Liposomal bupivacaine, pain relief and adverse events

2022 ◽  
pp. 291-307
Author(s):  
Hüseyin Oğuz Yılmaz ◽  
Alparslan Turan
Keyword(s):  
Pain Relief ◽  
Adverse Events ◽  
Liposomal Bupivacaine

Local Anesthetics for Neuraxial and Regional Techniques

2018 ◽  
Author(s):  
Michael J Schontz ◽  
Krystina Geiger
Keyword(s):  
Pain Relief ◽  
Adverse Effects ◽  
Local Anesthetic ◽  
Local Anesthetics ◽  
Lipid Emulsion ◽  
Systemic Toxicity ◽  
Duration Of Action ◽  
Liposomal Bupivacaine ◽  
Provide Pain Relief ◽  
Local Anesthetic Systemic Toxicity

Local anesthetics are used with neuraxial and regional techniques to provide pain relief, most commonly postoperatively. Each agent is a sodium-channel blocker, although each agent differs in onset of action, potency, duration of action, and safety profile. Chemical structure and lipophilicity are the main determinants of these characteristics. The agents may be used alone or in combination with an additive which alters the local anesthetic’s properties . Clinically, local anesthetics provide pain relief in a multimodal approach. This reduces opiate consumption, opiate-related adverse effects, and length of stay. Additional benefits when using neuraxial techniques include decreases in mortality, venous thromboembolism, myocardial infarction, pneumonia, respiratory depression, and duration of ileus. Although there are many adverse effects, the most serious include neurologic and cardiovascular. Seizures and cardiac arrest may result from local anesthetic systemic toxicity when systemic levels are elevated or the patient is predisposed. Dose adjustment, removal, or reversal of the agent may be clinically indicated. Lipid emulsion therapy is a reversal agent which acts as a sequestering vehicle for the local anesthetic. Liposomal bupivacaine, the newest formulation of local anesthetic, may provide an increased duration of action compared with standard formulations, although more evidence is needed. This review contains 5 figures, 5 tables, and 59 references. Keywords: amide, ester, epidural, local anesthetic, local anesthetic systemic toxicity, lipid emulsion therapy, liposomal bupivacaine, peripheral nerve block

scholarly journals P129: A phase IV real world study on the use of low dose methoxyflurane (PENTHROX™) for the treatment of moderate to severe trauma pain in the Canadian emergency department (ADVANCE-ED): an interim report on secondary outcomes

CJEM ◽  
2020 ◽  
Vol 22 (S1) ◽  
pp. S111-S111
Author(s):  
S. Campbell ◽  
E. Simard ◽  
A. Arcand ◽  
L. Blagrove ◽  
P. Piraino ◽  
...  
Keyword(s):  
Pain Relief ◽  
Adverse Events ◽  
Acute Pain ◽  
Real World ◽  
Rescue Medication ◽  
Low Dose ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
Phase Iv

Introduction: Inhaled low dose methoxyflurane (MEOF) was recently approved in Canada for the short-term relief of moderate to severe acute pain associated with trauma or interventional medical procedures in conscious adult patients. ADVANCE-ED is an ongoing phase IV, prospective open label study undertaken to generate real-world evidence to complement the global clinical development program through evaluation of the effectiveness of low dose MEOF in Canadian emergency departments (EDs). Methods: This multi-centre study is enrolling adult (≥18 yrs) patients with moderate to severe acute pain (NRS0-10 ≥ 4) associated with minor trauma. To address limitations from the pivotal study, this study allows patients who were excluded in the pivotal trials: namely, those with severe (≥7) pain, and those using OTC or stably dosed analgesics for other conditions, including chronic pain. Eligible patients receive a single treatment of up to 2 x 3 mL MEOF (2nd 3 mL to be provided only upon request), self-administered by the patient under medical supervision. Rescue medication is permitted at any time, if required. Results: Here we describe the patient demographics and treatment satisfaction (Global Medication Performance, GMP) at 50% enrolment (n = 49). Mean (SD) patient age is 48.0 (17.1) yrs and 55.1% are female. Mean pain (SD) reported at enrolment is 8.3 (1.5), with 73.4% of patients with NRS0-10 ≥ 8. Injuries are overwhelmingly limb trauma (87.8%). The most common type is sprain/strain (40.8%), followed by fracture (32.7%). At 5 minutes post-start of administration (STA) of MEOF, 80.4% of patients reported pain relief; this increased to 91.3% at 15 minutes, and 100% of patients reported pain relief by 30 minutes post-STA. GMP was assessed as “good”, “very good” or “excellent” by ≥80% of patients both 20 minutes post-start of administration (STA) of MEOF (83.3%) and at discharge (85.8%). When asked to what extent their expectation of pain relief had been met, 32.7% responded good, 26.5% responded “very good” and 22.4% responded “excellent”. Three quarters of enrolled patients (75.5%) did not require rescue medication. The most common (≥5%) treatment-related adverse events were dizziness (n = 14, 28.6%) and euphoric mood (n = 4, 8.2%). No serious adverse events have been reported. Conclusion: Based on 50% of the patients enrolled in this prospective, open label study, responses to inhaled low-dose MEOF are within expectation for both effectiveness and tolerability.

