetics compared to ropivacaine alone (WMD: 4.14h; 95%CI: 3.29~5.0h; P<0.00001; I2 = 99%). There was evidence of high heterogeneity between studies. The duration of sensory and motor block was significantly increased, and consumption of sufentanil for analgesia and the incidence of postoperative nausea and vomiting were significantly reduced in patients who received ropivacaine combined with dexmedetomidine compared to ropivacaine alone. There was no significant difference in length of hospital stay. Conclusions: Compared to ropivacaine alone, ropivacaine combined with dexmedetomidine significantly prolonged the duration of postoperative analgesia and sensory and motor block, and reduced consumption of sufentanil for analgesia and the incidence of postoperative nausea and vomiting, across an array of surgeries. [ABSTRACT FROM AUTHOR]

Introduction: Regional anesthesia is preferred for cesarean section as it allows a parturient to remain awake and participate in the birth of her baby while avoiding the risks of general anesthesia. The combined spinal-epidural (CSE) technique is frequently used to provide anesthesia and analgesia for labor and delivery. To improve the quality of intraoperative anesthesia, postoperative analgesia and aid early ambulation and recovery of motor block, several agents have been employed such as opioids and α-2 adrenergic agonist. Some recent placebo-controlled studies suggested that α-2 adrenergic agonist have both analgesic and sedative properties when used as an adjuvant in regional anesthesia. Materials and Methods: After obtaining written consent from the 180 patients, they were randomly divided into three groups of thirty each. All the patients were pre-operatively assessed and the technique for study was explained to them. Patient’s age ranging from 25 to 60 years, of either sex, belonging to ASA I and II and no contraindications to epidural analgesia or the drugs were taken into consideration. The three groups were comparable in terms of baseline demographic parameters like age, sex, and weight. Basal haemodynamic parameters were comparable. Patients of ASA III and above, allergic to study drugs were excluded from the study. Results: 180 patients were enrolled in the study. In group A, 60 patients, in group B 60 patients, in Group C 60 patients. In group A, 34 patients were male, 26 patients were females, In group B, 32 patients were male, 28 patients were females. In group C, 30 patients were male, 30 patients were females. Analgesia and sedation was more in Group C than the other two groups. Cardiovascular stability was good in groups A and B. Conclusion: Since sensitivity to a drug depends on numerous factors, the search for an ideal dose in endless. We found that epidural dexmeditomidine 50 mcg dose gave satisfactory analgesia and sedation with minimal side effects. [ABSTRACT FROM AUTHOR]

Introduction: This comprehensive review delves into the intricate and multifaceted relationship between anesthesia and melatonin, aiming to provide essential insights for perioperative clinical anesthesiologists and stimulate interest in related research. Anesthesia and surgery have the potential to disrupt melatonin secretion, leading to sleep disorders, postoperative neurocognitive dysfunction and other symptoms. In comparison to previous reviews, this review provides a comprehensive summary of the various aspects linking melatonin and anesthesia, going beyond isolated perspectives. It explores the potential benefits of administering melatonin during the perioperative period, including alleviating anxiety, reducing pain, enhancing perioperative sleep quality, as well as demonstrating immunomodulatory and anti-tumor effects, potentially offering significant advantages for cancer surgery patients. Recent Findings: Anesthesia and surgery have a significant impact on melatonin secretion, the hormone crucial for maintaining circadian rhythms. These procedures disrupt the normal secretion of melatonin, leading to various adverse effects such as sleep disturbances, pain, and postoperative neurocognitive dysfunction. However, the administration of exogenous melatonin during the perioperative period has yielded promising results. It has been observed that perioperative melatonin supplementation can effectively reduce anxiety levels, improve pain management, enhance the quality of perioperative sleep, and potentially decrease the occurrence of postoperative delirium. In recent years, studies have found that melatonin has the potential to improve immune function and exhibit anti-cancer effects, further underscoring its potential advantages for patients undergoing cancer surgery. Summary: In summary, melatonin can serve as an adjuvant drug for anesthesia during the perioperative period. Its administration has demonstrated numerous positive effects, including anti-anxiety properties, sedation, analgesia, improved postoperative sleep, and the potential to reduce the incidence of postoperative delirium. Furthermore, its immune-modulating and anti-tumor effects make it particularly valuable for cancer surgery patients. However, further studies are required to determine the optimal dosage, long-term safety, and potential adverse reactions associated with melatonin administration. [ABSTRACT FROM AUTHOR]

Background: The lack of local guidelines and regulations for the administration of anesthesia in magnetic resonance imaging (MRI) units presents a potential risk to patient safety in Saudi Arabia. Hence, this study aimed to evaluate the extent to which hospitals in Saudi Arabia follow international guidelines and recommendations for the safe and effective administration of anesthesia in an MRI environment. Methods: This study used a questionnaire that was distributed to 31 medical facilities in Saudi Arabia that provided anesthesia in MRI units. Results: The findings of the study revealed that the mean compliance with the 17 guidelines across the 31 sites was 77%; 5 of the 31 sites (16.1%) had a compliance rate of less than 50% with the recommended guidelines. Only 19.4% of the institutes provided general safety education. Communication breakdowns between anesthesia providers and MRI teams were reported. Conclusions: To conclude, this survey highlights the status of anesthesia standards in Saudi Arabian MRI units and emphasizes areas that require better adherence to international guidelines. The results call for targeted interventions, including the formulation of specific national anesthesia guidelines for MRI settings. Communication breakdowns between anesthesia providers and MRI teams were reported at a rate of 83.9% during the administration of a gadolinium contrast agent. There were additional breakdowns, particularly for high-risk patients with implants, such as impaired respirators (74.2%), thus requiring further investigation due to potential safety incidents during MRI procedures. While considering the limitations of this study, such as potential biases and the low response rate, it provides a valuable foundation for refining protocols and promoting standardized practices in Saudi Arabian healthcare. [ABSTRACT FROM AUTHOR]

