Local anesthetic dosing and toxicity of adult truncal catheters: a narrative review of published practice.

BACKGROUND/IMPORTANCE: Anesthesiologists frequently use truncal catheters for postoperative pain control but with limited characterization of dosing and toxicity. OBJECTIVE: We reviewed the published literature to characterize local anesthetic dosing and toxicity of paravertebral and transversus abdominis plane catheters in adults. EVIDENCE REVIEW: We searched the literature for bupivacaine or ropivacaine infusions in the paravertebral or transversus abdominis space in humans dosed for 24 hours. We evaluated bolus dosing, infusion dosing and cumulative 24-hour dosing in adults. We also identified cases of local anesthetic systemic toxicity and toxic blood levels. FINDINGS: Following screening, we extracted data from 121 and 108 papers for ropivacaine and bupivacaine respectively with a total of 6802 patients. For ropivacaine and bupivacaine, respectively, bolus dose was 1.4 mg/kg (95% CI 0.4 to 3.0, n=2978) and 1.0 mg/kg (95% CI 0.18 to 2.1, n=2724); infusion dose was 0.26 mg/kg/hour (95% CI 0.06 to 0.63, n=3579) and 0.2 mg/kg/hour (95% CI 0.06 to 0.5, n=3199); 24-hour dose was 7.75 mg/kg (95% CI 2.1 to 15.7, n=3579) and 6.0 mg/kg (95% CI 2.1 to 13.6, n=3223). Twenty-four hour doses exceeded the package insert recommended upper limit in 28% (range: 17%-40% based on maximum and minimum patient weights) of ropivacaine infusions and 51% (range: 45%-71%) of bupivacaine infusions. Toxicity occurred in 30 patients and was associated with high 24-hour dose, bilateral catheters, cardiac surgery, cytochrome P-450 inhibitors and hypoalbuminemia. CONCLUSION: Practitioners frequently administer ropivacaine and bupivacaine above the package insert limits, at doses associated with toxicity. Patient safety would benefit from more specific recommendations to limit excessive dose and risk of toxicity.

Local anesthetic dosing and toxicity of pediatric truncal catheters: a narrative review of published practice.

BACKGROUND/IMPORTANCE: Despite over 30 years of use by pediatric anesthesiologists, standardized dosing rates, dosing characteristics, and cases of toxicity of truncal nerve catheters are poorly described. OBJECTIVE: We reviewed the literature to characterize dosing and toxicity of paravertebral and transversus abdominis plane catheters in children (less than 18 years). EVIDENCE REVIEW: We searched for reports of ropivacaine or bupivacaine infusions in the paravertebral and transversus abdominis space intended for 24 hours or more of use in pediatric patients. We evaluated bolus dosing, infusion dosing, and cumulative 24-hour dosing in patients over and under 6 months. We also identified cases of local anesthetic systemic toxicity and toxic blood levels. FINDINGS: Following screening, we extracted data from 46 papers with 945 patients.Bolus dosing was 2.5 mg/kg (median, range 0.6-5.0; n=466) and 1.25 mg/kg (median, range 0.5-2.5; n=294) for ropivacaine and bupivacaine, respectively. Infusion dosing was 0.5 mg/kg/hour (median, range 0.2-0.68; n=521) and 0.33 mg/kg/hour (median, range 0.1-1.0; n=423) for ropivacaine and bupivacaine, respectively, consistent with a dose equivalence of 1.5:1.0. A single case of toxicity was reported, and pharmacokinetic studies reported at least five cases with serum levels above the toxic threshold. CONCLUSIONS: Bolus doses of bupivacaine and ropivacaine frequently comport with expert recommendations. Infusions in patients under 6 months used doses associated with toxicity and toxicity occurred at a rate consistent with single-shot blocks. Pediatric patients would benefit from specific recommendations about ropivacaine and bupivacaine dosing, including age-based dosing, breakthrough dosing, and intermittent bolus dosing.

Ropivacaine-loaded hydrogels for prolonged relief of chemotherapy-induced peripheral neuropathic pain and potentiated chemotherapy.

