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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 -
International Journal of Molecular... Feb 2022Breast cancer (BC) is one of the most common types of cancer and the second leading cause of death in women. Local anaesthetics (LAs) and opioids have been shown to... (Review)
Review
Breast cancer (BC) is one of the most common types of cancer and the second leading cause of death in women. Local anaesthetics (LAs) and opioids have been shown to influence cancer progression and metastasis formation in several pre-clinical studies. However, their effects do not seem to promote consensus. A systematic review was conducted using the databases Medline (via PubMed), Scopus, and Web of Science (2010 to December 2021). Search terms included "lidocaine", "ropivacaine", "levobupivacaine", "morphine", "methadone", "breast cancer", "breast carcinoma" and "breast neoplasms" in diverse combinations. The search yielded a total of 784 abstracts for initial review, 23 of which met the inclusion criteria. Here we summarise recent studies on the effect of analgesics and LAs on BC cell lines and animal models and in combination with other treatment regimens. The results suggest that local anaesthetics have anti-tumorigenic properties, hence their clinical application holds therapeutic potential. Regarding morphine, the findings are conflicting, but this opioid appears to be a tumour-promoting agent. Methadone-related results are scarce. Additional research is clearly required to further study the mechanisms underlying the controversial effects of each analgesic or LA to establish the implications upon the outcome and prognosis of BC patients' treatment.
Topics: Anesthetics, Local; Animals; Breast Neoplasms; Cell Line, Tumor; Female; Humans; Levobupivacaine; Lidocaine; Morphine; Ropivacaine; Xenograft Model Antitumor Assays
PubMed: 35163815
DOI: 10.3390/ijms23031894 -
BMC Pediatrics Jun 2023To characterize clinical profile of pediatric local anesthetic (LA) systemic toxicity (LAST) and to identify determinants of life-threatening outcomes.
PURPOSE
To characterize clinical profile of pediatric local anesthetic (LA) systemic toxicity (LAST) and to identify determinants of life-threatening outcomes.
METHODS
Spontaneous reports notified to the French Pharmacovigilance Network were retrieved and followed by a case-by-case review, according to the following criteria: LA as suspected drug, age < 18 years, adverse drug reactions related to nervous system, cardiac, respiratory, psychiatric or general disorders. Multivariate logistic regression analysis was performed to identify factors leading to life-threatening reaction (i.e. continuous seizures or cardiorespiratory arrest).
RESULTS
Among 512 cases retrieved, 64 LAST cases were included (neonates 11%, infants 30%, children 36%, adolescents 23%) mainly involving lidocaine (47%), lidocaine + prilocaine (22%) and ropivacaine (14%). Toxicity profiles were neurological (58%), cardiac (11%) or mixed (20%) and 7 patients (11%) developed methemoglobinemia. LAST was life-threatening for 23 patients (36%) and 2 patients died. Doses were above recommendations in 26 patients (41%) and were not different between life-threatening and non-life-threatening cases. The context of use (general and orthopedic surgery, p = 0.006) and the type of LA agent (lidocaine, p = 0.016) were independently associated with a life-threatening outcome.
CONCLUSION
In this national retrospective analysis, LAST in children appear to be a rare event. Neurological and cardiac signs were the most frequently reported reactions. LAST in children can be life-threatening, even at therapeutic doses. Although a fatal outcome may anecdotally occur, the vast majority of patients recovered after appropriate medical care.
Topics: Infant; Infant, Newborn; Adolescent; Humans; Child; Anesthetics, Local; Pharmacovigilance; Retrospective Studies; Lidocaine; Ropivacaine; Lidocaine, Prilocaine Drug Combination
PubMed: 37355586
DOI: 10.1186/s12887-023-04126-7 -
Medical Gas Research 2021Postoperative pain control is recognized as a challenging surgical issue receiving high priority in the healthcare system, and opioids are routinely prescribed for... (Randomized Controlled Trial)
Randomized Controlled Trial
An investigation of the effects of dexmedetomidine and fentanyl as an adjuvant to ropivacaine on pain scores and hemodynamic changes following laparoscopic cholecystectomy.