Introduction: Dexmedetomidine (DXM) is widely used as an adjuvant to anesthesia or a sedative medicine, and differences in individual sensitivity to the drug exist. This study aimed to investigate the effect of genetic polymorphisms on these differences. Methods: A total of 112 patients undergoing hand surgery were recruited. DXM 0.5 μg/kg was administered within 10 min and then continuously injected (0.4 μg/kg/h). Narcotrend index, effective dose and onset time of sedation, MAP, and HR were measured. Forty-five single nucleotide polymorphisms (SNPs) were selected for genotype. Results: We observed individual differences in the sedation and hemodynamics induced by DXM. ABCG2 rs2231142, CYP2D6 rs16947, WBP2NL rs5758550, KATP rs141294036, KCNMB1 rs11739136, KCNMA1 rs16934182, ABCC9 rs11046209, ADRA2A rs1800544, and ADRB2 rs1042713 were shown to cause statistically significant (p < 0.05) influence on the individual variation of DXM on sedation and hemodynamics. Moreover, the multiple linear regression analysis indicated sex, BMI, and ADRA2A rs1800544 are statistically related to the effective dose of DXM sedation. Discussion: The evidence suggests that the nine SNPs involved in transport proteins, metabolic enzymes, and target proteins of DXM could explain the individual variability in the sedative and hemodynamic effects of DXM. Therefore, with SNP genotyping, these results could guide personalized medication and promote clinical and surgical management. [ABSTRACT FROM AUTHOR]

Purpose: To investigate analgesic effect and safety of dexmedetomidine combined with ropivacaine in ultrasound-guided brachial plexus block in intercostal space. Methods: A total of 90 patients were scheduled to undergo upper limb surgery and divided into control and study groups, respectively. Patients in control group were given ropivacaine nerve block, while those in study group were given ropivacaine combined with dexmedetomidine mixture nerve block. The efficiency of sensory and motor block, secondary evaluation of block effect, visual analogue scale (VAS) scores at different postoperative moments, remedial analgesia and adverse reactions were compared between the two groups after 30 min of drug injection. Results: The success rate of sensory block was not significantly different between control group (91.11 %) and study group (93.33 %; X2 = 0.155, p > 0.05) but success rate of the motor block was significantly higher in study group (93.33 %) than in control group (71.11 %; X2 = 7.601, p < 0.05). Compared with control group, onset of sensory block and motor block were significantly shorter in study group, while the duration of sensory block and motor block was significantly longer (p < 0.05). The VAS scores at 12, 24, and 48 h postoperatively were significantly lower in study group than control group (p < 0.05). The number of self-administered analgesia, number of patients, dose used, and overall incidence of adverse reactions in study group were significantly lower than in control group (p < 0.05). Conclusion: Dexmedetomidine and ropivacaine, when administered together, have a significant anesthetic effect during nerve block, which is safe and enhances their analgesic effect. However, the mechanism of improving analgesic effect of the combined plan, using a larger number of samples should be further investigated. [ABSTRACT FROM AUTHOR]

Background: Erector spinae plane block (ESPB) improves postoperative analgesia and significantly enhances the quality of recovery (QoR) after video-assisted thoracoscopic lobectomy surgery (VATLS). However, it is not known whether the use of dexmedetomidine (Dex) as an adjunct for ropivacaine to ESPB affects the QoR after VATLS. The purpose of this study was to explore the effects of different Dex dosages as an adjunct for ropivacaine in combination with ultrasound-guided ESPB on the quality of postoperative recovery in patients with VATLS. Methods: In this single-center, double-blind, randomized study, 120 patients between the ages of 18 and 65 who were scheduled for VATLS from december 2021 and october 2022 in our hospital under general anesthesia were randomly divided into three groups: ultrasound-guided ESPB with 30 mL of 0.5% ropivacaine (Group R), ultrasound-guided ESPB 0.5% ropivacaine plus 0.5 µg/kg Dex (Group RD1), and ultrasound-guided ESPB 0.5% ropivacaine plus 1.0 µg/kg Dex (Group RD2), ultrasound-guided ESPB was administrated at the T5 vertebral level before surgery. The primary outcome was the QoR-15 score 24 h after the surgery. The secondary outcomes included the QoR-15 scores at 12 h, 48 h, and 72 h after the operation, visual analogue scale (VAS) scores at 8 h, 12 h, 24 h, and 48 h after surgery, cumulative flurbiprofen consumption, postoperative nausea and vomiting (PONV), postoperative bradycardia, and hypotension. Results: The QoR-15 scores were higher in group RD2 than the R and RD1 groups on postoperative day 1 (P < 0.05), in addition, no significant difference was found in the QoR-15 scores between groups R and RD1 on postoperative day 1. The VAS scores were significantly lower in group RD2 than in groups RD1 and group R 12–24 h after surgery (P < 0.05). No significant differences were observed in the QoR-15 and VAS scores at 48 and 72 h after surgery between the three groups. The cumulative flurbiprofen consumption was markedly reduced during the 72 h after surgery in the RD2 group (P < 0.05). The incidence of postoperative nausea and vomiting was lower in the RD2 group (P < 0.05). Conclusions: The combination of 1 µg/kg dexmedetomidine as an adjunct with 0.5% ropivacaine 30 ml for erector spinae plane block significantly improved the postoperative quality of recovery and provided better postoperative analgesia on postoperative day 1 in patients undergoing Video-assisted thoracoscopic lobectomy surgery. However, dexmedetomidine (1 µg/kg) as an adjunct for ropivacaine combined with erector spinae plane block did not enhance the postoperative quality of recovery at 48 and 72 h postoperatively. Trial registry number: The number of this clinical trial registry is ChiCTR2100053230, date of registration: 16/11/ 2021) [ABSTRACT FROM AUTHOR]