Chemotherapy can cause severe pain for patients, but there are currently no satisfactory methods of pain relief. Enhancing the efficacy of chemotherapy to reduce the side effects of high-dose chemotherapeutic drugs remains a major challenge. Moreover, the treatment of chemotherapy-induced peripheral neuropathic pain (CIPNP) is separate from chemotherapy in the clinical setting, causing inconvenience to cancer patients. In view of the many obstacles mentioned above, we developed a strategy to incorporate local anesthetic (LA) into a cisplatin-loaded PF127 hydrogel for painless potentiated chemotherapy. We found that multiple administrations of cisplatin-loaded PF127 hydrogels (PFC) evoked severe CIPNP, which correlated with increased pERK-positive neurons in the dorsal root ganglion (DRG). However, incorporating ropivacaine into the PFC relieved PFC-induced CIPNP for more than ten hours and decreased the number of pERK-positive neurons in the DRG. Moreover, incorporating ropivacaine into the PFC for chemotherapy is found to upregulate major histocompatibility complex class I (MHC-I) expression in tumor cells and promote the infiltration of cytotoxic T lymphocytes (CD8+ T cells) in tumors, thereby potentiating chemotherapy efficacy. This study proposes that LA can be used as an immunemodulator to enhance the effectiveness of chemotherapy, providing new ideas for painless cancer treatment.

Delayed Nonimmune Anaphylaxis Caused by Ropivacaine for Preoperative Nerve Blocks: A Case Report.

Ropivacaine is an amide local anesthetic with rare reports of anaphylaxis. To our knowledge, this is the first report of delayed nonimmune anaphylaxis induced by ropivacaine. A 70-year-old man underwent general anesthesia with a nerve block for a total knee arthroplasty. The patient developed symptoms of anaphylaxis 3.5 hours after receiving ropivacaine for femoral and tibial nerve blocks. A basophil activation test (BAT) revealed ropivacaine as the causative agent. Notably, anaphylaxis can be caused by medications even hours after their administration, and all administered drugs should be suspected of potentially causing anaphylaxis.

A randomized trial: The safety, pharmacokinetics and preliminary pharmacodynamics of ropivacaine oil delivery depot in healthy subjects.

INTRODUCTION: Ropivacaine oil delivery depot (RODD) can slowly release ropivacaine and block nerves for a long timejavascript:;. The aim of the present work was to investigate the safety, pharmacokinetics, and preliminary pharmacodynamics of RODD in subcutaneous injection among healthy subjects. METHODS: The abdomens of 3 subjects were subcutaneously administered with a single-needle RODD containing 12~30 mg of ropivacaine. The irritation, nerve blocking range and optimum dose were investigated. Forty-one subjects were divided into RODD groups containing 150, 230, 300, 350 and 400 mg of ropivacaine and a ropivacaine hydrochloride injection (RHI) 150 mg group. Multineedle subcutaneous injection of RODD or RHI was performed in the abdomens of the subjects. The primary endpoint was a safe dose or a maximum dose of ropivacaine (400 mg). Subjects' vital signs were observed; their blood was analyzed; their cardiovascular system and nervous systems were monitored, and their dermatological reactions were observed and scored. Second, the ropivacaine concentrations in plasma were determined, pharmacokinetic parameters were calculated, and the anesthetic effects of RODD were studied, including RODD onset time, duration and intensity of nerve block. RESULTS: Single-needle injection of RODD 24 mg was optimal for 3 subjects, and the range of nerve block was 42.5±20.8 mm. Multineedle subcutaneous injection of RODD in the abdomens of subjects was safe, and all adverse events were no more severe than grade II. The incidence rate of grade II adverse events, such as pain, and abnormal ST and ST-T segment changes on electrocardiography, was approximately 1%. The incidence rate of grade I adverse events, including erythema, papules, hypertriglyceridemia, and hypotension was greater than 10%. Erythema and papules were relieved after 24 h and disappeared after 72 h. Other adverse reactions disappeared after 7 days. The curve of ropivacaine concentration-time in plasma presented a bimodal profile. The results showed that ropivacaine was slowly released from the RODD. Compared with the 150 mg RHI group, Tmax was longer in the RODD groups. In particular, Tmax in the 400 mg RODD group was longer than that in the RHI group (11.8±4.6 h vs. 0.77±0.06 h). The Cmax in the 150 mg RODD group was lower than that in the 150 mg RHI group (0.35±0.09 vs. 0.58±0.13 µg·mL-1). In particular, the Cmax increased by 48% when the dose was increased by 2.6 times in the 400 mg group. Cmax, the AUC value and the intensity of the nerve block increased with increasing doses of RODD. Among them, the 400 mg RODD group presented the strongest nerve block (the percentage of level 2 and 3, 42.9%). The corresponding median onset time was 0.42 h, and the duration median was 35.7⁓47.7 h. CONCLUSIONS: RODD has a sustained release effect. Compared with the RHI group, Tmax was delayed in the RODD groups, and the duration of nerve block was long. No abnormal reaction was found in the RODD group containing 400 mg of ropivacaine after subcutaneous injection among healthy subjects, suggesting that RODD was adequately safe. TRIAL REGISTRATION: Chictr.org: CTR2200058122; Chinadrugtrials.org: CTR20192280.

