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BMC Anesthesiology Sep 2022Ropivacaine is commonly applied for local anesthesia and may cause neurotoxicity. Dexmedetomidine (DEX) exhibits neuroprotective effects on multiple neurological...
BACKGROUND
Ropivacaine is commonly applied for local anesthesia and may cause neurotoxicity. Dexmedetomidine (DEX) exhibits neuroprotective effects on multiple neurological disorders. This study investigated the mechanism of DEX pretreatment in ropivacaine-induced neurotoxicity.
METHODS
Mouse hippocampal neuronal cells (HT22) and human neuroblastoma cells (SH-SY5Y) were treated with 0.5 mM, 1 mM, 2.5 mM, and 5 mM ropivacaine. Then the cells were pretreated with different concentrations of DEX (0.01 μM, 0.1 μM, 1 μM, 10 μM, and 100 μM) before ropivacaine treatment. Proliferative activity of cells, lactate dehydrogenase (LDH) release, and apoptosis rate were measured using CCK-8 assay, LDH detection kit, and flow cytometry, respectively. miR-10b-5p and BDNF expressions were determined using RT-qPCR or Western blot. The binding of miR-10b-5p and BDNF was validated using dual-luciferase assay. Functional rescue experiments were conducted to verify the role of miR-10b-5p and BDNF in the protective mechanism of DEX on ropivacaine-induced neurotoxicity.
RESULTS
Treatment of HT22 or SH-SY5Y cells with ropivacaine led to the increased miR-10b-5p expression (about 1.7 times), decreased BDNF expression (about 2.2 times), reduced cell viability (about 2.5 times), elevated intracellular LDH level (about 2.0-2.5 times), and enhanced apoptosis rate (about 3.0-4.0 times). DEX pretreatment relieved ropivacaine-induced neurotoxicity, as evidenced by enhanced cell viability (about 1.7-2.0 times), reduced LDH release (about 1.7-1.8 times), and suppressed apoptosis rate (about 1.8-1.9 times). DEX pretreatment repressed miR-10b-5p expression (about 2.5 times). miR-10b-5p targeted BDNF. miR-10b-5p overexpression or BDNF silencing reversed the protective effect of DEX pretreatment on ropivacaine-induced neurotoxicity, manifested as reduced cell viability (about 1.3-1.6 times), increased intracellular LDH level (about 1.4-1.7 times), and elevated apoptosis rate (about 1.4-1.6 times).
CONCLUSIONS
DEX pretreatment elevated BDNF expression by reducing miR-10b-5p expression, thereby alleviating ropivacaine-induced neurotoxicity.
Topics: Animals; Apoptosis; Brain-Derived Neurotrophic Factor; Dexmedetomidine; Humans; Lactate Dehydrogenases; Mice; MicroRNAs; Neuroblastoma; Neuroprotective Agents; Ropivacaine
PubMed: 36163004
DOI: 10.1186/s12871-022-01810-6 -
Journal of Orthopaedic Surgery and... Sep 2023Local anesthetics (LAs) are widely used to infiltrate into surgical wounds for postoperative analgesia. Different adjuvants like dexamethasone and dexmedetomidine, when... (Randomized Controlled Trial)
Randomized Controlled Trial
Dexamethasone and dexmedetomidine as adjuvants to ropivacaine do not prolong analgesia in wound infiltration for lumbar spinal fusion: a prospective randomized controlled study.
BACKGROUND AND OBJECTIVES
Local anesthetics (LAs) are widely used to infiltrate into surgical wounds for postoperative analgesia. Different adjuvants like dexamethasone and dexmedetomidine, when added to LA agents, could improve and prolong analgesia. The aim of this trial was to evaluate the analgesic efficacy and opioid-sparing properties of dexamethasone and dexmedetomidine when added to ropivacaine for wound infiltration in transforaminal lumbar interbody fusion (TLIF).
METHODS
We conducted a controlled study among 68 adult patients undergoing TLIF, which was prospective, randomized and double-blind in nature. The participants were divided into four equal groups at random. Group R was given 150 mg of 1% ropivacaine (15 mL) and 15 mL of normal saline. Group R + DXM received 150 mg of 1% ropivacaine (15 mL) and 10 mg of dexamethasone (15 mL). Group R + DEX received 150 mg of 1% ropivacaine (15 mL) and 1 µg/kg of dexmedetomidine (15 mL). Lastly, group R + DXM + DEX was given 150 mg of 1% ropivacaine (15 mL), 10 mg of dexamethasone and 1 µg/kg of dexmedetomidine (15 mL). The primary focus was on the length of pain relief provided. Additionally, secondary evaluations included the amount of hydromorphone taken after surgery, the numerical rating scale and safety assessments within 48 h after the operation.