Background: We sought to explore the relationship between dexmedetomidine as an anesthetic adjuvant in cardiac surgery and postoperative complications and length of stay (LOS) in the cardiac intensive care unit (CICU). Methods: We conducted a retrospective study of patients aged 18 years and older who underwent heart valve surgery between October 2020 and June 2022. The primary endpoint of the study was major postoperative complications (cardiac arrest, atrial fibrillation, myocardial injury/infarction, heart failure) and the secondary endpoint was prolonged CICU LOS (defined as LOS > 90th percentile). Multivariate logistic regression analysis was performed for variables that were significant in the univariate analysis. Results: A total of 856 patients entered our study. The 283 patients who experienced the primary and secondary endpoints were included in the adverse outcomes group, and the remaining 573 were included in the prognostic control group. Multivariate logistic regression analysis revealed that age > 60 years (odds ratio [OR], 1.68; 95% confidence interval [CI], 1.23–2.31; p < 0.01), cardiopulmonary bypass (CPB) > 180 min (OR, 1.62; 95% CI, 1.03–2.55; p = 0.04) and postoperative mechanical ventilation time > 10 h (OR, 1.84; 95% CI, 1.35–2.52; p < 0.01) were independent risk factors for major postoperative complications; Age > 60 years (OR, 3.20; 95% CI, 1.65–6.20; p < 0.01), preoperative NYHA class 4 (OR, 4.03; 95% CI, 1.74–9.33; p < 0.01), diabetes mellitus (OR, 2.57; 95% CI, 1.22–5.41; p = 0.01), Intraoperative red blood cell (RBC) transfusion > 650 ml (OR, 2.04; 95% CI, 1.13–3.66; p = 0.02), Intraoperative bleeding > 1200 ml (OR, 2.69; 95% CI, 1.42–5.12; p < 0.01) were independent risk factors for prolonged CICU length of stay. Intraoperative use of dexmedetomidine as an anesthetic adjunct was a protective factor for major complications (odds ratio, 0.51; 95% confidence interval, 0.35–0.74; p < 0.01) and prolonged CICU stay. (odds ratio, 0.37; 95% confidence interval, 0.19–0.73; p < 0.01). Conclusions: In patients undergoing heart valve surgery, age, duration of cardiopulmonary bypass, and duration of mechanical ventilation are associated with major postoperative complication. Age, preoperative NYHA classification 4, diabetes mellitus, intraoperative bleeding, and RBC transfusion are associated with increased CICU length of stay. Intraoperative use of dexmedetomidine may improve such clinical outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Bisphosphonates (BPs) are bone-protecting osteoclast inhibitors, typically used in the treatment of osteoporosis and skeletal complications of malignancies. When given in the adjuvant setting, these drugs may also prevent relapses and prolong overall survival in early breast cancer (EBC), specifically among postmenopausal patients. Because of these findings, adjuvant nitrogencontaining BPs (N-BPs), such as zoledronate (ZOL), are now the standard of care for high-risk EBC patients, but there are no benefit-associated biomarkers, and the efficacy remains low. BPs have been demonstrated to possess anti-tumor activities, but the mechanisms by which they provide the beneficial effects in EBC are not known. Methods: We used stably transfected 4T1 breast cancer cells together with suppression of CD73 (sh-CD73) or control cells (sh-NT). We compared ZOL effects on tumor growth and infiltrating lymphocytes (TILs) into tumors and lung metastases using two mouse models. B cell depletion was performed using anti-CD20 antibody. Results: Sh-CD73 4T1 cells were significantly more sensitive to the growth inhibitory effects of n-BPs in vitro. However, while ZOL-induced growth inhibition was similar between the tumor groups in vivo, ZOL enhanced B and T lymphocyte infiltration into the orthotopic tumors with down-regulated CD73. A similar trend was detected in lung metastases. ZOL-induced tumor growth inhibition was found to be augmented with B cell depletion in sh-NT tumors, but not in sh-CD73 tumors. As an internal control, ZOL effects on bone were similar in mice bearing both tumor groups. Discussion: Taken together, these results indicate that ZOL modifies TILs in breast cancer, both in primary tumors and metastases. Our results further demonstrate that B cells may counteract the growth inhibitory effects of ZOL. However, all ZOL-induced TIL effects may be influenced by immunomodulatory characteristics of the tumor. [ABSTRACT FROM AUTHOR]

Simple Summary: Analgesia is an important part of peri-operative protocols in humans and animals. The direct administration of analgesic drugs to a specific nerve is more effective than the systemic administration of such drugs. With the aid of ultrasound, the success rate of nerve blocks can be further improved. We developed an ultrasound-guided approach to perform a block of the sciatic and femoral nerves in rabbits. After a first evaluation of the anatomy, we successfully tested the technique in 20 hind limbs of 10 cadavers. This technique can now be assessed in rabbits undergoing hind limb surgery for clinical or experimental purposes. The rabbit is a popular animal model for human biomechanical research involving surgery on the hind limb. Mortality is higher in rabbits when undergoing general anesthesia compared to dogs and cats. Moreover, due to their nature as prey animals, rabbits have a tendency to hide signs of pain, making it challenging to detect discomfort at an early stage. Incorporating regional anesthesia into an anesthetic protocol can greatly reduce the requirements for systemic anesthetic and analgesic drugs, thereby minimizing associated side effects. In other species, a block of the sciatic (ScN) and the femoral nerves (FN) is usually applied in patients undergoing hind limb surgery. In phase 1 of this study, the ScN and the FN have been localized and an appropriate approach has been evaluated under sonographic guidance. In phase 2, a mixture of new methylene blue and lidocaine have been administered to the ScN and the FN in 10 cadavers (20 hind limbs). Staining of the nerves was evaluated by dissection. Ultrasonographically, the ScN appeared as a binocular structure surrounded by a hyperechoic rim. The FN appeared as a hypoechoic structure in the dorsal part of the iliopsoas muscle (IPM), becoming hyperechoic/honey-comb-like in the ventral part. Both nerves could be successfully stained in all animals over a median length of 2.3 cm which was considered effective. This technique allows feasible and accurate access to block the ScN and the FN and may lead to successful analgesia in rabbits undergoing hind limb surgery. [ABSTRACT FROM AUTHOR]