Safety and efficacy of combined ropivacaine and sufentanil compared with ropivacaine for cesarean sections: A systematic review and meta-analysis.

Cesarean sections are the most common operations in the United States and one of the most common worldwide. Using the lowest possible dose of anesthetic that provides painless delivery with the lowest adverse events is a major concern. We investigated the efficacy and safety of combined ropivacaine and sufentanil by pooling data from relevant studies. We searched PubMed, Web of sciences, Scopus, and Cochrane Library until the end of December 2021 and included all records with data about combined ropivacaine and sufentanil. We used Review Manager to pool data as a mean difference for continuous outcomes or risk ratio for dichotomous outcomes with a 95% confidence interval. Methodological quality was appraised using version one of the Cochrane risks of bias tool. Seven Randomized clinical trials with a total sample size of 730 women were included; the mean age of enrolled parturients ranged from 28 to 35 years. We found that combined sufentanil and ropivacaine were significantly associated with decreased risk of being aware and nervous during CS (presented by Sedation level 1) (RR: 0.05, 95%CI [0.01,0.33], P=0.002), decreased risk of shivering (RR=0.29, 95%CI [0.19,0.44], P<0.00001), nausea (RR=0.62, 95%CI [0.41, 0.92], P=0.02), and vomiting (RR=0.27, 95% CI [0.12, 0.61], P=0.002). However, combined sufentanil and ropivacaine slightly were associated with late-onset of sensory blockade (MD=0.41, 95%CI [0.13, 0.68], P=0.004) and less motor blockade of leg flexion at hip joint presented by Bromage Scale 0 (RR=7.15 95%CI [2.71, 18.86], P<0.0001). Combined ropivacaine and sufentanil were associated with a reduction in visceral pain and lower risks of hypotension, shivering, nausea, and vomiting, compared to isolated ropivacaine, with no difference regarding the incidence of bradycardia. Although Combined ropivacaine and sufentanil were associated with a higher risk of pruritus, the incidence of pruritus was reportedly proportionate with the used dose of sufentanil. However, combined ropivacaine and sufentanil may slightly delay the onset of the sensory blockade to pinprick at T10 with less motor blockade but with a smaller probability for women to be aware and nervous during CS.

Dexmedetomidine protects against Ropivacaine-induced neuronal pyroptosis via the Nrf2/HO-1 pathway.

Dexmedetomidine (DEX) has been demonstrated to protect against ropivacaine (Ropi)-induced neuronal damages. This study was conducted to explore the protective role of DEX in Ropi-induced neuronal pyroptosis and provide a strategy to eliminate Ropi-induced neurotoxicity. The impacts of different concentrations of Ropi and DEX on neurotoxicity in SK-N-SH cells were evaluated by cell counting kit-8 assay and lactic dehydrogenase assay kits. Levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), NLR family pyrin domain containing 3 (NLRP3), cleaved Caspase-1, cleaved N-terminal gasdermin D, interleukin (IL)-1ß, and IL-18 were measured by real-time quantitative PCR, Western blotting, and enzyme linked immunosorbent assay. The Nrf2 level after nuclear/cytoplasmic separation was quantified. SK-N-SH cells were treated with si-Nrf2, Nigericin (NLRP3 activator), and Zinc Protoporphyrin (HO-1 inhibitor) to validate the mechanism. Ropi reduced SK-N-SH cell viability in a concentration- and time-dependent manner. DEX treatment alleviated Ropi-induced toxicity and inhibited pyroptosis. Ropi increased the expression levels of Nrf2 and HO-1, and DEX further enhanced the increases and promoted Nrf2 nuclear translocation. Nrf2/HO-1 inhibition or NLRP3 activation both neutralized the inhibitory role of DEX in Ropi-induced pyroptosis of SK-N-SH cells. Overall, DEX promoted the Nrf2/HO-1 pathway to inhibit NLRP3 expression, thus alleviating Ropi-induced neuronal pyroptosis.