RESULTS
Based on the p value (P > 0.05), there was no significant variance in the duration of pain relief or the total usage of hydromorphone after surgery across the four groups. Similarly, the numerical rating scale scores at rest and during activity at 6-, 12-, 24- and 48-h post-surgery for all four groups showed no difference (P > 0.05). However, the incidence of delayed anesthesia recovery was slightly higher in group R + DEX and group R + DXM + DEX when compared to group R or group R + DXM. Furthermore, there were no significant differences between the four groups in terms of vomiting, nausea, dizziness or delayed anesthesia recovery.
CONCLUSION
For wound infiltration in TLIF, the addition of dexamethasone and dexmedetomidine to ropivacaine did not result in any clinically significant reduction in pain or opioid consumption and could prompt some side effects.
Topics: Adult; Humans; Analgesia; Analgesics, Opioid; Dexamethasone; Dexmedetomidine; Hydromorphone; Lumbar Vertebrae; Pain; Prospective Studies; Ropivacaine; Spinal Fusion; Adjuvants, Anesthesia; Pain, Postoperative; Anesthesia, Local
PubMed: 37667295
DOI: 10.1186/s13018-023-04145-1 -
PloS One 2023Ropivacaine is a long-acting local anesthetic that is used to treat postoperative pain. Adjuvant use of dexmedetomidine in regional anesthesia may prolong the duration... (Meta-Analysis)
Meta-Analysis
Effects of dexmedetomidine as an adjuvant to ropivacaine or ropivacaine alone on duration of postoperative analgesia: A systematic review and meta-analysis of randomized controlled trials.
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.
Topics: Humans; Ropivacaine; Dexmedetomidine; Sufentanil; Postoperative Nausea and Vomiting; Randomized Controlled Trials as Topic; Anesthetics, Local; Pain, Postoperative; Analgesia
PubMed: 37819905
DOI: 10.1371/journal.pone.0287296 -
Anaesthesia May 2001This study was undertaken: (i) to quantify the effects of labour and epidural analgesia on plasma alpha1-acid glycoprotein concentration, (ii) to examine the effects of...
This study was undertaken: (i) to quantify the effects of labour and epidural analgesia on plasma alpha1-acid glycoprotein concentration, (ii) to examine the effects of changes in plasma alpha1-acid glycoprotein concentration on plasma protein binding and placental transfer of ropivacaine, and (iii) to examine the association between umbilical venous ropivacaine concentration and neurobehavioural function in the neonate. Multiparous patients undergoing induction of labour received a continuous epidural infusion of 0.1% ropivacaine following an epidural bolus. A significant association was demonstrated between maternal plasma alpha1-acid glycoprotein concentration and 1/free fraction of ropivacaine 60 min after starting ropivacaine administration (r(2) = 0.77) but not at delivery. No significant correlation was demonstrable between maternal unbound ropivacaine concentration and either neonatal (cord) ropivacaine concentration or UV/MV (a measure of placental transfer). Thirty minutes after delivery, 9/10 neonates had neurological and adaptive capacity scores < 35, whereas only three infants had scores < 35 at 2 h. All scores exceeded 35 16 h after delivery. No association between mean (SD) umbilical venous ropivacaine concentration [0.09 (0.08) mg x l(-1)] and neurological and adaptive capacity scores was demonstrated.
Topics: Adult; Amides; Analgesia, Epidural; Analgesia, Obstetrical; Anesthetics, Local; Apgar Score; Female; Fetal Blood; Glycoproteins; Humans; Infant, Newborn; Linear Models; Maternal-Fetal Exchange; Neurologic Examination; Pregnancy; Prospective Studies; Protein Binding; Ropivacaine
PubMed: 11350325
DOI: 10.1046/j.1365-2044.2001.01908.x -
Regional Anesthesia and Pain Medicine Mar 2024Anesthesiologists frequently use truncal catheters for postoperative pain control but with limited characterization of dosing and toxicity. (Review)
Review
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.
Topics: Adult; Humans; Anesthetics, Local; Ropivacaine; Amides; Pain, Postoperative; Nerve Block; Bupivacaine; Catheters
PubMed: 37451826
DOI: 10.1136/rapm-2023-104667 -
Medicine Jun 2022To provide a basis for treating postherpetic neuralgia (PHN), we compared the efficacy of lidocaine and ropivacaine stellate ganglion block (SGB) in PHN treatment in the...
