IU Indianapolis ScholarWorks :: Browsing by Subject "Analgesia"

Browsing by Subject "Analgesia"

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A multicenter study to evaluate the pharmacokinetics and safety of liposomal bupivacaine for postsurgical analgesia in pediatric patients aged 6 to less than 17 years (PLAY)
(Elsevier, 2021) Tirotta, Christopher F.; de Armendi, Alberto J.; Horn, Nicole D.; Hammer, Gregory B.; Szczodry, Michal; Matuszczak, Maria; Wang, Natalie Q.; Scranton, Richard; Ballock, Robert Tracy; Anesthesia, School of Medicine
Study objective: To evaluate the pharmacokinetics and safety of liposomal bupivacaine in pediatric patients undergoing spine or cardiac surgery. Design: Multicenter, open-label, phase 3, randomized trial (PLAY; NCT03682302). Setting: Operating room. Patients: Two separate age groups were evaluated (age group 1: patients 12 to <17 years undergoing spine surgery; age group 2: patients 6 to <12 years undergoing spine or cardiac surgery). Intervention: Randomized allocation of liposomal bupivacaine 4 mg/kg or bupivacaine hydrochloride (HCl) 2 mg/kg via local infiltration at the end of spine surgery (age group 1); liposomal bupivacaine 4 mg/kg via local infiltration at the end of spine or cardiac surgery (age group 2). Measurements: The primary and secondary objectives were to evaluate the pharmacokinetics (eg, maximum plasma bupivacaine concentrations [Cmax], time to Cmax) and safety of liposomal bupivacaine, respectively. Main results: Baseline characteristics were comparable across groups. Mean Cmax after liposomal bupivacaine administration was lower versus bupivacaine HCl in age group 1 (357 vs 564 ng/mL); mean Cmax in age group 2 was 320 and 447 ng/mL for spine and cardiac surgery, respectively. Median time to Cmax of liposomal bupivacaine occurred later with cardiac surgery versus spine surgery (22.7 vs 7.4 h). In age group 1, the incidence of adverse events (AEs) was comparable between liposomal bupivacaine (61% [ 19/31] ) and bupivacaine HCl (73% [ 22/30 ]). In age group 2, 100% (5/5) and 31% (9/29) of patients undergoing spine and cardiac surgery experienced AEs, respectively. AEs were generally mild or moderate, with no discontinuations due to AEs or deaths. Conclusions: Plasma bupivacaine levels following local infiltration with liposomal bupivacaine remained below the toxic threshold in adults (~2000-4000 ng/mL) across age groups and procedures. AEs were mild to moderate, supporting the safety of liposomal bupivacaine in pediatric patients undergoing spine or cardiac surgery.
A Quality Improvement Initiative to Decrease Time to Analgesia in Patients With Sickle Cell and Vaso-Occlusive Crisis: A Population With Disparities in Treatment
(Springer Nature, 2022-09-25) Arnold, Tyler; Coffee, R. Lane, Jr.; Rosenberg, Leon; Jacob, Seethal A.; Thompson, Sean; Saavedra, Heather; Cico, Stephen John; Wagers, Brian; Emergency Medicine, School of Medicine
Introduction: Vaso-occlusive crises (VOCs) are the leading cause of emergency department (ED) visits and hospitalizations in patients with sickle cell disease (SCD). Timely administration of analgesia, within 60 minutes of patient registration, is the standard of care for SCD patients with VOCs. Patients with VOCs have longer times to initial analgesia compared to similar painful conditions. The primary aim of the project is to have 75% of patients with VOCs receive initial analgesia within 60 minutes of being registered, the current recommended time frame from the National Heart, Lung, and Blood Institute (NHLBI). Methods: A multi-disciplinary team used quality improvement (QI) methodology to develop a plan involving multiple Plan-Do-Study-Act (PDSA) cycles. A rapid evaluation process was employed which included notification of a patient with a VOC being placed in a room, rapid evaluation by all team members and use of an electronic order set. Results: The aim was met 72% of the time during our intervention period, compared to 17% pre-intervention. Average time to initial analgesia was decreased from 61 minutes to 42 minutes (p-value < 0.001), while time to disposition was also decreased when time goals were achieved. Conclusion: Using a rapid evaluation process we were able to decrease time to initial analgesia in a patient population that has previously experienced delays in care and decrease overall time to disposition.