Postoperative pain control is recognized as a challenging surgical issue receiving high priority in the healthcare system, and opioids are routinely prescribed for anesthesia and pain relief. This study aimed to investigate the effects of ropivacaine administered intraperitoneally alone or combined with dexmedetomidine or fentanyl on postoperative pain control following laparoscopic cholecystectomy. This randomized double-blind clinical trial recruited three equal-size block-randomized groups of patients (n = 138) scheduled for elective laparoscopic cholecystectomy at Valiasr Hospital, Arak, Iran, in 2019-2020 who received ropivacaine (40 mL/0.5%), ropivacaine (40 mL/0.5%) + dexmedetomidine (1 μg/kg), and ropivacaine (40 mL/0.5%) + fentanyl (1 μg/kg). No significant differences were observed among the three groups according to the vital signs (mean arterial pressure/heart-rate/oxygen saturation) in the study period and during surgery (P > 0.05). Lower pain was revealed in the ropivacaine + dexmedetomidine group (P = 0.001), with the lowest opioid dose in postoperative 24 hours (P = 0.001). Moreover, no clinically significant differences were observed in complications among the three groups (P = 0.483), and no patient developed ileus. Intraperitoneal ropivacaine administered with dexmedetomidine could relieve pain and reduce opioid use in postoperative 24 hours, without any complication and ileus. Therefore, intraperitoneal ropivacaine administered with dexmedetomidine is recommended for postoperative pain control in patients undergoing laparoscopic cholecystectomy. This study was approved by the Ethical Committee of Arak University of Medical Sciences (approval No. IR.ARAKMU.REC.1397.267) on December 30, 2018 and was registered in the Iranian Registry of Clinical Trials (No. IRCT 20141209020258N117) on July 13, 2019.
Topics: Cholecystectomy, Laparoscopic; Dexmedetomidine; Fentanyl; Hemodynamics; Humans; Iran; Pain; Ropivacaine
PubMed: 33942777
DOI: 10.4103/2045-9912.314327 -
Human & Experimental Toxicology 2022Ovarian cancer is a malignant tumor in women all over the world. Ropivacaine is identified as a potential drug for the treatment of malignant tumors, but the role and...
PURPOSE
Ovarian cancer is a malignant tumor in women all over the world. Ropivacaine is identified as a potential drug for the treatment of malignant tumors, but the role and mechanism of ropivacaine in ovarian cancer remains unknown.
MATERIALS AND METHODS
Ovarian cancer cells were treated with different doses of ropivacaine. The function of ropivacaine in ovarian cancer was assessed using Cell Counting Kit-8 assay, flow cytometry, sphere-formation assay, Western blot, Fe level analysis, and immunofluorescence. Meanwhile, the mechanism of ropivacaine in ovarian cancer was investigated by multiple molecular experiments. The protective function of ropivacaine in ovarian cancer was further confirmed by in vivo assay.
RESULTS
The functional research data indicated that the growth and stemness of ovarian cancer cells were restrained after ropivacaine treatment, while the ferroptosis in ovarian cancer cells was facilitated. The mechanism results confirmed that ropivacaine inactivated the PI3K/AKT signaling pathway in ovarian cancer cells. Furthermore, in vivo assay demonstrated that ropivacaine repressed the proliferation of ovarian cancer cells in vivo and had a protective function in ovarian cancer.
CONCLUSION
Ropivacaine restrained ovarian cancer cell stemness and accelerated cell ferroptosis by inactivating PI3K/AKT signaling pathway.
Topics: Cell Line, Tumor; Cell Proliferation; Female; Ferroptosis; Humans; Ovarian Neoplasms; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Ropivacaine; Signal Transduction
PubMed: 36124980
DOI: 10.1177/09603271221120652 -
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 -
Scientific Reports Jun 2022Ropivacaine-induced myotoxicity in surgically incised muscles has not been fully investigated. We evaluated the effects of infiltration anesthesia with ropivacaine on...
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.
Topics: Abdominal Muscles; Amides; Anesthetics, Local; Animals; Inflammation; Pain; Pain Measurement; Pain, Postoperative; Rats; Ropivacaine
PubMed: 35672375
DOI: 10.1038/s41598-022-13628-w -
BMC Anesthesiology Jul 2023Various approaches using epidural analgesia have been employed for relieving labor pain and promoting spontaneous delivery. We aimed to evaluate the effect of nalbuphine...