Background and Aims: This prospective randomized study designed to evaluate the efficacy of dexmedetomidine either added to LA mixture or administered IV during subtenon block for cataract surgery. Material and Methods: 75 patients, undergoing cataract surgery with subtenon anesthesia, were assigned randomly into three equal groups, Group I received subtenon bupivacaine 0.5% (1 ml) + lidocaine 2% (1 ml) + saline 0.9% (0.5 ml) and IV infusion of normal saline. Group II received subtenon bupivacaine 0.5% (1 ml) + lidocaine 2% (1 ml) + 0.5 μg/kg dexmedetomidine (0.5 ml) and IV infusion of normal saline. Group III received subtenon bupivacaine 0.5% (1 ml) + lidocaine 2% (1 ml) + saline 0.9% (0.5 ml) and IV infusion of 0.5 μg/kg dexmedetomidine over 10 min. before subtenon block. We recorded onset and duration of sensory and motor block, pain during subtenon injection, intraoperative hemodynamics, intraocular pressure, sedation and postoperative pain score. Results: There was a significant decrease in the onset of action and an increase in the duration of sensory block in Group II. Pain during subtenon injection was significantly less in group III. Sedation Score was higher in Group III, while heart rate showed a significant reduction in the same group. The VAS was significantly decreased in group II. After the end of surgery, the intraocular pressure was significantly decreased in Groups II and III. Conclusion: Subtenon dexmedetomidine shortens onset time, prolongs sensory block durations and significantly decreases the postoperative pain score with hemodynamic stability, while, IV dexmedetomidine substantially reduces pain during subtenon block and produces intra-operative sedation. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Bilateral peripheral block (TAP - block) is usually performed under ultrasonography (US) guidance in the plane between the inner oblique abdominal muscle and the transversal abdominal muscle, and it aims to block the thoracoabdominal nerves from Th6 to L1 by infiltrating local anesthetic. TAP block is effective tool of managing pain control, especially in the first twenty-four hours after surgery. It improves recovery pathway following minimally invasive surgery and reduces narcotic and non-steroidal anti-inflammatory drugs (NSAIDs) use for postoperative pain management in various different abdominal surgery. AIM: The purpose of this research was to assess the analgesic efficacy of TAP block in regard to used NSAIDs concentrations during the first 24 hours following laparoscopic inguinal hernioplasty. METHODS: The study was conducted with 60 patients, who were randomized into two groups. Control group - were patients who received general anesthesia (GA), and experimental group, were patients who have received GA and a bilateral TAP block. All patients received NSAIDs in the postoperative period. RESULTS: From the acquired data, during the first postoperative hour (POH) only 20% of the experimental group required Paracetamol in a dosage of 1000 mg. Control patients used three times more NSAIDs (60%). Compared to the control group, 63.3% of TAP-block patients did not require analgesia from the 6th to the 12th POH. In the control group average amount of paracetamol was 5167 mg, while in experimental group it was twice lower. Similar finding was established in regard to Ketonal consumption. The control group (without TAP-block) consumes around twice as many NSAIDs as the experimental group at all post-operative time intervals. CONCLUSION: The findings of our research demonstrate that patients undergoing bilateral laparoscopic inguinal repair, administering ropivacaine as part of an US-guided bilateral TAP-block decreases the requirement of NSAIDs in the first twenty-four hours after surgery. TAP-block is a component of multimodal anesthesia and an adjuvant for intraoperative and postoperative analgesia. [ABSTRACT FROM AUTHOR]

Cataract surgery ranks among the commonest procedures performed worldwide. Approximately 51% of blindness worldwide is related to cataracts, affecting about 65.2 million people worldwide and more so in developing countries. Over the years, there has been a significant evolution in the surgical techniques of cataract extraction. The advancement in phacoemulsification machines, phaco-tips, and the availability of ophthalmic viscoelastic devices have played a substantial role in cataract surgery such that they are faster and more controlled than before. Similarly, anesthetic techniques in cataract surgery have advanced significantly from retrobulbar, peribulbar, and sub-Tenon's blocks to topical anesthesia. Though topical anesthesia eliminates the possible complications of injectable anesthesia, it is not suitable for use in uncooperative, anxious patients, pediatric age groups, and patients with cognitive disabilities. Hyaluronidase is an enzyme that breaks down hyaluronic acid in the retrobulbar tissue, facilitating uniform diffusion of the anesthetic drug and hastening the onset of anesthesia and akinesia. Hyaluronidase has been used in the last 80 years successfully as an adjuvant in retrobulbar, peribulbar, and sub-Tenon's blocks. Initially, the hyaluronidase enzyme was animal-derived and of bovine and ovine sources. Recombinant human-derived hyaluronidase, which has lesser allergic reactions, impurities, and toxicity, is now available. There is conflicting evidence regarding the efficacy of hyaluronidase as an adjuvant in retrobulbar and peribulbar blocks. This article summarizes a brief review of the literature on the role of hyaluronidase as an adjuvant in local anesthetic blocks in ophthalmic surgeries. [ABSTRACT FROM AUTHOR]