Effects of oxycodone pharmacogenetics on postoperative analgesia and related clinical outcomes in children: a pilot prospective study
(Taylor & Francis, 2023) Aruldhas, Blessed W.; Quinney, Sara K.; Packiasabapathy, Senthil; Overholser, Brian R.; Raymond, Olivia; Sivam, Sahana; Sivam, Inesh; Velu, Sanjana; Montelibano, Antoinette; Sadhasivam, Senthilkumar; Medicine, School of Medicine
Background: Variability in the pharmacokinetics and pharmacodynamics of oxycodone in children undergoing surgery could be due to genetic polymorphisms. Materials & methods: The authors studied the association between clinical outcomes and pharmacogenes in children undergoing major surgery. A total of 89 children (35 undergoing pectus excavatum repair and 54 undergoing spinal fusion) were recruited. Results: OPRM1 SNP rs6902403 showed an association with maximum pain score and total morphine equivalent dose (p < 0.05). Other polymorphisms in OPRM1 SNP, PXR, COMT and ABCB1 were also shown to be associated with average morphine equivalent dose, length of hospital stay and maximum surgical pain (p < 0.05). Conclusion: This study demonstrates novel associations between the above pharmacogenes and oxycodone's pharmacokinetics as well as postoperative outcomes in children.
Gender, genetics, and analgesia: understanding the differences in response to pain relief
(Dovepress, 2018-11-08) Packiasabapathy, Senthil; Sadhasivam, Senthilkumar; Anesthesia, School of Medicine
Genetic variations and gender contribute significantly to the large interpatient variations in opioid-related serious adverse effects and differences in pain relief with other analgesics. Opioids are the most commonly used analgesics to relieve moderate-to-severe postoperative pain. Narrow therapeutic index and unexplained large interpatient variations in opioid-related serious adverse effects and analgesia negatively affect optimal perioperative outcomes. In surgical, experimental, chronic, and neuropathic pain models, females have been reported to have more pain than males. This review focuses on literature evidence of differences in pain relief due to multiple genetic variations and gender of the patient.
Genetics of perioperative pain management
(Lippincott, Williams & Wilkins, 2018-12) Packiasabapathy, Senthil; Horn, Nicole; Sadhasivam, Senthilkumar; Anesthesia, School of Medicine
PURPOSE OF REVIEW: The current review will discuss the current literature on genetics of pain and analgesia, with special emphasis on perioperative setting. We will also discuss pharmacogenetics-based management guidelines, current clinical status and future perspectives. RECENT FINDINGS: Recent literature suggests that the interindividual variability in pain and postoperative analgesic response is at least in part because of one's genetic make-up. Some of the well characterized polymorphisms that are associated with surgical pain and opioid-related postoperative adverse outcomes are described in catechol-O-methyl transferase, CYP2D6 and μ-opioid receptor (OPRM1), ATP-binding cassette subfamily B member 1, ABCC3, organic cation transporter 1 genes. Clinical Pharmacogenetics Implementation Consortium has put forth recommendations on CYP2D6 genotype-based opioid selection and dosing. The list of drug-gene pairs studied continue to expand. SUMMARY: Pharmacogenetic approach marks the dawn of personalized pain medicine both in perioperative and chronic pain settings.