To provide a basis for treating postherpetic neuralgia (PHN), we compared the efficacy of lidocaine and ropivacaine stellate ganglion block (SGB) in PHN treatment in the upper limbs.Data from 252 patients with upper-limb PHN were retrospectively analyzed. The lidocaine group (n = 118) was treated with oral pregabalin capsules 75 mg twice a day, tramadol hydrochloride sustained release tablets 100 mg twice a day, and amitriptyline 25 mg once at night combined with ultrasound-guided lidocaine SGB; the ropivacaine group (n = 134) was orally administered the same medicines combined with ultrasound-guided ropivacaine SGB. The visual analog scale (VAS), self-rating anxiety scale (SAS), and adverse reactions were compared between the groups before treatment and at 1 week, 1 month, and 3 months after treatment.There were no significant differences between the lidocaine and ropivacaine groups in terms of sex, age, height, weight, and pain duration (P > .05). There was no significant difference between the groups in VAS and SAS scores before treatment (P > .05). At 1 week, 1 month, and 3 months after ultrasound-guided SGB treatment, the VAS and SAS scores were significantly lower in the ropivacaine group than in the lidocaine group (P < .05). There were no significant differences between the groups in terms of adverse reactions (P > .05).For ultrasound-guided SGB treatment of upper limb PHN, ropivacaine is superior to lidocaine. Ultrasound-guided ropivacaine SGB is safe and effective for the treatment of upper limb PHN.
Topics: Anesthetics, Local; Humans; Lidocaine; Neuralgia, Postherpetic; Retrospective Studies; Ropivacaine; Stellate Ganglion; Upper Extremity
PubMed: 35687777
DOI: 10.1097/MD.0000000000029394 -
BMC Anesthesiology Apr 2022Ropivacaine oil delivery depot (RODD) can be used to treat postoperative incision pain. The aim was to study pharmacodynamics, toxicity and toxicokinetics of RODD.
BACKGROUND
Ropivacaine oil delivery depot (RODD) can be used to treat postoperative incision pain. The aim was to study pharmacodynamics, toxicity and toxicokinetics of RODD.
METHODS
The base research of RODD were conducted. Thirty rabbits were randomly divided into saline, solvent, ropivacaine aqueous injection (RAI) 0.9 mg, RODD 0.9 mg and RODD 3 mg groups. The sciatic nerve of rabbits were isolated, dripped with RODD and the effect of nerve block were observed. In toxicity study, the rats were divided into saline, solvent and RODD 75, 150 and 300 mg/kg groups, 30 rats per group. In toxicokinetics, rats were divided into RODD 75, 150 and 300 mg/kg groups, 18 rats per group. The rats were subcutaneously injected drugs.
RESULTS
The analgesic duration of RODD 3 mg and RAI 0.9 mg blocking ischiadic nerve lasted about 20 h and 2 h, respectively, and their blocking intensity was similar. The rats in RODD 75 mg/kg did not show any toxicity. Compared with saline group, in RODD 150 mg/kg group neutrophils and mononuclear cells increased, lymphocytes decreased and albumin decreased(P < 0.05), and pathological examination showed some abnormals. In RODD 300 mg/kg group, 10 rats died and showed some abnormalities in central nerve system, hematologic indexes, part of biochemical indexes, and the weights of spleen, liver, and thymus. However, these abnormal was largely recovered on 14 days after the dosing. The results of toxicokinetics of RODD 75 mg/kg group showed that the C was 1.24 ± 0.59 µg/mL and the AUC was 11.65 ± 1.58 h·µg/mL.
CONCLUSIONS
Subcutaneous injection RODD releases ropivacaine slowly, and shows a stable and longer analgesic effect with a large safety range.
Topics: Animals; Rabbits; Rats; Anesthetics, Local; Pain, Postoperative; Ropivacaine; Sciatic Nerve; Solvents; Toxicokinetics
PubMed: 35448955
DOI: 10.1186/s12871-022-01653-1 -
African Health Sciences Sep 2023The 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. (Randomized Controlled Trial)
Randomized Controlled Trial
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.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Analgesia, Obstetrical; Analgesics; Anesthetics, Local; Double-Blind Method; Ropivacaine; Sufentanil
PubMed: 38357150
DOI: 10.4314/ahs.v23i3.66 -
Anesthesiology Dec 2022Long-lasting local anesthetic use for perioperative pain control is limited by possible cardiotoxicity (e.g., arrhythmias and contractile depression), potentially...
BACKGROUND
Long-lasting local anesthetic use for perioperative pain control is limited by possible cardiotoxicity (e.g., arrhythmias and contractile depression), potentially leading to cardiac arrest. Off-target cardiac sodium channel blockade is considered the canonical mechanism behind cardiotoxicity; however, it does not fully explain the observed toxicity variability between anesthetics. The authors hypothesize that more cardiotoxic anesthetics (e.g., bupivacaine) differentially perturb other important cardiomyocyte functions (e.g., calcium dynamics), which may be exploited to mitigate drug toxicity.