Background: Many intrathecal adjuvants are being used with local anesthetics to prolong the intraoperative anesthesia and postoperative analgesia. Clonidine and buprenorphine are known to potentiate the effects of local anesthestics. Aims and Objectives: This study was designed to compare the duration of postoperative analgesia as well as duration of sensory and motor block onset, intraoperative hemodynamic changes, and perioperative complications between buprenorphine and clonidine when used as an adjuvant to intrathecal hyperbaric bupivacaine. Materials and Methods: A randomized double-blind study for 80 patients undergoing lower abdominal surgeries and lower limb surgeries was designed with Group B receiving 50 mcg of buprenorphine and Group C receiving 50 mcg of clonidine with 15 mg of hyperbaric bupivacaine 0.5%. Student's t-test and Chi-square were used for comparing the data. Results: The time of onset of duration of post-operative analgesia as well as sensory and motor block was significantly higher in buprenorphine group as compared to clonidine group. In present study, incidence of bradycardia as well as hypotension was significantly higher in group C as compared to group B (P<0.05). Conclusion: Addition of intrathecal buprenorphine and clonidine potentiates the duration of analgesia, sensory and motor block, with buprenorphine has a longer analgesic effect when compared to clonidine. [ABSTRACT FROM AUTHOR]

delirium, and prolonged recovery time. Recently, there has been a growing interest in combining subanesthetic doses of ketamine with subanesthetic doses of drugs such as propofol and dexmedetomidine to mitigate the unwanted effects of ketamine. Hence, we aimed to compare the effectiveness, in terms of postoperative Aldrete scores, intraoperative pain, sedation scores, hemodynamic changes, respiratory effects, surgeon satisfaction, and postoperative delirium, of continuous infusions of ketamine with adjuvant dexmedetomidine versus continuous infusions of ketamine with adjuvant propofol among patients undergoing elective upper limb surgery under brachial plexus block. Methods: We performed a double-blind, randomized, controlled trial among 60 participants randomly allocated into two groups. Group A patients (n = 30) received ketamine 0.5 mg/kg mixed with dexmedetomidine 0.5 µg/kg in 100 mL/h lipid emulsion as an infusion, whereas Group B patients received ketamine 0.5 mg/kg mixed with propofol 1 mg/kg in 100 mL/h normal saline as an infusion. Results: The mean Aldrete score at 0 min, 30 min, and 1 h was significantly higher among Group B patients (P = 0.001, P = 0.001, and P = 0.043, respectively). The mean diastolic blood pressure at 2 h was significantly higher in Group A compared to Group B (87.8 vs. 77.8, P = 0.001). Similarly, the mean arterial pressure at 45 min and 90 min was significantly higher in Group A compared to Group B (97.1 ± 6.7 vs. 92.2 ± 6.0, P = 0.004; 95.5 ± 5.5 vs. 90.8 ± 6.3, P = 0.005, respectively). The mean sedation score was not significantly different between groups. Conclusion: Propofol, when used as an adjuvant to ketamine, provides better hemodynamic stability and better Aldrete score in patients who receive brachial plexus block for elective upper limb surgeries compared to adjuvant dexmedetomidine. [ABSTRACT FROM AUTHOR]

Abstract Background Dexmedetomidine (DEX) has been thought to be an effective adjuvant to local anesthetics (LAs) in erector spinae plane block (ESPB), however, this method of use is not recorded in the drug instructions. Hence, our meta-analysis will evaluate its efficacy and safety for the first time. Methods A systematic search of published articles was conducted in the PubMed, Embase, Web of science, and Cochrane Library databases up to July 17, 2022, using specific keywords related to our aims. The time first to request rescue analgesia, number of patient controlled intravenous analgesia (PCIA) presses, rate of rescue analgesia use, postoperative nausea and vomiting (PONV), arrhythmia, and hypotension were calculated by using random-effect models. This systematic review and meta-analysis was registered with PROSPERO (registration number: CRD42022345488). Results Numerous electronic databases were searched and finally 8 studies with a total of 570 patients, 303 in the DEX arm, 267 in the control arm were included. As an adjuvant to LAs, DEX significantly increased the time to first request of rescue analgesia (mean difference [MD] = 8.40, 95% confidence interval [CI] = 4.70–12.10, P

The document contains several abstracts from the Indian Journal of Anaesthesia. The first abstract discusses a retrospective analysis of 22 neonates who received dexmedetomidine sedation with caudal anesthesia for lower abdominal surgery. The study found that this combination was effective and avoided the need for endotracheal intubation. The second abstract compares the sedation and mask acceptance in two different routes of administration of dexmedetomidine in children undergoing elective surgery. The study found that intranasal dexmedetomidine had better mask acceptance than the nebulized route. The third abstract compares low flow and standard flow induction of sevoflurane in pediatric patients. The study found that the time taken for induction and minimum alveolar concentration of sevoflurane were similar in both groups, but the consumption of sevoflurane was significantly reduced in the low-flow group. The fourth abstract examines the efficacy of dexamethasone as an adjuvant to local anesthesia in ultrasonography-guided transversus abdominis plane (TAP) block for analgesia in pediatric laparoscopic abdominal surgeries. The study found that TAP block with dexamethasone as an adjuvant provided better postoperative analgesia compared to TAP block with ropivacaine alone. [Extracted from the article]