BACKGROUND
Various approaches using epidural analgesia have been employed for relieving labor pain and promoting spontaneous delivery. We aimed to evaluate the effect of nalbuphine and ropivacaine versus fentanyl and ropivacaine on the duration of delivery in parturients.
METHODS
Clinical data of 160 full-term primiparous women who received either nalbuphine or fentanyl in combination with ropivacaine infusion for epidural labor analgesia in our hospital from December 2020 to May 2022 were retrospectively analyzed. The participants were divided into two groups based on anesthesia methods: nalbuphine group (NR group, n = 78) received 0.2 mg/mL nalbuphine combined with 0.1% ropivacaine hydrochloride for patient-controlled epidural analgesia (PCEA) and fentanyl group (FR group, n = 82) received 2 ug/mL fentanyl citrate and 0.1% ropivacaine hydrochloride for PCEA. Both groups received an epidural blockade for labor analgesia at lumbar 2-3 interspace. The duration of the first, second, and third stages of labor, the onset of analgesia, and time before delivery (T0), 15 min of analgesia (T1), 30 min of analgesia (T2), full opening of the uterine opening (T3),exerts force during childbirth(T4), heart rate (HR), blood pressure (BP), blood saturation (SpO2), visual analogue pain scale (VAS) score, Ramsay sedation score, and modified Bromage score, and 5 min were recorded at 2 h postpartum (T5). The neonatal Apgar score, neonatal behavioral neurological assessment (NBNA) score, maternal nausea, vomiting, and itchy skin were recorded.
RESULTS
Compared with the FR group, the first stage of labor duration (p < 0.05) and total duration of labor (p < 0.05) were shortened and the onset of analgesia (p < 0.05) was increased in the NR group. NR group had lower incidence of urinary retention than FR group (p < 0.05). The maternal and neonatal investigational parameters and scores had no significant difference between the two groups.
CONCLUSIONS
Nalbuphine combined with ropivacaine in epidural block labor has a faster onset of analgesia and has a lower incidence of urinary retention than fentanyl combined with ropivacaine, and nalbuphine shortens the duration of the first and total stages of labor. Both nalbuphine and fentanyl can reduce pain during labor, have little effect on maternal hemodynamics, and have no significant effect on neonatal Apgar or NBNA scores.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Analgesia, Epidural; Ropivacaine; Nalbuphine; Retrospective Studies; Urinary Retention; Pain; Fentanyl
PubMed: 37481510
DOI: 10.1186/s12871-023-02209-7 -
Medicine Oct 2015To compare the analgesic efficacy and safety of the sole local anesthetic ropivacaine with the combination of both local anesthetic ropivacaine and opioidergic analgesic... (Comparative Study)
Comparative Study Randomized Controlled Trial
To compare the analgesic efficacy and safety of the sole local anesthetic ropivacaine with the combination of both local anesthetic ropivacaine and opioidergic analgesic sufentanil given epidurally on the labor pain control.After institutional review board approval and patient consent, a total of 500 nulliparas requesting epidural labor analgesia were enrolled and 481 eventually were randomized into 2 groups: a sole local anesthetic group (ropivacaine 0.125%) and a combination of local anesthetic and opioidergic analgesic group (0.125% ropivacaine + 0.3 μg/mL sufentanil). After the test dose, a 10-mL epidural analgesic solution was given in a single bolus, followed by intermittent bolus injection of 10 to 15 mL of the solution. The primary outcome was the analgesic efficacy measured using Numerical Rating Scale (NRS) of pain. Other maternal and infant variables were evaluated as secondary outcomes.A total of 346 participants completed the study. The median NRS pain score during the 1st stage of labor was significantly lower in the combination group 2.2 (interquartile range [IQR]: 1.8-2.7) comparing to the sole local analgesic group 2.4 (IQR: 2.0-2.8) (P < 0.0001). No significant difference was observed in NRS pain score prior epidural analgesia and during the 2nd stage of labor. Patients in both groups rated same satisfaction of analgesia. Patients in the sole local analgesic group experienced fewer side effects than those in the combination group (37.7% vs 47.2%, P = 0.082). The individual analgesia-related cost in the sole local analgesic group was less ($5.7 ± 2.06) than that in the combination group ($9.76 ± 3.54) (P < 0.0001). The incidence of 1-minute Apgar ≤ 7 was lower in the sole local analgesic group 2 (1.2%) than the combination group 10 (5.5%) (P = 0.038). No difference was found between other secondary outcomes.The sole local anesthetic ropivacaine produces a comparable labor analgesic effect as the combination of both local anesthetic ropivacaine and opioidergic analgesic sufentanil at different stages of labor (ΔNRS = 0.2) but the former has less side effects, lower cost, and less incidence of lower 1-minute Apgar scoring. These results imply the necessity of a systematic reevaluation of epidural labor analgesia with sole local anesthetics against combination regimens of local anesthetics and other opioids.