Methods for pragmatic randomized clinical trials of pain therapies: IMMPACT statement
(Wolters Kluwer, 2024) Hohenschurz-Schmidt, David; Cherkin, Dan; Rice, Andrew S. C.; Dworkin, Robert H.; Turk, Dennis C.; McDermott, Michael P.; Bair, Matthew J.; DeBar, Lynn L.; Edwards, Robert R.; Evans, Scott R.; Farrar, John T.; Kerns, Robert D.; Rowbotham, Michael C.; Wasan, Ajay D.; Cowan, Penney; Ferguson, McKenzie; Freeman, Roy; Gewandter, Jennifer S.; Gilron, Ian; Grol-Prokopczyk, Hanna; Iyengar, Smriti; Kamp, Cornelia; Karp, Barbara I.; Kleykamp, Bethea A.; Loeser, John D.; Mackey, Sean; Malamut, Richard; McNicol, Ewan; Patel, Kushang V.; Schmader, Kenneth; Simon, Lee; Steiner, Deborah J.; Veasley, Christin; Vollert, Jan; Medicine, School of Medicine
Pragmatic, randomized, controlled trials hold the potential to directly inform clinical decision making and health policy regarding the treatment of people experiencing pain. Pragmatic trials are designed to replicate or are embedded within routine clinical care and are increasingly valued to bridge the gap between trial research and clinical practice, especially in multidimensional conditions, such as pain and in nonpharmacological intervention research. To maximize the potential of pragmatic trials in pain research, the careful consideration of each methodological decision is required. Trials aligned with routine practice pose several challenges, such as determining and enrolling appropriate study participants, deciding on the appropriate level of flexibility in treatment delivery, integrating information on concomitant treatments and adherence, and choosing comparator conditions and outcome measures. Ensuring data quality in real-world clinical settings is another challenging goal. Furthermore, current trials in the field would benefit from analysis methods that allow for a differentiated understanding of effects across patient subgroups and improved reporting of methods and context, which is required to assess the generalizability of findings. At the same time, a range of novel methodological approaches provide opportunities for enhanced efficiency and relevance of pragmatic trials to stakeholders and clinical decision making. In this study, best-practice considerations for these and other concerns in pragmatic trials of pain treatments are offered and a number of promising solutions discussed. The basis of these recommendations was an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) meeting organized by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks.
Novel associations between CYP2B6 polymorphisms, perioperative methadone metabolism and clinical outcomes in children
(Future Medicine, 2021-07) Packiasabapathy, Senthil; Aruldhas, Blessed W.; Zhang, Pengyue; Overholser, Brian R.; Quinney, Sara K.; Sadhasivam, Senthilkumar; Anesthesia, School of Medicine
Aim: Methadone exhibits significant variability in clinical response. This study explores the genetic influence of variable methadone pharmacokinetics. Methods: This is a prospective study of methadone in children undergoing major surgery. CYP2B6 genotyping, plasma methadone and metabolite levels were obtained. Clinical outcomes include pain scores and postoperative nausea and vomiting (PONV). Results:CYP2B6 poor metabolizers (*6/*6) had >twofold lower methadone metabolism compared with normal/rapid metabolizers. The incidence of PONV was 4.7× greater with CYP2B6 rs1038376 variant. AG/GG variants of rs2279343 SNP had 2.86-fold higher incidence of PONV compared with the wild variant (AA). Nominal associations between rs10500282, rs11882424, rs4803419 and pain scores were observed. Conclusion: We have described novel associations between CYP2B6 genetic variants and perioperative methadone metabolism, and associations with pain scores and PONV.
Perioperative Multimodal General Anesthesia Focusing on Specific CNS Targets in Patients Undergoing Cardiac Surgeries: The Pathfinder Feasibility Trial
(Frontiers Media, 2021-10-14) Shanker, Akshay; Abel, John H.; Narayanan, Shilpa; Mathur, Pooja; Work, Erin; Schamberg, Gabriel; Sharkey, Aidan; Bose, Ruma; Rangasamy, Valluvan; Senthilnathan, Venkatachalam; Brown, Emery N.; Subramaniam, Balachundhar; Anesthesia, School of Medicine
Multimodal general anesthesia (MMGA) is a strategy that utilizes the well-known neuroanatomy and neurophysiology of nociception and arousal control in designing a rational and clinical practical paradigm to regulate the levels of unconsciousness and antinociception during general anesthesia while mitigating side effects of any individual anesthetic. We sought to test the feasibility of implementing MMGA for seniors undergoing cardiac surgery, a high-risk cohort for hemodynamic instability, delirium, and post-operative cognitive dysfunction. Twenty patients aged 60 or older undergoing on-pump coronary artery bypass graft (CABG) surgery or combined CABG/valve surgeries were enrolled in this non-randomized prospective observational feasibility trial, wherein we developed MMGA specifically for cardiac surgeries. Antinociception was achieved by a combination of intravenous remifentanil, ketamine, dexmedetomidine, and magnesium together with bupivacaine administered as a pecto-intercostal fascial block. Unconsciousness was achieved by using electroencephalogram (EEG)-guided administration of propofol along with the sedative effects of the antinociceptive agents. EEG-guided MMGA anesthesia was safe and feasible for cardiac surgeries, and exploratory analyses found hemodynamic stability and vasopressor usage comparable to a previously collected cohort. Intraoperative EEG suppression events and postoperative delirium were found to be rare. We report successful use of a total intravenous anesthesia (TIVA)-based MMGA strategy for cardiac surgery and establish safety and feasibility for studying MMGA in a full clinical trial.