Background: Patients who undergo gastrointestinal endoscopy often require propofol-based sedation combined with analgesics. At present, the efficacy and safety of esketamine as an adjunct to propofol for sedation during endoscopic procedures in patients remains controversial. Moreover, there is no universal agreement regarding the appropriate dose of esketamine supplementation. This study aimed to assess the efficacy and safety of esketamine as an adjunct to propofol for sedation during endoscopic procedures in patients. Methods: Seven electronic databases and three clinical trial registry platforms were searched and the deadline was February 2023. Randomized controlled trials (RCTs) evaluating the efficacy of esketamine for sedation were included by two reviewers. Data from the eligible studies were combined to calculate the pooled risk ratio or standardized mean difference. Results: Eighteen studies with 1962 esketamine participants were included in the analysis. As an adjunct to propofol, the administration of esketamine reduced the recovery time compared to normal saline (NS). However, there was no significant difference between the opioids group and ketamine group. For propofol dosage, the administration of esketamine required a lower propofol dosage compared to the NS group and opioids group].For complications, the esketamine group had fewer complications compared to the NS group and opioid group in patients, but there were no significant differences between the esketamine group and ketamine group. Notably, the coadministration of esketamine was associated with a higher risk of visual disturbance compared to the NS group. In addition, we used subgroup analysis to investigate whether 0.2–0.5 mg/kg esketamine was effective and tolerable for patients. Conclusion: Esketamine as an adjunct to propofol, is an appropriate effective alternative for sedation in participants undergoing gastrointestinal endoscopy. However, considering the possibility of its psychotomimetic effects, esketamine should be used with caution. [ABSTRACT FROM AUTHOR]

Background: Preservative-free chloroprocaine (CP) 1% is being investigated for short surgeries but lacks immediate postoperative analgesia. Adding opioids to local anesthetic increases the quality of spinal anesthesia with prolongation of postoperative analgesia. Aim: The aim of this study is to compare the postoperative analgesic efficacy of intrathecal nalbuphine versus intrathecal fentanyl as an adjuvant to chlorprocaine 1% for short surgical lower limb procedures. Materials and Methods: After ethical committee approval, a prospective randomized double-blind comparative study was conducted on 90 patients of the American Society of Anesthesiologists classes 1 and 2, aged between 18 and 60 years who were scheduled for elective short surgical lower limb procedures. Group CP (n = 30) received CP 1% 40 mg (4 ml) plus saline (0.5 ml), Group CP with fentanyl (CF) (n = 30) received CP 1% 40 mg (4 ml) plus fentanyl 25 mcg (0.5 ml), and Group CP with nalbuphine (CN) (n = 30) received CP 1% 40 mg (4 ml) plus nalbuphine 0.8 mg (0.5 ml) intrathecally. After performing subarachnoid block, the parameters observed were - Onset, height, duration of sensory and motor blockade, duration of postoperative analgesia, hemodynamics, and adverse effects between the three groups noted. Results: The onset of sensory and motor block (min) is faster in Group CF (4.2 ± 0.2, 3.4 ± 0.4) compared to Group CN (4.8 ± 0.4, 3.7 ± 0.4) and Group CP (6.2 ± 0.4, 4 ± 0.4) (P < 0.001). The total sensory duration and motor duration are prolonged in Group CN (96.5 ± 5.2, 90 ± 3.9) compared to Group CF (94 ± 4, 87 ± 4.5) and Group CP (77 ± 3, 74 ± 4.5) (P < 0.001). The duration of postoperative analgesia was prolonged in Group CN (130 ± 5.3) compared to Group CF (111 ± 6.2) and Group C (93 ± 4.2) (P < 0.001). Conclusion: We conclude that intrathecal nalbuphine prolongs postoperative analgesia maximally compared to intrathecal fentanyl as an adjuvant to CP 1% for short surgical lower limb procedures. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate the efficacy and safety of neoadjuvant programmed cell death-1 (PD-1) inhibitors plus apatinib and chemotherapy (PAC) in patients with locally advanced gastric cancer (LAGC). Materials and Methods: Seventy-three patients with resectable LAGC were enrolled and named the PAC group (n=39) or apatinib plus chemotherapy (AC) group (n=34) based on the treatment they chose. Neoadjuvant therapy was administered in a 21-day cycle for 3 consecutive cycles, after which surgery was performed. Results: The PAC group exhibited a higher objective response rate than the AC group (74.4% vs. 58.8%, P=0.159). Moreover, the PAC group showed a numerically better response profile than the AC group (P=0.081). Strikingly, progression-free survival (PFS) (P=0.019) and overall survival (OS) (P=0.049) were prolonged, whereas disease-free survival (DFS) tended to be longer in the PAC group than in the AC group (P=0.056). Briefly, the 3-year PFS, DFS, and OS rates were 76.1%, 76.1%, and 86.7% in the PAC group and 46.9%, 49.9%, and 70.3% in the AC group, respectively. Furthermore, PAC (vs. AC) treatment (hazard ratio=0.286, P=0.034) was independently associated with prolonged PFS in multivariate Cox regression analyses. The incidence of adverse events did not differ between the two groups (all P>0.05), where leukopenia, anemia, hypertension, and other adverse events were commonly observed in the PAC group. Conclusions: Neoadjuvant PAC therapy may achieve a preferable pathological response, delayed progression, and prolonged survival compared to AC therapy with a similar safety profile in patients with LAGC; however, further validation is warranted. [ABSTRACT FROM AUTHOR]

Background. Spinal anesthesia was a commonly used technique in anesthetic practice for lower abdominal and lower limb surgeries. To prolong the duration of bupivacaine spinal anesthesia adjuvants like a2 agonists and opioids have been used intrathecally. Clonidine and dexmedetomidine have also been found to prolong the duration of spinal anesthesia when given intravenous. Dexmedetomidine was more suitable adjuvant to spinal anesthesia compared to clonidine as it has more sedative and analgesic effects due to more selective a2A receptor agonist activity. Dexmedetomidine has been shown to prolong the duration of analgesia of spinal anaesthesia in various studies. Here we compare the two doses of Dexmedetomidine in prolonging the duration of analgesia. Material and methods. 60 American Society of Anaesthesiologists(ASA) physical status I/II patients scheduled for elective lower abdominal and lower limb surgeries under spinal anesthesia were randomized into two groups of 30 each. Immediately after subarachnoid block with 3.5ml of 0.5% hyperbaric bupivacaine, Group A patients received a loading dose of 0.5µg/kg of dexmedetomidine intravenously in 100ml NS over 10 mins whereas Group B received 1.0µg/kg of dexmedetomidine intravenously in 100ml NS over 10 mins. Results. Time for rescue analgesic were higher in Group B compared to Group A which was statistically significant but clinically the extra duration was insignificant. Time for two segment regression and duration of motor blockade was significantly prolonged in Group B. Requirement of Mephentermine was comparable in both the groups. There was no excessive sedation in both the groups. Conclusions. Dexmedetomidine administered as isolated loading dose of 0.5 µg/kg IV immediately after spinal anaesthesia was clinically equi-efficacious in prolonging the duration of analgesia of spinal anaesthesia compared to a larger dose of 1.0 µg/kg. The side effect profile, hemodynamic stability, sedation levels, need for vasopressors and atropine were comparable in both groups. [ABSTRACT FROM AUTHOR]