Effectiveness and safety of intrathecal morphine for percutaneous endoscopic lumbar discectomy under low-dose ropivacaine: a prospective, randomized, double-blind clinical trial.

BACKGROUND CONTEXT: Percutaneous endoscopic lumbar discectomy (PELD) is a surgical setting that requires minimal motor impairment. Low-dose spinal ropivacaine induces little motor blockade and could be ideal for maintaining safety of PELD, but its analgesic efficacy is questionable. An adjunct analgesic approach is needed to maximize the benefits of low-dose spinal ropivacaine for PELD. PURPOSE: This study aimed to explore the effectiveness and safety of 100 µg intrathecal morphine (ITM) as an adjuvant analgesic method for PELD under low-dose spinal ropivacaine. STUDY DESIGN: A double-blind, randomized, placebo-controlled trial. TRIAL REGISTRATION: ChiCTR2000039842 (www.chictr.org.cn). SAMPLE: Ninety patients scheduled for elective single-level PELD under low-dose spinal ropivacaine. OUTCOME MEASURES: The primary outcome was the overall intraoperative visual analogue scale (VAS) score for pain. Secondary outcomes were intraoperative VAS scores assessed at multiple timepoints; intraoperative rescue analgesic requirement; postoperative VAS scores; disability scale; patients' satisfaction with anesthesia; adverse events; and radiographic outcomes. METHODS: Patients were randomized to receive low-dose ropivacaine spinal anesthesia with (ITM group, n=45) or without (control group, n=45) 100 µg ITM. RESULTS: The overall intraoperative VAS score in the ITM group was significantly lower than that in the control group (0 [0, 1] vs 2 [1, 3], p<.001). During operation, the VAS scores at cannula insertion, 30 minutes after insertion, 60 minutes after insertion, and 120 minutes after insertion were all significantly lower in the ITM group (all p<.05). Less patients in the ITM group required rescue analgesia during operation compared with those in the control group (14% vs 42%, p= .003). The VAS score for back pain in the ITM group was lower than that in the control group at 1 hour, 12 hours, and 24 hours postoperatively. Besides, the satisfaction score in the ITM group was significantly higher than that in the control group (p=.017). For adverse events, 8/43 of ITM and 1/44 of control participants experienced pruritus (p=.014), with a relative risk (95% confidence interval) of 8.37 (1.09-64.16). The incidence of other adverse events was similar between the two groups. Of note, respiratory depression occurred in one ITM-treated patient. CONCLUSION: The addition of 100 µg ITM to low-dose ropivacaine appears to be effective in analgesia without compromised motor function for PELD; however, ITM increased the risk of pruritus and clinicians should be vigilant about its potential risk of respiratory depression.

Effects of 0.15% ropivacaine alone and combination with sufentanil on epidural labor analgesia and adverse reactions.

Objective: The aim of this study was to compare the impacts of 0.15% ropivacaine alone and 0.15% ropivacaine combined with sufentanil on epidural labor analgesia. Methods: A total of 297 eligible primiparae were randomly divided into group A (n=149, 0.15% ropivacaine + sufentanil) and group B (n=148, 0.15% ropivacaine). Visual analogue scale (VAS) scores prior to analgesia and 20 min following epidural medication, the maximum VAS score during labor, dosage of analgesic drugs, modified Bromage score, satisfaction degree, labor duration, delivery mode, 1-min and 5-min Apgar scores of newborns, adverse reactions during analgesia, and fever during labor were recorded. Results: Group A and B had similar VAS scores 20 min following epidural medication and maximum score during labor (P>0.05), which significantly fell compared with those before labor analgesia (P<0.05). The occurrence rates of nausea and vomiting were of significant difference (P<0.05). Conclusion: 0.15% ropivacaine alone achieves a comparable epidural labor analgesia effect to that of 0.15% ropivacaine + 0.05 µg/mL sufentanil on primiparae.

Pre-incisional infiltration with ropivacaine plus dexamethasone palmitate emulsion for postoperative pain in patients undergoing craniotomy: study protocol for a prospective, randomized controlled trial.

