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Anesthesia and Analgesia Dec 2020In women undergoing cesarean delivery under spinal anesthesia with intrathecal morphine, transversus abdominis plane (TAP) block with bupivacaine hydrochloride (HCl) may... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
In women undergoing cesarean delivery under spinal anesthesia with intrathecal morphine, transversus abdominis plane (TAP) block with bupivacaine hydrochloride (HCl) may not improve postsurgical analgesia. This lack of benefit could be related to the short duration of action of bupivacaine HCl. A retrospective study reported that TAP block with long-acting liposomal bupivacaine (LB) reduced opioid consumption and improved analgesia following cesarean delivery. Therefore, we performed a prospective multicenter, randomized, double-blind trial examining efficacy and safety of TAP block with LB plus bupivacaine HCl versus bupivacaine HCl alone.
METHODS
Women (n = 186) with term pregnancies undergoing elective cesarean delivery under spinal anesthesia were randomized (1:1) to TAP block with LB 266 mg plus bupivacaine HCl 50 mg or bupivacaine HCl 50 mg alone. Efficacy was evaluated in a protocol-compliant analysis (PCA) set that was defined a priori. The primary end point was total postsurgical opioid consumption (oral morphine equivalent dosing [MED]) through 72 hours. Pain intensity was measured using a visual analog scale. Adverse events (AEs) after treatment were recorded through day 14.
RESULTS
Total opioid consumption through 72 hours was reduced with LB plus bupivacaine HCl versus bupivacaine HCl alone (least squares mean [LSM] [standard error (SE)] MED, 15.5 mg [6.67 mg] vs 32.0 mg [6.25 mg]). This corresponded to an LSM treatment difference of -16.5 mg (95% confidence interval [CI], -30.8 to -2.2 mg; P = .012). The area under the curve of imputed pain intensity scores through 72 hours supported noninferiority of LB plus bupivacaine HCl versus bupivacaine HCl alone (LSM [SE], 147.9 [21.13] vs 178.5 [19.78]; LSM treatment difference, -30.6; 95% CI, -75.9 to 14.7), with a prespecified noninferiority margin of 36 (P = .002). In an analysis of all treated patients, including those not meeting criteria for inclusion in the PCA, there was no difference in postsurgical opioid consumption between groups. In the LB plus bupivacaine HCl group, 63.6% of patients experienced an AE after treatment versus 56.2% in the bupivacaine HCl-alone group. Serious AEs after treatment were rare (≈3% in both groups).
CONCLUSIONS
TAP block using LB plus bupivacaine HCl as part of a multimodal analgesia protocol incorporating intrathecal morphine resulted in reduced opioid consumption after cesarean delivery in the PCA set. Results suggest that with correct TAP block placement and adherence to a multimodal postsurgical analgesic regimen, there is an opioid-reducing benefit of adding LB to bupivacaine TAP blocks after cesarean delivery (ClinicalTrials.gov identifier: NCT03176459).
Topics: Abdominal Muscles; Adult; Anesthetics, Local; Bupivacaine; Cesarean Section; Double-Blind Method; Female; Humans; Liposomes; Middle Aged; Nerve Block; Pain, Postoperative; Pregnancy
PubMed: 32739962
DOI: 10.1213/ANE.0000000000005075 -
Anesthesia Progress 1978A review of current significant literature concerning bupivacaine hydrochloride (Marcaine) is presented with particular emphasis on clinical use in oral surgery. The... (Review)
Review
A review of current significant literature concerning bupivacaine hydrochloride (Marcaine) is presented with particular emphasis on clinical use in oral surgery. The major advantages compared with other presently used local anesthetics are an increased duration of action and a favorable potency to toxicity ratio.
Topics: Anesthesia, Dental; Anesthesia, Local; Bupivacaine; Humans; Mouth
PubMed: 373511
DOI: No ID Found -
European Journal of Hospital Pharmacy :... Mar 2023Bupivacaine hydrochloride (BH) and ketorolac tromethamine (KT) are commonly used in parenteral admixtures to manage postoperative pain. However, stability and...
OBJECTIVE
Bupivacaine hydrochloride (BH) and ketorolac tromethamine (KT) are commonly used in parenteral admixtures to manage postoperative pain. However, stability and compatibility data for these admixtures applicable to current practice are limited, posing the patient to potential risk.