This study aimed to compare intrathecal nalbuphine and dexmeditomidine as an adjuvant in spinal anesthesia for lower limb and lower abdominal surgeries to improve the quality of spinal anesthesia (onset, duration, and side effects) and prolongation of duration of postoperative analgesia Hyperbaric bupivacaine, a local anesthetic, has a short half-life of 2 to 2 1/2 hours. Hence several adjuvants have been tested to enhance and prolong its analgesic effect. Initially, the preemptive combination of intrathecal opioids like fentanyl, nalbuphine, buprenorphine were extensively studied and found to have its own side effects and of late alpha -2 agonist like dexmeditiomidine with this local anesthetic for regional anesthesia, is being studied. Aim: In the present study we tried to compare intrathecal nalbuphine and dexmedetomidine as adjuvants in spinal anaesthesia for lower limb and lower abdominal surgeries. Methods: The present study was conducted in the department of anaesthesiology, KIMS, Narketpally during Oct 2021 to Sep 2022. This study was a prospective, randomised controlled, single blind, study conducted in 60 patients of ASA grade I and II undergoing elective surgeries under spinal anaesthesia. The patients were divided randomly with computer randamizer software into two groups, containing 30 patients in each group. Drugs selected are divided as Group BN: Patients received 3 ml of 0.5% hyperbaric bupivacaine (15mg) plus 1mg nalbuphine and Group BD: Patients received 3 ml of 0.5% hyperbaric bupivacaine (15mg) plus 5 µg Dexmedetomidine. Spinal block characteristics, blood pressure, pulse rate and side effects were studied during intra-operative and postoperative period. Results: It was observed from present study that in Dexmedetomidine group onset and complete motor blockade was early and duration of anaesthesia and analgesia was significantly prolonged compared to the Nalbuphine group. Hemodynamic parameters were preserved both intra-operatively and postoperatively in both groups. However there were a small percentage of patients who developed hypotension and bradycardia with dexmedetomidine which were easily managed without any untoward effect. Conclusions: Intrathecal low dose Dexmedetomidine in a dose of 5 µg along with 0.5% hyperbaric bupivacaine is associated with prolonged onset, duration, and side effects sensory and motor blockade compared to 1mg of nalbuphine for spinal anaesthesia in patients undergoing elective lower abdominal and lower limb surgeries. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy, safety, and satisfaction for the use of adjuvant; magnesium sulfate (MgSO4) in sub-Tenon anesthesia for cataract surgery. Methods: This single centered randomized, double blind trial was held in 2021 after approval of ethical committee at the Eye Hospital, Riyadh, Saudi Arabia. Cataract patients to be operated using local anesthesia were randomly assigned to two groups; Group magnesium sulfate (MS) received 50 mg/0.5 ml of magnesium sulfate and Group normal saline (NS) received 0.5 ml of normal saline added to the standard mixture, respectively. Absence of eyelid dropping and akinesia of the globe at different time after anesthesia were considered as ineffective anesthesia. The age and sex-adjusted generalized estimating equation (GEE) analysis was carried out. Complications, patient's and surgeon's satisfaction were also compared. Results: Each group had 100 cataract patients. Effectiveness of block was not significantly different in two groups (adjusted odds ratio, 0.90; 95% confidence interval [CI], 0.62, 1.31; P = 0.594). The likelihood of "no eye-opening" significantly increased with time (adjusted odds ratio, 1.26; 95% CI, 1.18-1.34; P < 0.001). Subconjunctival bleeding was significantly higher in the MS versus NS Group (36 of 98 [36.7%] vs. 11 of 102 [10.8%], P < 0.001). Chemosis was not significantly different between the groups (P = 0.95). Patient's satisfaction score was very good (9/10) but slightly higher in NS group than MS (P = 0.001) while surgeon's satisfaction score was similar in both groups (P = 0.149). Conclusions: Although safe, adding 50 mg of magnesium sulfate did not improve the effect of sub-Tenon anesthesia for cataract surgery. Risk of subconjunctival bleeding was higher in cataract patients operated using MgSO4 compared to those managed with the conventional sub-Tenon anesthetic. [ABSTRACT FROM AUTHOR]