METHODS
The authors investigated the effects of clinically relevant concentrations of racemic bupivacaine, levobupivacaine, or ropivacaine on human stem cell-derived cardiomyocyte tissue function. Contractility, rhythm, electromechanical coupling, field potential profile, and intracellular calcium dynamics were quantified using multielectrode arrays and optical imaging. Calcium flux differences between bupivacaine and ropivacaine were probed with pharmacologic calcium supplementation or blockade. In vitro findings were correlated in vivo using an anesthetic cardiotoxicity rat model (females; n = 5 per group).
RESULTS
Bupivacaine more severely dysregulated calcium dynamics than ropivacaine in vitro (e.g., contraction calcium amplitude to 52 ± 11% and calcium-mediated repolarization duration to 122 ± 7% of ropivacaine effects, model estimate ± standard error). Calcium supplementation improved tissue contractility and restored normal beating rhythm (to 101 ± 6%, and 101 ± 26% of control, respectively) for bupivacaine-treated tissues, but not ropivacaine (e.g., contractility at 80 ± 6% of control). Similarly, calcium pretreatment mitigated anesthetic-induced arrhythmias and cardiac depression in rats, improving animal survival for bupivacaine by 8.3 ± 2.4 min, but exacerbating ropivacaine adverse effects (reduced survival by 13.8 ± 3.4 min and time to first arrhythmia by 12.0 ± 2.9 min). Calcium channel blocker nifedipine coadministration with bupivacaine, but not ropivacaine, exacerbated cardiotoxicity, supporting the role of calcium flux in differentiating toxicity.
CONCLUSIONS
Our data illustrate differences in calcium dynamics between anesthetics and how calcium may mitigate bupivacaine cardiotoxicity. Moreover, our findings suggest that bupivacaine cardiotoxicity risk may be higher than for ropivacaine in a calcium deficiency context.
Topics: Female; Rats; Humans; Animals; Anesthetics, Local; Calcium; Cardiotoxicity; Myocytes, Cardiac; Amides; Bupivacaine; Ropivacaine; Arrhythmias, Cardiac
PubMed: 36170651
DOI: 10.1097/ALN.0000000000004389 -
PloS One 2020The aim of the present study was to determine and compare the degree and duration of corneal anesthesia following topical application of 0.4% oxybuprocaine hydrochloride...
The aim of the present study was to determine and compare the degree and duration of corneal anesthesia following topical application of 0.4% oxybuprocaine hydrochloride ophthalmic solution and 1% ropivacaine hydrochloride treatment in healthy rats. A randomized, blinded, crossover study was conducted on 20 healthy adult Wistar rats, following complete physical and ophthalmological examination. Baseline corneal touch threshold (CTT) was determined in the central corneal area of both eyes with a Cochet-Bonnet aesthesiometer, in mm filament length. Oxybuprocaine was randomly applied to one eye and 0.9% sterile sodium chloride solution was instilled into the contralateral eye. Subsequent CTT measurements were performed in both eyes 5 minutes after topical application and at 5-minute intervals thereafter for 75-minutes in the anesthetized eye. Following a 2-week washout period, this protocol was repeated with ropivacaine. Quantitative data were summarized as mean ± standard deviation, median and inter-quartile range (Q1-Q3). Repeated measures data were analyzed over time and between treatments using Friedman test and Wilcoxon signed-rank test with Bonferroni adjustment (p < 0.05). Baseline CTT values were 60 mm in all eyes. With oxybuprocaine, CTT values decreased significantly for 65 minutes (0-55 mm; p = 0.002) when compared with baseline; the maximal anesthetic effect (no blink response at 5 mm filament length) was maintained for up to 15 minutes (p < 0.0001). With ropivacaine, CTT values were significantly lower than baseline for 30 minutes (0-55 mm; p = 0.002), with a maximal anesthetic effect recorded at 5 minutes in 18 eyes (p < 0.0001). Oxybuprocaine induced a significantly lower CTT than ropivacaine (p = 0.002) from 10 to 65 minutes following topical application. Both anesthetic agents induced significant corneal anesthesia; however, oxybuprocaine provided a greater and longer anesthetic effect, making it more suitable for potentially painful ophthalmologic procedures.
Topics: Administration, Topical; Animals; Cornea; Female; Male; Ophthalmic Solutions; Procaine; Rats, Wistar; Ropivacaine; Sensory Thresholds
PubMed: 33151993
DOI: 10.1371/journal.pone.0241567