scholarly journals Post Hoc Analyses of Data from a 90-Day Clinical Trial Evaluating the Tolerability and Efficacy of Tapentadol Immediate Release and Oxycodone Immediate Release for the Relief of Moderate to Severe Pain in Elderly and Nonelderly Patients

2011 ◽  
Vol 16 (4) ◽  
pp. 245-251 ◽  
Author(s):  
Gary Vorsanger ◽  
Jim Xiang ◽  
David Biondi ◽  
David Upmalis ◽  
Jacqueline Delfgaauw ◽  
...  
Keyword(s):  
Back Pain ◽  
Pain Relief ◽  
Adverse Events ◽  
Elderly Patients ◽  
Lower Back Pain ◽  
Severe Pain ◽  
Immediate Release ◽  
Osteoarthritis Pain ◽  
Lower Back ◽  
Post Hoc

OBJECTIVE: To evaluate the tolerability and efficacy of tapentadol immediate release (IR) and oxycodone IR for relief of moderate to severe pain in elderly and nonelderly patients.METHODS: Post hoc data analyses were conducted on a 90-day randomized, phase 3, double-blind, flexible-dose study (ClinicalTrials.gov: NCT00364546) of adults with moderate to severe lower back pain or osteoarthritis pain who received tapentadol IR 50 mg or 100 mg, or oxycodone HCl IR 10 mg or 15 mg every 4 h to 6 h as needed for pain relief. Treatment-emergent adverse events and study discontinuations were recorded.RESULTS: Data from 849 patients randomly assigned (4:1 ratio) to treatment with a study drug (tapentadol IR [n=679] or oxycodone IR [n=170]) were analyzed according to age (younger than 65 years of age [nonelderly], or 65 years of age or older [elderly]) and treatment group. Among elderly patients, incidences of constipation (19.0% versus 35.6%) and nausea or vomiting (30.4% versus 51.1%) were significantly lower with tapentadol IR versus oxycodone IR (all P<0.05). Initial onsets of nausea and constipation occurred significantly later with tapentadol IR versus oxycodone IR (both P≤0.031). Tapentadol IR-treated elderly patients had a lower percentage of days with constipation than oxycodone IR-treated patients (P=0.020). For tapentadol IR- and oxycodone IR-treated elderly patients, respectively, incidences of study discontinuation due to gastrointestinal treatment-emergent adverse events were 15.8% and 24.4% (P=0.190). Tapentadol IR and oxycodone IR provided similar pain relief, with no overall age-dependent efficacy differences (mean pain scores [11-point numerical rating scale] decreased from 7.0 and 7.2 at baseline, to 4.9 and 5.2 at end point, respectively).CONCLUSIONS: Tapentadol IR was safe and effective for the relief of lower back pain and osteoarthritis pain in elderly patients, and was associated with a better gastrointestinal tolerability profile than oxycodone IR.

Predictors of pain relief and adverse events in patients receiving opioids in a prehospital setting

2011 ◽  
Vol 29 (5) ◽  
pp. 512-517 ◽  
Author(s):  
Vincent Bounes ◽  
Caroline Barniol ◽  
Vincent Minville ◽  
Charles-Henri Houze-Cerfon ◽  
Jean Louis Ducassé
Keyword(s):  
Pain Relief ◽  
Adverse Events ◽  
Prehospital Setting

scholarly journals Study of Peri-Articular Anaesthetic for Replacement of the Knee (SPAARK): statistical analysis plan for a randomised controlled trial assessing the effectiveness of peri-articular liposomal bupivacaine plus bupivacaine hydrochloride compared with bupivacaine hydrochloride alone

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jamie R. Stokes ◽  
Ariel Wang ◽  
Lisa Poulton ◽  
Ines Rombach ◽  
Hemant Pandit ◽  
...  
Keyword(s):  
Statistical Analysis ◽  
Randomised Controlled Trial ◽  
Pain Relief ◽  
Knee Replacement ◽  
Controlled Trial ◽  
Statistical Analysis Plan ◽  
Liposomal Bupivacaine ◽  
Bupivacaine Hydrochloride ◽  
Secondary Outcomes ◽  
Randomised Controlled