METHODS
The stability of BH/KT admixtures in commonly used parenteral fluids was studied in Eppendorf tubes and glass vials at ambient room temperature using a newly developed and validated stability-indicating high-performance liquid chromatography (HPLC) method capable of the simultaneous quantification of both drugs. The chemical compatibility of BH/KT was assessed using Fourier transform infrared spectroscopy (FTIR) and thermal analysis. Additionally, the validity of the developed HPLC method for the quantification of BH/KT in human plasma was evaluated.
RESULTS
BH and KT demonstrated <10% loss of their initial concentrations when prepared in Ringer, normal saline or dextrose solution at ambient temperature for up to 4 weeks. FTIR and thermal analysis demonstrated mild intermolecular interactions between BH and KT in solution, with no evidence of incompatibility. The developed HPLC method demonstrated satisfactory accuracy and precision for the simultaneous quantification of BH and KT in human plasma over the range of 0.2-3.2 µg·mL.
CONCLUSION
BH/KT parenteral admixtures are chemically stable for a period of 4 weeks when stored at room temperature. The stability-indicating HPLC method is valid for BH/KT simultaneous determination in human plasma, facilitating pharmacokinetics studies.
Topics: Humans; Ketorolac Tromethamine; Bupivacaine
PubMed: 34663584
DOI: 10.1136/ejhpharm-2021-003003 -
Obstetrics and Gynecology Jul 2020To evaluate bupivacaine concentrations in maternal plasma and transfer into breast milk in women undergoing liposomal bupivacaine infiltration in the transversus...
OBJECTIVE
To evaluate bupivacaine concentrations in maternal plasma and transfer into breast milk in women undergoing liposomal bupivacaine infiltration in the transversus abdominis plane after cesarean birth.
METHODS
Prospective cohort study of healthy pregnant women who underwent cesarean birth at term followed by a transversus abdominis plane block using 52 mg bupivacaine hydrochloride 0.25% (20 mL) and 266 mg liposomal bupivacaine 1.3% (20 mL). Simultaneous blood and milk samples were collected in a staggered fashion, three to four samples per patient at the following timepoints after block administration: 2, 6, 12, 24, 48, 72, and 96 hours. Quantification of bupivacaine was performed by liquid chromatography-tandem mass spectrometry. Neonatal drug exposure was modeled by calculating milk/plasma area under the curve (AUC) ratios, neonatal dosage, and relative neonatal dosage of bupivacaine at each sampling time.
RESULTS
Thirty patients were enrolled. Concentrations in breast milk peaked at 6 hours (mean 58 ng/mL), followed by constant and steady decline to low levels at 96 hours (mean 5.2 ng/mL). Maternal plasma concentrations had two peaks, first at 6 hours (mean 155.9 ng/mL) and then at 48 hours (mean 225.8 ng/mL), followed by steady decline. Milk/plasma AUC0-t ratios ranged between AUC0-2 of 0.45 (80% CI 0.38-0.52) and AUC0-96 of 0.15 (80% CI 0.14-0.17). Neonatal dosage ranged between a mean of 355.9 ng/kg at 0-2 hours and a mean of 15,155.4 ng/kg at 0-96 hours. Relative neonatal dosage was less than 1% at all time intervals. No serious adverse reactions occurred in any neonate.
CONCLUSION
Bupivacaine is excreted in breast milk after local infiltration of liposomal bupivacaine and bupivacaine hydrochloride mixture into transversus abdominis plane blocks after cesarean birth. Relative neonatal dosages of less than 1% (less than 10% is considered to be unlikely to be of clinical concern) suggest minimal risks for breastfeeding healthy, term neonates after the administration of this combination of local anesthetics to mothers.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, NCT03526419.
Topics: Adult; Anesthetics, Local; Area Under Curve; Bupivacaine; Cesarean Section; Cohort Studies; Dose-Response Relationship, Drug; Female; Humans; Infant, Newborn; Milk, Human; Nerve Block; Pregnancy; Prenatal Care; Prospective Studies; Young Adult
PubMed: 32541292
DOI: 10.1097/AOG.0000000000003886 -
JAMA Surgery Jun 2022More than half of patients who undergo knee replacement surgery report substantial acute postoperative pain. (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy of Liposomal Bupivacaine and Bupivacaine Hydrochloride vs Bupivacaine Hydrochloride Alone as a Periarticular Anesthetic for Patients Undergoing Knee Replacement: A Randomized Clinical Trial.