BACKGROUND: Post-craniotomy pain is a common occurrence which is associated with poor outcomes. Pre-emptive scalp infiltration with dexamethasone and ropivacaine has been proven effective in previous studies but with limited clinical significance. Dexamethasone palmitate emulsion (D-PAL) is a pro-drug incorporating dexamethasone into lipid microspheres with greater anti-inflammatory activity and fewer side effects than free dexamethasone. However, its effects in post-craniotomy pain management remain unknown. This study hypothesizes that pre-emptive scalp infiltration with ropivacaine plus D-PAL emulsion can achieve superior analgesic effects to ropivacaine alone in adult patients undergoing craniotomy. METHODS/DESIGN: This is a single center, randomized controlled trial enrolling 130 patients scheduled for supratentorial craniotomy, which is expected to last longer than 4 h. We compare the efficacy and safety for postoperative pain relief of ropivacaine plus D-PAL group and ropivacaine alone group following pre-emptive scalp infiltration. Primary outcome will be pain Numerical Rating Scale at 24 h postoperatively. Secondary outcomes will include further analgesia evaluations and drug-related complications within a follow-up period of 3 months. DISCUSSION: This is the first randomized controlled trial aiming to assess the possible benefits or disadvantages of D-PAL emulsion for incisional pain in craniotomy. It may provide an alternative to optimize pain outcome for neurosurgical patients. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04488315). Registered on 19 July 2020.

Cardiac Arrest after Small Doses Ropivacaine: Local Anesthetic Systemic Toxicity in the Course of Continuous Femoral Nerve Blockade.

BACKGROUND: The paper presents a case report of an episode of local anesthetic systemic toxicity (LAST) with cardiac arrest after continuous femoral nerve blockade. CASE REPORT: A 74-year-old patient burdened with hypertension and osteoarthritis underwent elective total knee replacement surgery. After surgery, a continuous femoral nerve blockade was performed and an infusion of a local anesthetic (LA) was started using an elastomeric pump. Five hours after surgery, the patient had an episode of generalized seizures followed by cardiac arrest. After resuscitation, spontaneous circulation was restored. In the treatment, 20% lipid emulsion was used. On day two of the ICU stay, the patient was fully cardiovascularly and respiratorily stable without neurological deficits and was discharged to the orthopedic department to continue treatment. CONCLUSION: Systemic toxicity of LA is a serious and potentially fatal complication of the use of LA in clinical practice. It should be noted that in nearly 40% of patients, LAST deviates from the classic and typical course and may have an atypical manifestation, and the first symptoms may appear with a long delay, especially when continuous blockades are used. Therefore, the proper supervision of the patient and the developed procedure in the event of LAST is undoubtedly important here.

Analgesic Effects, Birth Process, and Prognosis of Pregnant Women in Normal Labor by Epidural Analgesia Using Sufentanil in Combination with Ropivacaine: A Retrospective Cohort Study.

Objective: The objective is to evaluate the analgesic, labor, and prognostic effects of patient-controlled epidural analgesia (PCEA) versus sufentanil in conjunction with ropivacaine in normal labor. Methods: Sixty pregnant women who had a normal delivery at our hospital between February 2019 and April 2021 were included. Pregnant women were arbitrarily assigned to a control group and a research group. Pregnant women in the control group received lidocaine analgesia and PCEA with sufentanil combined with ropivacaine in the research group. Satisfaction with care, fetal umbilical artery blood flow, VAS score, labor and bleeding, neonatal Apgar score and incidence of adverse events were analyzed. Results: First, we made a comparison of satisfactory performance of nursing care. The satisfaction rate of the research group was 100.00%, compared to 83.33% for the control group. Nursing satisfaction was higher in the research group, and the difference was statistically significant (P < 0.05). Following analgesia, PI, RI, and S/D values of umbilical artery blood flow were lower in the research group than those in the control group, but the difference was not statistically significant (P > 0.05). The VAS scores at 10 min, 20 min, and 30 min were found to be lower in the research group than in the control group after analgesia, and the difference was statistically significant (P < 0.05). Bleeding was significantly lower in the research group for all stages of labor, and the difference was statistically significant (P < 0.05). Apgar scores at 1 minute, 5 minutes, and 10 minutes postpartum were greater in the research group than in the control group, and the difference was statistically significant (P < 0.05). As a final note, the incidence of pruritus, hypotension, respiratory depression, nausea, and vomiting was found to be lower in the research group than in the control group, and the difference was statistically significant (P < 0.05). Conclusion: PCEA with sufentanil coupled with ropivacaine was used to perform labor analgesia. With significant reduction in maternal pain and assurance of labor, ropivacaine combined with sufentanil epidural labor analgesia did not reduce fetal umbilical artery blood flow without extended labor. It could not affect the labor process or the safety of the fetus, which is safe for the mother and fetus.