Research objectives and general considerations for pragmatic clinical trials of pain treatments: IMMPACT statement
(Wolters Kluwer, 2023) Hohenschurz-Schmidt, David J.; Cherkin, Dan; Rice, Andrew S. C.; Dworkin, Robert H.; Turk, Dennis C.; McDermott, Michael P.; Bair, Matthew J.; DeBar, Lynn L.; Edwards, Robert R.; Farrar, John T.; Kerns, Robert D.; Markman, John D.; Rowbotham, Michael C.; Sherman, Karen J.; Wasan, Ajay D.; Cowan, Penney; Desjardins, Paul; Ferguson, McKenzie; Freeman, Roy; Gewandter, Jennifer S.; Gilron, Ian; Grol-Prokopczyk, Hanna; Hertz, Sharon H.; Iyengar, Smriti; Kamp, Cornelia; Karp, Barbara I.; Kleykamp, Bethea A.; Loeser, John D.; Mackey, Sean; Malamut, Richard; McNicol, Ewan; Patel, Kushang V.; Sandbrink, Friedhelm; Schmader, Kenneth; Simon, Lee; Steiner, Deborah J.; Veasley, Christin; Vollert, Jan; Anesthesia, School of Medicine
Many questions regarding the clinical management of people experiencing pain and related health policy decision-making may best be answered by pragmatic controlled trials. To generate clinically relevant and widely applicable findings, such trials aim to reproduce elements of routine clinical care or are embedded within clinical workflows. In contrast with traditional efficacy trials, pragmatic trials are intended to address a broader set of external validity questions critical for stakeholders (clinicians, healthcare leaders, policymakers, insurers, and patients) in considering the adoption and use of evidence-based treatments in daily clinical care. This article summarizes methodological considerations for pragmatic trials, mainly concerning methods of fundamental importance to the internal validity of trials. The relationship between these methods and common pragmatic trials methods and goals is considered, recognizing that the resulting trial designs are highly dependent on the specific research question under investigation. The basis of this statement was an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) systematic review of methods and a consensus meeting. The meeting was organized by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership. The consensus process was informed by expert presentations, panel and consensus discussions, and a preparatory systematic review. In the context of pragmatic trials of pain treatments, we present fundamental considerations for the planning phase of pragmatic trials, including the specification of trial objectives, the selection of adequate designs, and methods to enhance internal validity while maintaining the ability to answer pragmatic research questions.
What Is the Best Pain Control After Major Hepatopancreatobiliary Surgery?
(Elsevier, 2018-09) Kim, Bradford J.; Soliz, Jose M.; Aloia, Thomas A.; Vauthey, Jean-Nicolas; Surgery, School of Medicine
In the modern era, hepato-pancreato-biliary (HPB) surgery has become safe with significant reductions in morbidity and mortality at high volume centers for both liver and pancreas surgery. While laparoscopic surgery has provided a safe approach with superior pain control laparotomy is still needed for the majority of HPB operations. Inadequate pain control is not only associated with poor patient experience but contributes to inferior outcomes. Specifically, inadequate pain control affects the neuroendocrine stress response, increases complication rates, and prolongs length of stay. Furthermore, there is an ongoing opioid epidemic and all fields of medicine should strive to reduce narcotic use to limit transformation into chronic opiate dependence. As such, successful pain control after HPB surgery continues to be a challenge and rigorous studies evaluating postoperative results are needed. The following article reviews the modalities debated to be the best strategies for pain control after major HPB surgery, as well as a discussion of other important considerations when executing these plans.

Browsing by Subject "Analgesia"

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