Abstract Background Up to three quarters of surgical patients receive inadequate pain relief, with 40% of patients reporting severe pain following knee replacement, which may indicate the current pain relief strategies using opiate-based analgesia cannot achieve patient satisfaction. Liposomal bupivacaine is liposome-encapsulated bupivacaine which has been reported to be effective for up to 72 h. The study of Peri-Articular Anaesthetic for Replacement of the Knee (SPAARK) trial has been designed to assess the effectiveness of peri-articular liposomal bupivacaine and bupivacaine hydrochloride compared with peri-articular bupivacaine hydrochloride alone in the management of post-operative pain following knee replacement. Methods/design The SPAARK trial is a multi-centre, patient-blinded, randomised controlled trial. The co-primary outcomes are post-operative recovery assessed by global QoR-40 scores at 72 h and cumulative pain VAS score from 6 to 72 h following surgery. Longer-term measures of the co-primary outcomes are collected at 6 weeks and 6 and 12 months post randomisation, together with secondary outcomes, i.e. the Oxford Knee Score, and the American Knee Society Score. Cumulative opiate use and fitness for discharge are measured up to 72 h post-surgery. The analysis approaches for the primary and secondary outcomes are described here, as are the descriptive statistics which will be reported. The full SPAARK protocol has already been published. Results The co-primary outcomes will be analysed using multivariate linear regression adjusting for stratification factors and other important prognostic variables, including baseline scores in the case of the QoR-40. The adjusted mean difference between the two groups together with 97.5% confidence intervals will be reported for each of the primary outcomes. Other continuous variables will be assessed using the same method. Binary outcomes will be assessed using chi-squared tests. Discussion The paper provides details of the planned statistical analyses for the SPAARK trial and aims to reduce the risk of outcome reporting bias from prior data knowledge. Any changes or deviations from this statistical analysis plan will be described and justified in the final study report. Trial registration ISRCTN54191675. Registered on 13 November 2017.

127 Impact of CYP2D6, CYP3A4, and CYP2C9 pharmacogenomic profile on pain relief and adverse events in Canadian children treated with oxycodone and ibuprofen

2021 ◽  
Vol 26 (Supplement_1) ◽  
pp. e90-e90
Author(s):  
Aran Yukseloglu ◽  
Samina Ali ◽  
Amy Drendel ◽  
Bruce Carleton ◽  
Colin Ross ◽  
...  
Keyword(s):  
Pain Management ◽  
Pain Relief ◽  
Adverse Events ◽  
Functional Limitations ◽  
Clinical Effectiveness ◽  
Pediatric Emergency ◽  
Pain Scale ◽  
Genomic Variation ◽  
Children's Pain ◽  
Ibuprofen Group

Abstract Primary Subject area Clinical Pharmacology and Toxicology Background Genomic variation impacts drug pharmacokinetics for commonly used children’s pain medications such as oxycodone and ibuprofen. In order to personalize and best treat children’s pain, how cytochrome enzyme polymorphisms for CYP2D6, CYP3A4, and CYP2C9 impact clinical effectiveness and safety for oxycodone and ibuprofen were studied. Objectives Primary objectives were to evaluate if allelic variations of CYP2D6, CYP2C9, and CYP3A4 would a) alter clinical effectiveness of ibuprofen and oxycodone for pain relief, and b) impact the occurrence of adverse events. Secondary objectives were to determine the degree to which these genetic and other clinical factors influence analgesic effectiveness and safety. Design/Methods This prospective, observational cohort included children aged 4-16 years who were seen in a pediatric emergency department (between June 2010 - July 2014) with an acute fracture and used ibuprofen OR oxycodone for at-home pain management. Saliva samples were obtained prior to discharge, and daily telephone follow-up collected self-reported pain scores, medication use, adverse events, and functional limitations for 3 days. Genotyping identified allelic variants of CYP2D6, CYP3A4, and CYP2C9. Pain was measured using the Faces Pain Scale-Revised. CYP2D6 metabolic phenotypes were determined based on identified variants. Regression analyses were employed to determine relationships between clinical and genomic patient characteristics, pain relief, and adverse events. Results We included 210 children (n=140 ibuprofen, n=70 oxycodone); mean age was 11.1 (±3.5) years, 66.2% were male, and 79.5% self-identified as Caucasian. The median pain reduction in the ibuprofen group was 4 (±2.0) and 4 (±3.5) in the oxycodone group on Day 1 (p = 0.69). Adverse events were experienced by 53.2% of the ibuprofen group and 78.3% of the oxycodone group (p &lt; 0.001). CYP2D6 Intermediate Metabolizers had significantly less pain relief using oxycodone than Extensive Metabolizers (p = 0.04). CYP3A4 variants did not significantly impact pain relief or adverse events. Those with the decreased functioning CYP2C9*2 allele experienced less adverse events compared to the normal functioning allele CYP2C9*1 (p = 0.003) when using ibuprofen. Males (p = 0.035) and all children using non-pharmacological pain strategies (p = 0.02) experienced less pain relief with oxycodone. Conclusion A better understanding of pharmacogenomic variation could help personalize medication choice. Sex and non-pharmacologic pain management impact pain relief with oxycodone, warranting further study to better understand their relationship with opioid pain relief in children.