Continuous Transversus Abdominis Plane Infusion via Surgically Inserted Catheter for Postoperative Analgesia After Abdominal Aortic Surgery by Retroperitoneal Approach: TAPCACAO Study.

BACKGROUND: The purpose of our study was to evaluate the analgesic properties of continuous transversus abdominis plane (TAP) infusion with ropivacaine compared to placebo for postoperative analgesia in elective surgery of the abdominal aorta by retroperitoneal exposure. METHODS: We conducted a prospective, single-center, randomized, double-blind study comparing a group of patients with a TAP catheter undoing ropivacaine infusion with a placebo group. Patients received a left retroperitoneal pararectal exposure for abdominal aortic surgery. A continuous infusion catheter was placed under visual control by the surgeon before closure and removed after 48 hr. All patients had postoperative patient-controlled analgesia with morphine. The primary endpoint was morphine consumption during the first 24 hr. RESULTS: The analysis included 25 patients in the placebo group and 24 in the ropivacaine group. The average morphine consumption during the first 24 hr was significantly different, with 31 ± 16 mg in the ropivacaine group and 41 ± 17 mg in the placebo group (P = 0.019). At 48 hr, morphine consumption was still lower in the ropivacaine group (42 ± 26 mg) than in the placebo group (64 ± 25 mg) (P = 0.003). The opioid narcotic-related side effects of opioid infusion (postoperative nausea and vomiting, constipation) and length of hospital stay were similar in both populations. CONCLUSIONS: Our study showed that continuous TAP block with ropivacaine via surgically inserted catheter significantly decreased morphine consumption at 24 and 48 hr after elective abdominal aortic surgery by retroperitoneal exposure.

Subfascial infiltration of 0.5% ropivacaine, but not 0.25% ropivacaine, exacerbates damage and inflammation in surgically incised abdominal muscles of rats.

Ropivacaine-induced myotoxicity in surgically incised muscles has not been fully investigated. We evaluated the effects of infiltration anesthesia with ropivacaine on damage, inflammation and regeneration in the incised muscles of rats undergoing laparotomy. Ropivacaine or saline was infiltrated below the muscle fascia over the incised muscles. Pain-related behaviors and histological muscle damage were assessed. Macrophage infiltration at days 2 and 5 and proliferation of satellite cells at day 5 were detected by CD68 and MyoD immunostaining, respectively. Pain-related behaviors were inhibited by 0.25% and 0.5% of ropivacaine for 2 h after surgery. Single infiltration of 0.5% ropivacaine did not induce injury in intact muscles without incision, but single and repeated infiltration of 0.5% ropivacaine significantly augmented laparotomy-induced muscle injury and increased the numbers of CD68-positve macrophages and MyoD-positive cells compared to those in rats with infiltration of saline or 0.25% ropivacaine. In contrast, there were no significant differences in them between rats with saline infusion and rats with 0.25% ropivacaine infiltration. In conclusion, single or repeated subfascial infiltration of 0.25% ropivacaine can be used without exacerbating the damage and inflammation in surgically incised muscles, but the use of 0.5% ropivacaine may be a concern because of potentially increased muscle damage.

Opioid-Free Labor Analgesia: Dexmedetomidine as an Adjuvant Combined with Ropivacaine.