Background: Dexmedetomidine (DEX) has been thought to be an effective adjuvant to local anesthetics (LAs) in erector spinae plane block (ESPB), however, this method of use is not recorded in the drug instructions. Hence, our meta-analysis will evaluate its efficacy and safety for the first time. Methods: A systematic search of published articles was conducted in the PubMed, Embase, Web of science, and Cochrane Library databases up to July 17, 2022, using specific keywords related to our aims. The time first to request rescue analgesia, number of patient controlled intravenous analgesia (PCIA) presses, rate of rescue analgesia use, postoperative nausea and vomiting (PONV), arrhythmia, and hypotension were calculated by using random-effect models. This systematic review and meta-analysis was registered with PROSPERO (registration number: CRD42022345488). Results: Numerous electronic databases were searched and finally 8 studies with a total of 570 patients, 303 in the DEX arm, 267 in the control arm were included. As an adjuvant to LAs, DEX significantly increased the time to first request of rescue analgesia (mean difference [MD] = 8.40, 95% confidence interval [CI] = 4.70–12.10, P < 0.00001), reduced the number of PCIA presses (MD = -4.12, 95% CI = -7.79 to -0.45, P = 0.03) and the rate of rescue analgesia (odds ratio [OR] = 0.33, 95% CI = 0.17–0.65, P = 0.002). Moreover, the combination reduced the risk of PONV (OR = 0.57, 95% CI = 0.36–0.91, P = 0.02). In addition, there was no difference in the incidence of hypotension (OR = 1.01, 95% CI = 0.37–2.74, P = 0.99) and arrhythmia (OR = 0.76, 95% CI = 0.19–3.07, P = 0.70). Conclusion: DEX can reduce analgesic requirements after various surgical procedures when used as an adjuvant to LAs for ESPB. Moreover, there was no significant difference between the two groups in terms of safety indicators (arrhythmia, hypotension). [ABSTRACT FROM AUTHOR]

aim,1 Bin Zhou,2 Robert B Schonberger,1 Jinlei Li11Department of Anesthesiology, Yale University School of Medicine, New Haven, CT, USA; 2Yale Center for Analytical Sciences, Department of Biostatistics, Yale University School of Public Health, New Haven, CT, USACorrespondence: Jinlei Li, Department of Anesthesiology, Yale University School of Medicine, 20 York Street, New Haven, CT, 06510, USA, Tel +1 917 601 6828, Fax +1 203 785 6664, Email [email protected] Purpose: Glucocorticoids are commonly used as regional anesthesia adjuvants to improve blockade quality and duration. There are limited data in the literature regarding the potential systemic effects and safety of perineural glucocorticoids. This study examines the effects of perineural glucocorticoids on serum glucose, potassium, and white blood cell count (WBC) in the immediate postoperative period after primary total hip arthroplasty (THA). Patients and Methods: A retrospective cohort study was carried out at a tertiary academic medical center utilizing electronic health records of 210 patients who underwent THA, for which patients received either a periarticular local anesthetic injection alone (PAI, N=132) or additional peripheral nerve blocks (PNB, N=78) containing 10 mg dexamethasone and 80 mg methylprednisolone acetate (PAI+PNB). The primary outcome was change in serum glucose from a preoperative baseline on postoperative days (POD) 1, 2, and 3. Secondary outcomes included changes in WBC and serum potassium. Results: The change in serum glucose from baseline was found to be significantly higher in the PAI+PNB group compared to the PAI group on POD 1 (mean difference 19.87 mg/dL, 95% CI [12.42, 27.32]; P< 0.001) and POD 2 (mean difference 17.5 mg/dL, 95% CI [9.66, 25.44], P< 0.001). No significant difference was found on POD 3 (mean difference − 8.18 mg/dL, 95% CI [− 19.07, 2.70], P=0.14). Statistically significant but clinically insignificant differences were detected in serum potassium in the PAI+PNB group compared to the PAI group on POD1 (mean difference 0.16 mEq/L, 95% CI [0.02, 0.30], P=0.03) and WBC on POD 2 (mean difference 3.18 × 1000/mm3, 95% CI [2.14, 4.22], P< 0.001). Conclusion: Patients who underwent THA and received PAI+PNB with glucocorticoid adjuvants demonstrated higher elevations in serum glucose for the first two PODs compared to patients who received PAI alone. These differences resolved by a third POD and are likely to be of no clinical significance. [ABSTRACT FROM AUTHOR]

Objective: Therapeutic hypothermia (TH) is the current standard of care for neonatal hypoxic-ischemic encephalopathy (HIE), yet morbidity and mortality remain significant. Adjuvant neuroprotective agents have been suggested to augment hypothermic-mediated neuroprotection. This analysis aims to identify the classes of drugs that have been used in combination with hypothermia in the treatment of neonatal HIE and determine whether combination therapy is more efficacious than TH alone. Methods: A systematic search of PubMed, Embase and Medline from conception through December 2022 was conducted. Randomized- and quasi-randomized controlled trials, observational studies and retrospective studies evaluating HIE infants treated with combination therapy versus TH alone were selected. Primary reviewers extracted information on mortality, neurodevelopmental impairment and length of hospitalization for meta-analyses. Effect sizes were pooled using a random-effects model and measured as odds ratio (OR) or mean difference (MD) where applicable, and 95% confidence intervals (CI) were calculated. Risk of bias was assessed using the tool from the Cochrane Handbook for Systematic Reviews of Interventions. Results: The search strategy collected 519 studies, 16 of which met analysis inclusion criteria. HIE infants totaled 1,288 infants from included studies, 646 infants received some form of combination therapy, while 642 received TH alone. GABA receptor agonists, NMDA receptor antagonists, neurogenic and angiogenic agents, stem cells, glucocorticoids and antioxidants were identified as candidate adjuvants to TH that have been evaluated in clinical settings compared to TH alone. Length of hospitalization was significantly reduced in infants treated with combination therapy (MD −4.81, 95% CI [−8.42. to −1.19], p = .009) compared to those treated with TH alone. Risk of mortality and neurodevelopmental impairment did not differ between combination therapy and TH alone groups. Conclusion: Compared to the current standard of care, administration of neuroprotective adjuvants with TH reduced the duration of hospitalization but did not impact the risk of mortality or neurodevelopmental impairment in HIE infants.Meta-analysis was limited by a moderate risk of bias among included studies and small sample sizes. This analysis highlights the need for preclinical trials to conduct drug development studies in hypothermic settings to identify relevant molecular targets that may offer additive or synergistic neuroprotection to TH, and the need for larger powered clinical trials to determine the dose and timing of administration at which maximal clinical benefits are observed for adjuvant neuroprotectants. [ABSTRACT FROM AUTHOR]