Extended-release tramadol (tramadol ER) in the treatment of chronic low back pain

2018 ◽  
Vol 4 (2) ◽  
pp. 87 ◽  
Author(s):  
Gary J. Vorsanger, PhD, MD ◽  
Jim Xiang, PhD ◽  
Theophilus J. Gana, MD, PhD ◽  
Maria Luz G. Pascual, MD, MPH ◽  
R. Rosanna B. Fleming, MS
Keyword(s):  
Low Back Pain ◽  
Back Pain ◽  
Pain Relief ◽  
Adverse Events ◽  
Pain Intensity ◽  
Chronic Low Back Pain ◽  
Low Back ◽  
Open Label ◽  
Once Daily ◽  
To Receive

Background: This study evaluated the safety and efficacy of tramadol ER 300 mg and 200 mg versus placebo once daily in the treatment of chronic low back pain, using an open-label run-in followed by, without washout, a randomized controlled study design.Methods: Adults with scores ≥40 on a pain intensity visual analog scale (VAS; 0 = no pain; 100 = extreme pain) received open-label tramadol ER, initiated at 100 mg once daily and titrated to 300 mg once daily during a three-week open-label run-in. Patients completing run-in were randomized to receive tramadol ER 300 mg, 200 mg, or placebo once daily for 12 weeks.Results: Of 619 patients enrolled, 233 (38 percent) withdrew from the run-in, primarily because of adverse event (n = 128) or lack of efficacy (n = 41). A total of 386 patients were then randomized to receive either 300 mg (n = 128), 200 mg (n = 129), or placebo (n = 129). Following randomization, mean scores for pain intensity VAS since the previous visit, averaged over the 12-week study period, increased more in the placebo group (12.2 mm) than in the tramadol ER 300-mg (5.2 mm, p = 0.009) and 200-mg (7.8 mm, p = 0.052) groups. Secondary efficacy scores for current pain intensity VAS, patient global assessment, Roland Disability Index, and overall sleep quality improved significantly (p ≤ 0.029 each) in the tramadol ER groups compared with placebo. The most common adverse events during the double-blind period were nausea, constipation, headache, dizziness, insomnia, and diarrhea.Conclusions: In patients who tolerated and obtained pain relief from tramadol ER, continuation of tramadol ER treatment for 12 weeks maintained pain relief more effectively than placebo. Adverse events were similar to those previously reported for tramadol ER.

scholarly journals Antagonism of Nerve Growth Factor-TrkA Signaling and the Relief of Pain

2011 ◽  
Vol 115 (1) ◽  
pp. 189-204 ◽  
Author(s):  
Patrick W. Mantyh ◽  
Martin Koltzenburg ◽  
Lorne M. Mendell ◽  
Leslie Tive ◽  
David L. Shelton ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Pain Relief ◽  
Adverse Events ◽  
Tissue Injury ◽  
Sympathetic Neurons ◽  
Nerve Growth ◽  
Cognate Receptor ◽  
Kinase A

Nerve growth factor (NGF) was originally discovered as a neurotrophic factor essential for the survival of sensory and sympathetic neurons during development. However, in the adult NGF has been found to play an important role in nociceptor sensitization after tissue injury. The authors outline mechanisms by which NGF activation of its cognate receptor, tropomyosin-related kinase A receptor, regulates a host of ion channels, receptors, and signaling molecules to enhance acute and chronic pain. The authors also document that peripherally restricted antagonism of NGF-tropomyosin-related kinase A receptor signaling is effective for controlling human pain while appearing to maintain normal nociceptor function. Understanding whether there are any unexpected adverse events and how humans may change their behavior and use of the injured/degenerating tissue after significant pain relief without sedation will be required to fully appreciate the patient populations that may benefit from these therapies targeting NGF.

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