Background: Side effects of the use of opioid analgesics during painless delivery are the main factors that affect rapid postpartum recovery. Opioid use can result in dangerous respiratory depression in the patient. Opioids can also disrupt the baby's breathing and heart rate. The nonopioid analgesic dexmedetomidine, a new a2-adrenergic agonist, possesses higher selectivity, greater analgesic effects, and fewer side effects. Moreover, epidural administration of dexmedetomidine also reduces local anesthetic consumption. Objective: Our study aims to compare the analgesic effects as well as the side effects of ropivacaine with dexmedetomidine against sufentanyl as an epidural labor analgesia. Methods: This study is a randomized, double-blinded, controlled trial (registration no. ChiCTR2200055360) involving 120 primiparous (a woman who has given birth once), singleton pregnancy women who are greater than 38 weeks into gestation and have requested epidural labor analgesia. The participants were randomized to receive 0.1% ropivacaine with sufentanyl (0.4 µg/ml) or dexmedetomidine (0.4 µg/ml). The primary outcomes included Visual Analogue Score (VAS), duration of first epidural infusions, the requirement of additional PCEA bolus, and adverse reactions during labor analgesia. Results: Of the 120 subjects who consented, 91 parturient women (women in the condition of labor) had complete data for analysis. Demographics and VAS, as well as maternal and fetal outcomes, were similar between the groups. The duration of first epidural infusions in dexmedetomidine was significantly longer than sufentanyl (median value: 115 vs 68 min, P < 0.01); the parturient women who received dexmedetomidine and who required additional PCEA bolus were fewer in comparison to those who received sufentanyl (27.5% vs 49.0%, P < 0.05). Furthermore, the incidence of pruritus in the dexmedetomidine group was lower in comparison to the sufentanyl group (0% vs 11.8%, P < 0.05). Conclusions: Dexmedetomidine, a nonopioid, is superior to the opioid analgesic sufentanyl in providing a prolonged analgesic effect as an epidural during labor. It also reduces local anesthetic consumption and has fewer side effects. The trial is registered with ChiCTR2200055360.

Postoperative Analgesic Efficacy and Safety of Ropivacaine Plus Diprospan for Preemptive Scalp Infiltration in Patients Undergoing Craniotomy: A Prospective Randomized Controlled Trial.

BACKGROUND: Preemptive injection of local anesthetics can prevent postoperative pain at the incision site, but the analgesic effect is insufficient and is maintained only for a relatively short period of time. Diprospan is a combination of quick-acting betamethasone sodium phosphate and long-acting betamethasone dipropionate. Whether Diprospan as an adjuvant to local anesthetic can achieve postcraniotomy pain relief has not been studied yet. METHODS: This is a prospective, single-center, blinded, randomized, controlled clinical study, which included patients ages 18 and 64 years, with American Society of Anaesthesiologists (ASA) physical statuses of I to III, scheduled for elective supratentorial craniotomy. We screened patients for enrollment from September 3, 2019, to August 15, 2020. The final follow-up was completed on February 15, 2021. Eligible patients were randomly assigned to either the Diprospan group, who received incision-site infiltration of 0.5% ropivacaine plus Diprospan (n = 48), or the control group, who received 0.5% ropivacaine alone (n = 48), with a distribution ratio of 1:1. Primary outcome was the cumulative sufentanil (µg) consumption through patient-controlled analgesia (PCA) within 48 hours after surgery. Primary analysis was performed based on the intention-to-treat (ITT) principle. RESULTS: Baseline characteristics were not significantly different between the 2 groups ( P > .05). In the Diprospan group, the cumulative sufentanil consumption through PCA was 5 (0-16) µg within 48 hours postoperatively, which was significantly lower than that in the control group (38 [30.5-46] µg; P < .001). CONCLUSIONS: Infiltration of ropivacaine and Diprospan can achieve satisfactory postoperative pain relief after craniotomy; it is a simple, easy, and safe technique, worth clinical promotion.

Hyaluronic Acid as a Carrier Supports the Effects of Glucocorticoids and Diminishes the Cytotoxic Effects of Local Anesthetics in Human Articular Chondrocytes In Vitro.

The current study aimed to investigate the cytotoxicity of co-administrating local anesthetics (LA) with glucocorticoids (GC) and hyaluronic acid (HA) in vitro. Human articular cartilage was obtained from five patients undergoing total knee arthroplasty. Chondrocytes were isolated, expanded, and seeded in 24-well plates for experimental testing. LA (lidocaine, bupivacaine, ropivacaine) were administered separately and co-administered with the following substances: GC, HA, and GC/HA. Viability was confirmed by microscopic images, flow cytometry, metabolic activity, and live/dead assay. The addition of HA and GC/HA resulted in enhanced attachment and branched appearance of the chondrocytes compared to LA and LA/GC. Metabolic activity was better in all LA co-administered with HA and GC/HA than with GC and only LA. Flow cytometry revealed the lowest cell viability in lidocaine and the highest cell viability in ropivacaine. This finding was also confirmed by live/dead assay. In conclusion, HA supports the effect of GC and reduces chondrotoxic effects of LA in vitro. Thereby, the co-administration of HA to LA and GC offers an alternative less chondrotoxic approach for treating patients with symptomatic osteoarthritis of the knee.