IMPORTANCE
More than half of patients who undergo knee replacement surgery report substantial acute postoperative pain.
OBJECTIVE
To evaluate the efficacy and cost-effectiveness of periarticular liposomal bupivacaine for recovery and pain management after knee replacement.
DESIGN, SETTING, AND PARTICIPANTS
This multicenter, patient-blinded, pragmatic, randomized clinical superiority trial involved 533 participants at 11 institutions within the National Health Service in England. Adults undergoing primary unilateral knee replacement for symptomatic end-stage osteoarthritis were enrolled between March 29, 2018, and February 29, 2020, and followed up for 1 year after surgery. Follow-up was completed March 1, 2021. A per-protocol analysis for each coprimary outcome was performed in addition to the main intention-to-treat analysis.
INTERVENTIONS
Two hundred sixty-six milligrams of liposomal bupivacaine admixed with 100 mg of bupivacaine hydrochloride compared with 100 mg of bupivacaine hydrochloride alone (control) administered by periarticular injection at the time of surgery.
MAIN OUTCOME AND MEASURES
The coprimary outcomes were Quality of Recovery 40 (QoR-40) score at 72 hours and pain visual analog scale (VAS) score area under the curve (AUC) from 6 to 72 hours. Secondary outcomes included QoR-40 and mean pain VAS at days 0 (evening of surgery), 1, 2, and 3; cumulative opioid consumption for 72 hours; functional outcomes and quality of life at 6 weeks, 6 months, and 1 year; and cost-effectiveness for 1 year. Adverse events and serious adverse events up to 12 months after randomization were also assessed.
RESULTS
Among the 533 participants included in the analysis, the mean (SD) age was 69.0 (9.7) years; 287 patients were women (53.8%) and 246 were men (46.2%). Baseline characteristics were balanced between study groups. There was no difference between the liposomal bupivacaine and control groups in QoR-40 score at 72 hours (adjusted mean difference, 0.54 [97.5% CI, -2.05 to 3.13]; P = .64) or the pain VAS score AUC at 6 to 72 hours (-21.5 [97.5% CI, -46.8 to 3.8]; P = .06). Analyses of pain VAS and QoR-40 scores demonstrated only 1 statistically significant difference, with the liposomal bupivacaine arm having lower pain scores the evening of surgery (adjusted difference -0.54 [97.5% CI, -1.07 to -0.02]; P = .02). No difference in cumulative opioid consumption and functional outcomes was detected. Liposomal bupivacaine was not cost-effective compared with the control treatment. No difference in adverse or serious adverse events was found between the liposomal bupivacaine and control groups.
CONCLUSIONS AND RELEVANCE
This study found no difference in postoperative recovery or pain associated with the use of periarticular liposomal bupivacaine compared with bupivacaine hydrochloride alone in patients who underwent knee replacement surgery.
TRIAL REGISTRATION
isrctn.com Identifier: ISRCTN54191675.
Topics: Adult; Aged; Analgesics, Opioid; Anesthetics, Local; Bupivacaine; Female; Humans; Liposomes; Male; Pain, Postoperative; Quality of Life; State Medicine
PubMed: 35385072
DOI: 10.1001/jamasurg.2022.0713 -
Advances in Therapy May 2020This is a comprehensive review of the literature about the use of bupivacaine hydrochloride for the treatment of post-herpetic neuralgia (PHN). It briefly reviews the... (Review)
Review
PURPOSE OF REVIEW
This is a comprehensive review of the literature about the use of bupivacaine hydrochloride for the treatment of post-herpetic neuralgia (PHN). It briefly reviews the background, biology, diagnosis and conventional treatment for PHN, and then introduces and compares the recent evidence for the use of topical bupivacaine.