Topics: Adult; Amides; Anesthesia, Epidural; Female; Humans; Labor, Obstetric; Pregnancy; Ropivacaine; Sufentanil
PubMed: 26512604
DOI: 10.1097/MD.0000000000001882 -
Zhongguo Ying Yong Sheng Li Xue Za Zhi... Nov 2021To investigate the effects and molecular mechanism of ropivacaine hydrochloride on osteosarcoma cell proliferation, invasion, and apoptosis. The osteosarcoma...
To investigate the effects and molecular mechanism of ropivacaine hydrochloride on osteosarcoma cell proliferation, invasion, and apoptosis. The osteosarcoma doxorubicin-resistant cell line (U2OS/DOX) was established by gradually increasing the drug doses. U2OS/DOX cells were treated with ropivacaine hydrochloride at the concentrations of 0, 20, 50 and 100 μg/ml, respectively; as different concentrations treatment groups of ropivacaine hydrochloride. pcDNA3.1 and pcDNA3.1-Livin were transfected into U2OS/DOX cells and then treated with 100 μg/ml ropivacaine hydrochloride, which were defined as ropivacaine hydrochloride 100 μg/ml+pcDNA3.1 group, ropivacaine hydrochloride 100 μg/ml+pcDNA3.1-Livin group. MTT was used to detect the cell proliferation inhibition rate and inhibitory concentration (IC). Western blot was used to detect the expressions of cyclin-dependent kinase inhibitor 1A (P21) and activated cysteine aspartic protease-3 (Cleaved Caspase-3), E-cadherin, matrix metalloproteinase 2 (MMP-2) and Livin; clone formation experiments were used to detect the number of cell clones formed; flow cytometry was used to detect apoptosis; Transwell was used to detect cell migration and invasion; real-time fluorescent quantitative PCR (RT-qPCR) was used to detect Livin mRNA expression. When the concentration of doxorubicin was more than 1 μg/ml, the proliferation inhibition rate of osteosarcoma cells U2OS was significantly increased in a concentration-dependent manner (<0.05); when the concentration of doxorubicin was more than 10 μg/ml, the proliferation inhibition rate of osteosarcoma resistant cell U2OS/DOX was significantly increased, and it was dose-dependent (<0.05). In U2OS/DOX cells treated with ropivacaine hydrochloride, the expressions of P21, Cleaved Caspase-3, and E-cadherin were increased significantly, the expression of MMP-2 was decreased significantly, the cell proliferation inhibition rate was increased significantly, the number of colony formation was decreased significantly, and the cells apoptosis rate was increased significantly, the number of cell migration and invasion was decreased significantly, and the expression of Livin was significantly reduced, in a concentration-dependent manner (<0.05). Overexpression of Livin partially reversed the inhibitory effect of ropivacaine hydrochloride on proliferation, migration, invasion, and promotion effect on apoptosis of cell U2OS/DOX. Ropivacaine hydrochloride can significantly inhibit the proliferation, migration and invasion of doxorubicin-resistant osteosarcoma cells, and significantly promote osteoma cell apoptosis. The mechanism may be related to Livin.
Topics: Apoptosis; Bone Neoplasms; Cell Line, Tumor; Cell Movement; Cell Proliferation; Humans; Matrix Metalloproteinase 2; Osteosarcoma; Ropivacaine
PubMed: 34821101
DOI: 10.12047/j.cjap.6082.2021.088