Immediate Effects of a Continuous Peripheral Nerve Block on Postamputation Phantom and Residual Limb Pain: Secondary Outcomes From a Multicenter Randomized Controlled Clinical Trial.

BACKGROUND: We recently reported that a 6-day continuous peripheral nerve block reduced established postamputation phantom pain 3 weeks after treatment ended. However, the immediate effects of perineural infusion (secondary outcomes) have yet to be reported. METHODS: Participants from 5 enrolling academic centers with an upper or lower limb amputation and established phantom pain received a single-injection ropivacaine peripheral nerve block(s) and perineural catheter insertion(s). They were subsequently randomized to receive a 6-day ambulatory perineural infusion of either ropivacaine 0.5% or normal saline in a double-masked fashion. Participants were contacted by telephone 1, 7, 14, 21, and 28 days after the infusion started, with pain measured using the Numeric Rating Scale. Treatment effects were assessed using the Wilcoxon rank-sum test at each time point. Adjusting for 4 time points (days 1, 7, 14, and 21), P < .0125 was deemed statistically significant. Significance at 28 days was reported using methods from the original, previously published article. RESULTS: Pretreatment average phantom and residual pain scores were balanced between the groups. The day after infusion initiation (day 1), average phantom, and residual limb pain intensity was lower in patients receiving local anesthetic (n = 71) versus placebo (n = 73): median [quartiles] of 0 [0-2.5] vs 3.3 [0-5.0], median difference (98.75% confidence interval [CI]) of -1.0 (-3.0 to 0) for phantom pain (P = .001) and 0 [0-0] vs 0 [0-4.3], and median difference 0.0 (-2.0 to 0.0) for residual limb pain (P < .001). Pain's interference with physical and emotional functioning as measured with the interference domain of the Brief Pain Inventory improved during the infusion on day 1 for patients receiving local anesthetic versus placebo: 0 [0-10] vs 10 [0-40], median difference (98.75% CI) of 0.0 (-16.0 to 0.0), P = .002. Following infusion discontinuation (day 6), a few differences were found between the active and placebo treatment groups between days 7 and 21. In general, sample medians for average phantom and residual limb pain scores gradually increased after catheter removal for both treatments, but to a greater degree in the control group until day 28, at which time the differences between the groups returned to statistical significance. CONCLUSIONS: This secondary analysis suggests that a continuous peripheral nerve block decreases phantom and residual limb pain during the infusion, although few improvements were again detected until day 28, 3 weeks following catheter removal.

P53 inhibitor pifithrin-α inhibits ropivacaine-induced neuronal apoptosis via the mitochondrial apoptosis pathway.

The neurotoxicity of local anesthetics (LAs) has attracted more and more attention, However, they lack preventive and therapeutic measures. Many studies have shown that apoptosis plays an important role in the process of LA-induced neurotoxicity. As an important signaling molecule to activate apoptosis, p53 has been proved to be involved in the neurotoxicity induced by LAs, but the mechanism is unclear. In this study, we explored the effect of pifithrin-α (PFT-α), a p53 inhibitor, on apoptosis by ropivacaine (Rop) in vivo and in vitro. Cell viability and apoptosis detected by CCK-8 and a JC-1 apoptosis detection kit, the changes of spinal cord structure observed after hematoxylin and eosin staining, apoptosis of the spinal cord measured by terminal deoxynucleotidyl transferase dUTP nick end labeling staining, behavioral assessment of the nerve Injury evaluated by the detection of sciatic nerve conduction velocity (SNCV) andmechanical withdrawal threshold (MWT), the expression of p53 and many apoptosis-related genes included Bax, Bcl-2, and caspase-3 detected by quantitative real-time polymerase chain reaction, Western blot analysis, immunofluorescence, and immunohistochemistry. Results showed that PC12 cell viability decreased because of Rop, but the pretreatment of PFT-α could protect it. And PFT-α reduced the injuries in the spinal cord by Rop included vacuoles or edema. The results of immunofluorescence and immunohistochemistry testing showed that PFT-α inhibited the p53 protein upregulated by Rop. Apoptosis rate and many proapoptotic genes include p53, Bax, caspase-3 messenger RNA, and proteins were increased by Rop, but PFT-α could decrease it. In conclusion, PFT-α inhibited cell apoptosis and spinal cord injuries induced by Rop.