RECENT FINDINGS
PHN is defined by pain lasting 90 days or more after the initial presentation of herpes zoster ("Shingles", HZ) rash and is the most common complication of this disease. A product of re-activation of the Varicella-Zoster virus (VZV), HZ is diagnosed more than 1 million times annually in the United States. Approximately 20% of patients with HZ will experience PHN and will continue to suffer intermittent neuropathic symptoms, including itching and pain, that is sharp, stabbing, throbbing or burning, with the pain localized to the site of their original rash. This long-lasting pain compares with the severity of long-standing rheumatics and osteo-arthritis and is accompanied by severe allodynia causing significant suffering, and a financial burden that is manifested in both healthcare costs and loss of quality-adjusted life years. Prevention of PHN may be achieved with the Zoster vaccine, although there is still a large segment of unvaccinated population. Moreover, the Zoster vaccine is not always effective for prevention. Current treatment includes medical (systemic tricyclic antidepressants, anticonvulsants and opioids, topical lidocaine and capsaicin) and interventional (subcutaneous Botox injections, nerve blocks and nerve stimulation) therapies. These therapies are not always effective, and each carries their own profile of side effects and risks. Moreover, up to 50% of patients with PHN are refractory to management. Recent evidence is emerging to support the use of topical local anesthetics for the treatment of PHN. Two small studies recently found topical lidocaine spray to be effective in treating paroxysmal pain attacks associated with PHN. Bupivacaine is a longer-lasting local anesthetic, and a film-forming formulation allows easy and durable application to the affected skin. Recent studies show that topical film-forming bupivacaine is safe and as effective as lidocaine for the treatment of PHN. PHN is an important though common complication of HZ and can cause long-lasting pain and disability. Current treatment for PNH is limited by efficacy and safety profiles of individual therapies. Recent evidence points to topical local anesthetics as an effective and safe alternative to conventional therapy. Film-forming bupivacaine may offer a durable and safe option for this otherwise difficult to treat syndrome.
Topics: Analgesics; Analgesics, Opioid; Bupivacaine; Chronic Pain; Health Care Costs; Herpes Zoster; Humans; Neuralgia, Postherpetic
PubMed: 32297285
DOI: 10.1007/s12325-020-01335-9 -
BMC Veterinary Research Jul 2020Long-acting local anaesthetics (e.g. bupivacaine hydrochloride) or sustained-release formulations of bupivacaine (e.g. liposomal bupivacaine) may be neurotoxic when...
BACKGROUND
Long-acting local anaesthetics (e.g. bupivacaine hydrochloride) or sustained-release formulations of bupivacaine (e.g. liposomal bupivacaine) may be neurotoxic when applied in the setting of diabetic neuropathy. The aim of the study was to assess neurotoxicity of bupivacaine and liposome bupivacaine in streptozotocin (STZ) - induced diabetic mice after sciatic nerve block. We used the reduction in fibre density and decreased myelination assessed by G-ratio (defined as axon diameter divided by large fibre diameter) as indicators of local anaesthetic neurotoxicity.
RESULTS
Diabetic mice had higher plasma levels of glucose (P < 0.001) and significant differences in the tail flick and plantar test thermal latencies compared to healthy controls (P < 0.001). In both diabetic and nondiabetic mice, sciatic nerve block with 0.25% bupivacaine HCl resulted in a significantly greater G-ratio and an axon diameter compared to nerves treated with 1.3% liposome bupivacaine or saline (0.9% sodium chloride) (P < 0.01). Moreover, sciatic nerve block with 0.25% bupivacaine HCl resulted in lower fibre density and higher large fibre and axon diameters compared to the control (untreated) sciatic nerves in both STZ-induced diabetic (P < 0.05) and nondiabetic mice (P < 0.01). No evidence of acute or chronic inflammation was observed in any of the treatment groups.
CONCLUSIONS
In our exploratory study the sciatic nerve block with bupivacaine HCl (7 mg/kg), but not liposome bupivacaine (35 mg/kg) or saline, resulted in histomorphometric indices of neurotoxicity. Histologic findings were similar in diabetic and healthy control mice.
Topics: Anesthetics, Local; Animals; Bupivacaine; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Female; Injections; Liposomes; Mice, Inbred C57BL; Mice, Mutant Strains; Nerve Block; Sciatic Nerve
PubMed: 32680505
DOI: 10.1186/s12917-020-02459-4 -
Journal of Cardiothoracic and Vascular... May 2021The objective of this study was to compare the effects of liposomal bupivacaine (Lipo-B) and bupivacaine hydrochloride (B-HCl), in the presence of multimodal analgesia,... (Observational Study)
Observational Study
OBJECTIVES
The objective of this study was to compare the effects of liposomal bupivacaine (Lipo-B) and bupivacaine hydrochloride (B-HCl), in the presence of multimodal analgesia, on postoperative analgesia and opioid consumption in minimally invasive thoracic surgery (MITS) lobectomy.
DESIGN
Retrospective observational cohort study.
SETTING
Tertiary care cancer center.
PARTICIPANTS
A total of 60 patients who underwent MITS lobectomy and received intercostal nerve blockade (ICNB) with either 0.66% Lipo-B (n = 29) or 0.5% B-HCl (n = 31).
INTERVENTIONS
All patients received intravenous patient-controlled analgesia for the first 12 hours postoperatively, followed by opioids and nonsteroidal anti-inflammatory drugs as needed.
MEASUREMENTS AND MAIN RESULTS
Perioperative opioid and nonopioid consumption and pain scores were compared between groups at 12-hour intervals for the first 72 hours. Between the two groups, there were no statistically significant differences in demographic characteristics, intraoperative (p = 0.46) and postoperative opioid consumption, Richmond Agitation-Sedation Scale scores and pain scores upon postanesthesia care unit arrival and after four hours, length of postanesthesia care unit stay (p = 0.84), or length of hospital stay (p = 0.55). Both groups received intra- and postoperative multimodal analgesia.
CONCLUSIONS
In this cohort, no differences in opioid consumption or pain scores were observed in the immediate postoperative period following MITS lobectomy between patients given ICNB with Lipo-B and those given ICNB with B-HCl in the presence of multimodal analgesia.
Topics: Analgesics, Opioid; Anesthetics, Local; Bupivacaine; Humans; Intercostal Nerves; Pain, Postoperative; Retrospective Studies; Thoracic Surgery
PubMed: 33376072
DOI: 10.1053/j.jvca.2020.11.067 -
BMC Anesthesiology Jul 2021Liposomal bupivacaine (LB) is a long-acting formulation of bupivacaine. The safety and efficacy of LB has been demonstrated across surgical procedures. However,...
BACKGROUND
Liposomal bupivacaine (LB) is a long-acting formulation of bupivacaine. The safety and efficacy of LB has been demonstrated across surgical procedures. However, pharmacokinetic (PK) parameters and safety of LB in the Chinese population have not been assessed.
METHODS
In this single-arm, single center, phase 1, open-label study, PK and safety of local infiltration with LB 266 mg were assessed in healthy Chinese adults. Eligible participants were aged 18 to 55 years with biologic parents and grandparents of Chinese ethnicity, in generally good health (i.e., no clinically significant abnormalities), and with a body mass index (BMI) 19.0 to 24.0 kg/m (inclusive) and body weight ≥ 50 kg.
RESULTS
Participants (N = 20) were predominantly men (80 %); mean age was 32 years; and mean BMI was 21.8 kg/m. After LB administration, mean plasma levels of bupivacaine rapidly increased during the first hour and continued to increase through 24 h; plasma levels then gradually decreased through 108 h followed by a monoexponential decrease through 312 h. Geometric mean maximum plasma concentration was 170.9 ng/mL; the highest plasma bupivacaine concentration detected in any participant was 374.0 ng/mL. Twenty-two treatment-emergent adverse events were reported (mild, n = 21; moderate, n = 1).
CONCLUSIONS
After single-dose administration of LB, PK measures were similar to a previously reported profile in US adults. The highest observed peak plasma concentration of bupivacaine was several-fold below the plasma concentration threshold accepted as being associated with neurotoxicity or cardiotoxicity (2000-4000 ng/mL). These data support that LB is well tolerated and safe in individuals of Chinese descent.
TRIAL REGISTRATION
NCT04158102 (ClinicalTrials.gov identifier), Date of registration: November 5, 2019.
Topics: Adult; Anesthetics, Local; Asian People; Bupivacaine; Female; Humans; Liposomes; Male; Young Adult
PubMed: 34315419
DOI: 10.1186/s12871-021-01407-5 -
Anesthesiology May 2024
Topics: Bupivacaine
PubMed: 38592361
DOI: 10.1097/ALN.0000000000004934